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P K Ray

Publications and source records attributed to P K Ray.

At least 37 records · Page 2Linked to original sources
PubMed1999

Stress genes and species survival.

Stress genes can be ascribed to have been generated by the organism for their intrinsic urge to survive against the changing environmental odds, during the evolutionary process. This concept has been supported by a large number of reports describing individual types of phenomena. These have been reconciled and globalised in terms of their relevance in this article. Supporting evidences have been drawn from the literature which indicated that by using different types of inducer one can express heat shock proteins. Similarly, several types of stress inducers, such as calorie restriction, LPS stimulation and Staphylococcal Protein-A stimulation, it was possible to induce a wide array of biological, biochemical and immunological reactions. Such biological reactions rendered protection against toxic, carcinogenic, metabolic, as well as biological stresses induced by microorganisms. Heat shock proteins have been implicated as having a role in providing resistance to the host against different types of stressors. In this article, some mechanistic schemes have been proposed as possible pathways globalising such phenomena. A minute amount of stress inducers has been observed to have helped expression of stress resistance genes, providing increased capability to the host to protect itself against myriads of both biotic and abiotic stressors. More understanding about such phenomena would help in keeping our physiological systems vigilant and our bodies healthy, fighting out the stress-related events effectively.

Animals↗
PubMed1998

Protein A induces NO production: involvement of tyrosine kinase, phospholipase C, and protein kinase C.

Protein A of S. aureus exhibits a wide array of immunopotentiating activities. Since the role of nitric oxide (NO) in bioregulation has been well envisaged; we studied the effect of Protein A on NO production by immunocytes both in vivo and in vitro. Our data indicate that PA at a comparable dose of LPS (lipopolysaccharide) increases the NO levels in the serum of Swiss albino mice by about 12-fold from its basal level. The peak level is reached at about 12 hours after i.p. inoculation of PA. However, NO concentration returns to the basal value 15 hours posttreatment. Splenic lymphocytes and peritoneal macrophages showed appreciable increase in NO production when cultured with PA in vitro. Interestingly, inhibitors of tyrosine kinase, phospholipase C, and protein kinase C (PKC) inhibited NO production in splenic lymphocytes. Thus, it appears that these enzymes participate in the signaling cascade induced by PA, which culminates in the production of NO downstream of PKC. It is possible that PA-induced NO production may have relevance with the anti-tumor and anti-parasitic properties of PA, described earlier.

Animals↗
PubMed1998

Mechanism of protein A-induced amelioration of toxicity of anti-AIDS drug, zidovudine.

Long-term treatment with 3-azido-3-deoxy thymidine (AZT) is often associated with myelosuppression. In AZT-treated Swiss mice, similar toxicological manifestations in terms of reduction of red blood and white blood cell counts and hemoglobin content had been observed as in AZT-treated AIDS patients. Pretreatment of animals with Protein A (PA) of Staphylococcus aureus Cowan I (1 microgram/ml), twice a week for two weeks, alleviated such hematopoietic toxicity due to AZT. AZT-induced reduction in colony-forming unit-erythroid (CFU-E) and colony-forming unit-granulocyte monocyte (CFU-GM) were also reversed by the combined treatment of AZT and PA. PA treatment showed an increased level of erythropoietin in the blood plasma, and cellularity of spleen, thymus, and bonemarrow was also increased in the group receiving combined treatment (PA+AZT), higher than that in the AZT group. AZT or its metabolites inhibited the activities of liver microsomal monooxygenases, which, however, could be regenerated in an accelerated manner by pretreatment of mice with PA. Moreover, the PA-treated group showed an accelerated clearance of AZT and/or its metabolites. These results suggest that such an immunopharmacologic approach might substantially reduce the toxic effects of drugs, such as AZT.

Anemia↗
PubMed1997

Protein A induced protection against experimental candidiasis in mice.

