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Biomedical subjects

E J Schaefer

Publications and source records attributed to E J Schaefer.

At least 307 records · Page 17Linked to original sources
PubMed1982

Phenotype study of apolipoprotein E isoforms in hyperlipoproteinaemic patients.

It has been suggested that apolipoprotein E (apoE) is inherited at a single genetic locus with three common alleles designated E2, E3, and E4. The products of these three alleles are apoE2, apoE3, and apoE4. The apoE phenotypes of 74 normal subjects and 226 hyperlipoproteinaemic subjects were ascertained by gel isoelectrofocusing. Patients with type I, type IIa, type IIb, and type IV hyperlipoproteinaemia had an apoE phenotypic distribution which was similar to that of normal subjects, with 40.0 to 60.0% being homozygous for E3. In contrast, 75% of type III patients had an E2 phenotype and 25% were E2/3 heterozygotes. Among type V patients 31.4% had an E4 phenotype, and 42.9% were E4 heterozygotes. No type III patient and only 5.7% of type V patients had E3 phenotype. The results suggest that apoE2 and apoE4 are associated with two distinctly different dyslipoproteinaemias and that apoE has at least two different physiological functions.

Apolipoproteins↗
PubMed1982

POEMS syndrome: studies in a patient with an IgG-kappa M protein but no polyneuropathy.

A 48-year-old woman had a variation of the syndrome of polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (the so-called POEMS syndrome). The patient's neurological findings were entirely normal, but she had splenomegaly, hyperprolactinemia with galactorrhea and oligomenorrhea, a thyroid nodule with evidence of mild thyroiditis on aspiration biopsy specimen, and IgG-kappa monoclonal gammopathy, and hyperpigmentation and thickening of the skin. A short course of plasmapheresis (twelve 4-L exchanges in one month) did not alter any of the clinical abnormalities, but did result in a 70% decrease in the monoclonal IgG level (from 2.2 to 0.7 g/dl).

Biopsy, Needle↗
PubMed1982

Plasma lipid alterations in leukemia and lymphoma.

Plasma lipids and lipoproteins were studied at presentations in 25 patients with acute leukemia and non-Hodgkin's lymphoma. All patients demonstrated an abnormally in at least one plasma lipid fraction, and most exhibited a predictable pattern of lipid alterations that consisted of extremely low levels of high-density lipoprotein cholesterol (median [Xm] = 23), elevated triglyceride (Xm = 165) and elevated very-low-density lipoprotein (Xm = 26). Patients restudied during remission demonstrated a return to normal values. The degree of lipid abnormality was directly related to the underlying tumor burden and particularly to the presence of bone marrow involvement. However, even patients with minimal tumor bulk demonstrated plasma lipid abnormalities. The results suggest that an abnormality in systemic lipid metabolism, possibly in triglyceride clearance, is present in these patients and that its incidence in this population is high.

Adolescent↗
PubMed1982

Tangier disease: a structural defect in apolipoprotein A-I (apoA-I Tangier).

Tangier disease is a familial disorder characterized by orange tonsils, cholesterol ester deposition in reticuloendothelial cells, abnormal chylomicron remnants, and a marked reduction in high density lipoproteins. Plasma concentrations of the apolipoproteins apo-A-I and apoA-II in patients with Tangier disease are approximately 1% and 7% of those in normal subjects, respectively. Previous studies have shown that the low plasma concentrations of apoA-I and apoA-II are due to increased fractional catabolism with a relatively normal apoA-I and apoA-II synthesis. Plasma apoA-I and apoA-II were isolated to electrophoretic homogeneity from delipidated plasma lipoproteins from a patient with Tangier disease. ApoA-I Tangier differed from apoA-I from control subjects in amino acid composition, electrophoretic mobility, apparent molecular weight on sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and heterogeneity of isoforms on isoelectric focusing. ApoA-II Tangier, however, appeared to be identical to normal apoA-II in amino acid composition and in immunological as well as chemical properties. These results have been interpreted as indicating that apoA-I Tangier has a different covalent structure than does normal apoA-I, and apoA-II Tangier is identical to normal apoA-II. This structural change in apoA-I Tangier is associated with rapid catabolism of apoA-I Tangier-and apoA-II Tangier-containing plasma lipoproteins, and it leads to the deficiency in high density lipoproteins, abnormal chylomicron remnants, and the intracellular accumulation of cholesterol ester characteristic of Tangier disease.

