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Biomedical subjects

J G Brook

Publications and source records attributed to J G Brook.

At least 55 records · Page 3Linked to original sources

Effect of plasma lipoproteins on cholesterol accumulation in macrophages: comparison of lipoproteins from normal and homozygous familial hypercholesterolemic subjects.

Total cholesterol (TC) content of mouse peritoneal macrophages (MPM) increased when incubated with increasing concentrations of normal low density (N-LDL) or very low density (N-VLDL) lipoprotein. Incubation with increasing concentrations of normal high density lipoprotein (N-HDL) caused a decrement in cellular mass of TC in MPM. Incubation of MPM with serum from normal subjects as well as from subjects with homozygous familial hypercholesterolemia (HFH) resulted in a 25% increment in cellular mass of TC, due to an increment in both free cholesterol (FC) and cholesteryl ester (CE) fractions. Accumulation of TC in MPM, due mainly to elevation of CE, was observed when the macrophages were incubated in the presence of LDL or VLDL derived from either group of subjects. N-LDL caused a higher increment in cellular CE compared to HFH-LDL. However, the presence of HFH-VLDL in the medium caused elevation in the cellular TC and CE content to a higher level than did N-VLDL. The presence of N-HDL as well as of HFH-HDL in the medium resulted in a similar decrement in the cholesterol content of MPM. The decrement was expressed in both FC and CE fractions. The present study shows different abilities of normal and HFH plasma lipoproteins to cause cholesterol accumulation in MPM.

Adolescent↗

Reduced plasma high-density lipoprotein and increased platelet activity in arterial versus venous blood.

Plasma lipid and lipoprotein pattern and platelet activity were studied in blood samples derived from veins and arteries of 10 healthy male subjects. A significant reduction in plasma high-density lipoprotein (HDL) cholesterol, triglyceride and protein levels, as well as in plasma apolipoprotein A-I, was found when lipoproteins were derived from arterial blood in comparison to venous blood. All other lipoproteins were not significantly changed. Platelet activity measured as plasma beta-thromboglobulin levels and as collagen-induced platelet aggregation and 14C-serotonin release in platelet-rich plasma was markedly elevated when platelets were derived from arterial blood. Since reduced plasma HDL concentration and platelet activation are known risk factors for atherosclerosis, our study may suggest a further explanation for the presence of atherosclerotic lesions in arteries but not in veins.

Arteries↗

Benign recurrent intrahepatic cholestasis--25 years of follow-up.

Only 70 cases of recurrent intrahepatic cholestasis have been reported in the literature since the original description of this entity in 1959. The benign nature of the disease has been questioned, some authors suggesting progression to biliary cirrhosis. We report our follow-up of one such patient for over 25 years with no adverse physical consequences or histological deterioration. Sequential liver biopsies were obtained during this period. A conservative approach to diagnosis and treatment is therefore indicated.

Adult↗

Meso-2,3-dimercaptosuccinic acid in the diagnosis and treatment of lead poisoning.

Lead poisoning remains one of the hazards of industrialized civilization. CaNa2 EDTA and dimercaprol, the usual therapeutic measures, have many side effects and can be given by parenteral route alone. The authors present a case of chronic lead poisoning caused by ingestion of contaminated flour ground in a primitive flour mill. The diagnosis was confirmed by the CaNa2 EDTA provocative test. Dimercaptosuccinic acid (DMSA) was given orally as a further provocation and resulted in an 11-fold increase in urinary lead excretion. A 5-day course of treatment with DMSA was instituted, during which symptoms abated, urinary lead excretion increased and the blood lead level decreased. No side effects were noticed. There has been no relapse over several months of follow-up. The authors conclude that the oral use of DMSA is effective, safe and convenient both as a provocative test in establishing the diagnosis of lead poisoning and as a therapeutic tool.

Adult↗

Sudden deafness in a patient with temporal arteritis.

A patient with anemia and elevated erythrocyte sedimentation rate presented with sudden hearing loss. The diagnosis of temporal arteritis was verified by temporal biopsy. Initiation of corticosteroid therapy reversed the disease manifestations and within a short period improved the patient's hearing.

Aged↗

Dietary soya lecithin decreases plasma triglyceride levels and inhibits collagen- and ADP-induced platelet aggregation.

