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1.
BBA Adv ; 1: 100007, 2021.
Article in English | MEDLINE | ID: mdl-37082005

ABSTRACT

In genomic DNA, G-quadruplex (G4)-forming DNA can form either a duplex or G4 structure, suggesting that understanding the factors regulating G4 formation is important for revealing the cellular functions controlled by G4 formation. Cytosine DNA methylation in the CpG islands is known to play an important role in transcriptional regulation. Additionally, CpG methylation increases the thermal stability of G4 structures such as BCL2 and VEGF G4. In this study, we evaluated the effects of CpG methylation in three G4 structures (c-kit2, c-kit*, and c-kit1) produced by the c-KIT promoter. Each was analyzed using circular dichroism (CD) melting analysis. The results demonstrate that CpG methylation does not alter the thermal stability of c-kit2 G4 structure when formed in the presence of K+; a single-CpG methylation at C1 or C11 decreases the thermal stability of any c-kit2 G4 structure formed in the presence of Na+ and Mg2+ while methylation at C5 increases the thermal stability; CpG methylation does not alter the thermal stability of c-kit1 or c-kit* G4 structures formed in the presence of K+; and the c-kit1 and c-kit* G4-forming oligonucleotides do not form G4 structures in the presence of Na+ and Mg2+. These results provide important clues for understanding the regulatory mechanisms underlying the formation of CpG methylation-induced G4 structures.

2.
J Clin Biochem Nutr ; 67(3): 232-239, 2020 Nov.
Article in English | MEDLINE | ID: mdl-33293763

ABSTRACT

Non-thermal plasma (NTP) is applicable to living cells and has emerged as a novel technology for cancer therapy. NTP affect cells not only by direct irradiation, but also by an indirect treatment with previously prepared plasma-activated liquid. Histone deacetylase (HDAC) inhibitors have the potential to enhance susceptibility to anticancer drugs and radiation because these reagents decondense the compact chromatin structure by neutralizing the positive charge of the histone tail. The aim of the present study was to demonstrate the advantage of the combined application of plasma-activated acetated Ringer's solution (PAA) and HDAC inhibitors on A549 cancer cells. PAA maintained its ability for at least 1 week stored at any temperature tested. Cell death was enhanced more by combined regimens of PAA and HDAC inhibitors, such as trichostatin A (TSA) and valproic acid (VPA), than by a single PAA treatment and was accompanied by ROS production, DNA breaks, and mitochondria dysfunction through a caspase-independent pathway. These phenomena induced the depletion of ATP and elevations in intracellular calcium concentrations. The sensitivities of HaCaT cells as normal cells to PAA were less than that of A549 cells. These results suggest that HDAC inhibitors synergistically induce the sensitivity of cancer cells to PAA.

3.
Arch Biochem Biophys ; 693: 108565, 2020 10 30.
Article in English | MEDLINE | ID: mdl-32871135

ABSTRACT

Applications of non-thermal plasma (NTP) discharges in medicine, particularly cancer therapy, have increased in recent years. The aim of the present study was to investigate the advantages of the combined application of NTP-irradiated acetated Ringer's solution (PAA) and hyperthermia, a heat treatment at 42 °C, on A549 cancer cell death and elucidate the underlying mechanisms. Cell death was enhanced more by the above combined treatment and was accompanied by increases in intracellular calcium ([Ca2+]i). The activation of transient receptor potential melastatin 2 (TRPM2) may enhance cell death because the addition of TRPM2 inhibitors and knockdown of TRPM2 significantly abrogated the above phenomena. TRPM2 is a temperature-sensitive, Ca2+-permeable, non-elective cation channel and hydrogen peroxide (H2O2) and ADP ribose are its main agonists. PAA functioned as a donor of reactive oxygen species, mainly H2O2, and a treatment with PAA under hyperthermia induced both mitochondrial and nuclear damage with DNA breaks. The activation of poly(ADP-ribose) polymerase-1 as the DNA repair mechanism induced TRPM2 activation because this enzyme accumulates ADP ribose. The sensitivity of fibroblasts as normal cells to PAA was less than that of A549 cells. These results suggest that hyperthermia synergistically induces the sensitivity of cancer cells to PAA.