Amino Acids↗
PubMed1982

Production of Maltase by Wild-Type and a Constitutive Mutant of Saccharomyces italicus.

The production of maltase, an inducible and repressible catabolic enzyme in Saccharomyces italicus, was studied and compared in batch, fed-batch, and continuous fermentations. Tight genetic controls on maltase synthesis limited the effect of environmental manipulations such as fed-batch or continuous culture in enhancement of maltase synthesis, and neither approach was able to improve the performance above the batch process for maltase production. S. italicus was mutated, and a constitutive producer of maltase was isolated. The mutant was detected by its ability to grow on sucrose, which is a noninducing substrate that is hydrolyzed by maltase; S. italicus does not possess invertase and will not normally grow on sucrose. Maltase production by this mutant was studied during growth on sucrose in batch and continuous cultures and marked improvement in enzyme productivity was observed. The specific activity of maltase produced by this mutant was more than twice that of the parent wild type: 2,210 and 1,370 U/g of cells for the mutant versus 890 and 510 U/g of cells for the wild type in batch and continuous cultures, respectively. Maltase specific productivity was increased from 74 to 288 U/g of cells per h by switching from batch growth of the wild type to continuous cultivation of the mutant.

Journal Article↗
PubMed1982

Increased prevalence of apolipoprotein E4 in type V hyperlipoproteinemia.

Type V hyperlipoproteinemia (HLP) is characterized clinically by hepatosplenomegaly, occasional eruptive xanthomas, and an increased incidence of pancreatitis. These patients have striking hypertriglyceridemia due to increased plasma chylomicron and very low density lipoprotein concentrations in the fasting state, without a deficiency of lipoprotein lipase or its activator protein, apolipoprotein (apo) C-II. ApoE, a protein constituent of triglyceride-rich lipoproteins, has been implicated in the receptor-mediated hepatic uptake of these particles. ApoE has three major alleles: E2, E3, and E4, and the products of these alleles are apoE2, apoE3, and apoE4, respectively. ApoE phenotypes were determined in 30 type V HLP patients as well as in 37 normal volunteers. Among the type V patients, 33.3% were noted to be homozygous, and 40.0% heterozygous for E4 (normal, 2.7 and 21.6%, respectively). These data suggest that apoE4 may play a role in the etiology of the hyperlipidemia in a significant number of type V HLP patients.

Apolipoprotein E4↗
PubMed1982

Tangier disease. High density lipoprotein deficiency due to defective metabolism of an abnormal apolipoprotein A-i (ApoA-ITangier).

Tangier disease is a rare familial disorder characterized by enlarged orange tonsils, transient peripheral neuropathy, hepatosplenomegaly, and lymphadenopathy, as well as striking reductions in plasma high density lipoproteins (HDL) and their major protein constituents, apolipoproteins (apo)A-I and A-II. In order to test the hypothesis that Tangier patients have abnormal apoA-I or apoA-II, the in vitro lipoprotein binding and in vivo metabolic characteristics of these proteins isolated from normal and Tangier plasma, were studied in normal subjects and patients with Tangier disease. After incubation with normal plasma, significantly greater percentages of radiolabeled Tangier apoA-I were associated with the 1.063-g/ml supernate (6%) and the 1.21 g/ml infranate (19%), and a lower percentage with HDL (75%), than those observed for normal apoA-I (2, 8, and 90%, respectively). In contrast, the lipoprotein binding properties of normal and Tangier apoA-II were very similar. Following the injection of radiolabeled normal and Tangier apoA-I into normal subjects (n = 4), the mean residence times of the specific activity for apoA-I(Tangier) were significantly lower, both in plasma (1.29 d) and in HDL (1.34 d), than those observed for normal apoA-I (3.80 and 4.06 d). In Tangier homozygotes the decay rates of these tracers were very rapid and were similar. No significant differences between the kinetics of normal and Tangier apoA-II were observed in normal subjects (n = 2). Tangier homozygotes (n = 3) had mean plasma HDL cholesterol, apoA-I, and apoA-II concentrations that were 4, 2, and 11% of normal (n = 24), respectively, whereas for heterozygotes (n = 3) these values were 46, 62, and 68% of normal. In homozygotes, in contrast to normals or heterozygotes, a significant fraction of both apoA-I and apoA-II were found in the 1.063-g/ml supernate instead of in HDL. Homozygotes had apoA-I(Tangier) synthesis rates and residence times that were 41 and 5% of values observed for normal apoA-I in normal subjects, and for apoA-II in homozygotes, these parameters were 63 and 18% of normal. Heterozygotes had apoA-I synthesis rates and residence times that were 92 and 66% of normal, and for apoA-II these values were 101 and 64% of normal. These data are consistent with the concept that apoA-I(Tangier) is functionally and metabolically distinct from normal apoA-I, and is the cause of the striking hypercatabolism of apoA-I and apoA-II, and the lipoprotein abnormalities observed in Tangier disease.

