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Biomedical subjects

S B Wilson

Publications and source records attributed to S B Wilson.

At least 55 records · Page 3Linked to original sources

The effect of oxygen supplementation on post-occlusive reactive hyperaemia in human forearm skin.

The effects of raised tissue oxygen levels on reactive hyperaemia (RH) in the skin following arterial occlusion of short duration were investigated. Oxygen levels were increased by breathing 100% oxygen at 1 and 2 atmospheres absolute (ATA) in a hyperbaric chamber. Superficial skin blood flow and oxygen tension were measured throughout using a laser Doppler flowmeter and a transcutaneous oxygen monitor. The basal pre-occlusion and the maximum post-occlusion blood flows (Flb and Flmax), the time taken for flow to fall to half maximum (TR1/2), and the time for flow to return to its basal level (TR) were measured. Pre- and end-occlusion transcutaneous oxygen levels were also recorded. Oxygen breathing at 1 ATA significantly reduced TR1/2 (p less than 0.05) and at 2 ATA significantly reduced TR1/2 and TR (p less than 0.005 and p less than 0.0001) compared with control measurements during air breathing at 1 ATA. Flmax was not significantly reduced breathing oxygen at 1 or 2 ATA. These findings support the view that maximum post-occlusion blood flow in superficial skin is determined mainly by myogenic mechanisms, whereas the recovery of blood flow to basal levels is influenced largely by oxygen tension. We conclude that the direct vasoconstrictor effect of high oxygen levels is small and that the faster recovery at high tissue oxygen tensions may result from a decrease in vasodilators formed during hypoxia.

Adult↗

Quantification of sympathetic vascular responses in skin by laser Doppler flowmetry.

An improved physiological test of focal sympathetic nervous function using a laser Doppler flowmeter is presented. The test evaluates rapid reflex changes in skin blood flow at the finger tip where there are abundant arteriovenous anastomoses with dense sympathetic innervation. Indirect body heating was employed in all subjects to induce central vasodilation and to obtain stable comparable finger tip blood flows prior to stimulus. The reflex vasoconstriction which occurs following inspiratory gasp and contralateral hand cold challenge was quantified and its reproducibility investigated on three separate occasions in 20 young subjects. The variability in responses both within and between young subjects was small. The test was applied to 10 diabetic patients with autonomic neuropathy and to 10 age-matched control subjects. Vasoconstrictor reflexes were significantly lower in the diabetic group (p less than 0.005) with responses lower than 2 SD from the mean for age-matched controls. In conclusion, the test provides an assessment of focal autonomic damage which can be applied to other regions of the body rich in arteriovenous anastomoses and may have application in clinical studies investigating autonomic activity.

Adult↗

The plant mitochondrial F1-ATPase. The identity of the delta' (20 kDa) subunit.

The N-terminal amino acid sequence of the 20 kDa (delta') subunit of the turnip (Brassica napus L.) mitochondrial F1-ATPase has been determined. Comparison of the sequence obtained with those of the epsilon subunits of chloroplast CF1, E. coli F1 and the delta subunit of bovine F1 shows that the turnip delta' subunit is another member of this family of homologous proteins. The delta' subunit of sweet potato F1-ATPase [(1989) J. Biol. Chem. 264, 3183-3186] is very similar to the turnip sequence and thus can also be considered to belong to this family.

Amino Acid Sequence↗

Plant mitochondrial F1-ATPase. The presence of oligomycin-sensitivity-conferring protein (OSCP).

Purified pea (Pisum sativum) cotyledon F1-ATPase contains six subunits rather than the five usually reported for F1-ATPases. The additional 26.5 kDa (delta) subunit is shown by immunoblotting and N-terminal amino acid sequencing to be similar to bovine oligomycin-sensitivity-conferring protein (OSCP). It is concluded that the delta subunit of plant mitochondrial F1-ATPase is the plant OSCP. This OSCP subunit occurs in all mono- and di-cotyledonous species of plants tested (maize, oats, peas, potatoes, sweet potatoes and turnips).

Adenosine Triphosphatases↗

Dynamic thermographic imaging method for quantifying dermal perfusion: potential and limitations.

