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Biomedical subjects

I Weiss

Publications and source records attributed to I Weiss.

At least 19 recordsLinked to original sources
PubMed2004

Expression of receptors for plasminogen activators on endothelial cell surface depends on their origin.

Receptors for plasminogen activators present on endothelial cell (EC) surface regulate local plasmin activity. Plasmin generation by human ECs, derived from cerebral cortex, skin and lung, iliac artery, iliac vein, aorta and coronary artery, was studied. The respective ECs were treated with recombinant tissue plasminogen activator (rt-PA) or with recombinant urokinase-type plasminogen activator (ru-PA), washed, plasminogen added and the plasmin generated then assayed. The largest amounts of plasmin were generated by cerebral ECs, under baseline conditions or after exposure to rt-PA or ru-PA (P < 0.0001). Exposure to rt-PA also resulted in more plasmin generation than ru-PA in the cerebral ECs (P < 0.0001) but not in the other ECs. Heparin enhanced plasmin generation by both rt-PA and ru-PA. Specific antibody against annexin II, a t-PA receptor, blocked plasmin generation by rt-PA. Western blotting showed higher amounts of annexin II on the cell membrane in cerebral ECs. This suggests that expression of annexin II in ECs depends on their location, being greatest in cerebral ECs. In contrast, expression of u-PA receptor was the same for all ECs. This has implications for higher risk of intracranial bleeding during thrombolytic therapy, and for a role of t-PA in neurological development and function.

Annexin A2↗
PubMed2001

Thrombogenic role of cells undergoing apoptosis.

Apoptosis is involved in many biological processes, especially during chemotherapy in cancer patients. Chemotherapy is also associated with an increased risk of thrombosis. The relationship between thrombogenicity and apoptosis was studied in various human tumour cell lines and non-tumour cell lines. Apoptosis was induced by the chemotherapeutic agent camptothecin and by Fas ligand, then quantified by staining with fluorescein isothiocyanate-conjugated annexin V and propidium iodide. A significant correlation between thrombin generation and degree of apoptosis was observed (P < 0.0005). Addition of anti-tissue factor antibody in excess or of tissue factor pathway inhibitor partially inhibited thrombin generation, suggesting that tissue factor activation was responsible for this process. A statistical correlation between tissue factor activity and degree of apoptosis was also found (P < 0.005). Both thrombin generation and tissue factor activity were blocked by the addition of annexin V, which binds and inhibits phosphatidylserine. This indicates that the exteriorization and exposure of phosphatidylserine on the cell surface membrane during apoptosis were essential for both thrombin generation and tissue factor activation.

Annexin A5↗
PubMed2001

Extubation failure in a large pediatric ICU population.

OBJECTIVE: To review a large population of children receiving mechanical ventilation to establish a baseline rate of extubation success and failure and to identify those characteristics that place a patient at greater risk of failing planned extubation. DESIGN: Retrospective chart review. SETTING: University-affiliated children's hospital with a 20-bed pediatric ICU. PATIENTS: All 632 patients receiving mechanical ventilation during the 2-year period from July 1, 1996, to June 30, 1998. METHOD: Patients receiving mechanical ventilation were identified via a computerized database. Charts were reviewed of all patients who were reintubated within 72 h of extubation. MEASUREMENTS AND RESULTS: There were 548 planned extubation events, of which 521 were successful. Twenty-seven patients failed planned extubation at least once; only the first attempt at extubation was included in the analysis. The failure rate of planned extubations was 4.9%. Including only patients who had received mechanical ventilation for > 24 h before extubation, the failure rate was 6.0%. For patients intubated > 48 h, the failure rate was 7.9%. The patients who failed extubation were found to be significantly younger and to have received mechanical ventilation longer than those who succeeded, in both the analysis of all patients receiving mechanical ventilation and the subgroup of those receiving mechanical ventilation > 24 h. When only patients who had received mechanical ventilation for > 48 h were analyzed, the difference in age was no longer significant, but the duration of ventilation before extubation was still significantly longer for those who failed. CONCLUSION: We determined the overall failure rate of planned extubations in a large population of pediatric patients to be 4.9%. Those patients who were younger and had received mechanical ventilation longer were more at risk for extubation failure.

Case-Control Studies↗
PubMed1998

Spatial memory, habituation, and reactions to spatial and nonspatial changes in rats with selective lesions of the hippocampus, the entorhinal cortex or the subiculum.

