Apolipoprotein E2/E2 genotype in combination with mutations in the LDL receptor gene causes type III hyperlipoproteinemia.

The primary genetic cause of type III hyperlipoproteinemia is the homozygous presence of the apolipoprotein E2 allele. However, only approximately 1% of subjects with the apolipoprotein E2/E2 genotype develop type III hyperlipoproteinemia. Other factors are therefore necessary to express type III hyperlipoproteinemia.

The gene encoding ATP-binding cassette transporter 1 is mutated in Tangier disease.

Tangier disease (TD) is an autosomal recessive disorder of lipid metabolism. It is characterized by absence of plasma high-density lipoprotein (HDL) and deposition of cholesteryl esters in the reticulo-endothelial system with splenomegaly and enlargement of tonsils and lymph nodes. Although low HDL cholesterol is associated with an increased risk for coronary artery disease, this condition is not consistently found in TD pedigrees.

Fluorescence-based single-strand conformation polymorphism analysis of the low density lipoprotein receptor gene by capillary electrophoresis.

We describe here a new method to screen for unknown mutations in the low density lipoprotein (LDL) receptor gene by the use of capillary electrophoresis in single-strand conformation polymorphism (SSCP) analysis. To analyze the promoter and all 18 exons, 20 different amplification reactions were necessary. For each polymerase chain reaction (PCR), the forward and reverse primers were 5' fluorescent-labelled with FAM and HEX, respectively.

Mutation analysis of exon 3 of the LDL receptor gene in patients with severe hypercholesterolemia.

Single-strand conformation polymorphism analysis was used to screen for mutations in exon 3 of the low density lipoprotein receptor gene in a group of 218 unrelated patients with severe hypercholesterolemia (low density lipoprotein cholesterol > 6.7 mmol/l) living in the Cologne area of Germany. Including the complementary primers the fragment studied had a length of 176 bp.

Changes of hemorheological and biochemical parameters after plasma perfusion using a tryptophan-polyvinyl alcohol adsorber leading to clinical improvement in patients suffering from maculopathy.

Background: Selective adsorption is an extracorporeal treatment able to reduce high-molecular-weight proteins and lipids. We evaluated its efficacy in lowering hemorheological parameters to achieve a better microcirculation of the retina.

Patients And Methods: Ten patients suffering from maculopathies of various origin underwent a selective plasma adsorption procedure using the TR-350.

A single nucleotide substitution in the promoter region of the apolipoprotein C-II gene identified in individuals with chylomicronemia.

Apolipoprotein (apo) C-II plays a major role as a cofactor for lipoprotein lipase, the enzyme involved in the hydrolysis of triglyceride-rich particles. We identified in two relatives of a family (mother and son) massive hypertriglyceridemia with chylomicronemia. In these individuals apoC-II was not measurable in plasma by radial immunodiffusion.

Screening for mutations in the LDL receptor gene and apolipoprotein B-100 gene in 218 patients with severe hypercholesterolemia.

A group of 218 patients with severe hypercholesterolemia (LDL cholesterol > 260 mg/dl) living in the Cologne area were screened for mutations in the LDL receptor gene and apolipoprotein B-100 gene. In the LDL receptor gene Southern blotting was used for detection of major DNA rearrangements and the single-strand conformation polymorphism (SSCP) method was used to screen for micro-deletions and insertions and single base alterations. The Arg3500-->Glu mutation, which is the only relevant mutation in the apolipoprotein B-100 gene causing hypercholesterolemia, was detected by a modified PCR and restriction enzyme digestion.

Change in hemorrheological and biochemical parameters following membrane differential filtration.

Introduction: The elimination of high molecular weight proteins may have a positive influence on disorders of the microcirculation due to an improvement in rheological parameters. We therefore attempted to evaluate the rheological efficacy of membrane differential filtration (MDF).

Patients And Methods: Ten patients suffering from macular disease underwent MDF.

Screening for mutations in exon 4 of the LDL receptor gene in a German population with severe hypercholesterolemia.

A group of 218 patients with severe hypercholesterolemia (LDL cholesterol > 260 mg/dl) living in the Cologne area were screened for mutations in the 3 half of exon 4 of the low density lipoprotein (LDL) receptor gene by the single-strand conformation polymorphism (SSCP) method. The analysed fragment was 242 bp in length and comprised approximately 6% of the coding region. In 11 patients an abnormal SSCP pattern was observed.

[Absorption of di-linoleoylphosphatidylcholine after oral administration].

Essentiale and Lipostabil contain "essential" phospholipids from the soybean, mainly 1,2-dilinoleoyl-phosphatidylcholine (CAS 998-06-1, DLPC) which is considered as the main active ingredient. A single oral dose of d15-DLPC loaded with deuterium 9 times in the choline and 6 times in the linoleic acid of the 1-position was given to volunteers. Sera from 11 blood samples taken within 48 h after application were examined by means of mass spectrometry with regard to d9-choline and d6-linoleic acid in the 1- and 2-position of serum phosphatidylcholines (PC) as well as in the serum triglycerides.

Effects of interactions of apolipoprotein A-II with apolipoproteins A-I or A-IV on [3H]cholesterol efflux and uptake in cell culture.

