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1.
Diabet Med ; 32(2): 213-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25255697

RESUMO

AIM: To analyse the effects of thyroid hormones on ß-cell function and glucose metabolism in people with prediabetes who are euthyroid. METHODS: A total of 111 people who were euthyroid underwent 75-g oral glucose tolerance tests, of whom 52 were assigned to the normal glucose tolerance and 59 to the prediabetes groups. Homeostatic model assessment of ß-cell function, insulinogenic index and areas under the curve for insulin and glucose were evaluated as indices of pancreatic ß-cell function. RESULTS: In both groups, BMI, fasting insulin, homeostasis model assessment ratio and HDL cholesterol correlated significantly with all indices of pancreatic ß-cell function. Free triiodothyronine correlated positively with all insulin secretion indices in the prediabetes group. Multiple linear regression analysis showed that free triiodothyronine was an independent variable that had a positive correlation with all indices of ß-cell function in the prediabetes group. By contrast, no such correlation was found in the normal glucose tolerance group. CONCLUSIONS: Free triiodothyronine is associated with both basal and glucose-stimulated insulin secretion in people with prediabetes who are euthyroid; therefore, the regulation of insulin secretion by thyroid hormones is a potentially novel therapeutic target for the treatment of diabetes.


Assuntos
Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Estado Pré-Diabético/fisiopatologia , Glândula Tireoide/metabolismo , Tri-Iodotironina/metabolismo , Regulação para Cima , Adulto , Idoso , Índice de Massa Corporal , HDL-Colesterol/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Resistência à Insulina , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Sobrepeso/complicações , Estado Pré-Diabético/sangue , Estado Pré-Diabético/complicações , Estado Pré-Diabético/metabolismo , Índice de Gravidade de Doença , Solubilidade , Tri-Iodotironina/sangue , Tri-Iodotironina/química
2.
Dis Esophagus ; 27(8): 737-43, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24917486

RESUMO

The survival benefit of second-line chemotherapy with docetaxel in platinum-refractory patients with advanced esophageal cancer (AEC) remains unclear. A retrospective analysis of AEC patients with Eastern Cooperative Oncology Group performance status (PS)≤2 was performed, and major organ functions were preserved, who determined to receive docetaxel or best supportive care (BSC) alone after failure of platinum-based chemotherapy. The post-progression survival (PPS), defined as survival time after disease progression following platinum-based chemotherapy, was analyzed by multivariate Cox regression analysis using factors identified as significant in univariate analysis of various 20 characteristics (age, sex, PS, primary tumor location, etc) including Glasgow prognostic score (GPS), which is a well-known prognostic factor in many malignant tumors. Sixty-six and 45 patients were determined to receive docetaxel and BSC between January 2007 and December 2011, respectively. The median PPS was 5.4 months (95% confidence interval [CI] 4.8-6.0) in the docetaxel group and 3.3 months (95% CI 2.5-4.0) in the BSC group (hazard ratio [HR] 0.56, 95% CI 0.38-0.84, P=0.005). Univariate analysis revealed six significant factors: treatment, PS, GPS, number of metastatic organs, liver metastasis, and bone metastasis. Multivariate analysis including these significant factors revealed three independent prognostic factors: docetaxel treatment (HR 0.62, 95% CI 0.39-0.99, P=0.043), better GPS (HR 0.61, 95% CI 0.46-0.81, P=0.001), and no bone metastasis (HR 0.31, 95% CI 0.15-0.68, P=0.003). There was a trend for PPS in favor of the docetaxel group compared with patients who refused docetaxel treatment in the BSC group (adjusted HR 0.61, 95% CI 0.29-1.29, P=0.20). Docetaxel treatment may have prolonged survival in platinum-refractory patients with AEC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/mortalidade , Platina/uso terapêutico , Taxoides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Progressão da Doença , Docetaxel , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Platina/administração & dosagem , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Taxoides/administração & dosagem
3.
Transplant Proc ; 40(2): 631-3, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18374148

