RESUMO
The King AbdulAziz City for Science & Technology in the Kingdom of Saudi Arabia plans to build a 10âMeV, 15âkW linear accelerator (LINAC) for electron beam and X-ray. The accelerator will be supplied by EB Tech, Republic of Korea, and the design and construction of the accelerator building will be conducted in the cooperation with EB Tech. This report presents the shielding analysis of the accelerator building using the Monte Carlo N-Particle Transport Code (MCNP). In order to improve the accuracy in estimating deep radiation penetration and to reduce computation time, various variance reduction techniques, including the weight window (WW) method, the deterministic transport (DXTRAN) spheres were considered. Radiation levels were estimated at selected locations in the shielding facility running MCNP6 for particle histories up to 1.0×10+8. The final results indicated that the calculated doses at all selected detector locations met the dose requirement of 50âmSv/yr, which is the United State Nuclear Regulatory Commission (U.S. NRC) requirement.
Assuntos
Aceleradores de Partículas , Proteção Radiológica , Elétrons , Desenho de Equipamento , Método de Monte Carlo , Proteção Radiológica/instrumentação , Proteção Radiológica/métodos , Raios XRESUMO
OBJECTIVES: Serous cystic neoplasm (SCN) is a cystic neoplasm of the pancreas whose natural history is poorly known. The purpose of the study was to attempt to describe the natural history of SCN, including the specific mortality. DESIGN: Retrospective multinational study including SCN diagnosed between 1990 and 2014. RESULTS: 2622 patients were included. Seventy-four per cent were women, and median age at diagnosis was 58â years (16-99). Patients presented with non-specific abdominal pain (27%), pancreaticobiliary symptoms (9%), diabetes mellitus (5%), other symptoms (4%) and/or were asymptomatic (61%). Fifty-two per cent of patients were operated on during the first year after diagnosis (median size: 40â mm (2-200)), 9% had resection beyond 1â year of follow-up (3â years (1-20), size at diagnosis: 25â mm (4-140)) and 39% had no surgery (3.6â years (1-23), 25.5â mm (1-200)). Surgical indications were (not exclusive) uncertain diagnosis (60%), symptoms (23%), size increase (12%), large size (6%) and adjacent organ compression (5%). In patients followed beyond 1â year (n=1271), size increased in 37% (growth rate: 4â mm/year), was stable in 57% and decreased in 6%. Three serous cystadenocarcinomas were recorded. Postoperative mortality was 0.6% (n=10), and SCN's related mortality was 0.1% (n=1). CONCLUSIONS: After a 3-year follow-up, clinical relevant symptoms occurred in a very small proportion of patients and size slowly increased in less than half. Surgical treatment should be proposed only for diagnosis remaining uncertain after complete workup, significant and related symptoms or exceptionally when exists concern with malignancy. This study supports an initial conservative management in the majority of patients with SCN. TRIAL REGISTRATION NUMBER: IRB 00006477.
Assuntos
Cistadenoma Seroso , Neoplasias Pancreáticas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/mortalidade , Cistadenoma Seroso/patologia , Cistadenoma Seroso/terapia , Europa (Continente) , Feminino , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos , Sociedades Médicas , Adulto JovemRESUMO
AIM: The frequent presence of acellular mucin in specimens showing pathological complete response to preoperative chemoradiotherapy (CRT) and the poor response to preoperative CRT in mucinous rectal cancer have been reported. However, the prevalence and prognostic significance of cellular and acellular mucin have not been evaluated in resected specimens from patients with mucinous rectal cancer who undergo preoperative CRT. METHOD: We retrospectively evaluated the clinicopathological features and prognostic significance of mucin in resected specimens from 59 consecutive patients with mucinous rectal cancer who underwent long-course CRT followed by resection between January 2000 and December 2009. Patients were categorized according to the presence of mucin, as identified by pathological analysis. The clinicopathological findings and oncological results were compared. RESULTS: Mucin was identified in 25 of 59 patients with mucinous rectal cancer (42.4%). Mucin was more frequent in men (hazard ratio = 23.94, 95% confidence interval = 1.875-305.504, P = 0.015) and in specimens showing a good tumour response grade (hazard ratio = 64.26, 95% confidence interval = 6.940-595.045, P < 0.001). With a median follow-up of 67.7 (range 8.6-133.2) months, the 5-year overall survival (60.7% without mucin vs 51.4% with mucin, P = 0.898) and disease-free survival (59.9% without mucin vs 56.9% with mucin, P = 0.813) did not differ between the groups. CONCLUSION: The presence of mucin in rectal cancer with mucinous differentiation after preoperative CRT and resection is associated with male gender and a good tumour response grade, without significant impact on oncological outcome.
