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J Mowbray

Publications and source records attributed to J Mowbray.

At least 55 records · Page 3Linked to original sources
PubMed1979

Evidence for the rapid direct control both in vivo and in vitro of the efficiency of oxidative phosphorylation by 3,5,3'-tri-iodo-L-thyronine in rats.

1. Examination of the distribution of L-tri-iodothyronine among rat liver tissue fractions after its intravenous injection into thyroidectomized rats focused attention on mitochondria at very short times after administration. By 15 min this fraction contained 18.5% of the tissue pool; however, the content had decreased sharply by 60 min and even further over the next 3 h. By contrast, the content in all other fractions was constant or increased over 4 h. About 60% of tissue hormone was bound to soluble protein. 2. Mitochondria isolated from thyroidectomized rats showed P/O ratios that were about 50% of those found in normal controls, with both succinate and pyruvate plus malate as substrates. There was no evidence of uncoupling; the respiratory-control ratio was about 6. 3. Mitochondria isolated 15 min after injection of tri-iodothyronine into thyroidectomized rats showed P/O ratios and respiratory-control ratios that were indistinguishable from those obtained in mitochondria from euthyroid animals. The oxidation rate was, however, not restored. 4. Incubation of homogenates of livers taken from thyroidectomized animals injected with L-tri-iodothyronine before isolation of the mitochondria restored the P/O ratio to normal; by contrast, direct addition of hormone to isolated mitochondria had no effect. The role of extramitochondrial factors in rapid tri-iodothyronine action is discussed. 5. Possible mechanisms by which tri-iodothyronine might rapidly alter phosphorylation efficiency are considered: it is concluded that control of adenine nucleotide translocase is unlikely to be involved. 6. The amounts of adenine nucleotides in liver were measured both after thyroidectomy and 15 min after intravenous tri-iodo-thyronine administration to thyroidectomized animals. The concentrations found are consistent with a decreased phosphorylation efficiency in thyroidectomized animals. Tri-iodothyronine injection resulted in very significant changes in the amounts of ATP, ADP and AMP, and in the [ATP]/[ADP] ratio, consonant with those expected from an increased efficiency of ADP phosphorylation. This suggests that the changes seen in isolated mitochondria may indeed reflect a rapid response of liver in vivo to tri-iodo-thyronine.

Animals↗
PubMed1979

Enzyme replacement therapy by fibroblast transplantation: long-term biochemical study in three cases of Hunter's syndrome.

We have assessed the effectiveness of transplanted histocompatible fibroblasts as a long-lived source of lysosomal enzymes for replacement therapy in three patients with Hunter's syndrome, over periods ranging from 2.5 to 3.75 yr. The level of Hunter corrective factor excreted by all three patients increased after transplantation, as did the activity of alpha-L-idurono-2-sulfate sulfatase in serum, when measured directly with a radioactive disulfated disaccharide substrate. Sulfatase activity was also raised in leukocyte homogenates from the two patients that we were able to assess. These increases in enzyme activity were accompanied by corresponding increases in catabolism of heparan and dermatan sulfates, as shown by (a) a decrease in sulfate:uronic ratios of urinary oligosaccharides, (b) an increase in iduronic acid monosaccharide, and (c) a normalization of Bio-Gel P-2 gel filtration profiles. Both the increase in enzyme activity and increased catabolism were maintained during the period of study and were not affected by either a gradual decrease or total withdrawal of immunosuppressive therapy.

Child↗
PubMed1979

The effect of local anaesthetics and barbiturates on myogenesis and myotube integrity in rat skeletal muscle cultures.

Several cationic anaesthetics and barbiturates including bupivacaine, lignocaine and pentobarbital reversibly inhibit myoblast fusion in rat primary muscle cultures. The same drugs also cause disruption of myotube structure, which is normally complete within 2 h; fusion of myoblasts and reformation of myotubes takes place on removal of the drugs. The disruption of myotubes caused by tertiary amine anaesthetics observed in vitro appears to mimic muscle fibre disruption caused by the same drugs in vivo. The effects of temperature, culture age, medium constitution and calcium flux on anaesthetic-induced myotube breakdown have been examined.

Anesthetics↗
PubMed1978

Systematic variations in the content of the purine nucleotides in the steady-state perfused rat heart. Evidence for the existence of controlled storage and release of adenine nucleotides.

