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Biomedical subjects

J A Anderson

Publications and source records attributed to J A Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Human excimer laser keratectomy. Immunohistochemical analysis of healing.

OBJECTIVE: To analyze human corneal responses to excimer laser by immunohistochemistry. METHODS: Corneas cultured for 3 weeks after laser ablation or taken from patients 5 to 16 months after laser treatment were exposed to antibodies to beta, integrin; types VII, IV, and III collagen; fibronectin; type I procollagen; and prolyl 4-hydroxylase. Antibody distributions were compared with those of normal corneas and unablated regions of treated corneas. RESULTS: After 3 weeks, distribution of beta, integrin, and types VII and IV collagen was patchy; heavy deposits of fibronectin appeared subepithelially. Keratocytes stained for prolyl-4-hydroxylase and type I procollagen. With increasing postoperative time, fibronectin diminished, and beta 4 integrin and type VII collagen became linear, stromal staining of types III and IV collagen increased and their diminished. CONCLUSIONS: Components of basement membrane, attachment complexes, and stromal matrix are synthesized shortly after laser treatment. Changes in these elements persist for 16 months in the human cornea.

Adult↗
PubMed1996

Excimer laser effects on human corneal endothelium. Modulation by serum factor(s).

OBJECTIVE: To determine the possibility of endothelial cell damage after excimer laser ablation. METHODS: Endothelial cell densities and morphology of human corneas after photoablations or mechanical keratectomy were compared with those of the untreated mates after 1 week of culture with or without serum. RESULTS: Corneas cultured in serum-free medium after ablation to a depth of 150 microns showed endothelial cell densities reduced to 60% of untreated, mate corneas; ultrastructural analysis showed endothelial cell damage not seen in untreated mates. Corneas ablated to the same depth and cultured in serum-enriched medium showed no endothelial cell density loss, nor did corneas cultured in serum-free medium after an ablation to a depth of 50 microns or mechanical keratectomies averaging 95 microns. CONCLUSIONS: Endothelial cell loss in deep laser resections may be prevented by factor(s) in fetal bovine serum. The apparent lack of cell loss in clinical studies may be related to the protective action of similar factors in aqueous humor.

Aged↗
PubMed1996

Fertility and general reproduction studies in rats with the HMG-CoA reductase inhibitor, atorvastatin.

Fertility and reproduction studies were conducted in rats with the 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin. Male rats received vehicle (0.5% methylcellulose) or atorvastatin at 20, 100, or 175 mg/kg by oral gavage for 11 weeks prior to mating with untreated females; treatment continued throughout mating and until necropsy on Day 115. An untreated control group of males was also included in the same procedures. Dose-related body weight gain suppressions of 17 and 25%, and food consumption suppressions of 7 and 16%, occurred during the 11-week premating treatment period at 100 and 175 mg/kg, respectively, compared with vehicle controls. There were no treatment-related effects on testes, epididymides, or accessory organs weights, testicular or epididymal sperm counts, sperm motility, or sperm morphology during Week 15 of treatment. Plasma drug concentrations during Week 15 increased with dose to a Cmax of 1820 +/- 1020 ng eq/ml at 175 mg/kg. There were no effects on copulation or fertility indices, number of days to mating, or female reproductive parameters (number of implants, live fetuses, or pre- and postimplantation loss). In the female fertility study, female rats received vehicle (0.5% methylcellulose) or atorvastatin at 20, 100, or 225 mg/kg by oral gavage for 2 weeks prior to mating with untreated males; treatment continued throughout mating and until Gestation Day 7. Sperm-positive females were sacrificed on presumed Gestation Day 13 to 15 for evaluation of reproductive parameters. Body weight gain in atorvastatin groups was comparable to controls during the premating period, but was suppressed by 35% at 225 mg/kg during the treatment period of gestation (Days 0-8), and was significantly increased at 225 mg/ kg during the posttreatment period of gestation (Days 8-13). Plasma drug concentrations on premating treatment Day 14 increased with dose to a Cmax of 7030 +/- 3680 ng eq/ml at 225 mg/ kg. The mean number of estrous cycles, copulation and fertility indices, number of days to mating, and number of viable litters were comparable between groups. In addition, term sacrifice parameters (number of corpora lutea, implants, live fetuses, pre- and postimplantation loss) were not significantly different between groups. Thus, these studies demonstrate no adverse effects of atorvastatin on fertility and reproduction in rats at doses up to 175 and 225 mg/kg in males and females, respectively, and 20 mg/kg was a no-effect dose.

Animals↗
PubMed1996

The effects of interleukin-1 receptor antagonist protein (IRAP) infusion following spinal cord transection in rats.

