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1.
BJOG ; 128(12): 1997-2002, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34021948

RESUMEN

We describe a successful surgical technique of abdominal trachelectomy and re-vaginoplasty for cervico-vaginal stenosis following unsuccessful uterovaginal anastomosis and vaginoplasty in a patient with congenital cervical and vaginal aplasia. After the surgical procedure, cervico-vaginal stenosis was resolved and periodic menstruation without dysmenorrhoea resumed. While long-term follow-up is essential to ensure successful pregnancy and delivery, we conclude that this novel surgical procedure is a promising alternative for improvement of the quality of life and normal sexual function, and for preservation of fertility in patients with cervical and vaginal aplasia.


Asunto(s)
Procedimientos de Cirugía Plástica/métodos , Complicaciones Posoperatorias/cirugía , Traquelectomía/métodos , Vagina/cirugía , Enfermedades Vaginales/cirugía , Adolescente , Anastomosis Quirúrgica/efectos adversos , Anastomosis Quirúrgica/métodos , Cuello del Útero/anomalías , Cuello del Útero/patología , Constricción Patológica/cirugía , Femenino , Humanos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/patología , Embarazo , Reoperación , Vagina/anomalías , Vagina/patología , Enfermedades Vaginales/etiología , Enfermedades Vaginales/patología
2.
Infection ; 41(2): 415-23, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23471823

RESUMEN

PURPOSE: In Japan, a national surveillance study of antimicrobial consumption has never been undertaken. This study aimed to describe antimicrobial consumption and resistance to Pseudomonas aeruginosa in 203 Japanese hospitals, to identify targets for quality improvement. METHODS: We conducted an ecological study using retrospective data (2010). Antimicrobial consumption was collected in the World Health Organization (WHO) anatomical therapeutic chemical/defined daily dose (ATC/DDD) format. Rates of imipenem (IPM), meropenem (MEPM), ciprofloxacin (CPFX), or amikacin (AMK) resistance were expressed as the incidence of non-susceptible isolates. Additionally, hospitals were asked to provide data concerning hospital characteristics and infection control policies. Hospitals were classified according to functional categories of the Medical Services Act in Japan. RESULTS: Data were collected from 203 Japanese hospitals (a total of 91,147 beds). The total antimicrobial consumption was 15.49 DDDs/100 bed-days (median), with consumptions for penicillins, carbapenems, quinolones, and glycopeptides being 4.27, 1.60, 0.41, and 0.49, respectively. The median incidences of IPM, MEPM, CPFX, and AMK resistance were 0.15, 0.10, 0.13, and 0.03 isolates per 1,000 patient-days, respectively. Antimicrobial notification and/or approval systems were present in 183 hospitals (90.1 %). In the multivariate analysis, the piperacillin/tazobactam, quinolones, and/or total consumptions and the advanced treatment hospitals showed a significant association with the incidence of P. aeruginosa resistant to IPM, MEPM, CPFX, and AMK [adjusted R (2) (aR (2)) values of 0.23, 0.30, 0.22, and 0.35, respectively). CONCLUSION: This is the first national surveillance study of antimicrobial consumption in Japan. A continuous surveillance program in Japan is necessary in order to evaluate the association among resistance, antimicrobial restriction, and consumption.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Utilización de Medicamentos/estadística & datos numéricos , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Amicacina/uso terapéutico , Antibacterianos/uso terapéutico , Ciprofloxacina/uso terapéutico , Revisión de la Utilización de Medicamentos/métodos , Hospitales/normas , Humanos , Imipenem/uso terapéutico , Incidencia , Japón/epidemiología , Meropenem , Pruebas de Sensibilidad Microbiana , Programas Nacionales de Salud , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/aislamiento & purificación , Estudios Retrospectivos , Encuestas y Cuestionarios , Tienamicinas/uso terapéutico
3.
J Chem Phys ; 137(13): 134308, 2012 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-23039600

RESUMEN

In view of recent tremendous advance in astronomical observations in the submillimeter to THz region brought by the Herschel space craft, laboratory high-resolution spectroscopic investigations in that frequency region into unstable molecules, in particular, light hydride ions, are urgently needed. As a part of such endeavor, rotational transitions of H(2)F(+) were observed in the THz-region by using a tunable far-infrared spectrometer. These newly detected lines together with the submillimeter-wave lines obtained previously and the combination differences derived from infrared vibration-rotation lines were subject to a least-squares analysis that yielded a set of molecular constants with much better accuracy. The measured and predicted THz transition frequencies should prove to be a useful probe into detection of interstellar H(2)F(+).

