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Biomedical subjects

D Chatterjee

Publications and source records attributed to D Chatterjee.

At least 55 records · Page 3Linked to original sources

Glucuronic acid- and branched sugar-containing glycolipid antigens of Mycobacterium avium.

The pentasaccharide hapten of the dominant glycopeptidolipid antigen of serovariant 19 of the Mycobacterium avium complex is noteworthy because of the uniqueness of its distal glycobiose, the presumed antigen determinant, which contains a 3,4-di-O-methyl glucuronic acid and a novel branched sugar. The detailed structure of the entire pentasaccharide has been established by high field 1H and 13C NMR, fast atom bombardment/mass spectrometry, and various specific degradations as 3,4-di-O-Me-beta-D-GlcAp-(1----3)-2,4-di-O-Me-3-C-Me-3,6-dideox yhexosyl-(1----3)-alpha-L-Rhap-(1----3)-alpha-L-Rhap-( 1----2)-6-dT al; the extreme acid lability of the novel penultimate sugar presented special structural challenges. Thus, the task of defining the variable epitopes of M. avium serovariants in order to charter the epidemiology of opportunistic mycobacterial diseases continues to reveal an unexpected order of sugar diversity and complexity.

Glucuronates

A fixed-point alignment technique for detection of recurrent and common sequence motifs associated with biological features.

A fixed-point alignment analysis technique is presented which is designed to locate common sequence motifs in collections of proteins or nucleic acids. Initially a program aligns a collection of sequences by a common sequence pattern or known biological feature. The common pattern or feature (fixed-point) may be a user-specified sequence string or a known sequence position like mRNA start site, which may be taken directly from the annotated feature table of GenBank. Once all alignment markers are located, the sequences are scanned for occurrences of given oligomers within a specified span both upstream and downstream of the fixed-point. The occurrences may then be plotted as a function of the position relative to the fixed-point, displayed as an actual sequence alignment or selectively summarized via various program options. Applications of the technique are discussed.

Amino Acid Sequence

The presence of novel glucuronic acid-containing, type-specific glycolipid antigens within Mycobacterium spp. Revision of earlier structures.

Previously, we had described the structures of the haptenic oligosaccharides of the surface glycopeptidolipid antigens from serotypes 9 and 25 of the Mycobacterium avium complex and had synthesized these units as putative antigenic probes. The lack of chemical concordance between the synthetic products and the haptens has prompted a re-examination of these structures utilizing the instrumental techniques not previously available of fast atom bombardment-mass spectrometry, Fourier transform infra-red, and high resolution NMR spectroscopy. With the additional information thus available, more extensive chemical fragmentations by base degradation, followed by alkylation, have furnished supportive evidence to allow formulation of revised and novel structures, all of which contain glucuronic acid: serotype 9, 2,3-di-O-Me-L-Fucp(alpha 1----4)-D-GlcAp(beta 1----4)-2,3-di-O-Me-L-Fucp(alpha 1----3)-L-Rhap(alpha 1----2)-6dTal; and serotype 25, 4-acetamido-4,6-dideoxy-2-O-Me-hexosyl(alpha 1----4)-D- GlcAp(beta 1----4)2-O-Me-L-Fucp(alpha 1----3)-L-Rhap(alpha 1----2)6dTal. Glucuronic acid, acetamido sugars, and other novel sugars appear to be widespread in the glycopeptidolipid antigens of Mycobacterium spp. The revised structures will allow renewed synthesis of artificial antigen probes and rational approaches to preparing monoclonal antibodies, both necessary for the new diagnostics required to trace the sources of widespread infections due to M. avium and Mycobacterium intracellulare.

Antigens, Bacterial

Chemical synthesis and seroreactivity of O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-O-(2,3-di-O-methyl- alpha-L-rhamnopyranosyl)-(1----9)-oxynonanoyl-bovine serum albumin--the leprosy-specific, natural disaccharide-octyl-neoglycoprotein.

The outer disaccharide segment, namely, O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-2,3-di-O-methyl-alpha -L-rhamnopyranose, of the trisaccharide-containing, leprosy-specific, phenolic glycolipid I has been synthesized as the 8-(methoxycarbonyl)octyl glycoside in high yield and absolute stereospecificity by a series of modified Koenigs-Knorr and Helferich reactions. A particular feature of the synthetic pathway involves methylation of the 2-hydroxyl group of the rhamnose moiety under neutral conditions, after first preparing the 8-(methoxycarbonyl)octyl glycoside as the alpha anomer via the 1,2-orthoacetate, and thus precluding the possible formation of an anomeric mixture. The 8-(methoxycarbonyl)octyl O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-(1----4)-2,3-di-O-methyl-alpha -L-rhamnopyranoside was converted into the crystalline hydrazide, and this was coupled to bovine serum albumin (BSA), via intermediate acyl-azide formation, to produce the corresponding neoglycoprotein, O-(3,6-di-O-methyl-beta-D-glucopyranosyl)- (1----4)-O-(2,3-di-O-methyl-alpha-L-rhamnopyranosyl)- (1----9)-oxynonanoyl-BSA, the so-called natural disaccharide-octyl-BSA. Extensive serological testing of this product against sera from leprosy patients and control populations, and comparison with the native glycolipid and previously synthesized neoglycoproteins, have shown that it is unparalleled in terms of sensitivity and specificity, and highly suited to replace the native glycolipid for the serodiagnosis of worldwide lepromatous leprosy.