Subject(s)
Acetates/chemistry , Hyperthermia, Induced , Neoplasms/pathology , Ringer's Solution/pharmacology , A549 Cells , Cell Death/drug effects , Cell Nucleus/drug effects , Humans , Mitochondria/drug effects
4.
Case Rep Gastroenterol ; 7(2): 340-6, 2013.
Article in English | MEDLINE | ID: mdl-24019767

ABSTRACT

A 21-year-old man with a history of sudden rectal hemorrhage was referred to our hospital. Examination disclosed thrombocytopenia and hepatosplenomegaly. A liver biopsy specimen demonstrated Gaucher cells in Glisson's capsule. Additional investigations revealed a low level of leukocyte ß-glucosidase activity and common mutations of the glucocerebrosidase gene, L444P/D409H. We diagnosed the patient with Gaucher disease type 1. He underwent enzyme replacement therapy. Thrombocytopenia and hepatosplenomegaly improved at a rate of approximately 50 and 20%, respectively, within 6 months. This case suggests that we must pay attention to adult Gaucher disease as a differential diagnosis for cryptogenic thrombocytopenia.

5.
Shokuhin Eiseigaku Zasshi ; 54(4): 345-50, 2013.
Article in Japanese | MEDLINE | ID: mdl-24025215

ABSTRACT

In order to ensure compliance of raw bean paste products with the Japanese Food Sanitation Law, we examined the performance characteristics of an analytic procedure based on steam distillation followed by carbonate-pyrazolone assay to determine cyanogenic compounds in raw bean paste. The present method includes a procedure for decomposition cyanogenic glycosides using linamarase due to the possibility that cyanogenic glycoside-hydrolyzing enzymes might be deactivated in raw bean pastes. The performance of the method was evaluated using two types of bean paste spiked with a cyanogenic glycoside (linamarin) corresponding to cyanide ion concentrations of 5 and 10 mg/kg. The trueness of the method was 86-90%, and the repeatability (RSD) was 1.0-2.4%, while the intermediate precision (RSD) was 2.6% to 4.9%. A surveillance of cyanogenic compounds in 28 raw bean pastes manufactured in Japan was then carried out with the validated method. One sample contained 15 mg/kg (as hydrogen cyanide), while the other samples contained less than 5 mg/kg.


Subject(s)
Fabaceae/chemistry , Food Analysis/methods , Food Contamination/analysis , Glycosides/analysis , Hydrolysis , Japan , Reproducibility of Results , beta-Glucosidase
6.
J Med Virol ; 85(7): 1199-205, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23918538

ABSTRACT

Prolactin is not only a pituitary hormone but an immunoregulatory hormone secreted from lymphocytes. Prolactin induction in relation to hepatitis C virus (HCV) infection has not been elucidated. The serum levels of prolactin were examined in 232 HCV-infected subjects positive for anti-HCV antibody and 65 healthy controls negative for it, who were recruited in the cohort study. The prolactin mRNAs were measured in peripheral blood mononuclear cells (PBMCs) of eleven healthy volunteers including five men and six women before and after stimulation by HCV in vitro. The serum level of prolactin and prolactin mRNA in PBMCs were measured by chemiluminescence immunoassay and real-time PCR, respectively. The serum levels of prolactin were significantly higher in the HCV-infected subjects (median: 7.5, IQR: 5.7-10.9 ng/ml) than in the controls (median: 5.6, IQR: 4.4-8.3 ng/ml) (P < 0.01). They were significantly higher in HCV-infected males (median: 8.0, IQR: 5.9-11.8 ng/ml) than in the controls (median: 4.8, IQR: 4.2-5.9 ng/ml) (P < 0.001), however, the difference was not significant between HCV-infected females (median: 7.3, IQR: 5.6-10.5 ng/ml) and the controls (median: 6.4, IQR: 5.3-9.8 ng/ml). The mRNA expression of prolactin was induced in PBMCs of all males, but it was induced in PBMCs of the two of six females examined in vitro. These results suggest that the serum level of prolactin is higher in HCV-infected males than in healthy males, and that HCV infection induces the mRNA expression of prolactin in PBMCs that is more apparent in male than in females.


