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Biomedical subjects

M Yuki

Publications and source records attributed to M Yuki.

At least 19 recordsLinked to original sources

Effects of famotidine, mosapride and tandospirone for treatment of functional dyspepsia.

BACKGROUND: An effective therapeutic strategy for functional dyspepsia (FD) has not been well-established. AIM: We investigated and compared the therapeutic effects of famotidine, mosapride and tandospirone for the control of dyspeptic symptoms. METHODS: Fully examined FD patients of outpatient clinics at seven different medical centres were enrolled in the study. They were randomly assigned to three groups based on the type of drug administered: famotidine, mosapride and tandospirone. The effects of treatment over 4 weeks were assessed by visual analogue scales. RESULTS: All of the drugs showed beneficial effects, although famotidine was the most effective for symptom relief, which was significantly greater than tandospirone, while the effect of mosapride was similar to that of famotidine. No subtype of FD showed a better response to a particular type of drug. CONCLUSIONS: For the treatment of FD, famotidine demonstrated the best therapeutic effect, followed by mosapride, while that of tandospirone was significantly lower.

Anti-Anxiety Agents↗

Expression of dentin matrix protein 1 (DMP1) during fracture healing.

Dentin matrix protein 1 (DMP1) is one of the acidic phosphorylated extracellular matrix proteins called the SIBLING (small integrin-binding ligand, N-linked glycoproteins) family. Recent studies showed that DMP1 is expressed in the mineralized tissues and suggested that DMP1 is involved in the mineralization. We investigated the precise localization of DMP1 messenger RNA (mRNA) and protein during fracture healing. In situ hybridization demonstrated that DMP1 mRNA was strongly expressed in preosteocytes and osteocytes in the bony callus during intramembranous and endochondral ossification while DMP1 mRNA was not detected in osteoblasts and chondrocytes. During endochondral ossification, however, a low number of DMP1-expressing cells were identified in the cluster of hypertrophic chondrocytes. However, these DMP1-expressing cells were not hypertrophic and were likely to be osteoblast-lineage cells, which were embedded in the matrix of bone or cartilage, because type I collagen-expressing cells and invasion of capillary vessels were observed in the same area. Northern blot, in situ hybridization, and immunohistochemical analyses showed that DMP1 mRNA and protein expressions were increased until day 14 postfracture, when bony callus was formed, and then declined to a lower level during remodeling of the bony callus. Therefore, DMP1 is likely to play an important role in the mineralization of the bony callus.

Animals↗

Expression of midkine and receptor-like protein tyrosine phosphatase (RPTP)-beta genes in the rat stomach and the influence of rebamipide.

BACKGROUND: Midkine has been reported to bind to receptor-like protein tyrosine phosphatase (RPTP)-beta and to play important roles in growth and differentiation of various cells. Midkine is expressed in rat stomach during experimental ulcer healing, suggesting that the midkine-RPTP-beta system has some physiological functions in the stomach. Rebamipide is a mucoprotective drug used for the treatment of gastric ulcers. We have tested the hypothesis that the ulcer healing mechanism stimulated by rebamipide is linked physiologically to the gastric midkine-RPTP-beta system. MATERIALS AND METHODS: Seven-week-old-male Wistar rats were used. Midkine and RPTP-beta gene expression in rat stomach was investigated by laser capture microdissection coupled with the reverse transcription-polymerase chain reaction (RT-PCR). The effects of rebamipide on midkine and RPTP-beta expression in rat stomach and the gastric epithelial cell line RGM1 were evaluated by RT-PCR and Northern blot analyses. RESULTS: Midkine and RPTP-beta expression was detected in the gastric mucosal, submucosal and muscle layers. Rebamipide stimulated both midkine and RPTP-beta expression in rat stomach and RGM1 cells. CONCLUSION: Rebamipide may protect the gastric mucosa by regulating midkine and RPTP-beta expression.

Alanine↗

Nizatidine and cisapride enhance salivary secretion in humans.

