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Hiroyuki Kato

Publications and source records attributed to Hiroyuki Kato.

At least 55 records · Page 3Linked to original sources
PubMed2004

Pretreatment evaluation of combined HIF-1alpha, p53 and p21 expression is a useful and sensitive indicator of response to radiation and chemotherapy in esophageal cancer.

Tumor hypoxia has been known to be associated with resistance to radiation and chemotherapy (CRT). Hypoxia-inducible factor-1alpha (HIF-1alpha), a transcription factor induced by hypoxic condition, plays a major role in the pleiotropic response observed under hypoxic conditions. It encodes proteins that play key roles in critical development and physiologic processes, including angiogenesis, glucose transport and erythropoiesis. On the other hand, cell cycle- and apoptosis-control genes p53 and p21 may play major roles in the tumor response to cytotoxic agents such as radiation and chemotherapy. Previous reports have suggested that the regulation of p53 and p21 is HIF-1-dependent. Our aim was to evaluate the expression of the HIF-1alpha, p53 and p21 proteins by immunohistochemistry in biopsy specimens of esophageal squamous cell carcinoma, which were obtained endoscopically from 65 patients before CRT, and then determine whether the levels of expression of these proteins predicted the clinical effectiveness of CRT in individual cancers. Also, to assess the relationship between expression of these proteins and cell death and cellular proliferation activity, we evaluated Ki67 expression and the apoptosis index (TUNEL). HIF-1alpha expression in esophageal cancer was significantly and negatively related to the response to CRT, independently of p53 and p21 expression. Interestingly, 44.4% (12/27) of the HIF-1alpha-negative group showed a complete response to therapy. There was no significant correlation between the expression of HIF-1alpha, p53 and p21 and proliferation and apoptosis. HIF-1alpha overexpression may predict resistance to CRT and may be a helpful guide in choosing between therapeutic strategies, such as intensive combined modality therapy vs. palliative therapy. Combined immunohistochemical evaluation of HIF-1alpha, p53 and p21 protein expression at the pretreatment biopsy is a very useful and powerful indicator of sensitivity to CRT in human esophageal cancer. Our data also indicate the importance of having a clear grasp of the degree of hypoxia (HIF-1alpha) of a tumor, rather than its cellular character (proliferation and apoptosis), to indicate the likely impact of CRT.

Biomarkers, Tumor↗
PubMed2004

ER-60 domains responsible for interaction with calnexin and calreticulin.

ER-60 is a thiol oxidoreductase family protein of the endoplasmic reticulum that facilitates the oxidative folding of glycoproteins via interaction with calnexin (CNX) and calreticulin (CRT). In this study, we tried to identify the site of interaction with CNX and CRT in the ER-60 molecule. ER-60 was shown to be composed of at least four domains, named a, b, b', and a', by limited proteolysis. Recombinant fragments of ER-60, a, b', and a'c, were each expressed in Escherichia coli as an individual soluble folded protein that underwent a cooperative unfolding transition along a urea gradient. These fragments each gave the circular dichroism (CD) spectrum of the folded protein. On the other hand, fragment b, which did not undergo the cooperative unfolding transition along a urea gradient gel, did not show any sign of the folded structure on the CD measurement. However, subtraction of the spectra showed that the b domain was folded in wild-type ER-60 or abb'. Both a and a'c, which have a catalytic center CGHC motif, showed activity almost equivalent to half of that of wild-type ER-60. Extension from a or a'c to ab and abb' or b'a'c had little effect on their isomerase activity, suggesting that the b and b' domains hardly contribute to the catalytic activity of ER-60. The contribution of both the b and b' domains to the binding with CNX and CRT was revealed by surface plasmon resonance analysis and oxidative-refolding experiments of monoglucosylated RNase B with addition of the luminal domain of CNX.

Binding Sites↗
PubMed2004

Expression of brain-derived neurotrophic factor immunoreactivity and mRNA in the hippocampal CA1 and cortical areas after chronic ischemia in rats.

