Search PubMed⌕ Search

Biomedical subjects

T Yagi

Publications and source records attributed to T Yagi.

At least 73 records · Page 4Linked to original sources

Apoptotic signaling pathway activated by Helicobacter pylori infection and increase of apoptosis-inducing activity under serum-starved conditions.

The enhanced gastric epithelial cell apoptosis observed during infection with Helicobacter pylori has been suggested to be of significance in the etiology of gastritis, peptic ulcers, and neoplasia. To investigate the cell death signaling induced by H. pylori infection, human gastric epithelial cells were incubated with H. pylori for up to 72 h. H. pylori infection induced the activation of caspase -8, -9, and -3 and the expression of the proapoptotic Bcl-2 family proteins Bad and Bid. The peak of the activity of the caspases occurred at 24 h. At this time, the inhibition of caspase-8 or -9 almost completely suppressed H. pylori-induced apoptosis. Inhibition of caspase-8 suppressed the expression of Bad and Bid and the subsequent activation of caspase-9 and -3. These observations indicate that H. pylori induces apoptosis through a pathway involving the sequential induction of apical caspase-8 activity, the proapoptotic proteins Bad and Bid, caspase-9 activity, and effector caspase-3 activity. Activation of the pathway was independent of CagA or vacuolating toxin. A membrane fraction of H. pylori was sufficient to activate this pathway, and treatment with proteinase K eliminated the activity. Apoptotic activity of the membrane fraction was significantly increased by incubating the bacteria under serum-starved conditions for 24 h. These observations suggest that environmental conditions in the human stomach could induce H. pylori-mediated pathogenesis, leading to a variety of clinical outcomes.

Apoptosis↗

Guidance of glial precursor cell migration by secreted cues in the developing optic nerve.

Oligodendrocyte precursors are produced in restricted foci of the germinative neuroepithelium in embryo brains and migrate to their sites of function, while astrocytes are produced in a wider area in the neuroepithelium. We investigated the guidance mechanisms of glial precursor (GP) cell migration in the optic nerve. GP cell migration in newborn rat optic nerve was monitored by the UV-thymine-dimer (TD) method. A double labeling study using NG2 and TD revealed that many of these in vivo migrating cells were NG2 positive, while some of them with large TD-positive nuclei were NG2 negative. An in vitro cell migration study using optic nerve with chiasma and/or eyeball tissue revealed that the GP cells migrated under the guidance of repulsive cues secreted from the optic chiasma. We detected the expression of netrin 1 and Sema3a in the optic chiasma, and that of Unc5h1 and neuropilin 1 in the optic nerve. Co-culture experiments of the optic nerve with cell clusters expressing guidance cues revealed that the migrating GP cells in the optic nerve were heterogeneous. Netrin 1 repelled a subtype of NG2-positive and PLP-positive GP cells with small nuclei. Sema3a repelled a subtype of GP cells with large nuclei.

Animals↗

Molecular phylogeny of butterflies Parnassius glacialis and P. stubbendorfii at various localities in East Asia.

The phylogeny of butterflies, Parnassius stubbendorfii and P. glacialis, collected at various localities in the Japan archipelago and the eastern part of the Asian continent was analyzed using mitochondrial DNA sequences coding for NADH dehydrogenase subunit 5 (805 bp). The molecular phylogenetic trees revealed that P. glacialis and P. stubbendorfii diverged from a common ancestor, and then the populations inhabiting the Japan archipelago and the Asian continent diverged in each species. The reliability of these divergences was supported by high bootstrap values. The divergences within the Japan archipelago and within the Asian continent in each species were unclear because of low bootstrap values. The genetic distance and a rough time-estimation in the UPGMA tree suggest that the both populations of P. glacialis and P. stubbendorfii may have been isolated in the Japan archipelago at the early time (about 1.7-2.0 Mya) of the glacial period in the Pleistocene. The genetic distance between the Japanese and the continental subspecies may be large enough that they can be classified as different species, in comparison with the genetic distances among some other parnassian species.

Animals↗

Production of pyridoxal phosphate by a mutant strain of Schizosaccharomyces pombe.

