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1.
J Viral Hepat ; 22(10): 777-83, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25608086

RESUMO

The FIB-4 index is a simple formula using age, aspartate aminotransferase, alanine aminotransferase (ALT) and platelet count to evaluate liver fibrosis. We investigated the ability of the FIB-4 index for hepatocarcinogenesis in hepatitis C virus (HCV) carriers with normal ALT levels. A total of 516 patients with ALT levels persistently at or below 40 IU/L during an observation period of over 3 years were included. Factors associated with the development of HCC were determined. Hepatocellular carcinoma (HCC) developed in 60 of 516 patients (11.6%). The incidence rate of HCC at 5 and 10 years was 2.6% and 17.6%, respectively. When patients were categorized according to the FIB-4 index as ≤ 2.0 (n = 226), >2.0 and ≤ 4.0 (n = 169), and > 4.0 (n = 121), the cumulative incidence of HCC at 5 years was 0.5%, 1.3% and 8.0%, respectively, and 2.8%, 25.6% and 37.1% at 10 years, respectively. Patients with FIB-4 index >4.0 were at the highest risk (P < 0.001). Factors that were significantly associated with HCC in the multivariate analysis were FIB-4 index >2.0 (hazard ratio (HR), 7.690), FIB-4 index >4.0 (HR, 8.991), α-fetoprotein (AFP) >5 ng/mL (HR, 2.742), AFP >10 ng/mL (HR, 4.915) and total bilirubin >1.2 mg/dL (HR, 2.142). A scoring system for hepatocarcinogenesis that combines the FIB-4 index and AFP predicted patient outcomes with excellent discriminative ability. The FIB-4 index is strongly associated with the risk of HCC in HCV carriers with normal ALT levels.


Assuntos
Alanina Transaminase/sangue , Carcinoma Hepatocelular/diagnóstico , Testes Diagnósticos de Rotina/métodos , Hepatite C Crônica/complicações , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Aspartato Aminotransferases/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Prognóstico , Medição de Risco
2.
Br J Cancer ; 109(12): 3042-8, 2013 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-24231951

RESUMO

BACKGROUND: In multicellular organisms, precise control of cell cycle and the maintenance of genomic stability are crucial to prevent chromosomal alterations. The accurate function of the DNA damage pathway is maintained by DNA repair mechanisms including homologous recombination (HR). Herein, we show that both TFII-I and DBC1 mediate cellular mechanisms of cell-cycle regulation and DNA double strand damage repair. METHODS: Regulation of cell cycle by TFII-I and DBC1 was investigated using Trypan blue dye exclusion test, luciferase assay, and flow cytometry analysis. We also analysed the role of TFII-I and DBC1 in DNA double strand damage repair after irradiation by immunofluorescence study, clonogenicity assay, and HR assay. RESULTS: Flow cytometry analysis revealed a novel function that siRNA-mediated knockdown of endogenous DBC1 resulted in G2/M phase arrest. We also have shown that both endogenous TFII-I and DBC1 activate DNA repair mechanisms after irradiation because irradiation-induced foci formation of TFII-I-γH2AX was observed, and the depletion of endogenous TFII-I or DBC1 resulted in the inhibition of normal HR efficiency. CONCLUSION: These results reveal novel mechanisms by which TFII-I and DBC1 can modulate cellular fate by affecting cell-cycle control as well as HR pathway.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Pontos de Checagem do Ciclo Celular/fisiologia , Quebras de DNA de Cadeia Dupla , Reparo do DNA , Fatores de Transcrição TFII/fisiologia , Pontos de Checagem do Ciclo Celular/genética , Divisão Celular/genética , Divisão Celular/fisiologia , Linhagem Celular , Linhagem Celular Tumoral , DNA/química , DNA/genética , DNA/metabolismo , DNA/efeitos da radiação , Citometria de Fluxo , Pontos de Checagem da Fase G2 do Ciclo Celular/genética , Pontos de Checagem da Fase G2 do Ciclo Celular/fisiologia , Humanos , Fatores de Transcrição TFII/genética , Fatores de Transcrição TFII/metabolismo
3.
Br J Cancer ; 104(8): 1349-55, 2011 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-21407215

