Five-year study of cimetidine or surgery for severe duodenal ulcer dyspepsia.
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Biomedical subjects
Publications and source records attributed to G R Gray.
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We investigated the possibility that dissolved mannan polysaccharide from Candida may have an inhibitory influence on the host defense mechanisms associated with neutrophils and thereby contribute to the pathogenesis of candidoses. We created a model for this hypothesis by using mannan derived from bakers' yeast (Saccharomyces cerevisiae) and mannan isolated from the serum of a patient with chronic mucocutaneous candidosis. We observed that these mannans inhibited the respiratory burst and release of myeloperoxidase stimulated by phagocytosis of serum-opsonized zymosan in vitro. Mannan did not inhibit release of three other lysosomal enzymes. The selective inhibition of release of myeloperoxidase was attributable to a carbohydrate-binding property of the enzyme, with the mannan causing co-sedimentation of the enzyme with the cellular fraction.
Erythrocyte membrane abnormalities in 3 members of a family with a hereditary haemolytic syndrome (HHS) were compared to those previously described in a family with lecithin:cholesterol acyltransferase (LCAT) deficiency. Despite similarities including an increase in membrane phosphatidylcholine, a decrease in phosphatidylethanolamine, stomatocytosis, and a marked decrease in erythrocyte osmotic fragility a number of differences were observed. These included membrane cholesterol content (increased in homozygotes with LCAT deficiency), changes in sodium and potassium content and Na+,k+-ATPase activity (the latter being increased in HHS), changes in acetylcholinesterase and sulfhydryl group latency (present in LCAT deficiency, but not in HHS) and 2,3 DPG content (decreased in HHS, normal in LCAT deficiency. Full compensation of the erythrocyte defect occurred in HHS but the homozygotes for LCAT deficiency were slightly anaemic. It is concluded that, although similar abnormalities in phospholipid composition, osmotic fragility, and erythrocyte morphology exist in these two disorders, the molecular nature of the erythrocyte membrane structural and functional changes in HHS and LCAT deficiency is clearly different.
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The positions of localization of the single carbon-carbon double bond in homologs of C series mycolic acids from Mycobacterium smegmatis have been established by 1) combined ammonia chemical ionization mass spectrometry/gas-liquid chromatography of aldehyde ozonolysis products, and 2) high resolution electron impact mass spectral analysis of vicinal glycol derivatives as their trimethylsilyl ethers. These studies have revealed that each homolog is a mixture of two isomers differing in double bond location. In each of the three homologs examined, approximately equal amounts of two isomers were present as follows: (formula: see text).
The positions of esterification of the 4 to 5 acetyl residues in the acetylated methylmannose-containing polysaccharide from Streptomyces griseus have been established by the methyl replacement technique, wherein ester substituents are specifically replaced with methyl ether substituents. The newly incorporated methyl groups were distinguished from 3-O-methyl groups by the use of polysaccharide containing radioactively labeled endogenous methyl groups. The positions of methyl group localization were established by a proton magnetic resonance study of the intact methyl-replaced polysaccharide combined with an analysis of the constituent monosaccharides by gas-liquid chromatography-electron impact mass spectrometry of their alditol acetate derivatives. These studies demonstrate that the acetyl groups are located at position 6 of approximately half of the 10 contiguous alpha(1 leads to 4)-linked 3-O-methyl-D-mannose residues. Purification of the polysaccharide was accomplished by an added step involving affinity chromatography on a column containing immobilized palmitoyl residues. The affinity of the polysaccharide for this long chain lipid suggests that its plays a role similar to the methylmannose-containing polysaccharide of Mycobacterium smegmatis in its regulation of the bacterium's fatty acid synthetase.
The clinical efficacy of intralesional immunotherapy utilizing Mycobacterium smegmatis cell wall skeleton (CWS) and trehalose dimycolate attached to oil droplets was investigated in 15 patients with advanced malignant melanoma. Patients received 300 microgram to 1050 microgram of the CWS combined with one-half that amount of trehalose dimycolate every 1 to 2 weeks for a total of 8 treatments. Therapy was continued if regression of injected lesions only occurred. Therapy was discontinued if regression of noninjected disease also occurred. Six of the 15 patients had regression of at least one injected lesion. Four of these 6 patients also had regression of noninjected disease lasting 4+, 6, 16 and 18+ months. Response was highly related to immune status. Six (83%) of 7 patients who reacted to one of a battery of skin tests responded. All 8 patients who did not react to skin tests failed to respond to therapy. There was no correlation of response with sex, prior therapy, disease-free interval or presence of visceral disease. Mycobacterial CWS and trehalose dimycolate is an effective immunotherapeutic agent. Additional studies of purified immunoadjuvants are warranted.
