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Biomedical subjects

J A Little

Publications and source records attributed to J A Little.

At least 73 records · Page 4Linked to original sources

The association of dyslipoproteinemia with corneal arcus and xanthelasma. The Lipid Research Clinics Program Prevalence Study.

The prevalence rates of xanthelasma and corneal arcus were computed for normolipidemic and dyslipoproteinemic participants in the Lipid Research Clinics population surveys. The prevalence of both xanthelasma and corneal arcus increased with age, was highest in persons with type II phenotype, and usually low in those with type IV phenotype. The relative effects of age and use of gonadal hormones were different in the two lesions. Both xanthelasma and corneal arcus were associated with increased levels of plasma cholesterol and low-density lipoprotein cholesterol (LDL-C), especially in young males. In general, persons with either lesion had increased odds of having type IIa dyslipoproteinemia but decreased odds of having type IV. Xanthelasma and corneal arcus were highly associated with each other, especially in young people. There was no consistent univariate association of xanthelasma and corneal arcus with smoking, alcohol consumption, blood pressure, obesity, sedentary lifestyle, family history of ischemic heart disease, or glucose and uric acid plasma concentrations. Adjusted odds ratios for ischemic heart disease in participants with xanthelasma and corneal arcus were generally increased, except in older female nonusers of gonadal hormones, in whom they were significantly decreased. Neither xanthelasma nor corneal arcus showed a consistent association with manifestations of peripheral arterial disease. Thus the clinical findings of xanthelasma or corneal arcus, especially in young people, seem to identify persons with plasma lipoprotein abnormalities.

Adult↗

Customary diet, anthropometry, and dyslipoproteinemia in selected North American populations. The Lipid Research Clinics Program Prevalence Study.

The intake of nutrients, determined by 24 hr diet recall, and body measurements were obtained in 8250 free-living white study participants divided into 20 to 49 and 50 + age groups for males and female nonusers and users of gonadal hormones. They were classified into dyslipoproteinemia (DLP) phenotypes: hyperHDL, hypoHDL, IIA, hpypoLDL, IV, and normal. The dyslipoproteinemia DLP phenotypes, compared with the normal, had biologically meaningful differences in nutrient intake and indexes of obesity that were most marked for males aged 20 to 49 years as shown in the table (below). Those with the hyperHDL phenotype were thinner and ingested more energy and more alcohol and less carbohydrate as percent kilocalories (%kcal). Individuals classified as hypoHDL were fatter and tended to ingest less energy and less alcohol as %kcal. Persons with the type II phenotype were fatter and ingested less energy. Those with hypoLDL tended to be thinner and ingested more energy. Individuals with the type IV phenotype were fatter, ingested less energy and carbohydrate and more alcohol as %kcal. Similar trends were observed in female nonusers of hormones aged 20 to 49 and to a lesser extent in the 50 + age groups and in female users of hormones. Dietary protein, cholesterol, total fat, and polyunsaturated and saturated fatty acids had no consistent associations with DLP phenotype, and sucrose and starch had no association independent of total carbohydrate. This is the first evidence of an association of customary diet and DLP phenotypes in the free-living population. Equating energy intake with energy expenditure, persons with the high-risk phenotypes, IIA, IV, and hypoHDL, compared with the normal, had decreased energy expenditure and were fatter, whereas those with the low-risk phenotypes, hyperHDL and hypoLDL, had increased energy expenditure and were thinner.

Adult↗

Comparative studies of triacylglycerol structure of very low density lipoproteins and chylomicrons of normolipemic subjects and patients with type II hyperlipoproteinemia.

