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Biomedical subjects

S Verma

Publications and source records attributed to S Verma.

At least 235 records · Page 13Linked to original sources
PubMed1991

Standardized Assessment of Depressive Disorders: a replicated study from northern India.

A total of 91 subjects with depressive disorder have been studied using the WHO-standardized Standardized Assessment of Depressive Disorders (SADD). The 10 most frequently reported symptoms were sadness, anxiety, joylessness, lack of energy, hopelessness, loss of interest, disruption of social functioning, irritability, loss of ability to concentrate and lack of appetite. The results of this study are compared with other available work on SADD.

Adolescent↗
PubMed1991

Isolation and serological characterization of a Plasmodium vivax recombinant antigen.

A genomic library for Plasmodium vivax was constructed in lambda gt11 and immunologically screened with pooled serum samples from vivax patients. Six seroreactive clones were isolated, and one clone, denoted PV9, was studied further. This clone has an unusual base composition (65% G + C), does not share any homology with P. falciparum, and codes for an entirely new antigenic determinant. Antibodies (immunoglobulin G type) against the PV9-encoded polypeptide were produced in all vivax patients older than 15 years. This seroreactivity was lower among patients younger than 15 years (53%). The antigenic epitope(s) of the PV9-encoded polypeptide was recognized at a similar rate by serum samples from P. vivax patients who were living 350 to 973 km apart. Fifty percent of uninfected Indian adults were also seropositive, whereas all European and American (United States) sera tested were negative, suggesting that anti-PV9 antibodies persist after infection. The seroreactivity pattern of this antigen is similar to that of the immunity developed in malaria after repeated infections.

Adolescent↗
PubMed1991

The cytoplasmic tail of CD4 targets chimeric molecules to a degradative pathway.

Many different cell surface receptors undergo endocytosis via coated pits. Once having entered the cell, the receptors are sorted into diverse pathways. Which path a given receptor will follow is determined by signals inherent in the receptor's structure. The nature of these structural features is not yet known. In this study, we have taken the approach of constructing chimeric molecules to localize the domain of the T-cell surface molecule CD4 which is responsible for targeting it for degradation. Chimeric molecules bearing the cytoplasmic domain of CD4 and the extracellular domain of either the low-density lipoprotein receptor or a major histocompatibility complex (MHC) class I molecule were both internalized in response to phorbol 12-myristate 13-acetate and were subsequently degraded, indicating that the cytoplasmic tail of CD4 contains all the information required for both processes. The ability to modulate the level of MHC class I molecules on the cell surface offers an approach to investigating quantitative aspects of antigen presentation, the initial possibilities of which are explored herein.

CD4 Antigens↗
PubMed1990

Superoxide dismutase as a regulatory switch in mammalian testicular steroidogenesis.

The delta 4-pathway of testosterone biosynthesis in leydig cells, widely believed to proceed through pregnenolone--greater than pregnenedione--greater than progesterone route catalyzed by 5 delta-3 beta-hydroxysteroid dehydrogenase and delta 5-delta 4-isomerase respectively is shown to pass through an alternate pathway mediated by superoxide dismutase and peroxidase. A built-in regulatory switch is incorporated in this route, with the superoxide dismutase inducible upon LH-stimulation of the leydig cells.

Animals↗
PubMed1990

Superoxide anion radical induces lipid phase transitions that mimic temperature-induced phase-transition phenomenon of membrane lipids.

A biological membrane is shown to undergo lipid-phase transition leading to increased membrane fluidity when exposed to extraneously generated superoxide anion radical. This phase-transition is several folds higher in magnitude when compared to the temperature-induced fluidity change at the transition temperatures. This finding could have significant importance since an altered membrane configuration may involve aspects of biochemistry, biophysics or physiology.

Animals↗
PubMed1990

Activation of iodine into a free-radical intermediate by superoxide: a physiologically significant step in the iodination of tyrosine.

A pivotal biochemical event in the thyroid physiology is identified unravelling a superoxide anion radical-mediated activation of iodine into an active I.- form, which could be the intermediate that is incorporated onto tyrosine. This active iodine species gives fairly stable spin-adducts with PBN that could be characterized using EPR spectroscopy. Thus, a long-lasting puzzle regarding the iodine intermediate formed before iodination of tyrosine seems to be solved.

Animals↗
PubMed1990

Discovery of a novel and alternate hydrogen peroxide generation machinery in the mammalian thyroid gland that modulates iodination of tyrosine.

