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Biomedical subjects

H Roels

Publications and source records attributed to H Roels.

At least 73 records · Page 4Linked to original sources

Assessment of the causality of the cadmium--protein relationships in the urine of the general population with reference to the Cadmibel study.

The assessment of acceptable exposure levels to cadmium in the work or general environment frequently relies on the analysis of the relationships between urinary cadmium (an indicator of the body burden) and proteins used as markers of nephrotoxicity. A possibility which cannot be excluded a priori is that the relationships between cadmium and proteins in urine might sometimes result from renal dysfunction unrelated to cadmium toxicity. To test this hypothesis, we have measured cadmium in the urine of 114 pregnant women of whom about 20% had developed a reversible tubular proteinuria. Cadmium excretion was correlated significantly with age but not with duration of pregnancy nor with low molecular weight urinary proteins. This indicates that tubular dysfunction unrelated to cadmium exposure does not necessarily increase cadmium excretion. Hence, these data support the conclusion of the recent Cadmibel Study on the renal tubular effects of cadmium on the general population of Belgium.

Acetylglucosaminidase↗

Analytical quality control of cadmium and lead in blood and cadmium in urine: results of its implementation during a five-year epidemiological study.

Quality-control programmes are very important in assessing the reliability of biological analyses. Such programmes are essential if misleading results in epidemiological studies dealing with low levels of exposure to heavy metals present in the general environment (e.g., cadmium, lead) are to be avoided. Internal and external quality-control programmes for the measurement of cadmium and lead in blood and of cadmium in urine were implemented from 1985 to 1989 in support of a national epidemiological study, Cadmibel (2327 participants), conducted in Belgium to assess the effects of environmental exposure to cadmium and lead on the general population. Apart from these programmes, inter-comparisons between the two participating laboratories were carried out on 10% of the samples. The results of these quality-control programmes met external acceptability criteria, emphasizing the analytical proficiency of these measurements at the relatively low concentrations in the Cadmibel study.

Cadmium↗

Histopathology of laryngeal tumours.

A description is given of the frequent as well as of the less frequent epithelial and mesenchymal tumours of the larynx. The description is based on the light microscopical and histochemical characteristics of these tumours. The relation to the clinical presentation is briefly mentioned. The correlation between the subtypes and prognosis is discussed.

Carcinoma↗

Spondylarthropathy and gut inflammation: immunopathogenetic mechanisms.

In 62% of patients with spondylarthropathy (SpA) we found clinically unsuspected gut inflammation to feature acute or chronic enterocolitis on ileocolonoscopy. A proportion of patients of the latter group had subclinical Crohn's disease as demonstrated clinically, endoscopically, genetically, histologically and immunopathologically. There is a relation between the activity of the gut inflammation and clinical rheumatic symptoms. A pathogenetic mechanism is increased handling of luminal (bacterial or nutritional) antigen, hence inducing T-cell activation and intestinal inflammation. In ileal mucosal biopsies we showed two different cellular events: increased enterocytic expression of class II molecules in active inflammation and an increase of membranous (M) cells overlying lymphocytes in inflamed mucosa. Although the number of intraepithelial lymphocytes was not increased in inflammation, intraepithelial T lymphocytes had protruding processes in close apposition to the tips of epithelial plasma membranes. Lymphocytes crossing the basement membrane were a frequent finding. These features indicate that the intestinal immune response caused by increased antigen processing in the terminal ileum induces an inflammatory immunocascade responsible for the clinical picture of SpA.

Adolescent↗

Combined leiomyomatosis of the small intestine and colon.

We report a case of leiomyomatosis that involved the small intestine and colon. On gross examination, the bowel wall was irregularly thickened at various levels. Histologically, the lesions were characterized by multifocal, diffuse tumor masses that were present in the muscular layers. These masses consisted of proliferating smooth-muscle cells that often surrounded prominent blood vessels. Cytologic atypia was not observed, and the mitotic count was low, illustrating the benign nature of the tumors. Findings from immunohistochemical analysis of the lesions were essentially negative; vimentin, cytokeratin, actin, desmin, and S100 stains showed no reactivity in the tumor cells, despite positive internal controls. By reviewing the literature, we found several reports on related lesions that occurred in the gastrointestinal tract; diffuse leiomyomatosis of the esophagus and the colon have been reported. We did not find any report on the small intestinal variant of the disease; therefore, it seemed useful to term this new localization as leiomyomatosis of the small intestine and colon.

