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Biomedical subjects

S Bakshi

Publications and source records attributed to S Bakshi.

At least 19 recordsLinked to original sources
PubMed2005

Composition and dynamics of plasma in Saturn's magnetosphere.

During Cassini's initial orbit, we observed a dynamic magnetosphere composed primarily of a complex mixture of water-derived atomic and molecular ions. We have identified four distinct regions characterized by differences in both bulk plasma properties and ion composition. Protons are the dominant species outside about 9 RS (where RS is the radial distance from the center of Saturn), whereas inside, the plasma consists primarily of a corotating comet-like mix of water-derived ions with approximately 3% N+. Over the A and B rings, we found an ionosphere in which O2+ and O+ are dominant, which suggests the possible existence of a layer of O2 gas similar to the atmospheres of Europa and Ganymede.

Atmosphere↗
PubMed2003

Venous thrombosis associated with Salmonella: report of a case and review of literature.

We describe here the first case of Salmonella paratyphi A bacteremia associated with deep vein thrombosis in a 10-year-old patient. In spite of aggressive antibiotic therapy and supportive care, the patient died of progressive respiratory distress and septic shock. Awareness of unusual clinical presentation of Salmonella infection in important. A review of the previously reported cases of Salmonella associated venous thrombosis worldwide is also presented.

Child↗
PubMed2001

Immunophenotypic analysis of HIV-infected children: alterations within the first year of life, changes with disease progression, and longitudinal analyses of lymphocyte subsets.

Perinatal infection with human immunodeficiency virus (HIV) results in tremendous activation of the pediatric immune system. An important component of understanding the pathogenesis of this disease is to characterize and quantify antigenic indicators of activation within the peripheral lymphocyte population. We measured T-lymphocyte activation and maturation antigens in a cohort of 112 HIV-infected children treated with antiretroviral therapy according to the current standard of care. Changes in expression of CD95, HLA-DR, and CD45RO were evident in 22 HIV-infected children younger than 1 year of age. A comparison of phenotypic profiles of children in mild, moderate, and severe immune categories revealed perturbations of CD28, CD38, CD45RA, CD45RO, CD95, and HLA-DR. Finally, a novel analysis of 56 HIV-infected children based on the repeated collection of data over time (median of seven observations over 33 months) demonstrated a strong negative correlation between the percentage CD4 and the percentage of CD45RO, CD95, and HLA-DR on both CD4 and CD8 cells. Our data implicate persistent immune activation, beginning within the first year of life, as a major driving force in the pathogenesis of perinatally acquired HIV disease.

ADP-ribosyl Cyclase↗
PubMed2001

Evaluation of T cell receptor gene rearrangement excision circles after antiretroviral therapy in children infected with human immunodeficiency virus.

Immune reconstitution after antiretroviral therapy in human immunodeficiency virus (HIV)infected patients may result from the recovery of thymus function, peripheral redistribution, or decreased T cell destruction. This study investigated levels of T cell receptor gene rearrangement excision circles (TRECs) as a measure of recent thymic emigrant cells in peripheral blood lymphocytes of 50 HIV-infected infants and children who were followed-up for 40 months after the start or change of antiretroviral therapy. At baseline, patients exhibited fewer TRECs than did uninfected control subjects. The increase in TRECs after antiretroviral therapy was greater in infants than in older HIV-infected children. Of interest, patients who demonstrated discordant responses (i.e., increased CD4 T cell counts without significant virologic suppression) also had substantial gains in TRECs. Furthermore, TRECs correlated positively with the number of CD4 and naive T cells and negatively with age and virus load. Measurement of TRECs may serve as a useful tool for evaluating immune reconstitution in HIV-infected children receiving antiretroviral therapy.

Adolescent↗
PubMed2001

Possible linkage of amprenavir with intracranial bleeding in an HIV-infected hemophiliac.

The use of protease Inhibitors (PI) has been associated with many adverse effects including increased tendency to bleed, which is particularly problematic in individuals with congenital coagulation disorders. We report the occurrence of spontaneous intracranial bleeding in an human immunodeficiency virus (HIV)-infected adolescent with hemophilia A who was receiving amprenavir (APV). The bleeding resolved on discontinuation of APV. This case report highlights a need for awareness of increased bleeding as a potentially serious complication associated with the use of all currently licensed PIs in individuals with hemophilia.

Adult↗
PubMed2001

Identification of bacterial genes required for in-vivo survival.