RESUMO

BACKGROUND: The TFII-I is a multifunctional transcriptional factor known to bind specifically to several DNA sequence elements and to mediate growth factor signalling. A microdeletion at the chromosomal location 7q11.23 encoding TFII-I and the related family of transcription factors may result in the onset of Williams-Beuren syndrome, an autosomal dominant genetic disorder characterised by a unique cognitive profile, diabetes, hypertension, anxiety, and craniofacial defects. Hereditary breast and ovarian cancer susceptibility gene product BRCA1 has been shown to serve as a positive regulator of SIRT1 expression by binding to the promoter region of SIRT1, but cross talk between BRCA1 and TFII-I has not been investigated to date. METHODS: A physical interaction between TFII-I and BRCA1 was explored. To determine pathophysiological function of TFII-I, its role as a transcriptional cofactor for BRCA1 was investigated. RESULTS: We found a physical interaction between the carboxyl terminus of TFII-I and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous TFII-I and BRCA1 form a complex in nuclei of intact cells and formation of irradiation-induced nuclear foci was observed. We also showed that the expression of TFII-I stimulates the transcriptional activation function of BRCT by a transient expression assay. The expression of TFII-I also enhanced the transcriptional activation of the SIRT1 promoter mediated by full-length BRCA1. CONCLUSION: These results revealed the intrinsic mechanism that TFII-I may modulate the cellular functions of BRCA1, and provide important implications to understand the development of breast cancer.


Assuntos
Proteína BRCA1/fisiologia , Fatores de Transcrição TFII/fisiologia , Animais , Proteína BRCA1/metabolismo , Células COS , Linhagem Celular Tumoral , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Chlorocebus aethiops , Dano ao DNA/fisiologia , Regulação Neoplásica da Expressão Gênica , Células HeLa , Humanos , Ligação Proteica , Sirtuína 1/genética , Sirtuína 1/metabolismo , Transativadores/metabolismo , Transativadores/fisiologia , Fatores de Transcrição TFII/metabolismo , Ativação Transcricional/fisiologia
4.
Eur J Gynaecol Oncol ; 32(3): 269-73, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21797114

RESUMO

PURPOSE: This study was designed to assess the safety and efficacy of a splenectomy and to analyze the prognostic factors of Müllerian carcinoma with spleen metastasis. METHODS: We reviewed the medical records of 11 patients with Müllerian carcinoma who underwent a splenectomy between 1997 and 2007. The treatment outcome of these patients was examined and the possible prognostic factors were investigated by univariate analysis. RESULTS: Four and seven patients underwent a splenectomy for primary and recurrent disease, respectively. A complete resection was achieved in eight patients. A blood transfusion was not required and only two mild postoperative complications were observed. The median and five-year survivals of all patients following treatment were 39 months and 39%, respectively. Older patients (> or = 60 years old) and patients with a poor performance status (PS2) had a poorer prognosis by univariate analysis. CONCLUSIONS: A splenectomy can be performed safely and effectively during debulking surgery for appropriately selected patients with primary or recurrent Müllerian carcinoma.


Assuntos
Carcinoma/cirurgia , Neoplasias das Tubas Uterinas/cirurgia , Ductos Paramesonéfricos/patologia , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Baço/cirurgia , Esplenectomia/efeitos adversos , Adulto , Idoso , Carcinoma/patologia , Neoplasias das Tubas Uterinas/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Prognóstico , Estudos Retrospectivos , Baço/patologia , Resultado do Tratamento
5.
Br J Cancer ; 102(6): 1061-7, 2010 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-20160719

RESUMO

BACKGROUND: DBC1/KIAA1967 (deleted in breast cancer 1) is a putative tumour-suppressor gene cloned from a heterozygously deleted region in breast cancer specimens. Caspase-dependent processing of DBC1 promotes apoptosis, and depletion of endogenous DBC1 negatively regulates p53-dependent apoptosis through its specific inhibition of SIRT1. Hereditary breast and ovarian cancer susceptibility gene product BRCA1, by binding to the promoter region of SIRT1, is a positive regulator of SIRT1 expression. METHODS: A physical interaction between DBC1 and BRCA1 was investigated both in vivo and in vitro. To determine the pathophysiological significance of DBC1, its role as a transcriptional factor was studied. RESULTS: We found a physical interaction between the amino terminus of DBC1 and the carboxyl terminus of BRCA1, also known as the BRCT domain. Endogenous DBC1 and BRCA1 form a complex in the nucleus of intact cells, which is exported to the cytoplasm during ultraviolet-induced apoptosis. We also showed that the expression of DBC1 represses the transcriptional activation function of BRCT by a transient expression assay. The expression of DBC1 also inhibits the transactivation of the SIRT1 promoter mediated by full-length BRCA1. CONCLUSION: These results revealed that DBC1 may modulate the cellular functions of BRCA1 and have important implications in the understanding of carcinogenesis in breast tissue.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/fisiologia , Proteína BRCA1/metabolismo , Regulação Neoplásica da Expressão Gênica , Ativação Transcricional , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Apoptose/genética , Proteína BRCA1/química , Proteína BRCA1/fisiologia , Células Cultivadas , Células HeLa , Humanos , Ligação Proteica , Estrutura Terciária de Proteína/fisiologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/fisiologia , Sirtuína 1/genética , Distribuição Tecidual , Ativação Transcricional/genética
6.
J Viral Hepat ; 15(9): 651-8, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18637076

