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Biomedical subjects

H Arai

Publications and source records attributed to H Arai.

At least 307 records · Page 17Linked to original sources
PubMed1998

Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia.

A disturbance of glutamatergic transmission has been suggested to contribute to the development of schizophrenic pathophysiology based primarily on the ability of glutamate receptor antagonists to induce schizophrenic-like symptoms, and recent studies suggesting reduced glutamatergic function in the prefrontal cortex (PFC) of individuals with a diagnosis of schizophrenia. In order to investigate this hypothesis further, the expression of several 'glutamatergic' markers, the metabotropic glutamate receptors (mGluRs; mGluR3, 5) and the human excitatory amino acid transporter (EAAT2) were compared in the PFC of normal individuals and schizophrenics. The present results showed that glial cells in the pyramidal layers of the PFC from schizophrenics had decreased EAAT2 mRNA content relative to controls in Brodmann areas 9 and 10. The cellular levels of expression of the two mGluR signals investigated (mGluR3, and 5) were not significantly changed relative to controls except for an increase in the neuronal mGluR5 in the pyramidal cell layers of area 11. Comparing the ratio of cellular mGluR expression to that of EAAT2, the mGluR/EAAT2 ratio showed that schizophrenics had a significantly increased mGluR/EAAT2 ratios in the pyramidal cell layers of all three PFC regions examined. The glutamate content of consecutive sections analyzed by high pressure liquid chromatography (HPLC), although decreased in schizophrenics did not reach significance and did not correlate with either EAAT2 or mGluR mRNA content. These results are discussed in the light of current results on the neurochemistry and pharmacology of schizophrenia.

Aged↗
PubMed1998

Regulation of Pseudomonas aeruginosa hemF and hemN by the dual action of the redox response regulators Anr and Dnr.

The oxidative decarboxylation of coproporphyrinogen III catalysed by an oxygen-dependent oxidase (HemF) and an oxygen-independent dehydrogenase (HemN) is one of the key regulatory points of haem biosynthesis in Pseudomonas aeruginosa. To investigate the oxygen-dependent regulation of hemF and hemN, the corresponding genes were cloned from the P. aeruginosa chromosome. Recognition sequences for the Fnr-type transcriptional regulator Anr were detected -44.5 bp from the 5' end of the hemF mRNA transcript and at an optimal distance of -41.5 bp with respect to the transcriptional start of hemN. An approximately 10-fold anaerobic induction of hemN gene expression was mediated by the dual action of Anr and a second Fnr-type regulator, Dnr. Regulation by both proteins required the Anr recognition sequence. Surprisingly, aerobic expression of hemN was dependent only on Anr. An anr mutant did not contain detectable amounts of hemN mRNA and accumulated coproporphyrin III both aerobically and anaerobically, indicating the importance of HemN for aerobic and anaerobic haem formation. Mutation of hemN and hemF did not abolish aerobic or anaerobic growth, indicating the existence of an additional HemN-type enzyme, which was termed HemZ. Expression of hemF was induced approximately 20-fold during anaerobic growth and, as was found for hemN, both Anr and Dnr were required for anaerobic induction. Paradoxically, oxygen is necessary for HemF catalysis, suggesting the existence of an additional physiological function for the P. aeruginosa HemF protein.

Aerobiosis↗
PubMed1998

Effect of Helicobacter pylori infection on gastric juice pH.

BACKGROUND: How Helicobacter pylori infection affects gastric acid secretion is still unclear. METHODS: Gastric juice pH, ammonia concentration in gastric juice, serum gastrin level, and grade of gastritis in accordance with the Sydney System were determined for patients with gastric ulcer (GU) and duodenal ulcer (DU) before and after treatment with lansoprazole and amoxicillin, and results were compared with those of H. pylori-negative controls. RESULTS: Scores for H. pylori density, atrophy, metaplasia, and activity of gastritis in the corpus were higher in patients with GU, especially those with proximally located GU, than in those with DU. Gastric juice pH was significantly higher in GU patients than in DU patients and controls. After H. pylori eradication, gastric juice pH and serum gastrin levels in both GU and DU patients were significantly decreased to control levels. In patients without eradication, no significant changes in these factors were observed. CONCLUSIONS: These findings suggest that H. pylori infection and gastritis in the corpus suppress acid secretion and increase gastric juice pH, resulting in hypergastrinemia, and that eradication of H. pylori normalizes acid secretion and serum gastrin levels.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Clipping of an aneurysm of a fenestrated basilar artery.

