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1.
Eur J Gynaecol Oncol ; 37(3): 327-31, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27352558

RESUMEN

PURPOSE: Cervical conization is the definitive treatment for women of any age who have cervical intraepithelial neoplasia (CIN). However, complications of the procedure have not been fully investigated in postmenopausal patients. The aim of this retrospective study was to evaluate the results and complications of cervical conization performed on premenopausal and postmenopausal patients. MATERIALS AND METHODS: This study recruited 405 patients who had undergone cervical laser conization. The median age was 36 years (range 20 to 75), and there were 361 (89.1%) premenopausal and 44 (10.9%) postmenopausal women. RESULTS: The length of the cone removed from the postmenopausal patients was significantly longer than the length from the premenopausal patients (17.9 ± 3.9 mm vs. 15.7 ± 3.6 mm, respectively; p = 0.02). The rate of positive endocervical cone margins from the premenopausal patients was significantly higher than the rate from the postmenopausal patients (9.1% vs. 0%, respectively; p = 0.037). The rate of cervical stenosis was significantly higher in postmenopausal patients than in premenopausal patients (59.1% vs. 8.3%; respectively; p < 0.0001). There was no difference in the rates of frequency of intraoperative complications. CONCLUSIONS: Although deep incision is mandatory for complete excision of CIN in postmenopausal patients, it increases the incidence of cervical stenosis. Cervical conization may be a less invasive surgical procedure for older women with CIN than hysterectomy; however, the risk of postoperative complications remains, causing a dilemma for physicians treating postmenopausal women with CIN.


Asunto(s)
Cuello del Útero/patología , Conización/efectos adversos , Displasia del Cuello del Útero/cirugía , Neoplasias del Cuello Uterino/cirugía , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Posmenopausia , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Displasia del Cuello del Útero/patología
2.
Eur J Dent Educ ; 18(4): 241-51, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25318559

RESUMEN

INTRODUCTION: Simulated patients (SPs) need education and training in required skills to be effective resources in education. This study was conducted to examine the effectiveness of an SP training programme based on the accuracy of trainee responses and the appropriateness of their feedback. METHODS: Thirty-two applicants to the training programme and 35 experienced SPs were included in this study. The experienced SPs served as a reference group. The rate of accurate responses and the rate of appropriate feedback were assessed with pre- and post-training tests, and these two outcome measures were compared with those of the experienced SPs. RESULTS: No significant differences were found in trainee response accuracy or appropriateness of feedback between pre- and post-training tests. The response accuracy rate of the trainees on the pre-training test was significantly lower than that of SPs with 1-2 years of experience, whilst there was no significant difference between these SPs and the trainees on the post-training test. CONCLUSIONS: Although our study suggests that more training is needed to improve the skills of SPs, the training programme may contribute to helping trainees reach a novice level in the skill of providing accurate responses. SP training should be encouraged to contribute to the effectiveness of such teaching and to establish the validity of the assessment.


Asunto(s)
Competencia Clínica , Educación en Odontología/métodos , Evaluación Educacional , Simulación de Paciente , Adulto , Retroalimentación , Femenino , Humanos , Japón , Masculino , Reproducibilidad de los Resultados
3.
J Viral Hepat ; 19(10): 694-703, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22967100

RESUMEN

Pegylated interferon-α (PEG-IFN-α) plus ribavirin (RBV) treatment fails to achieve a sustained virological response (SVR) in approximately 20-50% of patients with chronic hepatitis C virus (HCV) infection. We assessed the contribution of an anti-IFN-α neutralizing antibody (NAb) on the nonresponse to treatment. NAbs were detected using an antiviral assay that assessed the neutralizing effects of serum samples against IFN. Serum samples were obtained at the end of the treatment and evaluated for the presence of NAbs using recombinant IFN-α as a standard. We studied 129 PEG-IFN-α/RBV-treated patients. In the 82 end-of-treatment responders, no NAbs were detected. Of the 47 patients who did not respond, seven (15%) were positive for NAbs. We also examined an additional 83 patients who had not responded to PEG-IFN-α treatment, and detected 12 with NAbs. Patients with good IFN-responsive characteristics, including HCV genotype 2/3 and major allele homozygotes for interleukin-28B, were included in the 19 patients with NAbs. No NAbs interfered with the antiviral activity of natural human IFN-ß (nIFN-ß) and re-treatement of patients with NAbs with nIFN-ß/RBV achieved SVR. Our analyses revealed that the emergence of anti-IFN-α NAbs was a candidate causal factor of PEG-IFN-α-treatment failure. Therefore, these antibodies should be assayed in patients who do not respond to PEG-IFN-α therapy, and if detected, other effective treatments, i.e., medications that are not neutralized by anti-IFN-α NAbs, should be considered.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Hepatitis C Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Interferón-alfa/inmunología , Ribavirina/administración & dosificación , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Neutralización , Resultado del Tratamiento
4.
Ultrasound Obstet Gynecol ; 37(1): 22-6, 2011 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-20878679

