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1.
BMC Gastroenterol ; 21(1): 321, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372774

RESUMO

BACKGROUND: Hepatic steatosis has a pivotal role in the development of chronic liver diseases, even in alcohol-related liver disease. Alcoholic fatty liver disease is an important phenotype among alcohol-related liver diseases. While metabolic syndrome is a dominant risk factor of incident nonalcoholic fatty liver disease, the role of metabolic syndrome in alcoholic fatty liver disease has not been clarified yet. METHODS: A retrospective cohort study was performed at a health check-up center in Japan. Subjects consisted of male participants without fatty liver who consumed ethanol of 420 g/week or higher. Adjusted hazard ratios and 95% confidence intervals at the baseline examinations for incident alcoholic fatty liver disease were estimated using Cox model. RESULTS: A total of 640 participants were included in this study. During 3.91 years (IQR 1.63-7.09) of follow-up, 168 new cases of alcoholic fatty liver disease developed (49.1 cases per 1000 persons per year). After adjustment for age, smoking status, alcohol consumption, the hazard ratio for a 1 kg/m2 increase in body mass index was 1.2 (1.12-1.28). The hazard ratio of subjects with high triglyceride and low high-density lipoprotein-cholesterol levels were 1.56 (1.12-2.18) and 1.52 (1.03-2.25), respectively. CONCLUSIONS: Obesity, high triglyceridemia, and low high-density lipoprotein-cholesterolemia are independent risk factors of alcoholic fatty liver disease in Japanese men who consumed alcohol habitually. In people with these risks, triglyceride lowering and high-density lipoprotein-cholesterol raising by improving insulin resistance and weight maintenance in addition to abstinence from alcohol would be effective in preventing the development of alcoholic fatty liver disease.


Assuntos
Fígado Gorduroso Alcoólico , Síndrome Metabólica , Hepatopatia Gordurosa não Alcoólica , Fígado Gorduroso Alcoólico/epidemiologia , Humanos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Estudos Retrospectivos , Fatores de Risco
2.
PLoS One ; 16(6): e0252420, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34081716

RESUMO

BACKGROUND/AIM: Patients with attention-deficit hyperactivity disorder (ADHD) manifest symptoms of hyperactivity, impulsivity, and/or inattention. ADHD medications available in Japan are limited compared with those in Western countries. Prescribing status has not been sufficiently evaluated in clinical settings in Japan. This study investigated the current use of ADHD medications and characteristics of patients who received multiple ADHD medications in a clinical setting in Japan. METHODS: Study participants were those who visited the Department of Child and Adolescent Psychiatry, Kohnodai Hospital between April 2015 and March 2020. We investigated patients who received osmotic-controlled release oral delivery system methylphenidate, atomoxetine, or guanfacine. A retrospective case-control design was used to evaluate the characteristics of patients who received multiple ADHD medications. Patients who were given three ADHD medications were defined as the case group. Randomly sampled sex- and age-matched patients diagnosed with ADHD were defined as the control group. We compared data for child-to-parent violence, antisocial behavior, suicide attempt or self-harm, abuse history, refusal to attend school, and two psychological rating scales (the ADHD-Rating Scale and Tokyo Autistic Behavior Scale). RESULTS: Among the 878 patients who were prescribed any ADHD medications, 43 (4.9%) received three ADHD medications. Logistic regression revealed that children with severe ADHD symptoms, autistic characteristics, or tendency of child-to-parent violence were more likely to have been prescribed three medications during their treatment. CONCLUSIONS: Our findings suggest the approach to prevent the use of multiple ADHD medications. A prospective study to investigate the causality between prescribing status and clinical characteristics is warranted.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/metabolismo , Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Criança , Feminino , Guanfacina/uso terapêutico , Humanos , Japão , Modelos Logísticos , Masculino , Metilfenidato/uso terapêutico , Pacientes Ambulatoriais , Estudos Prospectivos , Estudos Retrospectivos
3.
Glob Health Med ; 3(2): 119-121, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33937577

