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Biomedical subjects

J G Brook

Publications and source records attributed to J G Brook.

At least 73 records · Page 4Linked to original sources
PubMed1985

Chylomicrons from patients with type V hyperlipoproteinemia inhibit platelet function.

Platelet aggregation and [14C]serotonin release induced by collagen and also by ADP and thrombin were significantly decreased in patients with primary Type V hyperlipoproteinemia. Platelets derived from these patients lost their hyporesponsiveness to thrombin and ADP (but not to collagen) after washings and isolation from their plasma environment. On incubation of platelets derived from normolipidemic controls with plasma derived from patients, platelet aggregation and [14C]serotonin release were lowered by 20% and 30%, respectively. On incubation of these platelets with 100 mg/dl of chylomicron triglyceride, a 40% reduction in both platelet aggregation and [14C]serotonin release was observed. The inhibition of platelet activity was positively correlated with chylomicron concentration up to a concentration of 225 mg/dl by chylomicron triglyceride. In 2 patients, bezafibrate administration (600 mg/day) resulted in marked reduction of plasma triglyceride concentration and a parallel improvement in platelet function. The platelet hyporesponsiveness in patients with Type V hyperlipoproteinemia appears to be a consequence of platelet-chylomicron interaction. This depressed platelet function may be responsible for the absence of overt atherosclerosis noted in these patients.

Adenosine Diphosphate↗
PubMed1985

Platelet function in a case with abetalipoproteinemia.

Platelet aggregation, [14C]serotonin release and platelet malondialdehyde production were determined in a patient with abetalipoproteinemia (ABL) and found to be normal. The patient demonstrated complete absence of apolipoprotein (apo) B and decreased apo A-I concentration in plasma. The high density lipoprotein (HDL) composition of plasma was abnormal, with an increased cholesterol/protein ratio, increased apo E levels and reduced apo C concentration. The patient's platelets, like platelets derived from a normolipidemic control, possessed receptors capable of binding lipoproteins. On incubating washed platelets derived from a control subject with HDL obtained from the ABL patient, an enhancement in platelet function was observed. A similar concentration of HDL derived from the control had the opposite effect, a depression of platelet function. Lipoprotein-deficient plasma (LPDP) derived from the patient, on the other hand, decreased platelet aggregation and [14C]serotonin release in comparison to the LPDP obtained from the control. The normal platelet function observed in the patient appears to be the result of the platelet-enhancing effect of an abnormal HDL, thus compensating for the absence of low and very low density lipoproteins from the patient's plasma which, when present, stimulate platelet function.

Abetalipoproteinemia↗
PubMed1985

Hypocholesterolaemia and abnormal high-density lipoprotein in rheumatoid arthritis.

Plasma lipid and lipoprotein patterns were determined in 54 female patients with rheumatoid arthritis (RA). The patients were divided into four groups, on the basis of the treatment that was being administered (gold, penicillamine, hydroxychloroquine and nonsteroidal anti-inflammatory drugs). Plasma cholesterol levels were significantly reduced in all groups. The reduced plasma cholesterol level was a result of 26% and 36% reductions in low- and high-density lipoproteins (LDL and HDL), respectively. Very-low-density lipoprotein cholesterol was reduced only in the group receiving hydroxychloroquine, and this was associated with decreased plasma triglycerides in this group. Plasma apolipoprotein (apo) B, the LDL protein moiety, demonstrated a pattern similar to that shown for LDL cholesterol. Plasma apo A-I, the major HDL protein, was, however, in the normal range, suggesting an abnormal HDL fraction. Even though reduced HDL cholesterol was found in RA patients, the HDL/LDL ratio was normal and the apo A-I/apo B ratio was increased, suggesting that these patients are not at increased risk for atherosclerosis.

Anti-Inflammatory Agents↗
PubMed1985

Familial combined hyperlipidemia and otosclerosis--the occurrence in a large kindred.

The occurrence of otosclerosis and hyperlipidemia in four generations of a single family is described. The lipid abnormality fulfilled the characteristics of combined familial hyperlipidemia. Whereas a genetic linkage between combined hyperlipidemia and otosclerosis is feasible, our study indicates that both conditions are inherited through autosomal but unlinked genes.

