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ABSTRACT: A 58-year-old woman with severe constipation and a habit of straining at defecation was diagnosed to have mucosal prolapse syndrome. One year later, her primary symptom changed to bloody diarrhea. The colonoscopic and histological findings were consistent with the characteristics of cap polyposis. After nine years, her symptoms and colonoscopic abnormalities disappeared completely without treatment. For two years since that time, the patient has remained well with normal endoscopy findings and a high value of anti-Helicobacter pylori immunoglobulin G. In this case, cap polyposis might have developed via mucosal prolapse syndrome and then regressed completely, irrespective of the Helicobacter pylori infection.
Internal Medicine 01/2013; 52(3):351-354. · 0.94 Impact Factor
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Toshihide Shima,
Hirofumi Uto,
Kohjiro Ueki,
Toshinari Takamura,
Yutaka Kohgo, Sumio Kawata,
Kohichiroh Yasui,
Hyohun Park,
Naoto Nakamura,
Tatsuaki Nakatou,
Nobuyoshi Tanaka,
Atsushi Umemura,
Masayuki Mizuno,
Junko Tanaka,
Takeshi Okanoue
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ABSTRACT: BACKGROUND: The Japan Society of Diabetes Mellitus reported that the leading cause of death in patients with diabetes mellitus (DM) was chronic liver disease; however, there are limited studies investigating the cause of liver injury in these patients. Our study aimed to clarify the clinicopathological features of liver injury and the characteristics of nonalcoholic fatty liver disease (NAFLD) in DM patients. METHODS: In total, 5,642 DM patients and 365 histologically proven NAFLD patients were enrolled. Clinical and laboratory parameters and liver biopsy results were, respectively, recorded and analyzed for the two sets of patients. RESULTS: Positivity rates for Hepatitis B surface antigens (HBsAg) and anti-hepatitis C virus antibodies (anti-HCV Ab) were 1.7 and 5.1 %, respectively. The proportion of drinkers consuming 20-59 g and ≥60 g alcohol daily was 14.9 and 4.3 %, respectively. The percentage of DM patients with elevated serum alanine aminotransferase (ALT) levels (≥31 IU/L) was 28.6 %. Alcohol consumption had no significant effect on serum ALT levels. Seventy-two percent of HBsAg-positive patients were serum hepatitis B virus (HBV)-DNA negative, whereas 10 % exhibited high levels of the same (>4.0 log copies/ml). Thirty-eight percent of anti-HCV Ab-positive patients were serum HCV-RNA negative. Among the NAFLD patients, the frequencies of NASH and advanced stage NASH were significantly higher in male DM patients than in male patients without DM. CONCLUSIONS: Although HBsAg- and anti-HCV Ab-positivity rates were high in our Japanese DM patients, a majority of liver injuries could be associated with NAFLD/nonalcoholic steatohepatitis.
Journal of Gastroenterology 08/2012; · 4.16 Impact Factor
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ABSTRACT: It has been suggested that intestinal lymph flow plays an important role in insulin secretion and glucose metabolism after meals. In this study, we investigated the influence of ligation of the mesenteric lymph duct on glucose metabolism and islet β-cells in rats.
Male Sprague-Dawley rats (10 weeks old) were divided into two groups: one underwent ligation of the mesenteric lymph duct above the cistern (ligation group), and the other underwent a sham operation (sham group). After 1 and 2 weeks, fasting plasma concentrations of glucose, insulin, triglyceride, glucose-dependent insulinotropic polypeptide (GIP), and the active form of glucagon-like peptide-1 (GLP-1) were measured. At 2 weeks after the operation, the oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT) were performed. After the rats had been sacrificed, the insulin content of the pancreas was measured and the proliferation of β-cells was assessed immunohistochemically using antibodies against insulin and Ki-67.
