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1.
Phys Rev Lett ; 120(25): 251101, 2018 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-29979069

RESUMEN

We present an interpretation of the time variability of the x-ray flux recently reported from a multiepoch campaign of 15 years of observations of the supernova remnant Cassiopeia A by Chandra. We show for the first time quantitatively that the [4.2-6] keV nonthermal flux increase up to 50% traces the growth of the magnetic field due to a vortical amplification mechanism at a reflection inward shock colliding with inner overdensities. The fast synchrotron cooling as compared with shock-acceleration time scale qualitatively supports the flux decrease.

2.
J Int Med Res ; 38(1): 253-65, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20233537

RESUMEN

Calcium channel blockers (CCBs) can prevent cardiovascular events in patients with coronary artery disease (CAD). This study looked retrospectively at the prognosis of CAD in hypertensive patients with CAD who had undergone a coronary angiograph, had been given a CCB (benidipine [n = 66], amlodipine [n = 45], or long-acting nifedipine [n = 31]) on hospital discharge and were then followed up for a mean +/- SD of 5.2 +/- 2.9 years. Systolic/diastolic blood pressure for all 142 patients decreased significantly from a mean +/- SD of 137 +/- 20/74 +/- 15 mmHg to 129 +/- 20/71 +/- 12 mmHg. Major adverse cardiovascular events (MACE) occurred in 15 patients. Chronic kidney disease (CKD) was a significant risk factor for MACE (hazard ratio 2.35, 95% confidence intervals 1.45, 3.80). Benidipine was superior to nifedipine in preventing MACE in patients both with and without CKD. In conclusion, benidipine and amlodipine reduced the frequency of MACE in hypertensive patients with CAD, particularly in those with complicating CKD.


Asunto(s)
Amlodipino/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/etiología , Dihidropiridinas/farmacología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/tratamiento farmacológico , Nifedipino/farmacología , Anciano , Presión Sanguínea/efectos de los fármacos , Femenino , Humanos , Hipertensión/complicaciones , Hipertensión/tratamiento farmacológico , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
3.
Science ; 248(4958): 1009-12, 1990 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-2343305

RESUMEN

Lesions of atherosclerosis occur in the innermost layer of the artery wall and consist primarily of proliferated smooth muscle cells surrounded by large amounts of connective tissue, numerous lipid-laden macrophages, and varying numbers of lymphocytes. Growth-regulatory molecules may be involved in intimal accumulation and proliferation of smooth muscle cells responsible for the occlusive lesions of atherosclerosis. Platelet-derived growth factor (PDGF) B-chain protein was found within macrophages in all stages of lesion development in both human and nonhuman primate atherosclerosis. Thus macrophages may play a critical role in the disease by providing PDGF, a potent chemotactic and growth-stimulatory molecule, to the intimal smooth muscle cells.


Asunto(s)
Arteriosclerosis/metabolismo , Macrófagos/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Animales , Anticuerpos Monoclonales/inmunología , Northern Blotting , Dieta Aterogénica , Humanos , Inmunohistoquímica , Macaca nemestrina , Monocitos/metabolismo , Factor de Crecimiento Derivado de Plaquetas/genética , ARN Mensajero/genética
4.
J Comp Pathol ; 137(2-3): 146-50, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17673248

RESUMEN

A histological investigation of the atrioventricular (AV) conduction system was performed in two young adult dogs with complete AV block. In both cases, infiltration of lymphocytes and plasma cells into the AV node and loss and disappearance of the conduction fibres were observed. Such inflammatory lesions of the AV conduction system were associated with complete AV block. The aetiology of these changes and the cause of its location at the AV node were not elucidated.


Asunto(s)
Bloqueo Atrioventricular/patología , Bloqueo Atrioventricular/veterinaria , Nodo Atrioventricular/patología , Enfermedades de los Perros/patología , Miocarditis/veterinaria , Animales , Bloqueo Atrioventricular/etiología , Nodo Atrioventricular/fisiopatología , Enfermedades de los Perros/etiología , Enfermedades de los Perros/fisiopatología , Perros , Electrocardiografía , Femenino , Sistema de Conducción Cardíaco/fisiopatología , Linfocitos/patología , Miocarditis/patología , Miocarditis/fisiopatología , Células Plasmáticas/patología
5.
J Clin Pathol ; 59(9): 990-2, 2006 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-16935975

