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1.
Genes Dev ; 27(15): 1650-5, 2013 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-23913920

RESUMO

It is now well appreciated that the apoptosome, which governs caspase-dependent cell death, also drives nonapoptotic caspase activation to remodel cells. However, the determinants that specify whether the apoptosome acts to kill or remodel have yet to be identified. Here we report that Tango7 collaborates with the Drosophila apoptosome to drive a caspase-dependent remodeling process needed to resolve individual sperm from a syncytium. In these cells, Tango7 is required for caspase activity and localizes to the active apoptosome compartment via its C terminus. Furthermore, Tango7 directly stimulates the activity of this complex in vitro. We propose that Tango7 specifies the Drosophila apoptosome as an effector of cellular remodeling.


Assuntos
Apoptossomas/metabolismo , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Caspases/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/citologia , Drosophila melanogaster/enzimologia , Animais , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Proteínas de Drosophila/genética , Fertilidade/genética , Variação Genética , Masculino , Mutação , Espermatogênese/genética , Espermatozoides/enzimologia , Espermatozoides/metabolismo
2.
Biol Blood Marrow Transplant ; 25(8): 1475-1485, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31163266

RESUMO

Mobilization of hematopoietic stem and progenitor cells (HSPCs) has become increasingly important for hematopoietic cell transplantation. Current mobilization approaches are insufficient because they fail to mobilize sufficient numbers of cells in a significant fraction of patients and are biased toward myeloid immune reconstitution. A novel, single drug mobilization agent that allows a more balanced (myeloid and lymphoid) reconstitution would therefore be highly favorable to improve transplantation outcome. In this present study, we tested commercially available IL-33 molecules and engineered novel variants of IL-33. These molecules were tested in cell-based assays in vitro and in mobilization models in vivo. We observed for the first time that IL-33 treatment in mice mobilized HSPCs and common myeloid progenitors more efficiently than clinical mobilizing agents granulocyte colony-stimulating factor (G-CSF) or AMD3100. We engineered several oxidation-resistant IL-33 variants with equal or better in vitro activity. In vivo, these variants mobilized HSPCs and, interestingly, also hematopoietic stem cells, common lymphoid progenitor cells, and endothelial progenitor cells more efficiently than wild-type IL-33 or G-CSF. We then engineered an IL-33-Fc fusion molecule, a single dose of which was sufficient to significantly increase the mobilization of HSPCs after 4 days. In conclusion, our findings suggest that long-acting, oxidation-resistant IL-33 may be a novel approach for HSPC transplantation. IL-33-mobilized HSPCs differ from cells mobilized with G-CSF and AMD3100, and it is possible that these differences may result in better transplantation outcomes.


Assuntos
Fator Estimulador de Colônias de Granulócitos/farmacologia , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/metabolismo , Compostos Heterocíclicos/farmacologia , Interleucina-33/farmacologia , Animais , Benzilaminas , Ciclamos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos
3.
Biochemistry ; 52(13): 2319-27, 2013 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-23521171

RESUMO

Apoptosome assembly is highly regulated in the intrinsic cell death pathway. To better understand this step, we created an improved model of the human apoptosome using a crystal structure of full length Apaf-1 and a single particle, electron density map at ~9.5 Å resolution. The apoptosome model includes N-terminal domains of Apaf-1, cognate ß-propellers, and cytochrome c. A direct comparison of Apaf-1 in the apoptosome and as a monomer reveals conformational changes that occur during the first two steps of assembly. This includes an induced-fit mechanism for cytochrome c binding to regulatory ß-propellers, which is dependent on shape and charge complementarity, and a large rotation of the nucleotide binding module during nucleotide exchange. These linked conformational changes create an extended Apaf-1 monomer and drive apoptosome assembly. Moreover, the N-terminal CARD in the inactive Apaf-1 monomer is not shielded from other proteins by ß-propellers. Hence, the Apaf-1 CARD may be free to interact with a procaspase-9 CARD either before or during apoptosome assembly. Irrespective of the timing, the end product of assembly is a holo-apoptosome with an acentric CARD-CARD disk and tethered pc-9 catalytic domains. Subsequent activation of pc-9 leads to a proteolytic cascade and cell death.