Various spatial memory deficits have been described in rats with damage to the hippocampal formation (including the subiculum and the entorhinal cortex) and particularly in rats with selective lesions of the hippocampus proper. So far, the involvement of the entorhinal cortex in spatial memory is still controversial and the role of the subiculum is poorly documented. The aim of the present study was to compare the behavioural effects of selective lesions of the hippocampus, the entorhinal cortex or the subiculum in (a) a water-maze task using testing procedures sensitive to the disruption of reference or working memory and (b) in an object exploration task designed to evaluate habituation and subsequently reactions to changes of the spatial layout of objects (spatial change) or to the substitution of a familiar object by a new one (nonspatial change). Our results showed several similarities between the behavioural consequences of damage to each of the three structures. A few differences were also noted. Hippocampal rats were impaired in all spatial tasks, but they reacted like controls to a nonspatial change. The rats sustaining lesions of the entorhinal cortex or the subiculum were not impaired in the reference-memory procedure of the water-maze task and showed a deficit in reacting to a nonspatial change. Overall, our results confirm the central role of the hippocampus in spatial memory and also suggest a role for the entorhinal cortex and the subiculum in processing spatial informations. In addition, they indicate that the entorhinal cortex and the subiculum may have a hippocampal-independent role in memory.

Animals↗
PubMed1998

[Osmolarity of solutions used in nebulization].

Inhaled medications are widely used in patients suffering from bronchial diseases. Beside their pharmacological properties, nebulised solutions have physico-chemical characteristics that can alter bronchial reactivity. Non-isotonic solutions can induce a bronchial hyperresponsiveness and/or a severe bronchonconstriction. Nevertheless, multiple drugs are used for nebulisation despite their unknown osmolarity. The aim of this study was to measure the tonicity of drug solutions commonly used for nebulisation in patients suffering from bronchial disease. Drug solutions were prepared either according to manufacturer recommendations or by diluting the stock in 5 ml of NaCl (0.9%) or H2CO3 (0.14%). Although bronchodilatator solutions (i.e. salbutamol, terbulatine, ipratropium bromide) were nearly isotonic, some drugs prepared for nebulisation had either a very high (e.g. mesna, netilmicine) or a very low (e.g. gomenol, sodium cromoglycate) tonicity. These values may be responsible for bronchoconstriction. Some hypertonic solutions, prepared with drugs such as acetylcytein or netilmycin, are not commercialised for nebulisation but are commonly used for aerosol therapy. In addition, solutions initially isotonic could become significantly hypertonic towards the end of nebulisation. Taken together, these results suggest that non-isotonic solutions should be used with caution specially in patients with bronchial hyperresponsiveness, even when aerosol therapy is prescribed for upper airways.

Acetylcysteine↗
PubMed1997

Serotyping and susceptibility to macrolides and other antimicrobial drugs of Streptococcus pyogenes isolated from patients with invasive diseases in southern Israel.

Fifty-seven strains of Streptococcus pyogenes isolated from septic patients and 52 isolates from nonbacteremic patients in southern Israel were investigated for their susceptibility to new macrolides and other antimicrobial drugs. In addition, typing of the isolates by M protein and T antigen was performed. All organisms were susceptible to penicillin and chloramphenicol, 59% to tetracycline, and 7% to trimethoprim-sulfamethoxazole. All isolates but one (99%) were susceptible to clarithromycin, azithromycin, erythromycin, and clindamycin. The MIC90 of clarithromycin, erythromycin, and clindamycin was 0.064, 0.125, and 0.094 microgram/ml, respectively. Overall, 96% of the isolates could be typed by T antigen, but only 43% were M-protein typeable. No predominance of any particular M-protein type was observed. No significant differences between blood isolates and organisms derived from other sources were observed in the antibiotic susceptibility patterns or the distribution of serotypes. It is concluded that invasive Streptococcus pyogenes infections in southern Israel are caused by multiple unrelated strains. The organism remains susceptible to macrolides and clindamycin.

Anti-Bacterial Agents↗
PubMed1996

Respiratory and cardiac function in children after acute hypoxemic respiratory failure.

