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1.
Pancreatology ; 24(4): 592-599, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38548551

RESUMO

PURPOSE: We investigated true indication of neoadjuvant therapy (NAT) in resectable pancreatic cancer and the optimal surgical timing in borderline resectable pancreatic cancer. METHODS: A total of 687 patients with resectable or borderline resectable pancreatic cancer were enrolled. Survival analysis was performed by intention-to-treat analysis and propensity score matching (PSM) was conducted. RESULTS: In resectable disease, the NAT group showed better overall survival (OS) compared with the upfront group. Multivariate analysis identified CA19-9 level (≥100 U/mL) and lymph node metastasis to be prognostic factors, and a tumor size of 25 mm was the optimal cut-off value to predict lymph node metastasis. There was no significant survival difference between patients with a tumor size ≤25 mm and CA19-9 < 100 U/mL and those in the NAT group. In borderline resectable disease, OS in the NAT group was significantly better than that in the upfront group. CEA (≥5 ng/mL) and CA19-9 (≥100 U/mL) were identified as prognostic factors; however, the OS of patients fulfilling these factors was worse than that of the NAT group. CONCLUSIONS: NAT could be unnecessary in patients with tumor size ≤25 mm and CA19-9 < 100 U/mL in resectable disease. In borderline resectable disease, surgery should be delayed until tumor marker levels are well controlled.


Assuntos
Terapia Neoadjuvante , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/patologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Antígeno CA-19-9/sangue , Prognóstico , Análise de Sobrevida , Metástase Linfática , Pontuação de Propensão , Pancreatectomia , Adulto , Idoso de 80 Anos ou mais
2.
Surg Today ; 54(7): 734-742, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38112860

RESUMO

PURPOSES: This study explored the association between the nutritional status and survival outcomes after pancreatic cancer surgery and reconsidered surgical indications in octogenarians. METHODS: Three hundred and ninety-three consecutive pancreatic cancer patients who underwent resection were analyzed and grouped according to age (< 70 years old; septuagenarians [70-79 years old], and octogenarians [80-89 years old]). The Charlson age comorbidity index and nutritional parameters were recorded. Survival outcomes and their association with nutritional parameters and prognostic factors were examined. RESULTS: The overall survival was worse in the octogenarians than in other patients. The median overall survivals in the < 70 years old group, septuagenarians, and octogenarians were 27.2, 26.4, and 15.3 months, respectively (P = 0.0828). DUPAN-2 ≥ 150 U/mL, borderline resectable/unresectable tumors, blood loss volume ≥ 500 mL, and blood transfusion were predictors of the overall survival among octogenarians. Nutritional parameter values were worse in the octogenarians than in other patients. The octogenarian age group was not an independent predictor of postoperative complications in a univariate analysis. CONCLUSIONS: Survival outcomes were poor in octogenarians. However, an age ≥ 80 years old alone should not be considered a contraindication for pancreatic cancer surgery. The maintenance of perioperative nutritional status is an important factor associated with the survival.


Assuntos
Estado Nutricional , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/mortalidade , Idoso de 80 Anos ou mais , Idoso , Masculino , Feminino , Fatores Etários , Taxa de Sobrevida , Prognóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Pancreatectomia
3.
Surg Today ; 51(11): 1819-1827, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34014389

RESUMO

PURPOSE: The peripancreatic arterial system forms various arterial arcades and collateral branches; therefore, it stands to reason that the arterial supply into the pancreatic head region should be controlled as a whole peripancreatic arterial arcade rather than as the three major supplying arteries during isolated pancreatoduodenectomy (PD). We investigated the clinical importance of early control of the whole peripancreatic arterial arcade during PD. METHODS: The subjects of this retrospective study were 63 consecutive patients who underwent PD via a mesenteric approach at our hospital between October, 2014 and February, 2017. The patients were divided into an early control group (n = 27) and a late control group (n = 36) for comparative analysis. RESULTS: The peripancreatic arterial arcades and collateral branches were seen on preoperative multidetector row computed tomography (CT) images and during PD in all 63 patients. The early control group had significantly less intraoperative blood loss than the late control group. Early control of the whole peripancreatic arterial arcade was an independent factor associated with lower intraoperative blood loss in the multivariable analysis (P = 0.012). CONCLUSION: The arterial supply into the pancreatic head region should be controlled as a whole peripancreatic arterial arcade rather than as the three major supplying arteries during isolated PD.


