Histology and histopathology Vol.18, nº 1 (2003)
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- PublicationOpen AccessExploring the connection between chronic renal fibrosis and bone morphogenic protein-7(Murcia : F. Hernández, 2003) Kalluri, R.; Zeisberg, M.Tubulointerstitial fibrosis is a hallmark feature of chronic renal injury. Specific therapies to control the progression of renal fibrosis towards endstage renal failure are still limited. Transforming growth factor-ß1 (TGF-ß1) has been identified as a major mediator of renal fibrosis. Recent reports have suggested that Bone Morphogenic Protein-7 (BMP-7), another member of the TGF-ß superfamily, accelerates repair of acute renal injury and ameliorates progression of chronic renal fibrosis in a variety of animal models. Interestingly, BMP-7, an endogenous molecule which is present in the normal kidney, vastly decreases its expression during renal injury. Although, the mechanism of BMP-7 action in the kidney is not yet fully understood, the idea of an endogenous molecule with reno-protective function is intriguing
- PublicationOpen AccessDiagnostic differentiation of essential thrombocythaemia from thrombocythaemias associated with chronic idiopathic myelofibrosis by discriminate analysis of bone marrow features - a clinicopathological study on 272 patients(Murcia : F. Hernández, 2003) Thiele, J.; Kvasnicka, H.M.Until now diagnosis of essential thrombocythaemia (ET) is generally performed by following the criteria of the Polycythaemia Vera Study Group (PVSG) that only marginally regards morphological features. Bone marrow biopsies were studied from 272 patients with ET in strict accordance with the PVSG guidelines and also from 35 control patients with reactive thrombocytosis. To define morphological features of distinctive impact more accurately, we performed a stepwise discriminant analysis of 16 morphological parameters based on histochemical staining reactions and semiquantitative grading of standardized features. A clear-cut separation into three distinctive histological patterns was accomplished that showed in more than 96% a correct predicted classification. Variables of significant impact included fibre content, quantity and cytological abnormalities of megakaryopoiesis like bulbous (cloudlike) nuclei, degree of nuclear lobulation and presence of giant forms. These changes were not detectable in the control group. The different constellations of histopathological features could be assigned to true ET (98 patients) and false ET, i.e. 136 patients with prefibrotic and 38 patients with early fibrotic chronic idiopathic myelofibrosis (IMF) accompanied by thrombocythaemia. A re-evaluation of clinical findings was in keeping with this classification into three categories that exerted significant differences to develop myelofibrosis during observation time and also different survival patterns. Contrasting IMF true ET is characterized by a pronounced proliferation of the megakaryocyte lineage showing large to giant cells without maturation defects and no relevant increase in reticulin fibres. Discrimination between these entities is warranted, because of a significant difference in presenting haematological data, follow-up and life expectancy.
- PublicationOpen AccessA comparison between double and triple therapies of octreotide, galanin and serotonin on a rat colon carcinoma(Murcia : F. Hernández, 2003) Sitohy, B.; El-Salhy, M.Sixty female nude mice (C578L/6jBom-nu) were injected with 100µl cell suspension containing 2x106 viable cells of an N-methyl-N-nitroguanidineinduced rat colonic adenocarcinoma. After seven days the animals were divided into five groups. The first group received only saline and served as a control group. The second group received a triple therapy of octreotide, galanin and serotonin (20 µg/kg). The last three groups received double therapies of octreotide/galanin, octreotide/serotonin or galanin/serotonin (20 µg/kg). They were treated twice a day for five days. Tumour volume and weight, relative volume density of tumourfeeding blood vessels and of tumour necrotic tissue, as well as apoptotic and proliferation indices were determined. Animal weight, food consumption, faeces weight and its water content were recorded before and after treatment. Tumour volume was significantly reduced only in the group that received the triple therapy. The volume density of the tumour-feeding blood vessels was significantly reduced in the treated groups with the exception of the group that received octreotide and serotonin. Increased relative volume density of tumour necrotic tissue occurred only in the group treated with triple therapy. Apoptotic indices were significantly increased in all treated groups. No statistical difference was found between treated animals and controls regarding proliferation indices, food consumption, faeces weight and water content or animal weight. In conclusion, double therapy using two of the gastrointestinal bioactive substances, octreotide, galanin and serotonin, has certain effects on colon cancer cells. To cause a considerable tumour necrosis, triple therapy seems to be required. Both double and triple therapy seem to lack obvious side-effects.
- PublicationOpen AccessMetabotropic glutamate receptors promote neuronal and vascular plasticity through novel intracellular pathways(Murcia : F. Hernández, 2003) Chong, Z.Z.; Kang, J.Q.; Maiese, K.During the initial development and maturation of an individual, the metabotropic glutamate receptor (mGluR) system becomes a necessary component for the critical integration of cellular function and plasticity. In addition to the maintenance of cellular physiology, the mGluR system plays a critical role during acute and chronic degenerative disorders of the central nervous system. By coupling to guanosinenucleotide- binding proteins (G-proteins), the mGluR system employs a broad range of signal transduction systems to regulate cell survival and injury. More commonly, it is the activation of specific mGluR subtypes that can prevent programmed cell death (PCD) consisting of two distinct pathways of genomic DNA degradation and membrane phosphatidylserine (PS) residue exposure. To offer this cellular protection, mGluRs modulate a series of down-stream cellular pathways that include protein kinases, mitochondrial membrane potential, cysteine proteases, intracellular pH, endonucleases, and mitogen activated protein kinases. Prevention of cellular injury by the mGluR system is directly applicable to clinical disability, since immediate and delayed injury paradigms demonstrate the ability of this system to reverse PCD in both neuronal and vascular cell populations. Further understanding of the intricate pathways that determine the protective nature of the mGluR system will provide new therapeutic avenues for the treatment of neurodegenerative disorders.
- PublicationOpen AccessMolecular pathogenesis of urothelial bladder cancer(Murcia : F. Hernández, 2003) Theodorescu, D.Carcinoma of the urinary bladder is the second most common urologic malignancy. In addition, these tumors are one of the best understood genitourinary neoplasms with a well defined etiology, natural history, tumor biology, treatment options and outcome. This level of understanding arises as a consequence of multiple factors and represents a convergence of knowledge from diverse scientific disciplines. Insight provided by these disciplines, coupled with unique features of this neoplasm which make it assessable for detection, monitoring and treatment, combine to make this disease a model system for modern oncology. The intent of this review is to provide the reader an overview of our current understanding of this tumor from the standpoint of its molecular biology as related to tumor development and progression.