Adolescent↗
PubMed1985

Differential effect of platelet inhibitors in normal and in hypercholesterolaemic subjects.

Dibutyryl cyclic AMP, forskolin, dipyridamole and butyl imidazole inhibited platelet aggregation (induced by ADP or collagen) in washed platelets more than in platelet-rich plasma preparations. Aspirin, indomethacin and epoprostenol (prostacyclin, PGI2) showed no preferential inhibition of these platelet preparations. When platelet-rich plasma from either normal or familial hypercholesterolaemic (FH) subjects was used, aspirin, indomethacin and dipyridamole (but not forskolin) inhibited platelet aggregation in normal subjects more than in FH patients. When low doses of aspirin (75 mg daily for 7 days) or dipyridamole (250 mg, single dose) were administered in vivo, platelet aggregation was inhibited more in the normal subjects in comparison to the patient group.

Adult↗
PubMed1985

Chylomicronaemia in multiple myeloma.

A patient with multiple myeloma presented with an accumulation of chylomicron-like particles. This rare finding resembled that of the type V hyperlipoproteinaemia phenotype. The lipid and lipoprotein concentration and composition were compared with values obtained from other patients with multiple myeloma, patients with the type V hyperlipoproteinaemia phenotype (accumulation of chylomicrons and very low density lipoproteins), and normal subjects. An immunoglobulin-lipid complex was demonstrated in our patient. This complex was found not to be associated with the chylomicrons and was detected only in the lipoprotein-deficient plasma. Lipid and lipoprotein concentration and composition differed from the other groups. Very low density lipoprotein concentration was reduced, and there was thus a marked difference from the type V phenotype. The chylomicrons derived from this patient were also richer in apolipoprotein C compared to chylomicrons derived from the patients with type V hypolipoproteinaemia. It appears that the abnormal composition of the triglyceride-rich lipoproteins observed in this patient renders her refractory to the normal pathways of metabolism.

Cholesterol↗
PubMed1985

Increased plasma triglycerides, cholesterol and apolipoprotein E during prolonged fasting in normal subjects.

Plasma lipid and high density lipoprotein (HDL) levels were studied in 20 normal, healthy, non-obese males while fasting (150 kcal/d with free intake of water) for 6 d in a hunger strike. Plasma triglyceride and cholesterol levels were increased by 18% after 6 d of fasting. HDL-cholesterol concentration was not significantly changed for 4 d, but decreased by 22% after 6 d. Platelet aggregation induced by adenosine diphosphate (ADP) or collagen after 6 d of fasting was in the normal range. In 3 subjects fasted for 9 d, a complete plasma lipoprotein analysis was done. Very low and low density lipoprotein (VLDL and LDL) levels were elevated, whereas HDL was reduced after 9 d of fasting. On isoelectric focusing analysis, a marked reduction in apolipoprotein (apo) E concentration in both VLDL and HDL was noted. Liver function tests showed a reduction in hepatic enzyme activity; and since apo E is of hepatic origin also, we suggest that long fasting inhibits liver function in normal subjects.

Adult↗
PubMed1985

Platelet adhesion in hyperlipidemic and hypertensive patients.

Platelet adhesion was studied in whole blood using a simple stagnation flow method in patients at high risk for the development of atherosclerosis. Fourteen patients with hypercholesterolemia, 26 with hypertriglyceridemia and 25 normolipidemic hypertensive subjects were compared with 75 normal (normotensive and normolipidemic) subjects. Increased platelet adhesion was found in hypercholesterolemic (but not hypertriglyceridemic) patients only when native blood with no anticoagulants was used. In hypertensive patients, platelet adhesion was significantly elevated, but remarkably reduced by beta-blocker drugs. Propranolol and atenolol significantly reduced platelet adhesion, but this effect was found to take a longer time than that required for significant blood pressure reduction.

Adult↗
PubMed1985

Increased platelet aggregation following splenectomy in patients with myeloproliferative disease.

