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Biomedical subjects

W R Anderson

Publications and source records attributed to W R Anderson.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1991

Antibodies raised against trifluoroacetyl-protein adducts bind to N-trifluoroacetyl-phosphatidylethanolamine in hexagonal phase phospholipid micelles.

The delayed fulminant form of halothane hepatotoxicity is thought to be triggered by an immune response to haptenic adducts formed by a metabolite, trifluoroacetyl chloride. In this study we demonstrate that antibodies purified from the sera of rabbits sensitized to a trifluoroacetyl-protein adduct will cross-react with a trifluoroacetyl-phosphatidylethanolamine adduct. Trifluoroacetyl adducts of both rabbit serum albumin (TFA-RSA) and dioleoylphosphatidylethanolamine (TFA-DOPE) were prepared. The TFA-RSA was coupled to an Affigel-10 affinity column to purify hapten-selective immunoglobulin (Ig) G antibodies (anti-TFA-RSA IgG) from the sera of rabbits given i.m. injections of TFA-RSA. The TFA-DOPE was purified by high-performance liquid chromatography and the structure confirmed with direct chemical ionization mass spectrometry. Lamellar liposomes containing a mixture of 5% TFA-DOPE, 71% DOPE and 24% dioleoyl-phosphatidylcholine, as well as hexagonal phase micelles containing 5% TFA-DOPE and 95% DOPE, were prepared by sonication. Anti-TFA-RSA IgG antibodies were added to each of these lipid mixtures for 30 min, fluorescein-conjugated goat-antirabbit IgG antibodies were added next for an additional 30 min and then binding of anti-TFA-RSA IgG antibodies to TFA-DOPE was quantified by flow cytometry. Anti-TFA-RSA IgG antibodies bound to TFA-DOPE only when it was incorporated into hexagonal phase micelles. These findings suggest that TFA-phosphatidylethanolamine adducts that reside in nonlamellar domains on the hepatocyte surface could be recognition sites for anti-TFA-adduct antibodies and potentially participate in immune-mediated hepatotoxicity.

Animals↗
PubMed1990

Ultrastructural study of hepatic regeneration following one-lobe, two-lobe, and subtotal hepatectomy in the rat.

The sequential and comparative ultrastructural features of regenerating rat liver following one-lobe, two-lobe, and subtotal hepatectomy were studied. All three groups demonstrated glycogen depletion at the 12 h post-hepatectomy interval with reaccumulation occurring at 24 h in the first two groups but not until 72 h in the subtotal hepatectomy group. Other hepatocellular alterations attributed to regenerative activity were similar in the three groups, however the onset and magnitude of those changes occurring in the two-lobe and subtotally hepatectomized rats differed significantly from those alterations occurring in the one-lobe hepatectomy group. These changes were characterized by a greater and more prolonged mitotic activity, increased proliferation of RER and smooth endoplasmic reticulum (SER), and by increased Golgi bodies. These two groups also manifested greater hepatocellular accumulation of phagolysosomes, myelin figures, and lipid bodies when compared with the one-lobe hepatectomy group.

Animals↗
PubMed1990

Cross-reactivity of antibodies raised against acetaldehyde adducts of protein with acetaldehyde adducts of phosphatidyl-ethanolamine: possible role in alcoholic cirrhosis.

This study measured the possible cross-reactivity of hapten-specific IgG antibodies purified from the sera of rabbits sensitized to an albumin-acetaldehyde conjugate [N-ethyl-rabbit serum albumin (N-ethyl-RSA)] with acetaldehyde-phosphatidylethanolamine adducts. The N-ethyl-RSA was coupled to an Affigel-10 column to affinity purify the IgG (anti-N-ethyl-RSA IgG). Dioleoyl-phosphatidylethanolamine (DOPE) was reacted with acetaldehyde to form a Schiff base, which was reduced to N-ethyl-DOPE, purified by high pressure liquid chromatography, and analyzed with direct chemical ionization mass spectrometry. Lamellar liposomes containing either 5% by weight N-ethyl-DOPE and 95% egg phosphatidylcholine or a mixture of 5% N-ethyl-DOPE, 71% DOPE, and 24% dioleoylphosphatidylcholine, as well as hexagonal phase micelles containing 5% N-ethyl-DOPE and 95% DOPE, were prepared by sonication. Anti-N-ethyl-RSA IgG was then incubated with each of these lipid mixtures for 30 min, a fluorescein-conjugated goat anti-rabbit IgG was added for an additional 30 min, and then binding of anti-N-ethyl-RSA IgG to N-ethyl-DOPE in the liposomes or micelles was measured by flow cytometry. Anti-N-ethyl-RSA IgG bound to N-ethyl-DOPE in both vesicles and hexagonal phase micelles, but the affinity was 16 times greater for the hapten in the hexagonal phase. This result demonstrates that physical presentation of the hapten can affect antibody recognition and that antibodies raised against N-ethyl-RSA can cross-react with acetaldehyde-phospholipid adducts.

Acetaldehyde↗
PubMed1989

Studies of interactions of porphyrins with transfer RNA by high-resolution NMR.

