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Biomedical subjects

M Steiner

Publications and source records attributed to M Steiner.

At least 361 records · Page 20Linked to original sources
PubMed1985

Multimodal approach (surgery, chemotherapy, and radiotherapy) in the treatment of advanced ovarian carcinoma.

Forty-five patients with advanced ovarian carcinoma without prior chemotherapy were treated with cisplatin-Adriamycin (doxorubicin) combination, 50 mg/m2 intravenously, for 11 cycles. Second-look operation (SLO) was performed in patients without evidence of disease at the end of chemotherapy. Abdominopelvic irradiation was administered to those found to have microscopic or minimal disease (tumor less than 2 cm) at SLO. Forty patients were evaluable. Chemotherapy induced complete response in 56.7% and partial response in 16.7%. In 25% of the reoperated patients, no tumor was found; 30% had microscopic disease; 25% had minimal disease; and 20% had larger tumors. Two-year survival rate was 45%. The residual tumor left at initial operation, the histologic grade, and the response to chemotherapy influenced survival. Toxicity was moderate. There were three treatment-related deaths (one due to sepsis, one due to cardiotoxicity, and one at SLO, respectively). Radiotherapy was poorly tolerated after chemotherapy. The median duration of follow-up was 21.5 months. Further follow-up is needed to study the long-term benefits of this multimodal approach.

Actuarial Analysis↗
PubMed1985

Platelet-associated IgG is a specific protein.

The immunoglobulin binding to normal human platelets (PaIgG) was isolated on cell columns in which platelets or their membranes were attached via concanavalin A to an inert support matrix. Normal human IgG isolated from pooled serum was applied to the cell columns. The absorbed material which was eluted at low pH with a buffer of high ionic strength was immunologically and biochemically pure IgG. When the nonadherent IgG of the first passage through the platelet cell column was reapplied a second time virtually no IgG was retained. Isoelectric focusing on urea SDS polyacrylamide gels revealed only 2 major bands with pIs of 8.2 and 8.4 whereas the precolumn IgG contained a wide range of molecular species with pIs ranging from less than 6.0 to 9.0.

Blood Platelets↗
PubMed1985

Dynamics of platelet tubulin in response to changes in free sulfhydryl groups.

Pools of polymerized and total tubulin were measured in human platelets as a function of free sulfhydryl groups both in acid-soluble and acid-precipitable cell fractions. Changes in free thiols were produced either by storage of platelets at room temperature or by addition of the potent oxidizing agent diazene dicarboxylic acid (diamide) and were correlated with shifts in the dynamic equilibrium between assembled and disassembled microtubules and platelet aggregation. Diamide at concentrations of 0.5 to 5 mM depleted acid soluble SH groups and reduced protein thiols while causing a progressive decrease in polymerized tubulin. Similar changes, although not as severe, were initiated by storage of platelets at room temperature. Platelet aggregation especially that induced by collagen showed a positive correlation with the pool of polymerized tubulin. Our results indicate that the state of oxidation of sulfhydryl groups especially in the acid-precipitable fraction plays an important role in determining the position of equilibrium between polymerized and depolymerized tubulin.

Adenosine Diphosphate↗
PubMed1985

Primary drug-resistant tuberculosis in children. Correlation of drug-susceptibility patterns of matched patient and source case strains of Mycobacterium tuberculosis.

The purpose of this study is to compare the drug-susceptibility patterns of Mycobacterium tuberculosis isolated from patients (children) and from their corresponding adult contacts. We wished to ascertain if the susceptibility pattern of the isolate from the adult contact could be used as a guide in the initial selection of the antituberculous drug regimen in the child. Strains resistant to one or more antituberculous drugs were emphasized in our study. For 120 children with positive cultures, adults were identified who had positive cultures and who were the source of the children's infections. All strains had susceptibility tests for isoniazid, streptomycin, aminosalicylic acid, ethionamide, and, when they became available, ethambutol and rifampin. There were 29 instances in which either the adult's and/or the child's strain were resistant to one or more antituberculous drugs. In 111 (92.5%) instances the organism isolated from the child and that from the adult contact had identical drug-susceptibility patterns. Fourteen (93%) of 15 of the adult/child pairs were both resistant to isoniazid. The drug-susceptibility pattern of isolates obtained from the source of a child's illness is useful as a guide in planning initial drug therapy. In addition, knowledge of isoniazid-resistant strains in adult contacts may alert the physician to the potential failure of isoniazid prophylaxis.

Adolescent↗
PubMed1985

The photocycle of the chloride pump halorhodopsin. I: Azide-catalyzed deprotonation of the chromophore is a side reaction of photocycle intermediates inactivating the pump.

