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Biomedical subjects

A Kawamura

Publications and source records attributed to A Kawamura.

At least 19 recordsLinked to original sources

Structure and mechanism of arylamine N-acetyltransferases.

Arylamine N-acetyltransferases (NATs) are a family of phase II drug-metabolising enzymes which are important in the biotransformation of various aromatic and heterocyclic amines and hydroxylamines, arylhydrazines and arylhydrazides. NATs are present in a wide range of eukaryotes and prokaryotes. Humans have two functional NAT isoforms, both of which are highly polymorphic. The pharmacogenetics of NATs is an area which has been extensively studied. The determination of the X-ray crystal structure of NAT from Salmonella typhimurium led to the identification of the catalytically essential triad of residues: Cys-His-Asp, which is present in all functional NAT enzymes. Recent co-crystallisation data and in silico docking studies of NAT from Mycobacterium smegmatis with substrates and inhibitors have aided the identification of important contact residues within the active site. The X-ray crystal structures of four prokaryotic NAT proteins have now been determined, and these have been used to generate structural models of eukaryotic NATs, providing valuable insight into their active-site architecture. In addition to aiding crystallographic experiments, recent progress in the production of recombinant prokaryotic and eukaryotic NATs has allowed comparative studies of the kinetics and activity profiles of these enzymes. In this review we present an overview of recent structural and activity studies on NAT enzymes, and we outline how in silico methods may be used to predict NAT protein-ligand interactions based on the current knowledge.

Animals↗

[New method for preparing proximal anastomotic system].

Heartstring is a useful device. However, the device failure at the time of loading the seal into the delivery device is a troublesome issue. To avoid this problem, we invent a new method using 2 tourniquets made of 5 mm-wide woven Teflon tapes and plastic tubes. Using our method, the loading procedure became easier and more reliable.

Anastomosis, Surgical↗

[Successful surgical management of papillary muscle rupture following acute myocardial infarction in an elderly patient].

Papillary muscle rupture is rare but catastrophic complication of acute myocardial infarction. We report a 91-year-old woman who underwent successful management of papillary muscle rupture following acute myocardial infarction. She was transferred to our hospital because of severe pulmonary edema and cardiogenic shock. Echocardiography revealed severe mitral valve regurgitation due to total rupture of anterolateral papillary muscle. After intubation, intraaortic balloon pumping (IABP) and percutaneous cardiopulmonary support (PCPS) insertion, mitral valve replacement was successfully performed. She was discharged 134 days after operation. In papillary muscle rupture deteriorating hemodynamics, early diagnosis and immediate cardiopulmonary support are required before surgical treatment. She was, to the best of our knowledge, the oldest among the reported cases of successful surgical treatment of papillary muscle rupture in Japan.

Aged, 80 and over↗

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↗

A case of bullous pemphigoid associated with autoantibodies targeting antigenic sites other than the NC16a domain of BP180.

Bullous pemphigoid (BP) is associated with autoantibodies to the 180-kDa BP antigen (BP180), and the antigenic site exists on noncollagenous 16a (NC16a) domain of BP180. We now report a male BP patient whose IgG autoantibodies did not react against the NC16a domain of BP180 by either immunoblotting or ELISA, whereas they did react with BP180 extracted from normal human keratinocytes. Anti-BP180 cicatricial pemphigoid was ruled out due to the lack of conjunctival mucosal involvement and the absence of scarring in the oral cavity. Our findings indicate that there is an antigenic reactive region other than NC16a on the extracellular domain of BP180. There have been few reports describing detailed clinical features of BP caused by autoantibodies targeting antigenic sites other than the NC16a domain. We conclude that it is difficult to differentiate their clinical features from those associated with autoantibodies targeting the NC16a domain of BP180.

Autoantibodies↗

The origins of polypoidal choroidal vasculopathy.

BACKGROUND/AIM: There are two theories on the pathogenesis of polypoidal choroidal vasculopathy (PCV): variants in choroidal neovascularisation (CNV) and inner choroidal vessel abnormalities. On indocyanine green angiography (IGA) with a video camera system, PCV has a characteristic appearance, but inadequate image quality has made detailed interpretation difficult. This study aims to improve imaging, using confocal scanning laser ophthalmoscopy (SLO), to elucidate the pathogenesis of PCV. METHODS: High speed IGA with confocal SLO of 45 eyes (44 patients) showed typical PCV findings of a branching vascular network and polypoidal lesions. RESULTS: Vessels comprising branching networks began to fill simultaneously with the surrounding choroidal arteries in 38 eyes. Small numbers of vessels filling within a branching network, in the arterial and arteriovenous phases of IGA, showed focal dilatation, constriction, and tortuousity. Vessel abnormalities, corresponding to polypoidal lesions, existed within a network in eight eyes and included loops similar in calibre to network vessels, and numerous microaneurysmal dilatations of small vessels. Vessel pulsation was seen in 24 eyes. CONCLUSION: PCV is caused by inner choroidal vessel abnormalities, not CNV.

