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H Watanabe

Publications and source records attributed to H Watanabe.

At least 127 records · Page 7Linked to original sources
PubMed2002

Hypoxia enhances the expression of autocrine motility factor and the motility of human pancreatic cancer cells.

The incidence of distant metastases is higher in the tumours with low oxygen pressure than in those with high oxygen pressure. It is well known that hypoxia induces the transcription of various genes involved in angiogenesis and anaerobic metabolism necessary for the growth of tumour cells in vivo, suggesting that hypoxia may also induce the transcription of metastasis-associated genes. We sought to identify the metastasis-associated genes differentially expressed in tumour cells under hypoxic conditions with the use of a DNA microarray system. We found that hypoxia enhanced the expression of autocrine motility factor mRNA in various cancer cells and also enhanced the random motility of pancreatic cancer cells. Autocrine motility factor inhibitors abrogated the increase of motility under hypoxic conditions. In order to explore the roles of hypoxia-inducible factor-1alpha, we established hypoxia-inducible factor-1alpha-transfectants and dominant negative hypoxia-inducible factor-1alpha-transfectants. Transfection with hypoxia-inducible factor-1alpha and dominant-negative hypoxia-inducible factor-1alpha enhanced and suppressed the expression of autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA and the random motility, respectively. These results suggest that hypoxia may promote the metastatic potential of cancer cells through the enhanced autocrine motility factor/phosphohexase isomerase/neuroleukin mRNA expression and that the disruption of the hypoxia-inducible factor-1 pathway may be an effective treatment for metastasis.

Blotting, Northern↗
PubMed2002

Clinical and pathologic characteristics of nontyphoidal salmonella encephalopathy.

OBJECTIVE: To investigate the clinical and pathologic characteristics of primary encephalopathy caused by nontyphoidal salmonellosis (NTS). METHODS: Case records of six Japanese hospitals from 1994 to 1999 were reviewed. Eight cases of primary NTS encephalopathy were identified based on strictly defined criteria: 1) encephalopathic feature defined as altered state of consciousness, altered cognition or personality, or seizures; 2) detection of nontyphoidal Salmonella species in stool; 3) absence of other viral or bacterial infection associated with CNS abnormalities; and 4) absence of alternative explanation by underlying neurologic or systemic disease. Three patients died, three had severe sequelae, and two recovered completely. The authors analyzed their clinical course, neurologic symptoms, and histopathologic findings. RESULTS: NTS encephalopathy was clinically characterized by diffuse and rapidly progressive brain dysfunction and circulatory failure that developed following enteritis. There was no evidence of severe dehydration or sepsis, and encephalopathy was rarely accompanied by abnormal laboratory data, except elevated CSF opening pressure, brain edema on CT, and slow waves on EEG. Pathologic findings included minimal ischemic damage and mild edema in the brain, microvesicular fatty change of the liver, severe enterocolitis but no evidence of dehydration, and no fatal organ damage including microvasculature and endothelial cells. CONCLUSION: Noninfectious encephalopathy associated with nontyphoidal salmonella infection is a distinctive clinical entity that can be differentiated from Reye's syndrome and Ekiri.

Adolescent↗
PubMed2002

ABO-incompatible auxiliary partial orthotopic liver transplant for late-onset familial amyloid polyneuropathy.

A 60-year-old Japanese man with late-onset familial amyloid polyneuropathy type I (FAP transthyretin Met30) showed clinical improvement following auxiliary partial orthotopic liver transplantation (APOLT) from an ABO-incompatible living related donor. Preoperatively, plasmapheresis and immunosuppressant drugs were used to reduce serum antibodies against the donor's ABO type. APOLT was chosen so the residual liver could sustain the patient in the event of hyperacute rejection. OLT is applicable to late-onset FAP transthyretin Met30, and APOLT can be considered in ABO-incompatible cases.

ABO Blood-Group System↗
PubMed2002

New endo-beta-1,4-glucanases from the parabasalian symbionts, Pseudotrichonympha grassii and Holomastigotoides mirabile of Coptotermes termites.