We describe the case of a fenestrated basilar artery aneurysm successfully clipped by means of a right presigmoid petrosal approach. Three-dimensional CT angiography enabled the surgeon to plan an approach to an aneurysm in this unique location, and the presigmoid petrosal approach was suitable for clipping of the aneurysm.

Cerebral Angiography↗
PubMed1998

Analyses of mutation and loss of heterozygosity of coding sequences of the entire transforming growth factor beta type II receptor gene in sporadic human gastric cancer.

Mutations in the transforming growth factor beta type II receptor (TGFbetaRII) gene have been detected in several human cancer types exhibiting microsatellite instability. Using intron primers previously reported for examination of the entire coding region of the TGFbetaRII gene, 29 sporadic gastric cancers were screened with non-radioactive single strand conformation polymorphism and subsequent DNA sequencing analysis. Mutations of the TGFbetaRII gene were detected in three out of 29 tumors (10%). Two cases showed deletions in a polyadenine tract in both alleles and was positively associated with replication error. One case had an insertion of GA dinucleotide sequence in one allele. Mutations of the TGFbetaRII gene were restricted to exon 3 and other coding regions were not affected. Loss of heterozygosity was detected by analyzing a polymorphic site in intron 2. Three out of nine (33%) informative cases, which were all of intestinal type and advanced cases, showed loss of heterozygosity but neither TGFbetaRII mutation nor replication error was found in these cases. Immunoreactivity of TGFbetaRII in tumor tissues was reduced to a different extent in the gastric cancer with genetically abnormal transforming growth factor. Although the numbers studied are small, homozygous (A)10 deletion or loss of heterozygosity of TGFbetaRII is involved in tumorigenesis and progression of at least some part of sporadic gastric cancer.

Humans↗
PubMed1998

Amount of Helicobacter pylori in gastric mucus during anti-H. pylori treatment.

Helicobacter pylori is present in infected patients not only on the gastric epithelial cell surface but also in gastric mucus. We developed a competitive polymerase chain reaction (cPCR) method for quantitative measurement of H. pylori in gastric mucus. The aim of this study was to determine the number of H. pylori in gastric mucus before and after anti-H. pylori treatment. Patients with duodenal ulcer were treated with lansoprazole alone (n = 11) or lansoprazole and amoxycillin (n = 12). The amount of H. pylori in gastric mucus was measured over time by a cPCR assay. Helicobacter pylori infection was also tested for using histology, culture, and the rapid urease test (RUT). Although most patients treated with lansoprazole alone had become H. pylori-negative by the end of treatment when tested by histology, RUT, and culture, a large number of H. pylori organisms were found in the gastric mucus at that time by cPCR. These patients returned to being H. pylori positive 1 to 12 months later on the basis of histology, RUT, and culture. However, cPCR results indicated eradication of H. pylori by the end of treatment in eight of the 12 patients treated with lansoprazole and amoxicillin, and these patients remained H. pylori negative on histology, RUT, culture, and cPCR 1 to 12 months later. Testing for H. pylori in gastric mucus is thus useful for precise determination of the success or failure of H. pylori eradication therapy.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

Changes in work performances in obstructive sleep apnea patients after dental appliance therapy.

The effects of dental appliances on work performances of obstructive sleep apnea syndrome (OSAS) is not well examined. This study evaluated the polysomnographic and psychological findings before and after therapy. Nine patients were diagnosed OSAS by nocturnal polysomnography. The psychological batter, was performed from 13:00 to 14:00, which consisted of Uchida-Kraepelin psychodiagnostic test (U-K's test) and Bourdon's cancellation test (Bourdon's test). Approximately 3 months after the treatment, the examinations were performed. Apnea and desaturation index decreased significantly after the therapy. In addition, sleep architecture improved after the therapy compared with that before the therapy. Dysfunction of task performances, such as mean level of work amounts in U-K's test, mean error, mean performance time and mean deviation in Bourdon's test improved after therapy. We conclude that dental appliances therapy is effective not only to apnea but also to work performance in OSAS.

