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Biomedical subjects

R A Owen

Publications and source records attributed to R A Owen.

At least 19 recordsLinked to original sources
PubMed1992

Successful treatment of a primary endodermal sinus tumor of the liver.

A 27-year-old woman had a large hepatic tumor and a markedly increased serum alpha-fetoprotein (AFP) level. A diagnosis of endodermal sinus tumor was made after a needle biopsy was performed on the liver. Clinical and radiologic examinations did not show an alternative primary site. Treatment with cisplatin, etoposide, and bleomycin was started, but, after three cycles, was changed to cisplatin, vincristine, methotrexate, bleomycin, dactinomycin, cyclophosphamide, and etoposide because the serum AFP level was decreasing too slowly. After additional chemotherapy was given, the patient was well but had an increased AFP level and a large residual mass in the liver. A right hemihepatectomy was performed, but no viable tumor was present. The patient is alive and disease-free 5 years later. Thus, AFP levels may be misleading in the presence of large necrotic tumors. The authors stress the need to make a diagnosis of these rare tumors early because aggressive treatment with combination chemotherapy may result in cure.

Adult↗
PubMed1992

Rat urinary bladder hyperplasia induced by oral administration of carbonic anhydrase inhibitors.

The carbonic anhydrase inhibitors, acetazolamide and MK-0927, were given by oral route to male Sprague-Dawley rats at 200 mg/kg/day and 25 mg/kg/day, respectively, for up to 4 weeks. Sequential necropsies were performed and urinary bladders were examined by light microscopy (LM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Similar urinary bladder changes were seen with both compounds. SEM evidenced slight multifocal urothelial changes consisting of cell swelling, dissociation, degeneration, and exfoliation after 3 and 5 days of treatment. After 2 and 4 weeks of treatment, elevated or leafy microridges on the luminal cell surfaces were seen together with foci of swollen cells. After a 2-month-recovery-period, the urothelial surfaces were normal. LM and TEM showed multifocal vacuolation of the urothelium associated with inflammation of the underlying lamina propria after 3 and 5 days of treatment. Cellular hypertrophy and hyperplasia of the transitional epithelium was seen after a 5-day treatment, persisted without increasing severity after 2 and 4 weeks of treatment, and totally regressed after the recovery period. It was concluded that, in the rat urinary bladder, oral administration of acetazolamide and MK-0927 induced early degeneration and inflammation followed by epithelial regeneration, resulting in a reversible hyperplasia of the transitional epithelium.

Acetazolamide↗
PubMed1992

Urothelial hyperplasia induced by carbonic anhydrase inhibitors (CAIs) in animals and its relationship to urinary Na and pH.

Investigations of MK-0927 and acetazolamide, both carbonic anhydrase inhibitors (CAIs), showed that urothelial hyperplasia develops in rats and mice, but not in rabbits, dogs, or monkeys. Rats given MK-0927 orally had a rapid onset of the change which regresses often completely despite continued treatment. Increased urinary pH and Na excretion, pharmacologic effects of CAIs, tended to be correlated with lesions. Rats given MK-0927 orally and fed either a 5% potassium phosphate meal or a 5% ammonium chloride meal had reduced urinary pH and/or urinary Na excretion and a reduced incidence of urothelial hyperplasia. Rats given MK-0927 orally and fed a low Na diet had very low urinary Na and essentially no urothelial hyperplasia. It was concluded that a clear relation exists between increased urinary Na excretion and pH, and urothelial hyperplasia induced by CAIs. These results in rats confirm the importance of increased Na and pH as stimuli for the development of urothelial hyperplasia.

Acetazolamide↗
PubMed1990

An intragenic region downstream from the dihydrofolate reductase promoter is required for replication-dependent expression.

The gene encoding dihydrofolate reductase (DHFR) is down-regulated as myoblasts withdraw from the cell cycle and commit to terminal differentiation. To localize cis-acting elements involved in regulating DHFR gene expression, the DHFR promoter and upstream region, together with differing amounts of contiguous intragenic sequence, were fused to the bacterial chloramphenicol acetyltransferase (CAT) gene. The resulting fusion genes were stably transformed into muscle cells, and CAT mRNA levels were measured in proliferative myoblasts and committed myocytes. A gene consisting of the -850/+465 region of DHFR (numbers refer to distance in base pairs from transcription initiation site) fused to CAT was efficiently expressed in proliferating myoblasts and was appropriately down-regulated during commitment. A gene consisting of the -850/+60 region of DHFR fused to CAT was poorly expressed in proliferating myoblasts and was not down-regulated during commitment. When inserted between the Rous sarcoma virus promoter and CAT sequence of RSVpCAT, the +61/+465 region of the DHFR gene augmented CAT mRNA expression in muscle cell transformants but did not confer a regulated pattern of expression. Our data indicate that DHFR sequences between +60 and +465 are required but are not sufficient for replication-dependent expression. The DHFR sequences may be operating at either a transcriptional or posttranscriptional level.

