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1.
BJS Open ; 5(4)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34355240

RESUMO

BACKGROUND: Hepatectomy with vascular resection (VR) for perihilar cholangiocarcinoma (PHCC) is a challenging procedure. However, only a few reports on this procedure have been published and its clinical significance has not been fully evaluated. METHODS: Patients undergoing surgical resection for PHCC from 2002-2017 were studied. The surgical outcomes of VR and non-VR groups were compared. RESULTS: Some 238 patients were included. VR was performed in 85 patients. The resected vessels were hepatic artery alone (31 patients), portal vein alone (37 patients) or both (17 patients). The morbidity rates were almost the same in the VR (49.4 per cent) and non-VR (43.8 per cent) groups (P = 0.404). The mortality rates of VR (3.5 per cent) and non-VR (3.3 per cent) were also comparable (P > 0.999). The median survival time (MST) was 45 months in the non-VR group and 36 months in VR group (P = 0.124). Among patients in whom tumour involvement was suspected on preoperative imaging and whose carbohydrate antigen 19-9 (CA19-9) value was 37 U/ml or less, MST in the VR group was significantly longer than that in the non-VR group (50 versus 34 months, P = 0.017). In contrast, when the CA19-9 value was greater than 37 U/ml, MST of the VR and non-VR groups was comparable (28 versus 29 months, P = 0.520). CONCLUSION: Hepatectomy with VR for PHCC can be performed in a highly specialized hepatobiliary centre with equivalent short- and long-term outcomes to hepatectomy without VR.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Tumor de Klatskin , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Colangiocarcinoma/cirurgia , Hepatectomia , Humanos , Tumor de Klatskin/cirurgia
2.
BJS Open ; 5(1)2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33609394

RESUMO

BACKGROUND: Hepatectomy with extrahepatic bile duct resection is associated with a high risk of posthepatectomy liver failure (PHLF). However, the utility of the remnant liver volume (RLV) in cholangiocarcinoma has not been studied intensively. METHODS: Patients who underwent major hepatectomy with extrahepatic bile duct resection between 2002 and 2018 were reviewed. The RLV was divided by body surface area (BSA) to normalize individual physical differences. Risk factors for clinically relevant PHLF were evaluated with special reference to the RLV/BSA. RESULTS: A total of 289 patients were included. The optimal cut-off value for RLV/BSA was determined to be 300 ml/m2. Thirty-two patients (11.1 per cent) developed PHLF. PHLF was more frequent in patients with an RLV/BSA below 300 ml/m2 than in those with a value of 300 ml/m2 or greater: 19 of 87 (22 per cent) versus 13 of 202 (6.4 per cent) (P < 0.001). In multivariable analysis, RLV/BSA below 300 ml/m2 (P = 0.013), future liver remnant plasma clearance rate of indocyanine green less than 0.075 (P = 0.031), and serum albumin level below 3.5 g/dl (P = 0.015) were identified as independent risk factors for PHLF. Based on these risk factors, patients were classified into three subgroups with low (no factors), moderate (1-2 factors), and high (3 factors) risk of PHLF, with PHLF rates of 1.8, 14.8 and 63 per cent respectively (P < 0.001). CONCLUSION: An RLV/BSA of 300 ml/m2 is a simple predictor of PHLF in patients undergoing hepatectomy with extrahepatic bile duct resection.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Colangiocarcinoma/cirurgia , Hepatectomia/efeitos adversos , Falência Hepática/etiologia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ductos Biliares Extra-Hepáticos/cirurgia , Corantes/farmacocinética , Feminino , Hepatectomia/métodos , Hepatectomia/mortalidade , Humanos , Verde de Indocianina/farmacocinética , Falência Hepática/sangue , Falência Hepática/fisiopatologia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/sangue , Período Pós-Operatório , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise
3.
Skin Health Dis ; 1(3): e37, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35663139