Assuntos
Cuidados Intraoperatórios/métodos , Artérias Mesentéricas , Pâncreas/irrigação sanguínea , Pâncreas/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/prevenção & controle , Circulação Colateral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores , Pâncreas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Estudos Retrospectivos
4.
HPB (Oxford) ; 19(9): 785-792, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28629642

RESUMO

BACKGROUND: Superior mesenteric vein-portal vein confluence resection combined with pancreatoduodenectomy (SMPVrPD) is occasionally required for resection of pancreatic head tumors. It remains unclear whether such situations require splenic vein (SV) reconstruction for decompression of left-sided portal hypertension (LSPH). METHODS: The data from 93 of 104 patients who underwent pancreatoduodenectomy (PD) for pancreatic head malignancies were reviewed. Surgical outcomes in three groups-standard PD (control group), PD combined with vascular resection and SV preservation (SVp group), and SMPVrPD with SV resection (SVr group)-were compared. The influence of division and preservation of the two natural confluences (left gastric vein-portal vein and/or inferior mesenteric vein-SV confluences) on portal hemodynamics were evaluated using three-dimensional computed tomographic portography. RESULTS: No mortality occurred. The morbidity rates were not significantly different among the three groups (18/43, 8/21, and 7/29, respectively; p = 0.306). In the SVr group, three patients had gastric remnant venous congestion, and three had esophageal varices without hemorrhagic potential. No patients had splenomegaly, or severe or prolonged thrombocytopenia. These LSPH-associated findings were less frequently observed when the two confluences were preserved. CONCLUSIONS: SMPVrPD without SV reconstruction can be safely conducted. Additionally, preservation of these two confluences may reduce the risk of LSPH.


Assuntos
Veias Mesentéricas/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Procedimentos de Cirurgia Plástica , Veia Porta/cirurgia , Veia Esplênica/cirurgia , Procedimentos Desnecessários , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Angiografia por Tomografia Computadorizada , Estudos de Viabilidade , Feminino , Hemodinâmica , Humanos , Hipertensão Portal/etiologia , Hipertensão Portal/fisiopatologia , Hipertensão Portal/prevenção & controle , Masculino , Veias Mesentéricas/diagnóstico por imagem , Veias Mesentéricas/fisiopatologia , Pessoa de Meia-Idade , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Flebografia/métodos , Veia Porta/diagnóstico por imagem , Veia Porta/fisiopatologia , Portografia/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos
5.
J Gastrointest Oncol ; 15(3): 1245-1254, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38989443

RESUMO

Background: Recent advances in anticancer treatment and prolonged survival are the background of this study. The study aimed to reappraise the Japan Pancreas Society (JPS) resectability criteria in pancreatic cancer and to propose optimal treatment strategies. Methods: Three hundred ninety-six consecutive patients with curative-intent surgery for pancreatic cancer from April 2011 to December 2022 were included. Overall survival based on the resectability criteria was analyzed, and Cox regression analyses were performed to identify factors associated with overall survival. Results: The median survival times (MSTs) based on the current resectability status were 37.4, 20.1, and 26.6 months in resectable (R), in borderline resectable (BR), and unresectable (UR) disease, respectively (P<0.001), revealing an inversion phenomenon between BR and UR. Using the International Association of Pancreatology (IAP) criteria, the MST of biological BR disease was demonstrably worse than that of R disease (27.1 vs. 40.7 months, P=0.04), but no difference was observed between classical BR and UR locally advanced disease (18.8 vs. 18.7 months, P=0.97). Rather, ≤180° superior mesenteric artery (SMA) invasion was a more powerful prognostic factor than >180° SMA/celiac artery invasion in multivariate analysis (hazard ratio: 2.101, 95% confidence interval: 1.296-3.404, P=0.003). When biological BR was combined with BR, and BR with artery invasion was considered locally advanced disease as a new resectability criterion, the MSTs were 38.8, 23.5, and 18.5 months in the new R, new BR, and locally advanced groups, respectively (P<0.001). Conclusions: The decision-making and treatment strategies based on our new classification in pancreatic cancer are considered reasonable for clinical practice.

