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Biomedical subjects

M Midgley

Publications and source records attributed to M Midgley.

At least 37 records · Page 2Linked to original sources

Characteristics of ethidium uptake by the trypanosomatid flagellates Crithidia fasciculata and Leptomonas seymouri.

The uptake of the phenanthridinium ethidium by the trypanosomatids Crithidia fasciculata and Leptomonas seymouri was studied. The time course of uptake of ethidium was biphasic for both organisms, consisting of an initial rapid phase and a protracted slow phase. The characteristics of these phases were consistent with the hypothesis that the initial phase represented specific external binding, while the second phase represented transport into the cells. In L. seymouri the transport phase was inhibited by inhibitors of energy transduction and putative inhibitors of a transport ATPase. Ethidium transport could not be saturated over a large concentration range of ethidium. Phenanthridiniums and related compounds displayed both inhibitory and stimulatory effects on ethidium transport.

Adenosine Triphosphatases↗

Transport of alpha-aminoisobutyrate into Trypanosoma brucei brucei.

The uptake of alpha-aminoisobutyrate (AIB) by washed cell suspensions of bloodstream forms of Trypanosoma brucei brucei has been shown to be an energy-dependent process. No metabolism of AIB was detected under conditions leading to a 100-fold accumulation of AIB within the organism. Kinetic studies revealed that AIB uptake involved two components; that operating at low substrate concentrations had an apparent Km of 4.6 mM. Experiments with ionophores such as gramicidin and carbonylcyanide m-chlorophenylhydrazone were consistent with the AIB uptake system operating as a H+-symporter responding to the electrochemical gradient of H+, the major component of which was the membrane potential.

Aminoisobutyric Acids↗

Sociobiology.

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Biological Evolution↗

Further evidence for the existence of a membrane potential in Trypanosoma brucei brucei.

The distribution of 137Cs+, in the presence of valinomycin, has been used to measure the magnitude of the membrane potential (delta psi) in bloodstream forms of Trypanosoma brucei brucei. Values of the delta psi falling in the range -100 mV to -160 mV were observed and the maintenance of this delta psi was sensitive to certain ionophores and protonophores.

Animals↗

Effect of starvation on transport, membrane potential and survival of Staphylococcus epidermidis under anaerobic conditions.

When washed suspensions of Staphylococcus epidermidis were starved under anaerobic conditions the viability declined to less than 10% within 12 h. Although RNA was slightly degraded during this period the principal substrate for endogenous metabolism was protein and the intracellular amino acid pool. The adenylate energy charge and the ability to transport serine declined markedly within the first 6 h of starvation. With the majority of batches of organism investigated the membrane potential, as measured by the accumulation of Cs+ by valinomycin-treated organisms, also decreased significantly during this period. Addition of glucose or serine during starvation reversed these effects to varying extents provided that feeding took place during an early phase (2 h) of starvation. There was no apparent correlation between the magnitude of the membrane potential and viability.

Adenosine Triphosphate↗

The transport of alpha-aminoisobutyrate into Crithidia fasciculata.

The transport of alpha-aminoisobutyrate into Crithidia fasciculata was characterized under aerobic and anaerobic conditions. Kinetic data for alpha-aminoisobutyrate transport were consistent with the operation of a single system of broad specificity that showed no marked dependence on Na+. Under anaerobic conditions alpha-aminoisobutyrate transport was inhibited by uncouplers such as 2,4-dinitrophenol, lipophilic cations such as methyltriphenylphosphonium ion and adenosine triphosphatase inhibitors such as dicyclohexylcarbodi-imide and NaN3. A working model in which alpha-aminoisobutyrate enters this organism by an H+-symport mechanism, the electrochemical gradient of protons being maintained by an H+-translocating adenosine triphosphatase on the cytoplasmic membrane, is proposed.

Aerobiosis↗

Transport of alpha-aminoisobutyrate by cells and membrane vesicles of Pseudomonas fluorescens.

The transport of alpha-aminoisobutyrate into Pseudomonas fluorescens NCIB 8865 and membrane vesicles prepared from this organism has been studied. Uptake by cells was mediated by two active transport systems with different apparent Km values, while transport into membrane vesicles was mediated by a single component. The effect of inhibitors on the energy-coupling mechanism for alpha-aminoisobutyrate transport in these systems suggests that a membrane potential may play a significant role in supporting alpha-aminoisobutyrate transport. The magnitude of the membrane potential in the vesicle system, and the sensitivity of its generation to inhibitors, has been measured using 137Cs in the presence of valinomycin. Direct attempts to demonstrate a protonsymport mechanism for alpha-aminoisobutyrate transport were negative.

Aminoisobutyric Acids↗

Anaerobic transport of serine and 2-aminoisobutyric acid by Staphylococcus epidermidis.

A membrane-bound ATPase detected in extracts of anaerobically grown Staphylococcus epidermidis was inhibited by a variety of compounds which inhibit ATPases in other organisms. Serine and 2-aminoisobutyric acid (AIB) were shown to enter the organism via the same transport system. The transport of AIB, the membrane potential and the transmembrane pH gradient were partially or completely abolished by the same inhibitors and also by uncoupling agents and lipid-soluble ions. It is proposed therefore that this ATPase generates and maintains an electrochemical gradient of protons across the cytoplasmic membrane of S. epidermidis capable of driving AIB uptake. Studies of AIB-induced proton movements suggested that AIB enters via a proton symport mechanism.