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Adenocarcinoma Mucinoso/metabolismo , Quimiorradioterapia , Mucinas/metabolismo , Terapia Neoadjuvante , Neoplasias Retais/metabolismo , Reto/cirurgia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias Retais/patologia , Neoplasias Retais/terapia , Estudos Retrospectivos , Fatores Sexuais , Taxa de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of this study was to determine the clinical efficacy of the newly developed OrthoMTA and RetroMTA, compared to conventionally used ProRoot MTA, for pulpotomy in primary teeth. MATERIAL AND METHODS: In this randomized clinical trial, 151 molars from 102 children, who met the inclusion criteria and were 3-10 years old, were enrolled. Ultimately, 143 teeth were divided in a randomized, single-blind manner into three groups according to the planned treatment: RetroMTA (n = 49 teeth), OrthoMTA (n = 47 teeth) or ProRoot MTA (n = 47 teeth). Clinical and radiographic follow-up examinations were conducted at 3, 6 and 12 months postoperatively. RESULTS: By the end of the study period, 109 teeth were evaluated at 12 months. The radiographic success rates in these three groups were 100%, 94.7% and 94.7%, respectively; the corresponding clinical success rates were 100%, 97.4% and 100%. The Kaplan-Meier survival function curves relative to clinical and radiographic cumulative survival rates did not differ significantly between the three groups. CONCLUSIONS: The success rates of RetroMTA, OrthoMTA and ProRoot MTA are indistinguishable, indicating that pulpotomy can be carried out successfully in primary molars with the newly developed materials.
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Compostos de Alumínio/uso terapêutico , Compostos de Cálcio/uso terapêutico , Óxidos/uso terapêutico , Agentes de Capeamento da Polpa Dentária e Pulpectomia/uso terapêutico , Pulpotomia , Silicatos/uso terapêutico , Dente Decíduo , Criança , Pré-Escolar , Combinação de Medicamentos , Feminino , Humanos , Masculino , Método Simples-Cego , Dente Decíduo/diagnóstico por imagem , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to investigate the clinical relevance of splenic vein thrombosis (SVT) in the splenic vein remnant following minimally invasive distal pancreatosplenectomy (DPS). METHODS: Medical records of patients who underwent laparoscopic or robotic distal pancreatectomy (DP) with or without splenectomy between January 2006 and August 2012 were reviewed. Rates of SVT and clinically relevant postoperative pancreatic fistula (POPF) were compared in a group of patients undergoing DPS and a group having spleen-preserving DP. RESULTS: Seventy-nine patients had minimally invasive DP, of whom 38 (48 per cent) developed SVT in the splenic vein remnant. DPS was associated with POPF (P = 0.001) and SVT (P < 0.001). SVT length was closely related to the amount of peripancreatic fluid collection (P = 0.025) and POPF (P = 0.045). In a comparison of splenic vessel-sacrificing, spleen-preserving DP and DPS, postoperative platelet count was significantly higher in the DPS group (P < 0.001). In addition, grade of SVT (P = 0.092) and POPF (P = 0.065) tended to be associated with DPS, suggesting that SVT may be related to both splenectomy and POPF. CONCLUSION: Minimally invasive DPS is associated with SVT and POPF. Preservation of the spleen should be considered when treating patients with benign and borderline malignant tumours of the distal pancreas.
