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Biomedical subjects

Susumu Suzuki

Publications and source records attributed to Susumu Suzuki.

At least 19 recordsLinked to original sources
PubMed2006

A novel method for evaluating human carotid artery elasticity: possible detection of early stage atherosclerosis in subjects with type 2 diabetes.

We recently developed a novel method for evaluating the elasticity of arterial walls, the phased tracking method. Herein, we evaluated atherosclerosis of the carotid artery with this method in 242 individuals with type 2 diabetes. In multiple regression analysis of subject status, age, systolic blood pressure and hyperlipidemia were found to be independently associated with carotid artery elasticity values. We also measured currently established values for atherosclerosis, carotid artery IMT and baPWV, in these subjects. Carotid artery elasticity correlated with max IMT (r=0.291, p<0.01), plaque score (PS) (r=0.220, p<0.01) and baPWV (r=0.345, p<0.01). Elasticity, max IMT and plaque score, all correlated with the number of risk factors for atherosclerosis, i.e. hypertension, hyperlipidemia and smoking, in addition to diabetes, consistent with the view that these values reflect atherosclerosis. Importantly, however, in subjects with IMT <1.1mm, who are classified as not having atherosclerosis as defined by IMT criteria, only carotid artery elasticity correlated with the number of risk factors (p<0.05). These results suggest that (1) the measured carotid artery elasticity values reflect atherosclerosis and (2) our novel method has potential for detecting atherosclerosis in its early stage.

Aged↗
PubMed2006

Reduced frequency, diversity, and function of human T cell leukemia virus type 1-specific CD8+ T cell in adult T cell leukemia patients.

Human T cell lymphotropic virus type 1 (HTLV-1)-specific CTL are thought to be immune effectors that reduce the risk of adult T cell leukemia (ATL). However, in vivo conditions of anti-HTLV-1 CTL before and after ATL development have yet to be determined. To characterize anti-HTLV-1 CTL in asymptomatic HTLV-1 carriers (AC) and ATL patients, we analyzed the frequency and diversity of HTLV-1-specific CD8+ T cells in PBMC of 35 AC and 32 ATL patients using 16 distinct epitopes of HTLV-1 Tax or Env/HLA tetramers along with intracellular cytolytic effector molecules (IFN-gamma, perforin, and granzyme B). Overall frequency of subjects possessing Tax-specific CD8+ T cells was significantly lower in ATL than AC (53 vs 90%; p = 0.001), whereas the difference in Env-specific CD8+ T cells was not statistically significant. AC possessed Tax11-19/HLA-A*0201-specific tetramer+ cells by 90% and Tax301-309/HLA-A*2402-specific tetramer+ cells by 92%. Some AC recognized more than one epitope. In contrast, ATL recognized only Tax11-19 with HLA-A*0201 and Tax301-309 with HLA-A*2402 at frequencies of 30 and 55%. There were also significant differences in percentage of cells binding Tax11-19/HLA-A*0201 and Tax301-309/HLA-A*2402 tetramers between AC and ATL. Anti-HTLV-1 Tax CD8+ T cells in AC and ATL produced IFN-gamma in response to Tax. In contrast, perforin and granzyme B expression in anti-HTLV-1 CD8+ T cells of ATL was significant lower than that of AC. Frequency of Tax-specific CD8+ T cells in AC was related to proviral load in HLA-A*0201. These results suggest that decreased frequency, diversity, and function of anti-HTLV-1 Tax CD8+ T cell clones may be one of the risks of ATL development.

Adult↗
PubMed2006

Omega-3 fatty acids improve appetite in cancer anorexia, but tumor resecting restores it.

