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Biomedical subjects

W R Anderson

Publications and source records attributed to W R Anderson.

At least 19 recordsLinked to original sources
PubMed1992

Plasma membrane Ca(2+)-ATPase isoforms: distribution of mRNAs in rat brain by in situ hybridization.

Several mRNAs which encode for isoforms of the plasma membrane Ca(2+)-transport ATPase (PMCA) are present in adult rat brain. Using in situ hybridization with antisense oligonucleotide probes we found complex patterns of specific hybridization for three isoforms (PMCA1-3). Each rat brain region studied exhibited a distinct pattern of expression of isoforms. PMCA1 mRNA, which is widely distributed in rat tissues, was highest in CA1 pyramidal cells of hippocampus and very low in hypothalamic nuclei, cerebellum and choroid plexus. PMCA2 mRNA was highest in Purkinje cells of cerebellum and low in caudate-putamen, hypothalamic nuclei, habenula and choroid plexus. The highest levels of PMCA3 mRNA were found in habenula and choroid plexus. The PMCA1-3 isoforms appeared to be expressed primarily in neurons since hybridization was detected neither in white matter nor in regions rich in astrocytes. In different regions, different levels of expression of each PMCA mRNA may underlie specialized requirements for calcium homeostasis in specific neurons.

Animals↗
PubMed1992

Effects of transforming growth factor-beta on murine astrocyte glutamine synthetase activity. Implications in neuronal injury.

Cytokines have been implicated in the pathogenesis of a number of brain diseases in which neurological dysfunction has been attributed to a change in amino acid neurotransmitter metabolism. In the present in vitro study, we investigated the effects of cytokines on astrocyte glutamine synthetase (GS) activity and subsequently on N-methyl-D-aspartate (NMDA) receptor-mediated neurotoxicity. Proinflammatory cytokines IL-1 alpha, IL-1 beta, and IL-6 at a concentration of 20 ng/ml did not affect GS activity; however, tumor necrosis factor-alpha inhibited this activity by 20% in mixed neuronal/astrocyte cultures. Treatment for 24 h with transforming growth factor (TGF)-beta 1 or -beta 2 inhibited up to 60% GS activity. TGF-beta 2 also inhibited GS in enriched astrocyte cultures with an ED50 of 10 pg/ml. Antibodies specific to TGF-beta 2 blocked this effect. Treatment of astrocytes with TGF-beta 2 (250 pg/ml) resulted in markedly dilated rough endoplasmic reticulum. Since astrocyte GS may play a protective role in NMDA receptor-mediated neurotoxicity, we treated mixed neuronal/astrocyte cultures with TGF-beta 2 (250 pg/ml) and found a threefold potentiation of NMDA receptor-mediated neurotoxicity. These data suggest that TGF-beta impairs astrocyte GS function and enhances neurotoxicity, thus providing insight into understanding one mechanism of cytokine-mediated central nervous system disease.

Animals↗
PubMed1991

Development of aqueous parenteral formulations for carbamazepine through the use of modified cyclodextrins.

The poor aqueous solubility of carbamazepine was dramatically increased via complexation with various chemically modified beta-cyclodextrins and gamma-cyclodextrins. A preparation of carbamazepine and 2-hydroxypropyl-beta-cyclodextrin was found to be stable to steam sterilization and to storage under a variety of conditions. Carbamazepine, when solubilized in this manner, was found to exert potent anticonvulsant effects in various seizure models and the formulation was tolerated in animals at high doses (100 mg/kg carbamazepine and 1200 mg/kg of the cyclodextrin excipient). The onset of anticonvulsant action was rapid and consistent with almost instantaneous in vivo complex dissociation. The low toxicity of 2-hydroxypropyl-beta-cyclodextrin, when administered via the parenteral route, and its ability to enhance the aqueous solubility of carbamazipine highly favor the use of this excipient.

Animals↗
PubMed1991

Oxygen pipeline supply failure: a coping strategy.

Oxygen is the most vital drug administered during anesthesia. The delivery of hypoxic or even anoxic gas mixtures during anesthesia has been reported. Because such occurrences often meet with disaster, modern anesthesia machines have a system of alarms to warn against the delivery of hypoxic or anoxic gas mixtures and also to warn of the failure of the oxygen pipeline supply. We describe the occurrence of a sudden failure of the oxygen pipeline supply, and discuss a strategy for coping with this emergency.

Adult↗
PubMed1991

Colon perforation due to cholesterol embolism.

Embolization to the gastrointestinal tract is a common complication of systemic atheroembolism, but is rarely catastrophic. This study describes perforation of the colon with fatal peritonitis in a 65-year-old patient following cholesterol embolization to the intestinal tract.

Aged↗
PubMed1991

The effects of a brain-enhanced estradiol delivery system on testosterone and androgen-dependent tissues. I. Dose-response and time-course evaluation.

