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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

Nipah/Hendra virus outbreak in Siliguri, West Bengal, India in 2001.

BACKGROUND & OBJECTIVE: The viral encephalitides caused by animal or human viruses are characterized by sudden outbreaks of neurological disease in both tropical and temperate regions. An outbreak of acute encephalitis occurred in Siliguri (West Bengal) town of India between January 31 and February 23, 2001. This outbreak was investigated by a team of scientists from four major institutions, and the findings are presented here. METHODS: Detailed information about the outbreak was collected with the help of local health authorities. Limited entomological investigations were also done. Samples collected from cases and contacts were sent for analysis. RESULTS: A total of 66 probable cases and 45 deaths were reported. Epidemiological linkages between cases point towards person-to-person transmission and incubation period of around 10 days. There was neither any concurrent illness in animals nor was there any exposure of cases to animals. Centres for Disease Control and Prevention, Atlanta, USA concluded on the basis of tests carried out on serum specimen from four cases and two contacts that the causative pathogen appears to be Nipah/ Hendra or closely related virus. INTERPRETATION & CONCLUSION: This outbreak highlights the importance and urgency of establishing a strong surveillance system supported by a network of state-of-the-art laboratories equipped to handle and diagnose new pathogens and including patient isolation techniques, use of personal protective equipment, barrier nursing and safe disposal of potentially infected material in the prevention and control measures for Nipah/Hendra virus infection.

Adolescent↗

Health innovation networks to help developing countries address neglected diseases.

Gross inequities in disease burden between developed and developing countries are now the subject of intense global attention. Public and private donors have marshaled resources and created organizational structures to accelerate the development of new health products and to procure and distribute drugs and vaccines for the poor. Despite these encouraging efforts directed primarily from and funded by industrialized countries, sufficiency and sustainability remain enormous challenges because of the sheer magnitude of the problem. Here we highlight a complementary and increasingly important means to improve health equity: the growing ability of some developing countries to undertake health innovation.

Biomedical Research↗

The effect of type-1 fimbrial immunization on gut pathophysiological response in rats infected with Salmonella enterica subsp. enterica serovar Typhimurium.

The pathophysiological mechanism of Salmonella enterica subsp. enterica serovar Typhimurium (Salmonella typhimurium) induced gastroenteritis is controlled by interplay of various cell signaling events. Adherence of this organism through type-1 fimbriae is known to be a vital prerequisite for the establishment of infection. In the present investigation male albino Wistar rats were immunized with purified type-1 fimbriae and challenged intragastrically with S. typhimurium. Electrolyte transport and level of different second messengers were studied in four different groups of animals. Transepithelial fluxes of Na+ and Cl- revealed absorption in immunized-challenged group as observed in case of control and immunized group while secretion was observed in infected group. Ca2+ and 3-0-methyl-D-glucose fluxes did not show any change. Significant increase in the level of intracellular Ca2+, cAMP, membrane form of protein kinase C, prostaglandins, NADPH oxidase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, total oxygen free radicals, reactive nitrogen intermediates, citrulline and lipid peroxidation was found in the infected group. However, in the immunized-challenged group, the values of all the parameters were found to be same as that of control as well as immunized groups. Na+, K(+)-ATPase and calmodulin levels were found to be unaltered in all the groups of animals. Thus, the immunization with type-1 fimbriae has been found to be quite effective leading to the prevention of multiple physiologic derangements in isolated ileal cells suggesting the protective role of the fimbriae.

Animals↗

Mode of action of a potentially important excretory--secretory product from Giardia lamblia in mice enterocytes.

Giardia, a common enteric protozoan parasite is a well-recognized cause of diarrhoeal illness. The detailed mechanism of diarrhoea due to this infection is not well understood. A 58 kDa enterotoxin (ESP) was purified from the excretory-secretory product of the parasite. The present study was designed to investigate the mode of action of this enterotoxin of G. lamblia in mice enterocytes. An increase in cyclic adenosine monophosphate level, as well as intracellular Ca2+ concentration, was observed in the ESP-triggered enterocytes. The levels of phospholipase Cgamma1 and inositol triphosphate were found to be upregulated. The activity of protein kinase C (PKC) in the enterocytes was also enhanced following stimulation with the ESP. An increase in the level of reactive oxygen species in ESP-stimulated cells correlated well with the decline in the activity of antioxidant enzymes (superoxide dismutase and catalase). The significantly high levels of nitrite and citrulline indicated the generation of reactive nitrogen intermediates in the ESP-triggered enterocytes. Thus, ESP could induce cross-talk among the different signal transduction pathways in the enterocytes, which could together bring about a common secretory response.

