RESUMEN
The aim of the study was to determine by immunohistochemistry cellular localization and immunoreactivity levels of YAP1 and LATS1 proteins in paired sections of tumor and unchanged renal tissues of 54 clear cell renal cell carcinoma (ccRCC) patients. Associations between clinical-pathological and overall survival (OS; median follow-up was 40.6 months) data of patients and YAP1 and LATS1 immunoreactivity were analyzed by uni- and multivariate Cox regression model and log-rank test. YAP1 immunoreactivity was found in the nuclei of tumor cells in 64.8% of ccRCC patients, whereas only 24.1% of tumors revealed cytoplasmic YAP1 expression. LATS1 immunoexpression was observed only in the cytoplasm of tumor cells in 59.3% of patients. LATS1 immunoreactivity in cancer cells negatively correlated with the size of primary tumor. The overall YAP1 immunoreactivity did not correlate with clinical-pathological data of patients. However, the subgroup of ccRCC patients who presented with cytoplasmic YAP1 immunoexpression had significantly shorter OS (median = 26.8 months) than patients without cytoplasmic YAP1 expression (median undefined). Multivariate Cox analysis revealed that increased cytoplasmic YAP1 (HR = 4.53) and decreased LATS1 immunoreactivity levels (HR = 0.90) were associated with worse prognosis, being independent prognostic factors. These results suggest that YAP1 and LATS1 can be considered as new prognostic factors in ccRCC.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/metabolismo , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/inmunología , Neoplasias Renales/metabolismo , Fosfoproteínas/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Carcinoma de Células Renales/patología , Núcleo Celular/metabolismo , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Masculino , Análisis Multivariante , Modelos de Riesgos Proporcionales , Análisis de Supervivencia , Factores de Transcripción , Proteínas Señalizadoras YAPRESUMEN
The aim of the study was to examine the process of sciatic nerve regeneration and changes in the dorsal root ganglia (from which sensory fibres of the sciatic nerve extend) in animals intoxicated with ethanol. The experiment used 20 rats, divided into two groups: control and treated. The treated animals were intragastrically given 2g/kg b.w. of ethanol in 25% aqueous solution. In both groups the right sciatic nerve was transected and then sutured. After 5 months the animals were anaesthetized. The left and the right spinal dorsal ganglia-L5 and sections from the non-operated and operated sciatic nerves were collected for analysis. Ultrastructural examinations and morphometric measurements were conducted. It was found that ethanol administrated to rats inhibited regeneration of the transected and then sutured sciatic nerve, impairing the growth of axons in the transected nerve and destroying the regenerating sensory ganglion cells. The mechanism of the changes described may be associated with axonal transport disorders or with the suppressed production of biologically active substances, which affect nerve regeneration.
Asunto(s)
Etanol/envenenamiento , Regeneración Nerviosa/efectos de los fármacos , Nervio Ciático/patología , Animales , Masculino , Neuronas/patología , Neuronas/ultraestructura , Ratas , Ratas Wistar , Nervio Ciático/fisiología , Nervio Ciático/ultraestructura , Raíces Nerviosas Espinales/patología , Raíces Nerviosas Espinales/ultraestructuraRESUMEN
The aim of the study including 89 brain gliomas was to determine their proliferative activity assayed with immunohistochemical methods (PCNA and Ki-67) and with the method of AgNORs, as well as to evaluate the correlation between the proliferative activity and features of histological malignancy. The study reveals that the estimation of PCNA, Ki-67 and AgNORs are effective methods for the determination of the proliferative activity of brain gliomas. Statistically significant differences were noted in the proliferative PCNA, Ki-67 and AgNORs between groups of gliomas with lower and higher malignancy, which indicated a distinct correlation between histological malignancy of the tumours and their proliferative activity. High values of PCNA and Ki-67 (> 40%) and AgNORs (> 15) were found to considerably deteriorate prognosis in brain gliomas.