4.
Am J Transplant ; 11(7): 1509-16, 2011 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-21672149

RESUMEN

Living-donor lobar lung transplantation (LDLLT) is one of the final options for saving patients with pulmonary complications after hematopoietic stem cell transplantation (HSCT). We retrospectively investigated 19 patients who had undergone LDLLT after HSCT in Japan. Eight patients underwent LDLLT after HSCT in which one of the donors was the same living donor as in HSCT (SD group), while 11 received LDLLT from relatives who were not the HSCT donors (non-SD group). In the SD group, three patients underwent single LDLLT. The 5-year survival rate was 100% and 58% in the SD and non-SD groups, respectively. In the SD group, postoperative immunosuppression was significantly lower than in the non-SD group. Two patients died of infection and one died of post-transplant lymphoproliferative disease (PTLD) in the non-SD group, while only one patient died of PTLD 7 years after LDLLT in the SD group. Hematologic malignancy relapsed in two patients in the non-SD group. For the three single LDLLTs in the SD group, immunosuppression was carefully tapered. In our study, LDLLT involving the same donor as for HSCT appeared to have advantages related to lower immunosuppression compared to LDLLT from relatives who were not the HSCT donors.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Terapia de Inmunosupresión/métodos , Donadores Vivos , Trasplante de Pulmón , Adolescente , Adulto , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/terapia , Neoplasias Hematológicas/terapia , Humanos , Japón , Trastornos Linfoproliferativos/etiología , Masculino , Complicaciones Posoperatorias , Estudios Retrospectivos , Resultado del Tratamiento
6.
BJS Open ; 4(4): 693-703, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32472647

RESUMEN

BACKGROUND: Tumour budding is an important prognostic feature in early-stage colorectal cancer, but its prognostic significance in metastatic disease has not been fully investigated. METHODS: Patients with stage IV disease who had primary colorectal tumour resection without previous chemotherapy or radiotherapy from January 2000 to December 2018 were reviewed retrospectively. Budding was evaluated at the primary site and graded according to the criteria of the International Tumor Budding Consensus Conference (ITBCC) (BD1, low; BD2, intermediate; BD3, high). Patients were categorized by metastatic (M1a, M1b) and resectional (R0/R1, R2/unresected) status. Subgroups were compared for overall (OS) and recurrence-free (RFS) survival in R0/R1 subgroups; R2/unresected patients were evaluated for the rate of tumour progression, based on change in tumour size from baseline. RESULTS: Of 371 patients observed during the study, 362 were analysed. Patients with BD3 had a lower 5-year OS rate than those with BD1 + BD2 (18·4 versus 40·5 per cent; P < 0·001). Survival analyses according to metastatic and resection status also showed that BD3 was associated with shorter OS than BD1 + BD2. In multivariable analysis, BD3 (hazard ratio (HR) 1·51, 95 per cent c.i. 1·11 to 2·10; P = 0·009), T4 status (HR 1·39) and R2/unresected status (HR 3·50) were associated with decreased OS. In the R0/R1 subgroup, the 2-year RFS rate was similar for BD3 and BD1 + BD2 according to metastatic status. There was no significant difference between BD3 and BD1 + BD2 for change in tumour size in the R2/unresected subgroup (P = 0·094). Of 141 patients with initially unresectable metastases who had chemotherapy, 35 achieved conversion from unresectable to resectable status. The conversion rate was significantly higher for BD1 + BD2 than for BD3 (36 versus 18 per cent; P = 0·016). CONCLUSION: Stage IV colorectal cancer with high-grade tumour budding according to ITBCC criteria correlates with poor prognosis.


