Pooled analysis of genotoxicity markers in relation to exposure in the Flemish Environment and Health Studies (FLEHS) between 1999 and 2018.

BACKGROUND: The Flemish Environment and Health Studies (FLEHS) are human biomonitoring surveys running in Flanders since 1999. Additionally to biomarkers of exposure, markers of genotoxicity and oxidative stress have been measured, including the alkaline comet and micronucleus assay in peripheral whole blood cells, and urinary concentrations of 8-oxo-2'-deoxyguanosine (8-oxodG). AIM: Exposure-effect associations were explored in a pooled dataset of nine different cross-sectional FLEHS surveys. Data of adolescents collected in a time frame of about 20 years (1999-2018) were compiled. The aim of the study was to examine whether increased variation in exposure, lifestyle and environmental factors would lead to more powerful and robust exposure-effect associations. MATERIALS & METHODS: The biomarkers were measured in 2283 adolescents in the age range of 14-18 years. Exposure to polycyclic aromatic hydrocarbons [1-hydroxypyrene (1-OHP)], benzene (tt'-muconic acid), metals (arsenic, cadmium, copper, nickel, thallium, lead, chromium), persistent organochlorines and phthalates were assessed in blood or urine. Furthermore, outdoor air levels of particulate matter (PM10 and PM2.5) at the residences of the youngsters were calculated. Pooled statistical analysis was done using mixed models. Study-specific differences in the genotoxicity markers and in the strength/direction of the association were accounted for. This was done by incorporating the random factor 'study' and a random study slope (if possible). The exposure markers were centered around the study-specific mean in order to correct for protocol changes over time. RESULTS: A significant association was observed for the urinary oxidative stress marker 8-oxodG, which was positively associated with 1-OHP (5% increase for doubling of 1-OHP levels, p = 0.001), and with urinary copper (26% increase for doubling of copper levels, p = 0.001), a metal involved in the Fenton reaction in biological systems. 8-oxodG was also associated with the sum of the metabolites of the phthalate di(2-ethylhexyl) phthalate (DEHP) (3% increase for doubling of the DEHP levels, p = 0.02). For those associations, data pooling increased the statistical power. However, some of the associations in the individual surveys, were not confirmed in the pooled analysis (such as comet assay and 8-oxodG vs. atmospheric PM; and 8-oxodG vs. urinary nickel). This may be due to inconsistencies in exposure-effect relations and/or variations in the pollutant mix over time and regions. CONCLUSION: Pooled analysis including a large population of 2283 Flemish adolescents showed that 8-oxodG, a marker of oxidative DNA damage is a valuable marker to assess impact of daily life pollutants, such as PAHs, Cu and the phthalate DEHP.

[More Health in Urban Districts: The Integration of Health Promotion in Urban Development]. / Mehr Gesundheit im Quartier: Wie Gesundheitsförderung in die Stadtteilentwicklung integriert werden kann.

Poverty represents a considerable health risk. As social- and health-related disadvantages are spatially concentrated, municipalities must take up the task of forging a stronger link between urban district development and health promotion than has thus far been the case. Moreover, they must put health promotion as part of urban district development as an item on the agenda. The present contribution illustrates in which ways health promotion in disadvantaged urban districts and its scientific monitoring and evaluation can be successful.

A reappraisal of the binding of cytosolic enzymes to erythrocyte membranes.

Several cytosolic proteins have been shown to be associated with hypotonic erythrocyte ghosts via electrostatic interactions with the anion transport band 3 protein. This article considers the problems of demonstrating binding under physiological conditions and reviews the evidence for the relevance of enzyme binding to the membrane for the regulation of glycolysis. The hypotheses for the existence of topological and sequential multienzyme complexes of the glycolytic enzymes in erythrocytes are also discussed.

Erythrocyte band 3 protein strongly interacts with phosphoinositides.

