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1120401
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Characterisation of the human and mouse orthologues of the Drosophila ariadne gene.
The specificity of the ubiquitin degradation system is regulated through interaction between individual ubiquitin-conjugating enzymes (E2s) and multiple ubiquitin-protein ligases (E3s). Here we describe the characterisation of a novel gene (ARIH1) that encodes the human homologue of Drosophila ariadne which interacts with the E2s, UbcH7 and UbcH8 and represents a component of an E3 complex. Three PACs (189N19, 142P17 and 179H7) were isolated that contain this gene. Using these PACs as probes, we mapped ARIH1 to human chromosome 15q24 by fluorescence in situ hybridisation (FISH). Sequencing of the ARIH1 PACs showed that the gene has 13 introns. In addition, we isolated two PACs (345D8 and 571P19) containing the mouse orthologue (Arih1) of ARIH1. The intron-exon structure of Arih1 was identical to ARIH1 and the proteins demonstrated a 98% identity at the amino acid level. Furthermore, comparison of Drosophila ariadne with ARIH1 indicates an identity at the amino acid level of 70% and introns at 3/7 identical sites. The high degree of homology demonstrated by the mouse and human orthologues of Drosophila ariadne indicates an important, conserved biological function, consistent with a putative role in ubiquitylation.
| 196
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PubMed Abstracts
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1120406
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Angioleiomyoma within a histiocytoma.
We report an angioleiomyoma developed within a cellular histiocytoma on the calf of a 77-year-old man. The lesion consisted of a spherical nodule with two well-defined concentric areas. The outer circular area was a cellular histiocytoma and the inner central area consisted of an angioleiomyoma. Immunoperoxidase investigations for desmin demonstrated positivity in the angio-leiomyoma, whereas the histiocytoma remained negative. Serial sections of the lesion failed to demonstrate a connection between the angioleiomyoma and a normal vein which could have been trapped by the histiocytoma. The angioleiomyoma may have originated from a vessel in the histiocytoma.
| 98
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PubMed Abstracts
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1120417
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[Construction of an in vitro carotid artery bifurcation model].
To construct a solid carotid artery bifurcation model with general applicability that simulates the real shape. The diameter of the carotid artery was measured using ultrasonic cardiograph. A modified carotid artery model was constructed according to the tuning fork model geometry with the geometry size being rectified. The flow fields in the carotid artery model were detected by the particle imaging velocimetry technique. The characteristics of the distribution of the flow fields in the carotid artery model were similar to those in the human bodies. The carotid artery we constructed well resembles the real shape and has good representativeness and practicability, which provides a reliable experimental platform for further research.
| 118
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PubMed Abstracts
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1120421
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Drug discovery management, small is still beautiful: Why a number of companies get it wrong.
This review provides an account of why more companies involved in drug discovery fail than succeed at releasing the creative energy of gifted scientists, whose invention of new drugs they rely upon to remain at the forefront of the biopharma industry. Initiatives aimed at improving output of new chemical entities often have the opposite effect from that intended and scientists become demotivated. Those with drive, vision and enthusiasm may move to smaller companies to rediscover the spirit of discovery. Some executives fail to understand the psyche of researchers; an applied understanding of the intrinsic motivation of scientists would improve research performance. Entities that focus on smaller autonomous units and sound ethical values will discover the most innovative and successful new drugs.
| 135
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PubMed Abstracts
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1120423
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Ifosfamide in pediatric oncology.
Since the number of patients seen in a pediatric oncology center is relatively small, it is difficult to perform single drug phase two studies, even on a national base. This also probably explains the lack of information on ifosfamide, despite the fact that it has now been used for more than 10 years in pediatrics. As long as chemotherapy plays such an important role in childhood cancer it remains of the utmost importance to determine the role of ifosfamide in the treatment of young cancer patients.
| 89
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PubMed Abstracts
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1120435
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Alpha-ketoglutarate inhibits glutamine degradation and enhances protein synthesis in intestinal porcine epithelial cells.
α-Ketoglutarate (AKG) is a key intermediate in glutamine metabolism. Emerging evidence shows beneficial effects of AKG on clinical and experimental nutrition, particularly with respect to intestinal growth and integrity. However, the underlying mechanisms are unknown. Intestinal porcine epithelial cells (IPEC-1) were used to test the hypothesis that AKG inhibits glutamine degradation and enhances protein synthesis. IPEC-1 cells were cultured for 3 days in Dulbecco's modified Eagle's-F12 Ham medium (DMEM-F12) containing 0, 0.2, 0.5 or 2 mM of AKG. At the end of the 3-day culture, cells were used to determine L-[U-14C]glutamine utilization, protein concentration, protein synthesis, and the total and phosphorylated levels of the mammalian target of the rapamycin (mTOR), ribosomal protein S6 kinase-1 (S6K1) and eukaryotic initiation factor (eIF) 4E-binding protein-1 (4E-BP1). Compared with 0 mM of AKG (control), 0.2 and 0.5 mM of AKG dose-dependently reduced (P<0.05) glutamine degradation and the production of glutamate, alanine and aspartate in IPEC-1 cells. Addition of 0.5 and 2 mM of AKG to culture medium enhanced protein synthesis (P<0.05) by 78 and 101% without affecting protein degradation, compared to the control group. Rapamycin (50 nM; a potent inhibitor of mTOR) attenuated the stimulatory effect of AKG on protein synthesis. Consistent with these metabolic data, the addition of 0.5 or 2 mM of AKG to culture medium increased (P<0.05) the phosphorylated levels of mTOR, S6k1 and 4E-BP1 proteins. Collectively, these results indicate that AKG can spare glutamine and activate the mTOR signaling pathway to stimulate protein synthesis in intestinal epithelial cells.
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PubMed Abstracts
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1120452
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Stable isotope ratios using cavity ring-down spectroscopy: determination of 13C/12C for carbon dioxide in human breath.
We have constructed a cavity ring-down spectrometer employing a near-IR external cavity diode laser capable of measuring 13C/12C isotopic ratios in CO2 in human breath. The system, which has a demonstrated minimum detectable absorption loss of 3.2 x 10(-11) cm(-1) Hz(-1/2), determines the isotopic ratio of 13C16O16O/12C16O16O by measuring the intensities of rotationally resolved absorption features of each species. As in isotope ratio mass spectrometry (IRMS), the isotopic ratio of a sample is compared to that of a standard CO2 sample calibrated to the Pee Dee Belemnite scale and reported as the sample's delta13C value. Measurements of eight replicate CO2 samples standardized by IRMS and consisting of 5% CO2 in N2 at atmospheric pressure demonstrated a precision of 0.22/1000 for the technique. Delta13C values were also obtained for breath samples from individuals testing positive and negative for the presence of Helicobacter pylori, the leading cause of peptic ulcers in humans. This study demonstrates the ability of the instrument to obtain delta13C values in breath samples with sufficient precision to serve as a useful medical diagnostic.
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PubMed Abstracts
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1120458
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[Genetic control of interleukin-2 production in inbred mice].
BALB/c mice (H-2d haplotype) produced IL 2 better than C57BL/6 mice (H-2d haplotype). However genetic analysis in F2 generation demonstrated independent segregation of the IL 2 production intensity and H-2 haplotype. Investigation of the IL 2 production intensity in BALB/c, C57BL/6 and their F1 and F2 generation revealed that this was controlled by only one gene.
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PubMed Abstracts
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1120487
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Effects of angiotensin II on proximal tubular cells stably transfected with the c-mas oncogene.
Angiotensin II (ANG II) normally induces cellular hypertrophy in proximal tubular epithelium by engaging receptor systems that use a G-protein-signaling mechanism. The c-mas oncogene also encodes part of a superfamily of vasoactive peptide receptor-like moieties that couple to G proteins. To determine whether the stable expression of the c-mas gene might alter or modify the induction of cellular hypertrophy by ANG II in tubular epithelium, a rat c-mas cDNA was cloned into the pSV2 expression vector for use in cell transfection. Scatchard analysis of ANG II binding revealed no significant differences in ANG II receptor number or in the dissociation constant between pSV2mas-transfected or wild-type MCT cells, but rather an increase in the number of receptors not replaceable by known inhibitors. ANG II also induced proliferation in pSV2mas-transfected MCT cells that was not blocked by conventional inhibitors and increased intracellular levels of inositol trisphosphate. ANG II, furthermore, did not increase de novo protein synthesis in pSV2-transfected MCT cells and failed to lower their intracellular concentration of adenosine 3',5'-cyclic monophosphate, both expected parameters of cellular hypertrophy. Our findings demonstrate that expression of c-mas in tubular epithelium can modulate tubular cell phenotype toward proliferation rather than hypertrophy. This effect is likely mediated by a reshuffling of the heterogeneity of ANG II receptors on the cell surface, or perhaps by the emergence of a new ANG II receptor, followed by alterations in the process of signal transduction.
| 247
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PubMed Abstracts
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1120489
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High-level bacterial expression, purification and characterization of human calreticulin.
To investigate its cellular function and role in autoimmune disease pathogenesis, we have bacterially expressed human calreticulin, a major calcium-binding protein in the endoplasmic reticulum and a human autoantigen. This is the first report describing the heterologous expression of calreticulin from any source. The recombinant calreticulin constituted approximately 32% of the soluble Escherichia coli proteins, and was purified to apparent homogeneity by ion exchange and hydrophobic liquid chromatography. As does the bona fide protein, the recombinant calreticulin binds calcium and undergoes changes in its conformation upon Zn2+ binding. We take this as a strong indication that the folding of the E.coli-expressed calreticulin is very similar, if not identical, to that of the authentic protein. Moreover, the bacterially expressed calreticulin readily reacted with anti-human and anti-rabbit antibodies, and the anti-recombinant calreticulin antibodies immunoreacted with HeLa calreticulin. The availability of this expression system will allow us to carry out site-specific and deletion mutagenesis analysis in structure--function studies of calreticulin.
| 165
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PubMed Abstracts
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1120493
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Escherichia coli strains belonging to phylogenetic group B2 have superior capacity to persist in the intestinal microflora of infants.
Escherichia coli strains segregate into 4 phylogenetic groups, designated "A," "B1," "B2," and "D." Pathogenic strains belong to group B2 and, to a lesser extent, group D, which more frequently carry virulence-factor genes than do group A strains and group B1 strains. This study investigated whether the capacity of E. coli to persist in the human intestine is related to its phylogenetic type. Resident (n=58) and transient (n=19) commensal E. coli strains isolated during a longitudinal study of 70 Swedish infants and previously tested for virulence-factor-gene carriage were tested for phylogenetic type. Of the strains resident in the intestinal microflora, 60% belonged to group B2, compared with only 21% of the transient strains (P=.004). In logistic regression, group B2 type predicted persistence in the intestinal microflora, independent of carriage of all investigated virulence-factor genes, including genes for P fimbriae (P=.03). Thus, group B2 strains appear to possess yet unidentified traits that enhance their survival in the human intestine.
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PubMed Abstracts
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1120497
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Clinical results of charité lumbar total disc replacement.
To preserve segmental lumbar motion and to prevent adjacent segment disease, there has been a growing enthusiasm for the use of intervertebral disc prosthesis as an alternative to segmental lumbar fusion. To date, more than 100-disc prostheses have been designed, but only 10 prostheses have been approved and implanted in humans. The Charité Artificial Disc has had the longest clinical follow-up with more than 5000 implantations in over 30 countries and reported > 10-year satisfactory results.
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PubMed Abstracts
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1120500
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Amebic Liver Abscess.
Amebic liver abscess should be suspected in travelers returning from endemic areas or in immunocompromised patients who present with fever, right upper quadrant pain, hepatomegaly, and a liver lesion on an imaging study. Rapid initiation of therapy without serologic confirmation of infection, if necessary, is important to minimize complications. Metronidazole is given orally or intravenously for 14 days. The drug is generally well tolerated and leads to resolution of symptoms in most patients within 2 to 3 days. It is effective against luminal cysts in only 50% of patients and, therefore, must be followed by a course of treatment with paromomycin (Humatin; Parke-Davis, Morris Plains, NJ) or another luminal antiamebic agent to eradicate the parasite. Image-guided drainage of an amebic liver abscess is indicated in patients who do not respond to antimicrobial therapy or who are at risk of abscess rupture. Surgery is reserved for patients with a ruptured abscess. Although medical therapy is generally successful in the treatment of infection caused by Entamoeba histolytica, the development of potent vaccines will be needed for worldwide eradication of disease attributable to E. histolytica.
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PubMed Abstracts
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1120507
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Prognostic implications of the extent of surgical resection in patients with intracranial malignant gliomas.
The goal of treating patients with malignant gliomas by intracranial surgery has been to remove as much tumor as possible without causing new neurologic deficits. However, it is still debatable whether the degree of surgical resection correlates with survival times of patients with supratentorial gliomas. One hundred and one patients with supratentorial malignant gliomas who underwent either a gross total resection, a subtotal resection, and/or a partial resection were examined. A correlation between their length of survival and the degree of surgical resection was determined. The survival rates of patients who underwent total resections were significantly higher than those of patients who underwent subtotal or partial resections (P < 0.01). However, there was no significant difference in the survival rates between the subtotal and partial resection groups. These results also were confirmed by independent variables, such as age, location of the tumors, and histologic subtypes, with the exceptions of temporal gliomas and those younger than 60 years. The favorable prognosis of patients with malignant gliomas depends upon the total resection of these tumors. These findings should be of help in designing preoperative surgical intervention strategies.
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PubMed Abstracts
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1120510
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Oncology patients' perceptions of "the good nurse": a descriptive study in Flanders, Belgium.