Asunto(s)
Astrocitoma/patología , Neoplasias Encefálicas/patología , Movimiento Celular/fisiología , Glioblastoma/patología , Neuroglía/citología , Antígeno Nuclear de Célula en Proliferación/fisiología , Adulto , Anticuerpos Monoclonales , Astrocitoma/cirugía , Neoplasias Encefálicas/cirugía , Niño , Femenino , Glioblastoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios RetrospectivosRESUMEN
Ultrastructural examinations carried out on liver specimens collected from Wistar rats revealed that single administration of cyclophosphamide in a dose of 150 mg/kg body weight produced changes in the cytoplasmic structures, particularly in the smooth endoplasmic reticulum and mitochondria. The changes were reversible and subsided 14 days following cyclophosphamide administration. Administration of pentoxyfylline to rats in a dose of 30 mg/kg b.w./day for 10 days induced structural alterations in the intracytoplasmic structures of hepatocytes, similar to those caused by cyclophosphamide, although more intensified in the vicinity of the vascular pole. The pentoxyfylline-induced changes in hepatocytes retreated already 4 days after its withdrawal and can be considered adaptative. Simultaneous administration of both drugs to rats resulted in enhanced metabolic disturbances in hepatocytes and dissociation of adaptative mechanisms manifesting themselves in irreversible morphological changes in the intracytoplasmic structures and in the occurrence of collagen in the intercellular spaces.
Asunto(s)
Antineoplásicos Alquilantes/farmacología , Ciclofosfamida/farmacología , Hígado/efectos de los fármacos , Pentoxifilina/farmacología , Vasodilatadores/farmacología , Animales , Interacciones Farmacológicas , Hígado/ultraestructura , Microscopía Electrónica , Mitocondrias Hepáticas/efectos de los fármacos , Mitocondrias Hepáticas/ultraestructura , Orgánulos/efectos de los fármacos , Orgánulos/ultraestructura , Ratas , Ratas WistarRESUMEN
The correlation was described between the ultrastructural picture and DNA mass content of MK nuclei in experimental haemorrhagic shock in rats. Significant disproportions were revealed between the morphological pictures and the ploidy of MK nuclei in the successive phases of the shock. Abnormalities of the maturation of marrow MK nuclei were found in the first hours of the shock, being most pronounced in the 24th hour.
Asunto(s)
Megacariocitos/ultraestructura , Ploidias , Choque Hemorrágico/patología , Animales , Núcleo Celular/ultraestructura , ADN/análisis , Modelos Animales de Enfermedad , Femenino , Microscopía Electrónica , Ratas , Ratas WistarRESUMEN
Ultrastructural evaluation was performed of the MK cytoplasm in the successive phases of experimental haemorrhagic shock in rats. Qualitative abnormalities were revealed in the intracytoplasmic structures of MK. Platelets in the circulating blood were evaluated. A correlation was found between the changes in the intracytoplasmic organelles and the number and biological activity of blood cells. The results obtained indicate significant disturbances in the functioning of the thrombopoietic system in experimental haemorrhagic shock, which are caused by alterations within the intracytoplasmic structures of MK and lead to platelet production from morphologically differentiated but functionally immature MK.
Asunto(s)
Plaquetas/patología , Hematopoyesis , Megacariocitos/ultraestructura , Choque Hemorrágico/patología , Animales , Citoplasma/ultraestructura , Modelos Animales de Enfermedad , Femenino , Microscopía Electrónica , Recuento de Plaquetas , Ratas , Ratas WistarRESUMEN
The aim of the study was to examine morphological changes in the spinal dorsal ganglia (from which sensory fibres of the sciatic nerve extend) in animals intoxicated with ethanol, in which the sciatic nerve was transected and then sutured. By means of morphometric methods using a computer system of picture analysis and in ultrastructural examinations it was found that ethanol administered to rats to drink for 3 months caused only slight morphological alterations in the sensory nerve cells of the spinal vertebral ganglia on the non-operated side. However, ethanol or its metabolites destroyed the regenerating sensory nerve cells of the spinal vertebral ganglia of the transected and then sutured sciatic nerve.