RESUMEN

OBJECTIVES: The aim of this study was to evaluate the use of ultrasound assessment to predict risk of mortality in expectantly managed monochorionic twin fetuses with selective intrauterine growth restriction (sIUGR). METHODS: This was a retrospective study of 101 monochorionic twin pregnancies diagnosed with sIUGR before 26 weeks of gestation. All patients were under expectant management during the observation period. At the initial evaluation, the presence or absence of each of the following abnormalities was documented: oligohydramnios; stuck twin phenomenon; severe IUGR < 3(rd) centile of estimated fetal weight; abnormal Doppler in the umbilical artery; and polyhydramnios in the larger twin. The relationships between these ultrasound findings and mortality of sIUGR fetuses were evaluated using multiple logistic regression analysis. RESULTS: Of 101 sIUGR twins, 22 (21.8%) fetuses suffered intrauterine demise and nine (8.9%) suffered neonatal death; 70 (69.3%) survived the neonatal period. Multiple logistic regression analysis revealed that the stuck twin phenomenon (odds ratio (OR): 14.5; 95% CI: 2.2-93.2; P = 0.006) and constantly absent diastolic flow in the umbilical artery (OR: 29.4; 95% CI: 3.3-264.0; P = 0.003) were significant risk factors for mortality. CONCLUSIONS: Not only abnormal Doppler flow in the umbilical artery but also severe oligohydramnios should be recognized as important indicators for mortality in monochorionic twins with sIUGR.


Asunto(s)
Enfermedades en Gemelos/diagnóstico por imagen , Retardo del Crecimiento Fetal/diagnóstico por imagen , Transfusión Feto-Fetal/diagnóstico por imagen , Oligohidramnios/diagnóstico por imagen , Arterias Umbilicales/diagnóstico por imagen , Enfermedades en Gemelos/mortalidad , Enfermedades en Gemelos/fisiopatología , Femenino , Muerte Fetal/diagnóstico por imagen , Retardo del Crecimiento Fetal/mortalidad , Retardo del Crecimiento Fetal/fisiopatología , Transfusión Feto-Fetal/mortalidad , Transfusión Feto-Fetal/fisiopatología , Edad Gestacional , Humanos , Recién Nacido , Masculino , Oligohidramnios/mortalidad , Oligohidramnios/fisiopatología , Embarazo , Resultado del Embarazo , Pronóstico , Estudios Retrospectivos , Gemelos Monocigóticos , Ultrasonografía Prenatal
5.
Eur J Gynaecol Oncol ; 32(4): 381-6, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-21941957

RESUMEN

PURPOSE: There are currently no clinically available chemosensitivity assays for cervical cancer. In this study we evaluated whether the histoculture drug response assay (HDRA) could be used to predict chemosensitivity to nedaplatin (NDP) in cervical cancer. METHODS: Fifty-four surgical specimens and biopsies from patients with squamous cell carcinoma of the cervix were tested with the HDRA. The results were used to calculate the concentration resulting in 50% inhibition of tumor growth (IC50). We then determined the cut-off concentration for NDP, and investigated the chemosensitivity of NDP for each patient. Moreover, the correlations between chemosensitivity and the clinical response of NDP-containing chemotherapy, and the clinical outcomes of the patients with Stage I and II disease were also investigated. RESULTS: Fifty-one of 54 specimens (94.0%) were evaluable with this assay. The optimal cutoff concentration of NDP was determined to be 48 microg/ml. In 18 patients with measurable lesions, all nine patients in the high sensitive group by HDRA were judged as partial response (PR) to NDP containing chemotherapy. In contrast five of nine patients in the low sensitive group were classified as stable disease, and four were PR. The true positive rate was 100%, the true negative rate was 55.6%, and the accurate prediction rate was 77.8%. Furthermore, the disease-free survival of the high sensitive group tended to be better than that of the low sensitive group in the patients who received postoperative adjuvant chemotherapy with NDP. CONCLUSIONS: In the current study, the sensitivity of cervical tumors to nedaplatin was predicted by the HDRA.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Resistencia a Antineoplásicos/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales/métodos , Compuestos Organoplatinos/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Células Tumorales Cultivadas , Neoplasias del Cuello Uterino/patología
6.
Ultrasound Obstet Gynecol ; 36(3): 384-6, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20533442