RESUMO

Background: Deficiency of DNA mismatch repair (MMR) induces microsatellite instability (MSI). Pembrolizumab, an antibody targeting PD-1 (an immune checkpoint inhibitor), is more effective against MMR-deficient tumours than against MMR-proficient tumours. The status of MMR is a useful biomarker for predicting the effectiveness of pembrolizumab administration. Although the status of MMR has attracted attention in skin tumours, there are few reports on MSI in extramammary Paget's disease (EMPD). Objectives: To evaluate the status of MMR in patients with EMPD. Materials & Methods: One hundred one patients with EMPD were included. MMR status of the genomic DNA of each subject was analysed using Promega panel (approved as a companion diagnostic agent for the administration of pembrolizumab). Results: MSI testing showed the occurrence rates of MSI-high (more than two markers are unstable), MSI-low (one marker is unstable) and MSS (all markers are stable) tumour tissues were 0% (0/101), 1.0% (1/101) and 99.0% (100/101), respectively. Conclusion: The status of MMR may not be useful for the potential therapeutic application of pembrolizumab.

4.
Br J Surg ; 106(11): 1504-1511, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31386198

RESUMO

BACKGROUND: Differentiation between perihilar cholangiocarcinoma (PHCC) and benign strictures is frequently difficult. The aim of this study was to investigate the incidence and long-term outcome of patients with tumours resected because of suspicion of PHCC, which ultimately turned out to be benign (malignancy masquerade). METHODS: Patients who underwent surgical resection with a diagnosis of PHCC between 2001 and 2016 were reviewed retrospectively. RESULTS: Among 707 consecutive patients, 685 had PHCC and the remaining 22 (3·1 per cent) had benign biliary stricture. All patients with benign disease underwent major hepatectomy, with no deaths. Preoperative histological assessment using bile duct biopsy or aspiration cytology had a high specificity (90 per cent), low sensitivity (62 per cent) and unsatisfactory accuracy (63 per cent). Despite the increasing use of histological assessment, the incidence of benign strictures resected did not decrease over time, being 0·9 per cent in 2001-2004, 4·0 per cent in 2005-2008, 3·8 per cent in 2009-2012 and 2·9 per cent in 2013-2016. The final pathology of benign strictures included IgG4-related sclerosing cholangitis (9 patients), hepatolithiasis (4), granulomatous cholangitis (3), non-specific chronic cholangitis (3), benign strictures after cholecystectomy (2), and a benign stricture possibly caused by parasitic infection (1). The 10-year overall survival rate for the 22 patients with benign stricture was 87 per cent, without recurrence of biliary stricture. CONCLUSION: The incidence of benign strictures resected as PHCC as a proportion of all resections was relatively low, at 3·1 per cent. Currently, unnecessary surgery for suspected PHCC is unavoidable.


ANTECEDENTES: La diferenciación entre colangiocarcinoma perihilar (perihilar colangiocarcinoma, PHCC) y estenosis benignas es con frecuencia difícil. El objetivo de este estudio fue investigar la incidencia y el resultado a largo plazo de los tumores resecados con sospecha diagnóstica de PHCC, que finalmente resultaron ser benignos (malignidad enmascarada). MÉTODOS: Se revisaron retrospectivamente los pacientes con diagnóstico de PHCC que se sometieron a resección quirúrgica entre 2001 y 2016. RESULTADOS: Entre 707 pacientes consecutivos, 685 pacientes presentaban PHCC y los 22 restantes (3,1%) tenían una estenosis biliar benigna. Todos los pacientes con patología benigna se sometieron a una hepatectomía mayor, sin mortalidad. La evaluación histológica preoperatoria mediante biopsia de conducto biliar o citología por aspiración tuvo una alta especificidad (90%), una baja sensibilidad (62%) y una exactitud diagnóstica insatisfactoria (63%). A pesar del uso creciente de la evaluación histológica, la incidencia de estenosis benignas resecadas no disminuyó con el tiempo, con un 0,9% en 2001-2004, un 4,0% en 2005-2008, un 3,8% en 2009-2012 y un 2,9% en 2013-2016. La patología final de las estenosis benignas incluyó colangitis esclerosante relacionada con IgG4 (n = 9), hepatolitiasis (n = 4), colangitis granulomatosa (n = 3), colangitis crónica no específica (n = 3), estenosis benignas tras una colecistectomía (n = 2) y una estenosis benigna posiblemente causada por una infección parasitaria (n = 1). Los resultados a largo plazo de los 22 pacientes con estenosis benigna fueron mejores (tasa de supervivencia a 10 años; 87,4%) sin recidiva de la estenosis biliar. CONCLUSIÓN: La incidencia de pacientes con estenosis benignas resecadas como PHCC en comparación con todas las resecciones fue relativamente baja, del 3,1%. Actualmente, la cirugía "innecesaria" por sospecha de PHCC es inevitable.


