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Biomedical subjects

N K Ganguly

Publications and source records attributed to N K Ganguly.

At least 19 recordsLinked to original sources
PubMed1995

Calcium and protein kinase C play an important role in Campylobacter jejuni-induced changes in Na+ and Cl- transport in rat ileum in vitro.

The pathophysiological mechanism of Campylobacter jejuni (enterotoxigenic) induced secretory diarrhoea remains least understood. To investigate the mechanism(s) involved, the unidirectional fluxes of Na+ and Cl- were measured across the C. jejuni live culture infected and control (non infected) rat ileum (unstriped), in vitro by Ussing technique under short circuit conditions, in the presence or absence of: Ca2+ ionophore A23187 (5 microM), 1-verapamil (100 microM), calmodulin (CaM) antagonist W-7 (100 microM), dantrolene (25 microM), protein kinase C (PKC) activator PMA (100 ng/ml) and H-7 (60 microM), selective inhibitor of PKC. There was net absorption of Na+ and enhanced Cl- secretion in infected animals while in control animals there was net absorption of Na+ and marginal secretion Cl-.Ca2+ ionophore A23187 mimicked the effects of C. jejuni infection whereas 1-verapamil had significant antisecretory effect on Na+ and Cl- secretion in infected animals. In vitro measurement of undirectional 45Ca fluxes in Ussing chamber experiments revealed net absorption of Ca2+ in infected rat ileum as compared to net secretion of Ca2+ in control rat ileum. These observations clearly indicate that there is increased stimulation of Ca2+ uptake from extracellular milieu to the enterocytes during C. jejuni-induced diarrhoea. The intracellular calcium levels (Ca2+]i (as measured by fluorescent probe Fura-2AM) were found to be raised significantly (P < 0.0001) in enterocytes isolated from C. jejuni infected ileum as compared to the enterocytes from control ileum. The observed increase in [Ca2+]i in enterocytes isolated from C. jejuni live culture supernatant treated rat ileum further shows the involvement of enterotoxin in diarrhoeal process. Dantrolene decreased significantly C. jejuni-induced net Na+ and Cl- secretion but it could not reverse it to absorption suggesting the partial involvement of Ca2+ mobilised from intracellular stores in mediating secretion. W-7 failed to inhibit the C. jejuni-induced net Na+ and Cl- secretion. In addition the CaM activity estimated in intestinal microvillar core remained same in both the control and C. jejuni infected animals. This indicates that C. jejuni-induced diarrhoea is not mediated through the activation of Ca(2+)-CaM complex pathway of the Ca2+ messenger system. The PKC activator PMA, induced net secretion of Na+ and Cl- in the control animals but it could not enhance further the C. jejuni-induced Na+ and Cl- secretion, suggesting that there is overlapping effect of PMA and C. jejuni live culture infection.(ABSTRACT TRUNCATED AT 400 WORDS)

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Macrophage-T cell interaction in experimental visceral leishmaniasis: failure to express costimulatory molecules on Leishmania-infected macrophages and its implication in the suppression of cell-mediated immunity.

The most important immunopathological consequence of infection with Leishmania seen in murine and human hosts is the suppression of T cell-mediated immune responses to both mitogens and leishmanial antigens. It has been suggested that this suppression is mediated by macrophages, either by defective antigen processing and presentation or by the elaboration of suppressive mediators like prostaglandins. Optimum activation of T helper cells requires not only T cell receptor occupancy by the antigen-Ia complex, but also costimulatory signals provided by the antigen-presenting cells. We investigated the status of several costimulatory molecules on infected macrophages from both genetically susceptible BALB/c and resistant C57BL/6 mice. Our results demonstrate that upon parasitization, the macrophages become unable to deliver costimulatory signals to T helper cells, and that this effects is mediated by prostaglandins, as the inhibition of its synthesis by indomethacin recovered the defect. Upon infection with L. donovani, B7-1 expression was decreased, while ICAM-1 was marginally increased in BALB/c macrophages and there was no significant change in the expression of B7-1 and ICAM-1 in Leishmania-infected C57BL/6 macrophages. Expression of VCAM-1 did not change during infection. This selective alteration in the expression of costimulatory molecules on L. donovani-infected BALB/c macrophages was caused by the living parasite, as shown by the fact that killing of the parasites by stibogluconate led to no alteration in the levels of costimulatory molecules. We found that the change in B7-1 expression on the surface of infected macrophages resulted in the inhibition of delayed-type hypersensitivity-mediating functions of T helper cells from BALB/c mice. The results described in this study not only throw light on the possible mechanism of leishmanial pathogenesis, but also open up the possibility of immunotherapy of leishmaniasis by selective manipulation of costimulatory molecules.