The image of "the good nurse" is mainly studied from the perspective of nurses, which often does not match the image held by patients. Therefore, a descriptive study was conducted to examine oncology patients' perceptions of "the good nurse" and the influence of patient- and context-related variables. A cross-sectional, comparative, descriptive design was used. The sample comprised 557 oncology patients at one of six Flemish hospitals, where they were treated in an oncology day-care unit, oncology hospital ward, or palliative care unit. Data were collected using the Flemish Care-Q instrument. Factor analysis summarised the most important characteristics of "the good nurse". We reassessed the reliability and construct validity of the Flemish Care-Q and examined the influence of patient- and context-related variables on patient perceptions. Using factor analysis, we grouped the different items of the Flemish Care-Q according to three characteristics: "the good nurse" (I) has a supportive and communicative attitude towards patient and family, (II) is competent and employs a professional attitude, and (III) demonstrates personal involvement towards patient and family. Median factor scores of Factors I, II, and III, respectively, were 8.00, 9.00, and 8.00 (varying from 1, not important, to 10, very important). In order of importance, Factors II, I, and III were identified as valuable characteristics of "the good nurse". Gender, care setting, and province were influential variables. As perceived by oncology patients, "the good nurse" has a broad range of qualities, of which competence and professionalism are the most valuable.
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PubMed Abstracts
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1120516
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Informed consent: the consent component.
Individuals who participate in treatment or research protocols should perceive that their decision is a free choice and that they are acting of their own accord. However, these persons may feel as if they are being pressured to participate in the protocol being described. The author discusses the two components of consent: voluntariness and authorization and offers suggestions to nurses to fulfill their moral responsibility to be patient advocates.
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PubMed Abstracts
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1120521
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The Drosophila light-activated TRP and TRPL channels - Targets of the phosphoinositide signaling cascade.
The Drosophila light-activated Transient Receptor Potential (TRP) channel is the founding member of a large and diverse family of channel proteins. It is now established that TRP channels are evolutionarily conserved and are found in many organisms and tissues. This review outlines the progress made in our understanding of Drosophila phototransduction with a focus on the light sensitive TRP channels. The visual system of Drosophila has remarkable capabilities, such as single photon sensitivity, low dark noise, wide dynamic range of responses to changing ambient light intensities and an unusually wide range of frequency responses to modulated lights. These capabilities are obtained by a unique cellular structure called rhabdomere, which contains ∼40,000 microvilli, harboring a sophisticated molecular machinery performing phototransduction. The phototransduction cascade was discovered mainly by using the power of Drosophila molecular genetics and the ability to generate mutations in virtually every gene of the cascade. This allowed a detailed functional analysis and mechanistic description of the phototransduction cascade. Drosophila phototransduction has been a model system, instrumental for studying phosphoinositide signaling and its participation in TRP channel activation. Accordingly, the phosphoinositide signaling cascade activates the TRP/TRPL channels via Gq-protein-mediated PLCβ, while the gating mechanism of the channels following PLC activation is still under debate. Detailed studies of the single photon response (quantum bump) and the spontaneous dark bump has given important tools to investigate critical features of channel activation and regulation including: synchronization in channel activity, the existence of a Ca2+ regulated threshold of channel activation, positive and negative feedback and refractory period in bump generation. We anticipate that studies in Drosophila photoreceptors will continue shed light on mechanisms that operate in mammalian TRP channels.
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PubMed Abstracts
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1120527
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A proposal for a standard CORBA interface for genome maps.
The scientific community urgently needs to standardize the exchange of biological data. This is helped by the use of a common protocol and the definition of shared data structures. We have based our standardization work on CORBA, a technology that has become a standard in the past years and allows interoperability between distributed objects. We have defined an IDL specification for genome maps and present it to the scientific community. We have implemented CORBA servers based on this IDL to distribute RHdb and HuGeMap maps. The IDL will co-evolve with the needs of the mapping community. The standard IDL for genome maps is available at http:// corba.ebi.ac.uk/RHdb/EUCORBA/MapIDL.htm l. The IORs to browse maps from Infobiogen and EBI are at http://www.infobiogen.fr/services/Hugemap/IOR and http://corba.ebi.ac.uk/RHdb/EUCORBA/IOR CONTACT: [email protected], [email protected]
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PubMed Abstracts
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1120533
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Total tetra knockout of GP138 multigene family implicated in cell interactions in Dictyostelium discoideum.
The cellular slime mold Dictyostelium discoideum reproduces sexually under submerged and dark conditions. A cell surface glycoprotein gp138 has been identified as a target molecule for cell fusion-blocking antibodies, and is considered to be indispensable for the sexual cell fusion in this organism. Currently, four isoforms of gp138, DdFRP1alpha, DdFRP1beta, DdFRP2, and DdFRP3, are known. Genes encoding the latter three isoforms, GP138C, GP138A, and GP138B, have been isolated, comprising a GP138 multigene family. Here we isolated the fourth GP138 gene, GP138D, encoding DdFRP1alpha. These GP138 genes were found to cluster in a tandem array on chromosome 5, being bordered by two GP138-like sequences highly homologous to them but truncated. To clarify functional relationships among the GP138 family members, the entire GP138 region was deleted by a single knockout. Northern hybridization and western immuno-blotting analyses confirmed complete losses of GP138 mRNA and DdFRPs in the knockout strains, indicating that there are no more GP138 genes. Unexpectedly, however, the GP138-null mutants were fully potent for both sexual cell fusion and subsequent development. In addition, the original fusion-blocking antibodies detected a cell surface protein of close electrophoretic mobility to gp138 in the knockouts, suggesting the possibility that the actual target molecule of the fusion-blocking antibodies was not DdFRPs but this unidentified component. Since GP138-null mutants exhibited no obvious defects either in growth or asexual development, the real function of the GP138 family is unknown. Nevertheless, the expression levels of other developmental genes such as acaA, csaA, cotA-C, and spiA appeared to be altered in the GP138-null mutants. Therefore, it seems to have a non-critical but some role(s) during asexual development.
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PubMed Abstracts
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1120538
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Lumbar cerebrospinal fluid pulse wave rising from pulsations of both the spinal cord and the brain in humans.
There are two theories regarding the origin of the lumbar cerebrospinal fluid pulse wave (L-CSFPW): that it arises from the arteries supplying the spinal cord, and that it is due to the pulsations of the brain transmitted through the subarachnoid space of the spine. We investigated L-CSFPW of 11 myelopathic patients with a complete (five patients, CB-group) or an incomplete spinal block (six, ICB-group) on myelography to determine the origin of L-CSFPW. Since arterial pressure amplitude (APA), the energy source of L-CSFPW, is not the same between individuals or between before and after operation, not only L-CSFPW itself but also the transfer function between the arterial pressure wave and the L-CSFPW calculated by the system analysis method was analyzed to eliminate the influence of hemodynamic fluctuations. In the system analysis, the arterial pressure wave, L-CSFPW and transfer function were decomposed into five harmonic waves (HW). In the CB group, L-CSFPW was observed to be 0.72 mmHg on average (range, 0.25-1.00) in spite of blocking pulsations of the brain, showing that there was a contribution to L-CSFPW unrelated to the brain, that is, the spinal cord. In the CB group, however, the preoperative transfer function value of HW1 (mean, 0.056; range, 0.012-0.170) was lower than that in the ICB group (mean, 0.137; range, 0.061-0.236) (P < 0.05), indicating that the brain pulsation also contributed to L-CSFPW. In the ICB group, there was significant reduction of HW1 (P < 0.01) and HW2 (P < 0.05) transfer function after posterior decompression surgery in spite of improvement in the subarachnoid space narrowing: preoperative HW1, mean, 0.137, range, 0.061-0.236; postoperative HW1, mean, 0.065, range, 0.021-0.153; preoperative HW2, mean, 0.092, range, 0.011-0.148; postoperative HW2, mean, 0.044, range, 0.030-0.066. It has been reported that the spinal cord blood flow is decreased 20% or more by laminectomy, therefore, L-CSFPW measurement may be sensitive enough to detect a 20% or higher decrease in this flow. This suggests that L-CSFPW could possibly be used clinically as a non-invasive method of monitoring the spinal cord blood flow. For broad clinical application of CSFPW, however, further studies are needed, especially on the direct relationship between CSFPW and spinal cord blood flow itself.
| 377
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PubMed Abstracts
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1120540
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Bis(morpholino-1,3,5-triazine) derivatives: potent adenosine 5'-triphosphate competitive phosphatidylinositol-3-kinase/mammalian target of rapamycin inhibitors: discovery of compound 26 (PKI-587), a highly efficacious dual inhibitor.
The PI3K/Akt signaling pathway is a key pathway in cell proliferation, growth, survival, protein synthesis, and glucose metabolism. It has been recognized recently that inhibiting this pathway might provide a viable therapy for cancer. A series of bis(morpholino-1,3,5-triazine) derivatives were prepared and optimized to provide the highly efficacious PI3K/mTOR inhibitor 1-(4-{[4-(dimethylamino)piperidin-1-yl]carbonyl}phenyl)-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea 26 (PKI-587). Compound 26 has shown excellent activity in vitro and in vivo, with antitumor efficacy in both subcutaneous and orthotopic xenograft tumor models when administered intravenously. The structure-activity relationships and the in vitro and in vivo activity of analogues in this series are described.
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PubMed Abstracts
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1120544
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Systematic off-pump coronary artery bypass.
We assessed the feasibility of systematic off-pump coronary artery bypass (OPCAB) and identified risk factors for on-pump conversion. Between July 1, 2002 and December 31, 2003, OPCAB was attempted for all patients who required isolated coronary artery bypass in our institution. The perioperative results of patients were prospectively entered into a structured database, the results were analyzed to identify the risks of requirement of cardiopulmonary bypass. OPCAB was performed in all but 4 patients, giving an OPCAB success rate of 98.3% (229/233). The reason for cardiopulmonary bypass was hemodynamic instability occurring during reoperative surgery in 3, and cardiogenic shock in 1. The isolated risk factor for on-pump conversion was reoperation (relative risk 11.6). Mean number of distal anastomoses performed under OPCAB was 3.7+/-1.2, and the complete revascularization rate was 92.1% (211/229). There was one hospital death (0.4%). During a mean follow-up period of 1.0+/-0.4 years, two patients developed angina, which were treated with catheter intervention; otherwise, there was no death, or other cardiac events observed. Systematic OPCAB was feasible except in patients undergoing reoperative surgery or patients with on-going deep cardiogenic shock. Systematic OPCAB provided successful complete revascularization and its short term results were acceptable.
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PubMed Abstracts
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1120557
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Antiphospholipid antibodies and thrombosis.
Antiphospholipid antibodies are a diverse group of immunoglobulins initially thought to have specificity to phospholipid epitopes. It is apparent that autoimmune anticardiolipin antibodies require a serum cofactor beta-2-glycoprotein I (beta 2GPI) for their binding to phospholipids. Lupus anticoagulant also may bind to phospholipids by beta 2GPI or by prothrombin. The description of binding to protein-phospholipid epitopes may explain several perplexing features of these antibodies both in vitro and in vivo. Antiphospholipid antibodies have a well-established association with clinical disease--in particular thrombosis, thrombocytopenia and recurrent fetal loss. The mechanism of the predisposition to thrombosis seen with these antibodies is poorly understood. It has been suggested that they may cause endothelial dysfunction by causing increased tissue factor expression, by inhibiting prostacyclin secretion or by inhibiting fibrinolysis. Various platelet-activating activities have also been described. The evidence that antiphospholipid antibodies promote thrombosis by effects on endothelium or platelets is inconclusive. Inhibition of protein C activation, or of activated protein C action, has been demonstrated in vitro. A poor correlation between thrombosis in vivo and these inhibitory effects has been found. Beta-2-glycoprotein I has been identified as a cofactor for binding to phospholipid by thrombogenic anticardiolipin antibodies. That beta 2GPI may be a natural anticoagulant of importance remains to be proved. Inhibition by antiphospholipid antibodies of this anticoagulant function could explain the propensity to thrombosis seen in association with these antibodies.
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PubMed Abstracts
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1120560
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Therapeutic drug monitoring of amlodipine and the Z-FHL/HHL ratio: Adherence tools in patients referred for apparent treatment-resistant hypertension.
Non-adherence to antihypertensives is a cause of 'pseudo-treatment-resistant' hypertension. To determine whether monitoring plasma amlodipine concentrations and inhibition of angiotensin-converting enzyme (ACE) can be adjunct adherence tools. Patients with hypertension who were prescribed enalapril and amlodipine were enrolled. Blood pressures (BPs) were monitored and an adherence questionnaire was completed. Steady-state amlodipine was assayed using liquid chromatography-mass spectrometry and degree of ACE inhibition using the Z-FHL/HHL (z-phenylalanine-histidine-leucine/hippuryl-histidine-leucine) ratio. One hundred patients (mean (standard deviation) age 50.5 (12) years, 46% male) were enrolled. Based on plasma assays, 26/97 patients (26.8%) were unsuppressed by enalapril and 20/100 (20%) were sub-therapeutic for amlodipine. There were significant BP differences based on plasma levels of the medication: 21/20 mmHg lower in the group with suppressed ACE and 26/20 mmHg in the group with steady-state amlodipine concentrations. Monitoring antihypertensive adherence by assaying plasma medication concentrations is a feasible option for evaluating true v. pseudo-resistant hypertension.
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PubMed Abstracts
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1120564
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A "natural experiment" in childrearing ecologies and adolescents' attachment and separation representations.
Employing a quasi-experimental design, this study explored the long-term effects of different childrearing ecological contexts. Participants were 131 adolescents (aged 16-18) from four groups: some who lived in a city, some from a kibbutz familial setting, some from a kibbutz communal setting, and a transitional group that included adolescents raised in a communal setting as young children who moved to a familial sleeping arrangement before the age of six. Adolescents' state of mind with regard to attachment and representations regarding separation were examined. Participants were administered the Adult Attachment Interview, the Separation Anxiety Test, and background questionnaires. The group raised in a communal setting in the kibbutz showed a higher incidence of nonautonomous attachment representations and less competent coping with imagined separations than did the other groups. By contrast, the transitional group was comparable to the city and the kibbutz familial groups. These results are discussed in light of the plasticity and adaptability of children to changed circumstances.
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PubMed Abstracts
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1120579
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[Porphyrins in renal calculi (review)].
