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Biomedical subjects

R Pahwa

Publications and source records attributed to R Pahwa.

At least 19 recordsLinked to original sources
PubMed1992

Effect of human immunodeficiency virus-1 envelope glycoprotein on in vitro hematopoiesis of umbilical cord blood.

Although hypercellularity is a common bone marrow finding in patients with human immunodeficiency virus type 1 (HIV-1) infection, the effect of HIV-1 on the hematopoietic system, which has been investigated in in vitro studies, is still controversial. In this study, we have investigated the effects of HIV-1 envelope glycoprotein, gp160, on the differentiation of hematopoietic progenitor cells derived from cord blood. Culture of cord blood mononuclear cells with gp160 resulted in enhancement of the in vitro growth of myeloid hematopoietic progenitors. To investigate the mechanism of the enhancement, adherent cells, T cells, or CD34-bearing hematopoietic progenitors were isolated and cultivated with gp160 in a variety of culture conditions. We have shown that gp160 had no direct effect on highly purified hematopoietic progenitors but exerted its enhancing effect indirectly via T cells, by induction of a humoral colony-stimulating factor(s). The activity of gp160 on T cells was abrogated by preincubation of gp160 with recombinant CD4 molecule and goat anti-gp120 antibody. These data provide evidence for a novel biological activity of HIV envelope glycoprotein, that of T-cell-mediated stimulation of myelopoiesis. Binding of gp160 with the cell surface CD4 molecule appears to be necessary for secretion of the colony-stimulating factor(s).

Antibodies↗
PubMed1992

Superantigen staphylococcal enterotoxin B-induced T-helper cell activation is independent of CD4 molecules and phosphatidylinositol hydrolysis.

The role of the CD4 molecule in activation of T-helper cells was examined by investigating the effect of an anti-CD4 monoclonal antibody (Leu3a) in conventional peptide antigen-specific cloned T-helper cells that are also reactive to staphylococcal enterotoxin B (SEB). These T-helper cell clones are CD4+/CD45RO+/T-cell antigen receptor beta-chain variable region 12-positive and can respond to nominal peptide antigens and SEB by proliferation in the presence of class II major histocompatibility complex-expressing accessory cells. Although antigen and SEB were comparable in their ability to induce proliferative responses, interleukin 2 (IL-2) production, and IL-2 receptor alpha-chain expression, stimulation with SEB failed to trigger phosphatidylinositol hydrolysis or a rise in the intracellular free calcium ion concentration. Leu3a treatment inhibited antigen-induced proliferative responses of T cells with concomitant suppression of IL-2 production and IL-2 receptor expression. In contrast, SEB-induced responses were unaffected by Leu3a. These findings indicate that the functional consequences of binding (ligation) of conventional antigen and of superantigen with the T-cell receptor are distinct in the context of both signal transduction pathways and participation of CD4 molecules.

Antibodies, Monoclonal↗
PubMed1992

The effect of acetazolamide on essential tremor: an open-label trial.

We studied the effect of the carbonic anhydrase inhibitor acetazolamide on 24 patients with essential tremor by patient self-evaluation of functional disability, rating of motor task function, and clinical rating of tremor severity. Acetazolamide significantly reduced tremor severity, but there was no statistically significant change in patient self-assessment of function or motor task rating. Although side effects were common, over half the patients elected to remain on the drug.

Acetazolamide↗
PubMed1992

Olfactory function in essential tremor.

Olfactory function, assessed by the University of Pennsylvania Smell Identification Test, was normal in essential tremor (ET) patients and significantly reduced in patients with Parkinson's disease (PD). This finding further supports a lack of association between ET and PD.

Female↗
PubMed1991

Forensic toxicology and insects: a minireview.

In cases of suspicious death, various postmortem changes and the insect species infesting the corpse have been employed to compute the time of death. Recently, chemical analysis of the life stages of insects infesting the corpse has revealed poisons and drugs consumed for suicide in the body of the deceased. This new area can provide proof of the cause of death. It is recommended that whether or not there is suitable tissue samples for the analysis, the developmental stages of insects thriving on the carcass should always be collected as exhibits for analysis.

Adult↗
PubMed1990

Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes.

