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Biomedical subjects

R Dawson

Publications and source records attributed to R Dawson.

At least 55 records · Page 3Linked to original sources
PubMed2000

Effects of high salt diets and taurine on the development of hypertension in the stroke-prone spontaneously hypertensive rat.

Taurine is present in high concentrations in mammalian tissues and has been implicated in cardiovascular control mechanisms. The aim of the present study was to evaluate the ability of taurine to attenuate salt-induced elevations in blood pressure and markers of damage to the kidney and cardiovascular system in stroke prone spontaneously hypertensive rats (SPSHR). Male SPSHR (6 weeks old) were placed on high salt diets that contained 1% (w/w) NaCl added to their normal chow for 84 days and then were switched to 3% added NaCl for the remaining 63 days of the study. SPSHR was given 1.5% taurine in the drinking water (n = 8), a taurine free diet (n = 8) or normal chow (n = 8). A final control group (n = 6) was not given high salt diets. High salt diets caused an acceleration in the development of hypertension in all groups. Taurine supplementation reduced ventricular hypertrophy and decreased urinary excretion of protein and creatinine. The taurine free diet did not alter serum or urinary excretion of taurine, but did result in elevated urinary nitrogen excretion, increased serum cholesterol levels, and impaired performance in a spatial learning task. Alterations in dietary taurine intake did not alter urinary or serum electrolytes (Na+, K+), but taurine supplementation did attenuate a rise in serum calcium seen with the high salt diets. Urinary excretion (microg/24h) of epinephrine and dopamine was significantly reduced in SPSHR given 1% NaCl in the diet, but this effect was not seen in SPSHR on taurine free or supplemented diets. Taurine supplementation showed cardioprotective and renoprotective effects in SPSHR given high salt diets.

Animals↗
PubMed2000

Leptin resistance is associated with hypothalamic leptin receptor mRNA and protein downregulation.

It is well known that leptin plays a predominant role in body weight regulation. Leptin receptors are especially abundant in the hypothalamus, where the majority of leptin's biologic activity occurs. In instances where leptin has no or limited activity, it is easy to implicate leptin resistance and speculate as to the multiple levels where resistance may occur. We hypothesize that leptin resistance is associated with hypothalamic leptin receptor downregulation. Rats were randomly divided into 3 groups receiving phosphate-buffered saline (PBS) or low- or high-dose leptin continually over a 28-day period. Body weight and food intake were measured daily. Long-term leptin treatment resulted in a dose-dependent decrease in body weight for the duration of the study. It also resulted in a dose-dependent decrease in food intake, but only for the first half of the study. A test of leptin resistance was performed at week 3 demonstrating the development of resistance to the anorectic effects of leptin in both treatment groups. The results of the resistance test together with the food intake data suggest that resistance to the appetite-regulating effects of leptin developed during the final 2 weeks of the study. In addition, we show a downregulation of leptin receptor mRNA and protein in the hypothalamus, which may be one of the mechanisms by which the food-intake effects of leptin were lost.

Animals↗
PubMed2000

Clozapine in the treatment of refractory psychotic mania.

OBJECTIVE: The efficacy of clozapine was examined in a group of patients with treatment-refractory bipolar disorder, manic type with psychotic features. METHOD: Twenty-two subjects with treatment-refractory bipolar disorder with active manic and psychotic symptoms participated in a 12-week open-label trial of clozapine. After a 2-10-day drug washout period, patients began treatment with clozapine at 25 mg/day; the dose was increased 25 mg/day (as tolerated) to a maximum level of 550 mg/day. Patients were evaluated longitudinally over the course of the study with the Brief Psychiatric Rating Scale (BPRS), the Young Mania Rating Scale, and the Clinical Global Impressions (CGI) scale. RESULTS: Fourteen of the 22 subjects in the study continued taking clozapine for at least 10 of the 12 weeks. Among the entire group, mean improvements of 56. 7%, 56.6%, and 39.1% were seen on the BPRS, Young Mania Rating Scale, and CGI, respectively. Seventeen of the 22 subjects (77.3%) experienced at least a 20% improvement in scores on all three scales. CONCLUSIONS: The findings from this open-label study, which are consistent with previous retrospective studies, case reports, and one other open-label prospective study, suggest that clozapine is an effective agent for patients with treatment-refractory psychotic mania.