RESUMEN

The exact determination of amnionicity is a major issue for the clinical management of monochorionic twin pregnancies, due to the high risk of perinatal mortality and morbidity in monochorionic monoamniotic (MCMA) twins. Counting the number of yolk sacs is believed to be a good indicator of amnionicity in the early first trimester, and it has previously been suggested that the number of yolk sacs is equal to amnionicity in both MCMA and monochorionic diamniotic twin pregnancies. However, the accuracy of the relationship between number of yolk sacs and amnionicity has recently been called into question. To the best of our knowledge, no previous reports have shown two yolk sacs in MCMA twin pregnancies. We report two cases of MCMA twins with two yolk sacs on first-trimester ultrasonography, and confirmed monoamnionicity in the second trimester showing umbilical cord entanglement. Postnatal examination showed an MCMA placenta in both cases, and entangled umbilical cords confirmed monoamnionicity. The possibility of monoamnionicity must still be suspected when two yolk sacs are detected early in the first trimester on ultrasound examination in monochorionic twin pregnancies.


Asunto(s)
Amnios/diagnóstico por imagen , Placenta/diagnóstico por imagen , Saco Vitelino/diagnóstico por imagen , Adulto , Amnios/fisiopatología , Femenino , Humanos , Placenta/fisiopatología , Embarazo , Resultado del Embarazo , Primer Trimestre del Embarazo , Gemelos , Ultrasonografía Prenatal , Saco Vitelino/fisiología
7.
Ultrasound Obstet Gynecol ; 32(6): 813-8, 2008 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-18956440

RESUMEN

OBJECTIVE: To validate the Quintero stage III subclassification for twin-twin transfusion syndrome (TTTS) based on visibility of the bladder of the donor twin. METHODS: Between July 2002 and August 2006, there were 131 pregnant Japanese women affected by severe TTTS before 26 weeks' gestation, treated with fetoscopic laser surgery at five centers in Japan, whose pregnancies continued beyond 22 weeks. Outcome data were available in all cases and surviving infants were followed up for at least 6 years. This study focused on the Stage III TTTS patients. These were subclassified into Stage III atypical (abnormal Doppler flow with visible donor bladder) and Stage III classical (abnormal Doppler flow with non-visible donor bladder) groups. Perioperative data and postnatal outcomes were compared between the groups. RESULTS: Seven Stage I, 22 Stage II, 82 Stage III and 20 Stage IV pregnancies continued beyond 22 weeks. There was a significantly higher incidence of absent or reversed end-diastolic velocity in the umbilical artery (UA-AREDV) of the donor in Stage III atypical than in Stage III classical patients (83.8% vs. 53.3%, P = 0.004). Stage III atypical cases also had a significantly higher incidence of arterioarterial (AA) anastomoses (72.9% vs. 17.8%, P < 0.001) and intrauterine fetal demise (IUFD) of the donor (43.2% vs. 13.3%, P = 0.002). However, there were no differences in overall survival or in abnormal brain scans of surviving infants. Donors with both UA-AREDV and AA anastomoses had a significantly higher incidence of IUFD compared with the others (53.3%, P < 0.001). CONCLUSIONS: Quintero stage III atypical was characterized by a high incidence of AA anastomoses and UA-AREDV of the donor, resulting in IUFD. Subclassification of Stage III based on visibility of the bladder of the donor twin was adequate for and compatible with differentiating prognosis and pathophysiology.


Asunto(s)
Anastomosis Arteriovenosa/diagnóstico por imagen , Transfusión Feto-Fetal/clasificación , Arterias Umbilicales/diagnóstico por imagen , Vejiga Urinaria/diagnóstico por imagen , Anastomosis Arteriovenosa/fisiopatología , Anastomosis Arteriovenosa/cirugía , Femenino , Transfusión Feto-Fetal/diagnóstico por imagen , Transfusión Feto-Fetal/fisiopatología , Transfusión Feto-Fetal/cirugía , Fetoscopía , Edad Gestacional , Humanos , Japón , Embarazo , Resultado del Embarazo , Segundo Trimestre del Embarazo , Pronóstico , Índice de Severidad de la Enfermedad , Gemelos , Ultrasonografía Prenatal , Arterias Umbilicales/fisiopatología , Arterias Umbilicales/cirugía , Vejiga Urinaria/embriología
8.
Cytopathology ; 19(1): 19-27, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-17916089

