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Biomedical subjects

M K Sharma

Publications and source records attributed to M K Sharma.

At least 19 recordsLinked to original sources

Modulation of pituitary gonadotropins and prolactin secretion by testosterone in vitro.

Investigations were undertaken to study the differential modulation of LH, FSH and PRL secretion by testosterone (T) using whole pituitary (PI) or pituitary-hypothalamus coincubates (PHC) as in vitro constructs. PI and PHC from intact and castrated rats were incubated with or without T thrice, for 24 h each, (24 h x 3, total incubation period 72 h). The spent media was replenished every 24 h. At the end of 72 h, a few of the pituitary glands were challenged with 10 nM LHRH for 4 h. The spent media and pituitary glands were analyzed for LH, FSH and PRL using specific RIAs. Incubation of PI or PHC from intact rats with T stimulated the release of LH and FSH but inhibited the release of PRL. T had no effect on the intrapituitary contents of LH but inhibited intrapituitary contents of FSH and PRL, as compared to controls incubated without T. Castration increased intrapituitary contents of LH and FSH with concomitant decrease in PRL levels. Incubation of PI or PHC from castrated rats with T inhibited intrapituitary contents of LH to intact pituitary levels, while PRL levels were further reduced instead of being ameliorated. It is concluded that PI or PHC can be used as convenient in vitro models to monitor the effect of castration or of T modulation of pituitary and hypothalamus functions. T does not affect the synthesis of LH at the gonadotroph level but facilitates the regulation of intracellular LH and FSH levels. It is postulated that T inhibits the synthesis of FSH/PRL at the gonadotroph/lactotroph levels.

Animals

Detection of paradoxical cerebral echo contrast embolization by transcranial Doppler ultrasound.

Contrast echocardiography has been shown to be a sensitive method for detecting patent foramen ovale in embolic stroke, implying paradoxical embolization. However, not all two-dimensional echocardiographic studies are of diagnostic quality, and direct evidence for paradoxical cerebral embolization remains lacking. We addressed these problems by simultaneously using transcranial Doppler ultrasound and contrast echocardiography to compare relative sensitivity and concordance in the detection of right-to-left vascular shunting. Forty-six patients with stroke, transient neurologic defect, or question of atrial septal defect underwent study at rest and during Valsalva strain. Two-dimensional echocardiography detected shunting in 26% at rest and 15% during Valsalva strain, whereas transcranial Doppler study returned rates of 41% and 41%, respectively. Concordance was 82% and 75%, respectively. Discordant studies almost always had evidence of paradoxical contrast embolization by transcranial Doppler and intermediate findings by two-dimensional echocardiography. Transcranial Doppler is a sensitive, unambiguous technique for the detection of anatomic substrates and target organ involvement in patients suspected to have paradoxical cerebral embolization.

Adult

Circulating immune complexes in pre-eclampsia.

Serum samples from 20 non-pregnant women, 30 women with normal pregnancy and 50 women with pregnancy associated with pre-eclampsia were tested for circulating immune complexes using the polyethyleneglycol precipitation method. A highly significant positive correlation was found between circulating immune complexes and severe pre-eclampsia (BP greater than 140/90 mm Hg, albuminuria greater than 0.25 g/l). In contrast to this the difference in immune complex levels between non-pregnant subject, normal pregnancy cases and patients with mild pre-eclampsia was not statistically significant. A significant positive correlation was found between the level of circulating immune complexes and the severity of albuminuria. These findings suggest that circulating immune complexes, though not seeming to play an aetiological role in pre-eclampsia may very well be involved in its pathogenesis.

Antigen-Antibody Complex

Long-term bepridil monotherapy for angina pectoris.

