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Kurume, Japan

Kurume University is a private university, established in 1946. Kurume University is located in Kurume , Fukuoka prefecture , Japan. Wikipedia.

Yamagishi S.,Kurume University
Current pharmaceutical design | Year: 2011

Accelerated atherosclerosis and microvascular complications are the leading causes of coronary heart disease, end-stage renal failure, acquired blindness and a variety of neuropathies, which could account for disabilities and high mortality rates in patients with diabetes. Glucagon-like peptide-1 (GLP-1) belongs to the incretin hormone family. L cells in the small intestine secrete GLP-1 in response to food intake. GLP-1 not only enhances glucose-evoked insulin release from pancreatic β-cells, but also suppresses glucagon secretion from pancreatic α-cells. In addition, GLP-1 slows gastric emptying. Therefore, enhancement of GLP-1 secretion is a potential therapeutic target for the treatment of type 2 diabetes. Dipeptidyl peptidase-4 (DPP-4) is a responsible enzyme that mainly degrades GLP-1, and the half-life of circulating GLP-1 is very short. Recently, DPP-4 inhibitors and DPP-4-resistant GLP-1 receptor (GLP-1R) agonists have been developed and clinically used for the treatment of type 2 diabetes as a GLP-1-based medicine. GLP-1R is shown to exist in extra-pancreatic tissues such as vessels, kidney and heart, and could mediate the diverse biological actions of GLP-1 in a variety of tissues. So, in this paper, we review the pleiotropic effects of GLP-1-based therapies and its clinical utility in vascular complications in diabetes. Source

Reducing sugars can react nonenzymatically with the amino groups of proteins to form Amadori products. These early glycation products undergo further complex reactions, such as rearrangement, dehydration, and condensation, to become irreversibly cross-linked, heterogeneous fluorescent derivatives, termed advanced glycation end products (AGEs). The formation and accumulation of AGEs have been known to progress in a normal aging process and at an accelerated rate under diabetes. Nonenzymatic glycation and cross-linking of proteins not only leads to an increase in vascular and myocardial stiffness, but also deteriorates structural integrity and physiological function of multiple organ systems. Furthermore, there is accumulating evidence that interaction of AGEs with a cell-surface receptor, receptor for AGEs (RAGE), elicits oxidative stress generation and subsequently evokes inflammatory, thrombogenic, and fibrotic reactions, thereby being involved in atherosclerosis, diabetic microvascular complications, erectile dysfunction, and pancreatic β-cell apoptosis. Recently, AGE cross-link breakers have been discovered. Therefore, removal of the preexisting AGEs by the breakers has emerged as a novel therapeutic approach to various types of diseases that develop with aging. This article summarizes the potential clinical utility of AGE cross-link breakers in the prevention and management of age- and diabetes-associated disorders. © Copyright 2012, Mary Ann Liebert, Inc. Source

Yamagishi S.-I.,Kurume University
Experimental Gerontology | Year: 2011

A non-enzymatic reaction between ketones or aldehydes and the amino groups of proteins, lipids and nucleic acids contributes to the aging of macromolecules and to the development and progression of various age-related disorders such as vascular complications of diabetes, Alzheimer's disease, cancer growth and metastasis, insulin resistance and degenerative bone disease. Under hyperglycemic and/or oxidative stress conditions, this process begins with the conversion of reversible Schiff base adducts, and then to more stable, covalently-bound Amadori rearrangement products. Over a course of days to weeks, these early glycation products undergo further reactions and rearrangements to become irreversibly crossed-linked, fluorescent protein derivatives termed advanced glycation end products (AGEs). There is a growing body of evidence that AGE and their receptor RAGE (receptor for AGEs) interaction elicits oxidative stress, inflammatory reactions and thrombosis, thereby being involved in vascular aging and damage. These observations suggest that the AGE-RAGE system is a novel therapeutic target for preventing diabetic vascular complications. In this paper, we review the pathophysiological role of the AGE-RAGE-oxidative stress system and its therapeutic intervention in vascular damage in diabetes. We also discuss here the potential utility of the restriction of food-derived AGEs in diabetic vascular complications. © 2010 Elsevier Inc. Source

Cancer vaccine is one of the attractive treatment modalities for patients with castration-resistant prostate cancer (CRPC). However, because of delayed immune responses, its clinical benefits, besides for overall survival (OS), are not well captured by the World Health Organization (WHO) and Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Several surrogate markers for evaluation of cancer vaccine, including prostate-specific antigen doubling time (PSADT), are currently sought. The purpose of this study was to assess prospectively the PSA kinetics and immune responses, as well as the efficacy, safety, and biomarkers of personalized peptide vaccination (PPV) in progressive CRPC. One hundred patients with progressive CRPC were treated with PPV using 2-4 positive peptides from 31 candidate peptides determined by both human leukocyte antigen (HLA) class IA types and the levels of immunoglobulin G (IgG) against each peptide. The association between immune responses and PSADT as well as overall survival (OS) was studied. PPV was safe and well tolerated in all patients with a median survival time of 18.8 months. Peptide-specific IgG and T-cell responses strongly correlated with PSADT (p < 0.0001 and p = 0.0007, respectively), which in turn showed correlation with OS (p = 0.018). Positive IgG responses and prolongation of PSADT during PPV were also significantly associated with OS (p = 0.001 and p = 0.004) by multivariate analysis. PSADT could be an appropriate surrogate marker for evaluation of the clinical benefit of cancer vaccine. Further randomized trials are needed to confirm these results. UMIN000001850. Source

Ohgusu H.,Kurume University
Methods in enzymology | Year: 2012

Ghrelin is a gastric peptide hormone in which serine 3 (threonine 3 in frogs) is modified primarily by an n-octanoic acid; this modification is essential for ghrelin's activity. The enzyme that transfers n-octanoic acid to the third serine residue of ghrelin peptide has been identified and named GOAT for ghrelin O-acyltransferase. GOAT is the only known enzyme that catalyzes the acyl modification of ghrelin and specifically modifies the third amino acid serine and does not modify other serine residues in ghrelin peptides. GOAT prefers n-hexanoyl-CoA over n-octanoyl-CoA as the acyl donor, although in the stomach n-octanoyl form is the main acyl-modified ghrelin and the concentration of n-hexanoyl form is very low. Moreover, a four-amino acid peptide derived from the N-terminal sequence of ghrelin can be modified by GOAT, indicating that these four amino acids constitute the core motif for substrate recognition by the enzyme. Copyright © 2012 Elsevier Inc. All rights reserved. Source

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