Abstract. An endo-beta-1,4-glucanase (EG) was purified from the hindgut of an Australian mound-building termite, Coptotermes lacteus. The hindgut extract had a peak separate from those for extracts obtained from the salivary glands and the midgut based on sephacryl S-200 gel chromatography, and also demonstrated an origin different from the endogenous EGs of the termite itself. The recovery was further purified by SDS-PAGE, and its N-terminal amino acid sequence analyzed. This showed high homology to EGs from glycoside hydrolase family (GHF) 7. PCR-based cloning methods were applied to the hindgut contents of C. lacteus and individual protozoan symbionts from C formosanus. cDNAs encoding putative EGs homologous to GHF7 members were then identified. The functionality of one of the putative proteins was confirmed by its expression in Escherichia coli.

Amino Acid Sequence↗
PubMed2002

Cellulase genes from the parabasalian symbiont Pseudotrichonympha grassii in the hindgut of the wood-feeding termite Coptotermes formosanus.

Cellulase genes of Pseudotrichonympha grassii (Hypermastigida: Eucomonymphidae), the symbiotic flagellate in the hindgut of the wood-feeding termite Coptotermes formosanus, were isolated and characterized. The nucleotide sequences of the major cellulase component in the hindgut of C. formosanus were determined based on its N-terminal amino acid sequence. The five isolated nucleotide sequences (PgCBH-homos) had an open reading frame of 1350 bp showing similarity to catalytic domains of glycoside hydrolase family (GHF) 7 members, and primary structure comparison with GHF7 members whose tertiary structures are well-characterized revealed the overall similarity between PgCBH-homo and the catalytic domain of a processive cellulase Cel7A (formerly CBHI) from the aerobic fungus Trichoderma reesei. Functional expression of PgCBH-homos in Escherichia coli, using the carboxymethylcellulose-Congo red assay, demonstrated the actual cellulolytic activity of PgCBH-homo. RT-PCR showed that PgCBH-homos were expressed, from the three flagellates in the hindgut, specifically in P. grassii.

Amino Acid Sequence↗
PubMed2002

Evaluation of mitogen-induced responses in marine mammal and human lymphocytes by in-vitro exposure of butyltins and non-ortho coplanar PCBs.

The effects of exposure to butyltin compounds (BTs: tributyltin; TBT, dibutyltin; DBT and monobutyltin; MBT) and non-ortho coplanar PCBs (IUPAC 77, 126 and 169) on marine mammals and human lymphocyte were evaluated. Peripheral blood mononuclear cells (PBMCs) isolated from Dall's porpoises (Phocoenoides dalli), bottlenose dolphins (Tursiops truncatus), a California sealion (Zalophus californianus), a larga seal (Phocoa largha) and humans (Homo sapiens) were exposed at varying concentrations of BTs and coplanar PCBs. Concanavalin A (Con A)-stimulated mitogenesis found significantly suppressed (P<0.01) when the cells were exposed at 300 nM (89 ng/ml) of TBT and 330 nM of DBT (77 ng/ml), while MBT showed little cytotoxicity at treatment levels of up to 3,600 nM (620 ng/ml). BTs concentrations in the liver of Dall's porpoises from Japanese coastal waters ranged between 81-450 ng/g for TBT and 200-1,100 ng/g (wet wt.) for DBTs, which is greater than the cytotoxic levels registered in this study. In contrast, non-ortho coplanar PCBs did not suppress cell proliferation at concentrations of up to 30 nM (10 ng/ml). The residue levels of coplanar PCBs in the blubber of Dall's porpoises were 0.12-1.3 ng/g, which were one order of lower than those levels that do cell proliferation. When cells were exposed to a mixture of TBT/DBTand coplanar PCBs, the proliferation was significantly reduced to 33 nM DBT plus 34 nM CB-77 and 33 nM DBT plus 28 nM CB-169 mixtures, respectively. The investigations relating the contaminant-induced immunosuppression in marine mammals have been focused on persistent organochlorines such as PCBs. pesticides and dioxin compounds. However, this study suggested the possibility of BTs could also pose a serious threat to the immune functions in free-ranging marine mammals and humans.

Animals↗
PubMed2002

Dual cellulose-digesting system of the wood-feeding termite, Coptotermes formosanus Shiraki.