The triacylglycerols of very low density lipoproteins (VLDL) and of chylomicrons were analyzed in the fasting and postabsorptive states from normolipemic subjects and patients with Frederickson's Type II hyperlipoproteinemia, who subsisted on free choice diets, standard diets excluding lard, or were given a breakfast enriched in lard. The VLDL and chylomicrons were obtained by conventional ultracentrifugation, and the triacylglycerols were isolated by thin-layer chromatography (TLC). Representative sn-1,2-, sn-2-3- and sn-1,3-diacylglycerols were generated by partial Grignard degradation of the triacylglycerols and a stereospecific hydrolysis by phospholipase C of the mixed sn-1,2(2,3)-diacyl phosphatidylcholines prepared as intermediates. Representative sn-2-acylglycerols were obtained by hydrolysis with pancreatic lipase. Positional distribution of the fatty acids was established by subtracting in turn the fatty acid composition of the sn-2-position from the fatty acid composition of the sn-1,2- and sn-2,3-diacylglycerols. The molecular association of the fatty acids in the diacylglycerol moieties was determined by gas-liquid chromatography with mass spectrometry (GC/MS) of the tertiary-butyldimethylsilyl (t-BDMS) ethers. The molecular association of the fatty acids in the triacylglycerols was determined by 1-random 2-random 3-random calculation following experimental validation of the distribution. The results confirm a marked asymmetry in the positional distribution of the fatty acids in all triacylglycerol samples, with the palmitic acid predominantly in the sn-1-position, the unsaturated acids about equally divided between the sn-2- and sn-3-positions, and the stearic acid divided about equally between the sn-1- and sn-3-positions. The overall structure of the VLDL and chylomicron triacylglycerols from patients and control subjects was characterized by a non-correlative distribution of fatty acids under all dietary conditions.

Adult↗

Leucocyte esterase determination as a secondary procedure for urine screening.

The use of a dipstick to detect leucocyte esteraseuria (Chemstrip L) was compared with the visualisation of leucocytes in a Gram stained smear for the detection of pyuria. The sensitivity and specificity of the two systems using the predictive value theory were similar. The use of a dual screening procedure (automation plus dipstick) allowed reliable 4 h screening of urine specimens for the detection of urinary tract infections.

Esterases↗

Comparisons of specific crosses from Duroc, Hampshire and Spot backcross sows.

One hundred 3/4 Duroc-1/4 Landrace (DDL), 3/4 Hampshire-1/4 Landrace (HHL) and 3/4 Spot-1/4 Landrace (SSL) backcross sows were randomly mated to Yorkshire boars to produce a total of 299 litters and 3,271 pigs to determine the effect of dam breeding on preweaning and postweaning performance of the pigs and litters. Litter sizes born and born alive were not significantly different among the three dam breeds studied. However, litter sizes alive at 21 d out of HHL sows were significantly larger than litter sizes out of SSL sows, while the litter sizes out of DDL sows were intermediate to the other two dam breeds. The DDL sows had significantly heavier litters at birth than did SSL sows, but the dam breeds did not differ in the weights of their litters at 21 and 42 d. Pigs out of DDL sows were heaviest at birth but weighed the least at 21 d, while pigs out of SSL sows were heaviest at 21 and 42 d of age. Pigs out of HHL sows weighed the least at birth and at 42 d. There were no significant differences among the dam breeds in the survival rate of their pigs. In the postweaning period, pigs out of HHL sows were the slowest growing and took the most days to reach 100 kg. Feed conversion and average daily feed consumption did not differ significantly among the three dam breeds studied.

Animals↗

Two-chain disulphide-bonded structure of antigen-specific T-helper factor: both chains are necessary for activity and their interaction is I-A restricted.

The molecular structure of the antigen-specific T-helper factor (ThF) which augments contact sensitivity in mice was studied. ThF was split into two types of polypeptide chain by mild reduction and alkylation; one antigen binding (which determined the specificity), the other non-antigen binding. The two chains were, by themselves, inactive but complemented each other and reconstituted biological activity. In addition, a genetic restriction was observed in the complementation of the two chains which mapped to the I-A subregion of the H-2 complex.

Animals↗

Studies of triacyglycerol structure of very low density lipoproteins of normolipemic subjects and patients with type III and type IV hyperlipoproteinemia.

