PubMed Health⌕ Search

Biomedical subjects

D Chatterjee

Publications and source records attributed to D Chatterjee.

At least 19 recordsLinked to original sources
PubMed1992

Structures of the glycopeptidolipid antigens of serovars 25 and 26 of the Mycobacterium avium serocomplex, synthesis of allyl glycosides of the outer disaccharide units and serology of the derived neoglycoproteins.

The pentasaccharide hapten released from the glycopeptidolipid (GPL) antigen of M. avium serovar 26 has been characterized as O-(2,4-di-O-methyl-alpha-L-fucopyranosyl)-(1-->4)- O-beta-D-glucopyranosyluronic acid-(1-->4)-O-(2-O-methyl-alpha-L-fucopyranosyl)-(1-->3)-alpha-L- rhamnopyranosyl-(1-->2)-6-deoxy-L-talose. The allyl glycosides of the outer glycosyl and glycobiosyl units of this hapten have been synthesized, the latter by a route involving oxidation of the corresponding D-glucopyranose derivative. Conjugation of allyl glycosides to protein by ozonolysis and reductive coupling afforded neoantigens (neo 26-1 and 26-2), both of which interacted with antibodies to M. avium serovar 26. The terminal sugar residue of the pentasaccharide hapten of the serovar 25 GPL had been shown to have the galacto configuration on the basis of 1H-13C NMR correlation spectroscopy, but absolute configurational assignment for the sugar awaited the synthesis, as for neo 26, of two glycobiosyl NGPs bearing the terminal sugar in the D and L enantiomeric forms, respectively. Only the glycobiosyl NGP bearing the terminal sugar as the D-enantiomer interacted with antibodies to M. avium serovar 25, thus providing evidence for the absolute configuration of the sugar, and showing that the complete oligosaccharide hapten has the structure, O-(4-acetamido-4,6-dideoxy-2-O-methyl-alpha-D- galactopyranosyl)-(1-->4)-O-beta-D-glucopyranosyluronic acid-(1-->4)-O-(2-O-methyl-alpha-L-fucopyranosyl)-(1-->3)-O-alpha-L- rhamnopyranosyl-(1-->2)-6-deoxy-L-talose.

Allyl Compounds↗
PubMed1992

Sensitivity to vanadate and isoforms of subunits A and B distinguish the osteoclast proton pump from other vacuolar H+ ATPases.

Analysis of proton (H+) transport by inside-out vesicles derived from highly purified chicken osteoclast (OC) membranes has revealed the presence of a newly discovered type of vacuolar H+ ATPase (V-ATPase). Unlike vesicles derived from any other cell type or organelle, H+ transport in OC-derived vesicles is sensitive to V-ATPase inhibitors (N-ethylmaleimide and Bafilomycin A1) and vanadate (IC50, 100 microM), an inhibitor previously found to affect only P-type ATPases. The OC H+ ATPase contains several V-like subunits (115, 39, and 16 kDa) but subunits A and B of the catalytic domain of the enzyme differ from that of other V-ATPases. In OCs, subunit A has a mass of 63 kDa instead of the 67-70 kDa expressed in monocytes, macrophages, and kidney microsomes, which contain a vanadate-insensitive H+ ATPase. Moreover, two types of 57- to 60-kDa B subunits are also found: one is expressed predominantly in OCs and the other is expressed in kidney microsomes. The OC H+ pump may therefore constitute a class of H+ ATPase with a unique pharmacology and specific isoforms of two subunits in the catalytic portion of the enzyme. This H+ ATPase is involved in resorption of bone and may be expressed in a cell-specific manner, thereby opening possibilities for therapeutic intervention.

Animals↗
PubMed1992

Cytokine production induced by Mycobacterium tuberculosis lipoarabinomannan. Relationship to chemical structure.