Assuntos
Apoptossomas/metabolismo , Fator Apoptótico 1 Ativador de Proteases/química , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Apoptossomas/química , Citocromos c/química , Citocromos c/metabolismo , Humanos , Modelos Moleculares , Conformação Proteica
4.
Biochemistry ; 51(23): 4633-41, 2012 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-22631438

RESUMO

High-density lipoproteins (HDL, or "good cholesterol") are heterogeneous nanoparticles that remove excess cell cholesterol and protect against atherosclerosis. The cardioprotective action of HDL and its major protein, apolipoprotein A-I (apoA-I), is well-established, yet the function of the second major protein, apolipoprotein A-II (apoA-II), is less clear. In this review, we postulate an ensemble of apolipoprotein conformations on various HDL. This ensemble is based on the crystal structure of Δ(185-243)apoA-I determined by Mei and Atkinson combined with the "double-hairpin" conformation of apoA-II(dimer) proposed in the cross-linking studies by Silva's team, and is supported by the wide array of low-resolution structural, biophysical, and biochemical data obtained by many teams over decades. The proposed conformational ensemble helps integrate and improve several existing HDL models, including the "buckle-belt" conformation of apoA-I on the midsize disks and the "trefoil/tetrafoil" arrangement on spherical HDL. This ensemble prompts us to hypothesize that endogenous apoA-II (i) helps confer lipid surface curvature during conversion of nascent discoidal HDL(A-I) and HDL(A-II) containing either apoA-I or apoA-II to mature spherical HDL(A-I/A-II) containing both proteins, and (ii) hinders remodeling of HDL(A-I/A-II) by hindering the expansion of the apoA-I conformation. Also, we report that, although endogenous apoA-II circulates mainly on the midsize spherical HDL(A-I/A-II), exogenous apoA-II can bind to HDL of any size, thereby slightly increasing this size and stabilizing the HDL assembly. This suggests distinctly different effects of the endogenous and exogenous apoA-II on HDL. Taken together, the existing results and models prompt us to postulate a new structural and functional role of apoA-II on human HDL.


Assuntos
Apolipoproteína A-II/química , Lipoproteínas HDL/química , Transporte Biológico , Colesterol/metabolismo , Humanos , Modelos Químicos , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Isoformas de Proteínas , Estabilidade Proteica
5.
Nat Commun ; 11(1): 2992, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532974

RESUMO

Activated protein C (APC) is a plasma serine protease with antithrombotic and cytoprotective functions. Based on the hypothesis that specific inhibition of APC's anticoagulant but not its cytoprotective activity can be beneficial for hemophilia therapy, 2 types of inhibitory monoclonal antibodies (mAbs) are tested: A type I active-site binding mAb and a type II mAb binding to an exosite on APC (required for anticoagulant activity) as shown by X-ray crystallography. Both mAbs increase thrombin generation and promote plasma clotting. Type I blocks all APC activities, whereas type II preserves APC's cytoprotective function. In normal monkeys, type I causes many adverse effects including animal death. In contrast, type II is well-tolerated in normal monkeys and shows both acute and prophylactic dose-dependent efficacy in hemophilic monkeys. Our data show that the type II mAb can specifically inhibit APC's anticoagulant function without compromising its cytoprotective function and offers superior therapeutic opportunities for hemophilia.


Assuntos
Anticorpos Monoclonais/farmacologia , Hemofilia A/prevenção & controle , Fragmentos Fab das Imunoglobulinas/imunologia , Inibidor da Proteína C/farmacologia , Proteína C/antagonistas & inibidores , Animais , Anticorpos Monoclonais/classificação , Anticorpos Monoclonais/imunologia , Tempo de Sangramento , Permeabilidade da Membrana Celular/efeitos dos fármacos , Células Cultivadas , Cristalografia por Raios X , Hemofilia A/sangue , Hemorragia/prevenção & controle , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Células Endoteliais da Veia Umbilical Humana/fisiologia , Humanos , Fragmentos Fab das Imunoglobulinas/metabolismo , Macaca fascicularis , Masculino , Proteína C/química , Proteína C/imunologia , Proteína C/metabolismo , Inibidor da Proteína C/sangue , Inibidor da Proteína C/farmacocinética
6.
Exp Hematol ; 60: 73-82.e3, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29337222

