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Biomedical subjects

Y Ito

Publications and source records attributed to Y Ito.

At least 289 records · Page 16Linked to original sources

Structural analysis of the sugar chains of human urinary thrombomodulin.

The sugar chains of human urinary thrombomodulin were studied. N- and O-linked sugar chains were simultaneously liberated by hydrazinolysis followed by N-acetylation and were tagged with 2-aminopyridine. Then the structures of the N- and O-linked pyridylamino (PA-) sugar chains were analyzed by two-dimensional sugar mapping combined with exoglycosidase digestion. The major N-linked sugar chains of human urinary thrombomodulin were found to be monosialo- and disialofucosylbiantennary chains, while the major O-linked sugar chain was +/-Siaalpha2-3Galbeta1-3(+/-Siaalpha2-6)GalNAc. Thrombomodulin also contained the reported structure SO4-3GlcAbeta1-3Galbeta1-3(+/-Siaalpha2-6)Galbeta1-4Xyl [H. Wakabayashi, S. Natsuka, T. Mega, N. Otsuki, M. Isaji, M. Naotsuka, S. Koyama, T. Kanamori, K. Sakai, and S. Hase (1999) J. Biol. Chem. 274, 5436-5442]. In addition to these sugar chains, a single Glc was linked to Ser 287.

Acetylation↗

Demonstration of the pH sensitive binding of multivalent carbohydrate ligands to immobilized Shiga-like toxin 1 B subunits.

The cytotoxic effects of Shiga-like toxins from enterohemorrhagic Escherichia coli O157:H7 depend on the recognition of carbohydrate determinants by B subunits. As a specific carbohydrate ligand, globotriaosylceramide has been characterized. We developed an alternative binding assay using multivalent carbohydrate ligands. We prepared globotriose-conjugated poly-lysine, and measured their binding to immobilized recombinant B subunits by an ELISA format. The signals representing ligand binding were dependent on the amount of immobilized B subunits as well as on the concentration of the ligands. The ligand binding activity was lost in an acidic environment, in which changes in the local conformation of the B subunits have been reported. Furthermore, pH dependent dissociation of the ligands from the B subunits was observed. We also demonstrate that antiserum from mice immunized with the B subunits specifically interferes with ligand binding. This suggests further potential for an assay to screen for blocking antibodies that could inhibit toxin internalization into host cells.

Animals↗

Patterns of failure in carcinoma of the uterine cervix treated with definitive radiotherapy alone.

The purpose of this retrospective study was to evaluate the patterns of failure for the patients treated with definitive radiotherapy, and to discuss future treatment strategies for the uterine cervical cancer. From 1986 to 1995, 177 patients with stages I-III cervical cancer treated with a combination of two-axial conformal radiotherapy and radium brachytherapy were analyzed. The first treatment failures were pelvic failure in 11%, and distant metastases (DM) in 16% of the 177 patients. Paraaortic lymph nodes (PAN) were the most frequently metastatic regions (71%). In the pelvic control group, DM were in 6% of patients for stages I-II, and in 32% of patients for stage III. In the pelvic failure group, DM were in 75% of patients for stages I-II, and in 19% of patients for stage III. In stages I-II, the DM rate was significantly correlated with pelvic tumor control. However, there was no correlation in stage III. To improve survival, it is important to increase the pelvic tumor control rate for patients with stage I-II, and to increase the pelvic tumor and metastatic control rate in stage III. Additional treatments such as chemotherapy and/or PAN irradiation using conformal radiotherapy are required in stages I-II with locally bulky tumor and in stage III.

Adult↗

Correction of the bilateral complete cleft lip: transformation to a unilateral incomplete cleft lip closure.

The complete lip alveolus and cleft palate is the most difficult of all bilateral clefts to treat because of the deformity of and tissue insufficiency in the prolabium. A bilateral concomitant procedure is impractical for treatment of this condition because of the problems that have to be resolved postoperatively, including a short columella, a lack of philtrum, labial horizontal and vertical insufficiency, and vermilion and alveolar vestibulum insufficiency. A two-stage procedure called the transformation method has been developed to circumvent these problems, and the authors present it here. With this method one side is closed completely using the maximum amount of tissue available. Concomitantly, incomplete closure is performed on the other side. The result at the end of the first stage of the procedure is a condition approximating unilateral incomplete closure. The results were obtained from 6 patients who underwent complete bilateral closure and were followed for at least 2 years with satisfactory results.

Child, Preschool↗

Quantitative analysis of regional wall motion and thickening by quantitative gated SPECT: comparison with visual analysis.