The primary objective underlying hormone treatment of prostatic adenocarcinoma is to induce an effective androgen deprivation, and high dose estrogen therapy is as effective as surgical castration in abolishing the growth-promoting effects of androgens on prostatic tissue. An estradiol-chemical delivery system (E2-CDS), with sustained release of E2 in the brain, may be potentially useful in the treatment of prostatic cancer by virtue of the need for lower or less frequent doses of the estrogen. In this study we evaluated the dose- and time-dependent effects of the E2-CDS vs. 17 beta-E2 on serum testosterone (T) and weights of androgen-dependent tissues in male rats. Rats received a single iv injection of E2-CDS (0.1, 0.5, or 1.0 mg/kg), equimolar doses of 17 beta-E2, or the drug's vehicle. Sera and tissues were collected 1, 7, 14, or 21 days later for determination of hormone levels and tissue weights. The E2-CDS exhibited a dose- and time-dependent suppression of serum T and weights of the ventral prostate and seminal vesicles. In contrast, 17 beta-E2 had no significant effect on serum T or growth of these androgen-dependent tissues. Serum T levels were significantly reduced by 98%, 82%, and 59% at 1, 7, and 14 days, respectively, with the 1.0 mg/kg dose of E2-CDS. The E2-CDS significantly reduced prostate weight by 45% and 50% (1.0- and 0.5-mg/kg doses, respectively) 7 days and by 27% (0.5 mg/kg dose) 14 days after treatment. Similarly, seminal vesicle weights were reduced by 14-20% on day 1, maximally reduced by 39-48% on day 7, and still reduced by 24-36% on day 14 compared with the control levels. Weights of these tissues returned to control levels by day 21. Serum E2 was elevated through 7 days by E2-CDS or on day 1 only by 17 beta-E2. PRL secretion was stimulated for 1 week by both forms of estrogen. Anterior pituitary weights were increased by the E2-CDS through 14 days, while 17 beta-E2 had no significant effect. These data indicate that the E2-CDS causes chronic suppression of serum T, which subsequently results in regression of androgen-dependent tissue weight.

2-Hydroxypropyl-beta-cyclodextrin↗
PubMed1991

The effects of a brain-enhanced estradiol delivery system on testosterone and androgen-dependent tissues. II. The role of testosterone.

The present study was undertaken to evaluate the efficacy of an estradiol-chemical delivery system (E2-CDS) for the brain vs. estradiol benzoate (E2-BNZ) in suppressing serum testosterone (T) and weights of the ventral prostate and seminal vesicle in male rats. Also, the role of serum T in the weight reduction of androgen-dependent tissues observed after E2-CDS treatment was further evaluated in these studies. Intact male rats received a single iv injection of either E2-CDS at a dose of 1.0 mg/kg or an equimolar dose of E2-BNZ (0.95 mg/kg). Sera and tissue samples were collected 1, 7, 14, or 21 days after injection for determination of hormones and tissue weights. A single injection of E2-CDS suppressed serum T levels by 96%, 83%, 46%, or 63% 1, 7, 14, or 21 days after treatment, respectively. In contrast, an equimolar dose of E2-BNZ had no significant effect on serum T at any sampling time examined. Prostate weight was maximally reduced by 53% at 7 days and remained significantly suppressed by more than 31% throughout the 21-day time course. Similarly, seminal vesicle weight was reduced by 14% on day 1, maximally reduced by 41% on day 7 and remained significantly suppressed through day 21. In contrast, E2-BNZ was ineffective in inducing weight changes in either of these tissues. Serum PRL was significantly elevated through day 14, while E2 was elevated through day 7 by E2-CDS. Both the anterior pituitary and adrenal gland weights were stimulated by E2-CDS treatment. Testis weight was moderately reduced by both esters. In a subsequent study serum T was reduced by 98% and 97% 1 and 7 days, respectively, after E2-CDS treatment, and weights of the ventral prostate and seminal vesicle were reduced by 47% and 40%, respectively, at 7 days. In contrast, in rats treated with Silastic capsules containing T, the expected E2-CDS-induced weight regression was prevented in both prostate and seminal vesicles. These data indicate that the prolonged effects of E2-CDS on weights of androgen-dependent tissues are caused by its ability to produce profound suppression of the serum T concentration.

Adrenal Glands↗
PubMed1991

Multisystem failure and hepatic microvesicular fatty metamorphosis associated with tolmetin ingestion.

Multisystem toxicity including both renal and hepatic failure has been reported with the use of nonsteroidal anti-inflammatory drugs. We report a fatal case of multisystem failure associated with tolmetin ingestion in a 15-year-old girl. Microvesicular fatty change was found in the liver at autopsy. To our knowledge, this is the first reported case of nonsteroidal anti-inflammatory drug-associated multisystem failure to have this histopathologic finding.

Adolescent↗
PubMed1991

National seroprevalence of Toxoplasma gondii in pigs.

