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Biomedical subjects

J Shepherd

Publications and source records attributed to J Shepherd.

At least 379 records · Page 21Linked to original sources
PubMed1978

Metabolism of apolipoproteins A-I and A-II and its influence on the high density lipoprotein subfraction distribution in males and females.

Rate zonal ultracentrifugation of plasma samples from ten healthy age-matched volunteers (five males, five females) indicated that the high density lipoprotein subfraction ratio (HDL2:HDL3) in females was significantly higher than in males. The cause of this phenomenon was investigated by simultaneous examination of the metabolism of the major HDL apoproteins (apoA-I and apoA-II) in both groups. The results show that there is no significant sex-related difference in the plasma pool size, fractional catabolic rate, or synthetic rate of either apoprotein. We conclude that the increased HDL2:HDL3 ratio in femalse versus males does not derive from measurable differences in the metabolic handling of either apoprotein.

Adult↗
PubMed1978

Pyridoxol metabolism in vitamin B6-responsive convulsions of early infancy.

As there is uncertainty about the nature of the metabolic defect in vitamin B6-responsive convulsion, certain aspects of pyridoxol metabolism were studied in 3 patients who were believed on clinical grounds to have the condition. The findings were compared with those in healthy children and adults, and in children with mental handicap. The magnitude of the initial rise and the subsequent fall in plasma pyridoxal phosphate (PALP) concentrations after a load of pyridoxol suggested that the vitamin B6-responsive patients were able to synthesise PALP normally but were unable to maintain the prolonged high levels normally found in plasma. The urinary excretion of 4-pyridoxic acid was within normal limits, but the excretion of pyridoxol after the load was raised. It is suggested that there may be an instability of the PALP-albumin complex in this condition. Some of the biochemical features were also observed in an infant presenting with convulsions soon after birth but without evidence of clinical B6-dependency.

Adult↗
PubMed1978

Chemical and kinetic study of the lipoproteins in abetalipoproteinaemic plasma.

Abetalipoproteinaemic plasma lipoproteins were fractionated by molecular sieve chromatography into two classes on the basis of size. Each class had the same chemical and immunochemical composition and seemed to be interconvertible in vitro, presumably as a result of aggregation/disaggregation. The low levels of circulating apolipoprotein A-I found in abetalipoproteinaemic subjects have been shown by kinetic analysis to result from reduced synthesis of the apoprotein and not from increased catabolism or redistribution between vascular and extravascular compartments.

Abetalipoproteinemia↗
PubMed1978

Effects of dietary polyunsaturated and saturated fat on the properties of high density lipoproteins and the metabolism of apolipoprotein A-I.

In this study we have investigated, in four normal males the effects of dietary saturated and polyunsaturated fat on the chemical composition and thermotropic properties of human high density lipoproteins (HDL) and have measured the influence of the diets on the metabolism of that fraction of HDL apolipoprotein A-I (apoA-I) that undergoes exchange in vitro and accounts for approximately two-thirds of the lipoprotein's apoA-I complement. When compared with the saturated fat diet, the polyunsaturated diet reduced plasma cholesterol (24%, P < 0.01) by affecting the cholesterol content in the very low density lipoprotein ( downward arrow25%, P < 0.02), low density lipoprotein ( downward arrow20%, P < 0.01), and high density lipoprotein fractions ( downward arrow33%, P < 0.01). Plasma triglyceride was also lowered (by 13%, P < 0.01). Furthermore, polyunsaturated fat ingestion caused a significant fall in the palmitate and stearate content of HDL triglyceride (41 and 37%, respectively), cholesteryl esters (29 and 35%), and phospholipids (17 and 9%) with a concomitant increase in the linoleate content of these moieties (157, 28, and 29%, respectively). The polyunsaturated diet also produced reciprocal changes in the percentage protein ( downward arrow9%, P < 0.02) and phospholipid ( downward arrow11.5%, P < 0.01) in HDl. These compositional changes were associated with an increase in the microscopic fluidity of the polyunsaturated HDL, although both diets had little effect on the fluidity parameters of HDL at body temperature. Rate zonal ultracentrifugation indicated that the HDL(2)/HDL(3) ratio fell by 28% (P < 0.05) on the polyunsaturated fat diet. In addition to the above, this diet reduced plasma apoA-I by 21% (P < 0.01). No change was seen in the fractional catabolic rate or the distribution of the apoprotein between intravascular and extravascular compartments on the two diets. However, when compared with the saturated diet, the synthetic rate of apoA-I was reduced by 26% during polyunsaturated fat feeding. The results show that polyunsaturated fat alters the chemical composition, thermotropic properties, and subfraction distribution of HDL without changing the fractional rate of catabolism of their major protein, apoA-I.These findings deserve careful consideration in determining the applicability and efficacy of polyunsaturated fat diet therapy in the prevention of atherosclerosis in man.

