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Biomedical subjects

M G Subramanian

Publications and source records attributed to M G Subramanian.

At least 55 records · Page 3Linked to original sources

Gonadoblastoma presenting as isosexual precocious puberty in a genetic female.

A 6 1/2-year-old female with pseudoprecocious puberty was found to have a gonadoblastoma. Her karyotype was 46, XX; serum estradiol level was markedly elevated; and androgens were within the range of normal. The importance of the Y chromosome and dysgenetic gonad in the predisposition to development of a gonadoblastoma is reviewed. A further categorization of gonadoblastomas based on the presence or absence of the Y chromosome is suggested.

Child↗

High-dose ketoconazole therapy in patients with metastatic prostate cancer.

High-dose ketoconazole, 400 mg orally every 8 h, was administered in two groups of patients with metastatic prostate cancer. Group A consisted of 10 patients who had not undergone orchiectomy and Group B, eight patients who had orchiectomy prior to the study. Significant declines in testosterone, androstenedione, and dehydroepiandrosterone levels, reciprocal elevation of the gonadotropin levels (FSH and LH), and a persistent fall in serum acid phosphatase levels were observed in Group A patients. Three Group A patients achieved a partial objective remission (duration 9, 41+, and 69 weeks); four patients, stabilization of their disease for a median of 33.5 weeks (range 16-40+ weeks); and two progressed (The National Prostatic Cancer Project Criteria). Stable disease in two Group B patients (7 and 20 weeks) and progression in four patients were observed. Gastrointestinal irritation was the main toxicity and was similar in both groups. Two Group A patients developed symptomatology consistent with adrenal insufficiency. Ketoconazole can suppress androgen production and has a beneficial role in the hormonal therapy of patients with prostate cancer who have not undergone orchiectomy.

Adenocarcinoma↗

Olfactory bulbectomy prevents anti-gonadal effect of exogenous melatonin in male hamsters.

When male Golden hamsters are maintained on short days (less than 12.5 h of light/day) the testes gradually regress. This testicular regression is due to an inhibitory effect of pineal gland melatonin on gonadotropin secretion. A previous report from the author's laboratory has indicated that olfactory bulbectomy (BX) will prevent the testicular regression associated with short photoperiod. The present study examined whether BX would also prevent the testicular regression associated with exogenous melatonin (MEL) injections. Male Golden hamsters were BX or sham (SH) BX at 23-28 days of age and were maintained on 14:10 light-dark cycle. Six weeks following surgery, one half of each surgical group began receiving injections of melatonin (15 micrograms sc), whereas the other half was injected with vehicle at 1600 daily. The testes size of the SH group injected with MEL progressively decreased, whereas the testes of all other groups remained large. These results indicate that BX prevents the testicular regression associated with short photoperiod by interfering with the antigonadotropic effect of melatonin.

Animals↗

Carbohydrate influences the immunogenic and antigenic characteristics of the ZP3 macromolecule (Mr 55 000) of the pig zona pellucida.

The glycoprotein molecule ZP3 of the pig zona pellucida (Mr 55 000) was deglycosylated by trifluoromethane-sulphonic acid. While gas chromatography established that deglycosylation resulted in greater than 91% carbohydrate removal, deglycosylated ZP3 (DG-ZP3) still retained significant immunogenic potential as shown by its ability to elicit antibody production in the rabbit. Several lines of evidence, however, demonstrated that deglycosylation produced significant modifications in the ZP3 macromolecule which profoundly altered its antigenicity: 125I-radiolabelling procedures using chloramine-T consistently resulted in 125I-labelled ZP3 with a higher specific activity than 125I-labelled DG-ZP3; in competitive binding radioimmunoassays (RIAs) using an 125I-labelled-ZP3 vs anti-ZP3 system, unlabelled DG-ZP3 successfully displaced ZP3 in a dose-related manner; in direct binding RIAs comparing the reaction of labelled ZP3 and DG-ZP3 versus 5 different zona antisera, higher titres were consistently achieved with 125I-labelled ZP3; as compared to ZP3, 2-dimensional immunoelectrophoresis using DG-ZP3 as antigen yielded significantly modified precipitin arc patterns; with electrophoretic blotting procedures, antisera to ZP3 or DG-ZP3 cross-reacted with the heterologous antigen; treatment of pig zonae with anti-DG-ZP3 serum produced a dense precipitation layer on the zona surface. When evaluated collectively, these results provide grounds for an important role for protein and carbohydrate in establishing the immunological characteristics of the Mr 55 000 macromolecule of the pig zona pellucida.

Animals↗

Olfactory bulbectomy prevents the gonadal regression associated with short photoperiod in male golden hamsters.

