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H Nagata

Publications and source records attributed to H Nagata.

At least 37 records · Page 2Linked to original sources
PubMed2003

Reliability of clinical parameters for predicting the outcome of oral malodor treatment.

We conducted the present study to determine which clinical parameters for diagnosing halitosis are most reliable in the development of an accurate prognosis for oral malodor treatment. Clinical evaluation included a questionnaire, oral examination and volatile sulfur compounds (VSC) measurement, and organoleptic test (OLT) at baseline. Ninety-two patients classified with oral pathologic halitosis were treated in a similar manner. Improved treatment outcome was defined as < 0.25 ppm of total VSC, < or = 2 OLT score, and < 30 on the "sad feeling" scale as subjective stress level by oral malodor 6 months after baseline. Thirty-four patients demonstrated improvement due to the treatment. In a multiple logistic model, pocket depth, OLT score, intra-oral discomfort, and self-perception of oral malodor at baseline displayed significant association with "not improved outcome". These results suggest that malodor- and periodontal-disease-related parameters and self-estimation of malodor at baseline are effective for prediction of outcome.

Adolescent↗
PubMed2002

Characterization of binding and utilization of hemoglobin by Prevotella nigrescens.

The ability of Prevotella nigrescens to utilize and bind to hemoglobin was investigated. Growth studies showed that P. nigrescens was able to utilize hemoglobin efficiently as an iron source. Binding of P. nigrescens to hemoglobin was demonstrated by dot blot assay. Heat and trypsin treatments of the bacteria led to a decrease in activity. Globin gave nearly complete inhibition of activity. Additionally, lactoferrin partially inhibited activity. In contrast, transferrin, cytochrome C and catalase exerted little or no inhibitory effect. Although the sugars tested did not affect activity, several of the amino acids tested, including arginine, cysteine, histidine and lysine, inhibited activity. In a solid phase assay, 41-, 56- and 59-kDa proteins of P. nigrescens reacted with hemoglobin. These results suggest that P. nigrescens utilizes hemoglobin for growth and 41-, 56- and 59-kDa proteins may be involved in hemoglobin binding.

Arginine↗
PubMed2002

Increased expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and lymphocyte recruitment in murine gastritis induced by Helicobacter pylori.

Although T cell involvement in Helicobactor pylori-induced gastritis is known, mechanism about T cell recruitment is not understood. In this study we examined how mucosal addressin cell adhesion -molecule-1 (MAdCAM-1) is involved in lymphocyte recruitment in murine chronic gastritis induced by H. pylori. C57 BL/6 mice were infected with Sydney strain (SS1). Six months after infection, the stomach was removed. The expression of adhesion molecules, MAdCAM-1, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), and the cell surface antigens CD4, CD8, CD45R/B220 or beta7-integrin were determined by immunohistochemistry. A significant increase in CD4 lymphocytes was observed in the body portion of stomach in SS1-infected mice and most of these CD4 cells express beta7-integrin, a known counter ligand for MAdCAM-1 molecule. Strong MAdCAM-1 expression was observed adjacent to these cells in the lamina propria as well as in the submucosa of SS1-infected stomach. Quantitative analysis showed that the area of MAdCAM-1 expression well correlated with the infiltration of beta7-integrin positive lymphocytes. On the other hand, expression of ICAM-1 or VCAM-1 in the lamina propria was few even in the SS1-infected stomach. Increased expression of MAdCAM-1 was well correlated to the location of lymphocytes, which express CD4 and beta7-integrin. These results suggest the possibility that MAdCAM-1 may be largely involved in the lymphocyte recruitment in the gastritis mucosa with H. pylori.

Animals↗
PubMed2001

In situ expression of corticotropin-releasing hormone (CRH) and proopiomelanocortin (POMC) genes in human skin.

