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S Gautam

Publications and source records attributed to S Gautam.

At least 37 records · Page 2Linked to original sources
PubMed1994

p53-immunoreactive protein and p53 mRNA expression after transient middle cerebral artery occlusion in rats.

BACKGROUND AND PURPOSE: We investigated the temporal distribution of the p53-immunoreactive protein in conjunction with cellular damage and the expression of the p53 mRNA after focal cerebral ischemia in rats. METHODS: Male Wistar rats (n = 66; controls, n = 7) were subjected to 2 hours of middle cerebral artery occlusion and were killed at various times of reperfusion (0.5 to 168 hours) for p53 immunohistochemistry and Northern blot analysis. RESULTS: A cellular expression of mutant p53-immunoreactive protein was found localized to anatomic sites exhibiting severe neuronal damage. A maximal induction of mutant p53-immunoreactive protein was found at 12 hours after reperfusion and subsequently declined. No wild-type p53 protein expression was detected after ischemia. A time-dependent expression of p53 mRNA was observed in both hemispheres. The peak level of p53 mRNA occurred at 24 hours after reperfusion. CONCLUSIONS: Our data indicate that the expressions of p53-immunoreactive protein and p53 mRNA are upregulated after transient focal cerebral ischemic insult in rats. The concomitant appearance of p53 and cell damage in ischemic brain suggests that p53 expression may impact cell biological response to an ischemic insult.

Animals↗
PubMed1992

IL-4 suppresses cytokine gene expression induced by IFN-gamma and/or IL-2 in murine peritoneal macrophages.

The effect of IL-4 on inflammatory gene expression in murine peritoneal macrophages stimulated with IFN-gamma in combination with IL-2 has been examined. These agents cooperatively induce the expression of mRNA for TNF-alpha and IP-10. Murine rIL-4 suppresses cytokine mRNA expression depending on the stimulus used and the mRNA being measured. Expression of TNF-alpha mRNA in macrophages stimulated with IFN-gamma, IL-2, or the combination is markedly suppressed by IL-4 whereas LPS-induced TNF-alpha mRNA is unaffected. In contrast, IP-10 mRNA expression is more sensitive to suppression by IL-4 when stimulated by LPS than by IFN-gamma/IL-2. IL-4-mediated suppression does not alter the time course of mRNA expression. Treatment of IFN-gamma/IL-2-stimulated macrophages with cycloheximide blocks the suppressive effect of IL-4, suggesting that de novo synthesis of an intermediate protein is part of the suppressive mechanism. The IL-4-mediated suppression of IFN-gamma/IL-2-driven TNF-alpha gene expression appears to be mediated at the level of transcription. These findings support a role for IL-4 as an antiinflammatory cytokine and suggest that macrophage inflammatory function will be dependent on the precise stimulus composition of the tissue microenvironment.

Animals↗
PubMed1992

Restricted replication of vesicular stomatitis virus in T lymphocytes is coincident with a deficiency in a cellular protein kinase required for viral transcription.

Vesicular stomatitis virus (VSV) fails to replicate in mouse T lymphocytes unless the cells have been mitogenically stimulated with concanavalin A (Con A). We have examined the possibility that the failure of VSV to replicate in unstimulated T lymphocytes can be attributed to a deficiency in a host protein kinase which activates the viral P protein by phosphorylation, thus rendering it transcriptionally competent. Soluble extracts were prepared from purified mouse T lymphocytes, with or without prior treatment with Con A. The ability of these extracts to phosphorylate bacterially synthesized P protein of two VSV serotypes was measured in vitro. Activity of the protein kinase on the P proteins of the Indiana or New Jersey serotypes of VSV increased, on average 2.4- and 2.1-fold respectively, after treatment of the cells with 3 micrograms/ml Con A. Higher concentrations of Con A induced proportional increases (up to 10-fold) in the activity of the host protein kinase. Activities of the kinase phosphorylating the P protein in separate populations of CD4- and CD8-containing murine T lymphocytes increased similarly on mitogenic activation. No biochemical or immunological differences were observed between the T cell protein kinase and the previously characterized protein kinase (casein kinase II) from BHK-21 cells. The activity of the kinase that phosphorylates the P protein did not vary in CV-1 cells on treatment with alpha- or gamma-interferon, both of which inhibited VSV replication. Similarly, casein kinase II activities in Raji and SIRC cells, which do not normally support VSV growth, were the same as in BHK-21 cells. Thus restriction of VSV replication in these cells, in contrast to T lymphocytes, was not associated with a deficiency in the host casein kinase II activity.