Assuntos
Doenças dos Ductos Biliares/diagnóstico , Tumor de Klatskin/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças dos Ductos Biliares/cirurgia , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/cirurgia , Constrição Patológica/diagnóstico , Constrição Patológica/cirurgia , Humanos , Tumor de Klatskin/cirurgia , Pessoa de Meia-Idade , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Resultado do Tratamento
6.
Phys Rev Lett ; 122(19): 192501, 2019 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-31144924

RESUMO

We present a precision analysis of the ^{136}Xe two-neutrino ßß electron spectrum above 0.8 MeV, based on high-statistics data obtained with the KamLAND-Zen experiment. An improved formalism for the two-neutrino ßß rate allows us to measure the ratio of the leading and subleading 2νßß nuclear matrix elements (NMEs), ξ_{31}^{2ν}=-0.26_{-0.25}^{+0.31}. Theoretical predictions from the nuclear shell model and the majority of the quasiparticle random-phase approximation (QRPA) calculations are consistent with the experimental limit. However, part of the ξ_{31}^{2ν} range allowed by the QRPA is excluded by the present measurement at the 90% confidence level. Our analysis reveals that predicted ξ_{31}^{2ν} values are sensitive to the quenching of NMEs and the competing contributions from low- and high-energy states in the intermediate nucleus. Because these aspects are also at play in neutrinoless ßß decay, ξ_{31}^{2ν} provides new insights toward reliable neutrinoless ßß NMEs.

7.
Br J Surg ; 106(6): 774-782, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30889275

RESUMO

BACKGROUND: Little is known about the effect of additional resection for a frozen-section-positive distal bile duct margin (DM) in perihilar cholangiocarcinoma. METHODS: Patients who underwent surgical resection for perihilar cholangiocarcinoma between 2001 and 2015 were analysed retrospectively, focusing on the DM. RESULTS: Of 558 consecutive patients who underwent frozen-section examination for a DM, 74 (13·3 per cent) had a frozen-section-positive DM with invasive cancer or carcinoma in situ. Eventually, 53 patients underwent additional resection (bile duct resection in 44 and pancreatoduodenectomy in 9), whereas the remaining 21 patients did not. Ultimately, R0 resection was achieved in 30 of the 53 patients (57 per cent). No patient who underwent additional resection died from surgical complications. The 44 patients with additional bile duct resection had a 5-year overall survival rate of 31 per cent. Overall survival of the nine patients who had pancreatoduodenectomy was better, with a 10-year rate of 67 per cent. Survival of the 21 patients without additional resection was dismal: all died within 5 years. Multivariable analyses identified nodal status and additional resection as independent prognostic factors (lymph node metastasis: hazard ratio (HR) 2·26, 95 per cent c.i. 1·26 to 4·07; bile duct resection versus no additional resection: HR 0·32, 0·17 to 0·60; pancreatoduodenectomy versus no additional resection: HR 0·08, 0·02 to 0·29). CONCLUSION: Additional resection for frozen-section-positive DM in perihilar cholangiocarcinoma frequently yields R0 margins. It offers a better chance of long-term survival, and thus should be performed in carefully selected patients.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Ducto Hepático Comum/patologia , Tumor de Klatskin/cirurgia , Margens de Excisão , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias dos Ductos Biliares/mortalidade , Neoplasias dos Ductos Biliares/patologia , Feminino , Secções Congeladas , Hepatectomia , Ducto Hepático Comum/cirurgia , Humanos , Tumor de Klatskin/mortalidade , Tumor de Klatskin/patologia , Masculino , Pessoa de Meia-Idade , Pancreaticoduodenectomia , Reoperação , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
8.
Scand J Med Sci Sports ; 28(1): 95-106, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28314055

