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J Mowbray

Publications and source records attributed to J Mowbray.

At least 37 records · Page 2Linked to original sources

Histopathologic alterations in the decidua in human spontaneous abortion: loss of cells with large cytoplasmic granules.

The histopathology of decidua obtained from the placental bed was evaluated by phloxine-tartrazine staining, which allows clear definition of cells with cytoplasmic granules. Mononuclear cells with large granules were seen in biopsy specimens taken from women at 8-31 weeks of normal pregnancy. In contrast, cells with large granules were missing in sections taken from the decidua of five women who were aborting or were destined to abort. Since the presence of suppressor cell activity in murine decidua correlates with the success of pregnancy and since this suppression is associated with small lymphocytes with cytoplasmic granules, the observations made using human placental bed biopsy material suggest that a possible suppressor cell deficiency might occur in the early stages of spontaneous abortion in human females.

Abortion, Spontaneous↗

Evidence for the presence of oligophosphoglyceroyl-ATP in rat offney.

The inability to account for large systematic variations in total purine nucleotide content of perfused rat hearts led to the demonstration that the soluble adenine nucleotides are in rapid equilibrium with a highly phosphorylated hetero-oligomeric derivative whose structure appears to be 3-phospho[glyceroyl-gamma-triphospho-5'-adenosine-3'-3-phosp ho]4glyceroyl- gamma-triphospho-5'-adenosine [Hutchinson, Morris & Mowbray (1986) Biochem. J. 234, 623-627]. Analogous techniques to those used with hearts for specifically labelling tissue purine nucleotides followed by extration and purification of nucleotides from the trichloroacetic acid-precipitable fraction show the existence of a corresponding rapid equilibrium between ATP and an oligomeric tetraphosphoadenosine derivative in perfused kidneys.

Adenosine Triphosphate↗

The molecular structure of a rapidly formed oligomeric adenosine tetraphosphate derivative from rat heart.

The inability to account for large systematic variations with time in soluble adenine nucleotides in perfused rat hearts [Bates, Perrett & Mowbray (1978) Biochem. J. 176, 485-493; Mowbray, Bates & Perrett (1981) FEBS Lett. 131, 55-59; Mowbray, Perrett & Bates (1984) Int. J. Biochem. 16, 889-894] led us to show that the soluble nucleotides are in rapid equilibrium with some hitherto unrecognized trichloroacetic acid/methanol-precipitable highly phosphorylated heteropolymeric form [Mowbray, Hutchinson, Tibbs & Morris (1984) Biochem. J. 223, 627-632]. Selective digestion coupled to chromatographic analysis together with m.s. and 31P-n.m.r. spectrometry have now been used to show that the likely structure for a purified oligomer that is in specific-radioactivity equilibrium with tissue ATP is 3-phospho-[glyceroyl-gamma-triphosphoroyl-5'-adenosine-3'-3- phospho]4 glyceroyl-gamma-triphosphoroyl-5'-adenosine.

Adenine Nucleotides↗

The influence of thyroid hormone on the degree of control of oxidative phosphorylation exerted by the adenine nucleotide translocator.

Impaired phosphorylation efficiency in liver mitochondria from hypothyroid rats is paralleled by a defect in adenine nucleotide transport. Both of these lesions can be corrected within 15 min by a near-physiological dose of triiodo-L-thyronine. Measurement of the control strength of the translocator shows, however, that this step has a smaller share of the control for oxidative phosphorylation after thyroidectomy and that this is unaltered after 15 min by replacement therapy. Rapid control by triiodothyronine is thus exerted elsewhere than at this transfer and the effects of hormone on the translocator are likely to be indirect.

Animals↗

The efficiency of oxidative phosphorylation and the rapid control by thyroid hormone of nicotinamide nucleotide reduction and transhydrogenation in intact rat liver mitochondria.

In confirmation of previous work enhancement of the fluorescence emission of reduced nicotinamide nucleotides in intact rat liver mitochondria was found to depend on incubation conditions. Under standard conditions the enhancement is constant at 4.8-fold in states 3 and 4 and is not altered by thyroidectomy of the animal 6 weeks prior to experiment. The ADP-induced (state 4----state 3----state 4) fluorescence changes are significantly different in intact mitochondria from normal and hypothyroid animals and reflect the decreased rate and efficiency of oxidative phosphorylation after thyroidectomy. Incubation of liver homogenates in vitro for 15 min with 1 microM triiodothyronine before isolating mitochondria significantly restores their ADP response towards normal. Direct addition of hormone to isolated mitochondria was ineffective. Enzymatic measurement of mitochondrial extracts shows that thyroidectomy leads to increases in the contents of NAD(H) by 22% and NADP(H) by 33%. With glutamate as substrate ADP-induced changes in the reduced/oxidized ratio of NAD+ are not significantly altered in hypothyroid preparations. By contrast the NADP+ ratio remains substantially more reduced in state 3 than it does in normal mitochondria. The hypothesis is advanced that the decreased efficiency of hypothyroid preparations in phosphorylating ADP may be the result of increased energy-linked transhydrogenase activity. This is needed to supply NADPH via the glutathione peroxidase for reducing endogenously formed peroxides. Direct reduction of mitochondrial glutathione with dithiothreitol had no substantial effect on ADP/O ratios or on ADP-induced redox cycles in either normal or thyroidectomised preparations. This decisively eliminates the possibility that lowered phosphorylation efficiency is the result of a leak of reducing equivalents via glutathione peroxidase.