Subject(s)
Hepatitis C/immunology , Hepatitis C/pathology , Leukocytes, Mononuclear/immunology , Prolactin/blood , RNA, Messenger/blood , Serum/chemistry , Aged , Cohort Studies , Female , Humans , Immunoassay , Male , Middle Aged , Real-Time Polymerase Chain Reaction , Sex Factors
7.
BMC Gastroenterol ; 13: 112, 2013 Jul 10.
Article in English | MEDLINE | ID: mdl-23841691

ABSTRACT

BACKGROUND: Hepatic steatosis is often seen in patients with chronic hepatitis C (CH-C). It is still unclear whether these patients have an impaired mitochondrial ß-oxidation. In this study we assessed mitochondrial ß-oxidation in CH-C patients by investigating ketogenesis during fasting. METHODS: This study consisted of thirty patients with CH-C. Serum levels of insulin and hepatitis C virus (HCV) core protein were measured by chemiluminescence enzyme immunoassay. The subjects were then fasted, and venous blood samples were drawn 12 h and 15 h after the start of fasting. The levels of blood ketone bodies were measured by an enzymatic cycling method. The rate of change in total ketone body concentration was compared with that in eight healthy volunteers. RESULTS: The rate of change in total ketone body concentration between 12 h and 15 h after the start of fasting was significantly lower in CH-C patients than in healthy volunteers (129.9% (8.5-577.3%) vs. 321.6% (139.6-405.4%); P <0.01). The rate of change in total ketone body concentration in patients with a serum level of HCV core protein of 10000 fmol/L or higher was significantly lower than in patients with a level of less than 10000 fmol/L (54.8% (8.5-304.3%) vs. 153.6% (17.1-577.3%); P <0.05). The rate of change in total ketone body concentration in patients with a homeostasis model assessment of insulin resistance (HOMA-IR) of 2.5 or higher was significantly lower than in patients with a HOMA-IR of less than 2.5 (56.7% (8.5-186.7%) vs. 156.4% (33.3-577.3%); P <0.01). CONCLUSIONS: These results suggest that mitochondrial ß-oxidation is impaired, possibly due to HCV infection in patients with CH-C.


Subject(s)
Fatty Acids/blood , Hepatitis C, Chronic/blood , Insulin Resistance , Ketone Bodies/blood , Mitochondria/metabolism , Viral Load , Adult , Aged , Carnitine/analogs & derivatives , Carnitine/blood , Fasting , Fatty Liver/blood , Fatty Liver/virology , Female , Hepatitis C, Chronic/virology , Homeostasis , Humans , Insulin/blood , Male , Middle Aged , Oxidation-Reduction , Viral Core Proteins/blood , Young Adult
8.
Shokuhin Eiseigaku Zasshi ; 52(6): 321-9, 2011.
Article in English | MEDLINE | ID: mdl-22200798

