Genetic Mapping of , a New Lethal Allele of .

The mutation was generated in a Flp/FRT EMS screen for conditional mutations that cause growth and developmental defects in a genetic background that blocks apoptosis. The mutations were conditional, based on the allele being present on the starting chromosome, and blocking canonical apoptosis in a homozygous state. The mosaic eyes exhibit defects in eye development including patches of rough eye and irregular surface structure.

Slc26a3 deficiency is associated with loss of colonic HCO3 (-) secretion, absence of a firm mucus layer and barrier impairment in mice.

Aim: Downregulated in adenoma (DRA, Slc26a3) is a member of the solute carrier family 26 (SLC26), family of anion transporters, which is mutated in familial chloride-losing diarrhoea (CLD). Besides Cl(-) -rich diarrhoea, CLD patients also have a higher-than-average incidence of intestinal inflammation. In a search for potential explanations for this clinical finding, we investigated colonic electrolyte transport, the mucus layer and susceptibility against dextran sodium sulphate (DSS)-induced colitis in Slc26a3(-/-) mice.

The role of pancreatic ductal secretion in protection against acute pancreatitis in mice*.

Objectives: A common potentially fatal disease of the pancreas is acute pancreatitis, for which there is no treatment. Most studies of this disorder focus on the damage to acinar cells since they are assumed to be the primary target of multiple stressors affecting the pancreas. However, increasing evidence suggests that the ducts may also have a crucial role in induction of the disease.

The distinct roles of anion transporters Slc26a3 (DRA) and Slc26a6 (PAT-1) in fluid and electrolyte absorption in the murine small intestine.

The mixing of gastric and pancreatic juice subjects the jejunum to unique ionic conditions with high luminal CO2 tension and HCO3 − concentration. We investigated the role of the small intestinal apical anion exchangers PAT-1 (Slc26a6) and DRA (Slc26a3) in basal and CO2/HCO3 −-stimulated jejunal fluid absorption. Single pass perfusion of jejunal segments was performed in anaesthetised wild type (WT) as well as in mice deficient in DRA, PAT-1, Na+/H+ exchanger 3 (NHE3) or NHE2, and in carbonic anhydrase II (CAII).

Molecular transport machinery involved in orchestrating luminal acid-induced duodenal bicarbonate secretion in vivo.

The duodenal villus brush border membrane expresses several ion transporters and/or channels, including the solute carrier 26 anion transporters Slc26a3 (DRA) and Slc26a6 (PAT-1), the Na(+)/H(+) exchanger isoform 3 (NHE3), as well as the anion channels cystic fibrosis transmembrane conductance regulator (CFTR) and Slc26a9. Using genetically engineered mouse models lacking Scl26a3, Slc26a6, Slc26a9 or Slc9a3 (NHE3), the study was carried out to assess the role of these transporters in mediating the protective duodenal bicarbonate secretory response (DBS-R) to luminal acid; and to compare it to their role in DBS-R elicited by the adenylyl cyclase agonist forskolin. While basal DBS was reduced in the absence of any of the three Slc26 isoforms, the DBS-R to forskolin was not altered.

Telomere shortening is associated with reduced duodenal HCOFormula secretory but normal gastric acid secretory capacity in aging mice.

The incidence of duodenal ulcer, especially Helicobacter pylori-negative duodenal ulcer, strongly increases with age. In humans, telomere length shortening is considered to be one critical factor in cellular senescence and organ survival. In this study, we compared basal and stimulated gastric acid and duodenal HCO(3)(-) secretory rates in aged late-generation (G(3)) telomerase-deficient (mTERC(-/-)) mice, which are characterized by severe telomere dysfunction due to the inability to elongate telomeres during cell division.

[Etiology and pathophysiology of fibromyalgia syndrome].

Background: The scheduled update to the German S3 guidelines on fibromyalgia syndrome (FMS) by the Association of the Scientific Medical Societies ("Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften", AWMF; registration number 041/004) was planned starting in March 2011.

