Search PubMed⌕ Search

Biomedical subjects

N Ito

Publications and source records attributed to N Ito.

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

Hyperkeratosis and leukocytosis in transgenic mice carrying MHC class I chain-related gene B (MICB).

Major histocompatibility complex (MHC) class I chain-related gene A and B (MICA and MICB) are located very close to HLA-B. MICA is reported to be strongly associated with Behçet's disease (BD), a multisysytemic inflammation disorder characterized by oral apthous ulcers, skin lesions and genital ulcers. These two molecules are highly conserved at the amino acid levels. To determine the function of MICB in vivo and the relationship between the expression of MICB and BD experimentally, we produced several transgenic mouse lines (termed CAG-MICB) expressing human MICB cDNA under a ubiquitous promoter. They exhibited a 50% increase in the number of white blood cells compared with their non-transgenic littermates, and also exhibited a 10-20% reduction in body weight compared with non-transgenic littermates. Exfoliation of the skin first appeared around 7 days after birth and disappeared after 2 weeks of age. This was repeatedly observed in the transgenic offspring of two independent CAG-MICB lines examined. Histopathological analysis of skin of young mice exhibiting skin abnormalities revealed hyperkeratosis of the epidermis and thickening of the granular layer with slight infiltration of inflammatory cells in the dermis without any vasculitis. Other remarkable abnormalities associated with BD have not been observed in the CAG-MICB lines. Furthermore, fluorescein angiography of eyes of the CAG-MICB lines was performed, but there were no marked changes of BD-related uveitis in the ocular fundus. These findings suggest that (i) MICB expression is related to temporary skin inflammation, and (ii) expression of MICB is not directly associated with BD.

Animals↗
PubMed2003

Isolation of Mycoplasmas from nasal swabs of calves affected with respiratory diseases and antimicrobial susceptibility of their isolates.

Nasal swabs of 293 calves were examined for Mycoplasma. The samples were collected from calves affected with respiratory diseases on 71 farms in various parts of Japan between 1996 and 1997. Mycoplasma bovirhinis was isolated from 47 of 293 calves (16.0%). Mycoplasma alkalescens, M. bovis, M. arginini, M. bovigenitalium and Acholeplasma spp. were isolated from 19 (6.5%), seven (2.4%), four (1.4%), four (1.4%) and 18 (6.1%) calves, respectively. Pasteurella multocida and P. haemolytica were isolated from 60% of Mycoplasma-positive calves. However, other bacteria were not isolated from calves. To evaluate the antimicrobial susceptibility of their isolates, 68 M. bovirhinis, 21 M. alkalescens and 10 M. bovis strains were examined for 12 antimicrobial agents. All isolates showed higher susceptibility to tiamulin than to the other drugs used in the study. However, erythromycin had no effect on any of the Mycoplasma strains studied. The field isolates were less susceptible than the type strains to some drugs, such as spiramycin, oxytetracycline and tylosin.

Animals↗
PubMed2002

Augmentation effect of postprandial hyperinsulinaemia on growth of human hepatocellular carcinoma.

BACKGROUND: Cirrhotic patients with hepatocellular carcinoma (HCC) frequently have impaired glucose metabolism. AIMS: To investigate whether impaired glucose metabolism affects the growth rate of the tumour. PATIENTS AND METHODS: Tumour doubling time (DT), assessed by ultrasound imaging analysis, was measured in 60 patients with single small HCC (diameter <30 mm). DT was compared with plasma insulin and glucose concentrations following the oral glucose tolerance test (OGTT). The effect of continuous infusion of octreotide (a somatostatin analogue 200 microg/day) for three months on DT in five cases was assessed. RESULTS: The 60 patients were divided into two groups because the median DT was 140 days: rapid growth group (DT 140 days, n=30). Fasting plasma insulin concentration and area under the plasma insulin curve (AUC(ins)) of the OGTT (10.4 (6.2) microU/ml and 262 (152) microU/ml/h, respectively; mean (SD)) in the rapid growth group were significantly higher than those in the slow growth group (7.6 (4.3) and 146 (140), respectively) (p=0.041 and p=0.0006, respectively). In contrast, fasting plasma glucose concentration and area under the plasma glucose curve (AUC(gluc)) in the rapid growth group were significantly lower than those in the slow growth group (p=0.0003 and p=0.0012, respectively). Univariate and multivariate analyses of logistic regression models demonstrated that AUC(ins) was a significant factor contributing to the growth rate of HCC (p=0.001 and p=0.016, respectively). AUC(ins) significantly decreased after octreotide treatment (p<0.02) but AUC(gluc) did not significantly change. DT after treatment increased in three of the five patients and could not be calculated in the remaining two patients because of no change in the diameter of the tumour. CONCLUSIONS: These data suggest that postprandial hyperinsulinaemia is associated with accelerated HCC growth.

