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Bunkyō-ku, Japan

Iwakiri K.,Sendagi | Iwakiri K.,Nippon Medical School | Sano H.,Sendagi | Tanaka Y.,Sendagi | And 8 more authors.
Digestion | Year: 2010

Background and Aim: The reason that some reflux episodes evoke symptoms is poorly understood, therefore the aim of this study is to assess the determinants of reflux perception in patients with non-erosive reflux disease (NERD) on proton pump inhibitor (PPI) therapy. Methods: Ten NERD patients with persistent symptoms, despite double-dose PPI therapy, were included in this study. All patients had a positive symptom index (SI), which was determined by ambulatory 24-hour combined impedance-pH monitoring. Reflux episodes were identified and classified as acid, weakly acidic or weakly alkaline reflux and were considered symptomatic if patients recorded a symptom within 5 min after a reflux episode. Results: A total of 954 liquid reflux episodes were detected, including 135 (14.2%) acid, 782 (82.0%) weakly acidic, and 37 (3.9%) weakly alkaline. Overall, 59 (6.2%) reflux episodes were symptomatic and the majority (88.1%) of symptomatic reflux episodes were weakly acidic reflux. When reflux episodes were confined to the distal esophagus, there were very few reflux symptoms. Proximal reflux is significantly more likely to be associated with reflux symptoms, irrespective of the acidity of the refluxate or the duration of proximal reflux episodes. Conclusions: In NERD patients who have a positive SI on double-dose PPI therapy, the high proximal extent of refluxate is a major factor associated with reflux perception. © 2010 S. Karger AG, Basel.


Sekine K.,Sendagi | Ikezono T.,Sendagi | Ikezono T.,Nippon Medical School | Shindo S.,Sendagi | And 4 more authors.
Audiology and Neurotology | Year: 2010

Proteomic analysis of inner ear proteins revealed unique properties of cochlin, encoded by the COCH gene. We detected 3 cochlin isoforms, p63s, p44s and p40s, in the inner ear tissue and a short 16-kDa isoform, cochlin-tomoprotein (CTP), in the perilymph. The role of the cochlin isoforms has not been elucidated. To improve our understanding of the mechanism of cochlin isoform expression, we investigated rat cochlin mRNA expression in the inner ear and other organs. We performed RNA-ligation-mediated amplification of cDNA ends (RLM-RACE) using RNA isolated from the inner ear and spleen of rats, which are known to express abundant cochlin mRNA. We also examined the expression profile of full-length cochlin mRNA by nested RT-PCR in the cerebrum, cerebellum/brain stem, eye, inner ear, thyroid gland, thymus gland, lung, heart, liver, spleen, adrenal gland, kidney and blood. We verified CTP expression in rat perilymph by Western blot. By RLM-RACE, alternately spliced variants of cochlin mRNA with 3 different lengths were detected (2442, 2008 and 724 bp). The two longer mRNAs encode full-length cochlin with different polyadenylation signals in the 3′-untranslated region, which are expressed both in the ear and spleen. The short variant encodes the limulus factor C, cochlin, late gestation lung protein (LCCL) domain and the N-terminal sequence of the von Willebrand factor A (vWFA1) domain, and this variant was detected only in the ear. All 3 variants have the same transcriptional start site. By RT-PCR, we found that full-length cochlin was expressed in all organs examined, with a splice variant in the heart. By Western blot, we detected short isoforms (11-17 kDa) in the perilymph. Cochlin isoform formation is regulated, at least in part, by alternative splicing at the transcriptional level. The short mRNA was detected only in the inner ear, and this variant may provide a clue to understanding the formation and function of cochlin isoforms.

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