The hydrogen peroxide-dependent and peroxidase-mediated iodination of tyrosine, a pivotal step in the thyroxine biosynthesis in thyroid glands of mammals, has always been thought to be dependent on a glucose-glucose oxidase system to meet its demand for hydrogen peroxide. This report documents a novel and probably kinetically faster hydrogen peroxide-generating system operating in the thyroid gland cells involving the superoxide dismutase and superoxide anion radical. In the female cycling mice, the superoxide radical and superoxide dismutase activity are shown to be at persistently high levels, quite likely acting as a potent hydrogen peroxide synthesizer in the mammalian thyroid gland. The significance of this discovery in relation to the thyroid physiology is discussed.

Animals↗
PubMed1990

Determination of Senecio alkaloids by thermospray liquid chromatography/mass spectrometry.

A series of Senecio alkaloid and alkaloid N-oxide standards has been analyzed using positive and negative ion thermospray liquid chromatography/mass spectrometry (LC/MS) with an ammonium acetate-containing mobile phase. On-line separations of pyrrolizidine alkaloids from extracts of Senecio jacobaea (tansy ragwort) and Senecio vulgaris (common groundsel) were done using an ammonium hydroxide-containing mobile phase. All of the alkaloids known to be present in the extracts were detected by ammonium hydroxide thermospray LC/MS, as well as many other components which may be as-yet-unidentified alkaloids.

Acetates↗
PubMed1990

Phase I study of idarubicin administered orally on a daily x 3 schedule.

Twenty-one adult patients with refractory solid tumors were treated on a phase I study of idarubicin (4-demethoxydaunorubicin) administered daily for 3 days every 3 weeks. Nineteen of the patients had received previous chemotherapy (including 13 with prior anthracyclines), and 12 had received prior radiotherapy. Idarubicin dose levels of 10, 15, 17.5, 20, and 25 mg/m2 were explored. Hematological toxicity was dose-related. Other toxicity was acceptable. Only one patient (treated with an idarubicin dose of 17.5 mg/m2/day) developed neutropenic fever, from which he recovered. Further dose escalations beyond 25 mg/m2 were not carried out because of the increasing length of time required for recovery from granulocytopenia at higher doses. No patient experienced a major response, but minor responses were seen in 3 patients with carcinomas of the colon, breast, and kidney respectively. Further phase II studies of oral idarubicin at a starting dose of 20-25 mg/m2 daily times 3 days in patients with good bone marrow reserves are recommended. Because of the degree of neutropenia expected, patients would have to be observed carefully.

Administration, Oral↗
PubMed1990

Activity of intravenous menogaril in patients with previously untreated metastatic breast cancer. A National Cancer Institute of Canada Clinical Trials Group study.

We have carried out a phase II study of intravenous menogaril given every four weeks in a group of patients with breast cancer who had received no prior chemotherapy for metastatic disease. Myelosuppression, nausea and vomiting and local reactions were seen frequently. Six partial responses (median duration 154 days) were seen in 24 eligible patients. We conclude menogaril is active in breast cancer and recommend that because it can be delivered in high doses orally, future trials in this disease should focus on intense oral schedule.

Adult↗
PubMed1990

Phase I study of oral menogaril administered on a once weekly schedule.

Forty-seven patients with solid tumors were treated on a phase I study of menogaril administered by mouth once per week. Nausea and vomiting were excessive at weekly doses of 350 and 450 mg/m2/week but were tolerable and controlled reasonably well by antiemetics at lower doses. There appeared to be a relatively shallow dose-vs-granulocytopenia curve above a menogaril dose of 180 mg/m2/week. No patient receiving chronic dexamethasone for cerebral edema developed granulocytopenia, even at menogaril doses of 350-450 mg/m2/week. Two patients developed neutropenic infection. No patient developed thrombocytopenia. Mild arrhythmias were seen in 3 patients. Two patients suffered possible myocardial infarcts that may not have been related to treatment. Asymptomatic blood pressure fluctuations were common and were probably not related to treatment. Diarrhea was dose-related but was generally not severe. Alopecia and stomatitis occurred occasionally. Minor responses were seen in two patients with gliomas, and three of five evaluable prostate cancer patients experienced marked pain relief. The dose recommended for phase II studies is 250-300 mg/m2/week with antiemetic pretreatment. This schedule appears to allow an oral menogaril dose-intensity that is approximately double that attainable with other oral schedules that have been studied.

Administration, Oral↗
PubMed1990

Phase I and pharmacology study of intravesical mitoxantrone for recurrent superficial bladder tumors.