Systemic stresses induce corticotropin-releasing hormone (CRH) expression in hypothalamus. CRH is released to the pituitary gland, where it stimulates proopiomelanocortin (POMC) production acting via the CRH receptor (CRH-R). CRH and POMC peptides are also detected in sites outside of the central nervous system (CNS), such as the skin. However, it has not been elucidated whether these peptides detected in the skin are derived from CNS or are produced locally. Using immunohistochemical and in situ reverse-transcription (RT)-PCR techniques, we demonstrated coexpression of CRH and POMC mRNAs in the epidermis and pilosebaceous units of the human skin. This coexpression was confirmed by the combination of laser-capture microdissection (LCM) with RT-PCR, analyzing mRNA expressions in captured sebaceous cells. Immunoreactivities and expressions of CRH and POMC mRNAs were strong in inflammatory lesions, melanocytic nevus, seborrheic keratosis, and also in the periphery of the benign tumor. These findings suggest that CRH and POMC peptides are produced locally in the skin and are regulated by inflammatory cells as well as by autocrine mechanisms. The skin may have "a local stress response system," whose activity is mediated by CRH and POMC peptides, in an equivalent to hypothalamus-pituitary adrenal axis.

Corticotropin-Releasing Hormone↗
PubMed2001

Reduced sensitivity of inducible nitric oxide synthase-deficient mice to chronic colitis.

BACKGROUND: Overproduction of nitric oxide by the inducible form of nitric oxide synthase (iNOS) has been implicated in colitis. Different authors have postulated both toxic and protective effects of nitric oxide (NO) in the pathophysiology of active inflammation. The objective of this study was to examine the role of iNOS in experimental chronic colitis using iNOS-deficient mice. METHODS: For induction of colitis, mice received three cycles of 2% of dextran sodium sulfate (DSS) (M.W. 40,000) treatment in drinking water. The degree of colonic inflammation, leukocyte infiltration, and the expression of cell adhesion molecules were determined. INOS expression and nitrotyrosine were also determined by immunohistochemistry. RESULTS: After DSS treatment, a moderate colitis with marked cell infiltration was observed. Intense expression of iNOS was observed on infiltrating cells as well as on the colonic mucosal epithelium in these animals. In the iNOS-deficient mice, tissue damage was significantly diminished. No iNOS or nitrotyrosine staining was found in iNOS-deficient mice. The number of infiltrating cells and the expression of mucosal adressin cell adhesion molecule-1 were significantly attenuated in the DSS-treated colon of iNOS-deficient mice. CONCLUSION: Induction of iNOS seems to act as a critical toxic effector molecule in the pathogenesis of chronic colonic inflammation.

Animals↗
PubMed2001

Localization of a novel susceptibility gene for familial ovarian cancer to chromosome 3p22-p25.

We performed genome-wide linkage analysis in 58 patients and nine unaffected members among 28 families with no mutation in BRCA1 or BRCA2, employing a set of 410 microsatellite markers. We initially screened the whole genome, including the X chromosome, by a non-parametric method using the GENEHUNTER program. As a result, chromosome 3p22-p25 showed a suggestive score for linkage [LOD = 3.49 and non-parametric LOD (NPL) = 2.77 at D3S3611] based on a multipoint analysis. Additionally, based on a two-point analysis using dense markers, this 3p22-p25 region showed a P-value < 0.05 at 10 markers and there is suggestive evidence for linkage at two markers within approximately 19 cM (NPL = 2.60 and 2.49 at D3S1597 and D3S3611, respectively). To explore whether the candidate gene in this 3p22-p25 region contributed to carcinogenesis of familial ovarian cancer in a similar fashion to the tumor suppressor gene, we performed loss of heterozygosity (LOH) analysis. It was observed that the frequency of LOH at four markers in this region was >50% only in tumor tissues from patients with no mutation in BRCA1 or BRCA2, not in those with a BRCA1 mutation.

Adult↗
PubMed2001

Characterization of novel natural killer (NK)-cell and gammadelta T-cell lines established from primary lesions of nasal T/NK-cell lymphomas associated with the Epstein-Barr virus.

