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Biomedical subjects

S R Mehta

Publications and source records attributed to S R Mehta.

At least 55 records · Page 3Linked to original sources
PubMed1987

Low molecular weight B cell growth factor induces proliferation of human B cell precursor acute lymphoblastic leukemias.

Experiments were conducted to determine the effect of low mol wt B cell growth factor (L-BCGF) on B cell precursor acute lymphoblastic leukemia (ALL). L-BCGF induced a significant increase in 3H-TdR incorporation in 28 of 37 bone marrow aspirates from patients with B cell precursor ALL, with stimulation indices ranging from 2 to 129. Fluorescence-activated cell sorting confirmed that in five of seven patients the common acute lymphoblastic leukemia antigen (CALLA)/CD10 positive leukemic cells were responding directly to L-BCGF. L-BCGF was capable of inducing, in some patients, an increase in absolute viable cells and could also induce colony formation in vitro. The response of B cell precursor ALL was not attributable to beta IL 1, IL 2, or gamma interferon. These results indicate that the majority of B cell precursor ALL undergo a proliferative response to L-BCGF, suggesting a regulatory role for this lymphokine in the growth of B cell precursors.

Antigens, Neoplasm↗
PubMed1987

Heat stroke.

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Adult↗
PubMed1987

B-cell growth factor receptor expression and B-cell growth factor response of leukemic B cell precursors and B lineage lymphoid progenitor cells.

The purpose of this study was to analyze the expression of B cell growth factor (BCGF) receptors and to elucidate the biologic effects of biochemically purified natural BCGF at the B cell precursor stage of human B lineage lymphoid differentiation. The specific binding of radioiodinated high-mol-wt BCGF (125I-HMW-BCGF) and low-molecular-wt BCGF (125I-LMW-BCGF) to fresh marrow blasts from B cell precursor acute lymphoblastic leukemia (ALL) patients was initially investigated. The estimated number of radioiodinated BCGF molecules bound per blast ranged from undetectable to 24.3 X 10(3) for HMW-BCGF, and from 11.5 X 10(3) to 457.8 X 10(3) for LMW-BCGF. In 3H-TdR incorporation assays, 75% of cases showed a significant response to LMW-BCGF with a median stimulation index of 9.3. By comparison, only 33% of cases showed a significant response to HMW-BCGF with a median stimulation index of 2.4. Subsequently, B cell precursor colony assays were performed to assess and compare the biologic effects of BCGF on leukemic B lineage lymphoid progenitor cells. Among 28 cases studied, 57% responded to both HMW-BCGF and LMW-BCGF, 21% responded only to LMW-BCGF, and the remaining cases showed no proliferative response to either growth factor. The response patterns of virtually pure populations of FACS-sorted leukemic B cell precursors were essentially identical to the proliferative responses of unsorted leukemic B-cell precursors. Synergistic effects between HMW-BCGF and LMW-BCGF were observed in 80% of the cases that responded to both. The numbers of cell-bound radioiodinated BCGF molecules, the stimulation indices, as well as the number of B cell precursor colonies in BCGF-stimulated cultures showed a marked interpatient variation. Patients with structural chromosomal abnormalities (SCAs) involving 12p11-13 or patients with a Philadelphia chromosome showed a greater HMW-BCGF response at the level of leukemic progenitor cells than did other patients (P = .02). The LMW-BCGF response was significantly greater for patients with SCA than for patients without SCA (P = .04). The response of leukemic progenitor cells to HMW-BCGF or LMW-BCGF did not correlate with sex, age, disease status, FAB morphology, WBC at diagnosis, or immunophenotype. To our knowledge, this study represents the first detailed analyses of BCGF receptor expression and BCGF effects in B cell precursor ALL. The data presented provide direct evidence for the expression of functional receptors for both HMW-BCGF and LMW-BCGF in B cell precursor ALL.

Acute Disease↗
PubMed1986

Characterization of the cell surface receptors for human B cell growth factor of 12,000 molecular weight.

Quiescent normal human B cells have been shown to require an activation step before proliferating in response to B cell growth factor (BCGF) of 12,000 m.w. (12 kd). One effect of cell activation has been the putative acquisition of specific cell surface growth factor receptors. In this report, the existence of such receptors has been confirmed by using purified radioiodinated BCGF-12 kd. BCGF-12 kd receptors on activated B cells have been shown to be distinct form those interacting with IL 2. Scatchard analysis revealed both high affinity receptor sites with an apparent Kd of 28.6 pM and low affinity receptor sites with Kd of 1.2 nM on freshly prepared, anti-IgM activated peripheral blood B cells. Human B cells grown in culture for extended periods of time in the presence of BCGF-12 kd also displayed high affinity receptor sites (Kd, 41.4 pM) and low affinity receptor sites (Kd, 0.9 nM). The action of BCGF-12 kd therefore appears to be mediated by binding to its lineage-specific receptors on the cell surface.

