Search PubMed⌕ Search

Biomedical subjects

E Rubin

Publications and source records attributed to E Rubin.

At least 73 records · Page 4Linked to original sources
PubMed1996

Diagnosis of cytomegalovirus (CMV) infection in pediatric transplant patients by the antigenemia, shell vial, and conventional culture assays performed on blood: correlation with CMV disease.

BACKGROUND: Human cytomegalovirus (CMV) is a significant cause of morbidity and mortality in transplant recipients. Isolation of CMV from blood leukocytes (CMV viremia) is considered predictive of CMV disease in transplant recipients. Therefore, investigation of methods for the rapid detection of CMV in the blood is important for diagnosis and management of these patients. OBJECTIVE: To compare three techniques for the diagnosis and monitoring of CMV infection in a pediatric transplant population through the quantitative detection of CMV in peripheral blood leukocytes (PBL). METHODS: Serial blood specimens were obtained for most patients. After separation of the PBL from each specimen, aliquots of the PBL were used for direct detection of CMV antigenemia by immunoperoxidase staining of acetone-fixed cells (CMV-vue kit, INCSTAR), and by immunofluorescence staining of formaldehyde-fixed cells (Complete 1C3 kit, Biosoft Argene). PBL were also inoculated into conventional cell culture tubes and shell vials. Patients' medical records were reviewed to ascertain the clinical significance of the results. RESULTS: A total of 154 specimens obtained from 38 pediatric transplant recipients were evaluated. CMV was detected in 16 specimens obtained from eight patients: 11 specimens were found positive with the CMV-vue kit, 10 with the Complete 1C3 kit, four by conventional culture, and one by the shell vial assay. Seven of the eight patients with CMV-positive PBL had clinical signs and other laboratory evidence of active CMV infection. In general, a high-level antigenemia was demonstrated in the presence of clinical disease, but there were exceptions. CONCLUSIONS: The two antigenemia kits were more sensitive than conventional culture and the shell vial assay for the detection of CMV in the blood of pediatric transplant patients. Our results suggest that CMV antigenemia is a sensitive and specific rapid method for the diagnosis and monitoring of CMV infection in our patient population.

Journal Article↗
PubMed1996

Ethanol and cocaine cause additive inhibitory effects on the calcium transients and contraction in single cardiomyocytes.

The heart is a major locus for the toxic actions of cocaine and ethanol, each of which has been shown to interfere with excitation-contraction coupling in cardiac muscle cells. Because these drugs are frequently used in combination, the present study was designed to investigate how they interact to modify the Ca2+ transient and associated contraction in fura2-loaded cardiomyocytes. A high-speed imaging technique using a charge-coupled device as detector and short-term image store was used to measure cytosolic Ca2+ and contraction simultaneously from fluorescence images obtained during the contractile cycle. Ethanol (100 mM) and cocaine (50 microM) caused reversible reductions in Ca2+ transient amplitude of 24.3 +/- 3.0% and 25.1 +/- 3.6%, respectively. Neither agent modified basal Ca2+. Ethanol treatment decreased peak shortening by 44.3 +/- 3.5%, whereas the contractile depression by cocaine was 31.4 +/- 5.3%. The relatively greater effect of ethanol on contraction resulted from a Ca2+-independent component of ethanol action on contractility. When cardiomyocytes were exposed simultaneously to ethanol and cocaine, Ca2+ transient amplitude was reduced by 38.7 +/- 3.0%, and peak contraction was decreased by 55.1 +/- 3.5%. These values represent a significantly greater inhibition than observed with either drug alone (p < 0.02) and are compatible with additive effects of the two drugs acting at distinct loci within the excitation-contraction coupling pathway. Thus, simultaneous use of cocaine and ethanol leads to an enhanced depression of myocardial contractility, which is likely to contribute to the cardiotoxic actions of the combination of these two drugs.

Animals↗
PubMed1995

Convergent DNA synthesis: a non-enzymatic dimerization approach to circular oligodeoxynucleotides.