A serologically active, acidic arabinomannan has been isolated from Mycobacterium smegmatis. The polysaccharide contains approximately 56 arabinosyl and 11 mannosyl residues, and 2 phosphate, 6 monoesterified succinate, and 4 ether-linked lactate groups. After saponification to remove succinyl groups, the polysaccharide can be separated into phosphorylated (55%) and nonphosphorylated (45%) forms, the former containing a little more arabinose and a little less mannose than the latter. The structures of these polysaccharides were investigated by 1H- and 13C-n.m.r. spectroscopy and methylation analysis, before and after selective cleavage of furanosyl linkages. The phosphorylated and nonphosphorylated forms of the polysaccharide were found to have similar, if not identical, structures. The main structural feature of the polysaccharides is the presence of chains of contiguous arabinofuranosyl residues linked alpha-(1 leads to 5). These chains are attached at 0-4 of arabinopyranosyl residues that are present in a core region of the polysaccharide that also contains mannopyranosyl residues. Immunochemical studies demonstrated that the polysaccharide is an effective, precipitating antigen with antisera from rabbits immunized with cell walls or heat-killed cells of M. smegmatis. The polysaccharide is, however, more effective as a precipitating antigen after removal of the succinate groups, and completely ineffective after removal of arabinofuranosyl residues. The polysaccharide therefore contains an important antigen in common with the arabinogalactan lipopolysaccharide of the cell wall of the bacterium, i.e., chains of contiguous alpha-(1 leads to 5)-linked arabinofuranosyl residues.
A number of varieties of thalassemia were found to be common in the Vancouver area and in other parts of British Columbia. Of 3117 patients whose blood samples were studied by hemoglobin electrophoresis at the Vancouver General Hospital between Jan 1, 1965 and June 30,1977, 813 had the beta-thalassemia trait, 18 had homozygous beta-thalassemia, 97 had alpha-thalassemia trait, 24 had hemoglobin H disease and 14 had miscellaneous variants. Eight patients had interactions of beta-thalassemia with hemoglobin S,C, D, O arab or Vancouver, and one patient had alpha thalassemia associated with hemoglobin Constant Spring. Twelve other variants were noted. They included hemoglobins B2, E, Q, GHsi Tsou, J Bangkok, British Columbia, KOLN, Lepore, Rampa, Tacoma, St. Claude and an unidentified alpha-chain variant.
Mycolic acids derived from the cell walls of Mycobacterium bovis BCG, Mycobacterium bovis Bovinus I, Mycobacterium smegmatis, and Mycobacterium tuberculosis H37Rv have been fractionated as their p-bromophenacyl esters by a two-step high performance liquid chromatographic procedure: 1) adsorption chromatography on 10-micrometer particle size silica gel, and 2) reverse phase partition chromatography on a 10-micrometer particle size support containing a C18 bonded phase. This procedure has resulted in the isolation of approximately 24 mycolic acids from each bacterium (very likely homologs of various mycolate types) instead of the two to four that have previously been described. The implication of these results on the previously determined structures of these fatty acids is discussed.
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Structural, compositional, and functional abnormalities were found in the erythrocyte membranes of homozygotes for LCAT deficiency. Similar but less pronounced abnormalities were also present in the heterozygotes for this disorder. Some of the membrane alterations, which included decreased osmotic fragility, changes in phospholipid composition, and membrane sulfydryl group latency, as well as changes in the activity of membrane p-nitrophenylphosphatases and acetylcholinesterase, may be secondary to the changes in plasma lipids. However, since plasma lipids (and LCAT activity) were normal in the hereozygotes, the existence in both the homo- and the heterozygotes of erythrocyte membrane abnormalities unrelated to plasma LCAT activity seems likely.