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Biomedical subjects

J E Riley

Publications and source records attributed to J E Riley.

At least 19 recordsLinked to original sources
PubMed1995

Subcellular pathologic features of glucocorticoid-induced hepatopathy in dogs.

Dogs are particularly susceptible to development of glucocorticoid-induced hepatopathy, but the mechanisms are not well understood. We investigated the pathogenesis of glucocorticoid hepatopathy by examining sequential morphologic and biochemical changes in the liver of dogs during steroid administration. Six adult Beagles were given prednisolone acetate (4mg/kg of body weight, once daily for 24 days IM). Serum samples and percutaneous liver biopsy specimens were obtained before the start of the study (treatment day [TD] 0) and at TD 5, 10, 15, and 25. There were significant (P < 0.05) and progressive increases in serum activities of alkaline phosphatase, gamma-glutamyltransferase, and alanine transaminase. Light microscopic changes in liver biopsy specimens included progressive hepatocellular swelling and vacuolation. Electron microscopy revealed glycogen accumulation, peripheral displacement of organelles, and prominent dilatation of bile canaliculi, compared with findings at TD 0. Liver biopsy specimens taken at TD 25 had significantly (P < 0.05) increased activities of the plasma membrane enzymes, alkaline phosphatase and gamma-glutamyltransferase, and 5'-nucleotidase was significantly (P < 0.001) decreased. Subcellular fractionation on reorientating sucrose density gradients revealed high-density peaks of alkaline phosphatase and gamma-glutamyltransferase, compatible with a specific increase in the biliary canalicular component of the enzyme activities. Neutral alpha-glucosidase activity was shifted to the denser fractions, indicative of an increase in the proportion of rough to smooth endoplasmic reticulum and consistent with enhanced synthesis of plasma membrane proteins. There also was evidence for progressive increase in fragility of intracellular organelles, particularly lysosomes. These findings indicate that glucocorticoid hepatopathy in dogs is associated with progressive alterations not only to the plasma membrane, but also to other subcellular organelles.

Alanine Transaminase↗
PubMed1991

Detection of growth hormone and growth hormone-releasing hormone-related messenger RNA in rat leukocytes by the polymerase chain reaction.

To validate that growth hormone (GH) and growth hormone-releasing hormone (GHRH) can be produced by leukocytes, we have assessed the presence of GH and GHRH-related mRNA in leukocyte cultures by reverse transcription and the polymerase chain reaction. A sample of the polymerase chain reactions were size-fractionated by electrophoresis in a 0.8% agarose gel and examined with ultraviolet light after ethidium bromide staining. Single major DNA bands corresponding in length to the distance between the 5' ends of the two GH and GHRH specific primers, 603 base pairs and 260 base pairs, respectively, were obtained. The DNA bands hybridized specifically to GH- and GHRH-specific probes after Southern transfer to nitrocellulose. The identity of the GH polymerase chain reaction material was confirmed by restriction enzyme analysis. The results showed that GH and GHRH gene expression occurs in mononuclear leukocytes and support the idea that these neuroendocrine hormones may be common signal molecules between the immune and neuroendocrine systems.

Animals↗
PubMed1989

Biochemical changes in the jejunal mucosa of dogs with exocrine pancreatic insufficiency following pancreatic duct ligation.

The effects of exocrine pancreatic insufficiency on the small intestinal mucosa were examined in dogs following pancreatic duct ligation. There were no significant changes either in villus architecture or enterocyte height after duct ligation, but numbers of bacteria in duodenal juice increased then subsequently decreased following treatment with exogenous pancreatic enzymes. Pancreatic insufficiency resulted in a considerable increase in the proportion of microvillar membrane proteins of molecular mass over 200 kDa from 3.3 +/- 4 per cent (mean +/- SEM) to 13.6 +/- 7.2 per cent, and this decreased to 6.9 +/- 5.2 per cent following pancreatic enzyme supplementation. However, anticipated increases in activities of maltase and sucrase were not observed following duct ligation, and there was a reduction in lactase activity which was reversed by pancreatic supplementation. Activities of marker enzymes for the other subcellular organelles showed relatively minor or no changes throughout the study. These findings are consistent with a specific role for pancreatic enzymes in the post-translational processing of intestinal microvillar membrane proteins, and suggest that reduced degradation of brush border proteins in the absence of pancreatic secretions may be masked by quantitative and qualitative changes in the intestinal microflora.

