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F Roels

Publications and source records attributed to F Roels.

At least 55 records · Page 3Linked to original sources
PubMed1993

Human liver pathology in peroxisomal diseases: a review including novel data.

Results from electron microscopic morphometry, enzyme cytochemistry and immunolocalization in liver biopsies are reviewed. Emphasis is put on the following aspects: 1) relationship between peroxisomal size and enzyme concentration; 2) abnormal enlargement of peroxisomes in many congenital disorders with peroxisomal dysfunction; 3) normal localization of matrix enzymes in several patients with peroxisomal dysfunction, with the exception of catalase, which is mainly cytoplasmic; 4) ghost-like peroxisomes in the liver of several syndromes but not in nine cases labelled as Zellweger; 5) discrepancies between liver and cultured fibroblasts; 6) trilamellar, regularly spaced inclusions, large stacks of which are birefringent, indicate a peroxisomal dysfunction; their absence does not exclude it. The same rule holds for lipid in macrophages which is insoluble in acetone and n-hexane (after fixation). The chemical nature of these two storage materials remains unclear; and 7) proliferation of human peroxisomes is frequent in acquired liver diseases and drug toxicity, but is never accompanied by an increase in size, in contrast to the effect of the fibrates and phthalates in rat and mouse. Novel data from seven peroxisomal patients are included.

Adrenoleukodystrophy↗
PubMed1993

Altered adrenocortical response under the influence of experimentally increased serum very long chain fatty acids in rats.

C 26:0/C 22:0 ratio can be experimentally increased in serum of normal rats by oral administration of hexacosanoic acid (C 26:0) or of thioridazine, an inhibitor of peroxisomal beta-oxidation. This causes a decreased corticosterone response as well as decreased mobilization of cholesterol esters in zona fasciculata interna cells following ACTH administration. Zona fasciculata interna cells and their nuclei are enlarged and contain more Feulgen DNA in thioridazine-fed rats. The similarity of adrenocortical response to inhibition of peroxisomal beta-oxidation and to C 26:0 administration points to raised VLCFA as the common factor which is also operative in many peroxisomal diseases accompanied by adrenocortical function defects.

Adrenal Glands↗
PubMed1993

Experimental modification of vitellogenesis in Japanese quail by trypan blue in vivo.

Ovaries of adult Japanese quails were exposed in vivo to the acid bisazo dye trypan blue (TB) which binds to plasma albumin, the plasma precursor of the yolk protein alpha-livetin. By a combination of fluorescence microscopy and electron microscopy alpha-livetin could be localized in the subdroplets of intermediary and yellow yolk spheres. Trypan blue alters vitellogenesis in the non-disc region of follicles in rapid growth in a reversible and dose-dependent way. Less yolk is produced over 24 h and its morphology is different when compared to controls. This yolk is similar to yolk of the germinal disc region where vitellogenesis is known to be inhibited physiologically. Several ultrastructural features of the germinal disc region are also found in the non-disc region of TB-exposed follicles. Our results suggest that the morphology of yellow yolk is linked to the rate of deposition. We propose that the inhibitory action of TB on vitellogenesis can be explained by a defective receptor-ligand dissociation in endosomes.

Animals↗
PubMed1992

Growth behavior of human pancreatic carcinoma xenograft correlates with nuclear features.

Two human pancreatic ductal adenocarcinomas with different growth rates were serially transplanted into nude mice. Feulgen-stained 4 microns sections and imprints from the xenografts were studied with a VICOM automated image analysis system. After pooling the results from two passages, with three mice in each passage, it was shown that of 23 nuclear parameters measured the following were correlated with a fast tumor growth rate: in sections, a decrease in heterogeneity of the chromatin and an increase in perimeter and nuclear area; in imprints, an increase in lesser diameter, in mean grey level difference between second neighboring pixels, and in total integrated optical density (DNA content). Several parameters differed significantly between passages, and between animals in the same passage. These findings suggest that the growth speed of pancreatic tumors may be predicted by nuclear parameters.

