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Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 55 records · Page 3Linked to original sources
PubMed1996

Involvement of tachykinin receptors in oedema formation and plasma extravasation induced by substance P, neurokinin A, and neurokinin B in mouse ear.

The involvement of tachykinin receptors in skin inflammation induced by substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) was investigated in mouse ears. Intradermal injection of tachykinins (0.1-100 pmol/site) into the ear skin produced oedema formation. RP 67580 (ED50: 0.34 mg/kg, i.v.) and SR 140333 (ED50: 0.19 mg/kg, i.v.), the non-peptide NK1 receptor antagonists, inhibited SP-induced oedema. SR 140333 was also effective in preventing NKA- and NKB-induced oedema. SR 48968 (1 mg/kg, i.v.), a non-peptide NK2 antagonist, induced a significant inhibition of NKA-induced oedema but had no effect on the response to SP and NKB. SR 142801 (3 mg/kg, i.v.), a non-peptide NK3 antagonist, prevented only NKB-induced oedema. In contrast, phosphoramidon (0.1 and 0.5 mg/kg, i.v.), an endopeptidase inhibitor, enhanced the oedema response to tachykinins. SR 140333, SR 48968, and SR 142801 blocked the enhancement by phosphoramidon of the response to SP, NKA, and NKB, respectively. Plasma extravasation in ear skin was induced by i.v. injection of tachykinins (0.7-17.6 nmol/kg). RP 67580 (ED50: 0.15 mg/kg, i.v. for SP) and SR 140333 (ED50: 14.3 micrograms/kg, i.v. for SP) inhibited tachykinin-induced plasma extravasation in ear skin. However, SR 48968 and SR 140281 had no effect on the vascular response to tachykinins. Chlorpheniramine (4 mg/kg, i.v.), a histamine H1 blocker, inhibited the response to local SP but not to i.v. SP. These results suggest that in addition to the NK1 receptors, functional NK2 and NK3 receptors may participate in the oedema response to local NKA and NKB in the ear skin. However, it appears that NK1 receptors on blood vessels are involved predominantly in plasma extravasation induced by i.v. tachykinins in the ear.

Animals↗
PubMed1996

Effect of the tachykinin receptor antagonists, SR 140333, FK 888, and SR 142801, on capsaicin-induced mouse ear oedema.

We examined the effect of SR 140333, a nonpeptide NK1 receptor antagonist, FK 888, a peptide NK1 antagonist, and SR 142801, a non-peptide NK3 antagonist, on ear oedema induced by topical application of capsaicin (250 micrograms/ear) in mice. SR 140333 (ED50:39 micrograms/kg, i.v.) dose-dependently inhibited the oedema response to capsaicin, whereas FK 888 (1.0 mg/kg, i.v.) and SR 142801 (3.0 mg/kg, i.v.) had no effect. Furthermore, SR 140333 significantly (p < 0.001) suppressed ear oedema in response to intradermal injection of substance P (SP) (100 pmol/site) by i.v. administration (0.1 mg/kg,) and co-injection (50 pmol/site). In contrast, FK 888 (1.0 mg/kg, i.v. and 500 pmol/site) was ineffective in the response to SP. The present results suggest that the difference in effects of the two NK1 receptor antagonists on the oedema response to capsaicin is due to species differences in affinities for the NK1 receptor in the mouse skin. Moreover, it seems unlikely that the NK3 receptor is involved primarily in capsaicin-induced mouse ear oedema.

Animals↗
PubMed1996

Morphological identification of and collagen synthesis by periacinar fibroblastoid cells cultured from isolated rat pancreatic acini.

