Biomedical subjects

H Inoue

Publications and source records attributed to H Inoue.

At least 595 records · Page 33Linked to original sources

PubMed1998

Mammalian Polycomb group genes are categorized as a new type of early response gene induced by B-cell receptor cross-linking.

Polycomb group (PcG) genes were initially described in Drosophila melanogaster as regulators of the homeobox gene. Four mammalian homologues, mel-18, bmi-1, M33 and rae-28, are analyzed in this study. They not only regulate mammalian homeotic genes by analogy with their Drosophila counterparts, but also have some influence on the growth and differentiation of B lymphocytes. Here we report that these four mammalian PcG genes are rapidly induced after antigen-receptor cross-linking in B cells. Thus we would like to propose that mammalian PcG genes can be categorized as a new type of immediate early gene.

Animals↗

PubMed1998

Effects of thromboxane A2 antagonist on airway hyperresponsiveness, exhaled nitric oxide, and induced sputum eosinophils in asthmatics.

We examined effects of a thromboxane A2 (TXA2) antagonist seratrodast on airway hyperresponsiveness, exhaled nitric oxide (NO), and eosinophils in induced sputum in 14 asthmatics. Subjects were administered 80 mg of seratrodast once a day for 4 weeks. Respiratory conductance (Grs) was measured by the forced oscillation method and airway responsiveness was evaluated as the inhaled dose of methacholine, which induced 35% decrease in Grs. Subjects breathed into a Teflon bag, and NO concentration in the bag was measured by a chemiluminescence analyzer. Induced sputum comprised the entire expectorate produced during a 20 min inhalation of 3% saline, and was analyzed for total and differential cell counts. Airway hyperresponsiveness was significantly decreased by seratrodast. By contrast, no differences in either exhaled NO or percentage of eosinophils in sputum were observed before or after seratrodast. We conclude that seratrodast may attenuate airway hyperresponsiveness, presumably by antagonizing TXA2 released from the inflamed airways.

Anti-Asthmatic Agents↗

PubMed1998

mel-18 negatively regulates cell cycle progression upon B cell antigen receptor stimulation through a cascade leading to c-myc/cdc25.

mel-18 is a mammalian Polycomb group gene encoding a transcriptional repressor with tumor suppressive activity. Overexpression of mel-18 in mice results in cell cycle arrest of B cells upon B cell receptor stimulation with downregulation of c-myc. This phenotype is rescued in mel-18/c-myc double-transgenic mice, suggesting that c-myc locates downstream of mel-18. In mel-18 transgenic mice, the downregulation of cyclins D2 and E; CDK4, -6, and -7; and CDC25A causes the impairment in the activities of cyclin-dependent kinases, resulting in hypophosphorylation of the retinoblastoma protein. In contrast, the upregulation of c-Myc, CDC25, and CDC2/CDK2 kinase activities results in the augmentation of B cell proliferation in mel-18-deficient mice. We therefore propose that mel-18 negatively regulates the cell cycle through a c-myc/cdc25 cascade.

Animals↗

PubMed1998

Fibrinogen/fibrin and fibronectin in the dentin-pulp complex after cavity preparation in rat molars.

OBJECTIVE: The purpose of this study was to examine changes in distribution of fibrinogen/fibrin and fibronectin in the dentin-pulp complex after cavity preparation. STUDY DESIGN: Class V cavity preparations were prepared on maxillary first molars of 12 rats. The dentin and pulps were observed histologically and immunohistochemically for fibrinogen and fibronectin at 6 hours and 1, 2, and 3 days after the preparation. RESULTS: At 6 hours and 1 day after cavity preparation, positive staining for fibrinogen was noted in the exudative lesion and in the dentinal tubules under the cavity preparation. Fibronectin staining in the exudate showed a pattern with close similarity to the fibrinogen staining. At 3 days after cavity preparation, the irregularly shaped predentin under the cavity preparation showed strong positive staining for fibronectin. CONCLUSIONS: Fibrinogen/fibrin and fibronectin are present during the healing process of the dentin-pulp complex after cavity preparation.