We report a novel convergent approach to the construction of circular DNA oligonucleotides from two smaller linear precursors. Circular DNAs 34-74 nucleotides (nt) in size are constructed non-enzymatically in a single step from two half-length oligomers. A DNA template is used to assemble the constituent parts into a triple helical complex which brings the four reactive ends together for chemical ligation with BrCN/imidazole/Ni2+. A homodimerization reaction strategy is successfully used on a small scale to construct circles 42, 58 and 74 nt in size. In addition, a heterodimerization strategy is successfully used in two cases to construct circular 34mers from different 16mer and 18mer precursors. Measurement of preparative yields for one biologically active 34mer circle shows that the dimerization strategy gives a yield higher than that from conventional cyclization and nearly as high as that for a normally synthesized linear DNA, establishing that there is not necessarily a yield penalty for circle construction. Six additional preparative circle constructions, giving conversions of approximately 33-85% from precursors to circular product, are also described. Convergent strategies allow the construction of medium and large size DNA molecules in higher yields than can be achieved by standard linear synthesis alone.

Base Sequence↗
PubMed1995

Ionizing radiation stimulates a Grb2-mediated association of the stress-activated protein kinase with phosphatidylinositol 3-kinase.

The stress-activated protein (SAP) kinases are induced by tumor necrosis factor, oncoproteins, and UV light. The present studies demonstrate that ionizing radiation (IR) activates p54 SAP kinase. IR-induced activation of SAP kinase is associated with binding to the SH2/SH3-containing adaptor protein Grb2. This interaction is mediated by the SH3 domains of Grb2 and the proline-rich sequence PPPKIP in the carboxy-terminal region of SAP kinase. We also demonstrated that SAP kinase and the p85 alpha-subunit of phosphatidylinositol (PI) 3-kinase form a complex in irradiated cells. The results indicate that this complex involves binding of the p85 alpha subunit of PI 3-kinase to the SH2 domain of Grb2. The functional role of linking SAP kinase to PI 3-kinase is further supported by the finding that wortmannin, an inhibitor of PI 3-kinase, stimulates SAP kinase activity. These results suggest that the cellular response to IR may include regulation of SAP kinase by a PI 3-kinase-dependent signaling pathway.

Adaptor Proteins, Signal Transducing↗
PubMed1995

The greater risk of alcoholic cardiomyopathy and myopathy in women compared with men.

OBJECTIVE: To compare the cardiac and muscular status of male and female alcoholics to determine if the response of women to alcohol is different from that of men. DESIGN: Cross-section study. SETTING: An ambulatory alcoholism treatment unit in the Hospital Clínic of Barcelona. PATIENTS: Fifty asymptomatic alcoholic women, 100 asymptomatic alcoholic men, and 50 female nonalcoholic controls. MAIN OUTCOME MEASURES: Studies included clinical assessment of muscle strength, muscle biopsy, echocardiography, radionuclide cardiac angiography, and treadmill exercise electrocardiographic recording test. RESULTS: The mean strength of the deltoid muscle in alcoholic women was significantly lower than that in controls (P < .001) and half suffered clinical weakness (muscle strength > or = 2 SD below controls). Muscle biopsy specimens from half of all asymptomatic women showed histologic evidence of myopathy. Left ventricular ejection fractions tended to be depressed, and a third of the alcoholic women had evidence of cardiomyopathy. Muscular strength and ejection fractions in women were inversely correlated with the total lifetime dose of ethanol, whereas the left ventricular mass showed a direct correlation. Of the alcoholic men, 39% suffered clinical weakness, and 45% had histologic evidence of myopathy. Evidence of cardiomyopathy was found in almost a third of the men, and their ejection fractions also correlated inversely with the total lifetime dose of ethanol. However, the threshold dose for the development of cardiomyopathy was considerably less in women than in men, and the decline in the ejection fraction with increasing alcohol dose was significantly steeper (P < .001). CONCLUSIONS: Despite the fact that the mean lifetime dose of alcohol in female alcoholics was only 60% that in male alcoholics, cardiomyopathy and myopathy were as common in female alcoholics as in male alcoholics. This finding, together with a more pronounced response of the ejection fraction to the dose of ethanol, indicates that women are more sensitive than men to the toxic effects of alcohol on striated muscle.

Adult↗
PubMed1995

Regional cerebral blood flow in mood disorders: IV. Comparison of mania and depression.

Cortical regional cerebral blood flow (rCBF) was assessed in minimally medicated, relatively young adults in episodes of either acute mania (n = 11) or major depression (n = 11) and in matched normal control subjects (n = 11), using the 133xenon inhalation method, under eyes-closed, resting conditions. The three groups were equivalent in global CBF. Both patient groups showed significant reductions of rCBF in anterior cortical areas and reduction of the normal anteroposterior gradient. In addition, there was evidence of abnormal, albeit similar, patterns of flow lateralization on a regional basis in both clinical groups compared with normal subjects. An exploratory analysis revealed preliminary evidence of rCBF differences between the clinical groups, localized to the inferior frontal cortex. Otherwise, the evidence in this study suggests that young adult manic and depressed patients are predominantly similar in cortical rCBF parameters.

