In utero fetal muscle biopsy for the diagnosis of Duchenne muscular dystrophy

Deoxyribonucleic acid techniques can be used to diagnose Duchenne muscular dystrophy prenatally in male fetuses that are at risk. Deoxyribonucleic acid-based prenatal diagnosis can be impossible when there is only one prior affected male and there is no identifiable deletion or alteration. We performed fetal muscle biopsy in utero in such a case and documented the presence of dystrophin, thereby confirming normality in a male fetus at risk. This first in utero experience adds fetal muscle biopsy to the available procedures for fetal tissue diagnosis.     

Immunmodulation der Endometriose

Novel approaches for diagnosis and therapy of endometriosis require a more detailed understanding of the molecular pathomechanisms of the disease. The progression of endometriosis seems to be associated with activation of angiogenesis which could also be mediated by the local expression of chemokines. VEGF-A (VEGF: vascular endothelial growth factor) seems to be involved in the menstrual cycle-dependent regulation of vascularisation in normal endometrium and endometriotic implants. RANTES (Regulated upon Activation, normal T-cell-Expressed and Secreted) and Eotaxin are specific chemokines for monocytes and activated T-cells or eosinophil granulocytes, respectively. These chemokines are expressed in normal endometrium and endometriosis tissue and might contribute to endometriosis-associated infertility and pain by recruitment and activation of makrophages and other inflammatory cells. Since inflammatory cells are also a rich source of angiogenetic factors, the progression of the disease would be promoted.     

Overexpression of Endothelin-A-receptor in breast cancer: regulation by estradiol and cobalt-chloride induced hypoxia

Previous studies have demonstrated the potential significance of Endothelin (ET)-1 and its receptors, ETAR and ETBR, in the development and progression of breast cancer. The objective of this study was to assess the expression levels and potential regulation of the "ET axis" in human non-neoplastic and neoplastic breast tissue as well as in various human breast cancer cell lines. Expression of ET-1, ETAR and ETBR was evaluated in 31 neoplastic and 7 non-neoplastic breast tissue samples and in six human breast cancer cell lines using conventional and quantitative real-time RT-PCR, Western blotting and immunohistochemistry. The effects of 17beta-estradiol (E2) and cobalt-chloride (CoCl2) treatment on ET-1, ETAR and ETBR expression were studied in vitro. ETAR mRNA expression levels were found to be statistically significantly higher in breast cancer specimens than in non-neoplastic breast tissue (p<0.001). For ET-1 and ETBR mRNA expression, no significant difference was observed between the two groups. All cell lines exhibited expression of ET-1 and ETAR mRNA, whereas none showed significant ETBR mRNA expression. We observed a strong and reproducible induction of ETAR mRNA and protein expression by E2 and CoCl2 in MDA-MB-468 and BT-474 cells and in MDA-MB-453 and SK-BR-3 cells with a maximum increase after 8 and 16 h of treatment, respectively, while MCF-7 and HBL-100 cells showed a constitutive expression pattern. The present data suggest a novel mechanism in the regulation of ETAR expression in breast cancer. Based on these findings, a combination of ETAR-antagonists with adjuvant endocrine treatment seems to be a reasonable therapeutic strategy.     

Changes in the expression and subcellular distribution of galectin-3 in clear cell renal cell carcinoma

Background

Clear cell renal cell carcinoma, a solid growing tumor, is the most common tumor in human kidney. Evaluating the usefulness of β-galactoside binding galectin-3 as a diagnostic marker for this type of cancer could open avenues for preventive and therapeutic strategies by employing specific inhibitors of the lectin. To study a putative correlation between the extent of galectin-3 and the development of clear cell renal cell carcinoma, we monitored the quantity and distribution of this lectin in tissue samples from 39 patients.

Methods

Galectin-3 concentrations in normal, intermediate and tumor tissues were examined by immunofluorescence microscopy and on immunoblots with antibodies directed against galectin-3 and renal control proteins. The cell nuclei were isolated to determine quantities of galectin-3 that were transferred into this compartment in normal or tumor samples.

Results

Immunofluorescence data revealed a mosaic pattern of galectin-3 expression in collecting ducts and distal tubules of normal kidney. Galectin-3 expression was significantly increased in 79% of tumor samples as compared to normal tissues. Furthermore, we observed an increase in nuclear translocation of the lectin in tumor tissues.

Conclusions

Our data indicate that changes in the cellular level of galectin-3 correlate with the development of clear cell renal cell carcinoma, which is in line with previously published data on this specific type of tumor. In most of these studies the lectin tends to be highly expressed in tumor tissues. Furthermore, this study suggests that the increase in the proportion of galectin-3 affects the balance from a cytosolic distribution towards translocation into the nucleus.     