BACKGROUND: Salivation plays an important role in the defence of the oesophageal mucosa against gastric acidic reflux and can be evoked by cholinergic stimulation. Both nizatidine and cisapride have been reported to increase acetylcholine concentrations in the cholinergic system. AIM: To investigate the effect of nizatidine and cisapride on salivary secretion, salivary epidermal growth factor and bicarbonate output. METHODS: The salivary volume and concentration of salivary epidermal growth factor and bicarbonate were measured after the administration of nizatidine (150 mg), famotidine (20 mg) and cisapride (5 mg) in 30 male healthy volunteers. RESULTS: Basal and stimulated salivary secretions were found to be increased after the administration of nizatidine and cisapride. In contrast, salivary secretion was not increased by famotidine. Although epidermal growth factor content was not augmented, nizatidine and cisapride administration also increased the bicarbonate output in mastication-stimulated saliva. CONCLUSIONS: Increased salivary secretion and bicarbonate output induced by nizatidine may be useful for the treatment of patients with gastro-oesophageal reflux disease.

Adult↗

Correlation between microsatellite instability and metachronous disease recurrence after endoscopic mucosal resection in patients with early stage gastric carcinoma.

BACKGROUND: Since endoscopic treatment was first evaluated and established as a treatment for patients with early stage gastric carcinoma, metachronous disease recurrence at other sites in the stomach after endoscopic treatment has become a major problem. METHODS: A retrospective case-control study was conducted on 10 patients with metachronous recurrence of gastric carcinoma after undergoing successful endoscopic mucosal resection (EMR) therapy for early stage gastric carcinoma and on 14 patients without recurrence. Gastric mucosal tissues obtained during the initial EMR were dissected, and DNA samples from the tumor tissue and surrounding nonneoplastic mucosa were extracted separately. Microsatellite instability (MSI) was tested in five microsatellite markers (D2S137, D3S1067, TP53, TGFbetaRII, and BAX). The authors also looked for K-ras codon 12 point mutations in the tumor tissues. In addition, immunohistochemical staining was done to test for the presence of proliferating cell nuclear antigen (PCNA), p53, hMSH2, and hMLH1 in the mucosal tissues. Finally, the correlation between the presence or absence of metachronous recurrence and the characteristics of the primary tumor (MSI, K-ras, p53, etc.) were investigated. RESULTS: Three of 10 patients with recurrent disease showed MSI in more than two microsatellite markers among 3-5 investigated site (MSI-H), whereas none of the patients with nonrecurrent disease did so. There was no significant correlation between metachronous recurrence after EMR and immunohistochemical staining reactions, including those for PCNA, p53, hMSH2, and hMLH1. None of the patients showed K-ras mutations. CONCLUSIONS: Thirty percent of patients with recurrent disease showed MSI-H, whereas none of the patients with nonrecurrent disease did so.

Adaptor Proteins, Signal Transducing↗

Prevalence of functional dyspepsia and its relationship with Helicobacter pylori infection in a Japanese population.

AIM: To investigate the prevalence of functional dyspepsia and Helicobacter pylori infection and their relationship in a Japanese population. METHODS: Two thousand five hundred people who visited Shimane Institute of Health Science for their annual medical check-up from September 1998 to August 1999 were prospectively enrolled in the study. After routine medical examination, including an upper gastrointestinal study and an ultrasonographic examination, all subjects were asked standard questions to check for the presence of any symptoms that suggested dyspepsia. Helicobacter pylori infection was determined by using a serum IgG antibody concentration with an ELISA. RESULTS: Of the 2,500 persons investigated, 2,263 showed no abnormal finding in any medical examination. The presence or absence of symptoms and H. pylori infection was investigated in these 2,263 cases. Of these, 201 people (8.9%) experienced nausea, fullness and/or early satiety and were diagnosed as having dysmotility-like dyspepsia, while 118 people (5.2%) experienced pain localized to the epigastrium and were diagnosed as having ulcer-like dyspepsia. The frequency of these symptoms had a tendency to decline with age, although this was not statistically significant. In contrast, the rate of H. pylori infection increased with age. There was no significant relationship between H. pylori infection and any type of functional dyspepsia. CONCLUSIONS: Helicobacter pylori infection does not influence the prevalence of the dysmotility-like and ulcer-like dyspeptic symptoms.