Administration, Inhalation↗
PubMed1995

Activation of serine/threonine protein kinases and early growth response 1 gene expression by tumor necrosis factor in human myeloid leukemia cells.

The early growth response 1 (EGR-1) gene is induced by mitogenic and differentiating signals in diverse cell types. The present studies have examined the effects of TNF-alpha on the induction of EGR-1 expression in human myeloid leukemia cells and the potential cytoplasmic signaling cascades that transduce TNF-induced signals to the nucleus. The results demonstrate that treatment of HL-60 cells with TNF is associated with the transient induction of the EGR-1 gene. The results also demonstrate that TNF treatment is associated with activation of the serine/threonine kinase, pp90rsk, which acts upstream to EGR-1 gene induction. Partial purification of pp90rsk by affinity chromatography demonstrated an increase in S6 peptide phosphorylation in response to TNF treatment. Because TNF activates sphingomyelin hydrolysis, we also studied the effects of sphingomyelinase (SMase) on induction of EGR-1 and pp90rsk. The results demonstrate that SMase also activates pp90rsk and induces EGR-1 gene expression. Previous work has demonstrated that mitogen-activated protein (MAP) kinase activates pp90rsk. The present studies further show that treatment with TNF or SMase is associated with induction of both the pp42/44 MAP and the related Jun kinases. Induction of pp42/44 MAP kinase activity is temporally related to activation of pp90rsk and the EGR-1 gene. These findings support the involvement of an MAP kinase/pp90rsk/EGR-1 cascade in the response of myeloid leukemia cells to TNF.

Amino Acid Sequence↗
PubMed1995

Testing of medical students with open-ended, uncued questions.

A written examination based on material covered in the first year of medical school (anatomy, physiology, biochemistry, and neuroscience) was administered to medical students immediately before they began the pathology course to assess their knowledge of the basic science content that is important for the study of pathology. In alternate years the questions were presented in the standard multiple choice question (MCQ) format or in an open-ended, uncued question (Un-Q) format. The students' mean scores obtained by these two testing methods were comparable. The discrimination indices, which measure the ability of the test questions to distinguish between students of varying ability, were comparable. The Kuder-Richardson Formula 20 (KR-20), an estimate of the precision of the test given, was 0.53 for MCQ and 0.63 for Un-Q. We conclude that the Un-Q format is an acceptable alternative to the MCQ format and it has several advantages over MCQ. Because the answer sheets for Un-Q tests can be scanned optically and graded by computers, we recommend them as an alternative to MCQ tests.

Education, Medical↗
PubMed1995

Needle-localization biopsy of the breast: impact of a selective core needle biopsy program on yield.

PURPOSE: To determine the effect of a selective core biopsy program on the yield at needle-localization biopsy (NLB) of nonpalpable lesions. MATERIALS AND METHODS: Two hundred consecutive core biopsy samples of the breast were evaluated in an ongoing consecutive series of 1,172 NLB samples. RESULTS: Before implementation of the core biopsy program, the yield at NLB improved from 21% at 100 cases to 35% just before the introduction of core biopsy. After implementation, the yield increased gradually to 55% at 200 cases. The yield in masses increased from 21% at 100 cases to 43% just before the initiation of the core biopsy program and then increased dramatically to 72% at 200 cases. The percentage of small lesions detected did not change with implementation: 88% of invasive cancers measured less than 1.5 cm and 60% measured less than 1 cm in the last 100 cases. CONCLUSION: Appropriate selection of cases for core biopsy can more than double the yield of cancer in NLB samples without a decrease in the percentage of small cancers detected.

Adolescent↗
PubMed1995

Decreased early atherosclerotic lesions in hypertriglyceridemic mice expressing cholesteryl ester transfer protein transgene.

