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Biomedical subjects

A A Morris

Publications and source records attributed to A A Morris.

46 records · Page 3Linked to original sources
PubMed1995

Impaired ketogenesis in fructose-1,6-bisphosphatase deficiency: a pitfall in the investigation of hypoglycaemia.

Intermediary metabolite concentrations were measured in blood during fasting in two patients with fructose-1,6-bisphosphatase deficiency. Hypoglycaemia was accompanied by markedly raised levels of plasma free fatty acids, without the expected degree of ketosis. This suggests that there is secondary impairment of ketogenesis in this condition, and could lead to diagnostic confusion.

3-Hydroxybutyric Acid↗
PubMed1995

Neonatal Fanconi syndrome due to deficiency of complex III of the respiratory chain.

Fanconi syndrome is an important presentation of respiratory chain disease. We report three patients who presented in the neonatal period with Fanconi syndrome, lactic acidosis and intrauterine growth retardation. In all three patients the major biochemical defect was in complex III of the mitochondrial respiratory chain, a relatively uncommon defect. The diagnosis could only be made by muscle biopsy as the defect was not expressed in cultured skin fibroblasts. Treatment with vitamins C and K3 and ubiquinone did not alter the course of the disease and all patients died before the age of 4 months.

Acidosis, Lactic↗
PubMed1995

Presentation and clinical investigation of mitochondrial respiratory chain disease. A study of 51 patients.

Defects of the mitochondrial respiratory chain are associated with a great variety of clinical disorders. Whilst recognition of these conditions is increasing, the need for sophisticated biochemical and molecular studies has tended to limit both their investigation and diagnosis to a few specialist centres. Using a group of 51 patients with histochemically, biochemically and/or genetically defined respiratory chain defects, we have examined both the clinical heterogeneity of these disorders and how they may be investigated most effectively in non-specialist centres. We evaluated the use of the following routinely available clinical investigations--fasting intermediary metabolites (lactate, pyruvate, ketone bodies, etc.) in blood and cerebrospinal fluid, serum creatine kinase estimation, EMG, EEG, CT, MRI and histological/histochemical muscle biopsy analysis. Our studies show that, in addition to well-recognized syndromes (e.g. chronic progressive external ophthalmoplegia, mitochondrial encephalopathy lactic acidosis and stroke like episodes, and myoclonus epilepsy with ragged red-fibres, a significant number of patients present with non-specific encephalopathic disorders. Furthermore, even within those categories of respiratory chain disease which have been genetically defined, a wide variation of presenting symptoms and signs were found. Where there was initial doubt concerning the diagnosis, the following clinical features were helpful in suggesting respiratory chain disease: ophthalmoplegia; a maternal pattern of inheritance; the presence of myopathy or deafness in association with encephalopathy. Of the clinical investigations we assessed, elevated lactate in blood or cerebrospinal fluid and low density lesions in the basal ganglia were helpful in identifying patients with respiratory chain dysfunction. Histochemical analysis of muscle was, however, the single most useful investigation being diagnostic in patients with chronic progressive external ophthalmoplegia, Kearns-Sayre syndrome and myopathy, and of significant importance in patients presenting primarily with central nervous system disease. The results of our study are used to discuss the most appropriate approach to diagnosis of this group of disorders.

Adolescent↗
PubMed1994

The cDNA sequence of the flavoprotein subunit of human heart succinate dehydrogenase.

We report the full-length cDNA sequence for the flavoprotein subunit of human heart succinate dehydrogenase (succinate: (acceptor) oxidoreductase EC 1.3.99.1). Identical sequence was obtained for part of the cDNA of the human placental flavoprotein, in contrast to a previously published sequence. The human sequence, like the bovine one, contains a cysteine triplet and at the active site there is an additional cysteine when compared with yeast or prokaryotes.

Amino Acid Sequence↗
PubMed1994

Metabolic disorders in children.

