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Biomedical subjects

J C Williams

Publications and source records attributed to J C Williams.

At least 289 records · Page 16Linked to original sources
PubMed1986

The alteration of hamster serum elastase inhibitory capacities by chloramine T, in vitro and in vivo.

The major elastase inhibitor of human serum, alpha-1 proteinase inhibitor (A1PI), is susceptible to oxidative inactivation by a variety of agents, including chloramine T. We have examined the effects of chloramine T on the catalytic activity of porcine pancreatic (PPE) and human leukocyte elastase (HLE) and on the elastase inhibitory capacity of hamster, rat, and human serum as well as pure human A1PI. Both PPE and HLE, but not trypsin, were inhibited in a concentration-dependent manner by concentrations of chloramine T greater than 0.1 mM. The abilities of rat and human serum and pure human A1PI to inhibit both PPE and HLE were inhibited in a concentration-dependent manner by chloramine T. In contrast only the ability of hamster serum to inhibit HLE was altered by exposure to chloramine T: inhibition of PPE was not effected. Gel exclusion chromatography disclosed the existence of two major peaks of elastase inhibitory activity in hamster plasma: one, with an approximate molecular weight of 55 K, eluting in the region of A1PI that was sensitive to chloramine T inactivation and one with a molecular weight of approximately 180 K which was chloramine T insensitive. The parenteral administration of chloramine T to hamsters resulted in a modest and transient diminution of the serum HLE inhibitory activity and an equally modest and transient elevation of PPE inhibitory activity.

Animals↗
PubMed1986

Glutamyl ribose-5-phosphate storage disease: nephrotic syndrome and cerebral atrophy.

Storage of glutamyl ribose-5-phosphate was identified at autopsy in the brain and kidney of an 8-year-old male who had presented clinically with progressive renal failure and neurological deterioration. In a renal biopsy during life, glomeruli were focally sclerotic and contained foam cells. By electron microscopy, lysosomal accumulation was present in renal tubular and glomerular epithelial cells, hepatic Kupffer cells, and conjunctival connective tissue cells. Ganglion cells in the brain stem had swollen, PAS-positive cytoplasm with central chromatolysis. The cerebral cortex was atrophic and there was loss of Purkinje cells in the cerebellum. The identification of storage was based on biochemical isolation of the compound from the tissues at autopsy. The enzyme deficiency responsible for the storage has not yet been identified.

Atrophy↗
PubMed1986

Q fever vaccination of sheep: challenge of immunity in ewes.

Adult ewes (17 months of age) were vaccinated against Coxiella burnetii, using a formalin-inactivated whole cell (WC) phase I Henzerling strain vaccine or a chloroform methanol residue (CMR) vaccine. Nineteen pregnant ewes were placed in 3 categories [(i) unvaccinated, (ii) WC vaccine, and (iii) CMR vaccine] and were challenge exposed at approximately the 100th day of gestation with 210,000 plaque-forming units of C burnetii inoculated subcutaneously. Shedding of rickettsiae was measurably reduced, but was not prevented in vaccinated groups, as shown by inoculating ewes' placental tissues, amniotic fluid, and colostrum into mice, as well as by histopathologic lesions of placental tissues. The rickettsiae were shed in the placenta, amniotic fluid, or colostrum in 6 nonvaccinated ewes. In comparison, rickettsiae were detected in placental inoculations from 2 of 6 ewes in the WC vaccine group and 1 of 6 in the CMR group. In contrast to those in the vaccinated ewes, placentitis, high concentrations of rickettsiae in microscopic preparations, and weak lambs were typical for the nonvaccinated ewes.

Animals↗
PubMed1986

Response of nitrosomethylurea-induced rat mammary tumor to endocrine therapy and comparison with clinical response.

We have compared the response of the N-methyl-N-nitrosourea-induced rat mammary tumor to various endocrine agents with response in patients with breast cancer. To do this, we have induced tumors in 228 animals (65% of intact rats developed tumors but only 14% of ovariectomized rats developed tumors). In intact rats, 4-hydroxyandrostenedione, tamoxifen, and a combination of tamoxifen, aminoglutethimide (AG), and danazol induced significant tumor regression (P less than 0.001, P = 0.01, P = 0.04, respectively), whereas danazol, AG, and trilostane were ineffective when used singly. Further investigation showed that the inactivity of AG in the rat was due to extensive acetylation of this compound. In order to mimic postmenopausal breast cancer, we ovariectomized rats after N-methyl-N-nitrosourea administration. In ovariectomized animals, AG was again ineffective in inducing tumor regression but 4-hydroxyandrostenedione was highly active when compared to controls (P = 0.002). Comparison with response of this model to endocrine therapy with response in patients indicates that this has good predictive capacity since it shows that agents which have minor activity in human breast cancer such as danazol and trilostane are inactive in the model. The intact rat model does not, however, predict whether a drug will be useful for pre- or postmenopausal patients. We recommend that before committing large numbers of patients to clinical trials on the basis of this model, the metabolism of new compounds should be compared in humans and rats.