The distribution of endo-beta-1,4-glucanase (EG) components in the digestive system of the wood-feeding termite, Coptotermes formosanus Shiraki, was investigated by zymogram analysis using polyacrylamide gel electrophoresis, followed by N-terminal protein sequencing. EG components similar to glycoside hydrolase family (GHF) 9 members were restricted to the salivary glands, the foregut, and the midgut, whereas components similar to GHF7 members were confined to the hindgut where numerous cellulolytic flagellates were harbored. RT-PCR experiments revealed that five GHF9 EG mRNAs (1348 bp) homologous to other termite EGs were expressed in the salivary glands and the midgut. The crude extract prepared from the midgut as well as that from the hindgut produced glucose from crystalline cellulose. These data suggest that C. formosanus has two independent cellulose-digesting systems: one in the midgut where cellulose digestion is accomplished by endogenous cellulases and the other in the hindgut which makes use of other cellulases possibly from symbiotic flagellates.

Acrylic Resins↗
PubMed2002

PET evaluation of a tetracyclic, atypical antidepressant, [N-methyl-11C]mianserin, in the living porcine brain.

We synthesized [N-methyl-11C]mianserin by alkylation of N-desmethyl mianserin with [11C]methyl iodide followed by HPLC purification. We used PET for determining the regional cerebral pharmacokinetics of the radiotracer in anesthetized swine. [N-methyl-11C]Mianserin entered most brain regions readily (range of K1 values: 0.66-1.13), reaching highest levels in the basal ganglia and thalamus. The binding potential of [N-methyl-11C]mianserin was relatively low (range: 0.07-0.50), but regional differences were nonetheless observed, with highest values in the temporal cortex and lowest values in the brainstem. These PET findings, which are the first ones for a tetracyclic, antidepressant drug, show that [N-methyl-11C]mianserin has only a limited degree of regional specificity of binding in the living brain.

Animals↗
PubMed2002

Role of interleukin-8 secreted from human oral squamous cell carcinoma cell lines.

Interleukin-8 (IL-8) is an important cytokine involved in tumor growth and angiogenesis in a variety of malignancies. Furthermore, matrix metalloptoteinases (MMPs) also play important roles in the invasion and metastasis of carcinomas including oral squamous cell carcinoma (OSCC). We studied whether IL-8 and MMPs participate in tumorigenesis and metastasis of OSCC. First, we investigated the gene and protein expressions of IL-8 and IL-8 receptor (IL-8R), and the effect of IL-8 on proliferation, migration and invasion of OSCC. Second, we thus also investigated the effect of IL-8 on MMP release in OSCC cells. OSCC cell lines NA and HSC-4 constitutively expressed IL-8 mRNA and secreted its protein in vitro. The production of IL-8 was significantly enhanced by the addition of tumor necrosis factor (TNF)-alpha and IL-beta, but not interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor (GM-CSF) or IL-2. Flow cytometric analysis revealed the constitutive expression of both receptors of IL-8, IL-8RA and IL-8RB, in OSCC cell lines. The expression of IL-8 receptors in HSC-4 cells was stronger than that in NA cells. The intensity of IL-8RA expression was stronger than that of IL-8RB expression in each cell line. The expression of IL-8 receptors was not altered by the addition of cytokines such as TNF-alpha and IL-1beta. The conditioned medium containing IL-8 from OSCC cell lines induced migration and invasion of OSCC cells, but did not change cell proliferation. The differences in migrational and invasive ability between NA cells and HSC-4 cells were correlated with the expression intensity of IL-8 receptors in each cell line. Neutralizing antibodies to IL-8, IL-8RA and IL-8RB partially inhibited the chemotactic activity induced by conditioned medium. The expression of MMP-2, -7 and -9 was detected in culture supernatants from these OSCC cell lines. The expressions of MMP-7 protein and mRNA were enhanced by the addition of rIL-8, but that of other MMPs was not observed in a similar manner. These results suggest that IL-8 secreted from OSCC may contribute to the invasion of OSCC through the regulation of MMP-7 expression.