RESUMEN

OBJECTIVE: There are a number of unresolved issues in endometrial cytology. They include the significance of nuclear atypia for the diagnosis of grade1 adenocarcinoma (G1AC) and atypical endometrial hyperplasia (AEH), cytological criteria of endometrial hyperplasia without atypia, and recognition of stromal cell cluster (SC) and its distinction from epithelial cell cluster (EC). METHODS: We examined nuclear atypia, SC and EC in typical cases of five categories: normal endometrium (NEM), simple endometrial hyperplasia without atypia (SEH), complex endometrial hyperplasia without atypia (CEH), G1AC and grade2 adenocarcinoma (G2AC). We classified EC into four types: simple EC (SPEC), large regular EC (LREC), large irregular EC (LIEC) and small irregular EC (SIEC). Based on the results, we developed criteria of endometrial cytology and have evaluated 13 639 cases over 8 years. RESULTS: Nuclear atypia was significantly more frequent in G2AC than in any of the other four categories (P < 0.001). SC was significantly more frequent in NEM and SEH than in the other three categories (P < 0.001). G1AC and G2AC showed significantly higher frequency of LIEC than the other three categories (P < 0.001). CEH exhibited significantly higher frequency of LREC than the four categories (P < 0.001). The sensitivity and the specificity was 88.8% and 99.0% respectively. CONCLUSIONS: We could diagnose G1AC, G2AC and CEH with high accuracy using the established criteria mainly based on SC and EC. We think that the criteria may facilitate an effective screening and an objective interpretation of endometrial samples.


Asunto(s)
Adenocarcinoma/diagnóstico , Hiperplasia Endometrial/diagnóstico , Neoplasias Endometriales/diagnóstico , Células Epiteliales/patología , Células del Estroma/patología , Endometrio/patología , Femenino , Humanos , Sensibilidad y Especificidad
9.
Vet Rec Open ; 3(1): e000161, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27651913

RESUMEN

Recently, submandibular abscesses associated with Actinomyces denticolens have been reported in horses. The actinomycotic clumps have been observed in the tonsillar crypts. The aim of this study was to demonstrate colonisation of A denticolens in equine tonsils. Twelve equine tonsils obtained from a slaughterhouse were divided into two parts for histopathological examination and for isolation of A denticolens. When actinomycotic clumps were found in these tonsillar crypts, immunohistochemistry using hyperimmune serum against A denticolens (DMS 20671) was performed on the serial sections. To determine whether Actinomyces-like bacteria isolated using immunoantigenic separation technique were A denticolens, the isolates were analysed for the 16S rRNA gene sequence. Actinomycotic clumps were found in the tonsillar crypts of 11 (91.7 per cent) horses. The clumps were of the saprophytic type accompanied with the feedstuffs, but a few clumps were surrounded by inflammatory cells. A denticolens antigens were immunodetected not only in the clumps of 11 (100 per cent) tonsils, but also in the tonsillar parenchyma. Six isolates obtained from four tonsils showed 99.7-99.9 per cent similarity to A denticolens in the 16S rRNA gene sequence. In horses, the colonisation sites of A denticolens are the tonsils, thus the authors suggest that the tonsils provide the intrinsic infection site for A denticolens.

10.
J Perinatol ; 36(12): 1101-1105, 2016 12.
Artículo en Inglés | MEDLINE | ID: mdl-27684416

RESUMEN

OBJECTIVE: Cytomegalovirus (CMV) is the most common cause of congenital infection and can cause neurodevelopmental disabilities, although a majority of patients are asymptomatic. Biomarkers associated with disease severity would be desirable to distinguish asymptomatic from mildly symptomatic patients who may benefit from antiviral treatment. MicroRNAs (miRNAs) are noncoding RNAs that may have the potential to serve as biomarkers. STUDY DESIGN: Thirteen infants with congenital CMV infection were enrolled, and plasma levels of 11 human- and 3 CMV-encoded miRNAs were quantitated by real-time PCR. Plasma levels of miRNAs and their associations with clinical features were evaluated. RESULTS: The levels of miR-183-5p and miR-210-3p were significantly higher in patients with congenital CMV infection than in control infants, whereas no significant associations between levels of miRNAs and clinical features of congenital CMV infection were observed. CONCLUSION: Plasma miRNAs could be associated with the pathogenesis of congenital CMV infection and could be used as disease biomarkers.