A laminectomy was performed at the T5-T6 vertebral level in adult, male, Sprague-Dawley rats and the spinal cord transected with a scalpel. A group of sham animals was subjected to the same surgery without the transection step. A group of unhandled control rats was also included. A subgroup of transected animals received a subcutaneous osmotic minipump that dispensed IL-1 receptor antagonist protein (IRAP) at the transection site for 7 consecutive days. Another transected subgroup received a minipump that infused the vehicle only. IRAP-treated rats displayed a significant reduction in body temperature (p < 0.05) compared with vehicle-treated rats. The IRAP-treated rats were also less active when assessed for locomotor behavior using an HVS computerized tracking system (p < 0.01). IRAP treatment had no effect on serum corticosterone, beta-endorphin levels, Con A, PHA, or LPS-induced splenocyte mitogenesis when compared with vehicle-treated animals. However, half of the IRAP-treated animals exhibited a substantive reduction in the number of reactive astrocytes near the transection site, suggesting a possible effect of IRAP on astrocyte activation.

Animals↗
PubMed1996

Preclinical toxicology studies with the angiotensin-converting enzyme inhibitor quinapril hydrochloride (Accupril).

Acute, subacute, and chronic toxicity studies, carcinogenicity bioassays, and reproductive and genetic toxicology studies were performed with quinapril, an ACE inhibitor used in the treatment of hypertension. Acute toxicity is minimal in rodents, and repeated dosing elicits gastric irritation, juxtaglomerular apparatus (JGA) hypertrophy and hyperplasia and tubular degenerative changes in the kidney, and reduced red cell parameters and heart weights in rodents and/or dogs. Other manifestations of toxicity, including hepatic lesions in dogs, reduced offspring weights in rats, marked sensitivity of the rabbit, and clastogenic effects at cytotoxic doses in the in vitro V79 chromosome aberration assay, have been reported with other drugs of this class.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1995

Use of Saccharomyces cerevisiae for patch-clamp analysis of heterologous membrane proteins: characterization of Kat1, an inward-rectifying K+ channel from Arabidopsis thaliana, and comparison with endogeneous yeast channels and carriers.

Transport-deficient strains of the yeast Saccharomyces cerevisiae have recently proven useful for cloning, by functional complementation, of cDNAs encoding heterologous membrane transporters: specifically, H(+)-amino acid symporters and K+ channels from the higher plant Arabidopsis thaliana. The present study uses whole-cell patch-clamp experiments to show that yeast strains which grow poorly on submillimolar K+ due to the deletion of two K(+)-transporter genes (TRK1 and TRK2) are in fact missing a prominent K+ inward current present in wild-type cells. Rescue of such strains for growth on low K+ by transformation with a gene (KAT1) encoding an inward-rectifying K+ channel from Arabidopsis is accompanied by the appearance of an inward current whose characteristics are in qualitative agreement with previous studies in the Xenopus oocyte system, but differ in quantitative details. The ability to make such measurements directly on Saccharomyces should facilitate structure-function studies of any electrogenic or electrophoretic ion transporters which can be expressed in the plasma membrane (or tonoplast) of that organism.

Animals↗
PubMed1995

15-substituted lanosterols: post-transcriptional suppressors of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

The oxolanosterol oxime 3 beta-hydroxylanost-7-en-15-one 15-oxime and the structurally similar 3 beta-hydroxylanost-7-en-15-one are dual-action inhibitors of cholesterol synthesis which cause both inhibition of lanosterol 14 alpha-methyl demethylase and suppression of the rate-limiting enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR). This report examines the mechanism by which these compounds lower HMGR protein levels in Chinese hamster ovary fibroblasts. Data are presented which suggest that both sterols reduce the translational efficiency of the HMGR mRNA as well as increase the rate of enzyme degradation. The effect of these sterols on the concentration of the low-density lipoprotein receptor (LDLR) in normal human fibroblasts was also determined. In these cells, both lanosterol analogs lowered HMGR protein levels without affecting LDLR concentration. This in contrast to the previously reported coordinate transcriptional regulation of these two genes by the C27-sterol 25-hydroxy-cholesterol. These findings are consistent with the hypothesis that different sterols regulate HMGR activity through distinct mechanisms.

Animals↗
PubMed1995

Epithelial-stromal interactions in human keratotomy wound healing.