Aminoglutethimide↗
PubMed1985

Intracellular transport of high molecular weight intermediates of acid alpha-glucosidase in human fibroblasts.

Two transient, high molecular weight precursors of human acid alpha-glucosidase were detected by immune precipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The high molecular weight precursors were rapidly converted into lower molecular weight forms corresponding to previously identified intermediates of acid alpha-glucosidase. An accumulation of these precursors was observed in fibroblasts treated with monensin and nigericin, suggesting that these precursors are intermediates of acid alpha-glucosidase undergoing transport through the Golgi complex.

Animals↗
PubMed1985

The molecular basis for charge heterogeneity in human acid alpha-glucosidase.

The molecular basis for charge heterogeneity in human hepatic alpha-glucosidase (alpha-D-glucoside glucohydrolase, EC 3.2.1.20) was determined by analysis of the carbohydrate and polypeptide components of the enzyme. Only small remnants of high mannose chains that contained neither sialic acid nor mannose 6-phosphate were detected in the carbohydrate structure. Four enzymatically active forms of alpha-glucosidase separated by chromatofocusing were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were found to contain different polypeptides. The absence of charged residues in oligosaccharide chains and variability in the polypeptide subunits of the charge forms of hepatic alpha-glucosidase suggest that charge heterogeneity results from differences in the protein structure of the charge forms. The pattern of differences in the polypeptide subunits suggests that the charge forms for hepatic alpha-glucosidase may be the product of proteolysis.

Electrochemistry↗
PubMed1985

Proteolytic inactivation of human leukocyte elastase.

Human leukocyte elastase can be proteolytically inactivated by bovine pancreatic trypsin. Neither porcine pancreatic elastase nor bovine pancreatic chymotrypsin causes inactivation of leukocyte elastase, nor are trypsin, pancreatic elastase, or chymotrypsin themselves susceptible to proteolysis. The trypsin-catalyzed inactivation of leukocyte elastase can be slowed by inhibition of trypsin with benzamidine or by occupation of elastase's active site with elastatinal.

Benzamidines↗
PubMed1985

Persistence of dead Ostertagia ostertagi in the abomasal mucosa following anthelmintic treatment.

Anthelmintic trails, conducted with albendazole, fenbendazole and ivermectin for efficacy against gastrointestinal nematodes, principally inhibited early fourth larval stages of Ostertagia ostertagi in naturally infected cattle. Cattle wee slaughtered seven to 20 days after treatment. O ostertagi was the predominant abomasal nematode recovered with occasional small numbers of Haemonchus species and Trichostrongylus axei. Control calves uniformly had very large O ostertagi infections, primarily early fourth stage larvae. Viable surviving worms and variable numbers of dead and degenerate worms were recovered in abomasal contents and washings. These O ostertagi larvae and adults were characterised by adherent debris or proteinaceous material, degenerated cuticles and distortion of internal structures. This study demonstrated the necessity for proper timing of slaughter for anthelmintic trial evaluation to allow clearance of dead nematodes, specifically O ostertagi larvae which are sequestered in the abomasal glandular tissue. Nematode collection within seven to 12 days after treatment will include dead and degenerate larval nematodes. The peripheral coating of larvae was suggestive of the Splendore-Hoeppli effect which has been associated with immunological responsiveness. The antigenic stimulus for this material and the lymphocyte and eosinophil infiltration was suspected to be early fourth stage O ostertagi larvae within the mucosa but was not identified definitively.

Abomasum↗
PubMed1985

Detection of human acid alpha-glucosidase in fibroblasts using monoclonal antibodies in a biotin-avidin amplified ELISA.

A sensitive and specific immunological assay for detection of human lysosomal alpha-glucosidase was developed using a mouse monoclonal antibody incorporated into a biotin-avidin amplified ELISA. The immunoassay was more than 60 times more sensitive than the currently used enzymatic assay for alpha-glucosidase activity using a fluorimetric substrate. This methodology provides an alternative approach with increased sensitivity for screening individuals for alpha-glucosidase deficiency.