Studies on nasal T/natural killer (NK)-cell lymphoma have been hampered by its tendency to cause necrosis. Thus, the establishment of cell lines of this neoplasm would seem to be valuable. This study attempted to establish cell lines from primary lesions of this tumor, and successfully obtained 2 novel Epstein-Barr virus (EBV)-positive cell lines, SNK-6 and SNT-8, by means of high-dose recombinant interleukin 2. Flow cytometry showed that SNK-6 had an NK-cell phenotype, CD3- CD4- CD8- CD19- CD56+ T-cell receptor (TCR) alpha/beta- TCR gamma/delta-, whereas SNT-8 was CD3+ CD4- CD8- CD19- CD56+ TCR alpha/beta- TCR gamma/delta+. These were consistent with immunophenotypes of their original tumors, and the cell lines had monoclonal EBV clones identical to ones in their original tumors. Thus, the cell lines developed from cells forming the primary lesions. Genotypic analysis showed that SNK-6 had unrearranged TCR and immunoglobulin heavy-chain genes, supporting the conclusion that SNK-6 was of NK-cell lineage. On the other hand, SNT-8 had rearranged TCR beta-, gamma-, and delta-chain genes, and together with its phenotype, SNT-8 proved to be a gammadelta T-cell line. This is the first report of the establishment of cell lines from primary lesions of nasal T/NK cell lymphomas, and the results demonstrated that there are at least 2 lineages, NK- and gammadelta T-cell, in this neoplasm. Moreover, it has been suggested that nasal T/NK cell lymphomas of these lineages may belong to the same clinicopathologic entity because both types of cases shared common clinical and histopathologic features.

Blotting, Southern↗
PubMed2001

Inhibition of hepatic metastasis in mice treated with cell-binding domain of human fibronectin and angiogenesis inhibitor TNP-470.

BACKGROUND: To prevent tumor metastasis, we administered the cell-binding domain of fibronectin, in combination with the angiogenesis inhibitor TNP-470, to mice with hepatic metastasis. We then assessed the prevention of tumor metastasis resulting from the inhibition of adhesive interactions and the inhibition of angiogenesis. METHODS: A hepatic metastasis model was created by injecting 1 x 10(3) colon 26/TC-1 cells into the anterior mesenteric vein of CDF1 mice. The cell-binding domain obtained from fibronectin included the Arg-Gly-Asp (RGD) sequence. A fibronectin-binding domain (FND)-treated group, an FND plus TNP-470 group, and a control group were established. The animals were killed 4 weeks after the injections of the treatment agents had been completed and the number of metastatic liver nodules was counted. In a simultaneous experiment with the same design, the mice were not killed at 4 weeks, and their survival was observed. RESULTS: The mean number of nodules in the FND plus TNP-470 group was significantly lower than that in the control group (P = 0.019337). The inhibition rate was 51% in the FND group, 60% in the FND 10 micrograms plus TNP-470 10 mg/kg group, and 64% in the FND 10 micrograms plus TNP-470 100 mg/kg group compared with the control group. Mice from the FND group that were not killed died after 6-8 weeks, but mice from the FND plus TNP-470 group died after 8-12 weeks. CONCLUSION: The cell-binding domain of fibronectin may, potentially, be an effective form of antiadhesive therapy that competes with native adhesion molecules and blocks adhesion during the metastatic process. When the cell-binding domain of fibronectin is combined with TNP-470 to inhibit angiogenesis, more effective inhibition of metastatic tumor growth and prolongation of survival can be achieved than after treatment with the cell-binding domain alone.

Angiogenesis Inhibitors↗
PubMed2001

Anti-arthritic effects of KF20444, a new immunosuppressive compound inhibiting dihydroorotate dehydrogenase, on rat collagen-induced arthritis.

