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1.
Clin Genet ; 94(1): 70-80, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29023671

RESUMO

Pulmonary arterial hypertension (PAH) is a rare but serious disease with a grave prognosis. Bone morphogenetic protein type 2 receptor (BMPR2) gene is a strong pathogenic factor for PAH. As a collaborative team from Kyorin University and Keio University in Japan, we have analyzed the BMPR2 gene in 356 probands and more than 50 family members, including secondary patients. Importantly, the study population is a racially, ethnically, and socially homogeneous population. In PAH patients, there is a high incidence of unique mutations in BMPR2, and several mutations are frequently observed in the Japanese population, suggesting that these common and recurring mutations may be highly pathogenic or have high penetrance, explaining why they are found frequently throughout the world. We have also mapped each breakpoint of exonic deletions/duplications and found that most break and rejoining points are in the Alu elements. Reviewing the distribution of the reported mutations on each exon of BMPR2 revealed that the number and frequency of mutations are imbalanced among exons. The penetrance of BMPR2 gene mutations was 3-fold higher in females than males. Full elucidation of BMPR2-mediated pathogenic mechanisms in PAH requires persistent efforts to achieve precision or individualized medicine as a therapeutic strategy for PAH.


Assuntos
Povo Asiático/genética , Hipertensão Pulmonar Primária Familiar/epidemiologia , Hipertensão Pulmonar Primária Familiar/genética , Predisposição Genética para Doença , Alelos , Receptores de Proteínas Morfogenéticas Ósseas Tipo II/genética , Biologia Computacional/métodos , Variações do Número de Cópias de DNA , Bases de Dados Genéticas , Hipertensão Pulmonar Primária Familiar/diagnóstico , Hipertensão Pulmonar Primária Familiar/terapia , Estudos de Associação Genética , Testes Genéticos , Humanos , Japão/epidemiologia , Mutação , Penetrância , Fenótipo , Vigilância da População , Prognóstico
2.
Allergy ; 73(2): 511-515, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28960333

RESUMO

Endothelin-1 (ET-1) is associated with skin diseases such as atopic dermatitis (AD) and psoriasis. ET-1 is enhanced in the skin of patients AD and psoriasis. In addition, plasma levels of ET-1 are elevated in AD and psoriasis. Although both AD and psoriasis are T-cell-mediated skin diseases, the association between ET-1 and the T-cell immune response has not been clarified. To evaluate the role of ET-1 in inflammatory skin disease, we sought to investigate the effects of ET-1 on the functions of dendritic cells (DCs) and subsequent immune responses. For this purpose, we immunohistochemically confirmed the upregulation of ET-1 in the epidermis of patients with AD or psoriasis. ET-1 directly induced phenotypic maturation of bone marrow-derived DCs (BMDCs). In addition, ET-1 augmented the production of several cytokines and allogeneic stimulatory capacity of BMDCs. Interestingly, ET-1-activated BMDCs primed T cells to produce Th1 and Th17 cytokines, but not Th2 cytokines. These findings indicate that ET-1 polarizes the DC-T-cell response toward Th17/1 differentiation and may augment the persistent course of inflammatory skin diseases.


Assuntos
Células Dendríticas/imunologia , Dermatite Atópica/imunologia , Endotelina-1/imunologia , Psoríase/imunologia , Células Th1/imunologia , Células Th17/imunologia , Animais , Diferenciação Celular/imunologia , Ensaio de Imunoadsorção Enzimática , Epiderme/imunologia , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL
3.
Dis Esophagus ; 30(5): 1-7, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28375439

RESUMO

The aim of the present study is to evaluate the outcome of hand-sewn esophagogastric anastomosis during radical esophagectomy for esophageal cancer. The outcomes of 467 consecutive esophageal cancer patients who underwent cervical esophagogastric anastomosis using interrupted and double-layered sutures after radical esophagectomy via right thoracotomy or thoracoscopic surgery were retrospectively reviewed. Anastomotic leakage, including conduit necrosis, occurred in 11 of 467 patients (2.4%); 7 of 11 (63.6%) cases experienced only minor leakage, whereas the other four (36.4%) patients had major leakage that required surgical or radiologic intervention, including two patients of conduit necrosis. Anastomotic leakages were more frequently observed after retrosternal reconstruction compared with the posterior mediastinal route (P < 0.0001). The median time to healing of leakage was 40 days (range: 14-97 days). Two patients (2/467, 0.4%) died in the hospital due to sepsis caused by the leakage and conduit necrosis. Twelve patients (2.6%) developed anastomotic stenosis, which was improved by dilatation in all patients. Hand-sewn cervical esophagogastric anastomosis is a stable and highly safe method of radical esophagectomy for esophageal cancer.