A new method of quantifying dermal perfusion on a regional basis using a dynamic thermographic technique is investigated. The technique is based on the relationship between dermal perfusion and the rate of skin surface reheating following the application of a transient cold challenge predicted by a theoretical model. Measurements were made using images from a Philips thermographic camera under rigorously controlled conditions. Experimentation on undisturbed volar forearm skin of normal subjects showed that measurements could be repeated with good accuracy but that differences in normalised reheat temperatures between subjects were highly dependent on subcutaneous fat thickness. Comparisons between normal and occluded forearms indicated that reheat temperatures were not sensitive to changes in low levels of dermal perfusion. Conversely, stimulation of dermal blood flow with prostaglandin E2 did produce significant differences from control conditions, but quantifying the extent of this hyperaemia was limited by the effects of intersubject variations in fat thickness. Quantifying skin blood flow from skin temperature reheat rates is shown to be limited by a lack of sensitivity and a dependence on subcutaneous fat thickness, although dynamic thermography is able to provide useful information on regional variations in skin perfusion which could not be reliably obtained from static temperature measurements alone.

Adult↗

Nutritional and hormonal regulation of the gene for avian malic enzyme.

This paper reviews work from our laboratory on the molecular mechanisms involved in the nutritional and hormonal regulation of avian malic enzyme. The activity of hepatic malic enzyme, one of the set of "lipogenic" enzymes, is high in well-fed chickens and low in starved chickens. In chick embryo hepatocytes in culture, insulin and triiodothyronine (T3) are positive effectors and glucagon, acting via cyclic AMP, is a negative effector. Hormone concentrations in blood are consistent with insulin and T3 playing the major positive roles, and glucagon a major negative role, in regulating hepatic malic enzyme activity during the transitions between the fed and the starved states. New results indicate that insulin-like growth factor 1 also stimulates accumulation of malic enzyme. Our strategy has been to trace the intracellular signalling pathway from its distal end, altered enzyme activity, towards its proximal end, interaction of humoral factors with their appropriate cellular receptors. Nutrition- and hormone-induced changes in malic enzyme activity are due to altered concentrations of malic enzyme protein which, in turn, are due to altered rates of synthesis of malic enzyme. Synthesis of malic enzyme is controlled by regulating the level of malic enzyme mRNA which, in turn is regulated at initiation of transcription. The next step in this analysis will be to identify cis-acting sequence elements in the malic enzyme gene which bestow upon it a selective response to nutritional state and hormones. We are using transient expression systems and avian retroviral vectors to test the function of cis-acting elements involved in the regulation of transcription.

Animal Nutritional Physiological Phenomena↗

The switching of electron flux from the cyanide-insensitive oxidase to the cytochrome pathway in mung-bean (Phaseolus aureus L.) mitochondria.

The activities of the mung-bean (Phaseolus aureus L.) mitochondrial cyanide-insensitive oxidase and cytochrome pathways have been measured simultaneously. The results show that electrons can be diverted both from the alternative pathway to the cytochrome pathway and from the cytochrome to the alternative pathway. The competition of the two pathways for the available electron flux is discussed.

Cytochromes↗

A tissue heat transfer model for relating dynamic skin temperature changes to physiological parameters.

A physical and mathematical model of the superficial tissues of the body is presented which takes into account tissue physiology, structure and blood supply. The model relates transient temperature changes at the skin surface to underlying physiological parameters. The analysis is based on a one-dimensional finite difference version of the bioheat equation applied to a multi-layered model of the superficial 10 mm of body tissue. Application of the model to the volar forearm predicts that under steady-state conditions skin surface temperature is maintained primarily by heat transfer from tissues below 10 mm, to a lesser extent by perfusion and to a small extent by superficial tissue metabolism. Model predictions of the reheat curve following a 15 s cold challenge to the skin agree closely with preliminary experimental data provided by thermography. The model also provides a physical explanation for the shape of the skin temperature reheat curve. Calculations further suggest that transient skin surface temperature measurements can provide a better indication of dermal perfusion than static temperature measurements as the effects of variations in environmental conditions, deep tissue temperature and tissue metabolism can be reduced.

Hot Temperature↗

Hormonal regulation of lipogenic enzymes in chick embryo hepatocytes in culture. Expression of the fatty acid synthase gene is regulated at both translational and pretranslational steps.