PURPOSE: Electrocardiograph-gated myocardial SPECT permits a quantitative assessment of global and regional functions by quantitative gated SPECT software. To validate quantitative indexes of wall motion and wall thickening, the authors compared these indexes with visual scores. MATERIALS AND METHODS: Gated myocardial SPECT was performed 60 minutes after the administration of Tc-99m sestamibi at rest in 42 patients with coronary artery disease. Regional wall motion (measured in millimeters and wall thickening (expressed as a percentage) were calculated by quantitative gated SPECT software in nine left ventricular myocardial segments and the results were compared with the five-point visual score interpretations of cinematic display. RESULTS: A high correlation of wall motion was observed between the quantitative and visual analyses (r = 0.810; P < 0.001). In addition, a high but somewhat less significant correlation of wall thickening was observed between the quantitative and visual analyses (r = 0.606; P < 0.001). CONCLUSIONS: In conclusion, regional wall motion and wall thickening can be evaluated quantitatively by electrocardiograph-gated myocardial SPECT and quantitative gated SPECT software. This will be useful for functional assessments made with various interventions.

Aged↗

Optical coherence tomography for the noninvasive evaluation of the cornea.

PURPOSE: To determine the optical coherence tomographic (OCT) characteristics of normal corneas and to characterize the OCT images of abnormal corneal lesions. METHODS: Eleven eyes from 10 patients were examined at the Cornea Service of the Nagoya University Hospital: 4 had corneal pathologies, 4 underwent keratoplasty, and 2 were normal controls; 1 enucleated eye was also examined. OCT (OCT 2000 Zeiss-Humphrey) was used to study the normal cornea and various corneal abnormalities. We compared the OCT images to the observations made by slit-lamp biomicroscopy. RESULTS: Fluid spaces were detected as black images. A highly reflective reflex was observed at the interface of different tissues, and intensive backscattering (reflex) was seen when the incident ray hit the laminated layers vertically. Corneal opacities were not clearly imaged when they were diffuse and mild, or when they were arranged axially in a small area, as was the scar of the graft-host junction. It was possible to obtain images from the region of the cornea that was not clearly visible by slit-lamp examination because of a corneal opacity. CONCLUSION: OCT is a noncontact and noninvasive technique that can be performed safely on diseased corneas. OCT can provide objective documentation of corneal disorders that cannot be obtained by slit-lamp examination. The use of OCT in conjunction with other conventional instruments should provide a more complete image of the cornea.

Adult↗

Treatment of Bowen disease using the ultrasonic surgical aspirator.

In most cases, patients with Bowen disease lesions can be easily treated by surgical excision and direct closure; however, the ultrasonic surgical aspirator, an instrument in common use in many fields, offers a good treatment alternative with few drawbacks for patients with lesions that are large and/or located in joint areas, areas that are hard to heal, or areas that are surgically problematic such as the ears, nose, eyelids, and mucous membranes. The clinical application of the ultrasonic surgical aspirator in the treatment of Bowen disease promises considerable benefit in terms of patient comfort because removal of the lesion is easy, is noninvasive, and does not require hospitalization or result in restricted mobility. All of these factors, although benefiting patients, particularly the elderly, can also substantially lower the cost of treatment.

Aged↗

Expression of p57/Kip2 protein in pancreatic adenocarcinoma.

INTRODUCTION: Evaluation of the biologic character of carcinomas requires understanding of cell cycle regulators. AIMS: To investigate p57 expression in human pancreatic adenocarcinoma and cyst adenoma. METHODOLOGY: We examined the expression of p57(Kip2), a member of the Cip/Kip family, in 45 pancreatic adenocarcinomas, 7 cystadenomas, and 7 chronic pancreatitis cases. RESULTS: The p57 labeling index (LI) in duct epithelia in chronic pancreatitis averaged 32.8+/-8.3 and was significantly higher than in normal duct epithelia (18.8+/-6.6; p = 0.0011). For the carcinoma, the LI averaged 46.0+/-20.9, which was significantly higher than that for normal duct epithelia (p < 0.0001) and cystadenoma (16.0 11.2; p = 0.0007). However, it was significantly reduced in cases with stage IV disease (p = 0.0351), lymph node metastasis (p = 0.0003), larger size (p = 0.0094), capsular invasion (p = 0.0462), lymphatic invasion (p = 0.0351), and cell proliferating activity (p = 0.0002). In multivariate analysis, p57 LI in pancreatic adenocarcinoma was independently linked to high proliferating activity (p = 0.0230). CONCLUSION: These results suggest that p57 plays a role in the hyperplastic change of the ducts in chronic pancreatitis and that pS7 overexpression contributes to the downregulation of cell proliferation, and its decreased expression contributes to the progression of pancreatic adenocarcinoma.