Asunto(s)
Intoxicación Alcohólica/patología , Ganglios Espinales/ultraestructura , Regeneración Nerviosa , Nervio Ciático/fisiología , Intoxicación Alcohólica/fisiopatología , Animales , Microscopía Electrónica , RatasRESUMEN
The experiment was carried out on 45 male Wistar rats which were divided into 3 groups: group I-15 rats which were given water to drink during the experiment, group II-15 rats obtaining 10% ethanol solution during the experiment and group III-15 rats obtaining 20% ethanol solution during the experiment. All animals were injected 0.3 ml suspension of hepatoma Morris 5123 cells directly to the liver on the 14th day of the experiment. After the 9 weeks of the experiment the animals from all groups were narcotized, decapitated and the lungs were taken into the morphometric, histological and ultrastructural examinations. They showed that ethanol has a stimulating effect on formation and development of hepatoma Morris 5123 in rat lungs. The increase of number and extensiveness of metastases as well as the increase of mean metastases focuses volume, and the increase of lung weight in animals which obtained ethanol are the exponent of the influence. On the basis of ultrastructural examinations, it can be noted that promoting activity of ethanol can be connected: a) with the increase of neoplastic cells activity, b) with changes appearing in pulmonic epithelium and endothelium of vessel enabling neoplastic cells to adhere to basal membrane as well as their crossing the vessel wall.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Carcinógenos/toxicidad , Etanol/toxicidad , Neoplasias Hepáticas Experimentales/patología , Neoplasias Pulmonares/secundario , Administración Oral , Animales , Carcinógenos/administración & dosificación , Carcinógenos/farmacología , Etanol/administración & dosificación , Etanol/farmacología , Neoplasias Pulmonares/etiología , Masculino , Trasplante de Neoplasias , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Chordoma is one of rare intracranial neoplasms (0.2-0.5%). Apart from classic chordoma in 1973 r. Heffelfinger and al. separated chondroid chordoma which showed better prognosis. We studied 4 classic and 3 chondroid intracranial chordomas. All tumours contained chondroitine sulfate and keratan sulfate and showed positive immunohistochemical reactions to cytokeratin, S-100 protein and vimentin, supporting the concept of common origin of both types of chordomas. Immunohistochemical studies of PCNA and Ki-67 antigen and staining AgNOR's did not show significant differences in the proliferative activity between both types chordomas what attests to biological malignancy.
Asunto(s)
Biomarcadores de Tumor/análisis , Neoplasias Encefálicas/patología , Cordoma/parasitología , Adulto , Sulfatos de Condroitina/análisis , Femenino , Humanos , Inmunohistoquímica , Sulfato de Queratano/análisis , Queratinas/análisis , Antígeno Ki-67/análisis , Masculino , Persona de Mediana Edad , Antígeno Nuclear de Célula en Proliferación/análisis , Proteínas S100/análisis , Vimentina/análisisRESUMEN
Using electroneurographic and morphological methods the effect of Biogonadyl on the regeneration of sectioned and the sutured sciatic nerves was evaluated. The analysis of conduction parameters in the sciatic nerves during the 6-week experiment, although the results obtained were not statistically significant, suggests a beneficial effect of Biogonadyl upon regeneration processes in the nerves. Morphological and morphometric studies have demonstrated that Biogonadyl statistically significantly accelerated axon growth in the distal part of sciatic nerves. It did not, however, influence the processes of their maturation.
Asunto(s)
Factores de Crecimiento Nervioso/farmacología , Regeneración Nerviosa/efectos de los fármacos , Ratas Wistar , Nervio Ciático/efectos de los fármacos , Animales , Axones/efectos de los fármacos , Lateralidad Funcional , Masculino , Ratas , Nervio Ciático/citologíaRESUMEN
Quantitation and morphometric parameters of bone marrow MK in rats during acute haemorrhagic shock were analysed. The results were compared with group of normal rats and rats after surgical manipulation. In examining animals statistical significant differences were observed in localization, size, form factor, N/C ratio, forming cluster forms and phenomena of emperipolesis. These disturbances of MK were often observed in rats after surgical manipulation. The results indicate that the changes of MK have just observed after 60 min. from indication of haemorrhagic shock.
