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Biomedical subjects

J Shepherd

Publications and source records attributed to J Shepherd.

At least 307 records · Page 17Linked to original sources
PubMed1986

Effects of bezafibrate on apolipoprotein B metabolism in type III hyperlipoproteinemic subjects.

This study was designed to investigate the response of Type III hyperlipoproteinemic subjects to bezafibrate therapy. The metabolism of apolipoprotein B was examined in four lipoprotein subclasses of Sf 60-400 (large very low density lipoprotein (VLDL)), Sf 20-60 (small VLDL), Sf 12-20 (intermediate density lipoprotein (IDL)), and Sf 0-12 (low density lipoprotein (LDL)) before and during bezafibrate therapy. Treatment reduced the plasma concentration of VLDL and raised high density lipoprotein (HDL) cholesterol. There was no net change in LDL cholesterol or its associated apolipoprotein B. The decrease in plasma VLDL derived mainly from an inhibition of synthesis of both large and small subfractions which reduced the number of particles in the circulation without normalizing their lipid composition. Catabolism of the larger VLDL also increased, presumably as a result of lipoprotein lipase activation. Although the plasma concentration of LDL was unchanged, both its synthesis and catabolism were perturbed. Its fractional catabolic rate fell by 50%, but the impact that this would have had on its steady state level in the circulation was apparently blunted by a decrease in its synthesis from Sf 12-20 IDL. In the control phase of the study, most IDL apolipoprotein B was converted to LDL. Bezafibrate therapy channelled this material towards direct catabolism.

Adult↗
PubMed1986

The pathogenesis of hyperlipoproteinaemia.

The hyperlipoproteinaemias are among the most commonly encountered metabolic derangements seen in clinical practice, and are important because of their frequent association with atherosclerotic vascular disease. Although their underlying biochemical defects are not yet completely elucidated, sufficient comprehension of normal lipoprotein metabolism has now been acquired to permit us to ascribe mechanisms to these clinical conditions as we know them. This article briefly summarises the plasma lipoprotein transport system and classifies the major primary lipoprotein disorders according to current understanding of the pathological changes responsible for their presentation.

Humans↗
PubMed1985

The pathophysiology of cholesterol metabolism in man.

The concentration of low density lipoprotein in human plasma depends on the balance between its rates of synthesis and catabolism. Although both processes appear to be independently regulated they occur side by side in the liver and may be linked via the activity of the high affinity low density lipoprotein receptor on hepatocyte membranes. Dietary changes such as cholesterol feeding or variation in fat content can promote synthesis of the lipoprotein without changing catabolism while other interventions (e.g. sequestrant resin therapy) have the opposite effect. These different responses may be explained on the basis of compartmentalisation of regulatory sterol pools in the liver cell.

Apolipoproteins A↗
PubMed1985

123I radioiodinated antibody imaging of occult ovarian cancer.

A monoclonal antibody HMFG2 labeled with iodine 123 (123I) was given to a patient who had ovarian cancer. The scan taken 18 hours after administration of the antibody demonstrated the presence and the position of residual tumor in the pelvis that was not previously detected by ultrasonography and computerized tomography (CT) scanning. The presence of tumor was confirmed by surgery and histologic as well as immunoperoxidase examination of resected tissues. The tumor mass found was less than 0.8 cm in diameter. It is concluded that, in the search for residual or early ovarian cancer in the pelvis, monoclonal antibody scanning using 123I-labeled HMFG2 can complement ultrasonography and CT scanning.

Adenocarcinoma↗
PubMed1985

The effect of low-back pain on lumbar spinal movements measured by three-dimensional X-ray analysis.

Back pain patients have restricted spinal movements, and the pattern of disturbance from normal movements may indicate the pathology and the functioning of the lumbar spine. Biplanar radiography was used to measure the three-dimensional intervertebral movements of patients with back pain alone and with back pain plus nerve tension signs demonstrated by restricted straight leg raise. Statistically significant decreases in flexion/extension compared with a normal control group were demonstrated for both groups. Accompanying coupled movements were increased only in those patients without nerve tension signs indicating asymmetrical muscle action, while those with tension signs had symmetric splinting particularly of the lower levels. Conservative treatments had no effect either clinically or on the movements. Caudal epidural injections produced clinical improvement and increased movements demonstrating relaxation of muscle splinting. Biplanar radiography, although capable of differentiating between the groups was not able to provide clinically useful information concerning individual patients with this type of back pain.

Adult↗
PubMed1985

Is there instability in spondylolisthesis?

