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Biomedical subjects

G J Brook

Publications and source records attributed to G J Brook.

35 records · Page 2Linked to original sources
PubMed1991

Dual effect of lovastatin and simvastatin on LDL-macrophage interaction.

Lovastatin and simvastatin which are very potent cellular cholesterol biosynthesis inhibitors, significantly affect the plasma lipoprotein concentration. After incubation of plasma with 14C-labelled compounds, radioactivity was found in all lipoprotein fractions but mainly (40%) in high density lipoprotein (HDL), and in the lipoprotein-deficient plasma fraction (20-30%). Drug-treated lipoproteins showed reduced electrophoretic mobility on cellulose acetate in comparison with control lipoproteins. The lovastatin-treated low density lipoprotein (LDL) displayed 28% increased fluidity in comparison with control LDL. The immunoreactivity of drug-treated LDL with monoclonal antibody directed towards the LDL receptor binding domains (B1B6) was significantly less than that of control LDL, suggesting reduced binding to the LDL receptor. When drug-treated LDL was incubated with J-774 A.1 macrophage-like cell line, its binding (at 4 degrees C) was 28% less than that of control LDL, whereas a substantial increase in the cellular cholesterol esterification rate (by 83% with lovastatin and by 67% with simvastatin) was noted. Similarly, the degradation of lovastatin and simvastatin-treated LDL by macrophages was 87-89% greater than that of control LDL. The "apparent Vmax" for the macrophage degradation of lovastatin-treated LDL was 70% greater than that for control LDL. Thus, both drugs may have a dual effect on the macrophage uptake of LDL; they may increase the number of LDL receptors on the cell surface, but they may also reduce the affinity of LDL for its receptor, the former being the major effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Activated platelets secrete a protein-like factor that stimulates oxidized-LDL receptor activity in macrophages.

Platelet secretory products were shown to modulate the interaction between lipoproteins and their receptors on macrophages. Preincubation of macrophages for 2 h at 37 degrees C with platelet conditioned medium (PCM), followed by its removal and a further 5-h incubation in the presence of oxidized-LDL (Ox-LDL), resulted in increased cellular degradation of Ox-LDL (34%), stimulation of cellular cholesterol esterification (31%), and mass accumulation of esterified and nonesterified cholesterol (25% and 41%, respectively). These effects were found to be the result of a PCM-mediated increase in the number of Ox-LDL receptors on macrophages. PCM was shown to interact with the macrophage scavenger receptor. Enhanced Ox-LDL uptake by macrophages preincubated with PCM could not be reproduced when PCM remained in the incubation medium. Maintenance of PCM in the incubation medium reduced Ox-LDL uptake by macrophages (40%) and was shown to be PCM dose-dependent. Whereas incubation at 37 degrees C demonstrated enhanced uptake of Ox-LDL, preincubation of macrophages with PCM at 4 degrees C exhibited a 64% reduction in Ox-LDL-mediated cellular cholesterol esterification. Thus, PCM internalization by macrophages after its binding to the scavenger receptor is required to promote the enhancing effect of PCM on Ox-LDL uptake by macrophages. PCM activity was associated with platelet degranulation, and was recovered in the protein fraction of PCM. It was found to be heat- and trypsin-labile with a molecular weight greater than 25,000. PCM obtained from platelets derived from a patient with alpha granules deficiency failed to enhance the uptake of Ox-LDL by macrophages, suggesting that the active protein-like factor in PCM originated from platelet alpha granules. These results indicate that a platelet-secreted protein-like factor can modulate macrophage uptake of Ox-LDL with subsequent effect on foam cell formation.

Animals↗
PubMed1991

Decreased very low density lipoprotein fluidity in familial hypercholesterolemia.

