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E Rubin

Publications and source records attributed to E Rubin.

At least 19 recordsLinked to original sources
PubMed2001

Effect of angiotensin II and ethanol on the expression of connexin 43 in WB rat liver epithelial cells.

The turnover of connexin 43 (Cx43) is very rapid in many cells and involves both the lysosomal and proteasomal protease pathways. Here we show that Ca(2+)-mobilizing agonists such as angiotensin II (Ang II) can up-regulate the expression of Cx43 in WB rat liver epithelial cells. Vasopressin had the same effect in A7R5 smooth-muscle cells. The effect of Ang II was not prevented by pretreatment with proteasomal or lysosomal inhibitors and was associated with an enhanced biosynthesis of Cx43 as measured by metabolic labelling experiments. The accumulation of Cx43 occurred in intracellular compartments and at the cell surface, as determined by confocal immunofluorescence studies and by immunoblotting of fractions soluble and insoluble in Triton X-100. Chronic treatment of WB cells with ethanol inhibited Cx43 expression; this was associated with decreased biosynthesis of Cx43. Neither treatment with Ang II nor treatment with ethanol altered the levels of Cx43 mRNA. Incubation of WB cells with Ang II did not alter gap-junctional communication as judged by a dye-coupling assay. However, treatment with ethanol markedly decreased gap-junctional communication and this effect was diminished in Ang-II-treated cells, demonstrating that gap-junctional communication is linked to the level of Cx43 expression. We conclude that Cx43 biosynthesis is regulated by Ca(2+)-mobilizing agonists and ethanol in WB cells. The changes in Cx43 expression might have a role in modifying the conduction of metabolites and second messengers between cells.

Angiotensin II↗
PubMed2001

Site-specific and temporally-regulated retinoblastoma protein dephosphorylation by protein phosphatase type 1.

pRb is dephosphorylated at mitotic exit by the type 1 serine/threonine protein phosphatases (PP1). Here we demonstrate for the first time that mitotic pRb dephosphorylation is a sequential, temporally-regulated event. We also provide evidence that the three mammalian isoforms of PP1, alpha, gamma-1, and delta, differ in their respective preferences for site-specific pRb dephosphorylation and that the mitotic and G(1) PP1-isoform counterparts exhibit differential activities towards mitotic pRb. Finally, the physiological relevance of the striking contrast between the patterns of Thr821 and Thr826 dephosphorylation, sites known to be important for disrupting binding of LXCXE-containing proteins to pRb, is addressed.

Animals↗
PubMed2001

Human and mouse ABCA1 comparative sequencing and transgenesis studies revealing novel regulatory sequences.

The expression of ABCA1, a major participant in apolipoprotein-mediated cholesterol efflux, is regulated by a variety of factors, including intracellular cholesterol concentration. To identify sequences involved in its regulation, we sequenced and compared approximately 200 kb of mouse and human DNA containing the ABCA1 gene. Furthermore, expression of the human gene containing different 5' ends was examined in transgenic mice. Sequence comparison revealed multiple conserved noncoding sequences. The two most highly conserved noncoding elements (CNS1, 88% identity over 498 bp; CNS2, 81% identity over 214 bp) were also highly conserved in other organisms. Mice containing the human ABCA1 gene, 70 kb of upstream DNA, and 35 kb of downstream DNA expressed the transgene similarly to endogenous Abca1. A second transgene beginning 3' to exon 1 was expressed only in liver, providing strong evidence of an unsuspected liver-specific promoter. The identified conserved noncoding sequences invite further investigation to elucidate ABCA1 regulation.

ATP Binding Cassette Transporter 1↗
PubMed2001

Effects of chronic alcohol ingestion on the mesostriatal dopamine system in the rat.

The effects of chronic alcohol use on the mesostriatal dopamine (DA) system remain relatively unknown. The aim of the present study was to assess multiple measures of the status of the mesostriatal DA system in rats chronically fed an alcohol diet for approximately 1 year. Tissue levels of DA and its metabolite, 3,4-dihydroxyphenylacetic acid, were significantly decreased in both the dorsal striatum (34 and 33%, respectively) and ventral striatum (33 and 36%, respectively) in alcohol-fed rats compared to pair-fed matched controls. Western blotting revealed a mean 20% decrease in tyrosine hydroxylase protein levels in the dorsal and ventral striatum of alcohol-fed animals while dopamine transporter protein levels from the same animals were significantly increased compared to controls (mean 60% increase for the dorsal and ventral striatum). The present results demonstrate significant alterations in the mesostriatal DA system after 1 year of chronic alcohol use. It is possible that the observed changes in DA synthesis and re-uptake measures result in altered intracellular and extracellular DA levels, perhaps contributing to the addictive properties of alcohol.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

Reducing the cost of diagnosis of breast carcinoma: impact of ultrasound and imaging-guided biopsies on a clinical breast practice.

