[Show abstract][Hide abstract] ABSTRACT: Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in CFTR (CF transmembrane conductance regulator). Although CF is the most common hereditary disease in Caucasians, it is rare in Asian populations. Common disease-causing mutations of CFTR in Caucasians are rarely identified in Japanese patients with CF. In the present study, CFTR transcripts from nasal swab were analyzed in a Japanese boy, in addition to conventional PCR and direct sequence of all exons, their boundaries and promoter region of the CFTR gene. The boy was diagnosed with CF by chronic respiratory infection and the elevated sweat chloride level. None of the disease-causing mutations of CFTR was detected by the conventional analysis. Cloning and sequence of the CFTR transcripts revealed a heterozygous deletion spanning exons 16, 17a and 17b. The deletion was confirmed by multiplex ligation-dependent probe amplification and the direct sequence of the junction fragment obtained from the genomic DNA by primer walking, which revealed the mutation c.2908+1085_3367+260del7201. We also identified a splicing defect: deletion/skipping of exon 1 in the CFTR transcript from the other allele. The analysis of CFTR transcripts from nasal swab is recommended in the genetic analysis of CF in Japanese.
Journal of Human Genetics 05/2012; 57(7):427-33. DOI:10.1038/jhg.2012.46 · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: HCO3- -rich fluid in the pancreatic juice (2-3 L/day) is secreted by epithelial cells lining the pancreatic duct tree, while digestive enzymes are secreted by acinar cells with a small amount of Cl- -rich fluid. Ductal HCO3- secretion is not only regulated by gastrointestinal hormones and cholinergic nerves but is also influenced by luminal factors: intraductal pressure, Ca2+ concentration, pathological activation of protease and bile reflux. The maximum HCO3- concentration of the juice under secretin stimulation reaches 140-150 mM. Thus pancreatic duct cells secrete HCO3- against a approximately 7-fold concentration gradient. HCO3- secretion critically depends on the activity of CFTR, a cAMP-dependent anion channel localized in the apical membrane of various epithelia. In the proximal part of pancreatic ducts close to acinar cells HCO3 secretion across the apical membrane is largely mediated by SLC26A6 CI- -HCO3- exchanger. In distal ducts where the luminal HCO3- concentration is already high, most of the HCO3- secretion is mediated by HCO3- conductance of CFTR. CFTR is the causative gene for cystic fibrosis. Loss of function due to severe mutations in both alleles causes typical cystic fibrosis characterized by dehydrated, thick, and viscous luminal fluid/mucus in the respiratory and gastrointestinal tract, pancreatic duct, and vas deferens. A compound heterozygote of mutations/polymorphisms (causing a mild dysfunction of CFTR) involves a risk of developing CFTR-related diseases such as chronic pancreatitis. In cystic fibrosis and certain cases of chronic pancreatitis, the pancreatic duct epithelium secretes a small amount of fluid with neutral-acidic pH, which causes an obstruction of the duct lumen by a protein plug or viscous mucus.
Nagoya journal of medical science 02/2012; 74(1-2):1-18. · 0.75 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To compare how and to what extent ingestion of hydrogen water and milk increase breath hydrogen in adults.
Five subjects without specific diseases, ingested distilled or hydrogen water and milk as a reference material that could increase breath hydrogen. Their end-alveolar breath hydrogen was measured.
Ingestion of hydrogen water rapidly increased breath hydrogen to the maximal level of approximately 40 ppm 10-15 min after ingestion and thereafter rapidly decreased to the baseline level, whereas ingestion of the same amount of distilled water did not change breath hydrogen (p < 0.001). Ingestion of hydrogen water increased both hydrogen peaks and the area under the curve (AUC) of breath hydrogen in a dose-dependent manner. Ingestion of milk showed a delayed and sustained increase of breath hydrogen in subjects with milk intolerance for up to 540 min. Ingestion of hydrogen water produced breath hydrogen at AUC levels of 2 to 9 ppm hour, whereas milk increased breath hydrogen to AUC levels of 164 ppm hour for 540 min after drinking.
Hydrogen water caused a rapid increase in breath hydrogen in a dose-dependent manner; however, the rise in breath hydrogen was not sustained compared with milk.
[Show abstract][Hide abstract] ABSTRACT: Pancreatic duct cells secrete a HCO(3)(-)-rich (approximately 140 mM) fluid. Using a computer model of the pancreatic duct, Sohma, et al. have demonstrated that the activity of a Cl(-)/HCO(3)(-) exchanger with a 1: 1 stoichiometry at the apical membrane would have to be suppressed in order to achieve such a HCO(3)(-)-rich secretion. Recently the apical exchanger in pancreatic ducts has been identified as SLC26A6 and this probably mediates most of Cl(-)-dependent HCO(3)(-) secretion across the apical membrane. SLC26A6 is reported to mediate electrogenic Cl(-)/2HCO(3)(-) exchange when expressed in Xenopus oocytes. To assess the implications of this 1: 2 stoichiometry for HCO(3)(-) secretion, we have reconstructed the Sohma model using MATLAB/Simulink. To do this we have formulated an expression for the turnover rate of Cl(-)/2HCO(3)(-) exchange using network thermodynamics and we have estimated the constants from published experimental data. Preliminary data suggest that the 1: 2 stoichiometry of SLC26A6 would favor HCO(3)(-) secretion at higher concentrations.
The Journal of Medical Investigation 01/2009; 56 Suppl(Supplement):325-8. DOI:10.2152/jmi.56.325