85% of the phosphorus coisolated with band 3 protein during separation of the intrinsic proteins of the human erythrocyte membrane by zonal electrophoresis in high concentrations of acetic acid was found to be derived from phosphoinositides, mainly phosphatidylinositol 4,5-bisphosphate. When native band 3 protein and pyrene-labelled phospholipids were present in micelles of the nonionic detergent nonaethyleneglycol lauryl ether, strong resonance energy transfer was observed between the tryptophan residues and phosphatidylinositol 4,5-bisphosphate and, to a smaller degree, phosphatidylinositol 4-phosphate. We conclude that band 3 protein strongly interacts with phosphoinositides, in particular with phosphatidylinositol 4,5-bisphosphate.

Characterization of the N-terminal part of the neutralizing antigenic site I of coxsackievirus B4 by mutation analysis of antigen chimeras.

Coxsackievirus B3 (CVB3) as a potential RNA virus vector for the presentation of foreign antigenic epitopes was further characterized. Insertion mutagenesis of infectious CVB3 cDNA yielded viable antigen chimeras containing variant BC loops of VP1 of coxsackievirus B4 (CVB4). Analysis of three antigen chimeras allowed the mapping of the N-terminal part of the neutralizing antigenic site 1 (N-Ag1) of CVB4 which is located in the BC loop of the structural protein VP1. A significant neutralization of a viable chimera with the deletion of CVB4-specific amino acid Ser-83 at the amino terminus of the VP1 BC loop was obtained with CVB4 serotype-specific polyclonal antisera. This neutralization was reduced after further deletion of the adjacent Ala-84, suggesting that this amino acid either constitutes the beginning of N-Ag1 of CVB4 or is essential for the conformation of the adjacent epitope. In contrast, exchange of amino acid Ser-86 to alanine, in the middle of the BC loop, led to complete loss of reactivity with CVB4-specific antibodies, demonstrating the importance of this residue for binding of CVB4 neutralizing antisera. Furthermore, we observed that manipulations of the VP1 BC loop resulted in increased thermolability of the viable chimeras in comparison to CVB3, although replication efficiencies were similar.

The origin of the pseudoglandular spaces in metastatic smooth muscle neoplasm of uterine origin. Report of a case with ultrastructure and review of previous cases studied by electron microscopy.

The entity known as "leiomyomatous hamartoma," a term that has been used in reference to metastatic smooth muscle neoplasms of uterine origin (MSMNUO), is uncommon. Several articles have dealt with clinical and light microscopic aspects of this lesion. Four reports on the ultrastructure of this type of neoplasm have been published, but they have been primarily concerned with its smooth muscle component. Much controversy exists as to whether the glandular elements are part of the neoplastic process or preexisting pulmonary elements. This ultrastructural study confirms that the gland-like spaces represent entrapped alveoli and terminal respiratory bronchioles.

Pigmentosis tubae, a new entity: light and electron microscopic study.

The authors noted an unusual finding in the fallopian tubes of a 31-year-old woman who had received external and internal whole pelvis radiotherapy for squamous cell carcinoma of the cervix. Aggregates of macrophages containing pigment, identified in a subepithelial location, were reminiscent of melanosis coli, which is caused by abuse of anthracene-containing laxatives. Electron microscopic examination of the pigment revealed cytoplasmic material with the appearance of lipofuscin, identical to the pigment described in cases of colonic melanosis. After a careful study of possible etiologic agents, it was concluded that the pigment most likely resulted from cellular damage caused by radiotherapy. The authors are not aware of any other reported case of this entity, which will be called pigmentosis tubae.

Cellular expression of CCK-A and CCK-B/gastrin receptors in human gastric mucosa.