RESUMEN

A rare case of reactive lymphoid hyperplasia (RLH) of the liver in a 75-year-old woman admitted to hospital for surgical treatment of gastric, caecal and colon carcinomas is described here. Two nodular lesions in the left and right lobes of the liver were clinically diagnosed as metastatic tumours by computed tomography of the abdomen. A demarcating grey-white mass of size 1.4 cm was observed in a partially resected liver specimen. On examining the lesion microscopically, it was found to be composed of hyperplastic lymphoid follicles, lymphocytes, plasma cells, other inflammatory cells and interlaced hyalinised fibrous tissues. In the portal tracts around the lesion, chronic inflammatory cell infiltrates were seen, but no interface hepatitis or lymphoid follicle was observed. No evidence of monoclonality was observed by immunohistochemistry for B and T cell markers, in situ hybridisation for kappa and lambda light chains, and polymerase chain reaction analysis of immunoglobulin heavy chains or T cell receptor beta and gamma gene rearrangements. Bcl-2 immunoreactivity was not observed in the germinal centre. Epstein-Barr virus (EBV) antigen (latent membrane protein-1) and EBV-encoded small RNAs were not detected. A proliferation neither of myofibroblasts nor of cells positive for follicular dendritic cell markers was observed. RLH, formerly known as pseudolymphoma, has been reported of the liver in only 14 cases and is considered to be a differential diagnosis of small nodular lesions of the liver. That RLH has an inflammatory reactive nature, not a neoplastic disposition, and that EBV does not participate in the pathogenesis of RLH is supported by this case.


Asunto(s)
Hepatopatías/patología , Seudolinfoma/patología , Adenocarcinoma/patología , Adenocarcinoma/secundario , Anciano , Diagnóstico Diferencial , Femenino , Neoplasias Gastrointestinales/complicaciones , Humanos , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario
6.
J Clin Pathol ; 59(1): 105-7, 2006 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-16394290

RESUMEN

Large cell neuroendocrine carcinoma (LCNEC) is a high grade type of neuroendocrine tumour with an aggressive clinical course. This report describes the first case of LCNEC combined with an adenocarcinoma component in the common bile duct. A 68 year old man presented with jaundice. Severe stenosis of the bile duct was revealed by endoscopic retrograde cholangiography, and adenocarcinoma cells were detected by brush cytology. Pancreaticoduodenectomy was performed, and the patient died of disease three months after surgery. A tumour measuring 2.0 cm in diameter was located in the intrapancreatic portion of the bile duct. Histologically, the tumour consisted of a LCNEC component and a well differentiated adenocarcinoma component. There were transitional areas between the two components. Immunohistochemically, LCNEC cells were reactive for neuroendocrine markers, but no specific hormonal expression was found. Chromogranin A positive cells were found in some areas of the adenocarcinoma component. These findings are consistent with the theory that both of the carcinoma components originated from a common pluripotent stem cell.


Asunto(s)
Adenocarcinoma/patología , Carcinoma Neuroendocrino/patología , Neoplasias del Conducto Colédoco/patología , Neoplasias Primarias Múltiples/patología , Anciano , Resultado Fatal , Humanos , Masculino , Pronóstico
7.
Cancer Res ; 51(8): 2015-20, 1991 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-2009520

RESUMEN

The present work is a continuation of our studies to improve the graft versus leukemia (GVL) effect in autologous bone marrow transplantation. We have recently shown that the GVL effect of bone marrow transplantation (BMT) with interleukin 2 (IL-2)-activated bone marrow (ABM) followed by IL-2 therapy immediately after BMT is superior to the GVL effect of BMT with fresh, syngeneic bone marrow, with or without IL-2 therapy, in mice with acute myeloid leukemia. The present studies show that institution of IL-2 treatment 1, 2, or 3 weeks after BMT with ABM resulted in shortening of survival and fall in cure rate as compared to IL-2 therapy instituted immediately after BMT with ABM. Increasing the dose of IL-2 did not improve results. However, reducing the frequency of IL-2 administration to once a day instead of twice a day affected the results adversely. Commencing IL-2 therapy 1, 2, or 3 weeks after BMT with fresh, syngeneic bone marrow did not improve the GVL effect as compared to IL-2 therapy started immediately after BMT with fresh, syngeneic bone marrow. Cryopreserved bone marrow was effectively activated with IL-2 and used successfully for BMT after thawing. The animals cured of leukemia by BMT with ABM and and IL-2 therapy were not resistant to leukemia and died when reinfused with leukemic cells. Our findings suggest that for optimum GVL effect, activation of bone marrow is necessary and IL-2 therapy should be started immediately after BMT with ABM.