Adult↗
PubMed1998

Transforming growth factor beta type II receptor (TGF beta RII) mutation in gastric lymphoma without mutator phenotype.

A new mutation in the serine-threonine kinase domain of the transforming growth factor beta type II receptor (TGF beta RII) was found in a case of diffuse, B cell non-Hodgkin's lymphoma of the stomach. A missense mutation (ACA to GCA, Thr to Ala) was detected in exon 5, and a wild type allele was also present. This is the first naturally occurring mutation in the kinase domain of this gene identified in human primary lymphoma. The replication error at three loci was negative, and the poly A tract of exon 3, which is frequently a target of mismatch repair genes, was intact. Malignant lymphoma of B cell origin in the stomach is an addition to an expanding catalogue of tumors with TGF beta RII alterations, and the biological sequelae of the change in the functional domain and the clinical characteristics of the patient in this study are intriguing.

Aged↗
PubMed1998

A novel marker of Schwann cells and myelin of the peripheral nervous system.

Cellular markers are useful in the immunohistochemical studies of normal and pathological tissues. Herein, the development of a monoclonal antibody, Schwann/2E, which reacts with Schwann cells and myelin of the peripheral nervous system (PNS) is described. The Schwann/2E antibody was secreted by a hybridoma of mouse myeloma cells and mouse spleen cells that were immunized in vivo with a cytoskeletal fraction of the human spinal nerve. This antibody immunostained formalin-fixed, paraffin-embedded human, rat, and mouse tissue by the indirect immunoperoxidase method. Schwann cells and myelin of the PNS were intensely labeled by the Schwann/2E antibody. Both the nuclei and cytoplasm of the Schwann cells were labeled. As shown by a comparative light and an electron microscopic study, the Schwann/2E antibody immunoreacted with the Schwann cells that had myelinated axons, but not with those that had unmyelinated axons. The endoneurial fibroblast was not immunolabeled. This antibody slightly stained the endothelial cells of the lung and kidney. Myelin and oligodendroglia of the central nervous system did not react with the Schwann/2E antibody. The Schwann/2E antigen was stable in several histological fixatives. These results indicate that, under normal and pathological conditions, the Schwann/2E antibody could be a useful immunohistochemical marker of Schwann cells and myelin of the PNS.

Animals↗
PubMed1998

The inhibition of DNA synthesis by prostaglandin E2 in human gingival fibroblasts is independent of the cyclic AMP-protein kinase A signal transduction pathway.

In this study we attempted to clarify the mechanism of the inhibitory effects of PGE2 on DNA synthesis in Gin-1 (fibroblasts derived from healthy human gingiva) from the aspect of the cyclic AMP-dependent protein kinase signal transduction pathway. PGE2 upregulated intracellular cyclic AMP accumulation and inhibited DNA synthesis in Gin-1 in a dose-dependent manner. When the PGE2-induced intracellular cyclic AMP accumulation was further enhanced by treatment with the cyclic AMP-phosphodiesterase inhibitor, IBMX, the inhibitory effect of PGE2 on DNA synthesis was also enhanced. Furthermore, when we examined the effects of forskolin, an activator of cyclic AMP production, on intracellular cyclic AMP accumulation and DNA synthesis, similar results were obtained. However, inhibitors of cyclic AMP-dependent protein kinase (protein kinase A) such as HA1004 did not diminish the inhibitory effect of PGE2 on DNA synthesis in Gin-1. These results suggest that in Gin-1, PGE2-induced cyclic AMP accumulation may not lead to the activation of protein kinase A or protein kinase A activity may not relate directly to the growth inhibitory effect of PGE2, and that PGE2 does not inhibit DNA synthesis through the cyclic AMP-protein kinase A signal transduction pathway in Gin-1.

1-Methyl-3-isobutylxanthine↗
PubMed1998

Histamine-releasing properties of T-3762, a novel fluoroquinolone antimicrobial agent in intravenous use. I. Effects of doses and infusion rate on blood pressure, heart rate and plasma histamine concentration.

