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Biomedical subjects

B H Robinson

Publications and source records attributed to B H Robinson.

At least 217 records · Page 12Linked to original sources
PubMed1976

Results of 250 consecutive cadaver kidney transplants.

The results of 250 cadaver kidney transplants performed at this hospital between May 1968 and December 1974 were analysed. A functioning transplant was defined strictly as one that maintained the recipient in good health with a serum creatinine below 442 mumol/1 (5 mg/100 ml) without any need for dialysis. The proportions of kidneys functioning after one, two, and three years were 40-4%, 33-9%, and 31-1% respectively, the corresponding survival rates of patients being 62-6%, 57-4%, and 43-8%. The primary failure rate overall was 21-6%, while the failure rates for first, second, and third transplants were 18-1%, 39-9%, and 66-7% respectively. Half of the primary failures were attributed to the use of cadaver kidneys with abnormal vasculature or long ischaemic times or originating from non-ventilated donors. Of the initially successful transplants 49% were subsequently lost due to rejection (53%) or death of the patient with a functioning transplant (46%), and of the secondary losses 58% occurred within three months of transplantation. HLA matching of donor and recipient for two or more antigens was associated with a significant increase in transplant survival--46% at three years as opposed to 9-5% at three years for kidneys with poorer matches.

Adolescent↗
PubMed1976

Properties of the citrate transporter in rat heart: implications for regulation of glycolysis by cytosolic citrate.

The efflux of [14C]citrate from rat heart mitochondria was significantly greater with L-malate as the extramitochondrial substrate as compared with [12C]citrate, isocitrate or phosphoenolpyruvate. The concentration of L-malate required for half-maximal rate of efflux of citrate was 0.45 mM and the maximum velocity was 0.36 nmol min-1 mg-1 mitochondrial protein at 23 degrees C. This citrate transporter was inhibited by 1,2,3-benzenetricarboxylate and palmitoyl-CoA but not to the same extent as these compounds inhibit the tricarboxylate carrier in rat liver mitochondria. The apparent inability of these mitochondria to transport citrate in the inward direction necessitates the presence of a cytosolic citrate removal pathway. We propose that the enzymes of this pathway in rat heart could be ATP citrate (pro-3S)-lyase (EC 4.1.3.a) and carnitine acetyltransferase (EC 2.3.1.7), both of which we demonstrate to have adequate activity in both the fed and fasted state. An hypothesis has been put forward to account for the inhibition of rat heart phosphofructokinase by citrate in the fasted state incorporating these properties of the citrate transporter and ATP citrate (pro-3S)-lyase.

Animals↗
PubMed1976

Development of gluconeogenic enzymes in the newborn guinea pig.

The activities of key gluconeogenic enzymes in the liver of newborn guinea pigs delivered vaginally at term were monitored as a function of time following birth. The activities of glucose-6-phosphatase and fructose-1,6-diphosphatase did not show a significant increase over the first 72 h of life, neither did the activity of mitochondrial phosphoenolpyruvate carboxykinase. The mitochondrial enzyme pyruvate carboxylase and the cytosolic phosphoenolpyruvate carboxykinase (PEPCK) both increased significantly in the first 24 h postpartum. Mitochondrial protein and succinate dehydrogenase activities showed only slight increases in the 72-hour period. Rapid depletion of liver glycogen was evident in these animals following birth, but severe hypoglycaemia was not evident. Mitochondrial and cytosolic PEPCK showed similar kinetic behaviour with respect to their affinities for oxalacetate and divalent metal cation Mn++, though the mitochondrial enzyme would accept Mg++ as the divalent metal in place of Mn++. The role of the compartmented PEPCK activities is discussed.

Animals↗
PubMed1976

The effect of premature delivery on the development of gluconeogenic enzymes in the guinea pig.

