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Biomedical subjects

J A Anderson

Publications and source records attributed to J A Anderson.

At least 109 records · Page 6Linked to original sources

Oxolanosterol oximes: dual-action inhibitors of cholesterol biosynthesis.

A series of oxolanosterol oximes and oxime ethers have been prepared as potential dual-action inhibitors of cholesterol biosynthesis. The synthesis of these oximes along with the evaluation of their ability to inhibit lanosterol 14 alpha-methyl demethylase (P450DM) and to suppress 3-hydroxy-3-methylglutaryl coenzyme. A reductase (HMGR) activity is presented. 3 beta-Hydroxylanost-7-en-15-one 15-oxime XIX was found to be an effective inhibitor of P450DM in rat liver microsomal preparations. In [14C]acetate incorporation studies using Chinese hamster ovary (CHO) cells, compound XIX was found to cause a dramatic reduction in the incorporation of acetate into C27 sterols with a concomitant increase in radiolabeled C30 sterols which is consistent with the inhibition of P450DM. In addition, 15-oxime XIX was shown to suppress HMGR activity in both wild-type CHO and P450DM-deficient (AR45) cells, indicating that suppression of HMGR is independent of any effects of this oxime on P450DM. In both cell lines, parallel declines in HMGR activity and HMGR protein levels were observed suggesting that compound XIX suppresses HMGR activity by regulation of gene expression. These results demonstrate that, as predicted, 15-oxime XIX is indeed a dual-action inhibitor of cholesterol biosynthesis which causes both the inhibition of P450DM and a reduction in HMGR activity.

Animals↗

Electron microscopic findings in a cornea with recurrence of herpes simplex keratitis after excimer laser phototherapeutic keratectomy.

Excimer laser phototherapeutic keratectomy is emerging as an alternative therapy to corneal transplantation for the treatment of multiple corneal diseases. We report three cases of recurrence of herpes simplex keratitis after treatment of herpetic corneal scars with the excimer laser. In two cases, the patients underwent subsequent corneal transplantation. One corneal button examined with transmission electron microscopy (TEM) demonstrated a well-differentiated epithelium over the area of ablation, a linear, continuous basal lamina, and no viral particles. Anterior stromal scarring may have resulted from the laser treatment itself or may represent incomplete ablation of previous scars. Whether reactivation of the virus was stimulated by the laser or occurred as part of the natural history of the disease is uncertain. We recommend that patients who undergo excimer laser treatment for herpes simplex scarring receive careful follow-up including antiviral coverage.

Adult↗

Double-blind comparison of amlodipine and nifedipine retard in the treatment of mild to moderate hypertension.

The efficacy and safety profiles of amlodipine (5-10 mg once daily) and nifedipine retard (20-40 mg twice daily) were compared in 111 hypertensive patients (sitting DBP in 95-115 mmHg) during eight weeks of treatment in a randomised double-blind parallel group study. BP was measured 22-24 hours after the daily dose of amlodipine and 10-12 hours after a dose of nifedipine retard. Baseline sitting BPs of 175/105 mmHg and 168/104 mmHg were significantly reduced (P < 0.05) to 157/93 mmHg and 151/92 mmHg at the end of treatment in response to mean daily doses of amlodipine 7.3 mg and nifedipine retard 58.9 mg. There were no clinically significant changes in heart rate with either treatment. Three patients in the amlodipine group and five patients in the nifedipine retard group could not be considered in analysis. The total numbers of adverse events (considered related or possibly related to treatment) (42 vs. 36) as well as the numbers of patients experiencing such events (22 vs. 22) were similar in the amlodipine and nifedipine retard treated groups, respectively, but with a greater incidence of headaches in response to nifedipine retard and of oedema in response to amlodipine. Five patients in each treatment group discontinued therapy due to such events. Overall the results showed once daily amlodipine as equivalent to twice daily nifedipine retard in the management of mild to moderate hypertension.

Adult↗

Food restriction during organogenesis in rabbits: effects on reproduction and the offspring.

