Search PubMed⌕ Search

Biomedical subjects

K Bhatia

Publications and source records attributed to K Bhatia.

At least 127 records · Page 7Linked to original sources
PubMed1990

Dual isotope thallium and indium antimyosin SPECT imaging to identify acute infarct patients at further ischemic risk.

Forty-two patients (28 men and 14 women) with acute myocardial infarction (35 Q, seven non-Q wave) were injected with 2.0 mCi indium 111-labeled antimyosin (AM) monoclonal antibody (111In AM) within 48 hours of the onset of chest pain. Forty-eight hours later (72-96 hours after onset of chest pain), patients were injected with 2.2 mCi thallium 201, and two sets of single-photon emission computed tomography (SPECT) images were obtained simultaneously using dual energy windows set for the 247 keV indium photopeak and the 70 keV thallium peak. Seventeen patients had repeat scans at 4 hours. 111In AM uptake and 201Tl defects were localized to one or more of 24 coronal and sagittal segments. Scans with only 201Tl defects and corresponding 111In AM uptake were classified as matches; scans with unmatched 201Tl defects in addition to matching regions corresponding to electrocardiographic infarct location were classified as mismatches; and scans with 201Tl and 111In AM uptake in the same segments were classified as overlap. Scan patterns were correlated with clinical evidence for residual ischemia occurring within 6 weeks of infarct and including infarct extension, recurrent angina, and positive predischarge low-level or 6-week symptom-limited stress tests and with coronary anatomy. Fourteen patients had only matching patterns (group 1), 23 had mismatches (group 2), and five had 201Tl-111In overlap as the predominant pattern. None of the patients in group 1 had previous myocardial infarction; in each, the matched area corresponded to the Q wave location on electrocardiogram, and none had further in-hospital ischemic events or positive stress tests.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1989

Sequence and organization of the mouse poly (ADP-ribose) polymerase gene.

Using a human cDNA probe, we have isolated murine genomic and cDNA clones corresponding to the nuclear enzyme poly (ADP-ribose) polymerase (ADPRP). Northern analysis with the mouse cDNA clones reveals transcripts of 3.7-3.8 kb corresponding in size to the human ADPRP transcript. DNA sequence comparisons between mouse and human clones reveals extensive amino acid sequence conservation within regions harboring DNA binding, NAD+ binding or automodification domains. A survey among mouse inbred strains for restriction fragment length polymorphism (RFLP) reveals at least three distinct ADPRP alleles. The segregation of alleles among mouse genetic recombinants positions ADPRP on mouse chromosome 1 between the complement receptor-related gene At-3 and the Fc receptor locus FcR. Furthermore, ADPRP is closely associated with the autoimmune locus gld (generalized lymphadenopathy).

Amino Acid Sequence↗
PubMed1989

Family resemblance for glucose tolerance in a Melanesian population, the Tolai.

Path analysis of family resemblance for plasma glucose concentration, 2 h after an oral glucose challenge, failed to detect significant genetic heritability. There were no intergenerational differences and marital resemblance was moderate. Over one-third of sibling environmental similarity was due to non-inherited factors. Cultural inheritance was very strong, tending to mimic genetic inheritance, and cultural heritability was considerable. Measures of obesity were included in the environmental index, an estimate of familial environment, in this analysis, for comparability with previous studies. Since obesity appears, in part, to be a heritable trait, in future studies a bivariate approach to family resemblance for both glucose tolerance and obesity could yield important additional insight.

Adolescent↗
PubMed1989

Association between HLA type and antibody response to malaria sporozoite and gametocyte epitopes is not evident in immune Papua New Guineans.

HLA-A,B,C and DR types were determined for 46 adults living in the Madang area of Papua New Guinea. Sera from these individuals were tested by ELISA for antibodies against: (i) sonicated schizont extract of Plasmodium falciparum; (ii) circumsporozoite repeat regions of P. falciparum and P. vivax; and (iii) epitopes on the 230 and 48/45 kD gametocyte antigens of P. falciparum. All sera were from highly immune individuals and reacted strongly to the schizont antigen. The proportions responding to circumsporozoite repeat regions were 60.7% and 23.9% for P. falciparum and P. vivax, respectively. Between 32.6 and 47.8% of adults responded to each gametocyte epitope as assessed by inhibition of monoclonal antibodies. The limited number of alleles present at each HLA locus which is characteristic of coastal Papua New Guinea was observed. Five HLA-DR alleles were detected, of which only three (HLA-DR2, 4 and w5) were present at frequencies over 0.12. All individuals possessed at least one DR2,4 or w5 allele, and 96% of individuals possessed DR2, or 4 or both. There was no evidence for association between HLA type and antibody response to circumsporozoite repeat regions or the gametocyte epitopes. Homozygotes for DR2 and 4 were able to respond to each antigen. These results imply that either there is no HLA restriction of the response to these antigens or that each DR type is responding to a different variant of the T-epitope. Even in the latter case the results are encouraging for the prospects of inclusion of an HLA-restricted T-epitope in a malaria vaccine for Papua New Guinea since a limited number of versions would be required to cover a population with an HLA profile similar to that in Madang.

