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Biomedical subjects

J S Millar

Publications and source records attributed to J S Millar.

At least 19 recordsLinked to original sources

Measurement of human apolipoprotein B-48 and B-100 kinetics in triglyceride-rich lipoproteins using [5,5,5-2H3]leucine.

A primed-constant infusion of deuterated leucine was used in humans to determine the maximal level of enrichment at plateau of apolipoprotein (apo)B-48 and apoB-100 which are synthesized in the intestine and liver, respectively, and to compare the kinetics of these two proteins under identical conditions. Eight normal subjects (four post-menopausal females and four males) over the age of 40 were studied in the constantly fed state over a 20-h period by providing small hourly feedings of identical composition. [5,5,5-2H3]Leucine (10 mumol/kg body weight followed by 10 mumol/kg body weight per hour) was infused over 15 h intravenously. The enrichment of deuterated leucine in apoB-48 and apoB-100 triglyceride-rich lipoproteins isolated by ultracentrifugation (d less than 1.006 g/ml) was determined during the entire infusion period. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-48 was 3.96 +/- 1.41 tracer/tracee ratio (%) which was 39.7% of the plasma leucine enrichment level. The plateau level of enrichment in triglyceride-rich lipoprotein apoB-100 was 7.23 +/- 1.17 tracer/tracee ratio (%) which was 72.5% of the plasma leucine enrichment level. Mean fractional secretion rates of triglyceride-rich lipoprotein apoB-48 and apoB-100 were 4.39 +/- 2.00 and 5.39 +/- 1.98 pools per day, respectively, with estimated residence times of 5.47 and 4.45 hours, respectively. The data indicate that in the fed state there is about a twofold difference in the plateau enrichment of an intestinally derived protein, as compared to one of hepatic origin, most likely attributable to differences in the enrichment of the intracellular leucine in the two organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

The effects of intermittent dietary restriction on weight gain and body fat in white-footed mice, Peromyscus leucopus.

The effects of repeated food restriction-refeeding cycles were investigated in second generation captive Peromyscus leucopus. Mice were maintained on 50% of their individual predetermined ad lib diet for 5 days followed by 10 days of refeeding ad lib. Cycles were repeated 3 times. When compared with controls maintained ad lib for the same time period, no significant differences in final weight or fat content were observed. Restricted-refed mice were, however, observed to both lose and regain weight at increasing rates with each subsequent cycle.

Adipose Tissue

Measurement of very low density and low density lipoprotein apolipoprotein (Apo) B-100 and high density lipoprotein Apo A-I production in human subjects using deuterated leucine. Effect of fasting and feeding.

Six normolipidemic male subjects, after an 8-h overnight fast, were given a bolus injection and then a 15-h constant intravenous infusion of [D3]L-leucine. Subjects were studied in the fasted state and on a second occasion in the fed state (small, physiological meals were given every hour for 15 h). Apolipoproteins were isolated by preparative gradient gel electrophoresis from plasma lipoproteins separated by sequential ultracentrifugation. Incorporation of [D3]L-leucine into apolipoproteins was monitored by negative ionization, gas chromatography-mass spectrometry. Production rates were determined by multiplying plasma apolipoprotein pool sizes by fractional production rates (calculated as the rate of isotopic enrichment [IE] of each protein as a fraction of IE achieved by VLDL (d less than 1.006 g/ml) apo B-100 at plateau. VLDL apo B-100 production was greater, and LDL (1.019 less than d less than 1.063 g/ml) apo B-100 production was less in the fed compared with the fasted state (9.9 +/- 1.7 vs. 6.4 +/- 1.7 mg/kg per d, P less than 0.01, and 8.9 +/- 1.2 vs. 13.1 +/- 1.2 mg/kg per d, P less than 0.05, respectively). No mean change was observed in high density lipoprotein apo A-I production. We conclude that: (a) this stable isotope, endogenous-labeling technique, for the first time allows for the in vivo measurement of apolipoprotein production in the fasted and fed state; and (b) since LDL apo B-100 production was greater than VLDL apo B-100 production in the fasted state, this study provides in vivo evidence that LDL apo B-100 can be produced independently of VLDL apo B-100 in normolipidemic subjects.

Adult

Comparison of deuterated leucine, valine, and lysine in the measurement of human apolipoprotein A-I and B-100 kinetics.