Assuntos
Laparoscopia/efeitos adversos , Pancreatectomia/efeitos adversos , Fístula Pancreática/etiologia , Robótica , Veia Esplênica , Trombose Venosa/etiologia , Feminino , Humanos , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão , Pancreatectomia/métodos , Neoplasias Pancreáticas/cirurgia , Pancreatite/cirurgia , Contagem de Plaquetas , Estudos Retrospectivos , Esplenectomia/efeitos adversosRESUMO
BACKGROUND: Since there are known adverse health impacts of traffic-related air pollution, while at the same time there are potential health benefits from greenness, it is important to examine more closely the impacts of these factors on indoor air quality in urban schools. OBJECTIVE: This study investigates the association of road proximity and urban greenness to indoor traffic-related fine particulate matter (PM2.5), nitrogen dioxide (NO2), and black carbon (BC) in inner-city schools. METHODS: PM2.5, NO2, and BC were measured indoors at 74 schools and outdoors at a central urban over a 10-year period. Seasonal urban greenness was estimated using the Normalized Difference Vegetation Index (NDVI) with 270 and 1230 m buffers. The associations between indoor traffic-related air pollution and road proximity and greenness were investigated with mixed-effects models. RESULTS: The analysis showed linear decays of indoor traffic-related PM2.5, NO2, and BC by 60%, 35%, and 22%, respectively for schools located at a greater distance from major roads. The results further showed that surrounding school greenness at 270 m buffer was significantly associated (p < 0.05) with lower indoor traffic-related PM2.5: -0.068 (95% CI: -0.124, -0.013), NO2: -0.139 (95% CI: -0.185, -0.092), and BC: -0.060 (95% CI: -0.115, -0.005). These associations were stronger for surrounding greenness at a greater distance from the schools (buffer 1230 m) PM2.5: -0.101 (95% CI: -0.156, -0.046) NO2: -0.122 (95% CI: -0.169, -0.075) BC: -0.080 (95% CI: -0.136, -0.026). These inverse associations were stronger after fully adjusting for regional pollution and meteorological conditions. IMPACT STATEMENT: More than 90% of children under the age of 15 worldwide are exposed to elevated air pollution levels exceeding the WHO's guidelines. The study investigates the impact that urban infrastructure and greenness, in particular green areas and road proximity, have on indoor exposures to traffic-related PM2.5, NO2, and BC in inner-city schools. By examining a 10-year period the study provides insights for air quality management, into how road proximity and greenness at different buffers from the school locations can affect indoor exposure.
Assuntos
Poluentes Atmosféricos , Poluição do Ar em Ambientes Fechados , Cidades , Dióxido de Nitrogênio , Material Particulado , Instituições Acadêmicas , Emissões de Veículos , Material Particulado/análise , Dióxido de Nitrogênio/análise , Poluição do Ar em Ambientes Fechados/análise , Humanos , Poluentes Atmosféricos/análise , Emissões de Veículos/análise , Fuligem/análise , Fuligem/efeitos adversos , Exposição Ambiental/análise , Poluição Relacionada com o Tráfego/efeitos adversos , Poluição Relacionada com o Tráfego/análise , Monitoramento Ambiental , CriançaRESUMO
Domino kidney paired donation (KPD) is a method by which an altruistic living nondirected donor (LND) is allocated to a pool of incompatible donor-recipient pairs (DRP) and a series of KPDs is initiated. To evaluate the feasibility and clinical outcomes of multicenter domino KPD, we retrospectively analyzed a cohort of DRPs who underwent domino KPD between February 2001 and July 2007 at one of 16 transplant centers. One hundred seventy-nine kidney transplants were performed, with 70 domino chains initiated by altruistic LND. There were 45 two-pair chains, 15 three-pair chains, 7 four-pair chains, 2 five-pair chains and 1 six-pair chain. A majority of donors were spouses (47.5%) or altruistic LNDs (39.1%). DRPs with a blood type O recipient or an AB donor comprised 45.9% of transplanted DRPs. HLA mismatch improved in transplanted donors compared to intended donors in pairs enrolled to improve HLA mismatch (3.4 +/- 0.7 vs. 4.8 +/- 1.0, p < 0.001). One-year and 5-year graft survival rates were 98.3% and 87.7%, respectively, with a median follow-up of 46 months. One-year and 5-year patient survival rates were 97.2% and 90.8%, respectively. In conclusion, multicenter domino KPD could multiply the benefits of donation from LNDs, with patients and graft survival rates comparable to those seen with conventional KPD.
