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2.
Transplant Proc ; 50(10): 3521-3526, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30577230

RESUMO

BACKGROUND: In new organ allocation policy, patients with hepatocellular carcinoma (HCC) experience a 6-month delay in being granted Model for End-Stage Liver Disease exception points. However, it may not be fair for patients at risk of early progression of HCC. METHODS: All patients who were diagnosed as United Network for Organ Sharing (UNOS) stage 1 or 2 of HCC between January 2004 and December 2012 were included. Patients who received surgical resection or liver transplant (LT) as a primary treatment and who did not receive any treatment for HCC were excluded. Patients with baseline Model for End-Stage Liver Disease score ≥22 were also excluded because they have a higher chance of receiving LT. Patients who developed extrahepatic progression within 1 year were considered as high-risk for early recurrence after LT. RESULTS: A total of 586 patients were included. Mean (SD) age was 59.9 (10.3) years and 409 patients (69.8%) were men. The cumulative incidence of estimated dropout was 8.9% at 6 months; size of the maximum nodule (≥3 cm) and nonachievement of complete response were independent factors. Extrahepatic progression developed in 16 patients (2.7%) within 1 year; size of the maximum nodule (4 cm) and alpha-fetoprotein level (>100 ng/mL) were independent predictors. CONCLUSIONS: The estimated dropout rate from the waiting list within 6 months was 8.9%. Advantage points might be needed for patients with maximum nodule size ≥3 cm or those with noncomplete response. However, in patients with maximum nodule size ≥4 cm or alpha-fetoprotein level >100 ng/mL, caution is needed.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Transplante de Fígado , Seleção de Pacientes , Listas de Espera , Adulto , Idoso , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Progressão da Doença , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Listas de Espera/mortalidade
3.
Pharmacopsychiatry ; 49(2): 51-6, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26845588

RESUMO

INTRODUCTION: This study aimed to investigate the association of multiple candidate genes with weight gain and appetite change during antipsychotic treatment. METHODS: A total of 233 single nucleotide polymorphisms (SNPs) within 60 candidate genes were genotyped. BMI changes for up to 8 weeks in 84 schizophrenia patients receiving antipsychotic medication were analyzed using a linear mixed model. In addition, we assessed appetite change during antipsychotic treatment in a different group of 46 schizophrenia patients using the Drug-Related Eating Behavior Questionnaire. RESULTS: No SNP showed a statistically significant association with BMI or appetite change after correction for multiple testing. We observed trends of association (P<0.05) between 19 SNPs of 11 genes and weight gain, and between 7 SNPs of 5 genes and appetite change. In particular, rs696217 in GHRL showed suggestive evidence of association with not only weight gain (P=0.001) but also appetite change (P=0.042). Patients carrying the GG genotype of rs696217 exhibited higher increase in both BMI and appetite compared to patients carrying the GT/TT genotype. DISCUSSION: Our findings suggested the involvement of a GHRL polymorphism in weight gain, which was specifically mediated by appetite change, during antipsychotic treatment in schizophrenia patients.


Assuntos
Antipsicóticos/efeitos adversos , Predisposição Genética para Doença/genética , Grelina/genética , Esquizofrenia/genética , Aumento de Peso/efeitos dos fármacos , Aumento de Peso/genética , Adulto , Antipsicóticos/uso terapêutico , Apetite/efeitos dos fármacos , Apetite/genética , Índice de Massa Corporal , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Esquizofrenia/tratamento farmacológico , Adulto Jovem
4.
Nat Nanotechnol ; 10(7): 598-602, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25915196

RESUMO

Since the discovery of the high-transition-temperature superconductors (HTSs), researchers have explored many methods to fabricate superconducting tunnel junctions from these materials for basic science purposes and applications. HTS circuits operating at liquid-nitrogen temperatures (∼77 K) would significantly reduce power requirements in comparison with those fabricated from conventional superconductors. The difficulty is that the superconducting coherence length is very short and anisotropic in these materials, typically ∼2 nm in the a-b plane and ∼0.2 nm along the c axis. The electrical properties of Josephson junctions are therefore sensitive to chemical variations and structural defects on atomic length scales. To make multiple uniform HTS junctions, control at the atomic level is required. In this Letter we demonstrate all-HTS Josephson superconducting tunnel junctions created by using a 500-pm-diameter focused beam of helium ions to directly write tunnel barriers into YBa2Cu3O(7-δ) (YBCO) thin films. We demonstrate the ability to control the barrier properties continuously from conducting to insulating by varying the irradiation dose. This technique could provide a reliable and reproducible pathway for scaling up quantum-mechanical circuits operating at liquid-nitrogen temperatures, as well as an avenue to conduct novel planar superconducting tunnelling studies for basic science.

