PubMed Health⌕ Search

Biomedical subjects

M B Goren

Publications and source records attributed to M B Goren.

At least 55 records · Page 3Linked to original sources
PubMed1984

Cord-factor analogs: synthesis of 6,6'-di-O-mycoloyl- and -corynomycoloyl-(alpha-D-mannopyranosyl alpha-D-manno-pyranoside).

Selective triflation of 4,6:4',6'-di-O-benzylidene-alpha,alpha-trehalose gave 4,6:4',6'-di-O-benzylidene-2,2'-di-O-triflyl-alpha,alpha-trehalose , the structure of which was confirmed by the 1H-n.m.r. spectrum of its 3,3'-di-O-acetyl derivative (4). Treatment of 4 with sodium nitrite in hexamethylphosphoric triamide, followed by benzylation, afforded 2,3,2',3'-tetra-O-benzyl-4,6:4',6'-di-O-benzylidene-(alpha-D-mannopyrano syl alpha-D-mannopyranoside (7). Removal of the two benzylidene groups from 7, and selective tosylation of the product, gave a mixture of the 6,6'-ditosylate (11) and the 6-monotosylate (12), which were separated by chromatography. Treatment of 11 with potassium corynomycolate or potassium mycolate afforded the corresponding 6,6'-diesters, 14 and 15, respectively. Treatment of the monotosylate 12 with potassium corynomycolate gave the 6-monoester 18. Catalytic hydrogenolysis of 14, 15, and 18 gave the respective cord-factor analogs.

Cord Factors↗
PubMed1984

Sulfatides of Mycobacterium tuberculosis. Synthesis of the core alpha,alpha-trehalose 2-sulfate.

alpha,alpha-Trehalose 2-sulfate, the core carbohydrate of sulfatides of Mycobacterium tuberculosis, and the 3-sulfate isomer were synthesized by sulfation of 4,6:4',6'-di-O-benzylidene-alpha,alpha-trehalose with pyridine-sulfur trioxide complex to give the 2- and 3-sulfates, which were separated by column chromatography. The ammonium 2-sulfate salt wa was identical with the natural product obtained from the principal sulfatide (SL-I) of M. tuberculosis.

Chromatography, Thin Layer↗
PubMed1984

Fluorescent markers for studying phagosome-lysosome fusion.

Lysosomotropic fluorescent aminoacridines such as acridine orange and quinacrine have achieved prominence as markers for studying lysosome-phagosomes fusion, especially in macrophages. Experiments described demonstrate that because the aminoacridines traverse biological membranes with facility, they diffuse throughout the system, and ultimately accumulate intra- or extracellularly where they are most efficiently bound. Their presence or absence in phagosomes is therefore not unequivocally indicative of fusion or nonfusion. Alternative fluorescent lysosomal markers are described, and systems defined for which the aminoacridines may probably be used with confidence.

Acridine Orange↗
PubMed1984

The pathogenesis of trehalose dimycolate-induced interstitial pneumonitis. III. Evidence for a role for T lymphocytes.

Trehalose dimycolate, a glycolipid component of the cell walls of mycobacteria, induces interstitial pneumonitis and alveolar hemorrhages in C57BL/6 and C57BL/10 mice. Homozygous nude (nu/nu) mice of these backgrounds are not susceptible to this form of pulmonary injury. However, after administration of T-lymphocyte-enriched spleen cell preparations from syngeneic donors, homozygous nude mice become susceptible to trehalose dimycolate. The observations suggest that production of pulmonary lesions by this mycobacterial component is dependent on T lymphocytes. While the mechanisms are still under study, we propose that trehalose dimycolate can function as an activator of T lymphocytes and that products of activated T cells are responsible for production of the pulmonary lesions.

Animals↗
PubMed1984

The pathogenesis of interstitial pneumonitis induced by trehalose dimycolate. II. Reserpine prevents formation of lesions.