1. The contents of the major purine nucleotides in the isolated non-working perfused rat heart varied systematically during 80min of perfusion. In particular the amounts of ATP, ADP, GTP, cyclic AMP and cyclic GMP in the well-oxygenated myocardium showed changes ranging from 25 to 60% of the mean concentrations. The apparent periodicity was about 30min for some and about 60min for other nucleotides. 2. These data are in contrast with measurements of parameters reflecting heart performance, which remained constant over this period of perfusion. 3. The ATP/ADP ratio, the cyclic AMP content, the GTP content and the GTP/GDP ratio in the tissue bore a constant relationship to one another, and all showed the same temporal variation. 4. Increasing the energy demand on the heart by administration of bovine somatotropin (1mug/ml) tended to damp the variations, and generally lower the content of all the nucleotides. 5. The total extractable adenine nucleotide pool also showed systematic temporal variations of as much as 1.3mumol/g wet wt. of tissue within 10min. 6. These variations could not be accounted for as inter-conversion with adenosine, other purine nucleotides, nucleosides or purine-degradation products either in the tissue or in the perfusion medium. No evidence was found in this preparation of the purine nucleotide oscillations described by Lowenstein and his co-workers [see Tornheim & Lowenstein (1975) J. Biol. Chem.250, 6304-6314]. 7. Further, the pool size increases cannot be satisfactorily explained by either synthesis de novo or the breakdown of any purine macromolecular species in the cell. Thus it is suggested that an unsuspected substantial storage form of purine nucleotide may exist in heart.

Adenine Nucleotides↗
PubMed1977

Pityriasis lichenoides--an immune complex disease.

Circulating immune complexes have been detected in patients with pityriasis lichenoides during disease activity when IgM and C3 have been observed in dermal vessels on direct immunofluorescence of fresh lesions. This implies that pityriasis lichenoides is an immune complex disorder and that deposited complexes play a part in the pathogenesis of the condition. There is a characteristic pattern of immunofluorescence which may be a diagnostic aid.

Adolescent↗
PubMed1976

The tentative identification in Escherichia coli of a multienzyme complex with glycolytic activity.

Penicillin spheroplasts of Escherichia coli were ruptured osmotically, by freezing and thawing, or mechanically. Differential centrifugation sedimented 20-30% of the glycolytic enzymes without increasing their specific activities. There was, however, evidence of distinct groups of sedimenting enzymes; growth on different carbon sources could influence the distribution. Sucrose gradient studies gave no evidence of enzyme association but provided estimations of the molecular weight of each enzyme which were close to those subsequently observed on gel filtration. Using the determined molecular weight and a literature value for specific activity, the measured activity ratio of the enzymes was compared with that expected from an equimolar mixture. All values agreed within a factor of five, except for hexokinase. The relative roles of hexokinase and phosphotransferase in E. coli are briefly considered. An equimolar multienzyme aggregate of all the enzymes of glycolysis would have a molecular weight of about 1.6 X 10(6). Chromatography on a Biogel column yielded one fraction, corresponding to a molecular weight of 1.6 X 10(6), which contained a proportion of all the glycolytic enzyme studied; the remaining portion of each enzyme activity was eluted from the column at the position expected from its individual molecular weight. The fraction of mol. wt 1 600 000 was tested for complete glycolysis pathway activity and found not to be different from a reconcentrated mixture of the separated enzymes. Both the eluted and the reconstructed systems showed unexpected activity changes at different protein concentrations. The specific radioactivity of pyruvate formed by these systems from [14C]glucose 6-phosphate was reduced by the presence of unlabelled 3-phosphoglycerate, but by less than would have been expected had the latter been able to participate fully in glycolytic activity. This result indicates that these preparations were capable of selectivity compartmenting glycolytic intermediates. Electron microscope investigation of both systems showed large numbers of regular 30 nm diameter particles which, on disruption, appeared to be composed of smaller units: it is possible that these particles may have been aggregates containing glycolytic enzymes. The possible advantages of a glycolytic multienzyme complex are briefly discussed.

Carbohydrate Epimerases↗
PubMed1975

A mitochondrial monocarboxylate transporter in rat liver and heart and its possible function in cell control.

