Studies on stress-susceptibility: the relationship between serum enzyme changes and the degree of stress-susceptibility.
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Biomedical subjects
Publications and source records attributed to M V Reddy.
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Due to the non-availability of sufficient parasite material from Wuchereria bancrofti, a heterologous filarial antigen from Brugia malayi has been investigated for the diagnosis of bancroftian filariasis. B. malayi microfilarial excretory/secretory antigen (BmmfES) effectively inhibited the binding of circulating filarial antigen fractions (CFA2-1, 9, 11 and 12) from microfilaraemic cases, and of W. bancrofti microfilarial excretory/secretory antigen, to the immunoglobulin G (IgG) fraction of anti-filarial serum immunoglobulins. BmmfES was separated by ion-exchange chromatography on DEAE cellulose into 2 fractions, BmE DE1 and BmE DE2. BmE DE1 was marginally superior to whole BmmfES and BmE DE2 in detecting filarial IgG antibodies in human sera. 230 human sera from different groups of patients were screened against BmE DE1, which detected specific IgG in 83% of sera from microfilaraemic donors, 83% of sera from patients with clinical filariasis, 17% of sera from normal residents of an endemic area, and in none of the sera from persons living in a non-endemic area. The assay system using BmE DE1, with a sensitivity of 83% and specificity of 83%, should be very useful in detecting microfilaraemia, particularly in active clinical infections where the parasite is usually not seen.
Proteins secreted into the culture medium by Mycobacterium tuberculosis are shown to be a source of antigens of immunodiagnostic importance. In our earlier study, we had reported a 31-37 kDa seroreactive gel-eluted antigenic fraction (ESAS-7), isolated from culture filtrate proteins of Mycobacterium tuberculosis H37Ra. In this report, we describe further purification of excretory-secretory ESAS-7 antigen fraction by fast protein liquid chromatography (FPLC) on Resource 'S' cation-exchange column and isolation of a more active and purified protein antigen fraction ESAS-7F. ESAS-7F antigen was characterized as a 31 kDa molecular weight glycoprotein containing a metallo-serine protease activity. N-terminal sequence analysis showed the first five amino acids as NTGQS (Asp-Thr-Gly-Glu-Ser). The present study helped in the isolation of a well characterized 31 kDa mycobacterial glycoprotein antigen with protease activity and diagnostic potential in detection of tuberculosis infection.
Twelve normal healthy volunteers (6 males and 6 females) undergoing yoga training for 90 days were studied for the effect of yoga on exercise tolerance. Their ages ranged from 18 to 28 years. The volunteers were taught only Pranayama for the first 20 days and later on yogic asanas were added. Sub-maximal exercise tolerance test was done on a motorized treadmill by using Balke's modified protocol, initially, after 20 days (Phase-I) and after 90 days of yoga training (Phase-II). Pyruvate and lactate in venous blood and blood gases in capillary blood were estimated immediately before and after the exercise. Minute ventilation and oxygen consumption were estimated before and during the test. Post exercise blood lactate was elevated significantly during initial and Phase-I, but not in Phase-II. There was significant reduction of minute ventilation and oxygen consumption only in males in Phase-I and II at the time when the volunteers reached their 80% of the predicted heart rate. Female volunteers were able to go to higher loads of exercise in Phase-I and II.
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O6-Benzyl-2'-deoxyguanosine (O6-BzldGuo) was found to be a potent inhibitor of O6-methylguanine-DNA methyltransferase (MGMT) activity in vivo, despite its demonstrated lower activity compared to O6-benzylguanine (O6-BzlGua) for inactivation of MGMT in cell cultures or cell free extracts. This difference is probably due to metabolism and possibly to enhanced systemic availability of O6-BzldGuo compared to O6-BzlGua in animals. At doses above 50 mg/kg, O6-BzldGuo completely suppresses the MGMT activity in liver, lung and brain for 12 to 18 hrs following treatment. However, it fails to suppress the activity in jejunum and possibly in other tissues with low blood perfusion rates. O6-BzldGuo is metabolized mainly in the liver, and possibly in kidney and lung, to yield the more potent MGMT inhibitors O6-BzlGua and O6-Benzyl-7,8-dihydro-8-oxoguanine (O6-Bzl(8-OX)Gua), that reach maximum levels following the decline of the parent compound both in tissues and the circulation. Although O6-BzldGuo may cause the initial drop of MGMT activity, continued prolonged suppression is likely due to the persistence of its MGMT-inhibiting metabolites. Severe suppression of MGMT activity and the presence of O6-BzldGuo and its metabolites in the brain indicates that this inhibitor crosses the blood-brain barrier. Prolonged suppression of MGMT in brain following a complete disappearance of the parent compound from the tissue also demonstrates the importance of metabolites in MGMT suppression. Such metabolites, especially O6-Bzl(8-OX)Gua, appear to accumulate in brain, possibly due to their hydrophobic nature. Accumulation of the parent compound in the pancreatic ducts may explain the unusual high concentrations of this compound in pancreas as compared to the spleen. Similarly, high concentrations of O6-BzldGuo in kidneys may be related to accumulation of the compound in proximal tubules and its poor reabsorption into the circulation. Overall, O6-BzldGuo shows tissue specificity which is modulated by dose. Such specificity seems to be related to accumulation of the parent compound in certain tissues, but more importantly, to site-specific metabolism and the persistence of MGMT inhibitory metabolites in these tissues. The combination of enhanced systemic availability and site specific metabolic activation and/or inactivation of O6-BzldGuo may be related to the enhanced antitumor therapeutic index against human tumor xenografts for this compound which equals or even exceeds that of O6-BzlGua.