OBJECTIVE AND DESIGN: A newly synthesized inhibitor of pyrimidine de novo biosynthesis, KF20444 (6,7-dihydro-10-fluoro-3-(2-fluorophenyl)-5H-benzo [6,7] cyclohepta [1,2-b] quinoline-8-carboxylic acid), was evaluated as an inhibitor of dihydroorotate dehydrogenase (DHO-DHase) and tested in the rat collagen-induced arthritis (CIA) model. MATERIAL AND METHODS: Female Sprague Dawley rats, 5 weeks-old, were used for evaluation of KF20444 in the CIA model. Arthritis was evaluated by arthritis score, serum anti-type II collagen antibody titer, body weight loss, radiographical and histological changes. TREATMENT: KF20444 was orally administered 5 times per week (0.3, 1, 3 mg/kg/day). RESULTS: KF20444 inhibited rat liver dihydroorotate dehydrogenase in vitro with Ki = 8.5 +/- 3.2 nM, which was a comparable effect to that of brequinar sodium (Ki = 25.3 +/- 5.3 nM). The anti-proliferative effect of KF20444 was caused by cell cycle arrest at the S-phase. Treatment with 3 mg/kg/day of KF20444 completely prevented the development of CIA based on reduction of the arthritis score. The 50% effective dose (ED50) of KF20444 on arthritis score was 0.64 mg/kg. KF20444 ameliorated body weight loss associated with disease onset. The compound also inhibited the increase in serum anti-type II collagen antibody level, and reduced both pannus formation and bone erosion. Importantly, KF20444 suppressed the development of arthritis, even when it was administered after booster immunization of collagen. CONCLUSIONS: KF20444 is a novel immunosuppressant which inhibits DHO-DHase and its effects in CIA suggest that it could be useful in the treatment of rheumatoid arthritis.

Animals↗
PubMed2001

Association between nasal allergy and a coding variant of the Fc epsilon RI beta gene Glu237Gly in a Japanese population.

The gene for the beta-chain of the high-affinity receptor for IgE (Fc epsilon RI beta) has been proposed as a candidate gene for atopy. A coding variant Glu237Gly has been studied in various populations with asthma and atopy, and the results were controversial for association of the variant with atopy/asthma. Because nasal allergy is a more common atopic disease and shows less remission than asthma, we analyzed whether the Glu237Gly variant is correlated with nasal allergy. The study enrolled 233 patients with nasal allergy and 100 control subjects. Further, three subgroups were selected: patients with perennial nasal allergy (n=149), Japanese cedar pollinosis (n=189), and allergy to multiple allergens (n=45). The allele frequency of Gly237 in the controls and patients was 0.14 and 0.20, and the frequency of Gly237-positive subjects was 0.23 and 0.356, respectively. There was a significant association between Gly237-positivity and nasal allergy, perennial nasal allergy, Japanese cedar pollinosis, and allergy to multiple allergens. Among all 333 subjects we observed a significant relationship between Gly237 and elevated levels of serum total IgE (>250 IU/ml) and very high IgE (>1000 IU/ml). Among patients positive for a specific IgE, Gly237 was significantly associated with high IgE for house dust, mite, and Japanese cedar pollen. These results suggest that the Glu237Gly variant of the Fc epsilon RI beta gene is involved in the development of nasal allergy through the process for the production of both specific and nonspecific IgE antibodies.

Adolescent↗
PubMed2001

Expression and localization of leptin receptor in the normal rat pituitary gland.