Animals↗
PubMed1991

Phase I trial of continuous infusion interleukin-2 and doxorubicin in patients with refractory malignancies.

A phase I trial was performed to assess the immunomodulatory activities, maximum tolerated doses, and the toxicity of recombinant interleukin-2 (rIL-2) administered in combination with doxorubicin to patients with refractory malignancies. Therapy was administered to successive cohorts of four to six patients who were treated at three different dose levels (1A, 1B, 2A). Levels 1-2 refer to doxorubicin (40 or 60 mg/m2) given as an intravenous (i.v.) bolus on day 1, and levels A-B refer to rIL-2 (1.0 or 3.0 x 10(6) U/m2) given as a continuous i.v. infusion on days 2-5, 9-12, and 16-19. Cycles were repeated every 28 days. Seventeen patients were entered in the trial. Dose limiting toxicity consisted of neutropenia, and the maximum tolerated dose (MTD) of the combination was doxorubicin 40 mg/m2 and rIL-2 3.0 x 10(6) U/m2. No objective responses were observed. Lymphocytosis related to rIL-2 occurred and flow cytometry demonstrated significant increases in the following subsets: CD3+CD25+HLADr+ and CD11b-CD16c+CD8-. Natural killer cell activity and lymphokine-activated killer (LAK) cell precursors were increased in patients treated at dose levels 1A and 1B (40 mg/m2 doxorubicin), but no consistent changes in LAK activity were noted. No clinical responses were seen and the overall toxicity of this combination was moderate to severe. Administration of doxorubicin prior to rIL-2 does not enhance the immunologic effects of rIL-2.

Adult↗
PubMed1991

Glycosylated hemoglobin and diabetic retinopathy.

Estimation of glycosylated hemoglobin (HbA1c) levels by modified Fluckinger and Winterhalter's method was done in 25 normal persons, 25 diabetic patients without retinopathy, and 25 diabetic patients with retinopathy. The HbA1c values were significantly higher in diabetic patients with or without retinopathy than in the control group (P less than .001). In diabetic patients with retinopathy, the mean value of HbA1c was higher in proliferative retinopathy than in background retinopathy, but statistical analysis showed this was not significant (P greater than .6).

Adult↗
PubMed1989

Generation of tumoricidal effector cells by human C-reactive protein and muramyl tripeptide: a comparative study.

C-reactive protein (CRP) delivered in liposomes [CRP-multilamellar vesicles (MLV)] has been demonstrated to inhibit lung and liver metastases in C57 mice bearing the syngeneic tumors T241 fibrosarcoma and MCA-38 colon carcinoma, respectively. Also peritoneal exudate cells (PEC) from CRP-MLV-treated animals exhibited tumor inhibitory activity in the Winn neutralization assay, and the magnitude of this activity was comparable to that of PEC from muramyl tripeptide (MTP)-MLV-treated mice. The present studies were carried out to compare the mechanisms involved in generation of the tumoricidal effector cell by CRP-MLV and MTP-MLV. The antitumor activity of both CRP-MLV- and MTP-MLV-activated PEC was markedly inhibited by antimacrophage antiserum and complement in the Winn neutralization assay. Also, both activities were unaffected by treatment with anti-immunoglobulin antiserum and complement. However, antitumor activity of CRP-MLV-activated PEC was inhibited by anti-Thy 1.2 and antiasialo Gm 1 antisera in the presence of complement, whereas these reagents had no effect on MTP-MLV-activated PEC. Thus, the antitumor effect of MTP-MLV appears to be mediated principally by macrophages, whereas that of CRP-MLV may also involve other cells bearing T- and/or natural killer-cell markers.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Communicating with cancer patients.