ABSTRACT

2-Alkylcyclobutanones (ACBs) are specific radiolytic products in irradiated lipid-containing food and can be used to detect irradiation of foodstuffs. EN1785, a European Committee Standardization Method, can detect 2-dodecylcyclobutanone (DCB) and 2-tetradecylcyclobutanone (TCB), which are ACBs, using GC/MS, thereby allowing judgement as to whether foodstuffs have been irradiated. In this study, the performance of EN1785 as a qualitative test in a single laboratory was evaluated and its applicability to beef, pork, chicken and salmon was verified. In the performance evaluation test, lipids extracted from unirradiated food using the Soxhlet extraction method were used as negative samples. Further, negative samples, to which DCB and TCB were added at 0.05 µg/g lipid (equivalent to the amount generated in food when irradiated at 0.5 kGy or more), were used as positive samples. For each food type examined, 4 negative and 16 positive samples were analyzed by EN1785 to verify the method's ability to detect irradiation. All of the negative samples were judged negative and all of the positive samples were judged positive. Thus, the method should be able to detect irradiation in beef, pork chicken and salmon irradiated at 0.5 kGy or higher. Next, to confirm that this is the case, the same types of food examined above, both unirradiated and irradiated at doses of 0.5-4 kGy, were analyzed by the method. All of the unirradiated samples were judged negative and all of the irradiated samples were judged positive. In a laboratory different from the one where the aforementioned evaluation was conducted, a performance evaluation test was carried out. Blind coded samples, including unirradiated and irradiated samples, were then analyzed in the laboratory according to EN178S. Ten samples (2 unirradiated and 8 irradiated samples) were analyzed for each type of food and the verified method was found to be 100% accurate. Even after the irradiated foodstuffs had been frozen for 6-9 months, it was still possible to judge whether the foodstuffs had been irradiated or not using the EN1785 method.


Subject(s)
Cyclobutanes/analysis , Fatty Acids/analysis , Food Analysis/methods , Food Irradiation , Food Analysis/standards , Gas Chromatography-Mass Spectrometry
9.
Shokuhin Eiseigaku Zasshi ; 52(6): 370-5, 2011.
Article in English | MEDLINE | ID: mdl-22200805

ABSTRACT

The performance characteristics of an analytical method for cyanogenic compounds were evaluated. Specifically, we tested the trueness, repeatability and intermediate precision of the method using a spectrophotometric-based detection system for 4-pyridinecarboxylic acid and pyrazolone after steam distillation. The pH adjustment of the distillate was revealed to affect the trueness of the measurements. A pH of approximately 6 was found to be optimal. The targeted quantitation limit of the cyanide ion was set to 5 mg/kg. The performance of the method was evaluated using beans spiked with cyanide ion at one to two times the quantitation limit (5-10 mg/kg). The trueness of the method was between 78-90%, and the repeatability and intermediate precision were between RSD 1.2% to 6.0%. A surveillance of cyanogenic compounds in beans retailed in Japan was then carried out. All the results were below the quantitation limit of 5 mg/kg.


Subject(s)
Cyanides/analysis , Fabaceae/chemistry , Food Analysis/methods , Spectrophotometry/methods , Hydrogen-Ion Concentration , Japan , Pyrazolones , Pyridines , Reproducibility of Results , Sensitivity and Specificity
10.
Diabetes ; 60(7): 1926-37, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21617180

ABSTRACT

OBJECTIVE: Regulation of obesity development is an important issue to prevent metabolic syndromes. Gene-disrupted mice of phospholipase Cδ1 (PLCδ1), a key enzyme of phosphoinositide turnover, seemed to show leanness. Here we examined whether and how PLCδ1 is involved in obesity. RESEARCH DESIGN AND METHODS: Weight gain, insulin sensitivity, and metabolic rate in PLCδ1(-/-) mice were compared with PLCδ1(+/-) littermate mice on a high-fat diet. Thermogenic and adipogenetic potentials of PLCδ1(-/-) immortalized brown adipocytes and adipogenesis of PLCδ1-knockdown (KD) 3T3L1 cells, or PLCδ1(-/-) white adipose tissue (WAT) stromal-vascular fraction (SVF) cells, were also investigated. RESULTS: PLCδ1(-/-) mice showed marked decreases in weight gain and mass of epididymal WAT and preserved insulin sensitivity compared with PLCδ1(+/-) mice on a high-fat diet. In addition, PLCδ1(-/-) mice have a higher metabolic rate such as higher oxygen consumption and heat production. When control immortalized brown adipocytes were treated with thermogenic inducers, expression of PLCδ1 was decreased and thermogenic gene uncoupling protein 1 (UCP1) was upregulated to a greater extent in PLCδ1(-/-) immortalized brown adipocytes. In contrast, ectopic expression of PLCδ1 in PLCδ1(-/-) brown adipocytes induced a decrease in UCP expression, indicating that PLCδ1 negatively regulates thermogenesis. Importantly, accumulation of lipid droplets was severely decreased when PLCδ1-KD 3T3L1 cells, or PLCδ1(-/-) WAT SVF cells, were differentiated, whereas differentiation of PLCδ1(-/-) brown preadipocytes was promoted. CONCLUSIONS: PLCδ1 has essential roles in thermogenesis and adipogenesis and thereby contributes to the development of obesity.