RESUMO

COVID-19 causes very serious issues all over the world. In Japan, the number of new infections in Tokyo exceeded 2,000 for the first time on 7 January 2021, and the situation is becoming increasingly serious. Japan is in the midst of its third big outbreak. Japanese society will face several challenges regarding children's mental health during the COVID-19 pandemic. In order to develop healthy minds in children, it is important to view the changes in children's minds in a positive light and promote their healthy emotional development while correctly fearing COVID-19. This sense of social stagnation and uncertainty is likely to increase feelings of insecurity and isolation among children. It is also important to prevent the repetition of child abuse in the home due to parental unemployment, alcohol problems, and reduced contact with non-family members in stay home and the recession as a result of COVID-19. During the pandemic, adults should be sensitive to the unusual behavior of children. We propose six suggestions of care for children during the COVID-19 pandemic.

4.
Front Immunol ; 12: 648754, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790913

RESUMO

Background and Aims: Emerging evidence has revealed that innate lymphoid cells (ILCs) play a key role in regulating metabolic disorders. Here, we investigated the role of group 3 ILCs (ILC3s) in the modulation of Non-alcoholic fatty liver disease (NAFLD). Methods: RORγ gfp/gfp (RORgt KI/KI) and Rag2-/- mice with the administration of A213, RORgt antagonist, fed with a high-fat-diet (HFD) for 12 weeks, were used. We performed flow cytometry, real time PCR, and lipidomics analysis of serum and liver, and used RAW264.7 cells and murine primary hepatocytes in vitro. Results: HFD increased ILC3s and M1 macrophages in the liver, and RORgt KI/KI mice deficient in ILC3 showed significant fatty liver, liver fibrosis and significantly increased palmitic acid levels in serum and liver. In addition, administration of A213 to Rag2-/- mice caused significant fatty liver, liver fibrosis, and a significant increase in serum and liver palmitate concentrations, as in RORgt KI/KI mice. Addition of palmitc acid stimulated IL-23 production in cell experiments using RAW264.7. IL-22 produced by ILC3s inhibited the palmitate-induced apoptosis of primary hepatocytes. Conclusions: HFD stimulates IL-23 production by M1 macrophages, thus promoting ILC3 proliferation, whereas IL-22 secreted by ILC3s contributes to the upregulation of hepatic lipid metabolism and has anti-apoptosis activity.


Assuntos
Fígado Gorduroso/imunologia , Imunidade Inata/imunologia , Fígado/imunologia , Linfócitos/imunologia , Macrófagos/imunologia , Animais , Apoptose/imunologia , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Hepatócitos/citologia , Hepatócitos/imunologia , Fígado/metabolismo , Fígado/patologia , Linfócitos/metabolismo , Macrófagos/classificação , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Ácido Palmítico/sangue , Ácido Palmítico/imunologia , Ácido Palmítico/metabolismo , Substâncias Protetoras/metabolismo , Células RAW 264.7
5.
J Diabetes Investig ; 12(7): 1202-1211, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33145975

RESUMO

AIMS/INTRODUCTION: Body fluid volume imbalance is common in patients with kidney failure, and is associated with all-cause mortality. This study aimed to investigate the association between fluid volume imbalance and albuminuria in patients with type 2 diabetes mellitus without kidney failure. MATERIALS AND METHODS: Using data from one cohort study, a baseline cross-sectional study of 432 participants and a longitudinal cohort study of 368 participants who could follow up was carried out. Body fluid imbalance was determined by measuring the extracellular water (ECW)-to-intracellular water (ICW) ratio (ECW/ICW) using bioelectrical impedance analysis. A change in the urinary albumin-to-creatinine ratio (ACR) was defined as the ratio of urinary ACR at follow up to that at baseline. The ECW/ICW ratio was compared with the level of albuminuria. RESULTS: In this cross-sectional study, the ECW/ICW ratio increased with the level of albuminuria. There was an association between the ECW/ICW ratio and logarithms of urinary ACR after adjusting for covariates (ß = 0.205, P < 0.001). Furthermore, the ECW/ICW ratio was associated with a change in the urinary ACR after adjusting for covariates (ß = 0.176, P = 0.004) in this longitudinal study. According to the receiver operating characteristic curve, the optimal cut-off point of the ECW/ICW ratio for incident macroalbuminuria, defined as ACR >300 mg/gCr, was 0.648 (area under the curve 0.78, 95% confidence interval 0.58-0.90). CONCLUSIONS: The ECW/ICW ratio is independently associated with the level of albuminuria in patients with type 2 diabetes mellitus without kidney failure. This reinforces the importance of monitoring fluid balance in patients with type 2 diabetes mellitus.