The activities of key gluconeogenic enzymes in the livers of newborn guinea pigs were monitored as a function of time following birth either vaginally at term or prematurely by cesarian section at 62 days of gestation. The activity of hepatic glucose-6-phosphatase rose dramatically from 1.40 +/- 0.26 mumol/min/g at birth to a maximum of 6.8 +/- 0.9 mumol/min/g at 24 hr in prematurely delivered animals although there was little significant change in activity in full term animals. The activity of hepatic fructose-1,6-diphosphatase and mitochondrial phosphoenolpyruvate carboxykinase changed little over the first 3 days of life in either full term or premature animals. Cytosolic phosphoenolpyruvate carboxykinase, on the other hand, had low activity at birth being 0.11 +/- 0.03 mumol/min/g in full term and 0.06 +/- 0.04 mumol in premature animals rising to values of 0.71 +/- 0.06 and 1.12 +/- 0.12 mumol/min/g, respectively, at 24 hr of life. Pyruvate carboxylase activities in the premature animals remained significantly lower than those in full term animals in the first 72 hr of life. Transient hypoglycemia was evident in the prematurely delivered animals, but not in the full term animals, the blood glucose values being 82 +/- 7 mg/100 ml for the full term animals and 20 +/- 8 mg/100 ml for the premature infants at 2 hr of life.

Animals↗
PubMed1975

Agonal phase, ischaemic times, and renal vascular abnormalities and outcome of cadaver kidney transplants.

A retrospective study of 250 cadaver kidney transplants was carried out to determine the effects of the agonal period, the warm and cold ischaemic times, and the use of kidneys with vascular anomalies on the primary success and failure and the subsequent level of function of the transplants. Kidneys with vascular anomalies or from non-ventilated donors had a primary failure rate of over 30%, whereas those with normal vasculature or from ventilated donors had a rate of 17%. An initial warm ischaemic time of more than 60 minutes was associated with a primary failure rate of 57% and a cold ischaemic time of over 550 minutes with a primary failure rate of 47%. The interrelationship between the warm and cold ischaemic times in the primary success or failure of the transplants was examined and criteria defined for selecting potentially viable cadaver kidneys for transplantation, as follows: (1) The donor should be (a) ventilated, (b) aged 6-50 years, and (c) have normal ante-mortem renal function and have secreted more than 1-5 1 of urine in the 24 hours before death (or an equivalent volume if the urinary output was recorded for less than 24 hours before death); (2) the kidney should have normal renal vasculature enabling single arterial and venous anastomoses to be performed; (3) kidneys with I.W.I.T.s of longer than 60 minutes should not be used; (4) for kidneys with I.W.I.T.s of less than 20 minutes the C.I.T. is not critical but should not exceed 12 hours; (5) for kidneys with I.W.I.T.s of 20-60 minutes the C.I.T. should not exceed 450 minutes.

Adolescent↗
PubMed1975

The effect of adenosine triphosphate on the tricarboxylate transporting system of rat liver mitochondria.

ATP has two significant effects on the mitochondrial tricarboxylate transporting system. First, it alters the concentration gradients at equilibrium for the substrates of this transporter. ATP (2MM) caused the uptake of 10 nmol of citrate into the mitochondria coincident with the output of a similar amount of L-malate. This redistribution was dependent on ATP transport, the effect being inhibited by atractyloside and mimicked by the nonmetabolizable derivative adenylyl imidodiphosphate. A mechanism to account for these observations is proposed. Secondly, preincubation of mitochondria with ATP resulted in a 2- to 3-fold increase in the K-m of the mitochondrial citrate transporter. This effect of ATP was not produced by ADP and P-i, nor by N, N, N1, N1-tetramethyl-p-phenylenediamine and ascorbate. It was prevented by the addition of rotenone and antimycin A. This effect of ATP was observed in the presence of oligomycin and could not be attributed to a change in the content of the known tricarboxylate carrier inhibitor, palmitoyl-CoA, nor to the ATP concentration. The origin of possible regulatory factor (or factors) is discussed.

Adenosine Diphosphate↗
PubMed1975

Changes in protein-bound calcium in the serum of haemodialysis patients.

1. Ionized calcium, protein-bound calcium and total calcium in serum were measured in patients receiving haemodialysis treatment. 2. During dialysis, the ionized calcium fraction decreased and the bound calcium increased. The blood pH also increased. 3. Studies in vitro suggested that the fall in ionized calcium and rise in protein-bound calcium were larger than could be explained by the redistribution of calcium fractions due to the pH change. 4. An explanation could be that haemodialysis increases calcium binding by serum proteins. Such an effect may be implicated in the aetiology of hyperparathyroidism and bone disease in patients undergoing haemodialysis.