ANTECEDENTES: La esofaguectomía por cáncer se asocia con un descenso de la calidad de vida relacionada con la salud (health-related quality of life, HRQoL) a largo plazo. El objetivo de este estudio fue evaluar el efecto de las comorbilidades sobre la HRQOL entre pacientes supervivientes de cánceres de esófago o de la unión gastroesofágicas después de 10 años o más. MÉTODOS: Este estudio incluye una cohorte de base poblacional recogida de forma prospectiva que incluía todos los pacientes operados de cáncer de esófago o de la unión gastroesofágica en Suecia en 2001-2005 con seguimiento hasta el 31 de diciembre de 2016. Todos los datos relacionados con las características de los pacientes y del tumor, detalles del tratamiento y HRQoL se recogieron en una base de datos prospectiva. Se utilizaron modelos de regresión multivariable ANCOVA, ajustados por edad, sexo, histología del tumor, estadio, y técnica quirúrgica, para calcular las puntuaciones medias ajustadas con los i.c. del 95% para todas las variables de la HRQoL. RESULTADOS: Un total de 92 (88%) supervivientes respondieron a los cuestionarios. En función del impacto de las comorbilidades en la salud en general, se clasificaron a los pacientes en los grupos de bajo versus alto impacto. Los resultados muestran que los pacientes en el grupo de alto impacto presentaban un descenso clínicamente significativo de la HRQoL y un aumento en el nivel de síntomas, pero las diferencias entre estos dos grupos no fueron estadísticamente significativas. CONCLUSIÓN: A los 10 años de la esofaguectomía por cáncer, las comorbilidades con un alto impacto sobre la salud general siguen contribuyendo en el deterioro de la HRQoL.


Asunto(s)
Neoplasias Colorrectales/patología , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Colorrectales/mortalidad , Femenino , Humanos , Japón , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia
7.
Thorac Cardiovasc Surg ; 57(8): 484-8, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20013624

RESUMEN

OBJECTIVE: We evaluated the clinical outcomes of patients after lung resection with pulmonary artery (PA) plasty for non-small cell lung cancer (NSCLC). METHODS: From 1995 to 2006, 36 patients (26 males and 10 females) with NSCLC underwent lobectomy or segmentectomy with PA plasty at our institution. The mean age of the patients was 65.9 years old (range 45-87 years old). There were 17 left upper lobectomies, 10 right upper lobectomies, five left lower lobectomies, two right upper-and-middle bilobectomies, one right lower lobectomy, and one left upper division segmentectomy. Both bronchoplasty and PA plasty were performed in 15 patients. Six patients received preoperative chemotherapy, and one had preoperative radiotherapy. RESULTS: The postoperative morbidity rate was 27.8 % (10/36), and the mortality rate (30 days) was 2.8 % (1/36). One patient underwent completion pneumonectomy on postoperative day 13. Macroscopic residual cancer was identified in two patients at the thoracic wall and aorta, respectively; microscopic residual cancers were identified in two patients at the stumps of the pulmonary artery and in one patient at the bronchial stump. Postoperative radiation therapy was additionally given to those four patients, except one. The 5-year survival rate for all patients was 51.8 %. There was no significant difference in the 5-year survival rate between clinical N (cN) 0-1 patients and cN2 patients. However, in pathological N (pN) 0-1 patients, the 5-year survival rate was significantly better than that of pN2 patients (71.9 % versus 0.0 %; P < 0.001). CONCLUSIONS: PA plasty for NSCLC is acceptable and highly recommended for pN0-1 patients. Strict patient selection should be considered so as to avoid surgical operations in patients with pN2 staging.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/cirugía , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Arteria Pulmonar/cirugía , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/patología , Femenino , Humanos , Estudios Longitudinales , Neoplasias Pulmonares/patología , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Análisis de Supervivencia , Resultado del Tratamiento , Procedimientos Quirúrgicos Vasculares/instrumentación , Procedimientos Quirúrgicos Vasculares/métodos , Procedimientos Quirúrgicos Vasculares/mortalidad
8.
Acta Radiol ; 50(1): 28-33, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19160081