5.
World J Surg ; 38(3): 592-8, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24305928

RESUMO

BACKGROUND: The aim of the present study was to evaluate the influence of intraoperative neuromonitoring (NM) on surgical training. The results of thyroidectomy performed by inexperienced surgeons under the supervision of a consultant surgeon without intraoperative neuromonitoring (ioNM) were compared to those of the operations performed without experienced assistance but under neuromonitoring control. MATERIALS AND METHODS: The study included the thyroid operations performed in our Department between 2005 and 2012. Among them, residents or fellows performed 1,116 procedures. Seven hundred sixty-five operations were conducted without neuromonitoring (NV group) and 351 with NM group. In the NV group 375 unilateral and 390 bilateral operations were performed. In the NM group 149 unilateral and 202 bilateral operations were performed. Primary end point of the study was the incidence of postoperative recurrent laryngeal nerve palsy. A secondary end point was the impact of ioNM on operating time and operative strategy. RESULTS: The incidence of recurrent laryngeal nerve (RLN) palsy was 2.6 % in the NV group and 2.7 % in the NM group [p = ns]. One case of bilateral RLN palsy was observed in the NV group. The operative time was longer in the NM group for both lobectomy and total thyroidectomy (50 vs. 56 min and 76 vs. 81 min, respectively; p < 0.05). CONCLUSIONS: The routine use of intermittent intraoperative neuromonitoring during thyroid operations does not reduce the incidence of RLN palsy. Nevertheless, it allows inexperienced surgeons to perform a safe operation with a complication rate comparable to that obtained under supervision of an experienced surgeon. Moreover, ioNM could avoid the unfortunate occurrence of a bilateral RLN palsy.


Assuntos
Eletromiografia , Internato e Residência , Mentores , Monitorização Intraoperatória/métodos , Doenças da Glândula Tireoide/cirurgia , Tireoidectomia/educação , Paralisia das Pregas Vocais/prevenção & controle , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Alemanha , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tireoidectomia/efeitos adversos , Resultado do Tratamento , Paralisia das Pregas Vocais/epidemiologia , Paralisia das Pregas Vocais/etiologia , Adulto Jovem
6.
Br J Cancer ; 106(5): 923-30, 2012 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-22294188

RESUMO

BACKGROUND: CD151 is a member of the tetraspanin family, which interacts with laminin-binding integrins and other tetraspanins. This protein is implicated in motility, invasion, and metastasis of cancer cells, but the prevalence of CD151 expression in subtypes of breast cancers and its influence on clinical outcome remains to be evaluated. METHODS AND RESULTS: The immunohistochemistry-based tissue microarray analysis showed that 127 (14.3%) cases overexpressed CD151 among 886 breast cancer patients. CD151 overexpression was found to be significantly associated with larger tumour size, higher nodal stage, advanced stage, absence of oestrogen receptor and progesterone receptor, and human epidermal growth factor receptor 2 overexpression. CD151 overexpression resulted in poorer overall survival (OS) (P<0.001) and disease-free survival (P=0.02), and stage II and III patients with CD151 overexpression demonstrated substantially poorer OS (P=0.0474 and 0.0169). In the five subtypes analyses, CD151 overexpression retained its adverse impact on OS in the Luminal A (P=0.0105) and quintuple-negative breast cancer (QNBC) subtypes, one subgroup of triple-negative breast cancer (P=0.0170). Multivariate analysis that included stage, subtype, and adjuvant chemotherapy showed that CD151 overexpression was independently associated with poor OS in invasive breast cancer. CONCLUSION: CD151 overexpression may be a potential molecular therapeutic target for breast cancer, especially in QNBC subtype and more advanced stages of breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Invasividade Neoplásica , Tetraspanina 24/biossíntese , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/biossíntese , Intervalo Livre de Doença , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Terapia de Alvo Molecular , Prognóstico , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/biossíntese , Receptores de Progesterona/metabolismo , Análise Serial de Tecidos
7.
J Obes ; 2011: 860169, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21461399