6.
BMC Proc ; 14(Suppl 11): 11, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774453

RESUMO

Background and purpose: Mental health has emerged as an important public health concern in recent years. With a high proportion of children and adolescents affected by mental disorders, it is important to ensure that they are provided with proper care and treatment. With the goal of sharing the activities and good practices on child and adolescent mental health promotion, care, and treatment in Japan and the Philippines, the National Center for Global Health and Medicine conducted a training program on the promotion of mental health focused on treatment and care in Japan and the Philippines in September and November 2019. Key highlights: The training program comprised of a series of lectures, site visits, and round table discussions in Japan and the Philippines. The lectures and site visits focused on the current situation of child and adolescent psychiatry, diagnosis of childhood mental disorders, abuse, health financing for mental disorders, pharmacotherapy, psychotherapy, and disaster child psychiatry in both countries. Round table discussions provided an opportunity to explore the similarities and differences between the two countries in terms of the themes discussed during the lectures.The training program identified the need to collaborate with other professionals to improve the diagnosis of mental disorders in children and adolescents and to increase the workforce capable of addressing mental health issues among children and adolescents. It also emphasized the importance of cooperation between government efforts during and after disasters to ensure that affected children and their families are provided with the care and support that they need.

7.
Am J Physiol Gastrointest Liver Physiol ; 318(6): G989-G999, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32363890

RESUMO

Nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. However, NAFLD patients generally do not respond to treatment with testosterone alone. We investigated the innate immune mechanisms underlying the effects of treatment with testosterone alone, estrogen alone, or combined testosterone and estrogen on high-fat diet (HFD)-induced NAFLD due to testosterone deficiency. Orchiectomized (OCX) male Rag2-/- mice were used as a model of testosterone deficiency. To assess NAFLD severity, NAFLD activity score (NAS) is adopted. Moreover, immunological change was analyzed by multicolor flow cytometry. Treatment with both testosterone and estrogen significantly decreased body weight to that of the sham mice/normal diet (ND). NAS and liver fibrosis in OCX-HFD mice were significantly deteriorated, and treatment with testosterone and estrogen improved same as sham-ND mice. HFD increased the ratio of both type 2 and 3 innate lymphoid cells (ILC2s and ILC3s) to CD45-positive cells in the liver. Treatment with testosterone alone decreased the ratio of ILC2 to CD45 but not the ILC3-to-CD45 ratio. Addition of estrogen to the treatment reduced the ratios of ILC2-to-CD45 and ILC3-to-CD45 to the same level observed in sham-HFD mice. Moreover, OCX-HFD mice had a decreased proportion of M2 macrophages compared with sham-ND mice. Treatment with testosterone alone did not restore the proportion of M2 macrophages; however, combination treatment with both estrogen and testosterone increased that to the same level as that in sham-HFD mice. Treatment with both testosterone and estrogen improves liver fibrosis and decreases ILC3 and increases M2 macrophage abundance in the liver.NEW & NOTEWORTHY The progression of nonalcoholic fatty liver disease (NAFLD) is associated with testosterone deficiency. NAFLD patients generally do not respond to treatment with testosterone alone. In animal studies, treatment with testosterone and estrogen reduced the ratios of ILC2:CD45 and ILC3:CD45 and increased M2 macrophages in liver. Our study suggests, based on our immunological data, that a combination of estrogen and testosterone may be clinically relevant for the treatment of NAFLD in patients with male menopause.