Area Under Curve↗
PubMed2001

Selective encapsulation of chloride ions within novel cage host complexes in the presence of equimolar amounts of chloride and bromide ions.

Four macrotricyclic cage hosts which feature four positive binding sites oriented toward the center of the intramolecular cavity are presented as promising candidates for anion receptors and they have been expected to play a important role in the selective encapsulation of the halide ion Cl- or Br . The complementarity between a macrotricyclic quaternary ammonium ion and Cl- was achieved by fine-tuning of the four ammonium nitrogen atoms and the endocyclic methylene groups. The cage hosts [R4N4(C5H10)4(C6H12)2]4+ (abbreviated as [556]) showed perfect encapsulation of all chloride ions in acetonitrile at 0 < r= ([Cl-]o/[[556]]o) < or = 1 within the sensitivity of the 1H NMR spectra in combination with a rather slow chemical exchange of the Cl- ion in an encapsulation/decapsulation equilibrium with [556]. Further, the selective encapsulation of all the chloride ions into [556] cage occurs unambiguously at r = 1 in the presence of equimolar amounts of Br-. The structural complementarity of the newly designed [556] host prevails over the Hofmeister-series restraints determined by differences in Gibbs free energy of halide anion solvation.

Anions↗
PubMed2001

Pronounced inhibition by a natural anthocyanin, purple corn color, of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-associated colorectal carcinogenesis in male F344 rats pretreated with 1,2-dimethylhydrazine.

The potential of purple corn color (PCC), a natural anthocyanin, to modify colorectal carcinogenesis was investigated in male F344/DuCrj rats, initially treated with 1,2-dimethylhydrazine (DMH), receiving 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in the diet. After DMH initiation, PCC was given at a dietary level of 5.0% in combination with 0.02% PhIP until week 36. No PCC-treatment-related changes in clinical signs, body weight and food consumption were found. Incidences and multiplicities of colorectal adenomas and carcinomas in rats initiated with DMH were clearly increased by PhIP. In contrast, lesion development was suppressed by PCC administration. Furthermore, in the non-DMH initiation groups, induction of aberrant crypt foci by PhIP tended to be decreased by the PCC supplementation. The results thus demonstrate that while PhIP clearly exerts promoting effects on DMH-induced colorectal carcinogenesis, these can be reduced by 5.0% PCC in the diet, under the present experimental conditions.

1,2-Dimethylhydrazine↗
PubMed2001

Homophilic complex formation of MT1-MMP facilitates proMMP-2 activation on the cell surface and promotes tumor cell invasion.

Activation of proMMP-2 by MT1-MMP is considered to be a critical event in cancer cell invasion. In the activation step, TIMP-2 bound to MT1-MMP on the cell surface acts as a receptor for proMMP-2. Subsequently, adjacent TIMP-2-free MT1-MMP activates the proMMP-2 in the ternary complex. In this study, we demonstrate that MT1-MMP forms a homophilic complex through the hemopexin-like (PEX) domain that acts as a mechanism to keep MT1-MMP molecules close together to facilitate proMMP-2 activation. Deletion of the PEX domain in MT1-MMP, or swapping the domain with the one derived from MT4-MMP, abolished the ability to activate proMMP-2 on the cell surface without affecting the proteolytic activities. In addition, expression of the mutant MT1-MMP lacking the catalytic domain (MT1PEX-F) efficiently inhibited complex formation of the full-length enzymes and activation of pro MMP-2. Furthermore, expression of MT1PEX-F inhibited proMMP-2 activation and Matrigel invasion activity of invasive human fibrosarcoma HT1080 cells. These findings elucidate a new function of the PEX domain: regulating MT1-MMP activity on the cell surface, which accelerates cellular invasiveness in the tissue.

Animals↗
PubMed2001

Primary culture system of adrenocortical cells from dogs to evaluate direct effects of chemicals on steroidogenesis.