BACKGROUND: Tumor growth leads to cancer anorexia that is ameliorated using omega-3 fatty acids (omega-3FA). We hypothesize that omega-3FA modulates up-regulation of hypothalamic orexigenic neuropeptide Y (NPY) and down-regulation of anorexigenic alpha melanocyte-stimulating hormone (alpha-MSH) and serotonin 1B receptors (5-HT(1B)-receptors) in tumor-bearing rats. METHODS: Twenty-eight tumor-bearing rats were fed either chow (TB-Control) or omega-3FA (TB-omega-3FA). When anorexia developed in TB-Control rats, they and a cohort of TB-omega-pi-3 rats were killed. The rest had their tumor resected (R-Control and R-omega-3FA), and when anorexic TB-Controls normalized their food intake, brains were removed for hypothalamic immunocytochemical study of NPY, alpha-MSH, and 5-HT(1B)-receptor antibodies concentrations. Comparison among slides were assessed by image analysis and analyzed by ANOVA and t test. RESULTS: At anorexia, hypothalamic NPY in arcuate nucleus (ARC) increased by 38% in TB-omega3FA versus TB-Control, whereas alpha-MSH decreased 64% in ARC and 29% in paraventricular nucleus (PVN). Omega-3FA diet in anorexia (TB-omega-3FA vs R-omega-3FA) produced similar qualitative changes of NPY (22% increase) and alpha-MSH (31% decrease) in ARC, with concomitant decrease of 37% in 5-HT(1B)-receptors in PVN, confirming the influence of omega-3FA on the hypothalamic food intake modulators. However, after tumor resection (TB-Control vs R-Control) a 97% increase in NPY and a 62% decrease in alpha-MSH occurred that was significantly greater than in rats fed omega-3FA diet. CONCLUSION: Tumor resection and omega-3FA modifies hypothalamic food intake activity, up-regulating NPY and down-regulating alpha-MSH and 5-HT(1B)-receptors. Tumor resection in anorexic rats on chow diet restored hypothalamic NPY, alpha-MSH, and food intake quantitatively more than in rats fed omega3FA diet.

Animal Feed↗
PubMed2005

Secondary sulfonylurea failure: comparison of period until insulin treatment between diabetic patients treated with gliclazide and glibenclamide.

We retrospectively evaluated a possible difference in periods until start of insulin treatment between type 2 diabetic patients treated with gliclazide (GCZ) and glibenclamide (GBC), because GCZ might be protective for beta cells than GBC. Subjects were Japanese patients. GCZ group consisted of patients treated with GCZ alone or with GCZ and GBC in the separate treatment periods in combination with or without other oral hypoglycemic agents (OHAs), while GBC group consisted of patients with GBC alone or in combination with other OHAs except GCZ. The periods until the treatment of insulin commenced were calculated using the Kaplan-Meier method. Proportional hazards models were used to adjust the differing variables between GCZ and GBC groups. The periods until the start of insulin treatment from diabetes onset, diabetes treatment, or GCZ or GBC treatment were significantly longer in the GCZ group than those in GBC group (P<0.001 in each group). Independent variables affecting the period were average HbA1c levels during GCZ or GBC treatment (hazard ratio=2.5 per %), other OHAs combined (hazard ratio=1.9 on combination), and difference between GCZ and GBC groups (hazard ratio=0.5 on GCZ). These results imply that GCZ may be more protective against secondary beta cell failure than GBC.

Age of Onset↗
PubMed2005

Effects of omega-3 fatty acids on orexigenic and anorexigenic modulators at the onset of anorexia.

In cancer anorexia, a decrease in food intake (FI) occurs concomitant with changes in orexigenic peptides such as neuropeptide Y (NPY) and anorexigenic peptides such as alpha-melanocyte-stimulating hormone (alpha-MSH) and anorexigenic neurotransmitter serotonin. omega-3 Fatty acid (omega-3FA) inhibits cytokine synthesis, and delays tumor appearance, tumor growth, and onset of anorexia in tumor-bearing rats. We hypothesize that, in cancer anorexia, omega-3FA is associated with quantitative reversal of hypothalamic NPY, alpha-MSH, and serotonin receptor (5-HT(1B)-receptor) enhancing FI. Fischer rats were divided into: MCA tumor bearing fed chow (TB-Chow) or omega-3FA diet (TB-omega-3FA) and controls: non-tumor bearing fed chow (NTB-Chow) or omega-3FA diet (NTB-omega-3FA). Rats were euthanized at anorexia and brains were removed for hypothalamic immunohistochemical study, using NPY, alpha-MSH, and 5-HT(1B)-receptor-specific antibodies and slides assessed by image analysis. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. At anorexia, FI decreased (P < 0.05) in TB-Chow but did not change in TB-omega-3FA rats. In TB-omega-3FA vs. TB-Chow, NPY immunoreactivity increased 38% in arcuate nucleus (ARC; P < 0.05), and 50% in magnocellular paraventricular nucleus (mPVN; P < 0.05). alpha-MSH decreased 64% in ARC and 29% in mPVN (P < 0.05). 5-HT(1B)-receptor immunoreactivity decreased 13% only in supraoptic nucleus (P < 0.05). No immunoreactivity was found in the control sections. omega-3FA modified hypothalamic peptides and 5-HT-(1B)-receptor immunoreactivity at anorexia, concomitant with an increase in FI, were probably mediated by omega-3FA inhibition of tumor-induced cytokines.