Several hydroxy- and keto-substituted monocarboxylates were found to undergo co- as well as counter-exchange across the mitochondrial membrane. The results argue against a simple Donnan system and may be explained by the existence of a transporter for monocarboxylates. In support of this explanation it was apparently possible to 'pump' pyruvate to the sucrose-inaccessible space by using the dicarboxylate transporter. Further, several aromatic and aliphatic analogues of pyruvate, but not of di- or tri-carboxylate transport inhibitors, have been shown to prevent pyruvate-exchange reactions. Palmitoylcarnitine was found to have a much stronger affinity for the carrier than either carnitine or pyruvate and the possible consequences of this for carnitine-palmitoylcarnitine exchange and on the control of the pyruvate dehydrogenase complex are explored. In view of the range of transport inhibitors and substrates it is suggested that the carrier has a fairly broad specificity. 'Inhibitor-stop' kinetic studies show that the speed of translocation of pyruvate at 1 degrees C is of the same order as malate. The possible correlation between the role of a hydroxy-keto acid transporter in substrate exchange and some whole animal experiments is briefly discussed. It is proposed that for reasons of control the cell will require membrane monocarboxylate transporters no less than di- or tri-carboxylate carriers.

Animals↗
PubMed1975

Growth hormone, cyclic nucleotides and the rapid control of translation in heart muscle.

Perfused rat heart incorporated L-[14C]tyrosine into protein at a constant rate for up to 75 min. A purified bovine growth-hormone preparation (1 mug/ml) stimulated the incorporation to a new constant rate that was more than three times the control rate by 10 min after hormone addition to perfusate. The hormone, however, did not alter the intracellular tracer amino acid pool, and the relationship of this to the aminoacyl-tRNA precursor pool is discussed. It is concluded that the increased incorporation largely reflected a rapid increase in protein synthesis at the ribosomes. Measurements of cyclic nucleotide contents during the perfusion showed that these appeared to vary in a systematic way during the perfusion. This strands in contrast with the constant values given by several other parameters measured in this preparation. Futher, the cyclic nucleotide variation seems to be independent of external effectors. The steady-state performance of the heart correlates more closely the [cyclic AMP]/[cyclic GMP] ratio than with the content of the individual cyclic nucleotides. At 10 min after the addition of growth hormone a slight decrese in cyclic AMP content and a large decrease in cyclic GMP were found, suggesting that the hormone's effect in stimulating protein synthesis may be mediated by a decrease in cyclic nucleotide concentrations or an increase in the [cyclic AMP]/[cyclic |p] ratio. The findings are also consistent with an intracellularly directed role for these nucleotides, and the possibility that the cyclic nucleotide changes are an indirect result of growth-hormone action is discussed.

Amino Acids↗
PubMed1974

Evidence against the incorporation into protein of amino acids directly from the membrane transport system in rat heart.

The possibility suggested recently [Hider, R.C., Fern, E.B. and London, D.R. (1969) Biochem. J. 114, 171-178; Hider, R.C., Fern, E.B. and London, D.R. (1971) Biochem. J. 121, 817-827; van Venrooij, W.J., Poort, C., Kramer, M.F. and Jansen, M.T. (1972) Eur. J. Biochem. 30, 427-433; and Adamson, L.F., Herington, A.C. and Bornstein, J. (1972) Biochim. Biophys. Acta 282, 352-365] that protein synthesis takes place using amino acids directly from the membrane transport system and not from an intracellular pool has been investigated in rat heart. The tissue was perfused first for 30 min with either [14C]glycine or [14C]leucine and then for a further 30 min with identical medium containing [3H]glycine or [3H]leucine, respectively. After an initial lag, [14C]glycine was incorporated into protein at a linear rate up to 60 min. The [3H]glycine was accumulated into tissue water and incorporated just as readily as the [14C]glycine had been. The rate of total protein synthesis agrees with literature values only if intracellular and not extracellular specific activity values are used in the calculation. Some glycine was converted to serine or threonine. Leucine influx and efflux were very rapid in contrast to the relatively slow exchange reported for incubated tissues [Hider, R.C., Fern, E.B. and London, D.R. (1969) Biochem. J. 114, 171-178; Hider, R.C., Fern, E.B. and London, D.R. (1971) Biochem. J. 121, 817-827; van Venrooij, W.J., Poort, C., Kramer, M.F. and Jansen, M.T. (1972) Eur. J. Biochem. 30, 427-433]. The results are consistent with the existence of an intracellular precursor pool for glycine. Some possible reasons for the discrepancies between this and the other studies are discussed.

Amino Acids↗