Assuntos
Transplante de Rim , Doadores de Tecidos , Altruísmo , Humanos , Resultado do TratamentoRESUMO
INTRODUCTION: Kidney transplant recipients have a higher quality of life and consume fewer health care resources compared with patients on dialysis. However, optimal timing of transplantation has been controversial. Recent studies have clearly demonstrated that preemptive renal transplantation is associated with better graft survival, lower complications, and better cost-effective outcomes. We evaluated differential effects on long-term outcomes according to dialysis type/duration versus no dialysis. MATERIALS AND METHODS: We retrospectively analyzed 499 cases of first living-donor kidney transplantations performed in our center from January 1990 to January 2007. We compared 3 groups according to graft survival, acute and chronic rejection, postoperative complication, and delayed graft function rates. The mean duration of follow-up was 119.1 +/- 47.2 months. RESULTS: Among 499 cases, 81 cases were preemptive renal transplantations with 418 cases hemodialysis [HD], 343 cases, peritoneal dialysis [PD] 75 cases) performed after dialysis. The 1-, 5-, and 10-year graft survival rates were 98.8%, 89.5%, 79.4% among the preemptive renal transplantation group and 92.4%, 78.2%, and 69.2% and 85.3%, 74.5%, and 68.2% (P = .03) in the dialysis groups (HD, PD), respectively. The differential effect of pretransplantation HD or PD was not significant. However, the graft survival rates in the HD group were not significantly higher than the PD group (P = .61). The duration of dialysis was not associated with graft survival. CONCLUSION: We suggest that preemptive renal transplantation should be the first choice of treatment for patients with end-stage renal disease.
Assuntos
Sobrevivência de Enxerto/fisiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/fisiologia , Doadores Vivos , Adolescente , Adulto , Idoso , Creatinina/sangue , Família , Feminino , Seguimentos , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal , Complicações Pós-Operatórias/epidemiologia , Diálise Renal , Estudos Retrospectivos , Taxa de Sobrevida , Sobreviventes , Fatores de Tempo , Resultado do TratamentoRESUMO
Porcine-specific obstacles in islet isolation frequently result from the low purity or contamination with exocrine tissues. We implemented a new technique involving as capsulation of islets with excess exocrine tissue as a beneficial material to address those difficulties. Pig islets were hand-picked as high purity (HI) or low purity (LO) islets containing significant amounts of exocrine tissue. We performed static (ST) or shaking (SK) cultures of HI and LO islets. Islet function was examined after 24 hours by a glucose challenge test. Insulin secretion into the culture media was continuously measured using ELISA during a 6-day culture period. Islet function after 24 hours exhibited better maintenance under SK than ST culture as assessed by a stimulation index. The ideal islet morphology was seen in LO islets at 3 days of SK culture with typical islet shapes of a smooth surface and a spherical configuration. In contrast, typical islet morphology was not observed in HI islets under SK culture; maintenance of typical spherical appearances was difficult. Insulin secretion from LO islets under SK culture was higher than under other conditions during the 6-day period. Under SK culture conditions, exocrine-encapsulated LO islets showed enhanced islet function by condensing loose islet aggregates into firm spheroids with native exocrine tissues as a natural scaffold.
Assuntos
Transplante das Ilhotas Pancreáticas/fisiologia , Ilhotas Pancreáticas/citologia , Animais , Técnicas de Cultura de Células/métodos , Separação Celular/métodos , Sobrevivência Celular , Insulina/metabolismo , Secreção de Insulina , Ilhotas Pancreáticas/metabolismo , Cinética , Pâncreas/citologia , SuínosRESUMO
Fudosteine is a novel mucoactive agent, although little is known about how fudosteine decreases mucin production. The present study examined the effects of fudosteine on MUC5AC mucin synthesis and cellular signalling. An animal model of lipopolysaccharide (LPS)-induced inflammation and a bronchial epithelial cell line model of tumour necrosis factor (TNF)-alpha-induced inflammation were used. Fudosteine was administered before stimulation with LPS or TNF-alpha. The MUC5AC mucin levels were assayed and the expression of the MUC5AC gene was measured. Western blotting was carried out for the detection of phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated p38 mitogen-activated protein kinase (p-p38 MAPK) and phosphorylated extracellular signal-related kinase (p-ERK). MUC5AC mucin synthesis and the expression of the MUC5AC gene were increased by LPS in rats or TNF-alpha in NCI-H292 cells; these effects were inhibited by fudosteine treatment. After stimulation with LPS or TNF-alpha, the expression of p-EGFR, p-p38 MAPK and p-ERK were detected. Fudosteine treatment reduced the expression levels of p-p38 MAPK and p-ERK in vivo and of p-ERK in vitro. The present results suggest fudosteine inhibits MUC5AC mucin hypersecretion by reducing MUC5AC gene expression and the effects of fudosteine are associated with the inhibition of extracellular signal-related kinase and p38 mitogen-activated protein kinase in vivo and extracellular signal-related kinase in vitro.