Asunto(s)
Trasplante de Médula Ósea , Interleucina-2/uso terapéutico , Leucemia Mieloide/terapia , Enfermedad Aguda , Animales , Terapia Combinada , Criopreservación , Esquema de Medicación , Femenino , Interleucina-2/administración & dosificación , Leucemia Mieloide/mortalidad , Leucemia Mieloide/prevención & control , Ratones , Ratones Endogámicos C57BL
8.
Circulation ; 102(5): 572-8, 2000 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-10920071

RESUMEN

BACKGROUND: The precise molecular mechanism of Adriamycin-induced cardiomyopathy (ADR-CM) is still unknown. We address the demonstration of apoptotic myocardial cell death and the apoptosis-inducing molecules in ADR-CM induced in rats. METHODS AND RESULTS: Until 8 weeks after the first administration of ADR, there was no increase in the number of labeled cells by terminal deoxynucleotidyl transferase assay (TUNEL method). Apoptotic indices increased significantly at weeks 9 and 10 in hearts of the ADR-treated group but not in those of the control group (0.42+/-0.12% versus 0.10+/-0.02% and 0.86+/-0.11% versus 0.09+/-0.04% at weeks 9 and 10, respectively). DNA ladder formation was also observed in the myocardial tissues during the late stages of the ADR-CM of rats. There was no significant difference in expression of p53 gene between the ADR group and the control group at either the message or the protein level. An overexpression of Fas antigen was shown in myocardial cells of ADR-treated hearts at weeks 9 and 10 by both Western blotting and immunofluorescent staining. Furthermore, we confirmed that neutralization of anti-Fas ligand antibody inhibited ADR-induced apoptosis. CONCLUSIONS: Apoptotic cell death was observed in the hearts of ADR-CM rats, and the number of apoptotic myocardial cells increased with the deterioration of morphological findings and cardiac function, indicating that apoptosis may be an important mechanism of loss of myocardial cells and cardiac dysfunction in ADR-CM. Apoptosis in ADR-CM rats is not p53-dependent but rather is executed through a Fas-mediated pathway.


Asunto(s)
Cardiomiopatías/patología , Cardiomiopatías/fisiopatología , Doxorrubicina/toxicidad , Miocardio/patología , Receptor fas/fisiología , Animales , Apoptosis , Peso Corporal , Cardiomiopatías/inducido químicamente , Genes p53 , Corazón/efectos de los fármacos , Etiquetado Corte-Fin in Situ , Masculino , Tamaño de los Órganos , Ratas , Ratas Wistar , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Receptor fas/genética
9.
J Comp Pathol ; 133(1): 68-72, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15904926

RESUMEN

A case of complete atrioventricular (AV) block of congenital origin in a 16-month-old Holstein heifer was studied histologically with serial sectioning of the cardiac conduction system. The heart was enlarged and showed moderate dilatation of the left and right ventricles. Histologically, the abnormally placed and poorly formed AV bundle was observed in association with abnormality in the tricuspid extension of the central fibrous body, suggesting that the pathological state of the AV bundle had been responsible for the complete AV block. This type of anatomical fault in the AV bundle is considered to be part of an embryological, developmental malformation of the central fibrous body.


Asunto(s)
Bovinos/anomalías , Bloqueo Cardíaco/patología , Bloqueo Cardíaco/veterinaria , Sistema de Conducción Cardíaco/anomalías , Cardiopatías Congénitas/patología , Cardiopatías Congénitas/veterinaria , Animales , Electrocardiografía , Bloqueo Cardíaco/fisiopatología , Cardiopatías Congénitas/fisiopatología
10.
Cardiovasc Res ; 20(3): 195-200, 1986 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-3708654