RESUMO

Introduction. Type 2 diabetes mellitus (T2DM) is one of the most important obesity-related comorbidities. This study was undertaken to characterise the effect of the biliopancreatic diversion with duodenal switch (BPD-DS) in morbidly obese and nonmorbidly obese diabetic patients. Methods. Outcome of 74 obese diabetic patients after BPD-DS and 16 non-obese diabetic patients after BPD or gastric bypass surgery was evaluated. Insulin usage, HbA(1c)-levels, and index of HOMA-IR (homeostasis model assessment of insulin resistence) were measured. Results. A substantial fraction of patients is free of insulin and shows an improved insulin sensitivity early after the operation, another fraction gets free of insulin in a 12-month period after the operation and a small fraction of long-term insulin users will not get free of insulin but nevertheless shows an improved metabolic status (less insulin needed, normal HbA(1c)-levels). Conclusion. BPD-DS leads to an improvement of T2DM in obese and non-obese patients. Nevertheless, more data is needed to clarify indications and mechanisms of action and to adjust our operation techniques to the needs of non-obese diabetic patients.

8.
Ann Oncol ; 22(7): 1554-1560, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21242587

RESUMO

BACKGROUND: There has been reported that the association between nodal spread and tumor size was disrupted in triple-negative breast cancer (TNBC) and it showed characteristically early relapse. The TNM (tumor-node-metastasis) staging system might not be equally effective as a prognostic indicator for all subtypes. The aim of our study was to evaluate the usefulness of the staging according to subtypes. PATIENTS AND METHODS: We conducted a retrospective analysis of invasive breast cancer patients who received curative surgery at Samsung Medical Center from 2000 to 2004. Relapse-free survivals (RFS) by stage were analyzed. RESULTS: Thousand eight hundred and seventy-nine patients who were available clinicopathologic data were included. These patients were divided into three subtypes: hormone receptor (HR)+, human epidermal growth factor receptor 2+, and triple negative groups. As the stage became more advanced, the slope of each stage of the RFS curves of patients with HR+ and HER2+ steadily increased. In contrast, RFS curves intermingled and showed overlap from stage 1 to 3A in TNBC patients. There was only wide separation of RFS curves between stage 1-3A and 3B-3C in TNBC. CONCLUSIONS: The current TNM staging system might not be enough for encompassing the tumor biology and for predicting outcomes to make therapeutic decisions for all BCs, especially for TNBC patients.


Assuntos
Neoplasias da Mama/classificação , Neoplasias da Mama/patologia , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Antineoplásicos/uso terapêutico , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Taxa de Sobrevida
9.
Br J Cancer ; 103(6): 845-51, 2010 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-20700125

RESUMO

BACKGROUND: Our purpose was to evaluate thymidine synthase (TS), thymidine phosphorylase (TP), and excision repair cross-complementation group 1 (ERCC1) expression as biomarkers for capecitabine and cisplatin (XP) combination chemotherapy in patients with metastatic oesophageal squamous cell cancer. METHOD: A total of 113 patients with metastatic oesophageal squamous cell cancer were treated with XP chemotherapy at the Samsung Medical Center between 2003 and 2007, of whom 72 had available clinical data and paraffin blocks for immunohistochemistry of TS, TP, and ERCC1. RESULTS: The median age of the 72 patients was 62 years. The overall response rate (RR) was 51.4%. The median progression-free survival (PFS) and overall survival (OS) were 4.2 and 12.0 months, respectively. High expression of TS and TP was associated with a higher RR than was low expression of TS and TP (54.1 vs 40.5%, P=0.022). Strong ERCC1 expression and a low TS score were identified as unfavourable independent risk factors for PFS (HR 10.71, 95% confidence interval (CI) 2.1-54.7, P=0.004 for strong ERCC1 expression; and HR 2.9, 95% CI 1.0-7.9, P=0.044 for low TS score). Strong ERCC1 expression was identified as an unfavourable independent risk factor for OS (HR 3.73, 95% CI 1.39-10.0, P=0.009). CONCLUSION: These data indicate that expression of TS, TP, and ERCC1 may be predictive markers for response and survival in patients with metastatic oesophageal squamous cell cancer receiving XP chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Neoplasias Esofágicas/tratamento farmacológico , Timidina Fosforilase/metabolismo , Timidilato Sintase/metabolismo , Adulto , Idoso , Capecitabina , Carcinoma de Células Escamosas/enzimologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Neoplasias Esofágicas/enzimologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sobrevida , Resultado do Tratamento
10.
Br J Radiol ; 83(991): 585-9, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20442279