We performed a review of the porphyrines content in a type of black, charcoal-like, renal calculi exhibiting infrared spectra (IRS) similar to those characteristic of "organic material" which has not yet been fully elucidate. Several other types of renal calculi, mainly those of small size, spontaneous passage renal stone, may also have diffuse or isolated dark charcoal components showing "organic material" IRS. After observing that haemoglobin has an "organic material" IRS, we studied, by a sensitive thin layer chromatography method, the presence of porphyrines in several types of dark or charcoal renal stones, since porphyrines are the physiological precursors of haemo group biosynthesis. We found two types of porphyrine content: coproporphyrin, in patients suffering from hepatopathy, and uroporphyrin and heptacarboxil-porphyrin in patients with some types of porphyria or with chronic renal failure.
| 136
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PubMed Abstracts
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1120584
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Ileocecal Intussusception Caused by an Appendiceal Neoplasm.
Mucinous appendiceal neoplasm occurs in less than 1% of appendicectomies. Majority of what is known in the literature is about pseudomyxoma peritonei, which exists as its disseminated form. Pictorial imagery of its pre-disseminated form is rarely observed. We present in a case report form a case of low-grade mucinous neoplasm of the appendix resulting in focal intussusception including images captured from this unique case that will become a learning case for readers of the journal.
| 81
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PubMed Abstracts
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1120615
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Mitochondrial impairment by PPAR agonists and statins identified via immunocaptured OXPHOS complex activities and respiration.
Mitochondrial impairment is increasingly implicated in the etiology of toxicity caused by some thiazolidinediones, fibrates, and statins. We examined the effects of members of these drug classes on respiration of isolated rat liver mitochondria using a phosphorescent oxygen sensitive probe and on the activity of individual oxidative phosphorylation (OXPHOS) complexes using a recently developed immunocapture technique. Of the six thiazolidinediones examined, ciglitazone, troglitazone, and darglitazone potently disrupted mitochondrial respiration. In accord with these data, ciglitazone and troglitazone were also potent inhibitors of Complexes II+III, IV, and V, while darglitazone predominantly inhibited Complex IV. Of the six statins evaluated, lovastatin, simvastatin, and cerivastatin impaired mitochondrial respiration the most, with simvastatin and lovastatin impairing multiple OXPHOS Complexes. Within the class of fibrates, gemfibrozil more potently impaired respiration than fenofibrate, clofibrate, or ciprofibrate. Gemfibrozil only modestly inhibited Complex I, fenofibrate inhibited Complexes I, II+III, and V, and clofibrate inhibited Complex V. Our findings with the two complementary methods indicate that (1) some members of each class impair mitochondrial respiration, whereas others have little or no effect, and (2) the rank order of mitochondrial impairment accords with clinical adverse events observed with these drugs. Since the statins are frequently co-prescribed with the fibrates or thiazolidinediones, various combinations of these three drug classes were also analyzed for their mitochondrial effects. In several cases, the combination additively uncoupled or inhibited respiration, suggesting that some combinations are more likely to yield clinically relevant drug-induced mitochondrial side effects than others.
| 256
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PubMed Abstracts
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1120624
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Recurrence relations for the Cartesian derivatives of the Zernike polynomials.
A recurrence relation for the first-order Cartesian derivatives of the Zernike polynomials is derived. This relation is used with the Clenshaw method to determine an efficient method for calculating the derivatives of any linear series of Zernike polynomials.
| 47
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PubMed Abstracts
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1120631
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High-Q design of semiconductor-based ultrasmall photonic crystal nanocavity.
We report a high-Q design for a semiconductor-based two-dimensional zero-cell photonic crystal (PhC) nanocavity with a small mode volume. The optimization of displacements of hexagonal-lattice air holes in the Gamma-M direction, in addition to the Gamma-K direction, resulted in a cavity quality factor Q of 2.8 x 10(5) sustaining the small modal volume of 0.23(lambda(0)/n)(3). The momentum space consideration of out-of-plane radiation loss showed that the optimization of air hole displacements in both the in-plane x and y directions reduced FT components in the leaky region along the k(x) and k(y) axes, respectively. This high-Q cavity design is applicable to Si and GaAs semiconductor materials.
| 112
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PubMed Abstracts
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1120647
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Lack of correlation between phenotype and genotype in untreated 21-hydroxylase-deficient Indonesian patients.
Mutations in CYP21A2 lead to deficiency of 21-hydroxylase and can have either severe or moderate effects on phenotype, which can be prevented by early treatment. We studied long-term effects of this deficiency on phenotype in patients who had not been treated for prolonged periods and correlated these phenotypes with the mutations found in our patients. To assess the correlation between genotype and phenotype in untreated patients with 21-hydroxylase deficiency. Subjects with 21-hydroxylase deficiency were selected from a large population of Indonesian patients with disorders of sexual differentiation. CYP21A2 mutations in these patients were correlated with their phenotype in terms of genital development and steroid hormone levels. Fifteen 46,XX patients with ages between 1 and 33 years, of whom 12 had never been treated before. Mutations in CYP21A2, genital phenotype and steroid hormone levels. We found in all patients CYP21A2 mutations which affect enzyme activity, with a relatively high allele frequency of R356W (40%), I172N (20%) and IVS2 - 1A > G (13%). Clitoris length was directly correlated with levels of testosterone, but not with age. The phenotype was not always concordant with the genotype: different phenotypes (mild to severe virilization) were found in sibling pairs with the mutations IVS2 - 13A > G or I172N. The high frequency of homozygous mutants for R356W in patients aged from 1 to 11 years old is remarkable, as this mutation has been described only in salt-wasting patients. In our study, this mutation caused a urogenital sinus in three out of seven cases, whereas in the remaining cases the labia were at least partially fused. This mutation caused severe virilization with remarkably high serum levels of renin. We found one novel substitution in intron 2 (IVS2 - 37A > G), containing the branch site, which is likely to affect the CYP21-enzyme. Two additional intron 2 substitutions were discovered, which are supposed to affect the 21-hydroxylase (i.e. IVS2 + 33A > C and IVS2 + 67C > T). We conclude that a correlation exists between the concentration of androgens and the extent of virilization. However, there was no clear correlation between genotype and phenotype, except for the mutation R356W.
| 365
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PubMed Abstracts
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1120654
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[Gamma knife treatment of meningiomas].
From October 1995 to July 1997, 52 cases of meningioma were treated with gamma knife radiosurgery. Twenty-eight cases were followed up by CT or MR. The follow-up period was from 2 to 22 months. Follow-up imaging evaluation showed tumor size shrinkage in 8 cases, central density decrease in 10 cases, no change in 8 cases and tumor volume increase in 2 cases. The actual 1-year tumor growth control rate was 92%. Radiation-induced edema was noted in 9 cases, including 7 cases of the nonbasal tumor and 2 cases of basal one. The indications and efficacy of gamma knife treatment of the meningioma were discussed. Our preliminary experience suggests that gamma knife is an effective and safe technique for carefully selected patients with meningiomas.
| 127
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PubMed Abstracts
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1120657
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Electronic structure and stability of fluorophore-nitroxide radicals from ultrahigh vacuum to air exposure.
Thin film processes of organic radicals remain widely unknown, although these materials may have a significant technological potential. In aiming at their use in applications, we explore the electronic structure of thin films of a nitronyl nitroxide radical attached to a fluorophore core. According to our findings, this molecule maintains its radical function and, consequently, its sensing capabilities in the thin films. The films are characterized by a high structural degree of the molecular arrangement, coupled to strong vacuum and air stability that make this fluorophore-nitroxide radical an extremely promising candidate for application in electronics. Our work also identifies a quantitative correlation between the results obtained by the simultaneous use of X-ray photoemission and electron paramagnetic resonance spectroscopy. This result can be used as a standard diagnostic tool in order to link the (in situ-measured) electronic structure with classical ex situ paramagnetic investigations.
| 155
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PubMed Abstracts
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1120659
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[Laboratory determination of thiopurine levels in paediatric patients with inflammatory bowel disease].
Thiopurines are drugs widely used in patients for the maintenance of remission in inflammatory bowel disease. The optimal plasma levels are known, but there is controversy about whether the need for other drugs is reduced or is cost-effective. The aim of this study is to describe the use of the optimised treatment with thiopurines in paediatric patients with inflammatory bowel disease followed up in this Unit since the introduction of determining the drug levels. A descriptive retrospective study was conducted in which the plasma values of 6-thioguanine (6-TGN), 6-methyl-mercapto-purine (6-MMP), and their ratios were analysed using liquid chromatography. Other variables were collected, such as clinical status, analytical and demographic variables of patients with inflammatory bowel disease followed up in this Unit. A total of 72 patients were included, and 149 determinations of metabolites were performed. The 6-TGN levels were found to below the therapeutic range in 61.5% of patients (in 7 cases due to lack of adherence to therapy), and 6-MMP was in the toxicity range in 7.4%. After the determination of 77 specimens, some action was taken, such as modifying the dose, change of formula, or withdrawing the drug. Only 9 patients were scaled to a biological drug (13.4% of the total on single therapy). No association was found between the activity of the disease and the thiopurine levels. In our experience, the monitoring of thiopurine levels helped to modify the drug dose that the patient received, adjusting their therapeutic levels, and potentially avoiding the addition of new drugs.
| 261
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PubMed Abstracts
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1120664
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Temporary inactivation of the retrorubral fields decreases the rewarding effect of medial forebrain bundle stimulation.
Prior studies indicate that lesioning the retrorubral fields (RRF) decreases the rewarding effect of medial forebrain bundle (MFB) stimulation, although these studies did not make the RRF their primary target. This study directly investigates the role of the RRF in MFB self-stimulation using transient lidocaine-induced inactivation of target tissue rather than permanent lesioning. In 18 rats with MFB stimulation electrodes, inactivation of the RRF via 0. 5 and 1.0 microl of 4% lidocaine produced immediate, substantial upward shifts in the frequency required to maintain half-maximal self-stimulation response rates whereas injecting comparable volumes of saline did not. Bilateral inactivation was particularly effective, especially at medium and high stimulation currents, although unilateral inactivation ipsilateral to the stimulation site was also effective. Contralateral inactivation alone did not substantially change the stimulation's reward value, although contralateral inactivation appeared to contribute to the effectiveness of bilateral inactivation. The frequency required to maintain half-maximal responding returned to baseline levels by 15-20 min after lidocaine infusion. In seven rats whose infusion sites were not in the RRF, lidocaine inactivation did not consistently degrade the stimulation's reward value. These results indicate that some neural elements located in the RRF contribute to the rewarding effect of MFB stimulation. Possible roles for these elements in the anatomical substrate for MFB self-stimulation are discussed.
| 227
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PubMed Abstracts
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1120671
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Muscular dystrophy of mink: a new animal model.
Muscular dystrophies comprise an important group of inherited disorders of man. Although the disease has been studied extensively, little is known about the underlying primary pathomechanisms. Consequently, treatment of patients is difficult and prognosis is poor. An animal model of muscular dystrophy is a useful research tool for approaching the basic problems of pathogenesis in muscle diseases. An inherited progressive muscular dystrophy of mink which resembles the amyotonic forms of human muscular dystrophy is currently under study. Clinically, the earliest sign is progressive muscular weakness and atrophy. Muscle enzyme activities in serum are usually elevated to pathologic levels. Urinary creatine/creatinine ratio is elevated. Pathologic changes are limited to skeletal muscle and are typical of those seen in amyotonic forms of human muscular dystrophy. These changes include variation in diameter size of muscle fibers, centralized nuclei, floccular and hyaline degeneration of scattered muscle fibers, increase in connective tissue in endomysial and perimysial areas, and regenerative attempts. Both type I and type II muscle fibers are involved in the disease process. Genetic studies indicate an autosomal recessive mode of inheritance. Although the primary defect in muscular dystrophy is traditionally thought to reside in skeletal muscle, recent studies have produced theories of primary involvement of other tissues and organ systems. These theories are presented and relationships to the traditional theory are discussed.
| 226
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PubMed Abstracts
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1120686
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[Ionic mechanism of the stimulatory effect of noradrenaline on smooth muscle cells of the pulmonary artery].
Noradrenaline (NA) in a concentration of 5 X 10(-6) M produces depolarization of smooth muscle cells of the rabbit pulmonary artery and reduction of membrane resistance followed by contraction and increased excitability of muscle cells. Experiments with repolarization of the membrane exposed to NA in normal and Ca-free Krebs solutions have shown that activation of the NA-induced contraction is mainly due to Ca++ entering the cells through NA-sensitive potential-dependent Ca-channels. The NA-induced depolarization results from an initial decrease of K-permeability of the membrane subsequent increase of the permeability of NA-sensitive potential-dependent channels for Na+ and/or Cl-, which provides further depolarization of the membrane. Depolarization ceases after becoming sufficient for activation of potential-dependent non-inactivated K-channels. Voltage clamp experiments have shown that the NA-induced increased excitability is related to a reduction of slow, particularly of fast component of outward current, whose early activation prevents the development of regenerative process of action potential generation under normal conditions.
| 169
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PubMed Abstracts
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1120689
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Evaluation of the medical history.
Medical and dental interdisciplinary cooperation is critical in appropriate assessment of the medical history and the subsequent management of the medically compromised dental patient. This interdisciplinary, rather than multidisciplinary, cooperation must extend beyond the physician and include the patient, family, caregivers, therapists, and anyone else involved in the life of the particular individual. This article has discussed numerous medically compromising conditions that require cooperative efforts between dental health professionals and other health care professionals. Specific recommendations were made regarding certain medical problems that affect dental care. The patient with a medical condition has a significant disability affecting many facets of life, essentially no different than a person with a physical or mental disability. The critical activity on the part of the dentist in managing the medically compromised dental patient is the cognitive skill ability. Cognitive skills permit appropriate use of the proper technique and behavioral skills. Proper oral health care can contribute significantly to a person's quantity and quality of life. The concept of optimum dental treatment planning differs from ideal dental treatment planning but should not be considered compromised dental treatment planning. Finally, an evaluation tool, the DRAPE Scale, is a means to aid dental treatment planning for the medically compromised dental patient. Remember that optimum care may not be ideal and is influenced by patient-specific and situation-specific circumstances. When this approach to treatment is followed in the appropriate interdisciplinary fashion, the patient benefits, and an individual's quantity and quality of life should benefit. Dental care for the patient with medically compromising conditions can be difficult and infinitely challenging but ultimately rewarding.
| 267
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PubMed Abstracts
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1120690
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Immunostimulation protects microglial cells from nitric oxide-mediated apoptosis.