During the OGTT, the ligation group showed a significant decrease in the plasma glucose concentration at 120 min (p<0.05) and a significant increase in the plasma insulin concentration by more than 2-fold at 15 min (p<0.01). On the other hand, the plasma GIP concentration was significantly decreased at 60 min (p<0.01) in the ligated group, while the active form of GLP-1 showed a significantly higher level at 90 min (1.7-fold; p<0.05) and 120 min (2.5-fold; p<0.01). During the IVGTT, the plasma insulin concentration in the ligation group was significantly higher at 2 min (more than 1.4-fold; p<0.05). Immunohistochemistry showed that the ratios of β-cell area/acinar cell area and β-cell area/islet area, and also β-cell proliferation, were significantly higher in the ligation group than in the sham group (p<0.05, p<0.01 and p<0.01, respectively). The insulin content per unit wet weight of pancreas was also significantly increased in the ligation group (p<0.05).
In rats with ligation of the mesenteric lymph duct, insulin secretion during the OGTT or IVGTT was higher, and the insulin content and β-cell proliferation in the pancreas were also increased. Our data show that mesenteric lymph duct flow has a role in glucose metabolism.
Biochemical and Biophysical Research Communications 07/2012; 425(2):266-72. · 2.48 Impact Factor
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Junitsu Ito,
Takafumi Saito,
Akiko Iwaba,
Yoshihiro Suzuki,
Mai Sanjo,
Rika Ishii,
Chikako Sato,
Hiroaki Haga,
Kazuo Okumoto,
Yuko Nishise,
Hisayoshi Watanabe,
Koji Saito,
Hitoshi Togashi, Sumio Kawata
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ABSTRACT: A 52-year-old man suffering from monocular blindness, with light perception only, was admitted to our hospital. The symptom
had begun as low vision and developed rapidly within 3weeks into monocular blindness in the right eye, with no other systemic
manifestations. Imaging examinations revealed multiple hepatocellular carcinomas in the cirrhotic liver, and tumors at the
skull base and vertebra. A pathological and immunochemical study of specimens obtained by endoscopic transnasal tumor biopsy
and laminectomy revealed them to be metastatic hepatocellular carcinomas (HCCs). Although the patient underwent radiation
therapy and chemotherapy, he died 5months after admission to our hospital. The cranial HCC, involving only the optic canal,
may have disturbed the optic nerve in preference to the other cranial nerves. This is the first report of a HCC patient with
monocular blindness as the initial presentation of the disease.
KeywordsBlindness–Hepatocellular carcinoma–Metastasis
Clinical Journal of Gastroenterology 04/2012; 4(4):273-277.
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ABSTRACT: The molecular basis of antibody neutralization against hepatitis C virus (HCV) is poorly understood. The E2 glycoprotein of HCV is critically involved in viral infectivity through specific binding to the principal virus receptor component CD81, and is targeted by anti-HCV neutralizing antibodies. A previous study showed that a mutation at position 534 (N534H) within the sixth N-glycosylation motif of E2 of the J6/JFH1 strain of HCV genotype 2a (HCV-2a) was responsible for more efficient access of E2 to CD81 so that the mutant virus could infect the target cells more efficiently. The purpose of this study was to analyze the sensitivity of the parental J6/JFH1, its cell culture-adapted variant P-47 possessing 10 amino acid mutations and recombinant viruses with the adaptive mutations to neutralization by anti-HCV antibodies in sera of HCV-infected patients. The J6/JFH1 virus was neutralized by antibodies in sera of patients infected with HCV-2a and -1b, with mean 50% neutralization titers being 1:670 and 1:200, respectively (P < 0.00001). On the other hand, the P-47 variant showed 50- to 200-times higher sensitivity to antibody neutralization than the parental J6/JFH1 without genotype specificity. The N534H mutation, and another one at position 416 (T416A) near the first N-glycosylation motif to a lesser extent, were shown to be responsible for the enhanced sensitivity to antibody neutralization. The present results suggest that the residues 534, and 416 to a lesser extent, of the E2 glycoprotein are critically involved in the HCV infectivity and antibody neutralization.
