Göran Fex

The increase of plasma homocysteine concentrations with age is partly due to the deterioration of renal function as determined by plasma cystatin C.

Abstract One of the main determinants of plasma homocysteine in healthy subjects is serum creatinine. In the present study, we therefore investigated the relation between plasma homocysteine concentration, serum creatinine and a new marker for glomerular filtration rate, plasma cystatin C concentration. Cystatin C reflects the glomerular filtration better than serum creatinine and is not related to the muscle mass and formation of creatinine. The study group consisted of 255 healthy subjects from a well-defined area in the southern part of Sweden. The concentration of plasma homocysteine was increased in men compared to women. This difference disappeared when men and women were stratified by serum creatinine values. Statistically significant correlations were noted between plasma homocysteine and age, plasma cystatin C and serum creatinine. It is shown that plasma homocysteine is not only correlated to serum creatinine as a result of renal function but also as a result of the relationship between homocysteine production and creatine-creatinine synthesis. Using linear regression we were able to show that plasma cystatin C had a higher explanatory value than age. Serum creatinine showed a lower explanatory power than age. The findings in the present study might suggest that the increase of plasma homocysteine concentration with age could be partly due to the deterioration of renal function. Study

Reference intervals for the glomerular filtration rate and cell-proliferation markers: serum cystatin C and serum β2-microglobulin/cystatin C-ratio

Recent studies have indicated that serum and plasma cystatin C are better markers for glomerular filtration rate (GFR) than serum creatinine, ubiquitously used for this purpose. To fully exploit the value of serum and plasma cystatin C as GFR markers, reliable age and sex-correlated reference intervals are required. The present study comprised cystatin C determinations in plasma and sera from 259 individuals from a well-defined area in the southernmost part of Sweden. From demographic lists two men and two women were randomly selected from each one-year birth cohort above 20 years of age. No sex differences were found for plasma and serum cystatin C, whereas an increase in the cystatin C levels with age was noted, corresponding to the known age-related decrease in GFR. The following reference intervals are recommended for practical clinical use: S-Cystatin C (both sexes): 20-50 years, 0.70-1.21 mg l-1 and 50+ years, 0.84-1.55 mg l-1. The same samples were also used for determination of beta 2-microglobulin levels in order to calculate reference intervals for the beta 2-microglobulin/cystatin C-ratio, which is a more distinct marker for cell proliferation, particularly lymphoproliferation, than is the serum level of beta 2-microglobulin alone, since the ratio should be virtually uninfluenced by GFR. The beta 2-microglobulin/cystatin C-ratios were uninfluenced by sex and age and 1.45-2.43 is recommended as the serum reference interval for practical clinical use. Serum creatinine was determined in the same samples and the creatinine level was found to be strongly influenced by sex and weakly by age.

Serum γ-glutamyltransferase: Statistical distribution in a middle-aged male population and evaluation of alcohol habits in individuals with elevated levels

Abstract Serum γ-glutamyltransferase activity (GGT) was measured in two middle-aged, male Malmo birth-year cohorts. Increased GGT-values were found in 16% of this population sample. There were broad correlations, throughout both the normal and elevated range of GGT values with screening serum triglycerides, 120-min blood glucose in oral glucose tolerance tests, pulse and blood pressure indices, body weight, serum urate and, more weakly, serum cholesterol values. Results of other tests related to liver dysfunction were elevated in only about half of a study group of individuals with elevated screening GGT. Careful evaluation of alcohol habits in this group revealed heavy drinking as the most probable underlying factor in about three-fourths of the cases. We conclude that serum GGT, when included in a general medical screening examination, may help in detecting hidden alcoholism and may also be utilized in an individually oriented program aimed at the prevention of alcoholism.

Apolipoprotein E genotyping in Alzheimer’s disease and frontotemporal dementia

Alzheimers disease (AD) and frontotemporal dementia (FTD) are characterized by progressive neuronal loss and microvacuolization, although with different distributions of cortical involvement. In contrast to AD there is no amyloid, senile plaques or tangles in FTD. The involvement of chromosome 19 in AD has been associated with apoliprotein E (ApoE) and the epsilon 4 gene frequency has been related to increased risk and early onset of AD. Our analysis of frequency of the ApoE alleles in 38 patients with AD, 21 patients with FTD and 29 normal controls indicates an association of both AD and FTD with an increased frequency of the epsilon 4 allele and in AD also with homozygosity for epsilon 4. Our results might indicate that ApoE epsilon 4 is an important aggravating and pathoplastic factor in the presence of genetic and other determinants for the development of AD or FTD. A significantly higher epsilon 2 frequency in our FTD material compared to AD and normals might also indicate a connection with the distribution of cortical degeneration.

