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Biomedical subjects

P K Ghosh

Publications and source records attributed to P K Ghosh.

At least 19 recordsLinked to original sources

Somatotropic and lactotropic receptors in transgenic mice expressing human or bovine growth hormone genes.

The somatotropic and lactotropic receptors were studied in liver microsomal preparations from transgenic mice carrying the human growth hormone (hGH) or bovine growth hormone (bGH) gene fused to mouse metallothionein-I (MT) or phosphoenolpyruvate carboxykinase promoter/regulator (PEPCK). Specificity studies indicated that, similarly to normal mice, liver microsomes from the transgenic animals possess a mixed population of somatotropic and lactotropic binding sites. In transgenic animals of both sexes, the binding capacity of somatotropic receptors was significantly increased without corresponding changes in affinity. Expression of the MT-hGH hybrid gene was associated with the induction of somatotropic receptors which was approximately twice as great as that measured in animals expressing the MT-bGH hybrid gene. The binding capacity of lactotropic receptors in liver microsomes (quantitated by the use of labelled ovine prolactin) was increased 2-3 fold in transgenic females and approximately 10-fold in transgenic males as compared to the respective normal controls. We conclude that lifelong excess of GH up-regulates hepatic GH and prolactin receptors, and that lactogenic activity of GH is not essential for induction of prolactin receptors in the liver of transgenic mice.

Animals

Early evidence of beneficial effects of chordal preservation in mitral valve replacement on left ventricular dimensions.

Earlier authors have shown the improved left ventricular (LV) function after chordae-preserving mitral valve replacement (MVR) in follow-up studies. Seventy-nine consecutive patients undergoing MVR were studied preoperatively and pre-discharge with M-mode and two-dimensional Color Doppler echocardiography for early LV morphometric changes. Conventional MVR was performed in 42 patients (Group 1) and the posterior leaflet-chordae-papillary muscle complex was preserved in 37 patients (Group 2). Both cohorts were similar in age, sex, preoperative NYHA class and valve pathology. Four St. Jude bioprostheses, 9 Medtronic and 66 Sorin prostheses were implanted. The intraoperative and perioperative management protocol was uniform for both groups. The median left atrial dimension in both groups decreased to better physiological levels (53 to 46 mm in group 1, 52.5 to 46 mm in group 2). The median LV enddiastolic dimension increased from 47 to 48 mm in group 1 while it decreased from 56.5 to 49 min in group 2. The median LV endsystolic dimension remained unchanged in group 1 but decreased in group 2 (37.6 to 36 mm). Echocardiographic documentation of such early changes in the LV dimensions after modified MVR indicates that the beneficial effects of chordal preservation become evident early in the postoperative period and may explain the improved perioperative LV function after modified MVR compared to conventional MVR.

Adolescent

Epidemiological study of the victims of vehicular accidents in Delhi.

The mortality and morbidity connected with road traffic accidents are increasing at an alarming rate throughout the world as a direct result of the rapid industrialization and increase of fast moving vehicles combined with lack of traffic sense of road users of this country. Epidemiological aspects manifested in vehicular accidents in New Delhi during the year 1983-84 are illustrated here.

Accidents, Traffic

Coronary ostial reconstruction: technical issues.

Coronary ostial reconstruction may be the preferred alternative to reestablish antegrade myocardial revascularization in patients with isolated ostial stenosis. The technical steps of reconstruction are described. The ultrasonic aspirator is a helpful implement in the dissection of the left main and the proximal right coronary arteries. Satisfactory results of coronary ostial reconstruction in the current era seem to fulfill its promise.

Coronary Disease

Effect of lithium chloride on spermatogenesis and testicular steroidogenesis in mature albino rats: duration dependent response.

Quantitative evaluation of the different varieties of germ cells at stage VII of the seminiferous epithelium cycle, namely type-A spermatogonia (ASg), preleptotene spermatocytes (pLSc), midpachytene spermatocytes (mPSc) and step 7 spermatids (7 Sd) along with Leydig cell nuclear area (LCNA) and radioimmunoassay of plasma levels of gonadotropins (FSH and LH), prolactin (PRL) and testosterone (T), activities of testicular, delta 5-3 beta hydroxysteroid dehydrogenase (delta 5-3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) were measured in mature rats of the Wistar strain following treatment with lithium chloride at a dose of 200 ug/100 g body wt/day for 7,14 and 21 days. A remarkable reduction in plasma levels of FSH (P less than 0.001), LH (P less than 0.05, P less than 0.01), PRL (P less than 0.05, P less than 0.001) and T (P less than 0.001) along with significant diminution in the activities of testicular delta 5-3 beta-HSD (P less than 0.001) and 17 beta-HSD (P less than 0.001) were observed following lithium treatment for 14 and 21 days. 21 days of treatment also resulted a marked degree of degeneration of ASg (P less than 0.05) and 7Sd(P less than 0.001) at stage VII but 14 days of treatment did not exhibited any significant effect on testicular gametogenesis. LCNA was decreased after lithium chloride treatment for 14 and 21 days (P less than 0.001). 7 days of treatment did not exert any notable result in the above parameters. The results of our experiment suggest that duration of lithium treatment is the critical factor for its adverse effects on testicular activity when the plasma levels of lithium remain within the therapeutic range. The possibility of an indirect action of lithium at the level of the testes is also discussed. Hence the data of our experiments have potential clinical implication.