RESUMO

Serum ribavirin concentration is an important factor in antiviral therapy in combination with peginterferon (PEG-IFN) and ribavirin for patients with chronic hepatitis C in terms of both beneficial and adverse effects. We evaluated whether the serum ribavirin concentration can be predicted on the basis of renal function estimates. Serum creatinine and cystatin C concentrations were measured at the start of treatment in a total of 148 patients with chronic hepatitis C who underwent combination PEG-IFN and ribavirin therapy. Creatinine clearance (CrCl) and total clearance of ribavirin (CL/F) were calculated on the basis of the serum creatinine level. The glomerular filtration rate was calculated with two different formulae on the basis of the serum cystatin C level. These values were compared with serum ribavirin concentrations 4 weeks after the start of therapy. The cystatin C level increased with the progression of liver fibrosis, whereas the creatinine level was constant regardless of the degree of liver fibrosis. Significant correlation was not observed between the serum ribavirin concentration and serum creatinine level, cystatin C level, or calculated renal function estimates. However, significant correlation was found between the serum ribavirin concentration and CrCl and CL/F in patients who were given ribavirin >800 mg/day. Overall, renal function estimates do not correlate with the serum ribavirin concentration in Japanese patients with chronic hepatitis C who undergo combination PEG-IFN and ribavirin therapy. Serum creatinine-based renal function estimates might be predictive for the serum ribavirin concentration only in patients with a daily ribavirin intake of 800 mg or more.


Assuntos
Antivirais/farmacocinética , Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Testes de Função Renal , Ribavirina/farmacocinética , Ribavirina/uso terapêutico , Idoso , Povo Asiático , Creatinina/sangue , Cistatina C , Cistatinas/sangue , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/uso terapêutico , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Polietilenoglicóis , Proteínas Recombinantes , Soro/química , Estatística como Assunto
7.
Int J Gynaecol Obstet ; 99(3): 225-8, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17897648

RESUMO

OBJECTIVE: To identify the best operative approach for neuroendocrine cervical carcinoma (NECC). METHODS: The records of surgically treated patients with stages IB to IIB NECC were reviewed. RESULTS: Of 10 patients who met the study criteria for NECC and underwent radical hysterectomy, 4 had pT1bN0, 4 had pT1bN1, 1 had pT2aN0, and 1 had pT2bN1 disease. Those with pT1bN1 or pT2bN1 disease received postoperative adjuvant radiotherapy and/or chemotherapy, and recurrence occurred in 7 patients (70%). Among these 7 patients, 5 (71%) had a primary NECC tumor with deep stromal invasion and 5 (71%) had extrauterine disease (parametrium and/or lymph node). The recurrences in 6 patients (86%) were located outside the pelvis (lung, liver, or brain). Stromal invasion was 6 mm or less in the 3 patients who did not experience disease recurrence. CONCLUSIONS: Pelvic control by radical hysterectomy may not be beneficial for patients with NECC except for those with an early invasive lesion.


Assuntos
Carcinoma Neuroendócrino/cirurgia , Histerectomia , Neoplasias do Colo do Útero/cirurgia , Adulto , Carcinoma Neuroendócrino/patologia , Quimioterapia Adjuvante/métodos , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia/prevenção & controle , Prognóstico , Radioterapia Adjuvante , Neoplasias do Colo do Útero/patologia
8.
Oncogenesis ; 5(12): e280, 2016 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-27991914

RESUMO

Recent whole-exome sequencing of malignancies have detected recurrent somatic mutations in U2 small nuclear ribonucleoprotein complex (snRNP) components of the spliceosome. These factors have also been identified as novel players in the DNA-damage response (DDR) in several genome-wide screens and proteomic analysis. Although accumulating evidence implies that the spliceosome has an important role in genome stability and is an emerging hallmark of cancer, its precise role in DNA repair still remains elusive. Here we identify two distinct mechanisms of how spliceosome U2 snRNP factors contribute to genome stability. We show that the spliceosome maintains protein levels of essential repair factors, thus contributing to homologous recombination repair. In addition, real-time laser microirradiation analysis identified rapid recruitment of the U2 snRNP factor SNRPA1 to DNA-damage sites. Functional analysis of SNRPA1 revealed a more immediate and direct role in preventing R-loop-induced DNA damage. Our present study implies a complex interrelation between transcription, mRNA splicing and the DDR. Cells require rapid spatio-temporal coordination of these chromatin transactions to cope with various forms of genotoxic stress.