To assess the effects of markedly restricted food intake versus ad libitum feeding or a slightly restricted feeding regimen during the period of organogenesis we fed groups of 16-18 pregnant rabbits Purina Certified High Fiber Chow ad libitum, 150 g/day, 75 g/day, or 15 g/day on Gestation Days 6 to 18 inclusive. Prior to and after organogenesis the animals were provided food ad libitum (ad lib). Clinical observations, body weights, and food and water consumption were recorded daily. On Gestation Day 30 each doe was euthanatized and necropsied, and maternal and fetal data were collected. Each fetus was examined for external, visceral, and skeletal variations and malformations. Ossification parameters were also evaluated. Statistical analyses were conducted in two ways, first comparing the restricted groups to the ad lib group and second comparing the 15 and 75 g/day groups to the 150 g/day group. During Days 6-18, the 15 and 75 g/day groups had significantly decreased weight gain (actual weight loss), compared to the groups fed 150 g/day or ad lib. Water consumption was also significantly decreased in the 15 g/day group during this period, compared to the ad lib group. When food was provided ad lib on Days 19-30 to the restricted groups, weight gain was significantly higher in the 15 and 75 g/day groups than the group previously given 150 g/day and the ad lib group. There were no differences in water consumption during that period. Abortion occurred in three 15 g/day animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Homoeologous relationships of rice, wheat and maize chromosomes.

A set of cDNA clones, which had previously been mapped onto wheat chromosomes, was genetically mapped onto the chromosomes of rice. The resulting comparative maps make it possible to estimate the degree of linkage conservation between these two species. A number of chromosomal rearrangements, some of which must have involved interchromosomal translocations, differentiate the rice and wheat genomes. However, synteny of a large proportion of the loci appears to be conserved between the two species. The results of this study, combined with those from a recently published comparative map of the rice and maize genomes, suggest that rice, wheat and maize share extensive homoeologies in a number of regions in their genomes. Some chromosomes (e.g. chromosome 4 in rice, chromosomes 2 and 2S in wheat and maize, respectively) may have escaped major rearrangement since the divergence of these species from their last common ancestor. Comparative maps for rice, wheat and maize should make it possible to begin uniting the genetics of these species and allow for transfer of mapping information (including centromere positions) and molecular marker resources (e.g. RFLP probes) between species. In addition, such maps should shed light on the nature of chromosome evolution that accompanied the radiation of grasses in the early stages of plant diversification.

Chromosome Mapping↗

Effect of S-methyl cysteine sulphoxide and its metabolite methyl methane thiosulphinate, both occurring naturally in Brassica vegetables, on mouse genotoxicity.

S-methyl cysteine sulphoxide (SMCSO) and its metabolite methyl methane thiosulphinate (MMTSO), both naturally occurring compounds present in Brassica vegetables, were investigated for their putative ability to inhibit benzo[a]pyrene (B[a]P)-induced genotoxicity in ICR mice. The mouse bone marrow micronucleus assay was used as an indicator of in vivo genotoxicity. Doses of 0.5 mmol SMCSO and 0.05mmol MMTSO per kg body weight significantly inhibited the formation of B[a]P-induced micronucleated polychromatic erythrocytes (MPCEs) by 31 and 33%, respectively, compared with control mice. Two higher doses of MMTSO (0.5 and 1.0 mmol/kg body weight) administered to mice displayed severe acute toxicity. The inhibition of experimental genotoxicity by these two organosulphur compounds present in Brassica may, in part, be responsible for the anticarcinogenic effect of these vegetables.

Animals↗

A modified trichrome stain for light microscopic examination of plastic-embedded corneal tissue.

Corneal histopathology is essential to understanding the mechanisms of corneal disease and wound healing. We have developed a light microscopic trichrome stain for 1-micron, aldehyde-fixed, osmicated, epon/resin-embedded corneal sections. The stain consists of azure II, methylene blue, and basic fuchsin. This combination of stains provides a fast and effective method to clearly differentiate corneal cells from their surrounding extracellular matrix, and chromatically separates various ECM materials within the cornea. Correlative examination by light and transmission electron microscopy (TEM) provides multilevel understanding of corneal morphology and ultrastructure. Tissues examined using this staining procedure may be subsequently examined by TEM for ultrastructural morphology. This stain has proved beneficial in our research of both cellular and extracellular constituents of the cornea.

Adolescent↗

Smoking habits among physicians in two Gulf countries.

