Hyperpigmentation in North Sea dab Limanda limanda. I. Spatial and temporal patterns and host effects.

Hyperpigmentation is a term describing a specific pigment anomaly affecting common dab Limanda limanda in the North Sea and, less frequently, in adjacent areas, e.g. the English Channel, Irish and Celtic Seas, western Baltic Sea and Icelandic waters. Other North Sea flatfish species are also affected, but at a markedly lower prevalence. The condition is characterised by the occurrence of varying degrees of green to black patchy pigment spots in the skin of the upper (ocular) body side and pearly-white pigment spots in the skin of the lower (abocular) body side. In the course of fish disease monitoring programmes carried out by Germany and the UK (England and Scotland), a pronounced spatial pattern of hyperpigmentation has been detected in the North Sea. An increase in prevalence has been recorded in almost all North Sea areas studied in the past 2 decades. The prevalence recorded in hot spot areas of the condition increased from 5 to >40% between 1988 and 2009. Analysis of the German data indicates that the prevalence and intensity (degree of discolouration) of hyperpigmentation increase with size and age, indicating a temporal progression of the condition with size and age. Intense hyperpigmentation is associated with increased growth (length) and decreased condition factor. Potential causes of the condition (UV-B radiation nutrition, water temperature increase, demographic changes) and, in particular, of the spatial/temporal patterns recorded as well as the relationship to host-specific factors (sex, age, length, growth, condition factor) are discussed.

Incidence and risk factors for community-acquired acute gastroenteritis in north-west Germany in 2004.

In developed countries, acute gastroenteritis (AGE) is a major source of morbidity. However, only a few studies have estimated its incidence and the associated medical burden. This population-based study determined the incidence of community-acquired AGE patients seeking medical care and the relative role of various pathogens. Stool samples from patients with AGE presenting to a general practitioner (GP), pediatrician, or specialist in internal medicine for that reason were screened for various bacterial and viral enteropathogens. A control group was established as well. Incidences were calculated by the number of positive patients divided by the general population. The study was performed in north-west Germany in 2004. The incidence of AGE patients requiring medical consultation was 4,020/100,000 inhabitants. Children (<5 years of age) were at the highest risk (13,810/100,000 inhabitants). Of the patients, 6.6% were tested positive for an enteropathogenic bacteria and 17.7% for a viral agent. The predominant pathogens were norovirus (626/100,000) and rotavirus (270/100,000). Salmonella was the most frequently detected bacteria (162/100,000). The results presented confirm AGE and, specifically, AGE of viral origin as a major public health burden in developed countries.

Brominated indoles and phenols in marine sediment and water extracts from the north and baltic seas-concentrations and effects.

This work presents results from analytical as well as ecotoxicologic investigations of sediment and water samples from the North and Baltic Seas. A bioassay-directed procedure was used to investigate cause-effect relationships between observed effects in acute laboratory bioassays (luminescent bacteria assay with Vibrio fischeri and embryo test with Danio rerio) and analyte concentrations in extracted samples. Brominated phenols and indoles-including 4-bromophenol; 2,4-dibromophenol; 4- and 6-bromoindole; 3,4-, 4,6-, and 3,6-dibromoindole; and tribrominated compounds-were identified in partly remarkable concentrations (up to 40,000 ng g(-1) total organic carbon TOC for 4-bromophenol) in North Sea sediment samples and water samples (913 ng L(-1) 3,6-dibromoindole) from the German Bight. The toxicity of some of the identified brominated substances was low, with median effect concentration levels (EC(50)) ranging from 0.08 to 21.7 mg/L for V. fischeri and 4.3 to 46.3 mg/L for D. rerio. Comparison of the concentrations of analytes with ECs showed a toxicity contribution of brominated phenols and indoles to overall toxicity of the fraction. In the case of one water sample from the German Bight, brominated phenols and indoles accounted for the observed toxicity. Brominated phenols and indoles, which are assumed to be of biogenic origin, have rarely been discussed so far in the context of ecotoxicologic effects in marine ecosystems.

Toxic effects of brominated indoles and phenols on zebrafish embryos.

