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Biomedical subjects

H Ishii

Publications and source records attributed to H Ishii.

At least 19 recordsLinked to original sources

Long-term efficacy and safety of clarithromycin treatment in patients with diffuse panbronchiolitis.

Diffuse panbronchiolitis (DPB) can now be cured with long-term erythromycin treatment. Our group conducted a prospective open trial of long-term treatment with a macrolide antibiotic, clarithromycin. We studied ten patients who were treated for 4 years with oral clarithromycin (200 mg once a day). Pulmonary function test, blood gas analysis, comprehensive improvement score, and bacterial culture of sputum were examined at 3, 6, 12 months, and at 2, 3, 4 years after the initiation of the therapy. Pulmonary function improved in most of the patients within 6 months: the forced expiratory volume in one second showed a maximal increase from a mean (SE) value of 1.74 (0.12) l at baseline to 2.31 (0.22) l at 6 months (P < 0.01) and the volume (l) of forced vital capacity also showed a maximal increase within 6 months. The partial pressure of arterial oxygen at rest significantly increased at 3-6 months. The comprehensive improvement score also reached maximum within 6 months in nine of the patients. The majority of patients have developed sputum culture in which bacteria were negative within 6 months after the therapy. All of the patients maintained a stable condition with continued therapy, and no side effects of clarithromycin were observed during the study. This prospective study demonstrated that 6-month treatment with clarithromycin might be necessary to improve the clinical conditions of patients with DPB and the drug could be safely used for a long term.

Adult↗

Interaction of leptin with gastric myofibroblast transdifferentiation in Helicobacter pylori-infected Mongolian gerbils: the effect of rebamipide.

BACKGROUND: Our recent histochemical studies have revealed the marked increase of myofibroblasts in the Helicobacter pylori-infected Mongolian gerbil fundic mucosa, while the mediators, which facilitate the conversion of fibroblasts to the myofibroblasts have remained unknown. AIM: The present study was undertaken to clarify the alteration of leptin in the control and H. pylori-infected Mongolian gerbil stomach. The effector sites of rebamipide were also investigated in relation to leptin. METHODS: The localization of leptin was investigated by the indirect immunofluorescence. Plasma leptin levels were determined by ELISA method. The localization of 3H-rebamipide binding sites was investigated by autoradiography. RESULTS: Serum leptin content in H. pylori-infected Mongolian gerbils was significantly increased. The presence of leptin immunoreactivity was recognized in the endothelial cells of the microcirculatory network and very weakly in the glandular cells in the control group, while in the H. pylori-infected group leptin was markedly recognized in the mesenchymal cells. Rebamipide bound to the fibroblasts and surface mucous cells and decreased the leptin immunoreactivity in the gastric mucosa. CONCLUSIONS: Leptin was mostly found in the mesenchymal cells. Rebamipide administration brought about the decrease of leptin in the gastric mucosaof the H. pylori-infected gerbils.

Alanine↗

Effects of rebamipide, a gastro-protective drug on the Helicobacter pylori status and inflammation in the gastric mucosa of patients with gastric ulcer: a randomized double-blind placebo-controlled multicentre trial.

AIMS: To investigate the effects of rebamipide on the Helicobacter pylori eradication rate with amoxicillin and omeprazole. The trial also examined its histological effects on gastro-mucosal inflammation after eradication. METHODS: Two hundred and six H. pylori-positive patients with active gastric ulcer underwent 8-week based therapy (OA) consisting of 2-week amoxicillin with omeprazole and subsequent 6-week omeprazole. They randomly received either rebamipide (OA-R) or placebo (OA-P) for 16 weeks: combined with the OA based therapy, and subsequently for another 8 weeks. Besides eradication rate, inflammatory findings of gastric mucosa after eradication were evaluated histologically. RESULTS: Per Protocol Set analysis showed no significant difference in eradication rate between OA-R (64.6%; 95% confidence interval, 54.3-75.0%) and OA-P (67.9%; 95% CI, 57.6-78.3%). Histological findings in the gastric mucosa of the ulcer region, however, indicated a significant improvement (P = 0.017) in inflammation scores in OA-R (1.84 +/- 0.41) compared with that in OA-P (2.02 +/- 0.39) after 16-weeks of treatment. This suppressive effect on inflammation was observed even in the OA-R patients unsuccessfully eradicated. CONCLUSION: Rebamipide demonstrated a suppressive effect on the persistent and possibly chronic inflammation in the gastric mucosa of the ulcer region after eradication, but the drug did not improve the eradication rate.