Mechanisms involved in the multihormonal regulation of fatty acid synthase have been investigated by comparing levels of its mRNA with rates of enzyme synthesis in chick embryo hepatocytes in culture. Triiodothyronine or insulin caused about a 2.5-fold increase in the relative rate of synthesis of fatty acid synthase. Together, these hormones were synergistic, stimulating enzyme synthesis by nearly 40-fold (Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332-344). Addition of triiodothyronine stimulated increases in mRNA levels comparable to increases in enzyme synthesis whether insulin was present or not. Thus, triiodothyronine regulates fatty acid synthase primarily by controlling the amount of its mRNA. Addition of insulin, in the presence of triiodothyronine, stimulated enzyme synthesis by 14-fold and mRNA levels by only 2-fold. In the absence of triiodothyronine, insulin had no effect on mRNA levels. Thus, insulin has a major effect on the translation of fatty acid synthase mRNA. After the addition of triiodothyronine, fatty acid synthase mRNA accumulated with sigmoidal kinetics, approaching a new steady state about 48 h after the addition of hormone. Puromycin, an inhibitor of protein synthesis, blocked the effect of triiodothyronine. We suggest that the abundances of both fatty acid synthase and malic enzyme mRNAs are regulated by a common triiodothyronine-induced peptide intermediate which has a relatively long half-life. Glucagon caused an 80% decrease in the synthesis of fatty acid synthase (Fischer, P.W.F., and Goodridge, A.G. (1978) Arch. Biochem. Biophys. 190, 332-344) and a 60% decrease in the level of fatty acid synthase mRNA. Thus, glucagon regulates fatty acid synthase by controlling the concentration of its mRNA. The synthesis of malic enzyme also was inhibited by glucagon at a pretranslational step, but the inhibition was almost complete. Thus, despite coordinated regulation of the concentrations of these enzymes during starvation and refeeding, individual hormones sometimes regulate synthesis of the two enzymes at the same step and to about the same degree and sometimes at different steps or to very different degrees.

Animals↗

Hormonal regulation of lipogenic enzymes in chick embryo hepatocytes in culture. Thyroid hormone and glucagon regulate malic enzyme mRNA level at post-transcriptional steps.

Mechanisms involved in stimulation of the synthesis of malic enzyme by insulin and triiodothyronine and in inhibition of synthesis by glucagon have been investigated by assessing levels and rates of synthesis of malic enzyme mRNA in chick embryo hepatocytes in culture. Insulin alone had no effect on the level of malic enzyme mRNA, whereas triiodothyronine by itself caused a 7-fold increase. Insulin plus triiodothyronine caused an 11-fold increase. Glucagon caused a 93% decrease in the accumulation of malic enzyme mRNA caused by insulin plus triiodothyronine. Although the relative changes in mRNA level are smaller in magnitude, they are qualitatively similar to the effects of these hormones on synthesis of malic enzyme, suggesting that control is exerted primarily at pretranslational steps. After addition of triiodothyronine, malic enzyme mRNA accumulated with sigmoidal kinetics, approaching a new steady state at 36-48 h after adding hormone. Puromycin, an inhibitor of protein synthesis, blocked the effect of triiodothyronine if added 30 min prior to the hormone and inhibited further accumulation of malic enzyme mRNA if added 24 h after triiodothyronine. However, puromycin had no effect on the level of beta-tubulin mRNA (t1/2 = 3-5 h), suggesting that the effect of triiodothyronine on malic enzyme mRNA required synthesis of a peptide. Triiodothyronine increased transcription of the malic enzyme gene by 2-fold and level of its mRNA by 11-14-fold, indicating regulation is primarily at a post-transcriptional step. Glucagon caused malic enzyme mRNA to decay with a half-life of 1.5 h, whereas alpha-amanitin or actinomycin D, inhibitors of transcription, caused the mRNA to decay with a half-life of 8-11 h. The effect of glucagon was entirely post-transcriptional because the hormone had no effect on transcription. Taken together, these results suggest a model in which triiodothyronine regulates production of a peptide that stabilizes malic enzyme transcripts in the cytoplasm and/or nucleus. Glucagon may inhibit activity of the peptide induced by triiodothyronine.

Amanitins↗

Regulation of genes for enzymes involved in fatty acid synthesis.