Colonic Neoplasms↗

Does environmental exposure to cadmium represent a health risk? Conclusions from the Cadmibel study.

Cadmium is a very dispersive pollutant which has progressively accumulated in the environment mainly in the areas where nonferrous smelters have been in operation. An important toxicological feature of cadmium is its exceptionally long biological half-life in the human body. For the general population mainly exposed to cadmium by the diet and smoking, the kidney is the main target organ. Some studies have also suggested that cadmium might play a role in the pathogenesis of hypertension. A cross-sectional study (called Cadmibel) was undertaken to assess whether environmental pollution by cadmium in Belgium might represent a health risk. This paper does not present the detailed results of this study which are published elsewhere but simply report its main conclusions. A total number of 2327 subjects (stratified according to age and sex) was randomly sampled in two urban (Liège and Charleroi) and two rural (Hechtel-Eksel and Noorderkempen) areas, with different environmental pollution by cadmium. After allowing for the various factors known to influence cadmium accumulation, it was estimated that the cadmium body burden of the residents of the most polluted district (Noorderkempen) was 50 to 85% higher than in the less polluted areas. No statistical association was found between environmental exposure to cadmium and blood pressure elevation or the prevalence of cardiovascular diseases. However, the study has shown that the environmental exposure of the general population to cadmium may induce slight renal tubular dysfunction and may probably also affect cadmium homeostasis. The probability of tubular dysfunction (as assessed by sensitive tests) is about 10% when cadmium in urine reaches 2 micrograms/day. The morbidity associated with the changes in the renal proximal tubule and the calcium metabolism observed when the body burden of cadmium exceeds this value remains to be assessed.

Adult↗

Vimentin expression of renal cell carcinoma in relation to DNA content and histological grading: a combined light microscopic, immunocytochemical and cytophotometrical analysis.

An immunocytochemical and cytophotometrical analysis of 30 renal cell carcinomas was carried out in order to investigate the expression of cytokeratin and vimentin in relation to the ploidy and mitotic index. Thirty renal cell carcinomas were studied using monoclonal antibodies CAM 5.2 and anti-vimentin in a biotin-streptavidin staining procedure. The renal cell carcinomas were classified according to the criteria of Fuhrman with a nuclear grading from I to IV. All carcinomas expressed cytokeratin, whereas co-expression with vimentin was present only in 53%. Expression for both intermediate filaments was present in aneuploid tumours with a marked nuclear pleomorphism and was more frequently related to a tubulo-papillary and pseudosarcomatous growth pattern. It is suggested that vimentin expression in renal cell carcinomas may be useful as a prognostic index in addition to nuclear grade. DNA content, mitotic rate and tumour stage.

Biomarkers, Tumor↗

Thymoma: a clinicopathological comparative study of 25 cases.

We reviewed 25 patients with thymoma for clinical symptoms at presentation, X-ray findings and outcome. The tumours of all patients were classified using 3 different pathologic classification systems and each system was evaluated for its predictive power with respect to survival. The recent classification system by Müller-Hermelink allowed to distinguish thymomas with associated systemic syndromes from those without. However, no good prediction with respect to outcome could be made by any of the 3 systems.

Actuarial Analysis↗

The association between blood pressure, calcium and other divalent cations: a population study.