Staphylococcus aureus protein-A (SpA), an important multipotent immunostimulator, increased the resistance to infection with Candida albicans in Swiss albino mice. The mice treated with repeated immunologically active doses (1 microgram/mouse) of SpA, pre- and post-infection, showed one hundred percent protection against experimental candidiasis, and constituted the first such report. Protection could be demonstrated on the basis of leukocyte counts, colony forming unit (CPU) kinetics in liver, spleen, kidney and peritoneal cavity, and phagocytosis by monocyte-derived macrophages.

Animals↗
PubMed1997

Ontogeny of neurotransmitter amino acids in human fetal brains.

A wide spectrum of developmental profiles is presented for a few important neurotransmitter amino acids, namely gamma-aminobutyric acid, glycine, glutamic acid, aspartic acid and taurine as well as the key enzymes involved in their metabolism in human fetal brains of different gestational ages. Besides taurine almost all these amino acids and their key metabolic enzymes were found to be progressively enhanced upto the mid period of third trimester of pregnancy indicating a rapid growth of nerve processes, myelination and maturation of fetal brains particularly during this period. Interestingly taurine showed an inverse relationship of ontogenic pattern with respect to its biosynthesizing enzyme in fetal brains.

4-Aminobutyrate Transaminase↗
PubMed1996

Ontogeny of GABA pathway in human fetal brains.

The developmental profiles of gamma-aminobutyric acid (GABA), its biosynthesizing enzyme L-glutamic acid decarboxylase (GAD) and its degradating enzymes gamma-aminobutyric acid-alpha-ketoglutaric acid transaminase (GABA-T) and succinic semialdehyde dehydrogenase (SSADH) in four different regions of human fetal brains have been evaluated. The GABA pathway was found to be maximally active in fetal brains during the third trimester of pregnancy. The relative activities of the enzymes as well as GABA content were least in pons compared to cerebrum, cerebellum and mid brain regions throughout the period of fetal development.

4-Aminobutyrate Transaminase↗
PubMed1996

Antitumour activity of protein A in a mouse skin model of two-stage carcinogenesis.

Protein A (PA) is an immunostimulating glycoprotein (mol. wt. 43,000 kDa) obtained from Staphylococcus aureus cowan I. The antitumour property of PA is well documented in the literature in various transplantable tumours of rats and mice. In the present set of investigations, the antitumour property of PA was tested in Swiss albino mice in a two-stage initiation-promotion mouse skin carcinogenesis model. The animals were initiated topically with a single subcarcinogenic dose (52 microgram) of 7,12-dimethylbenzanthracene (DMBA). PA was administered intraperitoneally (1 microgram/animal), twice weekly for 2 weeks. Promotion was performed by twice weekly applications of 12-O- tetradecanoyl phorbol-13-acetate (TPA) at a dose of 5 microgram/animal for 32 weeks. The result showed that the treatment schedule can effectively check the onset of tumorigenesis, the cumulative number of tumours and the average number of tumours per mouse. In the PA administered group, 30% of the animals remained tumour free until the termination of the experiments (i.e. 32 weeks of promotion). Thus the present study proves that protein A can effectively inhibit DMBA initiated and TPA promoted mouse skin carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1995

Modulation of primary antibody response by protein A in tumor bearing mice.

Protein A (PA) is a cell wall glycoprotein of Staphylococcus aureus Cowan I, which possess a number of immunomodulatory and antitumor properties. We have previously shown that PA suppresses the anti-sheep erythrocyte primary antibody response in normal mice. The present investigation evaluates the effect of protein A on the anti-sheep erythrocyte primary antibody response in tumor-bearing mice. The primary antibody response in tumor-bearing mice immunized with sheep red blood cells (SRBC) was suppressed by the intraperitoneal administration of PA in a dose-dependent fashion. The plaque forming cell (PFC) assay was used to assess this response. Maximum suppression of the PFC response was observed at 12 micrograms PA/animal (p < 0.001) and could be observed at doses as low as 1 microgram PA/animal (p < 0.01). The amount of suppression was proportional to the number of PA doses administered. In addition this effect was critically dependent on the timing of PA administration. PA showed no significant effect on PFC when injected after immunization, but it produced pronounced suppression when injected prior to the immunization with SRBC. Maximum suppression of the PFC response was observed when PA was administered one day before the antigen challenge. PA also reduced splenic localization of 51Cr labeled SRBC to 42% (p < 0.01). The altered localization of antigen in spleen may be responsible for reduced PFC response in tumor-bearing mice. Depletion of B-lymphocyte is reported to exhibit tumor inhibition. Therefore, we propose that the suppression of the primary antibody response by PA helps in tumor regression by reducing the soluble immunosuppressive immune complexes.