Lipoarabinomannan (LAM), a major cell wall component of Mycobacterium tuberculosis, exhibits a wide spectrum of immunoregulatory effects. To identify cytokines produced by human PBMC in response to LAM, we used PCR amplification to detect cytokine mRNA. LAM-induced transcription of mRNA for cytokines characteristically produced by macrophages, including TNF, granulocyte-macrophage-CSF, IL-1 alpha, IL-1 beta, IL-6, IL-8, and IL-10. In contrast, LAM did not induce transcription of mRNA for cytokines produced predominantly by lymphocytes, such as lymphotoxin, IFN-gamma, IL-2, IL-3, or IL-4. Measurement of concentrations of TNF, granulocyte-macrophage-CSF, IL-6, IL-10, IFN-gamma, IL-2, and IL-4 in cell culture supernatants indicated that cytokine release correlated with mRNA patterns. Lipomannan (LM) and phosphatidylinositol mannosides (PIM) are simpler versions of LAM. LM lacks arabinan, whereas PIM lacks both arabinan and most mannan residues. LAM, LM, and PIM induced transcription of cytokine mRNA, elicited cytokine production, and suppressed Ag-induced T cell proliferation, indicating that most of the biologic activity of LAM was associated with the phosphatidylinositol end of the molecule. In support of this conclusion, deacylation of LAM abrogated its capacity to induce cytokine production and suppress Ag-induced proliferation. The production of macrophage-derived cytokines induced by LAM may mediate clinical manifestations of tuberculosis such as fever, weight loss, and tissue necrosis, as well as immunoregulatory effects such as inhibition of Ag-induced proliferation and hyperglobulinemia.

Adult↗
PubMed1992

Differentiation of Neuro-2a neuroblastoma cells by an antibody to GM3 ganglioside.

A monoclonal antibody against GM3 ganglioside (GM3Ab) was found to trigger differentiation of Neuro-2a cells in culture. The differentiation of Neuro-2a cells by GM3Ab was accompanied by increased levels of intracellular serotonin and amino acid neurotransmitters viz. aspartate, glutamate, glutamine, glycine and taurine. Further study indicated that the increase in the serotonin level was not due to a higher rate of serotonin synthesis but rather to a higher rate of active transport of serotonin from the medium. Studies on the cell surface gangliosides revealed that unlike the proliferating cells, the GM3Ab-mediated differentiated cells contained higher gangliosides in addition to GM3 and GM2 gangliosides. Analysis of total cellular proteins indicated the appearance of a 25 kDa protein, pI 5.4, in the GM3Ab-treated cells--a small amount of this protein was observed in dibutyryl cAMP (Bt2cAMP)-treated cells, however, the protein was totally absent in the 5-bromo-2'-deoxyuridine (BrdU)-treated cells. Investigation of the mode of action of GM3Ab indicated that the cellular differentiation was due to increased cAMP accumulation resulting from an increase in the adenylate cyclase activity. Further studies with different agents affecting protein kinase C (PKC) activity and direct assay of PKC ruled out the possibility that GM3Ab mediated its effect via PKC. This GM3Ab-induced differentiation could be inhibited by protein kinase A (PKA) inhibitor, H8, but could not be inhibited by sphingosine, an inhibitor of PKC. Pertussis toxin could mimic the effect of GM3Ab, suggesting that GM3Ab caused the elevation in the adenylate cyclase activity by reducing the Gi-protein inhibition of the adenylate cyclase. The data suggests that GM3Ab, after interaction with cell surface GM3, elevated intracellular cAMP level by withdrawing the inhibitory effect of some undefined factor(s) present in culture medium which normally keeps adenylate cyclase activity low through activation of Gi-protein.

Amino Acids↗
PubMed1992

Lipoarabinomannan. Multiglycosylated form of the mycobacterial mannosylphosphatidylinositols.

The lipopolysaccharides of mycobacteria, lipoarabinomannan (LAM) and lipomannan (LM), of key importance in host-pathogen interaction, were recently shown to contain a phosphatidylinositol "anchoring domain." We now have established that LAM and LM are based on the phosphatidylinositol mannosides, the characteristic glycophospholipids of mycobacteria. Digestion of the arabinose-free LM with an endo-alpha 1----6-mannosidase yielded evidence for the presence of the 1-(sn-glycerol-3-phospho)-D-myo-inositol-2,6-bis-alpha-D-mannopyranoside unit, indistinguishable from that derived from phosphatidylinositol dimannoside. This same inositol substitution pattern was shown to be present in LAM by methylation analysis before and after dephosphorylation. Positions C-2 and C-6 of the inositol unit of LAM are occupied by mannosyl residues and C-1 by a phosphoryl group. Partial acid hydrolysis of per-O-methylated LAM and comparison by gas chromatography-mass spectrometry of the resulting derivatized oligosaccharides with like products from phosphatidylinositol hexamannoside demonstrated that the C-6 of inositol is the point of attachment of the mannan core of LAM, which consists of an alpha 1----6-linked backbone with considerable alpha-1----2 side chains. Thus, a structural and presumably biosynthetic relationship is established between some of the membranous mannosylphosphatidylinositols described some 25 years ago and the newly emerging, biologically active lipopolysaccharides of mycobacteria.