In 30 patients with myeloproliferative disorders, decreased platelet aggregation in response to both ADP and collagen was demonstrated. The hypoaggregability was more drastic in patients with large spleens. Patients who had had splenectomy in the past showed normal platelet aggregation. In order to understand the role of the spleen in platelet function, platelet aggregation was studied in three patients with myeloproliferative disorders during the week following splenectomy and was compared to platelet aggregation in three control patients undergoing orthopedic operations. After splenectomy, platelet aggregation significantly increased, reaching a maximum after 3 to 4 days, but returned to presplenectomy values after 1 week. This is in contrast to the control patients, in whom no significant changes in platelet aggregation were observed. Our results suggest that the spleen retains or catabolizes the most hemostatically effective platelets.

Adult↗
PubMed1985

Plasma lipoprotein pattern and decreased platelet function in type V hyperlipoproteinemia.

Plasma lipid and lipoprotein pattern as well as platelet aggregation and [14C]serotonin release were studied in five male patients with primary Type V hyperlipoproteinemia and in age-matched healthy control subjects. Plasma very-low-density lipoprotein (VLDL) cholesterol, triglycerides (TG) and protein were significantly elevated in the patients, and this resulted in 54% and 32% increments in cholesterol:protein and TG:protein ratios, respectively. In both low-and high-density lipoproteins (LDL and HDL), the cholesterol:protein ratio was normal, but the TG:protein ratio increased threefold. In the patient VLDL, apolipoprotein (apo) E and the sialyzed apo C-III (C-III2) were elevated, but apo C-III0 was decreased; whereas in the patient HDL, sialyzed apo C-IIIs were lower than in the normal HDL. Platelet function was found to be decreased in our patients in comparison with the normal group. Upon incubation of plasma lipoproteins derived from both groups with normal washed platelets, all patient plasma lipoproteins caused decreased platelet function in comparison with the normal lipoproteins. This study indicates plasma lipoprotein abnormalities in Type V hyperlipoproteinemia and may suggest that depressed platelet aggregation and release in these patients are a result of this normal lipoprotein pattern.

Adult↗
PubMed1984

Native and modified low-density-lipoprotein interaction with human platelets in normal and homozygous familial-hypercholesterolaemic subjects.

The binding of low-density lipoproteins (LDL) as well as LDL modified by cyclohexanedione (CHD-LDL) to gel-filtered platelets (GFP) and its effect on platelet function were studied in normal and in homozygous familial hypercholesterolaemic (HFH) subjects. Only normal-derived LDL could significantly compete with normal 125I-labelled LDL for binding to normal platelets. When GFP from normal subjects were incubated with normal LDL at concentrations of 25-200 micrograms of protein/ml, platelet aggregation in the presence of thrombin (0.5 i.u./ml) was increased by 65-186%. CHD-LDL, at similar concentrations, caused the opposite effect and decreased platelet aggregation by 26-47%. Both LDL and CHD-LDL (100 micrograms/ml) from HFH patients, when incubated with normal GFP, caused a significant reduction in platelet aggregation (33 and 50% respectively). When HFH-derived platelets were used, both patient LDL and CHD-LDL (but not the normal lipoprotein) could markedly compete with the patient 125I-labelled LDL for binding to the platelets. LDL and CHD-LDL (100 micrograms/ml) from normal subjects decreased aggregation of HFH-platelets by 52 and 85% respectively, while corresponding concentrations of LDL derived from HFH subjects (HFH-LDL) and CHD-LDL derived from HFH subjects (CHD-HFH-LDL) increased platelet aggregation by 165 and 65% respectively. The present results support the following conclusions: platelet activation by LDL in normal subjects is through the arginine-rich apoprotein-binding site; more than one binding site for LDL exists on platelets; under certain circumstances, LDL binding can cause a reduction in platelet activity; specificity for LDL binding to the platelets resides in different regions of the lipoprotein in HFH and in normal subjects. We have thus suggested a model for LDL-platelet interaction in normal and in HFH subjects.

Adult↗
PubMed1984

Increased concentration of high density lipoprotein in plasma and decreased platelet aggregation in primary biliary cirrhosis.