BACKGROUND: The objective of this study was to determine whether the use of ultrasound and percutaneous breast biopsies in patients with screen-detected nonpalpable abnormalities can reduce benign open surgical biopsies of the breast without increasing cost or sacrificing detection of potentially curable breast carcinomas. METHOD: Using a computerized mammography database and consecutive logs of needle localization procedures and fine- and large core needle biopsies of a single university-based breast imaging practice, the authors determined the breast carcinoma yield and cost of diagnosis over a 14-year period and the changes that occurred over time with the sequential introduction of ultrasound, ultrasound-guided biopsies, and stereotactic biopsies. RESULTS: The overall breast carcinoma yield for needle localization biopsies of nonpalpable lesions increased from 21% in 1984 to 68% in 1998 (P < 0.0001). The yield for nonpalpable masses increased from 21% to 87% (P < 0.0001) over the same period. The selective use of ultrasound alone and percutaneous fine- and large core needle biopsy resulted in a substantial reduction in benign open surgical biopsies. A cost analysis showed a 50% reduction in the average expense of discovering breast carcinoma. The breast carcinomas detected after introduction of these methods were prognostically favorable with 88% measuring 1.5 cm or less in size and 66% measuring less than 1 cm. CONCLUSIONS: Selective use of ultrasound and imaging-guided percutaneous biopsies can significantly reduce the number of benign open surgical biopsies generated by mammographic screening. This can result in substantial cost savings without decreasing the sensitivity for detecting small potentially curable lesions.

Biopsy, Needle↗
PubMed2001

The potential for phytoremediation of MTBE.

This paper examines the potential for phytoremediation of MTBE, a gasoline additive that has become a prevalent and persistent groundwater pollutant, due to its' non-sorbing and non-reactive nature in water. A novel experimental design is developed to measure plant uptake and transpiration of MTBE from hydroponic systems, separating these processes from passive volatilization of the chemical. Plant uptake experiments indicate 30% reduction in MTBE mass in water over a 1-week period by small poplar saplings, at both high (1600 ppb) and low (300 ppb) MTBE concentrations. Active plant uptake of MTBE was approximately double that achieved by passive volatilization through a balsa wood control. MTBE was detected in biomass at the 100-ppb level, confirming passage of MTBE through the plant. A mass balance indicated that MTBE was largely untransformed during transport through the small poplar saplings to air. The high degree of MTBE removal achieved by small plants over a short period of time indicates great potential for successful phytoremediation of subsurface MTBE plumes using poplar trees. The fraction of MTBE removed from the hydroponic systems correlated well with volume of water transpired by the plants; the correlation enabled computation of the MTBE transpiration stream concentration factor of approximately 1, an important parameter for the design of engineered MTBE phytoremediation systems.

Biodegradation, Environmental↗
PubMed2001

A simulated reality scenario compared with the computerized Wisconsin card sorting test: an analysis of preliminary results.

Neuropsychologists and other clinicians often comment on the minimal relationship that frequently exists between formal assessments of executive functions, analysis of findings, recommendations, and the person's real-life functioning. The authors' believe that current assessments of executive functions do not transfer easily to real-world behavior. There are limitations in the current examinations and in the settings in which they are given. The tests are artificial and the test settings lack the usual stresses, distractions, and multiple demands common to real life. The interactions are unlike what they experience in everyday life. The examiner often, but unintentionally orients the participant to relevant information that in turn can help the person compensate for the difficulties with executive control processes and bias the findings. We believe that virtual reality (VR) more closely approximates real life settings, the distractions, and the common interchanges (VR) provides a "life-like," three-dimensional (3-D) highly interactive environment, and safety from potential dangers that could arise in actual situations. VR can increase motivation because of its gaming, interactive, and immersive qualities and features are easily modified and allow for multiple applications. Our goal is to develop VR assessments that can be administered under controlled and safe conditions, but which are more sensitive to difficulties with executive control processes critical to safe, independent living. This initial study compares several functions assessed by the Wisconsin Card Sorting Test (WCST) with our three-dimensional, stereographic scenario, Look for a Match (LFAM) Study participants completed questionnaires, alternately began with either the WCST or LFAM, and then took the second test. All participants completed motion sickness and follow-up questionnaires. The results demonstrated that the study participants found LFAM to be more enjoyable and interesting, but found the WCST to be easier. While there is an effect of order with participants doing relatively better on the assessment tool administered second, overall the LFAM performance was inferior to that on the WCST. However, even considering the order effect, LFAM seemed to be more difficult than the WCST.

Adolescent↗
PubMed2001

Structure and evolution of the hAT transposon superfamily.