RESUMO

The purpose of this study was to evaluate the high-resolution computed tomographic (HRCT) findings of five adult patients (either immunocompromised or immunocompetent) with herpes simplex virus (HSV) pneumonia. We retrospectively assessed HRCT images of 5 patients (all male patients, age range 39-70 years; mean 62 years) with HSV pneumonia. The specific pathological findings that allowed for a definite diagnosis of HSV pneumonia included the presence of intranuclear inclusion bodies on haematoxylin and eosin staining, or positive immunohistochemical staining. High-resolution CT scans (HiSpeed Advantage or LightSpeed QX/i, GE Healthcare) using 1- or 1.25-mm collimation at 10-mm intervals without intravenous contrast medium injection were assessed, in particular for the presence and distribution of parenchymal abnormalities including ground-glass attenuation, airspace consolidation, nodules and interlobular septal thickening. In two patients, pathological specimens were obtained from open lung biopsy or bronchoscopic biopsy, and were correlated with HRCT findings. Three HRCT patterns of pulmonary abnormalities were identified in our series of HSV pneumonia: predominant areas of diffuse or multifocal ground-glass attenuation, predominant areas of multifocal peribronchial consolidations, and a mixed pattern of both. Histopathologically, areas of ground-glass attenuation seen on HRCT corresponded to diffuse alveolar damage in one patient who underwent open lung biopsy. No specific differences in HRCT findings were seen between the immunocompromised and the immunocompetent patients. In patients suspected of having an acute lower respiratory infection, whether immunocompromised or immunocompetent, a possibility of HSV pneumonia can be included in differential diagnoses when diffuse or multifocal areas of ground-glass attenuation and/or consolidations are seen on HRCT.


Assuntos
Herpes Simples/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Simplexvirus , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Líquido da Lavagem Broncoalveolar/virologia , Meios de Contraste , Herpes Simples/imunologia , Herpes Simples/virologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Intensificação de Imagem Radiográfica , Estudos Retrospectivos , Escarro/virologia
11.
Phytomedicine ; 16(11): 1042-51, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-19427179

RESUMO

Large amounts of brain nitric oxide are produced over several hours after a stroke. This probably causes DNA strand nicks, nitration of cytosolic components of neurons, and ultimately neuronal death. Oxymatrine and matrine are two major alkaloids of the Chinese herb Sophora flavescens Ait. (Leguminosae); they have been demonstrated to inhibit liver injury during warm ischemia and reperfusion and to induce apoptosis, respectively, in vivo and in vitro. However, the neuroprotective efficacy of the EtOAc extract of S. flavescens (ESF) without the alkaloids has not been explored. This study investigated the inhibitory efficacy of ESF, which contain two major flavonoids kurarinone (45.5%) and sophoraflavone G (14.7%), in focal cerebral ischemia. Focal cerebral ischemia was induced using the middle cerebral artery occlusion (MCAO) method. After 1.5h of MCAO and 24h of reperfusion, the extent of neurological deficits and the infarct volume were measured in Sprague-Dawley rats. Compared with carnosine (50mg/kg), as positive control ESF (20mg/kg) significantly reduced infarct volume and neurological deficits. Treatment of human SH-SY5Y cells with sodium nitroprusside (SNP), a nitric oxide donor, decreased cell viability by causing apoptosis-like cell death. ESF significantly inhibited caspase-3-like enzyme activity and DNA fragmentation. The level of active caspase-3 was maximal 6h after SNP treatment. However, active caspase-3 and apoptosis were dose-dependently inhibited by ESF treatment. Flow cytometry analysis showed that ESF significantly inhibited cell apoptosis (p<0.05) and reduced the apoptotic index by 79.9% (p<0.01). These results indicate that ESF is neuroprotective in focal cerebral ischemia and the flavonoids in ESF might be responsible for its neuroprotective activity in rats, alone or in part.


Assuntos
Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/isolamento & purificação , Fitoterapia , Extratos Vegetais/uso terapêutico , Sophora/química , Animais , Apoptose/efeitos dos fármacos , Western Blotting , Caspase 3/metabolismo , Linhagem Celular Tumoral , Cromatografia Líquida de Alta Pressão , Fragmentação do DNA/efeitos dos fármacos , Humanos , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Nitroprussiato , Extratos Vegetais/farmacologia , Raízes de Plantas/química , Ratos , Ratos Sprague-Dawley
12.
Clin Exp Allergy ; 39(2): 203-12, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19187332

