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J Shepherd

Publications and source records attributed to J Shepherd.

At least 343 records · Page 19Linked to original sources
PubMed1982

Receptor-independent catabolism of low density lipoprotein. Involvement of the reticuloendothelial system.

In this study we examine the effects of intravenous ethyl oleate emulsions on the metabolism of native and cyclohexanedione-modified human low density lipoprotein in rabbits. Treatment produced a highly significant fall in receptor-independent catabolism as measured by the fractional clearance rate of cyclohexanedione-modified low density lipoprotein. Receptor-dependent catabolism (the difference between the fractional clearance rates of native and cyclohexanedione-modified low density lipoprotein) was variably affected with some animals showing a decrease in receptor activity. These data suggest that the reticuloendothelial system makes a substantial contribution to receptor-independent low density lipoprotein catabolism in the rabbit.

Animals↗
PubMed1982

Effects of bezafibrate on receptor-mediated and receptor-independent low density lipoprotein catabolism in type II hyperlipoproteinaemic subjects.

This study examines the effects of bezafibrate (200 mg t.i.d.) on LDL metabolism in 7 type II hyperlipoproteinaemic subjects. Eight weeks of treatment lowered plasma cholesterol and triglyceride by 10% and 30%, respectively (P less than 0.02). These reductions were associated with a fall in circulating VLDL (31%, P less than 0.02) and LDL (11%, P less than 0.05), while HDL cholesterol stayed the same. LDL metabolism changed during therapy. The plasma fractional clearance rate (FCR) of autologous [125I]LDL normalized from a low value of 0.256 +/- 0.048 (mean +/- SD) to 0.298 +/- 0.040 pools/day (P less than 0.001). This was attributable to a 65% increase (P less than 0.01) in receptor-mediated LDL catabolism since the clearance of simultaneously injected 1,2-cyclohexanedione-modified [131I]LDL, which measures the receptor-independent pathway, was unaltered (FCR of [131I]cyclohexanedione/LDL in control phase = 0.194 +/- 0.030 pools/day; during drug treatment = 0.194 +/- 0.024 pools/day). We conclude that bezafibrate lowers plasma LDL in type II hyperlipoproteinaemia by promoting its degradation via high affinity receptors.

Adult↗
PubMed1982

Scanning electron microscopy of post-ejaculatory spermiogenesis in the tick Ornithodoros moubata.

The final stages of spermiogenesis in ticks occur in the female genital tract. Scanning electron microscopy was used to follow the morphologic changes that occur in the sperm during this post-ejaculatory spermiogenesis in the African soft tick, Ornithodoros moubata, and to determine a time sequence for its occurrence in vivo. Characteristic features of the maturing and mature cell described include (1) differentiation and detachment of the operculum, (2) changes in cell shape corresponding to different developmental stages, (3) passive migration of the nucleus and acrosome from an anterior to a posterior position, and (4) eversion of that portion of the acrosomal canal containing the nucleus and acrosome. A possible fate for the remainder of the acrosomal canal is suggested by extrusion and detachment of spherical structures, the 'posterior bubbles', from the posterior end of the mature supermatozoon. A mechanism for cellular elongation resulting from contractions of the outer sheath is proposed.

Acrosome↗
PubMed1982

Measurement of receptor-independent lipoprotein catabolism using 1,2 cyclohexanedione-modified low density lipoprotein.

The utility of 1,2 cyclohexanedione-modified low density lipoprotein (CHD-LDL) as a marker for the measurement of receptor independent LDL catabolism has been assessed by examining its metabolic properties in cultured human fibroblasts and in rabbits. Cell culture studies showed that the inhibition of high affinity membrane receptor binding produced by the modification could be partially reversed by prolonged incubation of the CHD-LDL at 37 degrees C. Pre-exposure of the complex to alkaline pH (pH 10.5) prevented this and yielded a product that was apparently stable. Despite its regained ability to bind to the fibroblast receptor, 125I-labeled CHD-LDL incubated at 37 degrees C for 24 hr either in vivo or in vitro was removed from rabbit plasma in the same manner as freshly prepared 131I-labeled CHD-LDL and as 131I-labeled CHD-LDL that had been treated at pH 10.5. However, its plasma clearance was significantly faster than that of reductively methylated LDL. We believe that this may result from differential catabolism of these modified lipoproteins rather than from susceptibility of the CHD-LDL to receptor-directed catabolism.