Animals↗
PubMed1995

Designing of peptides with immuno-modulatory properties using protein A as a probe.

A series of reports from our laboratory have described the multifarious properties of protein A of Staphylococcus aureus Cowan I, apart from its IgG binding affinity. Original reports regarding its anti-tumor, anti-toxic, anti-carcinogenic and immunomodulatory properties published earlier by the authors have implicated some uniqueness of this bacterial protein. It was conceived that such diversified properties must lie in its specific peptide sequences, rendering it to act and behave as a multipotent "Biological Response Modifier" (BRM). The high resolution X-ray structure of protein A-Fc complex has been delineated earlier, and has been the foundation of many protein engineering studies. This structure along with the amino acid sequence data of its four repetitive domains provided us the basis for designing an octapeptide. This octapeptide was synthesized by solid phase peptide synthesis considering it as the probable site through which PA binds IgG. This octapeptide (NH2-Gln-Asn-Ala-Phe-Tyr-Glu-Ile-Leu-COOH) is present in the first helical segment of B-domain of protein A, and also is a part of domain D, A and C. This octapeptide has been shown to bind IgG by the immunoblotting technique. The binding affinity of the octapeptide appears to be significantly higher than that of intact protein A, as was revealed by calculation of Ka (association constant) and Kd (dissociation constant) values. This octapeptide might serve as a good immunoadsorbant for IgG and/or immune complexes.

Adjuvants, Immunologic↗
PubMed1994

Immunostimulating effects of protein A in immunosuppressed aflatoxin-intoxicated rats.

Aflatoxin B1, the potent carcinogenic compound produced by the Aspergillus flavus group of fungi on food and feed, induces immunosuppressive effects in rodents. In this communication, we report an immunomodulatory approach to abrogate aflatoxin B1-induced immunotoxicity in rats using protein A of Staphylococcus aureus Cowan 1. We have earlier demonstrated that protein A can protect the animals from toxicities induced by a number of drugs, chemicals and toxins. In the present study various combinations of aflatoxin B1 exposure and protein A treatment in animals were used. It was observed that protein A could provide protection to animals from aflatoxin B1-induced immunotoxicity, as measured by a battery of tests assessing cell-mediated immunity (CMI) profile of the host. Various parameters showing suppression of CMI following aflatoxin B1 exposure were reverted back towards normalcy in protein A-treated animals. It is concluded that protein A may prove to be a useful agent to protect the host from aflatoxin immunotoxicity, in view of its stimulatory effects on various immune functions even after their initial depression due to aflatoxin B1.

Adjuvants, Immunologic↗
PubMed1994

Acrylamide induced immunosuppression in rats and its modulation by 6-MFA, an interferon inducer.

