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Biomedical subjects

M Stein

Publications and source records attributed to M Stein.

At least 253 records · Page 14Linked to original sources
PubMed1991

Mutation of a negatively charged amino acid in thioredoxin modifies its reactivity with chloroplastic enzymes.

A new over-expression system has been set up for Escherichia coli thioredoxin, yielding 55 mg purified protein/10 g fresh cells. This system has been used to produce thioredoxin modified by site-directed mutagenesis. Taking advantage of the structural and enzymatic similarity between E. coli and spinach m-type thioredoxin, Asp61 of E. coli thioredoxin has been changed into Asn in order to investigate the impact of the suppression of a charged residue on the interaction of thioredoxin with target enzymes. The modification did not significantly alter the structure of the protein. Neither the rate of reduction of insulin and 5,5'-dithio-bis(2-nitrobenzoic acid) by the reduced thioredoxin, nor the reduction by NADPH-dependent thioredoxin reductase, have been modified. The major effect of the mutation was observed for chloroplast enzyme activation with thioredoxin reduced by dithiothreitol and with thioredoxin reduced by ferredoxin-dependent thioredoxin reductase in a light-activation reconstituted chloroplast system. The substitution of the negatively charged Asp61 by the neutral Asn led to an increase in the efficiency of spinach fructose-1,6-bisphosphatase activation by the dithiothreitol-reduced thioredoxin, and to an increase in both spinach fructose-1,6-bisphosphatase and corn NADP-dependent malate dehydrogenase activities in the light-activation system. This suggests that the suppression of the negative charge improves the reactivity of thioredoxin with chloroplast enzymes such as fructose-1,6-bisphosphatase and ferredoxin-dependent thioredoxin reductase.

Amino Acid Sequence↗
PubMed1991

[Primary malignant lymphoma of the testis].

Among 715 patients with non-Hodgkin's lymphoma referred to this oncology center between 1973-1989, there were 7 (0.9%) with primary lymphoma of the testis. The mean age was 55 (range 23-78). The presenting symptom in all the 7 was testicular mass or swelling. 6 of them underwent inguinal orchiectomy and 1 had a testicular biopsy. The pathological subtype of the lymphoma in all 7 was the diffuse large cell type. The disease stage was IE in 3, IIE in 3 and IVE in 1. Only 1 had bilateral testicular involvement. 6 were treated primarily with various combinations of chemotherapy and 1 by radiotherapy. 3 developed recurrent disease (2 treated primarily with chemotherapy and 1 by radiotherapy) and died 14, 19 and 27 months, respectively, after diagnosis. 3 are alive with no evidence of recurrent lymphoma. Follow-up in an additional patient has been too short for evaluation. Primary testicular lymphoma is a relatively rare form of extranodal lymphoma. It has a tendency to early systemic progression and is potentially curable by aggressive combination chemotherapy.

Adult↗
PubMed1991

Regulation of tumor necrosis factor (TNF) release by murine peritoneal macrophages: role of cell stimulation and specific phagocytic plasma membrane receptors.

In spite of the physiologic and pathologic importance of tumor necrosis factor (TNF), the cellular factors that govern its release by macrophages (M phi) are poorly understood, in comparison with other secretory products. We have studied the role of M phi heterogeneity and of plasma membrane receptors in regulating TNF release in vitro. Resident and various exudate murine peritoneal M phi populations were challenged with lipopolysaccharide (LPS) or different phagocytic particles, and TNF release assayed by cytotoxicity for L-929 fibroblasts. Resident peritoneal M phi (RPM phi) released a small amount of TNF in response to LPS whereas thioglycollate-elicited M phi (TPM phi) released high levels of TNF (5000 U/3 x 10(5) M phi/ml). M phi elicited by Bio-Gel polyacrylamide beads (BgPM phi), another nonspecific inflammatory stimulus, or early in the course of intraperitoneal Bacillus Calmette-Guérin infection, before recruited cells become immunologically activated, released tenfold less TNF after the same stimulus. By contrast, TNF release in response to various phagocytic triggers was similar (approximately 300-600 U/3 x 10(5) M phi/ml) in all M phi populations including RPM phi. The response by BgPM phi to LPS was enhanced by pre-treatment in vitro with interferon-gamma or thioglycollate broth. With respect to phagocytic receptor triggering we found that complement receptor type 3 (CR3) ligation or latex uptake did not mediate release of significant quantities of TNF (less than 48 U/3 x 10(5) M phi/ml) by any M phi, whereas ligation of the Fc receptor for IgG1/IgG2b subclasses or of receptors for zymosan particles sufficed, in the absence of ingestion, to induce release of circa 500 U/3 x 10(5) M phi/ml TNF by all M phi tested. Our studies show that M phi vary in respect to priming for TNF release and that heterogeneity should be related to a particular triggering stimulus. Furthermore, the capacity of some M phi populations to release unusually high levels of TNF depends on immune or nonspecific stimuli subsequent to the process of inflammatory recruitment.