7.
Appl Environ Microbiol ; 75(16): 5195-201, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19542348

RESUMO

Degradation of arylglycerol-beta-aryl ether is the most important process in bacterial lignin catabolism. Sphingobium sp. strain SYK-6 degrades guaiacylglycerol-beta-guaiacyl ether (GGE) to alpha-(2-methoxyphenoxy)-beta-hydroxypropiovanillone (MPHPV), and then the ether linkage of MPHPV is cleaved to generate alpha-glutathionyl-beta-hydroxypropiovanillone (GS-HPV) and guaiacol. We have characterized three enantioselective glutathione S-transferase genes, including two genes that are involved in the ether cleavage of two enantiomers of MPHPV and one gene that is involved in the elimination of glutathione from a GS-HPV enantiomer. However, the first step in the degradation of four different GGE stereoisomers has not been characterized. In this study, three alcohol dehydrogenase genes, ligL, ligN, and ligO, which conferred GGE transformation activity in Escherichia coli, were isolated from SYK-6 and characterized, in addition to the previously cloned ligD gene. The levels of amino acid sequence identity of the four GGE dehydrogenases, which belong to the short-chain dehydrogenase/reductase family, ranged from 32% to 39%. Each gene was expressed in E. coli, and the stereospecificities of the gene products with the four GGE stereoisomers were determined by using chiral high-performance liquid chromatography with recently synthesized authentic enantiopure GGE stereoisomers. LigD and LigO converted (alphaR,betaS)-GGE and (alphaR,betaR)-GGE into (betaS)-MPHPV and (betaR)-MPHPV, respectively, while LigL and LigN transformed (alphaS,betaR)-GGE and (alphaS,betaS)-GGE to (betaR)-MPHPV and (betaS)-MPHPV, respectively. Disruption of the genes indicated that ligD is essential for the degradation of (alphaR,betaS)-GGE and (alphaR,betaR)-GGE and that both ligL and ligN contribute to the degradation of the two other GGE stereoisomers.


Assuntos
Álcool Desidrogenase/genética , Álcool Desidrogenase/metabolismo , Éteres de Glicerila/metabolismo , Sphingomonadaceae/enzimologia , Álcool Desidrogenase/química , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Escherichia coli/enzimologia , Escherichia coli/genética , Regulação Bacteriana da Expressão Gênica , Éteres de Glicerila/química , Dados de Sequência Molecular , Mutação , Análise de Sequência de DNA , Sphingomonadaceae/classificação , Sphingomonadaceae/genética , Estereoisomerismo
8.
J Hepatobiliary Pancreat Sci ; 25(7): 329-334, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29747222

RESUMO

BACKGROUND: Early ligation of the inferior pancreatoduodenal artery has been advocated to reduce blood loss during pancreatoduodenectomy. However, the impact of early ligation of the dorsal pancreatic artery (DPA) remains unclear. This study was performed to investigate the clinical implications of early ligation of the DPA. METHODS: From October 2014 to April 2017, 34 consecutive patients underwent pancreatoduodenectomy using a mesenteric approach. The patients were divided into the early DPA ligation group (n = 15) and late DPA ligation group (n = 19). The clinical features were retrospectively compared between the two groups (H29-044). RESULTS: Preoperative multidetector row computed tomography and intraoperative findings revealed that the right branch of the DPA supplied the pancreatic head region in all cases. Intraoperative blood loss was significantly lower in the early than late ligation group (median 609 ml [range 94-1,013 ml] vs. 764 ml [range 367-1,828 ml], respectively; P = 0.008). Multivariable analysis revealed that early DPA ligation was independently associated with blood loss (P = 0.023). The DPAs arising from the superior mesenteric artery underwent early ligation at a significantly higher rate. CONCLUSIONS: Early ligation of the DPA during pancreaticoduodenectomy with a mesenteric approach could reduce intraoperative blood loss.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Ligadura/métodos , Artéria Mesentérica Superior/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Idoso , Artérias/cirurgia , Estudos de Coortes , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada Multidetectores/métodos , Análise Multivariada , Pâncreas/irrigação sanguínea , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/mortalidade , Prognóstico , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Resultado do Tratamento
9.
J Hepatobiliary Pancreat Sci ; 25(2): 150-154, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29143477

RESUMO

BACKGROUND: Gastric venous congestion and bleeding in association with total pancreatectomy (TP) were evaluated. METHODS: Thirty-eight patients of TP were retrospectively analyzed. TP was classified as TP with distal gastrectomy (TPDG), pylorus-preserving TP (PPTP), subtotal stomach-preserving TP (SSPTP), and TP with segmental duodenectomy (TPSD). RESULTS: Portal vein or superior mesenteric vein resection and reconstruction was performed in 24 patients (62.2%). Gastric bleeding occurred immediately after tumor resection in one of eight patients who underwent SSPTP, and urgent anastomosis between the right gastroepiploic and left ovarian vein stopped the bleeding. Another case of gastric bleeding was observed a few hours after TP in one of nine patients who underwent PPTP, and hemostasis was achieved after conservative therapy. Gastric bleeding was not observed in 16 patients who underwent TPDG and five who underwent TPSD. Some patients underwent preservation of gastric drainage veins (left gastric vein, right gastric vein, or right gastroepiploic vein). Neither patient with bleeding underwent preservation of a gastric drainage vein. CONCLUSIONS: To preserve the subtotal or whole stomach when performing TP, one of the gastric drainage veins should undergo preservation or reconstruction, and anastomosis between the right gastroepiploic vein and left ovarian vein may be beneficial.