Adult↗
PubMed1982

Human apolipoprotein A-I and A-II metabolism.

The kinetics of the major apolipoproteins (apo) of plasma high density lipoproteins (HDL), apoA-I and apoA-II, were examined in a total of 44 individual tracer studies in 22 normal male and female subjects. Following the intravenous injection of radioiodinated HDL, the specific radioactivity decay of apoA-I within HDL (residence time, 5.07 +/- 1.53 days), as determined by column chromatography, was significantly (P < 0.01) faster than that of apoA-II (residence time, 5.96 +/- 1.84 days). The specific radioactivity decay of apoA-I within HDL when labeled on HDL or as apoA-I was found to be almost identical. Similar results were obtained for apoA-II. Analysis of simultaneous paired radiolabeled apoA-I and apoA-II studies revealed that the mean apoA-I plasma residence time (4.46 +/- 1.04 days) was significantly (P < 0.01) shorter than that for apoA-II (4.97 +/- 1.06 days). Females had significantly (P < 0.01) higher apoA-I plasma concentrations (124 +/- 24 mg/dl) and apoA-I synthesis rates (13.58 +/- 2.23 mg/kg. day) than did males (108 +/- 16 mg/dl, and 11.12 +/- 1.92 mg/kg. day, respectively). Plasma apoA-I levels were correlated with plasma apoA-I residence times, but not synthesis rates; and apoA-II concentrations were correlated only with apoA-II whole body residence times. ApoA-I and apoA-II plasma residence times were inversely correlated with plasma triglyceride levels. These data are consistent with the following concepts: 1) labeling of apoA-I and apoA-II as apolipoproteins or on HDL does not affect their specific radioactivity decay within HDL; 2) the mean residence time of apoA-I both in plasma and in HDL is significantly shorter than that of apoA-II; 3) the increased apoA-I levels seen in female subjects are due to increased apoA-I synthesis; and 4) the plasma apoA-I residence time, which is inversely correlated with plasma triglyceride levels, is an important determinant of apoA-I concentration in both males and females.-Schaefer, E. J., L. A. Zech, L. L. Jenkins, T. J. Bronzert, E. A. Rubalcaba, F. T. Lindgren, R. L. Aamodt, and H. B. Brewer, Jr. Human apolipoprotein A-I and A-II metabolism.

Adult↗
PubMed1982

Transfer of human lymph chylomicron constituents to other lipoprotein density fractions during in vitro lipolysis.

