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Biomedical subjects

U Malhotra

Publications and source records attributed to U Malhotra.

At least 19 recordsLinked to original sources
PubMed2001

Pneumonia and sepsis due to fluoroquinolone-resistant Capnocytophaga gingivalis after autologous stem cell transplantation.

Human oral Capnocytophaga species have been only rarely described as a cause of sepsis in patients following stem cell or marrow transplantation, and pneumonia has not been reported in this setting. In addition, fluoroquinolone resistance is rarely seen in these species, and has never been reported in C. gingivalis. We report a case of pneumonia (confirmed by culture of bronchoalveolar lavage fluid) and sepsis due to fluoroquinolone- resistant Capnocytophaga gingivalis in a patient following autologous stem cell transplantation, who responded to treatment with linezolid and metronidazole. Capnocytophaga infections should be considered in patients with fever following stem cell or marrow transplantation, especially those with neutropenia and mucositis. Susceptibility testing is needed given the existence of multidrug-resistant isolates.

Adult↗
PubMed2001

Role for HLA class II molecules in HIV-1 suppression and cellular immunity following antiretroviral treatment.

HIV-1-infected patients treated early with combination antiretrovirals respond favorably, but not all maintain viral suppression and improved HIV-specific Th function. To understand if genetic factors contribute to this variation, we prospectively evaluated over 18 months 21 early-treated patients stratified by alleles of class II haplotypes. All seven subjects with the DRB1*13-DQB1*06 haplotype, but only 21% of other subjects, maintained virus suppression at every posttreatment measurement. Following HIV-1 p24 antigen stimulation, PBMCs from patients with this haplotype demonstrated higher mean lymphoproliferation and IFN-gamma secretion than did cells from patients with other haplotypes. Two DRB1*13-restricted Gag epitope regions were identified, a promiscuous one that bound its putative restriction element with nanomolar affinity, and another that mapped to a highly conserved region. These findings suggest that class II molecules, particularly the DRB1*13 haplotype, have an important impact on virologic and immunologic responses. The advantage of the haplotype may relate to selection of key HIV-1 Th1 epitopes in highly conserved regions with avid binding to class II molecules. Eliciting responses to the promiscuous epitope region may be beneficial in vaccine strategies.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Effect of combination antiretroviral therapy on T-cell immunity in acute human immunodeficiency virus type 1 infection.

T-cell responses were evaluated prospectively in 41 patients with acute human immunodeficiency virus type 1 (HIV-1) infection (30 untreated and 11 receiving zidovudine, lamivudine, and indinavir) and in 38 uninfected adults. By 6-12 months, treated patients had significantly greater median Candida and tetanus lymphoproliferative responses (stimulation index [SI], 76 and 55, respectively) than did untreated patients (SI, 7 and 6, P=.02 and.001, respectively), and the responses of treated patients surpassed those of uninfected adults (SI, 19 and 32, P= .002 and .101, respectively). Unlike the patients in the untreated group, the patients in the treated group mounted a 6-fold increased HIV-1 p24 response (SI increase, 1.0 to 5.7, P= .01) within 3 months. HIV-1-specific cytotoxicity remained detectable in most treated patients. Thus, combination therapy administered within 3-4 months of infection was associated with improved T-cell memory responses that were distinct from those of untreated patients. The amplified HIV-1-specific T-cell responses may help maintain cytotoxic activities.

Acute Disease↗
PubMed1992

Variability in T cell receptor V beta gene usage in human peripheral blood lymphocytes. Studies of identical twins, siblings, and insulin-dependent diabetes mellitus patients.

Recent studies focused on the diversity and molecular organization of the human TCR-beta complex have begun to establish the genetic basis for the potential repertoire of V beta specificities in T cells. The scope and variability of the actual repertoire derived from this potential repertoire, however, remains to be clarified. In this study, V beta usage by human peripheral T cells derived from serial samples of the same individual, identical twins, and the members of three nuclear families that include four members with insulin-dependent diabetes mellitus (IDDM) was assessed by both quantitative polymerase chain reaction and Northern blotting with V beta subfamily-specific probes. Samples taken from the same individual over a period of 21 months and analyzed in separate experiments indicated stability in the peripheral repertoire, whereas the similarity in peripheral V beta usage in a pair of identical twins suggested a strong role for genetics in shaping the peripheral T cell repertoire. In contrast, V beta usage in siblings and in unrelated individuals was observed to differ substantially. In particular, peripheral expression of V beta 3 and V beta 20 differed by more than sixfold among members of two different families. Segregation analysis of TCR and HLA haplotypes in these families suggested that variation in V beta 20 expression was TCR haplotype specific. Subsequent nucleotide sequence analysis of the V beta 20 gene segment in multiple members of these families revealed the presence of a null allele for V beta 20 expression. No consistent significant differences in V beta usage were observed in IDDM patients relative to their siblings or between identical twins discordant for IDDM. These results suggest that the repertoire of peripheral T cell specificities present in different individuals in human populations varies dramatically because of the effects of multiple factors, including TCR germ-line polymorphism.