In the present communication, we describe acrylamide (ACR) induced immunotoxicity and its modulation by an interferon inducer, the 6th mycelial fraction acetone (6-MFA) of Aspergillus ochraceus ATCC 28706. ACR administration to rats produced a significant decrease in the weight of spleen (p < 0.001), thymus (p < 0.001) and mesenteric lymph nodes (p < 0.05). A decrease in cellularity of spleen (p < 0.001), thymus (p < 0.001), bone marrow (p < 0.001) and circulating blood lymphocyte population (p < 0.001) was also recorded. ACR suppressed the humoral as well as cell mediated immunity as assessed by erythrocyte antibody complement (EAC)-rosettes (p < 0.001), hemagglutination titre (p < 0.001), PFC (p < 0.001) and the delayed type hypersensitivity response against sheep red blood cells (SRBC, p < 0.001). ACR treated immunosuppressed rats when treated with 6-MFA restored the circulating lymphocyte number to the normal level and a partial recovery in the weight of spleen and thymus. Potentiation of EAC-rosettes, hemagglutination titre, IgM-PFC and DTH response against SRBC was observed. It is concluded that 6-MFA ameliorate the ACR induced toxicity. This study may be of significance in prevention of ACR toxicity.

Acrylamide↗
PubMed1994

Modulation of anti-sheep erythrocyte primary antibody response by protein A in normal mice.

Protein A (PA), a cell wall glycoprotein of Staphylococcus aureus Cowan I, is known to possess immunomodulatory and antitumor activities. In the present study the effect of protein A on the anti-sheep erythrocyte primary antibody response in normal mice has been investigated. Intraperitoneal administration of PA resulted in suppression of primary antibody response in mice immunized with sheep red blood cells (SRBC) as assessed by plaque forming cell (PFC) assay. The suppressive effect was dose dependent. Maximum suppression in PFC response was observed at 12 micrograms PA/animal and could be observed as low as 1 microgram PA/animal. The suppression at 6 and 12 micrograms PA/animal was significant when compared with control values (p < 0.02 and p < 0.001, respectively). However, no significant suppression was recorded at 1 microgram dose. The suppression was proportional to the numbers of administrations of PA to the mice and critically dependent on the timing of inoculation of PA. PA produced pronounced suppression when injected prior to the immunization of animals with SRBC. PA reduced splenic localization of 51Cr labelled SRBC to 55%. It is proposed that the altered localization of antigen (SRBC) in spleen may be responsible for reduced plaque forming cells in normal mice.

Animals↗
PubMed1993

Modulation of benzene induced toxicity by protein A.

Administration of benzene (i.p. 1.0 mL/kg body weight) for 3 consecutive days produced leucopenia and lymphocytopenia in female albino rats. In addition, the total iron content, lipid peroxidation and superoxide dismutase activity of the liver and bone marrow were significantly (P < 0.001) increased. Low molecular weight (LMW) bleomycin-detectable iron accumulated only in bone marrow. Prior administration of Protein A (PA), a multipotent immunostimulant and interferon inducer (60 micrograms/kg body weight, i.v. twice weekly for 2 weeks), ameliorated most of the adverse effects of benzene. PA restored the changes in hepatic histological architecture, reversed leucopenia and superoxide dismutase activity, lipid peroxidation, total iron content and LMW iron content of bone marrow were normalized. Isozymes of glutathione-S-transferase (alpha, pi, mu) which decreased following benzene exposure increased in PA pretreated benzene exposed rats. This study suggests that pretreatment with PA modulates the toxicity of benzene.

Animals↗
PubMed1993

Immunosuppressive effects of aflatoxin in growing rats.

The immunosuppressive potential of aflatoxin B1 (AFB1), the carcinogenic metabolite of Aspergillus flavus, was evaluated in growing rats. The weanling rats were subchronically exposed to 60, 300 and 600 micrograms AFB1/kg body weight for four weeks on alternate days by oral feeding. Various parameters of cell mediated immunity (CMI) and humoral immunity were assessed in control and treated animals. CMI was evaluated by measuring delayed type of hypersensitivity (DTH) response and humoral by plaque forming cell (PFC) assay. The lymphoproliferative response assay for T- and B-cells was also performed. It was observed that AFB1 selectively suppressed cell mediated immunity in growing rats. AFB1 suppressed CMI at the 300 and 600 micrograms dose levels only as measured by DTH response assay. It is concluded that continuous low level exposure of aflatoxin to growing host may enhance its susceptibility to infection and tumorigenesis.