Assuntos
Cistina/análogos & derivados , Mucina-5AC/química , Mucinas/metabolismo , Animais , Linhagem Celular Tumoral , Cistina/farmacologia , Receptores ErbB/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Lipopolissacarídeos/metabolismo , Masculino , Modelos Biológicos , Mucina-5AC/biossíntese , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Laparoscopic colorectal resection has become popular. The recently developed da Vinci Surgical System promises to facilitate endoscopic surgery and overcome its disadvantages. This study therefore aimed to compare the short-term results between robotic tumor-specific mesorectal excision (R-TSME) using the da Vinci Surgical System and conventional laparoscopic tumor-specific mesorectal excision (L-TSME) in rectal cancer patients. METHODS: Between April 2006 and February 2007, 36 patients were randomly assigned to receive R-TSME or L-TSME. During the study, 18 patients underwent robotic low anterior resection using the da Vinci Surgical System, and 18 patients had conventional laparoscopic low anterior resection. Patient characteristics, perioperative clinical results, complications, and pathologic details were compared between the two groups. RESULTS: The patient characteristics were not significantly different between the two groups. The mean operating time, hemoglobin change, and conversion rate were not significantly different between the groups. Complications were treated conservatively and did not require surgical intervention in the R-TSME group. The average length of stay was 6.9 +/- 1.3 days in the R-TSME group and 8.7 +/- 1.3 days in the L-TSME group (p < 0.001). The specimen quality of the R-TSME group was acceptable. CONCLUSION: Tumor-specific mesorectal excision was performed safely and effectively using the da Vinci Surgical System and the perioperative outcomes were acceptable.
Assuntos
Laparoscopia , Neoplasias Retais/cirurgia , Robótica , Adulto , Idoso , Dor nas Costas/etiologia , Perda Sanguínea Cirúrgica , Edema/etiologia , Feminino , Humanos , Laparoscopia/efeitos adversos , Tempo de Internação , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/patologiaRESUMO
Optimal immunosuppression after pancreas islet transplantation has not yet been established to achieve long-term graft survival. Mycophenolic acid (MPA) is widely used as an immunosuppressive drug after transplantation including among recipients of pancreas islet cells. Previously, we reported MPA-induced islet apoptosis in the HIT-T15 cell line. In this study, we confirmed the effects of MPA on cell death and its potential implications on the mitogen-activated protein kinase (MAPK) family expression levels in primary isolated rat islets. Lewis islets isolated by collagenase digestion were purified by the density gradient method. Cell death was analyzed by methylthiazoletetrazolium assay. Activation of MAPK kinase 4 (MKK4), c-jun N-terminal protein kinase (JNK), p38 MAPK, and caspase-3 cleavage was examined by Western blot analyses. MPA treatments (> 25 micromol/L) increased cell death significantly at 24 hours and in a dose-dependent manner activated MKK4, JNK, and p38 MAPK at 20 hours. Caspase-3 cleavage was also increased by MPA treatment. These results suggested that MPA induced significant cell death among primary isolated rat islets by activation of MKK4, JNK, and p38 MAPK, as well as caspase-3 cleavage.
Assuntos
Morte Celular/efeitos dos fármacos , Ilhotas Pancreáticas/citologia , Ilhotas Pancreáticas/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Ácido Micofenólico/farmacologia , Animais , Caspase 3/metabolismo , Ativação Enzimática , Ilhotas Pancreáticas/enzimologia , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Cinética , Ratos , Ratos Endogâmicos Lew , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
BACKGROUND: Laparoscopic cholecystectomy (LC) for gallbladder carcinoma still is controversial except for the early stages of gallbladder carcinoma (Tis). This study was designed to evaluate and revisit the role of LC in treating gallbladder carcinoma. METHODS: Available medical records of patients with surgeries for gallbladder carcinoma were retrospectively investigated from August 1992 to February 2005. RESULTS: Among 219 patients treated for gallbladder carcinoma, 57 (26%) underwent LC. A total of 16 patients (28.1%) underwent subsequent radical cholecystectomy (LC-RC), and 41 (71.9%) were only followed up without radical surgery (LC). Tis was found in 11 patients (19.3%), T1a in 3 patients (5.3%), T1b in 8 patients (14%), T2 in 19 patients (33.3%), and T3 in 16 patients (28.1%). The findings showed R0 in 14 cases of the radical cholecystectomy group, and clinical R0 was noted in 30 cases of the LC-only group. No survival differences were noted between LC and LC-RC (p = 0.2575), especially in the case of T2 lesions (p = 0.6274), nor between the R0 and clinical R0 (p = 0.5839). However, significant survival differences were noted between the R2 and R0 groups, and between R2 and clinical R0, respectively (p < 0.001). CONCLUSIONS: The findings show that LC could be appropriate treatment for gallbladder carcinoma only in selected cases of clinical R0 lesions.