OBJECTIVE: To examine the pulmonary and cardiac function of children who survived an episode of acute hypoxemic respiratory failure. DESIGN: Descriptive cohort analysis. SETTING: Pediatric clinical research center of a university hospital. PATIENTS: Utilizing the criteria of PaO2 < 75 torr (< 10 kPa) with an FIO2 of > 0.5 while intubated, bilateral diffuse pulmonary infiltrates on chest radiograph, and exclusion of cardiogenic pulmonary edema, 147 patients were identified during the 6-yr period from July 1, 1986 to August 1, 1993. Fifty patients survived to discharge and 37 were alive at the time of follow-up. Fourteen patients were eventually entered into the study. INTERVENTIONS: The study patients were given a test battery consisting of a questionnaire specific for cardiopulmonary status, a physical examination, a chest radiograph, electrocardiography, echocardiography with detailed examination of the pulmonary circulation, pulse oximetry, complete blood count, and serum chemistries and pulmonary function testing with bronchoprovocation in selected patients. MEASUREMENTS AND MAIN RESULTS: The 14 follow-up patients were evaluated an average of 23 +/- 23 months (range 3 to 66) following intensive care unit discharge. No child reported a significant alteration in lifestyle or limitation of activities. Physical examinations were generally unremarkable. The room air oxyhemoglobin saturation was > or = 0.98 in all patients. Comparison of chest radiographs at the time of follow-up with those chest radiographs during the period of critical illness showed marked but not complete improvement in all. Electrocardiograms and echocardiograms showed new evidence of left ventricular hypertrophy in one child. The right ventricular preejection period to ejection time ratio was normal in all subjects. Eleven patients completed spirometry. Four patients were normal and the other patients had evidence of restrictive or obstructive disease either at baseline or after bronchoprovocation challenge. Ten children had lung volume measurements. Five children were normal, two showed increased volumes consistent with obstruction, and three showed decreased volumes indicative of restriction. Four of seven patients showed evidence of decreased diffusion capacity. Six of seven patients with evidence of abnormal pulmonary function had a positive response to bronchodilator administration. CONCLUSIONS: Although pediatric survivors of acute hypoxemic respiratory failure perceive neither a limitation in lifestyle nor chronic pulmonary morbidity, careful examination of the cardiopulmonary system demonstrates a significant number with abnormal chest radiographs and abnormalities in pulmonary function. These children require careful follow-up and may benefit from use of a bronchodilator.

Acute Disease↗
PubMed1995

Expression of plasminogen activator inhibitor type 1 by human prostate carcinoma cells inhibits primary tumor growth, tumor-associated angiogenesis, and metastasis to lung and liver in an athymic mouse model.

Expression of urokinase-type plasminogen activator (uPA) by malignant cells correlates with an aggressive phenotype, including increased invasiveness, tumor-associated angiogenesis, and metastases. Plasminogen activator inhibitor type 1 (PAI-1) is undetectable in cells of some aggressive malignancies, but present in the stroma of tumor-associated microvasculature. This analysis of an athymic mouse model of prostate carcinoma further defines the role of the uPA/PAI-1/plasmin system in primary growth and metastasis. A marked increase in PAI-1 expression was induced in clones of the aggressive human prostate carcinoma line, PC-3, by stable transfection. Primary PC-3 tumors, in mice, were significantly smaller when derived from PAI-1 expressing versus control cells. PAI-1 expression reduced the density of tumor-associated microvasculature by 22-38%. Microscopic metastases were quantitated using stable expression of the chromogenic label (beta-galactosidase) in control and PAI-1 expressing cells. PAI-1 expression resulted in a significant inhibition of lung metastases, and liver metastases. Expression of PAI-1 by malignant prostate cells resulted in a less aggressive phenotype, presumably by inhibition of uPA activity, suggesting pharmacologic or molecular inhibition of uPA activity as a potential therapeutic target.

Animals↗
PubMed1995

[Simulation of myocardial action potentials of various cell types in relation to neural parameters].

