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Biomedical subjects

D S Williams

Publications and source records attributed to D S Williams.

At least 109 records · Page 6Linked to original sources
PubMed1991

Effect of cyclosporine on hepatic energy status and on fructose metabolism after portacaval shunt in dog as monitored by phosphorus-31 nuclear magnetic resonance spectroscopy in vivo.

The effect of cyclosporin A on the hepatic energy status and intracellular pH of the liver and its response to a fructose challenge has been investigated using in vivo phosphorus-31 nuclear magnetic resonance spectroscopy in dogs. Three experimental groups were studied: (a) control dogs (n = 5), (b) dogs 4 days after the creation of an end-to-side portacaval shunt (n = 5), and (c) dogs 4 days after portacaval shunt and continuous infusion of cyclosporin A (4 mg/kg/day) by way of the left portal vein (portacaval shunt plus cyclosporin A, n = 5). The phosphorus-31 nuclear magnetic resonance spectra were obtained at 81 MHz using a Bruker BIOSPEC II 4.7-tesla nuclear magnetic resonance system equipped with a 40-cm horizontal bore superconducting solenoid. The phosphomonoesters (p less than 0.01), inorganic phosphate and ATP levels (p less than 0.05) were decreased significantly in portacaval shunt-treated and in portacaval shunt-plus-cyclosporin A-treated dogs compared with unshunted control dogs. After a fructose challenge (750 mg/kg body wt, intravenously), fructose-1-phosphate metabolism was reduced in portacaval shunt-treated dogs compared with either the normal or portacaval shunt-plus-cyclosporin A-treated dogs (p less than 0.05). Both portacaval shunt- and portacaval shunt-plus-cyclosporin A-treated dogs demonstrated a reduced decline in ATP levels after fructose infusion when compared with the controls (p less than 0.05). Immediately after the fructose challenge, the intracellular pH decreased from 7.30 +/- 0.03 to 7.00 +/- 0.05 in all animals (p less than 0.01) and then gradually returned to normal over 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

Cytoskeletal components of the adherens junctions between the photoreceptors and the supportive Müller cells.

The outer limiting "membrane" (OLM) of the vertebrate retina comprises a series of heterotypic adherens junctions between the photoreceptors and the supportive Müller cells. These junctions appear to support the photoreceptors, which in teleosts, anurans, and birds are motile, and thus help them maintain their orientation with respect to incoming light. In an unusual role for this type of junction, they also provide a semipermeable barrier, preventing the diffusion of some proteins out of the extracellular space that surrounds the inner and outer segments of the photoreceptors. Using immunoelectron microscopy, we examined the association of actin, myosin, alpha-actinin, and vinculin with the OLM junctions of the adult chicken retina. Vinculin was detected close to the plasma membrane in the cytoplasmic plaques of the junctions, as it was in the adherens junctions of the retinal epithelium. Labelling of actin, myosin, and alpha-actinin was spread more throughout the plaques and was distributed unevenly about the junctions; labelling was much more extensive in the Müller cells than in the photoreceptors. Thus, the junctions of the OLM show similarity to the other adherens junctions in that their cytoplasmic plaques contain actin, myosin, alpha-actinin, and vinculin. But the large aggregation of actin, myosin, and alpha-actinin in the Müller cells, and their resulting asymmetrical distribution about the junctions, is unusual, and possibly an adaptation for the special function of the OLM junctions, in providing both structural support for the motile photoreceptors and a semipermeable barrier.

Actins↗
PubMed1990

Nuclear magnetic resonance determination of flow, lactate, and phosphate metabolites during amphetamine stimulation of the rat brain.

The effects of amphetamine on rat cerebral blood flow, lactate, and phosphate levels were studied using in vivo nuclear magnetic resonance (NMR) spectroscopy. Proton NMR imaging was used to determine the region of brain being studied. Blood flow was estimated by detecting the washout of trifluoromethane using 19F NMR. A dose of 20 mg/kg D-amphetamine sulphate stimulated flow fourfold over control values for at least 1 h. Even though amphetamine stimulated a large increase in flow, there were no significant changes in levels of inorganic phosphate, ATP, phosphocreatine, pH or Mg2+ as determined by 31P NMR. This was true for doses of 10 and 20 mg/kg D-amphetamine sulphate. No significant changes occurred in 1H NMR detected levels of lactate with a 20 mg/kg dose of amphetamines. Lactate levels increased slightly 30 min after administration of 10 mg/kg D-amphetamine sulphate. The results call into question the central role of changes in levels of phosphates in coupling increased cortical activity to increases in metabolism.