Assuntos
Fístula Anastomótica/epidemiologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagostomia/métodos , Esôfago/cirurgia , Idoso , Anastomose Cirúrgica/efeitos adversos , Anastomose Cirúrgica/métodos , Fístula Anastomótica/etiologia , Esofagostomia/efeitos adversos , Esôfago/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
5.
Parasite Immunol ; 37(4): 171-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25545318

RESUMO

Age-associated alterations of Th2 immune responses against nematode parasites are largely unknown. We investigated primary and memory responses against two types of gastrointestinal nematode parasites, Heligmosomoides polygyrus (Hp) and Nippostrongylus brasiliensis (Nb), in aged mice. The small intestinal gene expression of Th2 cytokines was almost unchanged after primary (Nb and Hp) and secondary infection (Hp) in aged mice in contrast to strongly increased small intestinal gene expression of Th2 cytokines in young (3-month-old) mice. Mucus production decreased (Nb), and worm expulsion was impaired (Nb and Hp) compared with the young mice. Immunofluorescent staining revealed that after Hp infection, the number of alternatively activated macrophages, which are induced by Th2 cytokines, was lower in the aged mice. On the other hand, the number of CD4(+) T cells recruited to the worm cysts was normal compared with the young mice. These results suggest that migration of CD4(+) T cells to the host-parasite interface is not affected by ageing. Alterations in Th2 immune responses in aged mice might be due to inappropriate or insufficient activation of CD4(+) T cells in the submucosa.


Assuntos
Envelhecimento/imunologia , Enteropatias Parasitárias/imunologia , Nematospiroides dubius/fisiologia , Nippostrongylus/fisiologia , Infecções por Strongylida/imunologia , Animais , Citocinas/metabolismo , Feminino , Enteropatias Parasitárias/epidemiologia , Enteropatias Parasitárias/patologia , Macrófagos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Infecções por Strongylida/epidemiologia , Infecções por Strongylida/patologia , Células Th2/imunologia
6.
Dis Esophagus ; 27(2): 112-5, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-23441591

RESUMO

The usefulness of a covered self-expandable metallic stent for benign esophageal stricture and perforation was well established. In case of benign disease, early stent removal was recommended within 6-8 weeks after placement. A case with severe esophageal stricture caused by incomplete stent removal 7 years after stent placement for spontaneous esophageal rupture was reported. Residual stent fragments could be removed by step-by-step multimodal endoscopic treatment, producing satisfactory luminal diameter of the esophagus. In particular, stent trimming with argon plasma coagulation was safe and effective strategy. The endoscopic stent removal is minimally invasive and should be attempted before surgical intervention; however, it is most important to ensure early stent removal before tissue ingrowth or overgrowth can develop.


Assuntos
Remoção de Dispositivo/efeitos adversos , Estenose Esofágica/cirurgia , Esôfago/cirurgia , Tecido de Granulação/cirurgia , Stents/efeitos adversos , Doenças do Esôfago/cirurgia , Estenose Esofágica/etiologia , Esofagoscopia , Humanos , Masculino , Pessoa de Meia-Idade , Ruptura Espontânea/cirurgia , Índice de Gravidade de Doença
7.
Br J Cancer ; 109(1): 207-14, 2013 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-23778523