Animals↗

Prevention of tissue injury in an ascending mouse model of chronic pyelonephritis--role of free radical scavengers.

The role of free radical scavengers in preventing the tissue injury using a non obstructive, ascending mouse model for chronic pyelonephritis was assessed. The parameters taken into consideration are Luminol Dependent Chemiluminescence (LDCL), histopathology and some biochemical investigations. We have observed that both catalase and Dimethyl-Sulfoxide (DMSO, free radical scavengers) were able to prevent the free radical mediated tissue injury and ultimate renal scarring, irrespective of the bacterial strain studied.

Animals↗

The alteration in signal transduction parameters induced by the excretory-secretory product from Giardia lamblia.

The mechanism by which Giardia lamblia exerts its pathogenicity is likely to be multifactorial. A 58 kDa enterotoxin was purified and characterized from the excretory-secretory product (ESP) of the parasite (Kaur et al. 2001). In the present study an attempt has been made to elucidate the mechanism of action of the ESP, a potentially important enterotoxin. A 41 kDa glycoprotein was identified in the mouse enterocyte membrane fraction with which the ESP interacted in a GM1-specific manner. The GTPase activity was reduced in enterocytes stimulated with the ESP, resulting in an increase in the level of adenylate cyclase-dependent cyclic adenosine monophosphate (cAMP). The activity of protein kinase A (PKA) in the enterocytes was also upregulated after ESP treatment. Ultimately, a significant increase in intracellular Ca2+ concentration and decrease in cytosolic Cl- level were noticed in ESP-stimulated mouse enterocytes. Thus it is possible that the enterotoxic ESP could bind to the 41 kDa glycoprotein (receptor?) on the enterocytes and activate the G-protein-mediated signal transduction pathway resulting in alteration of electrolyte transport.

Animals↗

Molecular heterogeneity among north Indian isolates of Group A Streptococcus.

AIM: To monitor molecular heterogeneity among the clinical isolates of group A Streptococcus (GAS) from north India by Vir and emm typing. METHODS AND RESULTS: GAS isolates, 31 from pharyngitis and nine from rheumatic fever (RF)/rheumatic heart disease (RHD) patients were differentiated into 16 Vir types (VT). These isolates were further discriminated into 23 emm types. Most of emm types were Vir type specific, except few (7.5%), which revealed different Vir types within same emm type. The most prevalent emm type found was emm 49 (15%) followed by 7.5% of emm 69, emm 71 and emm 75 which were different from emm type distribution reported from south India. CONCLUSIONS: Analysis of data revealed 40% heterogeneity by Vir typing and 57.5% by emm typing among GAS isolates which is significant in view of small number of isolates studied. SIGNIFICANCE OF IMPACT OF THE STUDY: The molecular study for the first time demonstrates different emm types prevalent and circulating in northern region of India and such data may help in selection of types for vaccine development.

Adolescent↗

Medicine. The need for a global HIV vaccine enterprise.

A new collaborative model of research is needed to increase resources, to prioritize the R (ii) to increase the pace, reduce the overlap, and more systematically explore the elements of and delivery systems for vaccines; (iii) to use common standards for the prompt comparative testing of vaccine candidates; (iv) to expand resources for manufacturing vaccine candidates to speed their use in human trials; and (v) to increase the capacity for international clinical trials and to focus this effort toward quickly measuring the effectiveness of vaccine protection as prototype vaccine candidates are identified.

AIDS Vaccines↗

Influence of Mycobacterium tuberculosis on differential activation of helper T-cells.

