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Biomedical subjects

S Mukherjee

Publications and source records attributed to S Mukherjee.

At least 163 records · Page 9Linked to original sources

A mouse cytomegalovirus glycoprotein, gp34, forms a complex with folded class I MHC molecules in the ER which is not retained but is transported to the cell surface.

Murine cytomegalovirus (MCMV) interferes with antigen presentation by means of retaining major histocompatibility complex (MHC) class I molecules in the endoplasmic reticulum (ER). Here we identify and characterize an MCMV-encoded glycoprotein, gp34, which tightly associates with properly conformed MHC class I molecules in the ER. Gp34 is synthesized in large quantities during MCMV infection and it leaves the ER only in association with MHC class I complexes. Many but not all class I molecules are retained in the ER during the early phase of MCMV infection, and we observe an inverse correlation between amounts of gp34 synthesized during the course of infection and class I retention. An MCMV deletion mutant lacking several genes, including the gene encoding gp34, shows increased class I retention. Thus, MCMV gp34 may counteract class I retention, perhaps to decrease susceptibility of infected cells to recognition by natural killer cells.

Amino Acid Sequence↗

The proteasome-specific inhibitor lactacystin blocks presentation of cytotoxic T lymphocyte epitopes in human and murine cells.

We describe the effect of the proteasome specific inhibitor lactacystin on the metabolic stability of influenza nucleoprotein (NP) and on the generation of antigens presented by human and murine class I molecules of the major histocompatibility complex to cytotoxic T lymphocytes (CTL). We show that cells treated with lactacystin fail to present influenza antigens to influenza-specific CTL, but retain the capacity to present defined epitopes expressed as peptides intracellularly by recombinant vaccinia viruses. This block in antigen presentation can be overcome by expressing the viral protein within the lumen of the endoplasmic reticulum, confirming the specificity of lactacystin for cytosolic proteases. We also show that the effect of lactacystin on antigen presentation correlates with the block of breakdown of a rapidly degraded form of the influenza NP linked to ubiquitin. These results demonstrate that proteasome-dependent degradation plays an important role in the cytosolic generation of CTL epitopes.

Acetylcysteine↗

A longitudinal study of unsaturated iron-binding capacity and lactoferrin in unstimulated parotid saliva.

Availability of iron is one important nutritional parameter for microbial growth in saliva. This longitudinal study measured the diurnal and day-to-day variations in the total iron (TI), total iron-binding capacity (TIBC), unsaturated iron-binding capacity (UIBC), and lactoferrin (LF) in unstimulated human parotid saliva. Saliva was collected from 15 young male subjects in the morning and afternoon hours each day for five consecutive days. The TI and TIBC were determined by flameless atomic absorption spectroscopy, and UIBC was determined by subtraction of TI from TIBC. The LF was determined by "sandwich" enzyme-linked immunosorbent assay (ELISA). One peripheral blood sample of each subject was also analyzed for TI, TIBC, and ferritin. The results showed no significant diurnal or day-to-day variation of TI, TIBC, UIBC, or LF in saliva for most subjects. However, significant between-subject variations were observed for most parameters. Variations ranged from subjects with constantly positive UIBC values to subjects with constantly negative UIBC values. The relationship between the LF values and the TI and TIBC values suggests that other iron-binding protein(s) are present in saliva. Also, saliva had significantly lower TIBC values than serum. This finding indicated that iron may be easily available in saliva. However, further studies are required to determine the relationship between UIBC value of saliva and oral and dental diseases, and also to detect the presence of other iron-binding proteins in saliva.

Adult↗

Ionization, partitioning, and dynamics of tryptophan octyl ester: implications for membrane-bound tryptophan residues.

