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2.
World J Gastroenterol ; 22(17): 4403-10, 2016 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-27158210

RESUMO

AIM: To determine the efficacy of Mac-2 binding protein (Mac-2bp) for diagnosis of chronic pancreatitis. METHODS: Fifty-nine healthy volunteers (HV), 162 patients with chronic pancreatitis (CP), and 94 patients with pancreatic ductal adenocarcinoma (PDAC) were enrolled in this study. We measured serum Mac-2bp using our developed enzyme-linked immunosorbent assay kit. Additional biochemical variables were measured using an automated analyzer (including aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, triglyceride, C-reactive protein, and amylase levels) or chemiluminescent enzyme immunoassay (carbohydrate antigen 19-9 and carcinoembryonic antigen). The ability of Mac-2bp to predict CP diagnosis accurately was assessed using receiver operating characteristic (ROC) analyses. RESULTS: Serum Mac-2bp levels were significantly increased in CP patients compared to HV (P < 0.0001) and PDAC patients (P < 0.0001). Area under the ROC curve values of Mac-2bp for the discrimination of CP from HV and PDAC were 0.727 and 0.784, respectively. Multivariate analyses demonstrated that serum Mac-2bp levels were independent determinants for CP diagnosis from HV and PDAC patients. Immunohistological staining showed that Mac-2bp was expressed faintly in the pancreas tissues of both CP and PDAC patients. Serum aspartate aminotransferase, alanine aminotransferase, γ-glutamyltransferase, alkaline phosphatase, and triglyceride levels were significantly higher in patients with CP or PDAC. Serum Mac-2bp levels were highly correlated with protein levels of alanine aminotransferase, γ-glutamyltransferase, and C-reactive protein, but not amylase, suggesting that the damaged liver produces Mac-2bp. CONCLUSION: Measurement of serum Mac-2bp may be a novel and useful biomarker for CP diagnosis as well as liver fibrosis in the general population.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores/sangue , Glicoproteínas de Membrana/sangue , Pancreatite Crônica/diagnóstico , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Proteína C-Reativa/análise , Carcinoma Ductal Pancreático/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Pancreatite Crônica/sangue
3.
J Clin Lab Anal ; 30(6): 1086-1091, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27121214

RESUMO

BACKGROUND: We previously showed that glycated albumin (GA) is a useful glycemic control indicator in patients with neonatal diabetes mellitus (NDM), and that age-adjusted GA (Aa-GA) can reflect more accurately glycemic control status. Here, we investigated whether the age at diagnosis influences Aa-GA at diagnosis of NDM. METHODS: Eight patients with NDM whose GA was measured at diagnosis (age at diagnosis: 39 ± 18 days; GA: 31.3 ± 7.6%; Aa-GA: 47.1 ± 10.3%; plasma glucose: 525 ± 194 mg/dl) were included. Aa-GA was calculated as follows: Aa-GA = GA × 14.0/[1.77 × log-age (days) + 6.65]. Correlations of GA or Aa-GA at diagnosis with its logarithmically transformed age in days (log-age), plasma glucose, and their product were investigated. RESULTS: GA at diagnosis was not significantly correlated with log-age or plasma glucose. On the other hand, Aa-GA at diagnosis was significantly positively correlated with plasma glucose (R = 0.75, P = 0.031) and was more strongly positively correlated with the product of plasma glucose and log-age (R = 0.82, P = 0.012) although it was not correlated with log-age. CONCLUSION: Aa-GA at diagnosis is influenced by both age in days and plasma glucose. This finding is likely to show the aspect that age in days is almost equal to diabetes duration because glycemic control indicators including GA reflect the weighted mean of plasma glucose.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus/sangue , Albumina Sérica/metabolismo , Fatores Etários , Feminino , Humanos , Lactente , Recém-Nascido , Doenças do Recém-Nascido/sangue , Masculino , Estatística como Assunto
4.
Hepatol Res ; 46(3): E118-29, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26041473

