Nonsense-associated altered splicing of the Patched gene fails to suppress carcinogenesis in Gorlin syndrome.

Mutations in the gene coding for the transmembrane receptor protein Patched (PTCH) are implicated in the autosomal dominant disorder Gorlin syndrome (also known as naevoid basal cell carcinoma syndrome), characterized by congenital abnormalities and cancer predisposition. Tumour promotion is thought to be associated with aberrant function of PTCH, leading to misregulation of the hedgehog signalling network. However, the transcriptional events that underlie the reduced tumour suppression effects of PTCH have not been studied in detail.

Long-term prognosis of medullary thyroid carcinoma.

Objective: The clinical course of patients with medullary thyroid carcinoma (MTC) is variable, even in the subgroup of patients after surgery with curative intent and postoperatively persistent elevated calcitonin levels. This study aimed to evaluate the long-term prognosis of survival in patients with MTC.

Patients: Long-term survival was analysed in 32 patients with MTC being treated in an endocrine centre over a 40-year period.

The use of Duloxetine in the treatment of male stress urinary incontinence.

Stress urinary incontinence (SUI) is a known complication after prostate surgery. To date no pharmacologic treatment is available. Currently Duloxetine, a serotonin and norepinephrine reuptake inhibitor, is available for women with SUI.

New, small, fast acting blood glucose meters--an analytical laboratory evaluation.

Background: Patients and medical personnel are eager to use blood glucose meters that are easy to handle and fast acting. We questioned whether accuracy and precision of these new, small and light weight devices would meet analytical laboratory standards and tested four meters with the above mentioned conditions.

Methods: Approximately 300 capillary blood samples were collected and tested using two devices of each brand and two different types of glucose test strips.

High prevalence and undertreatment of hypercholesterolaemia in participants in a public stroke prevention programme in austria.

Background: There is remarkable consistency in large cohort studies regarding the relationship between serum cholesterol and the incidence of coronary heart disease (CHD), and increasing interest in the relationship between serum cholesterol and stroke. The aim of our investigation was to identify the prevalence and control of hypercholesterolaemia in participants in a public stroke prevention programme.

Patients And Methods: 9274 participants were categorised according to the guidelines of the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) and analysed with reference to risk category, treatment eligibility and treatment quality.

Gender-specific comparison of five QT correction formulae in middle-aged participants in an atherosclerosis prevention program.

Background: Analysis of QT duration limited to a single heart rate correction formula might be problematic in cross-sectional studies. The aim of this study was to investigate five frequently used equations with respect to over- and under-correction of QT intervals in a middle-aged population without manifest atherosclerotic disease.

Material/methods: A total of 1199 individuals (851 males, 348 females, aged 39 to 66 years) of the SAPHIR study (Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk) were investigated.

Fulvestrant ('Faslodex') in heavily pretreated postmenopausal patients with advanced breast cancer: single centre clinical experience from the compassionate use programme.

Background: Fulvestrant (Faslodex) is an oestrogen receptor (ER) antagonist with demonstrated efficacy in patients with advanced and pretreated breast cancer.

Patients And Methods: We present a single-centre experience with fulvestrant administered under the compassionate use programme (CUP) to a total of 54 postmenopausal women with metastatic breast cancer progressing on multiple endocrine and cytotoxic therapies. Patients received 250 mg fulvestrant i.

Rapid, high-quality and epidermal-specific isolation of RNA from human skin.

As global transcriptome analyses with a growing demand on layer-specific applications are widely used in cutaneous biology, we investigated the effect of established and optimized dermo-epidermal separation methods on the quality of RNA. We compared enzymatic separation with dispase, chemical separation with 1 M sodium chloride and heat separation to a treatment with 3.8% ammonium thioyanate.

Ocular involvement in anti-epiligrin cicatricial pemphigoid.

Purpose: To report an anti-epiligrin cicatricial pemphigoid (AECP) patient with severe ocular involvement and to provide a practical approach to distinguishing AECP patients from those with other subepidermal blistering diseases.

Methods: Techniques included direct and indirect immunofluorescence microscopy, Western blot and immunoprecipitation studies, as well as interdisciplinary examinations of mucous membranes and skin.

Results: This study describes a patient with clinical features of cicatricial pemphigoid, circulating anti-basement membrane zone IgG antibodies, and subepidermal blisters.

Galanin-like peptides exert potent vasoactive functions in vivo.

The cutaneous vasculature plays a key role in the pathophysiology of inflammatory skin diseases. The vascular activity is under the control of the peripheral nervous system that includes locally released neuropeptides. Recently, we detected receptors for the neuropeptide galanin in association with dermal blood vessels, suggesting a role of the galanin-peptide-family in the regulation of the cutaneous microvasculature.

Multiplex primer extension analysis for rapid detection of major European mitochondrial haplogroups.

The evolution of the human mitochondrial genome is reflected in the existence of ethnically distinct lineages or haplogroups. Alterations of mitochondrial DNA (mtDNA) have been instrumental in studies of human phylogeny, in population genetics, and in molecular medicine to link pathological mutations to a variety of human diseases of complex etiology. For each of these applications, rapid and cost effective assays for mtDNA haplogrouping are invaluable.

Gangliocytes in neuroblastic tumors express alarin, a novel peptide derived by differential splicing of the galanin-like peptide gene.

In neuroblastic tumors a relationship of differentiation of the tumor to galanin receptor expression and antiproliferative and apoptotic effects upon activation of galanin receptors in neuroblastoma cells was reported. To elucidate the expression of other components of the galanin peptide family in neuroblastic tumors, RT-PCR analysis of a variety of human neuroblastic tumor tissues was performed. Ganglioneuroma tissues revealed the presence of a splice variant of the galanin-like peptide (GALP) mRNA, which results in exclusion of exon 3 and a frame shift after the signal peptide sequence of GALP.