Carcinoma, Squamous Cell↗
PubMed2002

Gastric mucosal atrophy: interobserver consistency using new criteria for classification and grading.

BACKGROUND AND AIMS: Considerable difficulties persist amongst pathologists in agreeing on the presence and severity of gastric atrophy. An international group of pathologists pursued the following aims: (i) to generate an acceptable definition and a simple reproducible classification of gastric atrophy; and (ii) to develop guidelines for the recognition of atrophy useful for increasing agreement among observers. METHODS: After redefining atrophy as the 'loss of appropriate glands' and examining histological samples from different gastric compartments, three categories were identified: (i) negative; (ii) indefinite; (iii) atrophy, with and without intestinalization. Atrophy was graded on a three-level scale. Interobserver reproducibility of the classification was tested by kappa statistics (general and weighted) in a series of 48 cases. RESULTS: The medians of the general agreement and weighted kappa values were 0.78 and 0.73, respectively. The weighted kappa coefficients, obtained by cross-tabulating the evaluation of each pathologist against all others, were, with only one exception, > 0.4 (moderate to excellent agreement). CONCLUSIONS: By using the definition of atrophy as the loss of appropriate glands and distinguishing the two main morphological entities of metaplastic and non-metaplastic types, a high level of agreement was achieved by a group of gastrointestinal pathologists trained in different cultural contexts.

Atrophy↗
PubMed2002

Pathological appraisal of lines of resection for bile duct carcinoma.

BACKGROUND: The aim of this study was to determine the most appropriate line of resection for extrahepatic bile duct carcinoma. METHODS: A retrospective review was carried out of 253 resected specimens of extrahepatic bile duct carcinoma. Carcinomas were classified histologically as invasive or non-invasive in addition to assessment of the resection margin. RESULTS: Tumour was present microscopically at the resection margin in 80 (31.6 per cent) of 253 cases, with 46 showing marginal involvement by non-invasive carcinoma, 20 showing invasive carcinoma at a margin, and 14 showing both. Involvement of the resection margin by invasive carcinoma was encountered only when the margin was shorter than 10 mm, whereas non-invasive carcinoma was encountered even when the margin length reached 40 mm. The observed length of microscopic extension of invasive carcinoma beyond the macroscopically evident tumour mass was limited to 10.0 mm. Median microscopic extension of non-invasive carcinoma beyond the mass was 10 mm (75th percentile 19.5 and 14.5 mm in proximal and distal directions respectively; maximum 52 mm). Margins of 20 mm could be assured to be negative proximally in 89.0 per cent of cases and distally in 93.8 per cent. CONCLUSION: For eradication of invasive extrahepatic bile duct carcinoma, a 10-mm margin is required. However, additional removal of any non-invasive component requires a 20-mm margin. These guidelines should be followed in any operation performed with curative intent.

Adult↗
PubMed2002

CD161+ T (NT) cells exist predominantly in human intestinal epithelium as well as in liver.

It has been reported that human CD161 (NKR-P1A)+ T cells are counterparts of murine natural T (NT) cells and predominantly accumulate in the liver. However, NT cells in the human intestine have not been well analysed. The aim of this study was to assess the existence of NT cells in human intestinal epithelium and determine their phenotypical characterization. Intra-epithelial lymphocytes (IEL) were isolated from surgical specimens (jejunum, ileum and colon). The surface phenotype of IEL was analysed using a FACScan and compared with that of mononuclear cells (MNC) from other organs. CD161+ T cells were abundant in human intestinal epithelium as well as the liver. The majority of CD161+ T cells in IEL were CD8+ cells. About 50% of CD161+ T cells in hepatic lymphocytes (HL) expressed CD56, whereas only 14% of CD161+ T cells in IEL expressed CD56. The jejunum showed the greatest abundance of CD161+ T cells among the intestinal regions investigated. These results suggest that CD161+ T (NT) cells predominantly exist in human intestinal epithelium and may play an important role in local immunity.

Antigens, Surface↗
PubMed2002

Classification of abomasal displacement in cows according to histopathology of the liver and clinical chemistry.