Adult↗
PubMed1978

Dynamic properties of human high density lipoprotein apoproteins.

This study was designed to identify a method for the measurement of human high density lipoprotein subfraction (HDL2 and HDL3) metabolism. Apolipoproteins A-I, A-II, and C, the major HDL apoproteins, were radioiodinated and incorporated individually into HDL2 and HDL3 in vitro. Using a double label technique, the turnover of apoA-I in HDL2 and HDL3 was measured simultaneously in a normal male. The apoprotein exchanged rapidly between the two subfractions, evidenced by equilibration of their apoA-I specific activity. Radiolabeled apoA-II, incorporated into the subfractions, showed a similar exchange in vitro. Incubation of 131I-labeled very low density lipoproteins (VLDL) with HDL or its subfractions resulted in transfer of C proteins from VLDL to the HDL moiety. The extent of transfer was dependent on the HDL subfraction present; 50% of the VLDL apoC was transferred to HDL3, while the transfer to total HDL and HDL2 was 69% and 78%, respectively. ApoC also exchanged between HDL2 and HDL3, again showing a preference for the former and suggesting a primary metabolic relationship between VLDL and HDL2. Overall, the study indicates that apoA-I, apoA-II, and the C proteins exist in equilibrium between HDL2 and HDL3. This phenomenon precludes their use as probes for HDL subfraction metabolism in humans.

Apolipoproteins↗
PubMed1978

A comparison of two methods to investigate the metabolism of human apolipoproteins A-I and and A-II.

Two methods are compared for measuring the kinetic parameters of apolipoprotein A-I and A-II metabolism in human plasma. In the first, high density lipoprotein apoproteins were radioiodinated in situ in the lipoprotein particle (endogenous apoprotein labeling) while in the second, individually labeled apolipoprotein A-I or A-II was incorporated into the particle by in vitro incubation (exogenous apoprotein labeling). The catabolic clearance rate of exogenously labeled apolipoprotein A-I was consistently faster than that of endogenous apolipoprotein A-I. Conversely, endogenously and exogenously labeled apolipoprotein A-II were catabolized at identical rates. The fractional plasma clearance rates of endogenous apolipoproteins A-I and A-II were the same.

Adult↗
PubMed1977

Dielectric studies on self-associating nucleosides and bases in aqueous solution.

Measurments have been made of the dielectric properties of aqueous solutions in which aggregates are formed by stacking. The nucleosides cytidine, uridine and thymidine, and the bases purine, pyrimidine and 6-methylamino-9-methyl-purine (N6,N9-dimethyladenine) were investigated at around 1 MHz, where the static increments can be determined, and for cytidine, dimethyladenine, uridine and pyrimidine measurements were also made in the 100-2000 MHz range where the main relaxation of the solute dipoles is found. Whereas cytidine and purine show a positive static dielectric increment increasing linearly with concentration, dimethyladenine, uridine, thymidine and pyrimidine show a similar negative effect. Also, within the experimental accuracy, single relaxation times are found for the solute dispersions investigated. It is suggested that these relaxations correspond to the effects of free rotation of individual polar molecules in the plane of stacking. This phenomenon would also account for the linear variation of the dielectric increments with concentration. These increments are thought to be positive or negative due to the varying balance in the solutions between the loss of polarization due to displaced and "bound" water and the corresponding gain due to the polarity of the solute molecules.

Adenine↗
PubMed1977

Cue saliency in faces as assessed by the "Photofit" technique.

The present study attempted to assess the relative salience of different parts of the human face through the manipulation of the features contained in the Photofit Kit. Subjects observed a face constructed from the kit before attempting to identify the same face in an array of alternatives. The alternatives differed from the target in only one feature and this was systematically varied within the array. Nose changes were least likely to be noticed, followed by mouth and eyes, with foreheads producing the lowest rate of error. This order of features held irrespective of the similarity of the distractors or whether judgements were made in the presence or in the absence of the target. The chin region produced different results depending upon the similarity of the distractors. The results are discussed in relation to earlier experiments in which Photofit and previous studies of cue saliency were used.

Cues↗
PubMed1976

Extra-amniotic prostaglandin E2 and the unfavourable cervix.