Genetic approaches used for in-vivo studies of bacterial pathogenesis are providing insights into how bacteria disrupt host defences and exploit host molecules for their own advantage. Signature tagged mutagenesis (STM) provides a means of identifying the genes involved in the process of infection, particularly those genes that are important for bacterial proliferation in-vivo. In this review, the application of STM to the understanding of bacterial pathogenesis and findings from work on three human pathogens, Salmonella typhimurium, Mycobacterium tuberculosis and Neisseria meningitidis, are discussed. The next challenge is to understand how these and other genes influence the infective process at the molecular and cellular levels and to design novel interventions to block the progression of disease.

Bacteria↗
PubMed2000

Patterns of CD8 T cell clonal dominance in response to change in antiretroviral therapy in HIV-infected children.

OBJECTIVE: To examine the influence of change in antiretroviral therapy (ART) on patterns of CD8 T cell clonal dominance in HIV-infected children. DESIGN: Seventeen HIV-infected children with plasma virus loads between 3.1 and 5.7 log10 were investigated before and after changes in ART. METHODS: CDR3 spectratyping was performed in 22 T cell receptor (TCR) Vbeta subfamilies by multiplex polymerase chain reaction (PCR) in purified peripheral blood CD8 T cells in conjunction with CD4 cell counts, plasma HIV-RNA copies and lymphoproliferative assays (LPA). RESULTS: CD8 T cell clonal dominance in two or more Vbeta families was present in eight out of 17 children. After a change in therapy, 13 patients (76%) acquired new clones whereas three patients (17.6%) showed a loss in CD8 cell clones. An increase in the numbers of dominant clones correlated with an increase in percentage CD4 cell counts (P < 0.001) and with improved LPA responses to tetanus (P < 0.05) and alloantigens (P < 0.01). CD4 cell increase was associated with an initial mean gain of 3.1+/-2.1 CD8 cell clones, independent of a virological response. A loss of CD8 cell clones or failure to achieve CD4 T cell increase was associated with failure to achieve virological suppression. CONCLUSION: Children with chronic HIV infection manifest CD8 T cell clonal dominance, which appears to be dependent upon the adequacy of the CD4 cells. With optimization of therapy, a gain in clonal dominance is the predominant response, except in situations of failure to contain viral replication.

Adolescent↗
PubMed2000

An outbreak of gangrenous syndrome among buffaloes and cattle in West Bengal: clinicopathological studies.

Gangrenous syndrome/Degnala disease was recorded in a large number of buffaloes and cattle in Murshidabad district of West Bengal, India. Fusarium spp. had been isolated from the mouldy paddy straw which were fed to the animals. There was a reduction in the incidence of the disease following withdrawal of the mouldy paddy straw. Histopathological examination showed necrosis and loss of architectural details in the skin.

Animal Feed↗
PubMed2000

Functional genomics of Neisseria meningitidis pathogenesis.

The pathogenic bacterium Neisseria meningitidis is an important cause of septicemia and meningitis, especially in childhood. The establishment and maintenance of bacteremic infection is a pre-requisite for all the pathological sequelae of meningococcal infection. To further understand the genetic basis of this essential step in pathogenesis, we analyzed a library of 2,850 insertional mutants of N. meningitidis for their capacity to cause systemic infection in an infant rat model. The library was constructed by in vitro modification of Neisseria genomic DNA with the purified components of Tn10 transposition. We identified 73 genes in the N. meningitidis genome that are essential for bacteremic disease. Eight insertions were in genes encoding known pathogenicity factors. Involvement of the remaining 65 genes in meningocoocal pathogenesis has not been demonstrated previously, and the identification of these genes provides insights into the pathogenic mechanisms that underlie meningococcal infection. Our results provide a genome-wide analysis of the attributes of N. meningitidis required for disseminated infection, and may lead to new interventions to prevent and treat meningococcal infection.

Animals↗
PubMed2000

Indications for and outcomes of emergency peripartum hysterectomy. A five-year review.

OBJECTIVE: To review risk factors, management and outcomes of emergency peripartum hysterectomy performed in the last five years at Stony Brook University Hospital. STUDY DESIGN: Retrospective descriptive and cohort analyses from January 1990 to January 1995. Incidences of emergency peripartum hysterectomy and placenta accreta were determined. Relative risks of hysterectomy for specified risk factors were calculated. RESULTS: There were 39 cases of emergency peripartum hysterectomy, for an overall incidence of 2.7/1,000 births. Indications for emergency hysterectomy were placenta accreta, unspecified bleeding, uterine rupture, myomas and atony with placenta accreta, the most common. The crude relative risk of emergency hysterectomy was 46.9 (n = 37) for cesarean delivery, 15.24 (n = 31) for prior cesarean delivery and 110.83 (n = 21) for placenta previa. CONCLUSION: Cesarean delivery, prior cesarean delivery, placenta accreta and uterine atony were identified as risk factors for emergency peripartum hysterectomy, and abnormal placentation was the primary cause of cesarean hysterectomy.