RESUMO

Vaso-occlusive crisis (VOC) is the most common and debilitating complication of sickle cell disease (SCD); recurrent episodes cause organ damage and contribute to early mortality. Plasma placental growth factor (PlGF) levels are elevated in SCD and can further increase under hypoxic conditions in SCD mice. Treatment with a PlGF-neutralizing antibody (anti-PlGF Ab) in SCD mice reduced levels of monocyte chemoattractant protein-3, eotaxin, macrophage colony-stimulating factor, and plasminogen activator inhibitor-1 significantly, and of macrophage-derived chemokine and macrophage inflammatory protein-3ß moderately; this may contribute to inhibition of leukocyte recruitment, activation, and thrombosis. In subsequent experiments, anti-PlGF Ab treatment significantly reduced plasma lactate dehydrogenase levels, indicating possible reduction in cellular destruction and/or hemolysis. Histopathology studies revealed decreased incidence and severity of congestion in the lungs and spleen with repeated anti-PlGF Ab treatment. Furthermore, anti-PlGF Ab significantly reduced vaso-occlusion events under hypoxic conditions in a modified dorsal skinfold chamber model in SCD mice. Therefore, elevated PlGF levels may contribute to recruitment and activation of leukocytes. This can subsequently lead to increased pathology of affected organs in addition to mediating acute hypoxia/reoxygenation-triggered vaso-occlusion under SCD conditions. Thus, targeting PlGF may offer a therapeutic approach to reduce acute VOC and possibly alleviate long-term vascular complications in patients with SCD.


Assuntos
Anemia Falciforme/tratamento farmacológico , Anticorpos Neutralizantes/farmacologia , Proteínas/antagonistas & inibidores , Doenças Vasculares/tratamento farmacológico , Anemia Falciforme/sangue , Anemia Falciforme/complicações , Animais , Modelos Animais de Doenças , Humanos , Proteínas de Membrana , Camundongos , Proteínas/metabolismo , Doenças Vasculares/sangue , Doenças Vasculares/etiologia
7.
Zhonghua Wai Ke Za Zhi ; 45(17): 1170-2, 2007 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-18067708

RESUMO

OBJECTIVE: To investigate the clinical efficacy, feasibility and safety of sphincter-preserving procedure by casing anastomosis of colon and rectal mucosa in low rectal cancer. METHODS: A retrospective analysis was carried out in 231 cases of low rectal cancer performed casing anastomosis. RESULTS: One hundred and ninety-seven (197/231, 85.3%) cases were followed up, the median time of the follow up was 5.9 years (range, 2 months-14 years). Eight (3.4%) cases of stoma leak and 3 (1.2%) cases of stoma stenosis were found post operation. Defecating function recovered normally (1 - 3 times per day) in 12 - 24 weeks after operation in all patients. Local recurrence was found in 5.1% (10/197) of the cases. Hepatic and lung metastasis was found in 15.2% (30/197) and 2.5% (5/197) of the patients, respectively. The five-year survival rate was 71.6% totally. CONCLUSIONS: The casing anastomosis procedure with sphincter preservation is safe and efficacy for low rectal cancer. With the procedure, the anal function can be preserved well, stoma leak is decreased, and the five-year survival rate is the same as Miles operation.


Assuntos
Canal Anal , Anastomose Cirúrgica/métodos , Neoplasias Retais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
8.
Zhonghua Wai Ke Za Zhi ; 45(17): 1176-8, 2007 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-18067710

RESUMO

OBJECTIVE: To investigate and compare therapeutic effects of sphincter-preserving operation and Miles operation for rectal cancer. METHODS: A retrospective analysis was carried out in 572 cases of rectal cancer operations performed from January 1980 to December 2006. RESULTS: Sphincter-preserving operation was carried out in 403 cases and Miles procedure in 169 cases. The follow-up rate was 76.2% (436/572) with a period of 0.5 - 25.0 years (median, 9.5 years). Local recurrence occurred in 6.3% (20/317) of sphincter-preserving operation and 7.6% (9/119) of Miles operation, the differences was not significant (chi2 = 1.3942, P > 0.05). Distal metastasis was found in 50 cases (15.7%) of sphincter-preserving operation and 19 cases (16.2%) of the Miles operation with no significant difference (chi2 = 0.6672, P > 0.05). There was no significant difference in five-year survival rate between the two groups, with 67.8% in sphincter-preserving operation and 67.2% in Miles operation. CONCLUSIONS: Sphincter-preserving operations can improve the quality of life in rectal cancer although with the same five-year survival rate and recurrence rate as Miles operation. The operation for rectal cancer should be performed individually according to the location, the bionomics and the clinical stage.