Antigens, Bacterial

Synthesis of tetrasaccharides related to the antigenic determinants from the glycopeptidolipid antigens of serovars 9 and 25 in the Mycobacterium avium-M. intracellulare-M. scrofulaceum serocomplex.

The synthesis of the tetrasaccharides O-(2,3-di-O-methyl-alpha-L-fucopyranosyl)-(1----4)-O-(2,3- di-O-methyl-alpha-L-fucopyranosyl)-(1----3)-O-alpha-L-rhamnopyranosyl -(1----2)-6-deoxyl-L-talose (36) and O-(2-O-methyl-alpha-L-fucopyranosyl)-(1----4)-O-(2-O-methyl-alpha-L- fucopyranosyl)-(1----3)-O-alpha-L-rhamnopyranosyl-(1----2)-6-deoxy-L- talose (41) is described. The former and the latter structures, respectively, have been proposed as the carbohydrate chains in the polar glycopeptidolipid antigens of serovars 9 and 25 in the Mycobacterium avium-M. intracellulare-M. scrofulaceum serocomplex. Glycosylation of allyl 2,3-di-O-methyl-alpha-L-fucopyranoside with 4-O-benzoyl-2,3-di-O-methyl-alpha-L-fucopyranosyl chloride gave the alpha-linked disaccharide derivative, which was O-deallylated and converted into the corresponding disaccharide alpha-chloride. This was coupled with benzyl 3,4-di-O-benzyl-6-deoxy-2-O-(2,4-di-O-benzoyl-alpha-L-rhamnopyranosyl)- alpha-L-talopyranoside (32) to give a fully protected tetrasaccharide derivative, which was deprotected to furnish 36. Likewise, 3-O-benzyl-4-O-(3,4-di-O-acetyl-2-O-methyl-alpha-L- fucopyranosyl)-2-O-methyl-alpha-L-fucopyranosyl chloride, prepared by way of condensation of allyl 3-O-benzoyl-2-O-methyl-alpha-L-fucopyranoside with 2-O-methyl-3,4-di-O-(p-nitrobenzoyl)-alpha-L-fucopyranosyl bromide, reacted with 32, to provide, after removal of blocking groups, 41.

Epitopes

Comparative analysis of the membrane proteins and their specificities in neurons, protoplasmic astrocytes, and oligodendrocytes from rat brain.

Plasma membranes from neuronal perikarya (N), protoplasmic astrocytes (A) and oligodendrocytes (O) of rat brains were analysed with respect to their protein and glycoprotein contents and specificities. SDS-polyacrylamide gel electrophoresis revealed a total number of 23, 17, and 17 major proteins in N, A, and O respectively. Periodate-Schiff's staining showed that approximately 40-60% of these proteins were glycoproteins. The reactivity of these glycoproteins to Con A and WGA was also studied. Selective iodination of whole cells followed by electrophoresis and autoradiography indicated that of the major proteins, only 25% of neuronal and 60% of astroglial and oligodendroglial membrane proteins were exposed outside the cell surface. The overall results suggest that membrane proteins of each of the three cell types studied here have characteristically different internal and external markers differing in size, glycoprotein content, and reactivity of the glycoproteins to lectins.

Animals

Thyroidal induction of tubulin in brain development--identification of the target cell.

Exposure of organ cultures of newborn rat brains to tri-iodothyronine (T3) followed by cell fractionation as well as direct exposure of prefractionated neuronal (N) and glial (G) cells to the hormone results in an almost selective induction of tubulin in the glial cells. This is established from two independent assays of tubulin, viz. colchicine binding and vinblastin precipitation. In the newborn rat brain, the tubulin content of the G cells is almost 3-fold higher than that of the N cells. Treatment with T3 elicits 40-50% stimulation of tubulin in the G cells within 2 hr without any significant increase in the N cells. Brains from 8- or 50-day-old rats are irresponsive to induction to tubulin by T3. The rate of incorporation of [3H]leucine into total protein is very similar in both N and G cells of newborn rat brain but that into tubulin of G cells is about 3-fold higher than that of N cells. T3 promotes this incorporation by over 30% in the G cells with only a marginal 5% increase in the N cells. The overall results suggest that the glial cells represent the target cells for the T3-induced synthesis of tubulin, the major structural protein of the developing brain.