Adolescent↗
PubMed1999

Chemokine pattern in relation to disease state in human immunodeficiency virus-infected children.

Although beta chemokines can block human immunodeficiency virus (HIV) entry into target cells, their role in HIV disease progression is controversial. To determine the association of RANTES with HIV disease state, we examined constitutive mRNA expression by reverse-transcribed polymerase chain reaction (RT-PCR) in peripheral blood mononuclear cells (PBMCs) and induction of RANTES secretion by enzyme-linked immunosorbent assay (ELISA) in anti-CD3 monoclonal antibody (MAb)-stimulated cultures of PBMCs, and in CD4+ and CD8+ T cell subsets of 17 HIV-infected children. In comparison with uninfected subjects, PBMCs of HIV-infected children were deficient in both constitutive RANTES mRNA expression as well as in stimulus-induced RANTES production. Children in clinical category C were found to be more deficient than children in clinical category A. Expression of RANTES mRNA in PMBCs was inversely correlated with plasma virus load and correlated directly with CD4+ T cell counts. In T cell subsets, RANTES production was equivalent between CD4+ and CD8+ T cells in patients and controls but CD8+ T cells of children in clinical category A produced higher RANTES levels than those of children in clinical category C. The beta-chemokine RANTES may play an important role in slowing clinical disease progression in HIV-infected children.

Adolescent↗
PubMed1999

Clonal dominance patterns of CD8 T cells in relation to disease progression in HIV-infected children.

CD8 T cells are important mediators of cellular immune responses as evidenced by clonal expansions in the CD8 TCR V beta repertoire during primary HIV infection in adults. This study investigated the CD8 TCR V beta repertoire by complementarity-determining region 3 length analysis using multiplex PCR in purified peripheral blood CD8 T cells of 22 HIV-infected children (age range was 0.75-15 yr, mean was 8.2 +/- 4.1 yr). Evidence of clonal dominance in one or more V beta families was obtained in 15 of 22 children. The patterns of clonal dominance were designated as major, minor, single, and none to indicate the involvement of three or more, two, one, or no V beta families, respectively. A pattern of major or minor clonal dominance was observed in 12 children (group 1), whereas 10 children had single or no clonal dominance (group 2). In comparison with group 2, the children in group 1 had a higher percentage of CD4 cells (28.3 +/- 11.6 vs 8.6 +/- 4.8, p < 0.001); a higher stimulation index in lymphoproliferative responses to Candida (92.0 +/- 59.5 vs 12.3 +/- 14.4, p = 0.002), tetanus (76.3 +/- 51.2 vs 11.2 +/- 12.7, p = 0.002), and alloantigens (178.3 +/- 298.9 vs 32.9 +/- 35.2, p < 0.001); and a lower percentage of CD8+HLA-DR+CD38+ cells (37.4 +/- 13.1 vs 54.6 +/- 14.2, p < 0.01). The number of dominant CD8 T cell clones was significantly correlated with the percentage of CD4 T cells (r = 0.669, p < 0.001) but not with plasma HIV RNA. Compared with group 1, patients in group 2 had a 4.8 times greater probability of having < 15% CD4 cells. These findings indicate that CD8 clonal dominance in HIV-infected children reflects robustness of immune responses, regardless of time since infection and virus load.

Adolescent↗
PubMed1999

Assessment of the aging man.

Knowledge of the aging process and the care of older patients has been increasing at a rapid pace. It is important to recognize and separate disease from the physiologic aging process. It is important to do appropriate comprehensive assessments in aging men, so that problems may be identified early and interventions instituted at the right time to delay physical decline, maintain independent living, and ultimately improve the quality of life of this part of the population.

Aged↗
PubMed1998

Immunophenotypic analysis of peripheral blood mononuclear cells undergoing in vitro apoptosis after isolation from human immunodeficiency virus-infected children.