Serum samples from 11,842 commercial pigs killed in 1983-1984 throughout the United States were tested for anti-Toxoplasma gondii antibodies by the agglutination test in dilutions of 1:25, 1:50, and 1:500. Anti-T. gondii antibodies were found in 23.9% of pigs. At dilutions of 1:25, 1:50, and 1:500, 13.5%, 6.9%, and 3.5% were serologically positive, respectively. The prevalence of anti-T. gondii antibodies was higher in breeder pigs (42%) than in market pigs (23%). These results indicate that anti-T. gondii antibodies are widespread in the national swine herd.

Animals↗
PubMed1991

Variability in the morphological spectrum and clinical outcome of chronic liver disease in hepatitis B-positive and B-negative renal transplant recipients.

UNLABELLED: The impact of hepatitis B infection on the clinical outcome of renal transplantation has been controversial. Some investigators reported excess mortality from hepatic failure and/or concurrent sepsis while others found no such detrimental effect. Since the clinical or biochemical data do not reflect the severity or the course of liver disease in these immunosuppressed patients, we performed percutaneous liver biopsies and systematically analyzed the histological findings in 68 patients who had clinical evidence of chronic liver disease in the posttransplant period. Twenty-six of these patients were HBs Ag-positive and 42 were HBs Ag-negative. There were no significant differences in the demographic data, biochemical variables, or the mean follow-up between the two groups. RESULTS: HBs Ag-positive patients had more severe histological forms of liver disease, i.e., chronic persistent hepatitis (CPH) (38%) and chronic active hepatitis (CAH) (38%), compared with 17% CPH and 14% CAH in HBs Ag-negative patients (CPH, P = 0.08; CAH, P = 0.04). The incidence of cirrhosis was also higher in the HBs Ag-positive patients (42% vs. 19%, P = 0.07). During a mean follow-up of 82 +/- 58 months from the onset of hepatitis, 54% of hepatitis B-positive patients died from liver failure compared with 12% of the B-negative group, who were followed for a mean period of 74 +/- 47 months from the onset of hepatitis. The difference in mortality rate was highly significant (P = 0.002). Comparison of initial histology with a follow-up specimen in 25 patients (13 HBs Ag-positive, 12 HBs Ag-negative) also showed a trend towards higher frequency of liver cirrhosis in the B-positive patients compared with the B-negative group (P = NS). Our observations, based on liver histology, confirm earlier reports that hepatitis B infection is associated with a bad prognosis in renal allograft recipients, who have clinical evidence of chronic liver disease.

Adult↗
PubMed1979

The effect of transection of the accessory ligaments on reproduction in the rabbit.

The mesotubarium superius (MTS) and uterovarian ligament (UOL) contain smooth muscle, are mechanically active, and have been implicated in ovum transport in a number of species. To assess the reproductive importance of these ligaments, they were unilaterally transected in 27 rabbits and the effects on reproduction determined. Reproductive function was characterized in terms of the numbers of corpora lutea, uterine implants, and normal conceptuses resulting from breeding with fertile bucks. Fertility was defined by the proportion of ovulating follicles resulting in implantation and normal conceptuses. Grouped and paired sample analyses of these data showed no differences between the experimental and control sides of the reproductive tracts of animals in which the UOL, MTS, or both were transected. The structural integrity of these ligaments is thus not necessary for normal conception and fertility in the rabbit.

Animals↗
PubMed1978

Empirical model of intracranial pressure and head motion resulting from a vibrating seated rhesus.

A series of experiments was designed to measure the head X and Z accelerations and the intracranial pressure in the unrestrained head of a rhesus monkey. The subject was exposed to a continuum of vibration frequencies from 2 to 35 Hz and peak acceleration amplitudes of 5, 10, 20, and 40 m/s2. The resulting data was used to build a frequency response model relating the head accelerations and pressures to the torso acceleration. The head-to-torso relationships, based upon a single subject, were both repeatable and invariant for torso acceleration amplitudes of 10, 20, and 40 m/s2. At frequencies above the 10Hz, the model strongly suggested the presence of linear system, and the inherent advantages of superposition. The model demonstrates the validity of the experimental method, involving a slow sweep through a range of frequencies, and of the analysis procedures used. More importantly, it promises to be a useful approach to the study of human response to vibration.

Animals↗
PubMed1978

Predictive model of dynamic response of the human head/neck system to -Gx impact acceleration.

This paper describes the mathematical framework, underlying an empirical model, that predicts human head response using only the motion present at vertebra T1. Based on this framework, a model for --Gx impact acceleration was developed from data obtained on six volunteer subjects participating in the NAMRL impact acceleration experiments. Model performance was evaluated by comparing the errors in the predicted head responses with the normal variations observed between the responses of different subjects under identical impact accelerations. Independent sets of data were used for building and testing the model. The results of the evaluation indicate that the model will be useful in subsequent studies of human response to impact acceleration.

Acceleration↗