Leptin receptor (leptin-R) is a polypeptide consisting of a single transmembrane-spanning component. Recent studies performed by reverse transcriptase polymerase chain reaction (RT-PCR) have shown the production of leptin-R in various tissues including the pituitary, hypothalamus and reproductive organs. The localization of leptin-R protein in the pituitary gland, however, has not been extensively studied. This study deals with the expression of leptin-R in the normal rat pituitary gland, which was disclosed primarily in the plasma membrane fraction by immunoblotting and immunohistochemical staining methods. Double immunohistochemical staining revealed that the colocalization of leptin-R and anterior pituitary hormone expression was seen mainly in growth hormone (GH)-secreting cells (97.4 +/- 1.3%; GH-positive cells/leptin-R-positive cells), but in less than 1% of prolactin (PRL)-, adrenocorticotropic hormone (ACTH)-, thyroid-stimulating hormone-beta (TSH beta)- and follicle-stimulating hormone-beta (FSH beta)/luteinizing hormone-beta (LH beta)-positive cells. In contrast, leptin was localized most frequently in FSH beta/LH beta- and less frequently in TSH beta-positive cells. The above findings suggest that, in the rat anterior pituitary gland, there are paracrine relationships between leptin-producing cells and cells with leptin-R, which may regulate the function of GH cells.

Adrenocorticotropic Hormone↗
PubMed2001

Frequency and clinical features of patients with sensorineural hearing loss associated with the A3243G mutation of the mitochondrial DNA in otorhinolaryngic clinics.

The A3243G mutation of the mitochondrial gene is a cause of maternally inherited diabetes and deafness. The aim of this study was to evaluate the frequency and clinical features of this mutation in patients with sensorineural hearing loss (SNHL) in otorhinolaryngic clinics. The frequency of the A3243G mutation in 230 patients with SNHL was 1.74% (4/230). Three of the four patients had diabetes mellitus (DM) and were already aware that they had the mutation. The other had cardiomyopathy but not DM, and proved to have the mutation in this study. The frequency of the mutation was 12.9% (4/31) in patients with a family history of possible maternal inheritance of SNHL, 10.3% (3/29) in patients with DM, and 50% (3/6) in patients with both. The age of onset of SNHL in these patients and their families was between their teens and their forties. The chance of diagnosing the A3243G mutation in patients with SNHL in otorhinolaryngic clinics is probably less than 1%. Association of DM, cardiomyopathy, a family history of possible maternal inheritance of SNHL, and an onset of SNHL between the teens and the forties are signs suggesting the mutation. These signs provide us with a reason for genetic testing for the mutation.

Adolescent↗
PubMed2001

Japanese experience of telemedicine in oncology.

We started telemedicine projects from 1990 with a telepathology system within Tsukiji Campus of National Cancer Center. In 1994, we connected Tsukiji Campus and Kashiwa Campus by 6 Mbps optical fiber leased line using IP protocol for data transmission, for teleconference, telepathology, and teleradiology projects. We also started connection of regional cancer centers and are now forming a cancer center network of 14 cancer centers. We are at present organizing 130 teleconferences per year with an attendance of more than 16000 people as summary. We have also used a high-resolution image transferring system, such as SHD (2000 pixelsx2000 pixels resolution) system on one side, and an economical telemedicine system using JAVA and a WWW browser (NCC_image) on the other side. We think that providing information is another field of telemedicine. We began the experimental gopher and WWW service in 1993. We are now providing official up-to-date cancer information for patients and healthcare professionals. We are getting more than 400000 hits per month. We are also providing a teleconference video session which is held every week on the Internet using a Real Video system with synchronized slide presentation on the WWW browser. We are also organizing a Cancer Image Reference Database System including DICOM images with viewer software. This paper is a summary of the telemedicine projects performed at the National Cancer Center.

Community Networks↗
PubMed2001

Interferon-associated retinopathy in a uniform regimen of natural interferon-alpha therapy for chronic hepatitis C.

