Wakayama-shi, Japan
Wakayama-shi, Japan

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Hyodo E.,Osaka City University | Hirata K.,Wakayama Medical College | Hirose M.,Higashisumisyoshi Morimoto Hospital | Sakanoue Y.,Higashisumisyoshi Morimoto Hospital | And 9 more authors.
Journal of the American Society of Echocardiography | Year: 2010

Background: The aim of this study was to evaluate the diagnostic potential of coronary flow velocity reserve (CFR) measurement by transthoracic Doppler echocardiography (TTDE) to detect restenosis in the 3 major coronary arteries: the left anterior descending coronary artery, right coronary artery, and left circumflex coronary artery. Methods: The lesions of 175 patients who were scheduled for follow-up coronary angiography and TTDE 6 months after undergoing stents implantation were studied. CFR was assessed by TTDE in the targeted arteries into which stents had been implanted. Results: Coronary stents were implanted in a total of 238 angiographic lesions in 175 patients. Doppler recordings of coronary flow in the 3 major arterial lesions were obtained in 211 of the 238 angiographic lesions (89% feasibility). CFR was significantly lower in lesions with restenosis than those without restenosis (1.70 ± 0.32 vs 2.65 ± 0.66, P < .01). A CFR value < 2.0 was 89% sensitive and 91% specific for detecting restenosis in the 3 major coronary arteries. Sensitivity and specificity were 86% and 91%, respectively, in the left anterior descending coronary artery (95% feasibility); 92% and 92%, respectively, in the right coronary artery (85% feasibility); and 91% and 92%, respectively, in the left circumflex coronary artery (81% feasibility). Conclusion: CFR assessment by TTDE is an accurate method for monitoring restenosis, not only in the left anterior descending but also in the right and left circumflex coronary arteries in patients previously subjected to percutaneous coronary intervention. © 2010 American Society of Echocardiography.


PubMed | Wakayama Medical College and Kuma Hospital
Type: Journal Article | Journal: Journal of medical ultrasonics (2001) | Year: 2016

We report a case of hyalinizing trabecular tumor of the thyroid gland and describe the characteristic ultrasonographic features of this tumor. This was a rare tumor of follicular cell origin with a trabecular pattern of growth and marked intratrabecular hyalinization. The tumor had an irregular shape, a delicately jagged border, and hypoechoic and heterogeneous internal echoes on B-mode ultrasonography. Very rich intratumoral blood flow, the so-called tumor inferno was evident on power Doppler ultrasonography. In the clinical management of thyroid nodules, clinicians should be aware of this peculiar type of thyroid tumor and its characteristic ultrasonographic findings.


Chhabra D.,The Surgical Center | Oda K.,Aichi Cancer Center | Jagannath P.,The Surgical Center | Utsunomiya H.,Wakayama Medical College | And 2 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2012

Background: High incidence of gallbladder cancer (GBC) is reported from North India, with elevated concentrations of heavy metals in water and soil. This Indo-Japan collaborative study compared presence of heavy metals in gallbladder tissues. Methods: Heavy metal concentrations were estimated in Indian GBC and cholecystitis tissues and compared with Japanese GBC and cholecystitis tissues. Spectrophotometry was done for 13 Indian gallbladder tissues (8 GBC, 5 cholecystitis) and 9 Japanese (5 GBC, 4 cholecystitis). Transmission electron microscopy (TEM) thin foil element analysis was done in 10 Indian samples (6 GBC, 4 cholecystitis). Results: Chromium, lead, arsenic and zinc were significantly high in Indian GBC compared with Japanese GBC. Chromium, lead and arsenic were significantly high in the Indian cholecystitis tissues compared to the Japanese. TEM of Indian tissues demonstrated electron dense deposits in GBC. Conclusion: Heavy metals- chromium, lead, arsenic and zinc are potential carcinogens in Indian GBC from endemic areas. This preliminary study links presence of heavy metals in gallbladder cancer tissues in endemic areas.


