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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 181 records · Page 10Linked to original sources

Estrogen receptor levels and lipid peroxidation in hepatocellular carcinoma with hepatitis C virus infection.

AIMS/BACKGROUND: Our preliminary studies showed that estradiol suppresses hepatic carcinogenesis and fibrogenesis in animal models. Hepatic estrogen receptors (ERs) medicate estradiol action in the liver. This study was performed to assess possible implications of menopause and hepatic ER levels for the development of cirrhosis with hepatocellular carcinoma (HCC). METHODS: One thousand, one hundred and ninety-nine consecutive HCC patients with hepatitis C virus (HCV)-related cirrhosis were divided into two groups, based on a menopausal age of 49 years. Liver tissues were obtained during surgical resection of HCC and metastatic liver tumor. RESULTS: The proportion of females among the HCC subjects < or =49 years of age was significantly lower (15.0%) than was the proportion of females among subjects >49 years of age (29.8%). Univariate analysis showed that HCV-related cirrhotic patients who developed HCC were more likely to have low hepatic levels of ER and copper-zinc superoxide dismutase (CuZn-SOD) protein and a high hepatic level of a lipid peroxidation product, malondialdehyde (MDA). Logistic regression identified age greater than 49 years (odds ratio [OR]: 7.9, 95% confidence interval [CI]: 2.8-21.3), male sex (OR: 3.5, 95% CI: 1.3-10.2), a decreased ER level (OR: 16.8, 95% CI: 7.3-34.6), and an increased MDA (OR: 8.3, 95% CI: 2.8-24.0) as the variables independently associated with the development of HCC in HCV-infected patients with cirrhosis. ER level was significantly correlated with CuZn-SOD level (r=0.583) and was inversely proportional to MDA level (r=-0.553). The study also showed that ER levels in the cirrhotic livers from premenopausal females were significantly higher than in male cirrhotic livers. CONCLUSIONS: These findings suggest that increased lipid peroxidation and impaired SOD function in the liver may be associated with decreased hepatic ER levels in HCV-infected patients with cirrhosis and HCC, and that HCV-related cirrhotic women before menopause might have the ability to protect against developing HCC via hepatic ER.

Age Factors↗

Successful hyperbaric oxygen treatment of life-threatening hemorrhagic cystitis after allogeneic bone marrow transplantation.

Hemorrhagic cystitis (HC) is a major cause of morbidity after allogeneic bone marrow transplantation (BMT). Many therapies have been investigated to prevent or treat HC, but effective treatment for HC is still limited. While the efficacy of hyperbaric oxygen therapy has been established for HC due to chemotherapy and/or radiation therapy, its role in HC occurring after allogeneic BMT has yet to be defined. We report two cases of life-threatening late-onset HC after allogeneic BMT in children, which resolved after treatment with hyperbaric oxygen.

Bone Marrow Transplantation↗

Involvement of nitric oxide in chondrocyte cell death in chondro-osteophyte formation.

OBJECTIVE: To examine the nitric oxide (NO) production relevant to chondrocyte cell death in order to elucidate the mechanism of chondro-osteophyte formation in osteoarthrotic joints. DESIGN: Human chondro-osteophytes were obtained during total hip arthroplasty. Expression of inducible nitric oxide synthase (iNOS) mRNA was determined by in-situ hybridization. Localization of iNOS and nitrotyrosine at protein level were examined by immunohistochemistry. Cell death of chondrocytes were confirmed by both TUNEL method and transmission electron microscopy. RESULTS: The various populations of proliferative and hypertrophic chondrocytes expressed iNOS mRNA and iNOS as well as nitrotyrosine protein. Approximately 30% of hypertrophic chondrocytes forming chondro-osteophyte showed positive reaction to TUNEL staining. Electron microscopy confirmed both disintegrated and apoptotic chondrocytes in these zones. In the deep hypertrophic zone calcification was seen around each of the matrix vesicles and some masses of cell debris. CONCLUSION: Chondro-osteophyte formation involves NO production by chondrocytes. The expression and localization of iNOS and nitrotyrosine in chondro-osteophytes suggest the significant role of NO in chondrocyte hypertrophy and apoptosis.

