Yukimasa Yamashita

Prevalence of non-ulcer dyspepsia in the Japanese population

Background : Non‐ulcer dyspepsia (NUD) is one of the most frequently encountered disorders in general practice in Western countries. The prevalence of this disorder in the Japanese, however, has not been fully investigated. This study is designed to clarify the characteristics and prevalence of dyspepsia in the Japanese.

Presence of histamine H2-receptors on human gastric carcinoma cell line MKN-45 and their increase by retinoic acid treatment

Histamine dose-dependently stimulated cyclic AMP production in human gastric carcinoma cell line MKN-45, and this effect was inhibited by cimetidine but not by pyrilamine. Moreover, not only histamine but also cimetidine displaced the specific binding of [3H]tiotidine to these cells, whereas pyrilamine had no effect. On the other hand, pretreatment of MKN-45 cells with retinoic acid (RA) significantly enhanced histamine-induced increase of cyclic AMP production, although the cyclic AMP response to either forskolin or NaF was not affected. Finally, RA treatment increased the number of histamine receptor without altering its affinity. Thus, it appears that histamine H2-receptors are present on MKN-45 cells, and that RA treatment enhances the action of histamine on these cells by increasing the number of H2-receptors.

Characterization of gastrin/CCK receptors on gastric carcinoid tumor membrane of Mastomys natalensis

Recently, we identified the specific binding site for gastrin on the gastric carcinoid tumor of Mastomys (Praomys) natalensis. In this study, precise characterization of the gastrin binding site on these tumors was performed. Both 125I-human gastrin I (gastrin) and 125I-CCK-8 bound specifically to the cell membrane, and Scatchard analysis revealed a high affinity binding site for each ligand with similar Kd and Bmax values. The specific binding of both 125I-gastrin and 125I-CCK-8 was displaced in a concentration-dependent manner by various related peptides with a relative potency order of CCK-8 > or = gastrin < des(SO3)CCK-8. In addition, L364,718 as well as L365,260 displaced the binding of both ligands with similar potencies. Furthermore, not only gastrin but also CCK-8 increased [Ca2+]i in these tumor cells, the action of both being inhibited by L364,718 as well as by L365,260 (10(-7) M). These results suggest that the carcinoid tumor of Mastomys possesses a high affinity gastrin/CCK binding site coupled to the increase of [Ca2+]i.

Effects of islet amyloid polypeptide (amylin) and calcitonin gene-related peptide (CGRP) on glucose metabolism in the rat

In this study, we compared the effects of islet amyloid polypeptide (IAPP) and calcitonin gene-related peptide (CGRP) on glucose metabolism both in vivo and in vitro in the rat. Intravenous injection of rat CGRP caused a significant increase in plasma glucose concentration with a simultaneous increase in plasma insulin levels, whereas neither IAPP-NH2 nor IAPP-COOH had any effect. Moreover, intravenous infusion of CGRP decreased tolerance to intragastric administration of glucose (O-GTT) without altering plasma insulin levels, but again IAPPs had no effect. On the other hand, 125I-[Tyr0]rat CGRP specifically bound to the liver plasma membrane, and not only CGRP but also IAPP-NH2 dose-dependently displaced the specific binding of 125I-[Tyr0] CGRP, whereas IAPP-COOH had no effect. Conversely, CGRP as well as IAPP-NH2 but not IAPP-COOH evoked dose-dependent activation of adenylate cyclase in the membranes, and these effects were significantly inhibited by a CGRP receptor antagonist, human CGRP-I(8-37). However, neither CGRP nor IAPP-NH2 had any effect on glucose production in rat isolated hepatocytes. These results suggest that (1) IAPP-NH2 but not IAPP-COOH induces adenylate cyclase activation via CGRP receptors on rat liver plasma membranes, and (2) CGRP might not involve its action on the liver in the changes of glucose metabolism.