Adenosine Diphosphate↗

Short-term control of mitochondrial adenine nucleotide translocator by thyroid hormone.

An improved simple technique for measuring adenine nucleotide translocator activity at low medium substrate concentrations is described. Confirming previous reports, thyroidectomy was shown to lead to lowered translocator activity in rat liver mitochondria. The rapidly exchangeable portion of the matrix nucleotide also decreased in hypothyroid preparations even though the total nucleotides increased substantially. The apparent Km of translocator for ADP increased from 2.8 to 6.2 microM in hypothyroid preparations: Mg2+ ions raised this to about 20 microM. All of these changes in adenine nucleotide translocation were entirely reversed by 15 min after a single intravenous near-physiological dose of triiodothyronine.

Adenine Nucleotides↗

Post-ischaemic synchronous purine nucleotide oscillations in perfused rat heart.

Langendorff perfused rat hearts show synchronous, statistically significant, systematic variations in ATP and ADP. Here we show that AMP and IMP also vary in register with ATP and ADP and we suggest that the synchronizing trigger for these oscillations may be ischaemia. Oscillations in the ATP/ADP ratio were found to be significantly correlated with creatine phosphate content but by contrast these quantities vary quite differently from the GTP/GDP ratio. Cyclic GMP oscillations showed a significant negative correlation with variations in ADP. Epinephrine raised mean cyclic AMP content and stabilized cyclic GMP oscillations, but had little other effect on the purine nucleotide variations.

Adenosine Diphosphate↗

Genetic control of progressive autonomic failure: evidence for an association with an HLA antigen.

In 16 patients with progressive autonomic failure, a rare disease of unknown cause, the frequency of the HLA antigen Aw32 was 13 times more common than in healthy controls, giving a relative risk of progressive autonomic failure with Aw32 of 28.7. Such genetic predisposition to the disease might cause a defect of catecholamine metabolism In the brain or possibly affect the immune response to a virus.

Autonomic Nervous System Diseases↗

Erosive rheumatoid arthritis co-existing with systemic lupus erythematosus. A report of a case, also showing atlanto-axial subluxation.

A 28-year old female is described with a 12-year history of seropositive, erosive rheumatoid arthritis. Subsequently, she developed systemic lupus erythematosus diagnosed both serologically and on renal biopsy. As has previously been emphasised, these two diseases occur rarely in the same patient. HLA typing revealed the patient was HLA - B8 positive and that she had inherited this genetic marker from her mother who is Irish, rather than from her West Indian father. The patient has developed marked atlanto-axial subluxation, a feature not noted in six patients previously described as having both diseases.

Adult↗

In perfused rat hearts ischaemia promotes the reversible conversion of appreciable quantities of soluble adenine nucleotides to a stable trichloroacetic acid-precipitable form.

Radioactivity from [14C] adenosine was linearly incorporated into tissue nucleotides in perfused rat hearts. All the TCA-extractable 14C was confined to the purine nucleoside phosphates for up to 1 h of perfusion. Radioactivity was also incorporated linearly into the TCA-insoluble fraction, which by 40 min accounted for 24% of the tissue 14 C. Estimates based on precursor specific radioactivity suggest that at least 0.6 micro mol/g of the mononucleotide is in this stable insoluble form. Following 2 min total ischaemia, the tissue nucleotide content and soluble radioactivity decreased while the insoluble radioactivity showed a corresponding increase to account now for 35% of the tissue radiolabel. This redistribution was rapidly reversed by post-ischaemic reperfusion. A possible function for the rapid reversible sequestration of adenine nucleotides in ischaemia is proposed.

Adenine Nucleotides↗

The rapid transient stimulation of both cytoplasmic and mitochondrial ornithine decarboxylases in the liver of thyroidectomized rats by 3,5,3'-triiodo-L-thyronine.

Evidence is presented that liver from thyroidectomized rats has ornithine decarboxylase (ODC) in both mitochondrial and soluble fractions. The cytosolic activity was stimulated 7-fold and the mitochondrial activity 3-fold 15 min after the administration of triiodothyronine (T3). While the rapid transient stimulation of ODC could represent a direct intracellular response to T3, an incidental effect on a very-rapidly-turning-over enzyme seems more likely; this suggests that in vivo ODC may be controlled by a demand for polyamines.

Animals↗

Cyclosporin A for the treatment of systemic lupus erythematosus.

Cyclosporin A (CyA) was given to five patients with active systemic lupus erythematosus (SLE) at a dose of 10 mg/kg/day orally. No patient was able to take the drug for longer than seven weeks because of side effects including nephrotoxicity. Angio-oedema was noted in three patients and serum C1 esterase inhibitor levels were shown to be depressed in four out of five patients whilst taking CyA. Two patients did experience an improvement in their arthralgia but given the side effects induced we cannot, at present, recommend CyA for the treatment of SLE.

Adult↗