RESUMO

AIM: Glycosylation changes induce various types of biological phenomena in human diseases. N-Acetylglucosaminyltransferase V (GnT-V) is one of the most important glycosyltransferases involved in cancer biology. Recently, many researchers have challenged studies of lipid metabolism in cancer. To elucidate the relationships between cancer and lipid metabolism more precisely, we investigated the effects of GnT-V on lipid metabolism. In this study, we investigated the effects of aberrant glycosylation by GnT-V on hepatic triglyceride production. METHODS: We compared lipid metabolism in GnT-V transgenic (Tg) mice with that of wild-type (WT) mice fed with normal chow or a choline-deficient amino acid-defined (CDAA) diet in vivo. HepG2 cells and GnT-V transfectants of Hep3B cells were used in an in vitro study. RESULTS: Serum triglyceride levels and hepatic very low-density lipoprotein (VLDL) secretion in Tg mice were significantly elevated compared with that of WT mice. Hepatic lipogenic genes (Lxrα, Srebp1, Fas and Acc) and VLDL secretion-related gene (Mttp1) were significantly higher in Tg mice. Expression of these genes was also significantly higher in GnT-V transfectants than in mock cells. Knockdown of GnT-V decreased, while both epidermal growth factor and transforming growth factor-ß1 stimulation increased LXRα gene expression in HepG2 cells. Finally, we found that the blockade of VLDL secretion by CDAA diet induced massive hepatic steatosis in Tg mice. CONCLUSION: Our study demonstrates that enhancement of hepatic GnT-V activity accelerates triglyceride synthesis and VLDL secretion. Glycosylation modification by GnT-V regulation could be a novel target for a therapeutic approach to lipid metabolism.

5.
Hepatology ; 62(5): 1433-43, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26199205

RESUMO

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem; thus, discriminating nonalcoholic steatohepatitis (NASH) from NAFLD is of great clinical significance. For the diagnosis of NASH, liver biopsy-proven histological examination is the current gold standard, and noninvasive and reliable biomarkers are greatly needed. Recently, we found that two glycobiomarkers, fucosylated haptoglobin (Fuc-Hpt) and Mac-2 binding protein (Mac2bp), are useful independently for NASH diagnosis. In this study, we confirmed that serum Fuc-Hpt is suitable for the prediction of ballooning hepatocytes and that serum Mac2bp is suitable for the prediction of liver fibrosis severity in 124 biopsy-proven NAFLD patients (training cohort). In addition, we found that the combination of serum Fuc-Hpt and Mac2bp levels was an excellent tool for NASH diagnosis. Using receiver operating characteristic analyses, the area under the receiver operating characteristic curve, sensitivity, and specificity of the combination of these two glycobiomarkers were 0.854, 81.1%, and 79.3%, respectively. We established a prediction model for NASH diagnosis using logistic regression analysis: logit (p)=-2.700+0.00242×Fuc-Hpt+1.225×Mac2bp. To validate the prediction model, another 382 biopsy-proven NAFLD patients were enrolled (validation cohort). In the validation cohort, the area under the receiver operating characteristic curve of this model for NASH diagnosis was 0.844, with 71.4% and 82.3% sensitivity and specificity, respectively. In addition, we investigated the significance of our developed NASH diagnosis model in ultrasound-diagnosed NAFLD subjects who received medical health checkups (n = 803). Our model also could predict NAFLD disease severity in this larger population. CONCLUSION: The combination of serum Fuc-Hpt and Mac2bp can distinguish NASH from NAFLD patients. Our noninvasive model using two serum glycobiomarkers contributes to a novel NASH diagnostic methodology that could replace liver biopsy.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores/sangue , Fucose/metabolismo , Haptoglobinas/análise , Glicoproteínas de Membrana/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Curva ROC
6.
Mol Med Rep ; 11(5): 3573-84, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25572342

RESUMO

N­Acetylglucosaminyltransferase V (GnT­V) catalyzes ß1­6 branching in asparagine­linked oligosaccharides and is one of the most important glycosyltransferases involved in carcinogenesis, cancer metastasis and immunity. To investigate the biological functions of GnT­V, the present study developed GnT­V transgenic (Tg) mice and the role of GnT­V in experimental immune­mediated hepatitis, induced by concanavalin A (ConA), were investigated. It was found that the aberrant expression of GnT­V exacerbated ConA­induced hepatitis in the Tg mice compared with the wild­type (WT) mice. The survival rate of the ConA­induced hepatitis at a high­dose of ConA was significantly lower in the Tg mice. Intravenously injected ConA is known to initially bind predominantly to the mannose gland of the liver sinusoidal endothelial cell (LSEC) surface and to leads to the activation of various immune cells. In the present study, the binding affinity of ConA to the LSECs did not differ between the WT and Tg mice. In addition, T cell receptor stimulation by anti­cluster of differentiation (CD)3/CD28 antibodies produced lower levels of T helper (Th)1 cytokine (interferon­Î³) and higher levels of Th2 cytokine (interleukin­10) in the Tg mouse splenic lymphocytes compared with WT mice. The composition of the hepatic mononuclear cells revealed that CD11b­positive cells were significantly increased in the GnT­V Tg mice. In addition, F4/80­positive cells were significantly increased in the Tg mouse liver and the depletion of macrophages reduced the difference in the severity of ConA­induced hepatitis between the WT and Tg mice. In conclusion, the present findings indicated that the aberrant expression of GnT­V led to an increase in hepatic macrophage infiltration and enhanced ConA­induced hepatitis. Modulation of glycosylation may be a novel therapeutic target for immunity­associated acute hepatitis.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/patologia , N-Acetilglucosaminiltransferases/genética , Animais , Contagem de Células , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Concanavalina A/efeitos adversos , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Galectina 3/genética , Galectina 3/metabolismo , Hepatócitos/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Ativação Linfocitária/imunologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Baço/citologia , Baço/imunologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo
7.
Liver Int ; 35(3): 925-35, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25627311