9.
Biochim Biophys Acta ; 874(2): 137-43, 1986 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-3778915

RESUMO

It was shown that substoichiometric concentrations of chaetoglobosin J, one of the fungal metabolites belonging to cytochalasins, inhibited the elongation at the barbed end of an actin filament. Stoichiometric concentrations of chaetoglobosin J decreased both the rate and the extent of actin polymerization in the presence of 75 mM KCl, 0.2 mM ATP and 10 mM Tris-HCl buffer at pH 8.0 and 25 degrees C. In contrast, stoichiometric concentrations of cytochalasin D accelerated actin polymerization. Chaetoglobosin J slowly depolymerized F-actin to G-actin until an equilibrium was reached. Analyses by a number of different methods showed the increase of monomer concentration at equilibrium to depend on chaetoglobosin J concentrations. F-actin under the influence of stoichiometric concentrations of chaetoglobosin J only slightly activated the Mg2+-enhanced ATPase activity of myosin at low ionic strength. It is suggested that when the structure of the chaetoglobosin-affected actin filaments is modified, the equilibrium is shifted to the monomer side, and the interaction with myosin is weakened.


Assuntos
Actinas/metabolismo , Indóis/farmacologia , Micotoxinas/farmacologia , Animais , Citocalasina D , Citocalasinas/farmacologia , Alcaloides Indólicos , Cinética , Substâncias Macromoleculares , Músculos/metabolismo , Coelhos , Relação Estrutura-Atividade
10.
Prostaglandins Other Lipid Mediat ; 78(1-4): 279-90, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16303622

RESUMO

Interleukin (IL)-1 has been suggested to participate in regulation of many reproductive functions. To investigate the possible role of IL-1alpha as a local regulator in bovine endometrium, we determined the effects of IL-1alpha on prostaglandin (PG) E2 and PGF(2alpha) output by the bovine endometrium at different stages of the estrous cycle. The expressions of IL-1alpha and IL-1 receptor type 1 (IL-1RT1) mRNA in bovine endometrium were also studied. Bovine uteri were classified into six stages (estrus: day 0; early luteal: days 2-3; developing luteal: days 5-6; mid luteal: days 8-12; late luteal: days 15-17; and follicular: days 19-21). After 1h of pre-incubation, endometrial tissues (20-30mg) were exposed to 0 or 10ng/ml IL-1alpha for 4h. IL-1alpha significantly stimulated PGE2 output throughout the luteal stages, with the highest response during the mid luteal stage, while it did not stimulate PGE2 output during the estrus and the follicular stage. On the other hand, IL-1alpha significantly enhanced PGF(2alpha) output throughout the estrous cycle except in the endometrium from the mid luteal stage, with the highest response at the follicular stage (P<0.001). The treatment of endometrial tissue with IL-1alpha resulted in an increase of the PGE2:PGF(2alpha) ratio at the mid luteal stage, and in a decrease during the late luteal and follicular stages of the estrous cycle. A semiquantitative reverse transcription-polymerase chain reaction revealed that IL-1alpha and IL-1RT1 mRNA are expressed in the endometrium throughout the estrous cycle. IL-1alpha mRNA expression was greater in the early luteal stage than in the estrus, late luteal, and follicular stages (P<0.05). IL-1RT1 mRNA was greater in the late luteal stage than in the other stages (P<0.05). The overall results suggest that IL-1alpha is produced in bovine endometrium throughout the estrous cycle, and plays some roles not only in maintenance of CL, but also in luteolysis by regulating the local PGE2:PGF(2alpha) ratio in bovine endometrium during the estrous cycle.