Assuntos
Canal Anal , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Operatórios/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Neoplasias Retais/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
9.
Structure ; 25(1): 40-52, 2017 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-27916517

RESUMO

In Drosophila, the Apaf-1-related killer (Dark) forms an apoptosome that activates procaspases. To investigate function, we have determined a near-atomic structure of Dark double rings using cryo-electron microscopy. We then built a nearly complete model of the apoptosome that includes 7- and 8-blade ß-propellers. We find that the preference for dATP during Dark assembly may be governed by Ser325, which is in close proximity to the 2' carbon of the deoxyribose ring. Interestingly, ß-propellers in V-shaped domains of the Dark apoptosome are more widely separated, relative to these features in the Apaf-1 apoptosome. This wider spacing may be responsible for the lack of cytochrome c binding to ß-propellers in the Dark apoptosome. Our structure also highlights the roles of two loss-of-function mutations that may block Dark assembly. Finally, the improved model provides a framework to understand apical procaspase activation in the intrinsic cell death pathway.


Assuntos
Nucleotídeos de Desoxiadenina/metabolismo , Proteínas de Drosophila/química , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Mutação , Animais , Apoptose , Apoptossomas/química , Apoptossomas/metabolismo , Caspases/metabolismo , Microscopia Crioeletrônica , Proteínas de Drosophila/genética , Drosophila melanogaster/química , Modelos Moleculares , Ligação Proteica , Conformação Proteica , Estrutura Secundária de Proteína , Serina/metabolismo
10.
Elife ; 52016 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-27697150

RESUMO

In response to cell death signals, an active apoptosome is assembled from Apaf-1 and procaspase-9 (pc-9). Here we report a near atomic structure of the active human apoptosome determined by cryo-electron microscopy. The resulting model gives insights into cytochrome c binding, nucleotide exchange and conformational changes that drive assembly. During activation an acentric disk is formed on the central hub of the apoptosome. This disk contains four Apaf-1/pc-9 CARD pairs arranged in a shallow spiral with the fourth pc-9 CARD at lower occupancy. On average, Apaf-1 CARDs recruit 3 to 5 pc-9 molecules to the apoptosome and one catalytic domain may be parked on the hub, when an odd number of zymogens are bound. This suggests a stoichiometry of one or at most, two pc-9 dimers per active apoptosome. Thus, our structure provides a molecular framework to understand the role of the apoptosome in programmed cell death and disease.


Assuntos
Apoptossomas/química , Apoptossomas/ultraestrutura , Fator Apoptótico 1 Ativador de Proteases/análise , Caspase 9/análise , Microscopia Crioeletrônica , Humanos
11.
Zhonghua Wai Ke Za Zhi ; 43(19): 1259-61, 2005 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-16271224

RESUMO

OBJECTIVE: To investigate and analyse curative effects of Miles operation and anal sphincter preserving operation for rectal carcinoma in 20 years. METHODS: From 1984 to 2004, 618 cases of rectal carcinoma that underwent radical resection including Miles operation and anal sphincter preserving procedures were analysed retrospectively each 10 years, earlier 10 years from 1984 to 1994, and later 10 years from 1994 to 2004. RESULTS: Among the 618 cases, 492 (79.6%) were followed up. The median of the follow-up time was 5.4 years. In the earlier 10 years, local recurrence rate of post operation was 6.9% (14/201), for Miles operation and anal sphincter preserving procedures the local recurrence rate was 6.7% and 7.1% respectively. In the later 10 years, the local recurrence rate was 5.1% (15/291), 4.8% for Miles operation, 5.2% for anal sphincter preserving procedures. With the procedure of canular anastomosis of colon and rectal mucosa, the local recurrence rate was 4.9%. Overall five-year survival rate was 64.7% (130/201) in the earlier 10 years, 66.3% (59/89) for Miles operation, 63.4% (71/112) for anal sphincter preserving procedures. In the later 10 years, the five-year survival rate was 68.0% (198/291) in all, for Miles operation 66.3% (55/83), for anal sphincter preserving procedures 68.7% (143/208). With the procedure of canular anastomosis of colon and rectal mucosa, the five-year survival rate was 71.3% (62/87). CONCLUSIONS: The operation for rectal cancer should be chosen individually according to locus, biological character, and clinical stages. Anal sphincter preserving procedures are performed increasingly, and they provide the same five-year survival rate as Miles operation does, and the patient's quality of life can be improved obviously.