Aged↗

Cystic fibrosis presenting as kwashiorkor in a Sri Lankan infant.

Growth failure is a common presentation of patients with pancreatic insufficient cystic fibrosis. However, full blown kwashiorkor is extremely rare. Cystic fibrosis is also considered to be rare in the South Asian population. This report describes a Sri Lankan infant with cystic fibrosis who presented with clinical features of severe kwashiorkor.

Cystic Fibrosis↗

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↗

Development of a novel polycationic adsorbent for cryogel removal.

Cryogel, prevalent in the plasma of rheumatism patients, is a plasma fibronectin (pFN)-extra domain A containing FN (EDA(+)FN)-fibrinogen (Fbg) complex formed by adding heparin (HP) at a low temperature (4 degrees C). Although EDA(+)FN does not usually exist in normal plasma, its prevalence in rheumatic patients causes cryogelation in plasma. Removal of cryogel is thus a promising and novel approach to treating rheumatism. As HP-EDA(+)FN aggregate, which is induced by the main component of cryogel, is considered to be an anion, cationic materials capable of eliminating this anionic conjugate were innovated in this study. We found that an amino group density of 100-130 micromol/g (dry weight) of adsorbents prompted selective adsorption of the EDA(+)FN-HP complex. Elimination of EDA(+)FN as high as 80% accompanied by removal of the components of total FN (pFN) (10%) and Fbg (10%) in the model patient plasma was established.

Adsorption↗

Biological implication of conformational flexibility in ouabain: observations with two ouabain phosphate isomers.

Ouabain is a highly polar and unusually potent sodium pump inhibitor that possesses uncommon conformational flexibility in its steroid A-ring moiety. The biological significance of ring flection in the cardiotonic steroids has not been described. Accordingly, we prepared ouabain 1,5,19- and 1,11,19-phosphates. The former stabilizes the steroid A-ring chair conformation and the latter locks the A-ring in the half-boat conformation and decreases flection of the ABC-ring moiety. Using a dog kidney cell line (MDCK) in a pH microphysiometer (Cytosensor), ouabain and its 1,5,19-phosphate at 10(-5) M reduced the rate of extracellular acidification by 15-20%. During inhibitor washout, the rate of recovery from the 1,5,19-phosphate analogue was approximately 3 times faster than ouabain. The 1,11,19-phosphate at 10(-4) M elicited a weak ( approximately 7%) response, and the effects reversed approximately 44-fold faster than ouabain. Studies with purified Na(+),K(+)-ATPase showed that ouabain and its 1,5,19-phosphate analogue were of similar efficacy (EC(50) = 1.1 and 5.2 x 10(-7) M, respectively) and >100-fold more potent than the 1,11,19-phosphate analogue. Studies of the binding kinetics showed that the 1,5,19-phosphate analogue bound 3-fold and dissociated 16-fold faster from the purified Na(+),K(+)-ATPase than ouabain. Both analogues were competitive inhibitors of 3H-ouabain binding. Taken together, these results suggest that the marked conformational flexibility of the A-ring in ouabain ordinarily slows the initial binding of this steroid to the sodium pump. However, once ouabain is bound, flection of the steroidal A- and BC-rings is critical for the maintenance of high-affinity binding. Our results indicate that the ouabain-binding site is comprised of structurally mobile elements and highlight the roles that synchronization between receptor and ligand dynamics play as determinants of biological activity in this system.

Animals↗

An outbreak of food poisoning due to egg yolk reaction-negative Staphylococcus aureus.

An outbreak of staphylococcal food poisoning due to an egg yolk (EY) reaction-negative strain occurred in Japan. Twenty-one of 53 dam construction workers who ate boxed lunches prepared at their company cafeteria became ill, and eight required hospital treatment. The outbreak showed a typical incubation time (1.5-4 h with a median time of 2.7 h) and symptoms (vomiting and diarrhea) of staphylococcal food poisoning. Staphylococcus aureus, which produces staphylococcal enterotoxin (SE) A, was isolated from four fecal specimens of eight patients tested. Scrambled egg in the boxed lunches contained 20-40 ng/g of SEA, and 3.0 x 10(9)/g of viable S. aureus cells that produced this toxin. All isolates from patients and the food were EY reaction-negative, coagulase type II, and showed the same restriction fragment length polymorphism (RFLP) pattern. We concluded that the outbreak was caused by scrambled egg contaminated with EY reaction-negative S. aureus. In Japan, outbreaks of staphylococcal food poisoning are mainly caused by EY reaction-positive S. aureus, and EY reaction-negative colonies grown on agar plates containing EY are usually not analyzed further for detection of S. aureus. The present outbreak suggested that EY reaction-negative isolates should be subjected to further analysis to detect the causative agents of staphylococcal food poisoning.