Antibodies, Anti-Idiotypic↗
PubMed1986

Cellular interaction between B and T lymphocytes: enhanced release of B cell growth factor.

The release of a B cell growth factor (BCGF) in medium conditioned by peripheral blood T lymphocytes was shown to be dependent upon accessory cell derived signal(s). T lymphocytes activated with lectin and cultured in the presence of monocytes, or Interleukin 1, provided the in vitro components that were both necessary and sufficient for factor release. B, lymphocytes in the presence of both activated T cells and monocytes, were shown to further augment the amount of factor released by the T cell. The effects of the monocyte and B lymphocyte were, in part, mediated through the DR locus and these effects were consistent with a positive feedback mechanism for the regulation of the availability of BCGF. The data are discussed in terms of differing accessory cell roles for the monocyte and B cell in terms of the mechanisms underlying their augmentative effects on factor release.

Antibodies↗
PubMed1985

Pressor effects of alcohol in normotensive and hypertensive subjects.

The effects of acute alcohol consumption and abstinence on blood pressure were studied in normal healthy subjects and in non-drinking and regularly drinking hypertensive patients. All subjects drank alcohol (1 g/kg body weight daily) for 5 days then abstained for 5 days. There was no significant difference in blood pressure in normal subjects during and after alcohol ingestion. However, in hypertensive non-drinkers both systolic and diastolic pressures when standing were significantly higher during the period of alcohol intake; supine blood pressure was not significantly higher. In hypertensive patients who drank regularly, standing and supine systolic and diastolic blood pressures were significantly higher during the period of drinking.

Adult↗
PubMed1985

IL-2 production and response in vitro by the leukocytes of patients with acquired immune deficiency syndrome.

In order to investigate the nature of the T cell defect associated with the acquired immune deficiency syndrome (AIDS) we studied the ability of peripheral blood mononuclear cells from 8 patients with Kaposi's sarcoma (KS), 2 with opportunistic infection (OI), 23 with AIDS-related symptoms complex (ARC) without KS or OI (ARC), and 29 heterosexual controls to produce interleukin II (IL-2) on phytohemagglutinin (PHA) stimulation and to respond to exogenously supplied IL-2. Patients with AIDS as well as those with ARC produced adequate levels of IL-2 in response to lectin stimulation when compared to controls (AIDS, 3.07 +/- 1.98 units; ARC, 3.03 +/- 1.89 units; controls, 3.75 +/- 1.52 units). However, the ability of these patients' cells to respond in vitro to exogenously supplied IL-2 as measured on short-term PHA-stimulated T cell blasts, was found to be severely impaired in patients with AIDS and ARC (AIDS, 22.4 +/- 6.0 X 10(-3) cpm; ARC, 20.1 +/- 4.2 X 10(-3) cpm; control, 41.4 +/- 4.2 X 10(-3) cpm). This impairment was associated with diminished expression of the IL-2 receptor on 7-day-old lectin-stimulated T cells from both patient groups (AIDS, 17.7 +/- 5.7; ARC, 36.8 +/- 4.4; control 71.8 +/- 1.7). These results should be considered when IL-2 is proposed as potential therapy in the treatment of AIDS. They also suggest that the nature of the AIDS defect is related to impaired hormone receptor expression.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Growth factor-mediated proliferation in B cell non-Hodgkin's lymphomas.

The non-Hodgkin's lymphomas (NHLs) are a heterogeneous group of human lymphoid tumors, primarily of B cell lineage, which appear to represent arrested stages in B lymphocyte differentiation. Control of cell proliferation is a fundamentally important but poorly understood area of study in these tumors. We have studied a representative group of B cell NHLs to assess their potential for growth factor-mediated proliferation in vitro. Our results show that purified monoclonal NHL B cells of the small cell (well-differentiated lymphocytic lymphoma, nodular poorly differentiated lymphocytic lymphoma, etc) type, that were positive for the human malignancy-associated nucleolar antigen could be stimulated by human B cell growth factor (BCGF) to proliferate in vitro. Other B cell activators such as insoluble anti-Ig and the mitogen protein A also could stimulate thymidine incorporation in the lymphoma cell populations. In vitro lymphoma cell growth could be maintained in the presence of the growth factor for up to five weeks. The large B cell type NHL, however, appeared to be refractory to in vitro stimulation by BCGF as well as other stimulators of normal B cells. These studies suggest that human B cell lymphoid tumors are not only phenotypically similar to their normal B lymphocyte counterparts, but are also sensitive in some cases, to the same types of immunoregulatory molecules that control normal lymphoid cell growth.

Antigens, Surface↗
PubMed1985

Purification of human B cell growth factor.