Halorhodopsin, the light-driven chloride pump of halobacteria, undergoes a photochemical cycle in the 10 ms range. Two intermediates, HR640 and HR520, accumulate in the photosteady state after short times (within 100 ms) of illumination. Upon prolonged illumination a third species, HRL410 accumulates, which is formed from HR520/HR640 by deprotonation of the chromophore in a side reaction of the photocycle. In the dark, HRL410 requires several minutes to reconvert thermally to HR478. Thus, molecules in the HRL410 state must be inactive pumps since their maximal turnover number could only be a few per hour. Inorganic bases, such as azide, catalyze the deprotonation of HR520/HR640 as well as the reprotonation of HRL410. Both reactions are accelerated several hundred times by azide but the photosteady-state concentration of HRL410 remains unchanged.

Azides↗
PubMed1985

Inhibitors of "spontaneous" platelet aggregation in whole blood.

In vitro 'spontaneous' platelet aggregation has been studied in whole blood. The spectrum of activity of materials known to influence platelet aggregation in platelet-rich plasma proved different in whole blood. Thus dipyridamole and one of its analogues SH1242 had a striking effect in whole blood whilst aspirin, chlorpromazine and K3920 had little or no effect. The combination of aspirin and dipyridamole as currently employed in clinical practice had no greater inhibitory effect than dipyridamole alone. The possible clinical relevance of these findings is discussed.

Aspirin↗
PubMed1985

The effectiveness of multidrug treatment by bleomycin, methotrexate, and cis-platinum in advanced vaginal carcinoma.

A case of a female with advanced squamous carcinoma of the vagina is presented. Complete disappearance of the primary tumor and involved inguinal lymph nodes was achieved with three courses of the cis-platinum-containing chemotherapy regimen BMP administered prior to radiotherapy. The encouraging result obtained warrants the use of this combined treatment modality in other patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

3H-clonidine binding to membranes of platelets prepared under physiological conditions.

A reproducible binding assay has been established to measure alpha 2-adrenoreceptors on membranes of human platelets prepared under physiological conditions. Washed platelet suspensions were obtained from fresh blood by a modified method (Mustard et al., 1972) and membranes were prepared by mechanical homogenization. 3H-clonidine, a selective alpha 2-adrenoreceptor agonist was selected as the ligand in a concentration range of 2-64 nM. Specific binding of 3H-clonidine was defined as the difference between total bound radioactivity and that not displaced by excess cold clonidine (6.4 X 10(-5) M). Platelets from 14 healthy young male volunteers were analysed using this technique, and one high affinity binding site, with KD and Bmax values in the reported range was found (KD: 10.14 +/- 1.95 nM; Bmax: 428 +/- 53 fmol/mg protein (mean +/- S.E.M.)). This technique will be used in future studies that will examine alpha 2-adrenoreceptor changes in specific subgroups of depressed patients.

Adult↗
PubMed1985

Specificity of the combined dexamethasone suppression and TRH/TSH tests in melancholia.

Subjects for this study were 61 acute psychiatric inpatients. Forty two (42) qualified for a RDC diagnosis of Major Depressive Disorder (MDD) and 19 for other disorders. After a 7-10 days drug withdrawal period patients were subjected to the dexamethasone suppression and TRH/TSH tests. TSH was measured using a RIA. Cortisol was measured using a CPB technique. Eighteen (18) of the 42 MDD patients and 1 of the 19 others had an abnormal DST (sensitivity 43%, specificity 94%). Twenty two (22) depressed patients and 4 others had a blunted TSH response (sensitivity 52%, specificity 79%). Thirteen (13) depressives and none of the others had abnormal responses to both tests (sensitivity 31%, specificity 100%). DST nonsuppression alone and blunted TSH response alone were not a function of severity of illness, sex, age of onset, family history or RDC subtype. The 13 MDD patients with the combined neuroendocrine abnormality were more severely depressed, had longer episodes of illness, were older and had a later age of onset of their first episode. Our results add support to the suggestion that serial neuroendocrine challenge studies might be of particular relevance and significance in the diagnosis and management of elderly psychotic depressed patients.

Adolescent↗
PubMed1985

Inguinal lymph node metastases from testicular tumor.

The Northern Israel Cancer Center serves 1 million inhabitants. Between 1968 and 1982, 33 patients with a diagnosis of nonseminomatous tumors of the testis were referred to this center. Of these patients inguinal lymph node metastasis developed in 4, each of whom had had risk factors for such metastasis. Two patients had undergone previous orchiopexy, and 2 had extension of the tumor to the epididymis and the tunica vaginalis testis. The inguinal region should be examined and watched carefully in patients with testicular tumor, especially those at high risk for inguinal metastases. Today, disease in patients with inguinal metastasis is curable by lymph node dissection and/or combination chemotherapy.

Adolescent↗
PubMed1985

Impaired arteriolar vasodilation induced by thrombosis of a coronary arterial stenosis.