To ascertain whether chylomicron constituents would be transferred to low density lipoprotein (LDL, d 1.019-1.063 g/ml) and high density lipoprotein (HDL, d 1.063-1.21 g/ml) density fractions during lipolysis in the absence of other lipoproteins, the in vitro effect of bovine milk lipoprotein lipase on human thoracic duct lymph chylomicrons in the presence of albumin was examined. In incubations without lipase, over 90% of chylomicron constituents remained in the 1.006 g/ml supernate, and large particles ranging in diameter mainly from 750-6000 A were observed by electron microscopy. After the addition of lipase, lipolysis ranged from 69.0-94.6% and numerous collapsed particles with redundant surface were seen, as well as smaller particles within the LDL and HDL density region. With lipolysis, the majority of chylomicron cholesterol and phospholipid mass was transferred to LDL and HDL, while chylomicron apolipoprotein (apo) A-I, A-II, and C-II mass was transferred mainly to HDL. Utilizing either radioiodinated apoA-I and apoA-II reassociated with chylomicrons or radiolabeled chylomicrons, a similar redistribution of apoA-I and apoA-II radioactivity was noted with lipolysis. In contrast, chylomicron apoB (mainly B-48) radioactivity was transferred predominantly to LDL with lipolysis. These data are consistent with the concept that during lymph chylomicron triglyceride hydrolysis, chylomicron apolipoproteins, cholesterol, and phospholipid can be transferred to the LDL and HDL density regions in the absence of acceptor particles.

Animals↗
PubMed1981

Type III hyperlipoproteinemia associated with apolipoprotein E deficiency.

Subjects with type III hyperlipoproteinemia develop premature atherosclerosis and have hyperlipidemia due to an increase in cholesterol-rich very low density lipoproteins (VLDL) of abnormal electrophoretic mobility. Apolipoprotein E is a major protein constituent of VLDL and appears to be important for the hepatic uptake of triglyceride-rich lipoproteins. A new kindred of patients with type III hyperlipoproteinemia is described in which no plasma apolipoprotein E could be detected, consistent with the concept that type III hyperlipoproteinemia may be due to an absence or striking deficiency of apolipoprotein E.

Apolipoproteins↗
PubMed1981

Type III hyperlipoproteinemia: defective metabolism of an abnormal apolipoprotein E.

The apolipoprotein E isolated from plasma of individuals with type III hyperlipoproteinemia (HLP) shows an abnormal pattern when it is examined by isoelectric focusing. Compared to apolipoprotein E from normal subjects, apolipoprotein E isolated from subjects with type III HLP had a decreased fractional catabolic rate in vivo in both type III HLP patients and normal individuals. The delayed catabolism of apolipoprotein E in type III HLP patients may be responsible for the lipid and lipoprotein abnormalities characteristic of these patients.

Apolipoproteins↗
PubMed1981

Syndromatic hepatic ductular hypoplasia (arteriohepatic dysplasia): a clinical and hepatic histologic study of three patients.

Clinical and pathologic features of three patients with chronic intrahepatic cholestasis from birth are described. Each patient exhibited a paucity and hypoplasia of interlobular bile ducts, unusual facies, short stature, a pulmonary ejection systolic murmur, and structural anomalies of vertebrae. This constellation of defects constitutes a distinct syndrome to which the terms arteriohepatic dysplasia and syndromatic hepatic ductular hypoplasia are applied. Clinically, cholestasis was not progressive and, although the SGPT was chronically elevated (122--520 units/liter), features of liver cell failure did not develop. Changes in plasma lipids and lipoproteins and serum bile acids were consistent with chronic cholestasis. Liver biopsies from the three cases revealed pseudoxanthomatous change, increased stainable copper and mild hepatocellular degenerative changes. Electron microscopy of one of the liver biopsies revealed extension of thick bundles of collagen from portal areas into hepatic lobules with obliteration of the space of Mall. With increasing age, portal tracts contained fewer bile ducts. This apparent progression of the lesion was not associated with an inflammatory cell infiltrate, progressive fibrosis, or the development of cirrhosis.

Abnormalities, Multiple↗
PubMed1981

Plasma apolipoprotein concentrations in familial apolipoprotein A-I and A-II deficiency (Tangier disease).