Aging

A simplified serological test for leprosy based on a 3,6-di-O-methylglucose-containing synthetic antigen.

The recent advent of synthetic antigens containing the Mycobacterium leprae-specific epitope, 3,6-di-O-methyl-beta-D-glucopyranoside, has allowed the development of simple specific serological tests for leprosy. The incorporation of one such product, 8-carbonyloctyl O-[4-O-(3,6-di-O-methyl-beta-D-glucopyranosyl)-alpha-L- rhamnopyranoside]-BSA, into a simple "spot" test, diffusion-in-gel enzyme-linked immunosorbent assay (ELISA), allowed an over 90% detection rate of untreated lepromatous leprosy, and the results showed good concordance with conventional ELISA based on the native phenolic glycolipid I.

Antigens, Bacterial

Induction of brain tubulin by triiodothyronine: dual effect of the hormone on the synthesis and turnover of the protein.

The relative effects of triiodothyronine (T3) on the synthesis and turnover of tubulin in the developing rat and chick brain have been examined. Measurements of rates of turnover of radiolabeled tubulin in the hormone-sensitive tissues show that the half-life of tubulin turnover is 4-6 h in the absence of T3 and 10-12 h in the presence of the hormone. Analysis of short-term kinetic data on the stimulation of tubulin by T3 in the chick brain show that the rapid induction is due to a dual effect of the hormone on the metabolism of tubulin--an increase in the rate of synthesis as well as a decline in its rate of turnover.

Animals

Homology of adenoviral E3 glycoprotein with HLA-DR heavy chain.

The Mr 19,000 adenovirus glycoproteins coded by the E3 region that is expressed on the cell membrane and presumably binds to HLA class I antigen shows sequence homology to the alpha-chain of human HLA-DR and to the kappa-chain of human IgM. The homology extends to a conserved domain present in all of the major histocompatibility complex antigens, beta 2-microglobulins, and immunoglobulins. Predicted beta-sheet secondary structures are similar between the Mr 19,000 adenovirus protein and these immune system proteins. Evolutionary and functional implications of the homology are discussed.

Adenoviruses, Human

Isolation of protoplasmic astrocytes: a procedure based on controlled trypsin digestion.

Trypsinization of rat brain tissue for shorter (10 min) and longer (60-90 min) periods is shown to yield two distinctly different types of dissociated cell populations. The over-all yield of intact dissociated cells declines when the period of trypsinization exceeds 10 min. Comparison of the types of dissociated cells obtained after different lengths of trypsinization indicates that the protoplasmic astrocytes, which represent the bulk of the neuroglial cells in brain, are highly susceptible to degradation during tissue trypsinization. Based on this observation, a new procedure involving controlled trypsin digestion for tissue disruption and Percoll gradient centrifugation has been developed for the isolation of virtually pure populations of intact protoplasmic astrocytes (97-98% particle purity). Identification of the purified cells is based on morphological, histochemical staining, and biochemical (marker enzyme) characteristics.

Animals

Effect of delta 9-tetrahydrocannabinol on monoamine oxidase activity in bovine eye tissues, in vitro.

An investigation was undertaken to analyze the effects of delta 9-tetrahydrocannabinol (THC) on monoamine oxidase (MAO) activity from calf ocular tissues. Ciliary processes, retina, trabecular meshwork, choroid, and iris all demonstrated significant MAO activity in decreasing order of magnitude. THC in concentrations from 10(-8)M to 10(-12)M stimulated MAO activity in extracts from all five tissues, except for iris at 10(-8)M. Maximum stimulation of MAO activity occurred at the 1 x 10(-12)M level for all tissues. Retina, followed next by trabecular meshwork and then ciliary processes, exhibited the largest increase in MAO activity at 10(-12)M THC. This latter effect could possibly by related to the influence of THC on intraocular pressure.

Animals

Idiopathic chronic gastritis.

Idiopathic chronic gastritis is an autoimmune disease and the cause of this gastritis probably act through a final common immunologic pathway. Specific gastric antibodies are diagnostic of this gastritis and the tissue of the gastric mucosa is characterized by infiltrations of mononuclear cells damaging the glandular parenchyma with concomitant loss of gastric secretory function. With suitable predisposing factors operating, the patient with simple chronic gastritis can have pernicious anemia develop. Chronic gastritis is frequently associated with chronic gastric ulcer and carcinoma of the stomach but not with duodenal ulcer. Chronic gastritis clinically presents with vague dyspeptic symptoms. Females are more commonly affected than males and the incidence rises with advancing age. Treatment of chronic gastritis is supportive in nature and also similar to the treatment of other autoimmune diseases. The author has suggested a new treatment of duodenal ulcer whereby the patients are immunized against mucosal antigen with a view to induction of chronic gastritis. The resulting biochemical damage of the parietal cells will produce hypochlorhydria.

Adult