Phenomenological model for the phase-transition sequence in betaine calcium chloride dihydrate.
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Biomedical subjects
Publications and source records attributed to J Albers.
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The enzyme, lecithin cholesterol acyltransferase (LCAT), is responsible for the esterification of plasma cholesterol mediating the transfer of an acyl group from lecithin to the 3-hydroxy group of cholesterol. Deficiency of the enzyme is a well-known syndrome with a widespread geographic occurrence. We have cloned an allele from a patient homozygous for the LCAT deficiency. The only change that we could detect is a C to T transition in the fourth exon of the gene; this causes a substitution of Arg for Trp at position 147 of the mature protein. The functional significance of such a substitution with respect to the enzyme defect was demonstrated by transfecting the mutated LCAT gene in the cell line COS-1.
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Serum zinc and iron concentrations in a group of pregnant teen-agers supplemented with a multivitamin were compared during pregnancy with a group supplemented with a multivitamin containing 18 mg Fe. Serum measurements were at 13 wk of gestational age (prestudy) and during supplementation at 20, 32, and 38 wk, delivery, and 4 and 12 wk postpartum. Hematocrit measurements were used to adjust the measured metal concentrations for the diluting effect of the normal blood-volume increase. The non-Fe-group mean, adjusted serum Zn concentrations showed no change, but the serum Fe decreased to 28% below prestudy concentrations at 38 wk. In contrast, the Fe-supplementation group showed a progressive increase in Fe concentrations to a maximum of 38% above prestudy concentrations at 4 wk postpartum and a 35% decrease from prestudy Zn concentrations during the third trimester. The results of this study suggest that 18 mg Fe/d is adequate supplementation for nonanemic teen-age pregnancy and depresses the serum Zn concentration.
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The utility of omega-123I-hexadecanoic acid myocardial scintigraphy as a metabolic probe of cardiomyopathies was investigated. Sixteen patients with a variety of cardiomyopathies and myopathies that involve cardiac muscle and ten volunteers were imaged in the postabsorptive state in a 40 degrees LAO projection after a standard dose of omega-123I-hexadecanoic acid. An elimination T1/2 was calculated from the left ventricular myocardial time-activity curve. An uptake index, corrected for chest wall attenuation, was also computed in 7 of 10 volunteers and 8 of 16 patients. Of the 16 patients, only 2 had distinctly abnormal omega-123I-hexadecanoic acid myocardial tracer kinetics. The first patient had a metabolic disorder of which carnitine deficiency was one component. The second patient had endocardial fibroelastosis, a process which has been linked to disorders which deprive the myocardium of oxygen and energy. Therefore, the cardiomyopathy may have been caused by some abnormality of cardiac metabolism other than carnitine deficiency. Although of limited utility in the overall cardiomyopathic population, omega-123I-hexadecanoic acid myocardial scintigraphy should be further investigated as a screening test for carnitine deficiency and related metabolic abnormalities in patients at risk.
The use of long-range planning techniques is essential if health care organizations are to survive. The regulatory and competitive forces that exist right now are likely to become even stronger in the future. It is important to remember that these forces represent opportunities as well as risks. Health care organizations can best resolve the conflicts that exist by using the strategic planning process to identify alternate voluntary means to achieve the same goals.
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The automated (AutoAnalyzer II) determination of cholesterol in nine serum pools in the concentration range 3.465-8.871 mmol/l, gave results that were approximately 10% higher than reference values when the analyses were based on unesterified cholesterol standards containing the same amount of water as the sample extracts (1963 analyses in 12 laboratories during a 12 month period; automated value = 0.032 + 1.10 X (Reference value)). A serum calibration procedure was successful ilues, and was equally effective in correcting the values observed for aliquots of 368 fresh-frozen plasma samples analyzed in each of the 12 laboratories during a 38 month period.