Gastrin stimulates gastric acid secretion in various species, but the role of the structurally related CCK for the peripheral regulation of acid secretion in humans remains controversial. Moreover, species differences in CCK receptor function and expression have been reported. We therefore sought to identify the cellular targets of CCK and gastrin within the human gastric mucosa in situ. Gastric biopsies were collected from 15 patients without gastric disease. Expression of CCK receptor subtypes was detected in individual cells of the gastric mucosa by reverse transcription (RT)-PCR in situ, immunohistochemistry and confocal laser scanning microscopy, using antisera against the CCK-A or CCK-B/gastrin receptor subtype. Both CCK-A and CCK-B receptors were detected in antral and oxyntic mucosa at the mRNA and protein level. In fundic mucosa, CCK-A receptor mRNA and protein mapped to D cells (37.4+/-7.7). Besides, individual chief cells, mucous neck cells and parietal cells (12.3+/-4.7%) expressed CCK-A receptors. CCK-B/gastrin receptor mRNA and protein were detected in parietal cells (57.4+/-11.1%) and in neuroendocrine cells (33.2+/-4.4%) expressing chromogranin A. Furthermore, epithelial cells within the neck of the gastric gland were found to express the CCK-B/gastrin receptor. We conclude that (i) identification of CCK-A receptors on somatostatin producing D cells in humans provide the anatomical basis for a receptor-mediated mode of action of CCK on somatostatin release and (ii) detection of either CCK receptor subtype in the putative stem cell compartment implies a role of CCK in the maintenance of tissue homeostasis in human gastric mucosa.

Hormone-producing capabilities of renal cell carcinomas. Correlation with ultrastructural findings.

A retrospective study was conducted to evaluate ultrastructural aspects of hormone production by renal cell carcinomas. Fifteen renal cell carcinomas examined ultrastructurally were retrieved from the files. Six cases revealing abundant and diffusely distributed secretory granules in the neoplastic cells were found and correlated with clinical manifestations and laboratory findings. Five of these patients were hypercalcemic; the sixth patient was asymptomatic, and no abnormalities were detected in routine laboratory workup. Two additional cases showed focal aggregates of electron dense neurosecretory granules. These last 2 patients had no biochemical abnormalities and were entirely asymptomatic. The size and ultrastructural morphology of the cytoplasmic granules identified in the renal neoplasms were compared with the usual granular morphology associated with the specific hormones involved. Immunohistochemistry was used to confirm the parathormone hormone content of the granules in 7 of the 8 cases presented. The other case revealed granules with ultrastructural characteristics of prostaglandin granules.

A cross-cultural study of animal fears.

The present study represents a cross-cultural study of animal fears in which subjects from seven Western and Asian countries were asked to rate their fear of a range of familiar animals. Factor analyses of these ratings in all samples revealed a coherent three factor solution in which animals fell into a fear-irrelevant, fear-relevant (fierce) or disgust-relevant category. The core group of animals making up the disgust-relevant category were similar across cultures. Some views on how a universal disgust-relevant category of feared animals may have developed are discussed.

[Syntagmatically oriented reactions in the early phases of speech development]. / Syntagmatisch orientierte Reaktionen in Frühphasen des Spracherwerbs.

Within a longitudinal observational study of two children aged from 18 to 36 months spontaneous reactive utterances were analysed. It could be found syntagmatic reactions without topic coherence with the utterances of the previous speaker. The specialty of these utterances consists in the fact that the child, after having perceived certain words in the parental utterances, creates an association to the previously heard grammatical context. The results are discussed within the scope of problems of language acquisition in children.

[Use of pronouns: formal and functional aspects in the early phases of language development]. / Verweise mit Pronomen: formale und funktionale Aspekte in frühen Phasen des Spracherwerbs.

This article presents findings from empirical studies of the development of the use of pronouns in early child language. This presentation includes discussion of 1) when personal, reflexive, possessive, and indefinite pronominal forms appear in child-initiated contexts, 2) which errors emerge, and 3) which communicative functions utterances with pronouns have in dialogue. A first comparison of German-speaking and (American-)English-speaking children's usage is offered, focussing in particular on the use of the pronominal forms I/ich, you/du, and my/mein. This crosslinguistic comparison reveals differences in the age of first use, but simultaneously suggests similarities in functional characteristics of such usage. The findings are discussed in connection with the question of the development of children's communicative competence.