Animals↗
PubMed1995

Plasmodium falciparum: role of activated blood monocytes in erythrocyte membrane damage and red cell loss during malaria.

The role of Plasmodium falciparum and blood monocytes in the erythrocyte damage and pathogenesis of anemia has been investigated using two strains of the parasite; one laboratory-established strain (FSJ-M) and one wild, fresh, clinical isolate (PfPGI). Peripheral blood monocyte-induced growth inhibition of the parasites, erythrocyte membrane lipid peroxidation as seen by the formation of lipid peroxide products, and sensitivity to peroxide hemolysis at atmospheric oxygen were evaluated. The growth inhibition of FSJ-M by activated blood monocytes was greater than that of PfPGI. The extent of lipid peroxidation and sensitivity to hemolysis increased significantly as the parasites matured. These adverse effects were more marked following exposure to activated monocytes, especially in synchronized, parasitized RBCs. In addition, uninfected erythrocytes within the PfPGI parasite culture revealed a significant increase in the lipid peroxide formation (P < 0.01) and susceptibility to lysis (P < 0.05) under similar oxidant stress induced by monocytes from normal healthy donors. Furthermore, there was a direct correlation between membrane lipid peroxidation and peroxide hemolysis, both before and after monocyte exposure, suggesting a primary role of membrane peroxidation in red cell lysis. The contribution of intraerythrocytic parasites and nonspecific activation of blood monocytes in the pathophysiology of erythrocyte damage and anemia of P. falciparum infection is discussed.

Adult↗
PubMed1995

An ascending non-obstructive model for chronic pyelonephritis in BALB/c mice.

Chronic pyelonephritis was successfully produced in female BALB/c mice with Escherichia coli after introduction of the bacterial inoculum by the ascending route. E. coli strain 31-B, a nalidixic acid-resistant derivative of strain TN675 expressing type-1 pili, and E. coli strain BH-5, a mutant of 31-B, not expressing type-1 pili, were used in the model. Both the strains were able to induce chronic renal inflammation in the experimental animals. Whereas the initial colonisation was greater with strain 31-B, its non-pilate mutant BH-5 caused a significantly greater inflammatory response and also caused renal scarring observable 5 months after the infection.

Animals↗
PubMed1995

Role of calcium and protein kinase C in the activation of T cells in Takayasu's arteritis.

The roles of protein kinase C and calcium in the T cells of patients suffering from Takayasu's arteritis (TA) in response to the mitogens phorbol-myristate acetate (PMA) and streptococcal antigens have been studied. In TA there was an increased basal activity of protein kinase C (1.074 +/- 0.223 nmoles/mg protein/min) as compared with that of controls (0.570 +/- .12) (p < 0.001). There was 75% translocation from the cytosol to membrane fraction in response to PMA. Intracellular calcium levels showed increased basal levels in TA (177.07 +/- 12.56 nmoles) compared with the controls (112.83 +/- 10.6 nmoles) (p < 0.001) and there was a further rise on stimulation, indicating the T cells were in an activated state. There was a positive correlation between the calcium levels and the activity of protein kinase C (r = 0.71, p < 0.05). Unlike the situation in patients with rheumatic fever, T cells in TA showed no stimulation in response to streptococcal antigens. The low level of cAMP (1.12 +/- 0.169 pmoles/million cells) compared with that of controls (1.4 +/- 0.03) further supports the role of PKC-calcium in the T cell activation process. These findings suggest activation of the PKC-calcium pathway in TA.

Adolescent↗
PubMed1995

Release of reactive oxygen and nitrogen intermediates from monocytes of patients with pulmonary tuberculosis.