Adenocarcinoma↗
PubMed1992

Neonatal seizures and severe hypotonia in a male infant suffering from a defect in peroxisomal beta-oxidation.

In this paper, we describe a baby male born to healthy non-consanguineous parents presenting at birth with hypotonia and seizures. Additional salient clinical features included the development of glaucoma, the absence of significant facial dysmorphism and the absence of liver enlargement or renal cysts. The patient died at the age of 3 months. At autopsy, liver fibrosis and kidney glomerulosclerosis were noted. Neuropathological findings included pachygyria of the olivary nuclei and cerebellar neuronal heterotopias. There was no evidence for a demyelinating process. Biochemically, the patient was found to have elevated plasma levels of very-long-chain fatty acids (VLCFA) and abnormal bile acid intermediates, whereas other indicators of peroxisomal function (plasmalogen biosynthesis and plasma pipecolic acid) were normal. Catalase staining of a liver biopsy specimen revealed peroxisomes to be present in normal numbers, although some were abnormally large. Trilamellar inclusions typical of a peroxisomal fatty acid oxidation defect were present in macrophages. Indeed, beta-oxidation of the very-long-chain fatty acid hexacosanoic acid (C26:0) was found to be strongly deficient. Fatty acyl-CoA oxidase activity in the patient's liver was normal, however. Furthermore immunocytochemical studies using antibodies against acyl-CoA oxidase, bifunctional protein and peroxisomal thiolase, revealed the normal localization of all three enzyme proteins within the peroxisomes. We suggest that our patient has a selective peroxisomal beta-oxidation defect, a recently identified heterogeneous group of early-onset peroxisomal disorders distinct from the Zellweger syndrome and other generalized peroxisomal disorders.

Acyl-CoA Oxidase↗
PubMed1992

The rat liver cell nuclear imprint as a standard for DNA measurements.

Standards are used in DNA cytophotometry to determine the diploid reference value. Fixation and staining protocols have to be standardized because numerous sources of variation influence staining intensity of DNA. When Feulgen stained imprints of rat liver cell nuclei are used as an external DNA standard a significant difference of reference value of up to 60% between imprints, from the same liver and with all sources of variation minimized, is demonstrated. Different possible sources of intra-imprint variation were examined but its exact nature remains unknown. Due to this inter-imprint variation, the DNA-reference value from a single liver imprint is only an approximation with unknown error of the true diploid reference value. By drawing an aselective random sample of N diploid cells in M imprints the sampling distribution of TIOD (mean Total Integrated Optical Density) will have its expectation identical to the diploid reference value and is approached by TIOD (mean TIOD) with the confidence interval defined by the number, M, of imprints measured. The use of TIOD as an estimate of diploid reference value with known precision is proposed as a first approach for the definition of a standard for DNA measurements.

Animals↗
PubMed1991

Hepatocellular peroxisomes in human alcoholic and drug-induced hepatitis: a quantitative study.

The peroxisomes in the liver of four patients with alcoholic hepatitis and in six patients with drug-induced hepatitis are compared to eight control livers by catalase cytochemistry and morphometry. A decrease of catalase activity is observed in alcoholic, amitriptyline, aprindine, clomipramine and methiomazole hepatitis. Peroxisomes with a heterogeneous distribution of the catalase reaction product are found in most hepatitis livers. The number of organelles is increased 1.5 to 4.2 times in alcoholic, aprindine, methimazole and phenytoin hepatitis livers. In the last case, peroxisomes are also smaller. Changes in shape are seen in all hepatitis livers; they include invaginations, tails, funnel-like constrictions and gastruloid cisternae. In aprindine, phenytoin, methimazole and two alcoholic hepatitis livers, surface density exceeds the upper control value. These data indicate a loss of catalase activity in most hepatitis livers but also peroxisomal proliferation and shape modifications. It has been proposed that the latter changes are favorable for metabolic activity.

Biopsy↗
PubMed1991

Peroxisomal localization of the immunoreactive beta-oxidation enzymes in a neonate with a beta-oxidation defect. Pathological observations in liver, adrenal cortex and kidney.