Adult↗

Predominant nocturnal acid reflux in patients with Los Angeles grade C and D reflux esophagitis.

BACKGROUND AND AIMS: Nocturnal gastric acid breakthrough (NAB) is defined as an intragastric pH < 4.0 lasting more than 1 h during the night in patients taking a proton pump inhibitor (PPI). Gastroesophageal reflux disease (GERD) patients with nocturnal gastroesophageal acid reflux accompanied by NAB are thought to be refractory to PPI treatment. The aim of this study was to endoscopically identify the patients with predominant nocturnal gastroesophageal acid reflux. METHODS: The subjects were 37 patients with erosive reflux esophagitis (Los Angeles classification (LA) grade A, 12; B, 10; C, eight; and D, seven cases) and a control group of 20 patients without esophagitis. The results of ambulatory 24 h gastric and esophageal pH monitoring were compared among different grades of esophagitis. RESULTS: Gastroesophageal reflux during 24 h in patients with high-grade esophagitis was more frequent than for patients with low-grade esophagitis or no esophagitis. Although the length of esophageal acid exposure (percentage time with pH < 4.0) in patients with grade A or without esophagitis was longer in the daytime, that in patients with grades C and D was longer during the night. The reason for the delayed nocturnal acid exposure was the longer nocturnal acid clearance in high-grade reflux esophagitis. CONCLUSIONS: Nocturnal exposure of the esophagus to acid occurs frequently in patients with LA grades C and D esophagitis. Thus, the existence of NAB with resulting nocturnal acid reflux should be considered when the patient with high-grade esophagitis shows resistance to PPI treatment.

Adult↗

Influence of Helicobacter pylori infection on the prevalence of reflux esophagitis in Japanese patients.

BACKGROUND AND AIM: Reflux esophagitis is caused by esophageal motor dysfunction in patients with sufficient gastric acid secretion. Helicobacter pylori causes atrophic gastritis and influences gastric acid secretion. Hiatus hernia (HH) of the esophagus causes motor dysfunction in the lower esophagus. Therefore, this study aimed to test whether H. pylori infection, gastric mucosal atrophy and HH are predictive factors for reflux esophagitis. METHODS: Helicobacter pylori infection was examined in 781 patients by the measurement of serum immunoglobulin (Ig)G antibody, bacteriological culture and histological examination of biopsy specimens. The prevalence of HH, endoscopically identified gastric mucosal atrophy (closed- or open-type) and reflux esophagitis were investigated by reviewing endoscopic films. Investigated patients were divided into three age groups, under 49, 50-69, and over 70 years. The prevalence of esophagitis, H. pylori infection, gastric mucosal atrophy, and HH were compared to identify the possible predictive factors for reflux esophagitis by using logistic regression analysis. RESULTS: Sixty-nine patients with reflux esophagitis were found among the 781 investigated cases. The odds ratios of negative H. pylori infection, endoscopically identified closed-type gastric mucosal atrophy, and HH for the prevalence of reflux esophagitis were 1.342, 1.751 and 5.527, respectively. These results indicated that the presence of H. pylori infection was only a weak negative risk factor, and that HH was the most reliable endoscopic predictive factor for reflux esophagitis. CONCLUSION: Helicobacter pylori infection is a weak negative risk factor for the prevalence of reflux esophagitis, while HH is the most reliable predictive factor.

Aged↗

Selective antagonism by naloxonazine of antinociception by Tyr-D-Arg-Phe-beta-Ala, a novel dermorphin analogue with high affinity at mu-opioid receptors.