Assuntos
Proctocolectomia Restauradora/métodos , Neoplasias Retais/cirurgia , Adulto , Canal Anal , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Retais/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
12.
World J Gastroenterol ; 10(18): 2652-6, 2004 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-15309713

RESUMO

AIM: To identify the differential proteins associated with colorectal cancer genesis and hepatic metastasis. METHODS: Hydrophobic protein samples were extracted from normal colorectal mucosa, primary cancer lesion and hepatic metastatic foci of colorectal cancer. With two-dimensional electrophoresis and image analysis, differentially expressed protein spots were detected, and the proteins were identified by matrix assisted laser desorption/ionization-time of flight-mass spectrometry and peptide mass fingerprint analysis. RESULTS: Significant alterations of the proteins in number and expression levels were discovered in primary cancer and hepatic metastatic foci, the expression of a number of proteins was lost in 25-40 ku, but protein spots was increased in 14-21 ku, compared with normal mucosa. Nine differentially expressed protein spots were identified. Three proteins expressed in normal mucosa, but lost in primary cancer and hepatic metastasis, were recognized as calmodulin, ribonuclease 6 precursor and mannosidase-alpha. Proapolipoprotein was expressed progressively from normal mucosa to primary cancer and hepatic metastasis. The differentially expressed protein of beta-globin was found in normal mucosa and hepatic metastatic tumor, but lost in primary cancer lesion. Cdc 42, a GTP-binding protein, was identified in hepatic metastasis. The protein spots of C4 from primary cancer, M7 and M9 from hepatic metastasis had less homology with the proteins in database. CONCLUSION: Variations of hydrophobic protein expression in colorectal cancer initiation and hepatic metastasis are significant and can be observed with two-dimensional electrophoresis. The expression of calmodulin, ribonuclease 6 precursor and mannosidase-alpha is lost but the expression of proapolipoprotein is enhanced which is associated with colorectal cancer genesis and hepatic metastasis. Cdc 42 and beta-globin are expressed abnormally in hepatic metastasis. Protein C4, M7 and M9 may be associated with colorectal cancer genesis and hepatic metastasis.


Assuntos
Neoplasias do Colo/química , Neoplasias do Colo/patologia , Neoplasias Hepáticas/química , Neoplasias Hepáticas/secundário , Proteoma/análise , Adulto , Idoso , Eletroforese em Gel Bidimensional , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mapeamento de Peptídeos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
13.
Hepatobiliary Pancreat Dis Int ; 3(3): 411-6, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15313680

RESUMO

BACKGROUND: The molecular mechanism of hepatic metastasis of colorectal cancer is not well understood. The aim of this study was to assess the relations between phospholipid contents of cellular membrane and isoenzyme expression of protein kinase C (PKC) and their effects on hepatic metastasis of colorectal cancer. METHODS: High performance liquid chromatography was used to detect contents of cell membrane phospholipids: phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor mucosa and hepatic metastatic foci in patients with colorectal carcinoma. The mRNA expression levels of PKC-alpha, -betaII, -delta, -epsilon, -lambda, -zeta isoenzymes were detected with the QRT-PCR technique. RESULTS: The levels of PI, PC and PE in primary foci and hepatic metastatic foci were higher than those in paratumor mucosa. The level of PE in hepatic metastatic foci was much higher than that in primary foci (t=98.88, P<0.01); but the levels of PI and PC were not significantly different between primary foci and hepatic metastatic foci (t=1.73, 1.36, P>0.05). The expression levels of PKC-betaII, -delta, -epsilon, -lambda, -zeta were enhanced in primary foci and hepatic metastatic foci, but the level of PKC-alpha in primary foci was decreased as compared with that in paratumor mucosa. The levels of PKC-delta, -epsilon, -lambda, -zeta in hepatic metastatic foci were higher than those in primary foci. A positive correlation was observed between the expression levels of PI, PC and PKC-betaII and also between those of PE and PKC-delta, -epsilon, -lambda, -zeta. However, there was a close negative correlation between PE and PKC-alpha. CONCLUSION: Increased levels of PI and PC and decreased ratio of PKC-alpha to PKC-betaII are related to colorectal cancer genesis. Increased levels of PE, increased expression of PKC-delta, -epsilon, -lambda, -zeta isoenzymes and decreased level of PKC-alpha are related to hepatic metastasis in colorectal carcinoma.