Cellular oxidative stress from excess free radicals can initiate apoptosis in some cell types. Thus, we hypothesize that cells expressing nitric oxide synthase (NOS) will also express anti-oxidative stress mechanisms, in order to prevent self-intoxication by the free radical, nitric oxide (NO). To test this hypothesis, we investigated the vulnerability of microglial cells (BV-2 line) to NO produced by the NO donor sodium nitroprusside. Damage to the cells was measured by an in situ detection method of DNA fragmentation, an indicator of apoptosis. Activation by lipopolysaccharide (LPS) dose-dependently protected BV-2 cells against NO toxicity (up to 67%) while unactivated BV-2 cells were vulnerable to NO. Our results indicate that activation of BV-2 cells induces protection mechanisms against NO toxicity.
| 126
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PubMed Abstracts
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1120692
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[Experience feedback committees (CREX) in French radiotherapy departments in 2019].
Ten years after the beginning of CREX in radiotherapy departments we wanted to know about users' feeling. We sent a survey to 168 centers in the whole country and a hundred of them answer. The time, top management's involvement and professionals' training seem to be the key success factors. Systemic analysis methods and mainly the Orion© one are not identified as an issue. The main challenge for the next years will be the effectiveness check of actions.
| 86
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thePile
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PubMed Abstracts
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1120703
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Child labour for the benefit of the family in rural Poland.
Employing children to work in a family household or on a farm is a widespread phenomena in many countries worldwide. This paper presents the results of an investigation of the phenomenon of the involvement of children aged 11-14 years in work on family farms and in rural households in central and eastern Poland, a typical agricultural region. The data obtained are characterized by high reliability due to utilization of various research techniques: surveys and observations based on records of daily routines. Material collected by questionnaire survey is significant because of the relatively large group of respondents – 1,536 people, selected by stratified sampling. Records of the daily routines of 332 people randomly selected from the general sample of 1,536 people, were conducted over a total period of 2 months through all the seasons – 2 weeks in each season – provided reliable data. Analysis of the collected material allowed characterization of the phenomenon of children's engagement in the work in a family household and on a farm belonging to their parents or relatives, and an indication of the life and health hazards of children involved in work for a benefit of the family.
| 203
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PubMed Abstracts
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1120727
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Pathways utilized by dendritic cells for binding, uptake, processing and presentation of antigens derived from HIV-1.
The outcome following HIV infection depends on the nature and durability of the HIV-specific T cell response induced initially. The activation of protective T cell responses depends upon dendritic cells (DC), antigen-presenting cells which have the capacity to process and present viral antigens. DC pulsed with aldrithiol-2-inactivated HIV and delivered in vivo were reported to induce immune responses and promote virologic control in chronically HIV-1-infected subjects. To gain an understanding of this phenomenon, we characterized the steps involved in the presentation of antigens derived from aldrithiol-2-treated vs. infectious HIV-1 by DC. Antigen presentation, on both MHC class I and II, was independent of DC-specific ICAM-3-grabbing integrin, DEC-205 and macrophage mannose receptor, C-type lectins expressed by the DC. Inhibitor studies showed that presentation on MHC class I was dependent on viral fusion in a CD4/coreceptor-dependent manner, both at the cell surface and within endosomes, and access to the classical endosomal processing pathway. MHC class II presentation of HIV-associated antigens was dependent on active endocytosis, probably receptor-mediated, and subsequent degradation of virions in acidified endosomes in the DC. Our study brings forth new facts regarding the binding, uptake, and processing of chemically inactivated virions leading to efficient antigen presentation and should aid in the design of more effective HIV vaccines.
| 223
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PubMed Abstracts
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1120731
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Reconstruction method and optimal design of an interferometric spectrometer.
In this paper, we present a method to estimate the power spectral distribution of a source from input data acquired by an interferometric-based spectrometer. Our spectrometer shows distortions in the fringe pattern and a lack of data, making it impossible to apply the Fourier transform approach, which is the gold standard as a spectral recovery method for interferometric spectrometers. We combined linear inverse problem solving and iterative methods instead, considering that each detector of the spectrometer has a specific and known spectral response. Iterative methods are used to overcome problems caused by lack of input data. We show that a good spectral estimation of relatively simple spectra having a resolution of 400 points is typically achieved using fewer than 10 detectors with such a method. Since the quality of spectral restitution with such an approach relies both on signal processing and an optimal selection of the detector's spectral responses, the paper also shows that some sets of spectral responses selected for the detection and consequently a spectral repartition of the detectors are more successful than others in the spectral recovery process. We chose the condition number of the inversion matrix as an optimization criterion and evaluated how this criterion can be used within this framework. We found that maximizing it achieves better spectral restitution, within a range where noise remains low.
| 229
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thePile
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PubMed Abstracts
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1120739
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Towards more specific O6-methylguanine-DNA methyltransferase (MGMT) inactivators.
Searching for a novel family of inactivators of the human DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) which is known to bind to the DNA minor groove, we have computationally modelled and synthesised two series of 2-amino-6-aryloxy-5-nitropyrimidines with morpholino or aminodiaryl substituents (potential minor groove binders) at the 4-position. Synthesis of these compounds was achieved by successive substitution of each of the two Cl atoms of 2-amino-4,6-dichloro-5-nitropyrimidine by the corresponding amino and aryloxy derivatives. Biochemical evaluation of these compounds as MGMT inactivators showed poor activities, but in general the 4-bromothenyloxy derivatives showed better inactivation than the benzyloxy versions. DNA binding assessment was not possible due to insolubility problems.
| 113
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PubMed Abstracts
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1120754
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Roles of singlet oxygen and triplet excited state of dissolved organic matter formed by different organic matters in bacteriophage MS2 inactivation.
Inactivation of bacteriophage MS2 by reactive oxygen species (ROS) and triplet excited state of dissolved organic matter ((3)DOM*) produced by irradiation of natural and synthetic sensitizers with simulated sunlight of wavelengths greater than 320 nm was investigated. Natural sensitizers included purified DOM isolates obtained from wastewater and river waters, and water samples collected from Singapore River, Stamford Canal, and Marina Bay Reservoir in Singapore. Linear correlations were found between MS2 inactivation rate constants (kobs) and the photo-induced reaction rate constants of 2,4,6-trimethylphenol (TMP), a probe compound shown to react mainly with (3)DOM*. Linear correlations between MS2 kobs and singlet oxygen ((1)O2) concentrations were also found for both purified DOM isolates and natural water samples. These correlations, along with data from quenching experiments and experiments with synthetic sensitizers, Rose Bengal (RB), 3'-methoxyacetophenone (3'-MAP), and nitrite [Formula: see text] , suggest that (1)O2, (3)DOM*, and hydroxyl radicals ((•)OH) could inactivate bacteriophage MS2. Linear correlations between MS2 kobs and Specific Ultraviolet Absorption determined at 254 nm (SUVA254) were also found for both purified DOM isolates and natural samples. These results suggest the potential use of TMP as a chemical probe and SUVA254 as an indicator for virus inactivation in natural and purified DOM water samples.
| 222
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PubMed Abstracts
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1120768
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High-resolution space-shuttle polarimetry for farm crop classification.
A significant advance is reported in imaging the polarimetry of a terrestrial area of Earth located along the Mississippi River near New Madrid, Missouri. Color imagery was obtained with twin Hasselblad cameras with mutually perpendicular polarization analyzers. Digitization of the imagery in three colors (red, green, and blue) was accomplished at the Johnson Space Center Video Digital Analysis System Laboratory, Houston, Texas. A ground resolution of 80-90 m was achieved in the high-resolution imagery. Percent polarization was superior to photometry for recognition and characterization of farm crops such as rice, milo, cotton, and soybeans and of fallow areas. Statistical analyses of the percent-polarization data permit a unique classification of crops. Atmospheric effects may be deduced. Space-shuttle window distortion and viewing angle-sun geometry must be taken into account in analyzing the data.
| 137
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PubMed Abstracts
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1120771
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[Anti-alpha-gliadin antibodies. Sensitivity, specificity and correlation with blood xylose test in the 3 diagnostic stages of celiac disease in children].
The specificity and sensibility of IgA and IgG alfagliadin antibody test (AaGA) for screening, diagnosis and follow-up of childhood coeliac disease has been evaluated. We have compared AaGA test to D-xylose blood test and at last we have examined the false positive and negative results given by the test. Two groups of subjects were considered: 1) 90 children with untreated coeliac disease (21 newly diagnosed (I stage), 50 in gluten withdrawal (II stage), 19 in challenge (III stage); 2) 255 disease controls including: 157 healthy controls; 31 children with gastroenterological disorders other than coeliac disease; 31 children with food allergy and atopic dermatitis; 36 children with "constitutional" short stature (without GH deficiency and with normal intestinal mucosa). The sensibility of AaGA test in the first stage of coeliac disease has been of 95.2% for the IgG class antibody and 90.4% for the IgA class; on the other hand the showed a specificity of 83.6% for IgG class antibody and 96.9% for IgA class. In only two newly diagnosed coeliac children we have found false negative results: in the first case the patient was IgA-deficient, in the second the age was above 3 years. AaGA IgA resulted positive only in the 12.9% of the group of gastroenterological and atopic controls; particularly most cases were affected by multiple food allergies and two patients by chronic autoimmune disease of small intestine.(ABSTRACT TRUNCATED AT 250 WORDS)
| 251
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PubMed Abstracts
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1120773
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A global database of historic and real-time flood events based on social media.
Early event detection and response can significantly reduce the societal impact of floods. Currently, early warning systems rely on gauges, radar data, models and informal local sources. However, the scope and reliability of these systems are limited. Recently, the use of social media for detecting disasters has shown promising results, especially for earthquakes. Here, we present a new database for detecting floods in real-time on a global scale using Twitter. The method was developed using 88 million tweets, from which we derived over 10,000 flood events (i.e., flooding occurring in a country or first order administrative subdivision) across 176 countries in 11 languages in just over four years. Using strict parameters, validation shows that approximately 90% of the events were correctly detected. In countries where the first official language is included, our algorithm detected 63% of events in NatCatSERVICE disaster database at admin 1 level. Moreover, a large number of flood events not included in NatCatSERVICE were detected. All results are publicly available on www.globalfloodmonitor.org.
| 177
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PubMed Abstracts
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1120775
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Comparative analysis of different transformed Saccharomyces cerevisiae strains based on high-throughput Fourier transform infrared spectroscopy.
This study shows the application of the Fourier transform mid-infrared spectroscopy (FT-MIR) associated with high-throughput technology to study the biochemical fingerprints of different Saccharomyces cerevisiae strains transformed with the same expression system along the similar cultivation in bioreactor. The phenotype, as well as the cellular metabolism and recombinant cyprosin biosynthesis, were determined. The differences observed were confirmed by conventional cyprosin activity protocol, and the metabolic evolution was analyzed using high-performance liquid chromatography technique. The spectral analysis based on chemometrics tools, such as the principal component analysis, is a useful methodology for the phenotypes characterization as well as the specific metabolic states along the cultivations according to the clusters created. The ratio bands of spectra also represented a useful tool to evaluate the metabolic and biochemical differences between both expression systems, allowing to have an additional parameter to the biomolecular comparison. Therefore, high-throughput FT-MIR spectroscopy associated with multivariate data analysis represent a valuable strategy for extracting significant specific biomolecular information along the cultivation, providing a complete bioprocess analysis, once it detects slight molecular changes which it will be useful for screening and optimization process in the biotechnological or pharmaceutical industry.
| 203
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PubMed Abstracts
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1120779
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Impacts of dung combustion on the carbon cycle of alpine grassland of the north Tibetan plateau.
Alpine grassland of Tibet is a frangible ecosystem in terms of carbon (C) emission. Yak dung is an important resident energy with about 80 % of yak dung combusted for energy in the north Tibetan plateau. This paper investigated the impact of dung combustion on the C cycle of the alpine grassland ecosystem in north Tibet, China. During the growing season of 2011, from a field survey and household questionnaires, the main impacts of dung collection for fuel on the C cycle of the ecosystem were identified. (1) The C sequestration and storage capacity, including the dung-derived C stored in soil and C captured by vegetation, decreased. The net primary production decreased remarkably because of the reduction of dung returned to soil. (2) In a given period, more C was emitted to the atmosphere in the dung combustion situation than that in the dung returned to soil situation. (3) The energy grazing alpine meadow ecosystem changed into a net C source, and the net biome production of the ecosystem dropped to -15.18 g C/m2 year in the dung combustion situation, 42.95 g C/m2 year less than that in the dung returned situation. To reduce the CO2 emission derived from dung use, the proportion of dung combustion should be reduced and alternative renewable energy such as solar, wind, or hydro energy should be advocated, which is suitable for, and accessible to, the north Tibetan plateau.
| 249
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PubMed Abstracts
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1120780
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Mother's knowledge about antibiotic and role of self prescription.
antibiotic use is common and unrestricted in many developing countries. to explore knowledge of mothers about antibiotic regarding its indication, its side effects and to study some behavioral aspects associated with its usage. mothers attending outpatient clinic in Ain Shams University Pediatric Hospital were subjected to interviewing questionnaire which contains different items aimed to be explored. 577 mothers were interviewed with different educational levels. Regarding indication of antibiotic, 86% of mothers agreed to be given in case of tonsillitis and 15% in coryza. The most mentioned side effect was general weakness (77%). Regarding some behaviors associated with usage of antibiotic, 21% of mother keep the drug after usage to be reused, also 24% of them prescribe the drug to their children compared to 10% who seek pharmacist advice, further results will be discussed.
| 141
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PubMed Abstracts
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1120784
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The Study of Nursing NAVI.