We studied the expression of brain-derived neurotrophic factor (BDNF) immunoreactivity and mRNA in the ischemia-vulnerable cerebral hippocampal CA1 and cortical areas after permanent occlusion of bilateral internal carotid arteries. Four groups of rats were studied, including 1) young normotensive Wistar-Kyoto (WKY) rats, 2) aged normotensive WKY rats, 3) young spontaneous hypertensive rats (SHR), and 4) aged SHR. Each group contained rats from sham operation and 1 week, 4 weeks, and 8 weeks after cerebral ischemia (n = 3-5 at each time point). Hematoxylin and eosin staining and in situ apoptosis detection showed no neuronal damage from 1 week to 8 weeks in all the ischemic rats. Immunohistochemistry and Western blot showed that BDNF immunoreactivity increased only at 1 week in the CA1 area of young WKY rats (P < .001) and SHR (P = .002) and decreased only at 8 weeks in the cortical area of aged WKY rats (P = .02). In situ hybridization and TaqMan real-time RT-PCR showed that BDNF mRNA decreased consistently from 1 week to 8 weeks in both CA1 and cortical areas in young SHR (P < .05 and P < .01, respectively) and in aged WKY rats (P < .01 and P < .05, respectively) but was not changed in young WKY rats or aged SHR (P > .05) compared with the sham-operated rats. Our study demonstrates an expression disparity of BDNF immunoreactivity and mRNA in the hippocampal CA1 and cortical areas, especially in the young SHR and aged WKY rats after mild cerebral ischemia. Our study suggests that, under permanent occlusion of bilateral internal carotid arteries, aging and the level of blood pressure may have influence on the expression of BDNF.

Age Factors↗
PubMed2004

Relationship between skeletal muscle MCT1 and accumulated exercise during voluntary wheel running.

We examined whether the quantity of exercise performed influences the expression of monocarboxylate transporter (MCT) 1 and MCT4 in mouse skeletal muscles (plantaris, tibialis anterior, soleus) and heart. Wheel running exercise (1, 3, and 6 wk) was used, which results in marked variations in self-selected running activity. Differences in muscle MCT1 and MCT4 among animals, before the initiation of running, were not related to the quantity of exercise performed on the first day of wheel running. No changes in MCT4 were observed over the course of the study (P > 0.05). After 6 wk of running, were there significant increases in heart (50%; P < 0.05) and muscle MCT1 (31-60%; P < 0.05) but not after 1 and 3 wk (P > 0.05). Because skeletal muscle MCT1 and running distances varied considerably, we examined the relationship between these two parameters. Within the first week of training, MCT1 was negatively correlated with the accumulated running distance (r = -0.70, P < 0.05). On further analysis, it appears that, in the first week, excessive running (>20 km/wk) represses MCT1 (-16.1%; P < 0.05), whereas more modest amounts of running (<20 km/wk) increase MCT1 (+37%; P < 0.05). After 3 wk of running, a positive relationship was observed between MCT1 and running distance (r = +0.76), although there is a threshold that must be exceeded before an increase over the control animals occurs. Finally, in week 6, when MCT1 was increased in the tibialis anterior and plantaris muscles, there were no correlations with the accumulated running distances. These studies have shown that mild exercise training fails to increase MCT4 and that changes in MCT1 are complex, depending not only the accumulated exercise but also on the stage of training.

Adaptation, Physiological↗
PubMed2004

Plasma level of transforming growth factor beta1 measured from the azygos vein predicts prognosis in patients with esophageal cancer.