RESUMO

BACKGROUND: Expression of mucosa-associated lymphoid tissue 1 (MALT1) is inactivated in oral carcinoma patients with worse prognosis. However, the role in carcinoma progression is unknown. Unveiling genes under the control of MALT1 is necessary to understand the pathology of carcinomas. METHODS: Gene data set differentially transcribed in MALT1-stably expressing and -marginally expressing oral carcinoma cells was profiled by the microarray analysis and subjected to the pathway analysis. Migratory abilities of cells in response to MALT1 were determined by wound-healing assay and time-lapse analysis. RESULTS: Totally, 2933 genes upregulated or downregulated in MALT1-expressing cells were identified. The subsequent pathway analysis implicated the inhibition of epidermal growth factor and transforming growth factor-ß signalling gene expression, and highlighted the involvement in the cellular movement. Wound closure was suppressed by wild-type MALT1 (66.4%) and accelerated by dominant-negative MALT1 (218.6%), and the velocities of cell migration were increased 0.2-fold and 3.0-fold by wild-type and dominant-negative MALT1, respectively. CONCLUSION: These observations demonstrate that MALT1 represses genes activating the aggressive phenotype of carcinoma cells, and suggest that MALT1 acts as a tumour suppressor and that the loss of expression stimulates oral carcinoma progression.


Assuntos
Caspases/genética , Caspases/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Caspases/biossíntese , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Ativação Enzimática , Fator de Crescimento Epidérmico/antagonistas & inibidores , Fator de Crescimento Epidérmico/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Tecido Linfoide/metabolismo , Neoplasias Bucais/genética , Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa , NF-kappa B/metabolismo , Proteínas de Neoplasias/biossíntese , Interferência de RNA , RNA Interferente Pequeno , Transdução de Sinais , Fator de Crescimento Transformador beta/antagonistas & inibidores , Fator de Crescimento Transformador beta/genética
8.
Br J Cancer ; 108(2): 395-401, 2013 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-23322208

RESUMO

BACKGROUND: The regenerating gene Iα (REG Iα) is involved in gastric carcinogenesis as an antiapoptotic factor. Therefore, we investigated whether REG Iα confers resistance to chemotherapeutic drugs in gastric cancer (GC) cells and whether REG Iα expression is useful for predicting the response to chemotherapy and outcome in patients with GC. METHODS: A total of 70 patients with unresectable stage IV GC received first-line chemotherapy with S-1 and cisplatin (S-1/CDDP). The expression of REG Iα was evaluated immunohistochemically using biopsy samples obtained before chemotherapy, and its relationship to clinicopathological parameters was analysed statistically. The effects of REG Iα gene induction on resistance to 5-FU or CDDP treatment were examined by cell survival assay and flow cytometry. RESULTS: Of the 70 patients with unresectable stage IV GC, 19 (27%) were positive for REG Iα expression. The expression of REG Iα was independently predictive of poorer progression-free and overall survival in such patients (hazard ratio (HR) 2.46; P=0.002 and HR 1.89; P=0.037, respectively). The gene induction of REG Iα conferred resistance to cell death induced by 5-FU or CDDP in GC cells. CONCLUSION: In patients with stage IV GC, REG Iα, which confers resistance to chemotherapeutic drugs in GC cells, is a potential biomarker for predicting resistance to S-1/CDDP treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Fluoruracila/uso terapêutico , Litostatina/metabolismo , Ácido Oxônico/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Tegafur/uso terapêutico , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Sobrevivência Celular , Combinação de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Litostatina/genética , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/patologia , Resultado do Tratamento
9.
Opt Express ; 21(6): 6889-94, 2013 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-23546071

RESUMO

n-channel body-tied partially depleted metal-oxide-semiconductor field-effect transistors (MOSFETs) were fabricated for large current applications on a silicon-on-insulator wafer with photonics-oriented specifications. The MOSFET can drive an electrical current as large as 20 mA. We monolithically integrated this MOSFET with a 2 × 2 Mach-Zehnder interferometer optical switch having thermo-optic phase shifters. The static and dynamic performances of the integrated device are experimentally evaluated.


Assuntos
Interferometria/instrumentação , Refratometria/instrumentação , Processamento de Sinais Assistido por Computador/instrumentação , Silício/química , Transistores Eletrônicos , Condutividade Elétrica , Desenho de Equipamento , Análise de Falha de Equipamento , Temperatura Alta , Fótons , Integração de Sistemas
10.
Nat Genet ; 25(3): 302-5, 2000 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10888878

RESUMO

Autosomal recessive juvenile parkinsonism (AR-JP), one of the most common familial forms of Parkinson disease, is characterized by selective dopaminergic neural cell death and the absence of the Lewy body, a cytoplasmic inclusion body consisting of aggregates of abnormally accumulated proteins. We previously cloned PARK2, mutations of which cause AR-JP (ref. 2), but the function of the gene product, parkin, remains unknown. We report here that parkin is involved in protein degradation as a ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7, and that mutant parkins from AR-JP patients show loss of the ubiquitin-protein ligase activity. Our findings indicate that accumulation of proteins that have yet to be identified causes a selective neural cell death without formation of Lewy bodies. Our findings should enhance the exploration of the molecular mechanisms of neurodegeneration in Parkinson disease as well as in other neurodegenerative diseases that are characterized by involvement of abnormal protein ubiquitination, including Alzheimer disease, other tauopathies, CAG triplet repeat disorders and amyotrophic lateral sclerosis.


