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2.
Ann Oncol ; 26(5): 966-973, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25712457

RESUMO

BACKGROUND: Central nervous system (CNS) relapse is an uncommon but challenging complication in patients with mantle cell lymphoma (MCL). Survival after CNS relapse is extremely poor. Identification of high-risk populations is therefore critical in determining patients who might be candidates for a prophylactic approach. PATIENTS AND METHODS: A total of 608 patients (median age, 67 years; range 22-92) with MCL newly diagnosed between 1994 and 2012 were evaluated. Pretreatment characteristics and treatment regimens were evaluated for their association with CNS relapse by competing risk regression analysis. RESULTS: None of the patients received intrathecal prophylaxis. Overall, 33 patients (5.4%) experienced CNS relapse during a median follow-up of 42.7 months. Median time from diagnosis to CNS relapse was 20.3 months (range: 2.2-141.3 months). Three-year cumulative incidence of CNS relapse was 5.6% [95% confidence interval (95% CI) 3.7% to 8.0%]. Univariate analysis revealed several risk factors including blastoid variant, leukemic presentation, high-risk MCL International Prognostic Index and high Ki-67 (proliferation marker). Multivariate analyses revealed that Ki-67 ≥ 30 was the only significant risk factor for CNS relapse (hazard ratio: 6.0, 95% CI 1.9-19.4, P = 0.003). Two-year cumulative incidence of CNS relapse in patients with Ki-67 ≥ 30 was 25.4% (95% CI 13.5-39.1), while that in the patients with Ki-67 < 30 was 1.6% (95% CI 0.4-4.2). None of the treatment modalities, including rituximab, high-dose cytarabine, high-dose methotrexate or consolidative autologous stem-cell transplant, were associated with a lower incidence of CNS relapse. Survival after CNS relapse was poor, with median survival time of 8.3 months. There was no significant difference in the survival by the site of CNS involvement.


Assuntos
Neoplasias do Sistema Nervoso Central/química , Antígeno Ki-67/análise , Linfoma de Célula do Manto/química , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Nervoso Central/mortalidade , Neoplasias do Sistema Nervoso Central/patologia , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Humanos , Incidência , Japão/epidemiologia , Estimativa de Kaplan-Meier , Linfoma de Célula do Manto/mortalidade , Linfoma de Célula do Manto/patologia , Linfoma de Célula do Manto/terapia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
3.
Anaesthesia ; 70(4): 429-33, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25389044

RESUMO

We measured the effect of Patent Blue dye on oxyhaemoglobin saturations after injection into breast tissue: 40 women had anaesthesia for breast surgery maintained with sevoflurane or propofol (20 randomly allocated to each). Saturations were recorded with a digital pulse oximeter, in arterial blood samples and with a cerebral tissue oximeter before dye injection and 10, 20, 30, 40, 50, 60, 75, 90, 105 and 120 min afterwards. Patent Blue did not decrease arterial blood oxyhaemoglobin saturation, but it did reduce mean (SD) digital and cerebral oxyhaemoglobin saturations by 1.1 (1.1) % and 6.8 (7.0) %, p < 0.0001 for both. The falsely reduced oximeter readings persisted for at least 2 h. The mean (SD) intra-operative digital pulse oxyhaemoglobin readings were lower with sevoflurane than propofol, 97.8 (1.2) % and 98.8 (1.0) %, respectively, p < 0.0001.