Adult↗
PubMed2000

Prototype Web-based continuing medical education using FlashPix images.

Continuing Medical Education (CME) is a requirement among practicing physicians to promote continuous enhancement of clinical knowledge to reflect new developments in medical care. Previous research has harnessed the Web to disseminate complete pathology CME case studies including history, images, diagnoses, and discussions to the medical community. Users submit real-time diagnoses and receive instantaneous feedback, eliminating the need for hard copies of case material and case evaluation forms. This project extends the Web-based CME paradigm with the incorporation of multi-resolution FlashPix images and an intuitive, interactive user interface. The FlashPix file format combines a high-resolution version of an image with a hierarchy of several lower resolution copies, providing real-time magnification via a single image file. The Web interface was designed specifically to simulate microscopic analysis, using the latest Javascript, Java and Common Gateway Interface tools. As the project progresses to the evaluation stage, it is hoped that this active learning format will provide a practical and efficacious environment for continuing medical education with additional application potential in classroom demonstrations, proficiency testing, and telepathology. Using Microsoft Internet Explorer 4.0 and above, the working prototype Web-based CME environment is accessible at http://telepathology.upmc.edu/WebInterface/NewInterface/welcome.html.

Cell Biology↗
PubMed1999

Cysteine sulfinate decarboxylase and cysteine dioxygenase activities do not correlate with strain-specific changes in hepatic and cerebellar taurine content in aged rats.

Taurine is a free sulfur-containing amino acid that is found in abundance in mammalian tissues and fluids. Many biological roles have been proposed for this amino acid, including reducing oxidative stress and cytotoxicity. Taurine has previously been reported to decline in tissues during aging which could exacerbate an age-related increase in oxidative stress. The aim of the present study was to elucidate the mechanism responsible for the observed decline in tissue taurine content. We measured the activity of the major taurine biosynthetic enzymes, cysteine sulfinate decarboxylase and cysteine dioxygenase, in liver and cerebellar tissues of rats. Tissues from male adult and aged Fischer 344 (F344; 10 and 28 months), Sprague-Dawley (SD; 5, 20 and 25 months), and F344/Brown-Norway hybrid (FBNF1; 14 and 33.5 months) rats were used. We observed a significant decline in hepatic taurine content of the F344 animals but the decline in the liver of SD and FBNF1 animals was non-significant. Hepatic cysteine sulfinate decarboxylase and cysteine dioxygenase activities were significantly lower in aged F344 rats but not in the other strains. Cerebellar taurine content was significantly lower in aged F344 and SD rats without a concomitant decline in cysteine sulfinate decarboxylase activity. These results suggest that a decline in hepatic de novo taurine biosynthesis might be partially responsible for a reduction in tissue taurine content in F344 rats.

Aging↗
PubMed1999

Effects of dietary taurine supplementation or deprivation in aged male Fischer 344 rats.

Taurine is a sulfur amino acid that is present in high concentration in mammalian tissues and previously has been reported to decline in a number of tissues with advancing age. The aims of the present study were to examine: (1) the effects of dietary taurine supplementation; (2) the effects of taurine-free diets; (3) the ability of aged rats to conserve urinary taurine; and (4) the consequences of these dietary manipulations on some biochemical parameters. Male F344 rats (n = 30/group) 18 months of age were placed on control diets, diets supplemented with 1.5% taurine in the drinking water, or a taurine-free diet for 10 months. An adult control group (12 months old at the end of the study) on normal diets was included for comparison purposes. Significant (P < 0.05) age-related declines in taurine content were observed in the spleen, kidney, eye, cerebellum and serum. Taurine supplementation corrected these deficits in tissue content in aged rats and in many cases increased taurine content above that of adult controls. Urinary excretion of taurine was significantly (P < 0.05) reduced in aged rats indicating an increased need to conserve taurine. Taurine-deficient diets did not further exacerbate the age-related decline in tissue taurine content, suggesting biosynthetic adaptations to the lack of dietary taurine. Dietary taurine supplementation blunted age-related declines in serum IGF-1 and increases in serum creatinine and blood urinary nitrogen (BUN). These studies suggest that advanced aging results in a taurine-deficient state that can be corrected by dietary supplementation.