Aged↗

Effects of nitric oxide donor and nitric oxide synthase inhibitor on ruminal contractions in conscious sheep.

The present study was planned to evaluate a role of nitric oxide (NO) in the regulation of regular ruminal contractions in conscious sheep. Intravenous infusion of S-nitroso-acetyl-DL-penicillamine (SNAP) at doses of 3-30 nmol kg(-1) min(-1)for 30 minutes inhibited both the amplitude and frequency of ruminal contractions in a dose-dependent manner. However, intravenous infusion of Nomega-nitro-L-arginine-methyl ester (L-NAME) at doses of 0.3-3.0 micromol kg(-1) min(-1)did not alter the basal tone of intraruminal pressure and the amplitude of ruminal contractions. The frequency of contractions was slightly inhibited by L-NAME infusion at 1.0 micromol kg(-1)min(-1). The effects of L-NAME were abolished by simultaneous infusion of L -arginine at 30 micromol kg(-1) min(-1). These results suggest that exogenous NO can diminish the ruminal contractions, while endogenous NO is not involved in the regulatory mechanism of basal tone and regular phasic contractions of the rumen in healthy sheep.

Animals↗

The clinical significance of MMP-1 expression in oesophageal carcinoma.

Matrix metalloproteinase-1 (MMP-1) is involved in the degradation of interstitial collagen and thus thought to play a role in invasion of carcinoma. We investigated 51 oesophageal carcinoma patients to clarify the significance of MMP-1. MMP-1 mRNA was demonstrated to be expressed exclusively in almost all carcinoma tissue specimens (T) (94.1%) by reverse transcription-polymerase chain reaction, but not found in normal mucosal tissue specimens (N). The mean T/N ratio of MMP-1 was 42.5 and cases with T/N > or = 10 had a higher incidence of cases involving muscularis propria than those with T/N < 10 which included all the cases involving the submucosa (P< 0.05). MMP-1 mRNA was significantly associated with both 40 kD (putative active MMP-1) and 50 kD (putative latent MMP-1) gelatinolytic bands (n = 17). These findings indicated that MMP-1 mRNA reflected the net function of MMP-1 and suggested MMP-1 to be involved in carcinoma invasive process. On the other hand, MMP-1 mRNA was inversely correlated with the patient prognosis (P< 0.01). These results indicated that MMP-1 might therefore play a crucial role in local invasion, but not in systemic dissemination. As a result, MMP-1 might be a novel prognostic factor independent from those previously reported in oesophageal carcinoma.

Aged↗

Mechanical strength of intramedullary pinning and transfragmental Kirschner wire fixation for Colles' fractures.

Four methods of distal radius fracture fixation were tested in this experimental biomechanical study of an unstable Colles' fracture model. Sixty artificial radial bones and seven pairs of cadaveric radii were used. Seven additional pairs of paired cadaveric radial epiphyses were used in separate perforation and cut-out tests. Tests with the artificial bones showed that the rigidity of the four tested fixation methods was comparable, except for proximal intramedullary pinning. The rigidity of the NODE fixation in the cadaveric radii was greater than that of transfragmental pinning. The load at failure was significantly greater for the NODE system than for the Kirschner wire models. Rigidity and failure loads showed a positive correlation with bone mineral density. The current study indicates the NODE system was the strongest of the fixation methods.

Biomechanical Phenomena↗

Analysis of urinary prostacyclin and thromboxane/prostacyclin ratio in patients with rheumatoid arthritis using gas chromatography/selected ion monitoring.

We investigated production of prostacyclin and the urinary ratio of thromboxane and prostacyclin in patients with rheumatoid arthritis. The prostacyclin production level was assessed according to the level of urinary 2,3-dinor-6-keto-prostaglandin F(1 alpha)measuring by gas chromatography/selected ion monitoring. In patients receiving medication, the prostacyclin level was lower and the thromboxane/prostacyclin ratio was greater compare with that of healthy volunteers. The prostacyclin level in patients without medication was approximately 4-fold higher than that of healthy volunteers and 8-fold higher than those of medicated groups. Although the ratio of the group without medication was similar to that of healthy volunteers, the urinary levels of each prostanoid were higher than those of other groups. Then, the ratios of groups receiving steroids were higher than that of other groups owing to high TX level. The present findings demonstrated that endogenous prostacyclin and thromboxane production increased in patients without medication, and prostacyclin production decreased with medication.

