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At least 163 records · Page 9Linked to original sources

Molecular cloning and characterization of EndoGlyx-1, an EMILIN-like multisubunit glycoprotein of vascular endothelium.

EndoGlyx-1, the antigen identified with the monoclonal antibody H572, is a pan-endothelial human cell surface glycoprotein complex composed of four different disulfide-bonded protein species with an apparent molecular mass of approximately 500 kDa. Here, we report the purification and peptide analysis of two EndoGlyx-1 subunits, p125 and p140, and the identification of a common, full-length cDNA with an open reading frame of 2847 base pairs. The EndoGlyx-1 cDNA encodes a protein of 949 amino acids with a predicted molecular mass of 105 kDa, found as an entry for an unnamed protein with unknown function in public data bases. A short sequence tag matching the cDNA of this gene was independently discovered by serial analysis of gene expression profiling as a pan-endothelial marker, PEM87. Bioinformatic evaluation classifies EndoGlyx-1 as an EMILIN-like protein composed of a signal sequence, an N-terminal EMI domain, and a C-terminal C1q-like domain, separated from each other by a central coiled-coil-rich region. Biochemical and carbohydrate analysis revealed that p125, p140, and the two additional EndoGlyx-1 subunits, p110 and p200, are exposed on the cell surface. The three smaller subunits show a similar pattern of N-linked and O-linked carbohydrates, as shown by enzyme digestion. Because the two globular domains of EndoGlyx-1 p125/p140 show structural features shared by EMILIN-1 and Multimerin, two oligomerizing glycoproteins implicated in cell-matrix adhesion and hemostasis, it will be of interest to explore similar functions for EndoGlyx-1 in human vascular endothelium.

Amino Acid Sequence↗

Carriage of methicillin-resistant Staphylococcus aureus, ceftazidime-resistant Gram-negative bacilli, and vancomycin-resistant enterococci before and after intensive care unit admission.

OBJECTIVE: To measure patients' risk for acquiring antibiotic-resistant microorganisms associated with intensive care unit admission. DESIGN: Prospective, observational study. SETTING: Ten public hospitals including one university medical center. PATIENTS: Consecutive patients admitted to ten intensive care units. INTERVENTIONS: Serial patient surveillance cultures were screened for vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus (MRSA), ceftazidime-resistant Gram-negative bacilli (CR-GNB), Acute Physiology and Chronic Health Evaluation II score, and antibiotic and medical device exposures. MEASUREMENTS AND MAIN RESULTS: A total of 1,697 patient admissions in ten intensive care units were enrolled. The overall carriage rate of antibiotic-resistant bacteria at intensive care unit entry was 12.1% for MRSA, 14% for CR-GNB and 4.7% for both. At discharge from the intensive care unit, new carriage of MRSA, CR-GNB, and both was found in 11.1%, 14.2%, and 2.4% of the patients, respectively. The acquisition rates in the individual units correlated highly and positively with proportion of patients with carriage at intensive care unit entry for both MRSA (n = 10, Pearson's r =.89, p < 0.001) and CR-GNB (n = 10, Pearson's r =.92, p < 0.001). By logistic regression, severity of illness (odds ratio, 1.4), length of stay (odds ratio, 1.7), use of penicillins (odds ratio, 1.9), and number of antibiotics (odds ratio, 1.2) and medical devices (odds ratio, 1.2) were independently associated with intensive care unit acquisition of MRSA. In comparison, variables independently associated with intensive care unit acquisition of CR-GNB were Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.5), number of antibiotics (odds ratio, 1.1), and artificial airway (odds ratio, 1.5). CONCLUSIONS: These data suggest that hospitalization in the intensive care unit introduces significant risk to patients in terms of transmission of MRSA and/or CR-GNB. This risk seems to be influenced strongly by the proportion of patients with colonization at intensive care unit admission and is associated with severity of illness, length of stay, and exposures to antibiotics and medical devices.

Aged↗

Karl Wittmaack: his life, temporal bone collection, and publications. On the 100th anniversary of his birth.

Karl Wittmaack (1876-1972) was professor for Oto-Rhino-Laryngology at the universities of Jena (1908-1925) and Hamburg (1926-1946). He contributed a lot of pioneer work to experimental pathology of the ear. He left a unique collection of serial sections of temporal bones from animals (55,000 slides) and man (102, 000 slides). This paper gives some data on Wittmaack's life, his temporal bone collection and the unpublished list of his publications.

Animals↗

Adoption of spironolactone therapy for older patients with heart failure and left ventricular systolic dysfunction in the United States, 1998-2001.

