Clinical science and molecular medicine最新文献

1. Parenchymal, Kupffer and biliary tract cells were isolated from normal rat liver by perfusion with collagenase solution. 2. The specific activities (munits of enzyme activity/mg of protein) of marker enzymes for the principal subcellular organelles were determined in the isolated cell homogenates and compared with whole liver homogenates. 3. The cells were disrupted and the extracts subjected to analytical subcellular fractionation by sucrose-density-gradient centrifugation. Lysosomal integrity was determined by assaying latent beta-N-acetylglucosaminidase in the extracts. 4. Similar subcellular distributions were found for lysosomal, endoplasmic reticulum and plasma membrane marker enzymes in the whole liver and in parenchymal and biliary tract cells. In Kupffer cells, the proportion of these enzymes in the cytosol was significantly increased compared with the other fractions. In addition the equilibrium densities of the various organelles in these cells were lower than those from parenchymal cells.

1. Infusion of a triglyceride emulsion (Intralipid) into overnight fasted normal subjects produced a rise in plasma free fatty acids (FFA) and blood ketones. 2. Glucose given orally 60 min after the start of the Intralipid infusion produced a sharp fall in blood ketones without much change in plasma FFA. 3. An infusion of glucagon given together with Intralipid did not alter the reduction in blood ketones produced by oral glucose in normal subjects. 4. Oral glucose given 60 min after the start of the Intralipid infusion in three insulin-requiring diabetic subjects produced no fall in blood ketones. 5. The results suggest that glucose prevents the increase in blood ketones after Intralipid through an increase in insulin secretion rather than through a suppression of glucagon or as a direct effect of glucose. 6. It is most likely that the effect of insulin is to inhibit hepatic ketogenesis.

1. The haemodynamic effects of oral converting enzyme inhibitor (SQ 14225) were assessed in eight patients with severe essential or renovascular hypertension. 2. Mean arterial pressure fell (149 +/- 5 to 127 +/- 8 mmHg, P less than 0.02), because of a fall in total peripheral resistance (6.9 +/- 0.53 to 5.7 +/- 0.40 kPa 1(-1)s m2) without a significant change in cardiac index. Two of the eight patients were non-responders without pressure reduction or a haemodynamic change. Sodium restriction (10 mmol/day) while the same dose of SQ 14225 was continued further lowered arterial pressure (137 +/- 8 to 111 +/- 12 mmHg, P less than 0.05) through further resistance reduction (6.5 +/- 0.53 to 5.2 +/- 0.40 kPa 1(-1)s m2, P less than 0.05). 3. Haemodynamic responses to head-up tilt (increased heart rate and resistance, decreased cardiac index) were unaffected by SQ 14225 regardless of sodium intake. 4. The pattern of reduction in peripheral resistance, with unchanged cardiac index, was similar to that produced by vasodilators acting at both arteriolar and venular levels.

1. The blood flow in rabbit gastrocnemius, as measured by photoelectric drop-counter, increased when the muscle was vibrated at frequencies of 22--62 Hz. 2. Blood flow increased rapidly within 1--2 s of the start of vibration, and lasted for the whole time vibration was applied. 3. The increase in blood flow was negatively correlated with the initial blood flow, being greater with lower flows. 4. The magnitude of increase was similar in both innervated and acutely denervated muscles. 5. The arterial blood pressure did not change apart from a very brief fall at the beginning of vibration. Venous pressure rose and, consequently, the perfusion pressure was lower. The increase in blood flow thus indicates a considerable dilatation in the resistance vessels of skeletal muscle.

1. The effect of infusion of ovine prolactin was studied in anaesthetized dogs pretreated with bromocryptine to reduce the release of endogenous prolactin. 2. Prolactin, injected intravenously and also directly into one kidney, resulted in a 12--18% increase in glomerular filtration rate (GFR) by both kidneys. 3. This increased GFR was not associated with any demonstrable changes in whole-kidney blood flow, distribution of intrarenal blood flow, fractional excretion of sodium or osmolar or free-water clearance. 4. We conclude that ovine prolactin produced an increase in GFR not dependent on an increase in whole-kidney plasma flow.

1. In eight patients with a unilateral fistula between the radial artery and a nearby superficial vein, heat elimination from both hand and forearm, as measured by calorimetry, was always substantially greater on the side of the fistula (a mean excess from hand-plus-forearm 889 J/min). 2. Fistular blood flow measured by hand-plus-forearm plethysmography in these patients averaged 431ml/min. Correlation between fistular blood flow and heat elimination was poor (r = 0.70, P less than 0.06), probably because heat elimination due to the fistula takes place mainly from veins, whose pattern varies from patient to patient. 3. Approximately half of the total increased heat elimination due to the fistula is from the hand. Occlusion of the circulation to the hand caused fistular flow rate to be reduced by about half. This suggests that the main resistance to fistular is venous, proximal veins offering a similar resistance to distal veins. 4. The obligatory heat loss due to fistula is unlikely to embarrass temperature regulation, except in severe cold stress.

1. The mechanism underlying the raised leucocyte sodium content in fulminant hepatic failure was studied by measurement of sodium fluxes, (Na+ + K+)-dependent adenosine triphosphatase activity, and leucocyte ATP content. 2. The rate constant for sodium efflux in the leucocytes was significantly reduced, and attributable to reduced activity of the enzyme (Na+ + K+)-ATPase. Leucocyte ATP content was not significantly different from that of control cells. 3. Incubation of cells from patients in the sera of normal subjects resulted in a reversal of these changes. Inhibition of the leucocyte sodium efflux rate constants and (Na+ +K+)-ATPase of normal cells was achieved by incubation in sera from patients. 4. We suggest that the raised sodium content of leucocytes in fulminant hepatic failure is attributable to a defective sodium pumping mechanism, possibly due to a circulating toxin.

1. The placental transfer of urea was studied by perfusing the guinea-pig foetal placenta in situ with dextran solutions containing various amounts of urea, and radioactively labelled urea. 2. Transfer of urea was linearly related to the difference in concentration between the maternal and the foetal sides of the placenta, but transfer in both directions across the placenta was equal when the concentration of urea in the perfusing fluid was 2.5--3.5 mmol/l less than the maternal arterial value. This suggested that urea may be transferred against a concentration gradient. 3. Foetal plasma urea concentrations were found to be 0.5 mmol/l less than the maternal, suggesting that active transfer from the foetal circulation to the maternal can occur. However, because of the close relationship between foetal and maternal plasma urea (r = 0.96), it is concluded that the major control of foetal urea concentrations is by diffusion of urea between maternal and foetal extracellular fluids.

1. Hepatic elimination of renin was measured in 10 well-compensated cardiac patients with normal liver function during a control period and during a period of reduced hepatic plasma flow, induced by physical exercise (seven patients) or intravenous infusion of lysine vasopressin (three patients). 2. Hepatic renin elimination rate (hepatic plasma flow x arterial-hepatic vein difference of plasma renin activity) was found to be linearly correlated with arterial plasma renin activity (r = 0.986, P less than 0.001). 3. When hepatic plasma flow fell by 45% the hepatic extraction ratio of renin (arterial-hepatic vein plasma renin activity difference/arterial plasma renin activity) increased by 75%. Hepatic renin clearance (hepatic plasma flow x extraction ratio) remained constant. 4. The results indicate that changes in the hepatic elimination rate of renin do not contribute to changes in plasma renin activity during these events.