Familial apolipoprotein A-I and A-II deficiency (Tangier disease) is characterized by cholesterol ester deposition in histiocytes, decreased plasma cholesterol and low density lipoprotein cholesterol (C-LDL), and a striking deficiency of high density lipoproteins (HDL). We measured plasma lipid, lipoprotein cholesterol, and plasma apolipoprotein (apo) A-I, A-II, B, C-I, C-II, C-III, D, and E concentrations in 7 Tangier homozygotes, 2 obligate heterozygotes, and 50 normal subjects. Heterozygotes had modest reductions in high density lipoprotein cholesterol (C-HDL), plasma apoA-I, and apoA-II levels. Mean concentrations (+/- SD) of plasma C-HDL and apolipoproteins A-I, A-II, B, C-I, C-II, C-III, D, and E in mg% in normals were: 50 +/- 14, 134 +/- 24, 68 +/- 18, 98 +/- 20, 7 +/- 2, 3.7 +/- 2, 13 +/- 5, 10 +/- 4, and 10 +/- 4, respectively; and in homozygotes were: 1 +/- 1, 1.3 +/- 0.7, 4.8 +/- 2.5, 82.6 +/- 18, 4.1 +/- 1.7, 2.3 +/- 0.9, 6.5 +/- 3.8, 2.2 +/- 0.5, +/- 3.1, respectively. Homozygotes had C-HDL, apoA-I and apoA-II levels which were 2%, 1%, and 7% (p less than .001) of normal, respectively, and mean levels of apolipoproteins B, C-I, C-II, C-III, D, and E which were 84%, 59%, 62%, 50%, 22%, and 54% of normal, respectively. There was heterogeneity of these latter apolipoprotein concentrations among homozygotes. Mean apoC-I, apoC-III, apoD, and apoE levels were significantly less than normal (pp less than .05) in homozygotes. These data indicate that homozygotes have variable but generally decreased apoC and apoE levels, a deficiency of apoD, and a striking reduction in plasma apoA-I and apoA-II concentrations.

Adolescent↗
PubMed1981

The effects of low cholesterol, high polyunsaturated fat, and low fat diets on plasma lipid and lipoprotein cholesterol levels in normal and hypercholesterolemic subjects.

The effects of various cholesterol-lowering diets on plasma lipid and lipoprotein cholesterol levels were assessed in normal and hypercholesterolemic subjects. The base-line diet was an ad libitum hospital diet of normal composition. Diet A was a 20% protein, 40% carbohydrate, 40% fat, polyunsaturated:saturated fat ratio 0.1 to 0.3, 250 to 300 mg cholesterol diet, diet B was identical to diet A except that the polyunsaturated/saturated fat ratio was 1.8 to 2.2, and diet C was a 20% protein, 80% carbohydrate, very low fat (5 to 10 g), polyunsaturated/saturated fat ratio 0.1 to 0.3, 150 to 200 mg cholesterol diet. Diet A (low cholesterol) caused mean reductions in plasma, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol of 5.9, 5.6, and 6.3%, respectively, in 11 normal subjects. Diet B (low cholesterol, high polyunsaturated fat) caused significant decreases in plasma cholesterol, LDL cholesterol and HDL cholesterol of 17.0, 16.2, and 17.4%, respectively, in 12 normal subjects; and reductions of 11.0, 10.8, and 17.1%, respectively, in 19 hypercholesterolemic subjects. Diet C (low cholesterol, very low fat) produced significant mean decreases in plasma, LDL, and HDL cholesterol of 26.7, 29.9, and 27.9%, respectively, in 11 normal subjects, and in nine hypercholesterolemic patients of 22.6, 27.2, and 28.6%, respectively. The reductions in plasma cholesterol caused by these diets were therefore due to decreases in both LDL and HDL cholesterol with no significant changes in the LDL cholesterol:HDL cholesterol ratio.

Adult↗
PubMed1981

Transport of apolipoproteins A-I and A-II by human thoracic duct lymph.