Asunto(s)
Médula Ósea/patología , Megacariocitos/patología , Choque Hemorrágico/patología , Enfermedad Aguda , Animales , Femenino , Ratas , Ratas WistarRESUMEN
The circulating megakaryocytes (MK) in the central venous blood of rats during haemorrhagic shock have been studied. Nucleopore polycarbonate membranes with a pore size of 5 microns were used to isolate circulating MK. Different morphologic types of MK were analysed. The results showed an increased number of MK migrating from the bone marrow to blood and confirm that circulation MK are a normal physiologic component of blood. The number of the rise during haemorrhagic shock, especially large MK and MK with scant cytoplasm ("naked nuclei" MK).
Asunto(s)
Megacariocitos/clasificación , Choque Hemorrágico/sangre , Enfermedad Aguda , Animales , Femenino , Megacariocitos/fisiología , Ratas , Ratas WistarRESUMEN
The aim of the study was to evaluate the protease and antiprotease activity in the fluid obtained from the culture of cells isolated from the lungs of animals with experimental emphysema. An attempt was made to correlate the results of biochemical examinations with adherence degree and ultrastructural changes of the surface of BAL-isolated cells. The experiment was carried out on male Wistar rats, of 180-220 g b.w. Two i.p. injections of BCG-vaccine (4 x 10(8) microorganisms) on the 1st and 14th day were applied as macrophage mobilizing and activating agent. Papain (2 mg/l ml/100 g b.w.) was given once i.t. on the 21st day. The animals were sacrificed on the 28th day of the experiment. We found a correlation between the increase in the cell adherence and ultrastructural changes (in SEM), suggesting an increased activity of the cells isolated from BCG-treated rats. In the culture medium of cells isolated from the rats which were given BCG or papain and BCG+papain we observed an increased base protease activity and decreased Cathepsin D activity comparing with the control group. Increased antitrypsin activity in the BCG and BCG+papain-treated rats and decreased antitrypsin activity in papain-treated rats only was observed, too. There was no obvious difference in the levels of the antiplasmin and antichymotrypsin activities between the groups. The present results indicate that activated pulmonary macrophages are one of the sources of the protease-antiprotease intraalveolar imbalance. However, an increased production of proteolytic enzymes may not be the only factor responsible for the progression of lung emphysema in BCG-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Líquido del Lavado Bronquioalveolar/citología , Endopeptidasas/metabolismo , Enfisema Pulmonar/enzimología , Animales , Vacuna BCG/administración & dosificación , Líquido del Lavado Bronquioalveolar/química , Catepsina D/metabolismo , Adhesión Celular , Células Cultivadas , Macrófagos Alveolares/enzimología , Macrófagos Alveolares/ultraestructura , Masculino , Microscopía Electrónica de Rastreo , Inhibidores de Proteasas/metabolismo , Seudópodos/ultraestructura , Enfisema Pulmonar/patología , Ratas , Ratas WistarRESUMEN
Megakaryocytes were evaluated in the blood of the caval vein of rats in the acute stage of hemorrhagic shock. The number and morphological types of MK were analysed. Millipore filters were used for the evaluation. MK were found to be a physiological element of the blood. An increase in the MK number leaving the bone marrow in rats with the acute stage of hemorrhagic shock was observed. A rise in the total MK number was accompanied by an increase in the percentage of mature and "naked nucleus" MK.
Asunto(s)
Megacariocitos/patología , Choque Hemorrágico/sangre , Enfermedad Aguda , Animales , Recuento de Células Sanguíneas , Núcleo Celular/patología , Citoplasma/patología , Masculino , Ratas , Ratas WistarRESUMEN
Aim of the present study was to evaluate cathepsin D, base protease, antiplasmin, antitrypsin and antichymotrypsin activities and protein content in the 24h culture medium of the alveolar macrophages (AM) deriving from the rats treated BCG-vaccine and from rats with papain-induced emphysema. In the culture medium of cells isolated from the rats which were given BCG or papain and BCG+papain we observed an increase of base protease activity and a decrease of cathepsin D activity comparing with control group. Increased antitrypsin activity in BCG and BCG+papain-treated rats and decreased antitrypsin activity in papain-treated rats were observed. There were not significant differences in antiplasmin and antichymotrypsin activities between examined groups. The obtained results indicate that activated pulmonary macrophages are one of the sources of the protease-antiprotease intraalveolar imbalance. However, increased production of proteolytic enzymes may not be the only factor responsible for the progression of lung emphysema in BCG-treated rats.