PURPOSE: Transforming growth factor (TGF)-beta regulates cell growth inhibition. When tumor cells lose their sensitivity to TGF-beta growth inhibition, the excess TGF-beta that results may act on tumor cells to facilitate tumor development. Previously, we have shown that an elevated systemic TGF-beta 1 level is not related to tumor progression in esophageal cancer (Y. Fukai et al., Int J Cancer 2003;104:161-6). We considered that systemic inflammation or chronic disease, in addition to the tumor, may influence the plasma TGF-beta level. Therefore, we examined the hypothesis that the plasma TGF-beta level measured from the azygos vein would independently predict tumor progression and prognosis in patients with esophageal cancer. EXPERIMENTAL DESIGN: Fifty-seven plasma samples were obtained intraoperatively from the azygos vein in patients with esophageal cancer. ELISA was used to quantify the plasma TGF-beta 1 levels, which were correlated with pathological features and patient survival. RESULTS: The mean plasma TGF-beta 1 level measured from the azygos vein of esophageal cancer patients was 5.09 +/- 0.48 ng/ml (mean +/- SE). The survival rates of patients with a high TGF-beta 1 level (defined as a level above the 4.6 ng/ml level of normal controls) in the azygos vein were significantly lower than those of patients with a low TGF-beta 1 level (P = 0.0317). Moreover, the TGF-beta 1 level in the azygos vein was an independent prognostic factor for overall survival (P = 0.0474). CONCLUSIONS: The level of plasma TGF-beta 1 measured from the azygos vein is an independent predictor in patients with esophageal cancer and may reflect tumor progression more specifically because the azygos vein is responsible for venous return from the esophagus.

Adult↗
PubMed2004

Serum interleukin-12 and interleukin-18 levels as a tumor marker in patients with esophageal carcinoma.

Interleukin (IL)-12 and IL-18 participate in tumor immunology. Serum IL-12 and IL-18 levels were determined in patients with esophageal carcinoma, and the relationship between clinicopathologic factors and prognosis was investigated. Peripheral blood samples were obtained from 15 healthy volunteers and from 70 patients with esophageal carcinoma before curative surgery. IL-12 and IL-18 levels were determined in each serum sample by enzyme-linked immunosorbent assay. Mean serum IL-12 and IL-18 levels were significantly higher in patients with esophageal carcinoma compared with healthy volunteers (P < 0.05) and mean serum IL-12 and IL-18 levels increased in patients as the pathologic stage progressed. A positive correlation was observed between serum IL-12 and IL-18 levels (P < 0.01). In patients with esophageal carcinoma, increasing serum IL-12 and IL-18 levels correlated with tumor growth and progression. The function of these two interleukin in the host immune response remains unclear. However, this part of the host immune response did not appear to contribute to the postoperative prognosis. Serum IL-12 and IL-18 levels might correlate with a certain depth of invasion and might be useful tumor markers in patients with esophageal carcinoma.

Adult↗
PubMed2004

Increased expression of c-Ski as a co-repressor in transforming growth factor-beta signaling correlates with progression of esophageal squamous cell carcinoma.

Transforming growth factor-beta (TGF-beta) regulates cell growth inhibition, and inactivation of the TGF-beta signaling pathway contributes to tumor development. In our previous study, altered expression of TGF-beta, TGF-beta-specific receptors and Smad4 was shown to correlate with tumor progression in esophageal squamous cell carcinoma (SCC). These components, however, were maintained normally in some patients with esophageal SCC. In our study, the mechanism by which aggressive esophageal SCC maintains these components was investigated, with particular emphasis on the participation of c-Ski and SnoN as transcriptional co-repressors in TGF-beta signaling. Immunohistochemistry for c-Ski and SnoN was carried out on surgical specimens obtained from 80 patients with esophageal SCC. The expression of c-Ski and SnoN was also studied in 6 established cell lines derived from esophageal SCC and compared to an immortalized human esophageal cell line by Western blotting. High levels of expression of c-Ski, detected immunohistologically, were found to correlate with depth of invasion (p = 0.0080) and pathologic stage (p = 0.0447). There was, however, no significant correlation between expression of SnoN and clinicopathologic characteristics. A significant correlation between c-Ski and TGF-beta expression was observed. Moreover, in patients with TGF-beta negative expression, the survival rates of patients with c-Ski positive expression were significantly lower than those of patients with c-Ski negative expression (p = 0.0486). c-Ski was expressed at a high level in 5 of 6 cell lines derived from esophageal SCC compared to immortalized esophageal keratinocytes. Furthermore, the cyclin-dependent kinase (CDK) inhibitor, p21 that was up-regulated by TGF-beta signaling was expressed at a low level in the 5 cell lines. The expression of c-Ski protein as a transcriptional co-repressor in TGF-beta signaling seems to be correlated with tumor progression of esophageal SCC.