Assuntos
Circulação Cerebrovascular/efeitos dos fármacos , Corantes/farmacologia , Oxiemoglobinas/metabolismo , Corantes de Rosanilina/farmacologia , Idoso , Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Artefatos , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Erros de Diagnóstico , Feminino , Humanos , Éteres Metílicos/farmacologia , Pessoa de Meia-Idade , Monitorização Intraoperatória/métodos , Oximetria/métodos , Propofol/farmacologia , Sevoflurano
4.
J Gastroenterol ; 50(3): 305-12, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24952898

RESUMO

BACKGROUND: We recently demonstrated in humans that the extent of low-dose aspirin (LDA)-induced gastropathy was directly related to the individual gastric acid secretion level. We also established reliable cutoff serum pepsinogen (PG) values to predict gastric acid secretion status. In this study, we investigated the clinical usefulness of measuring the serum pepsinogen values for identifying a high-risk group for gastric mucosal injury among chronic LDA users. METHODS: One hundred long-term LDA users were enrolled in this analysis. Serum from each subject was subjected to determination of H. pylori status and measurement of pepsinogen values. According to our recent report, a PG I value ≥ 50 ng/mL was defined as estimated hyperchlorhydria in H. pylori-negative subjects, while a PG I/II ≥ 3.3 was defined as estimated hyperchlorhydria in H. pylori-positive subjects. The grade of gastric mucosal injury was assessed endoscopically, and multiple logistic regression analyses were used to estimate the risk. RESULTS: Estimated hyperchlorhydria was a strong independent risk for intensive gastric mucosal injury with an OR (95% CI): 34.0 (4.5-259) and for gastric ulcer with an OR (95% CI): 10.2 (1.8-58.3) in H. pylori-positive subjects, while it was not a significant risk in H. pylori-negative subjects. The association persisted even after excluding those with conventional risks for LDA-gastropathy such as ulcer histories. CONCLUSION: Using simple serum measurement of H. pylori antibody and pepsinogen concentrations, an extremely high-risk group for LDA-induced gastropathy could be extracted, and these patients should become a therapeutic target for prevention of LDA-induced gastropathy.


Assuntos
Aspirina/efeitos adversos , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Pepsinogênio A/sangue , Úlcera Gástrica/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antibacterianos/sangue , Aspirina/administração & dosagem , Biomarcadores/sangue , Esquema de Medicação , Feminino , Gastroscopia , Helicobacter pylori/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Medição de Risco/métodos , Índice de Gravidade de Doença , Úlcera Gástrica/diagnóstico , Úlcera Gástrica/microbiologia
5.
Mucosal Immunol ; 7(6): 1312-25, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24670424

RESUMO

It is well established that polymorphisms of the caspase activation and recruitment domain 15 (CARD15) gene, a major risk factor in Crohn's disease (CD), lead to loss of nucleotide-binding oligomerization domain 2 (NOD2) function. However, a molecular explanation of how such loss of function leads to increased susceptibility to CD has remained unclear. In a previous study exploring this question, we reported that activation of NOD2 in human dendritic cells by its ligand, muramyl dipeptide (MDP), negatively regulates Toll-like receptor (TLR)-mediated inflammatory responses. Here we show that NOD2 activation results in increased interferon regulatory factor 4 (IRF4) expression and binding to tumor necrosis factor receptor associated factor 6 (TRAF6) and RICK (receptor interacting serine-threonine kinase). We then show that such binding leads to IRF4-mediated inhibition of Lys63-linked polyubiquitination of TRAF6 and RICK and thus to downregulation of nuclear factor (NF)-κB activation. Finally, we demonstrate that protection of mice from the development of experimental colitis by MDP or IRF4 administration is accompanied by similar IRF4-mediated effects on polyubiquitination of TRAF6 and RICK in colonic lamina propria mononuclear cells. These findings thus define a mechanism of NOD2-mediated regulation of innate immune responses to intestinal microflora that could explain the relation of CARD15 polymorphisms and resultant NOD2 dysfunction to CD.


