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Biomedical subjects

G Fex

Publications and source records attributed to G Fex.

At least 19 recordsLinked to original sources
PubMed2003

Decreasing serum concentrations of all-trans, 13-cis retinoic acids and retinol during fasting and caloric restriction.

OBJECTIVES: To investigate the effects of caloric restriction on the serum concentrations of retinoids in man. DESIGN: Samples were drawn before and during caloric restriction by fasting or 4-6 weeks after gastric surgery. SUBJECTS: The fasting group included 17 healthy subjects (11 women and six men) and 16 obese patients (10 women and six men) who underwent bariatric surgery (vertical banded gastroplasty). MAIN OUTCOME MEASURES: Serum concentrations of all-trans, 13-cis, 4-oxo-13-cis retinoic acids and retinol. RESULTS: The serum concentrations of retinol, all-trans and 13-cis retinoic acids decreased by about 20% after 5 days of fasting. After gastroplasty, the serum concentration of retinol, all-trans, 13-cis retinoic acids, retinol-binding protein and transthyretin also decreased to a similar extent after 1 month. In both groups we found a correlation between the delta values of 13-cis retinoic acid and its metabolite 4-oxo-13-cis retinoic acid. In all subjects there were also correlations between the delta values of the retinoids. However, these correlations were comparatively weak (e.g. r2 = 0.36 for retinol--all-trans retinoic acid). The change in retinoid concentrations did not correlate to the change of weight or body mass index. CONCLUSION: Our results support the hypothesis that serum retinol is one of the determinants of serum concentrations of all-trans and 13-cis retinoic acid and that the catabolism of 13-cis retinoic acid is not affected by fasting. However, in the individual case, S-Retinol is a poor predictor of S-All-trans retinoic acid.

Adult↗
PubMed2002

Biological variation of retinoids in man.

This investigation was undertaken to assess biological variation, especially the within-subject variations of all-trans retinoic acid, 13-cis retinoic acid and retinol in human serum. Diurnal variation and variation over a week, a month and a year were studied in 11 males (aged 21-54 years) and 17 females (aged 22-63 years), all subjectively healthy. We found no diurnal variation with the exception of all-trans retinoic acid, which had maximal concentrations at noon irrespective of food intake. Seasonal variations were marginal. Both all-trans and 13-cis retinoic acids had fairly high within-subject (13.1%, and 12.6%, respectively) and between-subject coefficients of variation (15.9% and 21.0%, respectively), while the within-subject CV of retinol was less (5.6%, with a between-subject CV of 21.1%). Thus, the indices of individuality were < 1 for all retinoids. The critical differences between two consecutive samples were < 40% for the retinoic acids and < 20% for retinol. Women had higher all-trans retinoic acid concentrations in serum (5.1 nmol/L vs. 4.5 nmol/L), lower 13-cis retinoic acid concentrations (4.5 nmol/L vs. 5.5 nmol/L) and lower retinol concentrations in serum (2.1 micromol/L vs. 2.5 micromol/L) than men. Thus, samples for retinoid determinations should be drawn in the morning and evaluated using separate gender reference intervals.

Adult↗
PubMed2000

2,3,7,8-tetrachlorodibenzo-p-dioxin increases serum and kidney retinoic acid levels and kidney retinol esterification in the rat.

Halogenatedorganic environmental contaminants such as dioxins are well-known to affect tissue levels of retinoids. To further investigate the effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on retinoid homeostasis, adult male Sprague-Dawley rats were killed 1-112 days after a single oral dose of 10 microg TCDD/kg body wt. Additional groups of rats were killed three days after a single oral dose of 0.1, 1, 10, or 100 microg TCDD/kg body wt. Serum and renal retinoic acid levels were measured, as were levels of serum retinol-binding protein (RBP) in liver, kidneys, and serum. Hepatic and renal formation as well as hepatic hydrolysis of retinyl esters were determined, together with hepatic and renal retinoid levels. In addition, one of the retinyl ester hydrolase (REH) activities was investigated in isolated hepatocytes and hepatic stellate cells from rats killed 7 days after a single oral dose of 10 microg TCDD/kg body wt. No increased hepatic REH activity that could explain the decreased hepatic retinyl ester levels following TCDD treatment was found. In the liver, TCDD increased protein levels, but not mRNA levels, of RBP. A causal relationship is suggested for the increased renal lecithin:retinol acyltransferase (LRAT) activity and increased renal retinyl ester levels in TCDD-treated rats. Importantly, TCDD was shown to substantially increase serum and renal levels of retinoic acid. The ability of TCDD to cause increased tissue retinoic acid levels suggests that TCDD may alter the transcription of retinoic acid-responsive genes.

Animals↗
PubMed1999

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

The population sample of the Kristianstad survey, a reference intervals survey in the county of Kristianstad, 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 Mälmo. 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.

Adult↗
PubMed1998

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

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.

Adult↗
PubMed1997

The additive antiproliferative effect of all-trans retinoic acid and interferon-alpha2a on human cervical carcinoma cell lines is not associated with increased expression of retinoid receptors.

