Hyogo College of Medicine

About: Hyogo College of Medicine is a education organization based out in Nishinomiya, Hyôgo, Japan. It is known for research contribution in the topics: Cancer & Transplantation. The organization has 5030 authors who have published 10629 publications receiving 258734 citations. The organization is also known as: Hyōgo ika daigaku.

Identification of an antigenic epitope in Helicobacter pylori urease that induces neutralizing antibody production.

Abstract: We previously reported a mouse monoclonal antibody (MAb), termed L2, specific for Helicobacter pylori urease strongly inhibited its enzymatic activity. Here, to gain insight into how this antibody affects urease activity, the epitope that was recognized by the antibody was determined. By screening a panel of overlapping synthetic peptides covering the entire sequence of the two subunits (UreA and UreB), we identified a stretch of UreB-derived 19 amino acid (aa) residues (UB-33; aa 321 to 339, CHHLDKSIKEDVQFADSRI) that was specifically recognized by the L2 antibody. Further sequential amino acid deletion of the 19-mer peptide from either end allowed us to determine the minimal epitope as 8 amino acid residues (F8; SIKEDVQF) for L2 reactivity. This epitope appears to lie exactly on a short sequence which formed a flap over the active site of urease, suggesting that binding of the L2 antibody sterically inhibits access of urea, the substrate of urease. Finally, immunization of rabbits with either the 19-mer peptide or the 8-mer minimal epitope resulted in generation of antiurease antibodies that were capable of inhibiting the enzymatic activity. Since urease is critical for virulence of H. pylori, antigenic peptides that induce production of antibodies to inhibit its enzymatic activity may potentially be a useful tool as a vaccine for prevention and treatment of H. pylori infection.

Procedural Implications of Intravascular Ultrasound Morphologic Features of Chronic Total Coronary Occlusions

Abstract: Although the success rates of percutaneous coronary intervention of chronic total occlusions (CTOs) have improved, morphologic features are not well known. We analyzed experience at 4 centers where intravascular ultrasound (IVUS) was performed in 67 native artery CTO lesions (mean CTO duration 6.3 months) just after the lesion was crossed with a guidewire (n = 7) or after dilatation with a 1.5-mm (n = 46) or 2.0-mm (n = 14) balloon. IVUS detected calcium somewhere in the CTO in 96%; however, only 68% had mild calcium. IVUS identified a proximal end of the CTO in all lesions, but a distal end of the CTO in only 50%. An intramural hematoma was observed in 34% of CTOs, suggesting that the guidewire frequently entered the medial space during successful recanalization. CTOs were longer, vessel area was smaller, and total calcium index was greater in lesions with hematomas (p = 0.003, 0.05, and 0.03, respectively). Inadequate reflow after the procedure was observed in 9% and was associated with longer lesions and intralesional calcium. CTO length as measured with angiography was shorter than the length as measured with IVUS (p = 0.02). Calcium was detected on the angiogram in 61% (p = 0.054 vs IVUS). Most typical angiographic findings associated with a low rate of procedural success were not associated with different IVUS morphologies. In conclusion, CTO lesions had multiple small calcium deposits, intramural hematomas were common and were indicative of guidewire penetration into the medial space during the CTO procedure, especially in long calcified lesions in smaller vessels, and inadequate reflow after the procedure was correlated with more complex CTO morphology.

Increase in Circulating CD34-Positive Cells in Patients with Angiographic Evidence of Moyamoya-like Vessels:

Abstract: Increasing evidence points to a role for circulating endothelial progenitor cells, including populations of CD34-positive (CD34+) cells, in maintenance of cerebral blood flow. In this study, we investigated the link between the level of circulating CD34+ cells and neovascularization at ischemic brain. Compared with control subjects, a remarkable increase of circulating CD34+ cells was observed in patients with angiographic moyamoya vessels, although no significant change was observed in patients with major cerebral artery occlusion (or severe stenosis) but without moyamoya vessels. Our results suggest that the increased level of CD34+ cells associated with ischemic stress is correlated with neovascularization at human ischemic brain.

Germ line mutations of hMSH2 and hMLH1 genes in Japanese families with hereditary nonpolyposis colorectal cancer (HNPCC): usefulness of DNA analysis for screening and diagnosis of HNPCC patients

Abstract: Mutations in hMSH2 and hMLH1 genes were analyzed in patients from 11 Japanese families that had been diagnosed as carrying hereditary nonpolyposis colorectal cancer (HNPCC) by clinical examination. Germ line mutations of hMSH2 gene were identified in 5 independent families in which colorectal (87% of patients), endometrial (30%), ovarian (17%), gastric (14%), and other cancers existed. Five mutations detected between codons 136 and 811 included single-base substitutions (C→T and T→G), a T deletion, and an A insertion, all of which produced stop codons resulting in truncated proteins, and an A→T substitution at splice donor site of exon 5 which resulted in deletion of this exon. Moreover, one HNPCC family was presumed to have germ line mutation of hMSH2 gene because a somatic mutation of hMSH2 gene was detected in a cancer from a patient in this family. In addition to these 11 families already diagnosed with HNPCC, 3 new families with germ line mutations of hMSH2 gene and hMLH1 gene were found through analysis of DNA from patients who had multiple cancers with alteration in microsatellite DNA. These mutations included an AG deletion at codons 877–878 of hMSH2 gene, an AAG deletion at codons 616–618 of hMLH1 gene, and a C→T single-base substitution at codon 217 of hMLH1 gene. Seven of eight germ line mutations found in this study are new mutations that have not been reported previously. In families in which germ line mutations were identified presymptomatic examination was then carried out using polymerase chain reaction single-strand conformation polymorphism analysis of DNA from peripheral blood, and the result was the detection of family members predisposed to HNPCC who did not yet show signs of cancer. These results indicate the value of DNA analysis in the screening and diagnosis of HNPCC patients and families.

Methane Attenuates Hepatic Ischemia/Reperfusion Injury in Rats Through Antiapoptotic, Anti-Inflammatory, and Antioxidative Actions.

Abstract: Hepatic ischemia/reperfusion (I/R) injury, which occurs in various diseases, introduces severe tissue damage and liver dysfunction. However, no promising therapies for such a significant condition currently exist. Methane has been suggested to exert a protective effect against intestinal I/R injury. In this study, we introduced methane to treat hepatic I/R injury to show its promising protective effect. Also, intraperitoneal injection with methane-rich saline, which could have potential clinical applications, was applied as a new method. Partial liver warm ischemia was applied in Sprague-Dawley rats for 60 min followed by succedent reperfusion. In the test for effective dosage, methane-rich saline was administrated intraperitoneally to the rats at doses of 1, 5, 20, or 40 mL/kg at onset of reperfusion. In the test for protective effect, rats received methane-rich saline intraperitoneally at a dose of 10 mL/kg before the initiation of reperfusion. We found that methane-rich saline significantly decreased serum alanine aminotransferase, aspartate aminotransferase activity, and the occurrence of necrosis. Moreover, methane-rich saline reduced the amount of caspase-3 and the number of apoptotic cells. In addition, methane-rich saline increased the level of superoxide dismutase and decreased the level of malondialdehyde and 8-hydroxyguanosine. Furthermore, research indicated that methane-rich saline markedly decreased gene expression and content of tumor necrosis factor-α and interleukin-6. Also, reduced CD68-positive cells showed decreased inflammatory cells in the liver. Our results suggest that methane protects the liver against I/R injury through antiapoptotic, antioxidative, and anti-inflammatory actions.