Animals↗

PubMed1998

A gene encoding a transmembrane protein is mutated in patients with diabetes mellitus and optic atrophy (Wolfram syndrome).

Wolfram syndrome (WFS; OMIM 222300) is an autosomal recessive neurodegenerative disorder defined by young-onset non-immune insulin-dependent diabetes mellitus and progressive optic atrophy. Linkage to markers on chromosome 4p was confirmed in five families. On the basis of meiotic recombinants and disease-associated haplotypes, the WFS gene was localized to a BAC/P1 contig of less than 250 kb. Mutations in a novel gene (WFS1) encoding a putative transmembrane protein were found in all affected individuals in six WFS families, and these mutations were associated with the disease phenotype. WFS1 appears to function in survival of islet beta-cells and neurons.

Adult↗

PubMed1998

Pirfenidone induces intercellular adhesion molecule-1 (ICAM-1) down-regulation on cultured human synovial fibroblasts.

Pirfenidone has been shown to modify some cytokine regulatory actions and inhibit fibroblast biochemical reactions resulting in inhibition of proliferation and collagen matrix synthesis by fibroblast. We have investigated the effect of pirfenidone on the expression of cell adhesion molecules. The synovial fibroblasts were treated with IL-1alpha in the presence or absence of pirfenidone (range 0-1000 microM), and assayed for the expression of adhesion molecules such as ICAM-1 and endothelial-leucocyte adhesion molecule-1 (E-selectin) by cell ELISA. Pirfenidone significantly down-regulated the expression of ICAM-1 on cultured synovial fibroblasts in a dose-dependent manner. In contrast, expression of E-selectin was not affected. Furthermore, we examined whether pirfenidone affects the cellular binding between cultured lymphocytes and IL-1alpha-stimulated synovial fibroblasts by in vitro binding assay and found their mutual binding was significantly suppressed in a dose-dependent manner by pirfenidone. It is speculated that down-regulation of ICAM-1 might be one of the novel mechanisms of action of pirfenidone. These data indicate a novel mechanism of action for pirfenidone to reduce the activation of synovial fibroblasts.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1998

Limitations of percutaneous transhepatic cholangioscopy for the diagnosis of the intramural extension of bile duct carcinoma.

BACKGROUND AND STUDY AIMS: Vascular dilatation seen on percutaneous transhepatic cholangioscopy (PTCS) is diagnostic of intramural invasive carcinoma of the bile duct, but the limitations of the technique, including biopsy, for the diagnosis of intramural extension of bile duct carcinoma have not to our knowledge been investigated before. The aims of the present study were to estimate the thickness of the specimens of bile duct wall taken by biopsy, to assess the sensitivity of PTCS for detecting intramural invasive carcinoma, and to identify the characteristics of the intramural extension of bile duct carcinoma associated with vascular dilatation. PATIENTS AND METHODS: A total of 135 biopsy, and 16 surgical specimens obtained from 25 bile duct carcinomas were examined for: the thickness of the biopsy specimens and of the mucosa and combined mucosal-fibromuscular layers in the resected common bile ducts and common hepatic ducts; the presence of muscular and neural bundles in the biopsy specimens; the number of invasive carcinomas in the biopsy specimens that had been taken from stenosed regions; and the relation between intramural extension of invasive carcinoma and vascular dilatation. RESULTS: The mean thickness of the biopsy specimens did not differ from the mean thickness of the mucosa in the resected specimens, but was significantly lower than that of the combined mucosa and fibromuscular layer. Muscular bundles were included in only 13 (14%) of the biopsy specimens, and there were no neural bundles. Carcinomas and invasive carcinomas were diagnosed histologically from the biopsy specimen in 96% and 91% of the cases, respectively. The sensitivity of a single biopsy for diagnosis for invasive carcinoma in stenosed regions was 62%, almost the same as the sensitivity in non-stenosed regions with vascular dilatation (68%). On histologic examination of 16 resected specimens, the sensitivity and specificity of vascular dilatation as a marker of the intramural extension of an invasive carcinoma were 39% and 100%, respectively, and this was significantly more common in invasive carcinomas that were invading the mucosa beyond the adventitia than in those limited to the adventitia. CONCLUSION: Histologic examinations of specimens obtained by PTCS-guided biopsy can detect invasive carcinoma in only the superficial layers of the bile duct, such as the mucosa and the shallowest fibromuscular layer. Multiple specimens are needed for the diagnosis of invasive carcinoma because the sensitivity of examination of a single specimen for detecting invasive carcinoma is low. Vascular dilatation is characteristic of carcinoma that is invading the mucosa beyond the adventitia, so the diagnosis of intramural extension of bile duct carcinoma limited to the adventitia, particularly if it has spread to the deeper fibromuscular layer and the adventitia, is difficult to make by PTCS.