Adenosine Triphosphatases↗

Localization and possible role of an adenosine triphosphatase in Chlorobium thiosulfatophilum.

1. Evidence is presented that the ATPase activity detected in cell extracts of Chlorobium thiosulfatophilum is bound to the cytoplasmic membrane rather than to the chlorobium vesicles. 2. The activity of this ATPase is inhibited in vitro by various carbodiimides, phloridzin and sodium azide. 3. The apparent Km for ATP is approximately 0.2 mM and the enzyme shows product inhibition by ADP. 4. Photophosphorylation, characterized in vivo, is inhibited by many of the compounds that inhibit the ATPase.

Adenosine Diphosphate↗

The regulation of transport of glucose, gluconate and 2-oxogluconate and of glucose catabolism in Pseudomonas aeruginosa.

1. The induction by glucose and gluconate of the transport systems and catabolic enzymes for glucose, gluconate and 2-oxogluconate was studied with Pseudomonas aeruginosa PAO1 growing in a chemostat under conditions of nitrogen limitation with citrate as the major carbon source. 2. In the presence of a residual concentration of 30mM-citrate an inflowing glucose concentration of 6-8 mM was required to induce the glucose-transport system and associated catabolic enzymes. When the glucose concentration was raised to 20mM the glucose-transport system was repressed, but the transport system for gluconate, and at higher glucose concentrations, that for 2-oxogluconate, were induced. No repression of the glucose-catabolizing enzymes occurred at the higher inflowing glucose concentrations. 3. In the presence of 30mM-citrate no marked threshold concentration was required for the induction of the gluconate-transport system by added gluconate. 4. In the presence of 30mM-citrate and various concentrations of added glucose and gluconate, the activity of the glucose-transport system accorded with the proposal that a major factor concerned in the repression of this system was the concentration of gluconate, produced extracellularly by glucose dehydrogenase. 5. This proposal was supported by chemostat experiments with mutants defective in glucose dehydrogenase. Such mutants showed no repression of the glucose-transport system by high inflowing concentrations, but with a mutant apparently defective only in glucose dehydrogenase, the addition of gluconate caused repression of the glucose-transport system. 6. Studies with the mutants showed that both glucose and gluconate can induce the enzymes of the Entner-Doudoroff system, whereas for the induction of the gluconate-transport system glucose must be converted into gluconate.

Citrates↗

The role of glucose limitation in the regulation of the transport of glucose, gluconate and 2-oxogluconate, and of glucose metabolism in Pseudomonas aeruginosa.

The pathway of glucose metabolism in Pseudomonas aeruginosa was regulated by the availability of glucose and related compounds. On changing from an ammonium limitation to a glucose limitation, the organism responded by adjusting its metabolism substantially from the extracellular direct oxidative pathway to the intracellular phosphorylative route. This change was achieved by repression of the transport systems for gluconate and 2-oxogluconate and of the associated enzymes for 2-oxogluconate metabolism and gluconate kinase, while increasing the levels of glucose transport, hexokinase and glucose 6-phosphate dehydrogenase. The role of gluconate, produced by the action of glucose dehydrogenase, as a major inhibitory factor for glucose transport, and the possible significance of these regulatory mechanisms to the organism in its natural environment, are discussed.

Alcohol Oxidoreductases↗

The regulation of transport of glucose and methyl alpha-glucoside in Pseudomonas aeruginosa.

The methyl alpha-glucoside-transport system of Pseudomonas aeruginosa has been characterized with respect to its specificity, energy-dependence, kinetics and regulation. The uptake of glucose involved two components, one of which transported glucose (K(m)=8mum) and methyl alpha-glucoside (K(m)=2.8mm) whereas the other was more complex, involving the extracellular activity of glucose dehydrogenase. Mutants defective in this enzyme have been isolated and characterized. The methyl alpha-glucoside-glucose-transport system was repressed when the organism was grown in the absence of glucose; the induction of this transport system by glucose, and its activity once induced, were inhibited by products of citrate metabolism.

Azides↗

Within-program factors as predictors of drinking outcome following cognitive-behavioral treatment.

The relationship between a variety of within-treatment factors and the outcome of treatment for alcoholism was examined. One hundred and twenty-eight male and 68 female participants (consecutive referrals with an ICD-10 diagnosis of alcohol dependence syndrome) were followed at 12 months following in- and day-patient cognitive behavioral treatment on an addiction unit. Within-treatment factors (of self-efficacy, psychological symptoms, expectations for treatment, treatment satisfaction, treatment climate, therapeutic alliance, and treatment evaluation), were assessed to determine their relationship to global outcome categorization into abstinent, nonproblem drinker, drinking but improved, and unimproved participant groups. A logistic regression analysis identified five variables that were predictive of a more favorable outcome: higher self-efficacy in positive social situations, greater treatment program involvement, a lower perception of staff control, a greater perception of treatment as helpful, and a reduction in psychological symptoms during treatment. Findings confirm previous research that pinpoints the importance of self-efficacy as a treatment variable of significance in treatment planning and delivery. It also highlights the prognostic significance of a reduction in psychological distress and, thus, the value of dynamic predictors of treatment outcome. The failure of the therapeutic alliance to predict outcome is discussed. It is concluded that time-limited alcoholism treatment programs need to give equal emphasis to within-treatment change via the promotion of patient confidence and the perception of helpfulness, as well as to skill-based relapse prevention strategies.

Adult↗

Alchemy revived.

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Cloning, Organism↗