The ability of all-trans retinoic acid (atRA), interferon-alpha2a (IFN-alpha2a) or a combination thereof to modulate the growth of three human cervical carcinoma cell lines (ME180, MS751 and CaSki) and the relationship between responsiveness and the expression of cytosolic retinoid-binding proteins (CRBP and CRABP II), nuclear RA receptors (RAR-alpha, -beta and -gamma) and retinoid X receptor (RXR alpha) were investigated. atRA induced an antiproliferative effect on two of the cell lines (ME180 > MS751), whereas CaSki was much less responsive. An additive growth inhibition on the latter two cell lines was achieved with the combined treatment of atRA and IFN-alpha2a. Receptor expression appeared to be unrelated to growth inhibition in these cell lines in so far as atRA exerted minimal effect on the growth of CaSki, although these cells expressed four of these nuclear receptors. However, mRNA for CRABP II was not demonstrable in CaSki, in contrast to the other two atRA responsive cell lines, as evaluated with RT-PCR and ethidium bromide staining. Treatment with atRA or IFN-alpha2a did not induce any change in mRNA for the nuclear retinoid receptors or cellular retinoid binding proteins after 3 or 6 days of treatment.

Antineoplastic Agents↗
PubMed1997

Autosomal dominant retinitis pigmentosa with a rhodopsin mutation (Arg-135-Trp). Disease phenotype in a Swedish family.

We here present the clinical phenotype in 6 patients from a family with autosomal dominant retinitis pigmentosa found to carry a point mutation in the rhodopsin gene (arginine-135-tryptophan). The mutation is the second found by mutation screening of DNA from 20 Swedish families with dominant retinitis pigmentosa. With full-field electroretinography we could document a severe form of retinitis pigmentosa in patients belonging to the family, similar to the phenotype associated with the previously reported mutation (arginine-135-leucine). Our results indicate that different point mutations in the same region of the rhodopsin gene, resulting in amino acids with similar properties (both hydrophobic), may cause a similar clinical phenotype. Further, point mutations in this specific region seem to cause an agressive form of retinitis pigmentosa.

Adolescent↗
PubMed1997

Reference intervals for the glomerular filtration rate and cell-proliferation markers: serum cystatin C and serum beta 2-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.

Adult↗
PubMed1997

A mild phenotype of autosomal dominant retinitis pigmentosa is associated with the rhodopsin mutation Pro-267-Leu.

By screening blood samples from patients with autosomal dominant retinitis pigmentosa, we found in one of the families a rhodopsin mutation (Pro-267-Leu), which segregates with the disease in two affected and five unaffected family members. Here, we present the results of the clinical evaluation of the family, including full-field electroretinography from the two affected family members. A 25-year-old family member with the mutation had an almost normal electrophysiological retinal response. The patient's father, who was also heterozygous for the mutation and had mild subjective symptoms of retinitis pigmentosa, demonstrated a substantially preserved retinal function. Our results suggest that the Pro-267-Leu rhodopsin mutation is associated with a very mild phenotype of retinitis pigmentosa. Young patients with the disease may have minimal pathological changes in the electroretinogram and some patients with few symptoms may be affected without acquiring a diagnosis of eye disease.

Adult↗
PubMed1996

Retinoic acid concentrations in patients with squamous cell carcinoma of the head and neck.

The serum concentrations of all-trans (atRA) and 13-cis (13cRA) retinoic acid were determined by high performance liquid chromatography in 27 patients with squamous cell carcinoma of the head and neck and in 80 healthy controls. This investigation seemed relevant as ethanol is an aetiological factor in these cancers and has been suggested to interfere with the synthesis of atRA. Neither the serum concentration of atRA nor that of 13cRA differed between patients and controls. The serum atRA concentration did not differ between fasting and non-fasting patients, but the serum 13cRA concentration was significantly higher in non-fasting than in fasting patients, probably due to the dietary retinoid content.

Adult↗
PubMed1995

Expression of human all-trans-retinoic acid receptor beta and its ligand-binding domain in Escherichia coli.