Adult↗

PubMed1998

Modified soft-balloon methods during ultrasonic probe examination for superficial esophageal cancer.

BACKGROUND AND STUDY AIMS: In ultrasonic probe studies for early-stage esophageal cancer the original soft-balloon method utilizing a condom had succeeded in obtaining a clear and reproducible picture by keeping deaerated water in a condom; however, the condom, which covered the endoscope lens, eliminated the usual endoscopic sight. Therefore, the authors endeavored to develop a modified method which enables both normal endoscopic observation and ultrasonic probe study with only a single insertion of the endoscope. PATIENTS AND METHODS: Thirty-one patients with superficial esophageal cancer were included in this pilot study. As modifications of the soft-balloon technique, two novel methods of 'wrapping' and 'invagination' were developed. RESULTS: These modifications are considered to have solved the above-mentioned problem and enable one to acquire both normal endoscopic photos and ultrasonic probe images during the same insertion of the endoscope. CONCLUSION: In a pilot study novel modifications improved the method of ultrasonic probe study for superficial esophageal cancer.

Endosonography↗

PubMed1998

Differential production of monoclonal antibodies to carbohydrate moiety or peptides moiety of glycoproteins by different routes of immunization.

The administration of ABO blood group active glycoproteins via the rear footpads of BALB/c mice with subsequent fusion of popliteal lymph node lymphocytes produced hybridomas differentially secreting antibodies to the peptide moiety of antigens. On the other hand, conventional intraperitoneal immunization of the same antigens and intraperitoneal boost followed by splenic lymphocyte fusion produced hybridomas differentially secreting antibodies to the carbohydrate moiety of antigens. Similar results were obtained in the production of monoclonal antibodies to erythrocyte membranes. Almost all hybridomas obtained by rear foodpad immunization secreted antibodies to the peptide moiety of erythrocyte membrane proteins, and those obtained by intraperitoneal immunization secreted antibodies to both peptide and carbohydrate moieties of erythrocyte membrane components. These results suggest the possibility of differential production of monoclonal antibodies to the carbohydrate moiety and the peptide moiety of some glycoproteins by different immunization routes.

Animals↗

PubMed1998

Interplay of signal mediators of decapentaplegic (Dpp): molecular characterization of mothers against dpp, Medea, and daughters against dpp.

Decapentaplegic (Dpp) plays an essential role in Drosophila development, and analyses of the Dpp signaling pathway have contributed greatly to understanding of the actions of the TGF-beta superfamily. Intracellular signaling of the TGF-beta superfamily is mediated by Smad proteins, which are now grouped into three classes. Two Smads have been identified in Drosophila. Mothers against dpp (Mad) is a pathway-specific Smad, whereas Daughters against dpp (Dad) is an inhibitory Smad genetically shown to antagonize Dpp signaling. Here we report the identification of a common mediator Smad in Drosophila, which is closely related to human Smad4. Mad forms a heteromeric complex with Drosophila Smad4 (Medea) upon phosphorylation by Thick veins (Tkv), a type I receptor for Dpp. Dad stably associates with Tkv and thereby inhibits Tkv-induced Mad phosphorylation. Dad also blocks hetero-oligomerization and nuclear translocation of Mad. We also show that Mad exists as a monomer in the absence of Tkv stimulation. Tkv induces homo-oligomerization of Mad, and Dad inhibits this step. Finally, we propose a model for Dpp signaling by Drosophila Smad proteins.