Assuntos
Gastrectomia/métodos , Hemorragia Gastrointestinal/cirurgia , Hiperemia/cirurgia , Pancreatectomia/efeitos adversos , Neoplasias Pancreáticas/cirurgia , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/fisiopatologia , Hemostasia Cirúrgica/métodos , Hospitais Universitários , Humanos , Hiperemia/etiologia , Hiperemia/fisiopatologia , Japão , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Pancreatectomia/métodos , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/cirurgia , Reoperação/métodos , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
10.
Biochem J ; 395(1): 21-30, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16401186

RESUMO

A milk membrane glycoprotein, MFG-E8 [milk fat globule-EGF (epidermal growth factor) factor 8], is expressed abundantly in lactating mammary glands in stage- and tissue-specific manners, and has been believed to be secreted in association with milk fat globules. In the present paper, we describe further up-regulation of MFG-E8 in involuting mammary glands, where the glands undergo a substantial increase in the rate of epithelial cell apoptosis, and a possible role of MFG-E8 in mediating recognition and engulfment of apoptotic cells through its specific binding to PS (phosphatidylserine). Immunoblotting and RNA blotting analyses revealed that both MFG-E8 protein and MFG-E8 mRNA were markedly increased in mammary tissue within 3 days of either natural or forced weaning (pup withdrawal) of lactating mice. Using immunohistochemical analysis of the mammary tissue cryosections, the MFG-E8 signal was detected around the epithelium of such involuting mammary glands, but was almost undetectable at early- and mid-lactation stages, although strong signals were obtained for milk fat globules stored in the alveolar lumen. Some signals double positive to a macrophage differentiation marker, CD68, and MFG-E8 were detected in the post-weaning mammary tissue, although such double-positive signals were much smaller in number than the MFG-E8 single-positive ones. Total MFG-E8 in milk was also increased in the post-weaning mammary glands and, furthermore, the free MFG-E8 content in the post-weaning milk, as measured by in vitro PS-binding and apoptotic HC11 cell-binding activities, was much higher than that of lactation. In addition, the post-weaning milk enhanced the binding of apoptotic HC11 cells to J774 macrophages. Sucrose density-gradient ultracentrifugation analyses revealed that such enhanced PS-binding activity of MFG-E8 was present in membrane vesicle fractions (density 1.05-1.13 g/ml), rather than milk fat globule fractions. The weaning-induced MFG-E8 might play an important role in the recognition and engulfment of apoptotic epithelial cells by the neighbouring phagocytic epithelial cells in involuting mammary glands.


Assuntos
Antígenos de Superfície/genética , Antígenos de Superfície/metabolismo , Regulação da Expressão Gênica , Glândulas Mamárias Animais/metabolismo , Proteínas do Leite/genética , Proteínas do Leite/metabolismo , Fosfatidilserinas/metabolismo , Desmame , Animais , Animais Recém-Nascidos , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Apoptose , Células Epiteliais/citologia , Epitélio/metabolismo , Feminino , Imuno-Histoquímica , Lactação/metabolismo , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Leite/metabolismo , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Vesículas Secretórias/metabolismo , Frações Subcelulares
11.
Hepatogastroenterology ; 54(73): 180-5, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17419256

RESUMO

BACKGROUND/AIMS: The Doppler waveform of hepatic veins in healthy humans is a triphasic waveform (two negative waves and one positive). Recent studies emphasize the role of Doppler ultrasonography in the evaluation of liver cirrhosis. The analysis of the Doppler waveform of hepatic veins might be a useful and non-invasive method to assess hepatic functional reserve and the amount of the liver to be excised. METHODOLOGY: In 30 patients scheduled for hepatectomy, we performed quantitative analysis of the Doppler waveform of hepatic veins and correlated the Pulsatility Index (PI) and Resistance Index (RI) with ICG clearance values and histologic findings of resected liver specimens in order to ascertain the clinical utility of this method. RESULTS: The mean (+/-SE) values of PI and RI were 1.31 +/- 0.10 and 0.82 +/- 0.03, respectively, and both values are diminished according to the severity of cirrhosis and very closely correlated with fibrosis of the liver-reflected hepatic consistency (PI: r = -0.611, p = 0.0010; RI: r = -0.647, p = 0.0005). They were also correlated with ICG clearance values to some extent, but several discrepant cases were observed. In four of the discrepant cases (ICGR15 < or = 10%, but PI and RI