RESUMO

In order to develop articular cartilage grafts, one must control shape and safety. We have developed scaffold-free culture methods in which the cells form multicellular aggregates (organoids). In this study, we applied the organoid culture method to chondrocytes attempting to reconstitute articular cartilage grafts. Primary rat costal chondrocytes and subcultured human articular chondrocytes were immobilized in hollow fibers by centrifugation at a density of 3 x 10(8) cells/cm3 to induce the formation of cylindrical-shaped organoids. To improve convenience, we developed a culture device to form sheet-shaped organoids (organoid-sheet). Primary bovine articular chondrocytes were cultured in this device. These organoids were evaluated by histological and gene expression analyses. In the primary rat culture system, chondrocytes formed cylindrical organoids in hollow fibers. Histochemical analysis revealed the presence of extracellular matrix (collagen and proteoglycan). The organoid maintained cartilage-specific gene expression (type II collagen, aggrecan) for 1 month of culture. In the subcultured human chondrocyte system, the organoid regained the decreased cartilage-specific gene expression. In the primary bovine culture system, the cells formed a 300 microm thickness organoid-sheet including abundant extracellular matrix. In conclusion, our organoid formation method was effective to form cartilage-like tissue. This result suggested that the technique may be applicable for the development of an articular cartilage graft.


Assuntos
Cartilagem Articular/citologia , Cartilagem Articular/transplante , Técnicas de Cultura de Células/métodos , Transplante de Células/métodos , Organoides/anatomia & histologia , Agrecanas/genética , Animais , Cartilagem Articular/anatomia & histologia , Colágeno Tipo II/genética , Meios de Cultura , Marcadores Genéticos , Humanos , Organoides/transplante , Reação em Cadeia da Polimerase , Ratos
4.
Transplant Proc ; 40(2): 614-6, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18374144

RESUMO

BACKGROUND: We have previously developed a hybrid artificial liver (HAL) using polyurethane foam (PUF)/hepatocyte spheroid culture. The PUF-HAL has been successfully scaled up to a clinical level. However, one of the most difficult problems for clinical application of HALs is obtaining a cell source. We now focused our attention on embryonic stem (ES) cells as a potential source for HAL. In this study, we investigated the differentiation of mouse ES (mES) cells into functional hepatocytes in the PUF-HAL module. METHODS: The PUF-HAL module included a cylindrical PUF block having many capillaries for medium flow. mES cells were immobilized in the module. To induce hepatic differentiation, growth factors were added to the culture medium. We evaluated cell density, gene expression analysis, and liver-specific functions. RESULTS: mES cells spontaneously formed spherical multicellular aggregates (spheroids) in the pores of PUF. mES cells proliferated by 20 days, achieving a high cell density (about 1 x 10(8) cells/cm3 PUF). Differentiating ES cells expressed endodermal-specific genes such as alpha-fetoprotein, albumin, and tryptophan 2, 3-deoxygenase. The activity of ammonia removal of mES cells per unit volume of the module was detectable by 15 days and increased with culture time. Maximal expression levels were comparable to those of primary (porcine and human) hepatocytes. SUMMARY: mES cells immobilized in the PUF module expressed liver-specific functions at high level, because of high cell density in culture and hepatic differentiation. These results indicated that PUF module-immobilized mES cells may be useful as a biocomponent of HALs.


Assuntos
Reatores Biológicos , Técnicas de Cultura de Células/métodos , Células-Tronco Embrionárias/citologia , Fígado Artificial , Fígado/citologia , Animais , Agregação Celular , Hepatócitos/citologia , Camundongos , Poliuretanos
5.
Transplant Proc ; 40(2): 611-3, 2008 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-18374143

RESUMO

OBJECTIVE: The use of embryonic stem cells (ES cells) has recently received much attention as a novel cell source for various hybrid artificial organs. To use ES cells, it is necessary to be able to produce functional mature cells from ES cells in large quantities. We applied HF/organoid culture, where cultured cells formed cylindrical multicellular aggregates (organoids) in the lumen of hollow fibers, to mouse and cynomolgus monkey ES cells for hepatic differentiation. MATERIALS AND METHODS: ES cells were injected into hollow fibers. The hollow fibers were centrifuged to induce organoid formation and cultured in medium including factors for hepatic differentiation. To determine the characteristics of cells in the bundle, we evaluated gene expression and liver-specific functions. RESULTS: ES cells immobilized inside hollow fibers proliferated and formed cylindrical organoids. In mouse ES cell cultures, the expression of mRNAs of hepatocyte-specific genes increased with culture time. Ammonia removal activity detected at 15 days increased with culture time. Albumin secretion activity detected at 12 days increased by 21 days. In cynomolgus monkey ES cell cultures, ES cells showed spontaneous ammonia removal functions. The maximum levels of these functions per unit volume of the hollow fibers were roughly comparable to those of primary hepatocyte-organoids. CONCLUSIONS: ES cells differentiated into hepatocyte-like cells using the organoid culture technique. The results indicated that the combination of ES cells and an organoid culture technique was useful to obtain mature hepatocytes.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Embrionárias/citologia , Fígado/citologia , Animais , Meios de Cultura , Hepatopatias/terapia , Camundongos , Técnicas de Cultura de Órgãos/métodos , Transplante de Células-Tronco
6.
Int J Artif Organs ; 31(1): 55-61, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18286455