Asunto(s)
Infecciones por Citomegalovirus/congénito , Citomegalovirus/genética , MicroARNs/sangre , Antivirales , Biomarcadores/sangre , Infecciones por Citomegalovirus/sangre , ADN Viral/orina , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Reacción en Cadena en Tiempo Real de la Polimerasa
11.
Clin Cancer Res ; 4(1): 235-40, 1998 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9516977

RESUMEN

We analyzed the clinical features of 25 ovarian cancer patients who were associated with germ-line mutations of BRCA1 from four site-specific ovarian cancer families and seven breast-ovarian cancer families in Japan. The average age at diagnosis was 51.1 years (range, 38-77 years). Histological examination revealed 24 serous cyst adenocarcinomas in 25 patients. In 23 patients with clear clinical records, 3 patients had stage I disease, 17 had stage III disease, and 3 had stage IV disease. Thirteen patients with stage III disease who were treated with cisplatin-containing chemotherapy following tumor reduction surgery showed more favorable outcomes in both the survival rate and disease-free intervals, compared with age- and treatment course-matched controls (5-year survival rate, 0.786 versus 0.303; median disease-free interval, 91.43 versus 40.92 months; P < 0.05 for both, by logarithmic rank test). Our statistical model for the inheritance of susceptibility to ovarian cancer was derived from the analysis of 26 patients and 19 healthy carriers of 12 families. The expected lifetime risk of ovarian cancer is about 80% for women with mutations of BRCA1. These results suggest that the clinical outcome of ovarian cancer with germ-line mutations of BRCA1 appears to be more favorable than that with sporadic cases and that the disease penetrance among pedigrees with germ-line mutations of the BRCA1 gene is substantially high.


Asunto(s)
Genes BRCA1 , Mutación de Línea Germinal , Neoplasias Ováricas/genética , Adulto , Anciano , Femenino , Humanos , Persona de Mediana Edad , Neoplasias Ováricas/mortalidad , Tasa de Supervivencia
12.
Am J Surg Pathol ; 15(10): 1002-6, 1991 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-1718175

RESUMEN

We report a case of extramammary Paget's disease in ovarian mature cystic teratoma. The patient was a 70-year-old Japanese woman who complained of lower abdominal pain. Examination showed elevation of carcinoembryonic antigen and CA 19-9. Ultrasonography and computer tomography revealed a cystic tumor of the left ovary. The gross appearance of the resected ovary was typical for mature cystic teratoma. Microscopic observation revealed a lesion of Paget's disease within the squamous epithelium. The tumor cells had intracytoplasmic mucin and positive immunoreactivity for carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin; but they were negative for S-100 protein and vimentin. On multiple and serial sections, underlying adenocarcinomas were not found either in the ovary or other primary sites. From these pathological findings, we concluded that the disease was an intraepithelial adenocarcinoma, possibly derived from multipotential cells in squamous epithelium of ovarian mature cystic teratoma. This is the first reported case, to our knowledge, of extramammary Paget's disease arising in mature cystic teratoma of the ovary.


Asunto(s)
Adenocarcinoma/secundario , Quiste Dermoide/patología , Neoplasias Ováricas/patología , Enfermedad de Paget Extramamaria/secundario , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Anciano , Antígenos de Carbohidratos Asociados a Tumores/metabolismo , Antígeno Carcinoembrionario/metabolismo , Quiste Dermoide/metabolismo , Femenino , Humanos , Inmunohistoquímica , Queratinas/metabolismo , Glicoproteínas de Membrana/metabolismo , Mucina-1 , Neoplasias Ováricas/metabolismo , Enfermedad de Paget Extramamaria/metabolismo , Enfermedad de Paget Extramamaria/patología , Proteínas S100/metabolismo , Vimentina/metabolismo
13.
J Nucl Med ; 21(10): 914-8, 1980 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7420190

RESUMEN

The atrial myocardium has been barely visible with thallium-201 myocardial scintigraphy. This is probably related to the difference in size, distance from anterior chest wall, and small coronary blood flow of the atrium, compared with the ventricle. We have encountered eight cases of visualization of the right atrial appendix (RAA). All had disease involving the right side of the heart, such as mitral stenosis (four cases), congenital heart disease (two), cor pulmonale (one), and primary myocardial disease (one). The RAA was identified from multiple projections in all cases and sometimes confirmed by radionuclide angiocardiography. The RAA was seen at the right upper aspect of the ventricles and was distinguishable from them. Evidence derived from ECG, chest radiographs, and cardiac catheterization, indicated that the most important factor in the visualization might be the displacement of the RAA to a more anterior position.