6-Ketoprostaglandin F1 alpha↗

Treatment of esophageal and gastric tumors.

In the diagnosis of early cancer, there are differences in the pathological criteria used by Western and Asian (Japanese) pathologists. The Vienna classification advocated by pathologists offers standard pathological criteria common to all endoscopists, and it has clarified the indications for the treatment of superficial lesions, including high-grade dysplasia and mucosal cancer. Endoscopic mucosal resection (EMR) is increasingly being used in the treatment of early cancer. Experience with EMR in the treatment of Barrett's esophagus with cancer has been reported, and the preliminary results are encouraging. Some technical variations and improvements in EMR procedures have been described. As an injection agent, the use of mucinous substances such as sodium hyaluronate has been reported. A cutting knife with an insulated tip has been designed, making the use of the precutting technique much safer. Studies have been conducted comparing the freehand technique with the cap technique for EMR, and it was found that the cap technique is generally better. Ablative treatment has also been used in many cases, with satisfactory results. In advanced cancer, self-expanding metallic stents have been used for palliative treatment, with generally satisfactory results. The range of applications for therapeutic endoscopy has continued to expand during the last two years in the treatment of esophageal and gastric tumors.

Esophageal Neoplasms↗

Microwave recanalization: thermal effects with nitinol and stainless-steel stents.

BACKGROUND AND STUDY AIMS: A previous study we conducted evaluated the thermal effects of microwave irradiation when attempting recanalization of a nitinol stent occluded by tumor ingrowth. The present study evaluates the thermal effects of microwave irradiation on different stents in vitro. METHODS: The thermal response to microwave energy was evaluated in a muscle-equivalent phantom containing a nitinol (Accuflex) or stainless-steel stent (Wallstent). The phantom temperature was monitored continuously at different distances from an electrode, with either stent type in place. The tip of the electrode was either in contact with the stent or not in contact with it. RESULTS: The steel stent showed a smaller temperature increase than nitinol at 2 mm from the electrode. Without electrode contact, the stents did not differ significantly during the first 40s of irradiation. The stents did not differ significantly with regard to temperatures further from the electrode. When the electrode was in contact with the stent, the rise in temperature was significantly greater with the stainless-steel stent than with the nitinol one, but the phantom temperature did not exceed 45 degrees C with either of the stents. CONCLUSIONS: In patients with a Wallstent stainless-steel stent, microwave coagulation therapy to recanalize stent occlusions appears to be feasible in the same conditions as with an Accuflex nitinol stent.

Alloys↗

Transpapillary microwave coagulation therapy for recanalizing self-expandable metallic stents occluded by tumor ingrowth: initial experience.

Percutaneous microwave coagulation for recanalizing stents occluded by tumor ingrowth has been reported. With this technique, however, the percutaneous drain diminishes the quality of life in patients with unresectable tumors and a limited prognosis. Transpapillary microwave ablation was attempted in three patients with occluded stents. After a sheath had been inserted into the proximal hepatic duct across the occluded region, a microwave electrode was introduced into the intrahepatic duct via the sheath. We used microwave therapy with an output power of 40 W, based on our previous in vitro study. Except in one patient, the stents were successfully recanalized with one or two attempts. In one patient who underwent ablation in the intrahepatic duct, a 1.8-mm electrode enabled recanalization of the stent. In another who underwent ablation in the extrahepatic duct, however, a larger electrode was required. There were no procedure-related complications. Transpapillary microwave coagulation of occluded stents appears to be an alternative to percutaneous microwave coagulation with an electrode fitting the stent size. The technique might be easier with the use of a redesigned electrode with a guide wire lumen.