Asunto(s)
Enfisema/enzimología , Endopeptidasas/metabolismo , Macrófagos Alveolares/enzimología , Inhibidores de Proteasas/metabolismo , Animales , Vacuna BCG/uso terapéutico , Líquido del Lavado Bronquioalveolar/citología , Catepsina D/metabolismo , Células Cultivadas , Quimotripsina/metabolismo , Enfisema/inducido químicamente , Enfisema/terapia , Macrófagos Alveolares/patología , Masculino , Papaína , Ratas , Ratas Wistar , Tripsina/metabolismoRESUMEN
An evaluation of frequency and intensity degree of emperipolesis in megakaryocytes of the bone marrow in rats subjected to the hemorrhagic shock was performed. The results were compared with those obtained in the groups of animals undergoing a sham operation and not subjected to any surgical procedure at all. A statistically significant increase was found in the frequency of emperipolesis in the shocked rats compared with the remaining groups. The cytoplasm of megakaryocytes most frequently revealed the occurrence of granulocytes and erythroblasts. However, differences in the frequency of respective hematopoietic cells were not significant.
Asunto(s)
Médula Ósea/fisiopatología , Megacariocitos/fisiología , Choque Hemorrágico/fisiopatología , Animales , Médula Ósea/patología , Megacariocitos/patología , Ratas , Ratas Wistar , Choque Hemorrágico/patologíaRESUMEN
Quantitative and morphological analyses (in SEM) of blood platelets collected from the left and right ventricles of the rat heart in the course of experimental lung emphysema were done. Platelet aggregation index was estimated, too. Emphysema was induced by a single intratracheal instillation of papain solution in a dose of 20 mg/kg b.w/1 ml PBS. The animals were sacrificed after 2 and 24 hours and 7, 14, 28 days later. Within 24 hours of the experiment a slight decrease was observed in the number of platelets in the blood collected from the left ventricle compared to the right one as well as to control animals. Also a reduction in platelet aggregation coefficient value was noted. However, in the later period of emphysema progression (after 7th day), a statistically significant increase was found in the number of blood platelets in the left ventricle. A relation was noted between quantitative changes of blood platelets and emphysema progression evaluated morphometrically. The ultrastructural examinations in SEM suggest the occurrence of platelet satellitosis in animals intratracheally injected with papain solution. The present results indicate the possibility of a significant contribution of blood platelets to the pathogenesis of experimental lung emphysema.
Asunto(s)
Agregación Plaquetaria/fisiología , Recuento de Plaquetas , Enfisema Pulmonar/sangre , Animales , Ventrículos Cardíacos , Masculino , Papaína , Enfisema Pulmonar/inducido químicamente , Ratas , Ratas WistarRESUMEN
The platelets phagocytic activity has been measured in rats during experimental haemorrhagic shock determining the per cent of phagocytic platelets and phagocytic index. The authors have the decrease of phagocytic activity of platelets during haemorrhagic shock. Disturbances of phagocytic activity of platelets have been accompanied by changes of their shape and formation platelet aggregates.
Asunto(s)
Plaquetas/fisiología , Fagocitosis/fisiología , Choque Hemorrágico/sangre , Animales , Trastornos de las Plaquetas Sanguíneas/fisiopatología , Masculino , Agregación Plaquetaria , Recuento de Plaquetas , Ratas , Ratas WistarRESUMEN
Widespread fatal massive bone marrow embolism of the coronary and the pulmonary arteries are described in a 71-year-old man with a respiratory disease. Cardiac massage was carried out during the cardiac arrest. In autopsy findings there were no fractures of the ribs or the sternum. The authors suggested that the cardiac massage was the most important predisposing factor for the bone marrow embolism.