Materials And Methods: The development of the guidelines was coordinated by the German Interdisciplinary Association for Pain Therapy ("Deutsche Interdisziplinären Vereinigung für Schmerztherapie", DIVS), 9 scientific medical societies and 2 patient self-help organizations. Eight working groups with a total of 50 members were evenly balanced in terms of gender, medical field, potential conflicts of interest and hierarchical position in the medical and scientific fields.

Single-channel amplitude integrated EEG recording for the identification of epileptic seizures by nonexpert physicians in the adult acute care setting.

Objective: Although several studies have shown the potential of amplitude integrated electroencephalography (aEEG) in detecting neonatal seizures, no publications have evaluated the diagnostic use of aEEG for the detection of seizures in adult patients.

Methods: In this prospective blinded observational study, bifrontal single-channel electroencephalography (EEG) recordings were performed with a portable EEG monitor (CSM M3 ICU, Danmeter-Goalwick Holdings Limited, Odense, Denmark) during the out-of-hospital care of emergency cases. Four intensive care unit (ICU) physicians received training in the interpretation of aEEG recordings.

Immune response as a possible mechanism of long-lasting disease control in spontaneous remission of MLL/AF9-positive acute myeloid leukemia.

Spontaneous complete remission (CR) is a rare, poorly understood phenomenon in acute myeloid leukemia (AML). We describe the 10-year follow-up of a patient with MLL-AF9-positive AML (Müller et al. Eur J Haematol 73:62-66, 2004), including ex vivo antileukemic immune responses which may contribute to the long-lasting spontaneous CR (tantamount to cure).

Gene ablation for PEPT1 in mice abolishes the effects of dipeptides on small intestinal fluid absorption, short-circuit current, and intracellular pH.

PEPT1 function in mouse intestine has not been assessed by means of electrophysiology and methods to assess its role in intracellular pH and fluid homeostasis. Therefore, the effects of the dipeptide glycilsarcosin (Gly-Sar) on jejunal fluid absorption and villous enterocyte intracellular pH (pH(i)) in vivo, as well as on enterocyte[(14)C]Gly-Sar uptake, short-circuit current (I(sc)) response, and enterocyte pH(i) in vitro were determined in wild-type and PEPT1-deficient mice and in mice lacking PEPT1. Immunohistochemistry for PEPT1 failed to detect any protein in enterocyte apical membranes in Slc15a1(-/-) animals.

The switch of intestinal Slc26 exchangers from anion absorptive to HCOFormula secretory mode is dependent on CFTR anion channel function.

CFTR has been recognized to function as both an anion channel and a key regulator of Slc26 anion transporters in heterologous expression systems. Whether this regulatory relationship between CFTR and Slc26 transporters is seen in native intestine, and whether this effect is coupled to CFTR transport function or other features of this protein, has not been studied. The duodena of anesthetized CFTR-, NHE3-, Slc26a6-, and Scl26a3-deficient mice and wild-type (WT) littermates were perfused, and duodenal bicarbonate (HCO(3)(-)) secretion (DBS) and fluid absorptive or secretory rates were measured.

[Delirium in the intensive care unit].

In recent years delirium in the intensive care unit (ICU) has internationally become a matter of rising concern for intensive care physicians. Due to the design of highly sophisticated ventilators the practice of deep sedation is nowadays mostly obsolete. To assess a ventilated ICU patient for delirium easy to handle bedside tests have been developed which permit a psychiatric scoring.

Defective jejunal and colonic salt absorption and alteredNa(+)/H (+) exchanger 3 (NHE3) activity in NHE regulatory factor 1 (NHERF1) adaptor protein-deficient mice.

We investigated the role of the Na(+)/H(+) exchanger regulatory factor 1 (NHERF1) on intestinal salt and water absorption, brush border membrane (BBM) morphology, and on the NHE3 mRNA expression, protein abundance, and transport activity in the murine intestine. NHERF1-deficient mice displayed reduced jejunal fluid absorption in vivo, as well as an attenuated in vitro Na(+) absorption in isolated jejunal and colonic, but not of ileal, mucosa. However, cAMP-mediated inhibition of both parameters remained intact.