The triacylglycerols of very low density lipoproteins (VLDL-TG) were analyzed in samples from normal subjects and patients with Frederickson's Type III and Type IV hyperlipoproteinemia. VLDL were obtained by conventional ultracentrifugation, and the triacylglycerols were isolated by thin-layer chromatography (TLC). Representative sn-1,2(2,3)- and sn-1,3-diacylglycerols were generated by Grignard degradation of the triacylglycerols, and were resolved by TLC on borate-treated silica gel. The molecular association of the fatty acids in the diacylglycerol moieties was determined by gas-liquid chromatography with mass spectrometry (GC/MS) of the tertiary-butyldimethylsilyl ethers. The positional distribution of the fatty acids was established by the Brockerhoff stereospecific analysis. The results showed a marked asymmetry in the distribution of the fatty acids in all samples, with the saturated acids predominantly in the sn-1-position and the unsaturated fatty acids distributed about equally between the sn-2- and sn-3-positions. In all instances, the molecular species composition of the sn-1,2-, sn-2,3- and sn-1,3-diacylglycerols was found to be similar to that calculated for 1-random 2-random 3-random distribution of triacylglycerols. There were marked differences in the quantitative composition of the molecular species of the VLDL-TG between normal subjects and patients, but these discrepancies were attributed to differences in the fatty acid composition of the samples.

Diglycerides↗

Apolipoprotein C-II deficiency associated with nonfunctional mutant forms of apolipoprotein C-II.

Two previously unidentified apolipoproteins (apo) designated apo C-II-X and C-II-Y have been found in plasma of homozygotes and obligate heterozygotes of a family with apo C-II deficiency. Because the plasma of homozygotes do not activate lipoprotein lipase, apo C-II-X and C-II-Y are apparently nonfunctional. These apolipoproteins have isoelectric focusing points of 5.15 and 5.54, respectively, compared with 4.88 and 4.74 for the known isomorphs, C-II-1 and C-II-2, respectively. They have approximately similar molecular weights to apo C-II-1 and C-II-2 on two-dimensional sodium dodecyl sulphate-glycerol-polyacrylamide slab gel electrophoresis. They do not form insoluble antigen-antibody complexes with antibodies to apo C-II in single antibody immunodiffusion or electroimmunoassay systems. However, using a double-antibody technique in which immunoblotting is coupled with polyacrylamide isoelectric focusing slab gel electrophoresis, apo C-II-1, C-II-2, C-II-X, and C-II-Y have similar reactivity with antibodies to apo C-II. In this family the presence of apo C-II-X and C-II-Y discriminates obligate heterozygotes from normal subjects.

Apolipoprotein C-II↗

The role of lipoprotein lipase in the metabolism of triglyceride-rich lipoproteins by macrophages.

We have previously shown that cultured macrophages secrete lipoprotein lipase (LPL) into the culture medium. The purpose of these experiments was to determine the role of LPL in the uptake of very low density lipoproteins (VLDL). Both J774 cells and mouse peritoneal macrophages took up and degraded normotriglyceridemic VLDL in a saturable manner. Uptake of VLDL was effectively competed for by rabbit beta-VLDL, human VLDL, but not by native LDL or acetyl LDL. LPL activity accelerated saturable uptake of VLDL but was not a prerequisite for it. This was most clearly seen in experiments with apo-C-II-deficient VLDL. Although no hydrolysis of VLDL triglyceride occurred, saturable uptake and degradation of the C-II-deficient lipoprotein occurred. However, addition of apo-C-II enhanced saturable uptake. Normal VLDL also promoted cellular accumulation of both triglycerides and cholesteryl esters. Accumulation of triglyceride occurred by uptake of intact VLDL particles, by uptake of a triglyceride-depleted particle produced by the action of LPL, and by the direct uptake of free fatty acids generated by the activity of LPL. In turn, the latter process was influenced by the amount of albumin in the medium capable of being an acceptor for free fatty acids. Finally, we have shown that when albumin is present in the medium, the macrophage is capable of mobilizing most of its stored triglyceride over 24 h, even as its cholesteryl ester content remains constant. These studies may be relevant to the ability of VLDL to promote macrophage accumulation of cholesteryl ester, even as triglyceride accumulation is minimized.

Animals↗

Source of variance in 24-hour dietary recall data: implications for nutrition study design and interpretation. Carbohydrate sources, vitamins, and minerals.

