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Biomedical subjects

J G Brook

Publications and source records attributed to J G Brook.

105 records · Page 6Linked to original sources
PubMed1979

Low density lipoprotein metabolism in type IV and type V hyperlipoproteinemia.

Low density lipoproteins (LDL) are thought to arise largely from degradation of triglyceride-rich very-low-density lipoproteins (VLDL). LDL kinetics in patients with Type IV and Type V hyperlipoproteinmia were studied and compared with normal subjects. LDL labeled in the protein moiety with 125I was used as a tracer. There was no significant difference in LDL turnover between the three groups, suggesting that a catabolic defect in VLDL degradation to LDL may exist in both Type IV and Type V hyperlipoproteinemia.

Adult↗
PubMed1978

Defective high-density lipoprotein composition in patients on chronic hemodialysis. A possible mechanism for accelerated atherosclerosis.

We determined serum high-density lipoprotein cholesterol content and analyzed the approtein structure of the various lipoprotein fractions in 21 patients on chronic hemodialysis. High-density lipoprotein cholesterol was significantly reduced in all patients as compared with 11 normal persons (mean +/-1 standard deviation: 26 +/- 13 vs. 52 +/- 9 mg per 100 ml; P less than 0.001) whether or not triglyceride levels were raised. In seven of those with Type IV hyperlipoproteinemia, protein content of high-density lipoprotein and its subfractions 1, 2 and 3 were also reduced (P less than 0.001) in parallel with reductions in cholesterol in these fractions. Apoprotein electrophoresis showed an increase in "arginine-rich" peptide in very-low-density lipoprotein and high-density lipoprotein fraction 1, and a reduction in apoprotein Cll in very-low-density and high-density lipoprotein. In addition to their reduced high-density lipoprotein cholesterol levels, a major factor in the atherosclerosis of these patients may be their abnormal high-density lipoprotein composition. Their raised triglyceride levels could be due to defective lipoprotein lipase activation by the reduced very-low-density lipoprotein apoprotein.

Adolescent↗
PubMed1977

Tangier disease (alpha-lipoprotein deficiency).

A patient with asymptomatic hypocholesterolemia, mild hyperbilirubinemia, and splenomegaly was found, on lipoprotein analysis, to have Tangier disease (alpha-lipoprotein deficiency). He represents the first patient with the disease in the northeastern Unit States. Although free of clinical evidence of atherosclerosis at age 38 years, the patient has widespread tissue cholesterol ester deposition and a stron family history of atherosclerosis. Tangier disease may be much underdiagnosed; it should be suspected in every patient with hypocholesterolemia.

Adult↗
PubMed1977

The storage lipids in Tangier disease. A physical chemical study.

The physical states and phase behavior of the lipids of the spleen, liver, and splenic artery from a 38-yr-old man with Tangier disease were studied. Many intracellular lipid droplets in the smectic liquid crystalline state were identified by polarizing microscopy in macrophages in both the spleen and liver, but not in the splenic artery. The droplets within individual cells melted sharply over a narrow temperature range, indicating a uniform lipid composition of the droplets of each cell. However different cells melted over a wide range, 20-53 degrees C indicating heterogeneity of lipid droplet composition between cells. Furthermore, most of the cells (81%) had droplets in the liquid crystalline state at 37 degrees C. X-ray diffraction studies of splenic tissue at 37 degrees C revealed a diffraction pattern typical of cholesterol esters in the smectic liquid crystalline state. Differential scanning calorimetry of spleen showed a broad reversible transition from 29-52 degrees C, with a maximum mean transition temperature at 42 degrees C, correlating closely with the polarizing microscopy observations. The enthalpy of the transition, 0.86+/-0.07 cal/g of cholesterol ester, was quantitatively similar to that of the liquid crystalline to liquid transition of pure cholesterol esters indicating that nearly all of the cholesterol esters in the tissue were free to undergo the smectic-isotropic phase transition. Lipid compositions of spleen and liver were determined, and when plotted on the cholesterol-phospholipid-cholesterol ester phase diagram, fell within the two phase zone. The two phases, cholesterol ester droplets and phospholipid bilayers were isolated by ultracentrifugation of tissue homogenates. Lipid compositions of the separated phases approximated those predicted by the phase diagram. Extracted lipids from the spleen, when dispersed in water and ultracentrifuged, underwent phase separation in a similar way. Thus (a) most of the storage lipids in the liver and spleen of this patient were in the liquid crystalline state at body temperature, (b) the phase behavior of the storage lipids conformed to that predicted by lipid model systems indicating lipid-lipid interactions predominate in affected cells, (c) lipid droplets within individual cells have similar compositions, whereas droplet composition varies from cell to cell, and (d) cholesterol ester does not accumulate in the splenic artery. Since Tangier patients lack high density lipoprotein, we conclude that high density lipoprotein-mediated cholesterol removal from cells is essential only for those cells which have an obligate intake of cholesterol (macrophages).