Assuntos
Neoplasias Colorretais/patologia , Isoenzimas/genética , Neoplasias Hepáticas/secundário , Fosfolipídeos/metabolismo , Proteína Quinase C/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Membrana Celular/enzimologia , Feminino , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Hepáticas/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mucosa/enzimologia , Proteína Quinase C beta , Proteína Quinase C-alfa , Proteína Quinase C-delta , Proteína Quinase C-épsilon , RNA Mensageiro/análise
14.
Hepatobiliary Pancreat Dis Int ; 2(1): 66-8, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-14607649

RESUMO

OBJECTIVE: To investigate the effect of pericardial devascularization combined with preservation of Latarjet's innervation on portal hypertension. METHODS: Sixty-two patients (57 men and 5 women) have been undergone pericardial devascularization combined with Latarjet's innervation since 1984. Clinical results and postoperative complications were evaluated. RESULTS: The incidence of upper-digestive tract bleeding was 3.2% (2 patients) within 1 month after operation. Four patients (6.5%) died within 1 month after operation (3 patients received emergency operation and 1 selective operation). Among them, 3 patients died from hepatic failure, and one patient from sepsis due to subphrentic infection. Among these deaths, 3 were evaluated Child's C. After operation, the number of patients with abdominal distension, sudden diarrhea and gastric retension was 7 (11.3%), 3 (4.8%) and 0, respectively. CONCLUSION: Pericardial devascularization combined with Latarjet's innervation can preserve the normal function of gastric emptying, prevent acute lesion of the gastric mucosa, and reduce the incidence of esophageal varices rebleeding after operation.


Assuntos
Varizes Esofágicas e Gástricas/cirurgia , Hipertensão Portal/cirurgia , Pericárdio/cirurgia , Nervo Vago/cirurgia , Adulto , Varizes Esofágicas e Gástricas/etiologia , Feminino , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/prevenção & controle , Humanos , Hipertensão Portal/complicações , Masculino , Pessoa de Meia-Idade , Pericárdio/anatomia & histologia , Veia Porta/fisiopatologia
15.
Zhonghua Wai Ke Za Zhi ; 42(3): 155-7, 2004 Feb 07.
Artigo em Chinês | MEDLINE | ID: mdl-15062060

RESUMO

OBJECTIVE: To study clinical effects of modified radical mastectomy with preservation of major and minor pectoral muscles. METHODS: A retrospective analysis was carried out in 214 cases of breast cancer patients (including stage I 66 cases, stage II 141 cases and stage III 7 cases). Modified radical mastectomy with preservation of major and minor pectoral muscles was performed on all the patients. RESULTS: Out of 214 cases, 12 (5.6%) had subcutaneous fluid, 16 (7.4%) had skin flap margin necrosis. Upper limb lymphatic edema was found in 8 (3.7%) patients, and pectoral muscle contracture with dyspraxia of upper arm occurred in 11 (5.1%) cases. Three year survival rate was 82.3% and five year survival rate was 63.4%. For stage I patients, the five year survival rate attained to 79.6%, and stage II 56.3%. CONCLUSIONS: Preservation of lateral branch of pectoral nerve can avoid complication of pectoral muscle contracture with dyspraxia of upper arm. Early chemotherapy of postoperation prevents breast cancer occurrence and metastasis. Comprehensive treat approaches for operative wound avert subcutaneous fluid, and complex therapy improves long-term effect of breast cancer patients.


Assuntos
Neoplasias da Mama/cirurgia , Mastectomia Radical Modificada/métodos , Músculos Peitorais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
16.
Zhonghua Wai Ke Za Zhi ; 42(5): 279-81, 2004 Mar 07.
Artigo em Chinês | MEDLINE | ID: mdl-15062016

RESUMO

OBJECTIVE: To study the role of transrectal ultrasound in detecting and deciding rectal cancer margin and surgical incisal edge. METHODS: 33 surgical specimens of rectal carcinoma were examined with transrectal ultrasound. Cancerous margin and surgical incisal edge were determined. The results were compared with pathological examination. p53 and K-ras gene mutation as tumor molecular markers of residue cancer cells were detected in incisal edge tissue with PCR-SSCP method. RESULTS: General accuracy for cancer infiltration depth with transrectal ultrasound was 86.6%. For mucosa and submucosa infiltration lesions, the accuracy was 72.7%. For lamina muscularis, the accuracy was 90.9%. And for adventitia and peripheral tissue infiltration of rectum, the accuracy was 88.5% and 100% respectively. No remains of cancer cells and tumor molecular markers were detected at distal incisal edges of 1.0 cm, 2.0 cm and 3.0 cm determined with transrectal ultrasound. CONCLUSIONS: Rectal cancer margine and surgical incisal edge determined with transrectal ultrasound are close to examined by pathology. Transrectal ultrasound is helpful and reliable to define incisal edge in rectal cancer surgery.