A six-generation family with autosomal dominant retinitis pigmentosa and a rhodopsin gene mutation

This study documents the ophthalmological findings in a six-generation. Swedish family with autosomal dominant retinitis pigmentosa with a previously unknown rhodopsin, exon 2, mutation, Arg-135-Leu (CGG to CTG). Six affected patients from the family were available for analysis and were all found to be heterozygous for the mutation, whereas eight clinically normal family members and 29 unrelated normal individuals did not have it. The disease appears to be of a type with comparatively rapid progression to blindness.

Cellular origin of prealbumin in the rat

The synthetic rate of prealbumin and albumin in primary monolayer cultures of rat hepatocytes was measured by immunochemical methods. The isolated hepatocytes synthesized these proteins in the same ratio as that previously found for the whole body synthesis in vivo. It is concluded that the hepatocytes synthesize the main part of prealbumin in the rat.

Retinol transfer across and between phospholipid bilayer membranes

The transfer of retinol across and between bilayer membranes was studied in vitro using unilamellar liposomes and erythrocytes. Transmembrane movement of retinol in phospholipid bilayer membranes was a spontaneous and rapid process with a halflife of less than 30 s. Retinol transfer between liposomes and between liposomes and erythrocytes was also a spontaneous and rapid process with a halflife of less than 10 min. The results suggest that retinol transport in the cell might not need the participation of specific transfer proteins.

Towards common reference intervals in clinical chemistry. An attempt at harmonization between three hospital laboratories in Skåne, Sweden.

Abstract The population sample of the Kristianstad survey, a reference intervals survey in the county of Kristanstad, was used to establish new reference intervals in clinical chemistry at the laboratories of the Central Hospital in Kristianstad, the University Hospital in Lund and the University Hospital in Malmö. Three-hundred and fifty nine subjects, male and female, aged 20–80+ years, were invited to participate in the study, with a participation rate of 70 %. Up to 70 analyses were performed on each subject, general clinical chemistry parameters in all three laboratories, specialized analyses where available. Separate a priori exclusion criteria were defined for each test. In addition, the test pattern of each individual was evaluated for signs of preclinical disease. Twelve cases of preclinical disease were discovered and clinically confirmed. Details on all test methods are presented along with information concerning instruments used, calibration procedures, methods of calculation and obtained reference intervals. Although the methods were in general calibrated against acknowledged reference materials, in some instances differences were found that made common reference intervals across all laboratories impossible. Problems relating to the practical use of international recommendations and the establishment of reliable reference intervals are discussed.

Studies of the spontaneous transfer of retinol from the retinol: retinol-binding protein complex to unilamellar liposomes

The transfer of retinol from its complex with the retinol-binding protein to cell surfaces was studied using unilamellar liposomes as a cell surface model. The transfer of retinol to liposomes at 37 degrees C was rapid and reached an apparent equilibrium within 60 min. The amount of retinol transferred to the liposomes at equilibrium was directly proportional to the starting concentration of retinol:retinol-binding protein over a wide range of retinol:retinol-binding protein concentrations and also directly proportional to the concentration of liposomal phospholipid in the system, when the concentration of retinol:retinol-binding protein was held constant. The transfer increased slightly with temperature. Transfer was increased by a factor of 1.8 at pH 4.5 compared to pH around 7. Prealbumin in amounts sufficient to complex all retinol:retinol-binding protein, decreased retinol transfer to liposomes indicating that prealbumin increases the affinity of retinol-binding protein for retinol. Addition of apo retinol-binding protein to the system decreased the transfer of retinol to liposomes considerably probably through competition with the liposomes for retinol. In similarly designed experiments delipidated bovine serum albumin competed much less with liposomes for retinol. The results show that spontaneous transfer of retinol from the retinol:retinol-binding protein complex to liposomal membranes occurs in vitro and suggests that a similar transfer may occur in vivo from retinol:retinol-binding protein to cell surface membranes.

Changes in plasma high density lipoproteins and lipolytic enzymes after long-term, heavy ethanol consumption

Plasma high density lipoprotein (HDL) concentrations are often increased in chronic alcoholism. The mechanism for this hyperalphalipoproteinaemia was investigated in seven male chronic alcoholics. Determinations of lipoprotein lipase, hepatic lipase and lecithin-cholesterol acyl trailsferase activities and of lipid concentrations in plasma and lipoproteins were made immediately after a debauch and during an abstinence period of 10 days. The lipoprotein patterns registered immediately after cessation of ethanol intake were characterized by elevated concentrations of HDL, especially the HDL2 subclass. Postheparin plasma lipoprotein lipase activities were also increased. During the observation period HDL levels and lipoprotein lipase activities decreased by about 40%. Concomitantly there was a small but significant increase in the concentrations of plasma and very low density lipoprotein (VLDL) triacylglycerol, and of plasma and low density lipoprotein (LDL) cholesterol concentrations. The results suggest th...