BACKGROUND: Concerns have been raised about the appropriateness of spironolactone use in some patients with heart failure. We studied the adoption of spironolactone therapy after publication of the Randomized Aldactone Evaluation Study (RALES) in national cohorts of older patients hospitalized for heart failure. METHODS AND RESULTS: This is a study of serial cross-sectional samples of Medicare beneficiaries > or =65 years old discharged after hospitalization for the primary diagnosis of heart failure and with left ventricular systolic dysfunction. The first sample was discharged before (April 1998 to March 1999, n=9758) and the second sample after (July 2000 to June 2001, n=9468) publication of RALES in September 1999. We assessed spironolactone prescriptions at hospital discharge in patient groups defined by enrollment criteria for the trial. Using multivariable logistic regression, we identified factors independently associated with prescriptions not meeting these criteria. Spironolactone use increased >7-fold (3.0% to 21.3% P<0.0001) after RALES. Of patients meeting enrollment criteria, 24.1% received spironolactone, as compared with 17.4% of those not meeting the criteria. Of all prescriptions after RALES, 30.9% were provided to patients not meeting enrollment criteria. Spironolactone was prescribed to 22.8% of patients with a serum potassium value > or =5.0 mmol/L, to 14.1% with a serum creatinine value > or =2.5 mg/dL, and to 17.3% with severe renal dysfunction (estimated glomerular filtration rate <30 mL.min(-1).1.73 m(-2)). In multivariable analyses, factors associated with prescriptions not meeting enrollment criteria included advanced age, noncardiovascular comorbidities, discharge to skilled nursing facilities, and care provided by physicians without board certification. CONCLUSIONS: Spironolactone prescriptions increased markedly after the publication of RALES, and many treated patients were at risk for hyperkalemia. Simultaneously, many patients who might have benefited were not treated. These findings demonstrate the importance of balancing efforts to enhance use among appropriate patients and minimizing use in patients at risk for adverse events.

Aged↗

Differentially expressed genes in pancreatic ductal adenocarcinomas identified through serial analysis of gene expression.

Serial analysis of gene expression (SAGE) is a powerful tool for the discovery of novel tumor markers. The publicly available online SAGE libraries of normal and neoplastic tissues (http://www.ncbi.nlm.nih.gov/SAGE/) have recently been expanded; in addition, a more complete annotation of the human genome and better biocomputational techniques have substantially improved the assignment of differentially expressed SAGE "tags" to human genes. These improvements have provided us with an opportunity to re-evaluate global gene expression in pancreatic cancer using existing SAGE libraries. SAGE libraries generated from six pancreatic cancers were compared to SAGE libraries generated from 11 non-neoplastic tissues. Compared to normal tissue libraries, we identified 453 SAGE tags as differentially expressed in pancreatic cancer, including 395 that mapped to known genes and 58 "uncharacterized" tags. Of the 395 SAGE tags assigned to known genes, 223 were overexpressed in pancreatic cancer, and 172 were underexpressed. In order to map the 58 uncharacterized differentially expressed SAGE tags to genes, we used a newly developed resource called TAGmapper (http://tagmapper.ibioinformatics.org), to identify 16 additional differentially expressed genes. The differential expression of seven genes, involved in multiple cellular processes such as signal transduction (MIC-1), differentiation (DMBT1 and Neugrin), immune response (CD74), inflammation (CXCL2), cell cycle (CEB1) and enzymatic activity (Kallikrein 6), was confirmed by either immunohistochemical labeling of tissue microarrays (Kallikrein 6, CD74 and DMBT1) or by RT-PCR (CEB1, Neugrin, MIC1 and CXCL2). Of note, Neugrin was one of the genes whose previously uncharacterized SAGE tag was correctly assigned using TAGmapper, validating the utility of this program. Novel differentially expressed genes in a cancer type can be identified by revisiting updated and expanded SAGE databases. TAGmapper should prove to be a powerful tool for the discovery of novel tumor markers through assignment of uncharacterized SAGE tags.

Adenocarcinoma↗

Colorectal resection in Victoria:a comparison of hospital based and individual audit.