The human cholesteryl ester transfer protein (CETP) facilitates the transfer of cholesteryl ester from HDL to triglyceride-rich lipoproteins. The activity of CETP results in a reduction in HDL cholesterol levels, but CETP may also promote reverse cholesterol transport. Thus, the net impact of CETP expression on atherogenesis is uncertain. The influence of hypertriglyceridemia and CETP on the development of atherosclerotic lesions in the proximal aorta was assessed by feeding transgenic mice a high cholesterol diet for 16 wk. 13 out of 14 (93%) hypertriglyceridemic human apo CIII (HuCIII) transgenic (Tg) mice developed atherosclerotic lesions, compared to 18 out of 29 (62%) controls. In HuCIII/CETPTg, human apo AI/CIIITg and HuAI/CIII/CETPTg mice, 7 of 13 (54%), 5 of 10 (50%), and 5 of 13 (38%), respectively, developed lesions in the proximal aorta (P < .05 compared to HuCIIITg). The average number of aortic lesions per mouse in HuCIIITg and controls was 3.4 +/- 0.8 and 2.7 +/- 0.6, respectively in HuCIII/CETPTg, HuAI/CIIIg, and HuAI/CIII/CETPTg mice the number of lesions was significantly lower than in HuCIIITg and control mice: 0.9 +/- 0.4, 1.5 +/- 0.5, and 0.9 +/- 0.4, respectively. There were parallel reductions in mean lesion area. In a separate study, we found an increased susceptibility to dietary atherosclerosis in nonhypertriglyceridemic CETP transgenic mice compared to controls. We conclude that CETP expression inhibits the development of early atherosclerotic lesions but only in hypertriglyceridemic mice.

Animals↗
PubMed1995

The Behavior Rating Scale for Dementia of the Consortium to Establish a Registry for Alzheimer's Disease. The Behavioral Pathology Committee of the Consortium to Establish a Registry for Alzheimer's Disease.

OBJECTIVE: The purpose of the study was to develop a standardized instrument, the Behavior Rating Scale for Dementia, for rating psychopathology in patients with probable Alzheimer's disease and to conduct a multicenter pilot study of this instrument. METHOD: The rating scale was developed collaboratively on the basis of clinical experience and existing instruments. Items were scaled according to frequency of psychopathology and were administered to an informant who was familiar with the subject. The scale was administered in a standardized manner by trained examiners who had met predetermined certification standards. The study group consisted of 303 subjects with probable Alzheimer's disease who had undergone standardized clinical evaluations by the Consortium to Establish a Registry for Alzheimer's Disease. RESULTS: Subjects had an average of 15 problems rated as present in the preceding month. Wide variability in the nature of disturbances was found, with a number of items rated as present since the illness began but not in the past month. Interrater agreement was high. Factor analysis suggested eight preliminary factors that mapped onto clinically relevant domains: depressive features, psychotic features, defective self-regulation, irritability/agitation, vegetative features, apathy, aggression, and affective lability. CONCLUSIONS: The Behavior Rating Scale for Dementia provides a standardized, reliable measure that can be administered to caregivers of demented subjects. On the basis of the present study, the scale has been revised slightly. After additional studies in progress, the Behavior Rating Scale for Dementia will be available for general use in assessing a wide range of psychopathology in dementia.

Aged↗
PubMed1995

Cerebral metabolic topography in unilateral temporal lobe epilepsy.

OBJECTIVE: Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of temporal lobe epilepsy (TLE) generally report interictal hypometabolism in the vicinity of the seizure focus. Yet, other evidence suggests that interictal metabolic abnormalities might extend to remote brain areas. We used FDG-PET to evaluate metabolism in selected regions distant from the focus in TLE. SUBJECTS: Twenty adult patients with medically intractable TLE were selected by criteria favoring a unilateral mesiobasal temporal focus. Structural imaging in this sample were normal except for medial temporal sclerosis in 13 patients. Twenty normal volunteers were controls. DESIGN: PET imaging was performed interictally. Regional glucose metabolism normalized by global metabolism was analyzed using t tests and correlation analysis. RESULTS: Ipsilateral to the seizure focus, metabolism was depressed compared with normal in the temporal pole (p = 0.001), but relatively elevated in the mesiobasal region (p = 0.005). Contralateral to the focus, metabolism was elevated in lateral temporal cortex (p = 0.0003) and mesiobasal regions (p = 0.0001). Metabolic correlation between ipsilateral and contralateral mesiobasal regions was similar in normal subjects (r = 0.74) and patients (r = 0.68). In contrast, correlations were abnormal between temporal poles and other temporal lobe subregions, both ipsilateral and contralateral to the seizure focus. CONCLUSIONS: Relative to normal values, both elevations and depressions of metabolism exist interictally in TLE. Such abnormalities, and accompanying changes in interregional correlations, may have wide spatial distribution. These findings are atypical among PET studies but are consistent with other physiologic, anatomic, and neuropsychological investigations of TLE.

Adolescent↗