Journal of Medical Virology 02/2012; 84(2):229-34. · 2.82 Impact Factor
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Takahisa Kawaguchi,
Yoshio Sumida,
Atsushi Umemura,
Keitaro Matsuo,
Meiko Takahashi,
Toshinari Takamura,
Kohichiroh Yasui,
Toshiji Saibara,
Etsuko Hashimoto,
Miwa Kawanaka, [......], Sumio Kawata,
Yasuharu Imai,
Miki Kokubo,
Toshihide Shima,
Hyohun Park,
Hideo Tanaka,
Kazuo Tajima,
Ryo Yamada,
Fumihiko Matsuda,
Japan Study Group of Nonalcoholic Fatty Liver Disease
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ABSTRACT: Nonalcoholic fatty liver disease (NAFLD) includes a broad range of liver pathologies from simple steatosis to cirrhosis and fibrosis, in which a subtype accompanying hepatocyte degeneration and fibrosis is classified as nonalcoholic steatohepatitis (NASH). NASH accounts for approximately 10-30% of NAFLD and causes a higher frequency of liver-related death, and its progression of NASH has been considered to be complex involving multiple genetic factors interacting with the environment and lifestyle.
To identify genetic factors related to NAFLD in the Japanese, we performed a genome-wide association study recruiting 529 histologically diagnosed NAFLD patients and 932 population controls. A significant association was observed for a cluster of SNPs in PNPLA3 on chromosome 22q13 with the strongest p-value of 1.4 × 10(-10) (OR = 1.66, 95%CI: 1.43-1.94) for rs738409. Rs738409 also showed the strongest association (p = 3.6 × 10(-6)) with the histological classifications proposed by Matteoni and colleagues based on the degree of inflammation, ballooning degeneration, fibrosis and Mallory-Denk body. In addition, there were marked differences in rs738409 genotype distributions between type4 subgroup corresponding to NASH and the other three subgroups (p = 4.8 × 10(-6), OR = 1.96, 95%CI: 1.47-2.62). Moreover, a subgroup analysis of NAFLD patients against controls showed a significant association of rs738409 with type4 (p = 1.7 × 10(-16), OR = 2.18, 95%CI: 1.81-2.63) whereas no association was obtained for type1 to type3 (p = 0.41). Rs738409 also showed strong associations with three clinical traits related to the prognosis of NAFLD, namely, levels of hyaluronic acid (p = 4.6 × 10(-4)), HbA1c (p = 0.0011) and iron deposition in the liver (p = 5.6 × 10(-4)).
With these results we clearly demonstrated that Matteoni type4 NAFLD is both a genetically and clinically different subset from the other spectrums of the disease and that the PNPLA3 gene is strongly associated with the progression of NASH in Japanese population.
PLoS ONE 01/2012; 7(6):e38322. · 4.09 Impact Factor
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ABSTRACT: The liver possesses the capacity to restore its function and mass after injury. Liver regeneration is controlled through complicated mechanisms, in which the phosphoinositide (PI) cycle is shown to be activated in hepatocytes. Using a rat partial hepatectomy (PH) model, the authors investigated the expression of the diacylglycerol kinase (DGK) family, a key enzyme in the PI cycle, which metabolizes a lipid second-messenger diacylglycerol (DG). RT-PCR analysis shows that DGKζ and DGKα are the major isozymes in the liver. Results showed that in the process of regeneration, the DGKζ protein, which is detected in the nucleus of a small population of hepatocytes in normal liver, is significantly increased in almost all hepatocytes. However, the mRNA levels remain largely unchanged. Double labeling with bromodeoxyuridine (BrdU), an S phase marker, reveals that DGKζ is expressed independently of DNA synthesis or cell proliferation. However, DGKα protein localizes to the cytoplasm in normal and regenerating livers, but immunoblot analysis reveals that the expected (80 kDa) and the lower (70 kDa) bands are detected in normal liver, whereas at day 10 after PH, the expected band is solely recognized, showing a different processing pattern of DGKα in liver regeneration. These results suggest that DGKζ and DGKα are involved, respectively, in the nucleus and the cytoplasm of hepatocytes in regenerating liver.