Acrylic Resins↗
PubMed1991

Thyroid cancer and multiple primary malignancies in Israel.

The exact risk of multiple primary neoplasms in patients with thyroid cancer is difficult to ascertain from the data available in the literature. Three thousand seventy-two patients with thyroid cancer, listed in the Israel Cancer Registry during a 16-year time span, were studied to determine the true incidence of another primary cancer. Ninety-two cases were reported as having an additional primary cancer. The prevalence of multiple primary malignancies was 3%. The frequency was higher among patients of European rather than of Asian or African origin. The second primary cancers in order of decreasing frequency were of the breast, lung, colorectum, head and neck, and lymphoma/myeloma. Most of the deaths were due to the additional cancer. The 5-year survival rate was highest for head and neck and lowest for lung cancer patients. These results emphasize the need for greater awareness of the possibility of developing additional cancers, and indicate the need to incorporate strategies for the prevention, early detection, and treatment of multiple primary neoplasms.

Breast Neoplasms↗
PubMed1991

Intravenous digital subtraction arteriography in the evaluation of vascular grafts.

Between 1982 and 1986 intravenous digital subtraction arteriography was used to evaluate vascular grafts in 97 patients (54 males, 43 females). Indications included recurrent symptoms, absent or diminished pulses, a drop in Doppler pressure measurements, and clinical uncertainty with respect to graft patency. Problems identified included graft stenosis, stenosis of the anastomosis or its distal vessels, false aneurysm, arteriovenous fistula and emboli. Forty-eight operations were carried out following intravenous digital subtraction arteriography, and radiographic findings were verified surgically. Twice, intravenous digital subtraction arteriography did not show significant graft findings which were discovered at surgery. Thus intravenous digital subtraction arteriography showed a sensitivity of 95.8% and specificity of 100%. Complications following intravenous digital subtraction arteriography were: two patients developed urticaria, and one superficial thrombophlebitis. There were no cases of pulmonary edema or death. In conclusion intravenous digital subtraction arteriography is very useful in the diagnosis of graft-related problems if done on a selective basis looking at graft and anastomosis site only. Intravenous digital subtraction arteriography is done on an outpatient basis, has high sensitivity and specificity, good patient acceptance, is safe, fast and is less expensive than conventional arteriography.

Adult↗
PubMed1991

Neutrophil beta-adrenergic receptor responses are potentiated by acute exposure to phorbol ester without changes in receptor distribution or coupling.

Exposure to the phorbol ester, phorbol 12-myristate, 13-acetate (PMA, 100nM) for 10 minutes enhanced cyclic AMP accumulation in human neutrophils under basal conditions and in response to the beta-adrenergic receptor agonist isoproterenol (ISO), 1 microM) and the adenylate cyclase activator forskolin (FSK, 10mM). Potentiation of responses to ISO by PMA was dose-dependent between 0.1 and 100nM PMA. The diacylglycerol analogue, 1-oleoyl-2-acetylglycerol (OAG) (50 microM) also elevated beta-receptor responses, but 4 beta-phorbol (100nM), lacking the capacity to activate PMA, was ineffective. Short-term exposure (12 seconds) to the peptide n-formylmethionine leucyl-phenylalanine (FMLP, 1 microM) also elevated neutrophil cyclic AMP accumulation. All potentiating effects of PMA on cyclic AMP production were inhibited by the protein kinase inhibitor 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine (H7). Elevation of cyclic AMP by FMLP was insensitive to H7. PMA had no apparent effect on beta-receptor agonist-affinity, distribution between cell-surface and internalised compartments, or the capacity of ISO to induce beta-receptor internalisation. Responses to FSK or ISO in terms of fold-stimulation of basal cyclic AMP accumulation in the presence of PMA were not elevated by PMA. These findings indicate that PMA exerts a potentiating effect on neutrophil adenylate cyclase responses through protein kinase C activation. FMLP elevation of neutrophil cyclic AMP in the absence of other stimuli, appears however, to be insensitive to protein kinase inhibition.

Cells, Cultured↗
PubMed1991

Biochemical mechanisms of stress-induced impairment of rat T cell mitogenesis.