RESUMEN

The open loop gain of the rapidly acting arterial pressure control system was estimated in 15 Watanabe heritable hyperlipidaemic (WHHL) rabbits aged 3-31 months. Twenty five normal Japanese white rabbits, aged 6-30 months, were used as controls. After being anaesthetised by an intravenous injection of pentobarbital sodium, the rabbits were bled by 2 ml X kg-1 body weight within 1-2 s through a catheter inserted into the aortic arch. The arterial pressure change after this rapid haemorrhage was recorded for more than 2 min by a catheter placed in the aortic arch. The open loop gain was calculated as (delta API/delta APS)-1, where delta API was the immediate fall and delta APS the steady state fall. The pulse pressure, delta API, and delta APS increased and the open loop gain decreased with age in the WHHL rabbits, but the mean arterial pressure did not change significantly with age. After aortic denervation the open loop gain also decreased with age in the WHHL rabbits. These results indicate that the progress of atherosclerosis with aging in the Watanabe heritable hyperlipidaemic rabbit decreases the vascular compliance and impairs the arterial pressure restoring function of the rapidly acting arterial pressure control system.


Asunto(s)
Arteriosclerosis/fisiopatología , Presión Sanguínea , Hiperlipidemia Familiar Combinada/fisiopatología , Animales , Modelos Animales de Enfermedad , Retroalimentación , Hemorragia , Conejos
11.
Am J Surg Pathol ; 12(2): 115-20, 1988 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-3124642

RESUMEN

Immunoreactivity of glial fibrillary acidic protein (GFAP) in 38 schwannomas and 18 neurofibromas was evaluated and compared with the reactivity of vimentin, S-100 protein, and neurofilament protein. All cases were positive for vimentin and S-100 protein. GFAP was positively stained in the neoplastic cells of 15 of 38 schwannomas (38%) and in two of 18 neurofibromas (11%). The extensively stained GFAP-positive tumors tended to be deeply situated in the body. The GFAP-positive cells were usually spindle-shaped and appeared preferentially in the perivascular region of hyalinized, thick blood vessels.


Asunto(s)
Proteína Ácida Fibrilar de la Glía/análisis , Proteínas de Filamentos Intermediarios/análisis , Neurilemoma/análisis , Neurofibroma/análisis , Proteínas S100/análisis , Vimentina/análisis , Adolescente , Adulto , Anciano , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Neurilemoma/patología , Neurofibroma/patología , Proteínas de Neurofilamentos
12.
Neuroscience ; 128(4): 819-29, 2004.
Artículo en Inglés | MEDLINE | ID: mdl-15464289

RESUMEN

Hydrostatic pressure gradients due to the gravitational force in blood vessels disappear under conditions of microgravity during spaceflight, and the ability of the baroreceptor reflex to control arterial pressure and blood distribution may be altered. We hypothesized, on the basis of the results obtained in our previous experiments using the head-down tilt method in rats and rabbits, that the range of increase in arterial pressure caused by animal behavior narrows under conditions of microgravity, affecting the development of high-threshold unmyelinated fibers in the rat aortic nerve which sends signals from baroreceptors located in the aortic wall to the reflex center. We verified this hypothesis using 9-day-old rat neonates housed with their dams for 16 days on the space shuttle Columbia in outer space (STS-90, Neurolab Mission). Age-matched neonatal rats with the dams remained on the ground as controls. After breeding was carried out in the three experimental groups (FLT, spaceflight; AGC, asynchronous ground control; VIV, vivarium ground control), specimens of the 25-day-old rats were excised and five left aortic nerves in each group were examined by electron microscopy. The number of aortic unmyelinated fibers was significantly less in the FLT group than in each ground control (mean+/-S.D.; 139+/-37 in the FLT, 207+/-36 in the AGC, 283+/-121 in the VIV; P<0.05), which may be related to the weakness of the baroreceptor reflex under conditions of microgravity in space. This result may contribute to understanding of the several cardiovascular issues which occur under microgravity and after reexposure to gravity in human.


