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Biomedical subjects

E Rubinstein

Publications and source records attributed to E Rubinstein.

At least 37 records · Page 2Linked to original sources
PubMed2001

Linezolid (PNU-100766) versus vancomycin in the treatment of hospitalized patients with nosocomial pneumonia: a randomized, double-blind, multicenter study.

Linezolid, the first oxazolidinone, is active against gram-positive bacteria, including multidrug-resistant strains. This multinational, randomized, double-blind, controlled trial compared the efficacy, safety, and tolerability of linezolid with vancomycin in the treatment of nosocomial pneumonia. A total of 203 patients received intravenous linezolid, 600 mg twice daily, plus aztreonam, and 193 patients received vancomycin, 1 g intravenously twice daily, plus aztreonam for 7-21 days. Clinical and microbiological outcomes were evaluated at test of cure 12-28 days after treatment. Clinical cure rates (71 [66.4%] of 107 for linezolid vs. 62 [68.1%] of 91 for vancomycin) and microbiological success rates (36 [67.9%] of 53 vs. 28 [71.8%] of 39, respectively) for evaluable patients were equivalent between treatment groups. Eradication rates of methicillin-resistant Staphylococcus aureus and safety evaluations were similar between treatment groups. Resistance to either treatment was not detected. Linezolid is a well-tolerated, effective treatment for adults with gram-positive nosocomial pneumonia.

Acetamides↗
PubMed2001

The major CD9 and CD81 molecular partner. Identification and characterization of the complexes.

By associating with specific partner molecules and with each other, the tetraspanins are thought to assemble multimolecular complexes that may be especially relevant with respect to metastasis. We have previously identified a 135-kDa molecule (CD9P-1) as a major molecular partner of CD9 in cancer cell lines. This molecule was identified, after immunoaffinity purification and mass spectrometry analysis, as the protein encoded by the KIAA1436 gene and the human ortholog of a rat protein known as FPRP. Cross-linking experiments detected a complex of the size of CD9 plus CD9P-1, showing that these glycoproteins directly associate with each other, probably in the absence of any other molecule. The use of chimeric CD9/CD82 molecules revealed the role of the second half of CD9, comprising the large extracellular loop and the fourth transmembrane domain. CD9P-1 was also shown to form separate complexes with CD81 and with an unidentified 175-kDa molecule. It also associated with other tetraspanins under conditions maintaining tetraspanin/tetraspanin interactions. The identification of a protein strongly linked to the tetraspanin web and the production of a specific monoclonal antibody will help to further characterize the role of this "web" under physiological and pathological conditions.

Animals↗
PubMed2001

Tetraspanins.

The first tetraspanins were discovered on surface of human leucocytes, but it was rapidly demonstrated that they had a wider tissue expression. Twenty-six molecules display sufficient homology to belong to the same superfamily. Their function is not precisely known, but data coming from biochemical studies or knockout mice suggest that they play a major role in membrane biology. One of their outstanding properties is their ability to form a network of multimolecular complexes, the 'tetraspanin web', in which integrins are included. The structure of these complexes is under investigation, but some of the rules that govern their organization have already been unraveled. The challenge is to determine how the organization of the 'tetraspanin web' modifies the function of its constitutive molecules and consequently influences cellular behaviour. The implications may be considerable for the understanding of basic cellular processes such as migration and also of diseases related to loss or mutation of a single tetraspanin.

Animals↗
PubMed2001

Comparative safety of the different macrolides.

The macrolides are generally well tolerated when used for the treatment of acute infections. Even when given long term for prophylaxis, there are few discontinuations due to side-effects. There are isolated reports of QT(c) prolongation in patients treated with erythromycin and other 14-membered-ring macrolides. Since the 14-membered-ring macrolides are metabolized by P450 isoenzymes, there is the potential for interaction with other therapeutic agents also metabolized in this way. Pharmacokinetic studies have demonstrated interactions between either erythromycin or clarithromycin and cyclosporin, cisapride, pimozide, disopyramide, astemizole, carbamazepine, midazolam, digoxin, hydroxymethylglutaryl-coenzyme A reductase inhibitors (i.e. 'statins') and warfarin. In patients receiving such concurrent therapy, azithromycin may be superior to erythromycin and clarithromycin.

Anti-Bacterial Agents↗
PubMed2001

Gas and air embolization during hysteroscopic electrosurgical vaporization: comparison of gas generation using bipolar and monopolar electrodes in an experimental model.