Adult↗
PubMed2004

Proinflammatory activity of anti-IL-8 autoantibody:IL-8 complexes in alveolar edema fluid from patients with acute lung injury.

A significant fraction of IL-8 in lung fluids from patients with the acute lung injury (ALI) is associated with anti-IL-8 autoantibodies (anti-IL-8:IL-8 complexes), and lung fluid concentrations of these complexes correlate with development and outcome of ALI. In this study, we examined whether anti-IL-8:IL-8 complexes exhibit proinflammatory activity in vitro. These complexes were purified from pulmonary edema fluid samples obtained from patients with ALI. First, we found that IL-8 bound to the autoantibody retained its ability to trigger chemotaxis of neutrophils, whereas control antibody did not have significant chemotactic activity. Next, we examined the ability of anti-IL-8:IL-8 complexes to induce neutrophil activation, i.e., neutrophil respiratory burst and degranulation. Anti-IL-8:IL-8 complexes triggered superoxide and myeloperoxidase release from human neutrophils, and in contrast, the control antibody had no effect. We also demonstrated that IgG receptor, FcgammaRIIa, is the receptor involved in cellular activation mediated by these complexes. Blockade of FcgammaRIIa completely reverses activity of the complexes with the exception of chemotaxis. Both FcgammaRIIa and IL-8 receptors mediate chemotactic activity of anti-IL-8:IL-8 complexes, with FcgammaRIIa being, however, a predominant receptor. Furthermore, activity of the complexes is partially dependent on the activation of the mitogen-activated protein kinases, i.e., ERK and p38, important components of the FcgammaRIIa signaling cascade. Anti-IL-8:IL-8 complexes may therefore be involved in the pathogenesis of lung inflammation in clinical acute lung injury.

Antigen-Antibody Complex↗
PubMed2004

Improved healing of small-caliber, long-fibril expanded polytetrafluoroethylene vascular grafts by covalent bonding of fibronectin.

PURPOSE: To evaluate the intermediate performance of small-caliber, long-fibril expanded polytetrafluoroethylene (ePTFE) vascular grafts pretreated with covalent bonding of fibronectin in dogs. METHODS: Small-caliber (4 mm), long-fibril (60 microm), ePTFE vascular grafts, 10 cm in length, were pretreated by covalent bonding of fibronectin. Bilateral iliac grafting was done in dogs using a fibronectin-bonded graft on one side and a nonbonded control graft on the other side. The grafts were retrieved 12 weeks after implantation, and subjected to histomorphometric analysis. RESULTS: Although the patency rates of the fibronectin-bonded and control grafts were the same (3/7, 43%), the fibronectin-bonded grafts showed almost complete neointimal healing, whereas the nonbonded control grafts showed only partial neointimal healing, proximally and distally. CONCLUSIONS: Small-caliber, long-fibril ePTFE vascular grafts with covalent bonding of fibronectin achieved almost complete neointimal healing by the time of retrieval at 12 weeks. This indicates that, with further modifications, our new technique for covalent bonding of fibronectin has great potential in the development of small-caliber arterial prosthetic grafts.

Animals↗
PubMed2004

Assessment of microinvasion with reverse transcriptase polymerase chain reaction in a case of synovial sarcoma.

The purpose of our study was to assess microinvasion in a case of synovial sarcoma by means of the reverse transcriptase polymerase chain reaction (RT-PCR) for detecting SYT-SSX fusion transcripts. Furthermore, we tried to compare the RT-PCR results with those obtained by conventional histopathological examination. A 45-year-old man with synovial sarcoma in the left lower leg underwent above-knee amputation and partial resection of the right lung because of local recurrence and metastasis to the lung. We obtained samples from the tumor and from locations at distances of 1, 3, and 5 cm from the tumor margin in the amputated limb. Samples were also obtained from the resected pulmonary tumor and peripheral blood. SYT-SSX1 chimeric genes could be detected in the samples obtained from up to 3 cm outside the tumor by RT-PCR. Histopathological examination confirmed tumor cells up to 1 cm from the tumor margin. We believe that using a molecular assay in addition to a histopathological examination provides a more sensitive and accurate assessment of the surgical margin.

