Biomedical subjects
Publications and source records attributed to B Singh.
The study investigated the possible involvement of serotonin in the medial preoptic area in the regulation of sexual behavior of male rats. Injection of serotonin in the medial preoptic area resulted in an inhibition, whereas cyproheptadine (a serotonin antagonist) produced a slight facilitation, of male sexual behavior.
Previous studies have shown that vimentin, an intermediate filament protein, is reduced in amount in cells acutely infected with Moloney mouse sarcoma virus (Mo-MuSV). In this report, we provide evidence for specific alteration of vimentin in Mo-MuSV-transformed cells and demonstrate specific phosphorylation of vimentin by the p37mos protein kinase in vitro. Specificity of the phosphorylation reaction was demonstrated by using viral mos proteins encoded by various isolates of Mo-MuSV and p37mos produced in yeast. A phosphotransfer domain mutant lacking the ability to autophosphorylate p37mos failed to phosphorylate vimentin. Similarly, vimentin was not phosphorylated by the temperature-sensitive P85gag-mos kinase derived from infected cells maintained at the restrictive temperature. In ts110 MuSV-transformed NRK cells, vimentin was phosphorylated at both the permissive and nonpermissive temperatures for transformation. However, at the permissive temperature, an altered form of vimentin (about 50 kDa) with a more basic isoelectric point and lower apparent molecular weight was detected. This 50-kDa product was highly phosphorylated as compared to the bulk of the normal 55-kDa form of vimentin. On the basis of its mobility in two-dimensional gels, the 50-kDa form of vimentin should lack the carboxy terminus. This type of alteration could conceivably modulate the function of vimentin filaments in the transformed cell.
Desferrioxamine mesylate (desferal) an iron chelating agent was investigated in anaesthetized standard haemorrhagic shock (HS) dogs with elective hypotension at 35 +/- 5 mmHg for 4 h and return of withdrawn blood (ROWB) thereafter. Observations were made in respect of serum iron elevation over 4 h and survival and recovery pattern over 72 h after ROWB. Influence of the drug on histopathological changes of shock in liver were studied in non-survival experiments (dogs sacrificed after 4 h of elective hypotension). Desferal administration (25 mg/kg i.m.) at 30 min after initial bleeding, increased the 72 h survival from 10% (controls) to 50%, and reduced the serum iron elevation from 63.3% (controls) to 9.44%. The single control survivor remained unconscious till 24 h and sluggish in activity up to 72 h. Three of the drug treated survivors regained consciousness by 2 h, activity by 24 h and all were normally active by 72 h. Severe congestive and degenerative changes in liver, present in the controls, were markedly reduced in severity and incidence in those given desferal. It is suggested that iron decompartmentalization in the hypoxic tissues in HS with its consequent rise in serum and intracellular pool, plays a pivotal role in progression towards irreversibility. Desferal, an effective intracellular iron chelator, possibly arrests the widespread cellular damage caused through enhanced iron-catalysed .OH radical generation in shock state.
The influence of the ascending reticular activating system (ARAS) on the medial preoptic unit activity was studied in urethane anesthetized rats. Alterations in the unit activity were also correlated with cortical EEG changes. A fourth of the medial preoptic units showed alterations in their discharges with cortical EEG changes. These units were also influenced by high frequency stimulation of ARAS, which simultaneously produced EEG desynchronization. On the other hand they were generally not influenced by 1 Hz stimulation of ARAS. These results indicate that the anatomically demonstrated projections from midbrain (forming ARAS), involving very few synapses, may not be involved in the regulation of sleep-wakeful function of the medial preoptic area. Interaction of some of the inputs at the medial preoptic area is discussed.
Anti-inflammatory studies were conducted on an ethanol extract of Echinops echinatus whole plant. The extract effectively inhibited the acute inflammation induced in rats by carrageenan, formaldehyde and adjuvant and the chronic arthritis induced by formaldehyde and adjuvant. The extract was more effective parenterally than orally. The toxicity studies showed reasonable safety warranting further studies.
An alcoholic extract of Zizyphus sativa leaves was tested for hypoglycemic activity in normal and alloxan-diabetic rats. Single (100-400 mg/kg) oral doses of extract to normal animals showed a dose-dependent statistically significant lowering of blood glucose 2, 4 and 6 h later. The effect was most pronounced at 6 h with blood glucose returning to control values at 24 h. In alloxan-diabetic rats, no significant effect was observed with extract and tolbutamide. The minimum lethal dose was greater than 3000 mg/kg, orally in mice.