Assuntos
Dinoprosta/biossíntese , Dinoprostona/biossíntese , Endométrio/efeitos dos fármacos , Estro , Interleucina-1/farmacologia , Animais , Sequência de Bases , Bovinos , Primers do DNA , Relação Dose-Resposta a Droga , Endométrio/metabolismo , Feminino , Interleucina-1/genética , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
11.
J Clin Endocrinol Metab ; 85(2): 824-9, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10690897

RESUMO

Endometriosis, a common disease among women of reproductive age, is characterized by the presence of endometrial-like tissue outside the uterus. We and others showed that several cytokine levels, including interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNFalpha), are elevated in the peritoneal fluid of women with endometriosis compared with those in women without endometriosis. We also demonstrated that the addition of IL-8 to the culture medium stimulated the proliferation of cultured endometriotic stromal cells. TNFalpha is a multipotent cytokine that induces IL-8 production in various cell types. Therefore, we hypothesized that TNFalpha may also contribute to the pathogenesis of endometriosis by inducing the production of IL-8. To test this hypothesis, we analyzed the peritoneal fluid concentrations of IL-8 and TNFalpha using enzyme-linked immunosorbent assay (ELISA). We observed a significant correlation between the levels of TNFalpha and IL-8 in the peritoneal fluid of endometriosis patients. We also obtained the endometriotic stromal cells from chocolate cyst linings of the ovary. The expression of the receptors for TNFalpha (TNFR) was examined by RT-PCR. We observed the expression of both TNFR-I and TNFR-II genes in endometriotic stromal cells. The expression of IL-8 gene and protein was analyzed by Northern blot hybridization and enzyme-linked immunosorbent assay, respectively. TNFalpha induced the gene and protein expression of IL-8 in endometriotic stromal cells in a dose-dependent fashion. The addition of TNFalpha promoted the proliferation of the endometriotic stromal cells, and the stimulatory effects of TNFalpha were abolished by adding anti-IL-8 antibody. We demonstrated for the first time that TNFalpha stimulated proliferation of endometriotic stromal cells through induction of IL-8 gene and protein expression. We concluded that the TNFalpha may be one of the essential factors for the pathogenesis of endometriosis.


Assuntos
Endometriose/patologia , Interleucina-8/metabolismo , Células Estromais/patologia , Fator de Necrose Tumoral alfa/farmacologia , Adulto , Líquido Ascítico/metabolismo , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Endometriose/genética , Endometriose/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-8/genética , Concentração Osmolar , Receptores do Fator de Necrose Tumoral/metabolismo , Células Estromais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
J Clin Endocrinol Metab ; 83(4): 1239-42, 1998 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-9543148

RESUMO

The c-kit protooncogene receptor and its ligand stem cell factor (SCF) regulate the proliferation and survival of germ cells as well as hematopoietic cells and melanocytes. In adult rodent ovary, c-kit and SCF play important roles in follicular development. However, little information about c-kit in the human ovary is available. In this study, we examined the expressions of c-kit messenger ribonucleic acid (mRNA) and c-kit protein in human oocytes, granulosa cells, and follicular fluid obtained from the women who underwent in vitro fertilization or laparoscopic examination. Expression of c-kit mRNA was detected by RT-PCR in the oocytes and granulosa cells. Western blot analysis showed the presence of soluble c-kit protein in the follicular fluid, and lower levels of c-kit protein were detected in the granulosa cells and the supernatant of granulosa cell cultures. The concentration of soluble c-kit in follicular fluid measured by enzyme-linked immunosorbent assay showed significant correlation with fluid volume and follicular fluid concentrations of estradiol, testosterone, and androstenedione. In summary, we found for the first time the presence of c-kit mRNA and soluble c-kit protein in human oocytes and follicular fluid. The results suggested that in human ovary, c-kit may play an important role in follicular development.


Assuntos
Líquido Folicular/metabolismo , Células da Granulosa/metabolismo , Oócitos/metabolismo , Proteínas Proto-Oncogênicas c-kit/genética , RNA Mensageiro/biossíntese , Adulto , Androstenodiona/metabolismo , Estradiol/metabolismo , Feminino , Humanos , Infertilidade Feminina/metabolismo , Modelos Lineares , Reação em Cadeia da Polimerase/métodos , Progesterona/metabolismo , Solubilidade , Esteroides/metabolismo , Testosterona/metabolismo , Transcrição Gênica
13.
Pancreas ; 8(2): 240-7, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8460097