Animals↗
PubMed1989

HLA and nonspecific polyarthritis in the highlands of Papua New Guinea.

We have studied the HLA profile of a series of 49 patients (32 men, 17 women) presenting with asymmetric polyarthritis to the Goroka Base Hospital, Papua New Guinea. Antigens A11 and B27 were found to be significantly increased in patients when compared with a control sample of 100 healthy Papua New Guinean highlanders. Significant negative associations were also recorded with A24[A9] and Bw22. None of the patients studied presented with the complete triad of Reiter's disease although 6 patients, all men, had some extraarticular symptoms. On the basis of these additional symptoms, the 6 patients were diagnosed to have an incomplete form of Reiter's disease and were excluded from further comparisons. In the remaining 43 patients, who fit the nonspecific category that has been called tropical polyarthritis, B27 was present in 20.9% of the cases, which was not significantly different from the control frequency of 11.0%. But the positive association with A11 was still found in the nonspecific arthritis cases. Our data do not support the concept that the patients included in this study constitute a single diagnostic category which is related to Reiter's disease. It is suggested that these patients be regarded as suffering from nonspecific polyarthritis of unknown, probably multiple, aetiology, until further more specific diagnostic entities can be determined.

Adolescent↗
PubMed1989

Immunogenetic studies of two recently contacted populations from Papua New Guinea.

We have examined the HLA profiles of the Hagahai and the Haruai people, two linguistic groups in the remote western Schrader mountains who have only recently had administrative contact, and compared them with those of other populations in Papua New Guinea. None of the antigens detected in the two groups was found missing in other populations although significant differences in allele frequencies exist. Recent contact history does not appear to have played any significant role in shaping these differences. Similarly, no evidence of differential selection pressures contributing to HLA heterogeneity was found. The genetic profiles of the Hagahai and the Haruai appear to be a result of recent admixture between unrelated, genetically disparate groups.

Culture↗
PubMed1988

Antigen and haplotype frequencies at three human leucocyte antigen loci (HLA-A, -B, -C) in the Pawaia of Papua New Guinea.

The genetic profile of the Pawaia, a seminomadic, linguistic isolate from the highlands fringe of Papua New Guinea, is described in terms of antigen and haplotype frequencies at three class I human leucocyte antigen loci (HLA-A, -B, and -C). The Pawaia, like other Papua New Guinea populations, exhibit restricted polymorphisms at all three loci studied, both in the number of alleles segregating and in the level of average heterozygosity. An extremely high frequency (52.9%) of HLA-B27, the antigen implicated in the pathogenesis of seronegative arthropathies, was found. A novel HLA-C locus specificity, CNG, resulting probably from a gene duplication event, was also observed in significant numbers. Although the gene frequency comparisons suggest their strong affinities with the highlanders, the Pawaia haplotypes reveal significant admixture from other neighbouring groups as well. The usefulness of HLA haplotypes in tracing the movements of human populations in the New Guinea area is discussed.

Anthropology, Physical↗
PubMed1987

cDNA sequence, protein structure, and chromosomal location of the human gene for poly(ADP-ribose) polymerase.

Recently we described a full-length cDNA for the human nuclear enzyme poly(ADP-ribose) polymerase. Here, we report the chromosomal localization and partial map of the human gene for this enzyme as well as the complete coding sequence for this protein. The nucleotide sequence reveals a single 3042-base open reading frame encoding a protein with a predicted Mr of 113,135. A comparison of this deduced amino acid sequence with the amino acid sequence of three peptides derived from human poly(ADP-ribose) polymerase revealed a match of 27 amino acid residues. A computer-derived structural analysis of the enzyme and a search for similarities with other proteins confirmed that the polymerase belongs to a subfamily of DNA/NAD-binding proteins and DNA-repair proteins. Possible Zn2+-binding "fingers," a nucleotide-binding fold, and a nuclear transport signal were noted. Additionally, chromosomal mapping has identified polymerase-hybridizing sequences on human chromosomes 1 (the active gene), 13, and 14 (processed pseudogenes). Using the polymerase cDNA as a probe, we also have detected several DNA restriction fragment length polymorphisms in normal humans.