Amino Acid Sequence↗

PubMed1998

Genotype-phenotype correlation of patients with multiple endocrine neoplasia type 2 in Japan.

BACKGROUND: Multiple endocrine neoplasia type 2 (MEN 2) is a hereditary syndrome characterized by medullary thyroid carcinoma (MTC), pheochromocytoma and hyperparathyroidism. MEN 2 is caused predominantly by germ-line mutations of the RET proto-oncogene. This study aimed to clarify the genotype-phenotype correlation in MEN 2 patients in Japan in order to modify the clinical management according to the genotype. METHODS: Constitutive DNA of 64 MEN 2 patients (48 kindreds) were searched for mutations at exons 10, 11, 13, 14 and 16 of the RET proto-oncogene using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing and restriction enzyme digestion. The clinical characteristics of the patients were obtained from a previous nationwide questionnaire survey. RESULTS: Overall, 62 (96.9%) out of 64 patients had a germ-line point mutation at the hot spots. MTC and pheochromocytoma occurred equally in every genotype except C630S. Specific genotype had a correlation between tumor size and age at the operation for MTC or extent of MTC, i.e. C618S developed late onset type of MTC as compared with that of C634R, C634Y and M918T. Small MTC in C634R may be less aggressive than those in C634Y and M918T. CONCLUSIONS: DNA testing has good clinical implications for the management of patients with MEN 2 and the timing and operative procedures of thyroidectomy can be modified according to the genotype.

Adrenal Gland Neoplasms↗

PubMed1998

Nitric oxide mediates interleukin-1-induced gene expression of matrix metalloproteinases and basic fibroblast growth factor in cultured rabbit articular chondrocytes.

We recently reported that nitric oxide (NO), which is produced by chondrocytes treated with interleukin-1beta (IL-1), releases basic fibroblast growth factor (bFGF) stored in the matrix of articular chondrocytes. To clarify the mechanism of the IL-1-induced bFGF release, we investigated the production and gene expression of bFGF, matrix metalloproteinases (MMPs), syndecan 3, and inducible NO synthase (iNOS) by IL-1-treated rabbit articular chondrocytes. IL-1 stimulated not only the release of bFGF but also the production of it. Gelatin and casein zymography revealed that IL-1 stimulated the production of not only MMP-9 but also MMP-3. The increase in the production of these MMPs preceded the IL-1-stimulated bFGF release. An MMP inhibitor partially suppressed the release of bFGF, indicating that matrix degradation is at least partially involved in the IL-1-stimulated bFGF release even if increased production of bFGF is related to the release. IL-1 sequentially stimulated mRNA expression of iNOS, membrane type 1-MMP, MMP-9 and -3, and bFGF, in that order. NG-Monomethyl-L-arginine, an inhibitor of NO production, inhibited gene expression of MMP-9 and bFGF. These findings suggest that elevation of the NO level via iNOS mRNA expression stimulated by IL-1 mediates gene expression and production of MMPs and bFGF, resulting in the release of bFGF, and also reveal molecular mechanisms implicating the degradation of articular cartilage followed by angiogenesis in the synovium in arthritic joints.

Animals↗

PubMed1998

Changes in the brain monoamine metabolism in acute liver failure produced by ischemia-reperfusion injury in rats.

