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Biomedical subjects

R Pahwa

Publications and source records attributed to R Pahwa.

At least 109 records · Page 6Linked to original sources
PubMed1986

Pediatric acquired immunodeficiency syndrome: demonstration of B lymphocyte defects in vitro.

Acquired immunodeficiency syndrome (AIDS) in childhood is characterized by recurrent bacterial infections, a feature common in antibody deficiency disorders. The present study was aimed at investigating B lymphocyte function in 15 children aged 6 months to 6 years with AIDS or AIDS-related complex (ARC). Spontaneous secretion of immunoglobulins by freshly isolated peripheral blood B cells and the generation of immunoglobulin and antibody-secreting cells in lymphocyte cultures after polyclonal and antigenic stimulation were quantified in hemolytic plaque assays. Despite excessive spontaneous immunoglobulin secretion, responses elicited by B cells after in vitro stimulation were depressed in these children. Responses to T-dependent as well as to T-independent stimuli were affected. Studies of immunoregulatory T cells and intrinsic B cell function suggested that deficient precursor B cells and abnormal immunoregulation contributed to the defects in B cell differentiation. These findings indicate that B lymphocyte dysfunction is an integral feature of HTLV III infection in children who clinically present as either AIDS or AIDS-related complex.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Influence of the human T-lymphotropic virus/lymphadenopathy-associated virus on functions of human lymphocytes: evidence for immunosuppressive effects and polyclonal B-cell activation by banded viral preparations.

The etiologic agent for the acquired immunodeficiency syndrome (AIDS) is now firmly established as the retrovirus termed the human T-lymphotropic virus type III (HTLV-III) or the lymphadenopathy-associated virus, LAV. The disease is characterized by profound and progressive loss of immunity, but molecular evidence indicates that only a few cells in peripheral blood are being productively infected with this virus. In the present study we have investigated a disrupted HTLV-III viral preparation for biologic effects on normal lymphoid cells. Relatively dilute concentrations of this preparation were found to stimulate immunoglobulin secretion by peripheral blood lymphocytes; at the same dosages, the preparation was inhibitory for the B-cell differentiation responses that are induced with other known polyclonal B-cell activators, pokeweed mitogen, Staphylococcus aureus, and Epstein-Barr virus. This preparation was also inhibitory at high concentrations for T-lymphocyte proliferative responses to phytomitogens and antigens and resulted in a reduced expression of Tac antigen on phytohemagglutinin-activated lymphocytes. Paradoxically, incubation of lymphocytes of certain healthy donors with the HTLV-III preparation alone resulted in increased expression of Tac and Leu-12 antigens. These findings show that a disrupted preparation of HTLV-III virus can mimic many of the immunologic abnormalities present in patients with HTLV-III infection. Nonviable viral proteins may be responsible for some of the immunologic perturbations that occur in HTLV-III-infected states.

Acquired Immunodeficiency Syndrome↗
PubMed1985

T lymphocyte subpopulations in high-risk infants: influence of age and blood transfusions.

Methodology was established to analyze T lymphocytes and T cell subsets with monoclonal antibodies on microsamples of blood obtained by heel puncture in infants. Results in 39 high-risk infants indicated that during the early neonatal period they had a higher percentage of T4-bearing cells and a lower percentage of T8 antigen-positive cells as compared with adults. These values progressively approached adult values, and at 3 to 7 months the T cell subsets and the T4/T8 ratios were within the adult range. A significant inverse relationship was noted between the number of blood transfusions given to the infants between 2 and 12 weeks of age and the corresponding T4/T8 ratio. These findings suggest that interpretation of T cell subsets in frequently transfused infants should take into consideration not only the age of the infant but also the possible influence of transfusions per se on the distribution of T cell subsets in the peripheral blood.

Aging↗
PubMed1985

Ethnic heterogeneity in the distribution of the OKT4 antigen on lymphocytes: studies in three black families.

