Rising incidence of genital herpes in an STD clinic in north India.
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Biomedical subjects
Publications and source records attributed to M Rajagopalan.
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The effect of neighboring AT-rich sequences on the right-handed B to left-handed Z transition was investigated in plasmids. The supercoil stabilized Z-DNA structure in (CG) tracts 36 and 40 base pairs (bp) in length revealed an unexpected conformational aberration at defined C residues proximal to one end (colL) when the inserts were bilaterally flanked by an 80% AT-rich segment (90 bp on one side and 331 bp on the other). The presence of the perturbed Z-conformation required (CG) stretches longer than 32 bp and bilateral flanking by the AT-rich tracts, since plasmids with the (CG) tracts unilaterally flanked had an orthodox Z-structure. The thermodynamics of the negative super-coil-induced transitions were influenced only slightly by the neighboring AT-rich regions. Hence, the nature of Z-conformations in plasmids is markedly influenced by intrinsic structural features of the (Pur-Pyr) tract and by seemingly modest changes in the properties of neighboring sequences over a distance of several helical turns.
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Recently, a mammalian tRNA which was previously designated as an opal suppressor seryl-tRNA and phosphoseryl-tRNA was shown to be a selenocysteyl-tRNA (B. J. Lee, P. J. Worland, J. N. Davis, T. C. Stadtman, and D. Hatfield, J. Biol. Chem. 264:9724-9727, 1989). Hence, this tRNA is now designated as selenocysteyl-tRNA[Ser]Sec, and its function is twofold, to serve as (i) a carrier molecule upon which selenocysteine is biosynthesized and (ii) as a donor of selenocysteine, which is the 21st naturally occurring amino acid of protein, to the nascent polypeptide chain in response to specific UGA codons. In the present study, the selenocysteine tRNA gene was sequenced from Xenopus laevis, Drosophila melanogaster, and Caenorhabditis elegans. The tRNA product of this gene was also identified within the seryl-tRNA population of a number of higher and lower animals, and the human tRNA[Ser]Sec gene was used as a probe to identify homologous sequences within genomic DNAs of organisms throughout the animal kingdom. The studies showed that the tRNA[Ser]Sec gene has undergone evolutionary change and that it is ubiquitous in the animal kingdom. Further, we conclude that selenocysteine-containing proteins, as well as the use of UGA as a codon for selenocysteine, are far more widespread in nature than previously thought.
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AIDS and other sexually transmitted diseases are interlinked. VDRL positivity may indicate that the individual has an increased risk of being HIV positive as the epidemiological risk factors for developing syphilis and AIDS are similar. We analysed 323 (5.8%) VDRL positive serum samples (out of 5592 screened) for HIV positivity. All were HIV negative. While syphilitic infection in India at present is not commonly associated with HIV infection, experience in other countries indicates caution.
The introduction of a replication-inhibiting lesion into the DNA of Escherichia coli produces a marked elevation in mutation rate. The mutation pathway is a component of the induced, multigene SOS response. SOS mutagenesis is a tightly regulated process dependent on two RecA-mediated proteolytic events: cleavage of the LexA repressor to induce the UmuC and UmuD mutagenesis proteins, and cleavage of UmuD to UmuD' to activate the mutation pathway. To investigate the protein-protein interactions responsible for SOS mutagenesis, we have studied the interaction of UmuC, UmuD, and UmuD'. To probe intracellular interaction, we have used immunoprecipitation techniques with antibodies against UmuC or UmuD and UmuD'. We have found that antibody to UmuC precipitates UmuD' from cell extracts, and antibody to UmuD and UmuD' precipitates UmuC. Thus we conclude that UmuC probably associates tightly with UmuD' in cells. For biochemical studies, we have purified the UmuC and UmuD' proteins to use with the previously purified UmuD. UmuC associates strongly with an affinity column of UmuD and UmuD', eluting only under strongly dissociating conditions (2 M urea or 1.5 M KSCN). UmuC also associates efficiently with UmuD or UmuD' in solution, as judged by velocity sedimentation in a glycerol gradient. The likely stoichiometry is one UmuC with a dimeric UmuD or UmuD'. From these experiments and previous work, we infer that SOS mutagenesis depends on the action of the UmuC-UmuD' complex and probably RecA to rescue a stalled DNA polymerase III holoenzyme at the DNA lesion.