RESUMO

We studied the recovery of rats with fulminant hepatic failure (FHF) by treating them with our original hybrid artificial liver support system (HALSS). We developed an original artificial liver module having a liver lobule-like structure (LLS). This module consists of many hollow fibers regularly arranged in close proximity and hepatocyte aggregates (organoids) induced into the extra capillary space of the module by centrifugal force. The LLS module can express some liver specific functions at high levels and maintain them for several months in vitro. In this study, we evaluated the efficacy of our LLS-HALSS by using rats with FHF induced by a method that combined partial hepatectomy with hepatic ischemia. In the animal experiments, blood ammonia levels rapidly increased in the control group (sham-HALSS group). These rats died during or immediately after application of the sham-HALLS. On the other hand, in the LLS module application group (LLS-control group), the increase in blood ammonia was completely suppressed and all rats recovered. Blood constituents at 4 weeks after application were at normal levels, and the weight of the liver was the same as that of a normal rat. These results indicate that HALSS may be useful for treating liver failure patients until liver transplantation can be performed or until regeneration of the native liver occurs.


Assuntos
Falência Hepática Aguda/reabilitação , Regeneração Hepática/fisiologia , Fígado Artificial , Organoides/fisiologia , Animais , Modelos Animais de Doenças , Desenho de Equipamento , Hepatócitos/fisiologia , Masculino , Ratos , Alicerces Teciduais
7.
East Asian Arch Psychiatry ; 28(1): 23-27, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29576553

RESUMO

OBJECTIVE: Self-harm and attempted suicide are risk factors for suicide in psychiatric hospital in-patients. This study aimed to analyse the circumstances of self-harm and suicide attempts in a Japanese psychiatric hospital so as to improve management and care. METHODS: Incident reports of self-harm and suicide attempts during a 12.4-year period from November 2000 to March 2013 were reviewed. A descriptive analysis was conducted in terms of age, sex, and diagnosis of patients, as well as level, ward, situations, and causes of incidents. RESULTS: During the study period, 90 cases of self-harm and attempted suicide involving 58 patients were reported. The rate of self-harm and suicide attempts was 0.05 per 1000 patient-days. The types of selfharm and suicide attempts included hanging (n = 25), wrist cutting (n = 19), ingestion of foreign objects (n = 17), and others (n = 29). The single case of completed suicide involved hanging, in a patient with schizophrenia. Among 55 patients with relevant data, the most common clinical diagnosis was mood disorder (41.8%), followed by schizophrenia (36.4%). Mood disorder was 3.5 times as prevalent in females as in males (14 vs. 4). Fourteen patients with mood disorder (n = 8) or schizophrenia (n = 6) were repeatedly involved in 46 of 89 cases of self-harm or attempted suicide; 11 were female. One woman with mood disorder attempted suicide 9 times within the same year. The top 3 management and care factors related to self-harm and suicide attempts were failure to adhere to preventive procedures (28%), insufficient therapeutic communication (28%), and difficulty in predicting suicide (20%). CONCLUSION: Self-harm and suicide attempts at this psychiatric hospital occurred at a rate of 0.05 per 1000 patient-days between late 2000 and early 2013. Efforts are needed to increase compliance with suicide prevention procedures and therapeutic communication, so as to improve management and care of psychiatric in-patients and prevent them from committing suicide.


Assuntos
Transtornos do Humor/epidemiologia , Esquizofrenia/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Tentativa de Suicídio/estatística & dados numéricos , Adulto , Comorbidade , Feminino , Hospitais Psiquiátricos/estatística & dados numéricos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais
8.
Int J Artif Organs ; 29(3): 318-28, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16685676