Assuntos
Estradiol/farmacologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Testosterona/farmacologia , Aminoácidos , Animais , Carcinoma Hepatocelular , Linhagem Celular Tumoral , Cromo , Colágeno Tipo I/genética , Colágeno Tipo I/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação para Baixo , Estradiol/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Insulina , Cirrose Hepática , Neoplasias Hepáticas , Masculino , Camundongos , Camundongos Knockout , Ácidos Nicotínicos , Hepatopatia Gordurosa não Alcoólica/patologia , Orquiectomia , Células RAW 264.7 , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores CCR2/genética , Receptores CCR2/metabolismo , Testosterona/administração & dosagem , Testosterona/deficiência , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
8.
Breast Cancer ; 27(4): 706-715, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32133606

RESUMO

BACKGROUND: Eribulin, a nontaxane synthetic inhibitor of microtubule dynamics, is widely used to manage locally advanced or metastatic breast cancer (MBC). Eribulin has demonstrated immunomodulatory activity on the tumour microenvironment. Baseline neutrophil-to-lymphocyte ratio (NLR), a marker of immune status, may predict progression-free survival in eribulin treatment. This post hoc analysis assessed predictors for overall survival (OS). METHODS: The phase 3 open-label study (EMBRACE) of eribulin versus treatment of physician's choice (TPC) in patients with MBC provided source data. Baseline absolute lymphocyte counts (ALCs) and NLR were evaluable in 751 and 713 patients, respectively. RESULTS: Eribulin prolonged OS versus TPC in patients with baseline ALC ≥ 1500/µl (hazard ratio [HR] 0.586; 95% confidence interval [CI] 0.437-0.784; P < 0.001). There was no significant difference by treatment for ALC < 1500/µl (HR 1.002; 95% CI 0.800-1.253; P = 0.989). Univariate and multivariate analyses were performed and identified baseline ALC as a potential predictor of OS in eribulin-treated patients. Interaction analysis of OS supported 1500/µl as a potentially differential cutoff value. NLR at a cutoff value of 3 was associated with prolonged OS (eribulin group). However, similar results were also observed in the TPC group, without apparent interaction effect, suggesting that NLR may be a general prognostic marker rather than a specific predictor of OS for eribulin. DISCUSSION: This hypothesis-generating study speculates that baseline ALC may be an independent predictor for longer OS in eribulin-treated MBC patients and could be clinically impactful because it can be evaluated without the need for additional invasive procedures. TRIAL REGISTRATION: www.ClinicalTrials.gov code: NCT00388726.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Furanos/administração & dosagem , Cetonas/administração & dosagem , Linfócitos/imunologia , Idoso , Neoplasias da Mama/sangue , Neoplasias da Mama/imunologia , Neoplasias da Mama/mortalidade , Esquema de Medicação , Feminino , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Contagem de Linfócitos , Pessoa de Meia-Idade , Neutrófilos/imunologia , Prognóstico , Intervalo Livre de Progressão , Microambiente Tumoral
9.
ACS Omega ; 3(11): 15267-15271, 2018 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-30556001

RESUMO

Single-chamber microbial fuel cells (MFCs) were constructed using rice bran (carbon source) and pond bottom mud (microbial source). The total electric charge obtained in the MFC combining rice bran with pond bottom mud was four times higher than that in MFC using only rice bran. Phylogenetic analyses revealed dominant growth of fermentative bacteria such as Bacteroides and Clostridium species, and exoelectrogenic Geobacter species in the anode biofilms, suggesting that mutualism of these bacteria is a key factor for effective electricity generation in the MFC. Furthermore, rice bran, consisting of persistent polysaccharide, was pretreated by the hydrodynamic cavitation system to improve the digestibility and enhance the efficiency in MFC, resulting in 26% increase in the total production of electricity.

10.
J Chromatogr A ; 1439: 54-64, 2016 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-26585203

RESUMO

Detailed lipidomics experiments were performed on the extracts of cured tobacco leaf and of cigarette smoke condensate (CSC) using high-resolution liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (LC-Q-TOF MS). Following automated solid-phase extraction (SPE) fractionation of the lipid extracts, over 350 lipids could be annotated. From a large-scale study on 22 different leaf samples, it was determined that differentiation based on curing type was possible for both the tobacco leaf and the CSC extracts. Lipids responsible for the classification were identified and the findings were correlated to proteomics data acquired from the same tobacco leaf samples. Prediction models were constructed based on the lipid profiles observed in the 22 leaf samples and successfully allowed for curing type classification of new tobacco leaves. A comparison of the leaf and CSC data provided insight into the lipidome changes that occur during the smoking process. It was determined that lipids which survive the smoking process retain the same curing type trends in both the tobacco leaf and CSC data.


