Physiochemical characterization of rat liver glucocorticoid receptor during development.
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Biomedical subjects
Publications and source records attributed to S Gupta.
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The immunoregulatory activity of bone marrow leukemic blasts from five patients with null-cell acute lymphoblastic leukemia (ALL) and two children with T-cell ALL was evaluated. Blasts were studied in co-culture for their effects on the proliferative responses of normal allogeneic peripheral blood lymphocytes to phytohemagglutinin. Mitomycin C-treated null cell ALL blasts from two of five children suppressed the proliferative responses of normal responder cells by 80% and 58% whereas those from two other children enhanced the responses by 118% and 31%. T-cell leukemic blasts from one patient with T-cell ALL exhibited helper cell activity (26%) and T-leukemic blasts from the other demonstrated suppressor cell activity (53%). The helper cell activity of leukemic blasts was associated with stimulating capacity of null blasts in one-way mixed lymphocyte reactions. In six of seven cases, incubation of blast cells with concanavalin A (20 microgram/ml) for 48 hours prior to co-culture with responder cells did not result in the generation of significant suppressor cell activity. Our study suggests that leukemic blasts from certain patients with 'null' and T-cell ALL may possess spontaneous helper or suppressor cell immunoregulatory activity. This functional heterogeneity of leukemic blasts may help in subclassifying the ALL.
Radiation changes are observed in all postirradiated smears of squamous cell carcinoma of the cervix from 56 females, although to a variable degree. After 1 year the changes subside gradually. A high cornification index is a good guide for recurrence. The significance of dysplastic cells as premonition for recurrence is debatable. The presence of malignant cells at any stage was considered of grave significance, and indicates poor radiation response or recurrence.
Percentage of malignant cell exfoliation in relation to that of benign epithelial cells was studied in pretreatment vaginal smears of 251 patients of squamous cell carcinoma of the cervix. The rate of exfoliation did not increase with increasing clinical severity. Also, the various cell types of squamous cell carcinoma and clinical radiation response were independent of number of malignant cells shed in the vagina. However, the group of patients having a fewer number of malignant cells in their vaginal smears had a statistically significantly better five-year survival.
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Various reviews documenting the rarity, diagnostic problems, and poor survival statistics prompted this retrospective clinicopathological study of 58 cases of primary small bowel tumors, periampullary and mesenteric tumors excluded, over a 14-year period between 1966 and 1979 inclusive. Of these cases 36 were male and 22 were female, ranging in age from 13 to 65 years. Initially, the symptoms were vague and ill defined. Prominent clinical features were: intermittent abdominal pain (6+%), loss of weight (62%), abdominal lump (53%), and chronic bleeding (7%). Routine barium meal examination and laboratory investigations were not helpful in preoperative diagnosis. Of these tumors 28 were benign and 30 malignant, with the commonest benign and malignant tumors being leiomyoma and lymphoma, respectively. The commonest site of involvement was the ileum both for benign and malignant lesions. None of the benign tumors was found in the duodenum. All patients with benign tumors, discovered either at laparotomy for intestinal obstruction or during surgical procedures for other diseases, had excision of the tumor through enterotomy or resection of small bowel with end-to-end anastomosis. Of 30 patients with malignant tumors, 12 underwent resection of the growth and end-to-end anastomosis. Of the remaining 18 unresectable cases, 7 had by-pass procedures and 11 had only biopsy. All patients of benign tumors are well without any gastrointestinal symptoms. All the malignant cases, except three cases of adenocarcinoma and two of lymphoma who underwent resection, died within 5 years. The 5-year survival of only 8.6% in malignant tumors indicates the necessity of an early exploratory laparotomy in doubtful cases with vague abdominal symptoms. A bold interventionist approach should improve the otherwise dismal outlook of malignant small bowel tumors.
Thirty-eight patients of advanced adenocarcinoma of the stomach were randomly administered intensive courses of either 5-FU or mitomycin C by intravenous route, The 5-FU administration resulted in a slightly better response than mitomycin C, although the toxic effects of the two drugs were more or less the same. The selection of drug regime in the present study has been based on cost, availability, potential toxicity, and minimal alteration of the patients' life style.
Fish, Notopterus notopterus, in four sizes (4.5 +/- 1.0, 9.0 +/- 1.0, 14.5 +/- 1.2, and 22.6 +/- 1.8 cm in length) were exposed to phenol (P), 2,4-dinitrophenol (DNP), and pentachlorophenol (PCP) separately, and also to their three combinations (PCP + DNP)/P (highly antagonistic), (DNP + P)/PCP (additive), and (P + DNP)/PCP (highly synergistic) to evaluate the effect of fish size on the toxicity of these chemicals separately and in combination. The results reveal that with increased fish size (from 4.5 + 1.0 to 14.5 + 12 cm in length) toxicity of phenolic compounds decreased. On the contrary, the larger size fish (22.6 +/- 1.8 cm in length) was comparatively more susceptible. This indicates that change in fish size does influence the toxicity of phenolic compounds.
Peripheral blood mononuclear cells from 16 patients with common variable immunodeficiency and 4 with selective IgA deficiency were studied for the quantitative analysis of T-cells and T-cell subsets with distinct immunoregulatory properties, using a battery of monoclonal antibodies and the fluorescence-activated cell-sorter. The proportions of OKT4+ cells were decreased and OKT8+ cells were increased in patient groups when compared to normal controls analyzed simultaneously. 14/20 (70%) patients demonstrated a lower OKT4+/OKT8+ cell ratio compared to controls. Imbalance of immunoregulatory T-cells may explain one of the mechanisms of hypogammaglobulinemia in a subgroup of patients with primary immunodeficiency.