Twelve Lipid Research Clinic laboratories performed automated fluorometric triglyceride analyses on four control serum pools of known concentration by a modified Hantzsch reaction. The analyses were done during a two-year period, with use of common standards, methodology, and quality-control procedures. Estimates of analytical bias, variability, and short- and long-term trends for each instrument and for the entire group of LRC instruments are presented. High accuracy, precision, and interlaboratory comparability were achieved through rigorous standardization and control of the entire analytical procedure. Individual instrument biases varied from an average of 4.9% below to 1.0% above reference values. Between-run variability was often less than within-run variability and interlaboratory variation was substantially less than intralaboratory variation. The total standard deviation for all instruments ranged from 37 to 63 mg/liter. Only 5 to 14% of this variation was due to differences among instruments. The among-instruments standard deviation ranged from 12 to 17 mg/liter; the between-run, within-instrument standard deviation ranged from 29 to 46 mg/liter, and within-run standard deviation from 27 to 40 mg/liter. The significance of the results for long-term collaborative studies is discussed.
The ability of cultured human arterial smooth muscle cells to regulate low density lipoprotein (LDL) receptor activity was tested. In contrast to human skin fibroblasts incubated with lipoprotein deficient medium under identical conditions, smooth muscle cells showed significantly reduced enhancement of 125I-labeled LDL and 125I-labeled VLDL (very low density lipoprotein) binding. Smooth muscle cells also failed to suppress LDL receptor activity during incubation with either LDL or cholesterol added to the medium, while fibroblasts shoed an active regulatory response. Thus, in comparison with the brisk LDL receptor regulation characteristic of skin fibroblasts, arterial smooth muscle cells have and attenuated capacity to regulate their LDL receptor activity. These results may be relevant to the propensity of these cells to accumulate LDL and cholesterol and form "foam cells" in the arterial wall in vivo, a process associated with atherogenesis.
In order to elucidate the mechanism(s) of hyperlipidemia following glucocorticoid administration, dexamethasone (0.125 mg/Kg) was administered daily intramuscularly for 2 wk to male Sprague-Dawley rats and the effects on plasma triglyceride (TG) and cholesterol (Chol), lipoprotein neutral lipids, hepatic triglyceride secretion rates (TGSR; Triton), and epididymal fat lipoprotein lipase (LPL) were determined. Special measures were taken to maintain positive caloric balance and keep the weights of control and dexamethasone-treated animals comparable. Significant increases (p less than 0.001) in TG and very-low density lipoprotein (VLDL) triglyceride associated with no change in Chol and actual reduction in both triglyceride and cholesterol in low density lipoprotein (ldl) were observed in the steroid-treated animals. Dexamethasone treatment was associated with increased basal insulin and glucose levels, an insignificant increment in TGSR, and a highly significant reduction (p less than 0.001) in LPL. These findings suggest that glucocorticoid treatment increases splanchnic triglyceride production rates, but the resulting hypertriglyceridemia is primarily a consequence of impaired VLDL removal due to low adipose tissue LPL activity.
Since quantitative and qualitative alterations in plasma lipoproteins may provide insights into mechanism(s) of altered lipid transport in renal failure, whole plasma triglyceride (TG) and cholesterol (Chol) concentrations and lipoprotein neutral lipids and composition were examined in patients with chronic renal failure (undialyzed and dialyzed) and following successful renal transplantation. Both uremic groups demonstrated increased TG (p less than 0.001) and normal Chol in whole plasma and increased total TG and Chol in the very low-density lipoprotein fraction (VLDL). All hyperlipidemic subjects showed a Type IV phenotype. The percentage triglyceride in VLDL was slightly higher than control in the dialysis patients, and significantly increased in LDL in both undialyzed (p less than 0.001) and dialyzed (p less than 0.005) uremic groups. Transplant patients had significant increases (p less than 0.001) in both TG and Chol in whole plasma, and increased total TG and Chol in both the low-density lipoproteins (LDL) and VLDL fractions. Transplant patients with hyperlipidemia showed a variety of phenotypes and an enrichment of triglyceride in VLDL and LDL. These findings indicate that abnormalities in lipoprotein metabolism in renal failure patients are not appreciably affected by chronic dialysis treatment and continue following successful transplantation. The tendency toward increased VLDL and LDL triglyceride content in these patients resembles the lipoprotein neutral lipid composition found in nonrenal patients with similarly elevated plasma lipids. These alterations could result from primary disturbances in VLDL production and/or removal.
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