Humans↗
PubMed2004

Locking of the knee caused by localized pigmented villonodular synovitis: a case report.

Pigmented villonodular synovitis (PVS) occurs in two forms: diffuse PVS and localized pigmented villonodular synovitis. In this report, a 40-year-old woman presented with a history of recurrent episodes of knee locking and pain. Arthroscopy revealed a nodular pedunculated mass occupying the area anterior to the intercondylar notch of the femur. Histological examination of the tissue confirmed the diagnosis of PVS. After surgery, the patient's symptoms of pain and recurrent locking promptly resolved.

Journal Article↗
PubMed2004

Biochemical, behavioral and immunohistochemical alterations in MPTP-treated mouse model of Parkinson's disease.

The biochemical, behavioral and immunohistochemical manifestations were investigated in mice subjected to four experimental schedules with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) hydrochloride treatment. The mice were treated intraperitoneally with MPTP (20 mg/kg in saline) four times a day at 2-h intervals showed severe and persistent depletions of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and behavioral deficits, as compared with those (1) treated with MPTP (15 mg/kg in saline ip) once a day for 14 consecutive days; (2) MPTP (30 mg/kg in saline ip) twice a day for five consecutive days; and (3) MPTP (10 mg/kg in saline ip) four times a day at 1-h intervals for two consecutive days. The immunohistochemical study has shown that the acute treatment with MPTP caused severe loss of tyrosine hydroxylase (TH)- and dopamine transporter (DAT)-immunoreactive dopaminergic neurons and marked increase in glial fibrillary acidic protein (GFAP)-immunoreactive astrocytes in the striatum and the substantia nigra. Thus acute treatment of mice with MPTP was accompanied by sustained nigral degeneration and motor abnormalities. Furthermore, our results with Cu/Zn-superoxide dismutase (Cu/Zn-SOD) and manganese superoxide dismutase (Mn-SOD) immunostainings suggest that altered capacity of free radicals quenching may play a key role in the development of the neurons and interneuron damage after MPTP neurotoxicity. Thus, our findings provide valuable information on age-related disease progression and mechanisms of neurodegeneration.

Animals↗
PubMed2004

Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model.

We earlier reported that Fischer 344/jcl strain (F344) rats carrying a unique pX gene of human T lymphocyte virus type I (HTLV-I) under control of a rat lymphocyte-specific protein tyrosine kinase (p56lck) type I promoter (lck-pX rats) spontaneously developed epithelial thymomas from the thymic medulla. To investigate the role of bone marrow cells carrying the HTLV-I pX gene in development of thymomas, the bone marrow of normal F344 rats after lethal irradiation was reconstituted by bone marrow mononuclear cells (BMMC) of lck-pX rats. Epithelial thymomas similar to the original thymoma of lck-pX rats frequently developed in the nontransgenic recipients within 5 months after the BMMC transplantation. The thymomas expressed the pX gene, thereby indicating the thymoma cells to be of donor BMMC origin. Since the thymoma also developed in nontransgenic recipients reconstituted by BMMC depleted of adherent cells, it is suggested that nonadherent BMMC of donor lck-pX rats may migrate to and lodge in the thymus of recipient nontransgenic rats then transform into thymoma cells with epithelial characteristics. The thymoma cells were shown to bind to Ulex europaeus Agglutinin-1 (UEA-1) lectin, which binds epithelial cells in the thymic medulla. It was also shown that the nonadherent BMMC fraction used for bone marrow reconstitution contained a number of UEA-1-positive cells. Taken together, UEA-1 positive BMMC may be progenitor cells of the epithelial thymoma. The epithelial thymoma in lck-pX rats sheds light on epithelial cell development in thymic medulla and for oncogenesis of epithelial thymoma in humans.

Animals↗
PubMed2004

Pancreatic Cancer Registry in Japan: 20 years of experience.