Subject(s)
Adipogenesis/physiology , Obesity/prevention & control , Phospholipase C delta/genetics , Thermogenesis/physiology , 3T3-L1 Cells , Adipocytes, Brown/physiology , Adipose Tissue, White/growth & development , Animals , Cell Differentiation/drug effects , Cells, Cultured , Dietary Fats/administration & dosage , Gene Expression Profiling , Insulin , Ion Channels/genetics , Mice , Mice, Nude , Mitochondrial Proteins/genetics , NFATC Transcription Factors/physiology , Phospholipase C delta/deficiency , Protein Kinase C/physiology , Protein Kinase C-epsilon/physiology , Uncoupling Protein 1
11.
Ann Nucl Med ; 25(7): 520-3, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21461597

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.


Subject(s)
Drug Resistance, Viral , Hepatitis C, Chronic/diagnostic imaging , Hepatitis C, Chronic/drug therapy , Interferons/pharmacology , Technetium Tc 99m Aggregated Albumin , Technetium Tc 99m Pentetate , Tomography, Emission-Computed, Single-Photon , Female , Hepatitis C, Chronic/pathology , Humans , Interferons/therapeutic use , Middle Aged , Treatment Outcome
12.
Stem Cells Dev ; 20(9): 1503-10, 2011 Sep.
Article in English | MEDLINE | ID: mdl-21417817

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.


Subject(s)
Bone Marrow Transplantation , Liver Cirrhosis, Alcoholic/therapy , Aged , Antigens, CD/metabolism , Blood Proteins/metabolism , Collagen Type IV/blood , Humans , Infusions, Intravenous , Leukocytes, Mononuclear/metabolism , Liver/metabolism , Liver/pathology , Liver/physiopathology , Liver Cirrhosis, Alcoholic/blood , Liver Cirrhosis, Alcoholic/pathology , Liver Function Tests , Male , Middle Aged , Transplantation, Autologous , Treatment Outcome
13.
Clin J Gastroenterol ; 4(4): 273-277, 2011 Aug.
Article in English | MEDLINE | ID: mdl-26189533

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 3 weeks 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 5 months 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.

14.
Cell Tissue Res ; 343(2): 371-8, 2011 Feb.
Article in English | MEDLINE | ID: mdl-21152936

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.


Subject(s)
Bone Marrow Cells/cytology , Cell Differentiation , Cell Lineage , Epithelial Cells/metabolism , Fibroblast Growth Factor 2/metabolism , Hepatocytes/cytology , Stem Cells/cytology , Animals , Bone Marrow Cells/metabolism , Cell Proliferation , Epithelial Cells/cytology , Fibroblast Growth Factor 2/genetics , Hepatocytes/metabolism , Male , RNA, Messenger/metabolism , Rats , Rats, Sprague-Dawley , Stem Cells/metabolism
15.
J Med Virol ; 82(8): 1364-70, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20572079