Alkaline Phosphatase↗
PubMed1988

Investigation of the physical properties of dog intestinal microvillar membrane proteins by polyacrylamide gel electrophoresis: a comparison between normal dogs and dogs with exocrine pancreatic insufficiency.

Procedures have been validated for the investigation of the physical properties of canine microvillar membrane proteins by SDS-polyacrylamide gel electrophoresis. These have been used to examine mucosal samples from eight control dogs and from five dogs with naturally occurring exocrine pancreatic insufficiency (EPI) in order to evaluate the potential role of the pancreas in the normal turnover of microvillar membrane proteins in the dog. Gel scanning showed that the proportion of total membrane protein in bands corresponding to a molecular mass greater than 200 kDa was up to 20-times higher in dogs with EPI than in control dogs. In particular, a band of apparent molecular mass 218 kDa represented between 8 and 28% of membrane protein in all affected dogs, compared with only 0.5 to 1.8% in controls, and is most likely to contain single chains of both pro-maltase-glucoamylase and pro-sucrase-isomaltase. Incubation of microvillar membranes in vitro with either trypsin or canine pancreatic juice resulted in degradation of this high molecular mass band and a corresponding increase in the amount of protein in three bands representing molecular masses of 150, 133 and 106 kDa. In samples from control dogs aminopeptidase N was identified in the 133 kDa band by Western blotting and incubation with monospecific antiserum. These findings suggest that pancreatic enzymes play a major role in the normal post-translational processing of intestinal microvillar membrane proteins in the dog.

Animals↗
PubMed1988

Response of the jejunal mucosa of dogs with aerobic and anaerobic bacterial overgrowth to antibiotic therapy.

Dogs with naturally occurring aerobic or anaerobic bacterial overgrowth have been examined before and after antibiotic therapy in order to assess reversibility of damage to the jejunal mucosa. Histological changes in peroral jejunal biopsies were relatively minor before and after treatment, but sucrose density gradient centrifugation revealed specific biochemical abnormalities that responded to antibiotic therapy. Aerobic overgrowth was initially associated with a marked loss of the main brush border component of alkaline phosphatase activity; this recovered following treatment, suggesting that aerobic bacteria may cause reversible damage to the hydrophobic region of the brush border membrane. In contrast, anaerobic overgrowth was initially associated with a marked reduction in brush border density, indicative of a considerable fall in the glycoprotein-to-lipid ratio of the membrane. Density increased from 1.17 to 1.21 g/ml after antibiotic therapy, consistent with recovery from this relatively severe damage to the brush border caused by anaerobic bacteria. Reductions in soluble and peroxisomal catalase activities which could compromise mucosal protection against free radicals in dogs with aerobic overgrowth, and a loss of particulate malate dehydrogenase activity indicative of mitochondrial disruption in dogs with anaerobic overgrowth, were also reversed after treatment. These findings indicate that aerobic and anaerobic bacterial overgrowth can result in contrasting but potentially reversible damage to the jejunal mucosa which would not be detected by conventional investigative procedures.

Animals↗
PubMed1986

The cardiac donor: a six-year experience.