The prognosis of pancreatic cancer is defined by the histology and extent of disease. Preoperative histologic diagnosis and diagnostic imaging are fundamentals in managing the disease, but it is not rare to find unexpected peritoneal dissemination or liver metastasis at the time of operation. The overall resectability rate of pancreatic cancer is 40% in Japan. Resecting the portal vein and peripancreatic plexus were performed on 40% of the patients who underwent pancreatectomy for invasive cancer in the head of the pancreas. Long-term survival was only found in patients who underwent pancreatectomy. Radical lymph node dissection, or combined resection of the large vessels, did not seem to improve survival further than the standard resection. Multidisciplinary treatments combined with surgery were performed, and various effects of postoperative chemotherapy after pancreatectomy, intraoperative- and postoperative-radiation therapy, or postoperative chemotherapy for unresectable tumor, were shown. Development of unconventional therapies and refinement of the conventional therapy should be promoted on a randomized prospective trial basis. To promote this effort, which requires the international comparisons and cooperation, JPS developed a computerized JPS registration system downloadable from the JPS website (http://www.kojin.or.jp/suizou/index.html).

Adenocarcinoma↗
PubMed2004

Double endoscopic intraluminal operation for upper digestive tract diseases: proposal of a novel procedure.

BACKGROUND AND OBJECTIVE: Endoscopic treatment of digestive tract diseases, such as early esophageal and gastric neoplasia, has become increasingly popular in recent years as an alternative to surgical procedures in the hope of providing an improved quality of life for these patients. However, one of the limitations of a conventional endoscopic mucosal resection, such as an aspiration mucosectomy and a strip biopsy, has been the size of the lesions to be resected. Both an aspiration mucosectomy and strip biopsy are useful variants for removing flat lesions measuring less than 20 mm in maximal diameter. To overcome such limitations, we devised a double endoscopic intraluminal operation (DEILO), which enables us to resect mucosal lesions by using 2 fine endoscopes and monopolar shears. METHODS: DEILO was performed on patients with esophageal and gastric lesions measuring up to 40 mm in diameter. This novel technique is characterized by the use of 2 endoscopes (one for lifting the lesion and the other for cutting the lesions) inserted into the esophagus or stomach through an overtube. A mucosal resection is then performed by dissecting the mucosal margin with newly developed monopolar shears, thereby separating the mucosa from the submucosa. RESULTS: A total of 25 lesions in the esophagus (8 lesions) and stomach (17 lesions) were resected by DEILO. The sizes of the esophageal lesions ranged from 8 to 40 mm in diameter (mean, 21.1 mm) whereas gastric lesions ranged from 8 to 30 mm (mean, 13.3 mm) in diameter, and histopathologic examinations revealed the resection margin to be clear and without any tumor. No complications or instances of recurrence were observed in this series. CONCLUSIONS: DEILO is considered to be feasible for the mucosal resection of esophageal and gastric lesions measuring more than 10 mm in diameter without submucosal invasion, whereas conventional endoscopic mucosal resection is indicated for such lesions measuring less than 10 mm in size.

Adult↗
PubMed2004

A rare anomaly of the extensor digitorum longus.

We encountered the absence of the tendon to the fourth toe of the extensor digitorum longus muscle of the right leg in the body of a 73-year-old Japanese woman during the course of educational dissection at Nagoya City University Medical School. The tendon to the fourth toe of the extensor digitorum longus muscle was solely absent. To our knowledge, this anatomical variation has never been cited in the medical literature. We document the precise gross anatomical findings with some morphometric measurements. Moreover, we discuss the morphology of this anomaly in relation to previously described variations and anomalies of the extensor digitorum longus muscle.

Aged↗
PubMed2004

Establishment and characterization of JHUCS-1 cell line derived from carcinosarcoma of the human uterus.

The cell line designed JHUCS-1 was established from a carcinosarcoma (malignant mixed mesodermal tumor) of the uterus that was surgically removed from a 57-year-old Japanese woman. We carefully examined the histopathology of the original tumor after the cell line was established and noted differentiation into a neuroendocrine carcinoma within the tumor's epithelial components. Immunohistochemical staining of the tumorous tissue that had been heterotransplanted was positive for Leu7. Additionally, secretary granules were observed in the grafted cells as determined by electron microscopy. These results support the existence of neuroendocrine cells within the JHUCS-1 cell line.

Animals↗