Biplanar radiography was used to investigate the three-dimensional intervertebral movements of patients with symptomatic spondylolisthesis to assess whether there was evidence of instability. These movements were also compared with those of a group of normal subjects. The primary movements of flexion and extension were studied, and the three-dimensional analysis enabled intervertebral translations and any coupled movements of lateral bending and axial rotation to be examined. The results showed that symptomatic spondylolisthesis resulted in reduced mobility of all levels of the lumbar spine and the appearance of coupled movements at the higher levels. The pathology did not produce instability at the level of the slip in any of these patients.

Adult↗
PubMed1985

A monoclonal-antibody-based immunoradiometric assay for apoprotein B in low-density lipoprotein.

Five different mouse monoclonal antibodies were raised against apoprotein B, the major protein in human low-density lipoproteins (LDL). Competitive binding studies suggested that these antibodies recognized four different epitopes on the lipoprotein particle. All antibodies bound to very-low-density and intermediate-density lipoproteins, which are the metabolic precursors of LDL and also contain apoprotein B. One antibody (P1C1) displayed a relative specificity for apoprotein B in LDL as compared with that in very-low-density lipoprotein and was used as a radiolabeled first antibody in an immunoradiometric assay for this lipoprotein. Measurements, either on isolated LDL or directly on plasma samples, demonstrated that this assay provides a rapid and precise method of quantification.

Animals↗
PubMed1985

Effects of 1,2-cyclohexanedione modification on the metabolism of very low density lipoprotein apolipoprotein B: potential role of receptors in intermediate density lipoprotein catabolism.

The conversion of very low density (VLDL) to low density lipoproteins (LDL) is a two-step process. The first step is mediated by lipoprotein lipase, but the mechanism responsible for the second is obscure. In this study we examined the possible involvement of receptors at this stage. Apolipoprotein B (apoB)-containing lipoproteins were separated into three fractions, VLDL (Sf 100-400), an intermediate fraction IDL (Sf 12-100), and LDL (Sf 0-12). Autologous 125I-labeled VLDL and 131I-labeled 1,2-cyclohexanedione-modified VLDL were injected into the plasma of four normal subjects and the rate of transfer of apoB radioactivity was followed through IDL to LDL. Modification did not affect VLDL to IDL conversion. Thereafter, however, the catabolism of modified apoB in IDL was retarded and its appearance in LDL was delayed. Hence, functional arginine residues (and by implication, receptors) are required in this process. Confirmation of this was obtained by injecting 125I-labeled IDL and 131I-labeled cyclohexanedione-treated IDL into two additional subjects. Again, IDL metabolism was delayed by approximately 50% as a result of the modification. These data are consistent with the view that receptors are involved in the metabolism of intermediate density lipoprotein.

Adult↗
PubMed1984

Low-density lipoprotein metabolism in mice with soft tissue tumours.

This study examines the potential value of low-density lipoprotein (LDL) as a vehicle for directing cytotoxic drugs to tumour cells in mouse model systems. Control and MAC 13 tumour-bearing NMRI mice were injected with tracer doses of 125I-labelled native and cyclohexanedione-modified 131I-labelled LDL. 18 h later the animals were killed and the radioactivities assimilated by various tissues were measured relative to plasma activity at the time of death. These values were used to calculate specific tissue receptor-mediated LDL uptake. All tissues expressed receptors but the liver and adrenal gland were particularly active. In tumour-inoculated animals, the neoplastic lesions were second only to liver in their net assimilation of LDL. CFLP mice bearing virus-induced parotid adenomata gave results similar to those obtained in NMRI animals. In order to improve the selectivity of LDL assimilation we attempted to downregulate LDL receptors in the liver and adrenal gland by administration of the bile acid sodium taurocholate or by subcutaneous injection of hydrocortisone sodium succinate. These manoeuvres together reduced uptake of the lipoprotein into both organs without affecting tumour activity.

Adenoma↗
PubMed1984

Receptor-independent low-density lipoprotein catabolism. Evaluation of 2-hydroxyacetaldehyde-treated lipoprotein as a probe for its measurement.

This study examines the protein modification procedures available for inhibiting receptor recognition of low-density lipoprotein (LDL). Glycosylation with glucose, idose or ribose blocks the interaction of the lipoprotein with the high-affinity LDL receptor on cultured fibroblast membranes and delays its clearance from the plasma of rabbits. However, the prolonged incubation required in the process also changes the metabolic properties of the lipoprotein. An alternative approach using 2-hydroxyacetaldehyde-treated LDL completely blocks receptor recognition. This modified tracer has the same metabolic properties as the reductively methylated lipoprotein in rabbits and appears to be a suitable probe for the measurement of the receptor-independent LDL catabolic pathway in humans.

Acetaldehyde↗