The daily transport of human plasma apolipoproteins A-I and A-II, triglyceride, and total cholesterol from the thoracic duct lymph into plasma was measured in two subjects before and three subjects after renal transplantation. Lymph triglyceride transport was approximately 83% of the daily ingested fat loads, whereas lymph cholesterol transport was consistently greater than the amount of daily ingested cholesterol. Lymph apolipoprotein transport significantly (P < 0.05) exceeded the predicted apolipoprotein synthesis rate by an average of 659+/-578 mg/d for apolipoprotein A-I and 109+/-59 mg/d for apolipoprotein A-II among the five subjects. It is estimated that 22-77% (apolipoprotein A-I) and 28-82% (apolipoprotein A-II) of daily total body apolipoprotein synthesis takes place in the intestine. Lymph high density lipoprotein particles are mostly high density lipoprotein(2b) and high density lipoprotein(2a) and have a greater overall relative triglyceride content and a smaller relative cholesteryl ester content when compared with homologous plasma high density lipoproteins. The major quantity of both lymph apolipoprotein A-I (81+/-8%) and apolipoprotein A-II (90+/-11%) was found within high density lipoproteins with almost all of the remainder found in chylomicrons and very low density lipoproteins. The combined results are consistent with a major contribution of the intestine to total body synthesis of apolipoprotein A-I and apolipoprotein A-II. An important role of lymph in returning filtered apolipoprotein to plasma in association with high density lipoproteins is proposed. Accompanying the return of filtered apolipoprotein to the plasma is a probable transformation, both in size and composition, of at least some of the lymph high density lipoprotein(2b) and high density lipoprotein(2a) particles into high density lipoprotein(3).

Apolipoproteins↗
PubMed1981

Metabolism of high density lipoprotein subfractions and constituents in Tangier disease following the infusion of high density lipoproteins.

The metabolism of apolipoproteins A-I and A-II, as well as other high density lipoprotein (HDL) constituents, was studied in patients with homozygous familial HDL deficiency (Tangier disease) prior to and after plasma exchange or HDL infusion. Mean plasma apoA-I, apoA-II, and HDL cholesterol values in homozygotes (n = 2) were 2.0 mg/dl, 2.7 mg/dl, and 1.5 mg/dl, respectively, and in a normal control subject were 125.1 mg/dl, 23.0 mg/dl, and 53.0 mg/dl, respectively. Based on radioiodinated apoA-I and apoA-II kinetic studies in the baseline state, synthesis rates for apoA-I and apoA-II in mg/kg/day were 3.81 and 1.61, respectively, in one homozygote (patient B) and 11.82 and 1.99, respectively, in the normal subject. ApoA-I and apoA-II plasma residence times in days were 0.22 and 0.81, respectively, in the homozygote, and 4.04 and 4.44, respectively, in the normal subject. These data indicate that this homozygote had both a moderate decrease in the synthetic rates of apoA-I and apoA-II, as well as a marked decrease in the plasma residence times of these two apolipoproteins. In one homozygote (patient A) following a complete plasma exchange during cardiopulmonary bypass, plasma HDL cholesterol, apoA-I, and apoA-II levels were very similar to pre-exchange values within 64 hr after exchange. A second homozygote (patient B) received HDL intravenously as well as 125I-labeled apoA-I and 131I-labeled apoA-II. Following infusion, the residence time in days for HDL subfractions, HDL2b, HDL2a, and HDL3 were 0.1, 0.8, and 2.7, respectively. HDL protein and phospholipid both had a monoexponential decay, with residence times of 0.7 days, while HDL triglyceride disappeared monoexponentially with a residence time of 0.5 days. HDL cholesterol had a biexponential decay, with the residence time of the slow component being 0.7 days. Plasma and HDL apoA-I decayed down to baseline values significantly faster than did plasma and HDL apoA-II. ApoA-II specific radioactivity decreased throughout the course of the infusion study in both plasma and HDL, while apoA-I specific radioactivity decreased slightly, then rose, and subsequently declined in both plasma and HDL. The data indicate that the rapid and altered catabolism of apoA-I and apoA-II in Tangier homozygotes persists despite major increases in the plasma pool size of these proteins. In addition, following HDL infusion, HDL2b and HDL2a disappeared at a faster rate than HDL3, HDL cholesterol and triglyceride were catabolized at a faster rate than HDL protein and phospholipid, and apoA-I disappeared more rapidly than apoA-II. These observations may have important implications with regard to the catabolism of HDL subfractions and constituents in normal man.

Adult↗