Adult↗

Rebamipide binds to iNOS-positive cells in acetic acid-treated but not in ethanol-treated rat gastric mucosa.

BACKGROUND: Rebamipide is a gastroprotective agent to stimulate prostaglandin generation in gastric mucosa and attenuate the activity of neutrophils, but direct evidence for the effector sites of this agent has remained to be clarified. AIM: The present study was undertaken to show the effector sites of rebamipide in control and ulcer-provoked rats. METHODS: The rats were divided into control, acetic acid- and ethanol-treated rats. In the acetic acid-treated group, 100% acetic acid was attached to the serosal surface of the stomach for 30 s, 7 days before the experiments. In the ethanol-treated group, a dose of 0.5 mL/100 g body weight of 50% ethanol was administered through orogastric intubation 2 h before the experiments. Using the unfixed cryostat sections, aqueous solution of 3H-rebamipide was applied and the localization of the binding sites of rebamipide was investigated by autoradiography. RESULTS: In the control rats, rebamipide was found to bind to the surface epithelial cells. In the ethanol-treated group, few binding sites were observed in the damaged gastric mucosa. In the acetic acid-treated group, the marked accumulation of the binding sites of 3H-rebamipide was observed in the mesenchymal cells in the lamina propria mucosae between the regenerated gastric epithelial cells. Combination of autoradiography and immunohistochemistry has revealed that iNOS-immunoreactive cells had the strong binding of rebamipide in the acetic acid-treated group. Some of these cells were CD68-positive macrophages, while others were CD68-negative, corresponding to polymorphonuclear leucocytes. In the ethanol-treated acute gastric mucosal injury group, few binding sites were observed in the damaged gastric mucosa. CONCLUSIONS: Autoradiography has made it clear that rebamipide binds to iNOS-positive cells in the gastric mucosa 7 days after acetic acid-treatment.

Acetic Acid↗

Frameless stereotactic radiosurgery with mobile CT, mask immobilization and micro-multileaf collimators.

We present frameless stereotactic radiosurgery using mobile CT, thermal plastic mask fixation, a vacuum-form body immobilizer and micro-multileaf collimators. A linear accelerator and a self-moving helical CT scanner gantry were installed in the same room. The isocenter of irradiation can be also aligned with the center of the CT gantry by rotating the couch. A thermal plastic mask and vacuum-form body immobilizer was used for registration and immobilization. The advantages of this system are as follows: 1) Accurate and painless frameless fractionated irradiation can be performed smoothly, as the patient's head is fixed without exchanging the couch from CT scanning to irradiation system. 2) This mask system can be applied to children, infants or adults with a previous craniotomy bone flap that must have a fixation pin placed into it. This system can be also used for fractionated radiotherapy without painful skull pin-fixed frame. 3) 1 mm micro-multileaf collimators enable irregular contour irradiation. 4) Image fusion (among CT, MRI, angiography, and PET) and 3D images can be used for irradiation planning. 5) This system can be used on any part of the body. 6) This system can be installed in any irradiation room without any extension or new construction.

Brain Neoplasms↗

Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulphate colitis in mice.