T-3762, a newly developed fluoroquinolone antimicrobial agent, ciprofloxacin (CPFX) and ofloxacin (OFLX) were administered intravenously to anesthetized dogs by intravenous infusion, and blood pressure, heart rate and plasma histamine concentrations were monitored. T-3762 decreased blood pressure by 12.0%, without alterations in heart rate and plasma histamine concentration, only when infused at 150 mg/min. CPFX and OFLX both produced a rapid decrease in blood pressure in a dose-related manner, with an accompanying decrease in heart rate, but to a lesser extent. After infusion at 150 mg/min, CPFX caused death in 2 animals within a few minutes, while OFLX produced maximum decreases in blood pressure and heart rate, by 69.0% and 26.4%, respectively. The infusion of these 2 agents resulted in dose-related increases in plasma histamine concentrations parallel to the decreases in blood pressure: the maximum, attained with CPFX at 50 mg/min and OFLX at 150 mg/min, were 379.2 and 167.8 ng/ml, respectively. For CPFX and OFLX, the relationship between the maximum levels of decreased blood pressure and increased histamine concentration in plasma was highly significant. The hypotension induced by CPFX was efficiently reduced by the pretreatment of animals with antihistamines. The results from this study suggest that hypotension induced in dogs following the intravenous infusion of fluoroquinolone antimicrobial agents may be dependent on their ability to cause histamine release from cells and tissues, and indicates that T-3762 is devoid of this ability in comparison to CPFX and OFLX.

Animals↗
PubMed1998

Histamine-releasing properties of T-3762, a novel fluoroquinolone antimicrobial agent in intravenous use. II. Dermovascular permeability-increasing effect and action on peritoneal mast cells.

To predict the actions of T-3762, a newly developed fluoroquinolone antimicrobial agent, as well as ciprofloxacin (CPFX) and ofloxacin (OFLX), on injection sites when dosed parenterally, their ability to increase cutaneous vascular permeability in dogs and to release histamine from rat peritoneal mast cells was examined. CPFX and OFLX increased cutaneous vascular permeability in concentrations ranging from 16 to 32 microg/ml, while T-3762 was inactive at 2000 microg/ml. The vascular permeability-increasing activities of these drugs were inhibited efficiently by pretreatment with a combined dose of diphenhydramine and cimetidine. CPFX induced histamine release from rat mast cells in a dose-dependent manner, whereas T-3762 was ineffective. Therefore, it is concluded that fluoroquinolone antimicrobial agents may have the ability to cause an increase in cutaneous vascular permeability by releasing histamine from mast cells at the injection site when administered parenterally, and that T-3762 has minimum activity among the agents tested in this study.

Animals↗
PubMed1998

[Synthesis and antiulcer activity of N-2-(2-hydroxy-2-phenyl)ethyl-N"-(methanesulfonyl)guanidine analogue of ranitidine. Development of a new antiulcer agent T-593].

A series of the aryl-substituted N'-2-(2-hydroxy-2-phenyl)ethyl derivatives of N"-methanesulfonyl-N-2-((5-dimethylaminomethyl or 5-methylaminomethyl) furfurylthio)ethylguanidine have been synthesized as potential antisecretory and mucosal protective antiulcer agents. The synthetic routes involves, at the last stage, the reaction of 2-hydroxy-2-phenylethylamines with N-2-(furfurylthio)-ethyl-N'-methanesulfonyl-S-methylisothiourea or its O-phenylisourea counterpart. The primary screening test to assess the inhibitory activity of the synthetic compounds on histamine-induced gastric acid secretion was carried out in anesthetized rats by the lumen-perfusion technique of Ghosh and Schild and also by the pylorus-ligated preparation method. The best profile of histamine H2-antagonist activity was much better than that of the prototype ranitidine, and obtained with N'-(2-(2-hydroxy-2-(4-hydroxyphenyl)) ethyl-N"-methanesulfonyl-N-2-(5-(methylaminomethyl)furfurylthio)et hylguanidine (12f), which was also characterized by enhancing the gastric mucosal blood flow in rabbits as observed by the thermoelectric method. This compound 12f, designated as T-593, significantly inhibited the formation of the indomethacin-induced gastric lesions in rats; 3.5-fold more potent than ranitidine, but 4-fold less active than famotidine. On the other hand, T-593 and famotidine displayed comparable activities in healing the acetic acid-induced gastric ulcer with and without the dosing of indomethacin. Additional notable features of T-593, as determined in rats, are that its protective effect on the hemorrhagic shock-induced lesion under the prior dosing of histamine is ca. 10- and 2-fold greater than ranitidine and famotidine, respectively, and that a decrease in the gastric mucosal blood flow caused by a partial blood-withdrawal is more strongly recovered with T-593 than with famotidine. These experimental results suggest that the antiulcer efficacy of T-593 can be explained by its dual activities: antisecretion of gastric acid and, more importantly, protection of gastric mucous membrane.