The present study was conducted to confirm the usefulness of a primary culture system of adrenocortical cells from dogs for detecting the direct effects of the chemicals on adrenal cortex. Corticosteroid levels in the culture supernatant were measured using high-performance liquid chromatography (HPLC) following 24-h incubation with the chemicals. Ketoconazole, miconazole, metyrapone, aminoglutethimide, and 1-(o-chlorophenyl)-1-(p-chlorophenyl)-2,2-dichloroethane (o,p-DDD), which were known to inhibit cortisol production were evaluated in this system. Both viable cells and corticosteroid levels were decreased by o,p-DDD treatment. Other chemicals showed various inhibition patterns of corticosteroid levels as follows without affecting cell viability. Ketoconazole decreased total corticosteroids level by mainly due to the decreases in cortisol and 11-deoxycortisol levels. Miconazole decreased cortisol and 11-deoxycortisol levels, however, slightly increased corticosterone level. Metyrapone decreased cortisol and corticosterone levels as 11-deoxycortisol and 11-deoxycorticosterone levels were increased. Aminoglutethimide decreased total corticosteroids level by mainly decreasing cortisol, corticosterone and 11-deoxycortisol levels. These results suggested that determination of the pattern of corticosteroid levels by HPLC in this system well reflected the mode of their action on steroidogenesis. Thus, we conclude this simple system was useful to determine the direct effects of chemicals on steroidogenesis in the adrenal cortex.

Adrenal Cortex↗
PubMed2001

Suppression of integrin expression and tumorigenicity by sulfation of lactosylceramide in 3LL Lewis lung carcinoma cells.

To investigate the cellular functions of sulfated glycosphingolipids, we introduced the cerebroside sulfotransferase (CST) gene into J5 cells, a subclone of 3LL Lewis lung carcinoma cells. The J5 cells lack acidic glycosphingolipids but accumulate their common biosynthetic precursor, lactosylceramide. We established the stable CST transfectants, J5/CST-1 and J5/CST-2 clones, highly expressing sulfated lactosylceramide (SM3). Both clones exhibited more spherical morphology in comparison to mock transfectant, and their adhesiveness to fibronectin and laminin was significantly lower. The loss of cell-substratum interactions in these SM3-expressing cells could be attributed to decreased expression of integrins (alpha(5), alpha(6), and beta(1)) on the cell surface and their whole cellular levels. However, the levels of H-2K(b) and H-2D(b) antigens remained unchanged. Reverse transcriptase-polymerase chain reaction and Northern blot analyses for these integrins exhibited significant decrease of beta(1) gene expression in J5/CST-1 and 2, but there was no change in the levels of alpha(5) and alpha(6) transcripts. Deglycosylation by endoglycosidase H treatment clearly demonstrated that the precursor form of beta(1) integrin, possessing high mannose oligosaccharide chains, was preferentially decreased in the CST transfectants. These results demonstrate that endogenous SM3 negatively regulates beta(1) integrin expression at the transcriptional level, and the decrease of alpha integrin proteins in the CST transfectants was due to the post-transcriptional modification. We suggest the putative importance of the intracellular pre-beta(1) integrin pool for normal integrin maturation and subsequent function. Although the rates of cell proliferation in vitro for mock and CST transfectants were similar, tumorigenicity of J5/CST-1 and -2 cells inoculated into syngeneic C57/BL6 mice was greatly decreased or even absent. This was probably due to global loss of the efficient cell-matrix interactions, which are essential for the development of malignant tumors in vivo. Thus, we showed the evidence that cellular SM3 negatively regulates the cell-substratum interaction, resulting in the loss of tumorigenicity.

Animals↗
PubMed2001

The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation.

The inherited human disease tuberous sclerosis, characterized by hamartomatous tumors, results from mutations in either TSC1 or TSC2. We have characterized mutations in the Drosophila Tsc1 and Tsc2/gigas genes. Inactivating mutations in either gene cause an identical phenotype characterized by enhanced growth and increased cell size with no change in ploidy. Overall, mutant cells spend less time in G1. Coexpression of both Tsc1 and Tsc2 restricts tissue growth and reduces cell size and cell proliferation. This phenotype is modulated by manipulations in cyclin levels. In postmitotic mutant cells, levels of Cyclin E and Cyclin A are elevated. This correlates with a tendency for these cells to reenter the cell cycle inappropriately as is observed in the human lesions.

Animals↗
PubMed2001

Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial.