Autologous mixed lymphocyte reaction (AMLR) between T and non-T cells was studied in 12 patients with selective IgA deficiency. Seven of 12 patients demonstrated significantly (P less than 0.05) lower AMLR when compared to simultaneously studied age and sex matched controls. In the allogeneic MLR, T cells from patients responded normally to control non-T cells; however, non-T cells from patients were poor stimulators against normal responder T cells when compared to allogeneic MLR between different normal controls. The deficient AMLR in selective IgA deficiency further supports abnormal immune regulation and might explain the increased incidence of autoimmune phenomena and autoimmune diseases associated with selective IgA deficiency.
Peripheral blood from 25 patients with insulin-dependent diabetes mellitus was examined for any alteration in the proportions and or functions of immunoregulatory T-cell subsets, defined with monoclonal antibodies. Ten of 25 (40%) patients demonstrated deficiency of OKT8+ (suppressor/cytotoxic) T-cells. Eight of these 10 patients had abnormally high ratios of OKT4+/OKT8+ T-cells. Nine of 10 patients with abnormally low proportion of OKT8+ T-cells had deficient concanavalin A-induced suppressor cell activity against the proliferative response of autologous or allogeneic lymphocytes to phytohemagglutinin. No correlation was observed between the deficiency of suppressor T-cells and the control of diabetes. Therefore, it is likely that the deficiency of suppressor cells is related to insulin-dependent diabetes mellitus itself and not to the metabolic changes that are associated with diabetes mellitus. This study demonstrates both quantitative and qualitative deficiency of suppressor T-cells in at least some patients with insulin-dependent diabetes, that might play an important role in the pathogenesis and autoimmune manifestations of a proportion of patients with insulin-dependent diabetes mellitus.
Natural killer (NK) cells were enumerated in the peripheral blood mononuclears from 13 patients with primary immunodeficiency disease, using recently developed monoclonal antibody, Leu 7 (HNK-1). Eight of 13 patients demonstrated quantitative deficiency of NK cells when compared to simultaneously studied healthy controls, using monoclonal antibody and fluorescence-activated cell sorter (FACS). The quantitative deficiency of NK cells could be one of several factors responsible for increased susceptibility to infections and increased incidence of malignancies in patients with primary immunodeficiencies.
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The cell-mediated immune responses of 39 patients with common variable immunodeficiency (CVI) were studied in vitro, using Staphylococcus aureus and Escherichia coli prepared as whole cells and Candida albicans extract. These microbial activators wee found to require intact B-lymphocyte function for normal proliferative response. The patient group was observed to have significantly depressed lymphocyte responses compared wit those of controls studied in parallel (P less than 0.01). Negative lymphocyte response to one activator and strongly positive response to another were found in individual patients. Examination of patients' lymphocyte response to S. aureus and E. coli in association with serum IgG levels demonstrated that a rough correlation could be drawn, showing that patients with serum IgG less than 125 mg/dl had markedly lower (P less than 0.01) lymphocyte responses than those with serum IgG greater than 300 mg/dl. No similar correlation with phytohaemagglutinin activation was observed. Since depressed lymphocyte responses did not correlate with reduced B-cell number in these patients, intrinsic B-lymphocyte deficiency was indicated. These preparations of microbial activators are potentially useful tools in exploring lymphocyte subpopulation functions in primary immunodeficiency diseases.
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Bone marrow T leukaemic blasts from four patients with T-cell acute lymphoblastic leukaemia (ALL) were examined as effectors in natural killing (NK) and antibody-dependent cytotoxicity (ADCC). T leukaemic blasts demonstrated both Nk (against K-562 cells as targets) and ADCC (against chicken erythrocytes (CRBC) and cells of SB cell line as targets). NK activity and ADCC (against SB cells) were comparable to NK and ADCC (against SB cells) of peripheral blood T cells from healthy controls. ADCC against CRBC by leukaemic blasts was lower than that of peripheral T cells from normal controls. Of leukaemic blasts 20-42% possessed IgG Fc receptors. This study demonstrates that T leukaemic blasts are effectors in NK and ADCC assays.
Previous theoretical analysis has indicated that adequate mass transfer is possible in a dialyzer with reciprocating membrane motion provided that the dialysate concentration of uremic substances is kept low. Earlier models have utilized a collection of sorbents (charcoal, urease, and a cation exchanger) constrained next to the dialyzer membranes. We have designed a new dialyzer with a sorbent suspension having free access from a reservoir to the spaces between membrane packages. At a treatment rate of 150 ml/min/m2, the in vitro creatinine clearance is 75 ml/min/m2, which agrees within experimental accuracy with the theoretical prediction. The creatinine clearance, flow resistance, and compliance of the dialyzer are constant during four to six hours of testing. In vivo tests have been performed during urea and creatinine infusion in a normal dog and in a dog with 3/4 nephrectomy. The in vivo creatinine clearance agrees within 10% with the in vitro clearance. Sodium, potassium, calcium, and bicarbonate fluxes are acceptable for patients in renal failure. The new design allows a higher capacity for urea and creatinine, since larger amounts of sorbent may be used.