Asunto(s)
Atrios Cardíacos/diagnóstico por imagen , Cardiopatías/diagnóstico por imagen , Talio , Adulto , Anciano , Cateterismo Cardíaco , Electrocardiografía , Femenino , Cardiopatías Congénitas/diagnóstico por imagen , Humanos , Masculino , Persona de Mediana Edad , Estenosis de la Válvula Mitral/diagnóstico por imagen , Enfermedad Cardiopulmonar/diagnóstico por imagen , Cintigrafía
14.
Thromb Haemost ; 85(1): 152-9, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11204567

RESUMEN

Thrombopoietin (TPO), or megakaryocyte growth and development factor (MGDF), has been shown to potentiate the sensitivity of normal human platelets to various agonists in vitro. The present study investigated the functional and biochemical properties of platelets from mice rendered thrombocytopenic by sublethal irradiation with regard to the reactivity to recombinant murine MGDF (rmMGDF) in vitro. During the course of reversible thrombocytopenia following irradiation, platelets from irradiated mice which had lower platelet counts and reciprocally higher plasma TPO levels showed lower reactivity to rmMGDF in agonist-induced platelet aggregation. Intravenous injections of recombinant soluble murine c-Mpl (sMpl), which has the ability to capture TPO, after irradiation restored the reactivity of platelets at the platelet nadir to rmMGDF. On the other hand, platelets prepared from normal mice 3 h after a single intravenous injection of pegylated rmMGDF did not respond to rmMGDF. There was a marked decrease in c-Mpl and Janus kinase 2 (JAK2) in platelets from irradiated mice at the platelet nadir. Similar results were observed with platelets from mice administered pegylated rmMGDF. JAK2 was only moderately decreased, however, in platelets from mice given sMpl after irradiation. These results indicate that exposure of platelets to increased endogenous TPO levels in vivo in thrombocytopenic mice leads to a reduction in the platelet reactivity to rmMGDF in vitro. Further, these results suggest that the c-Mpl-mediated signaling pathway, which is essential for the priming effect of rmMGDF, is defective in thrombocytopenic murine platelets.


Asunto(s)
Plaquetas/efectos de los fármacos , Proteínas de Neoplasias , Receptores de Citocinas , Trombopoyetina/farmacología , Animales , Plaquetas/fisiología , Plaquetas/efectos de la radiación , División Celular/efectos de los fármacos , División Celular/efectos de la radiación , Modelos Animales de Enfermedad , Janus Quinasa 2 , Masculino , Ratones , Ratones Endogámicos BALB C , Agregación Plaquetaria/efectos de los fármacos , Agregación Plaquetaria/efectos de la radiación , Proteínas Tirosina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/administración & dosificación , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Proto-Oncogénicas/farmacología , Receptores de Trombopoyetina , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/farmacología , Transducción de Señal/fisiología , Trombocitopenia/metabolismo , Trombocitopenia/fisiopatología , Trombopoyetina/metabolismo , Trombopoyetina/efectos de la radiación
15.
Br J Pharmacol ; 111(2): 431-4, 1994 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-8004387

RESUMEN

1. We investigated whether or not pyrogallol, a generator of free radicals, is emetogenic in Suncus murinus, the house musk shrew. Pyrogallol (i.p.) caused dose-dependent emesis in suncus with an ED50 value of 77.3 mg kg-1. At a dose of 128 mg kg-1, all suncus vomited with mean latency of 18.8 +/- 5.2 min and the number of vomiting episodes was 8.6 +/- 2.9. 2. The prophylactic effects of N-(2-mercaptopropionyl)-glycine (MPG), an antioxidant, and tropisetron, a 5-hydroxytryptamine3 (5-HT3) receptor antagonist, were studied. Pyrogallol (128 mg kg-1, i.p.)-induced emesis was prevented by treatment with MPG (i.p.) or tropisetron (s.c.) with ID50 values of 149 mg kg-1 and 117 micrograms kg-1, respectively. 3. Pyrogallol-induced emesis was completely prevented by surgical abdominal vagotomy. 4. The present results indicate that pyrogallol-induced emesis is characteristically very similar to that caused by cisplatin and support the idea that generation of free radicals causes the release of peripheral 5-HT, which stimulates vagal afferent sensory nerves to cause emesis.