BACKGROUND: The results of personal audit have not been tested against a hospital-based audit previously and the results of two such audits of colorectal resection in the State of Victoria have provided this opportunity. In addition, data reflecting the results of colorectal resection across a range of hospitals and surgeons in the Victorian community have been obtained. METHODS: A total of 535 patients undergoing a colorectal resection, with an anastomosis performed, were studied in two serially conducted prospective audits arranged by the Standards Sub-Committee of the Victorian State Committee. One study was public hospital-based and the second was based on voluntary reporting by individual surgeons. RESULTS: Similar results were obtained in each study, demonstrating the accuracy of individual reporting. The combined results (wound infection rate 12.3%, anastomotic leak rate 3.7% and mortality 4.5%) are compared to previously published data. CONCLUSIONS: In the State of Victoria the results of audit by individual surgeons performing colorectal resection were similar to the hospital-based audit. The results obtained compare favourably with previously published data.

Aged↗

A decade of differential display.

It has been 10 years since the invention of differential display (DD), a conceptually simple methodology that allows the detection and identification of differentially expressed genes. In the past decade, the number of publications describing successful applications of DD has outnumbered those using any other competing methodologies, including subtractive hybridization, representational difference analysis, serial analysis of gene expression, and DNA microarrays. This review will provide a glimpse of the current progress made in DD technological development, refinement, and automation. Excellent examples of DD applications in studying a variety of biological problems, in such diverse biological systems as bacteria, yeast, flies, plants, and higher mammals, are presented to provide a roadmap for those who would like to pursue a fruitful gene "fishing" expedition. Some of the fundamental differences between DD and DNA microarrays are also discussed.

Animals↗

An update on the Kevorkian-Reding 93 physician-assisted deaths in Michigan: is Kevorkian a savior, serial-killer or suicidal martyr?

This report presents an update of the Kevorkian-Reding physician-assisted (or physician-aided) deaths to include the ninety-three publicly acknowledged cases as of November 25, 1998. These deaths are divided into ten distinct time phases. The following trends emerge. Over two-thirds of the decedents are women, the ratio of females to males varying widely with phase. The proportion of women seems to be the highest when Kevorkian is free to act as he wants and lowest when he seems to be acting under legal or political restraints. Based on autopsy results, only 29.0 percent of the cases are terminal, this percentage being higher among men (37.9%) than among women (25.4%). However, 66.7% of the decedents were disabled, no significant difference emerging between men and women. Further, five out of the six decedents showing no apparent anatomical sign of disease at autopsy were women. Over 80 percent of the physician-assisted deaths are cremated, approximately twice as high a proportion as that emerging for suicides in Michigan and four times as high as cremations occurring with regard to overall deaths. Finally, death by carbon monoxide decreases dramatically with time phase while the use of the contraption dubbed the "suicide machine" increases, suggesting an increasing routinization over time. Finally, during the ninth and tenth phases, Kevorkian's aims and his own suicidality emerge more clearly involving 1) harvesting organs and 2) threat of starving himself in prison if he is convicted. Phase 10 can be seen as an escalation from assisted death to overt euthanasia, repeating the same need for a demonstration (Thomas Youk) that was first exhibited in Phase I (Janet Adkins).

Chronic Disease↗

[Spontaneous aseptic osteonecrosis of the knee (Ahlbäck's disease). NMR imaging using GD-DTPA].

Whereas the MRT appearances of aseptic necrosis in various localisations, particularly the hip, are well described) there are only a few publications in the literature concerning Ahlbäck's disease. The present case has shown that MRT, using a T1-weighted dynamic serial gradient echo sequence with bolus injection of contrast, provides useful information for the early diagnosis of this condition. By using Gd-DTPA it is possible to evaluate the viability and vascularity of the affected bone.

Contrast Media↗

Radiation treatment of foods. II. Public health significance of irradiation-recycled Salmonella.

Salmonellae resistant to gamma irradiation were developed by repeated irradiation and subculturing in a nutrient broth-yeast extract medium. Few differences were noted in the biochemical characteristics of parent and resistant cultures; however, microculture studies revealed variations in morphology and in cell division patterns. A considerable decrease in pathogenicity for day-old chicks was apparent with resistant cultures, but their phenol-water extracts were as toxic as parent material for 10-day chick embryos. Five serial chick passages did not reverse the reduced pathogenicity or aberrant morphology of a resistant Salmonella typhimurium culture. Results of phage typing of both parent and serially irradiated S. typhimurium were inconclusive, whereas the O-1 genus-specific phage lysed all parent serotypes tested but only one of the serially irradiated cultures. Agglutination of parent S. typhimurium cells with their homologous rabbit antiserum was unaffected by prior absorption with resistant strains. The results indicate that radiation recycling altered Salmonella into strains of lesser public health significance.

Agglutination Tests↗

Topological analysis of the brainstem of the bowfin, Amia calva.