Lymphocytes of human immunodeficiency virus (HIV)-infected individuals undergo accelerated apoptosis in vitro, but the subsets of cells affected have not been clearly defined. This study examined the relationship between lymphocyte phenotype and apoptotic cell death in HIV-infected children by flow cytometry. Direct examination of the phenotype of apoptotic lymphocytes was accomplished using a combination of surface antigen labeling performed simultaneously with the Tdt mediated Utp nick end-labeling (TUNEL) assay. In comparison to live cells, apoptotic lymphocytes displayed an overrepresentation of CD45RO and HLA-DR expressing cells, while CD28 and CD95 expressing cells were underrepresented. Lymphocytes expressing CD4, CD8, and CD38 were equally represented in apoptotic and live populations. When percent lymphocyte apoptosis follow- ing culture was examined independently with lymphocyte subsets in fresh blood, apoptosis was negatively correlated with the percentage of CD4 cells, but not with specific CD4 T-cell subsets. Although not correlated with the percentage of total CD8 cells, apoptosis was positively correlated with specific CD8 T-cell subsets expressing CD45RO and CD95 and negatively correlated for CD8 T cells expressing CD45RA. These results provide direct evidence that a population of activated lymphocytes with the memory phenotype lacking the costimulatory molecule CD28 are especially prone to undergo apoptosis. The findings related to CD95 expression in fresh and apoptotic cells implicate Fas-dependent and Fas-independent pathways of apoptosis in HIV disease in children.

Adolescent↗
PubMed1998

Isolation and characterization of mouse minisatellites.

Minisatellites provide the most informative system for analyzing processes of tandem repeat turnover in humans. However, little is known about minisatellites and the mechanisms by which they mutate in other species. To this end, we have isolated and characterized 76 endogenous mouse VNTRs. Fifty-one loci have been localized on mouse chromosomes and, unlike in humans, show no clustering in proterminal regions. Sequence analysis of 25 loci revealed the majority to be authentic minisatellites with GC-rich repeat units ranging from 14 to 47 bp in length. We have further characterized 3 of the most polymorphic loci both in Mus musculus subspecies and in inbred strains by using minisatellite variant repeat mapping (MVR) by PCR to gain insight into allelic diversity and turnover processes. MVR data suggest that mouse minisatellites mutate mainly by intra-allelic nonpolar events at a rate well below 10(-3) per gamete, in contrast to the high-frequency complex meiotic gene conversion-like events seen in humans. These results may indicate a fundamental difference in mechanisms of minisatellite mutation and genome turnover between mice and humans.

Alleles↗
PubMed1998

Plasma virus load evaluation in relation to disease progression in HIV-infected children.

The objective of this study was to investigate the relationship of plasma HIV RNA load with survival and disease progression in HIV-infected children and to determine its correlation with cellular HIV DNA. Virus load (VL, HIV RNA copies/ml) was determined retrospectively by nucleic acid sequence-based amplification (NASBA) assay in 144 stored plasma samples between birth and 48 months in 50 children of whom 40 are alive (age range, 2-13 years). On the basis of clinical and immunologic status children were classified as rapid progressors (RPs), or nonrapid progressors (NRPs). Proviral HIV DNA quantitated by QC-PCR (quantitative competitive polymerase chain reaction) in 24 children was compared with plasma HIV RNA. At age <3 months, plasma VL <750,000 copies/ml was associated with significantly higher survival to age >2 years (p < or =0.01) compared with a VL of > or =750,000 copies/ml. Increasing mortality was observed with increasing plasma HIV RNA levels at ages 3-24 months and baseline VL of infants who died before age 24 months was significantly higher (p = 0.004) than baseline VL of those who survived beyond 24 months. Although baseline VL in infants classified as RPs was higher than that of NRPs, the difference was not statistically significant. Among surviving children 2-13 years of age, the baseline VL obtained at <24 months of age was not predictive of disease severity. Although no significant correlation was noted between plasma HIV RNA and proviral DNA, the concurrence of positive and negative results was >80%. We conclude that high plasma HIV RNA in infancy is associated with increased mortality.

Adolescent↗
PubMed1998

CD95 expression and apoptosis during pediatric HIV infection: early upregulation of CD95 expression.

Pediatric HIV infection is characterized by a progressive decline in CD4 T lymphocytes and faster disease progression than is typically seen in adults. Apoptosis, possibly mediated through the CD95 antigen, has been proposed as a mechanism for cell loss which eventually leads to immune dysfunction. In this study of peripheral blood lymphocytes from HIV-infected children, classified according to CDC immunologic categories, we found that the percentage of CD4 and CD8 T cells expressing CD95 and the percentage of lymphocytes undergoing apoptosis were increased in children with HIV infection and were greater in children from immunologic Category III as compared to those in Category I. Most striking was our observation that an increased percentage of CD95-positive cells appeared as early as 3 months of age, at a time when these children did not have elevated levels of apoptosis. These data demonstrate early upregulation of CD95 expression in HIV-infected infants, an abberation which may have profound implications for the pathogenesis of perinatally acquired HIV disease.

Age Factors↗