RESUMO

In recent years, use of hepatocyte aggregates has led to development of a hybrid artificial liver support system (HALSS) that has high performance. However, in general, their thickness is 100 microm or more, and generation of a dead cell layer due to oxygen exhaustion inside the aggregates has been a universal problem. The present study proposes a novel organoid culture method with better performance than previous organoid culture methods by forming a sheet-shaped organoid (organoid-sheet) with a thickness of approximately 100 microm. The cell number of the organoid-sheet was maintained at approximately 75% of the initial number at 4 days of culture. On the other hand, that of a cylindrical organoid (cylindroid), which formed inside of a plasma separation hollow fiber with 285 microm inner diameter in our previous study, decreased to approximately 50% within 2 days. The ammonia removal rate of the cells in the organoid-sheet was higher than that of the cells in the cylindroid on the first day, but it decreased during the culture time. At day 15, the rate was reduced by almost 50% with respect to the value on the first day. The cells in the cylindroid displayed a lower ammonia removal rate. A significant difference was not observed between the albumin synthesis rates of the two cultures on the first day. However, over a period of time the cells in the organoid-sheet showed a higher albumin synthesis rate than cells in the cylindroid. As this novel organoid maintains these functions for at least 1 month, it is expected to be applied for the development of a HALSS with higher performance.


Assuntos
Hepatócitos , Fígado/fisiologia , Organoides , Técnicas de Cultura de Tecidos/métodos , Animais , Organoides/anatomia & histologia , Ratos , Ratos Wistar , Fatores de Tempo
9.
Biochim Biophys Acta ; 1390(1): 8-20, 1998 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-9487137

RESUMO

A cDNA encoding cucumber root lipoxygenase was isolated and expressed in E. coli. The enzyme showed highest activity at pH 5.5 when alpha-linolenic acid dispersed with Tween 20 was used as a substrate but showed little activity at above pH 8.0. On the contrary, it showed the highest activity at pH 9.0 with trilinolenin emulsified with gum arabic. When the assay was performed with linolenic acid dispersed with different concentrations of Tween 20, little activity which could be seen up to the reaction solution became turbid as the linolenic acid/Tween 20 ratio increased, while the activity rapidly emerged afterward. The enzyme could also act on phosphatidylcholine, although the activity was strongly modified by freeze-thaw and sonication treatment on the lipid vesicles. Addition of deoxycholic acid to the phospholipid vesicles drastically enhanced the activity. Addition of free fatty acid was also revealed to be effective to enhance the activity. In the latter case, myristic acid exerted highest activity. Oleic acid enhanced the activity more highly than palmitic acid did. These lines of evidence suggested that the lipoxygenase strictly recognized a specific physical state of the phospholipid substrate in the reaction mixture. The enzyme was irreversibly inactivated as the reaction proceeded, however, the rate of the inactivation was much influenced by the additives. Furthermore, stoichiometry between consumed oxygen and formed conjugated diene could not be observed. (c) 1998 Elsevier Science B.V.


Assuntos
Cucumis sativus/enzimologia , Lipoxigenase/metabolismo , Fosfatidilcolinas/metabolismo , Sequência de Aminoácidos , Clonagem Molecular , DNA Complementar/química , DNA Complementar/isolamento & purificação , DNA de Plantas/química , DNA de Plantas/isolamento & purificação , Ácido Desoxicólico/farmacologia , Escherichia coli , Ácidos Graxos/farmacologia , Concentração de Íons de Hidrogênio , Dados de Sequência Molecular , Raízes de Plantas/enzimologia , Propriedades de Superfície
10.
Biochim Biophys Acta ; 486(1): 121-6, 1976 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-12833

RESUMO

Interaction of lipoxygenase with hydroperoxylinoleic acid, which is the product of this enzyme reaction and acts as an activator, was studied kinetically by the fluorescence stopped-flow method. The kinetic features are consistent with a two-step mechanism involving a fast bimolecular association process followed by a slow unimolecular process. The dissociation constant of the bimolecular process was 3 (+/-2) - 10(-5) M, which was appreciably dependent on temperature and pH, in contrast to the rate constant of the latter process. The enthalpy and the entropy of activation for the unimolecular process were estimated to be 21 kcal/mol and 20 e.u., respectively. The pH dependence of the rate constant indicated that an ionizable group with pK of about 8.6 is involved in the interaction. Linoleic acid, the substrate of lipoxygenase, and oleic acid inhibited the interaction between the lipoxygenase and the hydroperoxylinoleic acid by reducing the rate. A series of saturated monohydric alcohols also reduced the rate of the interaction as the chain length of the alcohols increases, though methanol and ethanol increased the rate of the interaction.