We have examined the nurses' thinking process in their professional judgment and action in the Partogram of 170 labors by 17 Midwifery students in 2 years.
| 30
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PubMed Abstracts
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1120790
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Malignant melanoma of the larynx.
Malignant melanoma of the larynx is a rare tumour. Only 31 cases of primary laryngeal melanoma have been reported in the literature. Cady et al., (1968) found only four cases in a group of 2,500 cases of laryngeal cancer seen over a 25-year period. A case of primary malignant melanoma of the larynx is presented along with a review of the literature. Problems associated with histological diagnosis are discussed. This patient was regarded as a poor risk for laryngectomy and appears to have control of local disease following application of Carbon dioxide laser.
| 97
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PubMed Abstracts
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1120792
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Role of En2 in the tectal laminar formation of chick embryos.
The chick optic tectum consists of 16 laminae. Here, we report contribution of En2 to laminar formation in chick optic tecta. En2 is specifically expressed in laminae g-j of stratum griseum et fibrosum superficiale (SGFS). Misexpression of En2 resulted in disappearance of En2-expressing cells from the superficial layers (laminae a-f of SGFS), where endogenous En2 is not expressed. Misexpression of En2 before postmitotic cells had left the ventricular layer indicated that En2-misexpressing cells stopped at the laminae of endogenous En2 expression and that they did not migrate into the superficial layers. Induction of En2 misexpression using a tetracycline-inducible system after the postmitotic cells had reached superficial layers also resulted in disappearance of En2-expressing cells from the superficial layers. Time-lapse analysis showed that En2-misexpressing cells migrated back from the superficial layers towards the middle layers, where En2 is strongly expressed endogenously. Our results suggest a potential role of En2 in regulating cell migration and positioning in the tectal laminar formation.
| 169
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PubMed Abstracts
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1120798
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Host population density as the major determinant of endoparasite species richness in floodplain fishes of the upper Paraná River, Brazil.
A comparative analysis of parasite species richness was performed across 53 species of fish from the floodplain of the upper Paraná River, Brazil. Values of catch per unit effort, CPUE (number of individuals of a given fish species captured per 1000 m(2) of net during 24 h) were used as a rough measure of population density for each fish species in order to test its influence on endoparasite species richness. The effects of several other host traits (body size, social behaviour, reproductive behaviour, spawning type, trophic category, feeding habits, relative position in the food web, preference for certain habitats and whether the fish species are native or exotic) on metazoan endoparasite species richness were also evaluated. The CPUE was the sole significant predictor of parasite species richness, whether controlling for the confounding influences of host phylogeny and sampling effort or not. The results suggest that in the floodplain of the upper Paraná River (with homogeneous physical characteristics and occurrence of many flood pulses), population density of different host species might be the major determinant of their parasite species richness.
| 198
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PubMed Abstracts
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1120805
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[Lipid peroxidation and tumor dimensions in stomach cancer].
The parameters of lipid peroxidation were examined in blood serum of 40 patients with stomach cancer by induced chemiluminescence (CL)--Republican Research Center of Oncology, Healthcare Ministry of Uzbekistan. The CL parameters were demonstrated to increase alongside with the growing tumor mass. The induced CL of blood serum characterizes the status of lipid peroxidation and is a direct reflection of the body's reaction to tumor growth. The method of induced CL can be used on in clinical practice as an additional diagnostic test describing the tumor growth course in stomach cancer.
| 97
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PubMed Abstracts
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1120819
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Inhibitory effect of calcium-binding protein regucalcin on ribonucleic acid synthesis in isolated rat liver nuclei.
The effect of regucalcin, a Ca2+-binding protein isolated from rat liver cytosol, on ribonucleic acid (RNA) synthesis in the nuclei of normal rat liver and of regenerating rat liver was investigated. The liver weight at 1 day after partial hepatectomy was increased about 50% of that of sham-operated (control) rats. Calcium chloride (1.0-20 microM Ca2+ as final concentration) was added into the reaction mixture of nuclear RNA synthesis. RNA synthesis was established by incorporation of [3H]-uridine 5'-triphosphate (UTP) into the nuclear RNA. Addition of Ca2+ (5 and 10 microM) caused a significant increase of RNA synthesis in the nuclei from control rat liver. Such effect of Ca2+ was potentiated in the nuclei of regenerating liver; nuclear RNA synthesis was increased about 2 fold by the 1.0 and 2.5 microM Ca2+ addition. The stimulatory effect of Ca2+ was significantly inhibited by the presence of alpha-amanitin (10(-8) M), an inhibitor of RNA polymerase II. The presence of regucalcin (0.25 and 0.5 microM) significantly inhibited RNA synthesis in the nuclei from control rat liver and from regenerating rat liver. The inhibitory effect of regucalcin was remarkable in the presence of EGTA (0.5 mM), and it was weakened by the addition of Ca2+ (5 microM). Such regucalcin effect was not seen in the presence of alpha-amanitin. The presence of anti-regucalcin IgG in the reaction mixture significantly increased RNA synthesis in the nuclei from control rat liver, indicating that the endogenous regucalcin may be involved in nuclear RNA synthesis. The present results demonstrate that regucalcin can inhibit nuclear RNA synthesis in rat liver. Regucalcin may have an inhibitory role in the regulation of liver nuclear RNA synthesis.
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PubMed Abstracts
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1120826
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Genesis of episodic growth hormone secretion.
The secretion of growth hormone (GH) is governed by the remarkably complex interaction of neural and feedback regulatory components. The net result is a striking pulsatile pattern of GH release evident in every mammalian species studied so far. Extensive experimental evidence indicates that the episodic pattern of GH release from the pituitary gland is generated by a delicate interplay between at least two hypothalamic hormones--a stimulatory GH-releasing factor (GRF) and an inhibitory hormone, somatostatin (SRIF). This paper will focus on the interrelation of GRF and SRIF, and on the modulatory influence of GH and insulin-like growth factor (IGF) feedback, in the genesis of episodic GH secretion.
| 111
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PubMed Abstracts
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1120834
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Uptake of heavy metals by vegetable plants grown on contaminated soil and their bioavailability in the human gastrointestinal tract.
Lettuce, spinach, radish and carrot were grown on compost that had previously been contaminated at different concentrations of Cd, Cu, Mn, Pb and Zn. Control plants of each vegetable were also grown on unadulterated compost. The experiment was carried out under greenhouse conditions. Mature plants were harvested and their roots and leaves collected. Soil samples from each growing pot and plant materials were acid digested and analysed to determine total metal concentration. Flame-Atomic Absorption Spectroscopy (FAAS) was employed to determine metal concentrations in soil and plant samples (Mn and Zn), while Cd, Cu and Pb in plant materials were analysed by Differential Pulse Anodic Stripping Voltammetry (DP-ASV). Soil (BCR 146R and GBW 07310) and plant (tea leaves, INCT-TL-1) certified reference materials were used to assess accuracy and precision. The edible part of plants, i.e. the leaves of lettuce and spinach and the roots of radish and carrot, were also extracted using an in vitro gastrointestinal (GI) extraction to assess metal bioavailability. The results showed that the uptake of Cd, Cu, Mn and Zn by plants corresponded to the increasing level of soil contamination, while the uptake of Pb was low. Soil-to-plant transfer factor (TF) values decreased from Mn >> Zn > Cd > Cu > Pb. Moreover, it was observed from this investigation that individual plant types greatly differ in their metal uptake, e.g. spinach accumulated a high content of Mn and Zn, while relatively lower concentrations were found for Cu and Pb in their tissues. From the in vitro gastrointestinal (GI) study, results indicate that metal bioavailability varied widely from element to element and according to different plant types. The greatest extent of metal releasing was found in lettuce (Mn, 63.7%), radish (Cu, 62.5%), radish (Cd, 54.9%), radish (Mn, 45.8%) and in lettuce (Zn, 45.2%).
| 314
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PubMed Abstracts
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1120838
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A hexanucleotide repeat expansion in C9ORF72 causes familial and sporadic ALS in Taiwan.
A GGGGCC hexanucleotide repeat expansion in the C9ORF72 gene was recently identified as an important cause of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia in Caucasian populations. The role of the C9ORF72 repeat expansion in ALS in Chinese populations has received little attention. We therefore performed mutation analyses in a Taiwanese cohort of 22 unrelated familial ALS (FALS) patients and 102 sporadic ALS patients of Han Chinese descent. The C9ORF72 mutation was found in 4 FALS (18.2%; 4/22) and 2 sporadic ALS patients (2.0%; 2/102). The C9ORF72 repeat numbers in the 300 healthy controls and the 118 ALS patients without the C9ORF72 mutation ranged from 3 to 15. Needle biopsy in the left frontal cortex of 1 patient with FALS-frontotemporal dementia revealed numerous cytoplasmic TAR DNA-binding protein 43 (TDP-43) inclusions and minimal neuritis, consistent with type B frontotemporal lobar degeneration with TDP-43 (FTLD-TDP) pathology. This study clearly demonstrates the existence and importance of the C9ORF72 hexanucleotide repeat expansion in a Taiwanese ALS cohort of Chinese origin, and supports the global presence of the C9ORF72 repeat expansion in ALS.
| 191
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PubMed Abstracts
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1120848
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Ultraviolet disinfection of antibiotic resistant bacteria and their antibiotic resistance genes in water and wastewater.
Disinfection of wastewater treatment plant effluent may be an important barrier for limiting the spread of antibiotic-resistant bacteria (ARBs) and antibiotic resistance genes (ARGs). While ideally disinfection should destroy ARGs, to prevent horizontal gene transfer to downstream bacteria, little is known about the effect of conventional water disinfection technologies on ARGs. This study examined the potential of UV disinfection to damage four ARGs, mec(A), van(A), tet(A), and amp(C), both in extracellular form and present within a host ARBs: methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus faecium (VRE), Escherichia coli SMS-3-5, and Pseudomonas aeruginosa 01, respectively. An extended amplicon-length quantitative polymerase chain reaction assay was developed to enhance capture of ARG damage events and also to normalize to an equivalent length of target DNA (∼1000 bp) for comparison. It was found that the two Gram-positive ARBs (MRSA and VRE) were more resistant to UV disinfection than the two Gram-negative ARBs (E. coli and P. aeruginosa). The two Gram-positive organisms also possessed smaller total genome sizes, which could also have reduced their susceptibility to UV because of fewer potential pyrimidine dimer targets. An effect of cell type on damage to ARGs was only observed in VRE and P. aeruginosa, the latter potentially because of extracellular polymeric substances. In general, damage of ARGs required much greater UV doses (200-400 mJ/cm² for 3- to 4-log reduction) than ARB inactivation (10-20 mJ/cm² for 4- to 5-log reduction). The proportion of amplifiable ARGs following UV treatment exhibited a strong negative correlation with the number of adjacent thymines (Pearson r < -0.9; p < 0.0001). ARBs surviving UV treatment were negatively correlated with total genome size (Pearson r < -0.9; p < 0.0001) and adjacent cytosines (Pearson r < -0.88; p < 0.0001) but positively correlated with adjacent thymines (Pearson r > 0.85; p < 0.0001). This suggests that formation of thymine dimers is not the sole mechanism of ARB inactivation. Overall, the results indicate that UV is limited in its potential to damage ARGs and other disinfection technologies should be explored.
| 348
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PubMed Abstracts
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1120850
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Acute viral hepatitis B with bridging necrosis: a follow-up study.
Forty patients with bridging necrosis (BN) on biopsies taken during the course of acute viral hepatitis B were included in a prospective study to assess the prognostic significance of this lesion. Of the 22 patients with complete clinical, biochemical and histological follow-up (histological follow-up 5-33 months), only two failed to eliminate HBs- and HBe-antigen in serum, a finding paralleled by transition to chronic active hepatitis and by the persistence of focal HBc- and HBs-antigen expression in liver tissue. Nineteen of 22 patients showed complete histological healing; one developed inactive cirrhosis. It is concluded that, in the setting of acute viral hepatitis B, the histological lesion of BN is of no particular prognostic significance, and that transition to chronic liver disease is much less frequent than has been assumed from previous studies of etiologically heterogeneous patient populations. Markers of poor prognosis are the failure of serological elimination of HBs- and HBe-antigen and the persistence of spotty expression of HBc- and HBs-antigen on immunofluorescence histology.
| 172
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PubMed Abstracts
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1120851
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Nuclear localization and regulation of Id protein through an E protein-mediated chaperone mechanism.
Members of the Id family of helix-loop-helix proteins function as negative regulators of DNA binding, E protein, helix-loop-helix transcription factors in the control of cell growth, differentiation, and development. By using transient transfection analysis of COS cells, we show that in the absence of its E protein target, the Id3 protein is localized exclusively to the cytoplasm/perinuclear region. Co-transfection with E protein (E47) results in nuclear translocation of the Id3 protein, a process requiring both a functional Id helix-loop-helix dimerization domain and an E protein nuclear localization signal. Id3 that is associated with E protein displays an extended half-life, while the E protein itself is more rapidly turned over. These observations demonstrate that E protein, by nuclear chaperoning Id, can regulate the available cellular pool of its own inhibitory partner.
| 142
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PubMed Abstracts
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1120860
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Digit speech reception threshold testing in Tswana/English speakers.