Assuntos
Carcinoma Hepatocelular/fisiopatologia , Veias Hepáticas/diagnóstico por imagem , Testes de Função Hepática/métodos , Neoplasias Hepáticas/fisiopatologia , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Feminino , Fibrose , Hepatectomia , Humanos , Fígado/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Necrose , Estudos Prospectivos , Fluxo Pulsátil , Ultrassonografia Doppler de Pulso
12.
Sci Rep ; 7(1): 2842, 2017 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-28588250

RESUMO

Sphingobium sp. strain TCM1 can degrade tris(2-chloroethyl) phosphate (TCEP) to inorganic phosphate and 2-chloroethanol. A phosphotriesterase (PTE), phosphodiesterase (PDE) and phosphomonoesterase (PME) are believed to be involved in the degradation of TCEP. The PTE and PME that respectively catalyze the first and third steps of TCEP degradation in TCM1 have been identified. However, no information has been reported on a PDE catalyzing the second step. In this study, we identified, purified, and characterized a PDE capable of hydrolyzing haloalkyl phosphate diesters. The final preparation of the enzyme had a specific activity of 29 µmol min-1 mg-1 with bis(p-nitrophenyl) phosphate (BpNPP) as the substrate. It also possessed low PME activity with p-nitrophenyl phosphate (pNPP) as substrate. The catalytic efficiency (k cat/K m) with BpNPP was significantly higher than that with pNPP, indicating that the enzyme prefers the organophosphorus diester to the monoester. The enzyme degraded bis(2,3-dibromopropyl) phosphate, bis(1,3-dichloro-2-propyl) phosphate and bis(2-chloroethyl) phosphate, suggesting that it is involved in the metabolism of haloalkyl organophosphorus triesters. The primary structure of the PDE from TCM1 is distinct from those of typical PDE family members and the enzyme belongs to the polymerase and histidinol phosphatase superfamily.


Assuntos
Hidrolases de Triester Fosfórico/metabolismo , Sphingomonadaceae/metabolismo , Sequência de Aminoácidos , Concentração de Íons de Hidrogênio , Hidrólise , Fosfatos/metabolismo , Hidrolases de Triester Fosfórico/química , Temperatura
13.
Hum Mutat ; 26(2): 104-12, 2005 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15981244

RESUMO

Familial exudative vitreoretinopathy (FEVR) is a hereditary blinding disorder that features defects in retinal vascular development. The mutations in the genes encoding the Wnt receptor pair, frizzled 4 (FZD4) and low-density-lipoprotein receptor-related protein 5 (LRP5), have been shown to cause FEVR. In this study we screened 56 unrelated patients with FEVR (31 familial and 25 simplex cases) for possible mutations in LRP5 and FZD4. Six novel mutations in either LRP5 or FZD4 were identified in six familial cases. Four novel mutations in LRP5 and one known mutation in FZD4 were detected in three simplex cases, and two of these patients carried compound heterozygous mutations in LRP5. Remarkably, c.1330C>T [p.R444C] in LRP5 was found in the family in which c.1250G>A [p.R417Q] in FZD4 had previously been identified. The phenotype of these patients suggested a synergistic effect of the two mutations in the independent FEVR-causing genes. We also demonstrated that reduced bone density is a common feature in patients with FEVR who harbor LRP5 mutations. The profile of the mutations obtained in the current study further illustrates the complexity of the disease and provides a better understanding of the spectrum, frequencies, and genotype-phenotype correlation.


Assuntos
Receptores Frizzled/genética , Proteínas Relacionadas a Receptor de LDL/genética , Mutação , Receptores Acoplados a Proteínas G/genética , Vitreorretinopatia Proliferativa/genética , Adulto , Sequência de Aminoácidos , Densidade Óssea , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Masculino , Modelos Biológicos , Osteoporose/genética , Fenótipo , Homologia de Sequência de Aminoácidos
14.
Invest Ophthalmol Vis Sci ; 44(3): 1275-81, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12601059

RESUMO

PURPOSE: To describe a hierarchical approach for efficient genetic diagnosis of autosomal dominant retinitis pigmentosa (adRP). METHODS: Forty di-, tri-, or tetra-nucleotide repeats tightly linked to 10 genes known to be responsible for adRP were identified from the human genome sequence and used as markers in multiplex amplification and genotyping, followed by linkage analysis. Discordance of cosegregation of markers and the disease excluded the majority of the examined genes as candidates, and mutation screening for the remaining genes was performed. RESULTS: With this strategy, examination of an adRP-affected family indicated that 3 of 10 candidate genes segregated concordantly with the disease. Further searches for mutations revealed a novel insertion and deletion in the last exon of a splicing factor gene, PRPF8. CONCLUSIONS: This systematic approach facilitates the molecular diagnosis of adRP, which is known to have a highly heterogeneous genetic background.