Beaton et al (Am J Clin Nutr 1979;32:2546-59) reported on the partitioning of variance in 1-day dietary data for the intake of energy, protein, total carbohydrate, total fat, classes of fatty acids, cholesterol, and alcohol. Using the same food intake data and the expanded National Heart, Lung and Blood Institute food composition data base, these analyses of sources of variance have been expanded to include classes of carbohydrate, vitamin A, vitamin C, thiamin, riboflavin, niacin, calcium, iron, total ash, caffeine, and crude fiber. The analyses relate to observed intakes (replicated six times) of 30 adult males and 30 adult females obtained under a paired Graeco-Latin square design with sequence of interview, interviewer, and day of the week as determinants. Neither sequence nor interviewer made consistent contribution to variance. In females, day of the week had a significant effect for several nutrients. The major partitioning of variance was between interindividual variation (between subjects) and intraindividual variation (within subjects) which included both true day-to-day variation in intake and methodological variation. For all except caffeine, the intraindividual variability of 1-day data was larger than the interindividual variability. For vitamin A, almost all of the variance was associated with day-to-day variability. One day data provide a very inadequate estimate of usual intake of individuals. In the design of nutrition studies it is critical that the intended use of dietary data be a major consideration in deciding on methodology. There is no "ideal" dietary method. There may be preferred methods for particular purposes.

Adult↗

Leguminous seeds in the dietary management of hyperlipidemia.

Seven male hyperlipidemic patients substituted approximately 140g dried beans daily for other sources of starch in their diet over a 4-month period. After this, mean fasting serum triglyceride levels were reduced by 25 +/- 5% (p less than 0.01) while total serum cholesterol levels were 7 +/- 2% (p less than 0.5) lower than the values measured during the previous five clinic attendances (12 +/- 2.5 months). However, low- and high-density lipoprotein cholesterol levels remained unaltered. While taking beans a nonsignificant fall (0.7 kg) was seen in body weight. Nevertheless no change was seen in macronutrient intake determined by 1-wk diet histories recorded both before and four times during the study, although cholesterol intake decreased by 80 mg (p less than 0.02). Reintroduction of dried leguminous seeds into a Western diet may be a useful adjunct to the management of hyperlipidemia.

Adult↗

Methods for dealing with fats of unknown type in dietary surveys: the Lipid Research Clinic Population Study.

The design of the nutrition analysis tables adopted by the Lipid Research Clinics program of the National Heart Lung Blood Institute provides a specialized opportunity for assessing the fat component of 1-day dietary recalls. When the fat added during preparation of foods was unknown, rules were adopted for imputing composition. In order to investigate the effect that unknown fats produce on the apparent fatty acid composition of the diet, a detailed examination was made of 923 one-day dietary recalls from three clinics within the program. Total fat per recall from this sample averaged 107.6 g as calculated from visit 2 information. The average amount of unknown fat per recall at these three clinics was about 15.5%. About half the unknown fat at one clinic (Toronto-McMaster) could be identified and characterized through a procedure elected under Lipid Research Clinics protocol, "postinterview enquiry." Using this information, hypothetical "composite values," based on weighted means derived from the relative frequency of known use of fats and oils, were substituted for the unknown fat designations. Comparison of these composite values with values for known fats supports this approach and suggests the recommendation that postinterview information be collected for each region at the time of the inception of a new nutrition trial.

Diet↗

Clinical comparison of the enterotube II and API 20E systems for bacterial identification.

The Enterotube II and API 20E were compared for their ability to identify clinical isolates of bacteria. They were found to have similar overall rates of correct identification. The Enterotube II possessed a lower requirement for extra tests in order to complete the identification, while the API system had fewer major errors. Both systems were found to be reliable and suitable for use in a clinical laboratory.

Bacteriological Techniques↗

Lipid class and molecular species interrelationships among plasma lipoproteins of type III and type IV hyperlipemic subjects.