Assuntos
Ligases/metabolismo , Doença de Parkinson/metabolismo , Enzimas de Conjugação de Ubiquitina , Humanos , Ligases/genética , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Células Tumorais Cultivadas , Ubiquitina-Proteína Ligases , Ubiquitinas/genética , Ubiquitinas/metabolismo
11.
J Viral Hepat ; 19(1): 32-8, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21129128

RESUMO

Approximately 30% of patients who have recurrent hepatitis C after liver transplantation achieve sustained virological response (SVR) by taking a combination therapy of pegylated interferon and ribavirin. For the remaining non-SVR patients, an effective management treatment has not yet been established. In this study, efficacy of long-term peginterferon maintenance therapy for non-SVR patients was evaluated. Forty patients who had previously received the combination therapy for hepatitis C after living donor liver transplantation were classified into one of the following three groups: the SVR group (n = 11); the non-SVR-IFN group (n =17), which received low-dose peginterferon maintenance therapy for non-SVR patients; and the non-SVR-Withdrawal group (n = 12), which discontinued the interferon treatment. We then compared histological changes among these three groups after 2 or more years follow-up. Activity grade of liver histology improved or remained stable in patients in the SVR and non-SVR-IFN groups, but deteriorated in half of the patients in the non-SVR-Withdrawal group. Fibrosis improved or remained stable in 10 of 11 SVR patients and in 13 of 17 non-SVR-IFN patients, but deteriorated in all non-SVR-Withdrawal patients. Mean changes in fibrosis stage between pretreatment and final liver biopsy were -0.18, +0.06 and +2.2 in the SVR, non-SVR-IFN and non-SVR-Withdrawal groups, respectively. Fibrosis stage deteriorated to F3 or F4 significantly more rapidly in the non-SVR-Withdrawal group than in the other two groups. In conclusion, continuing long-term maintenance therapy with peginterferon prevented histological progression of hepatitis C in patients who had undergone living donor liver transplantation.


Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Transplante de Fígado , Polietilenoglicóis/uso terapêutico , Adolescente , Adulto , Idoso , Antivirais/administração & dosagem , Progressão da Doença , Quimioterapia Combinada , Feminino , Seguimentos , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/patologia , Humanos , Fígado/patologia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Recidiva , Ribavirina/uso terapêutico , Resultado do Tratamento , Adulto Jovem
12.
Allergy ; 67(7): 936-42, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22583373

RESUMO

BACKGROUND: Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which regulate not only adipogenesis and proliferation/differentiation but also the immune response of cells. Because topical application of the activators of some PPAR isoforms improved clinical symptoms in patients with atopic dermatitis (AD), we investigated the role of PPAR activators using a murine AD model in NC/Nga mice; to the best of our knowledge, this has not been previously reported. METHODS: Activators of three PPAR isoforms (α, ß/δ, γ) were topically applied on inflamed skin in a murine AD model that was developed by repeated topical application of mite antigen in NC/Nga mice. The efficacy of each topical PPAR activator was evaluated immunologically and serologically. RESULTS: Topical application of the PPARα activator, but not of the activators of PPARß/δ or PPARγ, improved clinical dermatitis, reduced inflammatory cell infiltration in the dermis, and alleviated the elevation of serum IgE levels. In addition, PPARα expression was downregulated in the epidermis in our murine AD model, as is seen in patients with AD. CONCLUSIONS: Topical application of PPARα activator could be a potent therapeutic agent for patients with AD and could take the place of topical steroid treatments.