This paper presents a survey of the cell masses in the brainstem of the generalized actinopterygian fish Amia calva, based on transversely cut Nissl-, Klüver-Barrera-, and Bodian-stained serial sections. This study is intended to serve a double purpose. First it forms part of a now almost complete series of publications on the structure of the brainstem in representative species of all groups of vertebrates. Within the framework of this comparative program the cell masses in the brainstem and their positional relations are analyzed in the light of the Herrick-Johnston concept; according to this the brainstem nuclei are arranged in four longitudinal, functional zones or columns, the boundaries of which are marked by ventricular sulci. The procedure employed in this analysis essentially involves two steps: first, the cell masses and large individual cells are projected upon the ventricular surface, and next, the ventricular surface is flattened out, that is, subjected to a one-to-one continuous topological transformation (Nieuwenhuys [1974] J. Comp. Neurol. 156:255-267). The second purpose of the present paper is to provide a cytoarchitectonic basis for experimental analysis of the fiber connectivity in the brainstem of Amia. Five longitudinal sulci--the sulcus medianus inferior, the sulcus intermedius ventralis, the sulcus limitans, the sulcus intermedius dorsalis, and the sulcus lateralis mesencephali--could be distinguished. Some shorter grooves, present in the isthmal region, clearly deviate from the overall longitudinal pattern of the other sulci. Although in Amia most neuronal perikarya are contained within a diffuse periventricular gray, 40 cell masses could be delineated: Eight of these are primary efferent or motor nuclei, 10 are primary afferent or sensory centers, seven are considered to be components of the reticular formation, and the remaining 15 may be interpreted as "relay" nuclei. The topological analysis yielded the following results. In the rhombencephalon the gray matter is arranged in four longitudinal columns or areas, termed area ventralis, area intermedioventralis, area intermediodorsalis, and area dorsalis. The sulcus intermedius ventralis, the sulcus limitans, and the sulcus intermedius dorsalis mark the boundaries between these morphological entities. These longitudinal areas coincide largely, but not entirely, with the functional columns of Herrick and Johnston. The most obvious incongruity is that the area intermediodorsalis contains, in addition to the viscerosensory nucleus of the solitary tract, several general somatosensory and special somatosensory nuclei.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Recombinant sindbis/Venezuelan equine encephalitis virus is highly attenuated and immunogenic.

Venezuelan equine encephalitis virus (VEEV) is an important, naturally emerging zoonotic virus. VEEV was a significant human and equine pathogen for much of the past century, and recent outbreaks in Venezuela and Colombia (1995), with about 100,000 human cases, indicate that this virus still poses a serious public health threat. The live attenuated TC-83 vaccine strain of VEEV was developed in the 1960s using a traditional approach of serial passaging in tissue culture of the virulent Trinidad donkey (TrD) strain. This vaccine presents several problems, including adverse, sometimes severe reactions in many human vaccinees. The TC-83 strain also retains residual murine virulence and is lethal for suckling mice after intracerebral (i.c.) or subcutaneous (s.c.) inoculation. To overcome these negative effects, we developed a recombinant, chimeric Sindbis/VEE virus (SIN-83) that is more highly attenuated. The genome of this virus encoded the replicative enzymes and the cis-acting RNA elements derived from Sindbis virus (SINV), one of the least human-pathogenic alphaviruses. The structural proteins were derived from VEEV TC-83. The SIN-83 virus, which contained an additional adaptive mutation in the nsP2 gene, replicated efficiently in common cell lines and did not cause detectable disease in adult or suckling mice after either i.c. or s.c. inoculation. However, SIN-83-vaccinated mice were efficiently protected against challenge with pathogenic strains of VEEV. Our findings suggest that the use of the SINV genome as a vector for expression of structural proteins derived from more pathogenic, encephalitic alphaviruses is a promising strategy for alphavirus vaccine development.

Animals↗

Recent declines in reported syphilis rates in eastern Europe and central Asia: are the epidemics over?