The purpose of this study was to establish whether digit stimuli offer a more accurate measure for Speech Reception Threshold (SRT) testing when assessing first-language Tswana (or Setswana), second-language English speakers, as compared to an English wordlist (CID W-1) and a Tswana wordlist. Forty Tswana first language speaking participants (17 males and 23 females) aged between 18 and 25 years, participated in this study. All participants were undergraduate students at a tertiary institution in Johannesburg, Gauteng. This study utilized a quantitative single group correlation design which allowed for a comparison between three SRTscores (CID-SRT,T-SRT,and D-SRT). Participants underwent basic audiological assessment procedures comprising of otoscopy, tympanometry, conventional pure tone audiometry and SRT testing. SRT measures were established using monitored live voice testing. Basic audiometric data were descriptively analyzed to ensure that hearing function was within normal limits, and PTA-SRT averages and means were calculated. Furthermore, analysis of the SRT-PTA correlation data was conducted through the use of the nonparametric Spearman's correlation coefficient and linear regression. Results from this study were statistically significant (p < .05) and indicated that digit-pairs were not the most effective stimuli for establishing SRT, compared to the CIDW-1 and Tswana wordlists. On the contrary, findings of the current study revealed that PTA-SRT comparison was best in Tswana (r = 0.62), followed very closely by CIDW-1 (r = 0.61), and lastly digit-pairs (r = 0.60). The results however, confirm the efficacy of using digit pairs as alternative stimuli when more appropriate speech stimuli for the establishment of SRT are unavailable, as the correlation between SRT for digit pairs and PTA was also a strong one (r = 0.60). Linear regression analyses indicated that all three lists were acceptable speech stimuli for the population under investigation with the standard error of estimate being significantly smaller than the 5dB-step used to collect the data (1.62 for Tswana, 3.56 for CID W-1, and 3.80 for digit-pairs).
| 322
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PubMed Abstracts
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1120867
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Receptor-based models with hysteresis for pattern formation in hydra.
In this paper, we propose a new receptor-based model for pattern formation and regulation in a fresh-water polyp, namely hydra. The model is defined in the form of a system of reaction-diffusion equations with zero-flux boundary conditions coupled with a system of ordinary differential equations. The production of diffusible biochemical molecules has a hysteretic dependence on the density of these molecules and is modeled by additional ordinary differential equations. We study the hysteresis-driven mechanism of pattern formation and we demonstrate the advantages and constraints of its ability to explain different aspects of pattern formation and regulation in hydra. The properties of the model demonstrate a range of stationary and oscillatory spatially heterogeneous patterns, arising from multiple spatially homogeneous steady states and switches in the production rates.
| 134
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PubMed Abstracts
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1120870
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Promoters and serotypes: targeting of adeno-associated virus vectors for gene transfer in the rat central nervous system in vitro and in vivo.
The brain parenchyma consists of several different cell types, such as neurones, astrocytes, microglia, oligodendroglia and epithelial cells, which are morphologically and functionally intermingled in highly complex three-dimensional structures. These different cell types are also present in cultures of brain cells prepared to serve as model systems of CNS physiology. Gene transfer, either in a therapeutic attempt or in basic research, is a fascinating and promising tool to manipulate both the complex physiology of the brain and that of isolated neuronal cells. Viral vectors based on the parvovirus, adeno-associated virus (AAV), have emerged as powerful transgene delivery vehicles. Here we describe highly efficient targeting of AAV vectors to either neurones or astrocytes in cultured primary brain cell cultures. We also show that transcriptional targeting can be achieved by the use of small promoters, significantly boosting the transgene capacity of the recombinant viral genome. However, we also demonstrate that successful targeting of a vector in vitro does not necessarily imply that the same targeting works in the adult brain. Cross-packaging the AAV-2 genome in capsids of other serotypes adds additional benefits to this vector system. In the brain, the serotype-5 capsid allows for drastically increased spread of the recombinant vector as compared to the serotype-2 capsid. Finally, we emphasize the optimal targeting approach, in which the natural tropism of a vector for a specific cell type is employed. Taken together, these data demonstrate the flexibility which AAV-based vector systems offer in physiological research.
| 263
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PubMed Abstracts
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1120873
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Regulatory Measures Expedited Hip Fracture Surgery Without Lowering Overall Patient Mortality.
Previous observational research has shown that elderly patients with hip fractures who are operated early (within 48 hours from admission) benefit from less short- and long-term mortality compared to those operated later. The objective of this study was to present regulatory measures aimed at promotion of early hip fracture surgery and their effect on the rates of early surgery and on postoperative mortality. Retrospective cohort. Single inner-city medical center. Elderly patients with hip fractures operated during three time periods: 2006 to 2009 (n = 1735, no intervention), 2010 to 2013 (n = 2104, first intervention, positive reinforcement), and 2014 to 2016 (n = 1538, second intervention, positive and negative reinforcement). Two regulatory measures were introduced consecutively: staff extra wages for afternoon operations (positive reinforcement) in 2010 and making early operation rates publicly available as the Ministry of Health Quality Care Indexes (negative reinforcement) in 2013. Percentage of early surgeries and mortality at 1 month and 1 year postoperatively. A total of 5377 patients (1595 men, 3782 women; mean age, 83.1 ± 7.2 years) underwent hip surgery between 2006 and 2016. The three study groups did not differ significantly in age on admission, sex, type of hip fracture (intracapsular or extracapsular), American Society of Anesthesiologists' score, mean hemoglobin on admission, and mean socioeconomic status. The percentage of operations performed within 48 hours was 55%, 65%, and 85%, respectively (P < .001). One-month mortality was 3.9%, 5.1%, and 5%, respectively (P > .05), and one-year mortality was 19.2%, 18.7%, and 19.6%, respectively (P > .05). Management pressure on the staff to expedite hip surgery and avoid negative publicity in conjunction with additional wages for afternoon surgeries was successful at promoting earlier hip surgery. Despite the substantial increase in the rates of early surgery, however, mortality rates were not affected. J Am Geriatr Soc 67:777-783, 2019.
| 313
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PubMed Abstracts
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1120879
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Social capital, income inequality, and self-rated health in 45 countries.
There has been growing interest in the relationship between the social environment and health. Among the concepts that have emerged over the past decade to examine this relationship are socio-economic inequality and social capital. Using data from the World Values Survey and the World Bank, we tested the hypothesis that self-rated health is affected by social capital and income inequality cross-nationally. The merit of our approach was that we used multilevel methods in a larger and more diverse sample of countries than used previously. Our results indicated that, for a large number of diverse countries, commonly used measures of social capital and income inequality had strong compositional effects on self-rated health, but inconsistent contextual effects, depending on the countries included. Cross-level interactions suggested that contextual measures can moderate the effect of compositional measures on self-rated health. Sensitivity tests indicated that effects varied in different subsets of countries. Future research should examine country-specific characteristics, such as differences in cultural values or norms, which may influence the relationships between social capital, income inequality, and health.
| 182
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PubMed Abstracts
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1120880
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Biology of inherited coagulopathies: factor IX.
Characterization of the functional domains of FIX and related vitamin K-dependent proteins has been enhanced by the isolation and characterization of the genes encoding these proteins. A better understanding of the interactions between FIX's activators, cofactors, and substrate, FX, has been gained through the study of naturally occurring variants isolated from patients with hemophilia B and genetically engineered recombinant molecules. With the determination of specific mutations in hemophilia B kindreds, and through advances in molecular techniques, especially the polymerase chain reaction, more accurate determination of carrier status and prenatal diagnosis can now be made.
| 99
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PubMed Abstracts
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1120882
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Micronucleus induction in peripheral blood lymphocytes of patients under radiotherapy treatment for cervical cancer or Hodgkin's disease.
The genetic damage present in peripheral blood lymphocytes of patients treated with fractionated partial-body radiation therapy for cervical cancer or Hodgkin's disease was followed during treatment by means of the cytokinesis-block micronucleus assay. For each patient a dose-response relationship with respect to the number of micronuclei after in vitro irradiation of blood samples pretreatment was also determined. Comparing the individual in vivo-in vitro data, the micronucleus yields after the equivalent whole-body dose during radiotherapy were found to differ substantially from the in vitro dose-response. Contrary to the linear-quadratic dose dependence after in vitro irradiation the initial increase in the micronucleus yield during radiotherapy levelled off at elevated doses. The observed differences cannot be attributed only to the effects of interphase death and the partial irradiation of the lymphocyte pool. The correlation between the micronucleus yield and the equivalent whole-body dose for values up to 2 Gy, observed for the pooled data of the first part of the radiotherapy treatment, demonstrates the suitability of the cytokinesis-block micronucleus assay as a biological dosemeter after accidents involving partial-body irradiation.
| 192
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PubMed Abstracts
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1120896
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Elastolytic activity of Pseudomonas aeruginosa elastase.
Elastolysis of insoluble elastin by Pseudomonas aeruginosa elastase was found to be less specific (higher apparent Km value) but more active (higher activity) than with pancreatic elastase. Furthermore, pancreatic and P. aeruginosa elastases act synergistically during the initial stages of elastolysis. After extensive hydrolysis, the size distribution of digestion products was lower with P. aeruginosa than with pancreatic elastase. The higher extent of hydrolysis may be explained by the fact that, if pancreatic elastase needs at least six sub-sites for activity, P. aeruginosa elastase may hydrolyse tetrapeptides such as tetraalanine, or synthetic substrates such as furylacryloyltripeptides FA-X-Leu-Y, X and Y being Gly and/or Ala.
| 109
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PubMed Abstracts
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1120906
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[Infant mortality in Asker and Baerum in the 18th and 19th century].
The decline in infant mortality is an important part of the secular decline in mortality in the western world. The major causes of the decline are subject to controversy. Individual event records from censuses, church records and land registers from two Norwegian parishes during the years 1814-1878 were registered and linked into individual life course records. Around 15,000 infants, of whom 1500 died, were analysed in depth with Cox regression analysis. The total yearly counts of births and infant deaths from 1735 were analysed using ordinary linear regression. Infant mortality hovered around 23 per cent during the middle of the 18th century and fell to a level around 10 per cent by the end of the 19th century. The decline was strongest during the neonatal period. Women born during the first decade of the 19th century, a decade known for a succession of years with bad harvests, war and high infant mortality, gave birth to infants with increased neonatal mortality. The decline in infant mortality during the first part of the 19th century can thus be attributed to an improvement in the health of the mothers dating back to their own fetal or infant stage. The decline took place in the absence of trained medical personnel.
| 217
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PubMed Abstracts
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1120918
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Genetic dependence of the specific T-cell cytokine response to Porphyromonas gingivalis in mice.
Susceptibility to periodontal infections may, in part, be genetically determined. Porphyromonas gingivalis is a major periodontopathogen, and the immune response to this organism requires T-cell help. The aim of the present study was to examine the specific T-cell cytokine responses to P. gingivalis outer membrane antigens in a mouse model and their relationship with H-2 haplotype. BALB/c and DBA/2J (H-2d), CBACaH (H-2k), and C57BL6 (H-2b) mice were immunized with P. gingivalis outer membrane antigens weekly for 3 weeks. One week after the final injection, the spleens were removed, and 6 T-cell lines specific for P. gingivalis were established for each mouse strain. The percentage of CD4 and CD8 cells in the P. gingivalis-specific T-cell lines staining positive for intracytoplasmic interleukin (IL)-4, interferon (IFN)-gamma, and IL-10 was determined by 2-color flow cytometry. The cytokine profiles of T-cell lines from BALB/c and DBA/2J mice showed no significant differences. Significantly fewer IL-4+, IFN-gamma+, and IL-10+ CD4 cells than IL-4+, IFN-gamma+, and IL-10+ CD8 cells, respectively, were demonstrated for both strains. P. gingivalis-specific T-cell lines generated from CBACaH mice were similar to those generated from BALB/c and DBA/2J mice; however, the mean percentage of IL-4+ CD4 cells in CBACaH mice was lower than the percentage of IFN-gamma+ CD4 cells. Also, the mean percentage of IFN-gamma+ CD4 cells in CBACaH mice was significantly increased compared to DBA/2J mice. Unlike the other 3 strains, T-cell lines established from C57BL6 mice contained similar percentages of cytokine-positive cells, although the percentage of IL-4+ CD4 cells was reduced in comparison to the percentage of CD8 cells. However, comparisons with the other 3 strains demonstrated a higher percentage of IL-4+ CD4 cells than in lines established from the spleens of DBA/2J mice, IFN-gamma+ CD4 cells than in lines established from BALB/c and CBACaH mice, and IL-10+ CD4 cells than in lines established from all 3 other strains. No significant differences in the percentage of positive CD8 cells were demonstrated between lines in the 4 strains of mice. The specific T-cell response to P. gingivalis in mice may, in the case of the CD4 response, depend on MHC genes. These findings are consistent with the concept that patient susceptibility is important to the outcome of periodontal infection and may, in part, be genetically determined.
| 385
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PubMed Abstracts
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1120928
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Benzothiophene inhibitors of MK2. Part 1: structure-activity relationships, assessments of selectivity and cellular potency.
Identification of potent benzothiophene inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK2), structure-activity relationship (SAR) studies, selectivity assessments against CDK2, cellular potency and mechanism of action are presented. Crystallographic data provide a rationale for the observed MK2 potency as well as selectivity over CDK2 for this class of inhibitors.
| 64
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PubMed Abstracts
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1120932
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[Molecular detection of circulating cancer cells in patients with renal cell carcinoma].
We have developed a highly sensitive technique to detect circulating renal cell carcinoma (RCC) cells in the blood using the reverse transcriptase-polymerase chain reaction (RT-PCR) with primers specific for the MN/CA9 gene. RT-PCR analysis of RCC specimens resulted in the clear detection of MN/CA9 mRNA signal in 93%. In contrast, no expression of MN/CA9 was observed in normal kidney specimens. Highly sensitive RT-PCR analysis of blood samples from RCC patients revealed the presence of circulating MN-positive cancer cells in the blood. Fifty samples obtained from the patients with RCC and 31 samples from healthy donors were investigated. The sensitivity and specificity of this RT-PCR analysis were 72% and 78%, respectively. These findings suggest that the MN antigen may be a potential diagnostic biomarker for early detection of RCC.
| 139
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PubMed Abstracts
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1120941
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[Growth of some pathogenic microorganisms on chemically defined media which were proposed for sensitivity testing (author's transl)].
The growth of 16 bacterial cultures, which belong to the frequently encountered pathogens, in three different chemically defined fluid media was investigated through turbidity measurements in comparison with Mueller-Hinton-broth. E. coli, Salm. dublin, Salm. typhi-murium, Enterobacter cloacae, Proteus mirabilis, Pseud. aeruginosa and Bac. cereus grew in two of the three tested defined media with approximately the same intensity as in the Mueller-Hinton broth. Staph. aureus grew well only in one of the 3 tested defined media. Listeria monocytogenes, Erysipelothrix rhusiopathiae, Pasteurella multocida, Neisseria gonorrhoeae and Brucella abortus showed only in one of the three tested media a barely descernible growth, whereas Strept. faecalis, Strept. pneumoniae, Strept. pyogenes showed no growth in the three tested defined media after 34 hours of incubation. None of the tested defined media can be used for routine sensitivity testing but the use of two of the three tested defined media as a reference medium for the standardization of the complex sensitivity testing media remains theoretically possible.
| 177
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PubMed Abstracts
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1120951
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Association of short-term ambient air pollution concentrations and ventricular arrhythmias.
