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Biomedical subjects

R Pahwa

Publications and source records attributed to R Pahwa.

120 records · Page 7Linked to original sources

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↗

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↗

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↗

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↗

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↗

Aplastic anaemia: Evidence for an immunological mechanism.

The soft agar culture assay (C.F.U.-C) has been used in vitro as a measure of haemopoietic capacity of bone-marrow. In a patient with aplastic anaemia pretreatment of the patient's bone-marrow with horse anti-human-thymocyte globulin and complement (A.T.G. + C) prior to culture led to a dramatic increase in ability to form colonies in the soft agar assay; and co-culturing marrow from a normal donor and from the patient resulted in a distinct reduction in the number of expected C.F.U.-C. These findings point ot an immunological or autoimmune mechanism in this patient by selective destruction of the suppressing cells in the patient's marrow with A.T.G. and by suppression of normal myelopoiesis following addition of the patient's marrow to normal marrow.

Adult↗

Ontogeny of lymphocyte subpopulations in human fetal liver.

Lymphocytes were isolated from five fetal livers (13-17 weeks) and examined for different surface markers. Immunoglobulin M was found on 0.5-4.0% of lymphocytes. No membrane-bound surface IgD, IgA. or IgG was detected. Mouse erythrocyte rosette-forming lymphocytes ranged from 0.5 to 6.0%. Thymus-processed (T) lymphocytes, which were defined as those forming spontaneous rosettes with sheep erythrocytes, as well as lymphocytes with IgG Fc receptors, were present in a small proportion. No complement-receptor-bearing lymphocytes were found in the two cell populations of fetal liver studied. It is evident that during the ontogeny of bone-marrow-derived (B) lymphocytes IgM is the first surface immunoglobulin to appear. Receptors for the binding of mouse erythrocytes are present at the same time as surface IgM. The slight excess of mouse erythrocyte rosette-forming cells over cells having surface immunoglobulin M could mean that IgM appears later than do the receptors for the binding of mouse erythrocytes.

Animals↗

Effect and time course of deep brain stimulation of the globus pallidus and subthalamus on motor features of Parkinson's disease.

We studied the effect and temporal profile of deep brain stimulation (DBS) of the globus pallidus and subthalamic nucleus on the motor signs of Parkinson's disease (PD). Four patients with bilateral deep brain stimulators of the globus pallidus and four patients with bilateral deep brain stimulators of the subthalamus were studied while taking no medication and at 15 and 30 minutes and 1, 2, 4, and 6 hours after turning stimulation on. An immediate (15 minutes) and sustained (6 hours) benefit was observed for all the motor manifestations of PD for both stimulation sites. Deep brain stimulation of the globus pallidus and subthalamus is highly effective in reducing all the cardinal motor features of PD.

Electric Stimulation Therapy↗

Dopamine agonists in the treatment of Parkinson's disease.

Bromocriptine or pergolide can be used as initial monotherapy in Parkinson's disease. When used as an adjuvant to levodopa therapy, these drugs can result in clinical improvement and a decreased levodopa requirement. To avoid side effects, the starting dosage should be low (1.25 mg per day of bromocriptine or 0.05 mg of pergolide) and should be increased slowly. The standard daily dose of bromocriptine ranges from 7.5 to 60 mg, and of pergolide, from 0.75 to 4 mg. Combination therapy with low dosages of levodopa and a dopamine agonist may also decrease the incidence of side effects of both agents.

Bromocriptine↗

Gender differences in Parkinson's disease.

We examined data from 630 patients entered into the University of Kansas Medical Center's Parkinson's Disease (PD) Registry to determine if gender differences exist in terms of both cognitive and motor symptoms of PD. An analysis of the Mini-Mental State Examination scores indicated slightly higher scores for women relative to men. Although women had significantly better scores than did men on the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS), they had a significantly greater prevalence of dyskinesias compared with men. These motor differences were significant only in patients with PD of greater than 5 years duration. There were no gender differences for age of diagnosis, Hoehn and Yahr Staging, Schwab and England Scale, or the mentation and activities of daily living sections of the UPDRS. We conclude that as PD progresses, gender differences emerge, with men exhibiting more severe parkinsonian motor features and women experiencing more levodopa-induced dyskinesia.

Aged↗