Biomedical subjects
Publications and source records attributed to G R Gray.
Human enteric infection with Yersinia enterocolitica or Yersinia pseudotuberculosis may masquerade clinically as acute appendicitis but it is unusual for the appendix to be histologically inflamed. We report a case of Yersinia pseudotuberculosis infection in which acute appendicitis was present in the absence of terminal ileitis.
The fate of methylated 2-acetamido-2-deoxy-D-glucopyranosyl residues under reductive-cleavage conditions was investigated by using methyl 2-(acetylmethylamino)-2-deoxy-3,4,6-tri-O-methyl-beta-D-glucopyran oside (1), its alpha anomer (8), and fully methylated lacto-N-tetraitol as test compounds. Treatment of 1 with triethylsilane and trimethylsilyl trifluoromethanesulfonate in dichloromethane gave rise to (1,2-dideoxy-3,4,6-tri-O-methyl-alpha-D-glucopyrano)-2,3-dimethyl- [2,1-d]-2- oxazolinium trifluoromethanesulfonate. Quenching of the reaction by addition of aqueous sodium hydrogencarbonate resulted in hydrolysis of the oxazolinium salt. Compound 8 was fully stable to reductive-cleavage conditions. Thus, participation by the 2-acetamido group is necessary for glycosidic carbon-oxygen bond-cleavage to occur. Treatment of methyl 2-deoxy-2-(ethylmethylamino)-3,4,6-tri-O-methyl-alpha,beta-D-gluco pyranoside under reductive-cleavage conditions resulted in some anomerization, but neither hydrolysis nor reductive cleavage of the glycosidic carbon-oxygen bond was observed, as expected. Reductive cleavage of fully methylated lacto-N-tetraitol gave the products predicted on the basis of these and prior model studies, including 3-O-acetyl-2-(acetylmethylamino)-2-deoxy-4,6-di-O-methyl-D-glucopy ranose derived from the 3-linked 2-acetamido-2-deoxy-beta-D-glucopyranosyl residue.
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Catheter related sepsis (CRS) is the most serious complication of total parenteral nutrition. Frequently, however, low rates of CRS are associated with a high incidence of infection of the catheter tip, the clinical significance of which is unclear. The relationships between CRS, infection of the catheter tip and infection at the site of catheter insertion have been investigated in 283 catheters of 257 patients receiving total parenteral nutrition. CRS occurred in only ten patients (3.5 per cent) whereas organisms were isolated from 108 catheter tips (38.2 per cent). The most common organism isolated was Staphylococcus epidermidis (66.7 per cent). Eight catheter tips were colonized from a distant septic focus. Organisms were isolated from 90 catheter tips which were removed electively from patients who displayed no clinical evidence of sepsis. There was a poor correlation between infected catheter tips and infected catheter insertion sites. Asymptomatic infection of the catheter tip appears to be of little clinical relevance, resulting in no patient morbidity. Contamination of the catheter tip during or after removal seems to account for a significant proportion of these infections.
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The suitability of the reductive-cleavage method for analysis of the linkage positions in D-fructofuranosyl residues of D-fructans was examined by using sucrose, chicory-root inulin, and Aerobacter levanicum levan as models. Permethylation, and reductive cleavage with triethylsilane in the presence of either boron trifluoride etherate or trimethylsilyl trifluoromethanesulfonate, gave the expected methylated derivatives of 2,5-anhydro-D-mannitol and 2,5-anhydro-D-glucitol. With either catalyst, nonreducing (terminal) D-fructofuranosyl groups and D-fructofuranosyl residues linked at O-1 gave derivatives having the manno configuration as the major product, whereas D-fructofuranosyl residues linked at O-6, and at both O-1 and O-6, gave derivatives having the gluco configuration as the major product. The independent synthesis, and n.m.r.- and mass-spectral characterization, of the methylated 2,5-anhydro-D-mannitol and 2,5-anhydro-D-glucitol derivatives formed from these residues by reductive cleavage are reported.