Adenocarcinoma↗

Binding site for chitin oligosaccharides in the soybean plasma membrane.

Affinity cross-linking of the plasma membrane fraction to an (125)I-labeled chitin oligosaccharide led to the identification and characterization of an 85-kD, chitin binding protein in plasma membrane-enriched fractions from both suspension-cultured soybean cells and root tissue. Inhibition analysis indicated a binding preference for larger (i.e. degrees of polymerization = 8) N-acetylated chitin molecules with a 50% inhibition of initial activity value of approximately 50 nM. N-Acetyl-glucosamine and chitobiose showed no inhibitory effects at concentrations as high as 250 microM. It is noteworthy that the major lipo-chitin oligosaccharide Nod signal produced by Bradyrhizobium japonicum was also shown to be a competitive inhibitor of ligand binding. However, the binding site appeared to recognize the chitin portion of the Nod signal, and it is unlikely that this binding activity represents a specific Nod signal receptor. Chitooligosaccharide specificity for induction of medium alkalinization and the generation of reactive oxygen in suspension-cultured cells paralleled the binding activity. Taken together, the presence of the chitin binding protein in the plasma membrane fraction and the specificity and induction of a biological response upon ligand binding suggest a role for the protein as an initial response mechanism for chitin perception in soybean (Glycine max).

Binding Sites↗

Investigation of varicella-zoster virus DNA in lymphocyte subpopulations by quantitative PCR assay.

To investigate the nature of viremia during the acute phase of varicella, we studied the viral load in nine otherwise healthy children with varicella. Plasma and peripheral blood mononuclear cells (PBMC) were obtained, then PBMC were divided into CD4+T, CD8+T, and B lymphocytes and monocyte/macrophage fractions. The viral DNA in each component was quantified using a real-time quantitative polymerase chain reaction assay. Varicella-zoster virus (VZV) DNA was detected in plasma, PBMC and all subpopulations. The amount of viral DNA was similar in each PBMC subpopulation, suggesting that each lymphocyte fraction and monocytes carry similar amounts of VZV DNA during viremia.

Animals↗

Decrease in risk of lung cancer death in males after smoking cessation by age at quitting: findings from the JACC study.

To evaluate the impact of smoking cessation in individuals and populations, we examined the decrease in risk of lung cancer death in male ex-smokers by age at quitting in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk Sponsored by Monbusho (JACC Study), which was initiated from 1988 to 1990 in Japan. For simplicity, subjects were limited to male non-smokers, and former / current smokers who started smoking at ages 18 - 22, and 33654 men aged 40 - 79 years were included. We modeled the mortality rates in non-smokers and current smokers, and compared the rates in ex-smokers with those expected from the model if they had continued smoking. During the mean follow-up of 8.0 years, 341 men died from lung cancer. The mortality rate ratio for current smokers, compared to non-smokers, was 5.16, and those for ex-smokers who had quit smoking 0 - 4, 5 - 9, 10 - 14, 15 - 19 and > or = 20 years before were 4.84, 3.19, 2.03, 1.29 and 0.99, respectively. The functions of 3.20 x 10(-7) x (age)(4.5) and 1.96 x 10(-5) x (age - 29.6)(4.5) fitted the observed mortality rates (per 100000 person-years) in non-smokers and continuing smokers, respectively. A greater decrease in lung cancer mortality was estimated among those who quit smoking at younger ages. Stopping smoking earlier in life appears preferable to keep the individual risk low. The absolute rate, however, substantially decreased after smoking cessation even in those who quit at ages 60 - 69, reflecting the high mortality rate among continuing smokers in the elderly.

Adult↗

Dietary habits and risk of lung cancer death in a large-scale cohort study (JACC Study) in Japan by sex and smoking habit.

Lung cancer has increased and is the leading cause of cancer death among Japanese males. The associations of dietary habits with the risk of lung cancer death were evaluated by sex and smoking habits in this study. In the Japan Collaborative Cohort (JACC) Study, a cohort established in 1988 - 90 and consisting of 42 940 males and 55 308 females was observed for lung cancer deaths up to the end of 1997. During the observation period, 446 males and 126 females died of lung cancer. A self-administered food frequency questionnaire was used as the baseline survey. Hazard ratios for dietary factors were calculated by Cox's proportional hazards model. Among males, a high intake of ham and sausages, cheese, green-leafy vegetables, oranges, and other fruits significantly and dose-dependently decreased the risk of lung cancer death. Among females, a high intake of miso-soup, ham and sausages, and liver significantly and almost dose-dependently increased the risk. Vegetables and fruits rich in antioxidative and carcinogenic agents reduced the risk of lung cancer deaths among male smokers more than among female nonsmokers. The results among female nonsmokers were partially consistent with the hypothesis that high fat consumption increases the risk of lung cancer, especially that of adenocarcinoma.