This year has seen major progress in gene therapy, particularly that directed to the liver. Genes have been characterized for Wilson's disease, Krabbe's disease, Canavan's disease, adrenoleukodystrophy, glucose-6-phosphatase, and long-chain 3-hydroxyacyl-CoA dehydrogenase. Moreover, the identification of common mutations in many conditions promises to help with diagnosis and genetic counseling. The drama of progress in molecular biology can easily overshadow other research, but the application of tandem mass spectrometry to neonatal screening is a major advance. Other important papers concern the use of Lorenzo's oil in adrenoleukodystrophy and revised dietary recommendations for the treatment of phenylketonuria. This review focuses predominantly on diseases that affect the brain, but important advances in other conditions have been included.

Adrenoleukodystrophy↗
PubMed1981

Effect of N-[(S)-1-carboxy-3-phenylpropyl]-L-Ala-L-Pro and its ethyl ester (MK-421) on angiotensin converting enzyme in vitro and angiotensin I pressor responses in vivo.

The parent diacid (N-[(S)-1-carboxy-3-phenylpropyl]-L-Ala-L-Pro of MK-421 inhibited hog plasma angiotensin converting enzyme (ACE) by 50% (I50) at a concentration of 1.2 nM and was 17 times more potent than captopril. In vitro the I50 for MK-421, an ethyl ester, was 1200 nM because de-esterification did not occur. Similarly in the guinea-pig ileum, the diacid inhibitor and MK-421 potentiated the contractile effects of bradykinin at an AC50 of 77 pM and 18 nM, respectively. Inhibition of the pressor effects of angiotensin I by the diacid ACE inhibitor occurred at an ID50 of 8.2 micrograms/kg i.v. in rats and 6.4 micrograms/kg i.v. in dogs. Thus, the diacid was approximately 12 times more potent than captopril. The ID50 for MK-421 was 14 and 278 micrograms/kg i.v. in rats and dogs, respectively, because of differences in the rates of de-esterification. Oral ACE inhibitory activity was determined by blockade of the pressor effects of angiotensin I in conscious rats and dogs. In rats, but not in dogs, the diacid inhibitor was poorly absorbed, whereas MK-421 was well absorbed in both species. MK-421 inhibited the pressor effects of angiotensin I at 0.1 to 3.0 mg/kg p.o. for at least 6 hr in rats and dogs, and compared to captopril was 8.6 times more potent in rats and 4.6 times more potent in dogs. These data demonstrate that MK-421 and its parent diacid are potent, long-lasting orally active inhibitors of ACE. In addition, the low activity of MK-421 in vitro contrasts with its substantial in vivo activity, and supports the hypothesis that MK-421 is a prodrug that first must be de-esterified to permit full expression of its significant in vivo pharmacological activity.

Administration, Oral↗
PubMedDate not supplied

Cardiotonic effects of anthopleurin-A, a polypeptide from a sea anemone.

The positive inotropic effect of anthopleurin-A (AP-A) was studied in vitro on isolated cat heart papillary muscles and in vivo in anesthetized and conscious dogs. In vitro, in low Ca2+ solution (1.27 mM), AP-A increased the force of contractions of isolated cat heart papillary muscles at concentrations from 0.2 x 10(-8) M and higher; on a molar basis, AP-A was more than 200 times as potent as digoxin and on a weight basis, 33 times as potent. In vivo in anesthetized dogs, AP-A at 0.2 microgram/kg/min i.v. increased myocardial contractile force; the geometric mean dose of AP-A required to increase the contractile force by 25% was 2.6 micrograms/kg; the corresponding dose of digoxin (infused at 2.8 micrograms/kg/min) was 107.4 micrograms/kg. The geometric mean lethal dose of AP-A for 8 dogs was 19.3 and that of digoxin 263.2 micrograms/kg i.v. The therapeutic index of AP-A was significantly higher than that of digoxin. All animals that received either AP-A or digoxin died in ventricular fibrillation. The reversal of t-wave was typical for AP-A. As measured by left ventricular pressure telemetry, AP-A, 2 micrograms/kg i.v. single dose, increased LV dp/dt max in conscious dogs for longer than 2 hr.

Animals↗