To examine the role of mu-opioid receptor subtypes, we assessed the antinociceptive effect of H-Tyr-D-Arg-Phe-beta-Ala-OH (TAPA), an analogue of dermorphin N-terminal peptide in mice, using the tail-flick test. Intracerebroventricularly (i.c.v.) or intrathecally (i.t.) injected TAPA produced potent antinociception with tail-flick as a thermal noxious stimulus. The selective mu(1)-opioid receptor antagonist, naloxonazine (35 mg/kg, s.c.), or the selective mu-opioid receptor antagonist, beta-funaltrexamine, 24 h before testing antagonized the antinociceptive effect of i.t. or i.c.v. TAPA on the response to noxious stimuli. Pretreatment with beta-funaltrexamine completely antagonized the antinociception by both i.c.v. and i.t. administered TAPA and [D-Ala(2), Me-Phe(4), Gly(ol)(5)]enkephalin (DAMGO). Especially in the tail-flick test, pretreatment with naloxonazine produced a marked rightward displacement of the i.t. TAPA dose-response curve for antinociception. Though DAMGO is a highly selective mu-opioid receptor agonist, pretreatment with naloxonazine partially blocked the antinociceptive response to DAMGO after i.c.v., but not after i. t. injection. These results indicate that TAPA can act as a highly selective mu(1)-opioid receptor agonist (notable naloxonazine-sensitive receptor agonist) at not only the supraspinal level, but also the spinal level. These data also reveal different antinociceptive mechanisms for DAMGO and for TAPA.

Analgesics↗

CYP2C19 genotype status and intragastric pH during dosing with lansoprazole or rabeprazole.

BACKGROUND: CYP2C19 has an important role in the catabolism of several proton pump inhibitors. However, the relative contribution of CYP2C19-mediated metabolism varies among the different proton pump inhibitors. AIM: To determine the effect of CYP2C19 genotype status on intragastric pH during dosing with lansoprazole or rabeprazole. SUBJECTS AND METHODS: The subjects were 20 male volunteers without Helicobacter pylori infection. Their CYP2C19 genotype status was determined by a polymerase chain reaction-restriction fragment length polymorphism method. Twenty-four-hour monitoring of intragastric acidity was performed three times: once without medication, once on the last day of a 7-day course of rabeprazole, and once on the last day of a 7-day course of lansoprazole. RESULTS: Subjects were divided into three groups on the basis of their CYP2C19 genotype status: homozygous extensive metabolizers (homo-EMs, n=7), heterozygous extensive metabolizers (hetero-EMs, n=9), and poor metabolizers (PMs, n=4). The median pH during rabeprazole administration was not influenced by CYP2C19 genotype. On the other hand, the median pH in PMs during lansoprazole dosing was higher than in homo-EMs and hetero-EMs. The percentage of time with pH < 4.0 had a similar tendency to that of median pH. CONCLUSION: CYP2C19 genotype status influences gastric acid suppression by lansoprazole, but not by rabeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Differential involvement of mu-opioid receptor subtypes in endomorphin-1- and -2-induced antinociception.

We investigated the role of mu-opioid receptor subtypes in both endomorphin-1 and endomorphin-2 induced antinociception in mice using supraspinally mediated behavior. With tail pressure as a mechanical noxious stimulus, both intracerebroventricularly (i.c.v.) and intrathecally (i.t.) injected-endomorphins produced potent and significant antinociceptive activity. Antinociception induced by i.t. and i.c.v. injection of endomorphin-1 was not reversed by pretreatment with a selective mu1-opioid receptor antagonist, naloxonazine (35 mg/kg, s.c.). By contrast, antinociception induced by i.t. and i.c.v. endomorphin-2 was significantly decreased by mu1-opioid receptor antagonist. Antinociception of both i.t. and i.c.v. endomorphin-1 and -2 was completely reversed by pretreatment with beta-funaltrexamine (40 mg/kg, s.c.). The results indicate that endomorphins may produce antinociception through the distinct mu1 and mu2 subtypes of mu-opioid receptor.

Analgesics, Opioid↗

Percutaneous cephalic vein approach for permanent pacemaker implantation.