The functional anatomy of semantic retrieval is influenced by gender, menstrual cycle, and sex hormones

This study examines the neurobiology of semantic retrieval and describes the influence of gender, menstrual cycle, and sex hormones on semantic networks. Healthy right-handed subjects (12 men, 12 women) were investigated with 3T-fMRI during synonym generation. Behavioral performance and sex hormone levels were assessed. Women were examined during the early follicular and midluteal cycle phase. The activation pattern in all groups involved left frontal and temporal as well as bilateral medial frontal, cingulate, occipital, basal ganglia, and cerebellar regions. Men showed greater left frontal activation than women in both menstrual cycle phases. Women yielded high correlations of left prefrontal activation with estradiol in the midluteal phase and with progesterone in both phases. Testosterone levels correlated highly with left prefrontal activation in all three groups. In all, we describe a cerebral network involved in semantic processing and demonstrate that it is significantly affected by gender and sex steroid hormones.     

Transformation of BHK 21/CL 13 cells by various polycyclic aromatic hydrocarbons using the method of styles

Nine polycyclic aromatic hydrocarbons (PAHs) were investigated by the cell-transformation assay method of Styles. Benzo(a)pyrene [B(a)P], chrysene (CH), 3-methylcholanthrene (3-MC), benz(a)anthracene (BA), benzo(b)fluoranthene [B(b)F], and dibenz(a,h)anthracene (DBA) were tested, including liver homogenate, and showed dose-effect relationships and a more than 2-fold increase of transformation rates at LC₅₀. Due to variations of the test method our results differed quantitatively from the data published by Purchase and Styles. Discrimination between the known carcinogens listed above and the noncarcinogens, phenanthrene (PA) and anthracene (AC), lacking a dose-effect relationship was, however, possible. Benzo(e)pyrene [B(e)P] was regarded as positive although producing only a 2-fold increase in the number of transformed colonies.     

Antibiotikainduzierte Diarrh? und pseudomembran?se Enterokolitis

Zusammenfassung Das sporenbildende anaerobe Clostridium difficile ist ein problematischer Hospitalismuskeim. Die orale und parenterale Applikation von Antibiotika kann zu einer Störung des "ökologischen" Gleichgewichts der Darmflora führen mit Überwucherung präexistenter Mikroorganismen wie Clostridium difficile. Die Folge sind Durchfallerkrankungen, die ein Spektrum von asymptomatischen Diarrhöen bis hin zu schwersten pseudomembranösen Enterokolitiden zeigen. Clostridium difficile wird fäkal-oral oder über kontaminierte Oberflächen übertragen. In unserer Klinik traten von März 2000 bis März 2001 48 therapiebedürftige antibiotikaassoziierte Diarrhöen (AAD) auf, davon waren 21 durch Clostridium difficile verursacht. Die meisten Clostridium difficile assozierten Durchfallerkrankungen (CDAD) entstanden während/nach therapeutischer oder längerer prophylaktischer Gabe von Cephalosporinen der 2. Generation. Zu einer drastischen Abnahme von Clostridium difficile asoziierten Diarrhöen führten 1. ein Vermeiden von Cephalosporinen, 2. strikte "Single-shot-Prophylaxe", 3. Isolation erkrankter Patienten, 4. Einhaltung hygienischer Maßnahmen und 5. Komplettdesinfektion des Krankenzimmers. Ätiologie, Therapie, Prognose und Prophylaxe dieser Erkrankung werden diskutiert. Abstract The spore-forming anaerobic bacterium Clostridium difficile has become a serious enteropathogen. Oral and parenteral administration of antibiotics can cause ecological disturbances in the normal intestinal microflora. Suppression of the normal microflora may lead to reduced colonization resistance with subsequent overgrowth by pre-existing, naturally resistant microorganisms, such as C. difficile. C. difficile infection shows a range of clinical presentations between an asymptomatic carrier state, light diarrhea without inflammatory changes, and pseudomembranous colitis. C. difficile infection is acquired by the fecal-oral or environmental-oral routes. From March 2000 through March 2001 we assessed 48 cases of nosocomial antibiotic-associated diarrhea (AAD). Of these, 21 were due to C. difficile (CDAD). Cephalosporin was the agent most commonly associated with CDAD. Avoidance of cephalosporins, strict use of "single shot" prophylaxis, isolation of infected, symptomatic patients in single-bed rooms, improved hygiene and complete room disinfection lead to a rapid decrease of CDAD. The etiology, prognosis and prophylaxis are discussed in this paper.     

Counseling for low maternal serum alpha-fetoprotein should emphasize all chromosome anomalies, not just Down syndrome

In common usage, a low maternal serum alpha-fetoprotein (MSAFP) value is associated with an increased risk of Down syndrome. We have performed amniocenteses for the indication of age-adjusted low MSAFP in 1154 patients and found 13 chromosomally abnormal conceptions. Autosomal trisomies were detected in half the cases. Additional abnormalities included sex-chromosome aberrations, deletions, or triploidy in proportions consistent with those seen in an advanced-maternal-age population. Patients with low serum AFP should be counseled that not only Down syndrome, but other aneuploidies as well, may be diagnosed. The risk quoted should be that of all chromosomal abnormalities, which is about twice the risk calculated for Down syndrome.