The levels of malic enzyme and fatty acid synthase are increased by feeding and decreased by starvation in liver in vivo and are increased by triiodothyronine and decreased by glucagon in hepatocytes in culture. Cloned malic enzyme and fatty acid synthase cDNAs are being used to analyze regulation of these unique genes. Dietary regulation of both enzymes occurs at pretranslational steps. Increased transcription and increased mRNA stability contribute about equally to a 20-fold increase in malic enzyme mRNA level when starved ducklings are refed. In contrast, a 10-fold increase in the level of fatty acid synthase mRNA is largely accounted for by increased transcription of this gene. In chick-embryo hepatocytes incubated in serum-free medium containing insulin, triiodothyronine causes a greater than 10-fold increase in levels of both malic enzyme and fatty acid synthase mRNAs. Kinetic and inhibitor experiments suggest a protein intermediate in the increases of malic enzyme and fatty acid synthase mRNAs caused by triiodothyronine. For malic enzyme, the stimulation by triiodothyronine is predominantly posttranscriptional. Glucagon decreases the level of malic enzyme mRNA by 90 to 95%, with regulation occurring at a posttranscriptional step. Inhibitor experiments suggest that stimulation of the degradation of malic enzyme mRNA is partially responsible. Glucagon inhibited fatty acid synthase mRNA level by less than 50%; the inhibited step has not been identified. Thus, the coordinated regulation of malic enzyme and fatty acid synthase proteins by nutritional state may involve different hormones regulating at different points. A surprisingly large component of the regulation is posttranscriptional.

Animals↗

Cadmium-binding proteins in the scallop Pecten maximus.

Scallops, Pecten maximus, accumulate cadmium naturally in the digestive gland to a level of approximately 100 ppm wet weight. Of this cadmium, 60% was soluble and was composed of three weight classes as judged by Sephadex G-100 chromatography. Of the soluble cadmium, 60% was in the 55,000 molecular weight range and 20% each in an excluded fraction and a 10,000 molecular weight fraction. The 55,000 molecular weight fraction, after further purification, showed a maximum cadmium concentration of 1.4% by weight. The cadmium was thiolate bound but not as strongly bound as in the case of metallothionein. The 10,000 molecular weight fraction was a metallothionein-like protein.

Amino Acids↗

The influence of the polyphenols of cider on plasmin and plasminogen activators.

Preliminary findings suggested that the inhibitory activity on fibrinolysis produced by most varieties of cider is due to their content of polyphenols. In particular, the inhibitory activity co-eluted with the brown coloration on gel filtration, was removed by adsorption with polyvinylpyrrolidine, and was greatly reduced in a type of cider with a low concentration of phenolic compounds. The individual polyphenols of apple juice and ciders were examined for their ability to inhibit tissue activator, urokinase and plasmin. Neither phloridzin nor chlorogenic acid had any inhibitory activity at concentrations of 500 micrograms/ml while epicatechin had only a slight inhibitory effect at this concentration. The procyanidin fractions were markedly inhibitory on urokinase-induced clot lysis, the amidolytic activity of plasmin and on the fibrinolytic activities of plasmin, urokinase and tissue activator on fibrin plates: inhibition was noted at concentrations as low as 0.25 micrograms/ml. The order of inhibition was polymer greater than oligomer greater than trimer greater than dimer.

Alcoholic Beverages↗

Platelet antibodies of the IgM class in immune thrombocytopenic purpura.

The clinical course and response to therapy of patients with immune thrombocytopenic purpura (ITP) are not completely determined by the level of IgG present on the platelet surface. It is possible that antibodies of other immunoglobulin classes also play a role in platelet destruction in some of these patients. Therefore, we studied 175 patients with ITP for the presence of IgM anti-platelet antibodies using radiolabeled polyclonal or monoclonal anti-IgM. We observed that 57% of patients with clinical ITP had increased levels of IgM on their platelets, compared with normal controls and patients with thrombocytopenia who did not have ITP (less than 10%), (P less than 0.01). We obtained similar results using either radiolabeled polyclonal or monoclonal anti-IgM, reagents whose integrity was first characterized using erythrocytes coated with defined amounts of IgM antibody. Among patients with increased platelet-IgM there was a significant correlation both with the presence of increased platelet-C3 as well as the amount of platelet-C3 (P less than 0.01, r = 0.53). We demonstrated the presence of warm-reacting IgM anti-platelet antibodies in the plasma of two of these patients who were further studied. The isolated IgM fraction from these two plasmas was able to activate complement and place 3H-C3 on normal platelets. These studies demonstrate the presence of warm-reacting IgM anti-platelet antibodies in some patients with ITP. They suggest that the binding of complement to platelets by IgM antibodies may initiate platelet clearance as well as enhance the effect of IgG antibodies in ITP.