Animals↗
PubMed1982

The hepatobiliary axis and lipoprotein metabolism: effects of bile acid sequestrants and ileal bypass surgery.

Cholesterol excretion from the body is achieved almost exclusively via the hepatobiliary axis. Disruption of the integrity of this pathway by interruption of the enterohepatic circulation produces profound changes in cholesterol metabolism that affect every body tissue. This is particularly evident in the liver and gut which are the major sources of this sterol in the plasma. Elevated plasma cholesterol levels have been implicated in the pathogenesis of atherosclerosis and, in consequence, strenuous efforts have been made to find appropriate hypocholesterolemic therapy to reduce this risk. Medical or surgical interruption of the enterohepatic circulation is, to date, the most successful means of lowering plasma cholesterol, and in this review we examine the ramifications of such therapy on lipid and lipoprotein metabolism in the liver, gut, and plasma.

Animals↗
PubMed1982

High-density lipoprotein subfractions as measured by differential polyanionic precipitation and rate zonal ultracentrifugation.

Recent interest in the putative protective role of high-density lipoprotein (HDL) and its subfractions against atherosclerosis has highlighted the need for a rapid, simple subfractionation procedure. Here we compared HDL subfractionation by two recently developed polyanionic-precipitation methods with the values obtained by rate zonal ultracentrifugation. A similar result for total HDL cholesterol was obtained by all three methods. However, HDL2 cholesterol as measured by the precipitation procedures was significantly higher than the zonal value, and HDL3 was lower. This reflects the different underlying principles involved in the separations and highlights the need for a clearer understanding of the functional roles of the HDL fractions.

Adult↗
PubMed1981

Effect of saturated and unsaturated fat diets on molecular species of phosphatidylcholine and sphingomyelin of human plasma lipoproteins.

Four healthy 21-23-year-old males with normal lipoprotein patterns and plasma lipid concentrations were subjected voluntarily to two diets of 5 weeks duration each: I, highly saturated fat diet; II, highly polyunsaturated fat diet. The VLDL, LDL and HDL3 fractions were isolated by conventional ultracentrifugation from each subject on the high fat diets and the molecular species of the component phosphatidylcholines and sphingomyelins were identified and quantitated by GC-MS of the t-butyldimethylsilyl ethers of the corresponding diacylglycerols and ceramides. It was shown that the diet markedly and rather evenly affected the molecular species of the phosphatidylcholines of all lipoprotein classes. However, the changes in the corresponding major molecular species were reciprocal in nature and were consistent with a demonstrated relative resistance to alterations in surface fluidity. In contrast, the dietary fat had only a minor effect on the composition of the sphingomyelins, and did not alter the characteristic differential distribution of the molecular species among the low and high density lipoprotein classes. These results, which were free of the uncertainties introduced by analyses of derived fatty acid and which were obtained on samples isolated from the same subjects, clearly demonstrate that a complete equilibration of the molecular species of the phospholipids is not attained amont the plasma lipoprotein classes even in the fasting state. The possible physico-chemical and metabolic basis of these observations is briefly discussed.

Adult↗
PubMed1981

Concentration and distribution of human plasma apolipoprotein E.

(1) A sensitive, specific radioimmunoassay for human apolipoprotein E is described. (2) The method gave a plasma apolipoprotein E concentration of 0.107 +/- 0.051 g/l n = 55) in normal subjects. This value increased significantly (to 0.179 +/- 0.088 g/l) in type II hyperlipoproteinaemia (n = 31, p less than 0.01). Type III subjects formed a distinct group whose mean plasma apolipoprotein E concentration was increased four fold over normal (p less than 0.001). The level in type IV subjects (0.136 +/- 0.056, n = 30) did not differ significantly from the normal value. (3) When plasma was subjected to gel filtration on columns of 6% agarose, apolipoprotein E was located in three regions. Peak I corresponded to very low density lipoproteins, Peak II to the area between very low density and low density lipoproteins and Peak III to the leading edge of the high density lipoprotein fraction. No E protein eluted from the column after high density lipoproteins. (4) In contrast, ultracentrifugation of plasma resulted in up to 40% of apolipoprotein E appearing in the lipoprotein-free (d greater than 1.21 kg/l) fraction. This protein appears to hae been stripped largely from high density lipoprotein during ultracentrifugation. (5) Compositional analysis of very low density, intermediate density and low density lipoproteins isolated by a cumulative flotation procedure showed that the apoE/apoB ratio was the same in the first two species but fell to a very low value in low density lipoproteins.

