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Biomedical subjects

S R Mehta

Publications and source records attributed to S R Mehta.

At least 19 recordsLinked to original sources

Establishment and characterization of human B-cell lymphoma cell lines using B-cell growth factor.

B-cell non-Hodgkin's lymphomas (NHL-B) have been difficult to establish in long-term cell culture using standard techniques. We report the establishment of five representative cell lines from high grade NHL-B using B-cell growth factor (BCGF). The five NHL-B cell lines display the morphologic, immunophenotypic, genotypic, and biologic characteristics of the lymphoma cells present in the original diagnostic specimen. The cell lines showed at least a sevenfold dose-dependent increase in proliferation in vitro over background in the presence of BCGF. Other putative B-cell growth-stimulating cytokines showed no significant proliferative activity or were inhibitory in some cases. NHL-B cell lines secreted growth factor(s) into culture supernatants that mediated at least a fivefold dose-dependent increase in cell proliferation in autochthonous lymphoma cells and a 10-fold or greater stimulation in growth factor-dependent normal B cell lines in vitro. The cell lines show monoclonal rearrangements of IgH genes and nonrandom chromosomal abnormalities characteristic of NHL-B, while the expression of Epstein-Barr virus associated antigen (EBNA-I) is present in two of the five cell lines. The studies show that lineage-specific growth factors may be used to establish neoplastic B cell lines in vitro, which are important experimental systems for cellular and molecular studies in the NHL-B.

Adolescent

Traumatic heart disease.

Five cases of traumatic heart disease (THD) who sustained blunt chest injury in road accidents are reported. In addition to fracture of the ribs (observed in all the cases), there was fracture of the sternum and rupture of the liver and spleen in one case each. Two patients had flail chest. One presented with recurrent ventricular tachycardia lasting for 72 hours followed by changes suggestive of subendocardial infarction. The second case also had changes like subendocardial infarction and it was preceded by junctional tachycardia with aberrant conduction during the first 48 hours. Ventricular premature beats (VPB) were the only abnormality noted in one case and the remaining two had ST-T wave changes suggestive of inferolateral ischaemia without any arrhythmias. The patient with VPB developed pericardial rub without effusion. There was one death and postmortem revealed ruptured liver and spleen in addition to laceration of the right ventricle and haemopericardium. The electrocardiographic changes persisted for two to eight weeks. All four cases were symptom-free at 12 weeks and treadmill exercise test done after 12 to 18 weeks was normal.

Accidents

Normokalaemic periodic paralysis as the presenting manifestation of hyperthyroidism.

We report a 50 year old male admitted with complaints of episodic weakness. During the attack of paralysis there was no hypokalaemia. There were no clinical signs of thyrotoxicosis, but since thyroid function tests revealed hyperthyroidism, he was treated as a case of thyrotoxic periodic paralysis, with no recurrence of symptoms over 6 months.

Humans

Congenital afibrinogenaemia.

A case of congenital afibrinogenaemia in a young female child is described. She had haemorrhagic tendency since birth in the form of markedly prolonged umbilical bleeding and easy bruising afterwards. Two of her brothers had bleeding tendencies, one died shortly after birth due to uncontrollable umbilical bleeding and other died at the age of 12 years from internal haemorrhage. The family study indicates the mode of inheritance to be probably autosomal recessive. The principal laboratory findings are complete non-coagulability of blood, grossly abnormal coagulation tests, zero ESR value, failure to detect fibrinogen by heat coagulation or chemical precipitation tests and biuret reaction and correction of thrombin time after fibrinogen infusion.

Afibrinogenemia

Multigated radionuclide ventriculography during in-hospital phase of acute myocardial infarction.

Global and regional left ventricular performance was assessed by multigated radionuclide technique in thirty patients sustaining acute myocardial infarction on two occasions during in-hospital phase. Thirteen (76.5%) of the seventeen patients with anterior infarction had depressed initial left ventricular ejection fraction compared with seven (53.8%) of the thirteen patients with inferior infarction. From initial to discharge study, change in ejection fraction was statistically insignificant in either group of infarctions. All except three (10%) patients had regional wall motion abnormality on initial evaluation with little subsequent alteration. Our data demonstrates that ejection fraction changes variably during the course of illness, and location of infarction has profound effect upon degree of left ventricular dysfunction. Assessment by non-invasive radionuclide technique may have prognostic implications.

Adult

Falciparum malaria--present day problems. An experience with 425 cases.

Clinical details and present day problems encountered in 425 cases of falciparum malaria (PF) are reported. 10.11% had taken chloroquine prior to reporting to us. Parasitic count done in 23.05% cases lacked correlation with severity of disease. Pattern of fever varied markedly but 5.4% were afebrile throughout and presented only with bodyache and malaise. Apyrexial spell was noted in 5.64%. 28.70% had typical facial looks of anaemia and sallow complexion. Cerebral symptoms were noted in 3.05%. Other symptoms were severe headache 33.4%, pain abdomen 3.29%, gastroenteritis 5.64%, jaundice 2.58% and bronchitis in 7.50%. We encountered subconjunctival haemorrhages with purpura and/or urticaria in four cases, symptoms suggestive of shock lung in 3, pulmonary oedema in 2, severe anaemia (HB less than 4 g%) in seven pregnant ladies, extrapyramidal symptoms in follow up period in 5 and congenital malaria in 2 cases. 83.25% were cured with chloroquine and oxytetracycline. 8.47% (who deteriorated despite the above treatment) were treated with quinine for 6 days. 5.17% (with severe disease) were also given quinine as first line drug. 2.82% (unresponsive to chloroquine and oxytetracycline but with mild disease) were treated with pyrimethamine-sulphamezathine combination for 5 days. One case who did not respond to quinine was treated with quinidine. Recrudescence was seen in 3.67% of patients treated with chloroquine and oxytetracycline. There was no case with renal failure, haemolysis due to G6PD deficiency and black water fever. There was only one death (0.23%) in our series. Self-medication, haphazard therapy and the slogan "Fever may be malaria-take chloroquine" can lead to problems in falciparum malaria.

Adolescent

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

Heat stroke.

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Adult

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

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

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

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

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

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