A boy born to healthy, unrelated parents, presented at birth with hypotonia and seizures. Very long chain fatty acids in the plasma were strongly elevated; bile acid intermediates and plasmalogen biosynthesis were normal. Acyl-CoA oxidase activity was normal. The patient died at the age of 3 months. The cerebellum and medulla oblongata showed neuronal migration defects. The specific biochemical basis for the impaired peroxisomal beta-oxidation has not been found. The three immunoreactive peroxisomal beta-oxidation enzymes and catalase were localized in the hepatocellular peroxisomes. Aberrant features of the peroxisomes included: a subpopulation of organelles larger than 1 micron, an amorphous nucleoid in many organelles, and invaginations of the peroxisomal membrane into the matrix. Peroxisomes in the proximal renal tubules also contained the three immunoreactive beta-oxidation enzymes. Regularly spaced trilamellar inclusions were seen in hepatic macrophages; they were much more abundant in adrenocortical macrophages. The inclusions were birefringent and resistant to acetone extraction. Distinct hepatic fibrosis had developed over a period of 2.5 months. We speculate that the impaired beta-oxidation is due to a defect at the level of the peroxisomal carnitine octanoyl or -acetyl transferase, responsible for the export of beta-oxidation products.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1991

Very large peroxisomes in distinct peroxisomal disorders (rhizomelic chondrodysplasia punctata and acyl-CoA oxidase deficiency): novel data.

We report very large hepatic peroxisomes (d-circle greater than 1 micron) in a patient with rhizomelic chondrodysplasia punctata and a patient with acyl-CoA oxidase deficiency. The effects of peroxisomal enlargement on the enzymatic activity are discussed. As increase in peroxisomal size is also reported in at least 12 other patients with peroxisomal disorders, we propose a relationship between the enlargement of the organelles and their functional deficiency.

Acyl-CoA Oxidase↗
PubMed1991

Liver pathology and immunocytochemistry in congenital peroxisomal diseases: a review.

Diagnostic and pathogenetic investigations of peroxisomal disorders should include the study of the macroscopic and microscopic pathology of the liver, in addition to careful clinical observations, skeletal X-ray and brain CT scan, assays of very long-chain fatty acids and bile acid intermediates, and selected enzyme activities. This review of the literature also contains novel observations about the following syndromes: cerebro-hepato-renal (Zellweger) syndrome, X-linked and neonatal adrenoleukodystrophies (ALD, NALD), NALD-like syndromes, infantile phytanic acid storage, classical Refsum disease, rhizomelic and other forms of chondrodysplasia punctata (XD, XR, AR), hyperpipecolic acidaemia, primary hyperoxaluria I, pseudo-Zellweger and Zellweger-like syndromes, and single enzyme deficiencies. Microscopic data include catalase staining and morphometry of peroxisomes, immunolocalization of beta-oxidation enzymes, detection of trilamellar, polarizing inclusions in PAS-positive macrophages, fibrosis and iron storage. Peroxisomal enlargement appears to be related to functional deficit in beta-oxidation disorders as well as in rhizomelic chondrodysplasia punctata. Because normal peroxisomal localization of active beta-oxidation enzymes can accompany a C26 beta-oxidation deficit, other mechanisms such as impaired transport of metabolites should be investigated. 'Ghost'-like organelles are shown in the liver of an infantile Refsum patient and in an NALD-like case; immuno-gold labelling of membrane proteins did not reveal ghosts in Zellweger livers.

Humans↗
PubMed1991

Quantitative in situ hybridization in neuro-endocrinology.

In situ hybridization has become one of the most powerful tools for localizing specific gene products in a tissue. Labelled molecular probes are used on tissue sections or on cells for localization of their hybridization sites. In situ hybridization makes it possible to define the spatial and temporal distribution of specific genes. The use of probes dually labelled, or the combined use of a molecular probe and labelled antibodies provides unprecedented opportunities to examine gene expression in individual cells. In addition, the quantification of gene products can shed light on regulation of gene expression at the cellular level.