The production rates of apolipoprotein (apo)B-100 in very low density lipoprotein and in low density lipoprotein and apolipoprotein A-I in high density lipoprotein were determined using a primed-constant infusion of [5,5,5,-2H3]leucine, [4,4,4,-2H3]valine, and [6,6-2H2,1,2-13C2]lysine. The three stable isotope-labeled amino acids were administered simultaneously to determine whether absolute production rates calculated using a stochastic model were independent of the tracer species utilized. Three normolipidemic adult males were studied in the constantly fed state over a 15-h period. The absolute production rates of very low density lipoprotein apoB-100 were 11.4 +/- 5.8 (leucine), 11.2 +/- 6.8 (valine), and 11.1 +/- 5.4 (lysine) mg per kg per day (mean +/- SDM). The absolute production rates for low density lipoprotein apoB-100 were 8.0 +/- 4.7 (leucine), 7.5 +/- 3.8 (valine), and 7.5 +/- 4.2 (lysine) mg per kg per day. The absolute production rates for high density lipoprotein apoA-I were 9.7 +/- 0.2 (leucine), 9.4 +/- 1.7 (valine, and 9.1 +/- 1.3 (lysine) mg per kg per day. There were no statistically significant differences in absolute synthetic rates of the three apolipoproteins when the plateau isotopic enrichment values of very low density lipoprotein apoB-100 were used to define the isotopic enrichment of the intracellular precursor pool. Our data indicate that deuterated leucine, valine, or lysine provided similar results when used for the determination of apoA-I and apoB-100 absolute production rates within plasma lipoproteins as part of a primed-constant infusion protocol.

Adult

Effect of exercise and menstrual cycle status on plasma lipids, low density lipoprotein particle size, and apolipoproteins.

Habitual physical exercise has been reported to have beneficial effects on plasma lipoproteins. To examine this question in women, plasma cholesterol, triglyceride, and apolipoprotein (apo) A-I and B levels, and low density lipoprotein (LDL) particle size were determined in 25 women runners (9 of whom had exercise-related secondary amenorrhea) and 36 age-matched nonexercising women (controls). The eumenorrheic runners had significantly lower apo B levels and significantly greater mean apo A-I/apo B ratios and LDL particle sizes than did the control women (P less than 0.05). Lower apo B levels were correlated with decreased body mass index, a known exercise effect (P less than 0.0001). In addition, normally menstruating runners had cholesterol and triglyceride levels that were 7.6% and 25.4% lower, respectively, and apo A-I levels that were 6.4% higher than control women (P = NS). In amenorrheic runners all parameters were similar to values in control women, except that apo B levels were 20% lower (P less than 0.05). Amenorrheic runners had lower plasma apo A-I levels (13%) and significantly lower apo A-I/apo B ratios and estradiol levels than eumenorrheic runners, and serum estradiol values in the runners were correlated with apo A-I levels (P less than 0.01). These data indicate that the beneficial effects of strenuous exercise on plasma apo A-I levels and apo A-I/apo B ratios in women runners can be reversed by exercise-induced amenorrhea and decreased serum estradiol levels, and that women runners have lower apo B levels than nonexercising women, regardless of menstrual status.

Adult

Epidemic jejunitis.

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Disease Outbreaks

Meat consumption as a risk factor in enteritis necroticans.

The association between the consumption of animal protein and enteritis necroticans (EN) was investigated in a case-control study of 60 proven cases of acute surgical EN. A very high risk of EN was found in association with the recent ingestion of pork and other meats with the exception of tinned fish. The control group was characterized by the more frequent and regular ingestion of animal protein (predominantly in the form of tinned fish) suggesting a protective effect. No conclusions about the causality of the observed associations could be drawn but the implications for preventive intervention are discussed.

Adult

Analyses of vegetables from the highlands of Papua New Guinea.

Ten vegetable foods of the highlands were analysed for crude protein, amino acids and trypsin inhibitor. Pandanus nut, lima bean, fern, greens, pitpit and choko had good to acceptable crude protein contents and the proteins of fern, pitpit, Rungia klossii and Indian mustard were of good quality. Lima beans had a very high content of trypsin inhibitor and all others had small or zero amounts, including fern, which is used at pig feasts and hence does not contribute to pig bel.

Amino Acids

Respiratory failure revisited: acute exacerbations of chronic bronchitis between 1961-68 and 1970-76.

Factors determining survival have been analysed retrospectively in 157 admissions of 135 patients with an acute exacerbation of chronic bronchitis and emphysema causing hypoxaemia and carbon dioxide retention. All were treated with controlled oxygen therapy. The death-rate increased with the age of the patient, but was not correlated with the age of the patient, but was not correlated with the severity of hypoxaemia on admission, when the patient was breathing air. The death-rate was significantly higher in those patients in whom arterial [H+] rose above 55 nmol/1 (pH = 7.26) during controlled oxygen therapy. The absence of a rise in the arterial PCO2 during controlled oxygen therapy was not necessarily indicative of a good prognosis, since 5 out of 18 patients showing this response subsequently died in that admission. Only 28% of the 111 patients who left hospital alive survived for five years.

Acidosis, Respiratory

Growth of Clethrionomys gapperi and Microtus pennsylvanicus in captivity.

Growth of Clethrionomys gapperi and Microtus pennsylvanicus from southern Manitoba was documented from birth to 30 days. Clethrionomys gapperi were smaller and grew more slowly (g/day) than M. pennsylvanicus, although both species were weaned at the same age. There were significant differences in growth rates between sexes in M. pennsylvanicus and among litter sizes in both species. Most of the variability in growth was due to differences among litters. The patterns of development was similar to those reported for other North American species of Clethrionomys and Microtus.

Age Factors