OBJECTIVE: To investigate the relationship between behavioral alterations and changes in monoaminergic systems provoked by ischemia-reperfusion liver injury in rats. DESIGN: Prospective, randomized, controlled animal study. SETTING: University animal laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute liver failure was induced by occlusion of the left portal vein and the hepatic artery for 90 mins. Twenty animals were subjected to the behavioral examination. The brain water content was measured in 12 animals. Forty-two animals were used for the evaluation of brain monoamine turnover. Half of animals in each experiment were subjected to the ischemic operation. MEASUREMENTS AND MAIN RESULTS: A step-through passive avoidance test was used for the behavioral evaluation 48 hrs after the ischemic operation. Then, plasma concentrations of amino acids were determined. The brain water content was measured with the dry weight method. The brain monoamine turnover was evaluated by the depletion of norepinephrine and dopamine induced by alpha-methyl-p-tyrosine, or the accumulation of 5-hydroxyindoleacetic acid induced by probenecid. In the plasma analysis performed 48 hrs after the operation, marked damage was found in animals subjected to liver ischemia. Injured rats demonstrated impairment in the passive avoidance test. The plasma concentrations of branch-chain amino acids were decreased, and the plasma concentrations of aromatic amino acids were increased. However, the brain water content was not changed by liver ischemia. The turnover of both norepinephrine in the cerebral cortex and dopamine in the striatum was decreased. The turnover of 5-hydroxytryptamine in the cerebral cortex was increased markedly. CONCLUSION: In liver injury caused by liver ischemia, the excitatory neurotransmission by norepinephrine and dopamine is depressed and the inhibitory neurotransmission mediated by 5-hydroxytryptamine is facilitated, especially in the telencephalon.

Amino Acids↗

PubMed1998

Changes in endothelin-1, 6-keto-PG-F1 alpha, and TX-B2 in random pattern flaps.

In this study we investigated kinetic changes in the ratio of endothelin-1 (ET-1) and eicosanoids (6-keto-PG-F1 alpha TX-B2) in 20 x 60 mm random pattern flaps from rats. The ET-1 content of regions A (20 mm from the peripheral end) and B (20-40 mm) 6 h after surgery tended to decrease slightly compared to the ET-1 content immediately after surgery. The ET-1 content of region C (20 mm from the flap base) 6 h postoperatively increased significantly compared to that immediately after surgery. The ET-1 content of region C 6 h after surgery was significantly higher compared to that of regions A and B, which were obtained simultaneously. The ratios of eicosanoids in the three regions 6 h after surgery were significantly lower than those immediately after operation. However, the ratio in region A was higher than that in region C, showing that there was a difference in distribution in the flap between ET-1 and eicosanoids. The administration of an ETA receptor antagonist, FR-139317, extended the survival length of the flap. These results suggest that ET-1 can regulate the microcirculation in a flap directly and/or indirectly.

6-Ketoprostaglandin F1 alpha↗

PubMed1998

Different effects of class Ic and III antiarrhythmic drugs on vagotonic atrial fibrillation in the canine heart.

Effects of class Ic drug pilsicainide and class III drug MS-551 were determined in the canine model of atrial fibrillation (AF) induced under vagal stimulation. Pilsicainide injected intravenously at a dose of 1.0 mg/kg over 3 min terminated AF in six of six dogs. After pilsicainide injection, the effective refractory period (ERP) of the right atrium (RA) increased (104 +/- 22 to 122 +/- 31 ms; p < 0.05), and intraatrial conduction time (CT) increased (24%; p < 0.05) in the RA during vagal stimulation. Wavelength index (WLI; ERP/CT), an estimate of the wavelength for reentry, was decreased slightly but significantly (-2%; p < 0.05) in the RA after pilsicainide. MS-551 injected intravenously at a dose of 0.5 mg/kg over a 3-min period terminated AF in three of eight dogs. An additional dose of 0.5 mg/kg of MS-551 terminated AF in three of the remaining five dogs. After MS-551 injection, ERP increased (100 +/- 30 to 143 +/- 28 ms; p < 0.05), but CT remained unchanged in the RA, and therefore WLI was increased significantly (48%; p < 0.01). Immediately before termination of AF with test drugs, mean AF intervals (FF intervals) increased, whereas the standard deviation of FF intervals did not change significantly. In conclusion, both pilsicainide and MS-551 effectively terminated vagotonic AF after an increase in FF intervals. However, changes in WLI were different between the two test drugs. Vagotonic AF could, therefore, be terminated either by prolongation of ERP or suppression of conduction with antiarrhythmic drugs.