RESUMO

The effect of a novel synthetic trypsin inhibitor, 4-sulfamoylphenyl 4-guanidinobenzoate methanesulfonate (ONO-3307), on severe acute pancreatitis was studied by changing its timing, frequency, and dose in trypsin-taurocholate-induced acute experimental pancreatitis in rats. Rats were divided into four groups according to difference of ONO-3307 administration: group A, 2 mg/0.5 ml of ONO-3307 s.c. 1 h before and after induction of pancreatitis; group B, 2 mg/0.5 ml s.c. 1 and 3 h after; group C, 4 mg/1 ml s.c. 1 h before; group D, 4 mg/1 ml s.c. 1 h after. The survival rate at 24 h was significantly improved in group A (75% in A vs. 17% in control; p < 0.01) and in group B (57 vs. 29%; p < 0.05), but not in group C or D. Amylase and immunoreactive trypsin in serum and ascites of the treated were significantly lower than those of controls in both groups A and B. The survival rates were improved dose dependently when ONO-3307 was administered 1 h before and after induction of pancreatitis. ONO-3307 showed favorable effects on the initial stage of severe acute pancreatitis when given in divided doses to maintain the effective serum levels.


Assuntos
Guanidinas/farmacologia , Pancreatite/tratamento farmacológico , Inibidores da Tripsina/farmacologia , Doença Aguda , Animais , Relação Dose-Resposta a Droga , Masculino , Pancreatite/induzido quimicamente , Ratos , Ratos Wistar , Taxa de Sobrevida , Ácido Taurocólico
14.
Fertil Steril ; 56(6): 1060-5, 1991 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-1743322

RESUMO

STUDY OBJECTIVE: To investigate whether or not transvaginal ultrasound (US)-guided follicular aspiration can effectively induce ovulation and facilitate pregnancy in anovulatory patients with polycystic ovaries (PCO). DESIGN: Eight patients with polycystic ovarian disease (PCOD) and 10 patients with PCO were participants who failed to ovulate by the medical therapies. Most of persistent follicles were punctured, and their contents were thoroughly aspirated during the midluteal phase. The same ovarian stimulation regimen as used in the previous cycles were administered in the cycles after the aspiration. MAIN OUTCOME MEASURES: Evidence of ovulation and a subsequent pregnancy was ultrasonically monitored after the aspiration, and the responsiveness of pituitary gonadotropins to gonadotropin-releasing hormone was tested in these patients. RESULTS: The ovulation rates were 87.5% per patient, 52.6% per cycle monitored in PCOD patients and 100% per patient, 63.3% per cycle monitored in PCO patients, respectively. Half of the patients both with PCOD and PCO achieved pregnancy after the aspiration. A significant decrease (P less than 0.05) of the basal and peak levels of serum luteinizing hormone was observed after the aspiration. CONCLUSIONS: The US-guided follicular aspiration seems to be a new surgical method for treating anovulatory patients with PCO.


Assuntos
Anovulação/complicações , Infertilidade Feminina/terapia , Folículo Ovariano , Síndrome do Ovário Policístico/complicações , Sucção/métodos , Anovulação/diagnóstico , Feminino , Hormônios Esteroides Gonadais/sangue , Hormônio Liberador de Gonadotropina , Humanos , Infertilidade Feminina/sangue , Infertilidade Feminina/etiologia , Folículo Ovariano/diagnóstico por imagem , Ultrassonografia , Vagina
15.
Fertil Steril ; 73(2): 205-11, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10685516

RESUMO

OBJECTIVE: To compare the expression of interleukin-6 (IL-6) in endometrial and endometriotic cells. DESIGN: Prospective study. SETTING: Department of Obstetrics and Gynecology, Tottori University Hospital, Yonago, Japan. PATIENT(S): Twenty patients who underwent either hysterectomy or laparoscopic surgery. INTERVENTION(S): Endometrial and endometriotic stromal cells were obtained from normal endometrium and from chocolate cyst linings of the ovary. Peritoneal macrophages were isolated from peritoneal fluids. Cells were cultured in the presence or absence of tumor necrosis factor-alpha. MAIN OUTCOME MEASURE(S): Gene expression of IL-6 was examined by Northern blot analysis. Interleukin-6 protein production was examined by immunocytochemical staining and ELISA. RESULT(S): A single IL-6 messenger RNA band of approximately 1.3 kilobases was detected in endometriotic stromal cells. Tumor necrosis factor-alpha increased the expression of IL-6 messenger RNA in endometriotic cells in a dose-dependent manner. In endometrial stromal cells, IL-6 messenger RNA signals were much weaker. Endometriotic stromal cells produced significantly larger amounts of IL-6 compared with endometrial stromal cells under basal conditions and after stimulation with tumor necrosis factor-alpha. Interleukin-6 protein was detected in cells isolated from endometriotic tissues by immunocytochemical staining. Interleukin-6 production by cultured macrophages from patients with endometriosis and endometriotic stromal cells was comparable. CONCLUSION(S): Altered gene expression and protein secretion of IL-6 in patients with endometriosis may contribute to the pathogenesis of the disease and/or to endometriosis-associated infertility.