RESUMEN

BACKGROUND: Drainage of large amounts of shunt blood into deep veins via collaterals reduces resistance to venous outflow and decreases blood flow to the artery distal to the arterial anastomotic site, potentially resulting in steal syndrome. PURPOSE: To evaluate the effectiveness of transcatheter coil embolization for collateral veins of hemodialysis access in the treatment of steal syndrome. MATERIALS AND METHODS: Five hemodialysis patients (four male, one female; mean age 58.8 years, range 40-71 years) with symptomatic steal syndrome were treated. Steal syndrome was diagnosed based on decreased or absent distal pulse, coolness, pain, abnormal skin color, ischemic ulceration of digits, numbness, sensory impairment, or motor impairment. Coil embolization was performed to block collaterals communicating with deep veins, with conscious sedation and local anesthesia. Fistulography was performed before, immediately after, and 1 month after embolization. Ultrasonography was performed 2 days after embolization. Symptoms and signs were assessed 2 days after embolization. Clinical findings related to steal syndrome and access failure were observed at each hemodialysis. RESULTS: Blood flow in the collaterals was successfully blocked by coil embolization in all patients. Distal pulse, coolness, pain, and skin color improved in all patients. Numbness, sensory impairment, and motor impairment were unimproved in two patients. In all patients, hemodialysis following embolization was performed normally. The mean observation period after embolization was 33 months (range 9-75 months). CONCLUSION: Coil embolization of collaterals that drain shunt blood into deep veins is effective for steal syndrome for hemodialysis access originating in the brachial artery.


Asunto(s)
Derivación Arteriovenosa Quirúrgica/efectos adversos , Embolización Terapéutica/métodos , Diálisis Renal , Síndrome del Robo de la Subclavia/terapia , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiografía Intervencional , Síndrome del Robo de la Subclavia/diagnóstico por imagen , Síndrome del Robo de la Subclavia/etiología
9.
Cytopathology ; 20(6): 388-94, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-18657157

RESUMEN

OBJECTIVE: The aim of this study was to develop a new reporting format for endometrial cytology that would standardize the diagnostic criteria and the terminology used for reporting. METHODS: In previous studies, cytoarchitectural criteria were found to be useful for the cytological assessment of endometrial lesions. To apply these criteria, an appropriate cytological specimen is imperative. In this article, the requirements of an adequate endometrial cytological specimen for the new diagnostic criteria are first discussed. Then, the diagnostic criteria, standardized on a combination of conventional and cytoarchitectural criteria, are presented. Third, terminology that could be used, not only for reporting the histopathological diagnosis, but also for providing better guidance for the gynaecologist to determine further clinical action, is introduced. The proposed reporting format was investigated using endometrial cytology of 58 cases that were cytologically underestimated or overestimated compared to the histopathological diagnosis made on the subsequent endometrial biopsy or surgical specimens. RESULTS: Of the 58 cases, 12 were reassessed as being unsatisfactory for evaluation. Among the remaining 46 cases, 25 of the 27 cases, which had been underestimated and subsequently diagnosed as having endometrial carcinoma or a precursor stage on histopathological examination,were reassessed as recommended for endometrial biopsy. On the other hand, 19 cases overestimated by cytology were all reassessed as not requiring biopsy. CONCLUSIONS: The reporting format for endometrial cytology proposed in this article may improve diagnostic accuracy and reduce the number of patients managed inappropriately.