Mannitol has been labeled with 99mTc by using cuprous chloride as a reducing agent. Blood and kidney clearance of 99mTc(Cu)-mannitol was slightly faster than that of 99mTc(Sn)-DPTA in rat and maximum radioactivity ratio of kidneys to blood was 84.6 at 5 min. A comparative study of 99mTc(Cu)-mannitol, 99mTc(Sn)-DTPA was made in rabbits by taking serial images of kidneys and bladder with a gamma camera. Results show superiority of 99mTc(Cu)-mannitol over other agents for dynamic renal function studies.
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The complete cDNA for a human mitochondrial protein designated P1, which was previously identified as a microtubule-related protein, has been cloned and sequenced. The deduced amino acid sequence of P1 shows strong homology (40 to 50% identical residues and an additional 20% conservative replacements) to the 65-kilodalton major antigen of mycobacteria, to the GroEL protein of Escherichia coli, and to the ribulose 1,5-bisphosphate carboxylase-oxygenase (rubisco) subunit binding protein of plant chloroplasts. Similar to the case with the latter two proteins, which have been shown to act as chaperonins in the posttranslational assembly of oligomeric protein structures, it is suggested that P1 may play a similar role in mammalian cells. The observed high degree of homology between human P1 and mycobacterial antigen also suggests the possible involvement of this protein in certain autoimmune diseases.
The authors determined the prevalence of mental illness in 382 people representative of the occupants of shelters for the homeless and cheap single-room accommodations in inner-city areas of Melbourne. Clinicians were trained to use a standardized diagnostic instrument, the Structured Clinical Interview for DSM-III-R, to diagnose a range of severe mental disorders, including psychotic, affective, and substance-related disorders. Almost half the people interviewed received diagnoses of current disorders, and over 70% received lifetime diagnoses. There was considerable comorbidity. Many factors are likely to contribute to the concentration of people with mental disorders in such homeless and disaffiliated groups.
A community-based study in northern Natal/KwaZulu, South Africa, assessed the prevalence of hepatitis B virus (HBV) infection in rural Black adults. The prevalence of HBV carriers was 4.4 percent in women (N = 342) and 7.1 percent in men (N = 99). At least one marker of HBV infection was present in 81 percent of women and 86 percent of men. The relative risk (RR) of HBV marker positivity in women due to scarification, adjusted for the presence of pierced ears, was 1.37 (95% CI = 0.9, 2.1). Risk factors such as scarification and pierced earlobes need to be further investigated to assess their role in the transmission of the HBV.
Candida Kefyr cells and their spheroplasts grown in media enriched with choline, N,N'-dimethylethanolamine (DMEA) or ethanolamine (EA) showed decreased concanavalin A (Con A) and ph to hemagglutinin (PHA) mediated agglutination while supplementation with N-monomethylethanolamine (MMEA) increased PHA-mediated agglutination. In all cases, the amount of phospholipid was increased and, consequently, a decrease in the free sterol; phospholipid ratio was observed except in the case of MMEA where this ratio remained almost unchanged. In the cells grown in media enriched with choline. DMEA or MMEA, but not in the EA-supplemented medium, the phosphatidylcholine to phosphatidylethanolamine ratio was increased. Saturation of fatty acids as well as their chain length decreased, which could lead to increased membrane fluidity. No breakpoint in Arrhenius plots of Mg2+ -ATPase of the choline-supplmented cells was observed. Cells grown in media enriched with EA and MMEA did not show any sharp break in Arrhenius plots of Mg2+ -ATPase.
Rapid eye movement sleep deprivation for 3 to 4 days by the platform pedestal procedure produced an increase in sexual behaviour of male rats. The possible factors contributing towards the increase in sexual behaviour are discussed.
The lengths of the tendons and muscle belly connective tissue envelopes of the knee flexor muscles of 6 healthy and 11 children with cerebral palsy were measured. The restricted passive knee extension was found to be associated with abnormally short tendons in all cases of contracture. This correlation provided an experimental support for the surgical lengthening of the tendon.
Short-term (two weeks) feeding of isocaloric diets supplemented with polyunsaturated fatty acids (PUFA) is useful for the prevention or treatment of the enhanced uptake of glucose which occurs in rats with streptozotocin-induced diabetes, as compared with animals fed a diet supplemented with saturated fatty acids (SFA). The study was undertaken to compare the effects of long-term (seven weeks) feeding PUFA or SFA to diabetic rats. We have previously reported that diabetic animals fed PUFA had superior body weight gain, lower hemoglobin AlC values, lower plasma cholesterol and triglyceride levels, lower percentage decline in glucose (K value) following intravenous glucose tolerance testing, near-normal values of hepatic microsomal glucose-6-phosphatase activity and near-normal concentrations of 18:2(6) and 20:4(6) in liver microsomal phosphatidylcholine and phosphatidylserine. However, jejunal and ileal uptake of varying concentrations of glucose were similar in the three diet groups. Thus, the potential long-term beneficial effects of feeding diets with a high PUFA/SFA ratio probably have their explanation in metabolic effects distant to their uptake by the intestine.