Rat pancreatic periacinar fibroblastoid cells (PFCs) appear to be involved in intralobular fibrosis and acinar cell regeneration. We isolated pancreatic acini of the rat, cultured the fibroblastoid cells, and characterized the cells morphologically and immunohistochemically. Isolated acini were seeded on culture dishes, and spindle-shaped cells migrated and proliferated. On Electronmicroscopic examination, microfilament bundles were seen, and the intracellular localization of vimentin, alpha-smooth muscle actin, and non-muscle myosin was identified immunohistochemically. These findings strongly suggest that the cells were myofibroblast-like. The PFCs were also demonstrated, immunohistochemically, to contain prolyl hydroxylase, type-I procollagen, type-III procollagen, type-IV collagen, fibronectin, and laminin. Stimulation by transforming growth factor beta 1 (TGF beta 1) increased intracellular immunoreactive prolyl hydroxylase and collagen synthesis in the PFCs. These findings indicate that PFCs proliferate in culture as myofibroblast-like cells and synthesize extracellular matrix components. It is possible that PFCs are involved in intralobular fibrosis in response to stimulation with TGF beta 1.

Animals↗
PubMed1996

Ulcerative colitis complicated by gastroduodenal lesions.

A case of ulcerative colitis complicated with gastric and duodenal lesions is reported. The patient was a 17-year-old male who was admitted with bloody diarrhea and abdominal pain. Based on the endoscopic and histological findings of the colon, a diagnosis of ulcerative colitis was made. Upper gastrointestinal endoscopy showed multiple erosions and granular changes in the antral greater curvature of the stomach and descending portion of the duodenum. Histological examination of the stomach and duodenum revealed marked inflammatory cell infiltration and crypt abscesses. Clinically, the gastric and duodenal lesions did not respond to antiulcer drugs, but were alleviated by steroid. It was concluded that the pathogenesis of the gastric and duodenal lesions in this patient was similar to that of the colonic lesions of ulcerative colitis.

Adolescent↗
PubMed1996

Polyostotic fibrous dysplasia. A long-term follow up of 8 patients.

Eight patients who had polyostotic fibrous dysplasia were followed up for more than 10 years. One had the Albright syndrome. Two of 3 proximal femoral lesions which were treated before puberty by either curettage and bone grafting or by osteotomy, developed progressive deformity during the growth period. One of 2 proximal femoral lesions treated by curettage and bone grafting after the age of 18 also developed a deformity. Two tibial lesions operated on at the age of one and 30 years remained stable. The histological findings showed more active lesions in young patients compared with adults.

Adolescent↗
PubMed1996

The mus-8 gene of Neurospora crassa encodes a structural and functional homolog of the Rad6 protein of Saccharomyces cerevisiae.

We cloned a DNA repair gene, mus-8, of Neurospora crassa and sequenced the genomic DNA and cDNA. Nucleotide-sequence analysis indicated that the mus-8 gene contains an open reading frame (ORF) of 456 bp, interrupted by three small introns. The deduced amino-acid sequence showed that the mus-8 gene encodes a 17 kDa protein which has 77.5% and 83.3% identity to the Rad6 protein of Saccharomyces cerevisiae and the rhp6(+) protein of Schizosaccharomyces pombe, respectively. The Rad6 protein is a ubiquitin-conjugating enzyme (E2) and is required for DNA repair, mutagenesis, and sporulation in yeast. Introduction of the mus-8 gene into a S. cerevisiae rad6 mutant resulted in significant recovery of DNA repair functions, especially UV-mutagenesis, and also sporulation, both of which are defective in the rad6 mutant. It is therefore postulated that mus-8 of Neurospora has a function very similar to that demonstrated for RAD6 of S. cerevisiae.

Amino Acid Sequence↗
PubMed1996

Establishment of an in vitro assay system for screening hepatitis C virus protease inhibitors using high performance liquid chromatography.

The hepatitis C virus (HCV) genome contains the code for a conserved, serine-type protease, called NS3, for the processing of the non-structural protein region of the viral polyproteins. Furthermore, a related protein, NS4A, is an effector or cofactor of NS3 protease activity in the cleavage of NS3-4A, NS4A-4B, NS4B-5A and NS5A-5B junctions. To establish an in vitro assay system for the screening of those enzyme inhibitors that inhibit the protease NS3-4A, we prepared a maltose-binding protein-NS3-NS4A fusion protein and a synthetic peptide substrate that mimics the NS5A-5B junction. Cleavage of the synthetic peptide was analyzed by reversed-phase high performance liquid chromatography (HPLC). We showed that the enzymatic activity of the NS3-NS4A fusion protein was enhanced in comparison to the NS3 protein alone. The assay conditions for optimum NS3-4A protease activity were determined to be pH 7.6 and 37 degrees C. In addition, we evaluated several protease inhibitors using the same HPLC assay system. The activity of HCV protease NS3-4A was inhibited by 2714.4 microM diisopropyl fluorophosphate, 270.8 microM N-tosyl-L-lysyl chloromethyl ketone, and 825.5 microM chymostatin. The results of the present study indicated that the synthetic peptide substrate and HPLC assay system are suitable for studying HCV protease activity and may facilitate the development of anti-HCV therapeutic reagents.