Mutations in non-structural 5A and rapid viral response to pegylated interferon-α-2b plus ribavirin therapy are associated with therapeutic efficacy in patients with genotype 1b chronic hepatitis C

For patients chronically infected with hepatitis C virus (HCV), mutations in the non-structural 5A (NS5A) gene are important predictive factors for the response to interferon (IFN) therapy. In the present study, factor analysis of the therapeutic response of patients following pegylated IFN and ribavirin combination therapy was assessed in a multicenter study. Chronic HCV-infected patients with genotype 1b and high viral load (n=96, mean age 56.5 years; 59 males, 68 females) treated with pegylated IFN-α-2b and ribavirin combination therapy were enrolled. This study was conducted at Kobe University Hospital and 25 affiliated hospitals in Hyogo prefecture. Sixty-five patients (68%) completed treatment with both pegylated IFN and ribavirin at >80% of the weight-based scheduled dosages. Patients who reduced or terminated therapy were frequently aged women (mean age 60.8 years; 11 males, 17 females). Overall, a sustained viral response (SVR) was achieved in 42 (44%) patients out of 96. Based on per-protocol-based (PPB) analysis, the SVR rate in patients with ≥6 amino acid (aa) mutations in the IFN resistance-determining region (IRRDR) (75%) or ≥1 aa mutation in the IFN sensitivity-determining region (ISDR) (61%) was significantly higher than that in patients with <5 aa mutations in IRRDR (30%) or no mutation in ISDR (29%). Multivariate analysis revealed that rapid viral response (RVR) (odds ratio, 18.1) and mutations of ≥6 in IRRDR (odds ratio, 15.5) were significantly associated with SVR. In conclusion, mutations in the NS5A region, particularly in patients with ≥6 aa mutations in IRRDR were strongly associated with a therapeutic response to pegylated IFN and ribavirin combination therapy.

Calcitonin inhibits the growth of human gastric carcinoma cell line KATO III

Calcitonin has a wide variety of actions on gastrointestinal function. In this study, we investigated the effects of calcitonin on the growth of human gastric carcinoma cell line KATO III in comparison with those of calcitonin gene-related peptide (CGRP). Calcitonin, but not CGRP, significantly and dose-dependently inhibited the growth of KATO III cells. This inhibition of cell growth was accompanied by an increase in cyclic AMP production. The proliferation of KATO III cells was also inhibited by forskolin and dibutyryl cyclic AMP, although agents which do not stimulate cyclic AMP production had no effect. Furthermore, in the presence of GTP, calcitonin stimulated adenylate cyclase activity in KATO III cell membranes, and this increase was reduced in the absence of GTP. On the other had, neither calcitonin nor CGRP enhanced the turnover of inositolphospholipid or the intracellular Ca2+ level. In addition, 125I-labeled human calcitonin was specifically bound to KATO III cell membranes, and this binding was dose-dependently displaced by unlabeled calcitonin but not CGRP. Furthermore, the specific binding of 125I-labeled human calcitonin to KATO III cell membranes was significantly reduced by addition of GTP but not ATP. These results suggest that calcitonin inhibits the growth of human gastric carcinoma cell line KATO III by stimulating cyclic AMP production via a GTP-dependent process coupled to specific calcitonin receptors.

Correlation between serum pepsinogen concentration and gastric acidity measured by 24 h pH monitoring

Abstract The relationship between the intragastric pH measured by 24 h pH monitoring system and the serum pepsinogen I/II ratio was studied in 68 cases. When pepsinogen I/II ratio was compared with pH 3.0 holding time (the percentage time during which the gastric pH is above 3.0), there was a negative correlation between these two parameters (correlation coefficient r= ‐0.62, P < 0.001). Furthermore, there was also a strong negative correlation between the early morning (from 03.00 to 06.00 h) gastric pH and pepsinogen I/II ratio (r= ‐0.76, P < 0.001). Accordingly, by simply measuring serum pepsinogen I and II, it may be possible to infer gastric acidity and to obtain the information concerning the early morning intragastric pH.

Fistula Formation Secondary to Mucinous Appendiceal Adenocarcinoma May Be Related to a Favorable Prognosis: A Case Report and Literature Review

A 90-year-old man was referred to our hospital because of a positive fecal occult blood test. Colonoscopy revealed a lesion with multiple nodules covered with abundant mucus at the hepatic flexure. Computed tomography showed a dilated appendix attached distally to the hepatic flexure. Right hemicolectomy was performed, and the pathological examination revealed a mucinous appendiceal adenocarcinoma infiltrating the hepatic flexure without pseudomyxoma peritonei. The patient is doing well without recurrence 12 months postoperatively. Extraperitoneal drainage of the malignant ascites caused by the fistula may allow for an early diagnosis, while also making it possible to successfully resect the lesion, thus resulting in a favorable outcome.