Assuntos
Ácidos Linoleicos/metabolismo , Lipoxigenase/metabolismo , Álcoois Graxos/farmacologia , Concentração de Íons de Hidrogênio , Cinética , Ácidos Linoleicos/farmacologia , Ácidos Oleicos/farmacologia , Peróxidos , Espectrometria de Fluorescência , Temperatura , Termodinâmica
11.
Diabetes ; 27(12): 1156-66, 1978 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-363491

RESUMO

Functional alteration of the islet cells was investigated in dogs after the resection of different parts of the small intestine. Three weeks after jejunal or ileal resection, when the dogs might still have been in a catabolic state, insulin and pancreatic glucagon release in response to intravenously infused glucose and arginine was reduced. Three months after jejunal resection, both intravenous glucose tolerance and insulinogenic index in the intravenous glucose tolerance test were significantly below the preoperative values (P less than 0.001, P less than 0.05), while pancreatic glucagon release in response to arginine infusion release. This functional alteration three months after jejunal resection was similar to that seen in diabetes mellitus. On the other hand, three months after ileal resection, insulin and pancreatic glucagon release was almost normal. We conclude that the jejunum plays a more important role in the enteroinsular system than the ileum and that prolonged interruption of this enteroinsular axis can cause insular disorder and what could hypothetically be called enterogenic chemical diabetes, in view of the altered glucose tolerance test and the alteration in insulin secretory response.


Assuntos
Íleo/fisiologia , Ilhotas Pancreáticas/fisiologia , Jejuno/fisiologia , Animais , Arginina/farmacologia , Cães , Feminino , Glucagon/metabolismo , Teste de Tolerância a Glucose , Íleo/cirurgia , Insulina/metabolismo , Jejuno/cirurgia , Masculino
12.
Cell Transplant ; 14(10): 819-27, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16454356

RESUMO

The aim of this study was to investigate the feasibility of human hepatoblastoma cell line (Hep G2), which differentiates by spheroid formation, and treatment with sodium butyrate (SB) as a cell source for hybrid artificial liver (HAL). Hep G2 spontaneously formed spheroids in polyurethane foam (PUF) within 3 days of culture and restored weak ammonia removal activity. Treatment with SB, which is a histone deacetylase inhibitor, further increased the ammonia removal activity of Hep G2 spheroids in a concentration-dependent manner. The activation of ornithine transcarbamylase--a urea cycle enzyme--was significantly related to the upregulation of ammonia removal by spheroid formation, but scarcely contributed to the further upregulation following SB treatment. In contrast with ammonia removal, treatment with SB reduced the albumin secretion of Hep G2 spheroids in a concentration-dependent manner. In the PUF-HAL module in a circulation culture, the ammonia removal rate and albumin secretion rate (per unit volume of the module) of Hep G2 spheroids treated with 5 mM SB were almost the same as those of primary porcine hepatocyte spheroids. These results suggest that simultaneous use of spheroid formation and SB treatment in Hep G2 is beneficial in enhancing the functions of human hepatocytes with potential applications in regenerative medicine and drug screening.


Assuntos
Butiratos/farmacologia , Hepatoblastoma/patologia , Neoplasias Hepáticas/patologia , Fígado Artificial , Esferoides Celulares/fisiologia , Albuminas/metabolismo , Amônia/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ativação Enzimática/fisiologia , Feminino , Fibrinogênio/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica/fisiologia , Hepatoblastoma/metabolismo , Hepatoblastoma/fisiopatologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/fisiologia , Inibidores de Histona Desacetilases , Humanos , Ácido Láctico/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/fisiopatologia , Ornitina Carbamoiltransferase/genética , Ornitina Carbamoiltransferase/fisiologia , Poliuretanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/transplante
13.
Clin Cancer Res ; 6(8): 3193-8, 2000 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-10955803

RESUMO

Allelic losses of specific chromosomal regions in the DNA of tumor cells, which imply loss of tumor suppressor genes normally resident at those loci, may become useful postoperative prognostic indicators for breast cancers that have not yet metastasized to lymph nodes. To examine whether specific allelic losses might correlate with postoperative disease-free survival, we tested tumors from a cohort of 228 node-negative breast cancer patients for allelic losses at 18 microsatellite loci chosen to represent either a known tumor suppressor gene or a region where genetic alterations are frequent in breast tumors. We followed the patients clinically for 5 years or until death (if patient death occurred before completion of 5 years of follow-up). Patients whose tumors had lost an allele at 1p34-36 bore significantly higher risks of postoperative recurrence than those whose tumors retained both alleles of the markers in that region [the 5-year recurrence rate was 15% among patients with losses versus 2% among patients with retention (P = 0.001)]. Multivariate analysis demonstrated that allelic loss at 1p34-36 was an independent postoperative predictor of shorter disease-free survival (hazard ratio, 5.8; P = 0.0117). Thus, allelic losses at 1p34-36 in a tumor might have a potential to serve as a negative prognostic indicator to guide postoperative management of breast cancer patients, especially in the selection of high-risk women who will benefit from adjuvant chemotherapy and endocrine therapy.