Aged↗

Changes in the pattern of horseradish peroxidase diffusion into predentin and dentin after cavity preparation in rat molars.

OBJECTIVE: The purpose of this study was to examine the process of reducing dentin permeability in adult rat molars after cavity preparation with horseradish peroxidase as a tracer. STUDY DESIGN: Class V cavities were prepared on the upper first molars of 18 rats. Horseradish peroxidase was injected into the vascular system at intervals of 3 hours and 3, 5, 7, 10, and 14 days after cavity preparation, and frozen sections were processed by the diaminobenzidine procedure. RESULTS: Horseradish peroxidase reaction products were noted in the dentinal tubules immediately beneath the cavity up until 14 days after cavity preparation. An abrupt stoppage of reactive products caused by impermeable junctional zone formation at the interface of the primary dentin and reparative dentin was observed at 14 days after cavity preparation. CONCLUSION: Reparative dentin formation and subsequent impermeable junctional zone formation participate in the reduction of dentin permeability after cavity preparation.

Animals↗

Connectivity perception of partly occluded gratings in 4-month-old infants.

Four groups of eight 4-month-old infants were each habituated to one of four displays consisting of a grating of either low (0.4 cycle deg(-1) or high (1.2 cycles deg(-1) spatial frequency, whose central portion was covered up with a horizontal occluder which was either narrow (1.33 deg) or broad (4.17 deg). Posthabituation displays consisted of a complete grating of the same frequency as the habituated grating, along with a separate grating whose central portion was replaced with a black gap of the same height as the occluder in the habituation displays. All the infants, except those who were habituated to the high frequency with the broad occluder, looked longer at the separate grating than the complete grating display during posthabituation trials. Previously, we found that infants under 1 month of age perceive the grating continuation only when the occluder height is less than about 0.5 cycle of the grating; our present results show that this figure increases to about 1.6 cycles of the grating frequency in the case of 4-month-old infants. These findings indicate that those developmental changes depend on both the sufficiency of visual information available and the efficiency of the perceptual ability of infants for grasping spatial relationships.

Analysis of Variance↗

Rapid and simple determination of histamine-N-methyl transferase activity by high-performance liquid chromatography with UV detection.

A rapid, simple and low-cost assay method of histamine-N-methyltransferase activity was developed. Methylhistamine, which was separated from the enzymatic reaction system on reversed-phase high-performance liquid chromatography using an ion-paired chromatographic technique, was detected spectrophotometrically at 226 nm. The mobile phase used for the separation of methylhistamine was 0.05M NH4H2PO4 (pH 3.0) containing 2 mM of sodium octanesulfonate. The new assay technique could detect methylhistamine as an enzyme activity product of histamine-N-methyltransferase in the brain and kidney of rats. Chloropheniramine maleate, an antihistamine, activated the histamine-N-methyltransferase. Whether neurotransmitter or neuromodulator, the role of histamine in the brain has not yet been made clear. Therefore, the present method could be applicable for the enzymatic investigation of histamine metabolism in central nervous system or inflammatory reactions.

Animals↗

Effects of pranlukast, a leukotriene receptor antagonist, on airway inflammation in mild asthmatics.

To determine the anti-inflammatory actions of pranlukast, a cysteinyl leuklotriene receptor antagonist, we measured exhaled nitric oxide (NO) concentrations and eosinophil ratio in induced sputum of three groups of mild asthmatics (n = 30): treated with bronchodilators alone, with bronchodilators and inhaled steroid (beclomethasone dipropionate; 400 microg/day), and bronchodilators and pranlukast (450 mg/day). Pranlukast (450 mg/day) reduced the eosinophil ratio in the induced sputum significantly (p < 0.01) without a major effect on the concentration of exhaled NO. Pranlukast also increased values of peak expiratory flow significantly (p < 0.05). Pranlukast may be useful for mild asthmatics, in part through its ability to suppress eosinophilic airway infiltration.

Adult↗

Cloning and expression of the catalase gene from the anaerobic bacterium Desulfovibrio vulgaris (Miyazaki F).

