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Biomedical subjects

H Roels

Publications and source records attributed to H Roels.

At least 55 records · Page 3Linked to original sources

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↗

Relationship between atmospheric and urinary nickel in workers manufacturing electrical resistances using nickel oxide: role of the bioavailability of nickel.

The daily concentrations of nickel in total (ie inhalable) and respirable airborne dust (personal sampling) and in post-shift and pre-shift urine samples were monitored during five consecutive work days in 20 workers exposed to NiO in a workshop manufacturing electrical resistances. The individual daily atmospheric nickel concentrations ranged from 0.5 to 9586 micrograms Ni/m3 (geometric mean 22.9) for total dust and from 0.2 to 332 micrograms Ni/m3 (geometric mean 3.5) for respirable dust. The results of the urinary excretion of nickel suggested that the occupationally-related systemic absorption of nickel strongly differed in one subject (worker E) compared to the other 19 workers. In the latter group the nickel concentration in urine never exceeded 5 micrograms Ni/g creatinine, it did not differ between post-shift and pre-shift samples (geometric means: 1.1 versus 1.2 micrograms Ni/g creatinine), and it was only slightly higher than that measured in a group of 17 non-exposed subjects (mean 0.5 micrograms Ni/g creatinine; range 0.1-1.7); furthermore their nickel elimination in urine did not change during the days off or after two weeks of holiday. In worker E, the nickel concentration ranged from 21 to 101 micrograms Ni/g creatinine in post-shift urine, the next morning (after 16 h) it had dropped on average by 50 per cent, it decreased further during the days off, and amounted still to 4.4 micrograms Ni/g creatinine after two weeks of holiday. These divergent patterns of elimination of nickel in urine are most likely related to differences in the nature of exposure to airborne nickel involving both particle size and bioavailability of nickel. Worker E was exposed to NiO powder of 1-8 microns particle size resulting in nickel levels of the respirable fraction on average about 50 times that measured for the 19 other workers (3 micrograms Ni/m3). Transformation of the initial NiO powder into particles of 150 to 600 microns size and associated changes in physicochemical properties of NiO in the particles of the respirable fraction may explain why the urinary excretion of nickel in the 19 workers is hardly influenced by their occupational exposure to this metal. The pattern of urinary nickel elimination in worker E, however, most likely reflects very recent exposure to NiO, suggesting that the degree of bioavailability of nickel from this particular physicochemical form of NiO powder is much higher than that usually accepted for poorly soluble nickel compounds.

Adult↗

The prognostic significance of the DNA content in Ewing's sarcoma: a retrospective cytophotometric and flow cytometric study.

The DNA content of the cell nuclei of Ewing's sarcoma was analysed by means of cytophotometry in situ with image analysis in Feulgen-stained sections in 37 patients, and by retrospective flow cytometry according to the method of Hedley in 26 patients. Different histogram patterns were obtained: normal unimodal or bimodal DNA distributions and abnormal DNA distributions with one or two stem lines, or an abnormal DNA distribution with no stem lines. Both methods enabled us to make a distinction between two groups of Ewing's sarcomas with a different prognosis. All patients with aneuploid tumours died within 5 years after the initial diagnosis. Eleven of 19 (58%) patients with a normal DNA distribution in their tumour, as determined by cytophotometry, are still alive and in good health with a mean survival period of 7.5 years, ranging from 2 to 19 years. Of the group of patients in which flow cytometry revealed a normal DNA pattern, eight of 15 (53%) are still alive and in good health, with a mean survival period of 8 years. These results indicate that both techniques are reliable methods for obtaining prognostic information in Ewing's sarcomas. However, cytophotometry in situ yielded a better discrimination for the overall survival (P < 0.01) than did flow cytometry (P < 0.05). In 19% of the cases there was a discrepancy between the DNA histograms obtained with the two techniques. In five of 26 cases the DNA distributions were classified as normal by one method and aneuploid by the other. Tumour cell representation or selective loss of cells during enzymatic treatment may be responsible for this discrepancy.

Adolescent↗

Markers of early renal changes induced by industrial pollutants. I. Application to workers exposed to mercury vapour.