Adult↗

The novel triterpenoid CDDO induces apoptosis and differentiation of human osteosarcoma cells by a caspase-8 dependent mechanism.

The oleanane triterpenoid 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid (CDDO) is a multifunctional molecule that induces monocytic differentiation of human myeloid leukemia cells and inhibits proliferation of diverse human tumor cell lines. The present studies on human osteosarcoma cells demonstrate that CDDO induces mitochondrial cytochrome c release, caspase-3 activation, and internucleosomal DNA fragmentation. Overexpression of the caspase-8 inhibitor CrmA blocked CDDO-induced cytochrome c release and apoptosis. By contrast, overexpression of the antiapoptotic Bcl-x(L) protein blocked CDDO-induced cytochrome c release, but only partly inhibited caspase-3 activation and apoptosis. In concert with these findings, we demonstrate that CDDO: 1) activates caspase-8 and thereby caspase-3 by a cytochrome c-independent mechanism and 2) induces cytochrome c release by caspase-8-dependent cleavage of Bid. The results also demonstrate that treatment of osteosarcoma cells with CDDO induces differentiation, as assessed by alkaline phosphatase activity and osteocalcin production, and that this response is abrogated in cells that overexpress CrmA. These findings demonstrate that CDDO induces both osteoblastic differentiation and apoptosis by caspase-8-dependent mechanisms.

Apoptosis↗

Hemagglutinin-neuraminidase-independent fusion activity of simian virus 5 fusion (F) protein: difference in conformation between fusogenic and nonfusogenic F proteins on the cell surface.

The fusion (F) protein of simian virus 5 (SV5) strain W3A is known to induce cell fusion in the absence of hemagglutinin-neuraminidase (HN) protein. In contrast, the F protein of SV5 strain WR induces cell fusion only when coexpressed with the HN protein, the same as do other paramyxovirus F proteins. When Leu-22 in the subunit F2 of the WR F protein is replaced with the counterpart (Pro) in the W3A F protein, the resulting mutant L22P induces extensive cell fusion by itself. In the present study, we obtained anti-L22P monoclonal antibodies (MAbs) 21-1 and 6-7, whose epitopes were located in the middle (amino acids [aa] 227 to 320) of subunit F1. The amino-terminal region (aa 20 to 47) of subunit F2 was also involved in the formation of MAb 21-1 epitope. Flow cytometric analysis revealed that both the MAbs reacted very faintly with native WR F protein that was expressed on the cell surface whereas they reacted efficiently with native L22P irrespective of whether it is cleaved into F1 and F2. However, by heating the cells at 47 degrees C after mild formaldehyde fixation, the epitopes for MAb 6-7 and mAb 21-1 in the WR F protein were exposed and the reactivity of the MAbs with the WR F protein became comparable to their reactivity with L22P. Thus, the two MAbs seem to distinguish the difference in native conformation between fusogenic mutant L22P and its parental nonfusogenic WR F protein. The native conformation of L22P may represent an intermediate between native and postfusion conformations of a typical paramyxovirus F protein.

Amino Acid Sequence↗

High resistance of human parainfluenza type 2 virus protein-expressing cells to the antiviral and anti-cell proliferative activities of alpha/beta interferons: cysteine-rich V-specific domain is required for high resistance to the interferons.

Human parainfluenza type 2 virus (hPIV-2)-infected HeLa (HeLa-CA) cells and hPIV-2 V-expressing HeLa (HeLa-V) cells show high resistance to alpha/beta interferons (IFN-alpha/beta) irrespective of whether vesicular stomatitis virus or Sindbis virus is used as a challenge virus. When Sindbis virus is used, these cells show high susceptibility to human IFN-gamma. Furthermore, the multiplication of HeLa-V cells is not inhibited by IFN-alpha/beta. HeLa cells expressing the N-terminally truncated V protein show resistance to IFN-alpha/beta, showing that the IFN resistance determinant maps to the cysteine-rich V-specific domain. A complete defect of Stat2 is found in HeLa-CA and HeLa-V cells, whereas the levels of Stat1 expression are not significantly different among HeLa, HeLa-CA, HeLa-P, and HeLa-V cells, indicating that IFN-alpha/beta resistance of HeLa-CA and HeLa-V cells is due to a defect of Stat2. HeLa-SV41V cells show high resistance to all IFNs, and no expression of Stat1 can be detected. Stat2 mRNA is fully detected in HeLa-V cells. Stat2 was scarcely pulse-labeled in the HeLa-V cells, indicating that synthesis of Stat2 is suppressed or Stat2 is very rapidly degraded in HeLa-V cells. The V protein suppresses the in vitro translation of Stat2 mRNA more extensively than that of Stat1 mRNA. An extremely small amount of Stat2 can be detected in HeLa-V cells treated with proteasome inhibitors. The half-life of Stat2 is approximately 3.5 and 2 h in uninfected and hPIV-2-infected HeLa cells, respectively. This study shows that synthesis of Stat2 may be suppressed and Stat2 degradation is also enhanced in hPIV-2-infected HeLa and HeLa-V cells.