RESUMO

BACKGROUND: Toluene diisocyanate (TDI) is the most important cause of occupational asthma, but the genetic mechanism of TDI-induced asthma is still unknown. OBJECTIVE: The objective of the study was to identify susceptibility alleles associated with the TDI-induced asthma phenotype. METHODS: We conducted a genome-wide association study in 84 patients with TDI-induced asthma and 263 unexposed healthy normal controls using Affymetrix 500K SNPchip. We also investigated the relationships between genetic polymorphisms and transcript levels in Epstein-Barr virus-transformed lymphoblastoid cell lines from patients with TDI-induced asthma enrolled in this study. RESULTS: Genetic polymorphisms of CTNNA3 (catenin alpha 3, alpha-T catenin) were significantly associated with the TDI-induced asthma phenotype (5.84 x 10(-6) for rs10762058, 1.41 x 10(-5) for rs7088181, 2.03 x 10(-5) for rs4378283). Carriers with the minor haplotype, HT2 [GG], of two genetic polymorphisms (rs10762058 and rs7088181) showed significantly lower PC(20) methacholine level (P=0.041) and lower mRNA expression of CTNNA3 than non-carriers (P=0.040). A genetic polymorphism in the 3' downstream region of CTNNA3 (rs1786929), as identified by DNA direct sequencing, was significantly associated with the TDI-induced asthma phenotype (P=0.015 in recessive analysis model) and the prevalence of serum-specific IgG to cytokeratin 19 (P=0.031). CONCLUSION: These findings suggested that multiple genetic polymorphisms of CTNNA3 may be determinants of susceptibility to TDI-induced asthma.


Assuntos
Asma/induzido quimicamente , Asma/genética , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único/genética , Tolueno 2,4-Di-Isocianato/efeitos adversos , alfa Catenina/genética , Adulto , Linfócitos B/metabolismo , Testes de Provocação Brônquica , Linhagem Celular Transformada , Feminino , Expressão Gênica/genética , Frequência do Gene , Predisposição Genética para Doença/genética , Genótipo , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Queratina-19/imunologia , Masculino , Pessoa de Meia-Idade , Doenças Profissionais/genética , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Risco
13.
Transplant Proc ; 40(8): 2581-4, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18929807

RESUMO

BACKGROUND: The transplantation of isolated islets is believed to be an attractive approach for cure of diabetes mellitus. Heat-shock protein (HSP70), which plays a vital role in cellular protection, has been detected in various tissues subjected to stress. Glutamine (GLN) is an important cellular fuel and an essential precursor for the antioxidant glutathione (GSH). It is believed to enhance cellular survival against a variety of stressful stimuli through HSP70. Thus, we performed this study to examine the hypothesis that preoperative GLN administration induces HSP70 and GSH expression before islet transplantation attenuating ischemic damage to rat islets. METHODS: Adult male Sprague-Dawley (SD) rats were randomly divided into two groups according to the administration of GLN after islet isolation. Group A served as the controls, receiving no GLN. Group B islet cells were cultured with L-GLN (10 mmol/L) supplementation for 24 hours. The GSH levels were measured in islet cells. Both HSP70 and proteins related to apoptosis were analyzed in islet cells by Western blots. Isolated rat islets were cultured with interleukin (IL)-1beta. Nitrite production was measured using the Griess reagent. RESULTS: The GSH levels were significantly elevated in the glutamine-treated group. HSP70 expression in islets treated with GLN was markedly stronger compared with the control group. The basal Bcl-2 expression was markedly increased by GLN treatment. The GLN-treated group showed attenuated IL-1beta-induced injury in association with NO production. CONCLUSION: These results suggested that preoperative GLN administration induced HSP70 and GSH expressions before islet transplantation, thus attenuating IL-1beta-induced injury in association with NO production and apoptosis, which might be potential tool to mitigate the ischemic damage to islet cells and the early inflammation at the site of implantation through a self-protective mechanism.


Assuntos
Glutamina/farmacologia , Glutationa/biossíntese , Proteínas de Choque Térmico HSP70/biossíntese , Isquemia/prevenção & controle , Ilhotas Pancreáticas/fisiologia , Animais , Técnicas de Cultura de Células/métodos , Sobrevivência Celular/efeitos dos fármacos , Glucose/farmacologia , Temperatura Alta , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Ilhotas Pancreáticas/patologia , Transplante das Ilhotas Pancreáticas/fisiologia , Masculino , Ratos , Ratos Sprague-Dawley
14.
Clin Exp Rheumatol ; 26(4): 646-8, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18799097