A phase 1 study of intravesical mitoxantrone was done in patients with superficial bladder tumors recurrent after previous intravesical therapy. Mitoxantrone (5 to 10.5 mg.) was instilled in the bladder via catheter and was left in situ for 2 hours. Each patient received 6 treatments at 1-week intervals. Pharmacology studies were conducted in a subset of consenting patients. Dysuria, urinary frequency and hematuria were dose-limiting at 10 to 10.5 mg., the dose recommended for our phase 2 studies. One patient treated with 7.5 mg. mitoxantrone had bladder contracture after severe bladder injury caused by the drug. The interval free of recurrence increased in 5 of 8 patients treated with 10 to 10.5 mg. mitoxantrone and in 6 of 19 treated at lower dose levels. One patient who had residual evaluable tumor in the bladder at treatment experienced a complete remission for 16 months. Only 1 of 18 patients who underwent pharmacology studies had any mitoxantrone detectable in the blood after intravesical administration. This patient had severe irritative symptoms at treatment. No systemic toxicity was noted in any patient. Of the mitoxantrone instilled into the bladder 33 to 100% (mean 75%) was recovered in the specimen voided at the end of treatment. In summary, intravesical mitoxantrone is reasonably well tolerated and should be studied further at a dose of 10 mg. per week for 6 weeks. Caution should be exercised, since bladder contracture was seen in 1 patient. Systemic absorption and toxicity are negligible.

Administration, Intravesical↗
PubMed1990

A randomized phase II study of cisplatin alone versus cisplatin plus disulfiram.

Preclinical evidence has suggested that disulfiram (DS) and related compounds can decrease the toxicity and enhance the therapeutic index of cisplatin (CP). To study this further, we have performed a prospective randomized study wherein 53 patients with CP-sensitive malignancies were assigned to therapy with CP 100 mg/m2 alone (group I) or CP 100 mg/m2 and oral DS 2,000 mg/m2 (group II). Both groups were comparable with regard to sex distribution, age, performance status, prior chemotherapy, and radiotherapy. Twenty-three patients were not evaluable for response (3 refused follow-up, 18 had less than two courses, one had an early death, and one had excessive toxicity during the first cycle of treatment). Of the 30 evaluable patients (16 in group I, 14 in group II), only one in group II achieved a complete response. There was no statistically significant difference in response rate, time to progression, or median survival between the two groups. Fifty-two patients (98.1%) were evaluable for toxicity. Significant differences in toxicities were observed between the two groups: patients in group I encountered lower [Eastern Cooperative Oncology Group (ECOG) 0-1)] grades of nausea, vomiting, and ototoxicity, and patients in group II experienced higher grades (ECOG 2-3) of toxicity in general. In addition, there was no difference in nephrotoxicity between the two groups, as measured by the change in serum creatine or 24-h urine creatinine clearance over the first course of treatment. We conclude that, contrary to previously published reports, DS does not afford significant nephroprotection against CP and, in fact, enhances gastrointestinal and ototoxicities.

Aged↗
PubMed1990

Phase I study of acivicin and cisplatin in non-small-cell lung cancer. A National Cancer Institute of Canada study.

Seventeen previously untreated patients with metastatic non-small-cell lung cancer were entered in this phase I trial. Treatment consisted of a combination of acivicin and cisplatin at a starting dose of 12 and 15 mg/m2, respectively, given i.v. during 5 days and repeated every 28 days. A total of 46 cycles was given. Renal function abnormality was the dose-limiting toxicity of cisplatin with a maximum tolerated dose of 12 mg/m2. This toxicity occurred at a dose lower than expected, indicating a possible potentiation of platinum renal toxicity by acivicin. Myelosuppression was the dose-limiting toxicity of acivicin, with a maximum tolerated dose of 12 mg/m2. Other side effects included generalized weakness and gastrointestinal and neurological symptoms. In 15 patients evaluable for response seven progressed, six were stable for a median duration of 13 weeks, and two patients achieved a partial remission lasting 8 and 24 weeks, respectively. The overall response rate was 13%. The recommended phase II dose of both agents in this schedule was 12 mg/m2. The possible enhancement of cisplatin toxicity might have compromised the overall response rate of the combination and further studies using these drugs in this schedule are not recommended.

Adult↗
PubMed1989

Combination chemotherapy with doxorubicin, dacarbazine, and ifosfamide in advanced adult soft tissue sarcoma. Canadian Sarcoma Group--National Cancer Institute of Canada Clinical Trials Group.

Forty-three adult patients with locally advanced or metastatic soft tissue sarcoma entered a pilot study of combination chemotherapy comprising 50 mg of doxorubicin/m2 by intravenous bolus, 850 mg of dacarbazine/m2 by 1-hour infusion, and 5 g of ifosfamide/m2 by 24-hour infusion with mesna uroprotection. The overall response rate in 40 assessable patients was 25% with two complete remissions. Twenty-four episodes of infection occurred in 148 courses (16%). These infections were usually associated with neutropenia (granulocyte count less than 0.5 X 10(9)/L), which occurred in 70% of the courses. These results do not differ from those elicited by each agent alone, and may reflect inadequacies of dose intensity or scheduling, or evaluation in a study population with adverse prognostic factors.

Adolescent↗