In male rats, pre-pubertal olfactory bulbectomy (BX) unmasks photoperiodic responsiveness so that maintenance of BX animals on short photoperiod results in a pineal gland mediated gonadal regression (Nelson and Zucker, Neuroendocrinology, 32 (1981) 266). The objective of the present study was to determine the effect of BX in Syrian hamsters, a species where short photoperiod alone induces a pineal gland induced testicular regression. Pre-pubertal (25-days old) Syrian hamsters underwent either sham BX, BX, or pinealectomy (PX) plus BX. One half of each group was then placed on an LD 14:10 photoperiod and the other half on LD 6:18. Thirteen weeks later all animals were decapitated. In the animals on LD 14:10, BX resulted in a slight but highly significant increase in testes weight but had no effect on other parameters examined. Sham BX hamsters on LD 6:18 had regressed testes and reduced serum testosterone levels, but these effects of short photoperiod were reversed in BX hamsters, so that the testes and seminal vesicles remained large. In addition, serum LH and testosterone levels were elevated following BX of the animals on LD 6:18. These results indicate that the olfactory bulbs tonically inhibit the reproductive system even in male hamsters maintained on long photoperiod and that olfactory bulbectomy prevents gonadal regression in male Syrian hamsters on short photoperiod, an effect which is the opposite of results obtained in rats on short photoperiod. Elucidation of the neural pathways involved and the nature of the relationship between the olfactory bulb and the pineal gland or photoperiodism remains for further investigation.

Animals↗

Association of sperm receptor activity with a purified pig zona antigen (PPZA).

Three types of data are presented which suggest that sperm receptor activity is associated with a 58,000 Mr acidic glycoprotein (PPZA) isolated from pig zonae: (1) boar sperm fail to bind to pig zonae pretreated with univalent antibody to PPZA; (2) boar sperm pretreated with PPZA are inhibited in binding to intact pig zonae; (3) binding studies utilizing boar sperm and radiolabeled PPZA indicate an inhibition of radiolabeled PPZA binding to sperm by non-labeled PPZA in a dose-related manner. Collectively these data suggest that, at least in the pig system, the contraceptive action of zona antibodies is accomplished by a specific immunologic reaction between antibody and the zona sperm receptor site rather than to a non-specific blockage of this receptor.

Animals↗

Correlation and comparison of Nb2 lymphoma cell bioassay with radioimmunoassay for human prolactin.

Serum samples from groups of men and women with normal and elevated prolactin (PRL) levels were assayed by radioimmunoassay (RIA) and by Nb2 lymphoma cell bioassay (BA) for the presence of PRL. Because the Nb2 lymphoma cells respond to both PRL and growth hormone, BA for PRL activity was carried out before and after neutralization of growth hormone in the serum samples. There were excellent correlations between RIA and BA both in euprolactinemic (r = 0.7587; P less than 0.002) and hyperprolactinemic (r = 0.9558; P less than 0.001) subjects. On an absolute basis, RIA and BA values were similar in the euprolactinemic group (6.6 +/- 0.8 versus 6.2 +/- 1.0), whereas in the hyperprolactinemic group, RIA values were significantly higher than the BA results (89.41 +/- 22.4 versus 62.1 +/- 21.2). The two assay systems also appeared to correlate better in women who were hyperprolactinemic, with obvious menstrual cycle disturbances, than in hyperprolactinemic women without menstrual cycle disturbances.

Biological Assay↗

Investigation of sex hormones in male epileptic patients.

Testosterone (T), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and prolactin (PRL) levels were obtained in 33 male epileptic patients and 11 age-matched normal controls. The patients had significantly higher mean levels of FSH, LH, and PRL; T was decreased but not significantly so. Patients who had reported difficulties with sexual arousal on the Bear-Fedio Inventory had significantly lower T levels than those who did not. Increased LH levels correlated with younger age at onset of epilepsy and longer history of tonic clonic seizures. Increased PRL levels were related to a positive family history of epilepsy and nonfocal tonic clonic seizures. Anticonvulsant levels were unrelated to hormonal changes except for carbamazepine which was positively correlated with PRL levels.

Epilepsy↗

Hypothalamic-pituitary-adrenocortical function after the dexamethasone-promethazine adhesion regimen.

Dexamethasone and promethazine are widely used as an antiadhesion regimen in infertility surgery. A major argument against the routine use of dexamethasone has been the concern that suppression of the hypothalamic-pituitary-adrenal axis may result. To investigate this concern, 25 healthy women undergoing surgery for infertility were administered dexamethasone and promethazine preoperatively, intraoperatively, and postoperatively for 48 hours. Insulin hypoglycemia testing was performed on postoperative day 6. A normal rise in cortisol of at least 7 micrograms/dl was observed in 19 of 21 women. Two women failed to achieve this rise, despite adequate hypoglycemia. Short-term suppression of the hypothalamic-pituitary-adrenal axis may occur after administration of the dexamethasone-promethazine regimen. Patients receiving this regimen should be carefully supervised during the postoperative period.

Blood Glucose↗

Heteroimmunization of squirrel monkeys (Saimiri sciureus) with a purified porcine zona antigen (PPZA): immune response and biologic activity of antiserum.