M. tuberculosis, the aetiological agent of tuberculosis readily infects and multiplies within the macrophages of the host. Macrophage activation is known to occur through a series of stages, which results in the production of biologically active molecules such as the reactive oxygen and nitrogen intermediates. The following study was conducted on 20 patients with pulmonary tuberculosis, before and after initiation of antituberculous therapy, and on 10 normal healthy controls. The macrophages were isolated from peripheral blood of the patients and controls at a concentration of 1 x 10(6) cells ml-1. The generation of reactive oxygen intermediates was measured by a chemiluminescence technique. Reactive nitrogen intermediates, were measured following stimulation of macrophages with latex, lipopolysaccharide (LPS) and purified protein derivative-S (PPD-S). Citrulline levels and electron transport chain activity were also determined in the cell cultures. It was observed that there was a significant depression (p < 0.05) in the respiratory burst response in the patient group (0.46 x 10(3) +/- 0.11 cpm per 10(6) cells) compared with the controls (7.12 x 10(3) +/- 2.31 cpm per 10(6) cells). On the other hand, reactive nitrogen intermediates (671.03 +/- 2.18 nmol) and citrulline levels (193.07 +/- 2.38 nmol) were significantly (p < 0.001) higher before initiation of therapy compared with control values (24.36 +/- 2.81 and 18.91 +/- 2.12 nmol respectively). Their levels declined, during the post-therapy period of 3 months, to 60.81 +/- 2.03 and 38.17 +/- 2.13 nmol respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Role of reactive oxygen species in renal damage in experimental leprosy.

Renal involvement is known to occur in leprosy. In the present study the possible role of reactive oxygen species (ROS) in causation of renal damage in mice infected with Mycobacterium leprae has been investigated. At least six animals from each group (control and infected) were killed at 0 day, 3, 6 and 9 months postinfection. The results showed a significant increase in the chemiluminescence (CL) response of peritoneal macrophages which was maximum between 3 and 6 months. No significant increase was observed in CL response of blood neutrophils. A significant increase in lipid peroxidation was observed at 3 and 6 months as evident by an increase in malondialdehyde levels. The increased ROS production might be the cause of lipid peroxidation. The renal damage is alos evident by decrease in the activity of renal brush border membrane enzymes, namely, alkaline phosphatase, leucine aminopeptidase and r-glutamyl transpeptidase. Thus ROS might play a role during early stages of M. leprae infection but in the later stages other immunological mechanisms may overpower the effect of ROS.

Alkaline Phosphatase↗
PubMed1995

Composition of postnatal weight loss & subsequent weight gain in preterm infants.

To investigate the changes in body composition corresponding to postnatal weight loss and regaining of birth weight, total body water (TBW) and extracellular water (ECW) were measured at birth, on the day of maximum weight loss and on regaining of birth weight in 23 preterm appropriate for gestational age (AGA) infants (mean +/- SD birth weight 1902 +/- 242 g, gestational age 236 +/- 7 days). Intracellular water (ICW) was determined by the difference between TBW and ECW and body solids by the difference between TBW and body weight. Almost 90 per cent of early postnatal weight loss of 132 +/- 38 g (6.9% of birth weight) was because of loss of body water (117 +/- 30 ml; 7.9% of TBW at birth). ECW loss (mean +/- SD 106 +/- 35 ml) accounted for 90 per cent of the TBW loss. Of the subsequent weight gain (134 +/- 40 g) till regaining of birth weight, 48 per cent (64 +/- 28 ml) was TBW and 52 per cent (70 +/- 13 g) body solids. The major gain in body water was in ICW (47 +/- 21 ml). A gradual decrease in TBW and ECW, and a gain in ICW and body solids per kg body weight was observed throughout the study period. These findings favour the concept that in preterm (31-36 wk) infants (i) postnatal weight loss is primarily a reflection of ECW loss and subsequent weight gain is because of cellular growth, (ii) postnatal loss of ECW continues even when weight gain and accumulation of body solids has started.

Birth Weight↗
PubMed1995

Effect of sucralfate on gastric bicarbonate secretion in patients with duodenal ulcer.

BACKGROUND: Sucralfate is known to protect gastroduodenal mucosa and thereby facilitate healing of peptic ulcer. The mechanism of action of this drug is still not fully known. METHODS: We studied the effect of sucralfate treatment on gastric bicarbonate secretion in 16 patients with duodenal ulcer. RESULTS: Sucralfate administration (3 g daily for 4 weeks) stimulated bicarbonate secretion from 3.1 +/- 1.2 mmol/h to 4.6 +/- 2.0 mmol/h (p < 0.05). Gastric juice volume as well as non-parietal volume secretion also increased significantly after sucralfate therapy (p < 0.05). CONCLUSION: Sucralfate causes stimulation of non-parietal volume-dependent gastric bicarbonate secretion.