Asunto(s)
Técnicas Citológicas , Neoplasias Endometriales , Endometrio , Técnicas Citológicas/métodos , Técnicas Citológicas/normas , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/patología , Endometrio/citología , Endometrio/patología , Femenino , Humanos , Terminología como Asunto
11.
Kyobu Geka ; 61(11): 957-61, 2008 Oct.
Artículo en Japonés | MEDLINE | ID: mdl-18939432

RESUMEN

We reviewed Fukuoka University Hospital thoracic surgery data base of 60 sleeve lobectomy (SL) and 40 pneumonectomy (PN) [for T1-3 disease] for primary lung cancer during 1993-2006. Morbidity rates were 20.0% and 37.5% in SL and PN group, respectively (p = 0.054). Three and 1 patient from PN and SL group, respectively, presented with bronchial anastomotic complications. Multivariate analysis showed that adjuvant chemotherapy and preoperative concomitant respiratory disease, but not the surgical procedures SL or PN, were risk factors for surgical morbidity. SL requires special consideration on its surgical technique either bronchial anastomosis or associated angioplastic procedure, however, it is safe and valuable less invasive surgical option especially for elderly patients.


Asunto(s)
Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Anciano , Quimioterapia Adyuvante , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Complicaciones Posoperatorias/etiología , Pronóstico , Calidad de Vida , Estudios Retrospectivos , Factores de Riesgo
12.
Benef Microbes ; 9(4): 653-662, 2018 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-29633638

RESUMEN

Lipoteichoic acid (LTA) is a cell surface molecule specific to Gram-positive bacteria. How LTA localises on the cell surface is a fundamental issue in view of recognition and immunomodulation in hosts. In the present study, we examined LTA localisation using strain JCM 1131T of Lactobacillus gasseri, which is a human intestinal lactic acid bacterium, during various growth phases by immunoelectron microscopy. We first evaluated the specificity of anti-LTA monoclonal antibody clone 55 used as a probe. The glycerophosphate backbone comprising almost intact size (20 to 30 repeating units) of LTA was required for binding. The antibody did not bind to other cellular components, including wall-teichoic acid. Immunoelectron microscopy indicated that LTA was embedded in the cell wall during the logarithmic phase, and was therefore not exposed on the cell surface. Similar results were observed for Lactobacillus fermentum ATCC 9338 and Lactobacillus rhamnosus ATCC 7469T. By contrast, membrane vesicles were observed in the logarithmic phase of L. gasseri with LTA exposed on their surface. In the stationary and death phases, LTA was exposed on cell wall-free cell membrane generated by autolysis. The dramatic alternation of localisation in different growth phases and exposure on the surface of membrane vesicles should relate with complicated interaction between bacteria and host.


Asunto(s)
Antígenos de Superficie/metabolismo , Membrana Celular/metabolismo , Pared Celular/metabolismo , Lactobacillus gasseri/fisiología , Lipopolisacáridos/metabolismo , Ácidos Teicoicos/metabolismo , Anticuerpos Monoclonales/metabolismo , Membrana Celular/química , Membrana Celular/ultraestructura , Pared Celular/química , Limosilactobacillus fermentum , Lactobacillus gasseri/química , Lactobacillus gasseri/crecimiento & desarrollo , Lactobacillus gasseri/ultraestructura , Lacticaseibacillus rhamnosus , Probióticos , Unión Proteica
13.
J Clin Invest ; 96(3): 1288-94, 1995 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-7657803

RESUMEN

We recently demonstrated that chronic treatment with IL-1 beta induces coronary arteriosclerotic changes and vasospastic responses to autacoids in pigs in vivo and that those responses are importantly mediated by PDGF. The receptors for PDGF and other major growth factors are known to have tyrosine kinase activity. We therefore investigated the effects of a selective tyrosine kinase inhibitor, ST 638, on those responses induced by IL-1 beta in our swine model. Intimal thickening and coronary vasospastic responses to serotonin and histamine were induced at the site of the coronary artery where IL-1 beta was chronically and locally applied. These responses were significantly suppressed in a dose-dependent manner by cotreatment with ST 638. In addition, ST 494, which is an inactive form of ST 638, did not inhibit those responses. The treatment with ST 638 alone did not affect the coronary vasoconstricting responses to the autacoids. Immunoblotting using an antibody to phosphotyrosines confirmed the inhibitory effects of ST 638 on the tyrosine phosphorylations induced by IL-1 beta. These results thus suggest that tyrosine kinase activation may play an important role in mediating the effects of IL-1 beta, while also suggesting that ST 638 has an inhibitory effect on the arteriosclerotic changes and vasospastic responses to autacoids in our swine model in vivo.