Conditions for extracellular production of vitamin B6 compounds (B6), especially pyridoxal 5'-phosphate (PLP) by Schizosaccharomyces pombe leul strain were examined. The productivity was dependent on concentration of L-leucine in the culture medium: 30 mg/l gave the highest concentrations of total B6 and PLP. The viable cells harvested at different growth phases showed different productivity: middle and late exponential phase cells showed the highest productivity of total B6 and PLP, respectively. D-Glucose (1%, w/v) among other sugars gave the best productivity. Supplementation of air and ammonium sulfate significantly increased extracellular production of PLP. Superoxide anion producers, menadione and plumbagin, and H202 increased the productivity of PLP. Cycloheximide inhibited the increase of PLP by the oxidative stress and, in contrast, increased pyridoxine.

Air↗

[Laryngeal manifestations of gastroesophageal reflux disease (GERD) in pediatric patients: the usefulness of therapeutic (proton pump inhibitor (PPI)) trials].

Gastroesophageal reflux, common in infants, usually resolves spontaneously by 12 to 18 months. Gastroesophageal reflux disease (GERD) contributes to certain respiratory symptoms, but is reported to be due to other causal diseases, such as tracheolaryngeal anomaly, congenital esophageal hiatal hernia, and cerebral palsy, in pediatric patients. We report 4 pediatric cases with unusual laryngeal disorders, especially posterior glottic lesion, induced by gastroesophageal reflux without other causal disease. Subject 1 was a 1-year-old boy showing severe laryngeal spasm, Subject 2 a 3-year-old boy with life-threatening supraglottic stenosis, Subject 3 a 5-year-old boy whose voice had reached near aphonia with multiple laryngeal granulomatous lesions, and Subject 4 an 8-year-old boy with persistent abnormal throat sensations. Their symptoms were recalcitrant to conventional therapy. Their case histories (much belching and hiccups) and findings for the posterior glottitis, etc., suggested that symptoms might be induced by GERD, but, barium esophagography and esophagoscopy provided no conclusive proof. We could not monitor their ph because of the excessive physical and psychological stress involved. After therapeutic trials with a proton pump inhibitor (lansoprazole 10-15 mg) for 8 weeks, all had recovered almost completely without side effects.

2-Pyridinylmethylsulfinylbenzimidazoles↗

[A case of Behçet's disease presenting with Hughes-Stovin syndrome (multiple pulmonary arterial aneurysms remitting with corticosteroid therapy)].

A 32-year-old male suffering from thrombophlebitis of the right leg was admitted to our hospital because of massive hemoptysis. Chest radiography showed multiple rounded opacities in the right lung field. Pulmonary angiography revealed multiple aneurysms of the right pulmonary arteries and thromboembolism of the left pulmonary artery. Venography demonstrated obstruction of the deep veins of the right leg and the right femoral vein, and deep vein thrombosis was diagnosed. A more precise diagnosis was Hughes-Stovin syndrome, that is, venous thrombosis especially of the vena cava, accompanied by single or multiple pulmonary arterial aneurysms in young patients. Furthermore, the patient had an aphthous ulcer in the oral cavity, an ulcer in the genital region, leading to a diagnosis of the incomplete type of Behçet's disease. Chest radiographs 3 months after the initiation of corticosteroid showed complete resolution of the aneurysms. Repeated pulmonary angiography also showed partial recanalization of the occluded arteries. This report describes this very rare case of Behçet's disease presenting with Hughes-Stovin syndrome.

Adult↗

[Three-dimensional transesophageal echocardiographic measurement of left ventricular volumes using the average rotation method: comparison with the disk summation method].

OBJECTIVES: Three-dimensional(3-D) echocardiography accurately calculates left ventricular volumes without geometric assumptions. Conventional 3-D echocardiography using the disk summation method is limited in practical use because of the long analysis time. This study validated the average rotation method for rapid and accurate left ventricular volume measurement compared with the conventional disk summation method. METHODS: 3-D data acquisition using multiplane transesophageal echocardiography was performed in 13 patients. Left ventricular volumes and ejection fraction were calculated by the disk summation method with 20 parallel short-axis tomograms and by the average rotation method with 3, 6, 9 and 12 apical long-axis tomograms. RESULTS: 3-D left ventricular volumes and ejection fraction by the average rotation method in each subgroup of slice resolution had excellent correlation and close limits of agreement with those by the disk summation method. Intraobserver variability and interobserver variability were < or = 11%. With the use of three component tomograms, analysis time required for left ventricular volume measurement by the average rotation method was < or = 2 min. CONCLUSIONS: Transesophageal 3-D echocardiography using the average rotation method is a clinically useful tool for accurate and rapid measurement of left ventricular volume and function.