The potential for utilization as a contraceptive vaccine of a 60,000 Mr glycoprotein component, purified porcine zona antigen (PPZA), isolated from porcine zonae, was investigated in the squirrel monkey. Immunization resulted in production and maintenance of high antibody titers for at least 1 year. Comparable immune profiles were obtained using either monkey or pig zonae in assay systems, but dose-dependent variations in immune response were not observed. In situ antibody binding to monkey zonae was detected, but significantly fewer ovulated eggs were obtained from immunized monkeys than from controls. Exposure of antibody-pretreated pig, monkey, and human zonae to homologous sperm resulted in total inhibition of sperm attachment for the respective species. Thus, the contraceptive potential of PPZA antibodies in these species is demonstrated.

Animals↗

Isolation and preliminary characterization of a purified pig zona antigen (PPZA) from porcine oocytes.

A protocol was developed for isolation of a purified pig zona antigen (PPZA) under nondissociating conditions. Heating of isolated zona-encased porcine oocytes at 73 degrees C for 20 min resulted in optimal solubilization of zona antigen activity (ZAA) as assessed by radioimmunoassay. Subsequent fractionation of solubilized proteins by ammonium sulfate precipitation, ultrafiltration, gel filtration, and ion exchange chromatography yielded PPZA. Sodium dodecyl sulfate polyacrylamide gel electrophoresis of PPZA yielded a major diffuse band at 58,000 Mr which stained for protein and carbohydrate and which possessed ZAA. Two-dimensional gel electrophoresis confirmed the identity of the 58,000 Mr glycoprotein and one of the three major charge heterogeneous glycoprotein families of the porcine zona pellucida. These experiments established that the principal macromolecular and antigenic component of PPZA is a 58,000 Mr glycoprotein originating from the zona pellucida. The nature of PPZA antigenic determinants recognized by a rabbit antiserum to PPZA was studied by radioimmunoassay. ZAA of PPZA was sensitive to the action of mercaptans and proteases, indicating a contribution of polypeptide chain to PPZA antigenicity. Loss of ZAA upon periodate oxidation of PPZA also implicated carbohydrate residues. PPZA retains antigenic determinants of the intact zona pellucida as assessed by reactivity with antiserum to intact porcine zonae. Likewise, rabbit antiserum to PPZA reacts avidly with intact porcine zonae. These results demonstrate that PPZA is a suitable target antigen for further studies on immunocontraception.

Animals↗

Active immunization of mice with porcine zonae pellucidae: immune response and effect on fertility.

Female mice were heteroimmunized with varying dosages of intact and heat-solubilized porcine zonae. Mouse immune response was monitored by radioimmunoassay and the effect on mouse fertility of circulating antibodies to pig zonae was observed. Porcine zonae were a potent heteroimmunogen in the mouse and, for all dosages studied, the immune response was characterized by a rapid rise in titer, culminating in a peak which was followed by a plateau period of extended duration and of significantly high anti-zona activity. Maximum immune response was achieved using a dosage of 4000 heat-solubilized zonae per mouse. Studies involving alteration of immunization regimes, but use of a constant zonae dosage, indicated that maximal response to this antigenic target was obtained intact zonae applied over a series of injections rather than in a single application. In vitro studies involving proteolytic lysis or of sperm attachment to mouse zonae pretreated with either antibodies to mouse zonae (homologous system) or pig zonae (heterologous system) demonstrated that zona antibodies are considerably more biologically effective in the homologous system. Immunization of mice with pig zonae had no significant effect upon altering mouse fertility. The significance of these fertility results is discussed with respect to the information obtained from the in vitro studies and in respect to the continued consideration of the zona as an immunocontraceptive antigenic target.

Animals↗

Passage of zona antibodies via placenta and milk following active immunization of female mice with porcine zonae pellucidae.

Female mice heteroimmunized with heat-solubilized porcine zonae produced a significant antibody response to this immunogen as measured by radioimmunoassay (RIA) but their fertility was unaffected and normal litters were delivered. Monitoring for anti-zonae pellucidae activity in the sera of offspring from such immunized mothers by RIA indicated that the zonae antibodies were transferred from mother to young via the placenta and milk. Such transferred antibodies cross-reacted with and bound to the zonae of female offspring as demonstrated by immunofluorescent techniques. These data are significant to the future consideration of use of specific zona antigens for development of a contraceptive vaccine.

Animals↗

Comparison of intradermal pigeon crop-sac bioassay and double antibody radioimmunoassay for rat prolactin.

On an absolute basis, the intradermal pigeon crop-sac bioassay (PCA) gave results that were 20.5% higher than the radioimmunoassay (RIA) in rat anterior pituitary (AP) preparations. A highly significant correlation (r = 0.87) was obtained between RIA (in microgram) and PCA (in Reece-Turner units) when 58 medium samples obtained by culturing rat APs in vitro were assayed for prolactin (PRL) content.

Animals↗