OBJECTIVE: To evaluate epithelial-stromal interactions in the healing of stromal wounds and the relationship of such interactions to regional variations in healing throughout keratotomy wounds. METHODS: Ten radial keratotomy autopsy specimens were studied by using light and transmission electron microscopy. RESULTS: Underneath epithelial plugs, the epithelial-stromal interface was characterized by three adjacent morphological zones: a duplicated basement membrane complex, a zone that resembled Bowman's layer, and a third zone with collagenous fiber orientation parallel to the plugs. Scar tissue orientation was transverse at the base of the plug, and sagittal in deeper wound regions. CONCLUSIONS: Basement membrane duplication and a Bowman's layer-like region underneath a plug may result from complicated epithelial-stromal interaction. Asymmetrical organization of the scar, with subepithelial transverse and sagittal deeper scar tissue orientation, may characterize radial keratotomy wound healing, and may relate to variations in final refractive effect.

Adult↗
PubMed1995

Noise-induced hearing loss, nationality, and blood pressure.

Noise exposure has been associated with increased catecholamine production and blood pressure elevation in laboratory studies and in human volunteers. Epidemiologic studies have given conflicting results. In order to determine whether noise-induced hearing loss predicts a rise in blood pressure, we reviewed occupational medicine records in an occupational health center serving three companies where noise exposure is commonly found. Height, weight, blood pressure, and screening audiometry are obtained as part of routine occupational health screening, and the results of the screening visit are abstracted from written clinical records. The results of pure tone screening audiometry are reported in nonstandardized fashion (Normal, WNL, NAD, for example, for normal). We reviewed records from 1990 and 1991 inclusive. One investigator, blind to blood pressure status, assigned each record to "no hearing loss," "not codable," or "hearing loss assumed to be due to noise" on the basis of the written audiometry report. Hearing loss due to causes other than noise was considered not codable. No attempt was made to quantify severity of hearing loss. Two hundred and sixteen charts were excluded as "not codable," 1,535 were classified as having no hearing loss, and 610 had some degree of hearing loss, most probably due to noise exposure. To adjust for confounding covariates, multiple regression analysis was used and indicated that hearing status improves the regression model for predicting diastolic blood pressure (p = 0.04), following age, nationality, body mass index (BMI), and month of testing, although the effect is small. Stratification by age and BMI revealed increased diastolic pressure in the group with hearing loss under age 45, regardless of obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Developmental toxicity study in rats treated with the anticonvulsant, ralitoline.

The developmental toxicity of the anticonvulsant compound, ralitoline, was investigated in Sprague-Dawley rats administered oral doses of 0, 15, 60, 120, 180, or 240 mg/kg on days 6 through 15 of gestation. An untreated control group and a vehicle control group pair-fed to the high dose group were included. Maternal and fetal parameters were evaluated on day 21 of gestation. Fetuses were examined for external, visceral, and skeletal malformations and variations. Maternal death occurred at 180 and 240 mg/kg. Dose-dependent decreases in body weight, food consumption, and water consumption were observed at 60 mg/kg and above. Body weight gain during treatment was similar in the pair-fed and 240 mg/kg groups. Dose-related CNS signs (hypoactivity, ataxia, prostration, and/or convulsions) were observed at 60 mg/kg and above. Decreased numbers of live fetuses and increased postimplantation loss were observed in a dose-related manner at 120, 180, and 240 mg/kg while no changes occurred in pair-fed controls. Fetal body weights and placental weights were decreased in pair-fed controls and in the 120, 180, and 240 mg/kg groups. The percent fetuses per litter, and the percent litters with external/visceral malformations, were significantly increased at 120, 180, and 240 mg/kg compared with vehicle and pair-fed controls. Dose-related increases in cardiovascular malformations, specifically of the aortic arch (interrupted, stenotic, extra vessel), were apparent at 120 mg/kg and above. The incidence of skeletal variations was increased at 120 mg/kg and above.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗
PubMed1995

The effect of soluble tumor necrosis factor receptor-II on endotoxin-mediated hemodynamic instability.

Tumor necrosis factor-alpha (TNF-alpha), a central mediator in the hemodynamic response to injury and infection, is a primary mediator of endotoxin-induced hemodynamic instability. Two types of naturally occurring soluble TNF receptors circulate in human experimental endotoxemia and the recombinant proteins of both have been hypothesized as potential therapeutic agents antagonizing TNF-mediated effects of endotoxemia. The administration of recombinant sTNFr-I has been previously shown to attenuate the hemodynamic collapse of lethal bacteremia. In the current study, we investigated the role of recombinant sTNFR-II at low (0.5 mg/kg) and high (2.5 mg/kg) doses as a potential therapeutic agent for the inhibition of endotoxin lipopolysaccharide (LPS)-mediated hemodynamic instability. Eighteen male Sprague-Dawley rats were anesthetized and cannulated for continuous blood pressure monitoring and cardiac output measurement by thermodilution. Groups of animals received saline, LPS (1 mg/kg), or sTNFr-II (at 0.5 or 2.5 mg/kg) 15 min prior to LPS (1 mg/kg). Hemodynamic variables (blood pressure, cardiac output, heart rate) were monitored every 15 min for 2 hr. LPS caused a 30% decrease in mean arterial pressure by 60 min, which began to recover by 120 min. sTNFr-II was unable to prevent LPS-induced hypotension at low or high dose. Serum levels of immunoreactive TNF-alpha, undetectable in control animals, were significantly increased by sTNFr-II compared to LPS alone. Serum from animals treated with high-dose sTNFr-II showed significantly less TNF cytotoxicity than those treated with low-dose sTNFr-II, indicating that high doses of sTNFr-II are required for the inhibition of the bioactivity of TNF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