Assuntos
Colo/imunologia , Doença de Crohn/imunologia , Regulação para Baixo/imunologia , Fatores Reguladores de Interferon/imunologia , Proteína Adaptadora de Sinalização NOD2/imunologia , Proteína Serina-Treonina Quinases de Interação com Receptores/imunologia , Fator 6 Associado a Receptor de TNF/imunologia , Ubiquitinação/imunologia , Animais , Colo/patologia , Doença de Crohn/genética , Doença de Crohn/patologia , Células Dendríticas/imunologia , Células Dendríticas/patologia , Células HEK293 , Humanos , Inflamação/genética , Inflamação/imunologia , Inflamação/patologia , Fatores Reguladores de Interferon/genética , Camundongos , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Serina-Treonina Quinase 2 de Interação com Receptor , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Fator 6 Associado a Receptor de TNF/genética , Ubiquitinação/genética
7.
Endoscopy ; 45(4): 313-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23296362

RESUMO

The detection of early esophageal squamous cell carcinoma (ESCC) in patients following radiotherapy for squamous cell carcinoma of the head and neck (HNSCC) has increased with the development of endoscopic technologies. The aim of the current case - control study was to elucidate the risk factors of serious laryngeal edema, a lethal complication that occurs during endoscopic resection for ESCC. Among 184 consecutive patients who were treated by endoscopic resection for ESCC between January 2009 and May 2012, five of 22 patients with a history of radiotherapy for HNSCC suffered from serious laryngeal edema, which was not observed in patients who had not undergone radiotherapy. The susceptibility to serious laryngeal edema in patients with a history of radiotherapy followed by neck dissection for HNSCC was significantly greater than those without such histories. Despite the limited number of cases, we suggest that previous radiotherapy followed by neck dissection for HNSCC might be a predictive factor for serious laryngeal edema during endoscopic resection.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagoscopia/efeitos adversos , Edema Laríngeo/etiologia , Segunda Neoplasia Primária/cirurgia , Idoso , Distribuição de Qui-Quadrado , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia/efeitos adversos , Dosagem Radioterapêutica , Medição de Risco , Fatores de Risco , Estatísticas não Paramétricas
8.
Scand J Gastroenterol ; 45(3): 282-91, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20001645

RESUMO

OBJECTIVE: Dilatation of the intercellular space (DIS) of the esophageal epithelium is recognized as one of the earliest histological changes in gastroesophageal reflux disease patients. At the human gastroesophageal junction, reactive nitrogen oxide species (RNOS) are generated luminally through the entero-salivary re-circulation of dietary nitrate. In cases with gastroesophageal reflux, the site of luminal RNOS generation may shift to the distal esophagus. The aim of this study was to investigate whether luminal RNOS exposure could be involved in the pathogenesis of DIS. MATERIAL AND METHODS: Rat esophageal mucosa was studied with an Ussing chamber model. On the luminal side of the chamber, RNOS were generated by the acidification of physiologic concentrations of sodium nitrite (1.0 or 5.0 mM). Esophageal barrier function was assessed by means of electrophysiological transmembrane resistance and membrane permeability by means of (3)H-mannitol flux. The dimensions of the intercellular spaces were assessed by using transmission electron microscopy. RESULTS: Administration of acid plus sodium nitrite induced DIS of the esophageal epithelium, and this ultrastructural morphological change was accompanied by a concomitant decrease in the transmembrane resistance and an increase in the epithelial permeability. The DIS induced by luminal RNOS was also confirmed in an in vivo exposure model. CONCLUSIONS: The present animal study indicates that the RNOS generated by the acidification of salivary nitrite in the presence of refluxed gastric acid in the esophagus could be a luminal factor that is responsible for the induction of DIS. Further studies are warranted to investigate the clinical relevance of the present findings to the human situation.


Assuntos
Esôfago/fisiopatologia , Espaço Extracelular , Refluxo Gastroesofágico/fisiopatologia , Animais , Dilatação Patológica/etiologia , Masculino , Mucosa/fisiopatologia , Óxidos de Nitrogênio , Ratos , Ratos Wistar
10.
Cell Mol Life Sci ; 66(9): 1479-92, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19132292

RESUMO

A large number of compounds mimicking the structures of monosaccharides or oligosaccharides have been discovered from natural sources. Such sugar mimics inhibit carbohydrate-degrading enzymes because of a structural resemblance to the sugar moiety of the natural substrate. Carbohydrate-degrading enzymes are involved in a wide range of important biological processes, such as intestinal digestion, posttranslational processing of the sugar chain of glycoproteins, their quality control mechanisms, lysosomal catabolism of glycoconjugates, and some viral infections. It has now been realized that inhibitors of the enzymes have enormous therapeutic potential in diabetes and lysosomal storage disorders. In this review, the general bioactivity, current applications, and the prospects for new therapeutic applications are described.