Amino Acid Sequence↗
PubMed1987

Cloning and expression of cDNA for human poly(ADP-ribose) polymerase.

cDNAs encoding poly(ADP-ribose) polymerase from a human hepatoma lambda gt11 cDNA library were isolated by immunological screening. One insert of 1.3 kilobases (kb) consistently hybridized on RNA gel blots to an mRNA species of 3.6-3.7 kb, which is consistent with the size of RNA necessary to code for the polymerase protein (116 kDa). This insert was subsequently used in both in vitro hybrid selection and hybrid-arrested translation studies. An mRNA species from HeLa cells of 3.6-3.7 kb was selected that was translated into a 116-kDa protein, which was selectively immunoprecipitated with anti-poly (ADP-ribose) polymerase. To confirm that the 1.3-kb insert from lambda gt11 encodes for poly(ADP-ribose) polymerase, the insert was used to screen a 3- to 4-kb subset of a transformed human fibroblast cDNA library in the Okayama-Berg vector. One of these vectors [pcD-p(ADPR)P; 3.6 kb] was tested in transient transfection experiments in COS cells. This cDNA insert contained the complete coding sequence for polymerase as indicated by the following criteria: A 3-fold increase in in vitro activity was noted in extracts from transfected cells compared to mock or pSV2-CAT transfected cells. A 6-fold increase in polymerase activity in pcD-p(ADPR)P transfected cell extracts compared to controls was observed by "activity gel" analysis on gels of electrophoretically separated proteins at 116 kDa. A 10- to 15-fold increase in newly synthesized polymerase was detected by immunoprecipitation of labeled transfected cell extracts. Using pcD-p(ADPR)P as probe, it was observed that the level of poly(ADP-ribose) polymerase mRNA was elevated at 5 and 7 hr of S phase of the HeLa cell cycle, but was unaltered when artificial DNA strand breaks are introduced in HeLa cells by alkylating agents.

Carcinoma, Hepatocellular↗
PubMed1985

HLA and tropical splenomegaly syndrome in the Upper Watut Valley of Papua New Guinea.

Tropical splenomegaly syndrome (TSS) develops as a result of an atypical immune response to recurrent malarial infection. In general a low prevalence disorder, in the Upper Watut Valley of New Guinea TSS affects more than 80% of the inhabitants. We have studied the association of antigens and haplotypes of HLA-A,B,C, DR, and DQ loci with the severity of TSS as judged by the degree of splenomegaly in 77 unrelated Watut. The study confirmed the previously observed lack of association of TSS with HLA-A and B locus antigens. By contrast, HLA-DR2 was found to be more frequent in patients with gross splenomegaly than in those with moderate splenic enlargement. No two-locus haplotypes were, however, found to be significantly associated with TSS.

Adult↗
PubMed1985

HLA studies of Highland and Coastal New Guineans.

The HLA profile of three New Guinean populations, two Highland (Asaro, Watut), and one Coastal is presented. The Highland populations are characterized by a low average number of alleles segregating at the HLA loci and also by a low mean value of heterozygosity at these loci. The genetic affinities of the two Highland groups with other Melanesian populations in the Pacific are remote. The Coastal group, on the other hand, shows strong similarities in its antigenic diversity and haplotypic combinations with other Melanesian populations. Nonetheless, the two Highland groups show significant divergence from each other in terms of allelic and haplotypic frequencies. Two different waves of migration settled in the Highlands of New Guinea between 10,000 and 15,000 years ago, and it is possible that the Watut, an Angan speaking group, represents the remnants of the first migration into the interior, whereas the Asaro, members of the Eastern Central family of the Trans-New Guinea phylum, arrived at a later date.

Adult↗
PubMed1985

Repair of nonreplicating UV-irradiated DNA: cooperative dark repair by Escherichia coli uvr and phr functions.

The system previously used to study recombination of nonreplicating UV-irradiated phage lambda DNA was adapted to study UV repair. Irradiated phages infected undamaged homoimmune lysogens. Pyrimidine dimer content (by treatment with Micrococcus luteus UV endonuclease and alkaline sucrose sedimentation) and a biological activity endpoint (infectivity in transfection of uvrB recA recB spheroplasts) were followed. Unless room light was excluded during DNA extraction procedures, photoreactivation (Phr function) was significant. In uvr delta phr bacteria, repair, by both assays, was very low but not zero. Even when light was totally excluded, Phr function appeared to play a role in Uvr-mediated excision repair: both dimer removal and restoration of infectivity were two to five times as efficient in uvr+ phr+ bacteria as in uvr+ delta phr bacteria. Similarly, UV-irradiated phages plated with higher efficiencies on phr+ than delta phr bacteria even under totally dark conditions. In uvr phr+ repressed infections, removal of dimers from nonreplicating DNA did not increase infectivity as much as in uvr+ infections, suggesting a requirement for repair of nondimer photoproducts by the uvrABC system.

Bacteriophages↗