Several markers of renal changes have been measured in a cohort of 50 workers exposed to elemental mercury (Hg) and in 50 control workers. After application of selection criteria 44 exposed and 49 control workers were retained for the final statistical analysis. Exposed workers excreted on average 22 micrograms Hg/g creatinine and their mean duration of exposure was 11 years. Three types of renal markers were studied--namely, functional markers (creatinine and beta 2-microglobulin in serum, urinary proteins of low or high molecular weight); cytotoxicity markers (tubular antigens and enzymes in urine), and biochemical markers (eicosanoids, thromboxane, fibronectin, kallikrein, sialic acid, glycosaminoglycans in urine, red blood cell membrane negative charges). Several bloodborne indicators of polyclonal activation were also measured to test the hypothesis that an immune mechanism might be involved in the renal toxicity of elemental Hg. The main renal changes associated with exposure to Hg were indicative of tubular cytotoxicity (increased leakage of tubular antigens and enzymes in urine) and biochemical alterations (decreased urinary excretion of some eicosanoids and glycosaminoglycans and lowering of urinary pH). The concentrations of anti-DNA antibodies and total immunoglobulin E in serum were also positively associated with the concentration of Hg in urine and in blood respectively. The renal effects were mainly found in workers excreting more than 50 micrograms Hg/g creatinine, which corroborates our previous estimate of the biological threshold of Hg in urine. As these effects, however, were unrelated to the duration of exposure and not accompanied by functional changes (for example, microproteinuria), they may not necessarily represent clinically significant alterations of renal function.

Adult↗

Markers of early renal changes induced by industrial pollutants. II. Application to workers exposed to lead.

The present study has been carried out in the framework of a collaborative research project on the development of new markers of nephrotoxicity. A battery of more than 20 potential indicators of renal changes has been applied to 50 workers exposed to lead (Pb) and 50 control subjects. After application of selection criteria 41 exposed and 41 control workers were eventually retained for the final statistical analysis. The average blood Pb concentration of exposed workers was 480 micrograms/l and their mean duration of exposure was 14 years. The battery of tests included parameters capable of detecting functional deficits (for example, urinary proteins of low or high molecular weight), biochemical alterations (for example, urinary eicosanoids, glycosaminoglycans, sialic acid) or cell damage (for example, urinary tubular antigens or enzymes) at different sites of the nephron or the kidney. The most outstanding effect found in workers exposed to Pb was an interference with the renal synthesis of eicosanoids, resulting in lower urinary excretion of 6-keto-PGF1 alpha and an enhanced excretion of thromboxane (TXB2). The health significance of these biochemical alterations, detectable at low exposure to Pb is unknown. As they were not associated with any sign of renal dysfunction, they may represent reversible biochemical effects or only contribute to the degradation of the renal function from the onset of clinical Pb nephropathy. The urinary excretion of some tubular antigens was also positively associated with duration of exposure to Pb. Another effect of Pb that might deserve further study is a significant increase in urinary sialic acid concentration.

Adult↗

Markers of early renal changes induced by industrial pollutants. III. Application to workers exposed to cadmium.

Cadmium (Cd) was the third heavy metal investigated in the European collaborative research project on the development and validation of new markers of nephrotoxicity. Fifty workers exposed to Cd and 50 control workers were examined. After application of selection criteria 37 workers (mean age 43) exposed to Cd for an average of 11.3 years; and 43 age matched referents were retained for final analysis. The average concentrations of Cd in blood (Cd-B) and urine (Cd-U) of exposed workers were 5.5 micrograms Cd/l and 5.4 micrograms Cd/g creatinine respectively. By contrast with lead and mercury, Cd had a broad spectrum of effects on the kidney, producing significant alterations in amounts of almost all potential indicators of nephrotoxicity that were measured in urine--namely, low and high molecular weight proteins, kidney derived antigens or enzymes, prostanoids, and various other biochemical indices such as glycosaminoglycans and sialic acid. An increase in beta 2-microglobulin and a decrease of sialic acid concentration were found in serum. Dose-effect/response relations could be established between most of these markers and Cd-U or Cd-B. The thresholds of Cd-U associated with a significantly higher probability of change in these indicators were estimated by logistic regression analysis. Three main groups of thresholds could be identified: one around 2 micrograms Cd/g creatinine mainly associated with biochemical alterations, a second around 4 micrograms Cd/g creatinine for high molecular weight proteins and some tubular antigens or enzymes, and a third one around 10 micrograms Cd/g creatinine for low molecular weight proteins and other indicators. The recent recommendation by the American Conference of Governmental Industrial Hygienists (ACGIH) of 5 micrograms Cd/g creatinine in urine as the biological exposure limit for occupational exposure to Cd appears thus justified, although for most of the effects occurring around this threshold the link with the subsequent development of overt Cd nephropathy is not established. In that respect, the very early interference with production of some prostanoids (threshold 2 micrograms Cd/g creatinine) deserves further investigation; although this effect might contribute to protect the filtration capacity of the kidneys, it might also play a part in the toxicity of Cd on bone.

Adult↗

Nephropathies and exposure to perchloroethylene in dry-cleaners.