Hypotonicity and ethanol modulate BK channel activity and chloride currents in GH4/C1 pituitary tumour cells.

Aim: Description of the effects of hypotonic cell swelling and ethanol on maxi Ca2+-activated K+ channel (BK channel) activity and Cl- channel activity in GH4/C1 pituitary tumour cells.

Methods: Whole cell-, cell attached- and outside-out patch clamp measurements, fluorescence (fluo-3) measurements of intracellular Ca2+ concentration, cell size video monitoring.

Results: GH4/C1 pituitary tumour cells respond to both hypotonicity and ethanol with cell swelling which is followed by a regulatory volume decrease (RVD).

Genetic clonality is a feature unifying nephroblastomas regardless of the variety of morphological subtypes.

Nephroblastomas are embryonal tumors exhibiting a wide variety of different morphological features and genetic changes. Some of the genetic aberrations were associated with a certain histological subtype. It is generally assumed that nephroblastomas develop as subclonal proliferations from nephrogenic rests.

The adiponectin gene is associated with adiponectin levels but not with characteristics of the insulin resistance syndrome in healthy Caucasians.

Low concentrations of adiponectin, the protein product of the APM1 gene, have been reported to be associated with obesity and insulin resistance. However, contrasting results have been described on the genetic variability in APM1 and characteristics of the metabolic syndrome and adiponectin serum concentrations. In the present study, we investigated the association of the two most well-known SNPs of APM1 (+45T>G and +276G>T) and their haplotypes, with serum adiponectin concentrations, metabolic parameters and intima-media thickness of the carotid arteries in 1,745 well-phenotyped asymptomatic unrelated Caucasian subjects of the SAPHIR cohort.

Mitochondrial DNA mutations in renal cell carcinomas revealed no general impact on energy metabolism.

Previously, renal cell carcinoma tissues were reported to display a marked reduction of components of the respiratory chain. To elucidate a possible relationship between tumourigenesis and alterations of oxidative phosphorylation, we screened for mutations of the mitochondrial DNA (mtDNA) in renal carcinoma tissues and patient-matched normal kidney cortex. Seven of the 15 samples investigated revealed at least one somatic heteroplasmic mutation as determined by denaturating HPLC analysis (DHPLC).

Role of peroxisome proliferator-activated receptor-gamma coactivator-1alpha in the transcriptional regulation of the human uncoupling protein 2 gene in INS-1E cells.

A role of uncoupling protein 2 (UCP2) as negative modulator of insulin secretion has been suggested, but the transcriptional pathways regulating beta-cell UCP2 gene expression have been established in rodents only. We show here that the underlying sequence motifs are not conserved in the human gene and provide evidence for regulatory mechanisms involving the transcriptional cofactor peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1alpha). PGC-1alpha potentiates thyroid hormone (T(3))-mediated transcriptional activation of the human UCP2 gene in INS-1E cells.

Rapid screening of the entire mitochondrial DNA for low-level heteroplasmic mutations.

Alterations of the mitochondrial DNA (mtDNA) are implicated in various pathological conditions. In this study, we used denaturing high performance liquid chromatography (DHPLC) as a method to rapidly screen the entire mtDNA for mutations. Overlapping DNA fragments, amplified by one single cycling protocol from frozen pre-formulated PCR mixes, were subjected to DHPLC analysis.

Pharmacological and functional characterization of galanin-like peptide fragments as potent galanin receptor agonists.

The hypothalamic galanin-like peptide (GALP) was isolated by its ability to activate galanin receptors. The mature porcine GALP is a 60-amino acid neuropeptide proteolytically processed from a 120-amino acid precursor protein. It contains a region identical to the N-terminal 13-amino acids of the neuropeptide galanin.

Measuring cartilage morphology with quantitative magnetic resonance imaging.

Magnetic resonance imaging (MRI) is a three-dimensional imaging technique with unparalleled ability to delineate articular cartilage morphology in health and disease. In this article we will review work on the assessment of cartilage morphology with quantitative magnetic resonance imaging and its relevance to the study of cartilage anatomy, physiology, deformation, disease status, disease progression, and response to treatment. The review outlines available pulse sequences and techniques for segmentation and morphological analysis of cartilage morphology.

Complex haplotypes of the PGC-1alpha gene are associated with carbohydrate metabolism and type 2 diabetes.

Peroxisome proliferator-activated receptor coactivator-1alpha (PGC-1alpha) is a transcriptional coactivator implicated in transcriptional programs of hepatic gluconeogenesis, oxidative phosphorylation, and insulin release by beta-cells. To study associations of the PGC-1alpha gene locus with carbohydrate metabolism and type 2 diabetes in humans, we identified several polymorphisms in the promoter region that were located in a haplotype block distinct from a second haplotype block containing part of intron 2 and extending beyond exon 13. Each block contained five common haplotypes.

Decrease of mitochondrial DNA content and energy metabolism in renal cell carcinoma.

To elucidate the relationship between tumor genesis and the mitochondrial energy metabolism in renal neoplasms, we studied three individual enzyme activities of the oxidative phosphorylation, two components of the Krebs cycle and the mitochondrial DNA content of renal carcinomas including 29 conventional, five papillary, two unclassified carcinomas with sarcomatoid features and one collecting duct carcinoma. A significant reduction of all mitochondrial enzyme activities including complex V, as well as of the mitochondrial DNA content was detected in 34 of 37 renal carcinoma tissues as compared with control kidney. Mitochondrial enzyme activities and mitochondrial DNA levels were not statistically different between the conventional, papillary and unclassified sarcomatoid type of renal carcinoma and did not correlate with tumour grade, metastasis, ploidy and proliferative activity as determined by Ki-67 staining.