Carbohydrate Conformation↗
PubMed1992

Lipoarabinomannan of Mycobacterium tuberculosis. Capping with mannosyl residues in some strains.

Previously we had demonstrated that the termini of the arabinan component of mycobacterial cell wall arabinogalactan, the site of mycolic acid location, consists mostly of clusters of a pentaarabinofuranoside, [beta-D-Araf-(1----2)-alpha-D-Araf-(1----]2----(3 and 5)-alpha-D-Araf. Subsequently, the same arrangement was shown to dominate the non-reducing ends of lipoarabinomannan (LAM), a key component in the interaction of mycobacteria with host cell. Accordingly, we had proposed that mycobacteria universally elaborate the same Araf-containing motifs in two settings for different pathophysiological purposes. However, we now report that the termini of LAM from the virulent, Erdman, strain of Mycobacterium tuberculosis, unlike those from the attenuated H37Ra strain, are extensively capped with mannosyl (Manp) residues, either a single alpha-D-Manp, a dimannoside (alpha-D-Manp-(1----2)-alpha-D-Manp), or a trimannoside (alpha-D-Manp-(1----2)-alpha-D-Manp-(1----2)-alpha-D-Manp ). The use of monoclonal antibodies demonstrates a clear difference in the antigenicity of the basic and mannose-capped LAM. The possibility that these structures are a factor in the virulence of some strains of M. tuberculosis and represent an example of carbohydrate mimicry in mycobacterial infections is discussed.

Carbohydrate Conformation↗
PubMed1992

Posttranscriptional regulation of c-myc proto-oncogene expression and growth inhibition by recombinant human interferon-beta ser17 in a human colon carcinoma cell line.

Recombinant human interferon-beta ser17 (IFN-beta ser17), a cytokine that exhibits both antiviral and antiproliferative activity against a wide variety of cell types, causes a time- and dose-dependent inhibition of monolayer growth and of the expression of the c-myc proto-oncogene in DLD-1 Clone A human colon-carcinoma cells. The suppression of c-myc expression mediated by IFN-beta ser17 is due to a posttranscriptional destabilization of c-myc mRNA rather than to an inhibition of c-myc mRNA transcription. There is evidence suggesting that the selective reduction in the half-life of c-myc mRNA in IFN-beta ser17-treated cells occurs through an increase in the activity of the 2',5'-oligoadenylate synthetase/RNase L [2',5'-oligo (A) synthetase] pathway in DLD-1 Clone A cells. Cotreatment of these cells with IFN-beta ser17 and the anticancer agent N-methylformamide leads to the partial abrogation of 2',5'-oligo (A) synthetase activity and the stabilization of c-myc mRNA. These findings suggest that there is a correlation between the IFN-beta ser17-mediated suppression of c-myc expression and the induction of 2',5'-oligo (A) synthetase activity in DLD-1 clone A cells.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Thyroidal influence on the cell surface GM1 of granule cells: its significance in cell migration during rat brain development.

1. No difference was observed in the in vitro growing ability of granule cells isolated from hypothyroid or normal rat brain. When granule cells were taken from hypothyroid rat brain and grown in normal culture medium containing 10% fetal calf serum, they behaved similarly to the granule cells obtained from normal rat brain. 2. In both cases there were progressive losses of in vitro growing ability of the granule cells with the age of the animal and it became impossible to grow them when derived from 21 days or older animals. 3. A marked decrease in cell surface GM1 was observed when the cells were maintained under thyroid hormone-deficient conditions in culture. 4. Anti-GM1 antibody was found to inhibit significantly the migration of granule cells along the astrocyte fibers. 5. These results indicate that GM1 has an important role in thyroid hormone-dependent postnatal brain maturation in rat.

Age Factors↗
PubMed1992

Osteoclasts express high levels of pp60c-src in association with intracellular membranes.