Echocardiography, Three-Dimensional↗

[Trans mucosal insulin delivery].

Insulin is usually administered by s.c. injection to subjects with type 1 and type 2 diabetes. For a long time, non-parenteral delivery approach, such as conjunctiva, nasal cavity, oral cavity, alveolar space, intestine, and rectum, etc has been tried and showed that some portion of administered insulin was absorbed through trans-mucosal route. Short-term glycemic control on diabetic animal and patients was reported to be succeeded by intra-nasal insulin, oral insulin, and insulin suppository. After administration of these insulin, insulin was absorbed as rapid as intra-muscular injection of insulin and thus could effectively control postprandial glycemic excursion in diabetic patients.

Administration, Oral↗

[Clinical analysis of multidrug-resistant tuberculosis].

Forty-three patients with multidrug-resistant tuberculosis at National Chiba-Higashi Hospital were studied retrospectively. TB cases excreting tubercle bacilli which are resistant to both 0.1 microgram/ml of isoniazid and 50 micrograms/ml of rifampicin were defined as multidrug-resistant cases. From 1993 to 1997, we experienced 1627 patients with pulmonary tuberculosis, and among them 43 patients (23-79 years old, 35 males and 8 females) were proved to be multidrug-resistant. Six cases were initially treated cases and other 37 cases had been treated previously. On admission, 40 out of 43 cases (93.0%) were smear positive by sputum examination of mycobacteria and 38 out of 43 cases (88.4%) had cavitary lesions on chest X-ray. Six patients were complicated with diabetes mellitus, two with cancer, one with alcohol dependence, one with chronic hepatitis, and others did not have prominent complications. Three operated patients were cured, the fact shows that the surgical treatment is still a useful measure for cases with the indication. Sixteen patients were cured, eight were still under treatment, and thirteen were died of tuberculosis. One of reasons of poor prognosis of multidrug-resistant tuberculosis is that multidrug-resistant tubercle bacilli are usually resistant to other drugs, too. In case of multidrug-resistant tuberculosis, patients were obliged to be treated in a hospital long-term to prevent the spread of tubercle bacilli. Therefore, it is very important to find out new tuberculosis cases as an early as possible, treat them with proper regimen and prevent dropout by directly observed therapy, thus preventing the emergence of multidrug-resistant tuberculosis. Development of new antituberculous agents is strongly expected.

Adult↗

Is the pathology of horizontal canal benign paroxysmal positional vertigo really localized in the horizontal semicircular canal?

In order to clarify the pathological localization of horizontal canal benign paroxysmal positional vertigo (HC-BPPV), we performed 3D analysis of positional nystagmus in 11 patients with HC-BPPV. In addition, these results were compared with 3D analysis data of pressure nystagmus in patients with HC fistula. 3D analysis of nystagmus was carried out using a video image analysis system. In seven patients with HC-BPPV, the velocity vectors were well aligned with the axes of the HC and in four patients they were not. In addition, the 3D velocity vectors of the slow phase of pressure nystagmus in all 11 subjects with HC fistula were closely aligned with the axes of the HC. The pathology of HC-BPPV in most patients with apogeotropic positional nystagmus has been considered to be localized in the HC. However, our results strongly suggest that the pathology of HC-BPPV with geotropic nystagmus is localized in the utricle. This is the first report concerning the pathological localization of HC-BPPV based on physiological evidence.

Female↗

[Chylothorax as the initial manifestation of malignant pleural mesothelioma--a case report].