Assuntos
Alelos , Neoplasias da Mama/genética , Cromossomos Humanos Par 1/genética , Perda de Heterozigosidade , Adulto , Idoso , Idoso de 80 Anos ou mais , DNA de Neoplasias/genética , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais
14.
Clin Cancer Res ; 7(4): 876-82, 2001 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11309336

RESUMO

We previously defined 18 chromosomal regions in which frequent allelic losses were observed in breast cancers (T. Sato et al., Cancer RES:, 50: 7184-7189, 1990; Y. Harada et al., Cancer (PHILA:), 74: 2281-2286, 1994; I. Ito et al., BR: J. Cancer, 71: 438-441, 1995; K. Tsukamoto et al., Cancer (PHILA:), 78: 1929-1934, 1996; S. Matsumoto et al., Genes Chromosomes Cancer, 20: 268-274, 1997; T. Yokota et al., JPN: J. Cancer RES:, 88: 959-964, 1997; K. Tsukamoto et al., Cancer (PHILA:), 82: 317-322, 1998; A. Iida et al., Genes Chromosomes Cancer, 21: 108-112, 1998; K. Fukino et al., Genes Chromosomes Cancer, 24: 345-350, 1999; T. Yokota et al., Cancer (PHILA:), 85: 447-452, 1999; Y. Utada et al., JPN: J. Cancer RES:, 91: 293-300, 2000). To identify specific allelic losses that might correlate with postoperative recurrence, we examined tumors from a cohort of 504 breast cancer patients, who were followed clinically for 5 years postoperatively, for allelic losses of 18 microsatellite markers. Patients whose tumors had lost an allele at 3p25.1, 8p22, 13q12, 17p13.3, or 22q13 had significantly higher risks of recurrence than those whose tumors retained both alleles at those loci; at 3p25.1, the 5-year recurrence rate was 27% among patients with losses versus 18% with retention (P = 0.0131); at 8p22, 27% versus 14% (P = 0.0129); at 13q12, 28% versus 15% (P = 0.0109); at 17p13.3, 27% versus 20% (P = 0.0482); and at 22q13, 29% versus 20% (P = 0.0477). These data indicate that loss of heterozygosity at any one of these five specific loci is a significant predictor of postoperative recurrence among patients who have undergone surgery for breast cancer. These allelic losses can serve as negative prognostic indicators to guide postoperative management of patients.


Assuntos
Neoplasias da Mama/genética , Cromossomos , Perda de Heterozigosidade/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/prevenção & controle , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 22 , Cromossomos Humanos Par 3 , Cromossomos Humanos Par 8 , Intervalo Livre de Doença , Feminino , Marcadores Genéticos , Humanos , Pessoa de Meia-Idade , Recidiva
15.
FEBS Lett ; 394(1): 21-4, 1996 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-8925919

RESUMO

Fatty acid hydroperoxide lyases cleave a C-C bond adjacent to a hydroperoxide group in lipoxygenase derived lipid hydroperoxides to form short-chain aldehydes and oxo-acids. Previously, we showed that fatty acid hydroperoxide lyase from bell pepper fruits is a heme protein whose spectrophotometric properties greatly resemble a cytochrome P450. In order to ascertain the relationship of it to the P450 gene family, we have cloned cDNA encoding fatty acid hydroperoxide lyase from immature bell pepper fruits. The cDNA encodes 480 amino acids, and shares homology with P450s mostly at the C terminus. The heme binding cysteine is recognizable at position 441. The most closely related P450 is allene oxide synthase (CYP74A), with which it has 40% identity. It qualifies the lyase as a member of a new P450 subfamily, CYP74B. From this finding, the enzyme is thought to be a novel member of P450 specialized for the metabolism of lipid peroxides.