RESUMO

This study examined localization of muscle damage within the quadriceps femoris induced by different types of eccentric exercises by using transverse relaxation time (T2 )-weighted magnetic resonance imaging (MRI). Thirty-three young males performed either of the following three exercises: single-joint eccentric contraction of the knee extensors (KE), eccentric squat (S), or downhill walking (DW) (n=11/exercise). KE and S consisted of 5-set×10-lowering of 90% one-repetition maximum load. DW was performed for 60 minutes with -10% slope, 6 km/h velocity, and 20% body mass load carried. At pre- and 24-, 48-, and 72-hours post-exercise, T2 -MRI was scanned and T2 values for the rectus femoris (RF), vastus intermedius (VI), vastus lateralis (VL), and vastus medialis (VM) at proximal, middle, and distal sites were calculated. Additionally, soreness felt when static pressure was applied to these sites and maximal isometric knee extension torque were measured. Maximal torque significantly (P<.05) decreased (7%-15%) at 24-48 hours after all exercises. T2 significantly increased (3%-9%) at 24-72 hours after all exercises, with heterogeneities within the muscles found in each exercise. Effect size and peak change of T2 , as well as soreness, overall indicated that the proximal RF after KE and middle VM after S and DW were most affected by these exercises. The VL did not show any significant T2 increase after all exercises. These results suggest that muscle damage specifically localizes at the proximal RF by KE and at the middle VM by S and DW, while the VL is least damaged regardless of the exercises.


Assuntos
Mialgia/fisiopatologia , Músculo Quadríceps/lesões , Treinamento Resistido/métodos , Adulto , Humanos , Imageamento por Ressonância Magnética , Masculino , Músculo Quadríceps/diagnóstico por imagem , Torque , Adulto Jovem
9.
Lupus ; 23(11): 1112-23, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24847041

RESUMO

We examined the role of Mag, an autoimmune susceptibility locus encoded by the telomeric region of MRL/MpJ mouse chromosome 1, in the pathogenesis of autoimmune exocrinopathy. At nine to 12 months of age, strain-specific differences were observed in the pancreas of the animals. B- and T-cell-containing periductal/perivascular cell infiltrations in the pancreases of MRL/MpJ and B6.MRLc1 congenic C57BL/6-background Mag-carrying strains were more severe than were those of C57BL/6. Pancreatic periductal/perivascular cell infiltration was observed frequently in A/J, AKR/N, B6.MRLc1, C57BL/6, and MRL/MpJ, moderately in DBA/1 and DBA/2, and rarely in BALB/c and C3H/He strains. Females tended to have greater pancreatic periductal/perivascular cell infiltration than males. C57BL/6 mice possessed defined borders between cell infiltrations and acini, but borders were indistinct in MRL/MpJ and B6.MRLc1 mice. We attributed this to the invasion of inflammatory cells between each acinus and the disruption of acinar cells around cell infiltrations in the latter strains. No strain-specific differences were observed in the appearance of fibrotic lesions and high endothelial venules in the cell infiltrates. The levels of serum anti-dsDNA antibodies and amylase, and mRNA expression of tumor necrosis factor-α and Fc gamma receptor III (encoded on Mag) in the pancreases, were elevated in MRL/MpJ- and B6.MRLc1-strain mice relative to C57BL/6. These results emphasized the crucial roles of Mag in the molecular and genetic pathogenesis of autoimmune-mediated pancreatitis.


