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Biomedical subjects

R Whalen

Publications and source records attributed to R Whalen.

At least 37 records · Page 2Linked to original sources
PubMed1990

Inhibition of catalase and epoxide hydrolase by the renal cystogen 2-amino-4,5-diphenylthiazole and its metabolites.

Subchronic feeding of 2-amino-4,5-diphenylthiazole (DPT) to rats results in the development of renal cysts and has been used as a model system to study polycystic kidney disease. Because previous studies revealed changes in renal enzymes following DPT administration, a possible direct effect of DPT and its phenolic metabolites on catalase and a related enzyme, epoxide hydrolase, was examined. Experiments with three in vitro systems (suspensions of rabbit renal tubules, rat kidney homogenates, and commercially obtained bovine liver catalase) revealed direct inhibition of catalase activity by the diphenolic metabolite (diOH- DPT: 2-amino-4,5di(4'-hydroxyphenyl)-thiazole), the known renal cystogen nordihydroquaiaretic acid (NDGA) 2-amino-4(4'-hydroxyphenyl),5-phenyl-thiazole (4OH-DPT), and the known catalase inhibitor 3-amino-1,2,4-triazole; DPT did not inhibit catalase activity. Following oral administration to rats of the DPT congeners, 4OH-DPT caused the greatest decrease in both renal catalase and cytosolic epoxide hydrolase activities and the shortest time to onset of cystic lesions. In vitro, mouse liver cytosolic epoxide hydrolase activity was substantially inhibited by 4OH-DPT and dioH-DPT, and NDGA, but not by 2-amino-4-phenyl,5-(4'-hydroxyphenyl)-thiazole (5OH-DPT) or DPT itself. Microsomal epoxide hydrolase (mEH) activity was inhibited by 4OH-DPT, unaffected by DPT or dioH-DPT, and stimulated 2-fold by 5OH-DPT. Finally, mEH activity was substantially higher in samples of normal human kidney than in samples of kidney derived from a patient with autosomal recessive polycystic kidney disease; no differences were observed in cEH activity in these samples. Although the role of altered catalase and epoxide hydrolase activities in cystogenesis is unknown, DPT-induced cyst formation is associated with loss of these enzyme activities in kidney tissue. To our knowledge, this is the first report of an in vivo diminution of cytosolic epoxide hydrolase activity by xenobiotics.

8,11,14-Eicosatrienoic Acid↗
PubMed1989

Selective inhibition of cytosolic epoxide hydrolase activity in vitro by compounds that inhibit catalase.

The ability of a number of known inhibitors of catalase activity to affect cytosolic and microsomal epoxide hydrolase activities in vitro, measured as enzymatic trans-stilbene oxide hydrolysis and styrene oxide hydrolysis, respectively, was investigated. Catalase and cytosolic epoxide hydrolase activities are inhibited by hydroxylated metabolites of 2-amino-4,5-diphenylthiazole (DPT). The metabolite hydroxylated on the 4-phenyl ring (4OH-DPT) and the metabolite hydroxylated on both phenyl rings (4,5-DIOH-DPT) are potent inhibitors of both enzymes; the metabolite hydroxylated on the 5-phenyl ring (5OH-DPT) is less potent. Unmetabolized DPT has no effect on either enzyme. 4OH-DPT inhibits, but 5OH-DPT enhances, microsomal epoxide hydrolase activity. 4,5-DIOH-DPT and DPT have no effect on this enzyme. Other compounds that inhibit both catalase and cytosolic epoxide hydrolase activities, but do not inhibit microsomal epoxide hydrolase activity, are nordihydroguaiaretic acid and 2-aminothiazole. Microsomal epoxide hydrolase activity is enhanced by 2-aminothiazole and levamisole in vitro. Thus these inhibitors of catalase are selective epoxide hydrolase inhibitors in that they inhibit cytosolic epoxide hydrolase activity in vitro, but have either no effect on, or increase the activity of, microsomal epoxide hydrolase in vitro. Conversely, the selective cytosolic epoxide hydrolase inhibitors 4-phenylchalcone oxide and 4'-phenylchalcone oxide do not inhibit catalase activity, nor does trichloropropene oxide, a selective microsomal epoxide hydrolase inhibitor.

Animals↗
PubMed1989

Similarities between catalase and cytosolic epoxide hydrolase.

Cytosolic epoxide hydrolase, measured as trans-stilbene oxide hydrolase activity, was isolated and purified from human and guinea pig liver cytosol. Antiserum to the guinea pig liver preparation reacted strongly with bovine liver catalase. We determined that this lack of selectivity of the antiserum was due to catalase contamination of the epoxide hydrolase preparation. We also determined that several commercial catalase preparations are contaminated with cytosolic epoxide hydrolase. Our human epoxide hydrolase preparation contained no detectable catalase contamination, yet antiserum to this protein also cross-reacted slightly with catalase, indicating some intrinsic similarity between the two enzymes. We conclude that catalase and cytosolic epoxide hydrolase contain some similar immunogenic epitopes, and we surmise that similarities between the subunits of these two enzymes may lead to their partial copurification. Functional similarities between the two enzymes are also demonstrated, as several compounds that inhibit catalase are also shown to inhibit cytosolic epoxide hydrolase activity in the same concentration range and rank order.

Amino Acids↗
PubMed1987

Late vertex positivity in event-related potentials as a guilty knowledge indicator: a new method of life detection.