Assuntos
Proteínas de Transporte/genética , Mutação da Fase de Leitura , Ligação Genética , Repetições de Microssatélites/genética , Retinose Pigmentar/genética , Pré-Escolar , DNA/análise , Análise Mutacional de DNA , Feminino , Genes Dominantes , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Linhagem , Proteínas de Ligação a RNA , Retinose Pigmentar/diagnóstico , Sequências de Repetição em Tandem
15.
Invest Ophthalmol Vis Sci ; 45(12): 4433-9, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15557452

RESUMO

PURPOSE: To identify possible mutations in known candidate genes in patients with autosomal recessive (ar) and simplex retinitis pigmentosa (RP), by using an established strategy of flexible, multiplexed, microsatellite-based homozygosity mapping. METHODS: A total of 78 microsatellite markers corresponding to 16 genes known to be responsible for arRP were selected and used in 18 multiplex amplifications, followed by genotyping. Twelve consanguineous probands and 47 nonconsanguineous probands (59 patients with arRP or simplex RP) agreed to the screening. RESULTS: Of the 59 probands examined, 24 had a mean of 1.4 genes showing homozygosity for all markers within the corresponding gene region. Subsequent direct sequencing revealed three homozygous mutations. Two of them were novel mutations in the genes TULP1 (c.1145T-->C, F382S) and CNGB1 (c.3444 + 1G-->A). The other was a mutation in RPE65 (c.1543C-->T, R515W), which is known to cause Leber's congenital amaurosis. The clinical features of each patient, together with the cosegregation analysis, strongly support the pathogenicity of these mutations. CONCLUSIONS: This systematic approach facilitated the identification of genes that cause arRP, and the results provide a widened spectrum of the mutation severity associated with a broader range of phenotypic manifestations of arRP.


Assuntos
Povo Asiático/genética , Genes Recessivos , Homozigoto , Repetições de Microssatélites , Mutação , Retinose Pigmentar/genética , Adulto , Idoso , Sequência de Bases , Proteínas de Transporte , Mapeamento Cromossômico , Canais de Cátion Regulados por Nucleotídeos Cíclicos , Proteínas do Olho/genética , Feminino , Humanos , Canais Iônicos/genética , Masculino , Pessoa de Meia-Idade , Atrofia Óptica Hereditária de Leber/genética , Linhagem , Proteínas/genética , Retina/patologia , Retinose Pigmentar/patologia , cis-trans-Isomerases
16.
Am J Ophthalmol ; 138(2): 270-9, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15289137

RESUMO

PURPOSE: To determine whether ephrinB2 plays a role in ocular angiogenesis, we investigated the expression of ephrinB2 and EphB receptors on retinal fibroproliferative membranes. DESIGN: Experimental study of the expression of ephrinB2 and EphB receptors within fibroproliferative membranes in patients with ocular angiogenic diseases collected during vitrectomy. METHODS: Fibroproliferative membranes were obtained at the time of vitrectomy from 20 patients with proliferative diabetic retinopathy (PDR) and from 40 patients who had stage 5 retinopathy of prematurity. Specimens were investigated with immunohistochemistry using polyclonal antibodies directed against ephrinB2 and the EphB2, EphB3, and EphB4 receptors. Immunoreactivity for von Willebrand factor (factor VIII) and alpha-smooth muscle actin (alpha-SMA) was also determined to confirm the identity of the target vascular endothelial cells. RESULTS: Positive staining for ephrinB2 was observed on fibroproliferative membranes that were obtained from patients with PDR (65.0%) and retinopathy of prematurity (25.0%). Specifically, ephrinB2 was found to be present on endothelial cells, as confirmed by its colocalization with factor VIII and alpha-SMA staining. EphB2 and EphB3 expression was observed on fibroproliferative membranes that were harvested from patients with PDR (EphB2, 90.0%; EphB3, 70.0%) and retinopathy of prematurity (EphB2, 35.0%; EphB3, 45.0%). However, EphB4 expression was not observed in any of the membranes derived from patients with PDR or retinopathy of prematurity. The rate of ephrinB2 expression in patients with PDR was significantly higher than that seen in patients with retinopathy of prematurity, which probably reflected differences in the vascular density of their fibroproliferative membranes. CONCLUSION: These data suggest that the ephrinB2-EphB2/B3 system may play an important role in ocular angiogenesis.


