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81.
Maria I. Georgi Julia Rosendahl Franziska Ernst Dorothee Günzel Jörg R. Aschenbach Holger Martens Friederike Stumpff 《Pflügers Archiv : European journal of physiology》2014,466(9):1689-1712
It has long been established that the absorption of short-chain fatty acids (SCFA) across epithelia stimulates sodium proton exchange. The apically released protons are not available as countercations for the basolateral efflux of SCFA anions and a suitable transport model is lacking. Patch clamp and microelectrode techniques were used to characterize an anion conductance expressed by cultured cells of the sheep and bovine rumen and the sheep omasum and to localize the conductance in the intact tissue. Cells were filled with a Na-gluconate solution and superfused with sodium salts of acetate, propionate, butyrate, or lactate. Reversal potential rose and whole cell current at +100 mV decreased with the size of the anion. Anion-induced currents could be blocked by diisothiocyanato-stilbene-2,2′-disulfonic acid (DIDS), NPPB (200?μmol l?1), or pCMB (1 mmol l?1). In patches of bovine ruminal cells, single channels were observed with a conductance for chloride (327?±?11 pS), acetate (115?±?8 pS), propionate (102?±?10 pS), butyrate (81?±?2 pS), and gluconate (44?±?3 pS). Channels expressed by sheep rumen and omasum were similar. Microelectrode experiments suggest basolateral localization. In conclusion, forestomach epithelia express basolateral maxi-anion channels with a permeability sequence of chloride?>?acetate?>?propionate?>?butyrate. SCFA absorption may resemble functionally coupled transport of NaCl, with the Na+/K+-ATPase driving the basolateral efflux of the anion through a channel. Since protons are apically extruded, the model accurately predicts that influx of buffers with saliva is essential for the pH homeostasis of the ruminant forestomach. 相似文献
82.
Bodo B. Beck Jennifer B. Phillips Malte P. Bartram Jeremy Wegner Michaela Thoenes Andrea Pannes Josephina Sampson Raoul Heller Heike Göbel Friederike Koerber Antje Neugebauer Andrea Hedergott Gudrun Nürnberg Peter Nürnberg Holger Thiele Janine Altmüller Mohammad R. Toliat Simon Staubach Kym M. Boycott Enza Maria Valente Andreas R. Janecke Tobias Eisenberger Carsten Bergmann Lars Tebbe Yang Wang Yundong Wu Andrew M. Fry Monte Westerfield Uwe Wolfrum Hanno J. Bolz 《Human mutation》2014,35(10):1153-1162
We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next‐generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole‐exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in synapses of the outer plexiform layer. Knockdown of Poc1b in zebrafish caused cystic kidneys and retinal degeneration with shortened and reduced photoreceptor connecting cilia, compatible with the human syndromic ciliopathy. A recent study describes homozygosity for p.Arg106ProPOC1B in a family with nonsyndromic cone‐rod dystrophy. The phenotype associated with homozygous p.Arg106ProPOC1B may thus be highly variable, analogous to homozygous p.Leu710Ser in WDR19 causing either isolated retinitis pigmentosa or Jeune syndrome. Our study indicates that POC1B is required for retinal integrity, and we propose POC1B mutations as a probable cause for JBTS with severe PKD. 相似文献
83.
Miller AL Sims GP Brewah YA Rebelatto MC Kearley J Benjamin E Keller AE Brohawn P Herbst R Coyle AJ Humbles AA Kolbeck R 《The Journal of infectious diseases》2012,205(8):1311-1320
Respiratory syncytial virus (RSV), a common respiratory pathogen in infants and the older population, causes pulmonary inflammation and airway occlusion that leads to impairment of lung function. Here, we have established a role for receptor for advanced glycation end products (RAGE) in RSV infection. RAGE-deficient (ager(-/-)) mice were protected from RSV-induced weight loss and inflammation. This protection correlated with an early increase in type I interferons, later decreases in proinflammatory cytokines, and a reduction in viral load. To assess the contribution of soluble RAGE (sRAGE) to RSV-induced disease, wild-type and ager(-/-) mice were given doses of sRAGE following RSV infection. Of interest, sRAGE treatment prevented RSV-induced weight loss and neutrophilic inflammation to a degree similar to that observed in ager(-/-) mice. Our work further elucidates the roles of RAGE in the pathogenesis of respiratory infections and highlights the opposing roles of membrane and sRAGE in modulating the host response to RSV infection. 相似文献
84.