Deletion of the c-src gene in transgenic mice by homologous recombination leads to osteopetrosis, a skeletal defect characterized by markedly deficient bone resorption (Soriano, P., C. Montgomery, R. Geske, and A. Bradley. 1991. Cell. 64:693-702), demonstrating a critical functional role of pp60c-src in osteoclast activity. Since decreased bone resorption could result from a defect either within the osteoclast or within other cells present in its environment, indirectly affecting osteoclast functions, we determined which cell(s) in bone expressed high levels of pp60c-src Measuring pp60c-src protein and kinase activities in osteoclasts and immunolocalizing pp60c-src in bone, we find that expression of pp60c-src is nearly as high in osteoclasts as in brain and platelets. In contrast, other bone cells contain only very low levels of the protein. In addition, expression of the c-src gene product increases when bone marrow cells are induced to express an osteoclast-like phenotype by 1,25-dihydroxy-vitamin D3, further suggesting that high expression of pp60c-src is part of the osteoclast phenotype. Three other src-like kinases, c-fyn, c-yes, and c-lyn, are also expressed in osteoclasts at ratios to pp60c-src similar to what is found in platelets. These src-related proteins do not, however, compensate for the absence of pp60c-src in the src- mice, thereby suggesting that pp60c-src may have a specific function in osteoclasts. Although further work is necessary to elucidate what the critical role of pp60c-src in osteoclasts is, our observation that the protein is associated mostly with the membranes of intracellular organelles suggests the possibility that this role might be at least in part related to the targeting or fusion of membrane vesicles.

Animals↗
PubMed1992

Structural basis of capacity of lipoarabinomannan to induce secretion of tumor necrosis factor.

The results of this study show that lipoarabinomannans (LAM) isolated from a virulent strain and from an avirulent strain of Mycobacterium tuberculosis, which have recently been shown to differ markedly in terms of the structures of their nonreducing termini, also differ markedly in the capacity to induce the secretion of tumor necrosis factor from murine macrophages. It was found that LAM from the avirulent H37Ra strain was 100-fold more potent at inducing tumor necrosis factor secretion than LAM from the virulent Erdman strain, thus leading us to hypothesize that the structure of LAM from a given mycobacterial isolate may directly influence its ability to elicit, or avoid, cytokine-mediated mechanisms of host resistance.

Animals↗
PubMed1992

Tumor necrosis factor production in patients with leprosy.

The spectrum of host responses to Mycobacterium leprae provides a model for investigating the role of cytokines in the pathogenesis of mycobacterial disease. Of particular interest is tumor necrosis factor (TNF), a cytokine which may have both antimycobacterial and immunopathologic effects. To evaluate the potential role of TNF in leprosy, we measured TNF production in response to M. leprae and its defined constituents by peripheral blood mononuclear cells from patients across the spectrum of disease. The levels of TNF induced through the stimulation of cells with M. leprae or its dominant "lipopolysaccharide," lipoarabinomannan, were higher in patients with the tuberculoid form of the disease than in those with the lepromatous form. In patients with erythema nodosum leprosum (ENL), a reactional state of lepromatous leprosy, the levels of TNF release by peripheral blood mononuclear cells were higher than in any other form of the disease. Treatment of ENL patients with thalidomide reduced TNF secretion by more than 90%. The mycolylarabinogalactan-peptidoglycan complex of Mycobacterium species, the protein-peptidoglycan complex, and muramyl dipeptide all elicited significant TNF release. Therefore, TNF release appears to be triggered by at least two major cell wall structural constituents of M. leprae, lipoarabinomannan and segments of the cell wall skeleton. The prominent TNF release in patients with the paucibacillary tuberculoid form of the disease compared with that in patients with the multibacillary lepromatous form suggests that this cytokine contributes to a resistant immune response to mycobacterial infection. However, the marked TNF release in patients with ENL indicates that TNF may also mediate immunopathologic effects, such as fever and tissue damage.

Antigens, Bacterial↗
PubMed1992

Comprehensive approach to identification of serovars of Mycobacterium avium complex.

Serotyping of nontuberculous mycobacteria, especially those of the Mycobacterium avium complex, provides important epidemiological information, particularly in tracing origins of infections. Seroagglutination with whole cells and polyclonal rabbit antibodies was the original way of identifying serovars and is still commonly used. The discovery of the glycolipid nature of the typing antigens allows differentiation of serovars on the basis of thin-layer chromatography of whole antigens and gas chromatography-mass spectrometry of the characteristic sugars of the oligosaccharide haptens of these antigens. In particular, the generation of monoclonal antibodies to the glycolipid antigens allows facile differentiation of serovars through enzyme-linked immunosorbent assay. All of these protocols were applied in developing a comprehensive approach to the typing of members of the M. avium complex.

