Zahnanomalien in der Neuropädiatrie

Dental anomalies in children with neuropediatric disorders are easy to diagnose and can be essential in the diagnosis of different entities. They are present in well-known disorders as Incontinentia pigmenti, but also in rare diseases as in Kohlschütter-Tönz syndrome or the recently described ataxia, delayed dentition and hypomyelination. Anomalies of dental shape, enamel and in this case also teeth color, dental number and eruption are all encountered. Knowledge of these abnormalities is important for both clinical geneticist and child neurologist.     

Genetik der koronaren Herzkrankheit und des Herzinfarkts

Because of their high prevalence, cases of coronary artery disease (CAD) and myocardial infarction (MI) are frequently found when asking for a patient’s family history. It is common knowledge that a positive familial history constitutes a risk factor for CAD in its own right, in addition to smoking, increased alcohol intake, diabetes, obesity, hypertension, and hyperlipidemia. Nevertheless, for correct risk assessment it is crucial to accurately distinguish between sporadic and true familial cases of CAD and MI. Familial disposition is present when at least one male first-grade relative under the age of 55 or one female first-grade relative under the age of 65 has/had been diagnosed with myocardial infarction or significant coronary artery disease. In the review presented here, we compile the relevant epidemiological and genetic studies that constitute the scientific basis of this risk assessment. Furthermore, a short overview of the state of the art of genetic CAD/MI research is given.     

Characterization of EN-1078D, a poorly differentiated human endometrial carcinoma cell line: a novel tool to study endometrial invasion in vitro

Background  

To date, tools to study metastasis in endometrial cancers are insufficiently developed. The aim of this study was to characterize the cell line EN-1078D, a new endometrial carcinoma cell line derived from a metastasis to the ovary.     

1-Thiazol-2-yl-N-3-methyl-1H-pyrozole-5-carboxylic acid derivatives as antitumor agents

A class of substituted 1-thiazol-2-yl-N-3-methyl-1H-pyrozole-5-carboxylic acid derivatives was found to have potent anti-proliferative activity against a broad range of tumor cell lines. A compound from this class (14) was profiled across a broad panel of hematologic and solid tumor cancer cell lines demonstrating cell cycle arrest at the G0/G1 interphase and has potent anti-proliferative activity against a distinct and select set of cancer cell types with no observed effects on normal human cells. An example is the selective inhibition of human B-cell lymphoma cell line (BJAB). Compound 14 was orally bioavailable and tolerated well in mice. Synthesis and structure activity relationships (SAR) in this series of compounds are discussed.     

Effect of oral Bacillus coagulans administration on the density of vancomycin-resistant enterococci in the stool of colonized mice

AIMS: A mouse model of vancomycin-resistant enterococcus (VRE) stool colonization was used to study the effect of Bacillus coagulans, a biotherapeutic agent, on the density of colonization. METHODS AND RESULTS: VRE-colonized mice received orally administered B. coagulans (107 cfu) or saline daily for four days. For one VRE strain, the density of VRE at one and four days after treatment was 1.4 log10cfu x g(-1) lower in experimental vs. control mice (P=0.03), and 35% of experimental vs. 0% of control mice had no detectable VRE four days after treatment (P=0.03). For two additional strains, there was no statistically significant reduction of VRE density in the B. coagulans groups. CONCLUSION: B. coagulans therapy reduced the density of colonization for one of three VRE strains tested. SIGNIFICANCE AND IMPACT OF THE STUDY: This study suggests a potential role for biotherapeutic agents as a means to reduce the density of VRE intestinal colonization.     

Mosaiktrisomie 8p11.21q11.21 als Pr?disposition für myeloische Leuk?mien

Juvenile myelomonocytic leukemia (JMML) is a unique myeloproliferative disorder of early childhood in which mutations in NRAS, KRAS, PTPN11, NF1 and CBL are frequently found. Using high-resolution oligo array-based comparative genomic hybridization (aCGH), 20 JMML samples were investigated for submicroscopic genomic copy number alterations. Besides known cytogenetic aberrations, ten samples displayed additional submicroscopic alterations. Interestingly, an almost identical gain of chromosome 8 was identified in two patients. Subsequently, fluorescence in situ hybridization indicated a constitutional partial trisomy 8 mosaic (cT8M) in both patients. A survey on 27 cT8M patients with reported malignancies showed a predominance of myeloid malignancies including JMML. Our results dramatically reduce the critical region on chromosome 8 to 8p11.21q11.21. To determine how constitutional partial trisomy 8 mosaicisms may contribute to leukemogenesis in different mutational subtypes of JMML and other myeloid malignancies, further investigations are required.     