Chemotherapy is not effective for hepatocellular carcinoma (HCC). HMG-CoA redutase inhibitors have cytostatic activity for cancer cells, but their clinical usefulness is unknown. To investigate whether pravastatin, a potent HMG-CoA reductase inhibitor, prolongs survival in patients with advanced HCC, this randomized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital. 91 consecutive patients <71 years old (mean age 62) with unresectable HCC were enroled in this study. 8 patients were withdrawn because of progressive liver dysfunction; 83 patients were randomized to standard treatment with or without pravastatin. All patients underwent transcatheter arterial embolization (TAE) followed by oral 5-FU 200 mg(-1)d for 2 months. Patients were then randomly assigned to control (n = 42) and pravastatin (n = 41) groups. Pravastatin was administered at a daily dose of 40 mg. The effect of pravastatin on tumour growth was assessed by ultrasonography. Primary endpoint was death due to progression of HCC. The duration of pravastatin administration was 16.5 +/- 9.8 months (mean +/- SD). No patients in either group were lost to follow-up. Median survival was 18 months in the pravastatin group versus 9 months in controls (P = 0.006). The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival. Pravastatin prolonged the survival of patients with advanced HCC, suggesting its value for adjuvant treatment.

Adult↗
PubMed2001

Editorial.

Explore the source record for details and available documents.

Journal Article↗
PubMed2001

A novel CLCN1 mutation: P480T in a Japanese family with Thomsen's myotonia congenita.

At least 50 disease-causing mutations in the skeletal muscle voltage-gated chloride channel gene (CLCN1), almost all of which originate from Caucasian families, have been identified. We investigated a Japanese family with Thomsen's myotonia congenita that included 16 affected individuals (8 men and 8 women) through five generations. Polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) screening of 11 members showed an aberrant conformer in exon 13 of CLCN1 complementary DNA (cDNA) in 8 affected and 1 unaffected members. By sequence analysis, we identified a C-to-A transition at nucleotide position 1438, resulting in a substitution of proline for threonine at amino acid position 480 (P480T), the same position of the original mutation (P480L) in Thomsen's disease. The P480T mutation was novel and absent in 100 normal controls. Seven of the 8 affected individuals were heterozygous; another, from affected parents, was homozygous. Clinically, myotonia in the homozygous patient was more severe than that in heterozygous patients, probably due to the gene dosage effect. On a long-train nerve-stimulation test at a rate of 3 Hz, M-wave responses in the homozygous patient showed marked decrement followed by recovery. In contrast, the heterozygous patients showed just a slight decrement or no changes, and none of 2 patients with myotonic muscular dystrophy or 2 normal controls revealed any decrement. Thus, the long-train nerve-stimulation test at a low stimulus frequency may be a useful tool to assess the disease-severity/genotype relationship in myotonia congenita.

Adult↗
PubMed2001

Phenotypic changes associated with exogenous expression of p16INK4a in human glioma cells.

The tumor suppressor p16/CDKN2A/INK4a gene is frequently mutated, mostly by homozygous deletions in high-grade gliomas. Although the p16 protein suppresses cell proliferation primarily through inhibition of cell-cycle progression at the G1 phase, other phenotypic changes in glioma cells associated with p16INK4a alterations have not been fully described. To determine the roles of p16 alterations in glioma formation, we have established ecdysone-driven inducible p16 expression in the human glioblastoma cell line CL-4, which were derived from p16-null U87MG cells. Here we show that exogenous p16 expression in CL-4 cells results in morphological changes, with large and flattened cytoplasm, which are associated with increased formation of cytoplasmic actin-stress fibers and vinculin accumulation in the focal adhesion contacts. Adhesion of CL-4 cells to extracellular matrix proteins, such as laminin, fibronectin, and type IV collagen, significantly increased upon exogenous p16 expression, which correlated with increased expression of integrin alpha5 and alphav. Expression of a small GTP-binding protein, Rac, also decreased. Following epidermal growth factor stimulation, phosphorylation of MAP kinases ERK1 and 2 and induction of an early immediate gene product, c-Fos, were significantly reduced in CL-4 cells with p16 expression. These results suggest that the tumor suppressor p16 may exert its antitumor effects through modulation of multiple aspects of glioblastoma phenotypes, including proliferation, invasiveness, and responsiveness to extracellular growth stimuli.

Bradykinin↗
PubMed2001

Primary localized amyloidosis of the small intestine presenting as an intestinal pseudo-obstruction: report of a case.