Autoantibodies↗

Concentration-time course of niridazole and six metabolites in the serum of four Filipinos with Schistosoma japonicum infection.

Niridazole and six of its metabolites have been quantitated by high-pressure liquid chromatography in sera of four male Filipino patients with mild Schistosoma japonicum infections given single oral doses of niridazole (15 mg/kg) on two occasions 10 days apart. Of the five oxidative metabolites measured, 4-hydroxyniridazole and 4-ketoniridazole achieved the highest concentrations, reaching peak values of 0.9 +/- 0.3 microgram/ml of serum (mean +/- S.D., n = 4) and 0.7 +/- 0.1 microgram/ml of serum within 1 to 4 hr. 4-Ketoniridazole achieved peak serum levels 1 hr after the other oxidative metabolites in three of four patients and was the predominant metabolite in the serum of all patients 6 to 10 hr after dosing. By 24 hr, both 4-ketoniridazole and 4-hydroxyniridazole had largely disappeared from the serum. Niridazole and three other oxidative metabolites, 4,5-dihydroxyniridazole, 5-hydroxyniridazole and 4,5-dehydroniridazole, appeared within 1 hr in serum but failed to exceed 0.4 microgram/ml; none of these compounds were detected in the 24-hr serum samples. The pharmacokinetic pattern of niridazole and the oxidative metabolites showed marked interindividual variation but was quite reproducible in the same individual studied 10 days later. 1-Thiocarbamoyl-2-imidazolidinone was analyzed in serum samples by a different high-pressure liquid chromatographic procedure. This reductive metabolite attained maximal levels of 50 to 150 ng/ml of serum 6 to 12 hr after drug administration and remained at 40% or more of its peak concentration even after 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Hope Index Scale: an instrument for the objective assessment of hope.

Although many clinical observations suggest that Hope influences the onset, duration, prognosis, and recovery from mental and physical illnesses, a lack of direct scientific proof persists because no method exists for the objective assessment of hope. We have now constructed the Hope Index Scale, a testing instrument for the measurement of this rather elusive human attribute. Upon testing control and experimental subjects, it was found that score distribution on the Hope Index Scale correlates negatively with Beck's Hopelessness Scale (Pearson r = -.88, P <.001) and is independent of age, race, or sex. It is concluded that this tool can help identify individuals with varying degrees of psychosocial problems and that scores of 150 or below are indicative of pathologic hope deficit often associated with suicide.

Adult↗

Energy conservation by the plant mitochondrial cyanide-insensitive oxidase. Some additional evidence.

Several measures of energy conservation, namely ADP/O ratio, P/O ratio, ATP/O ratio and phosphorylation detected by continuous assay with purified firefly luciferase and luciferin, all show phosphorylation can occur with mung-bean mitochondria at cyanide concentrations sufficient to inhibit the cytochrome oxidase system. Phosphorylation in the presence of cyanide is uncoupler- oligomycin- and salicylhydroxamate-sensitive. The participation of phosphorylation site 1 is excluded, phosphorylation being attributable to a single phosphorylation site associated with the cyanide-insensitive oxidase. The cyanide-insensitive oxidase has also been shown to support a variety of other energy-linked functions, namely, Ca2+ uptake, reversed electron transport and the maintenance of a membrane potential detected by the dye probes 8-anilinonaphthalene-1-sulphonate and safranine. High concentrations of cyanide have uncoupler-like activity, decreasing the ADP/O ratio and the t 1/2 for the decay of a pH pulse through the the mitochondrial membrane. This uncoupler-like effect is most marked with aged mitochondria. The observations of energy conservation attributable to the cyanide-insensitive oxidase are compared with other reports where it is concluded that the alternative oxidase is uncoupled.

Adenosine Triphosphate↗