The presence of tryptophan residues as intrinsic fluorophores in most proteins makes them an obvious choice for fluorescence spectroscopic analyses of such proteins. Membrane proteins have been reported to have a significantly higher tryptophan content than soluble proteins. The role of tryptophan residues in the structure and function of membrane proteins has attracted a lot of attention. Tryptophan residues in membrane proteins and peptides are believed to be distributed asymmetrically toward the interfacial region. Tryptophan octyl ester (TOE) is an important model for membrane-bound tryptophan residues. We have characterized this molecule as a fluorescent membrane probe in terms of its ionization, partitioning, and motional characteristics in unilamellar vesicles of dioleoylphosphatidylcholine. The ionization property of this molecule in model membranes has been studied by utilizing its pH-dependent fluorescence characteristics. Analysis of pH-dependent fluorescence intensity and emission maximum shows that deprotonation of the alpha-amino group of TOE occurs with an apparent pKa of approximately 7.5 in the membrane. The fluorescence lifetime of membrane-bound TOE also shows pH dependence. The fluorescence lifetimes of TOE have been interpreted by using the rotamer model for the fluorescence decay of tryptophan. Membrane/water partition coefficients of TOE were measured in both its protonated and deprotonated forms. No appreciable difference was found in its partitioning behavior with ionization. Analysis of fluorescence polarization of TOE as a function of pH showed that there is a decrease in polarization with increasing pH, implying more rotational freedom on deprotonation. This is further supported by pH-dependent red edge excitation shift and the apparent rotational correlation time of membrane-bound TOE. TOE should prove useful in monitoring the organization and dynamics of tryptophan residues incorporated into membranes.

Fluorescent Dyes↗

Viruses use stealth technology to escape from the host immune system.

In this review, we focus on recent investigations that reveal novel mechanisms by which viruses evade detection and elimination by the host immune system. In particular, we consider the evasion mechanisms of five persistent viruses: herpes simplex virus, human cytomegalovirus, mouse cytomegalovirus, Epstein-Barr virus and adenovirus. Unravelling the strategies used by viruses to survive within the host could identify new targets for antiviral drugs and for improved vaccines. Identification of the mechanisms that underlie these strategies might also reveal new, fundamental features of biology that occur in uninfected cells and are exploited by viruses.

Adenoviridae↗

Plant immunomodulators for termination of unwanted pregnancy and for contraception and reproductive health.

Neem (Azadirachta indica) seed and leaf extracts have spermicidal, anti-microbial, anti-fungal and anti-viral properties. They are also immunomodulators that induce primarily a TH1 type response. These properties are being exploited to develop two different useful methods of fertility control. Neem extracts given orally at early post-implantation stage terminate pregnancy in rodents and primates. Treatment has no residual permanent effect and fertility is regained in subsequent cycles. The mechanism by which the action occurs is not fully clear. A transient increase in CD4 and more significantly in CD8 cells is noticed in mesenteric lymph nodes and spleen. A rise in immunoreactive and bioactive TNF-alpha and IFN-gamma in draining lymph nodes, serum and foetal-placental tissue is observed. A polyherbal cream and pessary have been developed containing three active ingredients of plant origin. These have synergistic spermicidal properties on human sperm as determined by the Sander Cramer test. Their use before mating has high contraceptive efficacy in rabbits and baboons. Another interesting property is their inhibitory action on a wide spectrum of micro-organisms, including Candida albicans, C. tropicalis, Neisseria gonorrhoeae, the multidrug-resistant Staphylococcus aureus and urinary tract Escherichia coli, Herpes simplex-2 and HIV-1. Phase I clinical trials have been completed in India, Egypt and the Dominican Republic, and indicate the safety of the formulation, its acceptability and beneficial action invaginosis due to infections.

Abortion, Induced↗

Injection drug use in Calcutta: a potential focus for an explosive HIV epidemic.