The authors evaluated the association between ventricular arrhythmias detected by implantable cardioverter defibrillators and ambient air pollution concentrations in the hours immediately before the arrhythmia. Patients given implantable cardioverter defibrillators at the New England Medical Center in Boston, Massachusetts, between mid-1995 and 1999 who lived within 40 km of a central monitoring site (n = 203) were followed until July 2002. The authors used a case-crossover design to study the association between ambient air pollution and up to 798 confirmed ventricular arrhythmias among 84 subjects. The authors found that interquartile range increases in 24-hour moving average particulate matter less than 2.5 mum in aerodynamic diameter and ozone were associated with 19% and 21% increased risks of ventricular arrhythmia, respectively. For each, there was evidence of a linear exposure response, and the associations appeared independent. These associations were stronger than associations with mean concentrations on the same calendar day and previous calendar days. The authors did not find associations with pollutant concentrations less than 24 hours before the arrhythmia. Cases with a prior ventricular arrhythmia within 72 hours had greater risk associated with air pollutants than did cases without a recent arrhythmia. These results confirm previous findings and suggest that matching of pollution periods to arrhythmias is important in detecting such associations.
| 220
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PubMed Abstracts
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1120954
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Autocratic strategies for alternating games.
Repeated games have a long tradition in the behavioral sciences and evolutionary biology. Recently, strategies were discovered that permit an unprecedented level of control over repeated interactions by enabling a player to unilaterally enforce linear constraints on payoffs. Here, we extend this theory of "zero-determinant" (or, more generally, "autocratic") strategies to alternating games, which are often biologically more relevant than traditional synchronous games. Alternating games naturally result in asymmetries between players because the first move matters or because players might not move with equal probabilities. In a strictly-alternating game with two players, X and Y, we give conditions for the existence of autocratic strategies for player X when (i) X moves first and (ii) Y moves first. Furthermore, we show that autocratic strategies exist even for (iii) games with randomly-alternating moves. Particularly important categories of autocratic strategies are extortionate and generous strategies, which enforce unfavorable and favorable outcomes for the opponent, respectively. We illustrate these strategies using the continuous Donation Game, in which a player pays a cost to provide a benefit to the opponent according to a continuous cooperative investment level. Asymmetries due to alternating moves could easily arise from dominance hierarchies, and we show that they can endow subordinate players with more autocratic strategies than dominant players.
| 213
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PubMed Abstracts
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1120966
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An alternative method for preventing extravasation complications in vascular access catheters with reservoirs for subcutaneous infusion: the double injection technique.
Long-term intravascular access catheters with reservoirs are a common requirement for cancer patients. Complications resulting from the use of these devices have been studied in several single-institution investigations, the consensus being that they are safe and have a low complication rate. However, extravasation may occur especially in obese patients due to accidental infusion of the subcutaneous tissue. To prevent this problem we describe an easy method that could be an alternative to the widely used ultrasonography-guided injection method.
| 97
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PubMed Abstracts
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1120971
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[Steroidal leukocytosis and immediate results of treatment in patients with sarcoidosis].
The occurrence of steroidal leukocytosis at early stages of an observation may, to a certain extent, serve an objective criterion for predicting the pronounced immediate results of treatment in first detected patients with sarcoidosis (that of intrathoracic lymph nodes and the lung in particular) and thus makes it possible to judge the adequacy of therapy in the inpatient setting. When steroidal leukocytosis is absent, it is necessary to differentiately decide whether it is expedient to correct a hormonal therapy regimen in order to achieve the optimal results of its efficiency.
| 100
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PubMed Abstracts
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1120976
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2,4,6-Trinitrotoluene (TNT) air concentrations, hemoglobin changes, and anemia cases in respirator protected TNT munitions demilitarization workers.
2,4,6-Trinitrotoluene (TNT) is an explosive used in munitions production that is known to cause both aplastic and hemolytic anemia in exposed workers. Anemia in a TNT worker is considered a sentinel health event (occupational) (SHE(O)) in the United States (US). Deaths have been reported secondary to aplastic anemia. Studies have shown that TNT systemic absorption is significant by both the respiratory and dermal routes. No studies encountered looked at hemoglobin change or anemia cases in respiratory protected workers. It is hypothesized that respiratory protection is insufficient to protect TNT workers from the risk of anemia development and hemoglobin concentration drop. A records review of eight groups of respiratory protected TNT workers' pre-exposure hemoglobin levels were compared with their during-exposure hemoglobin levels for statistically significant (alpha level 0.05) hemoglobin level changes, and anemia cases were recorded. A curve estimation analysis was performed between mean TNT air concentrations and mean hemoglobin change values. Statistically significant hemoglobin level drops and anemia cases were apparent at TNT air concentrations about the REL and PEL in respiratory protected workers. There were no anemia cases or statistically significant hemoglobin level drops at concentrations about the TLV, however. A statistically significant inverse non-linear regression model was found to be the best fit for regressing hemoglobin change on TNT air concentration. Respiratory protection may be inadequate to prevent workers who are at risk for TNT skin absorption from developing anemia. This study contributes evidence that the TLV should be considered for adoption as the new PEL.
| 263
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PubMed Abstracts
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1120978
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[Anastomosis of the thoracic duct and the esophagus in surgical treatment of cholestasis. Experimental research].
After brief recall of the pathophysiology of cholestasis, the authors describe a technic of internal drainage of lymph from the thoracic duct by an indirect anastomosis created surgically between the latter and the esophaghus. They conclude that the procedure definitely solves certain symptomatologic aspects of cholestasis, but has no effects on the underlying anatomopathological lesion, which does not regress once established.
| 75
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PubMed Abstracts
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1120984
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Quality of care for intimate partner violence in South African primary care: a qualitative study.
Intimate partner violence (IPV) makes a substantial contribution to the burden of disease in South Africa. This article explores the current quality of care for IPV in public sector primary care facilities within the Western Cape. Only 10% of women attending primary care, while suffering from IPV, were recognized. Case studies, based on in-depth interviews and medical records, were used to reflect on the quality of care received among the women who were recognized. Care tended to be superficial, fragmented, poorly coordinated, and lacking in continuity. The recognition, management, and appropriate documentation of IPV should be prioritized within the training of primary care providers. It may be necessary to appoint IPV champions within primary care to ensure comprehensive care for survivors of IPV.
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PubMed Abstracts
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1120985
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The role of histone acetylation in SMN gene expression.
Increasing survival motor neuron 2 (SMN2) gene expression may be an effective strategy for the treatment of spinal muscular atrophy (SMA). Histone deacetylase (HDAC) inhibitors have been shown to increase SMN transcript and protein levels, but the specific role of histone acetylation in regulating SMN gene expression has not been explored. Using chromatin immunopreciptation, we investigated the levels of acetylated H3 and H4 histones and HDACs associated with different regions of the human and mouse SMN genes in both cultured cells and tissues. We show that the SMN gene has a reproducible pattern of histone acetylation that is largely conserved among different tissues and species. A limited region of the promoter surrounding the transcriptional start site has relatively high levels of histone acetylation, whereas regions further upstream or downstream have lower levels. After HDAC inhibitor treatment, acetylated histone levels increased, particularly at upstream regions, correlating with a 2-fold increase in promoter activity. During development in mouse tissues, histone acetylation levels decreased and associated HDAC2 levels increased at the region closest to the transcriptional start site, correlating with a 40-60% decrease in SMN transcript and protein levels. These data indicate that histone acetylation modulates SMN gene expression and that pharmacological manipulation of this epigenetic determinant is feasible. HDAC2, in particular, may be a future therapeutic target for SMA.
| 225
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PubMed Abstracts
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1121008
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Intra-arterial thrombus visualized on T2* gradient echo imaging in acute ischemic stroke.
MR signal loss related to arterial thrombosis leading to vascular susceptibility artifacts (VSA) has recently been reported on gradient echo images. The time course and sensitivity of VSA in acute stroke patients has been scarcely investigated. The aim of this study was to assess the frequency and course of VSA in acute stroke patients, to compare its sensitivity to distinct features of arterial occlusion as detected on FLAIR images or on CT scan. Twenty-nine patients were scanned from 45 min to 6 h after stroke onset using identical MR parameters. All had an acute ischemic lesion identified on diffusion-weighted images, 25 had an occlusion of MCA or PCA confirmed by magnetic resonance angiography. VSA was detected in 22/25 patients having an occluded artery at the time of MRI examination. Flair disclosed a hyperintense vessel in all of these 25 cases, but CT scan revealed a hyperdense artery in only 15 cases. Follow-up studies showed that VSA can vanish or disappear after partial recanalization. When the artery remains occluded, VSA can decrease, disappear or increase in the next hours, possibly related to structural modifications of the thrombus with time. Most occlusions were due to cardiac and arterial emboli or to intracranial extension of carotid occlusion. VSA are frequent in the first hours of MCA or PCA occlusion in acute stroke patients. The sensitivity of VSA appears lower than the arterial hyperintensity on FLAIR images but higher than the hyperdense artery sign on CT scan. The extent and intensity of VSA can change with recanalization or structural modifications of the thrombus.
| 270
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PubMed Abstracts
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1121010
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Ice chromatography: current progress and future developments.
Ice chromatography, in which water-ice particles are employed as a chromatographic stationary phase, has proven an efficient technique for probing the solution/ice interface. The preparation of fine ice particles has allowed us to not only obtain higher-resolution separation but also investigate the molecular processes occurring on the ice surface in more detail. Chromatographic investigations have revealed that two or more hydrogen bonds are simultaneously formed between a solute and the dangling bonds on the ice surface when the solute gives measurable retention. Several compounds, including estrogens, amino acids, and acyclic polyethers, have been successfully separated by ice chromatography with a hexane-based mobile phase. In addition, this method effectively probes the surface melting of the ice stationary phase and the liquid phase that coexists with water ice at thermodynamic equilibrium. The thickness of the surface liquid layer and the size of the liquid phase that grows inside an ice particle have been evaluated. The perspectives of this method are also discussed.
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PubMed Abstracts
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1121020
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Translational regulation of SV40 early mRNA defines a new viral protein.
SP6-initiated in vitro transcripts, representing the three major classes of early SV40 mRNAs, early-early (EE) and two late-early (LE) transcripts, were assayed by in vitro translation to compare their relative efficiencies for synthesis of the SV40 T antigens. The presence of one or two potential AUG initiator codons in the leader sequences of the LE RNAs inhibits efficient translation from the downstream T-antigen initiator AUG. In vitro translation of the capped form of the shorter SV40 LE RNA resulted in the synthesis of a 2.7-kd protein. In vivo pulse labeling of SV40-infected CV-1 cells demonstrated the accumulation of a peptide of similar size at late times after lytic infection, indicating that it is an authentic viral protein encoded by the early leader sequence of SV40.
| 135
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PubMed Abstracts
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1121026
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The collection and processing of human brain tissue for research.
To further understand the neuroanatomy, neurochemistry and neuropathology of the normal and diseased human brain, it is essential to have access to human brain tissue where the biological and chemical nature of the tissue is optimally preserved. We have established a human brain bank where brain tissue is optimally processed and stored in order to provide a resource to facilitate neuroscience research of the human brain in health and disease. A donor programme has been established in consultation with the community to provide for the post-mortem donation of brain tissue to the brain bank. We are using this resource of human brain tissue to further investigate the basis of normal neuronal functioning in the human brain as well as the mechanisms of neuronal dysfunction and degeneration in neurodegenerative diseases. We have established a protocol for the preservation of post-mortem adult human brain tissue firstly by snap-freezing unfixed brain tissue and secondly by chemical fixation and then storage of this tissue at -80 degrees C in a human brain bank. Several research techniques such as receptor autoradiography, DNA and RNA analysis, are carried out on the unfixed tissue and immunohistochemical and histological analysis is carried out on the fixed human tissue. Comparison of tissue from normal control cases and from cases with neurodegenerative disorders is carried out in order to document the changes that occur in the brain in these disorders and to further investigate the underlying pathogenesis of these devastating neurological diseases.
| 251
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PubMed Abstracts
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1121042
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Intragastric pH in postlaparotomy patients--effects of cimetidine.
Intragastric pH was continuously monitored in 21 patients who underwent colorectal surgery. Monitoring was started before surgery, and was continued for two days after surgery. Intragastric pH tended to increase during surgery, compared with measurements obtained before and after surgery, but was not affected by the duration of anesthesia or of the surgical procedure, or surgical position. After surgery, patients were divided into two groups: the cimetidine group (10 patients) received intravenous cimetidine 200 mg 4 times a day, while the control group (11 patients) received no treatment. Postoperative intragastric pH was higher than 3.0 throughout the study in the cimetidine group, but was approximately 1.3 in the control group. Upper gastrointestinal bleeding occurred in 2 patients in the control group, with intragastric pH falling abruptly during the bleeding episode. To prevent post-operative upper gastrointestinal bleeding, in addition to the administration of H2-blockers or antacids, appropriate treatments in response to changes in intragastric pH are necessary. Continuous monitoring of intragastric pH in surgical patients is considered to be of clinical importance.
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PubMed Abstracts
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1121048
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Random locomotion and chemotaxis of human blood polymorphonuclear leukocytes from a patient with leukocyte adhesion deficiency-1: normal displacement in close quarters via chimneying.
