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Biomedical subjects

H Roels

Publications and source records attributed to H Roels.

At least 37 records · Page 2Linked to original sources

Association between NAG-B and cadmium in urine with no evidence of a threshold.

OBJECTIVES: To explore the significance of the increase in urinary excretion of the lysosomal enzyme beta-N-acetylglucosaminidase (NAG) at low exposures to cadmium (Cd) that is frequently found in the absence of any other sign of renal dysfunction. METHODS: The activity was measured of the two main isoenzymes of NAG (NAG-A secreted by exocytosis and NAG-B released with cell membranes) in the urine of 49 male workers employed in a Cd smelter and of 20 age matched controls. RESULTS: An increased urinary excretion of low molecular weight proteins was noted only in subjects who excreted > 10 micrograms Cd/g creatinine. The urinary activity of NAG-B showed a dose related increase that was already significant in the group excreting 0.5-2 micrograms Cd/g creatinine. In multiple regression analysis the NAG-B activity correlated with the excretion of Cd but not with that of lead or mercury. The NAG-A activity was by contrast unaffected by exposure to Cd but correlated with the urinary excretion of lead and copper. CONCLUSIONS: As NAG-B is considered to be the lesional form of NAG, the existence of a specific association between this enzyme and urinary Cd excretion with no detectable threshold suggests that this metal produces cellular alterations at exposures commonly found in the general population.

Acetylglucosaminidase↗

Potent inhibition of both human interferon-gamma production and biologic activity by the Clara cell protein CC16.

The Clara cell 16 kD protein (CC16), the predominant product of the Clara cells lining the bronchiolar epithelium, is thought to protect the respiratory and urogenital tract from unwanted inflammatory reactions through its immunosuppressive action. In this report, we show evidence that CC16 establishes an anti-inflammatory activity by interfering with the interferon-gamma (IFN-gamma)-mediated actions of the cytokine network. The HuIFN-gamma production of stimulated single-donor peripheral blood mononuclear cells is inhibited by the presence of doses of CC16 in the range of 10(-12) M, with a maximal inhibition (up to 95%) when interleukin-2 is used as a stimulating agent. CC16 also diminishes the biologic activity of IFN-gamma: both the antiviral activity and the stimulation of phagocytosis by IFN-gamma, measured by means of chemiluminescence, are reduced in the presence of CC16. These observations indicate that CC16 acts as an anticytokine and could give new insight in the potential role of the Clara cells.

Bronchi↗

Low-level lead exposure and blood pressure.

The possible association between low-level lead exposure and blood pressure (BP) remains debated. The purpose of this review was: (1) to determine whether the available studies in humans support a positive association, in particular at lower exposure levels (blood lead concentration < 1 mumol/l), and (2) to explore whether animal studies and the proposed pathophysiological mechanisms are supportive of a positive and causal association between lead exposure and hypertension. A meta-analysis of 23 studies included 33,141 subjects recruited from the general population in 13 surveys and from occupational groups in 10 studies. In all but four studies the results had been adjusted for age, and most studies also considered additional confounders. The association between BP and blood lead was similar in both sexes. In all 23 studies combined, a two-fold increase in blood lead concentration was associated with a 1 mm Hg rise in the systolic pressure (CI 0.4-1.6 mm Hg; P = 0.002) and with a 0.6 mm Hg increase in the diastolic pressure (CI 0.2-1.0 mm Hg; P = 0.02). Of 21 animal studies, one was carried out in dogs, one in pigeons and the remainder in various rat strains. In 15 studies, in which the lead dose in drinking water or food exceeded 1 p.p.m. the association between BP and exposure was found to be positive in seven, inconsistent in three, absent in four and negative in one. Of the six studies at lower exposure levels (< or = 1 p.p.m.), five found a pressor effect attributable to lead. Whether the lead doses in the animal studies are equivalent to the human exposure levels and to what extent one can extrapolate from genetically heterogeneous animals to humans, remains doubtful. If a causal relation between lead exposure and hypertension exists, the proposed mechanisms may include interference of lead with ion transport across cell membranes, interactions with calcium homeostasis and calcium-mediated processes, direct vasomotor actions and the potentiation of sympathetic stimulation. Interference of lead with the balance between the renin-angiotensin-aldosterone and the kallikrein-kinin systems and impairment of renal function are unlikely to be implicated. On balance, the published evidence suggests that there can only be a weak positive association between BP and lead exposure. The latter relation, which is barely visible at the horizon of epidemiological observation, may not be causal in nature and is unlikely to entail any public health implication in terms of hypertension-related complications.