17-Hydroxysteroid Dehydrogenases

Possible involvement of hypothalamic monoamines in mediating the action of alpha-2u-globulin on the pituitary-testicular axis in rats.

A major androgen-dependent urinary protein of male rodents, alpha 2u-globulin, has been shown to influence adenohypophyseal hormone release. In an attempt to elucidate the mechanisms of its action, we have examined several parameters of hypothalamic and pituitary function in adult male rats treated for 2 weeks with two injections daily of 0.75 mg alpha 2u-globulin and sacrificed 16 h after the last injection. This treatment led to an increase in plasma luteinizing hormone levels, a decrease in plasma prolactin levels, an increase in testosterone concentrations in both plasma and testicular tissue, and increases in testicular weights. The norepinephrine turnover in median eminence and anterior hypothalamus was increased in alpha 2u-globulin-injected animals, while the norepinephrine turnover in the remaining medial basal hypothalamus was reduced. alpha 2u-Globulin-treated animals had a significantly decreased dopamine turnover in the anterior hypothalamus, while in the medial basal hypothalamus the dopamine metabolism was increased. These data suggest that alpha 2u-globulin-induced changes in gonadotropin and prolactin secretion are mediated by changes in catecholamine metabolism in several hypothalamic regions. Increased testosterone secretion appears to be due to increased secretion of gonadotropins from the pituitary.

Alpha-Globulins

Elevated corticosterone levels in transgenic mice expressing human or bovine growth hormone genes.

Ectopic expression of human or bovine growth hormone (GH) genes in 6 lines of transgenic mice was associated with a significant increase in plasma corticosterone levels. Elevated corticosterone levels were detected in both sexes under basal conditions and after ether stress. The adrenal activity of 3 beta-hydroxysteroid dehydrogenase was measured in two of these lines and was found to be significantly increased in transgenic animals. Plasma corticosterone levels in transgenic mice did not correlate with known differences between the various lines in male and female fertility or in the life span.

3-Hydroxysteroid Dehydrogenases

Effect of immunoneutralization of neuropeptide Y on gonadotropin and prolactin secretion in normal mice and in transgenic mice bearing bovine growth hormone gene.

Immunoneutralization of endogenous neuropeptide Y (NPY) with specific antibodies was used to evaluate the possible physiological role of this neuropeptide in the regulation of gonadotropin and PRL secretion in the mouse. Because regulation of anterior pituitary function can be profoundly altered by chronic GH excess, we felt it was also of interest to have examined the effects of immunoneutralization of NPY in transgenic mice expressing bovine (b) GH gene with mouse metallothionein-I promotor. Intact or castrated transgenic and normal (nontransgenic) littermate adult male mice were injected with control rabbit serum or anti-NPY rabbit serum (anti-NPY). Blood samples were obtained 24 h later for hormone measurements. In intact transgenic mice expressing bGH gene, plasma LH levels were reduced and plasma PRL levels were increased, as compared to their normal littermates. Plasma levels of FSH were similar in normal and transgenic animals. Injection of anti-NPY increased plasma LH levels significantly in both intact normal and intact transgenic mice. However, plasma levels of FSH and PRL were increased significantly after anti-NPY treatment only in intact normal mice. In both normal and transgenic males, castration lead to the expected increase in plasma FSH and LH levels, whereas plasma levels of PRL remained unaltered. Administration of anti-NPY to castrated animals was followed by a significant increase in circulating LH levels in both transgenic and normal mice, whereas plasma levels of PRL were not changed. The results suggest that NPY plays a physiological role in the control of gonadotropin and PRL release in the adult male mouse, and that expression of the bGH gene in transgenic mice is associated with altered role of endogenous NPY in the control of pituitary function.

Animals

Effect of lithium chloride on testicular steroidogenesis and gametogenesis in immature male rats.