Subjects were allowed to choose an item to keep from nine items in a box. They then were shown one of nine words randomly selected on a display screen. One of these words described the chosen item, the others described novel items. The subjects were told to try not to react emotionally to any of the words, but to try to defeat this test of deception. It was found that large positive waves with latencies between 400 and 700 ms poststimulus were present in the ERPS to the chosen but not to the novel words.

Adolescent↗
PubMed1985

Immunocytochemistry of luteinizing hormone-releasing hormone during spontaneous and thyroxine-induced metamorphosis of bullfrogs.

Double-bridge peroxidase-antiperoxidase immunocytochemistry was used to compare the developmental appearance of immunoreactive LH-RH (ir-LH-RH) in brains of bullfrog (Rana catesbeiana) tadpoles during either spontaneous or thyroxine-induced metamorphosis. During spontaneous metamorphosis, ir-LH-RH was localized in fibers of the external layer of the median eminence (ME) of stage XIII-XXV animals, while immunoreactive perikarya and other immunostained brain structures were absent. The extent and intensity of ME immunostaining increased concomitantly with measured ME morphological development. Tadpoles induced with thyroxine to metamorphic stages XIX-XXI exhibited ME structural development and neurohypophysial neurosecretory staining similar to spontaneously metamorphosed individuals of equal stages. However, comparable ME ir-LH-RH immunostaining and gonadal size were both less developed in thyroxine-treated animals, although increased relative to non-metamorphic vehicle-injected controls. These results indicate that the hypothalamic LH-RH system changes concurrently with ME structural development during spontaneous metamorphosis. Reduced ME ir-LH-RH staining and gonadal size in thyroxine-treated animals suggest that during prometamorphosis, factors other than thyroxine alone may coordinate the normal maturation of the hypothalamo-pituitary-gonadal axis of the bullfrog.

Animals↗
PubMed1982

[Proliferation and differentiation of a myogenic line in synthetic media].

When plated in plastic culture dishes, muscle cells of the L6 cell line are unable to proliferate or to differentiate in a synthetic medium composed of Dulbecco's Minimal Essential medium (DME), bovine fetuin (1 mg/ml) and bovine insulin (10 micrograms/ml). In contrast, these cells will proliferate and differentiate morphologically and biochemically in this medium if the culture dishes have been previously treated with DME containing fetal Calf serum. Pretreatment of dishes does not increase cell attachment in synthetic medium but seems to act as a factor increasing cell viability.

Animals↗
PubMed1982

Volume compensation for left ventricle assist systems (LVAS): 18 month in vivo evaluation.

The smooth surface cycled chambers, both Biomer and silicone rubber, developed thick tissue capsules and exhibited persistent active tissue reactions at the diaphragm-capsule interface. Textured surface chambers (dacron velour), both the cycled and control, developed a thin, stable capsule, with no active tissue reaction. Textured surface chambers have been explanted and examined after 210 and 494 days. One experiment is continuing, approaching 2 yrs in vivo with good performance. Although the number of textured surface compliance chamber studies as yet is limited, the dramatic improvement in performance and tissue response between the smooth and textured surface studies demonstrates the biological feasibility of this method of variable volume compensation for use in completely intracorporeal LVAS.

Biocompatible Materials↗
PubMed1981

Promising results with a new textured surface intrathoracic variable volume device for LVAS.

The smooth surface cycled chambers, both Biomer and silicone rubber, developed thick tissue capsules and exhibited persistent acute tissue reaction at the interface. The silicone rubber noncycled chambers either developed no capsule or a very thin capsule without the acute inflammation observed with the cycled side. The dacron velour surface chambers, both the cycled and noncycled, developed a thin, stable capsule, with no acute inflammation. The cycled dacron velour surface chambers have achieved almost one year with acceptable performance and are continuing at this time. These results with the textured surface compliance chambers compare favorably with the smooth surface series. Although the number of studies as yet is limited, the performance of the textured series compliance chambers shows promise for the application of the compliance chamber for use with totally implantable blood pump systems.

Animals↗
PubMed1978

Detection of tubulin and actin in various cell lines by an immunoperoxidase technique.

This paper reports on the preparation of immunsera against tubulin and actin, and the purification of anti-tubulin and anti-actin antibodies on immunoadsorbent columns. These purified antibodies were used in an indirect immunoperoxidase assay to visualize microtubules and microfilaments in various cell lines. The specificity of antibodies and the methods of cell fixation required are discussed, as well as some aspects of microtubule and microfilament organization, as visualized by this technique.

Actins↗
PubMedDate not supplied

Oral correction of essential fatty acid deficiency in cystic fibrosis.

A combination of pancreatic insufficiency and inadequate caloric intake may produce essential fatty acids (EFA) deficiency in patients with cystic fibrosis. Seventy-five percent of the adolescents and young adults with poor weight gain in our clinic were EFA-deficient by total plasma linoleic acid criteria. Twenty of these patients were placed on an oral hyperalimentation regimen containing 230% of calories required for basal energy expenditure, 40% as fat. Forty percent of these (8/20) achieved normal EFA levels on this diet. Eight of the nonresponding patients were given an additional 5% of their caloric intake as linoleic acid monoglyceride. All who maintained caloric intake achieved normal EFA levels. Normalization of EFA levels was associated with a number of clinical benefits including increase in weight and activity and, in five teenage girls, regulation of menses. The 16 control patients who received standard pancrelipase therapy and nutritional supplements remained fatty acid deficient. We conclude that oral hyperalimentation can restore EFA levels in cystic fibrosis patients if adequate calories are available to provide energy needs.

Cystic Fibrosis↗