Reductive cleavage of per-O-ethylated or per-O-methylated Saccharomyces cerevisiae D-mannans and subsequent acetylation had previously been shown to produce the expected derivatives of 1,5-anhydro-D-mannitol. Described herein is the independent synthesis of each of these derivatives, namely, 1,5-anhydro-2,3,4,6-tetra-O-methyl-, -2,3,4,6-tetra-O-ethyl-, -2-O-acetyl-3,4,6-tri-O-methyl-, -2-O-acetyl-3,4,6-tri-O-ethyl-, -3-O-acetyl-2,4,6-tri-O-methyl-, -3-O-acetyl-2,4,6-tri-O-ethyl-, -6-O-acetyl-2,3,4-tri-O-methyl-, -6-O-acetyl-2,3,4-tri-O-ethyl-, -2,6-di-O-acetyl-3,4-di-O-methyl-, -2,6-di-O-acetyl-3,4-di-O-ethyl-, -3,6-di-O-acetyl-2,4-di-O-methyl-, and -3,6-di-O-acetyl-2,4-di-O-ethyl-D-mannitol. The 1H-n.m.r. spectra, chemical-ionization (NH3) mass spectra, and electron-impact mass spectra for all of these derivatives are tabulated.
The positions of linkage in the D-mannans derived from Saccharomyces cerevisiae X2180 and its mutants, mnn1, mnn2, and mnn4, were established by perethylation and subsequent reductive cleavage with triethylsilane in the presence of boron trifluoride etherate (BF3 . Et2O) or trimethylsilyl trifluoromethanesulfonate. With the latter as the catalyst, all glycosidic carbon-oxygen bonds were cleaved, to produce a mixture of ethylated 1,5-anhydro-D-mannitol derivatives. With BF3 . Et2O as the catalyst, 2-, 3-, and 6-linked residues were incompletely cleaved, and residues linked at both O-2 and O-6 were not cleaved at all. It was concluded that reductive cleavage is an attractive method for determination of the structure of polysaccharides.
It has previously been established that muramyl dipeptide (N-acetylmuramyl-L-alanyl-D-isoglutamine) is an effective immunostimulant whose primary target cell type is the macrophage. Muramyl dipeptide is known to be structurally identical to a portion of the monomer unit of peptidoglycan, a nearly ubiquitous component of bacterial cell walls. To establish whether muramyl dipeptide or glycopeptides structurally related to it are formed as a result of macrophage processing of peptidoglycan, Bacillus subtilis cell walls radiolabeled in the muramic acid, glucosamine, and alanine residues of the constituent peptidoglycan were incubated in the presence of the cultured macrophage-like cell line RAW264, and the glycopeptides which released into the medium were fractionated and analyzed. Although muramyl dipeptide was not found in the culture medium, at least three glycopeptides structurally related to it were found, namely GlcNAc-MurNAc-Ala-isoGln-Dap-Ala, GlcNAc-MurNAc-Ala-isoGln-Dap, and GlcNAc-MurNAc-Ala-isoGln.
We have examined 11 families of Asian Indian origin, who are segregating beta-thalassaemia alleles, for coupled restriction enzyme site markers. A beta-thalassaemia deletion allele, which removes over 600 base pairs, is a common cause of thalassaemia in this population. This deletion can be conveniently detected in AvaII restriction enzyme digests. Consequently AvaII digests are particularly informative in this population because both the deletion and a coupled restriction site polymorphism may be simultaneously observed.
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The reliability of overnight 8-hour infusion cholangiography in confirming the diagnosis of acute cholecystitis or biliary colic was assessed by a prospective study in 100 patients. 55 positive infusion cholangiograms were subsequently confirmed at operation in 45 patients and by cholecystogram in 10 patients who did not have surgical treatment. The absence of false positive examinations is of fundamental importance if early cholecystectomy is to be performed without the risk of an unnecessary laparotomy. Infusion cholangiography proved to be a safe, simple and reliable investigation in the confirmation of acute gall-bladder disease.