The smoking habit of physicians in United Arab Emirates (UAE) and Kuwait were studied as first step towards surveying the habit among medical professionals. A cross-sectional survey was conducted in Kuwait between January-June 1990. Out of the 300 physicians who were contacted 252 (84%) completed the questionnaires, 190 (75%) were males and 62 (25%) were females. Among male physicians, current smokers were 86 (45.3%), ex-smokers were 34 (17.9%) and non-smokers were 70 (36.8%), while among the female physicians 10 (16%) were smokers and 52 (84%) were non-smokers. Also, a cross-sectional study was conducted between December 1991-November 1992 to identify the extent of smoking among physicians in UAE. Of the 300 physicians, 275 (91.6%) responded, 214 (77.8%) were males and 61 (22.2%) were females. Among the males, current smokers were 94 (43.9%), ex-smokers were 32 (14.9%) and non-smokers were 88 (41.2%), while among the females 5 (8.2%) were smokers, 3 (4.9%) were ex-smokers and 53 (86.9%) were non-smokers. Most important factors responsible for non-smoking doctors for not taking up smoking were: 'Protection of health', 'Self-discipline' and 'To set a good example to others'. The majority of physicians in UAE (91.3%) and Kuwait (75.6%) strongly agreed that smoking is hazardous to health. The results revealed that less than 50% of physicians provide information to over 70% of smoking patients. The majority of physicians and health professionals were aware of association between smoking and various diseases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Requirement for vitamin A in long-term culture of human cornea.

PURPOSE: To develop an in vitro model for the study of vitamin A functions in the cornea by determining the morphologic responses to its absence and to the addition of varying concentrations in long-term (21-day) human organ culture. METHODS: Donor corneas were cultured for 21 days in an air-liquid environment designed to maintain normal corneal morphology in long-term culture. Corneas were graded by light microscopy and were further analyzed by transmission electron microscopy. RESULTS: Epithelium of human corneas cultured in the absence of vitamin A for 21 days showed characteristics of vitamin A deficiency: multilayering of squamous cells, bundling of tonofilaments to form keratofibrils, increased desmosomes, and loss of microplicae on the surface cells. The cells responded to the addition of vitamin A in concentrations ranging from 5 x 10(-9) to 5 x 10(-6) M. At the lowest concentration, cell differentiation and morphology appeared normal. Cells developed secretory morphology at higher concentrations of vitamin A, with intracellular vesicles, basement membrane overproduction, and reduced cell-cell and cell-substrate attachments. Keratocytes and endothelial cells showed increased intracellular vacuoles in the presence of higher concentrations of vitamin A. CONCLUSIONS: Cultured adult human corneas showed primary, dose-related responses to vitamin A in the absence of inflammatory, neuronal, or humoral factors. The epithelium was most sensitive to the absence of vitamin A and showed a dose-related response to additional vitamin A. All corneal cell layers showed morphologic changes at the highest concentration of vitamin A used.

Adult↗

Prevalence and risk factors for iron deficiency anemia in weanling rhesus macaques.

Standard epidemiologic methods were used to determine the prevalence and risk factors for iron deficiency at weaning in 143 weanling rhesus macaques (Macaca mulatta) raised indoors at the California Primate Research Center, Davis, CA. Maternal, infant, and management factors were investigated. Prevalence of iron deficiency anemia was 19%, as defined by mean corpuscular volume less than or equal to 66 femtoliters. It was found that animals raised entirely or partially in the nursery had less iron deficiency than dam-reared offspring. Results also suggest multiparous dams were more likely to have iron-deficient weanlings than primiparous dams. These results were discussed in relation to human and nonhuman primate pediatric medicine.

Anemia, Hypochromic↗

The niche of the gill parasite Dactylogyrus banghami (Monogenea: Dactylogyridae) on Notropis stramineus (Pisces: Cyprinidae).

Distribution of the monogenean Dactylogyrus banghami on the gills of the fish Notropis stramineus (Cyprinidae) was described by calculation of mean relative positions and Levins' niche breadths on the linear spatial resource gradients gill filament length and gill arch length. Thirty fish with 276 worms were examined; only 1 of the fish had an additional gill parasite species (Trichodina sp). Worms were more broadly and evenly distributed across the length of the gill arch than they were on the filament (breadths of 0.91 and 0.67, respectively). Mean worm positions were near the center of both resources: 54% of the distance from the arch cartilage on the filament, and 54% from the ventral end of the arch itself. The results are considered consistent with predictions about the niche structures of species in unsaturated noninteractive specialist communities.

Animals↗

Expression of an inward-rectifying potassium channel by the Arabidopsis KAT1 cDNA.