RESUMO

OBJECTIVE: The presence of hypoxia in rheumatoid synovium has been well known, but exact correlation between hypoxia and synovitis is unclear. The aim of our study was to investigate the time and spatial relationship and the correlation of severity between hypoxia and synovitis in pre-arthritic or early stage of inflammatory joint disease. METHODS: DBA/1J mice were injected intradermally with type II collagen and adjuvant solution to induce arthritis; mice injected with only adjuvant were used as a control group. CIA and control mice were sacrificed weekly after the injection to evaluate serial pathological changes. H&E stain and hydroxyprobe-1 stain were performed to look at the status of inflammation and hypoxia. RESULTS: In serial observations of tissue pathology, we could note the inflammation of synovium developing a week after the injection of type II collagen. Hypoxic change, measured by the hydroxyprobe-1 stain, was also identified in synovium as early as 1 week after the collagen injection, prior to clinically evident arthritis. In addition, we could observe that inflammation and hypoxia co-localize in the synovium and there was a positive correlation between the severity of hypoxia and the degree of synovitis. CONCLUSION: Our results demonstrate that hypoxia takes place in synovium at the pre-arthritic stage of disease and have a close spatial relationship and a positive severity correlation with synovitis.


Assuntos
Artrite Reumatoide/fisiopatologia , Hipóxia/fisiopatologia , Sinovite/fisiopatologia , Animais , Artrite Experimental , Artrite Reumatoide/patologia , Hipóxia/patologia , Camundongos , Sinovite/patologia
15.
Cancer Chemother Pharmacol ; 61(4): 569-77, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17508214

RESUMO

BACKGROUND: The aim of the study was to identify reliable predictive biological markers for treatment outcome following neoadjuvant adriamycin/docetaxel (AT) chemotherapy in locally advanced breast cancer patients. MATERIALS AND METHODS: This study was a phase II study on AT neoadjuvant chemotherapy in locally advanced breast cancer patients. Patients received 50 mg/m(2) of doxorubicin intravenously (IV) over 15 min followed by docetaxel 75 mg/m(2) infused over 1 h, repeated every 3 weeks for three cycles. Surgery was performed within 3-4 weeks following the last cycle of chemotherapy. We analyzed the pre-treatment and post-treatment expression levels of ER, PgR, HER-2, Ki-67 proliferation index, and p53 and examined the correlation between the markers and clinical parameters with treatment response, overall survival and relapse-free survival following neoadjuvant treatment. RESULTS: From July 2001 to September 2004, 61 patients were enrolled. The meaningful parameters adversely influencing survival were post-treatment ER(-) status (P = 0.013) and post-treatment Ki-67 index above 1.0% (P = 0.013). At the multivariate level, the post-treatment Ki-67 proliferation index < or = 1.0 was the only meaningful prognostic factor for better survival (P = 0.033). Notably, tumors with Ki-67 index < or = 1.0 were more likely to express ER with statistical significance (P = 0.002). Tumors with ER(+) and Ki-67 index < or = 1.0 showed the highest survival rate, followed by ER(+) and Ki-67 index > 1.0%, ER(-) and Ki-67 < or = 1.0%, and ER(-) and Ki-67 > 1.0% with the worst survival (P = 0.033). CONCLUSION: Collectively, post-treatment ER status and Ki-67 proliferation index were prognostic of overall survival following neoadjuvant AT chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/biossíntese , Terapia Neoadjuvante , Receptores de Estrogênio/biossíntese , Adulto , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antineoplásicos Fitogênicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Intervalo Livre de Doença , Docetaxel , Doxorrubicina/administração & dosagem , Feminino , Genes p53/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Receptores de Progesterona/biossíntese , Receptores de Progesterona/efeitos dos fármacos , Análise de Sobrevida , Taxoides/administração & dosagem
16.
AJNR Am J Neuroradiol ; 28(7): 1242-8, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17698523

RESUMO

BACKGROUND AND PURPOSE: Because of the high vascularization of hemangiomas, preoperative misinterpretation may result in unexpected intraoperative hemorrhage and incomplete resection, which results in the persistence of clinical symptoms or recurrence. Our purpose was to analyze various MR imaging features of a spinal epidural hemangioma with histopathologic correlation. MATERIALS AND METHODS: After searching through the pathology data bases in 3 hospitals, we included 14 patients (9 male and 5 female; mean age, 38 years; age range, 2-62 years) with spinal epidural hemangiomas confirmed by surgical resection after MR imaging. Three radiologists reviewed the MR imaging in consensus and categorized the features into subtypes on the basis of histopathologic findings. RESULTS: We categorized the MR imaging features as follows: type A for a cystlike mass with T1 hyperintensity (2 cases, arteriovenous type with an organized hematoma), type B for a cystlike mass with T1 isointensity (3 cases, venous type), type C for a solid hypervascular mass (7 cases, cavernous type), and type D for an epidural hematoma (2 cases, cavernous type with hematoma). Types A and B had frequent single segmental involvement (4/5), whereas types C and D had multisegmental involvement in all. Regardless of MR types, lobular contour (8/14) and a rim of low T2 signal intensity (8/14) of the mass were common. T1 hyperintensity of the mass was occasionally seen (5/14). CONCLUSIONS: Spinal epidural hemangiomas can have various MR imaging features according to their different histopathologic backgrounds. In addition to common features such as solid hypervascularity, lobular contour, and a rim of low T2 signal intensity, T1 hyperintensity or multisegmental involvement may also be a clue in the differential diagnosis of a spinal epidural hemangioma.