Myocardial iron overload in transfusion-dependent pediatric patients with acute leukemia.

For patients who regularly receive blood transfusions, cardiac failure is the major cause of death. This is most alarming because it progresses rapidly and is difficult to manage. We present three pediatric patients with acute leukemia whose therapy-induced anemia was treated with different amounts of red blood cell concentrates (RCC).

Factors associated with the steep increase in late-midlife stroke occurrence among US men.

Background: Data on recent stroke prevalence rates among middle-aged men in the United States indicate that men aged 55 to 64 years are 3 times more likely than men aged 45 to 54 years to have experienced a stroke. We aimed to determine potential risk factors that may contribute to this steep increase in late midlife stroke occurrence.

Methods: We analyzed the National Health and Nutrition Examination Survey 1999 to 2004 data sets, assessing stroke prevalence, predictors of stroke occurrence, and vascular risk factors in men across their midlife years.

Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and Glut5.

Increased dietary fructose in rodents recapitulates many aspects of the Metabolic Syndrome with hypertension, insulin resistance and dyslipidemia. Here we show that fructose increased jejunal NaCl and water absorption which was significantly decreased in mice whose apical chloride/base exchanger Slc26a6 (PAT1, CFEX) was knocked out. Increased dietary fructose intake enhanced expression of this transporter as well as the fructose-absorbing transporter Slc2a5 (Glut5) in the small intestine of wild type mice.

Localization, trafficking, and significance for acid secretion of parietal cell Kir4.1 and KCNQ1 K+ channels.

Background & Aims: K(+) recycling at the apical membrane of gastric parietal cells is a prerequisite for gastric acid secretion. Two K(+) channels are currently being considered for this function, namely KCNQ1 and inwardly rectifying K(+) channels (Kir). This study addresses the subcellular localization, trafficking, and potential functional significance of KCNQ1 and Kir4.

Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity.

Background: Probiotics are proposed to positively modulate the intestinal epithelial barrier formed by intestinal epithelial cells (IECs) and intercellular junctions. Disruption of this border alters paracellular permeability and is a key mechanism for the development of enteric infections and inflammatory bowel diseases (IBDs).

Methodology And Principal Findings: To study the in vivo effect of probiotic Escherichia coli Nissle 1917 (EcN) on the stabilization of the intestinal barrier under healthy conditions, germfree mice were colonized with EcN or K12 E.

Comparison of the confusion assessment method for the intensive care unit (CAM-ICU) with the Intensive Care Delirium Screening Checklist (ICDSC) for delirium in critical care patients gives high agreement rate(s).

Objective: In the intensive care unit (ICU) we assessed the agreement between the delirium ratings of two independent delirium assessment methods: (a) the Confusion Assessment method for the ICU (CAM-ICU); and (b) the Intensive Care Delirium Screening Checklist (ICDSC).

Design: Prospective, descriptive cohort study.

Setting And Patients: During a 6-month period, 174 patients (mean age 62.

EEG changes and serum anticholinergic activity measured in patients with delirium in the intensive care unit.

The aim of this study was to examine whether serum anticholinergic activity (SAA) is a reliable indicator of delirium in the ICU, and whether there is a significant correlation between SAA and quantitative electroencephalographic (EEG) data in delirious patients. In a prospective cohort study, we assessed ICU patients diagnosed with delirium (n = 37). EEG measurements and blood analysis including SAA were performed 48 h following ICU admission.

Sodium and chloride absorptive defects in the small intestine in Slc26a6 null mice.

PAT1 (Slc26a6) is located on the apical membrane of the small intestinal villi, but its role for salt absorption has not been studied. To ascertain the role of Slc26a6 in jejunal sodium and chloride absorption, and its interplay with NHE3, muscle-stripped jejuna from Slc26a6+/+ and -/- and NHE3 +/+ and -/- mice were mounted in Ussing chambers and electrical parameters, and (36)Cl(-) and (22)Na(+) fluxes were measured. In parallel studies, expression of the apical Na(+)/H(+) exchanger (NHE3) was examined by immunofluorescence labeling and immunoblot analysis in brush border membrane (BBM).