Antibodies, Monoclonal↗
PubMed1985

Cellular immunity in Q fever: specific lymphocyte unresponsiveness in Q fever endocarditis.

Human infection with the rickettsia Coxiella burnetii presents as acute influenza-like primary Q fever, subacute granulomatous hepatitis, or chronic endocarditis with hepatitis. To investigate whether persistent infection is associated with a possible immunologic defect, we tested lymphocyte proliferation specific for Coxiella in vitro in peripheral blood mononuclear cells from patients and controls. All four patients with endocarditis had profound lymphocyte unresponsiveness to Coxiella antigens with normal proliferation to control antigens. Hepatitis and primary Q fever were associated with vigorous responses in vitro to Coxiella antigens. Suppression of lymphocyte unresponsiveness was in part mediated by an antigen-nonspecific, glass-adherent cell. We hypothesize that specific T cell unresponsiveness is an important factor in persistent infection with C. burnetii and offer in vitro lymphocyte stimulation as a more specific diagnostic test to distinguish cases of endocarditis among those with chronic hepatitis due to Q fever.

Adult↗
PubMed1985

Electron microscopic studies of lipopolysaccharides from phase I and phase II Coxiella burnetii.

Lipopolysaccharides from phase I (LPSI) Coxiella burnetii Ohio and Nine Mile strains and from phase II (LPSII) Nine Mile stain were negatively and positively and examined with the electron microscope. The ultrastructure of LPSI and LPSII positively stained with uranyl formate or uranyl acetate was ribbon-like. When negatively stained with uranyl acetate, LPSI was ribbon-like but LPSII exhibited hexagonal lattice structures. However, LPSII stained negatively with sodium phosphotungstate and ammonium molybdate exhibited hexagonal lattice ultrastructures which were not identical to those observed when negatively stained with uranyl acetate. The hexagonal lattice structures formed in vitro were due to the interactions of LPSII and the staining reagents rather than to protein-LPS interactions. The differences in the ultrastructures of LPSI and LPSII are undoubtedly based on variations in their chemical composition.

Coxiella↗
PubMed1985

Suppression of in vitro lymphocyte proliferation in C57BL/10 ScN mice vaccinated with phase I Coxiella burnetii.

The effect of inactivated phase I and phase II Coxiella burnetii whole cell vaccine (WCV) on the response of murine spleen cells to mitogenic and antigenic stimuli was evaluated in C57BL/10 ScN endotoxin nonresponder mice with an in vitro lymphocyte proliferation assay. Intraperitoneal injection of phase I WCV into mice resulted in marked and persistent suppression of the proliferative response of spleen cells to concanavalin A, phytohemagglutinin, and pokeweed mitogen. This response was time and dose dependent and was not associated with decreased lymphocyte viability. By using a standard dose of 100 micrograms of phase I WCV, suppression of mitogenic responsiveness was first detected 3 days postinjection, attained maximum levels by day 14, and persisted for longer than 5 weeks. Suppression of mitogenic lymphocyte proliferation also was demonstrated after inoculation of animals with viable phase I organisms. The observed hyporesponsiveness of spleen cells from phase I WCV-injected animals was not either the result of a shift in the mitogenic dose optimum or due to a change in the day of in vitro peak response. Spleen cells from phase I WCV-injected mice were negatively regulated with homologous antigen. Investigation of the mechanism of action of phase I WCV, with a 51Cr-release assay, and trypan blue dye exclusion showed that phase I WCV was not directly cytolytic or cytotoxic to spleen cells from normal or vaccinated mice. Phase II WCV did not induce significant mitogenic hyporesponsiveness or negative modulation of spleen cells. These findings extend the observations of adverse host responses associated with the phase I WCV and underscore the need to develop a microbial fraction which possesses protective potency but which lacks the propensity to induce deleterious tissue reactions and immunosuppression.

Animals↗
PubMed1985

Glucagon, insulin, and growth hormone responses to glucose infusion in lactating dairy cows.

Early lactation in the dairy cow is associated with an increased demand for energy that can only be met by hormone-mediated partitioning of nutrients. The purpose of this study was to determine adaptive responses of basal and glucose-stimulated glucagon (IRG), insulin (IRI), and growth hormone (GH) concentrations to early lactation. Blood was collected via jugular cannulas from nonpregnant nonlactating (NPNL) cows and cows 14 days antepartum (AP) and 5 and 30 days postpartum (PP). Basal concentrations of IRI decreased with lactation, IRG was essentially unchanged, and GH was increased with lactation. The molar IRI/IRG (I/G) ratio was decreased from 4.6 at day 14 AP to 1.3 at day 30 PP. The effects of exogenous glucose (0.56 mM/kg body wt) on IRI were greatest during pregnancy and declined with lactation. IRG responses to glucose were similar except in NPNL cows, which had a minimal but prolonged IRG inhibition, GH responses to glucose infusion were absent in NPNL cows and were most significant at 5 days PP. The decreased I/G and elevated GH concentrations suggests that both IRG and GH play a role in nutrient partitioning during early lactation.