Assuntos
Aldeído Liases/química , Capsicum/enzimologia , Sistema Enzimático do Citocromo P-450/química , Peróxidos Lipídicos/metabolismo , Plantas Medicinais , Aldeído Liases/metabolismo , Sequência de Aminoácidos , Sequência de Bases , Sítios de Ligação , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Sequência Conservada , Sistema Enzimático do Citocromo P-450/metabolismo , DNA Complementar/isolamento & purificação , Immunoblotting , Dados de Sequência Molecular , Ligação Proteica , Análise de Sequência
16.
FEBS Lett ; 481(2): 183-8, 2000 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-10996320

RESUMO

Fatty acid hydroperoxide lyase (HPL) is a novel P-450 enzyme that cleaves fatty acid hydroperoxides to form short-chain aldehydes and oxo-acids. In cucumber seedlings, the activities of both fatty acid 9HPL and 13HPL could be detected. High 9HPL activity was especially evident in hypocotyls. Using a polymerase chain reaction-based cloning strategy, we isolated two HPL-related cDNAs from cucumber hypocotyls. One of them, C17, had a frameshift and it was apparently expressed from a pseudogene. After repairing the frameshift, the cDNA was successfully expressed in Escherichia coli as an active HPL with specificity for 13-hydroperoxides. The other clone, C15, showed higher sequence similarity to allene oxide synthase (AOS). This cDNA was also expressed in E. coli, and the recombinant enzyme was shown to act both on 9- and 13-hydroperoxides, with a preference for the former. By extensive product analyses, it was determined that the recombinant C15 enzyme has only HPL activity and no AOS activity, in spite of its higher sequence similarity to AOS.


Assuntos
Aldeído Liases/metabolismo , Cucumis sativus/enzimologia , Sistema Enzimático do Citocromo P-450 , Aldeído Liases/química , Aldeído Liases/genética , Aldeído Liases/isolamento & purificação , Aldeídos/metabolismo , Cromatografia Líquida de Alta Pressão , Mutação da Fase de Leitura/genética , Hidroliases , Peróxido de Hidrogênio/metabolismo , Hipocótilo/enzimologia , Oxirredutases Intramoleculares/química , Oxirredutases Intramoleculares/metabolismo , Cinética , Dados de Sequência Molecular , Peso Molecular , Filogenia , Pseudogenes/genética , RNA Mensageiro/análise , RNA Mensageiro/genética , RNA de Plantas/análise , RNA de Plantas/genética , Proteínas Recombinantes/metabolismo , Especificidade por Substrato
17.
Transplantation ; 23(5): 407-13, 1977 May.
Artigo em Inglês | MEDLINE | ID: mdl-141117

RESUMO

Using solid state radioimmunoassays developed by the first author, changes in the urine level of plasmin-like substances (PLS) and fibrin degradation products (FDP) before and after human kidney transplantation were determined in 49 transplant patients. Averages of urine PLS and FDP in a normal population of 51 persons were 0.13+/-0.10 (SD) and 0.14+/-0.07 microng/ml, respectively. In all transplant patients there was an initial rise of both PLS and FDP in urine immediately after transplantation. This elevation peaked on days 4 and 5 and the PLS and FDP levels returned to normal range within 2 weeks in patients without evidence of rejeciton. A secondary rise of urine PLS was detected before or with a rise in serum creatinine in all of the patients experiencing rejections. Of 11 patients who showed a rejection episode within 2 weeks of transplantation, the secondary rise of urine PLS was detectable in 55% of the patients slightly before the serum creatinine level changes; of 6 patients with a rejection episode more than 2 weeks after transplantation, 100% showed a secondary PLS rise 6.7+/-2.3 (SE) days before the serum creatinine increased. The appearance of the secondary rise of urine FDP in the rejecting recipients was slightly later than the rise of PLS. Serial determination of urine PLS levels following human kidney transplantation appears to be an early index of rejections which occurs more than 2 weeks after transplantation, although the clinical usefulness of this measurement is probably limited.