Aging↗
PubMed1999

Experimental demonstration that offspring sex ratio varies with maternal condition.

Sex ratio theory predicts that, if prevailing ecological or social circumstances differentially influence the fitness benefits of offspring of each sex, parents should adjust their production accordingly to maximize fitness. For species in which sex is chromosomally determined, such as birds and mammals, a differential effect of maternal condition on the fitness of male and female young is one important route whereby selection is expected to favor a bias in the offspring sex ratio at birth or egg laying. However, despite its central place in sex allocation theory, this hypothesis has rarely been tested in wild populations. We manipulated maternal condition upward and downward in a sexually dimorphic wild bird and examined the effect on offspring survival and on offspring sex ratio. The survival to fledging of male, but not female, young was substantially reduced if they came from less well provisioned eggs produced by females in relatively poor condition. As female condition, and thereby her capacity to produce high quality eggs, declined, she progressively skewed the sex ratio of her eggs toward females; i.e., she produced more of the sex with the higher survival prospects. The decline in the survival of male offspring, and the sex ratio bias, was removed when maternal condition was enhanced. These results provide experimental evidence of an adaptive, facultative adjustment of sex ratio in response to changes in maternal condition in wild birds.

Adaptation, Biological↗
PubMed1999

Endogenous GABA release is reduced in the striatum of cocaine-sensitized rats.

The magnitude of behavioral sensitization to cocaine is correlated with decreased striatal GABA(A) receptor function. We examined whether GABA release from striatal slices is also altered in cocaine-treated rats. Behavioral sensitization was measured in rats receiving either saline or cocaine (15 mg kg(-1)) daily for 14 days. Cocaine-treated rats showed a significant increase in locomotion and stereotypy over days. Potassium-stimulated endogenous GABA release was measured from superfused striatal slices of these rats. GABA release was significantly decreased in cocaine-treated rats. However, striatal slices preloaded with [(3)H]GABA exhibited a slight but significant increase in release after cocaine sensitization. Similar treatment with a nonsensitizing dose of cocaine (7.5 mg kg(-1)) did not change endogenous GABA release. Saline- and cocaine-treated rats showed no differences in striatal glutamic acid decarboxylase activity at either a saturating or K(m) concentration of glutamate. Therefore, the decrease in endogenous GABA release is not due to a decrease in GABA synthesis, but may reflect changes in GABA storage pools. These data are consistent with an overall decrease in GABA transmission, both pre- and postsynaptically, in the striatum of sensitized rats, which could contribute to enhanced striatal output and behavioral sensitization.

Animals↗
PubMed1999

Kainic acid (KA)-induced seizures in Sprague-Dawley rats and the effect of dietary taurine (TAU) supplementation or deficiency.

Male Sprague-Dawley rats received TAU supplementation (1.5% in drinking water) or TAU deficient diets for 4 weeks to test for a possible neuroprotective role of TAU in KA-induced (10 mg/kg s.c.) seizures. TAU supplementation significantly increased serum and hippocampal TAU levels, but not TAU content in temporal cortex or striatum. TAU deficient diets did not attenuate serum or tissue TAU levels. Dietary TAU supplementation failed to decrease the number or latency of partial or clonic-tonic seizures or wet dog shakes, whereas a TAU deficient diet decreased the number of clonictonic and partial seizures. This study does not support previous observations of an anticonvulsant effect of TAU against KA-induced seizures. KA-treatment decreased alpha 2-adrenergic receptor binding sites and TAU content in the temporal cortex across all dietary treatment groups, supporting previous evidence of severe KA-induced damage and neuronal loss in this brain region.