Assuntos
Retinopatia Diabética/metabolismo , Efrina-B2/metabolismo , Receptor EphB2/metabolismo , Receptor EphB3/metabolismo , Receptor EphB4/metabolismo , Retinopatia da Prematuridade/metabolismo , Actinas/metabolismo , Adulto , Idoso , Retinopatia Diabética/cirurgia , Feminino , Fibrose , Técnica Indireta de Fluorescência para Anticorpo , Humanos , Técnicas Imunoenzimáticas , Lactente , Recém-Nascido , Masculino , Membranas/metabolismo , Pessoa de Meia-Idade , Músculo Liso Vascular/metabolismo , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/cirurgia , Retinopatia da Prematuridade/cirurgia , Vitrectomia , Fator de von Willebrand/metabolismo
17.
Curr Eye Res ; 26(1): 9-14, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12789531

RESUMO

PURPOSE: To clarify the effect of the interaction between interleukin-6 (IL-6) and its soluble receptor (sIL-6R) on retinal pigment epithelial (RPE) cell proliferation in proliferative vitreoretinopathy (PVR). METHODS: Concentrations of IL-6 and sIL-6R molecules in vitreous fluids were measured in eyes with PVR and idiopathic macular hole (MH), and the localization of IL-6 and IL-6R on the PVR fibrous membrane was studied. Production of IL-6 and sIL-6R by cultured RPE cells and the effect of the IL-6/sIL-6R complex on growth of cultured RPE cells were analyzed. RESULTS: Positive staining of IL-6 and IL-6R was observed in proliferating membranes in all PVR cases. IL-6 and sIL-6R concentrations in vitreous fluid from eyes with PVR were significantly higher than in eyes with MH (p < 0.05). A time-dependent increase in IL-6 molecules was identified in the culture medium of RPE cells, although sIL-6R was not detected. Dose-dependent growth of RPE cells was observed in the three concentrations (50, 100, and 500 ng/ml) of sIL-6R used. CONCLUSION: IL-6 derived from blood during the breakdown of the blood-retinal barrier (BRB) and produced by RPE cells and hematogenous sIL-6R cause RPE proliferation.


Assuntos
Receptores de Interleucina-6/metabolismo , Vitreorretinopatia Proliferativa/metabolismo , Corpo Vítreo/metabolismo , Divisão Celular/fisiologia , Células Cultivadas , Meios de Cultura/metabolismo , Relação Dose-Resposta a Droga , Ensaio de Imunoadsorção Enzimática , Humanos , Imuno-Histoquímica/métodos , Interleucina-6/metabolismo , Concentração Osmolar , Epitélio Pigmentado Ocular/metabolismo , Epitélio Pigmentado Ocular/patologia , Perfurações Retinianas/metabolismo , Solubilidade , Coloração e Rotulagem , Fatores de Tempo , Vitreorretinopatia Proliferativa/patologia
18.
Nippon Ganka Gakkai Zasshi ; 107(12): 768-84, 2003 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-14733130