The interactions of tetra-4N-methylpyridyl porphyrin and its zinc(II), copper(II) and manganese(III) complexes with brewer's yeast type V phenylalanine specific tRNA have been evaluated by high-resolution NMR. Differences in chemical shifts have been noted for three proton resonances in response to the presence of small quantities of the free base and the zinc and copper complexes. The protons giving rise to these signals are located on bases T54 and psi 55, both of which are involved in the primary intraloop and interloop hydrogen bonds that hold the D and T psi C loops together in the tertiary structure. In addition, broadening of specific resonances due to hydrogen bonding protons in the D stem at low ratios of porphyrin to tRNA indicates that the association of porphyrins increases the rate of imino proton exchange. The titration of the tRNA with the manganese(III) complex did not reveal shifts or specific broadening comparable to the other porphyrins at low ratios. The changes induced in the NMR spectrum of tRNA by porphyrins define their site of interaction with the polynucleotide. This site, at the outside of the elbow-bend in the tRNA 'L', is different from the locus of binding in tRNA for other classical DNA intercalators. Furthermore, a new mode of binding may be involved that is neither intercalative nor simply electrostatic.

Binding Sites↗
PubMed1989

Insudative hyalin cap lesions of diabetic glomerulosclerosis.

Peripheral hyalin cap lesions of glomerular capillaries are a common finding in diabetic renal disease. Although these have been referred to as exudative in nature, most studies ascribe an insudative process in their pathogenesis. We report a case of diabetic renal disease in which glomeruli demonstrated both late and early developmental stages of peripheral cap lesions in which the presence of plasma constituents was indicative of an insudative process.

Adult↗
PubMed1989

Effects of a brain-enhanced chemical delivery system for estradiol on body weight and food intake in intact and ovariectomized rats.

Studies were undertaken to determine the effects on body weight of a brain-enhanced chemical delivery system for estradiol. This estradiol-chemical delivery system (E2-CDS) has a long half-life in the brain, where it slowly releases estradiol but is quickly cleared from peripheral tissues. We administered, by a single iv injection, E2-CDS (0.2, 1.0, or 5.0 mg/kg), equimolar doses of another 17-hydroxy-substituted estrogen, estradiol valerate (E2-VAL), or the dimethyl sulfoxide (DMSO) vehicle to female rats. Daily food intake and body weight was determined for 24 days thereafter. E2-CDS caused an initial dose-dependent suppression in body weight for up to 8 days and a suppression in food intake for up to 4 days. In response to E2-VAL, the initial declines in body weight and food intake were lower in magnitude, were shorter in duration, and showed no dose dependency. Following this period of weight loss, E2-CDS-treated rats gained weight at a rate greater than that of the DMSO controls, and at the 0.2- and 1.0-mg/kg doses, body weights achieved were greater than control levels. To determine the role of the ovaries on this biphasic response to E2-CDS, long-term ovariectomized rats were treated with E2-CDS (1.0 mg/kg) or the vehicle and parameters of body weight regulation were determined for 25 days. Ovariectomized rats responded to E2-CDS with a prompt and sustained decrease in body weight which did not recover over the 25-day course of the study. The body-weight loss in ovariectomized rats was associated with a marked reduction in food intake for 8 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Evidence for prolonged suppression of stress-induced release of adrenocorticotropic hormone and corticosterone with a brain-enhanced dexamethasone-redox delivery system.

We have developed a redox system for brain-enhanced delivery of dexamethasone based on an interconvertible dihydropyridine in equilibrium pyridinium salt carrier. Dexamethasone, when combined with the lipoidal carrier, readily crosses the blood-brain barrier. The carrier, when oxidized, reduces its rate of exit from the brain. The aim of the study was to evaluate the capacity of a dexamethasone-chemical delivery system (DX-CDS) and dexamethasone (DEX) to suppress stress-induced elevations of plasma adrenocorticotropic hormone (ACTH) and corticosterone (CORT). Adult male Sprague-Dawley (CD) rats were administered either DX-CDS (10 mg/kg), an equimolar dose of DEX or the drug vehicle (2-hydroxypropyl-beta-cyclodextrin) by a single tail vein injection. Rats then received either no stress or a restraint stress for a 5- or 15-min duration on days 1, 3, 5 or 7 after drug administration and trunk blood was rapidly collected. To assess peripheral effects of DX-CDS and DEX, 1 ml of blood was removed via orbital puncture and evaluated for total and differential leukocyte counts in a separate group of animals. Both DX-CDS and DEX were effective on day 1 in suppressing, by greater than 95%, ACTH secretion induced by a 5-min stress. However, DX-CDS was effective through day 5 (44% suppression) while DEX was not effective after 24 h. When 15 min of stress was applied, DX-CDS effected a significant ACTH suppression through 7 days while DEX was effective for only 3 days. DX-CDS was effective through day 7 (55%) in suppressing CORT after a 15-min stress while DEX was effective for 3 days only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1989

Cardiac myxomas correlative study by light, transmission, and scanning electron microscopy.

A correlative morphologic study of 17 cardiac myxomas surgically excised or observed at autopsy was performed by light (LM), transmission (TEM), and scanning electron microscopy (SEM). Tumor cells occurred singly (frequently in lacunae), in cords, as vascular-like aggregates, and in complex interdigitating clusters. By TEM, myxoma cells were predominantly undifferentiated mesenchymal cells. The surface topography by SEM revealed numerous clefts and crevices and a continuous cellular lining which, by TEM, appeared to be derived from underlying myxoma cells. The myxoid stroma by SEM was interspersed by numerous reticular fibers that appeared as a sponge-like supportive framework. Complex patterns of interdigitating myxoma cells corresponded well with similar patterns by LM and TEM, demonstrating the advantage of SEM in correlative morphologic studies.

Adolescent↗