Animals↗
PubMed1985

Effect of propionate infusion on plasma glucagon, insulin and growth hormone concentrations in lactating dairy cows.

Altered concentrations of metabolic hormones have been suggested as important mediators of energy partitioning during early lactation. This study was initiated to determine the effects of propionate (1.0 mmol/kg body weight) infusion on plasma concentrations of glucagon, insulin, growth hormone, propionate and glucose at 14 days ante-partum (AP) and days 5 and 30 postpartum (PP). No differences were seen in propionate concentrations between sampling days. Glucose concentrations were elevated following propionate infusion in pregnant cows but were not elevated in the PP cows. Insulin responses to propionate infusion did not differ between days while the glucagon response was blunted at day 5 PP. Basal glucagon concentrations were elevated between days 5 and 30 PP, insulin concentrations were unchanged between days, while the molar insulin/glucagon ratio was decreased during early lactation. Basal growth hormone (GH) concentrations were elevated between day 14 AP and day 30 PP. GH responsiveness to declining propionate concentrations was greatest at day 5 PP. These data further suggest a role for glucagon as well as GH in nutrient partitioning during early lactation.

Animals↗
PubMed1985

Seroepidemiology of Q fever among domestic animals in Nova Scotia.

We used the indirect microimmunofluorescence test to determine the presence of antibodies in sheep, cattle, goat, cat, and dog sera to phase I and II Coxiella burnetii antigens in Nova Scotia. Only 6.7 per cent of the 329 sheep tested had antibodies to phase II antigen and none had antibodies to phase I. Of 29 goats tested, 7 per cent and 3.5 per cent had antibodies to phase II and phase I antigens, respectively. In contrast, 23.8 per cent of the 214 cattle tested had antibodies to phase II antigen, and 24.2 per cent had antibodies to phase I antigen; 24.1 per cent of 216 cats tested had antibodies to phase II antigen and 6 per cent had antibodies to phase I antigen. None of the 447 dogs tested had antibodies detected. We conclude that cattle and cats may be reservoirs for human Q fever in Nova Scotia.

Animals↗
PubMed1985

Cellular immunity in Q fever: modulation of responsiveness by a suppressor T cell-monocyte circuit.

Human infection with the rickettsia Coxiella burnetii presents as an acute flulike primary Q fever, as a subacute granulomatous hepatitis, or, rarely, as chronic endocarditis. We have previously described lymphocyte unresponsiveness to Coxiella antigen in patients with Q fever endocarditis. This unresponsiveness was antigen specific and was mediated in part by adherent suppressor cells. In this report we show that the adherent suppressor cells work via prostaglandin E2 (PGE2)4 production. Addition of the cyclooxygenase inhibitor indomethacin to cultures of PBMC from patients with endocarditis or chronic laboratory exposure resulted in consistent increases in Coxiella-specific lymphocyte proliferation. The degree of increase in proliferation induced by indomethacin correlated strongly with the amount of PGE2 produced in a 4-hr culture stimulated by Coxiella antigen, but it also correlated with the sensitivity to inhibition of mitogenesis by PGE2. The suppressor mechanism was antigen nonspecific, because induction of suppression in vitro by Coxiella antigen also suppressed Candida-induced proliferation when both antigens were present in the same culture. Addition of indomethacin to these antigen cocultures totally reversed the Coxiella-induced suppression, confirming the evidence above that the nonspecific effector mechanism of suppression was prostaglandin (PG)-mediated. Elicitation of suppression, however, was antigen specific and involved a T cell-monocyte suppressor circuit. Supernatants from Coxiella-stimulated immune T cells and from the suppressor subset (OKT8+-enriched) of those T cells, but not unstimulated immune cells, induced augmented PGE2 production by unrelated nonimmune PBMC. We conclude that the lymphocyte unresponsiveness characterizing patients with Q fever endocarditis is modulated in part by an antigen-specific T suppressor cell which secretes a lymphokine to stimulate PGE2 production by adherent cells.

Adult↗