Animals↗
PubMed1998

[Characteristics of T-593, a novel antiulcer agent, and each of its enantiomers on pharmacodynamics].

T-593 consists of two optical isomers, (-)-S and (+)-R. Our previous report showed that T-593 has biphasic effects, that is a long-lasting antisecretory action and an improving effect on gastric mucosal blood flow (GMBF). In this study, we compared the sole potency of each isomer on these bi-phasic effects. On the anti-secretory action investigated by the pylorus-ligation method, the (-)-S-isomer showed strong inhibition, while the (+)-R-isomer showed no effect, whereas the GMBF improvement was provided by the (+)-R-isomer. These results show the bi-phasic effects of racemic T-593 are separately derived from each isomer. The (-)-S-isomer strongly inhibited acute gastric mucosal lesion formation, with a potency comparable to T-593 itself, while the (+)-R-isomer showed less effect. Chronic gastric ulcer induced by acetic acid was, however, not healed by the sole treatment of each optical isomer, while racemic T-593 showed a significant effect. This result shows not only anti-secretion but also GMBF improvement is necessary to heal the chronic ulcer. This interesting property of T-593 is expected to raise the quality of ulcer healing (QOUH) and also may prevent ulcer recurrence.

Animals↗
PubMed1998

[Effect of T-593 on gastric bleeding and lesions induced by indomethacin and water-immersion stress in rats: improving effect of T-593 on reduced gastric mucosal blood flow in rats].

The effect of T-593, a novel antiulcer agent, was investigated with respect to gastric bleeding and lesions induced by indomethacin (3 mg/kg, s.c.) and water (23 degrees C) immersion stress (IM-WIS) with perfusion of HCl (0.13N) into the rat stomach. It was found that the total amounts of gastric bleeding and lesions after IM-WIS with perfusion of HCl were more significantly decreased in T-593 (1 mg/kg, i.v., 0.1 mg/kg/hr, d.i.)- and secretion (15 CU/kg/hr, d.i.)-treated rats, respectively. On the other hand, famotidine (1 mg/kg, i.v.) did not affect gastric bleeding and lesions. The gastric mucosal blood flow (GMBF) reduction was induced by IM-WIS. T-593 (0.03-0.1 mg/kg/hr, d.i.) inhibited the GMBF reduction dose-dependently. The GMBF improvement by T-593 disappeared with pretreatment of L-NAME (2 mg/kg, s.c.) and was recovered by L-arginine (50 mg/kg, i.v.). This indicates that GMBF improvement by T-593 is dependent on EDRF (NO). This interesting property of T-593 is expected to contribute to the clinical promotion of ulcer healing.

Animals↗
PubMed1998

[Influence of T-593 on the recurrence and relapse of cryocautery-induced gastric ulcer in rats: sequential observation with an endoscope and histological evaluation].

We investigated the influence of T-593, a novel anti-ulcer agent, on the recurrence and relapse of cryocautery-induced gastric ulcer in rats, in comparison with the action of famotidine and ranitidine. The drugs were administered from the 7th to the 119th day and then discontinued to the 190th day after induction of gastric ulcer. The healing, recurrence and relapse process of gastric ulcer was sequentially observed with an endoscope. In the control group, the reduction of ulcer index was observed until the 76th day after ulcer induction followed by aggravation, suggesting the recurrence and relapse occurred on cryocautery-induced gastric ulcer in rats. In the famotidine and ranitidine groups, the recurrence and relapse occurred after cessation of administration. The recurrence and/or relapse rate of T-593 was lower than those of other drugs. In the histological measurement, the grades of heterotopic regenerated gland and inflammatory cell infiltration of T-593 was lower than those of the control and other drugs in the ulcer area. From these results, it is concluded that T-593 induces ulcer healing with a lower recurrence and/or relapse rate of ulcers than other conventional H2-antagonists, and T-593 may thus be a useful anti-ulcer drug for clinical therapy.

Animals↗