RESUMO

BACKGROUND & AIMS: Fetuin-A (α2HS-glycoprotein), a liver secretory glycoprotein, is known as a transforming growth factor (TGF)-ß1 signalling inhibitor. Serum fetuin-A concentration is associated with nonalcoholic fatty liver disease (NAFLD) and cardiovascular disease. However, the usefulness of serum fetuin-A as a predictive fibrosis biomarker in NAFLD patients remains unclear. In this study, we investigated the relationship between circulating fetuin-A levels and fibrosis-related markers [platelet count, NAFLD fibrosis score and carotid intima media thickness (IMT)] in subjects with NAFLD. METHODS: A total of 295 subjects (male, 164; female, 131) who received medical health check-ups were enrolled in this study. NAFLD was diagnosed using abdominal ultrasonography. Serum fetuin-A was measured by ELISA. IMT was assessed using a high-resolution ultrasound scanner. Using recombinant human fetuin-A, we investigated the effects of fetuin-A on hepatic stellate cells, which play a pivotal role in the process of hepatic fibrosis. RESULTS: Serum fetuin-A concentration was significantly correlated with platelet count (R = 0.19, P < 0.01), NAFLD fibrosis score (R = -0.25, P < 0.01) and mean IMT (R = -0.22, P < 0.01). Multivariate analyses revealed that the fetuin-A concentration is a significant and independent determinant of platelet count, NAFLD fibrosis score and mean IMT. Recombinant fetuin-A suppressed TGF-ß1 signalling and fibrosis-related gene expression and increased the expression of TGF-ß1 pseudoreceptor bone morphogenic protein and activin membrane-bound inhibitor (BAMBI). CONCLUSIONS: Serum fetuin-A level is associated with liver/vessel fibrosis-related markers in NAFLD patients. Circulating fetuin-A could be a useful serum biomarker for predicting liver and vascular fibrosis progression in NAFLD patients.


Assuntos
Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/sangue , alfa-2-Glicoproteína-HS/metabolismo , Idoso , Biomarcadores/sangue , Espessura Intima-Media Carotídea , Linhagem Celular , Feminino , Fibrose , Células Estreladas do Fígado/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Contagem de Plaquetas , Fator de Crescimento Transformador beta1
8.
Proteomics Clin Appl ; 7(9-10): 648-56, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23775887

RESUMO

PURPOSE: Mac-2 binding protein (Mac-2 bp) is one of the major fucosylated glycoproteins, which we identified with glycol-proteomic analyses. We previously reported that fucosylated glycoproteins are secreted into bile, but scarcely secreted into sera in normal liver and hypothesized that the fucosylation-based sorting machinery would be disrupted in ballooning hepatocytes due to the loss of cellular polarity. In the present study, we investigated the availability of Mac-2 bp for differential diagnosis of nonalcoholic steatohepatitis (NASH) from nonalcoholic fatty liver disease (NAFLD) as a biomarker. EXPERIMENTAL DESIGN: Serum Mac-2 bp levels were determined with our developed ELISA kit. Our cohort of 127 patients with NAFLD had liver biopsy to make a histological diagnosis of NASH and simple fatty liver. RESULTS: Mac-2 bp levels were significantly elevated in NASH patients compared with non-NASH (simple steatosis) patients (2.132 ± 1.237 vs. 1.103 ± 0.500 µg/mL, p < 0.01). The area under the receiver-operating characteristic curve for predicting NASH by Mac-2 bp was 0.816. Moreover, multivariate logistic regression analyses showed Mac-2 bp levels could predict the fibrosis stage and the presence of ballooning hepatocytes in NAFLD patients. CONCLUSIONS AND CLINICAL RELEVANCE: These results support the potential usefulness of measuring Mac-2 bp levels in clinical practice as a biomarker for NASH.