Analysis of Variance↗
PubMed2005

WRN gene 1367 Arg allele protects against development of type 2 diabetes mellitus.

Werner's syndrome is an autosomal recessive disease caused by mutation of the WRN gene, which may lead to DNA repair failure and acceleration of aging. A polymorphism at amino acid 1367 Cys (TTG)/Arg (CTG) reportedly reduces the risk of myocardial infarction in Japanese. We studied the possible involvement of this polymorphism in type 2 diabetes. When polymorphism of the WRN gene was analyzed in 272 randomly recruited type 2 diabetic subjects (age 64.5+/-11.1), we found those with Cys/Arg to be older than those with Cys/Cys (p=0.021) and that the age at diagnosis of diabetes was greater in Cys/Arg than in Cys/Cys subjects (p=0.011). Diabetes-free survival rate over the age, analyzed by Kaplan-Meier method, differed significantly between these two genotype groups (p=0.0125) and the survival curve was shifted to the right in the Cys/Arg group as compared to the Cys/Cys group. No difference in allele frequency was observed between our diabetic (n=272) and non-diabetic subjects (n=171, age 66.0+/-8.0). These results suggest that the 1367 Arg allele of the WRN gene protects against the development of type 2 diabetes mellitus in Japanese.

Adenosine Triphosphatases↗
PubMed2005

Changes in GI hormones and their effect on gastric emptying and transit times after Roux-en-Y gastric bypass in rat model.

BACKGROUND: We determined whether Roux-en-Y gastric bypass (RYGB)-induced protracted weight loss is associated with an increase in anorectic peptide YY (PYY) and decreased gastrointestinal (GI) motility. METHODS: RYGB and control sham-operated GI intact obese (SO Obese) and sham-operated GI intact pair-fed (PF) rats were studied. Postoperatively, body weight (BW) and food intake were measured for 90 days. Rats were killed to measure PYY, ghrelin, cholecystokinin (CCK), and glucagonlike peptide-1 (GLP-1). Ninety-day food intake trends were examined by quadratic trend analysis. On the basis of a 28-day weight loss rate, PYY also was measured at 14 and 28 days. Peak 28-day PYY results corresponded with peak BW loss rate; thus, gastric emptying (GE) and intestinal transit time were measured. Data were analyzed by analysis of variance and Tukey's pairwise multiple comparison. RESULTS: At 90 days, BW in SO Obese versus PF versus RYGB rats was 801 +/- 15 g versus 661 +/- 24 g versus 538 +/- 32 g respectively (P < .05). Concentrations of plasma PYY were increased, while plasma ghrelin was decreased in RYGB versus SO Obese and PF (P < .05). CCK and GLP-1 were unchanged. In RYGB versus controls, PYY was increased at 14 and 28 days but was most elevated at 28 days. In RYGB versus controls, GE was delayed (P < .05) and intestinal transit time was longer (P < .05). CONCLUSIONS: After RYGB, an increase in PYY and a decrease in ghrelin occurred, probably explaining the decrease in food intake, the slower GE and transit time, which contributed to weight loss. Longitudinal studies can be performed with the use of our RYGB model, providing insight into weight loss mechanisms by generating long-term follow-up data currently not available in human studies.

Anastomosis, Roux-en-Y↗
PubMed2005

Omega-3 fatty acids and anorexia.

PURPOSE OF REVIEW: To review the mechanisms of action of omega-3 fatty acids and their role in the brain, as well as their therapeutic implications in anorexia. RECENT FINDINGS: Recent studies have demonstrated that omega-3 fatty acids modulate changes in the concentrations and actions of several orexigenic and anorexigenic neuropeptides in the brain, including neuropeptide Y, alpha-melanocyte stimulating hormone and the neurotransmitters serotonin and dopamine. In patients with acute and chronic inflammatory conditions, low tissue concentrations of omega-3 fatty acids and high concentrations of proinflammatory cytokines are found, in association with anorexia and decreased food intake. The data suggest that omega-3 fatty acid supplementation suppresses proinflammatory cytokine production and improves food intake by normalizing hypothalamic orexigenic peptides and neurotransmitters. SUMMARY: Based on current data, omega-3 fatty acid supplementation has a role in the treatment of anorexia by stimulating the production and release of orexigenic neurotransmitters in food intake regulatory nuclei in the hypothalamus.