The maize transposon Activator (Ac) was the first mobile DNA element to be discovered. Since then, other elements were found that share similarity to Ac, suggesting that it belongs to a transposon superfamily named hAT after hobo from Drosophila, Ac from maize, and Tam3 from snapdragon. We addressed the structure and evolution of hAT elements by developing new tools for transposon mining and searching the public sequence databases for the hallmarks of hAT elements, namely the transposase and short terminal inverted repeats (TIRs) flanked by 8-bp host duplications. We found 147 hAT-related sequences in plants, animals, and fungi. Six conserved blocks could be identified in the transposase of most hAT elements. A total of 41 hAT sequences were flanked by TIRs and 8-bp host duplications and, out of these, 34 sequences had TIRs similar to the consensus determined in this work, suggesting that they are active or recently active transposons. Phylogenetic analysis and clustering of hAT sequences suggest that the hAT superfamily is very ancient, probably predating the plant-fungi-animal separation, and that, unlike previously proposed, there is no evidence that horizontal gene transfer was involved in the evolution of hAT elements.

Base Sequence↗
PubMed2001

In vitro activity of a novel ketolide ABT-773 against invasive strains of Streptococcus pneumoniae.

New ketolides such as ABT-773 are a promising group of antibiotics in an era of increasing antibiotic resistance. We tested 704 invasive strains of Streptococcus pneumoniae collected from 1990 to 1998. Overall resistance was 8.3, 4.6, 4.5 and 3.6% for penicillin, cefuroxime, erythromycin and clarithromycin, respectively. By using a recommended breakpoint for susceptibility of <0.5 mg/L, no strains showed reduced susceptibility to ABT-773. ABT-773 was very active against all penicillin-resistant strains (MIC > 2 mg/L, with a mean geometric mean <0.06 mg/L), and against all 33 erythromycin-resistant strains, irrespective of the mode of resistance [mef- or erm(B)-mediated]. ABT-773 is a very active and promising agent against invasive strains of S. pneumoniae, including multiresistant strains.

Anti-Bacterial Agents↗
PubMed2001

Effects of alcohol on the heart.

Some evidence suggests that light to moderate alcohol consumption protects against cardiovascular diseases. However, this cardioprotective effect of alcohol consumption in adults is absent at the population level. Approximately 20 to 30% of patients admitted to a hospital are alcohol abusers. In medical practice, it is essential that patients' levels of consumption are known because of the many adverse effects that might result in the course of routine care. Ethanol damage to the heart is evident if alcohol consumption exceeds 90 to 100 g/d. Heavy ethanol consumption leads to increased risk for sudden cardiac death and cardiac arrhythmias. In patients with coronary heart disease, alcohol use was associated with increased mortality. An early response to drinking was an increased ventricular wall thickness to diameter ratio, possibly proceeding with continuous drinking to alcoholic cardiomyopathy, which had a worse outcome compared with idiopathic dilative cardiomyopathy if drinking was not stopped or at least reduced (< 60 g/d). In the ICU, patients with chronic alcoholism have more cardiac complications postoperatively. These complications probably are caused by biventricular dysfunction, particularly with the occurrence of severe infections or septic shock, events that are three to four times more frequent among chronic alcoholics than occasional drinkers or nondrinkers. To prevent further complications from drinking and for long-term management of drinking, patients with alcohol abuse and heart failure should be treated in brief intervention and follow-up programs. Prognosis is good even in patients with New York Heart Association class IV heart failure caused by cardiomyopathy if complete abstinence is accomplished. Noncompliance to smoking and alcohol restrictions, which are amenable to change, dramatically increases the risk for hospital readmissions among patients with heart failure.

Alcohol Drinking↗
PubMed2000

Role of pRB dephosphorylation in cell cycle regulation.

pRB, the tumor suppressor product of the retinoblastoma susceptibility gene, is regarded as one of the key regulators of the cell cycle. This protein exerts its growth suppressive effect through its ability to bind and interact with a variety of cellular proteins. In turn, pRB binding and interacting ability is governed by its phosphorylation state. In recent years, this negative growth regulatory protein has captured a great deal of attention from investigators around the world due to its ability to modulate the activity of transcription regulatory proteins, enzymes which modify chromatin, and other cellular proteins which contribute to its complex role in mammalian cells. Hypophosphorylated pRB binds and sequesters transcription factors, most notably those of the E2F/DP family, inhibiting the transcription of genes required to traverse the G1 to S phase boundary. This cell cycle inhibitory function is abrogated when pRB undergoes phosphorylation mediated by cyclin/cdk complexes following cell stimulation by mitogens. Removal of these phosphates appears to be carried out by a multimeric complex of protein phosphatase type 1 (PP1) and noncatalytic regulatory subunits at the completion of mitosis. This dephosphorylation returns pRB to its active, growth suppressive state. While the mechanism of pRB phosphorylation has and continues to be extensively studied, dephosphorylation of pRB has received disproportionately less attention. The goal of this review is to revisit the role of pRB dephosphorylation in regulating the cell cycle. Emphasis will be placed on understanding the function and regulation of pRB during the cell cycle as well as our ever-expanding notions of pRB-PP1 interaction and the mechanism of pRB dephosphorylation at mitotic exit.