Assuntos
Endossonografia , Neoplasias Retais/cirurgia , Reto/diagnóstico por imagem , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Análise Mutacional de DNA , Genes ras/genética , Humanos , Mutação , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Neoplasias Retais/genética , Neoplasias Retais/patologia , Proteína Supressora de Tumor p53/genética
17.
Zhonghua Wai Ke Za Zhi ; 42(2): 84-7, 2004 Jan 22.
Artigo em Chinês | MEDLINE | ID: mdl-15009987

RESUMO

OBJECTIVE: To study cell membrane phospholipid variation and protein kinase C (PKC) isoenzyme expression and their effects on hepatic metastasis of large intestinal carcinoma. METHODS: High function liquid chromatography was used to separate and detect cell membrane phospholipids of phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor intestine mucosa and hepatic metastasis of large intestinal carcinomas. And mRNA expression levels of PKC-alpha, -beta II, -delta, -epsilon, -lambda, -zeta isoenzymes were detected using QRT-PCR technique. RESULTS: Fifty-eight cases of colorectal cancer were examined. CONTENTS: of PI, PC and PE in primary foci and hepatic metastasis were higher than those in paratumor mucosa. PE content in hepatic metastasis was much higher than that in primary foci (t = 98.88, P < 0.01). But PI and PC contents had no significant differences between primary and hepatic metastasis (t = 1.73, 1.36, P > 0.05). PKC-beta II, -delta, -epsilon, -lambda, -zeta expression were enhanced in primary foci and hepatic metastasis, but PKC-alpha level decreased in comparison with paratumor mucosa. And PKC-delta, -epsilon, -lambda, -zeta levels in hepatic metastasis were higher than those in primary foci (t = 4.31, P < 0.05). PI and PC had positive correlations with PKC-beta II expression. PE had positive correlations with PKC-delta, -epsilon, -lambda, -zeta, but a negative correlation with PKC-alpha. CONCLUSIONS: The increases of PI and PC and PKC-alpha/PKC-beta II ratio change are related with colorectal cancer genesis. High content of PE and enhanced expression of PKC-delta, -epsilon, -lambda, -zeta isoenzymes and decreased PKC-alpha level improved hepatic metastasis of large intestinal carcinoma.


Assuntos
Neoplasias Intestinais/patologia , Neoplasias Hepáticas/secundário , Lipídeos de Membrana/análise , Proteína Quinase C/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida , Feminino , Humanos , Isoenzimas/genética , Masculino , Pessoa de Meia-Idade , Fosfatidilcolinas/análise , Fosfatidiletanolaminas/análise , Fosfatidilinositóis/análise , Fosfatidilserinas/análise , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa
18.
Zhonghua Wai Ke Za Zhi ; 40(8): 561-3, 2002 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-12417063

RESUMO

OBJECTIVE: To separate and detect membrane phospholipids and study the relationship of metabolism and signal transduction pathways of membrane phospholipids with genesis and hepatic metastasis of large intestinal carcinoma. METHODS: Forty-eight cases of colorectal cancer were detected with high performance liquid chromatography. Membrane phospholipids of phosphatidylinosital (PI), phosphatidylserine (PS), phosphatidylethanolamine (PE) and phosphatidylcholine (PC) in primary foci, paratumor intestinal mucosa and hepatic metastasis of large intestine cancer were separated and analyzed. RESULTS: In primary foci, paratumor intestinal mucosa, and hepatic metastasis of the 48 cases, the contents (mg/g) of PI were: 0.92 +/- 0.12, 1.57 +/- 0.14, 1.54 +/- 0.15 respectively, and PC 56.47 +/- 5.33, 108.57 +/- 6.37, 116.35 +/- 6.85. The contents of PI and PC were higher in primary foci and hepatic metastasis than in paratumor mucosa (F = 363.10, 870.10, P < 0.01). The contents of PE in the three tissues were 18.23 +/- 3.56, 42.02 +/- 4.33, 79.51 +/- 5.52, and in hepatic metastasis was the highest (F = 1 149.63, P < 0.01). PI and PC in primary foci of hepatic metastatic group and nonmetastasis group were not significantly different (t = 3.55, P > 0.05). But the PE content was higher in hepatic metastasis than in primary foci (t = 115.87, P < 0.01). CONCLUSIONS: Membrane phospholipids have obvious variations in genesis and hepatic metastasis of large intestine cancer. Rises of PI and PC were associated with genesis of large intestine carcinoma. The increase of PE content is closely related to invasion and hepatic metastasis of large intestine cancer.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Lipídeos de Membrana/análise , Fosfolipídeos/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Mucosa Intestinal/química , Masculino , Pessoa de Meia-Idade
19.
Zhonghua Wai Ke Za Zhi ; 40(9): 653-6, 2002 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-12411132