Amphetamine↗
PubMed1990

Absence of pH changes during altered work in the in vivo sheep heart: a 31P-NMR investigation.

Saturation transfer from gamma-ATP to inorganic phosphate was used to assign the intracellular inorganic phosphate resonance of the phosphorus-31 nuclear magnetic resonance spectrum of heart obtained from adult sheep under Halothane anesthesia. The 31P chemical shift of intracellular inorganic phosphate was then used as a probe of myocardial pH. Resting myocardial pH was found to be 7.03 +/- 0.02. The effects of increasing myocardial work on myocardial pH were examined using external pacing and phenylephrine infusion alone or in combination to produce steady-state increases in the rate-pressure product. No alteration in myocardial pH was observed with up to 4-fold increases in rate-pressure product. No changes in high-energy phosphates were observed except at the highest rate-pressure products obtained, where small increases in inorganic phosphate and decreases in the phosphocreatine/ATP ratio were observed. In addition, the transition to a new steady state was studied with a 20-s time resolution after initiation of pacing. Again, no changes in pH or levels of phosphates were detected during the transition to increased work.

Adenosine Triphosphate↗
PubMed1990

The effect of olestra on systemic levels of oral contraceptives.

The effect of olestra, a nonabsorbable, noncaloric fat replacement, on the absorption and efficacy of a highly lipophilic oral contraceptive was investigated in a double-blind, placebo-controlled crossover study with 28 women. Subjects consumed 18 gm/day olestra for 28 days while taking an oral contraceptive containing 300 micrograms of norgestrel and 30 micrograms ethinyl estradiol (Lo/Ovral-28). Blood taken on days 12 to 14 of the treatment cycles was analyzed for ethinyl estradiol and norgestrel. There was no statistically significant difference in time to attain maximum concentration, maximum concentration, or area under the concentration-time curve between the olestra and placebo treatments for either drug component. Measurements of serum progesterone indicated that olestra ingestion did not reduce efficacy as indicated by ovulation. The data show that ingestion of 18 gm/day olestra did not affect the absorption or efficacy of the highly lipophilic oral contraceptive.

Adult↗
PubMed1990

Identification of actin filaments in the rhabdomeral microvilli of Drosophila photoreceptors.

The phototransductive microvilli of arthropod photoreceptors each contain an axial cytoskeleton. The present study shows that actin filaments are a component of this cytoskeleton in Drosophila. Firstly, actin was detected in the rhabdomeral microvilli and in the subrhabdomeral cytoplasm by immunogold labeling with antiactin. Secondly, the rhabdomeres were labeled with phalloidin, indicating the presence of filamentous actin. Finally, the actin filaments were decorated with myosin subfragment-1. The characteristic arrowhead complex formed by subfragment-1 decoration points towards the base of the microvilli, so that the fast growing end of each filament is at the distal end of the microvillus, where it is embedded in a detergent-resistant cap. Each microvillus contains more than one actin filament. Decorated filaments extend the entire length of each microvillus and project into the subrhabdomeral cytoplasm. This organization is comparable to that of the actin filaments in intestinal brush border microvilli. Similar observations were made with the photoreceptor microvilli of the crayfish, Procambarus. Our results provide an indication as to how any myosin that is associated with the rhabdomeres might function.

Actin Cytoskeleton↗
PubMed1990

Clostridium aldrichii sp. nov., a cellulolytic mesophile inhabiting a wood-fermenting anaerobic digester.