Elevated plasma lipid concentrations and increased platelet activation are risk factors in the development of atherosclerosis. Nine patients with type IIa hyperlipoproteinemia and nine patients with type IV hyperlipoproteinemia were given soya lecithin, 12 g/day, for 3 months. Plasma cholesterol and triglycerides were reduced by 15 and 23%, respectively, and HDL-cholesterol increased by 16% in the hypercholesterolemic patients. Platelet function was unchanged. In the hypertriglyceridemic patients, total cholesterol fell by 18%, triglycerides by 36%, and HDL-cholesterol increased by 14%. There was a 27% reduction in platelet aggregation (P less than 0.01). Seventeen hypertriglyceridemic patients then received increasing doses of soya lecithin for 1-month periods (6, 12, and 18 g/day). The optimal lipoprotein-lowering effect was achieved with a daily dose of 12 g soya lecithin per day. Both low-density lipoprotein and very-low-density lipoprotein levels were reduced, and HDL-cholesterol and apolipoprotein levels were reduced, and HDL-cholesterol and apolipoprotein A-I concentrations were increased. Platelet aggregation in response to collagen and ADP was significantly reduced, parallel with the reduction in triglyceride level. Soya lecithin supplementing the diet may be useful in the management of the hypertriglyceridemic patient.

Adenosine Diphosphate↗

Plasma lipoprotein and platelet function after heparin injection: studies in normal fasted and postprandial and in type V hyperlipoproteinemic subjects.

The effect of heparin injection (50 IU/kg body weight) on plasma lipoprotein concentration and composition as well as on platelet aggregation and 14C-serotonin release was studied in normal fasted subjects, normal subjects 4 hr after a fatty meal (postprandial state), and in primary type V hyperlipoproteinemic patients. Heparin injection resulted in a reduction in plasma triglyceride, cholesterol, and phospholipids as well as in the inhibition of platelet function in either the presence or the absence of the plasma environment. Heparin injection resulted in catabolism of triglyceride-rich lipoproteins and increment of cholesterol and protein in the high-density lipoprotein (HDL) density range. In fasted normal subjects, very-low-density lipoprotein (VLDL) was reduced by 50%; in the postprandial state, both VLDL and chylomicrons decreased similarly; but in phenotype V hyperlipoproteinemia, only chylomicrons (but not VLDL) degraded. Heparin injection also caused increased electrophoretic mobility of plasma lipoprotein. Upon incubation of similar lipoprotein concentration, derived before and after heparin injection, with normal washed platelets, we found that in all the groups all the lipoproteins (except HDL) derived after heparin injection caused reduction in platelet activity. High-density lipoproteins derived after heparin injection, especially from type V hyperlipoproteinemic subjects, increased normal platelet activity, and this probably represents an effect of chylomicron remnant particles in the HDL density range. Our study thus demonstrates altered composition and concentration of plasma lipoprotein after heparin injection and may suggest the appearance of remnant particles with atherogenic properties.

Adult↗

Increased low-density lipoprotein levels after splenectomy: a role for the spleen in cholesterol metabolism in myeloproliferative disorders.

Patients with myeloproliferative disorders demonstrate decreased plasma cholesterol and apolipoprotein B concentrations, and this has been related to the presence of a large spleen. Patients that underwent splenectomy in the past demonstrated normal plasma cholesterol levels. Plasma high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I were also reduced in these patients, but were normal after splenectomy. To study the immediate effect of splenectomy on the plasma lipid pattern, three patients with myeloproliferative disease and a large spleen who were undergoing splenectomy were compared with two control groups, one undergoing orthopedic operations and the second, cholecystectomy. In the control groups, plasma lipids tended to decrease for the first 2 days after surgery and then returned to preoperative levels. After splenectomy, however, plasma cholesterol, low-density lipoprotein (LDL), and apolipoprotein B significantly increased, reaching maximum levels after 4 days. Plasma HDL as well as apolipoprotein A-I decreased 1 day after splenectomy, but then increased over and above their preoperative concentrations. These results suggest an important role for the spleen in cholesterol metabolism in these patients. The spleen appears to be an important site for LDL catabolism in these patients.

Adult↗

Plasma lipoproteins and platelet aggregation during alimentary lipemia. Decreased atherogenic pattern in the elderly.

Ten healthy women in their tenth decade of life were compared with ten healthy women in their fourth decade of life regarding the response of plasma lipoproteins and platelet aggregation to one meal rich in saturated fats. In the elderly group, plasma cholesterol decreased in the postprandial state three hours after the meal in comparison to no significant changes in the younger group. This resulted from reduction in plasma lipoprotein cholesterol levels, except for the high-density lipoprotein (HDL) cholesterol, which was enhanced. A similar pattern was found for plasma lipoprotein levels. The increase in plasma triglyceride concentration in the elderly women was less than in the younger women, as fewer changes in their plasma triglyceride-rich lipoproteins (chylomicrons and very-low-density lipoprotein) were observed. Platelet aggregation in response to collagen was reduced in the elderly women, whereas in the younger group, increased platelet aggregation in the postprandial state was found. Our study thus demonstrates a clear advantage of the elderly women in comparison to the younger ones in reducing atherosclerosis and thrombotic risks. The elderly group responded to the saturated fat-rich meal by minimal plasma triglyceride elevation, an increase in HDL cholesterol concentration, and reduced platelet aggregation.

Adult↗

Bisalbuminaemia in pancreatic ascites.