This study tested the hypothesis that aggregation of platelets and release of thromboxane A2 at the site of a coronary arterial stenosis may contribute to myocardial ischemia by impairing flow regulation of the distal coronary bed. Measurements of hemodynamics, flow (microspheres), lactate metabolism, and prostaglandin (PG) metabolites (thromboxane B2 and 6-keto-PGF1 alpha) were made in closed-chest anesthetized pigs instrumented with a stenosis (65% diam reduction) in the left anterior descending (LAD) coronary artery. Data were acquired prior to stenosis insertion (control) and 5 and 15 min after insertion, during which time thrombotic occlusion of the device was occurring. Heart rate was controlled by atrial pacing. Distal LAD zone endocardial flow (ml X min-1 X g-1) declined versus control (1.15 +/- 0.20, mean +/- SD) at 5 min (0.89 +/- 0.40, P less than 0.05) and 15 min (0.41 +/- 0.36, P less than 0.01) of occlusion. Distal endocardial resistance (mmHg X ml-1 X min X g), however, did not change versus control (72 +/- 12) at 5 (66 +/- 12) or 15 min (61 +/- 38). Distal epicardial resistance (mmHg X ml-1 X min X g) declined versus control (90 +/- 17) at 5 (66 +/- 35, P less than 0.05) and 15 min (43 +/- 26, P less than 0.01) postinsertion. Finally, lactate extraction (%) at control (42 +/- 19) changed to production 15 min postinsertion (-36 +/- 93, P less than 0.05) and arterial-anterior interventricular vein thromboxane B2 difference (pg/0.1 ml) changed from 13.1 +/- 17.8 pre to -15.8 +/- 30.0 at 5 min post (P less than 0.05). Thus platelet aggregation and release at a spontaneously thrombosing stenosis contribute to ischemia not only by reduction of stenosis diameter but also by impairment of flow regulation in endocardial layers distal to it.

Animals↗
PubMed1985

Measurement by electrical impedance aggregometry of porcine platelets response to selected physiological agonists.

Although the domestic swine is commonly employed for physiological studies of the coronary circulation, there is relatively little data available concerning the responsiveness in whole blood of normal porcine platelets to standard physiological agonists. Such information is essential if the domestic swine is to be used as an animal model for studying potential interactions between platelets and the coronary circulation. Accordingly, the present study was undertaken to characterize the responses (aggregation and ATP release) observed in whole blood of normal porcine platelets to selected physiological agonists. The responses of platelets from 10 normal human volunteers also were studied with this system for comparison. Agents tested included ADP, arachidonic acid, collagen, epinephrine, norepinephrine, and thrombin. Studies were conducted with the Chronolog impedance aggregometer. The results demonstrate that platelets of domestic swine are reactive to ADP, arachidonic acid, and collagen. In contrast, neither epinephrine nor norepinephrine alone induced aggregation or release. Norepinephrine, however, caused modest potentiation of aggregation in response to ADP only. At 1 mM concentration each catecholamine inhibited the release response to collagen while at 10 mM each inhibited aggregation and release in response to either ADP or collagen. The data obtained indicate the domestic swine may be employed as a useful model to examine interactions between platelets and the coronary circulation.

Adenosine Diphosphate↗
PubMed1984

Changes in the distribution of platelet membrane proteins revealed by energy transfer.

The redistribution of platelet membrane proteins in response to platelet activation was studied. To investigate this process we prepared a variety of platelet ligands, including di- and tetrameric concanavalin A, IgG, thrombin, wheat-germ agglutinin and other lectins. These ligands were conjugated either with acceptor (rhodamine isothiocyanate) or donor (fluoresceine isothiocyanate) fluorophore. Platelets exposed to various combinations of ligand species were stimulated with different aggregating agents, and changes in sensitized fluorescence emission or donor quenching were recorded. Energy transfer was observed with thrombin, dimeric concanavalin A after addition of thrombin and various combinations of dimeric concanavalin A with other membrane ligands. The preincubation of platelets with colchicine prevented energy transfer between appropriate ligand pairs and platelet activator. Our studies show that nonradiative energy transfer can be used to analyze redistribution of membrane receptor sites in platelets.

Animals↗
PubMed1984

Affinity labeling of the exchangeable nucleotide binding site in platelet tubulin.

The exchangeable nucleotide binding site of platelet tubulin was labeled with [14C]p-fluorosulfonyl benzoylguanosine (FSBG). FSBG promoted polymerization of tubulin but depolymerization did not occur in the presence of this nucleoside analogue. GTP was able to block FSBG binding to tubulin. [14C]Iodoacetamide-treated tubulin which was first reacted with FSBG was digested with trypsin. The resultant peptides were analyzed by reverse phase high pressure liquid chromatography. One FSBG-labeled peptide could be identified both by its radioactivity and the characteristic UV absorbance spectrum associated with it. This may represent the exchangeable nucleotide site. A second peptide with a distinct nucleotide absorbance peak was found both in FSBG-treated and untreated tubulin preparations. This evidence is suggestive of the non-exchangeable nucleotide binding site.

Affinity Labels↗