Assuntos
Carcinoma/cirurgia , Colecistectomia Laparoscópica , Neoplasias da Vesícula Biliar/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/mortalidade , Carcinoma/patologia , Feminino , Neoplasias da Vesícula Biliar/mortalidade , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de SobrevidaRESUMO
We used 2D protein gel electrophoresis and DNA microarray technologies to systematically analyze genes under glucose repression in B:acillus subtilis. In particular, we focused on genes expressed after the shift from glycolytic to gluconeogenic at the middle logarithmic phase of growth in a nutrient sporulation medium, which remained repressed by the addition of glucose. We also examined whether or not glucose repression of these genes was mediated by CcpA, the catabolite control protein of this bacterium. The wild-type and ccpA1 cells were grown with and without glucose, and their proteomes and transcriptomes were compared. 2D gel electrophoresis allowed us to identify 11 proteins, the synthesis of which was under glucose repression. Of these proteins, the synthesis of four (IolA, I, S and PckA) was under CcpA-independent control. Microarray analysis enabled us to detect 66 glucose-repressive genes, 22 of which (glmS, acoA, C, yisS, speD, gapB, pckA, yvdR, yxeF, iolA, B, C, D, E, F, G, H, I, J, R, S and yxbF ) were at least partially under CcpA-independent control. Furthermore, we found that CcpA and IolR, a repressor of the iol divergon, were involved in the glucose repression of the synthesis of inositol dehydrogenase encoded by iolG included in the above list. The CcpA-independent glucose repression of the iol genes appeared to be explained by inducer exclusion.
Assuntos
Bacillus subtilis/efeitos dos fármacos , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Proteoma , Sequência de Aminoácidos , Bacillus subtilis/genética , Bacillus subtilis/metabolismo , Proteínas de Bactérias/efeitos dos fármacos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Divisão Celular/efeitos dos fármacos , Divisão Celular/genética , Meios de Cultura/farmacologia , Proteínas de Ligação a DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Eletroforese em Gel Bidimensional , L-Iditol 2-Desidrogenase/efeitos dos fármacos , L-Iditol 2-Desidrogenase/genética , L-Iditol 2-Desidrogenase/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Proteínas Repressoras/efeitos dos fármacos , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Transcrição GênicaRESUMO
BACKGROUND: Lymph node (LN) metastasis is an important prognostic factor in gallbladder cancer (GBCA). LN status has been adopted as a critical element of staging systems. However, the influence of total lymph node count (TLNC) remains unclear. We determined the optimal minimum TLNC and compared the prognostic significance of LN status indices in GBCA. METHODS: We retrospectively reviewed medical records of 128 patients with T2 or greater GBCA who underwent LN dissection. We analyzed overall survival (OS) and relevance of the number of metastatic LNs, ratio of metastatic LNs to retrieved LNs (LNR), and TLNC in predicting OS. RESULTS: The median OS durations were 120, 35, and 18 months in T2, T3, and T4 GBCA. Five-year OS rates were 73%, 43%, and 0% in T2, T3, and T4 GBCA. LN status did not significantly impact OS in T2 or T4 GBCA. However, all LN indices were significantly correlated with OS in T3 GBCA. Furthermore, multivariate analysis revealed that a metastatic LN count of more than four and a TLNC of more than eight were independent prognostic factors of OS in T3 GBCA. CONCLUSIONS: TLNC and the number of positive LNs may be more important prognostic factors than LNR in T3 GBCA. Additionally, accurate staging may not be achieved in cases of T3 GBCA if the total number of retrieved LNs is less than eight. Thus, to ensure proper staging, we recommend that surgeons harvest more than eight LNs in patients with T3 GBCA.