Adult↗
PubMed1975

Citrate transport in guinea pig heart mitochondria.

Guinea pig heart mitochondria loaded with [-14C]citrate show exchanges of radioactivity at 30 degrees C with added citrate, L-malate and phosphoenolpyruvate. These exchanges are inhibited by benzene-1,2,3-tricarboxylate. Measurements of rates of citrate transport indicate that the activity of this transporting system is low in heart mitochondria compared to that observed in liver mitochondria. The K(m) values obtained indicate a similarity to those obtained in liver. Citrate oxidation by coupled mitochondria was also found to be slow at 30 degrees C but was inhibited by benzene-1,2,3-tricarboxylate. The role of mitochondrial citrate transport in control of glycolytic flux in the heart is discussed.

Animals↗
PubMed1975

Pyruvate dehydrogenase phosphatase deficiency: a cause of congenital chronic lactic acidosis in infancy.

A male child presented on the first day of life with metabolic acidosis with elevated blood lactate (15 mM), pyruvate (0.4 mM), and free fatty acid (1.3 mM) levels and a blood pH of 7.16. The severity of the acidosis was diminished by intravenous administration of glucose in large doses and by bicarbonate. On two occasions, when the acidosis was particularly severe, peritoneal dialysis using an acetate buffer was required. Restriction of the dietary intake of saturated fatty acids or treatment with nicotinic acid also appeared to diminish the severity of acidosis. No improvement was achieved by the administration of thiamine or biotin. Tissues taken at postmortem showed normal activity of gluconeogenic enzymes and pyruvate dehydrogenase. The activity of pyruvate dehydrogenase in tissue homogenates preincubated with ATP was reduced by 60-75% both in liver of the patient and of the controls because of the inactivation of the enzyme by pyruvate dehydrogenase kinase. Addition of Ca++ and Mg++ to the inactivated enzyme caused a prompt return of the activity to normal in controls but not in the patient. This defect, which was apparent in muscle and liver but not in brain, we attribute to a markedly reduced activity of pyruvate dehydrogenase phosphatase in the patient.

Acidosis↗
PubMed1973

Serial estimation of urinary fibrin fibrinogen degradation products in kidney transplantation.

The urinary excretion of fibrin/fibrinogen degradation products (F.D.P.) of 81 human cadaver kidney transplants has been measured serially by the techniques of tanned red cell haemagglutination inhibition immunoassay and immunonephelometry. Acute rejection episodes in functioning transplants have been associated with increased F.D.P. excretion which in 80% of cases has preceded clinical diagnosis by periods of one to seven days. Recovery from these episodes has been associated with a rapid fall of F.D.P. excretion to undetectable levels. The level of F.D.P. excretion during a rejection episode is a guide to its ultimate outcome. Irreversibly rejected kidneys excrete high levels of F.D.P. for long periods. Viable kidney transplants with prolonged oliguric phases can be distinguished, while still oliguric, from rejected kidneys by their low F.D.P. excretion. F.D.P. cannot usually be detected in the urine of well-functioning transplants. Episodes of raised F.D.P. excretion in the absence of acute clinical rejection, however, occur occasionally and may be associated with permanent impairment of renal function.

Anuria↗
PubMed1972

Effects of palmitoyl CoA on citrate and malate transport by rat liver mitochondria.

Palmitoyl CoA inhibited citrate transport from isolated rat liver mitochondria. Under conditions described, 50% inhibition was observed at about 6-8 nmol/mg of mitochondrial protein per ml. The percentage inhibition was inversely proportional to the concentration of the counter-transporting anion in the medium. Although comparable levels of palmitoyl CoA had little effect on malate exit on the dicarboxylate carrier, higher concentrations inhibited both citrate and malate transport. The specificity of the inhibition by palmitoyl CoA was investigated by examination of the effects on the tricarboxylate transport system of fatty acids, CoASH, acetyl CoA, palmitoylcarnitine, deoxycholate, and other molecules with surface active properties. None of the above compounds, at sublytic concentrations, inhibited citrate transport appreciably. The inhibition of citrate transport by low concentrations of palmitoyl CoA was rapid and could be prevented or partially reversed by addition of albumin.

Albumins↗