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An opal suppressor phosphoserine tRNA gene and pseudogene have been isolated from a human DNA library and sequenced (O'Neill, V., Eden, F., Pratt, K., and Hatfield, D. (1985) J. Biol. Chem. 260, 2501-2508). Southern hybridization of human genomic DNA with an opal suppressor tRNA probe suggested that the gene and pseudogene are present in single copy. In this study, we have determined the chromosome location of the human gene and pseudogene by utilizing a 193-base pair fragment encoding the opal suppressor phosphoserine tRNA gene as probe to examine DNAs isolated from human-rodent somatic cell hybrids that have segregated human chromosomes. These studies show that the probe hybridized with two regions in the human genome; one is located on chromosome 19 and the second on chromosome 22. By comparing the restriction sites within these two regions to those previously determined for the human opal suppressor phosphoserine tRNA gene and pseudogene, we tentatively assigned the gene to chromosome 19 and the pseudogene to chromosome 22. These assignments were confirmed by utilizing a 350-base pair fragment which was isolated from the 5'-flanking region of the human gene as probe. This fragment hybridized only to chromosome 19, demonstrating unequivocally that the opal suppressor phosphoserine tRNA gene is located on chromosome 19. The flanking probe hybridized to a single homologous band in hamster and in mouse DNA to which the gene probe also hybridized, demonstrating that the 5'-flanking region of the opal suppressor tRNA gene is conserved in mammals. Restriction analysis of DNAs obtained from the white blood cells of 10 separate individuals demonstrates that the gene is polymorphic. This study provides two additional markers for the human genome and constitutes only the second set of two tRNA genes assigned to human chromosomes.
The interaction between a synthetic analogue (structure shown in fig. 1) of distamycin, and DNA has been studied with a view to understanding the conformational and chemical basis of the sequence specific binding of distamycin with DNA. The complex formation between the trimer and DNA is apparent from the red shift in the UV spectrum and appearance of the induced CD band in 300nm-350nm region. The relevant data suggest: (i) the binding is A-T base specific though the specificity is not as pronounced as in distamycin (1,2) and (ii) it occurs via the minor groove of DNA. The partial loss in A-T base specificity may be due to the replacement of N-methyl pyrrole by benzene or the increase in curvature of the backbone of the ligand as a result of this replacement.
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The Watson-Crick type of base pairing is considered to be mandatory for the formation of duplex DNA. However, conformational calculations carried out in our laboratory, have shown that some combinations of backbone torsion angles and sugar pucker lead to duplexes with Hoogsteen type of base pairing also. Here we present the results of energy calculations performed on A-T containing doublet sequences in the D-form with both Hoogsteen and Watson-Crick type of base pairing and the 3 viable models for the A-T containing polynucleotide duplex poly[d(A-T)].
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Poly(dA-dT).poly(dA-dT) can adopt the B- and D- forms in the fibrous state. Theoretical energy calculations and fiber diffraction analyses suggest that there can be three structural models of poly(dA-dT).poly(dA-dT) in each of these two forms viz right and left-handed Watson Crick models and left-handed Hoogsteen--a total of six possible models. Fiber data for the polymer in the B- or the D-form or energy calculations cannot distinguish any one model from the other. However, a comparison of observed proton chemical shifts with the theoretically computed ones and the NOE studies on exchangeable and nonexchangeable protons suggest that poly(dA-dT).poly(dA-dT) in low salt solution exists predominantly in the left-handed B-conformation.
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This is the first report of the rare association of acute febrile neutrophilic dermatosis (Sweet's syndrome) and myelodysplastic syndrome (MDS) in a child. The skin lesions showed a dramatic response to colchicine.
BACKGROUND: Research on psychiatric morbidity among patients with dermatological diseases generally focuses on outpatients and questionnaire-based surveys. The aim of this study was to determine the prevalence and nature of psychiatric morbidity among dermatological inpatients with diagnosis being made by psychiatric interview, and ascertain whether demographic and clinical details in dermatological inpatients with psychiatric morbidity differed from those without it. METHODS: Charts of all inpatients admitted by the dermatology department between 1 January 1991 and 31 July 1995 were analysed for socio-demographic data, clinical features, treatment and course in hospital. For those patients who were referred to a psychiatrist, all records of the psychiatric consultation were obtained and analysed. RESULTS: A total of 1073 patients were admitted during the study period. Ninety-eight patients (9%) were diagnosed to have a psychiatric illness. Patients with psychiatric illness were likely to have had more admissions and longer duration of hospital stay. The most common psychiatric diagnoses were depressive episodes (34%) and adjustment disorders (29%). The highest rates of psychiatric morbidity were found among patients with chronic urticaria, exfoliative dermatitis and sexually transmitted diseases, including human immunodeficiency virus infection. The prevalence of psychiatric disorders was significantly higher in those who had received long term (more than six weeks) treatment with high-dose steroids (more than 1 mg/kg body weight of prednisolone). CONCLUSION: Some dermatology inpatients have psychiatric morbidity, which affects the course of the dermatological condition as well as the duration of hospitalization. The availability of psychiatric consultation at dermatology clinics and regular liaison between psychiatrists and dermatologists are essential for appropriate management.