Asunto(s)
Pirogalol/farmacología , Musarañas/fisiología , Vómitos/inducido químicamente , Animales , Antieméticos/farmacología , Relación Dosis-Respuesta a Droga , Femenino , Radicales Libres/metabolismo , Radicales Libres/farmacología , Inyecciones Intraperitoneales , Pirogalol/administración & dosificación , Pirogalol/antagonistas & inhibidores , Serotonina/farmacología , Vagotomía
16.
Biochem Pharmacol ; 46(1): 186-9, 1993 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-8347131

RESUMEN

Trichlorobiphenyl induced only CYP1A2 mRNA, while pentachlorobiphenyl induced both CYP1A2 and CYP2B1 mRNAs in rat liver. The mRNA levels for these P450s were elevated when ascorbic acid-deficient ODS rats (mutant rats with a hereditary osteogenic disorder) were fed a diet supplemented with ascorbic acid. The amount of CYP2B1 mRNA increased rapidly and reached a maximum level of approximately double within 24 hr of injection of pentachlorobiphenyl. Thereafter, the amount of its mRNA decreased to a steady level. This pattern was roughly paralleled by changes in the amount of CYP1A2 mRNA.


Asunto(s)
Deficiencia de Ácido Ascórbico/genética , Enfermedades del Desarrollo Óseo/genética , Sistema Enzimático del Citocromo P-450/genética , Isoenzimas/genética , Hígado/efectos de los fármacos , Bifenilos Policlorados/toxicidad , ARN Mensajero/análisis , Animales , Ácido Ascórbico/análisis , Ácido Ascórbico/farmacología , Enfermedades del Desarrollo Óseo/inducido químicamente , Sistema Enzimático del Citocromo P-450/biosíntesis , Inducción Enzimática/efectos de los fármacos , Isoenzimas/biosíntesis , Hígado/metabolismo , Masculino , ARN Mensajero/aislamiento & purificación , Ratas , Ratas Mutantes
17.
Chest ; 95(6): 1257-61, 1989 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-2721261

RESUMEN

One hundred fourteen patients with sarcoidosis, who were diagnosed as having sarcoidosis histologically, have been typed for HLA class 1 (A, B, and C) and class 2 (DR and DQ) antigens. Controls consisted of 478 healthy Japanese subjects. The frequencies of HLA-A1, HLA-Bw46, HLA-Cx46, HLA-DRw8, HLA-DRw9, and HLA-DRw52 were significantly increased in sarcoidosis compared to control subjects, but only four patients were positive for HLA-A1. Increased frequencies of HLA-Bw46 and HLA-Cx46 were thought to be attributable to linkage disequilibrium with HLA-DRw8. Patients with HLA-DRw52 were the most frequent (84 cases of 113). No significant differences were observed between HLA-DRw52-positive and HLA-DRw52-negative patients in their clinical features, but all of the patients with muscular involvement (six cases) were positive for HLA-DRw52. Among patients positive for HLA-DRw52, those with HLA-DR5 showed a significantly better clinical course and earlier onset of the disease than those with HLA-DRw8. These results suggest that HLA antigens may play an important role in the pathogenesis of sarcoidosis.


Asunto(s)
Antígenos HLA/análisis , Antígenos HLA-DR/análisis , Sarcoidosis/inmunología , Adulto , Oftalmopatías/inmunología , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Enfermedades Musculares/inmunología , Pronóstico
18.
Phys Rev Lett ; 85(21): 4530-3, 2000 Nov 20.
Artículo en Inglés | MEDLINE | ID: mdl-11082588

RESUMEN

Ion-cyclotron heating was applied to the Large Helical Device. When the proton-cyclotron resonance was near the saddle point of the magnetic field-strength plane, strong ion-cyclotron damping occurred. Under these conditions efficient plasma heating was achieved for more than one minute. A high-energy ion tail was observed, and the effective tail temperature was determined by a balance between the wave acceleration and the electron-drag relaxation. There was no apparent sign of particle orbit loss effect in the investigated density range of 0.8-1.3x10(19) m(-3).