Splenic mononuclear cells isolated from rats exposed to two brief stressors (5 min of restraint or 2 min of footshock) showed a diminished response to the T cell mitogens, concanavalin A and phytohemagglutinin. Cells from these stressed animals also exhibited a diminished response to stimulation with the phorbol ester, tetradecanoylphorbol acetate (TPA), and/or the calcium ionophore, ionomycin. Since stimulation with these latter two agents mimics early signals generated by mitogen surface receptor binding including increased intracellular calcium and protein kinase C activation, the data indicate that stress-related defects in T cell proliferation occur at sites other than or in addition to these early events in cellular activation.

Analysis of Variance↗
PubMed1991

Polytetrafluoroethylene vs. polypropylene suture for endoscopic bladder neck suspension.

Between May 1989 and October 1989, 24 women underwent a prospective, randomized study comparing polypropylene (Prolene) and polytetrafluoroethylene (Gore-Tex) sutures for endoscopic bladder neck suspension. Polypropylene was associated with significantly more suture pain than polytetrafluoroethylene. Polytetrafluoroethylene was more difficult to tie at a predetermined tension.

Cystoscopy↗
PubMed1991

Angiographic assessment of arterial outflow: predictive value of a new classification system.

A prospective study with 4 years of follow-up involving 127 consecutive symptomatic patients (60.6% with claudication, 39.4% with critical ischemia) who underwent aortobifemoral bypass surgery is described. A new grading system for the classification of arterial outflow was applied to determine its usefulness in predicting the outcome of surgery. Preoperative angiograms were numerically scored according to the arterial outflow status at the level of main segmental involvement. Higher scores corresponded to worse outflows. Outflow scores ranged between 1 and 10 with a mean of 3.6 +/- 0.24. The main comparison was between patients with scores of less than 5 (group A, n = 80) and patients with scores of 5 or more (group B, n = 47). Better outflow was associated with higher postoperative mean increases in the ankle-brachial index (ABI) (group A, 0.35 +/- 0.03; group B, 0.17 +/- 0.04; P less than .001) and transcutaneous oximetry (PtcO2) (group A, 15.4 mm Hg +/- 1.8; group B, 8.4 mm Hg +/- 3.0; P = .01). At 4-year follow-up, group A had higher cumulative rates of patency (98.3% vs 78.0%, P less than .001), symptomatic relief (84.0% vs 23.3%, P less than .001), and palliation (67.0% vs 19.9%, P less than .001). In conclusion, angiographic outflow, as evaluated with the system described, successfully helped predict postoperative increases in ABI and PtcO2 and the cumulative rates of graft patency, symptomatic relief, and palliation.

Angiography↗
PubMed1991

Medical and social outcome in adolescents with end-stage renal failure.

Clinical information was collected on 118 adolescents who developed ESRF at age 143 months or older and were treated between 1966 and 1986 at the Toronto Hospital for Sick Children. The cumulative survival rate in transplanted patients (N = 109) was 80.1% after 15 years. Survival rates after four years were 93.9% in transplanted and 46.9% in nontransplanted patients (P less than 0.001). No patient receiving dialysis alone (N = 9) was followed longer than four years. Nine patients received three transplants and had an 89% survival rate. Six of these had a functioning graft at end of the follow-up. The cumulative survival of the entire group was 76.4% at eighteen years. Forty-two (35.6%) patients had a height below the third percentile. Functional status obtained by a structure telephone interview with a member of the present treating nephrology service was good (G) or excellent (E) for 66.7% of all patients (73.5% of transplant patients (N = 68) and 45% of dialysis patients (N = 20). Hemodialysis patients functioned less well [25% G/E (N = 12)] than peritoneal dialysis patients [75% G/E (N = 8)]. Most patients achieved an appropriate level of formal education although more slowly than normal adolescents. Only 11 patients were neither enrolled in an educational institution nor employed. We conclude that aggressive treatment for adolescents with ESRF is an appropriate application of health care resources.

Adolescent↗
PubMed1991

Adrenal steroid receptor activation in vivo and immune function.