Anorexia↗
PubMed2004

Nicotine infusion into rat ventromedial nuclei and effects on monoaminergic system.

Nicotine increases satiety and reduces food intake (FI). We hypothesize that nicotine influences FI via alteration of serotonin (5HT) and dopamine (DA) concentration in ventromedial nucleus (VMN) and lateral hypothalamic area (LHA). Microdialysis cannulas were implanted into ipsilateral VMN and contralateral LHA. Nicotine or vehicle was infused for 60 min into VMN of overnight food-deprived rats, followed by ad lib food for 40 min. Hypothalamic changes in 5HT and DA concentrations were measured every 20 min. Intra-VMN nicotine induced a long-lasting increase in 5HT concentration and an increase in DA for a short duration in the VMN, associated with an increase in 5HT in the LHA. Our data suggest that the nicotine-induced hypophagia correlates with VMN and LHA monoaminergic changes.

Animals↗
PubMed2004

Diabetes mellitus with mitochondrial gene mutations in Japan.

Diabetes mellitus due to the mitochondrial DNA 3243(A-G) mutation is reported to represent 0.5-1% of the general diabetic population in Japan. To further elucidate the clinical symptoms and course of diabetes mellitus with the 3243 mutation, we undertook a nationwide cross-sectional case-finding study and observational study of a genetically defined subject group. One hundred sixteen Japanese diabetic patients with the mutation were registered and analyzed. The patients had a higher maternal inheritance of diabetes or deafness, short stature, thin habitus, and early middle-aged onset of diabetes or deafness. Eighty-six percent of the patients required insulin therapy because of progressive insulin secretory defect. Although half of the patients had the phenotype of type 1 diabetes or slowly progressive type 1 diabetes, the patients lacked the presence of autoantibodies to glutamic acid decarboxylase. Diabetes in the mothers was characterized by early middle-aged onset, reduction in the insulin secretory capacity, early requirement of insulin therapy, and increases in the daily insulin dose. The heteroplasmic ratio of the 3243 mutation in leukocytes was low. The patients had mitochondria-related complications such as sensorineural deafness, cardiomyopathy, cardiac conductance disorders, encephalomyopathy, macular pattern dystrophy, and mental disorders. The patients also had advanced microvascular complications. Thus, this study has revealed that (1) diabetes mellitus with the 3243 mutation is a subtype of diabetes mellitus with mitochondria-related complications and (2) insulin secretory ability is more severely impaired in the patients whose mothers were also diabetic.

Adult↗
PubMed2004

Genetic variations at urotensin II and urotensin II receptor genes and risk of type 2 diabetes mellitus in Japanese.

Urotensin II is among the most potent vasoactive hormones known and the urotensin II (UTS2) gene is localized to 1p36-p32, one of the regions reported to show possible linkage with type 2 diabetes in Japanese. When we surveyed genetic polymorphisms in the UTS2 and urotensin II receptor (GPR14) gene, we identified two SNPs with amino acid substitutions (designated T21M and S89N and an SNP in the promotor region (-605G>A) of the UTS2 gene, and two SNPs in the non-coding region of the GPR14 gene. We then studied these three SNPs in the UTS2 gene and two SNPs in the GPR14 gene in 152 Japanese subjects with type 2 diabetes mellitus and two control Japanese populations. The allele frequency of 89N was significantly higher in type 2 diabetic patients than in both elderly normal subjects (P = 0.0018) and subjects with normal glucose tolerance (P = 0.0011), whereas the allele frequency of T21M and -605G>A in the UTS2 gene and those of two SNPs in the GPR14 gene were essentially identical in these three groups. Furthermore, in the subjects with normal glucose tolerance, 89N was associated with significantly higher insulin levels on oral glucose tolerance test, suggesting reduced insulin sensitivity in subjects with 89N. These results strongly suggest that subjects with S89N in the UTS2 gene are more insulin-resistant and thus more susceptible to type 2 diabetes mellitus development.