Asunto(s)
Aorta , Fibras Nerviosas Mielínicas/fisiología , Fibras Nerviosas Amielínicas/fisiología , Vuelo Espacial , Ingravidez , Análisis de Varianza , Animales , Animales Recién Nacidos , Aorta/inervación , Aorta/fisiología , Axones/fisiología , Medio Ambiente Extraterrestre , Femenino , Masculino , Microscopía Electrónica de Transmisión/métodos , Fibras Nerviosas Mielínicas/ultraestructura , Fibras Nerviosas Amielínicas/ultraestructura , Embarazo , Ratas , Ratas Sprague-Dawley , Estadísticas no Paramétricas
13.
J Nucl Med ; 42(10): 1476-83, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11585860

RESUMEN

UNLABELLED: In vitro studies have shown that (99m)Tc-sestamibi (MIBI) is a transport substrate for the P-glycoprotein (Pgp) pump and the multidrug resistance-associated protein (MRP) pump. However, whether MRP and lung resistance protein (LRP) affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer is not known. In this study, we explored whether Pgp and the other pumps, MRP and LRP, affect tumor accumulation and efflux of (99m)Tc-MIBI in lung cancer. METHODS: Thirty-four lung cancer patients who underwent surgery were examined. Before surgery, (99m)Tc-MIBI SPECT was performed 15 min and 180 min after injection, and early uptake, delayed uptake (L/Nd), and washout rate (L/Nwr) of (99m)Tc-MIBI were obtained. Pgp, MRP, and LRP expression were investigated by immunohistochemistry. The messenger RNA (mRNA) level of Pgp, MRP, and LRP was determined by real-time reverse-transcription polymerase chain reaction. The lung cancer (99m)Tc-MIBI images were correlated with protein and mRNA expression. RESULTS: The mean L/Nd of the Pgp (-) group was significantly higher than that of the Pgp (++) group (P = 0.0324). The Pgp (++) group had a higher L/Nwr than did the Pgp (-) group (P = 0.0269). The mean L/Nd of the Pgp mRNA low-expression group was significantly higher than that of the Pgp mRNA high-expression group (P = 0.0127). The Pgp mRNA high-expression group had a higher L/Nwr than did the Pgp mRNA low-expression group (P = 0.0825). No appreciable correlation was found between the lung cancer (99m)Tc-MIBI images and the expression of MRP or LRP on the level of protein or mRNA. CONCLUSION: These data suggest that an increased level of Pgp expression correlates with a low accumulation on delayed scans and a high L/Nwr of (99m)Tc-MIBI in lung cancer. Neither MRP nor LRP expression on the level of either protein or mRNA correlated significantly with tumor accumulation or efflux of (99m)Tc-MIBI in lung cancer.


Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Neoplasias Pulmonares/diagnóstico por imagen , ARN Mensajero/metabolismo , Radiofármacos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único , Adulto , Anciano , Anciano de 80 o más Años , Resistencia a Múltiples Medicamentos , Femenino , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/metabolismo , Masculino , Persona de Mediana Edad , Proteínas Asociadas a Resistencia a Múltiples Medicamentos , Proteínas de Neoplasias/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Partículas Ribonucleoproteicas en Bóveda/metabolismo
14.
J Nucl Med ; 42(10): 1489-96, 2001 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11585862

RESUMEN

UNLABELLED: Recent reports have indicated the value of [(18)F]FDG PET and (201)Tl SPECT in diagnosing lung cancer. In this study, we compared the diagnostic value of FDG PET and (201)Tl SPECT in the evaluation of pulmonary nodules. METHODS: Sixty-three patients with 66 pulmonary nodules suspected to be lung cancer on the basis of chest CT were examined by FDG PET and (201)Tl SPECT (early and delayed scans) within a week of each study. For semiquantitative analysis, the standardized uptake value (SUV) or the tumor-to-nontumor activity ratio (T/N) (or both) was calculated. All of these lesions were completely removed thoracoscopically or by thoracotomy and were examined histologically. RESULTS: Fifty-four nodules were histologically confirmed to be malignant tumors, and 12 were benign. Both techniques delineated focal lesions with an increase in tracer accumulation in 41 of 54 lung cancers. (201)Tl SPECT on early or delayed scans (or both) identified 4 additional lung cancers that FDG PET images did not reveal: 3 bronchioloalveolar carcinomas and a well-differentiated adenocarcinoma. FDG PET identified 3 additional lung cancers that (201)Tl SPECT images did not reveal; 2 of these lung cancers were <2 cm in diameter. The mean FDG SUV and T/N of bronchioloalveolar carcinomas (2.06 +/- 0.76 and 3.49 +/- 1.03, respectively) were significantly lower than those of poorly differentiated adenocarcinomas (5.55 +/- 2.01 [P = 0.026] and 8.23 +/- 2.16 [P = 0.01], respectively). However, no significant difference was found in (201)Tl T/N on early and delayed scans between bronchioloalveolar carcinomas (1.64 +/- 0.29 and 1.87 +/- 0.42, respectively) and poorly differentiated adenocarcinomas (1.58 +/- 0.32 and 2.76 +/- 1.36, respectively). Of the 12 benign nodules, FDG PET and (201)Tl SPECT showed false-positive results for the same 7 benign nodules (58.3%) (4 granulomas, 1 sarcoidosis, 1 inflammatory pseudotumor, and 1 aspergilloma). Negative FDG PET findings and positive (201)Tl SPECT findings were obtained only for bronchioloalveolar carcinomas or a well-differentiated adenocarcinoma but not for other histologic types of lung cancers or benign pulmonary nodules. CONCLUSION: No significant difference was found between FDG PET and (201)Tl SPECT in specificity for the differentiation of malignant and benign pulmonary nodules. The degree of differentiation of lung adenocarcinoma correlated with FDG uptake but not with (201)Tl uptake. Bronchioloalveolar carcinoma (a well-differentiated, slow-growing tumor) findings typically were positive with (201)Tl but were negative with FDG. The combination of FDG PET and (201)Tl SPECT may provide additional information regarding the tissue characterization of pulmonary nodules.