The beta2 integrins are known to be important in the motile function of leukocytes in general and in the adhesive response to inflammatory stimuli in particular. In the current study, under direct microscopic observation with concomitant time-lapse video recording, we examined the locomotion of human blood PMN from a patient with Leukocyte Adhesion Deficiency-1 (LAD), a disorder in which beta2 integrins on the cell surface are markedly deficient in number or function. In thin slide preparations such that the leukocytes were somewhat compressed between slide and cover slip, PMNLAD exhibited normal random locomotion and chemotaxis, apparently by using the opposing surfaces to generate the force for locomotion (chimneying). In thicker preparations, an adherence deficit was evident, but chemotaxis still occurred, even by PMNLAD anticoagulated in EDTA. Consistent with the paucity of beta2 integrins on the surface of the PMNLAD was their failure to aggregate in the presence of antibodies to beta2 integrins, even when they had been brought together by chemotaxis. We relate these findings to the reported independence from integrins of PMN in the lung vasculature in LAD, as well as in certain experimental conditions.
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PubMed Abstracts
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1121054
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Derivation of a simple clinical model to categorize patients probability of pulmonary embolism: increasing the models utility with the SimpliRED D-dimer.
We have previously demonstrated that a clinical model can be safely used in a management strategy in patients with suspected pulmonary embolism (PE). We sought to simplify the clinical model and determine a scoring system, that when combined with D-dimer results, would safely exclude PE without the need for other tests, in a large proportion of patients. We used a randomly selected sample of 80% of the patients that participated in a prospective cohort study of patients with suspected PE to perform a logistic regression analysis on 40 clinical variables to create a simple clinical prediction rule. Cut points on the new rule were determined to create two scoring systems. In the first scoring system patients were classified as having low, moderate and high probability of PE with the proportions being similar to those determined in our original study. The second system was designed to create two categories, PE likely and unlikely. The goal in the latter was that PE unlikely patients with a negative D-dimer result would have PE in less than 2% of cases. The proportion of patients with PE in each category was determined overall and according to a positive or negative SimpliRED D-dimer result. After these determinations we applied the models to the remaining 20% of patients as a validation of the results. The following seven variables and assigned scores (in brackets) were included in the clinical prediction rule: Clinical symptoms of DVT (3.0), no alternative diagnosis (3.0), heart rate >100 (1.5), immobilization or surgery in the previous four weeks (1.5), previous DVT/PE (1.5), hemoptysis (1.0) and malignancy (1.0). Patients were considered low probability if the score was <2.0, moderate of the score was 2.0 to 6.0 and high if the score was over 6.0. Pulmonary embolism unlikely was assigned to patients with scores < or =4.0 and PE likely if the score was >4.0. 7.8% of patients with scores of less than or equal to 4 had PE but if the D-dimer was negative in these patients the rate of PE was only 2.2% (95% CI = 1.0% to 4.0%) in the derivation set and 1.7% in the validation set. Importantly this combination occurred in 46% of our study patients. A score of <2.0 and a negative D-dimer results in a PE rate of 1.5% (95% CI = 0.4% to 3.7%) in the derivation set and 2.7% (95% CI = 0.3% to 9.0%) in the validation set and only occurred in 29% of patients. The combination of a score < or =4.0 by our simple clinical prediction rule and a negative SimpliRED D-Dimer result may safely exclude PE in a large proportion of patients with suspected PE.
| 462
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PubMed Abstracts
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1121056
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The role of adipose tissue asymmetric dimethylarginine/dimethylarginine dimethylaminohydrolase pathway in adipose tissue phenotype and metabolic abnormalities in subtotally nephrectomized rats.
The lipodystrophy-like phenotype has been suggested in early chronic kidney disease (CKD). It includes adipose tissue atrophy, systemic insulin resistance (IR), dyslipidemia and ectopic lipid accumulation. To elucidate its pathogenesis, we investigated the role of two uremic toxins that affect insulin sensitivity: an endogenous nitric oxide synthase inhibitor, and asymmetric dimethylarginine (ADMA) and indoxyl sulfate (IS). Six-week-old Sprague-Dawley rats were rendered CKD by subtotal nephrectomy (Nx) and compared with sham-operated rats. Cultured 3T3-L1 fibroblasts were differentiated into mature adipocytes with or without ADMA. Transgenic (Tg) mice overexpressing each isoform of ADMA degrading enzyme, dimethylarginine dimethylaminohydrolase 1 (DDAH1) and DDAH2 were subject to Nx and their phenotypes were investigated. In Nx rats, IR was evident and insulin stimulation failed to activate insulin signaling in adipose tissues. Adipose tissue weight, adipocyte size and adipocyte differentiation marker expressions decreased as a consequence of IR in Nx. Tissue lipid content in the liver and muscle increased in Nx rats. Tissue levels of ADMA, IS and oxidative stress increased in the adipose tissue of Nx rats. Both DDAH1 and DDAH2 expressions decreased, and a putative IS receptor, aryl hydrocarbon receptor, expression increased in the adipose tissue of Nx rats. ADMA inhibited adipocyte differentiation, triglyceride accumulation and insulin signaling, which were reversed by pretreatment with cGMP. In each type of Tg mice overexpressing DDAH1 or DDAH2, all lipodystrophy-like phenotypes induced by Nx were reversed. In mild CKD, dysregulation of the ADMA/DDAH pathway in adipose tissue triggers lipodystrophy-like phenotype changes, including ectopic fat depositions.
| 266
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PubMed Abstracts
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1121064
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Relaxant effects of quercetin methyl ether derivatives in isolated guinea pig trachea and their structure-activity relationships.
In the present study, we attempted to compare quercetin methyl ethers and to look for the structure-activity relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four present and two previously studied quercetin methyl ethers concentration-dependently relaxed histamine (30 microM), carbachol (0.2 microM) and KCl (30 mM) induced precontraction. According to their IC25 values to histamine-induced precontraction, the potency order was quercetin 3,3',4,'5,7-pentamethyl ether (QPME), quercetin 3-methyl ether > quercetin, quercetin 3,4',7-trimethyl ether (ayanin) > quercetin 4'-methyl ether (tamarixetin), quercetin 3,3',4',7,-tetramethyl ether (QTME). Therefore, the methylation at 3, at 5, and at both 3 and 7 positions of the A or/and C ring of quercetin nucleus may increase their tracheal relaxant activity. However, the methylation at the 3' and at the 4' position of the B ring of quercetin nucleus may decrease their tracheal relaxant activity.
| 157
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PubMed Abstracts
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1121066
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Science 2.0.
Science 2.0 generally refers to new practices of scientists who post raw experimental results, nascent theories, claims of discovery and draft papers on the Web for others to see and comment on. Proponents say these "open access" practices make scientific progress more collaborative and therefore more productive. Critics say scientists who put preliminary findings online risk having others copy or exploit the work to gain credit or even patents. Despite pros and cons, Science 2.0 sites are beginning to proliferate; one notable example is the OpenWetWare project started by biological engineers at the Massachusetts Institute of Technology.
| 98
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PubMed Abstracts
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1121071
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In silico metabolic engineering of Bacillus subtilis for improved production of riboflavin, Egl-237, (R,R)-2,3-butanediol and isobutanol.
Bacillus subtilis is a Gram-positive sporiferous bacterium widely used in a variety of industrial fields as a producer of high-quality vitamins, enzymes and proteins. Many genetic modifications and evolutionary engineering optimisations aiming at obtaining a better performing strain for its products have been studied. As genome-scale metabolic network models have gained significant popularity as effective tools in metabolic phenotype studies, we reconstructed a genome-scale metabolic network of B. subtilis-iBsu1147. The accuracy of iBsu1147 is validated by growth on various carbon sources, single gene knockout and large fragment non-essential gene knockout simulations. The model is used for the in silico metabolic engineering design of reactions over/underexpressed or knockout for increasing the production of four important products of B. subtilis: riboflavin, cellulase Egl-237, (R,R)-2,3-butanediol and isobutanol. The simulation predicted candidate reactions related to the improvement of strain performance on related products. The prediction is partly supported by previously published results. Due to the complexity of the biological system, it is difficult to manually find the factors that are not directly related to the production of the target compounds. The in silico predictions provide more choices for further strain improvement for these products.
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PubMed Abstracts
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1121086
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Development of a novel synergistic thermosensitive gel for vaginal candidiasis: an in vitro, in vivo evaluation.
The singular aim of the proposed work is the development of a synergistic thermosensitive gel for vaginal application in subjects prone to recurrent vaginal candidiasis and other microbial infections. The dual loading of Itraconazole and tea tree oil in a single formulation seems promising as it would elaborate the microbial coverage. Despite being low solubility of Itraconazole in tea tree oil, a homogeneous, transparent and stable solution of both was created by co-solvency using chloroform. Complete removal of chloroform was authenticated by GC-MS and the oil solution was used in the development of nanoemulsion which was further translated into a gel bearing thermosensitive properties. In vitro analyses (MTT assay, viscosity measurement, mucoadhesion, ex vivo permeation, etc.) and in vivo studies (bioadhesion, irritation potential and fungal clearance kinetics in rat model) of final formulation were carried out to establish its potential for further clinical evaluation.
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PubMed Abstracts
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1121090
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[Summation of maximal tetanic tensions developed by slow or fast motor units of the peroneus longus muscle in the cat].
The maximal tetanic tension developed by the simultaneous contraction of several slow motor units (measured tension) is always greater than the sum of the tensions developed by each unit individually (cumulated tension). Generally, the same holds true for fast units but, for measured tensions of same value, the difference between measured tensions and cumulated tensions is much smaller. It is sometimes negligible or even negative.
| 84
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PubMed Abstracts
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1121091
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Coexistence of Ductal Carcinoma Within Mammary Phyllodes Tumor: A Review of 557 Cases From a 20-year Region-wide Database in Hong Kong and Southern China.
Phyllodes tumor (PT) is an uncommon fibroepithelial tumor of the breast showing predominately proliferation of the stromal component. The presence of ductal carcinoma in situ (DCIS) or invasive ductal carcinoma is rare, with only a few cases reported in the literature. A retrospective review of a prospectively maintained database was performed. Patients who were treated for PT in 5 hospitals in Hong Kong and Shenzhen, China over a period of 20 years (1997-2016) were evaluated. All pathology slides were reported by specialist pathologists. Patients with coexisting ductal carcinoma were identified. A total of 557 patients were included in this cohort; 363 (65.2%) patients had benign PT, 130 (23.3%) had borderline PT, and 64 (11.5%) had malignant PT. There were 6 (1.1%) patients with coexisting ductal carcinoma in the PT; 5 were DCIS and 1 was invasive ductal carcinoma. The median age was 46.5 years (range, 25-54 years). Ductal carcinoma occurred more frequently in malignant PT than in benign or borderline PT (4.7% vs. 0.6%; P = .02). However, malignant PT was not associated with higher DCIS grade (P = .1). All patients underwent surgery with clear resection margins. After a median follow-up interval of 70 months (range, 2-101 months), all patients remained disease- and recurrence-free. We report 6 additional uncommon cases of ductal carcinoma complicating PT. The presence of ductal carcinoma was not adverse prognosticator as these are usually incidental and situated within the harboring PT.
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PubMed Abstracts
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1121104
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Experimental determination of optimal root-mean-square deviations of macromolecular bond lengths and angles from their restrained ideal values.
A number of inconsistencies are apparent in the recent research paper by Jaskolski et al. [(2007), Acta Cryst. D63, 611-620] concerning their recommendations for the values of the magnitude and resolution-dependence of the root-mean-square deviations (RMSDs) of bond lengths and angles from their restrained ideal values in macromolecular refinement, as well as their suggestions for the use of variable standard uncertainties dependent on atomic displacement parameters (ADPs) and occupancies. Whilst many of the comments and suggestions in the paper regarding updates for the ideal geometry values proposed by Engh and Huber are entirely reasonable and supported by the experimental evidence, the recommendations concerning the optimal values of RMSDs appear to be in conflict with previous experimental and theoretical work in this area [Tickle et al. (1998), Acta Cryst. D54, 243-252] and indeed appear to be based on a misunderstanding of the distinction between RMSD and standard uncertainty (SU). In contrast, it is proposed here that the optimal values of all desired weighting parameters, in particular the weighting parameters for the ADP differences and for the diffraction terms, be estimated by the purely objective procedure of maximizing the experiment-based log(free likelihood). In principle, this allows all weighting parameters that are not known accurately a priori to be scaled globally, relative to those that are known accurately, for an optimal refinement. The RMS Z score (RMSZ) is recommended as a more satisfactory statistic than the RMSD to assess the extent to which the geometry deviates from the ideal values and a theoretical rationale for the results obtained is presented in which the optimal RMSZ is identified as the calculated versus true Z-score correlation coefficient, the latter being a monotonic function of the resolution cutoff of the data. Regarding the proposal to use variable standard uncertainties, it is suggested that any departure from the current practice of using fixed weights for geometric restraints based on experimental values of standard uncertainties be subject to the same experiment-based validation.
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PubMed Abstracts
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1121112
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Uroplakin gene expression in normal human tissues and locally advanced bladder cancer.
The uroplakins are widely regarded as urothelium-specific markers of terminal urothelial cytodifferentiation. This study investigated the expression of the four uroplakin genes, UPIa, UPIb, UPII and UPIII, in a wide range of normal human tissues to determine tissue specificity and in advanced transitional cell carcinoma (TCC) to examine gene expression in primary and metastatic disease. In the urinary tract, all four uroplakins were expressed by urothelium and UPIII was also expressed by prostatic glandular epithelium. UPIa and UPII appeared to be urothelium-specific, but UPIb was detected in several non-urothelial tissues, including the respiratory tract, where it was associated with squamous metaplasia of tracheal and bronchial epithelia. The ten cases of primary TCC and corresponding lymph node metastases demonstrated that each uroplakin gene could be expressed at the mRNA level. No single uroplakin gene was expressed in all primary tumours or metastases, but 80% of the primary tumours and 70% of the lymph node metastases expressed at least one uroplakin gene. UPIII mRNA was often expressed in the absence of UPIII protein. These results confirm that in human tissues the expression of UPIa and UPII genes is highly specific to urothelium and suggest that the tight differentiation-restricted expression of uroplakin genes in normal urothelium is lost following malignant transformation.
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PubMed Abstracts
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