Human T lymphocytes bear characteristic membrane antigens which allow for identification on these cells and their subpopulations with monoclonal antibody reagents directed against the specific cell-surface antigens. During a study of T lymphocyte subpopulations in a group of 41 infants from a high risk nursery, three of the seven black infants studied were found to be missing cells reactive with the monoclonal antibody OKT4 which identifies the helper-inducer subset of T cells. Immunological evaluation of these infants and study of their family members revealed that the OKT4 non-reactive lymphocytes reacted normally with another antibody, OKT4A, which also identifies the helper-inducer subset of T cells. The deficiency of the antigen recognized by the OKT4 antibody appeared not to reflect T cell immaturity and was not associated with obvious immunodeficiency. The OKT4 negative phenotype appeared to be transmitted in an autosomal recessive mode. Our studies suggest that heterozygosity for this phenotype is relatively common among the black population and that heterozygotes are not easily distinguishable from the random population on the basis of lymphocyte reactivity with the OKT4 monoclonal antibody.

Antibodies, Monoclonal↗
PubMed1983

Persistent cytomegalovirus infection: association with profound immunodeficiency and treatment with interferon.

Cytomegalovirus (CMV) was repeatedly isolated from urine and saliva of a 20-month-old male child with recurrent episodes of pneumonia, high fever, rash, lymphadenopathy, oral ulceration, and neutropenia. Immunologic evaluation revealed decreased serum IgG and IgA, increased IgM, depressed T- and B-lymphocyte functions, and decreased natural killer (NK) activity for herpes simplex-type I virus-infected targets. NK activity was augmented following exposure of the patient's lymphocytes to interferon (IF) in vitro. The child was treated with interferon (four courses, dosage varying from 2 million U/day to 1 million U three times/week for periods of 10, 28, 80, and 67 days, respectively, interspersed over 9 months) and hyperimmune plasma infusions every 3 weeks. Toward the end of interferon therapy oral Levamisole was started and a feeding gastrostomy was inserted to provide nutritional support. Clinical recovery was associated with reversal of immunologic abnormalities except for the hypogammaglobulinemia. Aggressive antiviral therapy (e.g., with IF) followed by immunostimulation (e.g., with Levamisole) may prove effective in controlling certain viral infections in immunodeficiency disorders.

Agammaglobulinemia↗
PubMed1981

Specific immunosuppressive effects of constant infusion of 2'-deoxycoformycin.

The effect of continuous infusion into C57BL/6J mice of 2'-deoxycoformycin (DCF), a tight-binding inhibitor of adenosine deaminase, on the biological function of bone marrow stem cells and T- and B-lymphocytes was evaluated. Greater than 85% inhibition of adenosine deaminase in erythrocytes, thymus, and bone marrow was noted after DCF infusion at 0.4 mg per kg body weight per day, while lesser extents of inhibition were characteristic of spleen and lymph nodes. The reconstitution of lethally irradiated C57BL/6J mice with bone marrow cells from DCF- and 0.9% NaCl infused mice of the same strain was compared. The two groups of animals were virtually identical with respect to (a) the number of spleen colony-forming units, (b) the response of splenic lymphocytes to both B- and T-cell mitogens, (c) hematological analysis of peripheral blood elements, and (d) survival time, thus strongly supporting the lack of effect of DCF infusion on the capacity of stem cells to differentiate. In contradistinction, DCF infusion was highly lymphocytotoxic as noted by the severe necrosis in both B- and T-cell regions in lymph nodes and spleen and by the dramatic weight reduction in spleen and thymus. Histopathology of other tissues including bone marrow was normal except for the occurrence of hepatitis. A striking decrease in blastogenesis induced by the mitogens concanavalin A, phytohemagglutinin, and Escherichia coli lipopolysaccharides was also observed after DCF infusion. Consistent with these data, in vitro incubation of bone marrow cells with DCF did not impair the number of spleen colony-forming units produced in lethally irradiated mice. These data suggest a potential use for adenosine deaminase inhibitors in the prevention of graft-versus-host disease in hematopoietic transplantation.

Adenosine Deaminase↗
PubMed1980

A micromethod for determination of terminal deoxynucleotidyl transferase (TdT) in the diagnostic evaluation of acute leukemias.