Animals↗

[Lymph node tuberculosis in HIV-1 seropositive patients in Central Africa. A characteristic histopathologic picture].

Sixty two patients fulfilling the definition established by the Centers for Disease Control in 1982 for persistent lymphadenopathy syndrome, thought to be related to the human immunodeficiency virus (HIV) infection, were selected at the Butare university hospital, in Rwanda, between 1987 and 1988. Forty-five (73%) of them were indeed seropositive. Fifteen patients of sixty two (24%) presented unexpectedly evidence of tuberculous adenitis on biopsy. Three of them, found HIV-1 seronegative, showed a classical follicular adenitis, whereas the twelve other seropositive patients presented unusual histologic features, consisting of more or less immature tuberculoid granulomas with an abundant caseating and often granular necrosis, containing acid fast bacilli. Numerous blood vessels and abundant plasmacytosis were found in non-necrotic areas. Semi-quantitative evaluation of the granulomatous reaction components provided a histological spectrum probably related to the degree of impairment of the cellular immune response, which could be of prognostic significance. In areas where populations are exposed to both HIV and M. tuberculosis, it appears that lymph node biopsy with mycobacterial culture should be recommended in order to detect occult tuberculosis among HIV-seropositive persons, allowing accurate medical care and adequate public health surveillance.

AIDS-Related Opportunistic Infections↗

Static, dynamic and first-pass MR imaging of musculoskeletal lesions using gadodiamide injection.

Forty-five patients with known or suspected musculoskeletal tumors were examined with static and dynamic MR imaging to evaluate the safety, tolerability and diagnostic utility of gadodiamide injection and to assess the diagnostic value of dynamic MR imaging and parametric "first-pass" (FP) images. The proportion of patients presenting more diagnostic information on the contrast-enhanced compared to the precontrast spin-echo examinations was determined. The dynamic enhancement characteristics were evaluated with time-intensity curves and parametric images of the FP enhancement rate. The tolerance of gadodiamide injection was good. Contrast enhancement was useful for delineating tumor from muscle, and differentiating viable from necrotic tissue and cystic from solid lesions. Malignant tumors showed a significantly higher slope value, earlier onset of enhancement, and higher maximum enhancement than benign lesions. However, slope values could not be used to predict the malignant potential of a lesion, due to overlap between highly vascular benign and low vascular malignant lesions. By displaying highly vascular areas, parametric FP images provided useful information on the most active part in a tumor before biopsy and for assessing the incorporation of bone-chip allografts. Static, dynamic and FP MR imaging using gadodiamide injection appears safe and provides useful information for diagnosis, biopsy and follow-up of musculoskeletal lesions.

Adult↗

Computer-assisted chromatin texture characterization of Feulgen-stained nuclei in a series of 331 transitional bladder cell carcinomas.

The chromatin patterns of Feulgen-stained nuclei in a series of six specimens of normal mucosa and 331 transitional bladder carcinomas, including 293 superficial (Ta and T1) and 38 invasive (T2-T4) cases, were quantitatively described by means of eight parameters relating to densitometric, run-length distribution, and co-occurrence matrix features. The results show that the chromatin texture of the superficial lesions was markedly different from that of the invasive tumours, which exhibited a distinctly more dense and heterogeneous chromatin pattern. The data also show that the increasing level of malignancy, as revealed by the increasing clinical stage, was accompanied by an increase in the overall chromatin condensation level. Only some areas of the nucleus actually increased in density; other pale areas appeared concomitantly with these increasingly denser chromatin areas. This chromatin density increase corresponded to a marked increase in the frequency of small dense chromatin clumps; these joined together into very large dense chromatin clumps, which were distributed more and more heterogeneously in the nucleus as the clinical stage of the tumour increased.

Adult↗

The development of a decision support system for the pathological diagnosis of human cerebral tumours based on a neural network classifier.

This study describes the use of a topological mapping system in the classification of cerebral tumours and the development of a decision support system based upon that classifier. Fourteen pathological parameters from two hundred primary cerebral tumours are presented as vectors to a topological map. The map, consisting of a grid of neurones, learns the features of each tumour by means of a shortest Euclidean distance algorithm, after which self adaptation of the neurons occurs. An LVQ algorithm performs the final classification. Study of the map reveals that it can correctly classify tumors following their malignancy potential and their cytogenesis. The decision support system uses the network at its core and helps not only in reaching a diagnosis but also in finding the optimal way to reach that diagnosis. The usefulness of such a mapping system lies in the field of education, clinical research and medically acceptable cost reduction.