Our objective was to assess HIV risk perceptions, risk behaviours and factors that may facilitate an increase in injection drug use in Calcutta. Focus group discussions and in-depth interviews were conducted with a selected group of drug users to delineate drug use patterns, languages used to express addictive and related experiences and acceptance of harm minimization messages. Results from these were used to develop a semi-structured interview instrument which was used to interview 111 drug users (76 IDUs and 35 non-IDUs) recruited from jails and detoxification centres. Secondary data of narcotic seizures for the last 5 years were collected from the Calcutta police department. Data on percentage of IDUs admitted to large detox facility in the city was also collected. Findings show that HIV/AIDS knowledge and risk perceptions were low; sharing of injection equipment was reported by 66% of the injectors; and condom use was insignificant. Non-availability, rising cost and increasing tolerance to heroin were cited as factors contributing to switch to injection. Ecological association was found between intensified police activity and an increase in: the amount of smokable heroin seized; increased injection of buprenorphine; and admission to detoxification centres. In addition to HIV, IDUs were also found to be prone to hepatitis B and C. The findings suggest an urgent need for developing and implementing community-based HIV prevention interventions targeting drug users in Calcutta.

Journal Article↗

Induced termination of pregnancy by purified extracts of Azadirachta Indica (Neem): mechanisms involved.

PROBLEM: To develop a self-administered, orally delivered method for abrogation of early pregnancy. METHOD: Use of purified Neem extracts containing immunomodulators stimulating Th1 cells and macrophages; test animals, rats, baboons, and monkeys, onset of pregnancy confirmed by surgery and counting of implants on day 7 in rats and by chorionic gonadotropin (CG) and progesterone assays in primates; termination defined by complete resorption on day 15 in rats and by bleeding and decline of CG and progesterone in baboons. RESULTS: Pregnancy was terminated successfully in both rodents and primates with no significant side effects. Fertility was regained in both species after one or two irregular cycles. Progeny born had normal developmental landmarks and mothered normal litters in the course of time. The active principle in Neem has been partially fractionated by activity-guided purification. A cascade of events are involved in abrogation of pregnancy. In primates, a decrease in progesterone is an early event. A transient increase in CD4 and CD8 cells is noted in spleen at 96 hr and in mostly CD8 cells in mesenteric lymph nodes. Treatment causes an elevation of both immunoreactive and bioactive TNF-alpha and gamma-interferon in serum, mesenteric lymph nodes, and foetoplacental tissue. CONCLUSION: Immunomodulators of plant origin are potentially usable for termination of unwanted pregnancy

Abortifacient Agents, Nonsteroidal↗

Endocytosis.

Mammalian cells take up extracellular material by a variety of different mechanisms that are collectively termed endocytosis. Endocytic mechanisms serve many important cellular functions including the uptake of extracellular nutrients, regulation of cell-surface receptor expression, maintenance of cell polarity, and antigen presentation. Endocytic pathways are also utilized by viruses, toxins, and symbiotic microorganisms to gain entry into cells. One of the best-characterized endocytic mechanisms is receptor-mediated endocytosis via clathrin-coated pits. This type of endocytosis constitutes the major emphasis of this review, with a brief discussion of other endocytic mechanisms and their comparison with the receptor-mediated pathway. This review describes and evaluates critically current understanding of the mechanisms of entry of plasma membrane components such as the receptor-ligand complexes and membrane lipids as well as the extracellular fluid into cells. The intracellular sorting and trafficking of these molecules upon internalization are also described. The roles of endocytosis in physiological and pathological processes are discussed. These include maintenance of cell polarization, antigen presentation, glucose transport, atherosclerosis, Alzheimer's disease, and the endocytosis of toxins and viruses.

Animals↗

Evidence for the essential histidine at the NADPH binding site of enoyl-CoA reductase domain of pigeon liver fatty acid synthetase.

Pigeon liver fatty acid synthetase was inactivated by stoichiometric concentrations of diethylpyrocarbonate (DEP). The second order rate constant for the loss of synthetase activity was similar to the value for enoyl-CoA reductase indicating that ethoxyformylation destroys the ability of the enzyme to reduce the unsaturated acyl intermediate, without significant effect on beta-ketoacyl reductase activity. NADPH provided protection to the enzyme against inactivation by DEP indicating that essential histidine residues are present at the active site. DEP-modified enzyme showed a characteristic absorption maxima at 240 nm confirming the formation of ethoxyformic histidine. The reversal of inactivation by hydroxylamine and a pKa value of 7.0 obtained from the pH-rate profile for inactivation again confirmed the specificity of DEP for histidine. Stoichiometric results showed that two moles of histidine residue per mole of enzyme are essential for the activity of FAS.