Animals↗
PubMed1988

Transglutaminase-catalysed cross-linking of proteins phosphorylated in the intact glucose-stimulated pancreatic beta-cell.

Incubation of intact islets in the presence of [32P]Pi and stimulatory levels of glucose followed by separation of phosphorylated islet proteins by SDS-polyacrylamide gel electrophoresis revealed the presence of a high molecular weight phosphopolymer which did not transverse a 3% (w/v) acrylamide gel. The majority of this phosphopolymer (approx. 70%) was present in the 600 x g sedimented fraction of islet homogenates. Islet homogenates obtained from intact islets previously incubated with [32P]Pi and stimulatory levels of glucose when incubated under conditions that activated the islet transglutaminase resulted in an increase in the amount of phosphopolymer present in the 600 x g sedimented fraction. Inhibitors of transglutaminase activity which are known to inhibit glucose-stimulated insulin release led to a significant reduction in the fraction of phosphopolymer present in the glucose-stimulated intact islet. These findings suggest that protein cross-linking and phosphorylation reactions may be closely linked in the pancreatic beta-cell.

Animals↗
PubMed1988

The varied appearances of starch particles in smears and paraffin sections.

Evidence is presented to show that maize starch particles, usually recognized in histological sections by their Maltese cross birefringence under cross-polarized light, lose this characteristic appearance when transected by the microtome blade. Such particles are, therefore, likely to be overlooked. Though maize starch usually enters the abdomen during surgery, the female genital tract is another possible route from sources such as contraceptive devices. Other types of starch particle have different shapes, sizes and surface markings and these may be distinguished from maize starch by light and electron optical methods.

Adult↗
PubMed1987

Two cases of equine primary gastric impaction.

The clinical details of two cases of equine primary gastric impaction are described and the syndromes of gastric impaction and dilatation are discussed. Both cases of gastric impaction were successfully treated by gastrotomy and evacuation of the gastric contents.

Animals↗
PubMed1987

Clinical observations on the use of BCG cell wall fraction for treatment of periocular and other equine sarcoids.

Clinical observations on the use of BCG cell wall fraction in oil for treating seven horses with periocular sarcoids and five horses with sarcoids in other regions are described. Therapy was successful when used for periocular or solitary and smaller sarcoids. For sarcoids previously treated with cryosurgery, therapy appeared to be less efficient. A horse with a sarcoid on the stifle developed a septic gonitis due to necrosis of the sarcoid tissue adjacent to the joint. Sarcoids of the axilla appeared to be more aggressive than sarcoids at other locations and did not respond favourably to this form of therapy.

Animals↗
PubMed1986

Clinical course of renal adenocarcinoma associated with hypercupraemia in a horse.

A four-year-old shire mare with haematuria, colic, terminal weight loss and an abdominal mass had a large unilateral renal adenocarcinoma. Clinical signs were monitored for 11 months. Increased serum copper concentrations were measured on two occasions. Hypercupraemia is discussed as a possible paraneoplastic change.

Adenocarcinoma↗
PubMed1986

Asymptomatic microhematuria and urologic disease. A population-based study.

Asymptomatic microhematuria is a common finding, occurring in 13% of adult men and postmenopausal women in Rochester, Minn. Previous recommendations to perform cystoscopic and excretory urographic examinations on all patients with this finding were based on findings in referred patients. In the present population-based study, the frequency of serious urologic disease in patients with asymptomatic microhematuria was 2.3%; only 0.5% had bladder or renal cell carcinoma. Urologic malignant lesions occurred more frequently in the elderly. There was a trend toward more serious diseases in those with higher grades of hematuria. Complete urologic investigation of all patients with any degree of asymptomatic microhematuria cannot be recommended. The presence of other risk factors should be considered in opting for further evaluation.

Adult↗
PubMed1986

A role for transglutaminase in glucose-stimulated insulin release from the pancreatic beta-cell.