Assuntos
Lipídeos/análise , Fumaça/análise , Tabaco/química , Cromatografia Líquida , Espectrometria de Massas , Folhas de Planta/química , Proteoma/análise , Fumar , Extração em Fase Sólida , Produtos do Tabaco
11.
J Chromatogr A ; 1365: 191-203, 2014 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-25260341

RESUMO

Aroma characterization of whole cigarette smoke samples using sensory panels or electronic nose (E-nose) devices is difficult due to the masking effect of major constituents and solvent used for the extraction step. On the other hand, GC in combination with olfactometry detection does not allow to study the delicate balance and synergetic effect of aroma solutes. To overcome these limitations a new instrumental set-up consisting of heart-cutting gas chromatography using a capillary flow technology based Deans switch and low thermal mass GC in combination with an electronic nose device is presented as an alternative to GC-olfactometry. This new hyphenated GC-E-nose configuration is used for the characterization of cigarette smoke aroma. The system allows the transfer, combination or omission of selected GC fractions before injection in the E-nose. Principal component analysis (PCA) and discriminant factor analysis (DFA) allowed clear visualizing of the differences among cigarette brands and classifying them independently of their nicotine content. Omission and perceptual interaction tests could also be carried out using this configuration. The results are promising and suggest that the GC-E-nose hyphenation is a good approach to measure the contribution level of individual compounds to the whole cigarette smoke.


Assuntos
Cromatografia Gasosa/métodos , Nariz Eletrônico , Odorantes/análise , Fumaça/análise , Tabaco/química , Cromatografia Gasosa/instrumentação , Análise Discriminante , Folhas de Planta/química , Análise de Componente Principal , Olfato , Produtos do Tabaco
12.
J Chromatogr A ; 1358: 240-51, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25087743

RESUMO

A method is developed for identification of sulfur compounds in tobacco smoke extract. The method is based on large volume injection (LVI) of 10µL of tobacco smoke extract followed by selectable one-dimensional ((1)D) or two-dimensional ((2)D) gas chromatography (GC) coupled to a hybrid quadrupole time-of-flight mass spectrometer (Q-TOF-MS) using electron ionization (EI) and positive chemical ionization (PCI), with parallel sulfur chemiluminescence detection (SCD). In order to identify each individual sulfur compound, sequential heart-cuts of 28 sulfur fractions from (1)D GC to (2)D GC were performed with the three MS detection modes (SCD/EI-TOF-MS, SCD/PCI-TOF-MS, and SCD/PCI-Q-TOF-MS). Thirty sulfur compounds were positively identified by MS library search, linear retention indices (LRI), molecular mass determination using PCI accurate mass spectra, formula calculation using EI and PCI accurate mass spectra, and structure elucidation using collision activated dissociation (CAD) of the protonated molecule. Additionally, 11 molecular formulas were obtained for unknown sulfur compounds. The determined values of the identified and unknown sulfur compounds were in the range of 10-740ngmg total particulate matter (TPM) (RSD: 1.2-12%, n=3).


Assuntos
Fumaça/análise , Compostos de Enxofre/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Medições Luminescentes , Peso Molecular , Compostos de Enxofre/química , Espectrometria de Massas em Tandem/métodos , Tabaco/química
13.
Biochem Biophys Res Commun ; 408(2): 322-8, 2011 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-21513698