Algorithms↗

First-pass images of musculoskeletal lesions: a new and useful diagnostic application of dynamic contrast-enhanced MRI.

The purpose of this study was to evaluate the diagnostic value of parametric images which display the first-pass of Gd-DTPA after intravenous bolus injection. Single slice dynamic contrast-enhanced MRI (Turbo-FLASH) with a temporal resolution of 2.41 s was performed in 40 benign and malignant musculoskeletal lesions. Parametric 'first-pass' images were obtained by using a new postprocessing technique, derived from a home written computer program, which calculated the steepest slope of the time-intensity curve pixel by pixel. First-pass images provided qualitative and quantitative information, which was useful for diagnosis and therapy. Demonstration of the areas with the highest vascularization was very helpful in planning the best biopsy site in 6 patients and to delineate tumor from peritumoral muscle edema in 4 patients. In 10 patients the first-pass images provided additional information, which was not visible on the conventional spin-echo images. The most promising application was the ability to evaluate the response to preoperative chemotherapy in a patient with Ewing's sarcoma. Although a highly statistically significant difference (p < 0.001) was found between the first-pass slope values of benign and malignant lesions, the sensitivity (77%) and specificity (71%) of this method were too low to permit a definite differentiation of highly vascular benign from malignant lesions. Pathologic examination of 17 lesions, performed in the plane of the first-pass image, showed a good correlation between the first-pass slope values and the vascularization of the tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Is a positive association between lead exposure and blood pressure supported by animal experiments?

The possible association between low-level lead exposure and blood pressure and the causal nature of any such relationship continue to be debated. A recent meta-analysis of the human model data showed that on average a doubling of blood lead was associated with a rise in blood pressure averaging 1 mm Hg systolic and 0.6 mm Hg diastolic. The older animal studies, however, failed to show a significant pressure increase with massive lead exposure. This review therefore attempts to determine whether the more recent animal studies are supportive of a positive association between lead exposure and blood pressure elevation. Of the 21 animal studies published since 1977, one was carried out in dogs, one in pigeons, and the remainder in various rat strains. In the articles in which all the lead doses had been higher than 1 ppm, the association between blood pressure and exposure was found to be positive in seven, inconsistent in three, absent in four, and negative in one. Of the six animal experiments that employed lead doses not exceeding 1 ppm, five reported a small pressor effect. One of these five positive low-dose studies, however, failed to show a dose-effect relationship when exposure was increased from 0.1 to 1 ppm. In conclusion, most, but not all animal studies published since 1977 found a positive association between blood pressure and lead exposure. However, publication bias may have inflated the number of positive studies appearing in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Renal function and hyperfiltration capacity in lead smelter workers with high bone lead.

OBJECTIVE: The study was undertaken to assess whether the changes in urinary excretion of eicosanoids (a decrease of 6-keto-PGF1 alpha and PGF2 and an increase of thromboxane) previously found in lead (Pb) exposed workers may decrease the renal haemodynamic response to an acute oral protein load. METHODS: The renal haemodynamic response was estimated by determining the capacity of the kidney to increase the glomerular filtration rate (in terms of creatinine clearance) after an acute consumption of cooked red meat (400 g). A cross sectional study was carried out in 76 male Pb workers (age range 30 to 60 years) and 68 controls matched for age, sex, socioeconomic state, general environment (residence), and workshift characteristics. RESULTS: The Pb workers had been exposed to lead on average for 18 (range 6-36) years and showed a threefold higher body burden of Pb than the controls as estimated by in vivo measurements of tibial Pb concentration (Pb-T) (geometric mean 66 v 21 micrograms Pb/g bone mineral). The geometric mean concentrations of Pb in blood (Pb-B) and Pb in urine (Pb-U) were also significantly higher in the Pb group (Pb-B: 430 v 141 micrograms Pb/l; Pb-U: 40 v 7.5 micrograms Pb/g creatinine). These conditions of chronic exposure to Pb did not entail any significant changes in the concentration of blood borne and urinary markers of nephrotoxicity, such as urinary low and high molecular weight plasma derived proteins (beta 2-microglobulin, retinol binding protein, albumin, transferrin), urinary activities of N-acetyl-beta-D-glucosaminidase and kallikrein, and serum concentrations of creatinine, beta 2-microglobulin, urea, and uric acid. All participants also had normal baseline creatinine clearances (> 80 ml/min/1.73 m2) amounting on average to 115.5 in the controls v 121.3 ml/min/1.73 m2 in the Pb group. Both control and Pb exposed workers showed a significant increment in creatinine clearance (on average 15%) after oral protein load suggesting that the previously found changes in secretion of urinary eicosanoids apparently has no deleterious effect on renal haemodynamics in the examined Pb workers. CONCLUSIONS: The finding that both baseline and stimulated creatinine clearance rates were not only significantly higher in the Pb workers but also positively correlated with Pb-T, suggests that moderate exposure to Pb may be associated with a slight hyperfiltration state, which has been found to attenuate the age related decline in baseline creatinine clearance by a factor of two. Although the relevance of this effect for the worker's health is unknown, it can be concluded that adverse renal changes are unlikely to occur in most adult male Pb workers when their blood Pb concentration is regularly kept below 700 micrograms Pb/l. One should, however, be cautious in extra-polating this conclusion to the general population because of pre-employment screening of the Pb workers for the absence of renal risk factors.