A 47-year-old man with primary amyloidosis confined to the small intestine is reported. Thickening of the folds and multiple polypoid protrusions were found in the duodenum by upper gastrointestinal endoscopy. Because the patient presented with a persistent intestinal pseudo-obstruction, partial jejunectomy was performed. Histological examination of the resected tissue revealed massive deposits of amyloid throughout the jejunal wall. Neither a predisposing condition nor any other sites of deposition were found, and primary amyloidosis of the small intestine was diagnosed. This rare form of amyloid deposition should be recognized so that an early diagnosis can be made.

Amyloidosis↗
PubMed2001

Dissociation between T helper type 1 and type 2 differentiation and cytokine production in tumor-infiltrating lymphocytes in patients with lung cancer.

We recently reported the balance of T helper type 1 (Th1) cells and type 2 (Th2) cells in patients with lung carcinomas. This study was conducted to investigate their activity and role in tumors, which remain unclear. We determined the population of lymphocytes with intracellular interferon (IFN)-gamma or interleukin (IL)-4 by flow cytometry, and investigated cytokine production using enzyme-linked immunosorbent assay (ELISA) in 22 patients with non-small cell lung cancer. The IFN-gamma-positive subset showed a significant increase in the number of tumor-infiltrating lymphocytes (TIL) compared with the peripheral blood lymphocytes (PBL) (PBL, 13.8% +/- 1.5%; TIL, 34.3% +/- 3.4%; P < 0.001), and the IL-4 positive subset showed reverse results (PBL, 3.7% +/- 0.6%; TIL, 2.1% +/- 0.3%; P = 0.037). However, TIL did not produce more IFN-gamma than PBL. The results of intracellular IFN-gamma analysis and the production of IFN-gamma in PBL and TIL were significantly correlated (PBL: n = 22, r = 0.50, P = 0.025; TIL: n = 22, r = 0.44, P = 0.022). The dissociation between Th1 differentiation and IFN-gamma production in TIL was one of the host factors influencing the immune anergy against tumors.

Aged↗
PubMed2001

Characterization of the secretable ectodomain of thyrotropin receptor produced by the recombinant baculovirus system.

Thyrotropin receptor (TSHR) is a member of the glycoprotein hormone receptor family and an autoantigen of Graves' disease. Various attempts have been made to obtain a large amount of soluble ectodomain of TSHR in insect or mammalian cells, but most of them failed to secrete the overexpressed ectodomain. In the present study, we observed that about one-third of the ectodomain protein (sTSHR-gp), in which the signal peptide of TSHR was replaced by the baculovirus-encoded glycoprotein 67-signal peptide, was secreted into the culture medium and the remainder stayed within cells in the recombinant baculovirus system. Microsequencing the N-terminal of the purified protein confirmed that the baculovirus signal peptide was cleaved at the expected site. Carbohydrate studies using several glycosidases and lectins revealed that the secreted form of the ectodomain had biantennary carbohydrate, whereas the non-secreted form had high-mannose. Moreover, the secreted form of sTSHR-gp exhibited high-affinity ligand binding, whereas the non-secreted form did not show any significant ligand binding. Regarding the interactions of TSHR ectodomains with anti-TSHR antibodies, both the secreted and non-secreted forms of sTSHR-gp, almost completely neutralized the stimulatory and inhibitory anti-TSHR antibody activities. In conclusion, we succeeded in secreting the ectodomain of TSHR into culture medium, which was capable of binding to TSH and neutralizing anti-TSHR antibody activities.

Amino Acid Sequence↗
PubMed2001

MR imaging of primary leiomyosarcoma of the thyroid gland.

Primary leiomyosarcoma of the thyroid gland is extremely rare and radiological information on this tumor is scant. We presented radiological findings on primary thyroid leiomyosarcoma in a 66-year-old woman in which anaplastic carcinoma was suspected based on clinical and cytological features and discussed the radiological clues to distinguish between the two diseases. Ultrasonography showed an ill-defined hypoechoic mass without halo in the left lobe and the isthmus of the thyroid gland. Computed tomography depicted a low-density mass with calcification and necrosis, which invaded the thyroid cartilage. No lymphadenopathy was seen. The tumor was demonstrated as an isointense mass on T1-weighted MR images and a mass of intermediate signal on T2-weighted images. The tumor showed a fair enhancement on gadolinium-enhanced T1-weighted images. Although the radiological picture was nonspecific, primary thyroid leiomyosarcoma appeared less invasive and far less frequent in developing nodal metastasis than anaplastic carcinoma in light of the literature.

Aged↗