Assuntos
Metabolismo dos Carboidratos/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glicosídeo Hidrolases/antagonistas & inibidores , Monossacarídeos/química , Animais , Ligação Competitiva , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/enzimologia , Inibidores Enzimáticos/metabolismo , Glicogênio/metabolismo , Humanos , Doenças por Armazenamento dos Lisossomos/tratamento farmacológico , Doenças por Armazenamento dos Lisossomos/enzimologia , Camundongos , Monossacarídeos/metabolismo , Monossacarídeos/farmacologia , Dobramento de Proteína , Coelhos , Ratos
11.
Mucosal Immunol ; 1 Suppl 1: S5-9, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19079230

RESUMO

Nucleotide oligomerization domain (NOD)2 is a member of the NOD-like receptor family of proteins that initiate inflammatory responses when exposed to ligands derived from bacterial components that gain access to the intracellular milieu. It is thus somewhat paradoxical that polymorphisms in the gene that encode NOD2 (CARD15) that lead to impaired NOD2 function, are susceptibility factors in Crohn's disease, a condition marked by excessive inflammatory responses to normal bacterial flora. In an initial series of studies conducted in our laboratory to better define NOD2 function and to resolve this paradox we showed that NOD2 activation by its ligand, muramyl dipeptide (MDP) ordinarily downregulates responses to Toll-like receptor (TLR) stimulation, and thus cells lacking NOD2 mount increased responses to such stimulation. This fits with the fact that mice bearing an NOD2 transgene, and thus having cells with increased NOD2 function display decreased responses to TLR stimulation and are resistant to experimental colitis induction. In further studies, we showed that prestimulation of cells with NOD2 ligand renders them unresponsive to TLR stimulation, because such prestimulation results in the elaboration of inhibitory factor (IRF4), an inhibitor of TLR-induced inflammatory pathways. Furthermore, administration of MDP to normal mice induces IRF4 and prevents experimental colitis. These studies strongly suggest that NOD2 polymorphisms are associated with Crohn's disease because they lead to a decrease in the negative regulation of TLR responses occurring in the normal gut, and thus a pathologic increase in responses to the normal flora. The finding that MDP administration prevents experimental colitis opens the door to the possibility that such treatment might quell Crohn's disease relapses in patients without NOD2 abnormalities.


Assuntos
Doença de Crohn/genética , Doença de Crohn/metabolismo , Predisposição Genética para Doença/genética , Proteína Adaptadora de Sinalização NOD2/genética , Proteína Adaptadora de Sinalização NOD2/metabolismo , Animais , Regulação da Expressão Gênica , Humanos , Mutação/genética , Proteína Adaptadora de Sinalização NOD2/deficiência , Receptores Toll-Like/metabolismo
12.
Histopathology ; 52(5): 585-96, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18370955

RESUMO

AIMS: To investigate the clinicopathological features of six unusual cases of nodal CD56+ and Epstein-Barr virus (EBV)+ T/natural killer (NK)-cell lymphoma, a putative nodal counterpart of nasal NK/T-cell lymphoma (nodal T/NK-cell lymphoma of nasal type) in comparison with nasal NK/T-cell lymphoma with secondary lymph node involvement (n = 24) and peripheral T-cell lymphoma (PTCL) of cytotoxic molecule (CTM)+ and EBV+ type (n = 21). METHODS AND RESULTS: All cases of nodal T/NK-cell lymphoma of nasal type exhibited diffuse infiltration of pleomorphic medium-sized to large tumour cells, reminiscent of those in CTM+ EBV+ PTCL. The tumour cells had a typical phenotype of nasal NK/T-cell lymphoma: CD2+, CD3epsilon+, CD4-, CD5-, CD56+, T-cell intracellular antigen-1+, granzyme B+, perforin+ and EBV+. However, four of six cases demonstrated clonal T-cell receptor gamma-gene rearrangement on polymerase chain reaction analysis, unlike nasal NK/T-cell lymphoma. Comparison of clinical parameters and overall survival among the three groups demonstrated only minor differences. CONCLUSIONS: Nodal T/NK-cell lymphoma may occupy the grey zone between extranodal nasal-type NK/T-cell lymphoma and nodal CTM+ PTCL in a spectrum of NK to T-cell lymphomas that are EBV+. The close relationship between NK/T-cell lymphomas and cytotoxic T-cell lymphomas was also substantiated.