The fluidity of lipoproteins from normolipidemic subjects and from familial hypercholesterolemic patients was investigated by fluorescence polarization. The fluorescent probe DPH (1,6-diphenyl-1,3,5-hexatriene) was incorporated into the lipoprotein fractions, and assessment of the fluidity pattern of each particle was determined by fluorescence anisotropy measurements over a temperature range of 10 to 40 degrees C. The very low density lipoprotein (VLDL) of the hypercholesterolemic patients was found to be considerably more rigid than the respective VLDL of normolipidemic subjects. Analysis of the constituents of the various lipoproteins suggested that the large difference in the fluidity between hypercholesterolemic and normal VLDL patients might be due to increased VLDL cholesterol/triglyceride, cholesterol/protein and cholesterol/phospholipid ratios, which were 10, 2 and 1.4 fold higher, respectively, in the hypercholesterolemic VLDL patients. Decreased VLDL fluidity in familial hypercholesterolemic patients may be of importance in the pathogenesis of their accelerated atherosclerosis.

Adolescent↗
PubMed1989

Familial homozygous hypercholesterolemia: clinical and cardiovascular features in 18 patients.

Homozygous familial hypercholesterolemia (HFH) is a very rare autosomal dominant disease characterized by accelerated severe atherosclerosis. We examined 18 patients from 9 families with HFH. The age range was 6-30 years (mean = 16 years). Male to female ratio was equal. All patients had huge, multiple tuberous xanthomas on the skin and tendons. Mean +/- standard deviation of plasma cholesterol, triglycerides, low-density lipoproteins (LDL), and high-density lipoproteins (HDL) cholesterol levels were 608 +/- 89, 122 +/- 39, 550 +/- 88, and 26 +/- 8 mg/dl, respectively. Five patients (28%) had angina pectoris, two sustained a myocardial infarction, and one died at the age of 15 years. Two-dimensional echocardiography demonstrated supravalvular aortic stenosis in 3 of the 13 patients (23%). Coronary arteriography performed in 11 patients demonstrated significant obstruction in 6 patients, 2 each with single-, double-, and triple-vessel disease. Left main stenosis was present in 3 patients (27%). Supravalvular aortic narrowing was demonstrated in 6 patients (54%) and was associated with a gradient in 2 (25 and 35 mmHg, respectively). Segmental contraction abnormalities were detected in 2 of the 11 patients (18%). It is concluded that coronary artery disease is prevalent in patients with HFH and, based on the data presented, we recommend the performance of noninvasive technique, coronary arteriography and supravalvular aortography at an early age to detect and to follow the progression of the disease.

Adolescent↗
PubMed1986

Early enteral nutrition for mass burn injury: the revised egg-rich diet.

An aggressive enteral nutritional approach has been employed to support our severely burned patients. The diet is based on a daily intake of 5 eggs/10 kg of body weight, incorporated into milkshakes. Twelve patients with severe burns (age, 24 +/- 4 years; burns, 54 +/- 12 per cent of total body surface area (TBSA] were studied. Enteral feeding was initiated on the day of injury and gradually reached the full formula within 3-7 days. Feeding was carried out either orally or through a nasogastric drip or a combination of both, depending on the patient's condition. Each bottle of milkshake contained 2318 kJ, 29 g protein, 51 g carbohydrate and 28.6 g fat in 250 ml. Each millilitre of the diet contained 9.32 kJ. The protein provided 21 per cent of the total calorie intake, while the fat and carbohydrate provided 42 per cent and 37 per cent respectively. The mean daily intake consisted of protein (5 +/- 1.5 g/kg), carbohydrate (8 +/- 0.75 g/kg) and fat (5 +/- 1 g/kg), providing a daily administration of 378-420 kJ/kg. Plasma lipids remained within normal limits during the 40 days of the diet, while serum protein levels rose to normal levels within the first 3 weeks.

Adult↗
PubMed1984

Platelet adhesion determination in whole blood using a simple stagnation flow method.