BACKGROUND: Interleukin (IL)-12 and IL-18 are major interferon (IFN)-gamma-inducing factors that collaborate with each other. The present study was conducted to determine the distinct roles of IL-12 and IL-18 in the development of dextran sulphate sodium (DSS) colitis in mice. METHODS: Colitis was induced in IL-12p35(-/-), IL-18(-/-), IL-18 receptor(-/-) and control mice with DSS. Clinical and histopathological analysis was conducted using survival rate, weight loss score, diarrhoea score, bloody stool score and histological score. In addition, cytokine production by lamina propria mononuclear cells (LPMCs) was examined using the specific enzyme-linked immunoassay. RESULTS: IL-12p35(-/-) mice developed only a mild disease associated with no lethality and few histopathological abnormalities. In contrast, IL-18(-/-) and IL-18R(-/-) mice developed more severe colitis associated with high lethality and more histopathological abnormalities compared with control mice. LPMCs from DSS-fed IL-18(-/-) mice produced significantly higher amounts of IFN-gamma, while LPMCs from DSS-fed IL-12(-/-) mice produced lower amounts of IFN-gamma and tumour necrosis factor (TNF)-alpha compared with control mice. CONCLUSION: These results suggest that IL-18 might function with manners different from IL-12 at some pathological conditions in the development of colitis.

Animals↗

High serum concentrations of surfactant protein A in usual interstitial pneumonia compared with non-specific interstitial pneumonia.

BACKGROUND: The pathological diagnosis of interstitial lung diseases (ILD) by surgical lung biopsy is important for clinical decision making. There is a need, however, to use serum markers for differentiating usual interstitial pneumonia (UIP) from other ILD. Surfactant protein (SP)-A, SP-D, KL-6, sialyl SSEA-1 (SLX), and sialyl Lewis(a) (CA19-9) are useful markers for the diagnosis and evaluation of activity of ILD. We have investigated the usefulness of these proteins as markers of UIP. METHODS: Serum and bronchoalveolar lavage (BAL) fluid levels of the above five markers were measured in 57 patients with various forms of ILD (19 with UIP, 12 with non-specific interstitial pneumonia (NSIP), eight with bronchiolitis obliterans organising pneumonia (BOOP), and 10 with sarcoidosis), eight patients with the control disease (diffuse panbronchiolitis (DPB)), and nine healthy volunteers. RESULTS: Serum levels of SP-A, SP-D, and KL-6 in patients with UIP and NSIP were significantly higher than in healthy volunteers. In particular, the serum levels of SP-A in patients with UIP were significantly higher than in patients with NSIP (p<0.0001, mean difference -58.3 ng/ml, 95% confidence interval -81.6 to -35.0), and BAL fluid levels of SP-D in patients with UIP were significantly lower than in patients with NSIP (p=0.01, mean difference 322.4 ng/ml, 95% confidence interval 79.3 to 565.5). CONCLUSION: Serum SP-A levels may be clinically useful as a biomarker to differentiate between UIP and NSIP.

Adult↗

Contrast enhancement patterns of hepatic tumours during the vascular phase using coded harmonic imaging and Levovist to differentiate hepatocellular carcinoma from other focal lesions.

The purpose of the study was to assess contrast enhancement patterns of hepatic tumours during the vascular phase using contrast-enhanced ultrasound and Levovist to differentiate hepatocellular carcinoma from other hepatic tumours. 89 hepatic tumours in 82 consecutive patients were evaluated using coded harmonic ultrasound imaging. The procedure used a phase inversion harmonic technique and coded technology. We observed images for 2 min from the beginning of the administration as the vascular phase using continuous transmission and intermittent transmissions of 1 s or 2 s. The contrast agent Levovist was administered intravenously as a bolus infusion of 2.5 g. Tumour vessels with flow spreading into the tumour and/or homogeneously stained hyperechoic images were observed in 34 of the 41 hepatocellular carcinomas (sensitivity, 82.9%; specificity, 93.8%). Peripheral enhancements were characteristic of intrahepatic cholangiocarcinoma and metastatic hepatic tumours (sensitivity, 60.0% and 83.3%; specificity, 65.5% and 76.4%, respectively). Pooling at the periphery or throughout the tumour was apparent only in haemangioma (sensitivity, 76.5%; specificity, 100%). A tortuous feeding artery and spoke-like vascularization were evident only in the two focal nodular hyperplasias. Contrast-enhanced ultrasound using coded harmonic ultrasound imaging and Levovist provided detailed information about tumour vascularity and contrast enhancement patterns in hepatic tumours.