Amino Acid Sequence↗
PubMed1996

Comparison between Japan and North America in the post-hospital course after recovery from an acute coronary event.

We compared the post-hospital prognosis after an acute coronary event (acute myocardial infarction and unstable angina) in 106 patients in Japan vs. 789 patients in North America who were prospectively enrolled in the Multicenter Study of Myocardial Ischemia and were followed-up for an average of 26 months per patients. Risk factors more frequent in Japan were older age, males and smoking at enrollment, but the rest of many risk factors were similar. After adjusting for differences in clinical and medication variables, Cox analyses indicated patients in North America had a significantly greater risk of experiencing a primary end-point (cardiac death, non-fatal myocardial infarction or unstable angina) than patients in Japan (hazard ratio [North America:Japan] = 3.1, P = 0.003). There was a non-significant trend in the restricted end-points (cardiac death or non-fatal myocardial infarction) with North America having more frequent events than Japan (hazard ratio = 2.2, P = 0.12). The long-term outcome after recovery from an acute coronary event is more favorable in Japan than in North America, mostly due to a reduction in subsequent hospitalization for unstable angina. The reason for these findings cannot be explained by differences in the measured risk factors or medications.

Adult↗
PubMed1996

Peroral insertion techniques of self-expanding metal stents for malignant gastric outlet and duodenal stenoses.

Self-expanding metal stents (EMS) have gained widespread popularity for the palliative treatment of various stenoses in blood vessels, biliary ducts, bronchi, and the gastrointestinal tract. Regarding stenoses of the upper gastrointestinal tract, EMS insertion for gastric outlet and duodenal stenoses is considerably more difficult than for esophageal stenoses. We describe a reliable EMS insertion technique for malignant gastric outlet and duodenal stenoses.

Aged↗
PubMed1996

Histopathology of Kienböck's disease. Correlation with magnetic resonance and other imaging techniques.

Histopathological studies of extracted whole lunate bones obtained from 10 patients with Stage 3 Kienböck's disease at surgery for tendon-ball replacement were correlated with magnetic resonance imaging (MRI), computed tomography (CT) and tomography images made prior to surgery. A reforming zone, or a reactive interface between the reactive new bone and granulation tissue formation, and new vascularization were observed surrounding the bone necrosis area showing empty lacunae, fatty necrosis, and disappearance of osteoid. Findings of CT, tomography and microradiography of slices of extracted lunate bone confirmed that fractures of the articular cartilage and the subchondral bone occurred secondarily by overloading, and showed the extent of the collapsed area of the lunate. MRI showed complete loss of signal intensity in T1 images of the lesion of the lunate in advanced Stage 3 Kienböck's disease. MRI is at present unable to distinguish bone necrosis, the histological reactive interface or surrounding hyperaemia in detail. However, the low-intensity arc, or the reactive interface present on MRI in early Stage 3, sometimes correlates with the histological findings of osteoid and granulation zones.

Adult↗
PubMed1996

Dorsally displaced epiphyseal fracture of the phalangeal base.

A dorsally displaced epiphyseal fracture of the middle phalanx (Salter-Harris Type I) is described. The epiphyseal fragments were attached to the central slip of the extensor tendon and collateral ligaments. The articular surface of the PIP joint was intact and smooth. The epiphysis was reduced and fixed without cutting the central slip or the collateral ligaments 8 months after injury. This kind of fracture can occur in the PIP and DIP joints, and presents special diagnostic difficulties. Open reduction is evidently necessary to correct the displacement.

Child↗
PubMed1996

The Galeazzi-equivalent lesion in children revisited.