A single intraperitoneal injection of 10 micrograms of trehalose dimycolate (TDM) produced interstitial and hemorrhagic pneumonitis in C57BL/6 mice. As a part of an investigation of a possible role for cell-mediated immunity in the pathogenesis of this disorder, we found that reserpine, 3 mg/kg, given before, at the same time, or on Day 5 after administration of TDM, significantly reduced development of interstitial pneumonitis by Day 7. Smaller doses were less effective. Administration of reserpine, 3 or 2 mg/kg, 1 to 3 days after administration of TDM was lethal to most mice. Reserpine has been shown to inhibit expression of cell-mediated immune responses in mice, probably by causing intercellular release and degradation of vasoactive amines. Inhibition of pulmonary lesions by reserpine in TDM-treated mice suggests that a similar mechanism may be involved in the pathogenesis of TDM-induced lung injury.

Animals↗
PubMed1984

Observations on the ubiquity of the Mycobacterium tuberculosis sulfatides in mycobacteria.

Recent publications claimed improved selective extraction and recovery of the sulfatides ("sulfolipids") from Mycobacterium tuberculosis, and alleged their distribution among "all mycobacteria." Our evidence denies the selectivity, suggests that some ubiquitous mycobacterial glycolipid was mistaken for sulfatide, and that its occurrence in saprophytic species has not yet been unequivocally demonstrated.

Bacteriological Techniques↗
PubMed1983

Trehalose-containing lipooligosaccharides. A new class of species-specific antigens from Mycobacterium.

Mycobacterium kansasii is characterized by the presence of seven species-specific neutral lipooligosaccharide antigens. All react with hyperimmune anti-M. kansasii serum in enzyme-linked immunosorbent assays, and the more glycosylated members also react by gel diffusion. Both the native glycolipids and their inherent oligosaccharides were purified and the major features of their unique structures determined by acetolysis, partial acid cleavage, 1H-NMR and 13C-NMR, and chemical ionization and electron impact mass spectrometry of the permethylated products. They have in common a tetraglucose "core," beta-D-Glcp-(1 leads to 3)-beta-D-Glcp-(1 leads to 4)- alpha-D-Glcp(1 leads to 1)-alpha-D-Glcp where Glcp is glucopyranose, distinguished by the presence of an alpha,alpha-trehalose substituent. Variable residues of xylose, 3-O-methylrhamnose, fucose, and a novel N-acyl aminosugar, (4,6-dideoxy-2-O-methyl-3-C-methyl-4-(2'-methoxypropionamido)hexose; proof of this structure is not given) are linked to the core and the resulting oligosaccharides are acylated with 2,4-dimethyltetradecanoyl and acetyl functions to present a familial arrangement. Related but species-specific lipooligosaccharides typify Mycobacterium szulgai and apparently a host of other atypical mycobacteria. Thus, the antigenicity, and perhaps other features such as pathogenesis and drug resistance, of most atypical mycobacteria may be rationalized in terms of these new found cell wall lipooligosaccharides and the previously described glycopeptidolipids.

Antigens, Bacterial↗
PubMed1982

Interstitial and hemorrhagic pneumonitis induced by mycobacterial trehalose dimycolate.

Intraperitoneal injections of cord factor (trehalose dimycolate, TDM) provides a model for interstitial and hemorrhagic lung disease that is produced by a chemically defined substance. A single injection of 10 micrograms of TDM, in light mineral oil or hexadecane, into C57BL/6 mice produces interstitial and hemorrhagic pneumonitis. Following injection of TDM the pulmonary lesions increase gradually and become maximal by the seventh to ninth day, at which time 70% of the mice show both gross hemorrhages and dense mononuclear infiltrates; an additional 20% of the mice show only microscopic lesions. From day 14 onward the incidence and severity of the lesions decrease, and by day 28 the lungs are normal by both gross and light-microscopy examination. Only 5% of the mice succumb. Except for peritonitis other organs are not affected. Doses of 3.3 and 10 micrograms of TDM are equally effective in producing the lesions, but a dose of 1.0 microgram of TDM causes only mild interstitial inflammation and lesser doses do not induce lesions. A single subcutaneous injection of 10 micrograms of TDM causes lesions in only 20% of mice. Vehicle-injected mice do not develop lesions. Electron microscopy revealed that the majority of the infiltrating cells are monocytes and macrophages and that extensive interstitial damage is produced. The mechanism of the effects of TDM are unknown and is currently under study. Our preliminary data suggests that the phenomenon is dependent upon T-lymphocytes.