Assuntos
Doenças Autoimunes/genética , Cromossomos de Mamíferos/genética , DNA/imunologia , Pancreatite/genética , Animais , Doenças Autoimunes/imunologia , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Masculino , Camundongos , Camundongos Endogâmicos AKR , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos DBA , Camundongos Endogâmicos MRL lpr , Pancreatite/imunologia , RNA Mensageiro/metabolismo , Receptores de IgG/genética , Fatores Sexuais , Especificidade da Espécie , Fator de Necrose Tumoral alfa/genética
10.
Genes Immun ; 15(3): 182-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24477164

RESUMO

The autoimmune-prone BXSB/MpJ-Yaa mouse is a model of membranous proliferative glomerulonephritis (MPGN). Severe MPGN has been reported only in male BXSB/MpJ-Yaa mice because of the Y-linked autoimmune accelerator (Yaa) locus. However, we show that female BXSB/MpJ mice develop age-related MPGN without Yaa. Female BXSB/MpJ mice clearly developed MPGN characterized by increased mesangial cells, thickening of the glomerular basement membrane (GBM), double contouring and spike formation of GBM with T-cell infiltrations and podocyte injuries corresponding with increased autoantibody production and albuminuria. Analysis of the renal levels of the Fc gamma receptor (Fcgr) and interferon-activated gene 200 (Ifi200) family genes, which are MPGN candidate genes localized to the telomeric region of chromosome 1 (Chr.1), showed that Fcgr2b levels decreased, whereas Fcgr3 and Ifi202b levels increased in female BXSB/MpJ mice compared with healthy C57BL/6 mice. Furthermore, in isolated glomeruli, microarray analysis revealed that Fcgr3, Fcgr4 and Ifi202b expression was higher in male BXSB/MpJ-Yaa mice than in male BXSB/MpJ mice. These findings indicate that the BXSB/MpJ-type genome causes age-related MPGN with significant contribution from the telomeric region of Chr.1, and Yaa enhances the expression of genes localizing to this locus, thereby leading to severe MPGN in male mice.


Assuntos
Doenças Autoimunes/genética , Predisposição Genética para Doença , Glomerulonefrite/genética , Animais , Doenças Autoimunes/imunologia , Cromossomos de Mamíferos , Feminino , Expressão Gênica , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Glomerulonefrite/fisiopatologia , Testes de Função Renal , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Glomérulos Renais/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Podócitos/metabolismo , Podócitos/patologia , Telômero , Cromossomo Y
11.
Anat Histol Embryol ; 43(4): 265-72, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23829583

RESUMO

Previously, the structure of the adult goat parotid salivary glands (PGs) was studied. However, little information was elucidated of the juvenile ones. This study aimed to clarify the correlations between the structure of goats' PGs and the nature of food intake among milk-suckling kids (MSKs) and diet-fed goats (DFGs). The secretory endpieces of the goats' PGs are of the pure serous type. The serous cells in MSKs showed apical accumulation of numerous secretory granules (SGs) of smaller size and of more intense positive periodic acid-Schiff reaction. Ultrastructurally, most of the SGs in the DFGs contained peripherally located inclusions that showed dense reaction products for acid phosphatase. In MSKs, the PGs showed less-developed basal infoldings, sparseness of the inter-cellular inter-digitations, fewer inter-cellular canaliculi and microvilli and also less-developed myoepithelial cells with fewer and shorter cytoplasmic processes. In conclusion, the less-developed membrane specializations and myoepithelial cells, as well as the accumulated SGs in the PGs of MSKs, suggest that it secretes less saliva with a little secretory activity than that of DFGs, which may be correlated with the reduced masticatory activity.