Assuntos
Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/terapia , Excisão de Linfonodo , Linfonodos/patologia , Adulto , Idoso , Colecistectomia , Terapia Combinada , Feminino , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Low oxygen and nutrient depletion play critical roles in tumorigenesis, but little is known about how they interact to produce tumor survival and tumor malignancy. In the present study, we investigated the mechanism underlying hypoxia-modulated apoptosis of serum-deprived HepG2 cells. Our results showed that hypoxia blocked the apoptosis, which was accompanied with decreased Bax/Bcl-2 ratio, inhibited cytochrome c release, and reduced caspase-3 activity. More importantly, increased expressions of VEGF and its receptor-2 (KDR) under hypoxic/serum-deprived condition suggest that VEGF may act as a survival factor in a self-promoting manner. Data were further supported by results that recombinant human VEGF (rhVEGF) suppressed the serum deprivation-induced apoptosis, and anti-VEGF neutralizing antibody block anti-apoptotic activity of hypoxia. In addition, inhibitors of receptor tyrosine kinase blocked antiapoptosis of hypoxia. Our study further showed that rhVEGF or hypoxia induced ERK phosphorylation in serum-deprived cells, and that a specific inhibitor of MAPK/ERK, PD98059 eliminated the anti-apoptotic activity of rhVEGF or hypoxia by increasing Bax/Bcl-2 ratio and caspase-3 activity. Our data led us to conclude that induction of ERK phosphorylation and decrease of Bax/Bcl-2 ratio by rhVEGF implies that hypoxia-induced VEGF prevents apoptosis of serum-deprived cells by activating the MAPK/ERK pathway. Taken together, we propose that hypoxia enhances survival of nutrient-depleted tumor cells by reducing susceptibility to apoptosis, which consequently leads to tumor malignancy.
Assuntos
Apoptose/fisiologia , Hipóxia Celular/fisiologia , Meios de Cultura Livres de Soro/farmacologia , Fatores de Crescimento Endotelial/fisiologia , Regulação Neoplásica da Expressão Gênica , Linfocinas/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Proteínas de Neoplasias/fisiologia , Apoptose/efeitos dos fármacos , Comunicação Autócrina , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Caspase 3 , Caspases/metabolismo , Sobrevivência Celular , Grupo dos Citocromos c/metabolismo , Fatores de Crescimento Endotelial/biossíntese , Fatores de Crescimento Endotelial/genética , Fatores de Crescimento Endotelial/farmacologia , Inibidores Enzimáticos/farmacologia , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Genes bcl-2 , Humanos , Neoplasias Hepáticas/patologia , Linfocinas/biossíntese , Linfocinas/genética , Linfocinas/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mitocôndrias Hepáticas/enzimologia , Proteína Quinase 3 Ativada por Mitógeno , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases Ativadas por Mitógeno/fisiologia , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteínas Proto-Oncogênicas/biossíntese , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/biossíntese , Receptores Proteína Tirosina Quinases/efeitos dos fármacos , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/fisiologia , Receptores de Fatores de Crescimento/biossíntese , Receptores de Fatores de Crescimento/efeitos dos fármacos , Receptores de Fatores de Crescimento/genética , Receptores de Fatores de Crescimento/fisiologia , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão/farmacologia , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Fator A de Crescimento do Endotélio Vascular , Fatores de Crescimento do Endotélio Vascular , Proteína X Associada a bcl-2RESUMO
UNLABELLED: In renal transplantation, donor age and allograft size are known to have an important influence on the outcome of the graft reflecting functional renal mass. Women tend to have smaller kidneys with 17% fewer nephrons than male kidneys. The number of glomeruli per kidney as well as the mean glomerular volume closely correlate with kidney weight and negatively correlate with subject age. We evaluated the impact of gender and age matching in living-donor renal transplantation on long-term graft survival. MATERIALS AND METHODS: Four groups were discerned among 614 renal transplants, according to donor and recipient gender: Group 1 was male donor to male recipient; Group 2 was male donor to female recipient; Group 3 was female donor to male recipient; and Group 4 was female donor to female recipient. We analyzed long-term graft survival and risk factors between the four groups as well as according to age matching. Statistical significance was determined by the Kaplan-Meier method and log rank test (P < .05). RESULT: The graft survival rates at 1, 3, 5, and 10 years were 92.62%, 88.13%, 82.37%, and 76.07%, respectively. The risk factors affecting long-term graft survival were donor age, donor gender, acute rejection rate, and HLA-DR matching. Among the four groups, the graft survival rates of Group 3 (female donor to male recipient) were significantly different from the other groups (P = .0165). Also, the long-term graft survival rates according to age differences were significantly different between older donors than recipients and younger donors than recipients in each group (P = .0213). CONCLUSION: The importance of inadequate renal mass is magnified in high-risk recipients. Age matching could perhaps improve the results of transplantation, particularly when kidneys from older donors are used. Consideration of age and gender as criteria for the choice of donors and recipients may be considered in organ allocation.