A fracture at the medial end of the distal third of the radius with an epiphyseal separation of the distal ulna in a 16-year-old boy is described. This injury, known as the Galeazzi-equivalent lesion in children, is characterized by complete distal ulnar epiphyseal separation without rupture of the distal ligamentous stabilizing system between the radius and ulna, which includes the triangular fibrocartilage complex, interosseous ligaments and periosteal tube of the ulnar. The Galeazzi fracture-dislocation and the Galeazzi-equivalent lesion appear to be completely dissimilar in their pathological anatomy. We suggest calling the latter a "pseudo-Galeazzi injury".

Adolescent↗
PubMed1996

Thromboxane A2 mimetic (U-46619) induces hyperresponsiveness of smooth muscle in the canine bronchiole, but not in the trachea.

It has been reported that cholinergic agonists induce bronchoconstriction by directly stimulating M3 muscarinic receptors on the surfaces of smooth muscle cells. Although thromboxane A2 (TXA2) has been demonstrated to induce airway hyperresponsiveness to cholinergic agonists in vivo, it does not affect the contractile response of smooth muscle to cholinergic agonists in vitro. To investigate the causes for the discrepancy between the in vivo and in vitro data, we compared the effects exerted by a TXA2 mimetic, U-46619, on the smooth muscle of canine trachea and bronchiole. We measured the contractile response to exogenously applied acetylcholine (ACh) before and after the application of a subthreshold dose of U-46619. The subthreshold dose was determined as that dose which did not induce smooth muscle contraction, this being 10(-9) M in the present study. The contractile responses of tracheal strips to ACh were not affected by the subthreshold dose of U-46619. By contrast, the responses of bronchiolar rings were significantly enhanced by this subthreshold dose. The excitatory effect of U-46619 on the ACh-induced contraction was completely prevented by treatment with a TXA2 antagonist, BAY u3405. These results indicate that TXA2 directly increases the responsiveness of smooth muscle in the bronchiole, and suggest that increases in the responsiveness of small airways may play an important role in the development of the airway hyperresponsiveness induced by TXA2.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1996

The use of artificial dermis on the donor defect of the free forearm flap.

Microsurgical grafting of a free flap is an established technique of surgical reconstruction. The forearm free flap is frequently used following removal of oral and/or pharyngeal tumors. However, simple split-thickness skin grafting on full-thickness defects of the skin on the flexor side of the forearm results in deformations, pigmentation, and the adhesion of the graft to the tendons. The authors attempted to minimize such problems by repairing the flap donor site with a collagen sponge used as an artificial dermis. This artificial dermis was used to reconstruct postoperative defects in the skin of 5 patients. Split-thickness skin measuring 0.25 to 0.30 mm was grafted onto the defect. The donor site skin was successfully repaired in 2 to 3 weeks without adverse effects, without the development of depressed deformations, and with only slight pigmentation. The artificial dermis formed a matrix on the donor wound bed, with good cosmetic results.

Adolescent↗
PubMed1996

Mutations and oxidative DNA damage in phage M13mp2 exposed to N-nitrosomorpholine plus near-ultraviolet light.

Previously we reported that a direct-acting mutagen can be formed from N-nitrosomorpholine (NMOR) on exposure to near-ultraviolet light (UVA, 320-400 nm). We have now studied the spectrum of mutations caused by NMOR plus UVA. M13mp2 phages suspended in a sodium phosphate buffer were treated with NMOR under UVA irradiation and Escherichia coli NR9099 was then infected with the phage. Mutations induced in the phage DNA lacZ alpha region were analyzed. The majority (approximately 50%) of the induced sequence changes were G to T transversions. This suggested that modifications in guanine residues were responsible for these transversions. We explored the formation of 7,8-dihydro-8-oxodeoxyguanosine (8-oxodG) in the DNA. When the phage were treated with NMOR plus UVA, 8-oxodG/dG in DNA increased up to 12-fold over the value in untreated control. When a mutM-deficient mutant of E. coli CSH50 was used as the host, the mutation level was higher than that observed with CSH50. We conclude that 8-oxodG may be involved in mutations induced by NMOR plus UVA.

8-Hydroxy-2'-Deoxyguanosine↗