Conflicting evidence has accumulated with years regarding the putative negative effect of apolipoprotein A-II on apo A-I mediated cholesterol efflux. In this study, this question was reexamined and in addition to the interaction of apo A-II with apo A-I, its possible effect on apo E and apo A-IV was investigated as well. Free cholesterol (FC) donors were the main components of atheroma, namely, mouse peritoneal macrophages (MP), bovine aortic smooth muscle (SMC) and fibroblasts labeled with [3H]FC.

Technical and clinical experience with protein A immunoadsorption columns.

Protein A adsorption (Immunosorba, Excorim, Sweden) is a potent tool for the rapid removal of antibodies from the circulation. In comparison to conventional plasma exchange therapy, Protein A adsorption offers the advantage of processing large amounts of plasma, removing up to 87% of the initial level of IgG in one session without a clinically significant loss of fibrinogen. So far 61 treatments have been carried out in our department without serious side effects.

A prospective, randomized, and double-blind trial on the effect of fish oil on the incidence of restenosis following PTCA.

Restenosis after successful coronary angioplasty (PTCA) occurs in 25-35% of all procedures. To date, most pharmacologic strategies have failed to reduce the restenosis rate significantly. However, recent studies have suggested a potential benefit of dietary supplementation with omega-3 fatty acids (fish oil) on restenosis following PTCA.

[Long-term effects of low dosage fish oil on serum lipids and lipoproteins].

In a prospective and double-blind study, the long-term effects of low dose fish oil on serum lipids and lipoproteins was tested in patients with normal or moderately elevated serum lipids and compared to the effects of olive oil. The compliance to the study medication was evaluated by analysis of serum fatty acids and proved to be very good. Dietary supplementation with 9 g fish oil, respective 3.

Persistence of increased cholesteryl ester in human skin fibroblasts is caused by residual exogenous sphingomyelinase and is reversed by phospholipid liposomes.

Human skin fibroblasts (HSF) were exposed to sphingomyelinase 50 or 5 mU/ml for 60 min, washed with 5 mM EDTA or 20% serum and with phosphate-buffered saline, and postincubated for 24 h in the presence of [14C]16:0 sphingomyelin (SP) liposomes. The recovery of up to 48% of label in the medium in ceramide provided evidence of persistence of sphingomyelinase activity. The rate of hydrolysis of [14C]16:0 SP remained the same irrespective of whether the liposomes were added immediately after the wash, or 3 or 6 h thereafter.

Familial defective apolipoprotein B-100 in 12 subjects and their kindred.

Twelve unrelated subjects with heterozygous familial defective apolipoprotein B-100 were identified in a group of 252 patients with type IIa hypercholesterolaemia. Approximately 5% of hypercholesterolaemia can be explained by this mutation in the collective studied. Familial defective apolipoprotein B-100 is therefore the most common known mutation causing primary hypercholesterolaemia.

Behavior of lymphocyte subsets and expression of activation markers in response to immunotherapy with galactoside-specific lectin from mistletoe in breast cancer patients.

Cellular aspects of the immunomodulating activity of the galactoside-specific lectin from mistletoe (ML-1) were investigated in 10 cancer patients. Regular subcutaneous injections (4 weeks) of the optimal dosis of ML-1 (1 ng per kg body weight, twice a week) yielded notable increases in the apparent numbers of certain lymphocyte subsets [pan T cells; helper T cells; natural killer (NK) cells] which are generally believed to be involved in antitumor immunity. Moreover, ML-1 administration resulted in an increased level of expression of interleukin (IL)2 receptors on lymphatic cells, an indicator of cellular activation.

Pharmacokinetics of omega-3-fatty acids during ingestion of fish oil preparations.

An in vivo comparison of three dosages (3 g, 6 g, 12 g) of two different fish oil preparations in terms of plasma concentrations of their major active components eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was performed. The plasma accumulation was measured during 28 days of ingestion and an equally long wash out period. Data were scrutinized for bioavailability in order to distinguish between the efficiency of the two preparations.

Studies on an apolipoprotein C-II variant occurring in Caucasians.

Apolipoproteins C (apo C-II, apo C-III0, apo C-III1 and apo C-III2) from delipidated very low density lipoproteins (VLDL) of 522 normo- and hyperlipoproteinemic Caucasians were screened by analytical isoelectric focusing. The immobilized pH gradient used was pH 4.0-5.

Abnormalities in serum osteocalcin values in children receiving chemotherapy including ifosfamide.

In patients undergoing high-dose ifosfamide treatment tubular nephrotoxicity with hypophosphatemia has been described. Long-lasting hypophosphatemia may be associated with bone disease including rickets. Serum osteocalcin is considered a sensitive marker for reduced osteoblast activity and bone formation.

Activation of mononuclear immune cells in response to staphylococcal lipoteichoic acid.

The goal of the present study was to evaluate the influence of staphylococcal lipoteichoic acid (LTA) on the activation of mononuclear immune cells. A murine tumor necrosis-like factor (TNF-like) was induced in the sera of CD-1 mice which had been primed with heat/formalin-inactivated Propionibacterium avidum KP-40 and subsequently exposed to LTA extracted from Staphylococcus saprophyticus strain S 1. Monoclonal antibody against murine TNF (anti-TNF) significantly inhibited the cytostatic activity of mice sera against transformed L-929 cells.