The toxic, clinical, and immunological effects of suspensions of mycobacterial cell wall skeleton (CWS) and trehalose dimycolate (TDM) attached to oil droplets and given intravenously in doses of 100-2,000 micrograms/m2 (CWS) every 1 or 2 weeks was investigated in this Phase I study. The major limiting side effects were fever and chills at a dose of 2 mg/m2 body surface area. There was no significant hematopoietic, renal, hepatic, or pulmonary toxicity. Evaluation of changes in the white cell count and lymphocyte and monocyte populations and function showed an increase in the white blood count, an increase in the number of T cells, and a decrease in blood monocytes. Measurements of lymphocyte blastogenesis, monocyte suppressor activity, and monocyte cytostasis showed no consistent changes. Intravenous therapy with oil/CWS/TDM was associated with complete regression of a bronchial squamous cell carcinoma in one of three patients receiving 2 mg/m2 weekly. Subsequent Phase II studies can be conducted at a weekly dose of 1-2 mg/m2.
The toxicity and immunological effects of suspensions of mycobacterial cell wall skeleton (CWS) and trehalose dimycolate (TDM) attached to oil droplets and given intravenously in doses of 100 to 200 micrograms/M2 every one or two weeks was investigated. The major limiting side effect was fever and chills at a dose of 2 mg/M2. There was no major hematopoietic, renal, hepatic toxicity, or pulmonary toxicity. Intravenous therapy with CWS/TDM/Oil was associated with complete regression of a bronchial squamous cell arcinoma in one of three patients receiving 2000 micrograms/M2 weekly. The continued development and clinical study of surface attached purified and/or synthetic microbial adjuvants is a promising area of investigation.
We report our experience with a column chromatographic procedure for separating 3H-leucine-labelled alpha and beta globin. In non-thalassemic subjects the alpha: beta biosynthesis ratio was 1.04 +/- 0.10 S.D. An abnormal ratio was useful in defining thalassemia variants. The technique, although labour intensive, is not difficult and is recommended for any hospital laboratory acting as a reference centre for the diagnosis of hemoglobinopathies.
We have previously demonstrated the ability of human neutrophil myeloperoxidase to bind to mannan isolated from Candida albicans. Mannan may therefore be a primary component of the yeast cell wall which provides for binding of myeloperoxidase, a requirement potentially important for the candidacidal activity of the enzyme. In this report, we describe experiments to consider the relationship of the mannan-binding activity of myeloperoxidase to its candidacidal activity and the possibility that free mannan may inhibit myeloperoxidase-mediated candidacidal activity. We observed that binding of myeloperoxidase to the target yeasts was required for killing of C. albicans. We also observed that addition of soluble mannan significantly reduced myeloperoxidase-mediated killing of the yeasts in a dose-dependent manner by antagonizing binding of myeloperoxidase. Soluble mannan was demonstrated to have a similar dose-dependent inhibitory effect on neutrophil-mediated candidacidal activity without influencing phagocytosis of the organism. On the basis of these observations, we speculate that mannan solubilized in plasma and tissue fluid may interfere with neutrophil-mediated host defense against Candida infection.
A phase I study to determine the toxicity and immunologic effects of iv administered aqueous suspensions of mycobacterial cell wall skeleton (CWS) and CWS combined with trehalose dimycolate (TDM) was performed. A total of 26 patients received suspensions of either CWS or CWS/TDM given iv every 1 or 2 weeks in set doses of either 100, 250, 500, or 1000 micrograms/m2. The major dose-limiting side effects for both preparations were fever and chills at a dose of 1 mg/m2. This was more severe with the combined CWS/TDM. There was no renal or pulmonary toxicity. There was evidence of hepatic toxicity, with increases in the alkaline phosphatase and gamma glutamyl transferase, especially with high doses of CWS/TDM. Both the CWS and CWS/TDM groups had an increase in their wbc count. In the patients receiving CWS alone, there was a decrease in the peripheral blood monocytes. In the CWS/TDM group, there was an increase in the serum lysozyme, suggesting macrophage activation. No antitumor effect was seen in this phase I study. Aqueous suspensions of CWS and CWS/TDM can be administered safely iv over a period of time, with evidence of an effect on hematologic parameters.
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