Adult↗

[Acute massive pulmonary embolism occurring during orthopedic surgery].

We present an emergent surgical case of massive pulmonary embolism (MPE) that happened during orthopedic surgery. A 38-year-old man, who had bone fractures with his lumbar vertebra and ankle, underwent the internal fixation of the tibial bone with tourniquet under general anesthesia in our hospital. During this surgery, the pulse oxymeter showed a drop of arterial oxygen saturation suddenly. Immediately we installed a transesophageal echo (TEE) probe in the patient, and detected enlargement of the right ventricle and right atrial thrombus. Half an hour later, the thrombus disappeared from the right atrium and the patient showed hemodynamic shock. We performed emergent embolectomy immediately under moderate hypothermic complete cardiopulmonary bypass. The postoperative course was uneventful, and one month later, his orthopedic surgery underwent completely. We conclude that TEE was a useful devise for the diagnosis of intraoperative MPE.

Adult↗

Simultaneous detection and removal of organomercurial compounds by using the genetic expression system of an organomercury lyase from the transposon Tn MERI1.

Using a newly identified organomercury lyase gene (merB3) expression system from Tn MERI1, the mercury resistance transposon first found in Gram-positive bacteria, a dual-purpose system to detect and remove organomercurial contamination was developed. A plasmid was constructed by fusing the promoterless luxAB genes as bioluminescence reporter genes downstream of the merB3 gene and its operator/promoter region. Another plasmid, encoding mer operon genes from merR1 to merA, was also constructed to generate an expression regulatory protein, MerR1, and a mercury reductase enzyme, MerA. These two plasmids were transformed into Escherichia coli cells to produce a biological system that can detect and remove environmental organomercury contamination. Organomercurial compounds, such as neurotoxic methylmercury at nanomolar levels, were detected using the biomonitoring system within a few minutes and were removed during the next few hours.

Bacterial Proteins↗

Differential gene expression of vascular endothelial growth factor isoforms and their receptors in the development of the rat masseter muscle.

The capillary network in the masseter muscle develops dramatically with the differentiation of muscle fibres after birth, especially around weaning. Here, developmental changes in mRNA expression for four splicing variants of vascular endothelial growth factor (VEGF) and for two distinct VEGF receptors (Fms-like tyrosine kinase (Flt-1) and kinase insert domain-containing receptor/fetal liver kinase-1 (KDR/Flk-1)) were studied in rat masseter. The relative abundance of VEGF (120) mRNA was the highest, representing 35% of total VEGF mRNA on day 7 after birth and gradually decreased with age to become approximately 5% on day 37. In contrast, VEGF (188) mRNA was very low in the newborn rat, but increased sharply before weaning and reached 40-50% of the total on day 50. Neither VEGF (144) nor VEGF(164) mRNA showed any significant change in abundance after birth. The expression of KDR/Flk-1 mRNA was transiently high in the early postnatal stage and gradually decreased with age, Flt-1 mRNA was stably expressed at a constant level after birth. These findings suggest that different combinations of VEGF isoforms and their receptors regulate angiogenesis in the development of the masseter muscle.

Alternative Splicing↗

Role of endothelin receptors in endothelin-1-induced morphological changes of hepatic sinusoidal endothelial fenestrae: morphometric evaluation with scanning electron microscopy.