Adult↗
PubMed1977

Complete heart block following therapeutic irradiation of the left side of the chest.

Two female patients had received therapeutic irradiation of the left side of the chest for adenocarcinoma of the left breast and 18 and 23 years later, respectively, developed atrioventricular block. Both patients had early and late cutaneous reactions, as well as fibrosis of the left lung, lymphedema of the left arm, and pathologic rib fractures but had no signs of recurrence of the carcinoma. One patient developed signs of congestive heart failure while the electrocardiogram revealed second and third degree atrioventricular block; subsequent pacemaker implantation relieved the congestive heart failure. In the second patient, fatigue was the only symptom leading to the diagnosis of transient second and third degree atrioventricular block; this symptom subsided after pacemaker implantation. Based on reports of radiation-induced cardiac damage, it is assumed that the heart block in these two patients might have been due to postirradiation fibrosis of the atrioventricular node, either direct or mediated by fibro-occlusive changes in the coronary vessels.

Adenocarcinoma↗
PubMed1975

35 eggs per day in the treatment of severe burns.

A regime involving the dietary management of 8 severely burned patients has been described, the main feature of this diet being the high egg intake. The eggs were given in a variety of forms without any untoward effects and without any distaste being developed. No pathological levels of serum lipoproteins or cholesterol were attained. Serum proteins from an initial low level reached normal values within a relatively short time. It is felt that a high egg diet is a valuable and safe addition in the management of severely burned patients.

Adult↗
PubMed1974

New observations in the clinical spectrum of the Budd-Chiari Syndrome.

Some observations on the natural history, surgical management and metabolic phenomena in B.C.S. are presented. In one patient side to side portocaval shunt brought dramatic improvement with asymptomatic followup of 5 years. The patient died of causes unrelated to B.C.S. At postmortem the shunt was patent and normal liver architecture was preserved. The second patient presented with a fulminant course culminating in acute hepatorenal syndrome. There was marked hypofibrinogenemia and extreme elevation of SGOT. Emergency portocaval shunt was followed by marked improvement in liver status. The patient died of respiratory complications on the 8th postoperative day. The third patient is one year on conservative treatment only and well. In this patient excessive renal tubular reabsorption of sodium at a distal site was documented. This may explain the generalised edema formation in patients with B.C.S. even without inferior vena cava obstruction. This is apparently the first reported instance of renal tubular function studied in B.C.S.

Adult↗
PubMedDate not supplied

Rhabdomyolysis complicating acute Epstein-Barr virus infection.

Infection with Epstein-Barr virus (EBV) is common and induces a broad spectrum of illness. In the majority of cases the disease manifests with typical signs of heterophile-positive infectious mononucleosis in which myalgia may be seen in up to 20% of cases. In this study, a case of rhabdomyolysis is reported occurring during the clinical course of an 18-year-old patient with infectious mononucleosis. This severe form of muscle involvement has been rarely associated with EBV infections. Five similar cases previously published in the English literature are also reviewed. The clinical implications of rhabdomyolysis and infectious mononucleosis are discussed.