BACKGROUND/AIMS: The development of retinal lesions induced by a uniform regimen of interferon-alpha therapy for chronic hepatitis C was prospectively investigated. METHODS: Eighty-one patients received 6 mega units of natural interferon-alpha intramuscularly daily for 2 weeks and then 3 times a week for 22 weeks. The total dose of interferon-alpha administered was uniformly 478 mega units per patient. Two expert ophthalmologists prospectively examined the patients for retinal lesions before, during and after the therapy. RESULTS: Retinopathy was not found in comparison groups or any of the patients before treatment. In total 34.6% (28/81) of the patients showed cotton-wool spots or minor retinal hemorrhage, or both lesions, during therapy, but these lesions were reversed during or after interferon therapy. The occurrence rates of cotton-wool spots alone, retinal hemorrhage alone and both lesions were 13.6% (11/81), 6.2% (5/81), and 14.8% (12/81), respectively. The appearance of retinopathy did not correlate with patients' background including viral loads and response to the therapy, but was more frequently found in older patients and patients with hypertension and/or diabetes mellitus; disappearance of retinopathy was more prolonged than in patients without these complications. Almost all the lesions appeared 2-4 months after the start of the therapy, and the severity of the lesions did not differ between patients with and without hypertension and/or diabetes mellitus. CONCLUSION: Although it is not clear if interferon-associated retinopathy occurs in a dose-dependent manner, the present study shows a standard pattern of the occurrence of retinopathy in patients with chronic hepatitis C receiving a uniform dosage of natural interferon-alpha.

Age Distribution↗
PubMed2001

Involvement of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) in the pathogenesis of granulomatous colitis in rats.

Although increased expression of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) has been demonstrated in inflammatory sites of various diseases, its role in colitis remains unknown. In this study, we examined whether MAdCAM-1 is involved in the pathogenesis of granulomatous colitis induced by peptidoglycan-polysaccharide (PG-PS). Experimental colitis was induced by intramural injection of PG-PS to rat colon. After 3 weeks the colon was removed and the mucosal inflammation was assessed. The area of MAdCAM-1-positive venules and the subsets of infiltrating cells were determined in colonic mucosa by immunohistochemistry. In another experiment, monoclonal antibody against MAdCAM-1 was administered intraperitoneally to examine its attenuating effect on colitis. The intramural injection of PG-PS induced significant colonic inflammation with granuloma formation. The submucosa was drastically thickened with the infiltration of CD4 positive lymphocytes and ED-1 positive macrophages. Intense MAdCAM-1 expression was observed on endothelium of the submucosal venules in inflamed mucosa. Administration of anti-MAdCAM-1 antibody significantly attenuated the PG-PS-induced colonic damage and cell infiltration. Enhanced expression of MAdCAM-1 was demonstrated in venular endothelium of the inflamed colon in PG-PS-induced colitis. The attenuating effect of anti-MAdCAM-1 suggests the importance of the MAdCAM-1-dependent process in the formation of chronic granulomatous colitis.

Animals↗
PubMed2001

Presence of natural killer-cell clones with variable proliferative capacity in chronic active Epstein-Barr virus infection.

Chronic active Epstein-Barr virus infection (CAEBV) is a syndrome that takes diverse clinical courses and is often associated with lymphoproliferative disorders of T/natural killer (NK)-cell lineage. We describe a patient with CAEBV associated with persistent pharyngeal ulcer, and with subsequent nasal T/NK-cell lymphoma in her neck lymph nodes and nasopharynx. Immunophenotyping of lymphoid cells showed that the lineage of Epstein-Barr virus (EBV)-positive cells in the patient was of NK-cell origin. By means of high-dose recombinant interleukin-2, we established an EBV-positive cell line of NK-cell lineage from her peripheral blood. Southern blot analysis for the number of terminal repeat sequences of EBV detected three NK-cell clones in the patient's lymph node. One of these clones was identical to the established cell line but was not observed in the pharyngeal ulcer, while the other two clones were present in the pharyngeal ulcer. These results suggest that the patient had expansion of the three NK-cell clones, one of which had proliferative capacity in vitro and was involved in the formation of the lymphoma. Moreover, the results suggest that the proliferative capacity of EBV-positive cells can be variable even in a single patient, and this variability may explain the clinical diversity in CAEBV.

Adult↗