The present study was performed on immature male rats aged 35 days. Subcutaneous injections of lithium chloride at a daily dose of 2.0 mg/kg for 15 days resulted in significant inhibition of spermatogenesis at stage VII of the seminiferous epithelial cycle. Spermatogonia A, preleptotene spermatocytes and step 7 spermatids were decreased in number in comparison to controls. Serum levels of FSH, LH, PRL, and testosterone were decreased. Activities of testicular delta 5-3 beta-hydroxysteroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase were suppressed along with a low caudal epididymal sperm count in comparison with controls. When the treatment was prolonged for 20 and 25 days, it showed an additional significant diminution in accessory sex organ weights and number of midpachytene spermatocytes at stage VII in comparison to control animals of corresponding age. It is concluded that lithium has an adverse effect on testicular function in immature rats by reducing serum levels of FSH, LH, PRL, and testosterone. Furthermore, since hormonal changes and altered spermatogenic activities were evident when the serum concentration of lithium was within the therapeutic range, our data may have some potential clinical implications.

17-Hydroxysteroid Dehydrogenases

Studies on the effect of prolactin treatment on testicular steroidogenesis and gametogenesis in lithium-treated rats.

The effect of PRL supplementation in lithium-treated rats on spermatogenesis, testicular delta 5-3 beta-hydroxysteroid dehydrogenase and 17 beta-hydroxysteroid dehydrogenase activities, and serum levels of FSH, LH, PRL and testosterone were studied on the 22nd day of the experiment. Subcutaneous injections of lithium chloride at a dose of 2.0 mg.kg-1.day-1 for 21 days resulted in a significant inhibition of spermatogenesis at stage VII of the seminiferous epithelial cycle, along with remarkable diminution of serum levels of the above hormones and suppression of the activities of the above two testicular steroidogenic enzymes. Administration of bovine PRL at a dose of 0.25 mg.kg-1.day-1 plus lithium treatment resulted in a remarkable protection of spermatogenic and steroidogenic activities of the testes, along with restoration of serum levels of FSH and testosterone. It is concluded that PRL can markedly protect the testicular dysfunction induced by lithium chloride treatment in rats.

17-Hydroxysteroid Dehydrogenases

Changes in the testicular acid and alkaline phosphatase activities at different durations following prostatectomy: a correlative study with spermatogenesis.

The purpose of this investigation was to make a correlative study between spermatogenesis and testicular acid and alkaline phosphatase activities in mature prostatectomized animals at different post-operative periods. The results demonstrate that there was a significant augmentation in the activity of testicular acid and alkaline phosphatases subsequent to 14 and 21 days of prostatectomy. A parallel quantitative study of spermatogenesis at stage VII of the seminiferous cycle, namely, type A spermatogonia (ASg), preleptotene spermatocytes (pLSc), mid-pachytene spermatocytes (mPSc) and step 7 spermatids (7sd), revealed that there was a significant reduction in the number of step 7 spermatids after 14 and 21 days. No change was observed in the above testicular enzymes and spermatogenesis after 7 days of prostatectomy. Therefore, it is concluded that prostatectomy can alter the above testicular enzyme activities and spermatogenesis in chronic prostatectomized state.

Acid Phosphatase

Effects of a major androgen-dependent urinary protein, alpha 2u-globulin on the pituitary-gonadal axis and hypothalamic monoamines in adult male mice.

The purpose of the present study was to evaluate the effects of alpha-2u-globulin, a sex-dependent male rat urinary protein on pituitary-gonadal functions and hypothalamic monoamine contents in male mice. Adult male mice, maintained under standardized laboratory conditions (L:D, 14:10) were injected subcutaneously with alpha-2u-globulin at a dose of 1 mg/animal/day or with vehicle daily for 14 days and killed 16 h after the last injection. Plasma levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T) and testicular levels of T were measured by radioimmunoassays. The concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) in medial basal hypothalamus (MBH) and anterior hypothalamus (AH) were measured by high performance liquid chromatography. Administration of alpha-2u-globulin led to a significant increase in plasma FSH and LH levels (P less than 0.05) as well as in plasma and testicular T levels (P less than 0.025). In the MBH of alpha-2u-globulin treated mice, there were significant elevations of NE (P less than 0.025), DA (P less than 0.01) and 5-HT (P less than 0.025) contents. In the AH, both DA (P less than 0.025) and 5-HT (P less than 0.01) contents were decreased while NE content remained unaltered. These results indicate that administration of alpha-2u-globulin can lead to a significant stimulation of pituitary-testicular axis and that this effect may be mediated through alteration of hypothalamic monoamines.

Alpha-Globulins

Effect of dihydrotestosterone on serum concentrations of alpha 2u-globulin and on spermatogenesis in melatonin-treated rats.