Animals↗
PubMed2000

Sonography of palpable breast cancer.

PURPOSE: Because of the increasing use of sonography to rule out cancer in women with palpable breast abnormalities, this study was performed to determine the rate of sonographically occult malignancy in this clinical setting. METHODS: Women who were recommended for biopsy based on mammographic and/or clinical findings underwent breast sonography. This study retrospectively analyzed the subset of patients with palpable malignant lesions. Lesions were classified as visible or occult on mammography and sonography. Patients without a tissue diagnosis of tumor were excluded. RESULTS: Of 1,346 masses that underwent biopsy or aspiration, 616 lesions were palpable, and of these, 293 were malignant. Sonography detected all 293 palpable malignant lesions (95% confidence interval for sensitivity, 99-100%). Eighteen lesions were mammographically occult. The median lesion size as determined by sonography was 1.8 cm; for the lesions that were mammographically occult, the median size was 1.6 cm. The most common histopathologic diagnosis for both groups of lesions was infiltrating ductal carcinoma. CONCLUSIONS: All palpable malignant breast lesions were visible by sonography in patients in whom a biopsy was recommended. However, we caution that until the false-negative rate of sonography for equivocal palpable abnormalities is determined prospectively, sonography cannot be accurately applied to rule out malignancy in this setting.

Adolescent↗
PubMed2000

Potential use of ipatropium bromide for the treatment of clozapine-induced hypersalivation: a preliminary report.

Sialorrhea is reported by 31% of patients taking clozapine. Anticholinergic agents and adrenergic agonists are used for its treatment based on empirical evidence. In the present study, 10 patients who failed to respond to anticholinergic or adrenergic agents received intranasal ipatropium bromide (IPB) to minimize anticholinergic systemic absorption. Intranasal IPB was given to 10 patients for clozapine-induced sialorrhea who failed to respond to benztropine or clonidine. Pre-, post- and 6 month follow-up values were recorded on a single-item, 5-point Hypersalivation Rating Scale. The sign test was used for statistical comparison (P < 0.05). Eight patient reported initial improvement in sialorrhea values. Two patients reported no change and two patients discontinued IPB. At 6 months, six patients maintained improvement. Side-effects for IPB were minor. A significant trend was observed in the values pre- and post-treatment with IPB (P < 0.004). Improvement was maintained at 6 month follow-up (P < 0.008). This case series demonstrates the possible utility of intranasal IPB for clozapine-induced sialorrhea. Intranasal IPB lacks significant systemic anticholinergic effects when prescribed along with clozapine. This study shows only qualitative differences in salivation values and large controlled-comparative trials are needed.

Adult↗
PubMed2000

Pharmacokinetics of orally administered camptothecins.

Phase I trials of oral camptothecins, including camptothecin (CPT) and irinotecan (CPT-11), have reported substantial interpatient variability in systemic exposure, which could result in suboptimal antitumor activity in some patients or enhanced risk for toxicity in others. This investigation evaluates the contribution of intestinal absorption and first-pass metabolism in the disposition of oral CPT and CPT-11, respectively. The transport of CPT in Caco-2 cell lines (validated model of intestinal drug transport) was concentration dependent and saturable (Vmax: 34 x 10(-5) cm/sec and Km: 20 microM), and was temperature dependent with an activation energy (Ea) of 11.7 kcal/mole. Cumulatively, this data was indicative of carrier-mediated intestinal transport. In addition, a reduction of transport in the presence of sodium azide plus deoxyglucose suggested ATP dependence. Thus, variable expression and availability of intestinal transporters could contribute to the observed wide variability in the exposure to oral CPT. CPT-11 is hydrolyzed by the ubiquitous enzyme carboxyl esterase to active SN-38, and first-pass metabolism of oral CPT-11 would include both intestinal and hepatic hydrolysis. Incubation of CPT-11 with S9 fractions of human liver and intestinal tissues resulted in variable rates of formation of SN-38. The mean (+/- SD) specific activities (pmoles/min/mg) were: liver (8.57 +/- 10.4, n = 8), duodenum (5.06 +/- 3.7, n = 4), jejunum (6.44 +/- 2.8, n = 5), ileum (4.81 +/- 2.4, n = 5), colon (1.93 +/- 1.5, n = 6), and rectum (0.82, n = 1). Interestingly, there was a decrease in SN-38 formation by tumor tissue compared to matched normal liver and colon tissues. Therefore variable first-pass metabolism could contribute to the substantial differences in the systemic exposures to CPT-11 and SN-38 in patients receiving oral CPT-11.

Administration, Oral↗