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Biomedical subjects

P Chandra

Publications and source records attributed to P Chandra.

At least 73 records · Page 4Linked to original sources
PubMed1990

Epitope mapping of the low-molecular-mass subunits of reverse transcriptase in human immunodeficiency virus type 1 by monoclonal antibodies.

With the aid of monoclonal antibodies to the reverse transcriptase (RT) of human immunodeficiency virus type 1 (HIV-1), low-molecular-mass subunits (p29, p32, and p40) were identified in HIV-1 RT purified from HIV (HTLV-IIIB) virions by isoelectric focusing. Epitope mapping with synthetic polypeptides from various regions of the pol gene suggests that the low-molecular-mass subunits result from N-terminal cleavage of the p51 subunit. The subunits could be separated only by SDS-polyacrylamide gel electrophoresis and detected by immunoblotting. They could not be separated on chromatographic columns, suggesting that the subunits are complexed or conformationally arranged in such a way that their separation on the basis of molecular mass is not possible. The molecular mass of the active enzyme eluted from a chromatographic column (Sephacryl S-300) loaded with a mixture of the subunits was estimated to be 100 kDa.

Animals↗
PubMed1988

D-penicillamine inhibits transactivation of human immunodeficiency virus type-1 (HIV-1) LTR by transactivator protein.

D-Penicillamine, an amino acid analogue of cysteine, has been shown to inhibit the transactivation of HIV-1 LTR by the transactivator protein, tat protein. The transactivation was studied in Jurkat cells co-transfected with plasmids containing HIV-LTR sequences fused to the bacterial chloramphenicol acetyltransferase (CAT) gene and HIV tat gene. The expression of CAT activity was a measure of transactivation of LTR by the tat protein. Incubation of transfected Jurkat cells with D-penicillamine led to inhibition of CAT activity. This inhibition was found to be concentration-dependent; more than 90% inhibition of chloramphenicol acetylation was seen in extracts prepared from cultures incubated with 40 micrograms/ml of D-penicillamine. Earlier experiments have shown that D-penicillamine at 40 micrograms/ml can completely inhibit HIV-1 (HTLV-III B) replication in H9 cells [(1986) Drug Res. 36, 184-186]. These results suggest that inhibition of transactivation may be the molecular mechanism involved in the inhibition of HIV-1 replication by D-penicillamine.

Cell Line↗
PubMed1988

Effects of peristaltic and longitudinal wave motion of the channel wall on movement of micro-organisms: application to spermatozoa transport.

A mathematical model is presented to study the motion of the spermatozoa in the cervical canal by considering the transverse waves along its tail and the transverse and longitudinal motions of the cervical wall. In an attempt to control fertility by reducing the speed of sperm, the transverse waves have been considered in the direction opposite to the motion of the spermatozoa. It has been shown that by having appropriate transverse wave motion and longitudinal velocity, the sperm may not be able to move towards the oviduct even if it could continue to have its own propelling velocity. A particular case of the motion of a thin plane sheet in a channel under peristaltic motion of its walls has also been obtained and studied.

Female↗
PubMed1986

Serological relationship between reverse transcriptases from human T-cell lymphotropic viruses defined by monoclonal antibodies. Evidence for two forms of reverse transcriptases in the AIDS-associated virus, HTLV-III/LAV.

The immunological relationship between reverse transcriptases purified from human T-cell lymphotropic viruses (HTLV-I, HTLV-II, HTLV-III) was defined using monoclonal antibodies specific for HTLV-III reverse transcriptase, secreted by a mouse/mouse hybridoma clone (4F8) developed in our laboratory. The viral proteins from HTLV-I and HTLV-II do not bear any cross-reactive epitope to antibodies secreted by this clone. These antibodies specifically cross-react with HTLV-III reverse transcriptase. The antibodies failed to neutralize the catalytic activity of reverse transcriptase; however, after immunoprecipitation with a magnetic conjugate of goat anti-mouse IgG, the residual activity was completely inhibited. This shows that the antibodies are not directed towards the catalytic active center of the enzyme. Using an immunoblotting technique (Western blotting), we have found two cross-reactive proteins with HTLV-III lysate with molecular masses of 53 and 66 kDa. This suggests that HTLV-III possesses two reverse transcriptase activities with a common determinant recognized by the same epitope.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Biochemical heterogeneity of reverse transcriptase purified from the AIDS virus, HTLV-III.