Apolipoproteins↗
PubMed1981

Pressure changes after balloon distension of the colon wall in diverticular disease.

Balloon distension of the distal colon in diverticular disease does not produce the pressure change in response to increasing volumes that occurs in normal subjects. This phenomenon, though modified at first by resection, is not abolished by resection nor by myotomy or bran. This adaptive quality of the wall of the colon to balloon distension possibly reflects a structural change in its wall, as the phenomenon was present in the colon in diverticular disease in vitro as well as in vivo.

Colon↗
PubMed1980

Effects of cholestyramine on receptor-mediated plasma clearance and tissue uptake of human low density lipoproteins in the rabbit.

This study examines the effects of cholestyramine (2 g/day) on the plasma clearance and tissue uptake of human low density lipoprotein (LDL) in rabbits. 1,2-Cyclohexanedione modification of human LDL abolishes its recognition by high affinity cell membrane receptors in vitro and delays its plasma clearance in comparison to native LDL. Consequently, the difference between the fractional rates of catabolism of simultaneously injected native and cyclohexanedione-treated LDL is an index of in vivo receptor-mediated clearance of the lipoprotein. When human 125I-LDL and 131I-cyclohexanedione-treated LDL were injected into rabbits, 44% of the lipoprotein was cleared from the plasma by the receptor mechanism. Various tissues were removed from the animals at the end of the turnover study and their relative uptakes of 125I native and 131I-cyclohexanedione-treated LDL were measured. All exhibited receptor activity to some extent, incorporating more native than cyclohexanedione-modified LDL. The greatest receptor activity per g of tissue was found in lymph nodes, spleen, and liver and, in terms of whole organ uptake, the liver played a major role in LDL catabolism. Treatment of the rabbits with cholestyramine lowered the circulating LDL cholesterol level by promoting its clearance (120%, p < 0.001) via the receptor pathway. This was associated with a virtual doubling of receptor-mediated incorporation of the lipoprotein into the liver. These results suggest that the drain which cholestyramine induces in the hepatic cholesterol pool promotes LDL receptor activity in this organ and thereby lowers the level of circulating LDL.

Animals↗
PubMed1980

Cholestyramine promotes receptor-mediated low-density-lipoprotein catabolism.

We studied the influence of cholestyramine (24 g per day) on receptor-mediated and receptor-independent low-density-lipoprotein catabolism in five women with heterozygous familial hypercholesterolemia. Cholestyramine lowered the level of circulating low-density-lipoprotein apoprotein by doubling (P less than 0.01) its fractional clearance via the receptor path, but fractional catabolism by the receptor-independent route remained unchanged. Moreover, although the absolute rate of catabolism of the apoprotein was not affected by treatment, the amounts handled by each pathway altered. Catabolism via the physiologically controllable receptor route increased by 71 per cent (P less than 0.05), but there was a 12 per cent drop in clearance by the nonreceptor pathway. These data demonstrate the utility of cholestyramine in promoting low-density-lipoprotein catabolism via its specific physiologic clearance pathway. They also show that heterozygotes with familial hypercholesterolemia can increase the activity of their low-density-lipoprotein receptors when presented with an appropriate stimulus.

Adult↗
PubMed1980

Comparison of immunonephelometry and electroimmunoassay for estimation of plasma apolipoprotein A-I.

Immunonephelometry using a helium-neon laser as light-sources has been compared with the established technique of electroimmunoassay for estimation of plasma apolipoprotein A-I (apoA-I), the major protein component of high density lipoproteins (HDL). The within-batch coefficient of variation for immunonephelometry was 6.7% and for electroimmunoassay was 4.7%, but both methods showed similar between-batch precisions (6.9% and 7.0% respectively). Plasma from 122 subjects (62 male, 60 female) were analysed by both methods. Results showed good correlation but immunonephelometry gave consistently lower apoA-I values (mean +/- 1 S.D. = 1.32 +/- 0.25 g/l) than did electroimmunoassay (1.56 +/- 0.33 g/l). Plasma apoA-I concentrations obtained by both procedures were significantly higher (P less than 0.002) in females than in males. Both assays gave results which were highly correlated with high density lipoprotein cholesterol. Immunonephelometry is therefore considered to be satisfactory for estimation of plasma apoA-I concentration.

Apolipoproteins↗