Inward-rectifying potassium channels located in the plasma membrane of higher plant and animal cells contribute to cellular homeostasis and excitability. The genes encoding this specific class of K+ channels have not been functionally identified. This report shows that a single messenger RNA transcript from the Arabidopsis thaliana KAT1 complementary DNA confers the functional expression of a hyperpolarization-activated K+ channel in Xenopus oocytes. The channels encoded by KAT1 are highly selective for K+ over other monovalent cations, are blocked by tetraethylammonium and barium, and have a single channel conductance of 28 +/- 7 picosiemens with 118 millimolar K+ in the bathing solution. These functional characteristics, typical of inward-rectifying K+ channels in eukaryotic cells, demonstrate that KAT1 encodes an inward-rectifying K+ channel.

Animals↗

Functional expression of a probable Arabidopsis thaliana potassium channel in Saccharomyces cerevisiae.

We report the isolation of a cDNA (KAT1) from Arabidopsis thaliana that encodes a probable K+ channel. KAT1 was cloned by its ability to suppress a K+ transport-defective phenotype in mutant Saccharomyces cerevisiae cells. This suppression is sensitive to known K+ channel blockers, including tetraethylammonium and Ba2+ ions. The KAT1 cDNA contains an open reading frame capable of encoding a 78-kDa protein that shares structural features found in the Shaker superfamily of K+ channels. These include a cluster of six putative membrane-spanning helices (S1-S6) at the amino terminus of the protein, a presumed voltage-sensing region containing Arg/Lys-Xaa-Xaa-Arg/Lys repeats within S4, and the highly conserved pore-forming region (known as H5 or SS1-SS2). Our results suggest that the structural motif for K+ channels has been conserved between plants and animals.

Amino Acid Sequence↗

Purification and properties of versiconal cyclase from Aspergillus parasiticus.

Versiconal cyclase catalyzes the dehydration of versiconal to versicolorin B or versicolorin C [versicolorin B(C)]. The enzyme was purified from mycelia of Aspergillus parasiticus by DEAE-cellulose, hydroxylapatite, and Mono Q column chromatography. The protein contains two identical subunits of molecular weight 72,000 per molecule of native protein. The pI of the enzyme is 3.95. The pH activity curve had a broad maximum with a peak at 5.5. The Km and Vmax for versiconal at 30 degrees C and pH 6.0 are 3.1 microM and 0.15 mumol min-1mg-1, respectively. Most of the formation of versicolorin B(C) in the cell is attributed to the action of versiconal cyclase.

Aflatoxins↗

Developmental toxicity of CI-921, an anilinoacridine antitumor agent.

CI-921, an anilinoacridine compound active against leukemic and solid tumors, was evaluated for potential developmental toxicity. Intravenous injections of CI-921 in dextrose were given to female Sprague-Dawley rats (0.1, 0.5, and 1.0 mg/kg) on Gestation Days (GD) 6-15 and to female New Zealand White rabbits (0.1, 1.0 and 2.0 mg/kg) on GD 6-18. Appropriate vehicle and untreated controls were included. Maternal and fetal parameters, including external, visceral, and skeletal malformations and variations, were assessed. Treatment of rats with 1.0 mg/kg resulted in maternal toxicity, manifested as reduced body weight gain and food consumption during and after treatment. Reduced fetal body weight, an increased incidence of stunted fetuses, malformations of the axial and appendicular skeleton, microphthalmia, and an increased number of anatomical variations (including anomalies of the axial skeleton and apparent hydronephrosis) also occurred in rats at 1.0 mg/kg. Treatment of rabbits resulted in no apparent maternal toxicity. However, reduced fetal body weight, agenesis of the azygous lobe of the lung, and an increased incidence of variations of the axial skeleton occurred at 2.0 mg/kg in rabbits. These results indicate that CI-921, at the highest dose tested in each species, produced developmental toxicity in the presence of maternal toxicity in rats, but in the absence of maternal toxicity in rabbits.

Abnormalities, Drug-Induced↗

Cutaneous xanthogranulomatous inflammation: a potential indicator of internal disease.

Cutaneous xanthogranulomatous inflammation is usually regarded as a primary disease process. We describe two patients with xanthogranulomatous pyelonephritis and nephro-cutaneous fistulae, one patient with xanthogranulomatous cholecystitis and a chole-cutaneous fistula and one patient with xanthogranulomatous appendicitis and appendiceal-cutaneous fistula. After the first case, awareness that cutaneous xanthogranulomatous inflammation can be secondary to related internal disease played a vital diagnostic role in the subsequent cases.

Aged↗