This report investigated the associations between blood pressure and the levels of various divalent cations in blood and urine in the population at large. The 1,982 participants (963 men and 1019 women; mean age 48 years) constituted a stratified random sample of the population of 4 Belgian districts. Systolic/diastolic pressure averaged 133/78 mmHg in men, and 128/76 mmHg in women. Serum total calcium (2.37 mmol/l), serum magnesium (1.00 mmol/l) and blood cadmium (10.0 nmol/l) were on average similar in the two sexes. By contrast, serum zinc (13.1 and 12.6 mumol/l, respectively), blood lead (0.56 and 0.36 mumol/l) and the urinary excretions of calcium (4.86 and 3.95 mmol/24h), copper (0.16 and 0.13 mumol/24h), and cadmium (9.4 and 7.2 nmol/24h) were significantly higher in men than in women. After adjustment for significant blood pressure covariates (age, body mass index, pulse rate, log gamma-glutamyltranspeptidase, smoking habits, and in women the contraceptive pill), serum total calcium was independently and positively correlated with systolic pressure in both sexes, and with diastolic pressure in women. After similar adjustments systolic pressure was positively correlated with urinary copper in men and women. In addition, systolic pressure and blood lead, and diastolic pressure and urinary cadmium were negatively correlated in men. In conclusion, this population study demonstrated a positive relationship between systolic blood pressure and both serum total calcium and urinary copper.

Adult↗

Renal effects of cadmium body burden of the general population.

In a cross-sectional population study to assess whether environmental exposure to cadmium is associated with renal dysfunction, 1699 subjects aged 20-80 years were studied as a random sample of four areas of Belgium with varying degrees of cadmium pollution. After standardisation for several possible confounding factors, five variables (urinary excretion of retinol-binding protein, N-acetyl-beta-glucosaminidase, beta 2-microglobulin, aminoacids, and calcium) were significantly associated with the urinary excretion of cadmium (as a marker of cadmium body burden), suggesting the presence of tubular dysfunction. There was a 10% probability of values of these variables being abnormal when cadmium excretion exceeded 2-4 micrograms/24 h. Excretion reached this threshold in 10% of non-smokers. There was also evidence that diabetic patients may be more susceptible to the toxic effect of cadmium on the renal proximal tubule.

Acetylglucosaminidase↗

Major histocompatibility complex class II antigen (HLA-DR) expression by ileal epithelial cells in patients with seronegative spondylarthropathy.

Major histocompatibility complex molecules act as non-specific receptors for antigenic proteins and present them to T-cells. Presented antigen together with class II molecules activates antigen specific T-helper cells and may trigger a cellular immune response. The expression of HLA-DR antigens by epithelial cells was examined with an indirect peroxidase technique in ileal biopsies from 38 patients with seronegative spondylarthropathy and features of acute or chronic gut inflammation on biopsy, 14 patients with chronic inflammatory bowel disease, 10 rheumatic and 10 non-rheumatic controls. In acute ileitis, there was more HLA-DR expression in villous and crypt epithelial cells than in non-inflamed controls (p less than 0.01). In chronic inflammation and in chronic inflammatory bowel disease, class II antigens were more expressed in villus (p less than 0.02) and crypt epithelium (p less than 0.01). Strong HLA-DR expression in crypt epithelial cells was connected with active inflammation (p less than 0.02). These findings suggest binding of unknown enterobacterial or nutritional luminal antigens to HLA-DR antigens normally present in enterocytes. The enterocytes act as antigen presenting cells causing a local increase of targets for activated T-cells and trigger the gut inflammation responsible for the clinical symptoms of the seronegative spondylarthropathy.

Adolescent↗

Assessment of urinary protein 1 and transferrin as early markers of cadmium nephrotoxicity.

Transferrin and protein 1, a sex linked alpha 2-microprotein, were assayed in urine from 58 workers exposed to cadmium (Cd) in a non-ferrous smelter and from 58 age matched referents. These two new markers of nephrotoxicity were compared with urinary beta 2-microglobulin (beta 2-m), retinol binding protein (RBP), albumin, and beta-N-acetyl-glucosaminidase (NAG). The response of protein 1 to Cd tubulotoxicity was similar to that of beta 2-m, RBP, and NAG. In Cd workers, protein 1 had a correlation with urinary Cd (r = 0.56) similar to beta 2-m (r = 0.48), RBP (r = 0.58), and NAG (r = 0.49). Values of these three low molecular weight proteins and of NAG were increased only in workers with urinary Cd higher than 10 micrograms/g creatinine. Urinary transferrin and albumin were similarly affected by exposure to Cd. Their response, however, was clearly more sensitive than that of low molecular weight proteins. Prevalences of positive values of these two high molecular weight proteins were not only higher but also tended to rise at lower concentrations of Cd in urine or blood. This finding suggests that in some subjects subtle defects in glomerular barrier function may precede the onset of proximal tubular impairment after chronic exposure to Cd. It remains to be assessed whether these subjects are more at risk of developing renal insufficiency.