ABSTRACT

The aim of the study was to identify a predictive marker for the virological response in hepatitis C virus 1b (HCV-1b)-infected patients treated with pegylated interferon plus ribavirin therapy. A total of 139 patients with chronic hepatitis C who received therapy for 48 weeks were enrolled. The secondary structure of the 120 residues of the amino-terminal HCV-1b non-structural region 3 (NS3) deduced from the amino acid sequence was classified into two major groups: A and B. The association between HCV NS3 protein polymorphism and virological response was analyzed in patients infected with group A (n = 28) and B (n = 40) isolates who had good adherence to both pegylated interferon and ribavirin administration (>95% of the scheduled dosage) for 48 weeks. A sustained virological response (SVR) representing successful HCV eradication occurred in 33 (49%) in the 68 patients. Of the 28 patients infected with the group A isolate, 18 (64%) were SVR, whereas of the 40 patients infected with the group B isolate only 15 (38%) were SVR. The proportion of virological responses differed significantly between the two groups (P < 0.05). These results suggest that polymorphism in the secondary structure of the HCV-1b NS3 amino-terminal region influences the virological response to pegylated interferon plus ribavirin therapy, and that virus grouping based on this polymorphism can contribute to prediction of the outcome of this therapy.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C, Chronic/drug therapy , Hepatitis C, Chronic/virology , Interferon-alpha/therapeutic use , Polyethylene Glycols/therapeutic use , Ribavirin/therapeutic use , Viral Nonstructural Proteins/chemistry , Adult , Aged , Female , Hepacivirus/genetics , Hepacivirus/isolation & purification , Humans , Interferon alpha-2 , Male , Middle Aged , Molecular Sequence Data , Polymorphism, Genetic , Protein Structure, Secondary , RNA, Viral/genetics , Recombinant Proteins , Sequence Analysis, DNA , Treatment Outcome , Viral Load , Viral Nonstructural Proteins/genetics
16.
Metabolism ; 58(8): 1067-75, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19411086

ABSTRACT

Measurement of the serum alanine aminotransferase (ALT) level is used as an initial test for detection of liver diseases, and recent studies have also highlighted its potential value as a measure of overall health and survival as a marker of an increased risk of metabolic disorder. This study was designed to clarify the prevalence of elevated ALT levels in the Japanese population and to assess factors associated with ALT elevation. The subjects were 2165 individuals aged 40 to 85 years who participated in a Japanese community-based study referred to as the Takahata Study. Serum ALT levels and factors associated with ALT elevation were investigated. Among 2087 subjects who were negative for hepatitis B and C, the rates of elevated ALT greater than 30 U/L in men and greater than 25 U/L in women were 217 (22.7%) of 957 and 239 (21.2%) of 1130, respectively. These ALT cutoff levels had a specificity of more than 80% for exclusion of subjects with none or 1 of 3 metabolic risk factors: hypertension, lipid metabolism abnormality, and hyperglycemia. Multivariate analysis revealed 5 factors with a significant association with ALT elevation in men (n = 957): high gamma-glutamyltranspeptidase, low adiponectin, high low-density lipoprotein cholesterol, high body mass index, and high homeostasis model assessment insulin resistance index. Similarly, 4 factors were significantly associated with ALT elevation in women (n = 1130): high gamma-glutamyltranspeptidase, low adiponectin, high body mass index, and high homeostasis model assessment insulin resistance index. These results suggest that elevated ALT levels in the Japanese population older than 40 years have a strong association with metabolic syndrome-related features including obesity and insulin resistance.