The effects of oral pentoxifylline on interleukin-2 toxicity in patients with metastatic renal cell carcinoma.

Interleukin-2 (IL-2) mediates the regression of metastatic renal cell carcinoma, but clinical application has been limited by associated toxicities. Preclinical studies show that pentoxifylline (PTXF), a methylxanthine derivative, inhibits IL-2 toxicity while preserving anti-tumour efficacy. This study was designed to determine whether oral PTXF would alter IL-2-induced toxicities. Patients with disseminated renal cell carcinoma were treated with continuous infusion of 18 x 10(6) IU/m2/24 h for 4 days followed by 3 days without treatment, for 4 consecutive weeks. After a 2-week interval, the 4-week treatment cycle was repeated. All patients concomitantly received oral PTXF (2000 mg/24 h) in five divided doses. Despite the co-administration of PTXF, all patients demonstrated a spectrum and severity of toxicities consistent with previous reports of continuous infusion of IL-2 alone. There was considerably more nausea and vomiting associated with the administration of PTXF which improved on withdrawal of PTXF. Oral PTXF in IL-2 therapy did not show any substantiated benefit. Indeed, patients suffered more severe nausea and vomiting than if they had received IL-2 alone, resulting in the early termination of the trial.

Administration, Oral↗
PubMed1995

Molecular mapping of wheat: major genes and rearrangements in homoeologous groups 4, 5, and 7.

A molecular-marker linkage map of hexaploid wheat (Triticum aestivum L. em. Thell) provides a framework for integration with teh classical genetic map and a record of the chromosomal rearrangements involved in the evolution of this crop species. We have constructed restriction fragment length polymorphism (RFLP) maps of the A-, B-, and D-genome chromosomes of homoeologous groups 4, 5, and 7 of wheat using 114 F7 lines from a synthetic X cultivated wheat cross and clones from 10 DNA libraries. Chromosomal breakpoints for known ancestral reciprocal translocations involving these chromosomes and for a known pericentric inversion on chromosome 4A were localized by linkage and aneuploid analysis. Known genes mapped include the major vernalization genes Vrn1 and Vrn3 on chromosome arms 5AL and 5DL, the red-coleoptile gene Rc1 on 7AS, and presumptively the leaf-rust (Puccinia recondita f.sp. tritici) resistance gene Lr34 on 7DS and the kernel-hardness gene Ha on 5DS. RFLP markers previously obtained for powdery-mildew (Blumeria graminis f.sp. tritici) resistance genes Pm2 and Pm1 were localized on chromosome arms 5DS and 7AL.

Chromosome Mapping↗
PubMed1995

Multiple genes, tissue specificity, and expression-dependent modulationcontribute to the functional diversity of potassium channels in Arabidopsis thaliana.

K+ channels play diverse roles in mediating K+ transport and in modulating the membrane potential in higher plant cells during growth and development. Some of the diversity in K+ channel functions may arise from the regulated expression of multiple genes encoding different K+ channel polypeptides. Here we report the isolation of a novel Arabidopsis thaliana cDNA (AKT2) that is highly homologous to the two previously identified K+ channel genes, KAT1 and AKT1. This cDNA mapped to the center of chromosome 4 by restriction fragment length polymorphism analysis and was highly expressed in leaves, whereas AKT1 was mainly expressed in roots. In addition, we show that diversity in K+ channel function may be attributable to differences in expression levels. Increasing KAT1 expression in Xenopus oocytes by polyadenylation of the KAT1 mRNA increased the current amplitude and led to higher levels of KAT1 protein, as assayed in western blots. The increase in KAT1 expression in oocytes produced shifts in the threshold potential for activation to more positive membrane potentials and decreased half-activation times. These results suggest that different levels of expression and tissue-specific expression of different K+ channel isoforms can contribute to the functional diversity of plant K+ channels. The identification of a highly expressed, leaf-specific K+ channel homolog in plants should allow further molecular characterization of K+ channel functions for physiological K+ transport processes in leaves.

Amino Acid Sequence↗