Adult↗

Benign and malignant musculoskeletal lesions: dynamic contrast-enhanced MR imaging--parametric "first-pass" images depict tissue vascularization and perfusion.

PURPOSE: To assess the diagnostic value of parametric magnetic resonance images that display the first pass (FP) of gadopentetate dimeglumine. MATERIALS AND METHODS: Dynamic, contrast material-enhanced, fast low-angle shot MR imaging was performed of 100 musculoskeletal lesions in 36 female and 64 male patients (aged 9-81 years [mean, 34 years]). The highest slope value of the time-intensity curve was calculated pixel by pixel and displayed on the FP image, with a gray-scale value equal to the slope value. Tissue vascularization and perfusion were evaluated at pathologic and angiographic examinations in 33 lesions. RESULTS: A significant difference (P < .001) was found between the FP slope values of benign (mean, 36.2% per second) and malignant (mean, 67.4% per second) lesions. FP images depicted tissue vascularization and perfusion rather than benignity or malignancy, because there is an overlap in the slope values of highly vascular benign lesions and malignant lesions. CONCLUSION: FP images provide diagnostically useful information by depicting tissue vascularization and perfusion.

Adolescent↗

A 50 kDa protein present in conditioned medium of COLO-16 cells stimulates cell spreading and motility, and activates tyrosine phosphorylation of Neu/HER-2, in human SK-BR-3 mammary cancer cells.

A factor present in conditioned medium of COLO-16 human cancer cells causes fast spreading, fast plasma membrane ruffling, cell shape change, net translocation, stimulation of chemotaxis and growth arrest in human SK-BR-3 mammary cancer cells. Based on the spreading effect, the factor was purified to homogeneity and migrated as a 50 kDa protein in SDS-polyacrylamide gel electrophoresis. Addition of the purified 50 kDa factor to the target cells in culture results in tyrosine phosphorylation of the p185erbB2 receptor concomitant with a fast redistribution and clustering of the receptor. The 50 kDa factor is also specifically retained by affinity chromatography on the immobilized extracellular domain of p185erbB2. Antibodies directed against this domain also inhibit the induction of motility. These data suggest that the 50 kDa factor is a putative ligand of p185erbB2 in SK-BR-3 cells. Biochemical and immunological evidence further indicate that this factor differs from p185erbB2 ligands described so far. Its activity could play a role in the pathogenesis of breast cancer.

Animals↗

Hypertension caused by low-level lead exposure: myth or fact?

BACKGROUND: Several reports on the possible association between low-level lead exposure and blood pressure reflect diverging views. This meta-analysis aimed to find a common denominator in the published literature and to estimate whether a relationship exists between blood pressure and levels of lead in the blood. METHODS: Of the studies reviewed, 23 provided sufficient details to be considered. The meta-analysis included 33 groups with a total of 33 141 subjects, who had been recruited from the general population in 13 surveys and from occupational groups in 10 studies. In all but four studies the results were adjusted for age, and most studies took into account additional confounding factors. RESULTS: The association between blood pressure and blood lead was similar in both men and women. In the combined studies, a twofold increase in blood lead concentration was associated with a 1.0 mmHg rise in systolic pressure (confidence interval 0.4-1.6 mmHg; P = 0.002) and with a 0.6 mmHg increase in diastolic pressure (confidence interval 0.2-1.0 mmHg; P = 0.02). The association with systolic pressure strongly relied on the inclusion of a large study (n = 3851) in which women's blood pressure was measured at the end of pregnancy. The association with diastolic pressure was largely due to a population survey in the USA (n = 6289). There was no relationship across studies between the strength of the blood pressure-blood lead relationship and the mean blood lead concentration. CONCLUSION: The published evidence suggests that there can only be a weak positive association between blood pressure and lead exposure. Any such relationship may not be causal and is unlikely to entail any public-health implication in terms of hypertension-related complications. Nevertheless, these assumptions need to be confirmed in prospective population studies.