Human B cell growth factor (BCGF, 12,000 to 14,000 daltons) has been purified from lectin-stimulated, peripheral blood mononuclear cell-conditioned medium. The purification procedure involves a series of column chromatographic steps incorporating ion exchange, affinity binding, and gel filtration. This procedure is centered around a relatively high yield single chromatographic step, for the removal of co-eluting cytokines from BCGF, that is based on differential binding characteristics to the weak ion-exchange matrix, hydroxylapatite. Reverse-phase high-pressure liquid chromatographic separation on a C18-Bondapak column effectively separates the BCGF and TCGF moieties, yet is characterized by poor yields. High-pressure liquid chromatographic procedures on anion exchange and size exclusion provided the final purification step for BCGF, at an analytical level, resulting in a single band with a m.w. of 12,000 on a SDS-polyacrylamide gel.

Chromatography, Affinity↗
PubMed1984

Association of an interleukin abnormality with the T cell defect in Hodgkin's disease.

The cellular immune defect in untreated Hodgkin's disease (HD) has long been recognized. This defect appears to be responsible for at least some of the morbidity and ultimately the mortality associated with the disease. In recent years, many studies have shown that the T cell component of the immune response is the apparent site where the defect in HD exists and where the immunoregulatory abnormalities that may account for the deficit are observed. The discovery of the lymphokines and monokines, comprising the human interleukin system, has elucidated some aspects of the regulatory control of the functional pathways involved in T lymphocyte activation and proliferation. The interleukin system can therefore provide the framework to dissect immunodeficiency states, such as that seen in HD. The present study indicates that HD patients' interleukin 1 (IL1) response appears to be normal, as is their T cell proliferative response to exogenous IL2. Interleukin 2 production by HD patients' peripheral blood mononuclear cells, however, is decreased when compared with age/sex-matched controls. The inability to generate IL2 after appropriate stimulation may reflect either a primary cellular defect or a regulatory defect, such as excessive immunosuppression, giving rise to the characteristic T cell hyporesponsiveness seen in HD.

Adolescent↗
PubMed1983

Long-term growth of human B cells and their use in a microassay for B-cell growth factor.

Normal human B lymphocytes, prepared from peripheral venous blood, have been stimulated with intact anti-IgM (mu chain specific) bound to an insoluble matrix. The activation event, in a subfraction of human B cells, was associated with subsequent receptivity to the mitogenic effects of exogenously added B-cell growth factor. The ability of the cell population to specifically absorb the B-cell growth factor was dependent upon the time of stimulation with the anti-IgM. Continuous replenishment of the growth factor resulted in the ability to maintain long-term growth-factor-dependent human B-cell populations. These cultured B lymphocytes were shown to specifically absorb the B-cell growth factor, suggesting the presence of membrane receptors for it. The cultured B lymphocytes were routinely maintained in logarithmic-phase growth, in the presence of growth factor, with a population doubling time of 36 hr. These cultured B cells have been utilized in a microassay for the assessment of B-cell growth factor activity that is accurate, sensitive, and precise.

B-Lymphocytes↗
PubMed1981

Effect of interleukin 1 on human thymocytes and purified human T cells.

Human Interleukin 1 (IL-1) purified by molecular weight fractionation, isoelectric focusing, and gel electrophoresis has been tested on human thymocytes and highly purified human T cells. IL-1 prepared in this manner could not support the long-term growth of T cells yet would augment lectin-stimulated mitogenesis. The IL-1 preparations were shown to possess the lectin-augmenting activity at dilutions containing less than 1 ng of the measurable protein. These data are in agreement with the model that IL-1 stimulates production of IL-2 from lectin-stimulated lymphocytes.

Cell Separation↗
PubMed1981

Human T lymphocyte/monocyte interaction in response to lectin: kinetics of entry into the S-phase.

PHA-mediated mitogenesis of human peripheral blood T lymphocytes was studied by using highly purified cell populations. The kinetics of human, mature T cell [3H]-Tdr incorporation were examined with respect to those elements necessary and sufficient for the progression of the activated T cell into the S-phase of the cell cycle. These experiments indicated that although a lectin may independently initiate morphologic T cell blastogenesis, this event is not associated with significant progression through the G1 phase of the cell cycle. This blastogenic response is associated with the subsequent T cell receptivity to monocyte-initiated cell cycle progression, and the effect of monocytes can be substituted by partially purified Interleukin 1 (IL-1). Progression of a lectin exposed T cell into the S-phase of the cell cycle could also be achieved by exposing the activated T cell to partially purified Interleukin 2 (IL-2). Given the prior demonstrations that IL-1 functions to induce the T cell-dependent production of the IL-2, it appears that IL-2 is the requisite signal necessary for the activated human lymphocyte to actually progress through the prereplicative phase of the cycle into the S-phase.

Cell Communication↗