Asunto(s)
Fluorodesoxiglucosa F18 , Neoplasias Pulmonares/diagnóstico por imagen , Radiofármacos , Radioisótopos de Talio , Tomografía Computarizada de Emisión de Fotón Único , Tomografía Computarizada de Emisión , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma Bronquioloalveolar/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Células Escamosas/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad
15.
Cancer Lett ; 134(1): 43-51, 1998 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-10381129

RESUMEN

The effects of tamoxifen (TAM) on uterine carcinogenesis were investigated in female Donryu rats. The effects were initiated by a single intrauterine treatment with N-ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at a dose of 20 mg/kg body weight via the vagina at 10 weeks of age. TAM tubes (cholesterol tubes containing 50% TAM) were implanted into the backs of the rats for 13 months (full TAM group) or for the second-half of this period (half TAM group). In the control group treated with ENNG alone, various proliferative lesions were induced in the uterine endometrium and the incidence of endometrial adenocarcinomas was about 30%. In contrast, the uteri in both TAM-treated groups showed severe atrophy and the incidences of uterine proliferative lesions were limited to a few endometrial hyperplasias in the half TAM group. Most of the vaginas in both TAM-treated groups showed mucification, while cornification was common in the vaginal epithelium of controls. The ovaries demonstrated similar atrophy with cystic follicles and no corpora lutea in all groups. Other estrogen responsive endocrine organs, such as the pituitaries and adrenals, were small in the TAM-treated groups. Serum estrogen levels in the TAM-treated groups were lower than in the control group but progesterone levels did not differ. These results indicated that TAM acts as an anti-estrogen on the adult rat uterus, inhibiting the development of endometrial adenocarcinomas initiated by ENNG.


Asunto(s)
Anticarcinógenos/farmacología , Neoplasias Endometriales/prevención & control , Tamoxifeno/farmacología , Útero/efectos de los fármacos , Glándulas Suprarrenales/efectos de los fármacos , Glándulas Suprarrenales/patología , Animales , Peso Corporal/efectos de los fármacos , Pruebas de Carcinogenicidad , Neoplasias Endometriales/inducido químicamente , Neoplasias Endometriales/patología , Estradiol/sangre , Femenino , Gónadas/efectos de los fármacos , Gónadas/patología , Hígado/efectos de los fármacos , Hígado/patología , Metilnitronitrosoguanidina/análogos & derivados , Tamaño de los Órganos/efectos de los fármacos , Hipófisis/efectos de los fármacos , Hipófisis/patología , Progesterona/sangre , Ratas , Ratas Endogámicas , Útero/patología
16.
Autoimmunity ; 34(4): 265-74, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11905852