Konno-Shimizu M.,University of Tokyo | Yamamichi N.,University of Tokyo | Inada K.-I.,Aichi University | Kageyama-Yahara N.,University of Tokyo | And 11 more authors.
PLoS ONE | Year: 2013

Gastric cancer (GC) presents various histological features, though the mechanism underlying its diversity is seldom elucidated. It is mainly classified into well differentiated tubular adenocarcinoma (tub1), moderately differentiated tubular adenocarcinoma (tub2), poorly differentiated adenocarcinoma (por), signet-ring cell carcinoma (sig), mucinous adenocarcinoma (muc), and papillary adenocarcinoma (pap). By screening, we found cathepsin E (CTSE) expresses universally in sig-type, occasionally in por-type, and rarely in tub1/tub2-type GC cell lines. In surgically-resected specimens, CTSE was immunostained in 50/51 sig-type (98.0%), 3/10 tub1-type (30.0%), 7/18 tub2-type (38.9%), 15/26 por-type (57.7%), 4/10 pap-type (40.0%), and 0/3 muc-type (0.0%) GC. In endoscopically-resected specimens, 6/7 sig-type (85.7%), 7/52 tub1-type (13.7%), 5/12 tub2-type (41.7%), 2/7 pap-type (28.6%) GC and 0/6 adenoma (0.0%) expressed CTSE. For non-malignant tissues, CTSE is universally expressed in normal fundic, pyloric, and cardiac glands of stomach, but hardly in other digestive organs. In the precancerous intestinal metaplasia of stomach, CTSE is mostly observed in mixed gastric-and-intestinal type and deficient in solely-intestinal type. CTSE expression is positively correlated with gastric marker MUC5AC (p<0.0001) and negatively correlated with intestinal marker MUC2 (p = 0.0019). For sig-type GC, in both tumors and background mucosa, expression of MUC5AC and CTSE is high whereas that of MUC2 is low, indicating that sig-type GC reflects the features of background mucosa. For gastric adenoma and tub1/tub2-type GC, more undifferentiated tumors tend to show higher expression of CTSE with MUC5AC and lower expression of MUC2 in tumors, but they tend to present lower expression of CTSE, MUC5AC and MUC2 in background mucosa. These suggest that more malignant gastric adenocarcinoma with stronger gastric and weaker intestinal properties tend to arise from background mucosa with decreased both gastric and intestinal features. In conclusion, CTSE is a marker of both gastric differentiation and signet-ring cell carcinoma, which should shed light on the mechanism of gastric tumorigenesis. © 2013 Konno-Shimizu et al.


PubMed | Wakayama Medical College, Aichi University and University of Tokyo
Type: Journal Article | Journal: PloS one | Year: 2014

MUC5AC is a well-known gastric differentiation marker, which has been frequently used for the classification of stomach cancer. Immunohistochemistry revealed that expression of MUC5AC decreases accompanied with increased malignant property of gastric mucosa, which further suggests the importance of MUC5AC gene regulation. Alignment of the 5-flanking regions of MUC5AC gene of 13 mammal species denoted high homology within 200 bp upstream of the coding region. Luciferase activities of the deletion constructs containing upstream 451 bp or shorter fragments demonstrated that 15 bp region between -111 and -125 bp plays a critical role on MUC5AC promoter activity in gastrointestinal cells. We found a putative Gli-binding site in this 15 bp sequence, and named this region a highly conserved region containing a Gli-binding site (HCR-Gli). Overexpression of Gli homologs (Gli1, Gli2, and Gli3) clearly enhanced MUC5AC promoter activity. Exogenous modulation of Gli1 and Gli2 also affected the endogenous MUC5AC gene expression in gastrointestinal cells. Chromatin immunoprecipitation assays demonstrated that Gli1 directly binds to HCR-Gli: Gli regulates MUC5AC transcription via direct protein-DNA interaction. Conversely, in the 30 human cancer cell lines and various normal tissues, expression patterns of MUC5AC and Gli did not coincide wholly: MUC5AC showed cell line-specific or tissue-specific expression whereas Gli mostly revealed ubiquitous expression. Luciferase promoter assays suggested that the far distal MUC5AC promoter region containing upstream 4010 bp seems to have several enhancer elements for gene transcription. In addition, treatments with DNA demethylation reagent and/or histone deacetylase inhibitor induced MUC5AC expression in several cell lines that were deficient in MUC5AC expression. These results indicated that Gli is necessary but not sufficient for MUC5AC expression: namely, the multiple regulatory mechanisms should work in the distal promoter region of MUC5AC gene.