Action potentials of various myocardial cell types were simulated in a computer model based on current knowledge of the electrical properties of ionic channels and pumps in the ventricular cell membrane and the sarcoplasmic reticulum. The transport mechanisms of sodium, potassium, calcium and chlorine ions through the cell membrane are described mathematically, as is the exchange of calcium between the myoplasm and sarcoplasmic reticulum. Ten ionic channels and three pumps of the cell membrane are taken into account, while three channels and one pump of the sarcoplasmic reticulum are considered in the computations. For the first time, the transient outward potassium current IK,to was simulated, the effect of which on the early repolarisation phase of the action potential was reproducible in the model. Calcium buffers in the myoplasm and the sarcoplasmic reticulum are also considered. From the resulting ionic currents through the channels and pumps, the membrane potential is computed using an equivalent circuit diagram of the cell membrane. In particular the influence of neural activity on channel conductance and the probability of channel patency were taken into account. By means of this model, different shapes of ventricular action potentials were simulated. The action potentials of epicardial cells, M-cells, endocardial cells and Purkinje fibres were accurately simulated. In addition, the effects of sympathetic drive and various drugs were demonstrated in the model as well as the shortening of the action potential duration with increasing stimulation frequency.

Calcium↗
PubMed1993

Glucocorticoid and mineralocorticoid receptors in rat neocortical and hippocampal brain cells in culture: characterization and regulatory studies.

Glucocorticoid and mineralocorticoid binding sites were characterized in cell cultures derived from neocortical and hippocampal brain tissue from fetal (E18) rats. Specific and saturable binding was detected in living cells with a sensitive whole cell binding method using [3H]dexamethasone ([3H]DEX) and [3H]aldosterone ([3H]ALDO) (in the presence of RU 28362, a selective glucocorticoid receptor (GR) agonist) as ligands for the measurement of glucocorticoid and mineralocorticoid receptors (MRs), respectively. Specific corticosteroid binding was demonstrated as early as day 4 in culture in neocortical cells, with a time-dependent increase in binding sites during further culturing time. At 7-9 days in vitro, Scatchard analysis of [3H]DEX binding revealed a maximum binding capacity (Bmax) of 83.4 +/- 5.0 fmol/mg protein and a binding affinity (Kd) of 3.6 +/- 0.4 nM in neocortical brain cells. Competition binding studies with [3H]DEX demonstrated a glucocorticoid specificity of receptor sites (relative binding affinity: RU 28362 = DEX > PROG > ALDO). Similar binding characteristics were demonstrated for GRs in cultures derived from fetal hippocampal tissue (Bmax 49.1 +/- 5.8 fmol/mg protein, Kd 3.5 +/- 0.2 nM). Analysis of MRs with [3H]ALDO (+RU 28362) revealed specific and saturable binding in hippocampal cultures, with a Bmax of 8.0 +/- 0.5 fmol/mg protein and a Kd of 0.2 +/- 0.1 nM. Competition studies with [3H]ALDO showed a mineralocorticoid-like pattern of receptor binding (relative binding affinity: CORT = ALDO > PROG > DEX). In addition, small numbers of MRs were detectable in cortex-derived cultures (Bmax: 3.7 +/- 0.8 fmol/mg protein, Kd: 0.3 +/- 0.2 nM).(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Preparation of TEM foils from Nb-10 a/o Si.

Ductile phase toughened composites contain phases with significantly different physical properties. Consequently, these phases thin at different rates depending on the sample preparation procedure. A new TEM foil preparation method for the ductile phase toughened Nb-10 a/o Si material has been developed. The method involves chemical thinning in a 70% nitric acid/30% hydrofluoric acid solution followed by electropolishing in a 12.5% sulfuric acid/87.5% methanol electrolyte at -40 degrees C. This procedure for making TEM foils results in large thin areas with the minimum of artifacts. Mechanical grinding of a sample followed by either ion milling, dimpling, or electropolishing produced foils with large electron transparent areas, but with uncharacteristic features of the original Nb-10 a/o Si alloy microstructure. These artifacts were identified as dislocations, surface mottling, and antiphase domains.

Alloys↗
PubMed1992

Human alpha-globin gene expression is silenced by terminal truncation of chromosome 16p beginning immediately 3' of the zeta-globin gene.

The high level expression of the human alpha-globin genes in erythroid tissue appears to require a set of DNaseI hypersensitive sites located upstream of the human alpha-globin gene cluster. These sequences, termed the locus control region (LCR), include two erythroid specific and a number of less restricted DNaseI hypersensitive sites. In this report we describe an individual with alpha-thalassemia associated with a truncation of the short arm of chromosome 16 that removes the LCR region and inactivates the adjacent intact alpha-globin genes. This genetic study supports the critical role of the LCR in the transcriptional activation of the human alpha-globin gene cluster and substantiates the importance of LCR deletions in the etiology of alpha-thalassemia.

Blotting, Southern↗