The circulating T lymphocytes of a female child with recurrent opportunistic infections were normal in number and phenotype but exhibited poor proliferation and decreased synthesis of the T-cell growth factor interleukin (IL) 2 in response to mitogens. Recombinant IL-2 fully restored the proliferative responses of her T cells, suggesting that her poor immune function was related to IL-2 deficiency. Northern blot analysis of total cellular RNA from the patient's T cells revealed markedly decreased levels of IL-2 mRNA of normal size. In addition, mRNA levels of other lymphokines selectively expressed by T cells, which include IL-3, IL-4, and IL-5, were either severely depressed or absent. The levels of interferon gamma mRNA were moderately decreased, while those of granulocyte-macrophage colony stimulating factor, a lymphokine the production of which is not restricted to T cells, were unaffected. The decreased level of lymphokine mRNA in the patient's T lymphocytes was not from enhanced catabolism but resulted from a diminution in the transcription rate of the affected lymphokine genes. Normal transduction via the T-cell receptor/CD3 complex of biochemical signals necessary for the initiation of lymphokine gene transcription indicated that the defect was distal to the membrane signal-transducing apparatus. The defect is hypothesized to involve a T-cell-specific trans-acting regulatory factor required for transcription of the affected lymphokine genes.

Antibodies, Monoclonal↗
PubMed1990

Human immunodeficiency virus type 1 envelope glycoprotein gp120 produces immune defects in CD4+ T lymphocytes by inhibiting interleukin 2 mRNA.

Envelope glycoprotein gp120 of human immunodeficiency virus type 1 (HIV-1) is known to inhibit T-cell function, but little is known about the mechanisms of this immunosuppression. Pretreatment of a CD4+ tetanus toxoid-specific T-cell clone with soluble gp120 was found to exert a dose-dependent inhibition of soluble antigen-driven or anti-CD3 monoclonal antibody-driven proliferative response, interleukin 2 (IL-2) production, and surface IL-2 receptor (IL-2R) alpha-chain expression, all of which were reversed by the addition of exogenous IL-2. mRNA for the gene encoding IL-2 was suppressed by treatment with gp120, but IL-2R gene transcription was not inhibited. Bypass activation of the T-cell clone with phorbol 12-myristate 13-acetate plus ionomycin was unaffected by gp120 pretreatment. Thus, gp120-CD4 interaction interferes with an essential role of the CD4 molecule in signal transduction through the CD3-antigen receptor (Ti) complex. Such a mechanism of gp120-induced immunosuppression, if operative in vivo, could contribute to the depressed specific immune responses associated with HIV infection.

Antigens, CD↗
PubMed1990

The toxicity of yellow oleander (Thevetia neriifolia juss) seed kernels to rats.

Toxic effects of yellow oleander (Thevetia neriifolia Juss) seed kernels were evaluated against the roof rat (Rattus rattus Linn). Crushed ground seed kernels were fed with bait at 20 and 30% concentrations. The bait was fed up to mortality or for a maximum of 10 d. Major signs of poisoning observed were hind limb paralysis, rolling of the body on the long axis, circular flailing of the tail, muscular twitch, tetanic convulsions, tremors, collapse and death. Significant reductions in the rats' weights were observed. The observed mortalities were 16/20 and 18/20 with the above respective doses. Statistically significant reductions in hemoglobin, red blood cell count, total leucocyte count and neutrophils, and increased lymphocytes were observed. Reductions in blood glucose and serum proteins, and increased lymphocytes were observed. Reductions in blood glucose and serum proteins, and increased BUN, SGOT and LDH, were also significant. Histopathological studies showed inflammatory and degenerative changes in the liver and kidney. Severe to moderate fatty metamorphosis, congestion, hepatocytolysis, nuclear degeneration, pyknosis, and necrosis were major changes in the liver. Proliferation of glomerular endothelium, hypercellularity of the glomerulus, necrosis of convoluted tubular epithelium, disappearance of nuclei and pyknosis were important changes in the kidney cortical region. Atrophy, erosion and inflammatory changes were observed in the stomach mucosal linings.

Animals↗
PubMed1978

Successful transplantation of marrow from an HLA-A, -B, -D mismatched heterozygous sibling donor into an HLA-D-homozygous patient with aplastic anemia.

A patient with aplastic anemia who was found to be homozygous for an HLA-D determinant shared by her unrelated parents achieved sustained engraftment and full restoration of hematopoietic and lymphoid function following a transplant from an HLA-A and -B nonidentical, ABO incompatible sibling who was heterozygous for the shared HLA-D specificity. Transplantation was complicated by transient graft-versus-host disease of moderate severity, which resolved completely following treatment with antithymocyte globulin and prednisone. The case indicates that patients found to be HLA-D-homozygous may be successfully transplanted from HLA-D-heterozygous sibling donors despite HLA-A and HLA-B incompatibilities, and thus further demonstrates the importance of the HLA-D region as a marker of donor-host histocompatibility.

Anemia, Aplastic↗
PubMed1977

Reconstitution in severe combined immunodeficiency by transplantation of marrow from an unrelated donor.