Assuntos
Fibrinolisina/urina , Rejeição de Enxerto , Transplante de Rim , Creatinina/sangue , Produtos de Degradação da Fibrina e do Fibrinogênio/urina , Humanos , Fatores de Tempo , Transplante Homólogo
18.
Am J Cardiol ; 81(7): 828-33, 1998 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-9555770

RESUMO

There are patients in whom left ventricular (LV) wall motion decreases in the noninfarcted region and LV systolic function declines globally despite the presence of a localized myocardial infarct attributable to narrowing or occlusion of a single coronary artery. This study examines angiographic characteristics of patients with chronic hypokinesia of noninfarcted myocardium after anterior wall acute myocardial infarction (AMI) due to narrowing of a single coronary artery, namely, the left anterior descending (LAD) artery. The LV ejection fraction, abnormalities in the motion of the noninfarcted LV inferior wall (SD/chord value by Sheehan's technique), the angiographic characteristics of the infarct-related coronary artery, the effect of acute reperfusion therapy, and presence of coronary risk factors were examined in 85 consecutive patients. The SD/chord value in the noninfarcted region showed a positive correlation with the LV ejection fraction (r = 0.505, p <0.0001). By multivariate analysis, hypertension (odds ratio = 0.53, 95% confidence interval [CI] 0.36 to 0.80), an infarct-related narrowing proximal to the origin of the first diagonal branch (odds ratio = 0.56, 95% CI 0.38 to 0.84), and patency of the infarct-related lesion during AMI (odds ratio = 1.56, 95% CI 1.03 to 2.30) were independent predictors of wall motion in the noninfarct region. In some patients with single-vessel anterior wall AMI, the motion of the noninfarcted inferior LV wall decreases during the chronic stage and cardiac function declines severely. In most of these patients, the infarct-related narrowing or occlusion is proximal to the origin of the first diagonal branch of the LAD artery.


Assuntos
Doença das Coronárias/complicações , Contração Miocárdica/fisiologia , Infarto do Miocárdio/etiologia , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Cateterismo Cardíaco , Cineangiografia , Angiografia Coronária , Doença das Coronárias/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/fisiopatologia , Reperfusão Miocárdica , Fatores de Risco , Volume Sistólico/fisiologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia
19.
Keio J Med ; 48(4): 175-8, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10638140

RESUMO

The "Extensor habitus" phenomenon occurs in finger flexor tendon injuries and consists of a paradoxical extension of the interphalangeal joints after an attempt to flex the finger. The mechanism of extension is considered to be a contraction of the flexor digitorum profundus that is then transmitted via the lumbrical muscle structure to the extensor expansion. Using electromyography, we recorded the lumbrical muscle activity during the paradoxical extension phenomenon to determine whether the lumbrical muscle contributed to this event. Two patterns of electromyographical activity of the lumbrical muscle were observed. Group I (6 fingers) displayed electrical activities in the lumbrical muscle during flexion tasks, while group II (12 fingers) did not. In group I, the lesions were mainly located in zone V, and the response to range of motion exercises was satisfactory. In group II, nearly all of the lesion were located in zone II, and half of the cases required additional surgical interventions. Group II appeared to exhibit the "Extensor habitus" phenomenon, while group I exhibited an "Extensor habitus-like phenomenon." To distinguish between these two phenomena, an electromyographical examination of the lumbrical muscle must be performed.


Assuntos
Traumatismos dos Dedos/fisiopatologia , Traumatismos dos Tendões , Adolescente , Adulto , Criança , Eletromiografia , Feminino , Traumatismos dos Dedos/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/fisiopatologia , Tendões/fisiopatologia , Tendões/cirurgia
20.
J Cancer Res Clin Oncol ; 118(8): 565-6, 1992.
Artigo em Inglês | MEDLINE | ID: mdl-1517276

RESUMO

A 60-year-old woman with gastric cancer had undergone partial gastrectomy in September 1989. Pathological examination revealed a poorly differentiated adenocarcinoma of pT3pN3pM0 (not resected for cure), stage IV. Postoperative adjuvant therapy comprised 1-(tetrahydro-2-furanyl)-5-fluorouracil plus uracil and OK-432. On 11 August 1990, two forefinger-tip-sized tumors were palpated beneath the operation scar. They increase in size, the superior tumor reaching 4x3 cm, the inferior tumor 5x3 cm on 5 September. Then, on 17 September, the inferior tumor was resected but the superior tumor remained; the histological type was poorly differentiated adenocarcinoma. After the operation, from 20 September, she was given 4 mg irsogladine maleate orally every day. On 8 October, there was no increase in the size of the superior tumor. By 29 October, the superior tumor had disappeared and no further tumor appeared thereafter; the patient showed no sign of relapse.


Assuntos
Neoplasias Abdominais/tratamento farmacológico , Neoplasias Abdominais/secundário , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/patologia , Triazinas/uso terapêutico , Neoplasias Abdominais/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma/cirurgia , Feminino , Fluoruracila/administração & dosagem , Humanos , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Indução de Remissão/métodos , Triazinas/administração & dosagem
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