Fraysse B Weinberger F Bardswell SC Cuello F Vignier N Geertz B Starbatty J Krämer E Coirault C Eschenhagen T Kentish JC Avkiran M Carrier L 《Journal of molecular and cellular cardiology》2012,52(6):1299-1307
Hypertrophic cardiomyopathy (HCM) is frequently caused by mutations in MYBPC3 encoding cardiac myosin-binding protein C (cMyBP-C). The mechanisms leading from gene mutations to the HCM phenotype remain incompletely understood, partially because current mouse models of HCM do not faithfully reflect the human situation and early hypertrophy confounds the interpretation of functional alterations. The goal of this study was to evaluate whether myofilament Ca(2+) sensitization and diastolic dysfunction are associated or precede the development of left ventricular hypertrophy (LVH) in HCM. We evaluated the function of skinned and intact cardiac myocytes, as well as the intact heart in a recently developed Mybpc3-targeted knock-in mouse model carrying a point mutation frequently associated with HCM. Compared to wild-type, 10-week old homozygous knock-in mice exhibited i) higher myofilament Ca(2+) sensitivity in skinned ventricular trabeculae, ii) lower diastolic sarcomere length, and faster Ca(2+) transient decay in intact myocytes, and iii) LVH, reduced fractional shortening, lower E/A and E'/A', and higher E/E' ratios by echocardiography and Doppler analysis, suggesting systolic and diastolic dysfunction. In contrast, heterozygous knock-in mice, which mimic the human HCM situation, did not exhibit LVH or systolic dysfunction, but exhibited higher myofilament Ca(2+) sensitivity, faster Ca(2+) transient decay, and diastolic dysfunction. These data demonstrate that myofilament Ca(2+) sensitization and diastolic dysfunction are early phenotypic consequences of Mybpc3 mutations independent of LVH. The accelerated Ca(2+) transients point to compensatory mechanisms directed towards normalization of relaxation. We propose that HCM is a model for diastolic heart failure and this mouse model could be valuable in studying mechanisms and treatment modalities. 相似文献
85.
Jönsson F Mancardi DA Zhao W Kita Y Iannascoli B Khun H van Rooijen N Shimizu T Schwartz LB Daëron M Bruhns P 《Blood》2012,119(11):2533-2544
IgE and IgE receptors (FcεRI) are well-known inducers of allergy. We recently found in mice that active systemic anaphylaxis depends on IgG and IgG receptors (FcγRIIIA and FcγRIV) expressed by neutrophils, rather than on IgE and FcεRI expressed by mast cells and basophils. In humans, neutrophils, mast cells, basophils, and eosinophils do not express FcγRIIIA or FcγRIV, but FcγRIIA. We therefore investigated the possible role of FcγRIIA in allergy by generating novel FcγRIIA-transgenic mice, in which various models of allergic reactions induced by IgG could be studied. In mice, FcγRIIA was sufficient to trigger active and passive anaphylaxis, and airway inflammation in vivo. Blocking FcγRIIA in vivo abolished these reactions. We identified mast cells to be responsible for FcγRIIA-dependent passive cutaneous anaphylaxis, and monocytes/macrophages and neutrophils to be responsible for FcγRIIA-dependent passive systemic anaphylaxis. Supporting these findings, human mast cells, monocytes and neutrophils produced anaphylactogenic mediators after FcγRIIA engagement. IgG and FcγRIIA may therefore contribute to allergic and anaphylactic reactions in humans. 相似文献
86.