A patient with severe combined immunodeficiency received seven transplants of bone marrow from an HLA-B-compatible and HLA-D-compatible unrelated donor in an attempt to provide immunologic reconstitution. The first four transplants achieved restricted engraftment with evidence of rudimentary immunologic function. A fifth transplant, given after low-dose cyclophosphamide, produced reconstituion of cell-mediated immunity. Marrow aplasia developed after recontamination with a nonpathogenic microflora. Transplantation of marrow previously stored in liquid nitrogen was ineffective. A subsequent transplant, administered after high-dose cyclophosphamide, achieved durable engraftment, with complete hematopoietic and immunologic reconstitution. Seventeen months after transplantation, full functional engraftment persists. Graft-versus-host disease has been chronic and moderately severe, but limited to the skin and oral mucosa. Transplantation of marrow from unrelated histocompatible donors may provide a useful treatment for patients with severe combined immunodeficiency or aplastic anemia who lack a matched sibling or related donor.

Bone Marrow Transplantation↗
PubMed1977

Circulating thymic-hormone activity in congenital immunodeficiency.

Circulating thymic-hormone activity was assayed by measuring Thy 1-2 antigen induction on null lymphocytes from athymic mice incubated with human plasma or serum. Plasma from 19 normal children aged under 10 had inductive activity equivalent to 10-6-16-2 ng thymopoitin/ml. Plasma from 15 infants were severe combined immuno-deficiency, 2 of whom had appreciable immunoglobulin synthesis, and from 2 infants with DiGeorge syndrome had little or no inductive activity. Successful reconstitution with thymus or bone-marrow grafts and with red-cell infusions (if adenosine-deaminase deficiency is present) was followed by a rise in circulating thymic-hormone activity.

Agammaglobulinemia↗
PubMed1977

Rationale for combined use of fetal liver and thymus for immunological reconstitution in patients with variants of severe combined immunodeficiency.

Bone marrow cells from a patient with severe combined immunodeficiency were studied in vitro for thymus-dependent lymphocyte (T cell) differentiation by using, at varying times, thymic epithelial monolayers and culture supernatants, thymopoietin, ubiquitin, and thymic extract as inducing agents. On initial evaluation, with thymopoietin or human thymic extract, only a partial differentiation of marrow cells was achieved into cells bearing the human T cell antigenicity without the capacity to form rosettes with sheep erythrocytes, suggesting that the stem cells were defective. Two fetal liver transplantations aimed at reconstitution were unsuccessful, despite evidence of chimerism. Induction studies at that time demonstrated rosetting capacity (with sheep erythrocytes) of the patient's bone marrow cells after coculture with thymic epithelial monolayers but not with their supernatants. An 18-week fetal thymus (irradiated) was then transplanted, but the transplantation was unsuccessful and no clear evidence of chimerism was demonstrated. Subsequently, transplantation of another fetal liver resulted in chimerism and immunologic reconstitution. Serum thymic factor activity rose from 1:2 before transplantation to 1:16 after reconstitution. The combined use of fetal thymus and liver may provide effective immunological reconstitution in some variants of severe combined immunodeficiency.

Bone Marrow↗
PubMed1977

Cellular and humoral components of monocyte and neutrophil chemotaxis in cord blood.

Monocyte and polymorphonuclear neutrophil (PMN) chemotaxis was studied in cord blood from healthy term infants. Monocyte chemotaxis was normal to increased (115-126%) whereas PMN chemotaxis was decreased (79%) in comparison with that of healthy adult control subjects. Generation of chemotactic factors from cord sera was impaired, being 55% of that generated by pooled normal human serum (PNHS). Cord serum was less inhibitory than pooled adult human serum for adult monocytes when the cells were suspended in 10% serum and tested for chemotaxis. No inhibition of chemotactic factors by either cord or adult sera was observed. The dissociation of chemotactic response of the two different phagocytic cells may represent a protective mechanism whereby one cell can compensate for a defect in the response of the other.

Chemotaxis, Leukocyte↗
PubMed1977

Rosette formation with mouse erythrocytes. IV. T, B and third population cells in human tonsils.

Mononuclear cells from twenty human tonsils and peripheral blood lymphocytes were examined for T, B and 'third population cells'. Compared with peripheral blood lymphocytes, tonsils were found to have a higher proportion of B lymphocytes with surface IgM, IgD and IgA. Mouse erythrocyte rosette-forming cells were also present in increased proportions. However, 'third population cells' were found in very low proportions. Phagocytic cells as determined by latex ingestion and peroxidase staining were also present in low proportions. The lack of 'third population cells' in human tonsils may establish this organ as one of particular interest in the study of lymphocyte subpopulations because T and B lymphocytes can be purified without contaminating 'third population cells'. The role of the third population of lymphocytes in antibody-dependent cytotoxicity and spontaneous cytotoxicity may be supported by the absence of these functions along with absence of the 'third population' cells from tonsilar lymphoid cells.

Adult↗