Even in specific risk groups, the relation between exposure to organic solvents and chronic renal diseases remains controversial. Thus, in a collaborative European study, we assessed the renal effects of occupational exposure to perchloroethylene (PCE) in dry-cleaners compared with matched controls who were simultaneously examined. Single high and low molecular weight proteins, kidney-derived antigens and enzymes, and prostanoids were measured in urine. beta 2-microglobulin, creatinine, laminin fragments, and anti-glomerular basement membrane antibodies were also measured in serum. A canonical function based on 23 such variables correctly classified 93% of individuals as either PCE-exposed or controls; with 13 markers, group membership was identified in 87% of subjects. Increased high molecular weight protein in urine was frequently (17/50 vs 1/50, p less than 0.0001) associated with tubular alterations. Changes were consistent with diffuse abnormalities along the nephron in workers exposed to low levels of PCE (median 15 parts per million). Generalised membrane disturbances might account for the increased release of laminin fragments, fibronectin, and glycosaminoglycans, for high molecular weight proteinuria, and for the increased shedding of epithelial membrane components from tubular cells with different location along the nephron (brush-border antigens and Tamm-Horsfall glycoprotein). These findings of early renal changes indicate that solvent-exposed subjects, especially dry-cleaners, need to be monitored for the possible development of chronic renal diseases.

Adolescent↗

Fertility of male workers exposed to cadmium, lead, or manganese.

The effect of exposure to cadmium, lead, or manganese on male reproductive function was examined in 1988-1989 in Belgian blue-collar workers. The workers were exposed to cadmium in two smelters (n = 83; geometric mean urinary cadmium level = 6.94 micrograms/g of creatinine; mean duration of exposure = 24 years), to lead in a battery factory (n = 74; mean blood lead level = 46.3 micrograms/dl; mean duration of exposure = 10.7 years), or to manganese (manganese dioxide) in a dry alkaline battery plant (n = 70; median atmospheric concentration of total manganese dust = 0.71 mg/m3; mean duration of exposure = 6.2 years). Fertility in these workers and in an unexposed population (n = 138) was assessed by examining the birth experiences of their wives through a logistic regression model. The probability of a live birth was not different between the unexposed workers and the cadmium- or manganese-exposed workers before or after the onset of exposure. While the fertility of the lead-exposed workers was somewhat greater than that of the unexposed before the onset of exposure, a significant decrease in fertility was observed during the period of exposure to the metal (odds ratio = 0.65, 95% confidence interval 0.43-0.98).

Adult↗

Human urinary protein 1: evidence for identity with the Clara cell protein and occurrence in respiratory tract and urogenital secretions.

Protein 1 (P1), a low mol mass urinary protein of unknown function, has been purified, sequenced and quantified in human biological fluids. The molecular size, subunit composition and partial amino acid sequence of P1 are similar to those of the 10 kDa Clara cell protein (CC10), a lung secretory protein. P1 is found in high concentrations in sputum, bronchoalveolar lavages, urine and semen of healthy individuals and in urine of some pregnant women. Contrary to what is claimed, P1 or CC10 is not a specific and unique product of the lung, but like its homologue in rabbits (uteroglobulin) it is also present in urogenital secretions. P1 or CC10 may act as a natural immunosuppressor protecting the respiratory and urogenital tracts from unwanted inflammatory reactions.

Adolescent↗

Human and experimental studies on renal eicosanoid response to long-term cadmium exposure.

In order to assess the effects of long-term exposure to cadmium (Cd) on the renal metabolism of eicosanoids, the urinary excretion of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), prostaglandin E2 (PGE2), prostaglandin F2 alpha (PGF2 alpha), and thromboxane B2 (TXB2) was determined in 37 workers exposed to Cd and in female Sprague-Dawley rats given 100 ppm Cd in drinking water for 10 months. Urinary output of sodium and calcium was also determined. The Cd-exposed workers showed an increased urinary concentration of 6-keto-PGF1 alpha, PGE2, sodium, and calcium. The rise of 6-keto-PGF1 alpha was related to Cd levels in blood and weakly correlated with urinary sodium. Calcium in urine was not related to the concentration of the metal in blood and urine. A slight elevation in urinary TXB2 was also observed in workers with blood Cd higher than 5 micrograms/liter. After 10 months of exposure to Cd, female Sprague-Dawley rats presented an enhanced urinary excretion of albumin, transferrin, beta 2-microglobulin, sodium, and PGE2 in urine. The latter was significantly correlated with albuminuria and transferrinuria. In conclusion the results show that chronic exposure to Cd induces changes in the urinary excretion of some eicosanoids. The possible relation of these changes to Cd-induced kidney dysfunction are discussed.