Assuntos
Cabras/crescimento & desenvolvimento , Glândula Parótida/crescimento & desenvolvimento , Desmame , Animais , Feminino , Cabras/anatomia & histologia , Cabras/fisiologia , Masculino , Glândula Parótida/citologia , Glândula Parótida/fisiologia
12.
Scand J Med Sci Sports ; 24(1): 11-7, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22612425

RESUMO

To evaluate the effects of cooling between exercise sessions on intramuscular water movement and muscle performance, the lower extremities of nine untrained men were assigned to either a cooling protocol (20-min water immersion, 15 °C) or a noncooling protocol. Each subject performed two exercise sessions involving maximal concentric knee extension and flexion (three repetitions, 60°/s; followed by 50 repetitions, 180°/s). The peak torque at 60°/s and total work, mean power, and decrease rate of torque value at 180°/s were evaluated. Axial magnetic resonance diffusion-weighted images of the mid-thigh were obtained before and after each exercise session. Apparent diffusion coefficient (ADC) values for the quadriceps and hamstrings were calculated for evaluating intramuscular water movement. Both groups exhibited significantly increased ADC values for the quadriceps and hamstrings after each exercise session. These ADC values returned to the pre-exercise level after water immersion. No significant difference was observed in muscle performance from first exercise session to the next in either group, except for increased total work and mean power in knee flexion in the cooled group. Cooling intervention between exercise sessions decreased exercise-induced elevation of intramuscular water movement and had some beneficial effects on muscle endurance of knee flexors, but not knee extensors.


Assuntos
Temperatura Baixa , Deslocamentos de Líquidos Corporais/fisiologia , Contração Muscular/fisiologia , Força Muscular/fisiologia , Músculo Quadríceps/fisiologia , Adulto , Imagem de Difusão por Ressonância Magnética , Humanos , Masculino , Fadiga Muscular/fisiologia , Músculo Esquelético/fisiologia , Coxa da Perna , Torque , Adulto Jovem
13.
Histol Histopathol ; 26(10): 1243-55, 2011 10.
Artigo em Inglês | MEDLINE | ID: mdl-21870328

RESUMO

Podocytes cover the glomerulus and their adjacent foot processes form a principal barrier called the slit diaphragm. Podocyte dysfunctions, including podocyte loss and slit diaphragm disruptions, induce chronic kidney diseases (CKD). In this study, we analyzed the correlations between podocyte injuries and renal dysfunctions in domestic carnivores. Dogs and cats were divided into normal and CKD groups according to renal histopathology and plasma creatinine values. Immunostaining results showed that linear reactions of slit diaphragm molecules, e.g., nephrin, podocin, and ACTN4, were parallel to glomerular capillaries in all animals. However, in dogs, reactions of nephrin and ACTN4 were changed to a granular pattern in the CKD group, and their intensities significantly decreased with the number of podocytes in the glomerulus. Moreover, the expression of nephrin and ACTN4 negatively correlated with creatinine. Real-time PCR analysis showed that nephrin mRNA expression in the kidneys of CKD dogs was significantly lower than that in normal animals, and negatively correlated with creatinine. Although no significant correlation between renal dysfunction and podocyte injury was detected in cats, histoplanimetric scores of tubulointerstitial lesions in CKD cats were higher than those in both normal cats and diseased dogs. Furthermore, mRNAs of WT1 and SD molecules were detected in urine from CKD animals. In conclusion, podocyte injuries such as podocytopenia and decreased expression of nephrin and ACTN4 in the glomerulus were more strongly correlated with renal dysfunction in dogs than in cats. These findings suggest that the CKD pathogenesis, especially susceptibilities to podocyte injuries, differed between dogs and cats.


Assuntos
Falência Renal Crônica/patologia , Falência Renal Crônica/veterinária , Podócitos/patologia , Animais , Gatos , Cães , Imuno-Histoquímica , Peptídeos e Proteínas de Sinalização Intracelular , Falência Renal Crônica/metabolismo , Testes de Função Renal , Proteínas de Membrana/biossíntese , Microscopia Eletrônica de Transmissão , Podócitos/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Lupus ; 19(8): 897-905, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20167632