RESUMEN

In order to ascertain whether methimazole, a drug commonly used for the treatment of hyperthyroidism, interferes with the progression of autoimmune-mediated myocardial injury, we investigated the effect of methimazole on experimental autoimmune myocarditis (EAM) in rats. EAM was induced by immunization with porcine cardiac myosin. Methimazole administration markedly slowed the body weight growth in both normal and EAM rats, but did not induce morphologic change of cardiac tissue in normal rats. In EAM rats, macroscopic examination revealed discoloration of the cardiac surface, and histopathological examination by light microscopy showed extensive myocardial necrosis, infiltration by inflammatory cells and myocardial fibrosis. In the EAM rats treated with methimazole, the discolored areas on the cardiac surface were markedly diminished in size, and the myocardial necrosis, cellular infiltration and fibrosis were significantly less severe. To identify the mechanism responsible of this effect, we investigated the change of regulatory lymphocyte subsets in peripheral blood using an immunofluorescence technique with a flow cytometer. A decrease in the helper/suppressor T cell ratio as a result of the increased proportion of suppressor T cells and a decrease in the proportion of B cells were observed in normal rats after methimazole administration, and similar findings were made in the EAM rats treated with methimazole. These results indicate that methimazole interferes with the progression of EAM, and immunosuppression may, at least in part, be involved in the inhibitory effect of methimazole on EAM in rats.


Asunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Metimazol/uso terapéutico , Miocarditis/tratamiento farmacológico , Animales , Enfermedades Autoinmunes/inmunología , Peso Corporal/efectos de los fármacos , Relación CD4-CD8 , Masculino , Miocarditis/inmunología , Miocardio/patología , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Endogámicas F344
17.
Hum Pathol ; 23(7): 736-41, 1992 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-1351863

RESUMEN

The proliferative activity of gastric cancer cells with endocrine features was evaluated in five cases by means of a double-immunostaining procedure. The endocrine cells were recognized by a monoclonal antibody to chromogranin A (CGA) and the proliferative activity by a monoclonal antibody to proliferating cell nuclear antigen (PCNA). With the use of two different chromogens it was easy to determine whether CGA was located in the cytoplasm and whether PCNA was located in the nucleus of the same section. The CGA-positive endocrine cells of the normal gastric antral mucosa could be readily distinguished from the PCNA-positive cells scattered in the mucosal neck zones. Over 1,000 CGA-positive cancer cells were counted per case. A few cells (average, less than 1.0%) exhibited faint nuclear staining with anti-PCNA; in no instance was unequivocal PCNA reactivity demonstrable in the gastric cancer cells with endocrine differentiation. By contrast, the PCNA reaction was positive in one fourth to one third of the other cancer cells. These observations suggest that gastric cancer cells with endocrine features are differentiated and do not participate in the cell cycle.


Asunto(s)
Cromograninas/análisis , Proteínas Nucleares/análisis , Neoplasias Gástricas/química , Neoplasias Gástricas/patología , División Celular , Cromogranina A , Humanos , Técnicas para Inmunoenzimas , Antígeno Nuclear de Célula en Proliferación
18.
Hum Pathol ; 25(10): 1057-62, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7927310

RESUMEN

We examined the infection of herpes simplex virus (HSV), human cytomegalovirus (HCMV), and Epstein-Barr virus (EBV) in 61 autopsy cases with secondary diffuse interstitial pneumonia (SDIP) by immunohistochemistry and compared our findings with those in 46 individuals without lung complications. There was no significant difference in positivity of HSV infection between SDIP cases (28 of 61; 45.9%) and the controls (24 of 46; 52.2%). However, HSV was more extensively distributed in the lungs of seven SDIP cases than in those of controls and proliferated to form inclusion bodies in host cells of 11 SDIP cases. Twenty-two (36.1%) and 19 (31.1%) SDIP cases were positive for HCMV and EBV, respectively, whereas all the 46 controls were negative for both viruses. Eighteen of 22 HCMV-positive cases contained classical inclusion bodies in host cells. Epstein-Barr virus was detected extensively in the lungs of seven SDIP patients, but no viral inclusion bodies were observed in host cells. These findings indicate that the herpes viruses replicate excessively in a considerable number of SDIP cases, but classical inclusion bodies are not always associated with viral infection in the lungs. Major infected cells of these viruses were alveolar lining pneumocytes and intra-alveolar cells. Herpes simplex virus and EBV were detected in leukocytes as well as in pneumocytes. In addition, compared with HCMV and HSV, EBV frequently multiplied in bronchial or bronchiolar epithelial cells. Preferential host cells for these types of herpes virus were somewhat different from one another.