Aflatoxin B1↗
PubMed1993

Modulation of biochemical and cytological profile of bronchoalveolar lavage constituents in rats following split-dose multiple inhalation exposure to methyl isocyanate.

1. Studies were carried out to explore the acute pulmonary effects of equal, split-dose, multiple inhalation exposures of rats to methyl isocyanate (MIC), (0.32 mg l-1, 8 min x 10 exposures) as reflected by alterations in bronchoalveolar lavage fluid (BALF) constituents and to evaluate recovery, if any, following survival in a MIC-free environment, 10 d after the last MIC exposure. 2. In the BALF of MIC-exposed rats, there was an increase in the total number of cells and the number of cells showing enhanced dye uptake and reduction of nitroblue tetrazolium chloride. The cell-free BALF showed increases in total protein, sialic acids and lactic acid contents and lactate dehydrogenase activity. 3. In rats exposed to MIC and sacrificed 10 d after survival in a MIC-free environment, there was a reduction in the cellular and biochemical constituents of BALF. The phagocytic potential of macrophages was, however, also decreased under this regime.

Administration, Inhalation↗
PubMed1993

Effect of ASTA-Z 7575 (INN Maphosphamide) on human lymphokine-activated killer cell induction.

Recent studies combining chemotherapeutic agents with various biological response modifiers for the treatment of cancer have shown promising results. Cyclophosphamide (Cy) is the most widely used alkylating agent and a major constituent of combination chemotherapy regimens for many neoplastic diseases. It has been reported that Cy is a cytotoxic drug, which becomes immunosuppressive at higher doses. A synthetic metabolite of Cy, ASTA-Z, has recently been produced. ASTA-Z is more active and stable by itself and does not need to be metabolically converted to an active compound. The combined effect of Cy and interleukin-2 (IL-2) on the induction of lymphokine-activated killer (LAK) cells is not known. Therefore, we decided to investigate the effect of ASTA-Z on the induction and function of LAK. The coculture of peripheral blood mononuclear cells (PBMC) with various concentrations of ASTA-Z (0, 10(-6), 10(-5), 10(-4), and 10(-3) dilution) and IL-2 (50 U/ml) for 4 days produced significant suppression of cytotoxicity and lytic ability of the LAK cells against NK-sensitive (K562) and NK-resistant (M14) tumor cell lines. The lower doses of ASTA-Z did not affect the generation of LAK cells, its cytotoxicity and lytic ability of ASTA-Z against both NK-sensitive and NK-resistant tumor cell lines. Furthermore, the ASTA-Z produced dose-dependent suppression of the proliferative response of LAK cells. The significant therapeutic benefit in the cancer patient may be achieved by the low dose regimen of Cy and IL-2 because it has no deleterious effect on the induction and function of LAK cells.

Cyclophosphamide↗
PubMed1992

Protection against 7,12-dimethylbenzanthracene-induced tumour initiation by protein A in mouse skin.

Protein A is an immunostimulating glycoprotein obtained from Staphylococcus aureus Cowan I. Its antitumour activity is proven in various tumour models. Its ability to provide protection against tumour initiation by the chemical carcinogen 7,12-dimethylbenzanthracene (DMBA) has been investigated in the present study using a mouse skin model of two-stage carcinogenesis. Protein A was administered intraperitoneally (1 microgram/animal 20 g body wt.) twice a week for 2 weeks, prior to initiation by DMBA. The promotion was performed by twice weekly applications of 12-O-tetradecanoyl phorbol-13-acetate (TPA) (3 or 5 micrograms/animal in 100 microliters acetone). Protein A provided significant protection to animals from DMBA-induced tumour initiation as was observed by the decrease in cumulative number of tumours, percent of animals developing tumours, number of tumours per animal and rate of tumour growth. Our data indicate that protein A has anticarcinogenic properties.

9,10-Dimethyl-1,2-benzanthracene↗