RESUMO

Treatment of retinal detachment advanced markedly during the 20th century. The surgical approach to rhegmatogenous retinal detachment was first established by Joules Gonin, and treatment of traction retinal detachment by vitrectomy was developed by Robert Machemer. Although favorable outcomes are obtained in most cases of retinal detachment using current vitreoretinal surgical techniques, several special types of complicated retinal detachment can be refractory to treatment. The biologic mechanism and the strategy for treatment of a complicated retinal detachment will be discussed in this lecture. A discrepancy in the length between the retina and the outer shell, specifically in the extension of the sclera or shortening of the retina, is commonly seen in refractory cases. To correct this, shortening of the sclera should be the primary treatment approach. Relaxing retinotomy should not be a primary procedure in most cases, since retinotomy encourages further shortening of the retina. Equal extension of the scleral wall is frequently seen in eyes with Marfan's syndrome, buphthalmos, and blue sclera, and the discrepancy is corrected by equal shortening of the sclera by encircling and not by focal shortening of the sclera. Unequal extension of the sclera occurs in posterior staphyloma in highly myopic eyes, morning glory syndrome, and posterior coloboma of the choroid. Focal expansion of the posterior sclera should be corrected by placement of a posterior buckle or circumferential lamellar scleral resection and shortening in the same quadrant. Circumferential surgical shortening of the sclera is also indicated in extreme shortening of the retina in congenital retinal folds with persistent fetal vasculature. In cases with associated retinal detachment with retinal folds, radial surgical shortening of the sclera or radial buckling of the sclera corresponding to the retinal fold is indicated, and retinotomy must be avoided. In comparison, in the presence of the retinal shortening and folding that develops postnatally in retinopathy of prematurity, familial exudative vitreoretinopathy, and incontinentia pigment, spontaneous release of the shortening can be expected following surgical removal of the preretinal fibrous tissue, and associated encircling procedures can be effective in selected cases. Inadequate surgical procedures such as creation of multiple iatrogenic retinal breaks to remove extensive subretinal tissue, excessive photocoagulation for retinal angiomatous lesions, and inadequate indications for vitrectomy to treat a special form of rhegmatogenous retinal detachment frequently result in the most complicated form of traction retinal detachment. A large circumferential retinotomy is beneficial rather than multiple small breaks. Penetrating diathermy through a lamellar scleral flap and encircling carries less risk of inducing traction retinal detachment compared with excessive photocoagulation. For oral breaks or ciliary epithelial breaks commonly seen with blunt ocular trauma or atopic dermatitis, a scleral implant more anterior to the extraocular muscle insertion combined with separate encircling is safer and more effective than primary vitrectomy.


Assuntos
Descolamento Retiniano/cirurgia , Humanos , Recém-Nascido , Procedimentos Cirúrgicos Oftalmológicos/métodos , Descolamento Retiniano/patologia , Retinopatia da Prematuridade/cirurgia
19.
Carbohydr Polym ; 106: 172-8, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24721066

RESUMO

Chitin is high in crystallinity in its natural form and does not dissolve into high temperature water (HTW), which often leads to decomposition reactions such as hydrolysis, deacetylation and dehydration when hydrothermally processed. In this work, we investigated the reactions of mechanically milled chitin in HTW. Mechanical milling pretreatment combined with HTW treatment improved the liquefaction of chitin giving a maximum water soluble fraction of 80%, where the untreated chitin was 55%. The reaction mechanism of the milled and raw chitin in HTW was shown to be different. For milled chitin, the dissolution of chitin occurred during the heating period to supercritical water conditions (400°C) at short reaction times (1 min). Extended reaction time (10 min) led to decomposition products and aromatic char formation. For raw chitin, the dissolution of chitin in HTW did not occur, due to its high crystallinity, so that liquefaction proceeded via decomposition reactions.


Assuntos
Quitina/química , Indústria Química/instrumentação , Indústria Química/métodos , Cristalização , Temperatura Alta , Ligação de Hidrogênio , Solubilidade , Água
20.
Am J Ophthalmol ; 147(4): 661-666.e1, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19152870

RESUMO

PURPOSE: To determine the incidence and possible causes of a late recurrence of a retinal detachment (RD) in eyes with stages 4B and 5 retinopathy of prematurity (ROP), in which the retina was once reattached by lensectomy and vitrectomy. DESIGN: Retrospective, comparative case series. METHODS: The medical records of 124 eyes of 99 infants and children <2 years of age at the time of initial vitrectomy, in which the retina had been reattached for at least 1 year, were reviewed. The incidence of a recurrence of the RD >1 year after the initial surgery for eyes at stage 4B ROP (42 eyes) was compared with that in eyes at stage 5 ROP (82 eyes). The onset and symptoms were evaluated. RESULTS: A recurrent RD occurred in 2 eyes (5%) at stage 4B ROP and 18 eyes (22%) at stage 5 ROP (P = .01). The recurrence developed at 2 to 10 years of age (median, 4 years). Prior to the recurrence, clear signs of traction on the peripheral retina were detected in 10 eyes (50%): localized residual RDs in 8 eyes, and peripheral retinal breaks in 2 eyes. Dense vitreous hemorrhage was present in 5 eyes (25%) at the time of the recurrence. CONCLUSIONS: The retina of eyes at stage 5 ROP is more vulnerable to a recurrence of the RD than in eyes at stage 4B after being attached by vitrectomy. The time of recurrence varies widely, and the presence of traction on the peripheral retina may be a sign of a recurrence.


Assuntos
Complicações Pós-Operatórias , Descolamento Retiniano/etiologia , Retinopatia da Prematuridade/cirurgia , Vitrectomia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Recidiva , Descolamento Retiniano/cirurgia , Retinopatia da Prematuridade/classificação , Estudos Retrospectivos , Acuidade Visual
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