An anaerobic, mesophilic, spore-forming, cellulolytic bacterium was repeatedly isolated from a wood-fermenting anaerobic digester. Cells of this organism were gram-positive rods, motile with a bundle of polar flagella, and formed subterminal oblong spores. The colonies in agar had an irregular shape with many platelike structures and were greyish white. Cellulose, xylan, and cellobiose served as substrates for growth. Acetate, propionate, butyrate, isobutyrate, isovalerate, lactate, succinate, H2, and CO2 were products of cellobiose fermentation. The optimal temperature and pH for growth were 35 degrees C and 7, respectively. The DNA composition was 40 mol% G + C. The name Clostridium aldrichii sp. nov. is proposed. The type strain is P-1 (= OGI 112, = ATCC 49358).

Bacteria, Anaerobic↗
PubMed1989

Organization of actin filaments and immunocolocalization of alpha-actinin in the connecting cilium of rat photoreceptors.

A small discrete concentration of actin filaments in the connecting cilium of vertebrate photoreceptors appears to have a role in the morphogenesis of the phototransductive disk membranes (Williams et al., '88). We have visualized these actin filaments in rat rod photoreceptors by decorating them with myosin subfragment-1. At the site of disk morphogenesis, we observed a cluster of short filaments, with various orientations and their faster growing (barbed) ends at the ciliary plasma membrane. Their association with the liplike structure of an early nascent disk is consistent with their apparent involvement in the initiation of disk morphogenesis. A few longer decorated filaments extended along the core the connecting cilium, away from the site of disk morphogenesis, implying that they might have some function other than the shaping of a new disk. Most of the antiactin label was found in the region of the short filaments. The alpha-actinin immunolabel coincided with that of actin, suggesting that the filaments may be crosslinked by alpha-actinin.

Actinin↗
PubMed1989

Isolation of rod outer segments on Percoll gradients: effect of specific protease inhibition.

Rat rod outer segments (ROSs) were isolated by vortexing retinas and separating the detached components on performed Percoll gradients. A lighter band of 20 x 10(6) unsealed ROSs per ten retinas, and a heavier band of 60 x 10(6) sealed ROSs per ten retinas were obtained from each 12 ml gradient. The yield of sealed ROSs (but not unsealed ROSs) was increased up to twofold in the presence of the specific cysteine protease inhibitor, Ep-475. Aprotinin, pepstatin, PMSF, TPCK and EGTA plus EDTA had no effect. These results indicate that during isolation, ROSs are vulnerable to damage by cysteine protease activity either from damaged retinal cells or from within.

Animals↗
PubMed1988

Disruption of microfilament organization and deregulation of disk membrane morphogenesis by cytochalasin D in rod and cone photoreceptors.

Morphogenesis of photoreceptor outer segment disks appears to occur by an evagination of the ciliary plasma membrane (Steinberg et al., J Comp Neurol 190:501-519, '80). We tested if polymerized actin (F-actin) was necessary for the regulation of this postulated process by incubating Xenopus eyecups with 5 or 25 microM cytochalasin D for 6-28 hours. During the second hour, the incubation medium contained 3H-leucine. Both concentrations of cytochalasin resulted in: 1) dissolution of the rhodamine-phalloidin labeling pattern of photoreceptors, and 2) collapse of the calycal processes (which are normally filled with actin filaments) and disappearance of the inner segment microfilaments. In addition, the few most basal rod and cone outer segment disks appeared several times their normal diameter. These oversized disks had incorporated 3H-leucine and extended along the margin of the outer or inner segment. The nature of the overgrown disks is consistent only with a morphogenetic process involving evaginations of the ciliary plasma membrane. Deregulation by cytochalasin D was manifest by excessive growth of a few nascent disks rather than normal growth of many. Therefore, the normal network of actin filaments is apparently not necessary for continued evagination of the membrane, but it does seem to be an essential part of the mechanism that initiates the evagination of the ciliary plasma membrane and/or the mechanism that controls how far nascent disks grow.

Actin Cytoskeleton↗
PubMed1988

31P NMR measurements of myocardial pH in vivo.