Assuntos
Neoplasias Epidurais/patologia , Hemangioma/patologia , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento por Ressonância Magnética/métodos , Adolescente , Vértebras Cervicais/patologia , Criança , Pré-Escolar , Feminino , Humanos , Vértebras Lombares/patologia , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Estatística como Assunto , Vértebras Torácicas/patologia
17.
Allergy ; 62(8): 934-42, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17620072

RESUMO

BACKGROUND: Eosinophils are recruited into the affected tissue of asthma and atopic dermatitis (AD) patients. IL-5 and IL-5R are highly expressed in the AD skin lesions, yet the reported levels of IL-8 are controversial. METHOD: We genotyped 17 singlenucleotide polymorphisms (SNPs) from five genes of the 1120 case-control samples (646 AD and 474 controls). We measured the serum IL-5 concentrations in 87 individuals [36 ADe (AD extrinsic), 18 ADi (AD intrinsic) and 33 controls] by ELISA, and compared the results among these groups. RESULT: The rs2522411SNP and haplotype T-A in the IL-5 gene were significantly associated with the ADe. The serum IL-5 concentration was higher in the ADe than that in the ADi patients without any correlation with the rs2522411SNP. In the IL-5RA gene, the rs334809SNP showed a weak association with AD, and the rs6771148SNP and the haplotype T-C-T of the three adjacent tagged SNPs had an effect on the blood eosinophil counts and the serum ECP levels in the AD patients. However, we could not detect any relationship between AD and the SNPs in the IL-8 and IL-8R genes. CONCLUSION: We found that the rs2522411SNP and the haplotype T-A in the IL-5 gene and the serum IL-5 levels were strongly associated with the allergic type of AD, but not with the nonallergic type of AD. The association of the rs6771148SNP and the haplotype T-C-T in the IL5RA gene with the blood eosinophil counts and the serum ECP levels indicates that the IL5RA gene has a role for controlling eosinophils in the peripheral blood.


Assuntos
Dermatite Atópica/genética , Dermatite Atópica/imunologia , Subunidade alfa de Receptor de Interleucina-5/genética , Interleucina-5/genética , Polimorfismo de Nucleotídeo Único/imunologia , Adolescente , Adulto , Povo Asiático , Estudos de Casos e Controles , Criança , Dermatite Atópica/sangue , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Marcadores Genéticos/genética , Marcadores Genéticos/imunologia , Humanos , Interleucina-5/biossíntese , Subunidade alfa de Receptor de Interleucina-5/biossíntese , Masculino , Polimorfismo de Nucleotídeo Único/genética
18.
Clin Exp Allergy ; 37(6): 865-71, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17517100

RESUMO

BACKGROUND: IL-18 is a proinflammatory cytokine that plays an important role for T-helper type 1 (Th1) and Th2 cytokine in the presence/absence of IL-12. It has been recently shown that human IL-18 plays a role in atopic dermatitis (AD) by enhancing IL-4 and IL-13 production and by stimulating the synthesis of IgE. OBJECTIVE: We wanted to evaluate the associations of single-nucleotide polymorphism (SNP) and the haplotype in the IL-18 gene, hence we performed genotyping for the SNPs in the IL-18 gene in AD patients and normal controls. METHOD: We genotyped three SNPs from the IL-18 gene for the 1120 case-control samples (646 AD patients and 474 normal controls). We measured the serum IL-18, IL-4 and IL-13 concentrations in 74 individuals (25 ADe, 25 ADi and 24 controls) by performing ELISA. RESULT: The rs795467 SNP and haplotype T-T-C were significantly associated with AD, and especially between the ADe and normal control groups (P=0.03 and 0.01). The serum IL-18 concentration was higher in the AD group than in the normal controls without any correlation with the rs795467 polymorphism. We did not find any correlations between the serum IL-18 levels and the SCORing atopic dermatitis index, the blood eosinophil counts and the ECP, and there was no correlation between the serum IL-18 levels and the serum IL-4 and IL-13 levels. CONCLUSION: We found that the one SNP and the haplotype T-T-C were strongly associated with the allergic type of AD, but not with the non-allergic intrinsic type. These data support the hypothesis that IL-18 up-regulates IgE production, yet more experiments will be needed to prove the in vivo involvement of Th2 cytokine.