Assuntos
Endometriose/metabolismo , Endometriose/patologia , Endométrio/citologia , Interleucina-6/genética , Interleucina-6/metabolismo , Adulto , Endometriose/genética , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Regulação da Expressão Gênica , Humanos , Imuno-Histoquímica , Leiomioma/genética , Leiomioma/patologia , Macrófagos Peritoneais/metabolismo , Estudos Prospectivos , Células Estromais/efeitos dos fármacos , Células Estromais/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Neoplasias Uterinas/genética , Neoplasias Uterinas/patologia
16.
Fertil Steril ; 69(5): 924-30, 1998 May.
Artigo em Inglês | MEDLINE | ID: mdl-9591504

RESUMO

OBJECTIVE: To investigate the role of interleukin-8 (IL-8) in peritoneal fluid of patients with endometriosis in the pathogenesis of endometriosis. DESIGN: Peritoneal fluid was collected by laparoscopy. Endometrial and endometriotic stromal cells were obtained from normal endometrium and from chocolate cyst linings of the ovary. SETTING: Department of Obstetrics and Gynecology of Tottori University Hospital, Yonago, Japan. PATIENT(S): Forty women who underwent either laparoscopy or laparoscopic surgery. MAIN OUTCOME MEASURE(S): The peritoneal fluid concentration of IL-8 was analyzed by enzyme-linked immunosorbent assay, and the correlation between the IL-8 concentration and the extent of active endometriosis was investigated. The effect of IL-8 on cell proliferation was examined by tetrazolium bromide and thymidine incorporation. The expression of IL-8 receptor was examined in stromal cells by reverse transcription polymerase chain reaction. RESULT(S): The level of IL-8 in peritoneal fluid was significantly higher in patients with endometriosis than in patients without endometriosis. A significant correlation was noted with the extent of active endometriosis. Interleukin-8 significantly increased the number of cells and DNA synthesis in the endometrial and endometriotic stromal cells in a dose-dependent manner. Transcripts of IL-8 receptor type A were detected in stromal cells. CONCLUSION(S): The present study suggests that IL-8 found in the peritoneal fluid of patients with endometriosis contributes to the pathogenesis of endometriosis.


Assuntos
Líquido Ascítico/química , Endometriose/metabolismo , Interleucina-8/análise , Antígenos CD/análise , Divisão Celular , Células Cultivadas , Endometriose/etiologia , Endometriose/patologia , Feminino , Humanos , Receptores de Interleucina/análise , Receptores de Interleucina-8A , Células Estromais/fisiologia
17.
Fertil Steril ; 75(5): 973-9, 2001 May.
Artigo em Inglês | MEDLINE | ID: mdl-11334911

RESUMO

OBJECTIVE: To examine gene expression of hepatocyte growth factor (HGF), the receptor for HGF, c-met, and the receptor for stem cell factor (SCF), c-kit, in the human ovary and to investigate the effects of HGF and SCF on the proliferation and function of granulosa and theca cells. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Six premenopausal women. INTERVENTION(S): Follicular fluid and granulosa cells were collected during IVF cycles. Ovarian tissues were obtained from women who underwent surgery. MAIN OUTCOME MEASURE(S): Gene expression of HGF, c-met, and c-kit in the human ovary was determined. RESULT(S): Reverse-transcription polymerase chain reaction showed the presence of HGF and c-kit mRNA in the theca and stroma cells of the ovary, whereas c-met mRNA was observed in the granulosa, theca, and stroma cells. HGF increased the expression of SCF gene in granulosa cells, and SCF reciprocally increased the expression of HGF gene in theca cells. SCF stimulated the proliferation of theca cells. HGF stimulated progesterone production in granulosa cells. CONCLUSION(S): A positive feedback loop between theca cells and granulosa cells was identified that is mediated by HGF and SCF. HGF and SCF modulate the interplay between theca and granulosa cells by promoting cell proliferation and steroid hormone production.