Animals↗
PubMed1982

Role of lipid content and hydrogen peroxide susceptibility in determining the guinea-pig virulence of Mycobacterium tuberculosis.

Among isoniazid-sensitive strains of Mycobacterium tuberculosis, strong associations were found in 56 strains of phage type A and I from India, Burma and East Africa between attenuation in the guinea-pig, a low content of strongly acidic (SAL) and sulphatide (SL) lipids, the presence of the attenuation indicator (AI) lipid and phage type I, suggesting that lipid content might mediate attenuation. However, 22 strains of phage type B and I from Iran and Britain also had low contents of SAL and SL but were highly virulent. Although the finding of a strong association in all 78 strains between attenuation and H2O2 susceptibility in vitro supports other evidence that attenuation is often due to increased susceptibility to H2O2 secreted by macrophages, an alternative mediator of virulence probably exists since 8 of the strains were attenuated and also resistant to H2O2. Identification of South Indian attenuated strains for epidemiological purposes by in vitro tests would be best achieved by the presence of AI, H2O2 susceptibility and, if the strains originated in or near India, by phage type I.

Animals↗
PubMed1979

A facile permethylation of cord factor.

Small quantities of cord factor (trehalose-6,6'-dimycolates) can be readily and almost quantitatively permethylated in anhydrous diethyl ether/dimethylformamide mixtures with CH3I and NaH-oil dispersion in the presence of molecular sieve. Hydrolysis of the permethylated products from cord factor "Peurois" and 'P3-Aoyama-b' prove these to be 6,6'-dimycolates. Experiments with a 4-palmitoyl glucose suggest that acyl migration in this system may not occur.

Chemical Phenomena↗
PubMed1979

Cord factor (trehalose-6-6'-dimycolate) of in vivo-derived Mycobacterium lepraemurium.

Harvests of Mycobacterium lepraemurium obtained from livers of moribund infected mice yielded M. lepraemurium cell walls that were extracted with solvent to provide crude M. lepraemurium cell wall lipids. By solvent fractionation and chromatography on DEAE cellulose and cellulose, a cord factor-like glycolipids contaminated with mycoside C was obtained. Additional solvent treatment provided the purified glycolipid, which was identified as 6,6'-trehalose dimycolate, by infrared and chromatographic comparison with authentic samples from M. tuberculosis, by identification of trehalose and specific mycolates of M. lepraemurium, and by permethylation analysis. This constitutes the first unequivocal identification of cord factor as a product of in vivo-derived mycobacteria.

Animals↗
PubMed1979

Pseudo cord factors: derivatives of alpha-D-glucopyranuronosyl (1-1) alpha-D-glucopyranuronoside.

We describe the synthesis of 6 pseudo cord factors (psi CF), analogs of the natural trehalose-6,6'-dimycolate, but based instead upon the dicarboxylic acid (TDA) that is obtained from trehalose by Pt-catalyzed oxidation. From TDA, several bis-amides ('mirror amide' psi CF) and a diester ('mirror' psi CF) of intermediate to high molecular weight were prepared. These superficially resemble cord facotr, have similar infared spectra and, like the natural product, several have impressive toxicity in mice and tumor-regression activity; but the latter property does not depend upon the former. A curious abrogation of biological activities results from introduction of a hexamethylene diamine 'spacer' between the carbohydrate core and the lipid substituents. The results suggest that (excepting the 'spacer' effect) the type of covalent linkage between the carbohydrate and lipid moieties may be relatively unimportant for expression of some of the biological activities of cord-factor-like glycolipids.

Animals↗
PubMed1979

Regression of a transplanted guinea pig hepatoma after intralesional injection of an emulsified mixture of endotoxin and mycobacterial sulfolipid.

Mycobacterial sulfatides (sulfolipids) in admixture with endotoxin had tumor regressive activity comparable to trehalose-6,6'-dimycolate (TDM) and endotoxin in guinea pigs, but unlike TDM were neither toxic nor granulomagenic and had no antitumor activity in mice. The increased endotoxin lethality in mice pretreated with BCG was not observed in mice pretreated with sulfolipids or TDM instead of BCG.

Animals↗