Host defence against tuberculosis infection involves T-lymphocyte mediated cellular immune responses. In this study we assessed T-cell activation by studying the early signal transduction events and production of cytokines by human CD4+ T-cells. The study constituted of five groups of subjects: (a) untreated acid fast bacilli (AFB)+ve TB patients who have not started anti-tuberculosis therapy (ATT) [New]; (b) patients who have taken ATT for two months [2T]; (c) patients who have taken ATT for six months [6T]; (d) mantoux positive healthy controls [T+ve]; (e) mantoux negative healthy controls [T-ve]. We found that mantoux positive healthy controls produced significantly higher levels of IP3, intracellular Ca2+ and presented increased PKC activity when CD4+ T-cells were stimulated with M. tuberculosis H37Rv cell lysate as compared to mantoux negative controls. Furthermore, decreased expression of CD54 (ICAM-1) and reduced [Ca2+]i were seen in TB patients as compared to T+ve healthy controls. TB patients showed significantly lower levels of IL-2 and IFNgamma and higher levels of IL-4 as compared to normal healthy controls, suggesting a diminished Th1 response. Thus, the reciprocal changes in cytokines, reduced [Ca2+]i levels, and CD54 expression in patients imply phenotype shifting of Th precursors to Th2 type in TB patients.

Adult↗

Bilateral environmental and occupational health program with India.

In spite of considerable economic progress in recent years, India continues to face challenges dealing with poverty, unemployment, malnutrition, disease and disability. The governments of India and the United States have formed a collaborative effort to address outstanding issues in the fields of environmental and occupational health. The Joint Statement on Indo-U.S. Collaboration in Environmental and Occupational Health, which was approved by the Minister of the Indian Union of Health and Family Welfare and the Secretary of Health and Human Services of the United State in Geneva in May of 2002, formalizes the collaborative relationship and calls for the development of Implementation Guidelines. The Implementation Guidelines establish a Joint Working Group, which is responsible for identifying and implementing the collaborative projects. The collaborating organizations have identified three broad areas for collaboration: emergency preparedness and response; training, education, and technology transfer; and research. Within the three broad areas, the organizations have identified two subject areas for initiation: arsenicosis and asbestosis. Researchers and health officials in both India and the U.S. share interest in both research and interventions efforts in these subject areas. As many as 42 million people in the West Bengal area of India may be exposed to arsenic in drinking water at concentrations of health concern. Similarly, as many as 10 million industrial or mine workers in India may be exposed to asbestos or other dusts at concentrations of health concern. The first Joint Working Group meeting is scheduled for March 2003 in New Delhi and will consider these subject areas in developing collaborative projects. Other tasks being undertaken by the signatory agencies include expanding the relationship to include academic and nongovernmental organizations and obtaining funds for the various projects from governmental and nongovernmental sources.

Arsenic Poisoning↗

Outer-membrane-protein subtypes of Haemophilus influenzae isolates from North India.

Haemophilus influenzae serotype b and non-typable isolates from blood, cerebrospinal fluid, sputum and throat swabs of patients and carriers in North India were analysed by outer-membrane protein (OMP) profiling. OMP analysis could differentiate the samples into 18 different subtypes. The non-typable isolates were more variable than the serotype b samples. OMP subtypes 1-6 were found only among the serotype b isolates and subtypes 7-18 among the non-typable isolates, while subtypes 2 and 8 were exhibited by both. The OMP profiles of isolates from blood, cerebrospinal fluid and sputum are in complete agreement with their ribotypes and RAPD fingerprints. The present study demonstrates for the first time the subtyping of Indian H. influenzae isolates by an easy and less-expensive method that is applicable to developing countries like India.

Bacterial Outer Membrane Proteins↗

Decreased level of 2,3-diphosphoglycerate and alteration of structural integrity in erythrocytes infected with Plasmodium falciparum in vitro.

2,3-Diphosphoglycerate (2,3-DPG), an intracellular metabolite of glycolytic pathway is known to affect the oxygen binding capacity of haemoglobin and mechanical properties of the red blood cells. 2,3-DPG levels have been reported to be elevated during anaemic conditions including visceral leishmaniasis. 2,3-DPG activity in P. falciparum infected red blood cells, particularly in cells infected with different stages of the parasite and its relationship with structural integrity of the cells is not known. Chloroquine sensitive and resistant strains of P. falciparum were cultured in vitro and synchronized cultures of ring, trophozoite and schizont stage rich cells along with the uninfected control erythrocytes were assayed for 2,3-DPG activity and osmotic fragility. It was observed that in both the strains, in infected erythrocytes the 2,3-DPG activity gradually decreased and osmotic fragility gradually increased as the parasite matured from ring to schizont stage. The decrease in 2,3-DPG may probably be due to increased pyruvate kinase activity of parasite origin, which has been shown in erythrocytes infected with several species of Plasmodium. The absence of compensatory increase in 2,3-DPG in P. falciparum infected erythrocytes may aggravate hypoxia due to anaemia in malaria and probably may contribute to hypoxia in cerebral malaria. As 2,3-DPG was not found to be increased in erythrocytes parasitized with P. falciparum, the increased osmotic fragility observed in these cells is not due to increased 2,3-DPG as has been suggested in visceral leishmaniasis.