As a further appraisal of lipoprotein interconversion and equilibration of lipid components a detailed examination was made of the chemical class and molecular species interrelationships among the major fasting plasma lipoprotein fractions within each of six male Type IIi and Type IV hyperlipemic subjects subsisting on free choice diets. The lipoprotein fractions were prepared by conventional ultracentrifugation and the lipid class and molecular species composition of the corresponding lipoprotein fractions were determined by gas chromatography of the intact glycerol esters and ceramides. In general, each lipoprotein fraction possessed a well defined lipid class composition, which was characterized by a dramatically decreasing triacylglycerol and increasing phospholipid and cholesteryl ester content, when progressing from the very low (VLDL) to the low (LDL) and high (HDL) density lipoproteins, as already established for normolipemic subjects. Likewise, the LDL1, and LDL2 of the hyperlipemic subjects contained about two times higher proportion of total phospholipid as sphingomyelin than VLDL and HDL. Furthermore, the sphingomyelins of the HDL fraction contained about 30% more of the higher and 30% of the lower molecular weight species than the sphingomyelins of the VLDL. Smaller differences were seen in the molecular species composition of the phosphatidylcholines, cholesteryl esters and triacylglycerols among the corresponding lipoproteins. In comparison to normolipemic subjects analyzed previously, the hyperlipemic subjects showed greater individual variability. Despite this variability the lipid class and molecular species composition in the hyperlipemic subjects was again incompatible with the hypothesis which postulates direct VLDL conversion into LDL nd HDL under the influence of lipoprotein lipase and lecithin: cholesterol acyltransferase. The main differences between normolipemic and hyperlipemic plasma were found to reside in the number of the VLDL and LDL, lipoprotein particles and not in their chemical composition or physical structure, or in the apparent mechanism of their metabolic interconversion.

Adult↗

Apolipoprotein and lipoprotein concentrations in familial apolipoprotein C-II deficiency.

Lipoprotein and apolipoprotein concentrations were determined in 11 homozygous and 9 heterozygous subjects for familial apolipoprotein C-II (Apo C-II) deficiency. Apo C-II was not detectable in the homozygotes, with the exception of 1 subject who possessed immunochemically detectable quantities in one of two samples. Apolipoproteins C-III (Apo C-III) and E (Apo E) were elevated 2-3-fold in 9 of 11 homozygotes. Apo C-III, but not Apo E, correlated with triglyceride levels (1500-4100 mg/dl). However, both Apo C-III and Apo E correlated with the cholesterol levels and one another. Apolipoproteins A-I (Apo A-I), A-II (Apo A-II) and B (Apo B) were reduced to approximately 50-60% of normal values in association with very low levels of cholesterol in high density (HDL; 11 +/- 2 mg/dl) and low density (LDL; 19 +/- 6 mg/dl) lipoproteins in the homozygous subjects. These alterations were associated with a marked decrease in the proportion of plasma Apo C-III associated with HDL. The levels of apolipoprotein D (Apo D) were within the normal range. Nine obligate heterozygotes had Apo C-II concentrations (mean 1.8 +/- 0.5 mg/dl; range 1.2-2.7 mg/dl) which were approximately 40-50% of normal values (mean 2.9 +/- 0.9 mg/dl; range 1.7-5.6 mg/dl). The reduction in absolute amounts of Apo C-II was also reflected in a reduction of the ratio Apo C-II/Apo C-III in very low density lipoproteins (VLDL) and in a reduction in the ability of the sera to activate skim milk lipoprotein lipase. The concentrations of Apo A-II, Apo B, Apo C-III and Apo E were normal. Apo A-I concentrations were normal or slightly low in association with slightly reduced concentrations of HDL cholesterol and a low proportion of plasma Apo C-III in HDL in relation to LDL and VLDL in some heterozygotes. It is concluded that the marked alterations in the apolipoprotein levels in homozygous subjects are primarily a reflection of the deficiency of Apo C-II which results in severe hypertriglyceridemia. In heterozygotes, the partial deficiency of Apo C-II appears to result in a minor disturbance of the clearance of the triglycerides and Apo C-III rich particles but no marked changes in the concentrations of total lipids, lipoproteins and apolipoproteins in fasting plasma.

Adolescent↗

Immobilization hypercalcemia.

Hypercalcemia developed in our teen-aged patient after extended immobilization for a femoral fracture. In all patients immobilized from whatever cause, both blood pressure and serum calcium should be monitored. Since both the hypertension and hypercalcemia respond well to mobilization, every effort should be made to encourage activity as soon as possible.

Adolescent↗