6-Ketoprostaglandin F1 alpha↗

Expression of T cell receptors alpha beta and gamma delta in the ileal mucosa of patients with Crohn's disease and with spondylarthropathy.

The expression of the alpha beta and gamma delta heterodimer of the T cell receptor (TCR) was studied in normal human ileal mucosa or in ileal biopsies featuring Crohn's disease or acute and chronic spondylarthropathy-related gut inflammation. With an immunohistochemical technique we demonstrated that the increase of mucosal lymphocytes per mm mucosa in Crohn's disease and spondylarthropathy-related ileitis is exclusively due to expansion of the alpha beta + T cell compartment. In Crohn's disease and chronic ileitis observed in some spondylarthropathy patients the alpha beta + T cells were increased amongst intraepithelial lymphocytes (IEL). The lamina propria lymphocytes (LPL) were augmented in all studied inflammatory conditions. The gamma delta + T cells showed no changes in IEL or LPL and their proportions were not altered. They were evenly dispersed throughout the ileal mucosa and did not seem to participate in the inflammatory process. This study confirms that gamma delta T cells are a distinct subset in the intestinal mucosa. The increase in alpha beta + T cells suggests augmented mucosal antigen handling and involvement of the major histocompatibility complex in the pathogenesis of spondylarthropathy-related gut inflammation and Crohn's disease.

Biopsy↗

Relation between airborne arsenic trioxide and urinary excretion of inorganic arsenic and its methylated metabolites.

The relation between exposure to As2O3 fumes and dust, and the urinary excretion of inorganic arsenic metabolites (monomethylarsonic acid, dimethylarsinic acid, unchanged inorganic arsenic) has been studied in 18 workers from a sulphuric acid producing plant. The concentration of arsenic in the breathing zone of each worker was measured during five consecutive days and urine samples were obtained after one shift and before the next. The collection efficiency of the air sampling system exceeded 95%. The time weighted average exposure (TWA) concentrations of As2O3 ranged from 6 to 502 micrograms As/m3 and were log normally distributed. Although exposure probably occurred by ingestion as well as inhalation, statistically significant correlations (log scales) were found between airborne TWA of As2O3 and the inorganic arsenic metabolites in urine collected immediately after the shift, or just before the next shift. For a TWA of 50 micrograms As/m3, the mean concentration of the sum of the three inorganic arsenic metabolites in a postshift urine sample amounted to about 55 micrograms arsenic/g creatinine (95% confidence interval (95% CI) 47-62). Higher estimates of urinary arsenic reported by other authors are probably due either to the influence of dietary organoarsenicals when total arsenic is measured in urine or to a low retention efficiency of the air sampling system for As2O3 in the vapour phase.

Adult↗

Cadmium and health: the Belgian experience.

Studies in the 1970s on chronic cadmium poisoning in man in Belgium showed that the earliest effect was renal dysfunction with proteinuria. Subsequent studies were focused on the characterization of cadmium proteinuria, the diagnosis and prognosis of cadmium nephropathy and the assessment of the concentrations in urine and renal cortex leading to its occurrence. Chronic exposure to cadmium in industry gives rise to a proteinuria which may be tubular, glomerular or mixed in character. This proteinuria may be accompanied or preceded by a variety of other renal effects. In active male workers, three main groups of thresholds for urinary cadmium have been identified for the induction of these effects with corresponding thresholds in the renal cortex. However, these estimates probably cannot be extrapolated to the general population exposed to cadmium mainly by the oral route. The results of a large-scale cross-sectional study (Cadmibel) suggest that subclinical changes in tubular function may occur in the general population above a threshold of urinary cadmium as low as 2 micrograms/24h.

Belgium↗

Effects of cadmium exposure on the cardiovascular system and on calcium metabolism: results of a cross-sectional population study.

This paper summarizes the findings of the Cadmibel Study, a cross-sectional population study of the health effects of cadmium, but only with respect to the cardiovascular system and calcium metabolism. The study disproved the hypothesis that exposure to cadmium would lead to an increase in blood pressure and in the prevalence of hypertension and other cardiovascular diseases. On the other hand, there was a positive relationship between urinary cadmium (Cd-U) and both serum alkaline phosphatase activity and urinary excretion of calcium. The regression coefficients obtained after adjustment for significant co-variates indicated that, when Cd-U increased two-fold, serum alkaline phosphatase and urinary calcium rose by 4% and 0.25 mmol/24 h, respectively. These findings suggest that calcium metabolism is gradually affected as cadmium accumulates in the body. The morbidity associated with the latter phenomenon is still unknown, and requires further investigation, preferably in a longitudinal prospective population study, in which the incidence of morbid events would be monitored in relation to the cadmium body burden.

Adult↗