Antibodies, Monoclonal↗
PubMed1992

The osteoclast proton pump differs in its pharmacology and catalytic subunits from other vacuolar H(+)-ATPases.

Osteoclasts are multinucleated cells derived from the mononuclear phagocyte system in the hematopoietic bone marrow. Their function is to resorb bone during skeletal growth and remodeling. They perform this function by acidifying an enclosed extracellular space, the bone resorbing compartment. Analysis of proton transport by inside-out vesicles derived from highly purified chicken osteoclast membranes has revealed the presence of a novel type of multisubunit vacuolar-like H(+)-ATPase. Unlike H(+)-ATPases derived from any other cell type or organelle, proton transport and ATPase activity in osteoclast vesicles are sensitive to two classes of inhibitors, namely V-ATPase inhibitors [N-ethyl-maleimide (NEM) and bafilomycin A1] and vanadate (IC50 100 mumol l-1), an inhibitor previously found to affect only P-ATPases. The osteoclast V-ATPase morphologically resembles vacuolar proton pumps and contains several vacuolar-like subunits (115 x 10(3), 39 x 10(3) and 16 x 10(3)M(r)), demonstrated by Western blot analysis. Subunits A and B of the catalytic domain of the enzyme, however, differ from that of other V-ATPases. In osteoclasts, subunit A has an M(r) of 63 x 10(3) instead of 67 x 10(3)-70 x 10(3); in contrast, monocytes, macrophages and kidney microsomes, which contain a vanadate-insensitive H(+)-ATPase, express the classical subunit A (70 x 10(3)M(r)). Moreover, two types of 57 x 10(3)-60 x 10(3)M(r) B subunits are also found: they are differentially recognized by antibodies and one is expressed predominantly in osteoclasts and the other in bone marrow cells and in kidney microsomes. Preliminary cloning data have indicated that the B subunit expressed in osteoclasts may be similar to the brain isoform. The osteoclast proton pump may, therefore, constitute a novel class of V-ATPase, with a unique pharmacology and specific isoforms of two subunits in the catalytic portion of the enzyme.

Adenosine Triphosphatases↗
PubMed1992

Study of foetal antigen in haematological malignancy.

Forty patients with different varieties of leukaemia and lymphoma were studied before and after therapy. Red cells and lymphocytes from each patient were tested for foetal antigen by lectin-agglutination test. The antigen was detectable on red cells in all untreated cases, the highest titre being found in chronic myeloid leukaemia. The titre showed significant reduction after treatment in all cases. We conclude that foetal antigen on red cells is a useful diagnostic aid in haematological malignancy and is a good indicator of the outcome of therapy.

Antigens, Neoplasm↗
PubMed1991

Use of high-performance liquid chromatography for assay of glutamic acid decarboxylase. Its limitation in use for post-mortem brain.

Rat brain, obtained 10 min after death, contained high levels of endogenous gamma-aminobutyric acid (GABA) and glutamic acid. Incubation of this brain homogenate at 37 degrees C indicated decrease of GABA with time due to degradation by GABA-transaminase. Reported high-performance liquid chromatographic (HPLC) methods for glutamic acid decarboxylase (GAD) assay depend on the difference between the GABA content of the reaction mixture after and before the incubation period. None of the methods considered the degradation of GABA during incubation. Furthermore, during determination of the Michaelis constant (KM) for the reaction none of them considered the endogenous substrate. Here we have focused on these factors which seriously affect the maximum velocity (Vmax) and KM values during GAD assay by the HPLC technique. By a simple and rapid HPLC technique we have measured GAD activity in post-mortem rat brain after removing endogenous glutamic acid by charcoal treatment and using gabaquline to prevent GABA degradation during incubation period. By this method a Vmax value of 46 +/- 4 nmol/h/mg protein and a KM value of 7.5 +/- 0.6 mM were observed for GAD activity of crude brain homogenate. For a comparative study, we have carried out radiometric assay of GAD activity from the same sample and observed a Vmax of 48 +/- 6 nmol/h/mg protein and KM of 6.9 +/- 0.4 mM.

Animals↗