STUDY OBJECTIVE: To compare the composition of gases generated by bipolar hysteroscopic vaporizing electrodes using electrolyte-rich medium (normal saline) with those of monopolar vaporizing electrodes using nonelectrolytic medium (1.5% glycine). DESIGN: In vitro study (Canadian Task Force classification II-1). SETTING: Laboratory. INTERVENTION: Fresh morbid bovine cardiac muscle was fully immersed in normal saline for the bipolar vaporizing electrode and 1.5% glycine for the monopolar vaporizing electrode. Standard hysteroscopic electrodes were activated at usual and maximum power outputs from radiofrequency electrosurgical generators appropriate for each system. The gases generated were captured and analyzed by gas chromatography and fast Fourier transform. MEASUREMENTS AND MAIN RESULTS: Gaseous by-products of electrosurgical vaporization of test tissues largely consisted of hydrogen, carbon monoxide, and carbon dioxide. The composition of gases generated by hysteroscopic monopolar and bipolar electrodes in this laboratory model appear to be similar. CONCLUSION: These gases are all highly soluble in serum. This observation suggests that emboli of gaseous by-products of electrosurgery are unlikely to have an adverse impact on patients. On the other hand, air emboli, largely composed of relatively insoluble nitrogen, are more likely to result in clinically significant cardiopulmonary events.

Animals↗
PubMed2001

A study of the effect of nasal steroid sprays in perennial allergic rhinitis patients with rhinitis medicamentosa.

OBJECTIVE: To determine if rebound congestion can be reduced with concomitant nasal steroid spray usage. STUDY DESIGN AND SETTING: Randomized, double blind, controlled single center study. PARTICIPANTS: Twenty subjects with perennial allergic rhinitis with nasal congestion. INTERVENTION: All subjects received 3 weeks of twice-daily oxymetazoline. After 2 weeks, subjects were randomized to 2 additional weeks of concomitant budesonide aqueous nasal spray (n = 9) or placebo (n = 10). In the sixth week, all sprays were stopped. RESULTS: Both groups showed subjective and objective evidence of rebound congestion 24 hours after cessation of oxymetazoline (P < 0.05). Subjective rebound congestion resolved in 48 hours in the budesonide aqueous nasal spray group but persisted for over 1 week in the placebo group. CONCLUSION: Rebound congestion is objectively present in patients with perennial allergic rhinitis after 3 weeks of oxymetazoline spray. Rebound congestion is reduced by concomitant budesonide aqueous nasal spray use. SIGNIFICANCE: This study supports the common clinical practice of nasal steroid sprays to ameliorate rebound congestion concomitant with and after cessation of topical decongestant sprays.

Adult↗
PubMed2001

The effect of Escherichia coli heat-stable toxin on the trans-epithelial intestinal elimination of ciprofloxacin in the rabbit.

The effect of Escherichia coli heat-stable toxin (ST) on the intestinal trans-epithelial elimination of ciprofloxacin was studied in the rabbit model. Following a systemic 27 mg/kg dose, excreted amounts of ciprofloxacin during the 2 h experiment were: 9.3 (+/- 4.8); 12.5 (+/- 5.2) and 0.3 (+/- 0.1) microg/cm(2) surface of intestinal wall in ST-challenged jejunal, ileal and caecal loops, respectively. In control loops the corresponding amounts were: 5.0 (+/- 2.8), 6.5 (+/- 3.4) and 0.3 (+/- 0.1) microg/cm(2), respectively. The trans-epithelial elimination of ciprofloxacin was significantly higher in ST-challenged small bowel loops than in controls while caecal elimination was negligible.

Animals↗
PubMed2001

Adherence properties of Staphylococcus aureus under static and flow conditions: roles of agr and sar loci, platelets, and plasma ligands.