Assuntos
Infecções por Vírus Epstein-Barr/patologia , Células Matadoras Naturais/patologia , Linfonodos/patologia , Linfoma de Células T Periférico/patologia , Neoplasias Nasais/patologia , Linfócitos T Citotóxicos/patologia , Adulto , Idoso , DNA de Neoplasias/análise , Infecções por Vírus Epstein-Barr/metabolismo , Rearranjo Gênico do Linfócito T/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/isolamento & purificação , Humanos , Técnicas Imunoenzimáticas , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/virologia , Linfonodos/metabolismo , Linfonodos/virologia , Linfoma de Células T Periférico/etiologia , Linfoma de Células T Periférico/mortalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Nasais/etiologia , Neoplasias Nasais/mortalidade , RNA Viral/análise , Taxa de Sobrevida , Linfócitos T Citotóxicos/metabolismo , Linfócitos T Citotóxicos/virologia
13.
Histopathology ; 50(6): 705-15, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17493234

RESUMO

AIMS: The Revised European American Lymphoma classification uses the term Hodgkin's-like anaplastic large cell lymphoma (HD-like ALCL) for borderline cases with features of both anaplastic large cell lymphoma (ALCL) and classical Hodgkin's lymphoma (HL). The aim of this study was to clarify the association between cytotoxic molecule (CM) expression and clinical outcome in HD-like ALCL. METHODS AND RESULTS: Subjects were 59 patients with HD-like ALCL, defined by nodal presentation without mediastinal bulky lesions, T- or null-cell phenotype, CD30+ anaplastic lymphoma kinase (ALK)- phenotype and by confluent sheets or nodules of large cells mimicking classic Hodgkin and Reed-Sternberg cells. We evaluated the presenting features and prognosis of subjects on categorization into two defined groups, namely CM (TIA1 and/or granzyme B)-positive (n = 21) and CM-negative (n = 38). The series consisted of 18 women and 41 men ranging from 16 to 88 years of age (median 59 years). The CM+ group had poorer disease-specific survival than the CM- group (P = 0.02) despite the absence of differences in other clinical characteristics. Multivariate analysis confirmed that CM expression was an independent prognostic factor, in contrast to phenotypic categorization (T-cell vs. null-cell group), which had no prognostic impact on disease-specific survival. CONCLUSION: CM expression is predictive of prognosis in HD-like ALCL.


Assuntos
Granzimas/metabolismo , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/metabolismo , Proteínas de Ligação a Poli(A)/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Regulação Neoplásica da Expressão Gênica , Granzimas/genética , Doença de Hodgkin/patologia , Humanos , Linfócitos Nulos/patologia , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Fenótipo , Proteínas de Ligação a Poli(A)/genética , Valor Preditivo dos Testes , Prognóstico , Células de Reed-Sternberg/patologia , Análise de Sobrevida , Antígeno-1 Intracelular de Células T , Linfócitos T/patologia
14.
Clin Exp Dermatol ; 31(2): 278-80, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16487109