Assuntos
Fatores Etários , Sobrevivência de Enxerto/fisiologia , Transplante de Rim/fisiologia , Rim , Doadores Vivos/estatística & dados numéricos , Caracteres Sexuais , Adulto , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Humanos , Masculino , Complicações Pós-Operatórias/classificação , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Fatores de TempoRESUMO
UNLABELLED: The number of potential renal transplant recipients far exceeds the number of cadaveric donors. For this reason, living-related donors (LRD) and living-unrelated donors (LURD) have been used to decrease the cadaveric donor shortage. We analyzed 571 living donor transplants for 25 years in our center. MATERIALS AND METHODS: From 1978 to 2003, 571 patients underwent LRD (n = 253), or LURD (n = 318) kidney transplantation. The patients were divided into precyclosporine era (from 1978 to 1987, n = 44; era I), cyclosporine era (from 1988 to 1997, n = 367, era II), and cyclosporine plus mycophenolate-mofetil era (from 1998 to 2003, n = 160, era III). We compared the graft survival rate of the recipients according to the immunosuppressants, analyzing the variables of donor and recipient age, sex, HLA matching, and acute rejection rate. We also compared long-term survival rates between LRD and LURD. RESULTS: The 1- and 10-year graft survival rates of all patients were 93.4% and 77.4%, respectively. The 1- and 10- year graft survival rates were 75.0% and 36.3% in era I; and 94.8 % and 80.2% in era II. The 1- and 5-year graft survival rates were 96.6% and 93.3% in era III (P < .001). The occurrence rate of an acute rejection episode was 11.4% (era I), 21.8% (era II), and 14.4% (era III) (P = .056). The 1- and 5-year graft survival rates were 92.3% and 81.7% among LRD transplants, and 94.2% and 86.9% among LURD transplants, respectively (P = .122). DISCUSSION: The graft survival rates of living-donor transplants are improving due to advances in patient care and new immunosuppressive agents.
Assuntos
Sobrevivência de Enxerto/fisiologia , Transplante de Rim/fisiologia , Doadores Vivos , Ciclosporina/uso terapêutico , Feminino , Rejeição de Enxerto/epidemiologia , Antígenos HLA-DR/imunologia , Teste de Histocompatibilidade , Humanos , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Transplante de Rim/imunologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
It has been proposed that proteinuria occurring after renal transplantation may be not only a marker but also a culprit of allograft dysfunction. We retrospectively analyzed the data from 55 patients who underwent transplant renal biopsy for proteinuria and/or azotemia occurring beyond 1 year after transplantation. Proteinuria was considered as significant when > or = 30 mg/dL, and the results of transplant biopsy were categorized according to the Banff 97 classification. Logistic regression was used to estimate odds ratios (OR) for graft loss associated with proteinuria and transplant pathology. The patients were followed for 86.0 +/- 32.8 months after transplantation, and transplant biopsy was performed at 54.1 +/- 31.0 months. Proteinuria at 1 year after transplantation noted in 29.1% of patients was not significantly associated with graft loss (OR = 1.94, 95% CI from 0.59 to 6.41). In addition, proteinuria at the time of transplant biopsy was not significantly associated with graft loss. Chronic allograft nephropathy was the most frequent transplant pathology. Only glomerulonephritis was significantly associated with proteinuria at the time of the transplant biopsy. On the other hand, graft loss was significantly associated with the presence of proteinuria both at 1 year after transplant biopsy and at the final follow-up. These results suggest that posttransplantation proteinuria is an important marker of graft dysfunction, but is not predictive of graft loss in biopsy-proven cases. Appropriate management guided by the results of a transplant biopsy may improve the outcome.
Assuntos
Transplante de Rim/patologia , Proteinúria , Biópsia , Sobrevivência de Enxerto , Transplante de Rim/mortalidade , Transplante de Rim/fisiologia , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Transplante Homólogo/patologia , Transplante Homólogo/fisiologia , Falha de TratamentoRESUMO
Results from quantitative PCR analysis of the frequency of deleted mitochondrial genomes in male Fischer 344 rats reveal an age-related rise in this molecular abnormality. We used this model to examine the ability of dietary restriction (DR) to prevent this potentially pathogenic change. DR prevented age-related increase in frequency of mitochondrial deletions in the liver. In contrast, however, DR had no effect on the age-related increase in deletion frequency in the brain. These data suggest that the effects of DR on age-related accumulation of mitochondrial DNA deletions may be tissue specific.