A simple stagnation flow method for the determination of platelet adhesivity has been developed. The sensitivity of the method to its main operational parameters was tested, resulting in recommended standard flow conditions. The method was shown to be dependent on the surface properties of the test slide, on which platelets are deposited, thus proving its suitability to elucidate variations in the surface interaction of the platelets. Normal values were established for males and females.

Adult↗
PubMed1984

Plasma cholesterol concentration and extra lipid band in monoclonal gammopathies.

Plasma lipids and lipoproteins were studied in 21 patients with benign monoclonal gammopathy, 21 patients with multiple myeloma and seven patients with Waldenström's macroglobulinaemia. Results were compared with those of a control group, age and sex matched. Low plasma cholesterol levels in all three patient groups were associated with low HDL-cholesterol concentrations. Apo A-I, but not apo B, was significantly reduced. Sixty per cent of the patients exhibited an extra lipid band on plasma lipoprotein electrophoresis, which could be an immunoglobulin-lipid complex. In these patients plasma and LDL-cholesterol levels were significantly lower than in those patients in whom this band was absent. No correlation was found between the severity of the disease and plasma lipid pattern.

Aged↗
PubMed1983

Changes in lipoproteins and subfractions following oophorectomy and oestrogen replacement in peri-menopausal women.

Serum cholesterol concentrations in lipoprotein fractions and subfractions were determined in 11 peri-menopausal women both before and after bilateral oophorectomy, as well as 60 days after commencement of oral oestradiol replacement therapy. Pre-operatively, all subjects were found to have normal lipid and lipoprotein concentrations. There was a post-operative increase in the total cholesterol level, which was attributed to a raised very-low-density lipoprotein (VLDL) cholesterol. Changes in high-density lipoprotein (HDL) subfractions HDL-2 and HDL-3 were noted but since these were compensatory little difference in total HDL cholesterol was observed. Following oral oestrogen replacement, the cholesterol level decreased as a result of a drop in both VLDL and low-density lipoprotein (LDL) cholesterol. The oestradiol-induced HDL cholesterol increment reflected an increase in the levels of both HDL subfractions.

Castration↗
PubMed1982

The effect of human plasma on platelet function in familial hypercholesterolemia.

Using a platelet-rich plasma (PRP) preparation, platelets from subjects with familial hypercholesterolemia (FH) were found to be more reactive to the aggregating agents epinephrine, ADP and thrombin than platelets obtained from normal individuals. Gel-filtered platelets (GFP) i.e. platelets free of any plasma constituents also showed increased activation as determined by platelet aggregation and 14C-serotonin release. On incubating washed platelets from normal subjects with plasma obtained from FH subjects the platelet response to aggregating agents was significantly increased. Incubation of washed platelets from the FH patients with normal plasma, however, resulted in a significant decrease in platelet activity. Our data suggest that the increased platelet activation in FH patients is the result of a change in the platelets induced by abnormal plasma constituents.

Adenosine Diphosphate↗
PubMed1978

Effect of an egg-rich diet on plasma lipids and proteins in severely burned patients.

Eight severely burned young patients were maintained on an oral hyperalimentation regimen of about 7,000 calories--including 314 proteins, 600 g carbohydrates and 336 g fats, containing greater than 8 g cholesterol--based mainly on a daily ingestion of 35 eggs. Serum cholesterol and protein, and plasma lipoprotein levels were measured during period of 30 days on the diet. The mean serum cholesterol level prior to the egg-rich diet was low [108 +/- 42 (SD) mg/dl] and it remained within the normal range during the study. The initial mean serum total protein level of 4.1 +/- 0.5 (SD) rose to 6.5 +/- 0.7 g/dl by the 19th day and stayed high throughout the remainder of the study. Plasma lipoprotein levels, assessed by nephelometry and reported as concentrations of large, medium and small particles, were not increased. It is assumed that the high demand for energy during recovery from burns prevented abnormal rises in plasma lipid levels on fat-rich diet.

Adult↗