Recent studies have indicated significant differences among immune and other tissues in in vivo adrenal steroid receptor activation after a given hormone exposure. Nevertheless, the relationship between in vivo receptor activation and functional measures of the immune response has not been determined. Type I and type II adrenal steroid receptor binding in conjunction with mitogen-induced T-cell proliferative responses were measured in the spleens of Sprague-Dawley rats that were administered various concentrations of dexamethasone (DEX). A linear relationship between type II receptor binding and splenocyte proliferation was found, with decreases in measurable type II receptors (indicating in vivo receptor activation) being highly correlated with decreases in immune function. There was no evidence of spare type II receptors. In vitro studies using the type II receptor antagonist RU 486 confirmed that the inhibitory effect of DEX on splenocyte proliferation was mediated via the type II receptor. These findings provide a foundation for future studies evaluating glucocorticoid effects on immune system function and suggest that evidence of in vivo receptor activation may be critical for predicting when and in which tissues adrenal steroid hormones may be capable of modulating the immune response.

Analysis of Variance↗
PubMed1991

Mitoxantrone as second-line single agent in metastatic breast cancer.

Mitoxantrone (MIX), a member of the anthraquinone chemical class, was found to be a potential anticancer agent. It has a similar spectrum of activity as Adriamycin in experimental and human tumors. Thirty-five female patients with metastatic breast cancer, refractory to previous chemotherapy, were treated between 1986 and 1987 with MIX (14 mg/m2 i.v. every 3 weeks); patients with diffuse bone metastases or heavily pretreated patients received 10-12 mg/m2 MIX. All patients were evaluable for response and toxicity. Two patients achieved complete response and 4 partial response, giving an overall response rate of 17%. Median time of response was 5.5 months. The drug was well tolerated. Objective response was obtained mostly in patients with a performance status (Karnofsky scale) of more than 70%, and in those who received more than 12 mg/m2 MIX per course. One patient developed cardiomyopathy, another an acute myocardial infarction, and 3 patients had pathological changes on echocardiography or multigated nuclear angiography. Hematological and gastrointestinal toxicity was tolerable. We found MIX to be a potentially effective second-line treatment with mild toxicity in patients with metastatic breast cancer.

Breast Neoplasms↗
PubMed1991

Screening for sleep apnea using pulse oximetry and a clinical score.

Confirmation of the diagnosis of OSA currently requires overnight polysomnography. This study evaluates the usefulness of pulse oximetry together with a clinical score in identifying OSA. Forty patients were assigned a clinical score based on the presence or absence of loud snoring, observations of interrupted breathing during sleep, hypersomnolence, obesity and essential hypertension. Each underwent a night of domiciliary pulse oximetry followed by nocturnal polysomnography. Significant OSA was confirmed in 26. All 15 patients with positive pulse oximetry tracings had significant OSA (apnea index greater than or equal to 10). Five of eight with negative tracings were also shown to have significant OSA along with six of the seven patients with inadequate or indeterminate tracings. Clinical scores were significantly different for those with and without OSA. This study confirms the usefulness of nocturnal pulse oximetry in establishing the diagnosis of OSA and highlights the value of a clinical score in improving its sensitivity as a screening tool.

Adult↗
PubMed1991

The place of sociology in a drug education curriculum.

This article gives consideration to the part a sociological perspective can play in a drug education curriculum. Sociology's study of human behavior from the context of various social groupings is considered appropriate to any understanding of drugs and drug use, as are a number of substantive areas common to the discipline. The sociological perspective is examined from the broad foci of structure and process, and with each focus examples of a sociological approach to drug use is offered. The common concerns of these approaches, as well as their points of divergence, are discussed. A sample outline of a course in "Drugs and Society" is also presented, suggesting the ways in which the sociological issues discussed could provide an orientation to the study of drug use in a social context.

Curriculum↗
PubMed1991

[Primary brain lymphoma].

Between 1973 and 1989, 739 patients with non-Hodgkin's lymphoma were referred here for treatment, of whom 10 (1.4%) had primary brain lymphoma (PBL) and 1 had acquired immunodeficiency syndrome (AIDS). There were 7 females and 3 males (mean age 58 years, range 35-77). Duration of symptoms ranged from several days to 3 weeks. The presenting symptoms were secondary to increased intracranial pressure. Computerized tomography (CT) performed in 8 revealed a solitary lesion in 7. Other CT scan features were various degrees of contrast enhancement, edema and midline shift. The most common site was the frontal lobe; infratentorially, the cerebellum was the most frequent site. The diagnosis was established in 8 patients by surgery and in 2 at autopsy. The most common subtype was the diffuse, large cell, immunoblastic lymphoma. 5 patients were irradiated following subtotal excision and 2 had combined radiation therapy and high-dose methotrexate-based chemotherapy; only 1 had no postoperative treatment. All patients treated by radiotherapy alone died within 3-5 months after diagnosis. The 2 who received combined therapy are alive, 15 and 48 months after diagnosis, respectively.

Adult↗