Assuntos
Células da Granulosa/fisiologia , Fator de Crescimento de Hepatócito/fisiologia , Fator de Células-Tronco/fisiologia , Células Tecais/fisiologia , Adulto , Comunicação Celular/fisiologia , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Estradiol , Feminino , Líquido Folicular/fisiologia , Regulação da Expressão Gênica/fisiologia , Células da Granulosa/citologia , Fator de Crescimento de Hepatócito/biossíntese , Fator de Crescimento de Hepatócito/genética , Humanos , Modelos Lineares , Reação em Cadeia da Polimerase , Progesterona/biossíntese , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-kit/biossíntese , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/fisiologia , Proteínas Proto-Oncogênicas c-met/biossíntese , Proteínas Proto-Oncogênicas c-met/genética , Proteínas Proto-Oncogênicas c-met/fisiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Fator de Células-Tronco/biossíntese , Fator de Células-Tronco/genética , Células Tecais/citologia
18.
Masui ; 43(10): 1593-5, 1994 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-7815713

RESUMO

A 10-yr-old boy with an injured lower extremity received sevoflurane anesthesia 5 times within 40 days. Laboratory tests for hepatic and renal function i.e., serum transaminase (glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, gamma-glutamyl transpeptidase), serum cholinesterase, plasma protein, serum cholinesterase, serum bilirubine, serum lactic dehydrogenase, serum prothrombin time, blood urea nitrogen, serum creatinine, beta 2-microglobulin, N-acetyl-D-glucosamidase and 24 hr-creatinine clearance remained within normal ranges throughout his perioperative period. Repeated sevoflurane anesthesia did not exert any adverse effect on hepatic and renal function in this patient.


Assuntos
Anestesia por Inalação , Éteres , Rim/fisiopatologia , Fígado/fisiopatologia , Éteres Metílicos , Criança , Traumatismos do Pé/cirurgia , Humanos , Testes de Função Renal , Testes de Função Hepática , Masculino , Período Pós-Operatório , Reoperação , Sevoflurano
19.
Nihon Shokakibyo Gakkai Zasshi ; 93(8): 553-9, 1996 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-8810812

RESUMO

Percutaneous transhepatic cholecyst puncture (PTCCP) is a unique treatment for acute cholecystitis by using of 21 gauge PTC needle with ultrasoundimage control. The procedure is as follows. A percutaneous transhepatic puncture of the gallbladder is made with ultrasonic guidance. After suction removal of the contents of the gallbladder, saline with antibiotics is injected. Finally PTC needle is removed after removal of the injected saline. We carried out PTCCP in 35 patients with acute cholecystitis, and compared its clinical effect with those of PTCCD (46 cases) or conservative treatment of antibiotics administration (38 cases). The treatment of PTCCP removed the clinical symptoms of acute cholecystitis rapidly compared with the conservative treatment and it made the hospitalization shorter compared with the treatment of PTCCD. PTCCP was also performed without any severe complications for patients with underlying diseases. The curative rate of PTCCP was the same as those of other former treatments. It was concluded that PTCCP is a safe, convenient, and useful treatment of acute cholecystitis.


Assuntos
Colecistite/diagnóstico por imagem , Colecistite/terapia , Punções/métodos , Sucção/métodos , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Criança , Drenagem , Feminino , Humanos , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Ultrassonografia
20.
Nihon Shokakibyo Gakkai Zasshi ; 88(12): 2853-60, 1991 Dec.
Artigo em Japonês | MEDLINE | ID: mdl-1726222

RESUMO

We measured serum level of alpha 2-macroglobulin-trypsin complex (alpha 2M-T complex) using a colorimetric assay with a synthetic chromogenic substrate, D-gamma-tert-butyloxy-Gly-Arg-3-carboxy-4-hydroxyanilide dihydrochloride. Serum level of alpha 2M-T complex was greater in acute pancreatitis patients than in chronic pancreatitis or pancreatic cancer patients. In severe acute pancreatitis patients, both mean level and frequency of abnormal value of serum alpha 2M-T complex were significantly greater than in mild acute pancreatitis patients (13.1 +/- 12.9 vs 2.9 +/- 3.5 U/L, p less than 0.01; 100 vs 41%, p less than 0.01). In conclusion, the determination of serum level of alpha 2M-T complex can be useful for the diagnosis of severe acute pancreatitis.


Assuntos
Anilidas , Ensaios Enzimáticos Clínicos , Oligopeptídeos , Pancreatopatias/diagnóstico , Tripsina/metabolismo , alfa-Macroglobulinas/metabolismo , Doença Aguda , Compostos Cromogênicos , Colorimetria/métodos , Humanos , Pancreatopatias/sangue , Pancreatite/diagnóstico
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