Assuntos
Dermatite Atópica/tratamento farmacológico , PPAR alfa/agonistas , Animais , Dermatite Atópica/imunologia , Dermatite Atópica/patologia , Modelos Animais de Doenças , Eosinófilos/citologia , Epiderme/imunologia , Epiderme/metabolismo , Feminino , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Mastócitos/citologia , Camundongos , PPAR alfa/metabolismo , Pirimidinas/administração & dosagem , Pirimidinas/farmacologia
14.
Br J Cancer ; 105(11): 1693-6, 2011 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-22033274

RESUMO

BACKGROUND: A blood pressure drop after bevacizumab administration and its clinical significance have not been previously reported. METHODS: Blood pressure data at 0, 90, and 180 min after a total of 162 bevacizumab administrations in 81 advanced colorectal cancer patients were retrospectively investigated. RESULTS: Twenty-five patients (30%) demonstrated an average temporary drop of 20 mm Hg or more in systolic blood pressure. We classified these 25 patients as group A and the others as group B. Median time-to-treatment failure (TTF) was significantly longer in group A than in group B (291 vs 162 days; P=0.02). Furthermore, the proportion of patients who required intervention with antihypertensive drugs during bevacizumab treatment was significantly higher in group A than in group B (36% vs 4%; P<0.01). CONCLUSION: This study suggests that a temporary blood pressure drop after bevacizumab administration could be a predictive marker for bevacizumab treatment.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Hipotensão/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Bevacizumab , Neoplasias Colorretais/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Falha de Tratamento
15.
J Viral Hepat ; 18(10): e561-7, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21914077

RESUMO

Hepatitis C virus (HCV)-associated antigens, such as the core and nonstructural antigens, activate host innate immune systems via Toll-like receptors (TLRs). We previously showed that chronic exposure to the core antigen induces hyporesponsiveness to TLR ligands in antigen-presenting cells via activation of TLR2 and that stimulation with TLR ligands results in impaired IL-6 production by peripheral blood monocytes from HCV-infected patients. In the present study, peripheral blood mononuclear cells (PBMCs) isolated from patients with chronic HCV or hepatitis B virus (HBV) infection were stimulated with TLR ligands to determine the production of IL-6 and IL-8 and to identify the clinical parameters associated with hyporesponsiveness to TLR ligands in patients with chronic HCV infection. The results showed that pro-inflammatory cytokine responses to TLR ligands were suppressed in PBMCs isolated from HCV-infected, but not HBV-infected, patients. The reduced cytokine responses to TLR ligands seen in HCV-infected patients correlated with platelet counts and serum prothrombin time levels. In contrast, there was no correlation between TLR-induced cytokine responses and serum levels of core antigen. Thus, hyporesponsiveness to TLR ligands in HCV-infected patients is correlated with liver dysfunction. In conclusion, both host factors and viral factors may be involved in the generation of hyporesponsiveness to TLR ligands in patients with chronic HCV infection.


Assuntos
Antígenos Virais/imunologia , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Leucócitos Mononucleares/imunologia , Hepatopatias/fisiopatologia , Receptores Toll-Like/imunologia , Adulto , Idoso , Antígenos Virais/metabolismo , Feminino , Hepacivirus/imunologia , Hepatite B/imunologia , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Tempo de Protrombina , Receptores Toll-Like/metabolismo
16.
J Viral Hepat ; 18(10): e508-15, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21914070

RESUMO

Quantitative serology for hepatitis B surface antigen (HBsAg) is a new candidate marker for prediction of clinical outcome. The aim of this study was to investigate the clinical significance of quantifying HBsAg in patients with hepatitis B virus (HBV) infection. A total of 424 patients who tested positive for HBsAg and were referred to Chiba University Hospital between January 1985 and April 2008 were included in the study, and the following characteristics were analyzed: age, gender, status of hepatitis B e antigen (HBeAg), alanine aminotransferase level (ALT), HBV DNA level, number of platelets and development of hepatocellular carcinoma. Measurement of HBsAg was performed using the chemiluminescent enzyme immunoassay method. The study group consisted of 239 men and 185 women, and their average age was 40.6 ± 14.0 years. HBsAg showed a positive correlation with HBV DNA level (Pearson's product moment correlation, r = 0.586, P < 0.001) and a weak inverse correlation with age (r = 0.3325, P < 0.001). A control study, matched with age and sex, was performed between two groups with and without HBeAg seroconversion during follow-up period. Compared with the age and sex-matched controls, the change in HBsAg levels per year showed a significant decrease 2 years before seroconversion (paired t-test, P < 0.05). The serial measurement of quantitative HBsAg level has the possibility of predicting the occurrence of HBeAg seroconversion.