Global regulatory genes in Staphylococcus aureus, including agr and sar, are known to regulate the expression of multiple virulence factors, including cell wall adhesins. In the present study, the adherence of S. aureus RN6390 (wild type), RN6911 (agr), ALC136 (sar), and ALC135 (agr sar) to immobilized fibrinogen, fibronectin, von Willebrand factor (vWF), extracellular matrix (ECM), and human endothelial cells (EC) EAhy.926 was studied. Bacteria grown to postexponential phase were subjected to light oscillation (static condition) or to shear stress at 200 s(-1) (flow condition) on tissue culture polystyrene plates coated with either protein ligands, ECM, or EC. Adherence of nonlabeled bacteria to immobilized ligands was measured by an image analysis system, while adherence of [(3)H]thymidine-labeled S. aureus to ECM and EC was measured by a beta-scintillation counter. The results showed increased adherence of agr and agr sar mutants to immobilized fibrinogen and higher potential of these mutants to induce platelet aggregation in suspension, decreased adherence of sar and agr sar mutants to immobilized fibronectin and vWF as well as to ECM and EC, increased adherence of both S. aureus wild type and sar mutant to EC treated with platelet-rich plasma (PRP) compared to platelet-poor plasma (PPP) and to EC treated with PPP compared to the control, and increased adherence of S. aureus wild type to EC coated with PRP in which platelets were activated with phorbol 12-myristate 13-acetate compared to intact PRP. This finding paralleled the increased adherence to EC of activated compared to intact platelets. It is suggested that platelet-mediated S. aureus adherence to EC depends on platelet activation and the number of adherent platelets and available receptors on the platelet membrane. In conclusion, the agr locus downregulates S. aureus adherence to fibrinogen, while the sar locus upregulates S. aureus adherence to fibronectin, vWF, ECM, and EC. The effect of both agr and sar on S. aureus adherence properties develops primarily under flow conditions, which suggests different adhesion mechanisms in static and flow conditions.

Animals↗
PubMed2001

History of quinolones and their side effects.

Fluoroquinolone development from 1985 to the present was reviewed. Severe drug adverse events were noted for enoxacin, pefloxacin and fleroxacin, which were phototoxic. Temafloxacin was associated with severe hemolytic-uremic syndrome, lomefloxacin caused phototoxicity and central nervous system (CNS) effects, and sparfloxacin was associated with phototoxicity and QTc prolongation. Tosufloxacin caused severe thrombocytopenia and nephritis, and hepatotoxicity was reported for trovafloxacin. Grepafloxacin was withdrawn due to cardiovascular effects, and clinafloxacin was associated with phototoxicity and hypoglycaemia. The structure of the quinolones directly relates to both their activity and side-effect profiles. The relationship among specific substituents attached to the quinolone nucleus are clarified. The incidence of specific adverse events associated with individual fluoroquinolones was reviewed in a five-year post-marketing surveillance (PMS) study in Japan, in which a total adverse drug reaction (ADR) rate of 1.3% was found for levofloxacin, compared to total ADR rates of 3.3% for pazufloxacin, 3.6% for tosufloxacin, 4.5% for gatifloxacin and 5.4% for balofloxacin. Gastrointestinal effects were the most common adverse events for all fluoroquinolones. Levofloxacin had the lowest rate of CNS effects and skin adverse events among the agents listed.

Anti-Infective Agents↗
PubMed2001

The hepatitis C virus (HCV) induces a long-term increase in interleukin-10 production by human CD4+ T cells (H9).

Patients with chronic hepatitis C present an imbalance of Th1/Th2 cytokine production. Therefore, we investigated whether the exposure of the CD4+ T cell line H9 to HCV could induce activation of cells through synthesis of IL-10. Three infection protocols were performed to enhance HCV propagation. Viral particles were prepared by ultracentrifugation of serum from patients. From 3 to 81 days post-infection (p.i.), HCV-RNA was monitored both in supernatants and cells by nested RT-PCR, IL-10 protein in medium by ELISA, and IL-10 mRNA in cells by semi-quantitative RT-PCR. The expression of tetraspanins was analyzed by flow cytometry. The PKC signal pathway was studied using specific inhibitors. The H9 cells express CD81. HCV-RNA (+) was detected in cells until 21 days p.i, and in culture media over 39 days p.i. Up to day 81 p.i., HCV exposure induced a specific, 2-fold increase of IL-10 production by H9 cells. IL-10 production was inhibited by a PKC inhibitor (Calphostin C). This study shows that even if the infection of H9 T cells did not result in any viral progeny, HCV induced the activation of IL-10 secretion, which supports the role of IL-10 in HCV pathogenesis.

Base Sequence↗
PubMed2001

Characteristics of clients attending confidential versus anonymous testing clinics for human immunodeficiency virus.