A case of chylothorax associated with diffuse malignant pleural mesothelioma in a 53-year-old woman was reported. Chest radiography in a mass examination revealed right pleural effusion. A thoracentesis yielded fluid with characteristics consistent with chyle. In spite of our suggestion that thoracoscopy for further examination was necessary, the patient and her husband had refused the operation for months. Chest CT scanning revealed a nodule behind the xiphoid process. Lymphoscintigraphy suggested an obstruction of the right parasternal lymphatic vessel. Repeated thoracentesis did not yield a diagnosis. As bilateral pleural effusion and chylous ascites appeared, dyspnea worsened. About 2 years after the mass examination thoracoscopy was performed. On thoracoscopic exploration, a nodule was found in the anterior mediastinum and a biopsy was performed. Histological analysis revealed that the patient had the epithelial subtype of malignant pleural mesothelioma. Thoracoscopic pleural biopsy is a useful means of establishing the nature of a chylous effusion. In adult patients with chylothorax, thoracoscopic exploration should be performed as soon as possible to rule out malignancy.

Chylothorax↗

Expression of inducible nitric oxide synthase (iNOS/NOS II) in the hydropic vestibule after injection of keyhole limpet hemocyanin into the endolymphatic sac of guinea pigs.

This study was undertaken to examine the expression of inducible nitric oxide synthase (iNOS / NOS II) in the hydropic vestibule of guinea pigs. Animals were systemically sensitized with 500 microg of keyhole limpet hemocyanin. Two weeks after the first injection, keyhole limpet hemocyanin (100 microg/5 microl) was injected into the endolymphatic sac following the intradural approach, and the next day temporal bones were removed for the immunohistochemical examination. Endolymphatic hydrops was evidenced by the expansion of the Reissner's membrane in the cochlea after direct injection of keyhole limpet hemocyanin into the endolymphatic sac. Inducible nitric oxide synthase expression was increased in the sensory cells, supporting cells and vestibular ganglion cells, while temporal bones, where only phosphate buffered saline was injected, did not show any inducible nitric oxide synthase immunoreactivity. High levels of inducible nitric oxide synthase-catalyzed nitric oxide were detected prior to the development of the inner ear dysfunction. Our results suggest that the occurrence of inducible nitric oxide synthase immunoreactivity parallels the inner ear disturbance as seen in endolymphatic hydrops.

Animals↗

Evaluation of immunoglobulin G and its subclasses in aplastic anemia.

We selected 31 patients with aplastic anemia to measure their total immunoglobulin (Ig) G and IgG subclasses and compared the results obtained with those obtained in the normal control group (n=461). Patients with aplastic anemia were classified into three subgroups according to severity: mild subgroup (n=14), moderate subgroup (n=12) and severe subgroup (n=5). The decrease in total IgG was recognized in all these three subgroups (p<0.001). Although IgG1 decreased in severe subgroup (p<0.01), it showed no significant difference in mild and moderate subgroups. The decrease in IgG2 and IgG3 was observed in all these three subgroups (p<0.001 and p<0.01, respectively). Although IgG4 decreased in mild subgroup (p<0.05), it showed no significant difference in moderate and severe subgroups. We speculated that the measurement of IgG subclasses was useful in understanding the pathophysiology of humoral immunity in aplastic anemia.

Adult↗

Rescue of ischemic brain injury by adenoviral gene transfer of glial cell line-derived neurotrophic factor after transient global ischemia in gerbils.

Glial cell line-derived neurotrophic factor (GDNF), a member of the transforming growth factor (TGF)-beta superfamily, is one of the most potent neurotrophic factors and promotes survival of many populations of cells. We examined neuroprotective effect of an adenoviral vector encoding glial cell line-derived neurotrophic factor (AxCAhGDNF) on the transient global ischemia. Gerbils received administration of AxCAhGDNF or an adenoviral vector encoding bacterial beta-galactosidase gene (AxCALacZ) through the lateral ventricle. Two days later, occluding bilateral common carotid arteries for 5 min using aneurysm clips produced the transient global forebrain ischemia. Animals showed intense immunolabeling for GDNF in ependymal cells on 2, 4 and 7 days after the operation. The exogenous gene transducted by adenovirus in the same cells was detected by in situ hybridization. The treatment with AxCAhGDNF significantly prevented the loss of hippocampal CA1 pyramidal neurons 2 to 7 days after the operation, as compared to AxCALacZ treatment. Also terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) staining was markedly reduced in the case with AxCAhGDNF treatment at 7 days after the operation. These results indicated that the adenovirus-mediated gene transfer of GDNF might prevent the delayed neuronal death of stroke and other disorders of the cerebral vasculature.