In a prospective study, 100 cancer patients and their relatives were separately interviewed using a structured interview to examine whether the diagnosis of cancer should be communicated to patients and relatives; the reasons for doing so or not, the emotional reactions of patients and families; any change in the attitude of relatives; behaviour of patients and patient's expectation, on diagnosis, of the course of their illness. The majority of patients, who knew their diagnosis (71%), wanted to be told the truth. The majority of relatives wanted to know the truth themselves (81%) without the patients being told (77%). Patients did show immediate emotional reactions like anxiety and dejection, however they appeared to accept the diagnosis. Findings suggest that in an Indian setting the attitude of family members is more positive. The role played by sociocultural factors in the acceptance of the truth is discussed.

Adult↗
PubMed1987

Use of resealed erythrocytes as delivery system for C-reactive protein (CRP) to generate macrophage-mediated tumoricidal activity.

We have shown previously in several mouse tumor systems that multilamellar vesicles (MLV) are an effective delivery system for generation of macrophage-mediated tumoricidal activity by C-reactive protein (CRP). Here we show that resealed erythrocyte ghosts (red cell ghosts, RCG) can function in the same manner. CRP associated with red cell ghosts (CRP-RCG) inhibited established lung metastases of T241 fibrosarcoma in C57B1/6J mice. The degree of inhibition was comparable to that observed with CRP-MLV. In other experiments, peritoneal exudate cells, obtained from mice pretreated with CRP-RCG i.p., inhibited growth and pulmonary metastases of T241 tumor in the Winn neutralization assay. Similar results were obtained with MCA-38 colon carcinoma in the Winn assay. These studies indicate that erythrocytes deserve consideration as another delivery system for biological response modifiers.

Adjuvants, Immunologic↗
PubMed1984

Experimental beryllium-induced lung disease. II. Analyses of bronchial lavage cells in strains 2 and 13 guinea pigs.

In previous studies, we found that endotracheal administration of beryllium oxide (BeO) produced cell-mediated immunity and granulomatous lung disease in strain 2 but not strain 13 guinea pigs. This report describes phenotypic and functional studies of bronchial lavage cells from both guinea pig strains after BeO exposure. In BeO-treated strain 2 animals, the percentage of T (ER+)3 lymphocytes was significantly (p less than 0.05) elevated above normal by 2 weeks after BeO exposure, while T lymphocytes were not increased in strain 13. Giant cells containing crystalline material in fused, coalesced phagolysosomes were observed in treated animals of both strains. BeO-exposed strain 2 alveolar macrophages (AM) demonstrated enhanced killing of Listeria monocytogenes and enhanced chemiluminescence, while AM of strain 13 had responses below controls. Findings support the presence of BeO-induced cellular immunologic activity in strain 2 animals and, on the other hand, suggest BeO toxicity to lavage cells in strain 13.

Animals↗
PubMed1984

Macrophage activation and generation of tumoricidal activity by liposome-associated human C-reactive protein.

The effect of human C-reactive protein incorporated into multilamellar vesicles (CRP-MLV) was studied in assays of macrophage function. Peritoneal exudate macrophages from C57BL/6 mice phagocytosed CRP-MLV in vitro more rapidly than multilamellar vesicles bearing comparable amounts of immunoglobulin G. Exposure of peritoneal exudate macrophages in vitro to CRP-MLV resulted in development of tumoricidal activity against syngeneic T241 fibrosarcoma and B-16 melanoma cells and against allogeneic Sarcoma 1 cells. Peritoneal exudate macrophages obtained from mice given CRP-MLV i.p. demonstrated antitumor activity against the syngeneic T241 fibrosarcoma in a Winn-type assay, and when challenged in vitro with phorbol myristate acetate, they showed elevated superoxide anion production. Administration of CRP-MLV i.p. did not enhance natural killer activity of spleen cells, however. In superoxide anion assays, CRP-MLV were approximately 10 to 100 times more effective than free C-reactive protein. Results indicate that C-reactive protein is capable of activating macrophages, thus supporting the concept of C-reactive protein as an immunomodulator.

Animals↗
PubMed1984

Experimental beryllium-induced lung disease. I. Differences in immunologic responses to beryllium compounds in strains 2 and 13 guinea pigs.