Amino Acid Substitution↗
PubMed2004

Changes in hypothalamic neuropeptide Y and monoaminergic system in tumor-bearing rats: pre- and post-tumor resection and at death.

BACKGROUND: Cancer anorexia is influenced by the neuropeptidergic and monoaminergic systems. We hypothesize that serotonin (5-HT), dopamine (DA) and neuropeptide Y (NPY) concentrations in paraventricular (PVN), ventromedial (VMN), and lateral hypothalamus (LHA) areas are abnormal in tumor-bearing rats. METHODS: Fifty-five Fischer rats (240-280 g) were divided into MCA tumor-bearing (TB), nontumor-bearing (NTB), pair-fed (PF), TB sacrificed at the end of experiment (TB-Terminal), TB resection (TB-Resection), NTB sham-operated (NTB-Sham) and pair-fed sham-operated (PF-Sham) groups. Rats were sacrificed at onset of anorexia (TB, NTB, and PF) and 9 days after tumor resection (TB-Resection, NTB-Sham, PF-Sham, and TB-Terminal). Bilateral PVN, VMN, and LHA were harvested for NPY, 5-HT, and DA analyses. RESULTS: Food intake decreased in TB versus NTB (P < .05). In TB versus NTB, an increase of 5-HT in PVN and VMN occurred with a concomitant decrease in DA. NPY in PVN, VMN, and LHA decreased (P < .05). In TB-Resection versus NTB-Sham, 5-HT, DA, NPY, and FI normalized after tumor resection. CONCLUSIONS: Cancer anorexia is associated with abnormal serotonin, dopamine, and NPY concentrations, expressed by an increase in 5-HT and a decrease in DA and NPY. After tumor resection, these alterations normalized, providing evidence that the levels of these substances change with anorexia in tumor-bearing rats.

Animals↗
PubMed2004

Cancer anorexia-cachexia syndrome: cytokines and neuropeptides.

PURPOSE OF REVIEW: Cancer anorexia-cachexia syndrome is observed in 80% of patients in the advanced stages of cancer and is a strong independent risk factor for mortality. Numerous cytokines produced by tumor and immune cells, interacting with the neuropeptidergic system, mediate the cachectic effect of cancer. Since there is currently no effective pharmacological treatment and the anorexia-cachexia syndrome continues to be defined biochemically, we review the role of cytokines and neuropeptides in this process. RECENT FINDINGS: Currently data suggest that cancer anorexia-cachexia syndrome results from a multifactorial process involving many mediators, including hormones (e.g. leptin), neuropeptides (e.g. neuropeptide Y, melanocortin, melanin-concentrating hormone and orexin) and cytokines (e.g. interleukin 1, interleukin 6, tumor necrosis factor alpha and interferon gamma). It is likely that close interrelation among these mediators exists in the hypothalamus, decreasing food intake and leading to cachexia. SUMMARY: In the pathogenesis of cancer anorexia, cytokines play a pivotal role influencing the imbalance of orexigenic and anorexigenic circuits that regulate the homeostatic loop of body-weight regulation, leading to cachexia. Interfering pharmacologically with cytokine expression or neural transduction of cytokine signals can be an effective therapeutic strategy in anorectic patients before they develop cancer anorexia-cachexia syndrome.

Animals↗
PubMed2004

The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase.

Human Lats2, a novel serine/threonine kinase, is a member of the Lats kinase family that includes the Drosophila tumour suppressor lats/warts. Lats1, a counterpart of Lats2, is phosphorylated in mitosis and localized to the mitotic apparatus. However, the regulation, function and intracellular distribution of Lats2 remain unclear. Here, we show that Lats2 is a novel phosphorylation target of Aurora-A kinase. We first showed that the phosphorylated residue of Lats2 is S83 in vitro. Antibody that recognizes this phosphorylated S83 indicated that the phosphorylation also occurs in vivo. We found that Lats2 transiently interacts with Aurora-A, and that Lats2 and Aurora-A co-localize at the centrosomes during the cell cycle. Furthermore, we showed that the inhibition of Aurora-A-induced phosphorylation of S83 on Lats2 partially perturbed its centrosomal localization. On the basis of these observations, we conclude that S83 of Lats2 is a phosphorylation target of Aurora-A and this phosphorylation plays a role of the centrosomal localization of Lats2.

Aurora Kinases↗