A 31P NMR magnetization transfer method for measuring myocardial pH in vivo is demonstrated in the lamb, dog and cat. The method involves measuring the difference in chemical shift between the resonances of phosphocreatine and inorganic phosphate in magnetization transfer difference spectra in which the gamma-phosphate resonance of ATP has been saturated. The method has been verified by measuring the chemical shift difference between the resonances of 2-deoxyglucose 6-phosphate and phosphocreatine following infusion of the animals with 2-deoxyglucose. The measured pH values are significantly lower than those obtained in previous studies on the heart in vivo.

Animals↗
PubMed1988

Tunicamycin-induced degeneration in cone photoreceptors.

Tunicamycin (TM), an inhibitor of dolichylphosphate-mediated protein glycosylation, was injected intravitreally into the eyes of diurnal rodents with cone-dominated retinas. Injection of 1 microgram of the B2 isomer led to a progressive degeneration of the photoreceptor outer segments and disruption of the RPE-photoreceptor interface that took place over a 10-day period. Cone outer segments were shortened by postinjection day 6 and virtually absent by day 9. The microvilli that normally protrude from the apical surface of the retinal pigment epithelium were replaced by a fringe of shortened processes. The other retinal layers showed no morphological evidence of disruption. Retinal sensitivity, as measured by electroretinographic b-wave threshold, showed a significant and progressive decline over the 10-day course of the experiment that paralleled the disruption of retinal morphology. These results suggest that TM leads to similar morphological and electrophysiological effects on rod and cone photoreceptors.

Animals↗
PubMed1987

Identification of a peanut agglutinin-binding protein from human retina.

With the use of an antiserum raised to peanut agglutinin (PNA)-binding protein(s) from human retinas, we have identified a glycoprotein that has the same subunit molecular weight (135,000) as human interphotoreceptor retinol-binding protein (IRBP) on human retinal protein transblots, and, like IRBP, is localized in the interphotoreceptor matrix surrounding both rods and cones. We show that this PNA-binding protein is not IRBP by comparing the binding patterns of antiserum to the PNA-binding protein to binding patterns obtained with antisera to bovine and monkey IRBP.

Arachis↗
PubMed1987

Photoreceptor degeneration in a pure-cone retina. Effects of cyclic nucleotides, and inhibitors of phosphodiesterase and protein synthesis.

Previous studies have shown that disruption of cyclic nucleotide metabolism by phosphodiesterase inhibitors and cyclic nucleotide analogues damages photoreceptors in rod-enriched retinae. In these studies the cone photoreceptors appeared damaged only after the surrounding rods had begun to degenerate. Our aim was to test if cone photoreceptors were susceptible to similar treatments in the absence of rod photoreceptors. We treated pure-cone lizard retinae in an in vitro eyecup preparation. Degeneration of the cones was induced by 10(-3) M, but not 10(-5) M, of the phosphodiesterase inhibitor, isobutylmethylxanthine (IBMX). Changes in the morphology of the cone outer segments were first evident after 10 hr at 24 degrees C. After longer exposures, other retinal cells were also affected. Before morphology was affected, synthesis of proteins of all molecular weights was inhibited throughout the retina. In addition, both retinal cyclic AMP and cyclic GMP levels were elevated, particularly after 2-10 hr. The effects of 10(-3) M IBMX on all of these parameters were still reversible by removal from IBMX after 10 hr. Dibutyryl cyclic AMP at 10(-2) M also inhibited protein synthesis. It also induced degeneration, but less rapidly than 10(-3) M IBMX. Dibutyryl cyclic GMP (10(-2) M) or butyric acid did not significantly affect morphology, or inhibit uptake or incorporation of 3H-leucine by retinae. The concentration of puromycin or cycloheximide that inhibited retinal protein synthesis by the same amount as 10(-3) M IBMX did not affect retinal morphology or cyclic nucleotide levels. One hundred times this concentration induced pyknosis in the nuclear layers of the retina before disturbing cone outer segment organization. In conclusion, millimolar IBMX and dibutyryl cyclic AMP damage cones even without neighboring rods, indicating that elevated cyclic nucleotide levels are toxic to cones per se. Retinal protein synthesis is also inhibited by damaging levels of cyclic nucleotides, but it does not seem to be responsible for the deterioration of cone structure.

1-Methyl-3-isobutylxanthine↗