BACKGROUND: Since the early 1990s, major syphilis epidemics have occurred in the Newly Independent States (NIS) of the former Soviet Union. The new and rapidly changing societal and economic conditions in these countries challenge their traditional approaches to the control of sexually transmitted infections (STI). Nevertheless, following a steady increase until 1997, reported syphilis incidence has declined during the past 3 years in most parts of the region. We examine these trends against a background of ongoing changes in service delivery, care seeking behaviour, and case finding practices. METHODS: National syphilis surveillance data reported to the WHO Regional Office for Europe were compiled and analysed, and supplemented with information presented at recent expert meetings and with results from ongoing research. RESULTS: Since 1997, reported syphilis incidence either stabilised or declined in many locations in the NIS, but further increased in others, especially in rural areas. Congenital syphilis continued to increase in all countries, except Latvia. The proportion of self presenting cases versus cases detected through screening declined, and so did notifications of early compared with late forms of syphilis. Patients increasingly seek care in the private formal and informal healthcare sectors which hardly participate in case reporting. CONCLUSIONS: Recent declines in syphilis notifications in the NIS are at least partially a reflection of a reduced intensity of active case finding and of changes in reporting completeness because of a shift in service utilisation from the public to the private/informal sectors. Syphilis rates are still high, indicating that both public and private sectors have to respond more efficiently to the needs of many people at risk of STI. The collection of serial STI prevalence data is recommended to be able to validate trends in notifications.

Adolescent↗

The sustained release of antimicrobial drugs from bone cement. An appraisal of laboratory investigations and their significance.

The release of gentamicin sulphate, sodium fusidate and diethanolamine fusidate from Palacos and CMW cements was studied using elution and serial plate transfer tests. Further tests were made to assay the drug remaining in the cement after antibacterial activity could no longer be detected by the above methods, to detect the sustained slow release of the residual drug, and to ascertain the mechanism of release. The results confirmed that the release of gentamicin sulphate could be detected for longer from Palacos cement than from CMW cement, but the opposite was true for sodium fusidate. Little difference was found in the case of diethanolamine fusidate. Comparison of elution and serial plate transfer tests, and of results of elution in buffers of different pH, demonstrated that the test method employed had a significant effect on the results, and the omission of details of methodology from some publications made comparison and evaluation of results difficult. Varying quantities of residual drug were found in cement from which antibacterial activity could no longer be demonstrated; further tests for sustained, slow release showed that the antibiotic did not remain fixed in the cement but was released at a rate too slow to be detected in the elution and serial plate transfer tests. It is concluded that antibiotics are released from the cement by a process of diffusion, but tests to determine the mechanism of diffusion were unhelpful. The theory of diffusion of drugs through solid matrices, and the clinical implications of the experimental findings, are discussed.

Acrylic Resins↗

Common MRI acquisition non-idealities significantly impact the output of the boundary shift integral method of measuring brain atrophy on serial MRI.

Measuring rates of brain atrophy from serial magnetic resonance imaging (MRI) studies is an attractive way to assess disease progression in neurodegenerative disorders, particularly Alzheimer's disease (AD). A widely recognized approach is the boundary shift integral (BSI). The objective of this study was to evaluate how several common scan non-idealities affect the output of the BSI algorithm. We created three types of image non-idealities between the image volumes in a serial pair used to measure between-scan change: inconsistent image contrast between serial scans, head motion, and poor signal-to-noise (SNR). In theory the BSI volume difference measured between each pair of images should be zero and any deviation from zero should represent corruption of the BSI measurement by some non-ideality intentionally introduced into the second scan in the pair. Two different BSI measures were evaluated, whole brain and ventricle. As the severity of motion, noise, and non-congruent image contrast increased in the second scan, the calculated BSI values deviated progressively more from the expected value of zero. This study illustrates the magnitude of the error in measures of change in brain and ventricle volume across serial MRI scans that can result from commonly encountered deviations from ideal image quality. The magnitudes of some of the measurement errors seen in this study exceed the disease effect in AD shown in various publications, which range from 1% to 2.78% per year for whole brain atrophy and 5.4% to 13.8% per year for ventricle expansion (Table 1). For example, measurement error may exceed 100% if image contrast properties dramatically differ between the two scans in a measurement pair. Methods to maximize consistency of image quality over time are an essential component of any quantitative serial MRI study.

Adult↗

Evaluation of a method for detecting aberrations in public health surveillance data.

The detection of unusual patterns in routine public health surveillance data on diseases and injuries presents an important challenge to health workers interested in early identification of epidemics or clues to important risk factors. Each week, state health departments report the numbers of cases of about 50 notifiable diseases to the Centers for Disease Control and Prevention, and these reports are published weekly in the Morbidity and Mortality Weekly Report. A new analytic method and a horizontal bar graph were introduced in July 1989 to facilitate easy identification of unusual numbers of reported cases. Evaluation of the statistical properties of this method indicates that the results are fairly robust to nonnormality and serial correlation of the data. An epidemiologic evaluation of the method after the first 6 months showed that it is useful for detection of specific types of aberrations in public health surveillance.

Bias↗