T cell autoreactivity to insulin in type I diabetic and related non-diabetic individuals was analyzed. Peripheral T lymphocytes from both insulin-treated diabetic and untreated non-diabetic members of four families were found to proliferate in vitro in response to human insulin. T cell autoreactivity to insulin therefore does not appear to be diagnostic of the onset of type I diabetes. Highest T cell responses to human insulin were usually detected in insulin-dependent type I diabetes patients treated with a mixture of beef and pork insulin than with self insulin, the greater the dose of animal insulin the higher the T cell response. The T cell repertoires for self insulin appear to be similar in diabetics and non-diabetics based on their patterns of T cell reactivity to beef insulin, port insulin, human insulin, and various peptide of human insulin. The autoreactive T cells analyzed recognize two conformational epitopes of human insulin formed by interactions between A chain and B chain residues. One epitope is associated with the A chain loop and is present in the A1-A14/B1-B16 peptide, and the other epitope consists mainly of B chain residues located in the A16-A21/B10-B25 peptide. These two epitopes are present in amphipathic alpha-helical regions of insulin. HLA-DR (DR3, DR4, and DR5) and HLA-DQ (DQw2/DQw3) Ag can restrict these T cell responses to human insulin epitopes. The ability to detect insulin-specific autoreactive T cells in healthy non-diabetic individuals supports the hypothesis that autoreactive lymphocytes do not necessarily elicit autoimmune disease if present in an environment in which their activity is immunoregulated.
We have previously described a T cell hybridoma, A.1.1, that responds to specific Ag (P18, a synthetic polypeptide of defined sequence) in the context of I-Ad by producing lymphokines. Herein we report that this cell also releases, into culture supernatants and ascites fluid, an Ag-specific activity that functions in the induction of suppression of anti-SRBC PFC responses. This suppressive activity requires a) Ag-non-specific accessory molecules from a T suppressor inducer factor, b) Ly-2+ T cells in the assay cultures, and c) the specific Ag (P18) conjugated to the SRBC in the assay cultures. The specificity of the A.1.1-derived activity was demonstrated by the absence of suppression in cultures containing SRBC, BSA-SRBC, or conalbumin-SRBC rather than P18-SRBC. Further, the A.1.1-derived activity bound to, and could be eluted from, P18 but not conalbumin. Using a panel of synthetic variant peptides, we have mapped the critical residues in P18 required for Ag/I-Ad induced activation of A.1.1. These peptides were tested for their ability to act as targets for the A.1.1-derived suppressive activity when conjugated to SRBC and added to assay cultures. All peptides capable of stimulating the A.1.1 T cells to release lymphokines were similarly effective in the suppressor assay. Thus, the recognition of Ag by the T cells and by the T cell-derived activity appeared to be identical. The A.1.1-derived molecule was found to be capable of inducing L3T4- T cells to act as suppressor T cells following culture. These suppressor cells were active in inhibiting anti-SRBC responses in the absence of P18 and bore the Ly-2 surface marker. Thus, it is likely that the function of this Ag-specific molecule is to induce Ly-2+ suppressor T cells and thereby cause the inhibition of the response. This function is distinct from that normally associated with helper T cells and may shed new light on the possible relationship between the cell surface T cell receptor for Ag and Ag-specific T suppressor inducer molecules.
The hemodynamic effects of flestolol were evaluated in 30 patients undergoing routine cardiac catheterization. Hemodynamic measurements were obtained during baseline (prior to flestolol), at steady state during IV flestolol infusion (1, 5, and 10 micrograms/kg/min) and at 20 to 30 minutes after discontinuation (postinfusion). Flestolol-induced hemodynamic changes were similar to those induced by other beta blockers without intrinsic sympathomimetic activity. Significant dose-dependent reduction in heart rate, rate pressure product, and increase in peripheral vascular resistance were seen. Flestolol produced clinically insignificant decrease in myocardial contractility as shown by slight decrease in LVdp/dt, CI, and LVEF. Hemodynamic data from patients with paced heart rate, further confirms a direct mild cardiac depressant effect of flestolol, a finding common to other beta blockers. Consistent with the short elimination half-life of flestolol (t1/2 = 6.5 minutes), most of the hemodynamic changes rapidly returned to preinfusion level within 20 to 30 minutes following its discontinuation. Thus flestolol, with its unique pharmacokinetic profile and titrability, may be beneficial in the treatment of critically ill patients.