Plasma lipoprotein concentration and composition were studied in 7 female patients with primary biliary cirrhosis and compared with 6 normal, age-matched controls. The effect of the lipoproteins derived from these patients on the function of normal platelets was also tested. High levels of plasma cholesterol and phospholipids and a raised free/esterified cholesterol ratio were found. In 4 of the patients, both HDL cholesterol and HDL protein were increased, and high levels of plasma apoprotein A-I and A-II were evident. This abnormal HDL did not contain excess apolipoprotein E. The VLDL and LDL fractions were also abnormal, as evidenced by a high cholesterol/protein ratio. Little correlation between lipoprotein disorders and clinical condition was found. Platelet function was reduced in all patients. LDL from the patients reduced aggregation of normal platelets, whereas HDL had a minimal effect. The abnormal lipoproteins in these patients may contribute to their abnormal in vitro platelet aggregation.

Adult↗
PubMed1984

Abnormal plasma lipoprotein composition in hypercholesterolaemic patients induces platelet activation.

Increased platelet activation has been shown to be a feature of patients with familial hypercholesterolaemia. Plasma lipoprotein concentration and composition were studied in eleven male patients with familial hypercholesterolaemia and in ten age-matched healthy controls. Increased levels of cholesterol were found in very-low- and low-density lipoproteins (53 and 275%, respectively), whereas in high-density lipoprotein, both cholesterol and apolipoprotein A-I were decreased by 21 and 26%, respectively. On incubation of gel-filtered platelets derived from normolipidaemic controls with identical concentrations of lipoproteins derived from either nomolipidaemic controls or hypercholesterolaemic patients very-low- and low-density lipoproteins from the patients caused significantly greater thrombin-induced platelet aggregation (P less than 0.01). High-density lipoprotein from normal subjects reduced platelet release by 22%, whereas the patients' high-density lipoprotein had no significant effect on platelet release. Lipoprotein-deficient plasma from both groups augmented platelet function to a similar extent. Lipoprotein composition has an important effect on platelet function in vitro. The abnormal lipid and protein composition of the lipoproteins derived from hypercholesterolaemic patients appears to be the cause of platelet hyperactivity observed in these patients.

Adult↗
PubMed1984

High dose of L-carnitine increases platelet aggregation and plasma triglyceride levels in uremic patients on hemodialysis.

Uremic patients undergoing chronic hemodialysis demonstrate a secondary systemic carnitine deficiency. We studied the effect of carnitine replacement with high doses (L-carnitine, 3 g/day) similar to those used in the treatment of primary systemic carnitine deficiency. 10 uremic patients on hemodialysis were randomly selected into a control group (4 patients) treated by placebo and a treatment group (6 patients) treated by L-carnitine. Plasma lipoprotein concentration and composition as well as platelet aggregation were studied before and after treatment. Following carnitine administration, a paradoxical rise in plasma triglyceride concentration from 180 +/- 66 to 219 +/- 88 mg% (p less than 0.05) was noted. No other significant changes in lipoprotein concentration and composition or in plasma apoprotein A-I and B concentration were observed. Carnitine treatment caused a significant rise in platelet aggregation induced by epinephrine, ADP, and thrombin. These findings suggest a harmful effect of L-carnitine replacement therapy when given in high doses, causing aggravation of uremic hypertriglyceridemia and increased platelet aggregation in patients predisposed to thromboembolic phenomena.

Adult↗
PubMed1983

High density lipoprotein in octogenarians.

High density lipoprotein (HDL) cholesterol, total cholesterol, and total triglyceride levels were assayed in the plasma of 42 octogenarians. No differences were found in the levels of HDL cholesterol and total triglycerides when comparing subjects with and without ischemic heart disease. The average lipid profile of males in this age group shows significantly lower levels of triglycerides and total cholesterol when compared with the females. HDL cholesterol levels were 10% higher in the females. The distribution pattern of HDL cholesterol levels in this age group suggests a bimodal distribution with 85% of the population distributed around a low peak of 53 mg% and 15% around a high peak of greater than 70 mg%. This pattern suggests that the hyperalphalipoproteinemia phenotype does exist as a separate entity in a population demonstrating longevity, but its low incidence cannot provide an explanation for longevity in the majority of subjects. Subfractionation of HDL was performed by preparative ultracentrifugation and the subfraction profile of 17 female octogenarians was compared with a group of young controls. The younger individuals had greater fat to protein ratios in the HDL-1 and HDL-2 subfractions. This was only difference in lipoprotein composition. We conclude that neither the total level of HDL particles nor the distribution of lipoprotein components among the subfractions can account for the longevity of the majority of the study population.

Aged↗