RESUMO

OBJECTIVE: To study the long-term results of extended parietal cell vagotomy (EPCV) in the treatment of patients with duodenal ulcer and their complications. METHODS: Form 1979 to 2001, EPCV was performed in 321 patients with duodenal ulcer and their complications. Of these patients 56 had chronic duodenal ulcer, 204 perforation, 16 hemorrhage and 40 stenosis. The following items were evaluated: complications of operation, gastric secretion, gastric emptying, endoscopical and radiographical findings, nutritional status, absorption function, and Visick scale. RESULTS: Postoperative follow-up ranged from 0.5 to 22.0 years (mean 11.3 years) in 289 of the 321 patients with a follow-up rate of 90.0%. Neither operative mortality nor dumping syndrome was noted. Episodic postprandial fullness occurred in 19 patients (6.5%), acid regurgitation in 17 (5.8%) and adhesive ileus in 4 (1.4%). Ulceration recurred in 16 patients (5.5%). Duodenal ulcer was seen in 8 patients (19.5%), hemorrhage in 0 (0%), stenosis in 2 (5.3%), and perforation in 6 (3.1%). Ulcers healed rapidly after medical therapy in 10 patients. Six patients received antrectomy and gastrectomy. In 289 (91.7%) patients of Grade I and II of Visick scale, 191 (95.3%) had perforation. CONCLUSIONS: EPCV is easy to perform with a low rate of post operative complication and ulcer recurrence. It should be a treatment of choice for acute perforation, hemorrhage or stenosis due to duodenal ulcer.


Assuntos
Úlcera Duodenal/cirurgia , Úlcera Péptica Perfurada/cirurgia , Vagotomia/métodos , Feminino , Seguimentos , Ácido Gástrico/metabolismo , Gastroscopia , Humanos , Masculino , Complicações Pós-Operatórias/etiologia , Recidiva , Vagotomia/efeitos adversos
20.
Zhonghua Wai Ke Za Zhi ; 41(11): 812-4, 2003 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-14703453

RESUMO

OBJECTIVE: To investigate the reliability and feasibility of abdominal-anus resection with preservation of anal sphincter by telescopic anastomisis of colon rectal mucosa for middle-lower segment of rectal cancer. METHODS: A retrospective analysis was made for abdominal-anus resection with telescopic anastomosis of colon rectal mucosa in 102 cases of middle-lower segment of rectal cancer. RESULTS: No anastomotic fistula and anastomotic stenosis occurred in the 102 cases. The increased defecation was found during early stage of postoperation, about 6-12 times per day. But this was easily controlled by antidiarrheal drugs. Twelve to 18 weeks later, defecation returned to normal. Follow-up was performed in 91 patients, and the follow-up rate was 89.2%. Mean follow-up period was 4.7 years. Local recurrence rate of the carcinoma was 5.4% (5/91), and hepatic metastasis rate was 13.1% (12/91). Three-year survival rate of postoperation was 86.9% (60/80), and five-year survival rate was 70.7% (29/41). CONCLUSIONS: With telescopic anastomosis of colon rectal mucosa, colon stoma can be avoided, and anastomotic fistula can be prevented. The operation is safety and effective in preservation of anal sphincter for rectal cancer therapy.


Assuntos
Anastomose Cirúrgica/métodos , Colo/cirurgia , Neoplasias Retais/cirurgia , Reto/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos do Sistema Digestório , Feminino , Humanos , Mucosa Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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