Granulomatous lung disease was produced in strain 2 but not strain 13 guinea pigs by endotracheal injection of beryllium oxide (BeO), although isolated multinucleated giant cells containing crystalline material were found in lungs of both strains. Disease was also produced in (2 x 13) F1 hybrids, but of a milder form than in strain 2. In BeO-treated strain 2 and F1 animals, challenge with beryllium salts produced delayed hypersensitivity skin reactivity, and in vitro, enhanced tritiated thymidine uptake and lymphokine production by lymph node cells. No evidence was found for involvement of humoral immunity in the disease. Responses were not seen in BeO-treated strain 13 guinea pigs, and immunization of animals with BeO in complete Freund's adjuvant produced similar immunologic findings. These data emphasize the involvement of genetically determined cellular immune mechanisms in beryllium lung disease.

Animals↗
PubMed1983

Subsets of oncofetal antigen-induced T-cells: ability to mediate antitumor immune response.

The present study was performed to identify the subsets of oncofetal antigen-induced T-cells that mediate antitumor immune response in mice. In this study, performed on a weakly immunogenic, metastatic tumor, fetal antigen-sensitized spleen cells significantly inhibited the growth and metastases of tumors in Winn neutralization assay. Mixing of spleen cells from tumor-bearing inbred C57BL/6J mice with fetal antigen-sensitized spleen cells completely abolished the tumor inhibitory effect of fetal antigen-sensitized spleen cells. Further characterization of fetal antigen-sensitized spleen cells showed that they were Thy-1+. These findings reveal that tumor-associated fetal antigens on fetal cells can produce a tumor inhibitory T-cell immune response against the growth and metastases of a weakly immunogenic, metastatic tumor. The subset of oncofetal antigen-induced T-cells that mediates antitumor immune response was identified as Lyt-1+ and Lyt-2-. Adoptive transfer of fetal antigen-sensitized spleen cells to mice with preestablished metastases significantly inhibited the lung metastases in these mice, thus making this approach more relevant to a clinical situation in cancer patients.

Animals↗
PubMed1981

Dept. of Microbiology, School of Medicine, East Carolina University, Greenville, NC.

The responsiveness of spleen cells from C57BL/6J mice to various immunogenic stimuli was examined during the progressive growth of a poorly immunogenic fibrosarcoma T241. A strong correlation was observed between the progressive tumor growth and the depression of response to Concanavalin A, lipopolysaccharide, sheep red blood cells, and alloantigens in mixed lymphocyte reaction and cell-mediated lympholysis (CML). The maximum depression of these immune responses occurred when the animals had grown tumors for 3-4 weeks. Furthermore, serum from these animals collected 20 days after tumor transplantation was highly immunosuppressive. The possible mechanisms of tumor-induced immunosuppression have been discussed.

Animals↗
PubMed1981

T-cell-mediated antitumor immune response induced by oncofetal antigens.

The possibility that fetal antigens take part in tumor immunity has been investigated to a limited extent, but the results of these studies have been controversial. It is not clear that tumor inhibition shown in some systems is due to an immune reaction. In the present study, performed in a weakly immunogenic tumor system (Lewis T241 fibrosarcoma in inbred C57BL/6J mice), immunization of mice with syngeneic fetal cells resulted in striking inhibition of growth and metastases of tumors. Mice that had gone through single pregnancies also showed a decreased rate of tumor growth and tumor metastases. Further studies have shown that the tumor inhibitory response evoked by fetal cell immunization is due to fetal antigens, and the male specific HY antigen is not responsible for antitumor response. Injection of tumor cells mixed with spleen cells from mice immunized with syngeneic fetal cells into normal mice resulted in significant inhibition of tumor growth and metastases in the Winn neutralization assay. Syngeneic fetal cells, normal adult spleen cells, or spleen cells from C57BL/6 mice immunized with allogeneic fetal cells did not inhibit tumor growth or metastases. These results show that tumor inhibition following fetal cell immunization is due to an immune reaction and is not due to a nonimmune physiologic process. Further analysis of effector cells showed them to be of the T-cell type.

Animals↗