87.
88.
Friederike Weigel Anja Lemke Burkhard Tönshoff Lars Pape Henry Fehrenbach Michael Henn Bernd Hoppe Therese Jungraithmayr Martin Konrad Guido Laube Martin Pohl Tomáš Seeman Hagen Staude Markus J. Kemper Ulrike John 《Pediatric nephrology (Berlin, Germany)》2016,31(6):1021-1028
Background
Febrile urinary tract infections (fUTIs) are common after kidney transplantation (KTx); however, prospective data in a multicenter pediatric cohort are lacking. We designed a prospective registry to record data on fUTI before and after pediatric KTx.Methods
Ninety-eight children (58 boys and 40 girls)?≤?18 years from 14 mid-European centers received a kidney transplant and completed a 2-year follow-up.Results
Posttransplant, 38.7 % of patients had at least one fUTI compared with 21.4 % before KTx (p?=?0.002). Before KTx, fUTI was more frequent in patients with congenital anomalies of kidneys and urinary tract (CAKUT) vs. patients without (38 % vs. 12 %; p?=?0.005). After KTx, fUTI were equally frequent in both groups (48.7 % vs. 32.2 %; p?=?0.14). First fUTI posttransplant occurred earlier in boys compared with girls: median range 4 vs. 13.5 years (p?=?0.002). Graft function worsened (p?<?0.001) during fUTI, but no difference was recorded after 2 years. At least one recurrence of fUTI was encountered in 58 %.Conclusion
This prospective study confirms a high incidence of fUTI after pediatric KTx, which is not restricted to patients with CAKUT; fUTIs have a negative impact on graft function during the infectious episode but not on 2-year graft outcome.89.
Marco Bandini Maarten Albersen Juan Chipollini Filippo Pederzoli Yao Zhu Ding-Wei Ye Antonio A. Ornellas Nick Watkin Michael Ager Oliver W. Hakenberg Axel Heidenreich Daniele Raggi Mario Catanzaro Friederike Haidl Elio Mazzone Laura Marandino Alberto Briganti Francesco Montorsi Mounsif Azizi Philippe E. Spiess Andrea Necchi 《BJU international》2020,125(6):867-875
90.
OBJECTIVE: The phenotypic expression of partial lipodystrophy is present in two familial syndromes: familial partial lipodystrophy type 1 (FPLD1), with fat loss from the extremities, and central obesity and FPLD type 2, with fat loss from the extremities, abdomen, and thorax. The latter disorder is associated with mutations in the LMNA gene. FPLD1 is thought to be rare. Here, we report 13 subjects with FPLD1, suggesting that this syndrome is more common than previously thought. RESEARCH DESIGN AND METHODS: Fasting glucose, plasma lipids, leptin, HbA(1c), and anthropomorphic measurements were evaluated in 13 subjects with clinical features of FPLD1 and are compared with two age-matched control groups, with and without diabetes. RESULTS: Only women with clinical features of FPLD1 have been identified. Although they lack extremity and gluteal subcutaneous fat, they do have truncal obesity. Skinfold thickness on the arm and leg was significantly less than that in control subjects. The ratio of skinfold thickness from abdomen to thigh was significantly higher in subjects, suggesting an easy method for identifying affected patients. FPLD1 subjects also had components of the metabolic syndrome, including hypertension, insulin resistance, and severe hypertriglyceridemia resulting in pancreatitis. Premature coronary artery disease was present in 31% of subjects. None of the subjects had coding mutations in the LMNA gene or in the gene coding for peroxisome proliferator-activated receptor (PPAR)-gamma. CONCLUSIONS: FPLD1 is more common than previously described, but the diagnosis is often missed. Early recognition and intensive treatment of hyperlipidemia and diabetes in FPLD1 is important for prevention of pancreatitis and early cardiovascular disease. 相似文献