Saliva samples are a viable alternative to blood samples as a source of DNA for high throughput genotyping

ABSTRACT: BACKGROUND: The increasing trend for incorporation of biological sample collection within clinical trials requires sample collection procedures which are convenient and acceptable for both patients and clinicians. This study investigated the feasibility of using saliva-extracted DNA in comparison to blood-derived DNA, across two genotyping platforms: Applied Biosystems Taqman TM and Illumina Beadchip TM genome-wide arrays. METHOD: Patients were recruited from the Pharmacogenetics of Breast Cancer Chemotherapy (PGSNPS) study. Paired blood and saliva samples were collected from 79 study participants. The Oragene DNA Self-Collection kit (DNAgenotek(R)) was used to collect and extract DNA from saliva. DNA from EDTA blood samples (median volume 8 ml) was extracted by GenProbe, Livingstone, UK. DNA yields, standard measures of DNA quality, genotype call rates and genotype concordance between paired, duplicated samples were assessed. RESULTS: Total DNA yields were lower from saliva (mean 24 ug, range 0.2-52 ug) than from blood (mean 210 ug, range 58-577 ug) and a 2-fold difference remained after adjusting for the volume of biological material collected. Protein contamination and DNA fragmentation measures were greater in saliva DNA. 78/79 saliva samples yielded sufficient DNA for use on Illumina Beadchip arrays and using Taqman assays. Four samples were randomly selected for genotyping in duplicate on the Illumina Beadchip arrays. All samples were genotyped using Taqman assays. DNA quality, as assessed by genotype call rates and genotype concordance between matched pairs of DNA was high (>97%) for each measure in both blood and saliva-derived DNA. CONCLUSION: We conclude that DNA from saliva and blood samples is comparable when genotyping using either Taqman assays or genome-wide chip arrays. Saliva sampling has the potential to increase participant recruitment within clinical trials, as well as reducing the resources and organisation required for multicentre sample collection.     

Parkin promotes degradation of the mitochondrial pro-apoptotic ARTS protein

Parkinson's disease (PD) is associated with excessive cell death causing selective loss of dopaminergic neurons. Dysfunction of the Ubiquitin Proteasome System (UPS) is associated with the pathophysiology of PD. Mutations in Parkin which impair its E3-ligase activity play a major role in the pathogenesis of inherited PD. ARTS (Sept4_i2) is a mitochondrial protein, which initiates caspase activation upstream of cytochrome c release in the mitochondrial apoptotic pathway. Here we show that Parkin serves as an E3-ubiquitin ligase to restrict the levels of ARTS through UPS-mediated degradation. Though Parkin binds equally to ARTS and Sept4_i1 (H5/PNUTL2), the non-apoptotic splice variant of Sept4, Parkin ubiquitinates and degrades only ARTS. Thus, the effect of Parkin on ARTS is specific and probably related to its pro-apoptotic function. High levels of ARTS are sufficient to promote apoptosis in cultured neuronal cells, and rat brains treated with 6-OHDA reveal high levels of ARTS. However, over-expression of Parkin can protect cells from ARTS-induced apoptosis. Furthermore, Parkin loss-of-function experiments reveal that reduction of Parkin causes increased levels of ARTS and apoptosis. We propose that in brain cells in which the E3-ligase activity of Parkin is compromised, ARTS levels increase and facilitate apoptosis. Thus, ARTS is a novel substrate of Parkin. These observations link Parkin directly to a pro-apoptotic protein and reveal a novel connection between Parkin, apoptosis, and PD.     

Identification and characterization of the cAMP binding proteins of yeast by photoaffinity labeling.

Modulation of a membrane glycoprotein, approximate molecular weight 200,000, in concert with active ionic flux has been shown in a human neuroblastoma cell line. The modulating agent was 2% dimethyl sulfoxide. Other neuronal properties, acetylcholinesterase and choline acetyltransferase, were also modulated but to a lesser extent. The appearance of this glycoprotein on the surface of both human and mouse neuroblastoma cells only under conditions of differentiation leads to the suggestion that it is directly involved with the active Na⁺ channels.