Organobromine compounds in the marine environment have been the focus of growing attention in past years. In contrast to anthropogenic brominated flame retardants, other brominated compounds are produced naturally, e.g., by common polychaete worms and algae. Brominated phenols and indoles assumed to be of biogenic origin have been detected in water and sediment extracts from the German Bight. These substances as well as some of their isomers have been tested with the zebrafish embryo test and were found to cause lethal as well as nonlethal malformations. The zebrafish test was able to detect a log K(OW)-related toxicity for bromophenols, suggesting nonpolar narcosis as a major mode of action. Different effect patterns could be observed for brominated indoles and bromophenols. The comparison of effective concentrations in the zebrafish embryo test with the concentrations determined in water samples suggests the possibility that brominated indoles may affect early life stages of marine fish species in the North Sea.

High mobility group protein HMGA1 expression in breast cancer reveals a positive correlation with tumour grade.

Members of the HMGA protein (high mobility group protein A) family act as master switches of the chromatin structure by bending DNA and thus modulating the formation of transcription factor complexes of a number of target genes. Accordingly, HMGA proteins have been shown to be associated with the development and/or progression of a variety of benign and malignant tumours. Nevertheless, the HMGA1 expression studies published so far have not included primary breast cancer samples. In this study we have investigated the HMGA1 expression patterns in a series of 170 breast cancer samples by immunohistochemistry. We have found a strong variation in HMGA1 expression between the tumours. Based on an immunoreactive score (IRS) 14.1% of the tumour samples were scored to IRS 8-12 (strong positivity for HMGA1), 24.7% were scored to IRS 4-6 (moderate positivity), 25.3% were scored to IRS 1-3 (weak positivity), and 35.9% showed no positivity at all. Immunoreaction could be detected in all histological types of breast cancers analysed with the exception of invasive papillary and cribriform carcinoma. Statistical analysis revealed a strong correlation between tumour grade and HMGA1 expression (rs=0.3516, p<0.0001). Thus, the HMGA1 expression level can be considered a potential prognostic marker for breast cancer.

Significant correlation between the breakpoints of rare clonal aberrations in benign solid tumors and the assignment of HMGIY retropseudogenes.

Recently, we described a mechanism by which a retropseudogene, during evolution, becomes an exon of a pre-existing active gene. Similar mechanisms may account for the activation of processed genes by chromosomal rearrangements in neoplasms. Because genes of the high-mobility group protein family HMGI(Y) are known to be involved in the development of a variety of benign solid tumors, it was the aim of the present study to analyze breakpoints of clonal chromosome abnormalities in that group of benign tumors for a possible correlation with retropseudogenes of the HMGIY gene. Whereas the HMGIYL1 retrospeudogene has recently been mapped to Xp22.1, we assigned a further retropseudogene by FISH to 4q13, and database research allowed us to assign a third retropseudogene to 12q24.1. Sequence analyses of these retropseudogenes revealed high-identity indices to the HMGIY gene and no frame-shift divergences. Breakpoint information was obtained from cytogenetic aberrations in uterine leiomyomas, lipomas, pleomorphic adenomas, and pulmonary chondroid hamartomas because, in all of these tumor entities, cytogenetic subgroups involving genes of the HMGI(Y) family exist. Chromosomal bands harboring HMGIY retropseudogenes were affected with a significantly higher frequency than expected under the assumption of purely randomly occurring breakages. These results support our hypothesis that HMGIY-related retropseudogenes can be affected by chromosomal rearrangements in benign human tumors.

Annual cycles of apoptosis, DNA strand breaks, heat shock proteins, and metallothionen isoforms in dab (Limanda limanda): influences of natural factors and consequences for biological effect monitoring.

The present study was undertaken to investigate the influence of natural and anthropogenic stressors on the induction of apoptosis, metallothionein (MT) isoforms, heat shock proteins and DNA strand breaks in the marine flatfish dab (Limbanda limanda) Seasonal changes and possible physiological influences were evaluated over a 1-year period at a fixed location northwest of Helgoland in the German Bight. These results were compared with data from sampling sites in the North Sea and the Baltic Sea. Annual cycles could be observed for all parameters except for Cd. The data revealed that changes in biomarker are not only linked to physiological processes related to reproduction but also to factors like water temperature changes, lipid content and zinc content. Cd and organochlorines had no influence on biomarkers whereas an influence of Cd on MT levels revealed in the regional observations was possibly masked by the major changes in Zn content during the annual cycle. Due to different abiotic factors we supposed that the annual cycles at each sampling site in the North and the Baltic Sea might be shifted temporally and therefore measurements at different locations during a small time window of a few weeks may lead to misinterpretation in biomarker research.