Disease Outbreaks↗

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↗

Correlation between buccolingual inclination and wear of mandibular teeth in ancient and modern Japanese.

This study compared the correlation between the buccolingual inclination and the wear score of the mandibular teeth in Jomon (one of the ancestors of modern Japanese who lived from 5000 to 300 BC) and modern Japanese. Data were obtained from 40 modern male Japanese and 39 male Jomon skulls housed in the University Museum of the University of Tokyo and National Science Museum, Tokyo. For each specimen, three computed tomograms of coronal sections of the mandibular body were available. The second premolar, first molar and second molar of Jomon stood more vertically than those of modern Japanese. There were significant correlations between tooth wear and the buccolingual inclination of mandibular molars. When ancient and modern populations were compared, tooth wear was significantly greater and buccolingual tooth inclination was more vertical in the ancient people, who probably applied stronger masticatory forces than modern people. The results suggest that the mandibular molar orientation is more buccal and there is greater tooth wear in the first and second molars of people with strong masticatory function.

Bicuspid↗

Efficacy of ecabet sodium for Helicobacter pylori eradication triple therapy in comparison with a lansoprazole-based regimen.

BACKGROUND: The cytoprotective agent, ecabet sodium, inhibits urease activity and growth of Helicobacter pylori. AIM: To evaluate the efficacy and safety of ecabet sodium-based eradication of H. pylori infection, compared with a lansoprazole-based regimen, in a randomized multicentre study. SUBJECTS AND METHODS: A total of 120 H. pylori-positive patients were assigned to one of two treatment regimens for 2 weeks: ecabet sodium 1 g b.d., amoxicillin 500 mg t.d.s. and clarithromycin 400 mg b.d. (EAC: 60 patients); or lansoprazole 30 mg (o.m.) with the same antimicrobial agents (LAC: 60 patients). Cure of infection was assessed by a 13C-urea breath test 1 month after completion of treatment. RESULTS: One patient in the EAC group and two in the LAC group did not complete therapy because of an adverse event, and three did not undergo the 13C-urea breath test. Cure rates for the intention-to-treat, all-patients-treated and per protocol analysis in the EAC group were 85%, 86% and 88%, respectively, whereas those in the LAC group were 85%, 88% and 91%. There were no significant differences in cure rate or adverse events between the two regimens. CONCLUSIONS: Ecabet sodium in combination with amoxicillin and clarithromycin is as effective as lansoprazole-based eradication therapy for H. pylori.

2-Pyridinylmethylsulfinylbenzimidazoles↗

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↗

Influence of Helicobacter pylori infection and cetraxate on gastric mucosal blood flow during healing of endoscopic mucosal resection-induced ulcers.

BACKGROUND AND AIM: Helicobacter pylori (H. pylori) infection is known to affect the gastric microcirculation, and cetraxate is reported to accelerate gastric ulcer healing, possibly by augmenting gastric mucosal blood flow (MBF). The aim of this study is to clarify the effect of H. pylori infection and cetraxate on MBF during gastric ulcer healing. METHODS: Forty-two patients who had undergone endoscopic mucosal resection (EMR) were studied. Mucosal blood flow was measured by the use of a laser Doppler flowmeter in the surrounding mucosa and at the ulcer margin, before, 1 day, 1 week and 4 weeks after EMR. Helicobacter pylori infection was confirmed by the use of bacterial culture and histology. After EMR, patients were randomly assigned to receive 30 mg lansoprazole (u.i.d; L-regimen) or 30 mg lansoprazole (u.i.d.) with 200 mg cetraxate (q.i.d; LC-regimen) for 4 weeks. RESULTS: The MBF ratio (MBF at ulcer margin/MBF in surrounding mucosa) 1 week after EMR was significantly lower than that before or 4 weeks after EMR only in H. pylori-positive patients treated with the L-regimen. No such decrease in MBF was observed after 1 week in H. pylori-positive patients treated with the LC-regimen or in H. pylori-negative patients. CONCLUSION: A transient decrease in MBF was detected at the ulcer margin during healing of EMR-induced ulcers in H. pylori-infected patients. Cetraxate seemed to prevent this decrease in MBF.

2-Pyridinylmethylsulfinylbenzimidazoles↗

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↗