RESUMO

B6.MRLc1(82-100) congenic mice carrying the telomeric region of lupus-prone MRL chromosome 1 develop autoimmune glomerulonephritis (GN). The GN susceptibility locus of B6.MRLc1(82-100) contains the interferon activated gene 200 (Ifi200) family, which consists of Ifi202, 203, 204, and 205. Recently, Ifi202 was suggested as a candidate gene for murine lupus. In this study, we assessed the association between Ifi200 family and GN in several disease models. We compared the expression of Ifi200 family members in 24 organs between the C57BL/6 and B6.MRLc1(82-100). The expressions of Ifi200 family members differed between strains, and the most dramatic differences appeared in Ifi202 expression. Briefly, in the blood, immune organs, lungs, and testes mRNA expression was higher in B6.MRLc1(82-100) mice. In the kidney and immune organs, only Ifi202 expression increased with the development of GN in B6.MRLc1(82-100), and significant differences from C57BL/6 were observed even before disease onset. Ifi202 expression in the kidneys of BXSB, NZB/WF1, and MRL/lpr was also significantly high in the early- and late-disease stages. Furthermore, laser microdissection-reverse-transcriptase-polymerase chain reaction analysis confirmed the high Ifi202 expression in all areas of B6.MRLc1(82-100) kidneys. In conclusion, in the Ifi200 family, Ifi202 expressions in the kidney and immune organs significantly increased with GN progression.


Assuntos
Doenças Autoimunes , Cromossomos de Mamíferos , Regulação da Expressão Gênica , Glomerulonefrite , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos Endogâmicos MRL lpr , Animais , Doenças Autoimunes/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Progressão da Doença , Predisposição Genética para Doença , Glomerulonefrite/genética , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Rim/citologia , Rim/metabolismo , Camundongos , Camundongos Congênicos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NZB , Baço/citologia , Baço/metabolismo , Timo/citologia , Timo/metabolismo , Distribuição Tecidual
15.
Lett Appl Microbiol ; 49(4): 472-7, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19674290

RESUMO

AIMS: To isolate gamma-hexachlorocyclohexane (gamma-HCH)-degrading bacteria from a single field and to examine their genetic diversity. METHODS AND RESULTS: Gamma-HCH-degrading bacteria were screened from a long-term experimental field in which gamma-HCH has been continuously applied to, and a gamma-HCH-degrading sphingomonad strain SS86 was isolated from in 1986. As the result, five strains of sphingomonads were newly isolated. The sequences of several housekeeping genes separated the six strains, including SS86, into two genotypes. Among the genes involved in gamma-HCH degradation, the sequences of linC, linD and linE were identical among all six strains, that of linA was identical among five strains, and that of linB was diverse. CONCLUSIONS: We calculated that the gamma-HCH-degrading populations of the two genotypes arose independently. Not just one but diverse sphingomonads that degrade a particular xenobiotic compound possibly tend to arise and/or accumulate in fields, where that compound has been applied. SIGNIFICANCE AND IMPACT OF THE STUDY: This study indicates the potential usefulness of a long-term continuous application of xenobiotic compounds to an experimental field in that it would potentially generate diverse micro-organisms able to degrade the compounds.


Assuntos
Variação Genética , Hexaclorocicloexano/metabolismo , Microbiologia do Solo , Sphingomonas/isolamento & purificação , Sphingomonas/metabolismo , Proteínas de Bactérias/genética , Biodegradação Ambiental , DNA Bacteriano/genética , DNA Ribossômico/genética , Dados de Sequência Molecular , Filogenia , RNA Ribossômico 16S/genética , Poluentes do Solo/metabolismo , Sphingomonas/classificação , Sphingomonas/genética
16.
Osteoarthritis Cartilage ; 17(4): 529-38, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18922704