Adult↗
PubMed1994

Impairment of Na+,K(+)-ATPase activity following enterotoxigenic Campylobacter jejuni infection: changes in Na+, Cl- and 3-O-methyl-D-glucose transport in vitro, in rat ileum.

Unidirectional fluxes of Na+, Cl- and 3-O-methyl-D-glucose (3-MG) were measured in vitro across Campylobacter jejuni live culture-infected and control rat ileal short-circuited tissues by the Ussing Chamber technique. Net secretion of Na+ and enhanced secretion of Cl- ions was observed in the infected animals (P < 0.001, n = 6) as compared to the net absorption of Na+ and marginal secretion of Cl- ions in the control animals. There was a significant decrease in the mucosal-to-serosal fluxes of 3-MG in C. jejuni-infected rat ileum. The specific Na+,K(+)-ATPase activity when measured biochemically in the membrane-rich fraction of enterocytes was found to be significantly lower (58%) in the infected group as compared to the control group (P < 0.001). Our results therefore suggest that infection with an enterotoxigenic C. jejuni inhibits the Na+,K(+)-ATPase activity in rat enterocytes. The impairment of Na+,K(+)-ATPase activity thus appears to induce a secondary change in Na+,Cl- and 3-MG transport in vitro in rat ileum.

3-O-Methylglucose↗
PubMed1994

Involvement of intracellular calcium stores in Giardia lamblia induced diarrhoea in mice.

The transmucosal fluxes of Na+ and Cl- were studied in Giardia lamblia-infected mice in the presence or absence of dantrolene (1-(5(p-nitrophenyl)furfurilidene-amino) hydantoin sodium hydrate). There was net secretion of Na+ and Cl- in infected animals, while in control animals there was net absorption of these ions. The addition of dantrolene resulted in significant net increase in absorption of Na+ and Cl- in control and experimental groups. Further, mouse intestinal epithelial cells were labelled with [32P]Pi and then treated with G. lamblia trophozoites and their excretory secretory products separately. The optimum time for inositol triphosphate formation was 15 min in control enterocytes as well as in treated enterocytes. A plateau was formed at higher concentrations. Since raised inositol triphosphate levels mobilize Ca2+ from intracellular stores and dantrolene traps Ca2+ within intracellular calcium stores, the present study thus suggests that intracellular calcium stores are involved in G. lamblia-induced diarrhoea in mice.

Animals↗
PubMed1994

Purification and characterization of distinct type of mannose-sensitive fimbriae from Salmonella typhimurium.

The fimbriae (E4) of a virulent strain of Salmonella typhimurium were purified by ion exchange chromatography in an FPLC system. They had a channelled appearance under transmission electron microscope and showed a major structural subunit of 17-kDa on sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The purified fimbriae were found to agglutinate guinea pig erythrocytes, but this effect was inhibited in presence of D-mannose. Immune sera raised against the Mono-Q purified fimbriae (E4) showed cross-reactivity with the type-1 fimbriae (F1) composed of 21-kDa fimbrin subunit, purified by a different method from the same strain.

Animals↗
PubMed1994

Macrophage-T cell interaction in experimental mycobacterial infection. Selective regulation of co-stimulatory molecules on Mycobacterium-infected macrophages and its implication in the suppression of cell-mediated immune response.

The most important immunopathological consequence of experimental mycobacterial infection is the suppression of T cell-mediated immune response to both mitogens and mycobacterial antigens. We registered that there was decreased concanavalin A-induced spleen cell proliferation in infected susceptible BALB/c mice as compared to normal mice. In resistant (C3H/HeJ) mice, infection with the bacteria did not induce any suppression in the mitogen-induced lymphoproliferation. Likewise, delayed-type hypersensitivity (DTH) responses, to keyhole limpet hemocyanin and mycobacterial crude soluble antigen were suppressed in infected BALB/c mice but not in C3H/HeJ mice. This depressed T helper cell function may either be due to defective T cell-receptor occupancy by antigen-Ia complex or altered co-stimulatory signals provided by antigen-presenting cells. In the present study, we have investigated the status of certain co-stimulatory molecules on the infected macrophages from both susceptible and resistant mice. Our results demonstrate that upon mycobacterial infection, the macrophages are rendered incapable of delivering the co-stimulatory signals to T helper cells, possibly due to the involvement of prostaglandin, as inhibition of its biosynthesis by indomethacin reversed the defect. Furthermore, the selective regulation was bacteria-induced as killing of the bacteria by rifampicin abrogated the derangements in the expression of co-stimulatory molecules on the Mycobacterium-infected macrophages. Our observations revealed that upon infection with Mycobacterium tuberculosis, B7 was down-regulated while ICAM-1 was increased only in BALB/c but not in C3H/HeJ mice. Expression of VCAM-1 did not change during the infection in either strain of mice. We found that these changes in ICAM-1 and B7 expression on the surface of infected macrophages resulted in inhibition of DTH-mediating functions of T helper cells from BALB/c mice. The results obtained in this study describe not only a novel immune evasion strategy adopted by Mycobacterium, but also open up the possibility of immunotherapy of mycobacterial infection by selective manipulation of co-stimulatory molecules.