Animals↗

Short report: Leishmania DNA in Phlebotomus and Sergentomyia species during a kala-azar epidemic.

The presence of Leishmania donovani DNA in sand flies caught in Indian kala-azar patients' dwellings during the epidemic of 1990-1992 was studied using the polymerase chain reaction (PCR). Amplification of miniexon-derived RNA genes and gpG3 mRNA was achieved in single Phlebotomus argentipes, P. papatasi, and Sergentomyia babu flies. The data suggest the possible involvement of multiple sandfly species in kala-azar transmission.

Animals↗

Septic shock.

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Anti-Bacterial Agents↗

Interrelationship of dietary lipids and ascorbic acid with hepatic enzymes of cholesterol metabolic pathway.

Effect of unsaturated and saturated fats on cholesterol metabolism was studied in ascorbate sufficient and deficient guineapigs. Experimental animals were made chronic ascorbic acid deficient by allowing oral intake of 0.5 mg ascorbic acid/day/animal. Elevation in serum and liver cholesterol and triglyceride along with depression in cholesterol oxidation and 7 alpha-hydroxylation in liver was observed in unsaturated fat fed guineapigs with ascorbate deficiency. Liver microsomal cytochrome P-450 level was found to be low in ascorbate deficient animals. Polyunsaturated fat intake could not lower the serum cholesterol level in ascorbate deficiency. Today polyunsaturated fat in the diet is encouraged all over the world for its hypocholesterolemic effect. This study indicates that polyunsaturated fat intake with ascorbic acid deficiency may produce hypercholesterolemia.

Animals↗

Hepatoprotective effect of Swertia chirata on rat.

Present work was undertaken to ascertain the hepatoprotective effect of Swertia chirata in albino rats. Intraperitoneal injection of CCl4 (1 ml/kg body wt on every 72 hr. for 16 days) significantly increased serum aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT), and alkaline phosphatase (ALP) activities and bilirubin level in rat, but liver glycogen and serum cholesterol levels were decreased. Histologically it produced hepatocytic necrosis especially in the centrilobular region. Simultaneous treatments with S. Chirata (in different doses, viz, 20, 50 and 100 mg/kg body wt daily) and CCl4 (similar dose to that mentioned earlier) caused improvement at both biochemical and histopathological parameters compared to that of CCl4 treatment alone but it was most effective when S. chirata was administered in a moderate dose (50 mg/kg body wt).

Alanine Transaminase↗

Adult Wilms' tumour (report of two cases).

Wilms' tumour, an embryonic neoplasm, the most common renal tumour in childhood, had occasionally been reported in adults. Authors report two such cases and have reviewed the relevant literature. While Wilm's tumour in children classically demonstrates the curative potential of combined modality treatment, no such clear guide lines are available for those occurring during adulthood. Pathologic diagnosis of adult Wilm's tumour is difficult because of the multiplicity of undifferentiated adult tumours that must be considered in the differential diagnosis. As no predictive parameters for optimal therapy exist, a combination of surgery, irradiation and chemotherapy probably is indicated for all stages of disease.

Adult↗

A study of the distribution of ABO and Rh(D) blood groups amongst Lodha tribe in Midnapore district of West Bengal.

Distribution of ABO and Rh(D) blood group was studied in 206 Lodha subjects living in the Midnapore district of West Bengal. It was observed that incidence of group A was maximum and incidence of group AB was minimum; 99.5% of the subjects were 'Rh' positive. The highest incidence of group A amongst Lodhas indicates that they might belong to the proto-Australoid group anthropologically.

ABO Blood-Group System↗