Endothelin (ET)-1, a potent vasoconstrictor, is involved in the contraction of hepatic sinusoidal endothelial fenestrae (SEF) through ET-1 receptors. To clarify the role of each receptor (R) in ET-1 induced contraction of SEF, we studied the size of hepatic SEF under various experimental conditions. Scanning electron microscopy was used for morphometric analysis of the fenestrae of sinusoidal endothelial cells isolated from male Wistar rats under the following conditions: (1) control, (2) ET-1, (3) Bosentan (ET(A)-R+ET(B)-R antagonist)right arrowET-1, (4) BQ485 (ET(A)-R antagonist)right arrowET-1, (5) BQ788 (ET(B)-R antagonist)right arrowET-1. Each experiment was based on the observations of 200--205 fenestrae (15--20 fenestrae per cell, two cells per dish and six dishes). The diameter of the endothelial pores of the isolated sinusoidal endothelial cells was 123plus minus35 nm in group (1), 46plus minus21 nm in group (2), 130plus minus40 nm in group (3), 72plus minus28 nm in group (4), and 130plus minus27 nm in group (5). The differences between groups (2) and (4), and between groups (2) and (5), were statistically significant (P<0.05, P<0.01, respectively). Endothelin B receptor (ET(B)-R) antagonist pretreatment abolished the ET-1-induced contraction of SEF, whereas endothelin A receptor (ET(A)-R) antagonist pretreatment appeared to partially block this contraction. The present findings indicate that ET(B)-R plays a primary role in endothelin-1 induced SEF morphological changes, while ET(A)-R plays a subsidiary role.

Journal Article↗

No difference in the level of gastric mucosal cell apoptosis and proliferation in Helicobacter pylori-colonized p53 heterozygous knockout mice.

BACKGROUND: We previously reported that attenuated epithelial apoptosis and enhanced proliferation in comparison with mice might link to the specific carcinogenesis in Mongolian gerbils and suggested that the difference in both strains might be due to a difference in genetic background. p53 is a well-known tumour suppressor gene, mutation of which is also known to be involved in gastric cancer formation. AIM: The present study was designed to examine the level of gastric epithelial apoptosis and proliferation in p53 heterozygous knockout mice (p53+/-) colonized with Helicobacter pylori (Sydney strain: SS1). METHODS: Female p53+/- mice and wild-type controls were orally inoculated with SS1 and the stomachs were examined 24 weeks later. DNA fragmentation was measured by levels of cytoplasmic mono- & oligo-nucleosomes as well as by the TUNEL method. Gastric mucosal proliferative activity was morphometrically evaluated from the PCNA-stained tissue specimens. Gastric mucosal myeloperoxidase (MPO) activity was measured to evaluate mucosal inflammation. RESULTS: DNA fragmentation and the number of TUNEL-positive cells, as well as PCNA-positive cell number increased significantly in both groups of H. pylori-infected mice, suggesting that levels of apoptosis and proliferation may be independent of a deficiency of one p53 allele. MPO activity in p53+/- mice and wild-type controls increased to the same level. CONCLUSION: Although H. pylori inoculation per se induces an increase in cell turnover in mice, heterozygous mutation of p53 did not significantly modify the balance in cell apoptosis and proliferation.

Animals↗

Proton pump inhibitor modifies inflammatory reaction in human gastric mucosa infected by Helicobacter pylori.

AIM: To examine whether proton pump inhibitors modify the production of oxygen-derived free radicals and related cytokines in the human gastric mucosa infected with H. pylori. METHODS: Thirty-four H. pylori-positive peptic ulcer patients (23 gastric ulcer, 11 duodenal ulcer) were enrolled. Biopsy tissue samples were obtained endoscopically from the antrum and corpus. Tissue content of neutrophil myeloperoxidase (myeloperoxidase) and IL-8 was measured by ELISA. Mucosal production of oxygen-derived free radical was measured using luminol-dependent chemiluminescence (ChL). A proton pump inhibitor (either lansoprazole 30 mg, omeprazole 20 mg, or rabeprazole 10 mg) was administered daily by mouth to all patients for 8 weeks. Endoscopic examination was then repeated, and biochemical analysis was performed. RESULTS: Antral myeloperoxidase decreased significantly after proton pump inhibitor treatment (5.23 +/- 7.00-2.76 +/- 5.11 ng/mg, P < 0.02), but corpus myeloperoxidase was unchanged. IL-8 was also modified by proton pump inhibitors and these changes were parallel to those of myeloperoxidase. Corpus ChL was significantly increased from 88.5 +/- 69.8-159 +/- 172 counts/10 s/mg after proton pump inhibitor treatment, whereas antrum ChL was not altered. H. pylori infection rate was decreased in the antrum as well as the corpus. CONCLUSIONS: Proton pump inhibitor treatment stimulated oxygen-derived free radical production in the corpus mucosa.