Animals↗
PubMed1994

Atypical strain of hepatitis E virus (HEV) from north India.

Hepatitis E virus (HEV) infection was detected during an epidemic in North India. Virus particles present in the stool of an acutely ill patient (YAM-67) was transmitted intravenously into rhesus monkeys (M. mulata) and orally to a human volunteer. Virus-like particles (VLPs) of 32-34 nm were detected in the bile of monkeys and in the stools of the human volunteer by means of solid phase immune electron microscopy (SPIEM) with acute homologous and heterologous sera. The VLPs were confirmed to be HEV by a reverse transcription polymerase chain reaction (RT-PCR). Virus-like particles from human volunteer stools were passaged further into rhesus monkeys. A bimodal rise in aminotransferase levels were observed in the animals, and liver histopathology indicated mild to severe form of hepatitis. Further, SPIEM and RT-PCR analysis in monkey bile revealed presence of virus from 15 to 45 days post-inoculation. Rechallenge of the animals 6 months after recovery with the same viral inoculum failed to produce abnormal liver function tests indicating the presence of protective immunity during this period. The VLPs in the stool from the patient (YAM-67) with epidemic hepatitis were found to retain infectivity even after several cycles of freeze-thawing and exposure at 37 degrees C for 2 days. Moreover, these VLPs from the patient, human volunteer, and monkeys did not react with an anti-HEV chimpanzee serum from NIH, Bethesda, MD. These findings indicate that this North India isolate of HEV is an atypical strain of HEV. The present study further validates that the rhesus monkey is a suitable experimental model for HEV.

Animals↗
PubMed1994

Plasmodium falciparum and blood monocyte induced abnormalities in human erythrocyte cation homeostasis.

The role of Plasmodium falciparum and activated blood monocytes in bringing about erythrocyte membrane lipid peroxidation and in altering the enzyme activity associated with Ca2+ and K+ efflux was studied. An attempt was made to investigate the role of parasite and monocyte-mediated reactive oxygen species (ROS) in inhibiting Ca(2+)-Mg2+ ATPase and Na(+)-K+ ATPase in order to find out the cause of reported high intra-erythrocytic calcium and depleted potassium levels in parasitized erythrocytes (PRBC). The PRBC showed enhanced lipid peroxidation as indicated by increased malonyldialdehyde (MDA) formation which coincided with the maturity of the parasite. This was further enhanced following exposure of PRBC to activated blood monocytes. The Ca(2+)-Mg2+ ATPase activity was decreased as the parasite matured and was further hampered significantly in mature parasite-infected red cells exposed to activated blood monocytes. There was a good negative correlation between MDA formation and Ca(2+)-efflux from red blood cells suggesting the negative influence of ROS on Ca(2+)-efflux. The Na(+)-K+ ATPase activity did not reveal any significant change, both during parasite maturation as well as upon exposure to ROS from activated monocytes. We therefore suggest that inhibition of Ca(2+)-efflux and the resulting increased cytosolic Ca2+ in PRBC might have a role in structural and functional abnormalities of red blood cell, thus enhancing the red cell loss during P. falciparum infection.

Animals↗
PubMed1994

Evaluation of Salmonella porins as a broad spectrum vaccine candidate.

Porins were prepared from smooth strain of Salmonella typhi 0-901 and chemotype of rough mutant of S. typhimurium Ra-30. Mice were immunized with both the porin preparations in different groups and challenged with S. typhimurium LT2-71 and S. enteritidis SH-1269. Porin immunized mice showed significant protection (P < 0.01) against challenge with homologous as well as heterologous strains. Hence, the use of porins may be attempted in future to protect against salmonellosis.

Animals↗