Journal of Histochemistry and Cytochemistry 12/2011; 60(2):130-8. · 2.72 Impact Factor
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ABSTRACT: Aberrant expression of microRNAs (miRNA) is associated with phenotypes of various cancers, including pancreatic cancer. However, the mechanism of the aberrant expression is largely unknown. Activation of the mitogen-activated protein kinase (MAPK) signaling pathway plays a crucial role in gene expression related to the malignant phenotype of pancreatic cancer. Hence, we studied the role of MAPK in the aberrant expression of miRNAs in pancreatic cancer cells. The alterations in expression of 183 miRNAs induced by activation or inactivation of MAPK were assayed in cultured pancreatic cancer cells and HEK293 cells by means of the quantitative real-time PCR method. We found that four miRNAs, namely, miR-7-3, miR-34a, miR-181d, and miR-193b, were preferentially associated with MAPK activity. Among these miRNAs, miR-7-3 was upregulated by active MAPK, whereas the others were downregulated. Promoter assays indicated that the promoter activities of the host genes of miR-7-3 and miR-34a were both downregulated by alteration in MAPK activity. Exogenous overexpression of the MAPK-associated miRNAs had the effect of inhibition of the proliferation of cultured pancreatic cancer cells; miR-193b was found to exhibit the most remarkable inhibition. A search for target genes of miR-193b led to identification of CCND1, NT5E, PLAU, STARD7, STMN1, and YWHAZ as the targets. Translational suppression of these genes by miR-193b was confirmed by reporter assay. These results indicate that activation of MAPK may play a significant role in aberrant expression of miRNAs and their associated phenotypes in pancreatic cancer.
Molecular Cancer Research 12/2011; 10(2):259-69. · 4.29 Impact Factor
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Yu Sasaki,
Hiroaki Takeda,
Takeshi Sato,
Tomohiko Orii,
Shoichi Nishise,
Ko Nagino,
Daisuke Iwano,
Takao Yaoita,
Kazuya Yoshizawa,
Hideki Saito,
Yasuhisa Tanaka, Sumio Kawata
[show abstract]
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ABSTRACT: It is widely acknowledged that chronic low-grade inflammation plays a key role in the development of obesity-related insulin resistance and type 2 diabetes. The level of circulating interleukin-6 (IL-6), one of the major proinflammatory adipokines, is correlated with obesity and insulin resistance, which are known to be risk factors for colorectal adenoma. We examined the association between the circulating level of IL-6 and the presence of colorectal adenoma.
In a total colonoscopy-based cross-sectional study conducted between January and December 2008, serum levels of IL-6 were measured in samples of venous blood obtained from 336 male participants attending health checkups (118 individuals with colorectal adenoma and 218 age-matched controls) after an overnight fast.
In the colorectal adenoma group, the median levels of serum IL-6 (1.24 vs. 1.04 pg/mL; P = 0.01), triglyceride, insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) were to be significantly higher than those in the control group. When restricted to individuals with adenoma, levels of IL-6 were positively correlated with body mass index, insulin, and HOMA-IR. Multiple logistic analyses adjusted to include insulin or HOMA-IR showed that high levels of IL-6 were associated with the presence of colorectal adenoma. There was no significant interaction of IL-6 with HOMA-IR to modify this association.
Our findings suggest that increased serum levels of IL-6 are positively associated with the presence of colorectal adenoma in men, independently of insulin and HOMA-IR.
Clinical Cancer Research 11/2011; 18(2):392-9. · 7.74 Impact Factor
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ABSTRACT: Macrophage colony-stimulating factor (M-CSF) induces normal intestinal macrophages that have anti-inflammatory effects. Thus, M-CSF-rich conditions in colonic tissues seem to contribute to the improvement of pathological conditions in patients with inflammatory bowel diseases (IBD). However, it has not been clarified whether current therapies for IBD, including granulocyte/monocyte adsorptive apheresis using an Adacolumn, and ulinastatin, a serine protease inhibitor, affect the production of M-CSF. To clarify the effects of these therapies on M-CSF production, we investigated whether monocyte adsorption to cellulose acetate (CA) beads (carriers for Adacolumn therapy) and ulinastatin augmented M-CSF production in in vitro experiments. Peripheral blood was incubated with and without CA beads, and then M-CSF production was measured. Additionally, peripheral blood containing serial dilutions of ulinastatin was incubated with CA beads followed by measurement of M-CSF production. Monocyte adsorption to CA beads did not affect M-CSF production. A high concentration of ulinastatin augmented M-CSF production without inhibiting monocyte adsorption to CA beads, although a low concentration of ulinastatin conversely suppressed M-CSF production. The present study found that a high concentration of ulinastatin, which was administrated with CA beads, increased the production of M-CSF. Our results suggest that a combination of ulinastatin and Adacolumn therapy may provide more clinical efficacy for the treatment of IBD in terms of the production of M-CSF.
