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Agents in early development for treatment of bladder dysfunction–promise of drugs acting at TRP channels?

Introduction: In the lower urinary tract (LUT) several members of the TRP superfamily are involved in nociception and mechanosensory transduction. Animal studies have suggested a therapeutic potential of some of these channels, including TRPV1, TRPV4, TRPM8, TRPA1, and TRPM4, for treatment of bladder over- and underactivity and bladder pain disorders, but translation of this information to clinica

Dynamic changes in DNA methylation during embryonic and postnatal development of an altricial wild bird

DNA methylation could shape phenotypic responses to environmental cues and underlie developmental plasticity. Environmentally induced changes in DNA methylation during development can give rise to stable phenotypic traits and thus affect fitness. In the laboratory, it has been shown that the vertebrate methylome undergoes dynamic reprogramming during development, creating a critical window for env

Undifferentiated pleomorphic sarcomas with PRDM10 fusions have a distinct gene expression profile

Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive soft tissue tumor. A subset of UPS is characterized by a CITED2–PRDM10 or a MED12–PRDM10 gene fusion. Preliminary data suggest that these so-called PRDM10-rearranged tumors (PRT) are clinically more indolent than classical high-grade UPS, and hence important to recognize. Here, we assessed the spectrum of accompanying mutations and

Relating homology between the Epstein-Barr virus BOLF1 molecule and HLA-DQw8 β chain to recent onset Type 1 (insulin-dependent) diabetes mellitus

A role for the Epstein-Barr virus in initiating Type 1 (insulin-dependent) diabetes mellitus has been proposed since Epstein-Barr virus BOLF1(497-513) AVTPL RIFIVP PAAEY has an 11 amino acid identity with HLA-DQw8 β (49-60) AVTPL GPPAAEY. Rabbit antisera to the BOLF1 (496-515) peptide crossreacted with the homologous DQw8 β (44-63) peptide but not with the related DQw7 β(44-63) peptide, which diff

Effects of sodium butyrate on proliferation-dependent insulin gene expression and insulin release in glucose-sensitive RIN-5AH cells

A rat islet tumor subclone, RIN-5AH-T2-B, was cultured with 2 mmol/liter of the proliferation-arresting compound sodium butyrate (NaB). Insulin gene expression and glucose-stimulated insulin release were analyzed and compared with logarithmically proliferating and confluent control cells cultured without NaB. Logarithmically proliferating control cells revealed high insulin gene expression. In the

Interleukin-1 potentiates glucose stimulated insulin release in the isolated perfused pancreas

The acute effects of recombinant human interleukin-1 beta (rIL-1) on basal and glucose-stimulated insulin release were investigated in the isolated perfused pancreas. At a concentration of 20 μg/l rIL-1 had no effect on basal insulin release, but increased the total amount of insulin released during first and second phase insulin release in response to 20 mmol/l D-glucose in the rat pancreas (P <

The shear plate dowel joint : Research on a novel connection for heavy timber structures

An increased use of wood can reduce the environmental footprint of the building sector. In order to improve the competitiveness of heavy timber structures, the thesis presents a novel type of timber connection with a high degree of prefabrication. The connection includes a resilient bond line, meaning an elastic bond line with low stiffness yet high fracture energy.It has previously been shown tha

Autoimmunity of diabetes

Mechanisms underlying the etiology and pathogenesis of insulin-dependent diabetes mellitus (IDDM) are reviewed. Its natural history and associated autoimmune phenomena indicate that IDDM is a systemic disorder resulting in a specific disappearance of pancreatic β cells. Genetic aspects of the disorder include its linkage to HLA class II gene loci, although the manner in which this produces autoimm

Association of IDDM and attenuated response of 2',5'-oligoadenylate synthetase to yellow fever vaccine

Basal and yellow fever vaccination-induced 2',5'-oligoadenylate synthetase (2',5'A) activity was determined in blood mononuclear cells (peripheral blood lymphocytes [PBLs]) from insulin-dependent diabetes mellitus (IDDM) and matched control subjects. The live attenuated yellow fever vaccine represented a primary stimulus in all subjects. First, basal 2',5'A activity increased several-fold in respo

Checklist for gene/disease-specific variation database curators to enable ethical data management

Databases with variant and phenotype information are essential for advancing research and improving the health and welfare of individuals. These resources require data to be collected, curated, and shared among relevant specialties to maximize impact. The increasing generation of data which must be shared both nationally and globally for maximal effect presents important ethical and privacy concer

Medication errors in primary health care records; a cross-sectional study in Southern Sweden

BACKGROUND: Drug-related problems due to medication errors are common and have the potential to cause harm. This study, which was conducted in Swedish primary health care, aimed to assess how well the medication lists in the medical records tally with the medications used by patients and to explore what type of medication errors are present. METHODS: We reviewed the electronic medical records (EMR

Surface Microdialysis Detects Ischemia After Esophageal Resection—An Experimental Animal Study

Background: After an esophageal resection, continuity is commonly restored by a gastric tube reconstruction and an intrathoracic anastomosis to the remaining proximal esophagus. Ischemia of the anastomotic region is considered to play a pivotal role in anastomotic leakage. Microdialysis (μD) is an excellent method to measure local biochemical substances and parameters in a specific organ or compar

Quantitative analysis of islet glutamic acid decarboxylase p64 autoantibodies in insulin-dependent diabetes mellitus

Autoantibodies against the βcell Mr 64,000 protein (p64), recently identified as an isoform of glutamic acid decarboxylase (GAD), are prevalent in patients with insulin-dependent diabetes mellitus (IDDM). Dog islets were found to represent an abundant source of native p64 allowing the study of antigen-antibody interactions in IDDM. A quantitative, standardized assay for p64 antibodies based on dog