RESUMO

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is thought to play an important role in the pathogenesis of atopic dermatitis. To examine whether GM-CSF single nucleotide polymorphisms (SNPs) are associated with susceptibility to atopic dermatitis, we investigated the genotype and allele frequencies of the SNPs 3606T/C and 3928C/T of the GM-CSF gene in 181 Japanese patients with atopic dermatitis and 100 controls, using a PCR restriction fragment length polymorphism method. A strong linkage disequilibrium existed between the polymorphisms 3606 and 3928, suggesting two common GM-CSF haplotypes, 3606*T-3928*C and 3606*C-3928*T. However, there was no significant difference in genotype or allele frequencies between patients with atopic dermatitis and controls for either of the two polymorphisms, thus GM-CSF SNPs do not appear to be associated with susceptibility to atopic dermatitis in Japanese patients. A large-scale study is necessary to confirm these findings.


Assuntos
Dermatite Atópica/genética , Fator Estimulador de Colônias de Granulócitos e Macrófagos/genética , Polimorfismo Genético/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Dermatite Atópica/etnologia , Feminino , Humanos , Japão/etnologia , Masculino , Pessoa de Meia-Idade
15.
Leukemia ; 19(7): 1169-74, 2005 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15902300

RESUMO

Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL). One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs. The mechanisms of cell trafficking associated with the chemokine system have been investigated in NK cells. To clarify the mechanism of systemic migration of leukemic NK cells, we enrolled nine ANKL and six CNKL cases, and analyzed the expression profiles and functions of chemokine receptors by flowcytometry and chemotaxis assay. CXCR1 was detected on NK cells in all groups, and CCR5 was positive in all ANKL cells. Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors. ANKL cells showed enhanced chemotaxis toward the ligands of these receptors. These results indicated that the chemokine system might play an important role in the pathophysiology of ANKL and that chemokine receptor profiling might be a novel tool for discriminating ANKL cells from benign NK cells.


Assuntos
Células Matadoras Naturais/patologia , Leucemia Linfoide/genética , Linfocitose/genética , Receptores de Quimiocinas/genética , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/fisiologia , Movimento Celular/efeitos dos fármacos , Movimento Celular/fisiologia , Quimiocinas/farmacologia , Criança , Feminino , Perfilação da Expressão Gênica , Humanos , Células Matadoras Naturais/química , Células Matadoras Naturais/imunologia , Leucemia Linfoide/diagnóstico , Leucemia Linfoide/fisiopatologia , Linfocitose/diagnóstico , Masculino , Pessoa de Meia-Idade , Fenótipo , Receptores CCR5/genética , Receptores CCR5/fisiologia , Receptores de Quimiocinas/análise , Receptores de Quimiocinas/fisiologia , Receptores de Interleucina-8A/genética , Receptores de Interleucina-8A/fisiologia
16.
Gut ; 54(3): 330-5, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15710978

RESUMO

BACKGROUND: Helicobacter pylori infection is associated with variable clinical outcomes, including gastroduodenal diseases, and genetic factors may be relevant in this process. AIMS: We investigated the effects of an interleukin 8 (IL-8) gene polymorphism on the risk of gastroduodenal diseases, the degree of H pylori induced gastritis, and IL-8 gene transcription. SUBJECTS: The study was performed in 244 healthy control subjects and 690 H pylori positive patients with non-cardia gastric cancer, gastric ulcer, duodenal ulcer, or gastritis. METHODS: We identified the IL-8 -251 A/T polymorphism by direct sequence analysis, and measured the gastritis score and serum pepsinogen (PG). The transcriptional promoter activity of the IL-8 gene was assessed by luciferase assay. RESULTS: IL-8 -251A was associated with a higher risk of gastric cancer and gastric ulcer. Patients carrying IL-8 -251A showed an increased risk of gastric cancer (odds ratios (OR) 2.01 (95% confidence interval (CI) 1.38-2.92)) and gastric ulcer (OR 2.07 (95% CI 1.37-3.12)). Compared with patients younger than 49 years, atrophy and metaplasia scores in the antrum were significantly higher and the PG I/II ratio significantly lower in -251A carriers than in T/T carriers. In the in vitro assay, IL-8 -251A showed enhanced promoter activity in response to IL-1beta or tumour necrosis factor alpha. CONCLUSIONS: The IL-8 -251A allele may be associated with progression of gastric atrophy in patients with H pylori infection, and may increase the risk of gastric cancer and gastric ulcer in Japanese people.