A patient with pancreatic ascites is described. Electrophoresis of the patient's serum demonstrated bisalbuminaemia, which disappeared after resolution of the ascites.

Albumins↗

Increased platelet aggregation during alimentary hyperlipemia in normal and hypertriglyceridemic subjects.

The influence of 2 different fatty meals, rich in either saturated or polyunsaturated fatty acids, on platelet aggregation in 7 normolipemic subjects and in 10 patients with phenotype IV hyperlipemia, was studied. 3 h after ingestion of a saturated- or polyunsaturated-fat-rich meal, plasma triglycerides were similarly increased in both groups. 5 h after ingestion of fat of either origin, the plasma triglyceride level in normal subjects returned almost to the fasting level, whereas in patients with hypertriglyceridemia it was still elevated. Platelet aggregation induced by ADP in platelet-rich plasma significantly increased in the normal group 3 h after both meals, whereas in the patient group it increased only after the saturated-fat-rich meal. These results were not changed 5 h after the meals. Postprandial elevated platelet activity was not correlated with increased plasma triglyceride concentration. No changes were found in washed-platelet aggregation in normal subjects, whereas the patient-derived washed platelets showed increased aggregation after the saturated-fat-rich meal. Plasma chylomicrons prepared from both groups during alimentary hyperlipemia inhibited ADP-induced platelet aggregation as well as thrombin-induced platelet 14C-serotonin release. This study indicates that the intake of fatty meals induces acute disturbance in platelet aggregation, favoring thrombosis. These changes are more comprehensive in hyperlipemic patients and after a saturated-fat-rich meal.

Adult↗

Enhanced in vitro platelet aggregation in hemodialysis patients.

Hemodialysis patients suffer from premature atherosclerosis and various thrombotic and thromboembolic phenomena. Despite enhanced in vivo platelet activity, it is unclear whether in vitro platelet aggregation is increased or reduced in this population. We studied platelet aggregation in response to adenosine diphosphate and to epinephrine in 20 chronic hemodialysis patients and 21 controls. In the patient group the in vitro platelet aggregation was significantly enhanced in response to both aggregating agents. Our study demonstrated that in vitro platelet aggregation is enhanced in patients with chronic renal failure undergoing hemodialysis.

Adenosine Diphosphate↗

Postprandial plasma lipoproteins in normal and hypertriglyceridaemic subjects and their in vitro effect on platelet activity: differences between saturated and polyunsaturated fats.

The postprandial plasma lipoprotein pattern was studied in 10 normal and 10 hypertriglyceridaemic subjects after consumption of either a saturated or a polyunsaturated fat-rich meal. Plasma triglycerides increased in both groups 3 h after the meal, and this was followed after 5 h by a dramatic reduction in the normal subjects only; the reduction was less after the saturated fat meal than after the polyunsaturated fat meal. This plasma triglyceride pattern was a consequence of changes in the chylomicron and very-low-density lipoprotein (VLDL) fractions. No significant changes were found in high-density lipoprotein (HDL)- and low-density lipoprotein (LDL)-cholesterol, triglycerides or protein concentration. Plasma cholesterol and apolipoproteins (apo) A-I and B were not significantly altered. The VLDL-apo C-III/apo C-II ratio increased 3 h after the saturated fat-rich meal, but decreased after the polyunsaturated fat-rich meal in normals, but not in the patient group. The effect of these postprandial lipoproteins on platelet function was studied by incubating normal washed platelets with the lipoprotein and then determining aggregation and [14C]serotonin release. All chylomicron fractions decreased platelet activity, whereas postprandial VLDL increased platelet activity. Five hours after the meals, the effect of VLDL on platelet activation was reduced in normal subjects only. The effect of postprandial LDL and HDL on platelet function differed little from that of the fasting lipoproteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Chylomicron-like particles in severe hypertriglyceridemia.

Plasma lipoproteins in a diabetic patient with severe hypertriglyceridemia and turbid, milky plasma were studied and compared with those found in three primary type V hyperlipoproteinemic and in three normal subjects after a fatty meal. All subjects had normal post-heparin lipolytic activity. Lipoprotein electrophoresis of the patient's plasma revealed no chylomicron band, and upon short-time ultracentrifugation the patient's supernatant showed most lipid staining in the pre-beta-lipoprotein region. This supernatant, which in type V hyperlipoproteinemia as well as in normal subjects after a fatty meal, contains a large proportion of apolipoprotein B-48 (of intestinal origin), was found in our patient to contain mostly apolipoprotein B-100 (of liver origin). Upon incubation of normal washed platelets with chylomicrons derived either from type V hyperlipoproteinemic or from normal subjects after a fatty meal, platelet aggregation was decreased, whereas the chylomicron-like particles from the patient increased platelet activity. It is, thus, suggested that the triglyceride-rich, cholesterol-poor lipoproteins are of liver and not of intestinal origin.

Adult↗