Therapeutic apheresis and dialysis: official peer-reviewed journal of the International Society for Apheresis, the Japanese Society for Apheresis, the Japanese Society for Dialysis Therapy 08/2011; 15(4):379-84. · 1.39 Impact Factor
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Makoto Daimon,
Toshihide Oizumi,
Shigeru Karasawa,
Wataru Kaino,
Kaoru Takase,
Kyouko Tada,
Yumi Jimbu,
Kiriko Wada,
Wataru Kameda,
Shinji Susa,
Masaaki Muramatsu,
Isao Kubota, Sumio Kawata,
Takeo Kato
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ABSTRACT: The association of the clusterin (CLU) gene polymorphism (single nucleotide polymorphisms [SNPs] 1-4: rs1532278, rs1532277, rs2279590, and rs2279591, respectively) with type 2 diabetes mellitus was examined using a population of the Funagata study (n [male-female] = 1631 [741:884]; age, 62.0 ± 12.1 years), a Japanese community-based study. Single nucleotide polymorphisms 1 to 3 were significantly associated with hemoglobin A(1c) levels (P = .0154, .0021, and .0006, respectively) and diabetes (.0310, .0170, and .0021, respectively). A case-control association study of SNP 3 with diabetes by multiple logistic regression analysis showed a significant association of genotype AA (the at-risk genotype) with an odds ratio (OR) of 2.33 (P = .0039) independently of age and sex. The association was marginally validated by a study with another Japanese community-based sample, the Takahata Study (n [male-female] = 2.948 [1333:1615]; age, 63.0 ± 10.2 years) (OR, 1.59; P = .0595; χ(2)P = .0264). When the 2 samples were combined, the association became more significant (OR, 1.75; P = .0025). In subjects with the non-at-risk genotypes, the insulin resistance index--homeostasis model assessment of insulin resistance (HOMA-R)--increased significantly (P < .0001) and the insulin secretion index--HOMA-β--appeared to decrease (P = .1803 and .0097, respectively, for the genotypes AG and GG) as the glucose tolerance progressed toward diabetes (normal glucose tolerance to glucose intolerance to diabetes). However, in subjects with the at-risk genotype, HOMA-R and HOMA-β showed a significant increase already in the subjects with normal glucose tolerance (P = .0239 and .0305, respectively); and as the glucose tolerance progressed toward diabetes, HOMA-R stayed approximately the same, whereas HOMA-β decreased significantly (P = .0332). The CLU gene was associated with diabetes, probably through an increase in insulin resistance primarily and through an impairment of insulin secretion secondarily.
Metabolism: clinical and experimental 06/2011; 60(6):815-22. · 2.59 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 05/2011; 69 Suppl 4:23-8.