Subject(s)
Alanine Transaminase/blood , Insulin Resistance , Metabolic Syndrome/enzymology , Obesity/enzymology , Adult , Aged , Aged, 80 and over , Analysis of Variance , Asian People , Biomarkers/blood , Cross-Sectional Studies , Female , Hepatitis B/complications , Hepatitis B/immunology , Hepatitis C/complications , Hepatitis C/immunology , Humans , Japan , Male , Metabolic Syndrome/complications , Middle Aged , Obesity/complications , Risk Assessment , Risk Factors , Sensitivity and Specificity
18.
Nihon Shokakibyo Gakkai Zasshi ; 106(3): 405-10, 2009 Mar.
Article in Japanese | MEDLINE | ID: mdl-19262055

ABSTRACT

We report a case of chronic hepatitis C complicated with idiopathic thrombocytopenic purpura (ITP), successfully treated with interferon (IFN) beta. A 65-year-old woman was admitted to our hospital for the treatment of chronic hepatitis C with IFN beta. ITP was also diagnosed because of the presence of platelet associated IgG and the findings of bone marrow examination. We started IFN therapy, which resulted in normalization of transaminases, complete HCV eradication, and increased number of platelet.


Subject(s)
Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Interferon-beta/administration & dosage , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/etiology , Aged , Female , Humans , Treatment Outcome
19.
Nihon Shokakibyo Gakkai Zasshi ; 104(10): 1519-25, 2007 Oct.
Article in Japanese | MEDLINE | ID: mdl-17917401

ABSTRACT

This report describes our experience with two cases of pyogenic spondylitis with chronic hepatitis C during combination therapy of interferon alfa and ribavirin. The first patient, a 59-year-old man, was treated conservatively and improved, but the second patient, a 69-year-old woman, was not improved by conservative therapy and reconstructive operation was performed. The combination therapy of interferon alfa and ribavirin has a high risk of severe infectious diseases as side effects. CT scan and MRI are recommended immediately to diagnose pyogenic spondylitis, when patients has pyrexia and lumbago with laboratory data suspected inflammation during interferon therapy.


Subject(s)
Antiviral Agents/adverse effects , Hepatitis C, Chronic/drug therapy , Interferon-alpha/adverse effects , Ribavirin/adverse effects , Spondylitis/etiology , Aged , Antiviral Agents/therapeutic use , Female , Humans , Interferon-alpha/therapeutic use , Male , Middle Aged , Ribavirin/therapeutic use , Spondylitis/drug therapy , Spondylitis/microbiology , Spondylitis/surgery , Staphylococcal Infections , Streptococcal Infections , Suppuration , Treatment Outcome , Viridans Streptococci
20.
Hepatol Res ; 36(2): 130-8, 2006 Oct.
Article in English | MEDLINE | ID: mdl-16920400

ABSTRACT

The asialoglycoprotein receptor (ASGPR) is abundantly expressed on the sinusoidal surfaces of hepatocytes. However, regional expression and clinical significance of the ASGPR in acute hepatic damage is presently unknown. Our aim was to clarify the clinical significance of the regional expression of ASGPR in human livers with acute hepatitis (AH) and fulminant hepatic failure (FHF). Eighteen volunteers, 42 patients with AH and 10 with FHF were studied using a newly developed, conventional (99m)Tc-GSA SPECT analysis. Using Cantlie's line as a guide, ASGPR expression was analyzed separately in the right and left hepatic lobes, as well as in the whole liver, using novel indices (the liver uptake ratio [LUR] and liver uptake density [LUD], which reflect the amount and density of ASGPRs in the liver, respectively). Mean LUR and LUD values for the whole liver and the right and left lobes decreased in accordance with the severity of acute hepatic damage. In the FHF group, the reduction in LUR and LUD values in the right lobes was more significant than in the left lobes. The LUR and LUD values for the whole liver correlated well with hepatic functional reserve and total bilirubin levels. The right LUR and LUD values in particular correlated well with these parameters. A time-course observation of 13 patients with either AH or FHF revealed that the expression of ASGPRs in the right lobe recovered faster than in the left. We first evaluated the regional expression of AGSPRs by (99m)Tc-GSA SPECT analysis in both AH and FHF patients, which is a clinically useful and reliable indicator for assessing the severity of regional hepatic damage and evaluating regional liver regeneration.

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