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J R Schaefer

Publications and source records attributed to J R Schaefer.

41 records · Page 3Linked to original sources
PubMed1993

Evaluation of apoA-I kinetics in humans using simultaneous endogenous stable isotope and exogenous radiotracer methods.

Apolipoprotein A-I is the major apolipoprotein constituent of high density lipoproteins (HDL). Methods used to investigate in vivo kinetics of apoA-I include exogenous labeling with radioiodine and endogenous labeling with stable isotopically labeled amino acids. We report here a direct comparison of these methods to determine the in vivo kinetics of apoA-I in four normal subjects. Purified apoA-I was labeled with 125I, reassociated with autologous plasma, and injected into study subjects. At the same time, [13C6]phenylalanine was administered as a primed constant infusion for up to 14 hours. The kinetic parameters of apoA-I were determined from the 125I-labeled apoA-I plasma curves. For the analysis of data from stable isotope studies, very low density lipoprotein (VLDL) apoB-100, VLDL apoB-48, and total apoA-I were isolated by ultracentrifugation and subsequent preparative NaDodSO4-PAGE, hydrolyzed, and derivatized. The tracer/tracee ratio was determined by gas chromatography-mass spectrometry. Monoexponential function analysis was used to determine the tracer/tracee curves of VLDL apoB-100 and VLDL apoB-48, and total apoA-I. The mean plateau tracer/tracee ratio of VLDL apoB-100 (primarily liver-derived) was 5.19%, whereas that of VLDL apoB-48 (intestinally derived) was only 3.74%. Using the VLDL apoB-100 plateau tracer/tracee ratio as the estimate of the precursor pool enrichment for apoA-I, the mean apoA-I residence time (RT) was 5.14 +/- 0.41 days, compared with 4.80 +/- 0.30 days for the exogenous labeling method. The apoA-I RTs using these two methods were highly correlated (r = 0.874).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

In vivo metabolism of apolipoprotein A-I in a patient with homozygous familial hypercholesterolemia.

Familial hypercholesterolemia (FH), caused by a defect in the low density lipoprotein (LDL) receptor, results in high plasma concentrations of LDL cholesterol due to both overproduction and delayed catabolism of LDL. FH is also associated with significantly lower levels of plasma high density lipoprotein cholesterol and apolipoprotein (apo) A-I in both heterozygous and homozygous patients. However, the metabolic basis of the hypoalphalipoproteinemia in FH has not been elucidated. We investigated the kinetics of apo A-I in a homozygous FH patient and two normal control subjects by using endogenous labeling with a stable isotopically labeled amino acid. Study subjects were administered a primed constant infusion of 13C6-phenylalanine for 12 hours. Apolipoproteins were isolated from plasma drawn at selected time points and analyzed for their isotopic enrichment by gas chromatography-mass spectrometry. The fractional catabolic rate of apo A-I in the FH subject was found to be substantially increased (0.38 day-1) compared with that of the normal subjects (mean, 0.26 day-1). In addition, the apo A-I production rate was decreased in the FH subject (6.5 mg/kg.day-1) compared with the normal subjects (mean, 11.1 mg/kg.day-1). In conclusion, the low levels of high density lipoprotein cholesterol and apo A-I in this homozygous FH patient are due to the combined metabolic defects of increased apo A-I catabolism and decreased apo A-I production.

Apolipoprotein A-I↗
PubMed1992

In vivo metabolism of a mutant apolipoprotein, apoA-IIowa, associated with hypoalphalipoproteinemia and hereditary systemic amyloidosis.

Apolipoprotein (apo) A-I is the major protein constituent of plasma high density lipoproteins (HDL). A kindred has been identified in which a glycine to arginine mutation at residue 26 in apoA-I is associated with hypoalphalipoproteinemia and hereditary systemic amyloidosis. We isolated the mutant protein, termed apoA-IIowa, from the plasma of an affected subject and studied its in vivo metabolism compared to that of normal apoA-I in two heterozygous apoA-IIowa subjects and two normal controls. Normal and mutant apoA-I were radioiodinated with 131I and 125I, respectively, reassociated with autologous plasma lipoproteins, and simultaneously injected into all subjects. Kinetic analysis of the plasma radioactivity curves demonstrated that the mutant apoA-IIowa was rapidly cleared from plasma (mean fractional catabolic rate [FCR] 0.559 day-1) compared with normal apoA-I (mean FCR 0.244 day-1) in all four subjects. The FCR of normal apoA-I was also substantially faster in the heterozygous apoA-IIowa subjects (mean FCR 0.281 days-1) than in the normal controls (mean FCR 0.203 days-1). Despite the rapid removal from plasma of apoA-IIowa, the cumulative urinary excretion of its associated radioactivity after 2 weeks (44%) of the injected dose) was substantially less than that associated with normal apoA-I (78% of injected dose), indicating extravascular sequestration of radiolabeled apoA-IIowa.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