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Yusuke Mashima,
Tsuneo Konta,
Kosuke Kudo,
Satoshi Takasaki,
Kazunobu Ichikawa,
Kazuko Suzuki,
Yoko Shibata,
Tetsu Watanabe,
Takeo Kato, Sumio Kawata,
Isao Kubota
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ABSTRACT: Essential hypertension is a multifactorial disorder and a risk factor for renal failure and cardiovascular disease. Recently it was hypothesized that subtle acquired renal injury such as renal microvascular and tubulointerstitial damage induces salt-sensitive hypertension. The objective of this study was to examine the relationship between blood pressure and renal abnormalities in the Japanese general population. The participants in this community-based, cross-sectional study were 1,965 subjects over 40 years old, without renal insufficiency and antihypertensive medication. Urine albumin-creatinine ratio (UACR) and beta2-microglobulin-creatinine ratio (UBCR) were measured in single spot urine samples, as markers of renal microvascular and tubulointerstitial damage, respectively. Multiple linear regression analysis showed a significant positive correlation of blood pressure with UACR and UBCR, but not with estimated glomerular filtration rate. In multiple logistic regression analysis, the increases in UACR and UBCR were independently associated with hypertension, after adjustment for possible confounders. Higher levels of UACR (≥ 5.9 mg g(-1)) and UBCR (≥ 145 μg g(-1)) were associated with a significantly higher risk of hypertension, compared with UACR ≤ 5.8 mg g(-1) and UBCR ≤ 84.5 μg g(-1), respectively. Furthermore, there was a positive relationship between urinary sodium excretion and blood pressure in subjects with high UBCR tertile. This study showed that the increases in urinary albumin and beta2-microglobulin were independently associated with blood pressure in a general population. These renal abnormalities may be differentially related to the development of hypertension.
Hypertension Research 04/2011; 34(7):831-5. · 2.58 Impact Factor
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Sumio Kawata
Nihon Naika Gakkai Zasshi 04/2011; 100(4):975-82.
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Rika Ishii,
Hitoshi Togashi,
Akiko Iwaba,
Chikako Sato,
Hiroaki Haga,
Mai Sanjo,
Kazuo Okumoto,
Yuko Nishise,
Jun-Itsu Ito,
Hisayoshi Watanabe,
Koji Saito,
Akio Okada,
Kazuei Takahashi,
Takafumi Saito, Sumio Kawata
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ABSTRACT: We describe a 62-year-old woman with advanced chronic hepatitis C who showed no response to low-dose long-term interferon-beta monotherapy (3 MU, three times a week). The interferon monotherapy was continued for 2 years and 9 months. Despite this lack of response to interferon, the patient's clinical course was good and liver function assessed by (99m)Tc-galactosyl human serum albumin single photon emission computed tomography ((99m)Tc-GSA SPECT) analysis improved significantly. Improvement of the data obtained by (99m)Tc-GSA SPECT analysis justified continuation of the treatment. (99m)Tc-GSA SPECT analysis was clinically useful to evaluate the effect of interferon in a patient with interferon non-responsive chronic hepatitis C, despite a lack of reduction of the ALT level and HCV-RNA titer.
Annals of Nuclear Medicine 04/2011; 25(7):520-3. · 1.50 Impact Factor
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ABSTRACT: Both host and viral factors have been implicated in influencing the response to pegylated-interferon/ribavirin (PEG-IFN/RBV) therapy for hepatitis C virus (HCV) infection. Among the viral factors, sequence heterogeneity within NS5A and core regions has been proposed. This study aimed to clarify the relationship between virological responses to PEG-IFN/RBV therapy and sequence heterogeneity within NS5A, including the IFN/RBV resistance-determining region (IRRDR), the interferon sensitivity-determining region (ISDR) and the core region. Pretreatment sequences of NS5A and the core regions were analyzed in 57 HCV-1b-infected patients who were to be treated with PEG-IFN/RBV. Of 40 patients infected with HCV having an IRRDR with four or more mutations (IRRDR ≥ 4), 28 (70%) patients achieved a sustained virological response (SVR). On the other hand, only 4 (24%) of 17 patients infected with HCV having an IRRDR with three or fewer mutations (IRRDR ≤ 3) achieved a SVR (P = 0.001). Similarly, 22 (71%) of 31 patients infected with HCV and having an ISDR with one or more mutations (ISDR ≥ 1) achieved a SVR while 10 (38%) of 26 patients infected with HCV and having an ISDR without any mutations (ISDR = 0) achieved a SVR (P = 0.014). As for the core region, there was significant correlation between a single mutation at position 70 (Gln(70) ) and non-SVR (P = 0.02). Notably, Gln(70) was more prominently associated with the null response (P = 0.0007). In conclusion, sequence heterogeneity within the IRRDR and ISDR, and a single point mutation at position 70 of the core region of HCV-1b are likely to be correlated with virological responses to PEG-IFN/RBV therapy.