all-trans-Retinoic acid, one of the hormonally active derivatives of vitamin A, occurs physiologically in plasma at a concentration below 10 nmol/l. The methods currently used for its quantification are based on HPLC, need about 1 ml of serum, are relatively laborious and thus not well suited for mass analysis. The affinity and specificity of retinoic acid receptors for all-trans-retinoic acid encouraged us to express both the entire human retinoic acid receptor beta (RAR-beta) and two versions of its retinoic acid-binding domain in Escherichia coli in the hope that these recombinant proteins might be used as binders in a ligand-binding assay for all-trans-retinoic acid. The recombinant receptors, the whole receptor [RAR-beta-(V7-Q448)], corresponding to domains A-F, and the ligand-binding domain [RAR-beta-(E149-Q448)], corresponding to domains D-F, were expressed in the vector pET 3d/BL21 (DE3) as inclusion bodies, solubilized with guanidinium chloride, renatured and purified by ion-exchange chromatography. RAR-beta-(P193-Q448), corresponding to domains E-F, was expressed in the vector pET 3d/BL21(DE3)pLysS, and purified by reversed-phase chromatography. Under non-denaturing conditions, the expressed whole receptor [RAR-beta-(V7-Q448)] and the D-F construct (RAR-beta-(E149-Q448)] behaved chromatographically as monomeric proteins whereas the E-F construct [RAR-beta-(P193-Q448)] had a strong tendency to aggregate. RAR-beta-(V7-Q448) and RAR-beta-(E149-Q448) had similar Kd values for all-trans-retinoic acid (1.4 and 0.6 nmol/l respectively) whereas RAR-beta-(P193-Q448) bound all-trans-retinoic acid less avidly (Kd 9.6 nmol/l). 9-cis-Retinoic acid bound to RAR-beta-(E149-Q448) and RAR-beta-(V7-Q448) as avidly as all-trans-retinoic acid. Competition experiments showed weak or no binding of 4-oxo-all-trans-retinoic acid, 4-oxo-13-cis-retinoic acid, 13-cis-retinoic acid, acitretin and retinol by RAR-beta-(E149-Q448).

Base Sequence↗
PubMed1995

Low serum concentration of all-trans and 13-cis retinoic acids in patients treated with phenytoin, carbamazepine and valproate. Possible relation to teratogenicity.

All-trans retinoic acid deficiency resulting from ethanol's interference with the synthesis of all-trans retinoic acid from retinol was recently suggested to cause the malformations of the fetal alcohol syndrome. Phenytoin, carbamazepine and valproate, might be teratogenic because they lower the concentration of all-trans retinoic acid in serum, by inducing the enzyme systems in the liver responsible for the metabolism of the all-trans retinoic acid, or by other mechanisms. Here we show, that in patients given therapeutic doses of phenytoin, carbamazepine and valproate, serum all-trans and 13-cis retinoic acid concentrations are indeed significantly lowered. We propose that drugs with this ability should be considered as potential teratogens.

Adult↗
PubMed1995

Phenotype variations within a choroideremia family lacking the entire CHM gene.

A Swedish family with choroideremia and a deletion of the CHM gene has been studied with ophthalmological examination, full-field electroretinography, and DNA analysis in order to characterize the phenotype of the disease. Although all four patients studied had a complete deletion of the gene, they showed a considerable variability regarding the phenotype, including the electroretinogram tracings. Two of the affected males demonstrated a severe form of choroideremia with low or nondetectable ERG recordings, while the other two affected males showed a less severe phenotype with only a slight reduction of the ERG amplitudes. The variation of the clinical phenotype among family members carrying the same mutation indicates that the severity of choroideremia is not solely a function of the CHM gene.

Adult↗
PubMed1994

Retinyl palmitate is a reproducible marker for chylomicron elimination from blood.

To study the individual variation in chylomicron clearance rate, young healthy volunteers were given a p.o. dose of 50,000 IU retinyl palmitate in the morning to label their chylomicrons. Serial blood samples were then obtained in the time interval 4-8 h after retinyl palmitate intake, to closely monitor the clearance of retinyl ester from the blood. The procedure was repeated in an identical way two days later. The calculated individual halflives for retinyl palmitate clearance ranged from 1.54 to 9.90 h, i.e. a more than five-fold variation. The intraindividual variation was much less (relative SD 11%). Retinyl palmitate clearance (and probably chylomicron clearance) is, thus, relatively constant within the same individual on different occasions but varies considerably between individuals.

Adult↗
PubMed1992

A six-generation family with autosomal dominant retinitis pigmentosa and a rhodopsin gene mutation (arginine-135-leucine).

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.

Adult↗
PubMed1990

Apolipoprotein A-I:B ratio and B screening: a preliminary study of 10- and 11-year-old children.

The apolipoprotein (apo) A-I:B ratio and the apo B concentration were determined by radial immunodiffusion in dried blood spot samples from 1,767 10- and 11-year-old children. Children with either apo A-I:B ratios below the first percentile or apo B levels above the 99th were recalled and plasma lipid and apolipoprotein profiles were determined for both children and parents. Of 17 children (one family was lost to follow-up) recalled due to abnormal apo A-I:B ratios, apo B levels were above the 95th percentile in 13 children, and of 18 children with abnormal apo B screening levels (three of them also had abnormal apo A-I:B ratios), the plasma apo B level was elevated in 13 children. The 23 children with abnormal blood lipid and/or apolipoprotein concentrations were divided into two main groups: (a) children with type IIa hyperlipoproteinemia and (b) children with hyperapo B lipoproteinemia (hyperapo B) and normal blood lipid levels. Twelve children had the type IIa pattern. Five children likely had familial hypercholesterolemia (FH), the other seven children may have hypercholesterolemia due to obesity or environmental factors. Eleven children had the hyperapo B abnormality. In four children, the elevated apo B level probably was an indication of the occurrence of familial combined hypercholesterolemia (FCH) in the family. Of the remaining seven hyperapo B children, three children also had a parent with hyperapo B and a fourth family suffered from obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I↗