Adenoviridae↗

Use of the NADH-quinone oxidoreductase (NDI1) gene of Saccharomyces cerevisiae as a possible cure for complex I defects in human cells.

The Ndi1 enzyme of Saccharomyces cerevisiae is a single subunit rotenone-insensitive NADH-quinone oxidoreductase that is located on the matrix side of the inner mitochondrial membrane. We have shown previously that the NDI1 gene can be functionally expressed in Chinese hamster cells (Seo, B. B., Kitajima-Ihara, T., Chan, E. K., Scheffler, I. E., Matsuno-Yagi, A., and Yagi, T. (1998) Proc. Natl. Acad. Sci. U. S. A. 95, 9167-9171) and human embryonal kidney 293 (HEK 293) cells (Seo, B. B., Matsuno-Yagi, A., and Yagi, T. (1999) Biochim. Biochem. Acta 1412, 56-65) and that the Ndi1 protein is capable of compensating respiratory deficiencies caused by defects in the host NADH-quinone oxidoreductase (complex I). To extend the potential use of this enzyme to repair complex I deficiencies in vivo, we constructed a recombinant adeno-associated virus vector carrying the NDI1 gene (rAAV-NDI1). With rAAV-NDI1 as the gene delivery method, we were able to achieve high transduction efficiencies (nearly 100%) even in 143B cells that are difficult to transfect by lipofection or calcium phosphate precipitation methods. The NDI1 gene was successfully introduced into non-proliferating human cells using rAAV-NDI1. The expressed Ndi1 protein was shown to be functionally active just as seen for proliferating cells. Furthermore, when cells were cultured under the conditions where energy has to be provided by respiration, the NDI1-transduced cells were able to grow even in the presence of added complex I inhibitor such as rotenone and 1-methyl-4-phenylpyridinium ion. In contrast, control cells that did not receive the NDI1 gene failed to survive as anticipated. The Ndi1 protein has a great potential as a molecular remedy for complex I defects, and it is highly likely that the same strategy can be extended to correction of other mitochondrial disorders.

Dependovirus↗

Comparison of the mutations induced by p-benzoquinone, a benzene metabolite, in human and mouse cells.

Benzene is one of the chemicals widely contaminating the environment. Benzene is suggested to be a human leukemogen. When benzene is absorbed in the human body, it is metabolized firstly in the liver and subsequently in the bone marrow where it provokes initiation of leukemia. In the present study, we analyzed mutations induced by p-benzoquinone (p-BQ), a benzene metabolite, in human cells using a shuttle vector plasmid pMY189, and compared frequencies, types and spectra of the mutations with those of the mutations previously revealed in mouse cells using a similar plasmid pNY200. We found that p-BQ induces mutations in human and mouse cells at similar frequencies but with different types of mutagenesis. The proportion of tandem base mutations was significantly lower in human cells than in mouse cells. Most base substitutions were induced in G:C base pairs in both human and mouse cells. However, the proportion of G:C-->C :G transversion is significantly higher in human cells. These findings indicate that the p-BQ-induced DNA damage in human and mouse cells is processed in a different manner, and that extrapolation of mice findings on experimental benzene carcinogenesis to human cancer risk assessment should be conducted carefully.

Animals↗

Postlabelling analysis of DNA adducts formed in human hepatoma cells treated with 3-nitrobenzanthrone.

3-Nitrobenzanthrone (NBA) is one of the most mutagenic nitroaromatic compounds that has been found recently in diesel exhaust and airborne particles. A [32P]-postlabelling analysis was carried out to examine the adducts in DNA from human hepatoma HepG2 cells treated with NBA. Two major and two minor adduct spots were obtained in the analysis. The structure of the compound obtained from one of the minor adduct spots was identified to be N-acetyl-3-amino-2-(2'-deoxyguanosin-3', 5'-bisphosphate-8-yl)-benzanthrone, based on identical mobility of the compound with that of synthetic standards in thin-layer chromatography and high performance liquid chromatography. This substance is the identical adduct found in our previous in vitro study. The yet-unidentified major adduct spots may be guanosin- and adenosin-benzanthrone adducts without the N-acetyl group.

Benz(a)Anthracenes↗