Animals↗

PubMed1998

Macrolipasemia in Crohn's disease.

A 38-year-old male patient who had been treated for Crohn's disease was found to have serum lipase activity that was persistently increased approximately 10-fold above the normal upper limit. He was diagnosed with chronic pancreatitis based on slightly elevated elastase-1 level and retrograde pancreatography showing slight dilatation of the main pancreatic duct. Therefore, the hyperlipasemia was thought to be due to pancreatitis. However, the serum amylase and trypsin was not increased at any time, and no serious findings suggestive of pancreatitis were detected on morphologic examination. Thus, there were discrepancies between the serum lipase activity and other laboratory and clinical findings. Exclusion chromatography of the patient's serum suggested macromolecular lipase, and further immunologic testing including affinity chromatography, enzyme-linked immunosorbent assay, and immunoprecipitation assay showed that serum lipase was bound to immunoglobulin Gkappa. Therefore, the hyperlipasemia was caused by immunoglobulin-linked lipase, termed "macrolipasemia." Macrolipasemia has rarely been reported, and this is the first reported case of macrolipasemia accompanied by Crohn's disease.

Adult↗

PubMed1998

Proliferative effect of phospholipase A2 on rat periacinar fibroblastoid cells of the pancreas.

We have shown previously that rat pancreatic periacinar fibroblastoid cells (PFCs) can be cultured from isolated pancreatic acini. In the present study, immunocytochemical examination of the PFC extracellular matrix was performed using antibodies against prolyl hydroxylase alpha and beta subunits, types I, III, and IV collagen, fibronectin, and laminin. The PFC content of alpha-smooth muscle actin and platelet-derived growth factor (PDGF) receptor were studied by immunoblotting. We demonstrated that PFCs synthesized extracellular matrix and expressed alpha-smooth muscle actin and PDGF receptors. These results suggested that PFCs resemble myofibroblasts and may play a critical role in pancreatic fibrosis. Conversely, pancreatic-type phospholipase A2 (P-PLA2), one of the pancreatic digestive enzymes, has been shown to induce DNA synthesis of Swiss 3T3 fibroblasts. To determine whether this enzyme is involved in pancreatic fibrosis, we studied P-PLA2's proliferative and chemotactic effects on PFCs as well as its digestive activity. The proliferative and chemotactic effects were investigated using 3H-thymidine incorporation and a chemotactic assay, respectively. P-PLA2 had both proliferative and chemotactic effects. P-PLA2 is considered a growth factor for PFCs and is implicated in pancreatic fibrosis.

Actins↗

PubMed1998

Treatment outcome of osteofibrous dysplasia.

The disease course of six tibial lesions in five patients with osteofibrous dysplasia who were followed longer than 10 years (average: 16.8 years) was analyzed retrospectively. Three patients had a lesion of the unilateral tibia; one patient had lesions of the unilateral tibia and fibula; and one patient had lesions of the bilateral tibiae and ulnae. Curettage and autogeneic bone graft were performed on two lesions, which then healed. Of four lesions on which curettage and xenogeneic bone grafts were performed, three lesions healed, and one developed local recurrence. Curettage and xenogeneic bone graft were performed on the recurrent lesion, which finally healed and the deformity stopped. Three lesions healed without surgical treatment. During the long-term follow-up, this disease showed a clear tendency of healing. Surgical treatment should be considered in patients with disease uncontrollable by conservative treatment or those who have a high possibility of impending fracture and progressing deformity.

Adolescent↗