A small dose of prostaglandin E2 suspended in a viscous medium was instilled as a single application into the extra-amniotic space of patients with unfavourable induction features the day before planned induction in an attempt to improve the condition of the cervix. Two groups of 15 patients were studied, one receiving prostaglandin E2 250 mug suspended in methyl ethyl cellulose ('Tylose') 6% solution, and the other tylose alone. Cervical status did not change in those receiving tylose alone, whereas a significant improvement occurred in 14 out of 15 patients receiving the prostaglandin. Labour began before formal induction in 1 patient receiving tylose and in 8 receiving prostaglandin.

Adolescent↗
PubMed1976

Radioimmunoassay for human plasma apolipoprotein B.

We have developed a simplified double antibody radioimmunoassay for human apolipoprotein beta. The purified antigen, a narrow density subclass of beta lipoprotein (d 1.030-1.050 g/ml; was isolated by a combination of gel filtration and ultracentrifugationmthis material gave a single immunoprecipitin arc on crossed immunoelectrophoresis into an antibody to whole human serum. The antigen was radiolabelled using iodine monochloride at pH 10. The iodinated antigen was indistinguishable immunochemically from native material and eluted as a single radioactive peak from a Sephadex G-200 column. The lower limit of sensitivity of the assay was 15 ng protein, and the working range, 15-200 ng. The mean apolipoprotein B level (+/-1 S.D.) in 128 healthy control subjects was 86.6 +/- 29.6 mg/100ml and is in agreement the values published by other workers using unmodified assays.

Apoproteins↗
PubMed1976

Diagnosis of dyslipoprotein aemia by molecular sieve chromatography.

Agarose gel molecular sieve chromatography has been used as a tool in the diagnosis of dyslipoproteinaemias. The elution profile from control plasma contained three peaks, corresponding to very-low-density lipoproteins (VLDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). These accounted for 9.5%, 23.5% and 67% of the total lipoprotein absorption at 280 nm. Elution patterns from dyslipoproteinaemic serum showed alterations, not only in peak area, but also in peak migration rate through the agarose gel. These variations were reproducible and of such magnitude as to permit the use of molecular sieve chromatography as a tool in the diagnosis of dyslipoprotein-aemias of Type I, II (a + b), III, IV and V.

Blood Protein Disorders↗
PubMed1976

Radioiodination of human low density lipoprotein: a comparison of four methods.

A comparison has been made of four labelling techniques used to radioiodinate human low density lipoprotein (LDL). (1) Chloramine T iodination at pH 7.4 was 20-25% efficient and gave a product immunologically indistinguishable from native LDL. Approximately 30% of the incorporated radioactivity, however, was found in LDL lipids, and the metabolic decay of the labelled complex in rats did not obey first order kinetics. Radiolabelling at pH 10 reduced the uptake of 125I into lipids to 10% but also cut the overall incorporation of radioiodine by a factor of 7. (2) Lactoperoxidase labelling and (3) conjugation with iodinated N-succinimidyl-3-(4-hydroxyphenyl)propionate were highly efficient (100%), but incorporation of radioactivity into the lipid moiety was unacceptably high (approximately 30%). (4) The efficiency of iodine monochloride labelling was highly reproducible and the product was immunologically indistinguishable from native LDL. Incorporation of radioactivity into the lipid moiety was less than 4% when the I/protein ratio of the product was kept at or below 1 : 1. Decay of the radiolabelled LDL in rats was monoexponential.

Animals↗
PubMed1976

Low density lipoprotein metabolism in a family of familial hypercholesterolemic patients.

A low-density lipoprotein turnover study was performed on six heteroxygous familial hypercholesterolemic subjects and five control subjects. The diagnosis of the condition was clear-cut on biochemical, clinical, and genetic grounds. Kinetic analysis of the plasma decay curves gave the following mean values: (1) The plasma concentration of low density lipoprotein apoprotein (apoLDL) in the affected subjects was 247 mg/dl, a 2.5-fold increase over control values (98 mg/dl). (2) The calculated fractional catabolic rate of the intravascular apoLDL pool in the dyslipo-proteniemics was reduced with respect to control data (16.4%/day versus 31.2%/day), and the half-life of the apolipoprotein was correspondingly increased (6.07 days versus 3.63 days). (3) The absolute catabolic rate of the apoLDL was 15.6 mg/kg/day in contrast to the lower value of 11.6 mg/kg/day in the control group. (4) A strong negative correlation was observed between the plasma apoLDL concentration and the fractional catabolic rate (r = 0.96). We conclude from our data that increased apoLDL synthesis coupled with a defective or saturated catabolic mechanism is implicated in the pathogenesis of familial hypercholesterolemia.

Adult↗