Histopathological features of livers and blood chemical values in cows with abomasal displacement were investigated. Liver biopsy samples were collected during redressment operations in 92 cows with abomasal displacement, and the samples were stained with haematoxylin and eosin or periodic acid Schiff (PAS). Blood was collected for chemical tests. Livers were histopathologically divided into the following four types: normal histology cases (21%), fatty degeneration cases (36%), cloudy swelling cases (19%) and fatty degeneration cases with cloudy swelling (24%). The number of PAS-positive samples was significantly higher in the normal histology group and significantly lower in the severe fatty degeneration group and severe cloudy swelling group. Cows with fatty degeneration had significantly higher levels of serum 3-hydroxybutyric acid, non-esterified fatty acid and aspartate aminotransferase than did those with cloudy swelling or normal histology. The results indicate that the morbid conditions of cows with abomasal displacement can be classified into four types.

3-Hydroxybutyric Acid↗
PubMed2002

Relative contributions of myeloperoxidase and NADPH-oxidase to the early host defense against pulmonary infections with Candida albicans and Aspergillus fumigatus.

Generation of oxidative products by phagocytic cells is known to be an important host defense mechanism directed toward killing of invading microorganisms. The importance of two major oxidant-producing enzymes, myeloperoxidase (MPO) and NADPH-oxidase, in in vivo fungicidal action was directly compared in genetically engineered mice. Both MPO-deficient (MPO-/-) and NADPH-oxidase-deficient (X-linked chronic granulomatous disease [X-CGD]) mice showed increased susceptibility to pulmonary infections with Candida albicans and Aspergillus fumigatus compared with normal mice, and the X-CGD mice exhibited shorter survivals than MPO-/- mice. This increased mortality of X-CGD mice was associated with a 10- to 100-fold increased outgrowth of the fungi in their organs during the first 6 days. These results suggest that superoxide (O2-) produced by NADPH-oxidase is more important than hypochlorous acid (HOCl) produced by MPO, although both oxidative products obviously contribute to the host defense against pulmonary infection with those fungi. We also observed that MPO-/-/X-CGD double knockout mice showed comparable levels of susceptibility to the X-CGD mice against C. albicans and A. funigatus, indicating that MPO is unable to play a role in host defense in the absence of NADPH-oxidase. This strongly suggests that hydrogen peroxide, the precursor of HOCl, is solely derived from O2- produced by NADPH-oxidase.

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↗
PubMed2002

Non-invasive automated assessment of the ratio of pulmonary to systemic flow in patients with atrial septal defects by the colour Doppler velocity profile integration method.

BACKGROUND: The recent introduction of the automated cardiac flow measurement (ACM) method, using spatiotemporal integration of the Doppler velocity profile, provides a quick and accurate automated calculation of cardiac output. OBJECTIVE: To evaluate the ACM method against oximetry during cardiac catheterisation for estimating the Qp/Qs (pulmonary to systemic flow) ratio in patients with an atrial septal defect. METHODS: Left and right ventricular stroke volume (LVSV, RVSV) were calculated by ACM in 22 patients with an atrial septal defect who underwent cardiac catheterisation and in 11 patients without heart disease (control group). With ACM, the Qp/Qs ratio was estimated from RVSV divided by LVSV. In the patients with an atrial septal defect, the Qp/Qs ratio was assessed by oximetry at the time of cardiac catheterisation. RESULTS: There was a good correlation between LVSV and RVSV obtained by ACM in the control group (r = 0.98, y = 0.97x + 0.25, SEE = 2.9 ml). The mean difference between LVSV and RVSV by ACM was -1.25 (2.76) ml. The Qp/Qs ratio obtained by ACM in the control group was 0.98 (0.06). The Qp/Qs ratio in patients with an atrial septal defect was significantly higher than in the control group (3.11 (1.20), p < 0.001). ACM determination of the Qp/Qs ratio correlated well with oximetry determination (r = 0.86, y = 0.75x + 0.55, SEE = 0.64). The mean difference between ACM and oximetry for the measurement of the Qp/Qs ratio was -0.28 (0.69). CONCLUSIONS: The newly developed ACM method is clinically useful for non-invasive automated estimations of the Qp/Qs ratio in patients with an atrial septal defect.

Adult↗