The long-term efficacy of bepridil as once-a-day monotherapy was studied in 19 men with stable angina pectoris. After 2 weeks of single-blind placebo therapy and a 12-week parallel placebo-controlled, dose-response study, each patient received open-label bepridil. After a dose-titration period of 3 months, patients received bepridil (100 to 400 mg once a day, mean 290 mg) for 24 months. The response to treatment was assessed by patient diaries and serial treadmill exercise testing 24 hours after dose administration, every 3 months. Only 2 patients were released from the study due to therapeutic failure. Compared with placebo, 3 months of bepridil therapy resulted in a significant reduction in the weekly frequency of angina from 10.3 +/- 9.1 to 1.8 +/- 3.5 (p less than 0.002) and nitroglycerin consumption from 5.0 +/- 5.4 to 1.4 +/- 2.3 (p less than 0.01). In addition, there was a simultaneous significant increase in the walking time to angina from 5.2 +/- 2.3 to 7.9 +/- 2.6 minutes (p less than 0.001) and total exercise time from 7.1 +/- 2.2 to 8.8 +/- 1.9 minutes (p less than 0.001). These favorable effects were sustained throughout the 24 months of the study. Although resting QTc interval was prolonged by 36 to 42 ms (p less than 0.001) during bepridil therapy, ventricular dysrhythmias were not observed immediately before or during exercise testing and were not manifested by symptoms. Neurologic and gastrointestinal side effects of mild to moderate severity were observed, but none required discontinuation of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Cell-mediated immunity in professional and voluntary blood donors.

Cell-mediated immunity (CMI) was compared in professional and voluntary blood donors. Depressed CMI in professional donors was revealed by the presence of significantly lower numbers of positive delayed reactive hypersensitivity responses to Candida albicans, streptokinase and streptodornase, as well as a decrease in lymphoblast transformation response to phytohaemagglutinin. Furthermore, the serum protein and albumin levels in professional donors did not correlate with the depression in CMI. The blood of professional blood donors should be considered to be a poor source of therapeutic immune cell fractions.

Adult

Professional and voluntary blood: a preliminary study in Iran.

Among professional and voluntary blood donors in Tehran HBsAg carriers and RPR positives were found more frequently in the former group. The levels of haemoglobin, serum total protein and serum immunoglobulins G, A and M were significantly lower in commercial blood. Measurement of transferrin saturation showed that one-third of professional donors were quite severely iron deficient. For fractionation purposes the maximum theoretical yield from commercial plasma is 16% less IgG than from plasma of voluntary donors, 21% less total immunoglobulins and 20% less albumin.

Blood Donors

In vitro suppression of lymphocyte blastogenic response to mitogen and antigen by Leishmania tropica.

Cell-mediated immune (CMI) responses are important in the immunity against Leishmania spp. infection in man. However, an infection continues to persist for a limited or indefinite period of time in spite of demonstrable CMI. The factors which allow the infection to persist in the presence of the CMI are hitherto unknown. Evidence is presented here that Leishmania tropica or their products suppress the in vitro proliferative response of normal human lymphocytes to mitogen and specific antigens. The suppressive effect of L. tropica is neither due to a direct toxic action on lymphocytes nor to competition for nutrients or antigens. In vivo such an immunosuppressive effect could both facilitate macrophage parasitization and the intracellular survival of L. tropica, even after the CMI develops to processed L. tropica antigen. Persistence of infection is seen in many other bacterial, viral and fungal infections. The in vitro suppressive effect of L. tropica on the immune response observed in our study therefore becomes relevant to the understanding of the host-parasite interaction, which may determine the eventual outcome of infection in many other intracellular infections.

Animals

Specificity of transfer factor. In vitro lymphoblast transformation of peripheral lymphocytes to Leishmania major antigen in the presence of transfer factor.

The in vivo and in vitro demonstration of specificity of transfer factor (TF) has so far been hampered by lack of a suitable antigen. The host partiality of Leishmania suggested that in the case of leishmania antigen it should be possible to obtain lymphocytes of both donors and recipients of TF which were either sensitized or truly virgin. Lymphoblast transformation of normal donor lymphocytes to leishmania major antigen (LMA) was therefore measured in the presence of TF prepared from donors with a history of cutaneous leishmania infection (LSTFd) and normal donors (NSTFd). A clear augmentation of the lymphoblast transformation equal to that usually seen when lymphocytes from sensitized individuals are exposed to LMA was observed with LSTFd. An insignificant increase in lymphoblast transformation, however, occurred when NSTFd was used together with LMA and when LSTFd or NSTFd was used alone. The results, although limited by the number of TF preparations, tested, clearly substantiate the in vitro specificity of TF.

Antigens