Microbiology and Immunology 03/2011; 55(6):418-26. · 1.30 Impact Factor
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Yusuke Mashima,
Tsuneo Konta,
Kosuke Kudo,
Kazuko Suzuki,
Ami Ikeda,
Kazunobu Ichikawa,
Yoko Shibata,
Tetsu Watanabe,
Gen Tamiya,
Takeo Kato, Sumio Kawata,
Isao Kubota
[show abstract]
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ABSTRACT: A cluster of proinflammatory cytokines plays an important role in the development of various renal diseases, and the expression of these cytokines is genetically modified. To examine the association between polymorphisms of proinflammatory cytokine genes and albuminuria, a cross-sectional study was conducted in the general population.
Single nucleotide polymorphisms (SNPs) in six proinflammatory cytokine genes, including interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor (TNF)-α, CC chemokine ligand 1 (CCL1) and monocyte chemoattractant protein-1 (MCP-1), were genotyped in 2927 Japanese subjects. Urine albumin-creatinine ratio (UACR) was measured in morning spot urine samples.
Albuminuria (UACR ≥ 30 mg/g) was significantly associated with the A/A + A/G genotype at rs2069852 in the IL-6 gene (P = 0.01) and the A/A genotype at rs228269 in the CCL1 gene (P = 0.002). Multivariate analysis with adjustment for traditional risk factors showed that these genotypes independently predicted albuminuria [odds ratio (OR) 1.782, 95% confidence interval (CI) 1.171-2.712, P = 0.007 for the A/A + A/G genotype at rs2069852 in IL-6, and OR 1.432, 95% CI 1.128-1.770, P = 0.003 for the A/A genotype at rs228269 in CCL1]. The prevalence of albuminuria and the UACR were increased along with the increase of risk genotypes.
This study revealed that SNPs in the IL-6 and CCL1 genes were associated with albuminuria, and the combination of these genotypes had an additive effect on the prevalence and severity of albuminuria. This indicates that genetic factors influencing inflammatory responses may affect the development of renal injury in the Japanese general population.
Nephrology Dialysis Transplantation 03/2011; 26(12):3902-7. · 3.40 Impact Factor
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Takafumi Saito,
Kazuo Okumoto,
Hiroaki Haga,
Yuko Nishise,
Rika Ishii,
Chikako Sato,
Hisayoshi Watanabe,
Akio Okada,
Motoki Ikeda,
Hitoshi Togashi,
Tsuyoshi Ishikawa,
Shuji Terai,
Isao Sakaida, Sumio Kawata
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ABSTRACT: The present study was conducted to evaluate the application and efficacy of autologous bone marrow infusion (ABMi) for improvement of liver function in patients with alcoholic liver cirrhosis (ALC). Five subjects and 5 control patients with ALC who had abstained from alcohol intake for 24 weeks before the study were enrolled. Autologous bone marrow cells were washed and injected intravenously, and the changes in serum liver function parameters, and the level of the type IV collagen 7S domain as a marker of fibrosis, were monitored for 24 weeks. The distribution of activated bone marrow was assessed by indium-111-chloride bone marrow scintigraphy. The number of cells infused was 8.0±7.3×10(9) (mean±standard error). The serum levels of albumin and total protein and the prothrombin time were significantly higher during the follow-up period after ABMi than during the observation period in treated patients, whereas no such changes were observed in the controls. In the patients who received ABMi, the Child-Pugh score decreased in all 3 who were classified as class B; the serum levels of type IV collagen 7S domain improved in 4 of the 5 patients; and bone marrow scintigraphy demonstrated an increase of indium-111-chloride uptake in 3 of the 4 patients tested. ABMi for patients with ALC helps improve liver function parameters in comparison with observation during abstinence and ameliorates the degree of fibrosis in terms of serum markers and bone marrow activation in most cases.