Clinical assessment of fetal blood flow velocimetry.

A statistical procedure is presented to analyze the relation between Doppler indices (DIs) such as pulsatility index (PI), resistance index (RI), A/B and clinical data of pregnancy and fetal outcome of three groups: (1) uncomplicated pregnancy, eutrophic fetus (NF), (2) pregnancy-induced hypertension (PIH), and (3) pregnancy and delivery of a dystrophic fetus (IUGR), and the acidity classes according to Saling, respectively. Proceeding and mathematical requirements as well as the possibilities to validate the methodology are introduced, and an application to previously published data is presented. By multivariate analysis of the data a fair prognosis of NF, PIH and IUGR was possible. The variability inherent to the data sampling requires a mathematical postprocessing in the framework of an adequate model before any clinical conclusions can be derived from DIs.

[Short- and long-term results of tuberculosis therapy with a fixed combination of isoniazide, prothionamide and diaminodiphenylsulfone combined with rifampicin]. / Kurz- und Langzeitergebnisse der Tuberkulosetherapie mit einer fixen Kombination aus Isoniazid, Prothionamid und Diaphenylsulfon (IPD) in Verbindung mit Rifampicin.

This is a report on 912 patients treated during 1973 to 1979 for pulmonary tuberculosis and/or extrapulmonary organ involvement. These patients had been treated with a fixed tablet combination of isoniacide, prothionamide and diaphenyl sulfone in association with rifampicin and partly other substances. It was the aim of our study to examine this form of therapy in respect of side effects and effectivity. 535 of these 912 patients were followed up for as long as 13 years (maximum follow-up period). According to the criteria of the American Tuberculosis and Respiratory Diseases Association the patients were suffering from 182 cases of pulmonary tuberculosis of only slight extension, 490 of moderate extension and 130 of large extension, as well as 55 cases of pleuritis, 67 extrapulmonary organ tuberculoses and 1 tuberculosis of the bronchial mucosa. Allergic skin reactions occurred in 0.7% of the cases, and in 0.9% there were neurological disturbances such as vertigo, paroxysms and polyneuropathies. In 7.4% of the patients there was an increase in serum enzyme activities of SGOT, SGPT, Y-GT as a sign of hepatotoxicity. In 5.5% of the patients there were several gastrointestinal concomitant phenomena such as sensation of fullness, nausea, and vomiting. Under IPD therapy the hemoglobin valuedropped on the average by 12% up to the 5th or 6th week of treatment and rose subsequently to almost normal levels. No permanent damage was seen in any of the patients under observation. In the moderately extended tuberculosis cases disinfection occurred on the average between the 6th and 8th week of treatment, in the greatly extended cases on the average in the 9th to 13th week.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of the carcinogenic potency of 4 environmental polycyclic aromatic compounds following intrapulmonary application in rats.

The carcinogenic potential of 4 highly purified polycyclic aromatic compounds (PAC) was studied in the respiratory tract of rats. Using a beeswax/trioctanoin mixture as vehicle, 10, 3 and 1 mg phenanthrene (PHE), 3 and 1 mg chrysene (CHR), 0.1 mg dibenz(a,h)anthracene (DBahA) and 6, 3 and 1 mg benzo(b)naphto(2,1-d)thiophene (BNT) were injected into the lungs of 35 female Osborne-Mendel rats per group. Benzo(a)pyrene (BaP, 0.3, 0.1 and 0.03 mg) was used as the reference substance. Whereas only one squamous cell carcinoma developed at the highest PHE dose, a dose-dependent tumor incidence was found for CHR. BNT showed a carcinogenic effect similar to CHR, but an increasing incidence of neoplasms was not seen between the median and high dose. DBahA induced carcinomas in even more than half of the animals at the dose level of 0.1 mg and, therefore, has to be classified as the most potent PAC under investigation. BaP resulted in a clear dose-response relationship. According to probit analysis of the results, the carcinogenic potencies of the PAC relative to BaP (1.00) rank as follows: DBahA, 1.91; CHR, 0.03; BNT, 0.02; and PHE, 0.001. The estimated ED10- values were 0.031 mg for BaP, 0.016 mg for DBahA, 1.02 mg for CHR, 1.65 mg for BNT and 22.84 mg for PHE.