2,3-Diphosphoglycerate↗

Specific IgA response, T-cell subtype and cytokine profile in experimental intravaginal trichomoniasis.

Trichomoniasis caused by Trichomonas vaginalis may lead to either a complete absence of symptoms or to severe inflammatory manifestations in infected women. Studies of the role of immune responses in the pathogenesis and varied symptomatology of this disease are lacking. Mice may prove useful as an experimental model for intravaginal trichomoniasis in developing an understanding of the role of local immune responses in the pathogenesis and varied symptomatology of this disease. The present study reports the levels of anti-Trichomonas IgA antibodies in serum and vaginal washes, and T-cell subtype and cytokine profile in vaginal cervical tissues of mice infected intravaginally with T. vaginalis isolates from 15 symptomatic and 15 asymptomatic women. It also correlates the responses with symptomatology of the patients. Successful intravaginal infection was established by inoculating T. vaginalis in BALB/c mice preinoculated with Lactobacillus acidophilus and pretreated with oestradiol. A significant increase in specific IgA antibody levels was detected with enzyme-linked immunosorbent assay in vaginal secretions and serum samples collected on the 7th post-infection day from animals infected with isolates from asymptomatic women when compared with mice infected with isolates from symptomatic women. T-cell subset analysis showed significant differences, with increased CD4+ T-cell count in animals infected with isolates from asymptomatic women compared with animals infected using isolates from symptomatic women. No difference in CD8+ T cells was observed between the two groups. Cytokine profile revealed significantly higher (P < 0.001) production of gamma-IFN and IL-2 in mice infected with asymptomatic isolates compared with animals infected with symptomatic isolates, using T. vaginalis crude antigen extract and nonspecific mitogen (ConA) as stimulants for vaginal cervical lymphocytes. However, no difference in IL-4 levels was observed in the two groups of animals. In contrast, significant increase in tumour necrosis factor (TNF-alpha) levels was observed in animals infected with asymptomatic isolates compared with those infected with isolates from symptomatic women and controls, thereby indicating that TNF-alpha may play an important role in the inflammatory response to trichomoniasis. The study further suggests that specific IgA antibodies might help to protect asymptomatic individuals from severe infection and T-lymphocytes may play an important function in the eradication of the parasite. The cytokine profile indicated the involvement of Th-1 like responses in mice infected with asymptomatic isolates, compared with those infected with symptomatic isolates.

Animals↗

Identification of human hepatocyte protein(s), which binds specifically to the recombinant envelope-2/non-structural-1 protein of hepatitis C virus.

Hepatitis C virus (HCV), which is the major pathogen responsible for human chronic liver disease, has special tropism for hepatocytes. Although, low-density lipoprotein receptor, CD81 and negatively charged glycosaminoglycans have been proposed as candidate receptors for HCV, no confirmed receptor(s) on the hepatocytes have been identified to date. It is also suggested that additional, yet unidentified, cellular proteins may be involved in the host-viral interaction. Therefore, this study was conducted with the main aim to identify hepatocyte protein(s) that may have affinity for the HCV structural protein, envelope-2/non-structural-1 (E2/NS1) protein. For the binding studies, hepatocytes were isolated from fresh normal human liver tissues. The hepatocyte proteins on the nitrocellulose paper were reacted with recombinant E2/NS1 protein and anti-E2 (rabbit). In another approach, to rule out the possibility of binding of rec-E2/NS1 with the hepatocyte cytoplasmic proteins, hepatocyte plasma membrane proteins were passed through CNBr-activated and recombinant E2/NS1 bound sepharose-4B column. The recombinant E2/NS1 binding hepatocyte plasma membrane protein(s) were eluted and were then analyzed. Altogether, our data suggest that E2/NS1 protein of HCV binds to two hepatocyte proteins of molecular weights 25-28 kDa and 59-60 kDa. These results indicate the possible role of the above proteins (25-28 kDa and 59-60 kDa) in the viral binding to the hepatocytes.

Antibody Affinity↗