Stem cells and development 03/2011; 20(9):1503-10. · 4.15 Impact Factor
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Tomoyoshi Soga,
Masahiro Sugimoto,
Masashi Honma,
Masayo Mori,
Kaori Igarashi,
Kasumi Kashikura,
Satsuki Ikeda,
Akiyoshi Hirayama,
Takehito Yamamoto,
Haruhiko Yoshida, [......],
Shoji Tsuji,
Yutaka Yatomi,
Tadayuki Sakuragawa,
Hisayoshi Watanabe,
Kouei Nihei,
Takafumi Saito, Sumio Kawata,
Hiroshi Suzuki,
Masaru Tomita,
Makoto Suematsu
[show abstract]
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ABSTRACT: We applied a metabolome profiling approach to serum samples obtained from patients with different liver diseases, to discover noninvasive and reliable biomarkers for rapid-screening diagnosis of liver diseases.
Using capillary electrophoresis and liquid chromatography mass spectrometry, we analyzed low molecular weight metabolites in a total of 248 serum samples obtained from patients with nine types of liver disease and healthy controls.
We found that γ-glutamyl dipeptides, which were biosynthesized through a reaction with γ-glutamylcysteine synthetase, were indicative of the production of reduced glutathione, and that measurement of their levels could distinguish among different liver diseases. Multiple logistic regression models facilitated the discrimination between specific and other liver diseases and yielded high areas under receiver-operating characteristic curves. The area under the curve values in training and independent validation data were 0.952 and 0.967 in healthy controls, 0.817 and 0.849 in drug-induced liver injury, 0.754 and 0.763 in asymptomatic hepatitis B virus infection, 0.820 and 0.762 in chronic hepatitis B, 0.972 and 0.895 in hepatitis C with persistently normal alanine transaminase, 0.917 and 0.707 in chronic hepatitis C, 0.803 and 0.993 in cirrhosis type C, and 0.762 and 0.803 in hepatocellular carcinoma, respectively. Several γ-glutamyl dipeptides also manifested potential for differentiating between nonalcoholic steatohepatitis and simple steatosis.
γ-Glutamyl dipeptides are novel biomarkers for liver diseases, and varying levels of individual or groups of these peptides have the power to discriminate among different forms of hepatic disease.
Journal of Hepatology 02/2011; 55(4):896-905. · 9.26 Impact Factor
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Hiroaki Haga,
Takafumi Saito,
Kazuo Okumoto,
Satoshi Ugajin,
Chikako Sato,
Rika Ishii,
Yuko Nishise,
Junitsu Ito,
Hisayoshi Watanabe,
Koji Saito,
Hitoshi Togashi, Sumio Kawata
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ABSTRACT: The transplantation of bone marrow cells (BMCs) has been applied in liver regenerative cell therapy. However, details of the interaction between the transplanted BMCs and hepatic stem cells have not been elucidated. The aim of the present study was to investigate the interaction of BMCs with hepatic stem-like cells (HSLCs) and to determine the BMC factor that steers HSLC differentiation into the hepatocyte lineage. Both BMCs and HSLCs were obtained from an adult Sprague-Dawley rat, and a co-culture system was established. Cell proliferation was analyzed by a proliferation assay, and the differentiation of HSLCs into the hepatocyte lineage was evaluated by the detection of cellular mRNA for liver-specific proteins. DNA microarray analysis was applied to BMCs co-cultured with HSLCs to determine the genes upregulated by their interaction. The proliferation of HSLCs co-cultured with BMCs was significantly higher than that of HSLCs cultured alone, and the expression of mRNAs for both albumin and tryptophan-2,3-dioxygenase was detectable in the co-cultured HSLCs. DNA microarray analysis showed the upregulated expression of fibroblast growth factor 2 (FGF2) mRNA in BMCs co-cultured with HSLCs, and the expression of mRNAs for both albumin and tyrosine aminotransferase became detectable in HSLCs cultured with FGF2. Thus, BMCs stimulate both the proliferation of HSLCs and their differentiation into the hepatocyte lineage. FGF2 is one of the factors that is produced by the interacting BMCs and that stimulates this differentiation.
Cell and Tissue Research 02/2011; 343(2):371-8. · 3.11 Impact Factor