Acetylglucosaminidase↗

The selective counterstaining of the plasma membrane improves the immunoelectron microscopic detection of neu protein at the cell border.

The distribution of the neu protein has been studied with two monoclonal antibodies in a post-embedding immunogold method on glycolmethacrylate sections. Labeling of the cytoplasm was due to binding to mitochondrial cristae. The detection of label at the plasma membrane was optimized by selectively staining the plasma membrane with phosphotungstic acid at low pH. Strong labeling was observed in breast carcinoma cells and faint labeling in other tissues. Brush borders were also found to be reactive. neu protein can thus be localized to baso-lateral and apical cell membranes. An important homology exists with a mitochondrial protein.

Breast↗

Hypertension due to a renal renin-secreting tumour.

We report a case of a 25 year old man referred to our department because of a blood pressure of 162/122 mmHg, found during a general physical examination. A renal renin-secreting tumour was found to be the cause of the hypertension. It had a diameter of 4 cm and was enucleated from the right kidney. Subsequently the blood pressure returned to normal levels. Histological examination revealed a hemangiopericytoma.

Adult↗

The subcellular localization of the neu protein in human normal and neoplastic cells.

We have examined the subcellular localization of the neu protein by immunohistochemistry and immuno-electron microscopy, associated with immunoblotting of normal and neoplastic tissues with 2 monoclonal antibodies (MAbs). Immunoelectron microscopy clearly reveals that neu protein resides only on the lateral plasma membrane of the simple epithelium of the breast and on the plasma membrane of malignant breast cells. It is also found on the membranes of the microvilli and the apical vacuoles of the cells of the proximal convoluted tubule of the kidney. In the cytoplasm, the only immunoreactivity detected with both antibodies was on the membrane of the mitochondrial cristae of normal and malignant cells. Immunoblotting reveals that the molecular weight of the membrane protein is 185 and 155 kDa for the mitochondrial protein. The cell membrane staining pattern can be revealed by light microscopic immunohistochemistry only in malignant cells and is therefore specific for malignancy. The membrane expression in normal cells cannot be visualized in this way. The mitochondrial reactivity appears as a cytoplasmic granular staining when examined under the light microscope. Similar cytoplasmic staining has been described previously in other studies with other antibodies against the neu protein and has lead to speculation about its function in normal and malignant cells. However, it is demonstrated in this study that it is not the known neu-oncogene product.

Antibodies, Monoclonal↗

Detection of hand tremor in workers exposed to mercury vapor: a comparative study of three methods.

Hand tremor measurement was evaluated in a group of 54 male workers (mean age 38.5 years) exposed to mercury vapor (average duration of exposure 7.7 years) using an accelerometer test and two psychomotor tests (eye-hand coordination and hand steadiness). The results were compared with those obtained in a well-matched control group of 48 workers. The intensity of current mercury vapor exposure was rather moderate as reflected by the mean (geometric) levels of mercury in blood (2.4 micrograms/dl) and in urine (63 micrograms/g creatinine). The hand steadiness test and eye-hand coordination test revealed preclinical alterations in postural and intentional tremor, whereas the changes evidenced by the accelerometer test were not statistically significant. Furthermore the practical advantage of the psychomotor tests over the accelerometer test makes them most appropriate for the early detection of mercury-induced hand tremor. The present study also suggests that young adults (less than 21 years) may be more susceptible to the neurotoxic effect of mercury vapor.

Adult↗