19.
Bone Marrow Transplant ; 18(6): 1035-41, 1996 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-8971370

RESUMEN

We examined whether pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) is capable of improving thrombocytopenia and promoting thrombopoietic reconstitution following lethal irradiation and bone marrow transplantation (BMT) in mice. Immediately after receiving 10 Gy whole body irradiation (day 0), male C3H/HeN mice were inoculated with 10(6) bone marrow cells obtained from syngeneic mice. Circulating platelet counts decreased to below 4% of the normal counts with a nadir on day 10, and then returned to the normal level on day 28 in the control mice undergoing BMT. Subcutaneous consecutive treatment with PEG-rHuMGDF at doses from 10 to 300 micrograms/kg/day from day 1 for 13 days significantly improved the platelet nadir and promoted platelet recovery. The white blood cell counts and hemoglobin concentration following BMT were not influenced by the PEG-rHuMGDF. PEG-rHuMGDF-injection starting from day 5 did not improve the platelet nadir following BMT. Furthermore, administration with PEG-rHuMGDF on alternate days at 55.7 micrograms/kg/day for 7 days or at an interval of 3 days at 78 micrograms/kg/day for 4 days (twice a week for 2 weeks) had a significant efficacy, but these administration regimens had less efficacy than consecutive administration at 30 micrograms/kg/day for 13 days. The numbers of megakaryocytes and megakaryocyte progenitor cells decreased to 5 and 0.2% of normal level, respectively, in the control mice. Consecutive administration of PEG-rHuMGDF enhanced the recovery of the mean number of these cells compared to those in vehicle-treated mice, although such effects were not statistically significant except for the number of megakaryocyte progenitors on day 12. These results suggest that consecutive treatment with PEG-rHuMGDF beginning from the day after BMT may be effective in improving thrombocytopenia following BMT.


Asunto(s)
Trasplante de Médula Ósea , Polietilenglicoles/uso terapéutico , Trombocitopenia/tratamiento farmacológico , Trombopoyetina/uso terapéutico , Animales , Esquema de Medicación , Evaluación Preclínica de Medicamentos , Masculino , Ratones , Ratones Endogámicos C3H , Recuento de Plaquetas/efectos de los fármacos , Polietilenglicoles/administración & dosificación , Quimera por Radiación , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/uso terapéutico , Trombocitopenia/etiología , Trombopoyetina/administración & dosificación , Acondicionamiento Pretrasplante/efectos adversos , Irradiación Corporal Total/efectos adversos
20.
J Biochem ; 126(2): 287-95, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10423519

RESUMEN

Glucosyltransferase-I (GTF-I: 175 kDa) of a cariogenic bacterium, Streptococcus sobrinus 6715, mediates the conversion of water-soluble dextran (alpha-1,6-glucan) into a water-insoluble form by making numerous alpha-1,3-glucan branches along the dextran chains with sucrose as the glucosyl donor. The structures and catalytic properties were compared for two GTF-I fragments, GTF-I' (138 kDa) and GS (110 kDa). Both lack the N-terminal 84 residues of GTF-I. While GTF-I' still contains four of the six C-terminal repeats characteristic of streptococcal glucosyltransferases, GS lacks all of them. Electron microscopy of negatively stained samples indicated a double-domain structure for GTF-I', consisting of a spherical head with a smaller spherical tail, which was occasionally seen as a long extension. GS was seen just as the head portion of GTF-I'. In the absence of dextran, both fragments simply hydrolyzed sucrose with similar K(m) and k(cat) values at low concentrations (<5 mM). At higher sucrose concentrations (>10 mM), however, GTF-I' exhibited glucosyl transfer activity to form insoluble alpha-1, 3-glucans. So did GS, but less efficiently. Dextran increased the rate and efficiency of the glucosyl transfer by GTF-I'. On removal of the C-terminal repeats of GTF-I' by mild trypsin treatment, this dextran-stimulated transfer was completely lost and the dextran-independent transfer became less efficient. These results indicate that the N-terminal two-thirds of the GTF-I sequence are organized as a structurally and functionally independent domain to catalyze not only sucrose hydrolysis but also glucosyl transfer to form alpha-1,3-glucan chains, although not efficiently; the C-terminal repeat increases the efficiency of the intrinsic glucosyl transfer by the N-terminal domain as well as rendering the whole molecule primer-dependent for far more efficient insoluble glucan synthesis.


Asunto(s)
Proteínas Bacterianas , Glucanos/metabolismo , Glucosiltransferasas/metabolismo , Proteínas/metabolismo , Streptococcus/enzimología , Catálisis , Clonación Molecular , Codón , Dextranos/metabolismo , Relación Dosis-Respuesta a Droga , Escherichia coli/enzimología , Expresión Génica , Cinética , Espectroscopía de Resonancia Magnética , Microscopía Electrónica , Modelos Genéticos , Fragmentos de Péptidos/metabolismo , Estructura Terciaria de Proteína , Sacarosa/farmacología , Factores de Tiempo , Tripsina/farmacología
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