The reverse transcriptase from AIDS virus, HTLV-III, was purified and characterized. The purified enzyme has a very high affinity for template primers (rC)n X (dG)12 and (rCm)n X (dG)12 compared to that for (rA)n X (dT)12. In addition, the HTLV-III reverse transcriptase was able to transcribe (rAm)n X (dT)12 very efficiently. The ionic requirements are unique in the sense that HTLV-III reverse transcriptase prefers Mg2+ as divalent ions to transcribe (rC)n X (dG)12 and (rA)n X (dT)12. The Mr of the enzyme is 95 000-98 000. Unlike the HTLV-I reverse transcriptase, the HTLV-III enzyme is highly stable and has a much higher activity in the presence of (rC)n X (dG)12; the Vmax for HTLV-III reverse transcriptase is several-fold higher than that for HTLV-I enzyme. The enzyme activity of the purified reverse transcriptase from HTLV-III was resolved into two peaks on a preparative isoelectric column, one at pH 5.75 and the other at pH 6.25. This leads us to conclude that the reverse transcriptase of HTLV-III is biochemically heterogeneous.

Cations, Divalent↗
PubMed1986

Treatment of HTLV-III/LAV-infected patients with D-penicillamine.

13 asymptomatic, HTLV-III/LAV-infected male homosexuals with generalized lymphadenopathy were treated with oral D-penicillamine. All patients had depressed T4/T8 ratios and 12 had impaired T-cell function. An escalating dose schedule was employed over 2-6 weeks with doses from 0.5 to 2 g/day. Generalized skin rashes developed in 4 patients which required discontinuation of therapy in one patient. Two patients developed mild transient elevations of hepatocellular enzymes. Reversible decreases in lymph node size, absolute lymphocyte counts, and T-cell lymphoproliferative responses were observed in the majority of patients without change in baseline T4/T8 ratios. All 10 patients treated for at least 2 weeks exhibited evidence for suppression of HTLV-III/LAV replication; complete inhibition of virus expression was seen in 60% of patients treated for 6 weeks. Three of the patients treated for 6 weeks remained culture negative for at least 6 weeks after stopping the drug. D-Penicillamine appears to be an effective drug for suppressing HTLV-III/LAV expression in vivo. Its potential role in the treatment of patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex (ARC) will require further evaluation.

Acquired Immunodeficiency Syndrome↗
PubMed1986

Selective inhibition of replication of the AIDS-associated virus HTLV-III/LAV by synthetic D-penicillamine.

A new antimetabolite approach to block the replication of the AIDS (acquired immunodeficiency syndrome)-associated virus is described. In this communication the effect of a synthetic D-penicillamine (Trolovol) and L-penicillamine on the replication of HTLV-III/LAV was studied. The replication of HTLV-III/LAV in H9 cells was determined by measuring the expression of HTLV-III proteins p15 and p24 using monoclonal antibodies in an immunofluorescence assay system. A concentration dependent inhibition of HTLV-III replication by D- and L-penicillamine was observed. At lower concentrations L-penicillamine was more effective than D-penicillamine. However, at concentrations above 20 micrograms/ml the inhibitory response of both isomers is similar. To obtain a total inhibition a drug concentration of 40 micrograms/ml was needed for both isomers. Cytotoxicity of the compounds in uninfected H9 cells was observed only at high concentrations; e.g., at 500 micrograms/ml a 32% inhibition was found for D-penicillamine and a 24% inhibition for L-penicillamine. In the presence of D- or L-penicillamine there was a significant increase in cell density of infected H9 cell cultures, indicating that both the compounds have a protective effect on H9 cells. In view of the low cytotoxicity, a selective antiviral activity against HTLV-III/LAV, and a T-cell protective effect of D-penicillamine, the evaluation of D-penicillamine for clinical treatment of AIDS is implicated.

Antibodies, Monoclonal↗
PubMed1985

Antiemetic efficacy of high-dose dexamethasone versus placebo in patients receiving cisplatin-based chemotherapy: a randomized double-blind controlled clinical trial.