OBJECTIVES: To compare risk behavior between subjects attending anonymous and confidential clinics for human immunodeficiency virus testing, and to assess whether anonymous testing results in a higher accrual of persons at risk for HIV. METHODS: An anonymous questionnaire that addressed sociodemographic and risk behavior aspects was administered to 140 subjects attending an anonymous clinic and 124 attending a confidential clinic in the Tel Aviv area. A logistic regression analysis was used to compare the effects of various behavioral factors on the probability of attending each clinic. RESULTS: Chronological age, age at first sexual intercourse, and the percent of married subjects were similar in both clinics. However, there was a significant difference in the sex ratio and in educational attainment (85.0% versus 55.6% were males, P < 0.001; and 58% vs. 34% had over 12 years of education, P < 0.001, in the anonymous and confidential clinics respectively). There was a striking difference between the two clinics with regard to sexual experience characteristics: of the subjects reaching the anonymous clinic 21.4% were homosexual and 10.0% bisexual versus a total of 2.6% in the confidential clinic. A logistic regression analysis, comparing the effects of various behavioral factors on the probability of attending each clinic, showed that gender (male), high education, homosexuality, number of partners and sexual encounter with sex workers were the strongest predictors for selecting anonymous HIV examination. CONCLUSIONS: Individuals at high risk for HIV, such as homosexuals and bisexuals, prefer to attend an anonymous clinic.

AIDS Serodiagnosis↗
PubMed2001

A novel monoclonal antibody against the extracellular domain of GPIbbeta modulates vWF mediated platelet adhesion.

GPIbbeta is disulfide-linked to GPIbalpha to form GPIb, a platelet receptor for von Willebrand factor (vWF). GPIb is in turn non covalently linked to GPIX and GPV to form the GPIb/V/IX complex. Apart from its contribution to controlling surface expression of the complex, the exact function of GPIbbeta is not well established due to a lack of suitable ligands or antibodies. The present report describes a monoclonal antibody (RAM.1) that labeled the 26 kDa GPIbbeta subunit on western blots and coprecipitated the three subunits of the GPIb/IX complex from lysates of platelets and transfected CHO and K562 cells. RAM.1 bound to GPIbbeta deleted of its intracellular domain whereas Gi27, directed against intracellular GPIbbeta, did not. Using synthetic peptides, the RAM.1 epitope was mapped to a putative cysteine loop within the COOH-terminal leucine-rich flanking region. In functional assays, RAM.1 had no effect on platelet aggregation induced by ADP, collagen or thrombin, but inhibited ristocetin induced platelet agglutination and botrocetin induced vWF binding. RAM.1 inhibited adhesion of GPIb/V/IX transfected K562 cells to a vWF matrix under flow, increased their rolling velocity and decreased the resistance of cells to detachment at high shear. This study suggests a role of GPIbbeta in modulating the adhesive properties of GPIb/V/IX and describes a useful tool to analyze the exact functions of GPIbbeta.

Animals↗
PubMed2000

Sequence and expression of seven new tetraspans.

The tetraspans are components of large molecular complexes that include also non-tetraspan molecules, in particular integrins. We have identified and sequenced several new members of the tetraspan superfamily, called NET-1 to NET-7 (new EST tetraspan). Sequence analysis of the NET reveals a structure typical for tetraspans, with the presence of four transmembrane domains delimiting two extracellular regions as well as conserved amino acid residues. The NET are differentially expressed in human cell lines.

Amino Acid Sequence↗
PubMed2000

Severely reduced female fertility in CD9-deficient mice.

CD9 is a widely expressed cell surface molecule that belongs to the tetraspanin superfamily of proteins. The tetraspanins CD9, KAI-1/CD82, and CD63 are involved in metastasis suppression, an effect that may be related to their association with beta1 integrins. Knockout mice lacking CD9 were created to evaluate the physiological importance of CD9. CD9-/- females displayed a severe reduction of fertility. Oocytes were ovulated but were not successfully fertilized because sperm did not fuse with the oocytes from CD9-/- females. Thus, CD9 appears to be essential for sperm-egg fusion, a process involving the CD9-associated integrin alpha6beta1.

Animals↗
PubMed2000

CD46 (membrane cofactor protein) associates with multiple beta1 integrins and tetraspans.

The tetraspans associate with a large number of surface molecules, including a subset of beta1 integrins and, indirectly through CD19, with the complement receptor CD21. To further characterize the tetraspan complexes we have raised and selected monoclonal antibodies (mAb) for their ability to immunoprecipitate a molecule associated with CD9. A unique mAb was identified which recognizes the complement regulator CD46 (membrane cofactor protein). CD46 associated in part with several tetranspans and with all beta1 integrins that were tested (CD29/CD49a, CD29/CD49b, CD29/CD49c, CD29/CD49e, CD29/CD49f) but not with beta4 integrins. These data, together with cross-linking experiments showing the existence in living cells of CD46/integrin complexes, suggest that CD46 associates directly with beta1 integrins and indirectly with tetraspans. CD46 also acts as a receptor for measles virus; however, mAb to various integrins and tetraspans did not modify the virus fusion entry step.

Animals↗