Preincubation of rat islets of Langerhans with the potent inhibitors of islet transglutaminase activity, monodansylcadaverine (30-100 microM) and N-(5-aminopentyl)-2-naphthalenesulphonamide (100-200 microM), led to significant inhibition of glucose-stimulated insulin release from islets. In contrast, the respective N'-dimethylated derivatives of these two compounds, which did not inhibit islet transglutaminase activity, were much less effective as inhibitors of glucose-stimulated insulin release. None of the compounds inhibited rat spleen protein kinase C activity at concentrations which gave rise to inhibition of glucose-stimulated insulin release. When tested for their effects on calmodulin-stimulated bovine heart phosphodiesterase activity, of the compounds that inhibited insulin release, only monodansylcadaverine did not act as an effective antagonist of calmodulin at concentrations (up to 50 microM) that gave rise to significant inhibition of glucose-stimulated insulin release. Furthermore, at 50 microM, monodansylcadaverine did not inhibit methylation of islet lipids. The inhibition of glucose-stimulated insulin release by monodansylcadaverine is therefore likely to be attributable to its interference with islet transglutaminase activity. The sensitivity of islet transglutaminase to activation by Ca2+ was investigated by using a modified assay incorporating dephosphorylated NN'-dimethylcasein as a substrate protein. The Km for Ca2+ obtained (approx. 3 microM) was an order of magnitude lower than previously reported for the islet enzyme [Bungay, Potter & Griffin (1984) Biochem. J. 219, 819-827]. Mg2+ (2 mM) was found to have little effect on the sensitivity of the enzyme to Ca2+. Investigation of the endogenous substrate proteins of islet transglutaminase by using the Ca2+-dependent incorporation of [14C]methylamine into proteins of islet homogenates demonstrated that most of the incorporated radiolabel was present in cross-linked polymeric aggregates which did not traverse 3% (w/v) acrylamide gels. The radiolabelled polymeric aggregates were present in 71 000 g-sedimented material of homogenates, and their formation was transglutaminase-mediated. These findings provide new evidence for the involvement of islet transglutaminase in the membrane-mediated events necessary for glucose-stimulated insulin release.

Animals↗
PubMed1986

Age-related variations in renal structure and function in Sprague-Dawley rats.

Data from 500 male and 500 female Sprague-Dawley rats used as controls in studies performed at Huntingdon Research Centre to assess the safety of drugs were sampled at 17, 30, 56, 82, or 108 weeks of age. Plasma urea nitrogen levels remained constant, except in aged males. Aging caused increased proteinuria and decreased urinary concentrating ability, in addition to increased size, weight, and degree of cortical scarring of kidneys. Chronic progressive nephropathy, first seen histopathologically at 30 weeks of age, accounted for these changes and ultimately affected 81% of male and 44% of female rats. One-fifth of two-year-old male rats had diffuse parenchymal damage and a small number also had secondary hyperparathyroidism. Other notable changes included basophilic (often colloid-filled) cortical tubules, mononuclear cell infiltrations, parenchymal and pelvic mineralization, urothelial hyperplasia, and pyelonephritis. Miscellaneous low incidence findings included one lipomatous tumour and generalized lymphosarcoma.

Aging↗
PubMed1986

Strain-related susceptibility to nephrotoxicity induced by aspirin and phenylbutazone in rats.

Single doses of aspirin induce scattered foci of necrosis of proximal tubules in some strains of rats, whereas acute or sub-acute administration of phenylbutazone causes renal papillary necrosis. Initially, using Sprague-Dawley rats of CFY and CD strains, it became clear that these rats were not as susceptible to these drugs as the literature suggested. Aspirin-induced necrosis was apparently sex-related, being seen in females but could be induced by hormone treatment in males. Male Wistar and Sprague-Dawley rats had reacted differently to administration of phenylbutazone for two weeks. Two experiments were performed with four rat strains: Wistar, Lister-Hooded, Sprague-Dawley, and Fischer-344. The rats were six weeks old at the start of the experiments. Five males and five females of each strain were gavaged with either a single dose of 1,000 mg/kg of aspirin or 200 mg/kg phenylbutazone once daily for four weeks. The drugs were suspended in methylcellulose, which was given to equal numbers of control male and female rats in each experiment. The rats were maintained under standard conditions. Blood and 18-hour overnight urine samples were collected prior to sacrifice. There were no strain-related differences in the types of renal lesions seen, however there were differences in the degrees of responses to the two drugs. With aspirin the female Fischer-344 rats were the most susceptible showing necrosis of proximal tubules of both kidneys and markedly elevated urinary protein concentration and gamma-GT activity. Other females showed less change. Male rats were affected only slightly and males of the Wistar strain were not.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