RESUMO

Par1b/MARK2 is a serine/threonine kinase that plays key roles in the development of cell polarity, but its precise mechanism of action remains unknown. Here we report that GEF-H1, a guanine nucleotide exchange factor for Rho-family small GTPases, is a novel substrate for Par1b. GEF-H1 directly associates with microtubules via its N-terminal C1 domain, which is known to regulate the activity of GEF-H1. Ectopically expressed GEF-H1 markedly promotes stabilization of microtubules, resulting in acetylation of microtubules. We find that Par1b phosphorylates GEF-H1 at three serine residues conserved in vertebrates and releases GEF-H1 from microtubules, which abrogates stabilization and acetylation of microtubules induced by GEF-H1 overexpression. The alanine mutant for the three phosphorylation sites (3SA) of GEF-H1 strongly induces stabilization and acetylation of microtubules, which was resistant to Par1b. Time-lapse imaging analyses reveal that GFP-fused GEF-H1 dynamically moved on microtubules from one protrusion to another, whereas the 3SA mutant was static. These data suggest that Par1b-phosphorylation regulates turnover of GEF-H1 localization by regulating its interaction with microtubules, which may contribute to cell polarization.


Assuntos
Polaridade Celular , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Microtúbulos/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Acetilação , Sequência de Aminoácidos , Animais , Células COS , Chlorocebus aethiops , Cães , Fatores de Troca do Nucleotídeo Guanina/genética , Células HeLa , Humanos , Dados de Sequência Molecular , Fosforilação , Fatores de Troca de Nucleotídeo Guanina Rho , Tubulina (Proteína)/metabolismo
14.
Sci Signal ; 4(170): ra26, 2011 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-21521879

RESUMO

Semaphorin3A (Sema3A) is a repulsive guidance molecule for axons, which acts by inducing growth cone collapse through phosphorylation of CRMP2 (collapsin response mediator protein 2). Here, we show a role for CRMP2 oxidation and thioredoxin (TRX) in the regulation of CRMP2 phosphorylation and growth cone collapse. Sema3A stimulation generated hydrogen peroxide (H2O2) through MICAL (molecule interacting with CasL) and oxidized CRMP2, enabling it to form a disulfide-linked homodimer through cysteine-504. Oxidized CRMP2 then formed a transient disulfide-linked complex with TRX, which stimulated CRMP2 phosphorylation by glycogen synthase kinase-3, leading to growth cone collapse. We also reconstituted oxidation-dependent phosphorylation of CRMP2 in vitro, using a limited set of purified proteins. Our results not only clarify the importance of H2O2 and CRMP2 oxidation in Sema3A-induced growth cone collapse but also indicate an unappreciated role for TRX in linking CRMP2 oxidation to phosphorylation.


Assuntos
Cones de Crescimento/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Tiorredoxinas/metabolismo , Animais , Sequência de Bases , Células COS , Embrião de Galinha , Chlorocebus aethiops , Feminino , Gânglios Espinais/embriologia , Gânglios Espinais/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Peróxido de Hidrogênio/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Camundongos , Proteínas dos Microfilamentos , Proteínas Associadas aos Microtúbulos/antagonistas & inibidores , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Oxigenases de Função Mista/antagonistas & inibidores , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Células NIH 3T3 , Proteínas do Tecido Nervoso/genética , Oxirredução , Fosforilação , Gravidez , RNA Interferente Pequeno/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Semaforina-3A/metabolismo , Transdução de Sinais , Tiorredoxinas/antagonistas & inibidores , Tiorredoxinas/genética
15.
Jpn J Infect Dis ; 63(6): 447-8, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21099099

RESUMO

Human ascariasis is caused by infection with the common roundworm Ascaris lumbricoides, although the pig roundworm Ascaris suum has also been reported to infect humans and develop into the adult stage. To elucidate whether pig-derived Ascaris infects humans in Japan, 9 Ascaris isolates obtained from Japanese patients and a further 9 Ascaris isolates of pig origin were analyzed to determine their internal transcribed spacer-1 sequences. Six of the 9 clinical isolates showed the Ascaris genotype which predominantly infects humans in endemic countries, while the other 3 clinical isolates and 9 pig-derived isolates showed the genotype predominant in pigs worldwide. These results suggest that at least some cases of human ascariasis in Japan are a result of infection with pig-derived Ascaris.


