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Biomedical subjects

R Whalen

Publications and source records attributed to R Whalen.

At least 19 recordsLinked to original sources
PubMed1992

Bleeding tendency, platelet function, and pharmacokinetics of ibuprofen and zidovudine in HIV(+) hemophilic men.

The use of ibuprofen (IBP) in hemophilic men for chronic hemophilic arthropathy is associated with transient coagulation abnormalities, but usually does not cause bleeding symptoms. However, when hemophilic men are treated with ibuprofen while also receiving zidovudine (ZDV), excess bleeding has occurred in some. In order to evaluate platelet function and pharmacokinetics of combination IBP and ZDV, we measured platelet aggregation, platelet adhesive index, bleeding time, and IBP and ZDV drug levels by high performance liquid chromatography on five patients receiving chronic oral IBP, 400 mg every 6 hr, and on ten patients receiving both IBP and ZDV, 100 or 200 mg every 4 hr five times daily. Samples were obtained at baseline (ZDV alone), acutely (IBP+ZDV acutely), and chronically (2 weeks on IBP and ZDV). Abnormal platelet aggregation with arachidonic acid occurred in four of five (80%) of those receiving IBP alone and in 7 of 10 (70%) at baseline, 9 of 10 (90%) at acute, and 8 of 10 (80%) at chronic IBP and ZDV treatment, most commonly at 2 hr following dosing, when peak IBP levels occurred, and persisting 4 hr in those on chronic dosing. Half or more of those on combination IBP+ZDV showed a lowered platelet adhesive index and/or prolonged bleeding time. Excess bleeding symptoms occurred in three on chronic combination IBP+ZDV, two with increased frequency of spontaneous hemorrhages, and one with prolonged traumatic bleeding. Bleeding tendency was unrelated to the degree of platelet function abnormality, to peak drug levels of IBP or ZDV, or degree of liver function abnormality (SGPT). The clearance of IBP alone and ZDV alone were not different from the clearance of combination IBP and ZDV. Caution is urged regarding potential enhanced bleeding tendency in hemophiliacs receiving both IBP and ZDV in combination.

Acute Disease↗
PubMed1992

Bone mineral density, muscle strength, and recreational exercise in men.

Muscle strength has been shown to predict bone mineral density (BMD) in women. We examined this relationship in 50 healthy men who ranged in age from 28 to 51 years (average 38.3 years). BMD of the lumbar spine, proximal femur, whole body, and tibia were measured by dual-energy x-ray absorptiometry (Hologic QDR 1000W). Dynamic strength using one repetition maximum was assessed for the biceps, quadriceps, and back extensors and for the hip abductors, adductors, and flexors. Isometric grip strength was measured by dynamometry. Daily walking mileage was assessed by 9 week stepmeter records and kinematic analysis of video filming. Subjects were designated as exercisers and nonexercisers. Exercisers participated in recreational exercise at least two times each week. The results demonstrated that BMD at all sites correlated with back and biceps strength (p < 0.01 to p = 0.0001). Body weight correlated with tibia and whole-body BMD (p < 0.001); age negatively correlated with Ward's triangle BMD (p < 0.01). In stepwise multiple regressions, back strength was the only independent predictor of spine and femoral neck density (R2 = 0.27). Further, back strength was the most robust predictor of BMD at the trochanter, Ward's triangle, whole body, and tibia, although biceps strength, age, body weight, and leg strength contributed significantly to BMD at these skeletal sites, accounting for 35-52% of the variance in BMD. Exercisers and nonexercisers were similar for walking (3.97 versus 3.94 miles/day), age (37.8 versus 38.5) years, and weight (80.0 versus 77.7 kg). However, BMD and muscle strength were significantly greater in exercises than in nonexercisers.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1992

Modification of the dystrophic phenotype after transient neonatal denervation: role of MHC isoforms.

While it recently has been demonstrated that it is possible to modify the phenotypic expression of murine dystrophy (dy/dy) (i.e., prevent myofiber loss) by subjecting the extensor digitorum longus (EDL) muscle of 14-day-old dy/dy mice to transient neonatal denervation (Moschella and Ontell, 1987), the mechanism responsible for this phenomenon has not been determined. Since it has been suggested that the effects of dystrophy vary according to fiber type, the fiber type frequency in 100-day-old normal (+/+) and dy/dy EDL muscles subjected to transient neonatal denervation has been determined by immunohistochemical analysis of their myosin heavy chain (MHC) composition. This frequency has been compared with that found in the EDL muscles of 14- and 100-day-old unoperated +/+ and dy/dy mice, in order to determine whether the reinnervation of transiently denervated neonatal muscle results in a preponderance of fibers of the type that might be spared dystrophic deterioration. In unoperated dy/dy muscle there is a progressive decrease in the frequency and in the absolute number of fibers that express MHC2B, with 100-day-old dy/dy muscles having approximately 32% of the number of myofibers fibers containing MHC2B as is found in age-matched +/+ muscles. The number of fibers containing the other fast isoforms (MHC2A and MHC2X) is similar in +/+ and dy/dy muscles at this age, indicating that fibers with MHC2B are most affected by the dystrophic process. Reinnervation following transient neonatal denervation of both the +/+ and the dy/dy EDL muscles results in a similar decrease (approximately 62%) in the number of myofibers containing MHC2B and an increase in myofibers containing the other fast MHC isoforms (MHC2A and MHC2X). The selective effect of dy/dy on fibers containing MHC2B and the sparing of myofibers in transiently denervated dy/dy muscle (which contains a reduced frequency of fibers containing MHC2B) are consistent with, although not direct proof of, the hypothesis that alterations in the fiber type may play a role in the failure of myofibers in transiently denervated dy/dy muscles to undergo dystrophic deterioration. Evidence is presented suggesting that neurons that supply myofibers containing MHC2B may be at a selective disadvantage in their ability to reinnervate neonatally denervated muscles.

Animals↗
PubMed1992

Direct measurement of melphalan conjugation with glutathione: studies with human melanoma cells and mammalian liver.

The rate of formation of the major glutathione conjugate of the antitumor alkylating agent melphalan can be directly measured by high pressure liquid chromatography. Rates of melphalan-glutathione conjugate formation were determined in the presence and in the absence of human melanoma cell homogenates, or cell fractions from various tissue sources, and the relative contributions of enzyme-catalyzed and nonenzymatic conjugate formation to the overall rates of conjugation were determined. Significant rates of conjugation were observed in the absence of any enzyme-containing cell fractions. These rates were not increased by the addition of melanoma cell homogenates, animal liver microsomes or human liver cytosol or microsomes, even though these preparations all enhanced the rate of conjugation of 1-chloro-2,4-dinitrobenzene. Animal liver cytosol contains enzymes that provided a significant contribution to the overall rate of melphalan conjugate formation. We conclude that although liver cytosol contains enzymes that significantly enhance the rate of glutathione conjugation with melphalan, in the case of the tumor cells studied, cellular glutathione S-transferase-catalyzed activity appears to be, at best, a very minor determinant of the overall rate of melphalan-glutathione conjugate formation.

Animals↗
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↗