RESUMO

OBJECTIVE: The effect of the prostaglandin E2 (PGE2) signal through prostaglandin E receptor 2 (EP2) receptors on the repair of injured articular cartilage was investigated using a selective agonist for EP2. METHODS: Chondral and osteochondral defects were prepared on the rabbit femoral concave in both knee joints, and gelatin containing polylactic-co-glycolic acid microspheres conjugated with or without the EP2 agonist was placed nearby. Animals were sacrificed at 4 or 12 weeks post-operation, and regenerated cartilage tissues and subchondral structure remodeling were evaluated by histological scoring. The quality of regenerated tissues was also evaluated by the immunohistochemical staining of EP2, type II collagen, and proliferating cell nuclear antigen (PCNA). As an evaluation of side effects, the inflammatory reaction of the synovial membrane was analyzed based on histology and the mRNA expression of matrix metalloproteinase3 (MMP3), tissue inhibitor of metalloproteinase 3 (TIMP3), and interleukin-1 beta (IL-1 beta). Also, the activity of MMP3 and the amount of tumor necrosis factor-alpha (TNF-alpha) and C-reactive protein in joint fluid were measured. RESULTS: In both models, the EP2 agonist enhanced the regeneration of the type II collagen-positive tissues containing EP2- and PCNA-positive chondrocytes, and the histological scale of regenerated tissue and subchondral bone was better than that of on the control side, particularly at 12 weeks post-operation. No inflammatory reaction in the synovial membrane was observed, and no induction of pro-inflammatory cytokines was found in joint fluid. CONCLUSION: Selective stimulation of the PGE2 signal through EP2 receptors by a specific agonist promoted regeneration of cartilage tissues with a physiological osteochondral boundary, suggesting the potential usefulness of this small molecule for the treatment of injured articular cartilages.


Assuntos
Cartilagem Articular/lesões , Dinoprostona/fisiologia , Receptores de Prostaglandina E/fisiologia , Regeneração/fisiologia , Animais , Proteína C-Reativa/metabolismo , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Cartilagem Articular/fisiologia , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos/métodos , Metaloproteinase 3 da Matriz/metabolismo , Coelhos , Receptores de Prostaglandina E/agonistas , Receptores de Prostaglandina E Subtipo EP2 , Regeneração/efeitos dos fármacos , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Líquido Sinovial/metabolismo , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Fator de Necrose Tumoral alfa/metabolismo
18.
Int J Syst Evol Microbiol ; 51(Pt 3): 873-879, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11411709

RESUMO

Genomic DNA homologies were examined from six Microcystis (cyanobacteria) strains, including five different species, Microcystis aeruginosa, Microcystis ichthyoblabe, Microcystis novacekii, Microcystis viridis and Microcystis wesenbergii. All DNA-DNA reassociation values between two strains of M. aeruginosa and the other four species exceeded 70%, which is considered high enough for them to be classified within the same bacterial species. It is proposed to unify these five species into M. aeruginosa under the Rules of the Bacteriological Code and NIES843T (= IAM M-247T) is proposed as the type strain. Two other species, Microcystis flos-aquae and Microcystis pseudofilamentosa, should be regarded as morphological variations of this unified M. aeruginosa. The current taxonomy of cyanobacteria depends too much upon morphological characteristics and must be reviewed by means of bacteriological methods as well as traditional botanical methods.


Assuntos
Microcystis/classificação , Filogenia , Terminologia como Assunto , DNA Bacteriano/genética , DNA Ribossômico/genética , Evolução Molecular , Geografia , Hibridização de Ácido Nucleico , RNA Ribossômico 16S/genética
19.
Phys Rev Lett ; 86(18): 3950-4, 2001 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-11328068

RESUMO

TAMA300, an interferometric gravitational-wave detector with 300-m baseline length, has been developed and operated with sufficient sensitivity to detect gravitational-wave events within our galaxy and sufficient stability for observations; the interferometer was operated for over 10 hours stably and continuously. With a strain-equivalent noise level of h approximately 5x10(-21)/sqrt[Hz], a signal-to-noise ratio of 30 is expected for gravitational waves generated by a coalescence of 1.4M-1.4M binary neutron stars at 10 kpc distance. We evaluated the stability of the detector sensitivity with a 2-week data-taking run, collecting 160 hours of data to be analyzed in the search for gravitational waves.


Assuntos
Astronomia/métodos , Gravitação , Astronomia/instrumentação , Lasers , Sensibilidade e Especificidade
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