Animals↗
PubMed1991

Different types of peroxisomes in human duodenal epithelium.

Peroxisomes are ubiquitous organelles containing enzyme sequences for beta oxidation of fatty acids, synthesis of bile acids, and ether phospholipids. In the inherited peroxisomal diseases one or more enzymes are deficient in hepatic, renal, and fibroblast peroxisomes. We have examined peroxisomes by light and electron microscopy in 29 duodenal biopsy specimens (21 with normal mucosa) after staining for catalase activity, a marker enzyme. Peroxisomes were most numerous in the apices of the nucleus and at the villus base. Two types were distinguished: rounded to oval forms with a median lesser diameter of 0.23-0.31 microns, and tubular, vermiform organelles 0.1 microns thick and up to 3 microns long. Both types coexist in most patients. Tilting of sections and examination of semithin sections at 120 kV did not show connections between individual organelles. By morphometry, volume density was at least 0.45-0.62% of cellular volume, compared to 1.05% in human liver. In contrast, in four out of five individuals surface density of the peroxisomal membrane was 1.4-2.3 times higher than in control livers; this is expected to favour the exchange of metabolites. We suggest that intestinal peroxisomes contribute substantially to the breakdown of very long chain fatty acids.

Adult↗
PubMed1991

Influence of optical density on the automated segmentation of rat kidney lysosomes.

After staining for acid phosphatase, video-images were acquired from 0.5-micron sections of rat kidney. Lysosomes in proximal tubules were automatically segmented, using a VICOM digital image processor and measured for area, number and optical density (OD). The purpose of this study is to objectively evaluate the performance of the automated segmentation algorithm at different staining intensities (a) by measuring area after staining with different incubation times, reduced substrate concentration or by adding an inhibitor and (b) by 'simulating' a decrease in OD (reducing grey-values at each point of a digitized image). The results of the experiments showed that: (1) the algorithm will underestimate the size of lysosomes (a) when the OD in close to the local background and (b) when an area is larger than or close to the area of the lowpass square filter; (2) accuracy of the segmentation can be improved by comparing the results of feature extraction after segmentation of the same image at different relative OD levels; (3) lysosomes with very low OD, compared to background are delineated with a large error or not delineated at all and this cannot be corrected. Incorrectly delineated lysosomes can be identified and excluded from further calculations, or their measured area replaced by an estimate of the true area.

Acid Phosphatase↗
PubMed1991

Automated cytometry of muscle fibre sections: size and spatial distribution of the four fibre types in young and adult rats.

An automated cytometry program was applied to the extensor digitorum longus muscle of young and adult rats. Lesser diameter and spatial distribution of about 4000 fibres were measured in digital images from ATPase-stained muscle sections. All fibre types grow thicker with age, but the coefficient of variation of the diameter is age-independent. At both ages, 2B fibres have the largest mean diameter and are most frequent. 2A fibres in young rats present a diameter smaller or equal to type 1 but then show a faster increase in size; their relative number increases from 20 to 28%. Consequently type 2A displays the most important change with age. The spatial distribution of fibres is mathematically expressed; most images show a random distribution of type 1 and type 2 fibres. Taking into account the variation of fibre size of each type, the number of fibres which should be measured in order to reach a specified precision was calculated.

Analysis of Variance↗
PubMed1990

Experimental inhibition of peroxisomal beta-oxidation in rats: influence on brain myelination.

Oral administration of thioridazine, an inhibitor of peroxisomal beta-oxidation, to normal rats from weaning till day 60 causes a small increase of the very long chain fatty acid C26 in brain lipids. Myelination in the brain is decreased. In the genu of the corpus callosum the ratio of non-myelinated/myelinated axons is increased. In the commissura anterior the myelin sheaths of the axons are significantly thinner in treated than in control animals. Undernourishment caused by the drug is minimal in this experiment. Area and total DNA of glial nuclei are unaltered in both the genu and the commissura anterior of treated rats. The distribution of chromatin (texture), however, shows small differences in the corpus callosum.

Animals↗