Assuntos
Dermatite Atópica/genética , Haplótipos/genética , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Adulto , Povo Asiático , Estudos de Casos e Controles , Criança , Pré-Escolar , Dermatite Atópica/sangue , Dermatite Atópica/imunologia , Feminino , Haplótipos/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Interleucina-12/sangue , Interleucina-12/imunologia , Interleucina-13/sangue , Interleucina-13/imunologia , Interleucina-18/sangue , Interleucina-18/imunologia , Interleucina-4/sangue , Interleucina-4/imunologia , Coreia (Geográfico) , Masculino , Células Th1/imunologia , Células Th2/imunologia , Regulação para Cima/genética , Regulação para Cima/imunologia
19.
Clin Radiol ; 62(3): 227-32, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17293215

RESUMO

AIM: The objective of this study was to identify whether there were any significant differences in the computed tomography (CT) findings of an intracavitary aspergilloma and a cavitating lung cancer containing a mural nodule. MATERIALS AND METHODS: The CT and histopathological findings of 12 patients (male:female ratio 3:9; aged 51-76 years) with cavitating lung cancer containing a mural nodule and 26 patients (male:female ratio 14:12; aged 29-72 years) with intracavitary aspergilloma were retrospectively reviewed. RESULTS: The mural nodules within cavitating lung cancer were more enhanced (p<0.001) and showed a nondependent location more frequently (p=0.012) than those of intracavitary aspergillomas. The cavitary walls were thicker in cavitating lung cancer (mean 5.8mm thick) than those in intracavitary aspergillomas (mean 2.6mm thick; p=0.035). Adjacent bronchiectasis and volume decrease of the involved lobe were observed more frequently in intracavitary aspergillomas than in cavitating lung cancers (p<0.001 and p=0.008, respectively). CONCLUSION: Whether a mural nodule within a cavitary lesion is contrast-enhanced or not is one of the most important features in making a differential diagnosis between an intracavitary aspergilloma and a cavitating lung cancer. Assessment of dependent location of a mural nodule within the cavity and wall thickness of the cavity itself can also be helpful for differentiation.


Assuntos
Aspergilose/diagnóstico por imagem , Pneumopatias Fúngicas/diagnóstico por imagem , Neoplasias Pulmonares/diagnóstico por imagem , Nódulo Pulmonar Solitário/diagnóstico por imagem , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
20.
Cytopathology ; 18(1): 20-7, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17250599

RESUMO

OBJECTIVE: To analyse fine needle aspirates from solitary fibrous tumour (SFT) of the pleura and to elucidate the cytological features unique to these tumours and differential diagnostic findings of benign and malignant SFTs. METHODS: Fine needle aspiration (FNA) cytology slides from eight cases of SFT of the pleura, including six benign and two malignant SFTs, were reviewed. The subsequent histological slides were also examined. RESULTS: Cytological diagnoses from six histologically proven cases of benign SFTs were low-grade sarcoma (one), non-small cell carcinoma (one), malignant tumour (1) and benign (three). Two cases of malignant SFTs were cytologically diagnosed as malignancy. The aspirates showed a varying degree of cellularity. Most smears were composed of single, scattered fusiform cells, and irregular loose aggregates of oval to spindle cells intimately admixed with dense collagenous stroma. Two malignant SFTs had a greater number of cells in clusters, and displayed mitotic activity, without significant cytological atypia. CONCLUSIONS: The diagnosis of SFT may be suggested by a combination of cytological and radiological findings. The precise determination of malignancy for SFT, however, is not usually straightforward on the basis of cytological features alone. The findings of highly cellular clusters and mitotic activity in the FNA cytological smear can help differentiate malignant from benign SFTs.


Assuntos
Biópsia por Agulha Fina/métodos , Neoplasias de Tecido Fibroso/patologia , Neoplasias Pleurais/patologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias de Tecido Fibroso/diagnóstico , Neoplasias Pleurais/diagnóstico , Estudos Retrospectivos
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