A micromethod for the determination of TdT in peripheral leukocytes and bone marrow cells has been developed that allows unequivocal identification and quantitation of TdT in less than 1 X 10(6) leukocytes from ALL patients, i.e., in 1 ml of peripheral blood and/or 0.5 ml of bone marrow obtained during routine clinical sampling. The method involves disruption of cell pellet with high salt and detergent followed by centrifugation of extracts at 12,000 X g and partial purification on phosphocellulose matrix by a batch elution technique using a standard laboratory microcentrifuge. Using this microassay, TdT activities have been determined in 500 samples of peripheral blood and bone marrow of 240 adult patients with acute leukemias (86 ALL, 108 ANLL, 44 blastic CML, two acute leukemias following P. vera). From an analysis of our data based on TdT activity, cell surface markers and growth patterns in soft agar and observations published in the literature, it can be concluded that the frequencies of TdT + phenotypes in the various clinical-morphological diagnostic groups are approximately 95% in ALL, 10% in ANLL, 50% in AUL, and 35% in blastic CML. Since the presence of high TdT activity is clearly associated with clinical response to specific forms of chemotherapy in blastic CML and most probably, also in ANLL, the determination of TdT should be considered in all cases of acute leukemias to objectively define prognostically important subgroups which can not be diagnosed by conventional means.

Acute Disease↗
PubMed1980

Animal model for immune dysfunction associated with adenosine deaminase deficiency.

An in vivo murine model for immunodeficiency of both B and T cells is produced by continuous intraperitoneal infusion of 2'-deoxycoformycin (DCF), a specific tightly binding inhibitor of adenosine deaminase (ADase; adenosine aminohydrolase, EC 3.5.4.4). After DCF infusion, ADase of thymus, spleen, and lymph nodes was inhibited to varying degrees ranging from 57% to 100%. Immunodeficiency under these conditions was indicated by: (i) a striking decrease in lymphocyte response to the T-cell mitogens concanavalin A and phytohemagglutinin; (ii) an impairment of delayed hypersensitivity measured by the footpad reaction; (iii) a decrease in antibody production measured in both in vivo and in vitro plaque-forming cell assay; (iv) a significant prolongation of mouse skin allograft survival after transplantation into the C57BL/6J (H-2b) strain of skin from BALB/c (H-2d) mice; and (v) a marked lymphopenia. Histological examination indicated lymphoid degeneration in the thymus, lymph nodes, and spleen with no alterations in other tissues including bone marrow, kidney, lung, gastrointestinal tract, and liver except for the occurrence of hepatitis. A decrease in the number of Thy-1-positive cells in both spleen and lymph nodes further supported the fact of cytotoxicity of DCF to T cells. Anorexia and weight loss were observed within 5 days of continuous DCF infusion at 0.4 mg/kg body weight per day. These data indicate that this method provides an experimental model for future studies on the biochemical mechanisms responsible for the genetically determined severe combined immunodeficiency disease in man.

Adenosine↗
PubMed1980

Specific inhibitory activity against granulocyte-progenitor cells produced by non-T lymphocytes from patients with neutropenia.

Bone marrow and peripheral blood cells of patients with non-leukemic neutropenia contain and elaborate a granulocyte-progenitor cell inhibitory activity. The inhibitory activity is common to the neutropenias of the various etiologies studied, which included congenital, idiopathic, autoimmune, cyclical, common variable immuno-deficiency with hypogammaglobulinemia and drug induced states. It derives from non-adherent, low density, slowly sedimenting and non-E-rosetting cells and appears to require RNA and protein synthesis, but not cell division, for its production. The material is not species specific, inhibits autologous and allogeneic normal CFUgm and leukemic CFUgm, is not cell-cycle specific in action and is most effective against granulocyte colony forming cells (CFUg), less effective against mixed granulocyte-macrophage colony forming cells (CFUgm) and least or non-effective against macrophage colony forming cells (CFUm). This inhibitory activity has no influence on cells which generate CFUc in suspension culture or on the erythroid colony forming (CFUe) and burst forming (BFUe) units. It is different from other known inhibitory activities such as lactoferrin, leukemia inhibitory activity, E type prostaglandins, interferon and immunoglobulins. This inhibitory activity, while at present an in vitro phenomenon, may be produced as a secondary response within a compromised host.

Agranulocytosis↗
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↗