Assuntos
Antígenos de Superfície da Hepatite B/sangue , Hepatite B Crônica/diagnóstico , Hepatite B Crônica/patologia , Soro/química , Adulto , Biomarcadores/sangue , DNA Viral/sangue , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
17.
J Viral Hepat ; 18(7): e292-7, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21129130

RESUMO

Extremely low levels of serum hepatitis C virus (HCV) RNA can be detected by COBAS TaqMan HCV test. To investigate whether the COBAS TaqMan HCV test is useful for measuring rapid virological response (RVR) and early virological response (EVR) to predict sustained virological response (SVR), we compared the virological response to PEG-IFN-alfa 2a plus RBV in 76 patients infected with HCV genotype 1 when undetectable HCV RNA by the COBAS TaqMan HCV test was used, with those when below 1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test was used, which corresponded to the use of traditional methods. Among the 76 patients, 28 (36.8%) had SVR, 13 (17.1%) relapsed, 19 (25.0%) did not respond, and 16 (21.0%) discontinued the treatment due to side effects. The positive predictive values for SVR based on undetectable HCV RNA by COBAS TaqMan HCV test at 24 weeks after the end of treatment [10/10 (100%) at week 4, 21/23 (91.3%) at week 8 and 26/33 (78.7%) at week 12] were superior to those based on <1.7 log IU/mL HCV RNA [17/19 (89.4%) at week 4, 27/38 (71.0%) at week 8, and 27/43 (62.7%) at week 12]. The negative predictive values for SVR based on <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test [46/57 (80.7%) at week 4, 37/38 (97.3%) at week 8, and 32/33 (96.9%) at week 12] were superior to those based on undetectable HCV RNA [48/66 (72.7%) at week 4, 46/53 (86.7%) at week 8, and 41/43 (95.3%) at week 12]. The utilization of both undetectable RNA and <1.7 log IU/mL HCV RNA by COBAS TaqMan HCV test is useful and could predict SVR and non-SVR patients with greater accuracy.


Assuntos
Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Genótipo , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/genética , Humanos , Interferon-alfa/administração & dosagem , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Prognóstico , RNA Mensageiro/sangue , RNA Viral/sangue , RNA Viral/genética , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Ribavirina/administração & dosagem , Resultado do Tratamento
18.
Scand J Immunol ; 73(5): 478-85, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21284685

RESUMO

We and others have reported that human NF-κB inhibitor-like-1 (NFKBIL1) was a putative susceptible gene for autoimmune diseases such as rheumatoid arthritis (RA). However, its precise role in the pathogenesis of RA is still largely unknown. In this study, we generated transgenic mice expressing human NFKBIL1 (NFKBIL1-Tg) and examined whether NFKBIL1 plays some role(s) in the development of autoimmune arthritis. In both a collagen-induced arthritis model and a collagen antibody-induced arthritis model, NFKBIL1-Tg mice showed resistance to arthritis compared to control mice, indicating that the gene product of NFKBIL1 was involved in the control of thusly induced arthritis. Total spleen cells of NFKBIL1-Tg mouse showed decreased proliferation to mitogenic stimuli, consistent with its resistance to arthritis. Unexpectedly, purified T cells of NFKBIL1-Tg mouse showed increased proliferation and cytokine production. This apparent discrepancy was accounted for by the impaired functions of antigen-presenting cells of NFKBIL1-Tg mouse; both T/B cell-depleted spleen cells and bone marrow-derived dendritic cells of the Tg mouse induced less prominent proliferation and IL-2 production of T cells. Furthermore, dendritic cells (DCs) derived from NFKBIL1-Tg mouse showed lower expression of co-stimulatory molecules and decreased production of inflammatory cytokines when they were activated by lipopolysaccharide. Taken together, these results indicated that NFKBIL1 affected the pathogenesis of RA at least in part through the regulation of DC functions.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Proteínas de Ligação a DNA/imunologia , Células Dendríticas/imunologia , Fatores de Transcrição/imunologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Citocinas/genética , Citocinas/imunologia , Citometria de Fluxo , Humanos , Imunidade Inata/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos DBA , Camundongos Transgênicos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Baço/citologia , Baço/imunologia , Linfócitos T/imunologia
19.
Jpn J Clin Oncol ; 41(6): 803-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21478179