Asunto(s)
Citomegalovirus/aislamiento & purificación , Herpesvirus Humano 4/aislamiento & purificación , Enfermedades Pulmonares Intersticiales/virología , Neumonía Viral/virología , Simplexvirus/aislamiento & purificación , Antígenos Virales/análisis , Citomegalovirus/inmunología , Herpesvirus Humano 4/inmunología , Humanos , Inmunohistoquímica , Enfermedades Pulmonares Intersticiales/patología , Neumonía Viral/patología , Simplexvirus/inmunología
19.
Am J Clin Pathol ; 102(4): 495-502, 1994 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-7524303

RESUMEN

Using formalin-fixed and paraffin-embedded tissues from autopsy, the authors examined infection by human cytomegalovirus, Epstein-Barr virus, and herpes simplex virus in 54 patients with primary or secondary diffuse interstitial pneumonia (DIP) by polymerase chain reaction and immunohistochemistry and compared it with that in 32 persons without lung complications. Polymerase chain reaction and immunohistochemistry demonstrated that approximately 40% and 30% of DIP were positive for human cytomegalovirus and Epstein-Barr virus, respectively, but none of 32 controls had evidence of infection by human cytomegalovirus and Epstein-Barr virus. The polymerase chain reaction was more sensitive than the immunohistochemical technique for detection of herpes simplex virus. The former technique revealed herpes simplex virus infection in approximately 90% of DIP and controls and the latter in approximately 50% of each group. However, immunohistochemistry had the advantage of demonstrating the morphologic location of infected cells and of allowing their semiquantitative evaluation. Herpes simplex virus was more extensively distributed in the lungs of several DIP cases than in those of controls, suggesting the reactivation of herpes simplex virus. Only DIP patients (31 cases [57.4%]) were infected by two or three kinds of herpesviruses. The combination of polymerase chain reaction and immunohistochemistry revealed that these herpesviruses proliferated in many cases of DIP.


Asunto(s)
Citomegalovirus/aislamiento & purificación , Herpesvirus Humano 4/aislamiento & purificación , Enfermedades Pulmonares Intersticiales/microbiología , Simplexvirus/aislamiento & purificación , Secuencia de Bases , ADN Viral/genética , Humanos , Inmunohistoquímica/métodos , Enfermedades Pulmonares Intersticiales/patología , Sondas Moleculares/genética , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Coloración y Etiquetado
20.
J Biochem ; 108(5): 753-9, 1990 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-1982000

RESUMEN

Human neutrophil elastase was purified to homogeneity as two isozymes named E1 and E2. The isozymes degraded Type IV collagen, laminin, fibronectin, and heparan sulfate proteoglycan similarly to each other. The degradation of such basement membrane components by elastase may assist the extravasation of neutrophils in the process of inflammation. Among the substrates tested, only type V collagen, which is susceptible to neutrophil gelatinase, was resistant to elastase. This broad substrate specificity of the enzyme may also contribute to tissue destruction at the sites of inflammation. We produced a monoclonal antibody against the purified enzyme and applied it to immunohistochemical studies. In bronchopneumonia and polyarteritis nodosa, elastase was associated with the cleaved elastic fibers, indicating that the enzyme really destroys tissue in vivo. In the exudates of rheumatoid joint, elastase was stained as diffuse fine granules. Immunohistochemical studies with the monoclonal antibody will provide a complementary way to disclose the mechanism of diseases related to neutrophil infiltration.


Asunto(s)
Membrana Basal/metabolismo , Inflamación/enzimología , Neutrófilos/enzimología , Elastasa Pancreática/metabolismo , Anticuerpos Monoclonales/inmunología , Artritis Reumatoide/enzimología , Artritis Reumatoide/patología , Membrana Basal/ultraestructura , Bronconeumonía/enzimología , Bronconeumonía/patología , Proteoglicanos Tipo Condroitín Sulfato/metabolismo , Colágeno/metabolismo , Matriz Extracelular/enzimología , Matriz Extracelular/inmunología , Matriz Extracelular/ultraestructura , Fibronectinas/metabolismo , Proteoglicanos de Heparán Sulfato , Heparitina Sulfato/metabolismo , Humanos , Hidrólisis , Inflamación/patología , Isoenzimas/metabolismo , Laminina/metabolismo , Poliarteritis Nudosa/enzimología , Poliarteritis Nudosa/patología , Especificidad por Sustrato
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