Adult male rats were given s.c. injections of melatonin (400 micrograms/100 g body weight per day) for 14 days. On day 15, the weights of the testis and accessory sex organs were less, testicular 17 beta-hydroxysteroid dehydrogenase (17 beta-HSD) activity was inhibited, spermatogenesis was suppressed and serum levels of gonadotrophins, testosterone and alpha 2u-globulin were decreased compared with control animals injected with vehicle. In a third group of rats given the same dose of melatonin for 14 days, administration of dihydrotestosterone (DHT) at a dose of 25 micrograms/100 g body weight per day on days 8-14 resulted in serum levels of alpha 2u-globulin, FSH, LH and testosterone and testicular 17 beta-HSD activity similar to those seen in vehicle-injected control animals. Weights of the testes and accessory sex organs and spermatogenesis were normal after administration of DHT in melatonin-treated rats. In another group of rats, the depressive effects of melatonin treatment on plasma gonadotrophins were reversed by the administration of alpha 2u-globulin on days 8-14. It was concluded that treatment with DHT prevents the depressive action of melatonin on testicular function by inducing the synthesis of alpha 2u-globulin.

17-Hydroxysteroid Dehydrogenases

Effect of lithium chloride on adrenocortical activity in male rats: evidence of dose and duration dependent response.

Changes in the adrenal weight, adrenal 5-ene-3 beta-hydroxysteroid dehydrogenase (5-ene-3 beta-HSD) activity and serum levels of corticosterone were observed in male wistar rats after the treatment of lithium chloride in the doses of 100, 200 and 400 micrograms/100 g of body weight/day for 7, 14 and 21 days. The experiments indicate that 200 and 400 micrograms/100 g.b.w. administered for 14 and 21 days caused a significant stimulation in the activities of adrenal 5-ene-3 beta-HSD along with elevation of adrenal weights and serum levels of corticosterone. 100 micrograms of lithium chloride was not able to modulate the adrenal activity. Moreover, plasma levels of lithium remain in therapeutic range in this experiment at the doses of 200 and 400 micrograms/100 g body weight. Therefore, our data suggest that lithium can alter the adrenal activity within its therapeutic range according to the duration of treatment.

3-Hydroxysteroid Dehydrogenases

Direct effects of lithium chloride on testicular delta 5-3 beta and 17 beta-hydroxysteroid dehydrogenase activities in the rat--in vitro study.

Testicular delta 5-3 beta- and 17 beta-hydroxysteroid dehydrogenase (delta 5-3 beta- and 17 beta-HSD) activities of rat are inhibited in vitro by a wide range of lithium concentration. The inhibitory effects of lithium are evident at a concentration of 2.5 mM which is easily achieved during the treatment of acute manic patients with lithium. This suggests that lithium exerts a direct inhibitory effect on testicular hydroxysteroid dehydrogenase activities.

17-Hydroxysteroid Dehydrogenases

Lateral asymmetry of constitutive heterochromatin in human chromosomes.

Variations in lateral asymmetry of constitutive heterochromatin were studied in 30 normal individuals with reference to the chromosomal regions 1q12, 9q12, 15p11, 16q12 and Yq12. The technique consisted of growing human lymphocytes for one cell cycle in BrdU, staining with 33258 Hoechst, exposing them to UV light, treating them with 2 x SSC, and staining with Giemsa. This procedure revealed asymmetric staining in the region of constitutive heterochromatin in these chromosomal regions. Chromosomes 15, 16, and Y showed simple lateral asymmetry, whereas chromosome 1 showed both simple and compound asymmetry. In 15 cases, compound lateral asymmetry was evident in both homologues of chromosome 1, 12 cases showed compound lateral asymmetry in one homologue and simple lateral asymmetry in both the homologues. The centromere region of chromosome 9 stained symmetrically with this technique. The lateral asymmetry is presumed to reflect the strand bias in the distribution of thymine in satellite DNA fractions.

Bromodeoxyuridine

Reduced frequency of sister chromatid exchanges in human lymphocytes cultured with autologous serum.

The incidence of sister chromatid exchange (SCE) was determined in human lymphocytes cultured with fetal calf, human AB, and autologous serum. In each individual studied, cells grown in medium supplemented with fetal calf and human AB serum showed higher yields of SCE than those cultured with autologous serum. Increased concentration of fetal calf and human AB serum in the tissue culture medium resulted in elevated frequency of SCE. No such elevation in SCE frequency was observed with increased concentration of autologous serum. The results indicate the presence of extraneous SCE-inducing factors in fetal calf and human AB serum, the nature of which is not precisely known.

Animals