Blood Pressure↗

Urinary excretion of homovanillic acid in workers exposed to manganese.

Homovanillic acid, an end product of dopamine catabolism, and manganese (Mn) were measured in the urine of 68 male workers exposed to Mn-containing dust in a dry alkaline battery plant or an Mn oxide and salt producing plant, and in 35 control male subjects. The geometric mean of the airborne concentration of inhalable (total) dust amounted to 0.95 and 1.37 mg/m3 in the dry alkaline battery plant and the Mn oxide and salt producing plant, respectively. In the latter, a higher prevalence of increased values of urinary homovanillic acid concentration was found. In the total population, there was a low but statistically significant positive correlation between the concentration of homovanillic acid and Mn in urine (r = 0.20, P = 0.04) but there was no significant correlation between the level of homovanillic acid in urine and Mn in airborne dust or duration of exposure. This observation might be compatible with the stimulation of dopamine turnover in the brain, which has been observed in the early phase of Mn intoxication in animals. However, the large variability in urinary homovanillic acid excretion in control subjects precludes the use of this biological indicator to detect early interference of Mn with the dopaminergic system.

Adult↗

Cyanoacrylate tissue adhesive for closing skin wounds: a double blind randomized comparison with sutures.

A comparative double blind randomized study was undertaken in the rat, to compare the external cosmetic and the morphologic aspect of skin wounds, treated by the local application of adhesive glue (ethyl-2-cyanoacrylate-Mediglue) or classical suture technique. Skin incisions were applied and treated by a plastic surgeon, then photographed or biopsied, and evaluated and scored by independent observers, not aware of the initial treatment. Small (1.5 cm) or long (8 cm) incisions were made, on both sides of the back, and treated randomly on one side by glue and on the other side by sutures. Evaluations were performed at 1, 2, 4 and 8 wk. Both small and large wounds scored identically, irrespective of the treatment (overall score 1.5 cm wounds: 8.8 +/- 1.4 for glue versus 8.8 +/- 1.0 for sutures; 8 cm wounds: 8.3 +/- 1.9 versus 8.3 +/- 1.5; P = not significant). A morphological study demonstrated no adverse effects for the adhesive treatment, with a minor inflammatory infiltrate. Sutured wounds had a higher tendency to develop abscesses and/or major inflammation. Adhesive-treated wounds scored better than non-treated wounds (8.9 +/- 1.3 versus 7.4 +/- 3.3, P < 0.01). In conclusion, this controlled comparative study shows no difference in cosmetic aspect between adhesive and suture-treated skin incisions. Morphologically, the glue treatment is not related to any adverse effect or damage to the skin structures.

Adhesives↗

The immunophenotype of Ewing's sarcoma. An immunohistochemical analysis.

Since 1963, 53 cases of Ewing's sarcoma have been diagnosed at the N. Goormaghtigh Institute of Pathological Anatomy. All tumours were classified according to their growth pattern as described by Kissane: diffuse, lobular or organoid, the latter with pseudorosettes, or belonging to the fillagree type. In 45 cases, an immunohistochemical examination was carried out on routinely processed material in order to determine the immunophenotype of the tumours and to get more information on the histogenesis of the tumours. Antibodies against cytokeratin, desmin, vimentin, neurofilaments, neuron-specific enolase, Leu7, synaptophysin, chromogranin, the muscle-specific actin, the Von Willebrand factor and the common leucocyte antigen were used in a biotin-streptavidin procedure. The presence of neural markers such as neuron-specific enolase, synaptophysin and Leu7 was proved in the majority of the cases. The expression of the three markers was absent in only two cases. Neurofilaments were demonstrated to be present in 5 of the 6 cases for which fresh material was available. The results of this study point towards a possible neuroectodermal origin of Ewing's sarcoma. This is in agreement with the results of cell culture experiments and of cytogenetic studies.

Adolescent↗