We identified a gene encoding a catalase from the anaerobic bacteria Desulfovibrio vulgaris (Miyazaki F), and the expression of its gene in Escherichia coli. The 3.3-kbp DNA fragment isolated from D. vulgaris (Miyazaki F) by double digestion with EcoRI and SalI was found to produce a protein that binds protoheme IX as a prosthetic group in E. coli. This DNA fragment contained a putative open reading frame (Kat) and one part of another open reading frame (ORF-1). The amino acid sequence of the amino terminus of the protein purified from the transformed cells was consistent with that deduced from the nucleotide sequence of Kat in the cloned fragment of D. vulgaris (Miyazaki F) DNA, which may include promoter and regulatory sequences. The nucleotide sequence of Kat indicates that the protein is composed of 479 amino acids per monomer. The recombinant catalase was found to be active in the decomposition of hydrogen peroxide, as are other catalases from aerobic organisms, but its K(m) value was much greater. The hydrogen peroxide stress against D. vulgaris (Miyazaki F) induced the activity for the decomposition of hydrogen peroxide somewhat, so the catalase gene may not work effectively in vivo.

Amino Acid Sequence↗

Chimeric Na(+)/H(+) antiporters constructed from NhaA of Helicobacter pylori and Escherichia coli: implications for domains of NhaA for pH sensing.

In order to delineate regions which play a role in the regulation of Na(+)/H(+) antiporter NhaA activity by pH, we analyzed the antiporter activities of various chimeric mutants constructed from specific portions of NhaA from Escherichia coli and Helicobacter pylori (EC and HP NhaA). HP NhaA contains 10 residues at the amino-terminus, and 38 residues in a loop region between the eighth and ninth transmembrane spans (loop 8), which are absent in EC NhaA. Deletion from HP NhaA or insertion into EC NhaA of the sequences caused almost no change in pH-dependent antiport activities relative to in the case of the wild-type parent molecules. Chimeras consisting of various combinations of the amino-terminal (amino terminus to sixth or eighth transmembrane span) and carboxy-terminal (seventh or ninth transmembrane span to the carboxy-terminus) regions of EC and HP NhaA showed antiporter activity profiles intermediate between those of the parent molecules. These results show that the two HP-specific sequences are not directly involved in the mechanism of pH sensing by HP NhaA and that the pH sensitivity of NhaA activity is not determined by the amino- or carboxy-terminal regions of NhaA alone, but may be due to interaction between unconserved residues in the two domains. In addition, it was suggested that loop 8 functions primarily as a hinge in both NhaA molecules.

Amino Acid Sequence↗

A serine/threonine kinase which causes apoptosis-like cell death interacts with a calcineurin B-like protein capable of binding Na(+)/H(+) exchanger.

We surveyed proteins capable of binding to the cytoplasmic domain of Na(+)/H(+) exchanger (NHE)1 in a rat brain cDNA library with the yeast two-hybrid system. One clone obtained coded for a protein reported previously as a human calcineurin homologous protein (CHP). Since CHP is homologous to the regulatory subunit B of calcineurin, we expected a possible interacting partner of CHP like the catalytic subunit of calcineurin (calcineurin A), and surveyed this putative partner again with the yeast two-hybrid system. A clone thus obtained coded for a kinase, which is basically the same as that reported for human DRAK2. Overexpression of the rat homologue of DRAK2 caused apoptosis-like cell death of NIH3T3 cells, which was dependent on the kinase activity, confirming the previous result for DRAK2. The purified CHP and rat DRAK2 proteins synthesized in Escherichia coli could bind in vitro. CHP and rat DRAK2 expressed in COS-7 cells were found to be localized in the Golgi apparatus and nucleus, respectively. Some of them was also found in the membrane peripheral region. When they were co-expressed in the same cells, most of CHP moved to the nucleus where rat DRAK2 is located, suggesting in vivo interaction of these proteins. However, minor but significant fractions of both proteins were also found in the membrane peripheral region. Rat DRAK2 is expressed highly in thymus, spleen, and testis, where the apoptosis plays an important role in physiology.

Amino Acid Sequence↗