Assuntos
Antígenos de Neoplasias/sangue , Glicoproteínas de Membrana/sangue , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Antígenos de Neoplasias/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Estudos de Casos e Controles , Linhagem Celular , Feminino , Fucose/metabolismo , Humanos , Masculino , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Prognóstico
9.
PLoS One ; 8(6): e66328, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23805214

RESUMO

UNLABELLED: Nonalcoholic fatty liver disease (NAFLD) is a growing medical problem around the world. NAFLD patients with nonalcoholic steatohepatitis (NASH) can develop cirrhosis and hepatocellular carcinoma. The ability to distinguish NASH from simple steatosis would be of great clinical significance. Ballooning hepatocytes are characteristic of typical pathological NASH; here, the polarized secretion of proteins is disrupted due to destruction of the cytoskeleton. We previously reported that fucosylated glycoproteins are secreted into bile, but not into sera in normal liver. Therefore, we hypothesized that the fucosylation-based sorting machinery would be disrupted in ballooning hepatocytes, and serum fucosylated glycoproteins would increase in NASH patients. To confirm our hypothesis, we evaluated serum fucosylated haptoglobin (Fuc-Hpt) levels in biopsy-proven NAFLD patients (n = 126) using a lectin-antibody ELISA kit. Fuc-Hpt levels were significantly increased in NASH patients compared with non-NASH (NAFLD patients without NASH) patients. Interestingly, Fuc-Hpt levels showed a significant stepwise increase with increasing hepatocyte ballooning scores. Multiple logistic regression analysis showed that Fuc-Hpt levels were independent and significant determinants of the presence of ballooning hepatocytes. Moreover, Fuc-Hpt levels were useful in monitoring liver fibrosis staging. Next, to investigate the significance of serum Fuc-Hpt in a larger population, we measured Fuc-Hpt levels in ultrasound-diagnosed NAFLD subjects (n = 870) who received a medical health checkup. To evaluate NAFLD disease severity, we used the FIB-4 index (based on age, serum AST and ALT levels, and platelet counts). Fuc-Hpt levels increased stepwise with increasing FIB-4 index. CONCLUSION: Measurement of serum Fuc-Hpt levels can distinguish NASH from non-NASH patients, and predict the presence of ballooning hepatocytes in NAFLD patients with sufficient accuracy. These results support the potential usefulness of measuring Fuc-Hpt levels in clinical practice.


Assuntos
Haptoglobinas/metabolismo , Hepatócitos/metabolismo , Hepatopatia Gordurosa não Alcoólica , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Feminino , Hepatócitos/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/patologia
10.
Pediatr Infect Dis J ; 28(2): 166-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19106775

RESUMO

We report the case of a male infant born to a mother diagnosed as having measles before delivery. Although he was given standard immunoglobulin soon after delivery, he developed congenital measles. The diagnosis was confirmed by serology and PCR assay from the infant's pharyngeal secretions.


Assuntos
Transmissão Vertical de Doença Infecciosa , Sarampo/congênito , Sarampo/transmissão , Feminino , Humanos , Recém-Nascido , Masculino , Gravidez , Adulto Jovem
12.
J Org Chem ; 69(25): 8938-41, 2004 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-15575778

RESUMO

The reaction of lithium alkyneselenolate with alpha,beta-unsaturated ketone and then alkyl or acyl halide afforded 3-acyl-1-alkyl-2-alkylseleno-1-cyclobutene. The structure of the cyclobutene was elucidated by IR, MS, (1)H, (13)C, and (77)Se NMR, COSY, HMQC, and HMBC data and X-ray analysis.

13.
Am J Perinatol ; 19(5): 267-72, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12152145

RESUMO

We report a case complicated by oligohydramnios, pulmonary hypoplasia, bilateral renal dysplasia, and cystic lesion of the bladder. He was clinically compatible with Potter sequence. Congenital cystic bladder is the rarest form of the bladder. We can find no report of Potter sequence complicated by cystic lesion of the bladder. This lesion was similar to multilocular bladder. The diagnosis was confirmed it by autopsy, magnetic resonance imaging, and urography after his death.


Assuntos
Anormalidades Múltiplas/diagnóstico , Doença da Membrana Hialina/diagnóstico , Rim Displásico Multicístico/diagnóstico , Bexiga Urinária/anormalidades , Anormalidades Múltiplas/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Adulto , Autopsia , Evolução Fatal , Feminino , Retardo do Crescimento Fetal , Humanos , Doença da Membrana Hialina/complicações , Doença da Membrana Hialina/diagnóstico por imagem , Recém-Nascido , Imagem por Ressonância Magnética , Masculino , Rim Displásico Multicístico/complicações , Rim Displásico Multicístico/patologia , Oligo-Hidrâmnio , Gravidez , Bexiga Urinária/patologia , Urografia
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