Adult↗

Persistent increase in myofibroblasts in Helicobacter heilmannii-infected mice but not in Helicobacter pylori-infected Mongolian gerbils: colocalization of COX-2 and bFGF immunoreactivity.

BACKGROUND: The clinical significance of Helicobacter heilmannii infection remains uncertain, owing to the lack of a specific detection method. Recently, we reported a marked increase in myofibroblasts in the early stage of Helicobacter pylori infection in Monglian gerbils. AIM: The present study was designed to clarify changes in myofibroblasts, and in the immunoeactivities of basic fibroblast growth factor, cyclooxygenase-2 and inducible nitric oxide synthase after H. pylori infection in Monglian gerbils and H. heilmannii infection in mice. METHODS: After oral inoculation, changes in the location of bacteria and the immunoreactivity of myofibroblasts, basic fibroblast growth factor, cyclooxygenase-2 and inducible nitric oxide synthase were stained with the indirect immunofluorescent method and observed by confocal laser microscopy. RESULTS: In H. heilmannii-infected mice, the increases in myofibroblasts and in immunoreactivities of these three markers were sustained 12 months after infection. In H. pylori-infected Monglian gerbils, however, these increases were significant at 3 months but had returned to control levels at 12 months. CONCLUSIONS: Two types of Helicobacter infection showed different patterns of myofibroblast proliferation, coinciding with the extent of inflammation. These findings suggest that this difference may be related to the consequences of the infection.

Animals↗

Treatment with a proton pump inhibitor promotes corpus gastritis in patients with Helicobacter pylori-infected antrum-predominant gastritis.

BACKGROUND: Proton pump inhibitors have been reported to modify the level of Helicobacter pylori gastritis. AIM: To quantitatively investigate the effect of a proton pump inhibitor on the mucosal neutrophil reaction. METHODS: Forty-six H. pylori-infected patients (17 duodenal ulcer, 29 gastric ulcer) were enrolled. During endoscopic examination, biopsy samples were obtained from the antrum and the corpus. The tissue content of neutrophil myeloperoxidase was measured by enzyme-linked immunoabsorbent assay, and H. pylori infection was histologically assessed. A proton pump inhibitor was administered orally for 8 weeks. RESULTS: In the patients as a whole, antral myeloperoxidase decreased significantly after proton pump inhibitor treatment, but corpus myeloperoxidase remained largely unchanged. In duodenal ulcer patients, myeloperoxidase significantly decreased in the antrum, but increased in the corpus. In gastric ulcer patients, a significant reduction was observed in antral myeloperoxidase, but corpus myeloperoxidase remained unchanged. In the antral myeloperoxidase > corpus myeloperoxidase subgroup (n=24), antral myeloperoxidase significantly decreased, whereas corpus myeloperoxidase increased. No changes were observed at either site in the corpus myeloperoxidase > antral myeloperoxidase subgroup. Histology showed that the antral bacterial load of H. pylori decreased in all subgroups, but that it was mostly unchanged in the corpus. CONCLUSIONS: Proton pump inhibitor treatment stimulated the neutrophil reaction in the corpus mucosa of duodenal ulcer patients and of patients in whom antral neutrophil accumulation was more predominant than that of the corpus. This phenomenon may not be caused by increased bacterial density.

2-Pyridinylmethylsulfinylbenzimidazoles↗