Asunto(s)
Cinamatos/farmacología , Enfermedad de la Arteria Coronaria/prevención & control , Vasoespasmo Coronario/prevención & control , Vasos Coronarios/patología , Interleucina-1/toxicidad , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Sulfuros/farmacología , Animales , Angiografía Coronaria , Enfermedad de la Arteria Coronaria/inducido químicamente , Enfermedad de la Arteria Coronaria/patología , Enfermedad Coronaria/patología , Vasoespasmo Coronario/inducido químicamente , Vasoespasmo Coronario/patología , Vasos Coronarios/efectos de los fármacos , Humanos , Masculino , Proteínas Recombinantes/toxicidad , Porcinos
14.
Kyobu Geka ; 60(2): 165-7, 2007 Feb.
Artículo en Japonés | MEDLINE | ID: mdl-17305086

RESUMEN

A case of a 55-year-old man with descending necrotizing mediastinitis (DNM) after a tooth removal was reported. Chest computed tomography (CT) showed a fluid collection in the right thorax, in the cervical region and in the mediastinum. The patient underwent cervical drainage and thoracoscopic pleural dissective drainage. The cervical and right anterior thoracic drain was removed on the 6th day and posterior drain was removed on the 8th day after the operation. The patient was discharged on the postoperative day 13, and showed no recurrence.


Asunto(s)
Drenaje/métodos , Mediastinitis/cirugía , Humanos , Masculino , Mediastinitis/patología , Persona de Mediana Edad , Necrosis , Toracoscopía
15.
Peptides ; 27(11): 2738-49, 2006 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-16914228

RESUMEN

Leptin, an adipocytokine encoded by an obesity gene and expressed in adipose tissue, affects feeding behavior, thermogenesis, and neuroendocrine status via leptin receptors distributed in the brain, especially in the hypothalamus. Leptin may also modulate the synaptic plasticity and behavioral performance related to learning and memory since: leptin receptors are found in the hippocampus, and both leptin and its receptor share structural and functional similarities with the interleukin-6 family of cytokines that modulate long-term potentiation (LTP) in the hippocampus. We therefore examined the effect of leptin on (1) behavioral performance in emotional and spatial learning tasks, (2) LTP at Schaffer collateral-CA1 synapses, (3) presynaptic and postsynaptic activities in hippocampal CA1 neurons, (4) the intracellular Ca(2+) concentration ([Ca(2+)](i)) in CA1 neurons, and (5) the activity of Ca(2+)/calmodulin protein kinase II (CaMK II) in the hippocampal CA1 tissue that exhibits LTP. Intravenous injection of 5 and/or 50mug/kg, but not of 500mug/kg leptin, facilitated behavioral performance in passive avoidance and Morris water-maze tasks. Bath application of 10(-12)M leptin in slice experiments enhanced LTP and increased the presynaptic transmitter release, whereas 10(-10)M leptin suppressed LTP and reduced the postsynaptic receptor sensitivity to N-methyl-d-aspartic acid. The increase in the [Ca(2+)](i) induced by 10(-10)M leptin was two times greater than that induced by 10(-12)M leptin. In addition, the facilitation (10(-12)M) and suppression (10(-10)M) of LTP by leptin was closely associated with an increase and decrease in Ca(2+)-independent activity of CaMK II. Our results show that leptin not only affects hypothalamic functions (such as feeding, thermogenesis, and neuroendocrine status), but also modulates higher nervous functions, such as the behavioral performance related to learning and memory and hippocampal synaptic plasticity.


Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Hipocampo/fisiología , Leptina/farmacología , Potenciación a Largo Plazo/fisiología , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Animales , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Proteínas Quinasas Dependientes de Calcio-Calmodulina/efectos de los fármacos , Hipocampo/efectos de los fármacos , Leptina/fisiología , Potenciación a Largo Plazo/efectos de los fármacos , Masculino , Neuronas/efectos de los fármacos , Neuronas/fisiología , Fosforilación/efectos de los fármacos , Ratas , Ratas Wistar
17.
J Natl Cancer Inst ; 80(9): 683-7, 1988 Jul 06.
Artículo en Inglés | MEDLINE | ID: mdl-3373558

RESUMEN

By analyzing serial step-sections of whole prostate obtained at autopsy, we determined the chronologic change of the frequency of latent prostate tumor in Japan in two periods: 1965-1979 and 1982-1986. Methods of specimen preparation and examination were identical for both periods. The frequency with which latent prostate carcinoma was found in the 660 samples for 1982-1986 was 34.6% and was significantly higher than the 22.5% seen in the 576 observed for 1965-1979 (P less than .0001). This significant finding can be attributed to an increase in the frequency of latent infiltrative tumor (LIT). However, the increase in the frequency of noninfiltrative tumor (LNT) was less significant (P = .045). Both sets of specimens were subsequently combined and reanalyzed according to the year of birth of the decedents. The LIT has progressively increased in frequency in each age-specific category. By morphometry, we determined that the mean tumor volume decreased due to an increase in the number of smaller tumors during the study periods. Although the frequency of latent prostate carcinoma and the LIT:LNT in the samples obtained most recently were comparable to those of U.S. whites, cancer incidence and mortality rates remain lower in Japan. Apparently, the initial step in the induction of prostate carcinoma in indigenous Japanese is now similar to that in U.S. whites. The rates of clinical carcinoma in Japan are still low when compared with those in the United States and countries in Western Europe, but our findings may presage a time when these differences may be greatly reduced or nonexistent.


Asunto(s)
Adenocarcinoma/epidemiología , Neoplasias de la Próstata/epidemiología , Adenocarcinoma/patología , Factores de Edad , Anciano , Causas de Muerte , Humanos , Japón , Masculino , Persona de Mediana Edad , Tamaño de los Órganos , Neoplasias de la Próstata/patología , Factores de Tiempo
18.
Cancer Res ; 52(21): 5991-6, 1992 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-1382850

RESUMEN

The frequency of H-ras, K-ras, and N-ras mutations and the presence of high-risk human papillomavirus (HPV 16, 18, and 33) DNA were studied in 75 paraffin-embedded specimens obtained from 68 Japanese patients with a variety of prostate carcinomas by using polymerase chain reaction and DNA hybridization with sequence-specific oligonucleotides. Ten specimens each of normal and benign hyperplastic prostatic tissues from the same number of patients were also examined for this analysis. Of 68 carcinoma cases, ras gene mutations were present in 16 cases (24%) and HPV DNAs in 28 cases (41%). Eleven mutations were detected in codon 61 of H-ras, 4 in codon 12 of N-ras, and 2 in codon 61 of K-ras. HPV 16, 18, and 33 DNAs were found in 11, 17, and 5 cases, respectively. Eight of the 16 cases with ras mutation also harbored HPV DNAs. The frequency of ras mutations and the HPV infection increased in patients with advanced stages of the tumor and with the higher Gleason score. There was the predominant presence of H-ras codon 61.2 (CAG-->CTG) mutation and HPV 18 DNA in prostatic carcinomas metastasizing to the bone. None of the normal or benign hyperplastic prostatic specimens contained either ras mutation or HPV DNA. Our results suggest that ras gene mutations and HPV infections are relatively frequent, at least in prostate carcinoma of Japanese patients. These two factors appear to be related to the progression of the tumor. Moreover, H-ras codon 61.2 mutation and HPV 18 infection may have some predictive roles for bone metastasis in prostate carcinoma.