Antiviral Agents↗

Targeting of the c-Abl tyrosine kinase to mitochondria in endoplasmic reticulum stress-induced apoptosis.

The ubiquitously expressed c-Abl tyrosine kinase localizes to the nucleus and cytoplasm. Using confocal microscopy, we demonstrated that c-Abl colocalizes with the endoplasmic reticulum (ER)-associated protein grp78. Expression of c-Abl in the ER was confirmed by immunoelectron microscopy. Subcellular fractionation studies further indicate that over 20% of cellular c-Abl is detectable in the ER. The results also demonstrate that induction of ER stress with calcium ionophore A23187, brefeldin A, or tunicamycin is associated with translocation of ER-associated c-Abl to mitochondria. In concert with targeting of c-Abl to mitochondria, cytochrome c is released in the response to ER stress by a c-Abl-dependent mechanism, and ER stress-induced apoptosis is attenuated in c-Abl-deficient cells. These findings indicate that c-Abl is involved in signaling from the ER to mitochondria and thereby the apoptotic response to ER stress.

Animals↗

Helicobacter pylori infection induces hyperammonaemia in Mongolian gerbils with liver cirrhosis.

BACKGROUND AND AIMS: We previously reported the effect of Helicobacter pylori eradication on hyperammonaemia in patients with liver cirrhosis. However, the role of H pylori as a cause of hyperammonaemia is controversial. We developed an animal model with liver cirrhosis and investigated the effect of H pylori infection on hyperammonaemia. MATERIALS AND METHODS: Five week old male Mongolian gerbils were inoculated orally with broth culture of H pylori. Forty eight gerbils were divided into four groups. Gerbils not inoculated with H pylori were fed a commercial rodent diet (group A) or a choline deficient diet (group C). Gerbils inoculated with H pylori were fed the commercial rodent diet (group B) or the choline deficient diet (group D). Blood ammonia levels of the femoral vein and portal vein were measured 30 weeks later. RESULTS: All gerbils fed the choline deficient diet developed liver cirrhosis with fatty metamorphosis. The survival rate of group D was significantly lower than that of the other groups. Systemic and portal blood ammonia levels in group D were significantly higher than those in the other groups. CONCLUSIONS: H pylori infection induces hyperammonaemia in gerbils with liver cirrhosis.

Animals↗

Gastric leptin and Helicobacter pylori infection.

BACKGROUND: Leptin regulates feeding behaviour and therefore may be a mediator of anorexia associated with acute and chronic inflammation. Recently, leptin mRNA and leptin protein were found in the gastric epithelium. AIM: The aim of the present study was to examine the effect of Helicobacter pylori infection on gastric leptin expression to investigate the pathophysiological role of gastric leptin. METHODS: Surgically resected human stomach tissues were subjected to immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) to check for the presence of leptin in the human gastric epithelium. A total of 201 H pylori positive patients with chronic gastritis underwent eradication therapy for H pylori and were examined for the effect of infection cure in terms of body mass index (BMI) and serum leptin levels. Biopsy specimens from the gastric fundic mucosa were obtained from 40 of the 201 patients before and three months after eradication therapy. These samples were subjected to quantitative RT-PCR to examine the effect of eradication therapy on leptin expression in the gastric fundic mucosa. RESULTS: Leptin immunoreactive cells were detected in the lower half of the gastric fundic glands and a leptin PCR product was also found in the gastric fundic mucosa. H pylori infection significantly increased gastric leptin expression. In addition, cure of H pylori infection significantly reduced gastric leptin expression, with a concomitant increase in BMI. In contrast, serum leptin levels did not change significantly after cure of H pylori infection. CONCLUSION: Leptin is present in the human gastric mucosa. Gastric leptin may play a role in weight gain after eradication of H pylori infection. Gastric leptin may have a local rather than systemic action.

Adult↗