The antiemetic effect of short courses of high-dose dexamethasone was compared with that of placebo in 64 patients receiving cisplatin-based cancer chemotherapy, in a double-blind randomized clinical trial. All patients were receiving cisplatin for the first time. Dexamethasone was given intravenously (IV) at a dose of 20 mg, two hours before and 3, 6, 9, and 12 hours after chemotherapy. Patients were crossed over to dexamethasone on the second cycle of chemotherapy if they experienced unacceptable gastrointestinal (GI) toxicity after initial treatment with placebo. Nine of 32 patients receiving dexamethasone and seven of 32 patients receiving placebo did not vomit. The median duration of nausea was significantly shorter (one-half hour) for the dexamethasone-treated group compared with that of placebo (31/2 hours). The number of patients who experienced unacceptable GI toxicity was significantly greater (53%) for the placebo patients than for those treated with dexamethasone (25%). Patients crossing over to dexamethasone after initially receiving placebo had a median duration of nausea of 11/2 hours and 24% did not vomit, results comparable to the first treatment group. We conclude that high-dose dexamethasone is only minimally effective as an antiemetic agent in patients receiving cisplatin-based chemotherapy.

Adult↗
PubMed1985

Inhibitors of retroviral DNA polymerase: their implication in the treatment of AIDS.

Compared to other T-lymphotropic human retroviruses, human T-cell leukemia (lymphotropic) virus I (HTLV-I) and HTLV-II, the acquired immunodeficiency syndrome (AIDS)-associated virus, HTLV-III, is a nontransforming cytopathic virus without immortalizing activity. Thus the virus replication is an important event in the manifestation of this disease, and the interruption of viral replication offers an important strategy for the control of AIDS. For this reason we have purified the reverse transcriptase (RT) from HTLV-III and from HTLV-III infected cells to study the structure-activity relationship of RT inhibitors developed in our laboratory. The cellular DNA polymerases from H9 cells were also purified to study the selectivity of RT inhibitors. Purified HTLV-III RT has several distinguishing features: (a) unlike the HTLV-I enzyme it is highly stable and can be kept for several weeks without any loss of activity; (b) using identical procedures of isolation the HTLV-III enzyme shows a much higher activity than does the enzyme from HTLV-I; (c) the Vmax for HTLV-III RT is by severalfold higher than that for the HTLV-I enzyme in the presence of (rC)n X (dG)12 and (rCm)n X (dG)12, and besides the usual template-primers used for RT assay this enzyme has a relatively high affinity for (rAm)n X (dT)12; and (d) the cationic requirements for the transcription of various template-primers are unusual. The purified enzyme has a molecular weight of 95,000-98,000, as judged by the gel filtration method. The purified HTLV-III RT was inhibited by a partially thiolated polycytidylic acid (5-mercaptopolycytidylic acid); the cellular DNA polymerase beta from H9 cells was not sensitive to 5-mercaptopolycytidylic acid. Germanin (synonym, suramin), an antiprotozoan drug, also inhibits HTLV-III RT activity, but the DNA polymerase alpha activity was also sensitive to Germanin. The nonspecific effect of Germanin is probably due to the high content of sulfonic acid residues. This paper describes new approaches for designing specific inhibitors of retroviral reverse transcriptases which may be useful in developing a potential drug against AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Vecuronium and porcine malignant hyperthermia.

Vecuronium was studied in eight malignant hyperthermia (MH) susceptible pigs for its potential to either trigger or prevent MH. Two sets of experiments were performed in the same animals: 1-hr total neuromuscular blockade by vecuronium infusion with thiopental anesthesia in the absence of invasive monitoring and halothane; and 1-hr infusion of vecuronium with thiopental anesthesia with invasive monitoring in the absence of and then, followed by 30-min infusion in the presence of halothane, followed in turn by exposure to halothane alone. One-hour infusion of vecuronium in the absence of halothane and invasive monitoring did not trigger MH in any animal. During the second set of experiments, MH, evidenced by rising rectal temperature, elevated end-tidal PCO2, mixed venous oxygen desaturation and muscle rigor, occurred in one animal during vecuronium alone, in four animals during vecuronium infusion and simultaneous exposure to halothane, and in three animals during exposure to halothane alone after recovery from vecuronium neuromuscular blockade. In view of the results of control experiments, the development of MH during vecuronium neuromuscular blockade before exposure to halothane was attributed to surgical stress rather than to vecuronium itself. It is concluded that vecuronium is not a trigger to MH in susceptible pigs.

Anesthesia, General↗