Assuntos
Ascaríase/transmissão , Ascaris suum/isolamento & purificação , Doenças dos Suínos , Zoonoses , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Ascaríase/parasitologia , Ascaríase/veterinária , Ascaris suum/classificação , Ascaris suum/genética , DNA de Helmintos/análise , DNA de Helmintos/genética , DNA Espaçador Ribossômico/análise , DNA Espaçador Ribossômico/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Humanos , Japão , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Análise de Sequência de DNA , Suínos , Doenças dos Suínos/parasitologia , Doenças dos Suínos/transmissão , Adulto Jovem , Zoonoses/parasitologia , Zoonoses/transmissão
16.
Mol Cell Biol ; 30(9): 2206-19, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20194617

RESUMO

Here we report that Par1b/MARK2 regulates axon formation via phosphorylation of a kinesin superfamily protein GAKIN/KIF13B. Accumulating evidence indicated the importance of the evolutionarily conserved kinase Par1b in the regulation of cell polarity. Using hippocampal neurons in culture, it has been shown that Par1b regulates axon specification, but the underlying mechanism remains uncharacterized. We identify GAKIN/KIF13B as a novel Par1b-binding protein and reveal that GAKIN/KIF13B is a physiological substrate for Par1b, and the phosphorylation sites are conserved from Drosophila. In hippocampal neurons, GAKIN/KIF13B accumulates at the distal part of the microtubules in the tips of axons, but not of dendrites. Overexpression of GAKIN/KIF13B by itself can induce the formation of extra axons, which is inhibited by the coexpression of Par1b in a manner dependent on its kinase activity. In contrast, small interfering RNA (siRNA)-mediated knockdown of GAKIN/KIF13B severely retards neurite extension and promotes the axonless phenotype. The extra axon phenotype caused by Par1b siRNA is suppressed by cointroduction of GAKIN/KIF13B siRNA, thus placing the GAKIN/KIF13B function downstream of Par1b. We also find that GAKIN/KIF13B acts downstream of the phosphatidylinositol 3-kinase (PI3K) signaling via Par1b phosphorylation. These results reveal that GAKIN/KIF13B is a key intermediate linking Par1b to the regulation of axon formation.


Assuntos
Axônios/metabolismo , Cinesina/metabolismo , Proteínas Motores Moleculares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas 14-3-3/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Humanos , Cinesina/química , Modelos Biológicos , Dados de Sequência Molecular , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Ligação Proteica , Transporte Proteico , Ratos
17.
J Neurosci ; 27(48): 13098-107, 2007 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-18045904

RESUMO

Neurons are highly polarized cells that possess two morphologically and functionally different types of protrusions, axons and dendrites, that function in the transmission and reception of neural signals, respectively. A great deal of attention has been paid to the specification and guidance of axons, but the mechanism of dendrite development remains mostly unknown. We report here that a polarity-regulating kinase, partitioning-defective 1 (Par1b)/microtubule affinity-regulating kinase 2 (MARK2), specifically regulates development of dendrites in hippocampal neurons. Ectopic expression of Par1b/MARK2 shortens the length and decreases branching of dendrites without significant effects on axons. Knockdown of endogenous Par1b/MARK2 by RNA interference stimulates dendrite development. Wnt stimulation and Dishevelled expression, both of which are known to induce dendrite development, induced recruitment of Par1b/MARK2 to the membrane fraction. Expression of a Par1b/MARK2 mutant, that contains a myristoylation signal and accumulates exclusively in membranes, does not affect dendrite development. In addition, Par1b/MARK2 efficiently phosphorylated MAP2, which is localized mainly in dendrites. These results indicate that Par1b/MARK2 negatively regulates dendrite development through phosphorylation of MAP2.


Assuntos
Dendritos/fisiologia , Hipocampo/citologia , Neurônios/citologia , Proteínas Serina-Treonina Quinases/fisiologia , Animais , Células Cultivadas , Chlorocebus aethiops , Embrião de Mamíferos , Proteínas de Fluorescência Verde/metabolismo , Humanos , Camundongos , Proteínas Associadas aos Microtúbulos/metabolismo , Mutação/fisiologia , Nocodazol/farmacologia , RNA de Cadeia Dupla/genética , RNA de Cadeia Dupla/farmacologia , Ratos , Frações Subcelulares/metabolismo , Transfecção/métodos , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia , Proteínas Wnt/farmacologia , Proteína Wnt3
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