Assuntos
Infecções por Helicobacter/complicações , Helicobacter pylori , Interleucina-8/genética , Polimorfismo Genético , Gastropatias/microbiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Úlcera Duodenal/microbiologia , Feminino , Gastrite/microbiologia , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Regiões Promotoras Genéticas , Neoplasias Gástricas/microbiologia , Úlcera Gástrica/microbiologia
17.
Am J Physiol Endocrinol Metab ; 288(3): E534-40, 2005 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-15536204

RESUMO

D-mannose is an essential monosaccharide constituent of glycoproteins and glycolipids. However, it is unknown how plasma mannose is supplied. The aim of this study was to explore the source of plasma mannose. Oral administration of glucose resulted in a significant decrease of plasma mannose concentration after 20 min in fasted normal rats. However, in fasted type 2 diabetes model rats, plasma mannose concentrations that were higher compared with normal rats did not change after the administration of glucose. When insulin was administered intravenously to fed rats, it took longer for plasma mannose concentrations to decrease significantly in diabetic rats than in normal rats (20 and 5 min, respectively). Intravenous administration of epinephrine to fed normal rats increased the plasma mannose concentration, but this effect was negated by fasting or by administration of a glycogen phosphorylase inhibitor. Epinephrine increased mannose output from the perfused liver of fed rats, but this effect was negated in the presence of a glucose-6-phosphatase inhibitor. Epinephrine also increased the hepatic levels of hexose 6-phosphates, including mannose 6-phosphate. When either lactate alone or lactate plus alanine were administered as gluconeogenic substrates to fasted rats, the concentration of plasma mannose did not increase. When lactate was used to perfuse the liver of fasted rats, a decrease, rather than an increase, in mannose output was observed. These findings indicate that hepatic glycogen is a source of plasma mannose.


Assuntos
Glicogênio/metabolismo , Fígado/metabolismo , Manose/sangue , Administração Oral , Alanina/farmacologia , Animais , Arabinose , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Ácido Clorogênico/farmacologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/metabolismo , Modelos Animais de Doenças , Epinefrina/farmacologia , Glucose/metabolismo , Glucose/farmacologia , Glucose-6-Fosfatase/antagonistas & inibidores , Glicogênio Fosforilase/antagonistas & inibidores , Hexosefosfatos/análise , Hexosefosfatos/metabolismo , Imino Furanoses , Injeções Intravenosas , Insulina/sangue , Insulina/farmacologia , Ácido Láctico/farmacologia , Fígado/química , Fígado/efeitos dos fármacos , Masculino , Manose/metabolismo , Modelos Biológicos , Ratos , Ratos Endogâmicos , Ratos Wistar , Álcoois Açúcares/farmacologia
18.
J Bone Joint Surg Br ; 86(4): 607-12, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15174563

RESUMO

We investigated the rates of expression of bone morphogenetic protein-2 (BMP-2) in 29 adult patients with high-grade malignant fibrous histiocytoma of soft tissue, using the BMP-2-specific monoclonal antibody, AbH3b2/17, and found that they ranged from 1.9% to 78.9%. The survival at five years of the groups expressing high (> or = 30%) and low (< 30%) levels of BMP-2 was 85.7% and 36.3%, respectively. Multivariable analysis showed that only BMP-2 had prognostic significance for continuous disease-free survival and for overall survival (p < 0.05). Our findings indicate that over-expression of BMP-2 in malignant fibrous histiocytoma of soft tissue is the most reliable prognostic indicator of the parameters assessed.


Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Morfogenéticas Ósseas/metabolismo , Histiocitoma Fibroso Benigno/metabolismo , Proteínas de Neoplasias/metabolismo , Neoplasias de Tecidos Moles/metabolismo , Fator de Crescimento Transformador beta , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína Morfogenética Óssea 2 , Feminino , Histiocitoma Fibroso Benigno/patologia , Histiocitoma Fibroso Benigno/terapia , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/terapia , Análise de Sobrevida , Resultado do Tratamento
19.
J Pharm Pharmacol ; 55(6): 735-40, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12841932

RESUMO

The combined effects of (-)-epigallocatechin gallate (EGCg) and beta-lactams were investigated against various beta-lactamase-producing clinical isolates, including 21 Staphylococcus aureus, 6 Escherichia coli, 3 Klebsiella pneumoniae and 8 Serratia marcescens strains. Penicillin in combination with EGCg at 12.5 microg mL(-1) showed the most potent synergy against 100% penicillinase-producing S. aureus. However, cefotaxime or imipenem in combination with higher concentration of EGCg (100 microg mL(-1)) only showed slight synergy against 2 of 17 Gram-negative rods. Similar to the effect on the penicillinase from S. aureus, however, EGCg also directly inhibited the extracted beta-lactamases from the Gram-negative rods, thereby protecting beta-lactams from inactivation. The different effects of the combinations on different beta-lactamase-producing species were confirmed to be related to the cellular locations of beta-lactamases. In contrast to a 32.7% extracellular fraction of total beta-lactamase activity in a penicillinase-producing S. aureus, the fractions were 0.6%, 0.6% and 1.2% in a TEM-derived extended-spectrum beta-lactamase-producing E. coli, an inhibitor-resistant beta-lactamase-producing K. pneumoniae and an IMP-producing S. marcescens, respectively. In conclusion, the combination of penicillin with EGCg showed potent synergy against penicillinase-producing S. aureus in-vitro. The combinations of beta-lactams and EGCg against beta-lactamase-producing Gram-negative rods do indicate a limitation owing to the cellular location of beta-lactamases.


Assuntos
Antibacterianos/farmacologia , Catequina/análogos & derivados , Catequina/farmacologia , Bactérias Gram-Negativas/efeitos dos fármacos , beta-Lactamases , Catequina/isolamento & purificação , Sinergismo Farmacológico , Bactérias Gram-Negativas/metabolismo , Testes de Sensibilidade Microbiana , beta-Lactamases/biossíntese , beta-Lactamases/efeitos dos fármacos , beta-Lactamases/genética , beta-Lactamas
20.
Br J Dermatol ; 148(5): 1028-31, 2003 May.
Artigo em Inglês | MEDLINE | ID: mdl-12786837

RESUMO

BACKGROUND: Fusion of the collagen type I alpha 1 (COL1A1) gene with the platelet-derived growth factor B-chain (PDGFB) gene has been described in dermatofibrosarcoma protuberans (DFSP). Various exons of the COL1A1 gene have been shown to be involved in the fusion with exon 2 of the PDGFB gene. Objectives We examined the breakpoint of the COL1A1 gene using the tumour specimen from the patient with DFSP. METHODS: Reverse transcriptase-polymerase chain reaction (PCR) was performed using cultured DFSP tumour cells. Nucleotide sequence analysis was carried out using the PCR product to identify the breakpoint. RESULTS: The COL1A1-PDGFB fusion transcript was detected from the tumour specimen. Sequence analysis revealed that exon 18 of the COL1A1 gene was fused with exon 2 of the PDGFB gene. CONCLUSIONS: This study identified a novel COL1A1 breakpoint, namely, exon 18 of the COL1A1 gene.


Assuntos
Colágeno Tipo I/genética , Dermatofibrossarcoma/genética , Proteínas de Fusão Oncogênica/análise , Proteínas Proto-Oncogênicas c-sis/genética , Neoplasias Cutâneas/genética , Adulto , Sequência de Bases , Cadeia alfa 1 do Colágeno Tipo I , Éxons , Humanos , Masculino , Dados de Sequência Molecular , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA
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