Adolescent↗
PubMedDate not supplied

Platelet activation by plasma lipoproteins.

Enhanced platelet activity in patients with hypercholesterolemia and moderate hypertriglyceridemia can be attributed to increased LDL and VLDL and/or decreased HDL concentrations. In marked hypertriglyceridemia, where there is an accumulation of chylomicrons, platelet function is reduced. Treatment, whether by diet, medication, or plasmapheresis, that will result in a change in lipoprotein pattern is accompanied by a parallel change in platelet responsiveness. Incubation of lipoproteins with isolated platelets results in enhancement of platelet activation by LDL and VLDL and suppression of activity by HDL and chylomicrons. These findings have in vivo confirmation. They are even more pronounced and sometimes altered when the lipoproteins are derived from hyperlipidemic subjects. The effects of the lipoproteins on platelet activity appear to be dependent on lipoprotein composition and on factors such as cholesterol:protein ratio, apo C-III0:apo C-III2 ratio, apo B concentration, and triglyceride:protein ratio. The lipoproteins interact with platelets at specific receptor sites. Rapid change in platelet composition, particularly with regard to cholesterol, phospholipid, and fatty acid content, might ensue, with consequent alterations in membrane fluidity and enzyme activities and either suppression or activation of platelet function. This review has indicated that lipoproteins have a clear influence on platelet function. This interaction could be well of paramount importance in determining atherogenic risk.

Animals↗
PubMedDate not supplied

Platelet secretory products increase low density lipoprotein oxidation, enhance its uptake by macrophages, and reduce its fluidity.

Oxidized low density lipoprotein (Ox-LDL) is considered to be involved in the atherogenic process. Factors influencing the formation of Ox-LDL are thus of importance. Oxidation of LDL in a cell-free system in the presence of copper ions was significantly increased (up to 60%) by the presence of platelet-conditioned medium, (PCM) obtained from collagen-activated platelets for the duration of the oxidation period. The effect was time- and dose-dependent and was related to hydrogen peroxide and superoxide production, since PCM-induced enhanced LDL oxidation was inhibited by catalase and by superoxide dismutase, but not by protease treatments. PCM also reduced the fluidity of oxidized LDL by 45%. Upon incubation with a J-774 macrophage-like cell line, PCM-treated Ox-LDL enhanced cellular cholesteryl ester synthesis by 47% and lipoprotein degradation by 41%. Thus platelet secretory products appeared to enhance LDL oxidation through the involvement of oxidative agents. The resulting Ox-LDL demonstrated increased atherogenic properties.

Blood Platelets↗
PubMedDate not supplied

Platelet-modified lipoprotein induced by thrombin: effect of whole blood and plasma.

The effect of thrombin, the platelet-activating agent, on lipids and lipoprotein patterns in humans was studied in whole blood, in platelet-rich plasma (PRP) and in washed platelet/lipoprotein systems. Upon incubation of whole blood at 37 C for 24 h and then centrifugation of the cells, the content of plasma cholesterol and triglyceride decreased. In the presence of thrombin (10 u/ml), plasma high-density lipoprotein (HDL) levels also markedly decreased. In PRP, plasma lipids and lipoproteins were reduced to a lesser extent than in platelet-poor plasma (PPP). In the presence of thrombin, plasma HDL was decreased in PRP, but not in PPP. The electrophoretic mobility of low-density lipoprotein (LDL) was increased following incubation of whole blood, PRP or PPP, but decreased in the presence of thrombin. When washed platelets were incubated with LDL or HDL for 24 h at 37 C, there was a significant increment in the lipid and protein content of the lipoprotein medium, resulting from platelet-released particles; this phenomenon was increased in the presence of thrombin and more so with LDL. LDL--but not HDL--electrophoretic mobility was increased following incubation with washed platelets, but thrombin caused a reduction in lipoprotein electrophoretic mobility. This study demonstrates that platelets affect lipid and lipoprotein patterns and this is influenced by thrombin treatment. Platelets release lipid-protein particles, which then interact with and modify the lipoprotein.

Adult↗