RESUMO

The safety of chemotherapy for patients with systemic sclerosis is unclear, and there are few published reports documenting the side effects of chemotherapy in patients with this condition. Here, we report the case of a patient with systemic sclerosis who developed severe digital ischemia during combination gemcitabine/S-1 chemotherapy for pancreatic cancer. In spite of aggressive treatment, the digital ischemia progressively worsened and gangrenous changes developed in multiple fingers and toes. In this patient, the systemic sclerosis had been well controlled, with no digital ischemic symptoms for the previous 6 years, so this progressive clinical course in spite of aggressive treatment strongly suggests that the chemotherapy triggered or aggravated the digital necrosis. To the best of our knowledge, this is only the third reported case of a patient with systemic sclerosis developing digital necrosis after gemcitabine-based chemotherapy. The incidence of digital necrosis during chemotherapy in patients with systemic sclerosis is unknown, and the mechanism by which it occurs is unclear, but the three reports published to date, including the present case, suggest that physicians should be very cautious about administering gemcitabine-based chemotherapy to patients with systemic sclerosis. Any resulting digital ischemia might be refractory to treatment and worsen progressively, even if chemotherapy is withdrawn in the early stages of digital ischemia.


Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Desoxicitidina/análogos & derivados , Dedos/patologia , Isquemia/induzido quimicamente , Ácido Oxônico/efeitos adversos , Escleroderma Sistêmico/complicações , Tegafur/efeitos adversos , Dedos do Pé/patologia , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Progressão da Doença , Esquema de Medicação , Combinação de Medicamentos , Evolução Fatal , Gangrena/induzido quimicamente , Humanos , Isquemia/tratamento farmacológico , Isquemia/etiologia , Isquemia/terapia , Masculino , Necrose/induzido quimicamente , Ácido Oxônico/administração & dosagem , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Doença de Raynaud/induzido quimicamente , Tegafur/administração & dosagem , Gencitabina
20.
AJNR Am J Neuroradiol ; 42(8): 1403-1409, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34016589

RESUMO

BACKGROUND AND PURPOSE: Adult patients with ischemic Moyamoya disease are advised to undergo selective revascularization surgery based on cerebral hemodynamics. The purpose of this study was to determine the diagnostic accuracy of arterial spin-labeling MR imaging using Hadamard-encoded multiple postlabeling delays for the detection of reduced CBF in such patients. MATERIALS AND METHODS: Thirty-seven patients underwent brain perfusion SPECT and pseudocontinuous arterial spin-labeling MR imaging using standard postlabeling delay (1525 ms) and Hadamard-encoded multiple postlabeling delays. For Hadamard-encoded multiple postlabeling delays, based on data obtained from the 7 sub-boluses with combinations of different labeling durations and postlabeling delays, CBF corrected by the arterial transit time was calculated on a voxel-by-voxel basis. Using a 3D stereotaxic template, we automatically placed ROIs in the ipsilateral cerebellar hemisphere and 5 MCA territories in the symptomatic cerebral hemisphere; then, the ratio of the MCA to cerebellar ROI was calculated. RESULTS: The area under the receiver operating characteristic curve for detecting reduced SPECT-CBF ratios (<0.686) was significantly greater for the Hadamard-encoded multiple postlabeling delays-CBF ratios (0.885) than for the standard postlabeling delay-CBF ratios (0.786) (P = .001). The sensitivity and negative predictive value for the Hadamard-encoded multiple postlabeling delays-CBF ratios were 100% (95% confidence interval, 100%-100%) and significantly higher than the sensitivity (95% CI, 44%-80%) and negative predictive value (95% CI, 88%-97%) for the standard postlabeling delay-CBF ratio, respectively. CONCLUSIONS: ASL MR imaging using Hadamard-encoded multiple postlabeling delays may be applicable as a screening tool because it can detect reduced CBF on brain perfusion SPECT with 100% sensitivity and a 100% negative predictive value in adult patients with ischemic Moyamoya disease.


Assuntos
Doença de Moyamoya , Adulto , Circulação Cerebrovascular , Humanos , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Doença de Moyamoya/diagnóstico por imagem , Marcadores de Spin
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