Yamanaka O.,University of Cincinnati | Yuan Y.,University of Cincinnati | Coulson-Thomas V.J.,University of Cincinnati | Gesteira T.F.,Cincinnati Childrens Hospital Research Foundation | And 9 more authors.
PLoS ONE | Year: 2013

Lumican (Lum), a small leucine-rich proteoglycan (SLRP) family member, has multiple matricellular functions both as an extracellular matrix component and as a matrikine regulating cell proliferation, gene expression and wound healing. To date, no cell surface receptor has been identified to mediate the matrikine functions of Lum. This study aimed to identify a perspective receptor that mediates Lum effects on promoting wound healing. Transforming growth factor-β receptor 1 (ALK5) was identified as a potential Lum-interacting protein through in silico molecular docking and molecular dynamics. This finding was verified by biochemical pull-down assays. Moreover, the Lum function on wound healing was abrogated by an ALK5-specific chemical inhibitor as well as by ALK5 shRNAi. Finally, we demonstrated that eukaryote-specific post-translational modifications are not required for the wound healing activity of Lum, as recombinant GST-Lum fusion proteins purified from E. coli and a chemically synthesized LumC13 peptide (the last C-terminal 13 amino acids of Lum) have similar effects on wound healing in vitro and in vivo. © 2013 Yamanaka et al.


PubMed | Komaki City Hospital, Wakayama Medical College and Kobe University
Type: Journal Article | Journal: Clinical and experimental nephrology | Year: 2016

Autosomal dominant hypocalcemia type 1 (ADH1) is a relatively rare endocrine disorder characterized by hypocalcemia and inadequate parathyroid hormone secretion. ADH is caused by activating mutations in the calcium-sensing receptor (CaSR) gene, CASR. CaSR plays a crucial role in calcium and magnesium homeostasis in the kidney. ADH may be accompanied by hypokalemia and metabolic alkalosis when it is classified as type V Bartter syndrome. However, the mechanism underlying hypokalemia in this disease is unclear.We investigated a 33-year-old woman with hypocalcemia and hypoparathyroidism since childhood, whose mother also had hypocalcemia and hypoparathyroidism, but with no clinical symptoms. Blood examinations showed hypokalemia and metabolic alkalosis in the patient, but not her mother. We conducted mutation analysis and diuretic tests to clarify the patients and her mothers diagnosis and to investigate the onset mechanism of hypokalemia in ADH1. We also determined the localization of CaSR in the kidney by immunohistochemistry.We detected a known gain-of-function mutation in CASR in both the patient and her mother. Diuretic tests revealed a response to furosemide and no reaction to thiazide in the patient, although the mother responded well to both diuretics. CaSR co-localized with the Na(+)-Cl(-) cotransporter (NCCT) on distal tubular epithelial cells.These results indicate that the NCCT in the distal convoluted tubule was secondarily affected in this patient. We conclude that the main pathogenesis of secondary hypokalemia in ADH1 in this patient was secondary NCCT dysfunction.


PubMed | University of California at Irvine, Wakayama Medical College, University of Cincinnati and Cincinnati Childrens Hospital Research Foundation
Type: Journal Article | Journal: PloS one | Year: 2013

Lumican (Lum), a small leucine-rich proteoglycan (SLRP) family member, has multiple matricellular functions both as an extracellular matrix component and as a matrikine regulating cell proliferation, gene expression and wound healing. To date, no cell surface receptor has been identified to mediate the matrikine functions of Lum. This study aimed to identify a perspective receptor that mediates Lum effects on promoting wound healing. Transforming growth factor- receptor 1 (ALK5) was identified as a potential Lum-interacting protein through in silico molecular docking and molecular dynamics. This finding was verified by biochemical pull-down assays. Moreover, the Lum function on wound healing was abrogated by an ALK5-specific chemical inhibitor as well as by ALK5 shRNAi. Finally, we demonstrated that eukaryote-specific post-translational modifications are not required for the wound healing activity of Lum, as recombinant GST-Lum fusion proteins purified from E. coli and a chemically synthesized LumC13 peptide (the last C-terminal 13 amino acids of Lum) have similar effects on wound healing in vitro and in vivo.

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