Diabetes Mellitus, Type 1↗
PubMed1992

T cell receptor beta gene polymorphism and rheumatoid arthritis.

Susceptibility to rheumatoid arthritis is, in part, conferred by genetic factors. Previous studies have suggested that inheritance of a particular allele of a restriction fragment length polymorphism (RFLP) detected in the T cell receptor beta (TCR beta) gene complex is associated with rheumatoid arthritis (RA). We have specifically tested this hypothesis in ethnically and geographically matched populations of RA patients and controls. We were unable to confirm previous observations of a TCR beta association with RA even after stratifying our study and control populations by HLA type.

Arthritis, Rheumatoid↗
PubMed1991

HLA and T cell receptor polymorphisms in pauciarticular-onset juvenile rheumatoid arthritis.

The immunogenetic basis of pauciarticular-onset juvenile rheumatoid arthritis is unclear. We therefore analyzed the HLA and T cell receptor genes present in a clinically well-defined group of patients. We found that the DR8 haplotype contributes most of the HLA-associated risk, although alleles at other loci contribute independently. A candidate disease-associated T cell receptor polymorphism, in contrast, was not identified in this population. Mechanistic implications of these findings are discussed.

Arthritis, Juvenile↗
PubMed1990

The ataxia-telangiectasia gene (ATA) on chromosome II is distinct from the ETS-1 gene.

We have studied the segregation of an RFLP detected with a human ETS-1 genomic probe in 25 families containing members affected with ataxia-telangiectasia (AT) and in 27 families from the Centre d'Etude du Polymorphisme Humain (CEPH) panel. We have recently mapped a gene for AT to 11q22-23 by linkage to the markers THY1 and D11S144. Multipoint linkage analysis of the CEPH families indicated that ETS-1 is located on chromosome 11q approximately 19.2 centimorgans telomeric to THY1. Analysis of the segregation of ETS-1 alleles in AT families yields strongly negative LOD scores, excluding an AT gene from a region extending 15 cM to either side of ETS-1. Multipoint mapping of ETS-1, D11S144, THY1, and AT also excludes the possibility that an AT gene is telomeric to ETS-1.

Ataxia Telangiectasia↗
PubMed1990

Further mapping of an ataxia-telangiectasia locus to the chromosome 11q23 region.

We recently mapped the gene for ataxia-telangiectasia group A (ATA) to chromosome 11q22-23 by linkage analysis, using the genetic markers THY1 and pYNB3.12 (D11S144). The most likely order was cent-AT-S144-THY1. The present paper describes further mapping of the AT locus by means of a panel of 10 markers that span approximately 60 cM in the 11q22-23 region centered around S144 and THY1. Location scores indicate that three contiguous subsegments within the [S144-THY1] segment, as well as three contiguous segments telomeric to THY1, are each unlikely to contain the AT locus, while the more centromeric [STMY-S144] segment is most likely to contain the AT locus. These data, together with recent refinements in the linkage and physical maps of 11q22-23, place the AT locus at 11q23.

Alleles↗
PubMed1989

An antiprogestin steroid and PGE2 for an early pregnancy termination.

A non-surgical, preferably self-administered, procedure would be an attractive alternative to vacuum for the termination of early pregnancy. 20 patients with 49 days of amenorrhea and confirmation of pregnancy by ultrasound, urine testing and human chorionic gonadotrophin (beta-hCG) analysis, were administered RU 486, 25 mg twice daily for 4 days, (Group I). A further 20 patients received the same dose of RU 486 for 3 days (Group II). All patients received an intramuscular injection of the prostaglandin derivative sulprostone, 0.25 mg, on the last day of RU 486 treatment. Outcome of therapy was assessed on the second follow up visit (day 15) on the basis of clinical courses, ultrasound findings and hCG levels. In Group I, all patients had a complete abortion with a success rate of 100%. In Group II, a success rate of 95% was achieved. Side effects were minimal and did not require any medication. A dramatic fall was observed in the plasma beta-hCG and progesterone levels on days 8 and 14, correlating with the clinical course of abortion. Plasma cortisol levels remained within the normal range. It is concluded that sequential therapy with RU 486 and prostaglandin is a highly safe, simple and effective non-surgical method for termination of early pregnancy.

Abortifacient Agents↗
PubMed1979

Indian experience with a single long-acting vaginal suppository for the termination of pregnancies.

The Indian Council of Medical Research conducted a multicentric trial with a single vaginal suppository containing 3 mg 15-Me-PGF2 alpha for terminating pregnancies. Success rate in the 290 women investigated was 79.2 per cent at 30 hours observation. The mean induction-abortion interval was 14.7 hours and the incidence of complete abortions was 58.3 per cent. Vomiting and diarrhoea were the most common side-effects noted. Vomiting was experienced by 72.3 per cent women and diarrhoea by 76.8 per cent. Although the vaginal route for administering 15-Me-PGF2 alpha is simple and the induction-abortion interval short, it is suggested that the combination of a vaginal suppository and prostaglandins intra-muscularly may lead to higher percentage of complete abortions.

Abortion, Induced↗