Asunto(s)
ADN Viral/análisis , Genes ras/genética , Mutación/genética , Papillomaviridae/genética , Neoplasias de la Próstata/genética , Anciano , Anciano de 80 o más Años , Secuencia de Aminoácidos , Humanos , Japón , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Hiperplasia Prostática
19.
Cancer Res ; 59(5): 1096-101, 1999 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-10070968

RESUMEN

We previously identified and cloned human G protein gamma 7 (G-gamma 7) gene, which is down-regulated in pancreatic cancer. We examined G-gamma 7 expression in other gastrointestinal tract cancers. In 24 of 30 patients with gastrointestinal tract cancer, Northern blot assay and immunohistochemical staining revealed significantly lower G-gamma 7 expression in tumors than in normal tissues from the same patients. Semiquantitative reverse transcription PCRs also showed lower G-gamma 7 expression in tumors than in corresponding normal tissues in 69 of 90 patients. To examine the biological role of G-gamma 7 in cancer, the G-gamma 7 cDNA was transfected into a human esophageal carcinoma cell line, KYSE150, that lacks G-gamma 7 expression. G-gamma 7 expression suppressed cell growth and tritiated-thymidine uptake when cells were confluent G-gamma 7 expression also suppressed tumorigenicity in BALB/c nude mice until 3 weeks after transplantation. G-gamma 7 expression increased the Go/G1 population and decreased the S phase population when cells were at high density. We confirmed that this change was associated with p27K1P1 expression. These findings suggest that human G-gamma 7 is associated with p27kip1-induced growth arrest and may be a therapeutic target in cancers.


Asunto(s)
Proteínas de Ciclo Celular , Ciclo Celular , Neoplasias Colorrectales/genética , Neoplasias Esofágicas/genética , Proteínas de Unión al GTP/genética , Regulación Neoplásica de la Expresión Génica , Proteínas Asociadas a Microtúbulos/metabolismo , Neoplasias Gástricas/genética , Proteínas Supresoras de Tumor , Animales , División Celular , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Inhibidor p27 de las Quinasas Dependientes de la Ciclina , Inhibidores Enzimáticos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/cirugía , Proteínas de Unión al GTP/biosíntesis , Humanos , Cinética , Ratones , Ratones Desnudos , Proteínas Recombinantes/biosíntesis , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Transfección , Trasplante Heterólogo , Células Tumorales Cultivadas
20.
Cancer Res ; 49(9): 2374-8, 1989 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-2706625

RESUMEN

Inhibition by seven synthetic 4-hydroxycinnamamide derivatives, ST 271, ST 280, ST 458, ST 494, ST 633, ST 638, and ST 642, of tyrosine-specific protein kinases (tyrosine kinase) of oncogene or proto-oncogene products (p130gag-v-fps, p70gag-actin-v-fgr, pp60v-src, pp60c-src) and epidermal growth factor (EGF) receptor kinase were investigated. ST 638 (alpha-cyano-3-ethoxy-4-hydroxy-5-phenylthiomethylcinnamamide) strongly inhibited more of the tyrosine kinases than any of the other compounds. The susceptibilities of these tyrosine kinases to ST 638 increased in the following order: EGF receptor greater than p70gag-actin-v-fgr greater than pp60c-src greater than p130gag-v-fps, pp60v-src, with 50% inhibitory concentration values of 1.1, 4.2, 18, 70, and 87 microM, respectively. The phosphorylation of the tyrosine residues in particulate fractions from RR1022 cells expressing pp60v-src was inhibited by ST 638 in a dose-dependent way, while it had a negligible effect on the phosphorylations of threonine and serine residues. Kinetic analysis showed that ST 638 competitively inhibited the phosphorylation of an exogenous substrate by the EGF receptor kinase with a Ki of 2.1 microM. ST 638 noncompetitively inhibited autophosphorylation by EGF receptor kinase. These results indicate that ST 638 is a potent and specific inhibitor of tyrosine kinases in vitro, and that its inhibitory activity is caused by competing with the substrate protein for the tyrosine kinase binding site.


Asunto(s)
Cinamatos/farmacología , Ácidos Cumáricos/farmacología , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Adenosina Trifosfato/metabolismo , Animales , Unión Competitiva , Receptores ErbB/metabolismo , Humanos , Cinética , Fosforilación , Propionatos , Proto-Oncogenes Mas
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