Amino Acids↗
PubMed1999

Uptake of particulate lead via the gills of fish (Carassius auratus).

Carassius auratus were exposed to mixtures of constant free lead (0. 1 mg/L) and particulate lead (adsorbed on gibbsite particles) at varied concentrations (0, 0.4, 0.8, 1.2, 2.0, and 3.0 mg/L). The concentrations of lead and aluminum in the gills and intestines of the fish were determined after exposure. The gills were examined (after the exposure) with a light microscope for any particles adhering to the surface. The examination results revealed that lead accumulations on the gills increased with increased particulate lead concentrations in the ambient water (under conditions of a constant level of free lead), indicating the bioavailability of lead via the gills. Gibbsite particles were also observed on the gill surface after exposure. The ratio of lead and aluminum in the gills was much higher than that in the particles. Our results suggest that there was a two-step process involved in the uptake of particulate lead by fish gills: (1) adherence of the particles on the gill surface where mucus was attached; and (2) desorption of lead from the particles under conditions of the gill microenvironment.

Animals↗
PubMed1999

An age-related decline in striatal taurine is correlated with a loss of dopaminergic markers.

Taurine is present in high concentration in the mammalian brain and is known to decline with aging. The present studies examined the relationship between the loss of striatal neurotransmitters and spatial learning ability in aged male Long-Evans rats. The effects of intrahippocampal infusions of neurotrophic factors-nerve growth factor (NGF) and brain-derived neurotrophic factor-were also examined for their ability to ameliorate the age-related decline in brain amino acid content. Taurine content was found to be significantly reduced in the striatum of aged rats (26 months old) that were impaired in spatial learning performance when compared to young unimpaired rats (5 months old). Aged rats that were behaviorally unimpaired had more modest reductions in taurine. Striatal dopamine content was also significantly reduced in aged learning-impaired rats. There was a significant (p < 0.001) correlation (r=0.61) between the striatal content of taurine and dopamine, but no such correlation was found for other striatal transmitters (glutamate, serotonin, norepinephrine). Treatment with neurotrophins had little effect on the age-related decline in striatal amino acids, although NGF treatment did improve spatial learning. These studies suggest (1) a link between age-related declines in striatal dopamine and taurine and (2) that NGF-induced improvement in spatial learning is not related to mechanisms involving changes in taurine or glutamate content.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Radiotherapy for bone metastases: a critical appraisal of outcome measures.

Pain from bone metastases is a common problem in patients with advanced cancer, and radiotherapy plays an important role in its palliation. Single fraction treatments are often prescribed, but there is no clear consensus on this issue and clinical practice shows significant variability. This situation is unsatisfactory for all patients--the patient, the clinician, and the health care administrator. Randomized trials may use poor outcome measures and this contributes to practice variability. The credibility of outcome studies is often reduced due to poor study design, small sample sizes, and the use of endpoints that are both unreliable and unsuitable. The endpoints used have been narrowly defined, the patient's perspective has generally been overlooked, and quality of life has only once been used as an endpoint. A review of the current literature suggests that instruments specific to bone metastases are required. These must be based on patient experience, and rely on self-report. In addition, there is a need to understand the relative priority that patients attribute to treatment outcomes. The use of better instruments and methodologies in future trials will enhance the credibility of results and reduce practice variations.

Bone Neoplasms↗
PubMed1999

Pathology imaging on the Web. Extending the role of the pathologist as educator to patients.

The increasing role of patients in medical decision making and the growing availability of medical information are changing the physician-patient relationship. One aspect of this change is that patients are searching for medical information on the Internet and are visiting sites, including pathology sites, that were not originally intended for patient use. This article describes evidence for this activity and how the University of Pittsburgh Medical Center Department of Pathology has evolved mechanisms to handle patient use of its web site.

Diagnostic Imaging↗