From March 1, 1979, to March 1, 1985, the University of Arizona received 223 cardiac donor referrals. Sixty-two were accepted: 15 local, 23 regional (less than 370 km or 200 nautical miles), and 24 distant (370 to 1556 km or 200 to 840 nautical miles). Thirty-eight donor deaths were due to motor vehicle accidents, 10 to gunshot wounds, 6 to cerebral disease, and 8 to other closed-head lesions. The mean time from injury to brain death was 65 +/- 5 hours (+/- standard error of the mean [SEM]) and from brain death to organ donation, 12 +/- 3 hours. The mean ischemic time for the donor hearts ranged from 30 to 233 minutes (mean +/- SEM, 128 +/- 7 minutes). Fifty patients, otherwise acceptable, were refused as cardiac donors because an ABO-compatible recipient was not available. Two regionally procured hearts failed at operation, 1 because of unrecognized donor sepsis and 1 from a patient on large-dose inotropic support. Although there was no difference in myocardial function, median survival with follow-up through June 30, 1985, of patients receiving locally, regionally, and distantly procured organs was 59 months, 18 months, and 21 months, respectively. Cumulative proportion 1-year survival was 93%, 56%, and 61%, respectively. The 2-year survival was 85% for patients given locally procured hearts, 43% for those with regionally procured hearts, and 38% for those with a heart from a distant donor. Survival curves showed significantly longer survival for locally procured organs than regionally or distantly procured organs (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Cardiac transplantation in patients over 50 years of age.

Sixty-two patients underwent cardiac transplantation at the University of Arizona from March 1979 to March 1985. Thirteen patients (11 men and 2 women) were over 50 years of age at the time of transplantation and 49 were under the age of 50. The mean age (+/- SEM) of the patients over 50 was 53 +/- 1 years. Eight of these patients were treated with conventional immunosuppressive therapy (azathioprine, prednisone and rabbit antithymocyte globulin) and five, beginning in January 1983, were treated with cyclosporine, prednisone and rabbit antithymocyte globulin. Early mortality (0 to 90 days) was 16% in the group over 50 versus 18% for those under 50. The late mortality (greater than 90 days) was 36 and 33%, respectively. In both groups, rejection and infection were the principal causes of death. The incidence of infection was 1.9 +/- 0.5 episodes per patient in those patients over 50 and 1.9 +/- 0.4 in those under 50. The incidence of rejection was 1.3 episodes per patient-year in patients over 50 and 1.7 episodes per patient-year in those under 50. Actuarial survival at 1 year was 72 +/- 14% in the group over 50 and 66 +/- 7% in the group under 50 years of age. These data indicate that the results of cardiac transplantation for patients over 50 do not differ significantly from those for patients under 50. Therefore, it is concluded that a rigidly defined age criterion for cardiac transplant recipients is not acceptable. Each potential recipient must be evaluated in terms of individual risk and benefit from the procedure.

Age Factors↗
PubMed1986

Cyclosporine: an immunosuppressive panacea?

Between March 29, 1979, and March 1, 1985, 62 heart transplants were done in 61 patients at the University Medical Center, University of Arizona. There were two treatment groups with nearly equal numbers in each; conventional immunosuppression (1979 to 1982) and cyclosporine (1982 to the present). Comparison of actuarial survival, number of rejection episodes, number of fatal rejection episodes, number of infections, and number of "other complications" failed to reveal any significant difference between the two groups. The cyclosporine-treated patients had a documented increase in blood urea nitrogen and serum creatinine accompanied by an increase in diastolic blood pressure. The length of hospital stay of the cyclosporine group was approximately one half of that of the conventionally treated patients, and they required fewer rehospitalizations. The cost for initial hospitalization was not significantly different between the two groups. Therefore, in 1979 dollars, the cost for cyclosporine-treated patients has decreased. This difference in cost was only minimally diminished by the difference in expenditure for outpatient pharmaceuticals, which was four times higher in the cyclosporine group. We believe that cyclosporine is a potent immunosuppressive agent but that it has toxic, possibly irreversible effects on the kidney. In view of the minimal differences that we were able to demonstrate in survival rejection and infection, it seems prudent to reduce or modify present doses of cyclosporine in an attempt to avoid irreversible renal damage.

Actuarial Analysis↗