Implantation of permanent pacemaker leads into the cephalic vein within the deltopectoral groove is enhanced by introduction of a flexible guidewire into the brachial vein at the antecubital fossa, which is then advanced to the subclavian vein. The cephalic vein within the deltopectoral groove is easily found by incision with the guidewire as a marker. A pacing lead or leads can be inserted along the guidewire or by using a sheath advanced over the guidewire. The procedure was performed on 32 patients and the pacing leads of 28 procedures (DDD 15, VDD 9 and WI 4) were inserted using the cephalic vein without complications.

Aged↗

Identification of a 100-kb region of common allelic loss on chromosome bands 10q25-q26 in human endometrial cancer.

In human endometrial cancer, we have previously identified a 790-kb region of common allelic loss in chromosome bands 10q25-q26, flanked by D10S587 and D10S1723. We constructed a contig covering the entire deleted region using YACs, PACs, and BACs. Five overlapping cosmid clones derived from YAC clones completely covered the entire deleted region: its size was estimated to be no larger than 200 kb. We further performed two-color fluorescence in situ hybridization (FISH) analysis to confirm the deletion and narrowed down the deleted region to 100 kb or less; it was covered by three overlapping cosmid clones that were included in one BAC clone. Restriction endonuclease mapping identified a region in which NotI, SalI, SmaI, and Xhol were clustered, suggesting the possible existence of a CpG island.

Chromosome Banding↗

The PTEN, BAX, and IGFIIR genes are mutated in endometrial atypical hyperplasia.

To pursue the pathogenesis of endometrial carcinogenesis, we investigated microsatellite instability, mutations in the PTEN, TGF beta RII, IGFIIR, and BAX genes, and LOHs on 10q in 18 putative endometrial premalignant lesions (11 endometrial atypical hyperplasias (ATHs), 2 complex hyperplasias, and 5 simple hyperplasias) as well as 8 endometrial cancers (ECs). In the ATH cases, MSIs as well as LOHs at 10q were observed at frequencies similar to those in ECs. Mutations in PTEN, BAX, and IGFIIR were observed only in ATHs and ECs. These results suggest that (1) PTEN, BAX, and IGFIIR are already mutated in ATHs, and (2) ATH is one of the precursor lesions which could lead to EC.

Endometrial Neoplasms↗

Leukocyte emigration in normal calves and calves with leukocyte adhesion deficiency.

The emigration of leukocytes from calves with beta 2 integrin deficiency (BLAD) into bronchoalveolar spaces and scraped tissues was compared to that of normal calves. Polymorphonuclear neutrophils were found in bronchoalveolar lavage fluid from BLAD-affected calves showing chronic pneumonia. The neutrophils were complement receptor type 3 (CR3)-negative when characterized by flow cytometric analysis using anti-CD18 monoclonal antibody. Chemiluminescent response mediated by CR3 in neutrophils isolated from bronchoalveolar lavage fluid from BLAD-calves showed similar findings obtained from CR3-deficient neutrophils. Neutrophils from normal calves migrated into scraped tissue which was prepared in an upper gluteal surface area, whereas few leukocytes from calves with BLAD migrated to the scraped tissue, evaluated by skin window (Rebuck) method. These findings confirmed the extravasation of CR3-deficient leukocytes into bronchoalveolar lumen in BLAD calves, and demonstrated in vivo characteristics of extravasating property of normal and CR3-deficient neutrophils into scraped tissues.

Animals↗

Spermine binding to GC-rich DNA: experimental and theoretical studies.

The DNA binding of spermine has been studied using experimental and computational approaches. Spermine blocks 5'-GC interstrand crosslinking by 2,5-diaziridinylbenzoquinone in the oligonucleotide duplex 5'-CTTCCAAGATGCATCAGATG 5'-CATCTGATGCATCTTGGAAG (where the underlined nucleotide bases represent the crosslinking site). Molecular dynamics simulations suggest that this is a result of preferential spermine binding at the 5'-GC major groove site of the oligonucleotide. A further simulation with a GC-alternating sequence shows a similar preference for the 5'-GC step. In a simulation including multiple spermine molecules, occupation of alternate 5'-GC steps occurred. From this, we deduced a mechanism for the experimentally observed cooperativity of spermine binding to poly(dGdC)2.

Aziridines↗