Histology and histopathology Vol.20, nº 4 (2005)
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- PublicationOpen AccessAnagrelide does not exert a myelodysplastic effect on megakaryopoiesis: a comparative immunohistochemical and morphometric study with hydroxyurea(Murcia : F. Hernández, 2005) Thiele, J.; Kvasnicka, H.M.; Ollig, S.; Schmitt-Gräff, A.A comparative immunohistochemical and morphometric study was performed on megakaryocytes in 20 patients presenting with initial-early stage chronic idiopathic myelofibrosis and accompanying thrombocythemia to elucidate histological features developing after hydroxyurea (HU) versus anagrelide (ANA) therapy. Representative pre-and posttreatment bone marrow biopsies were involved including the monoclonal antibody CD61 for the identification of precursor and mature stages of megakaryopoiesis. An elaborate morphometric evaluation was in keeping with a left-shifting showing a more frequent occurrence of promegakaryoblasts and microforms in both therapy groups. However, contrasting ANA, HU generated defects of differentiation consistent with significant dysplastic changes. In conclusion, concern about a possible leukemogenic capacity following long-term HU therapy is supported by our findings.
- PublicationOpen AccessNestin expression in normal adrenal gland and adrenocortical tumors(Murcia : F. Hernández, 2005) Toti, P.; Regoli, M.; Nesi, G.; Occhini, R.; Bartolommei, S.; Fonzi, L.; Bertelli, E.Human adrenocortical cells have been shown to express cytokeratins and vimentin. Nestin is an intermediate filament protein that is mainly expressed in the developing nervous system and that has been recently reported in rat adrenal gland as well. Using immunohistochemical and biochemical approaches, the present study demonstrates that nestin is constantly expressed in situ in the cortex of normal human adrenal glands. Nestin expressing cells were prevalently located in the zona reticularis but some positive cells could be spotted in the zona fasciculata as well. Moreover, patches of nestin-positive cells have been constantly detected on sections of cortical adenomas. In contrast, adrenal carcinomas displayed a variable number of nestin-immunoreactive cells that in some cases were virtually absent. Samples of renal clear cell carcinoma metastasis in the adrenals were also examined which did not show nestin-immunoreactivity. We propose that a positive nestin-immunoreaction could be useful in differential diagnosis of clear cell tumors in adrenal glands.
- PublicationOpen AccessHypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: Putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes(Murcia : F. Hernández, 2005) Mobasheri, A.; Richardson, S.; Mobasheri, R.; Shakibaei, M.; Hoyland, J.A.Articular cartilage is an avascular connective tissue in which the availability of oxygen and glucose is significantly lower than synovial fluid and plasma. Glucose is an important metabolic fuel and structural precursor that plays a key role in the synthesis of extracellular matrix macromolecules in articular cartilage. However, glucose concentrations in cartilage can fluctuate depending on age, physical activity and endocrine status. Chondrocytes are glycolytic cells and must be able to sense the quantities of oxygen and glucose available to them in the extracellular matrix and respond appropriately by adjusting cellular metabolism. Consequently chondrocytes must have the capacity to survive in an extracellular matrix with limited nutrients and low oxygen tensions. The molecular mechanisms responsible for allowing chondrocytes to adapt to these harsh environmental conditions are poorly understood. In this article we present a novel “dual” model of oxygen and glucose sensing in chondrocytes based on recent experimental data. This model incorporates the hypoxiainducible factor alpha (HIF-1a) as an oxygen sensor and the hypoxia responsive facilitative glucose transporters, GLUT1 and GLUT3 as putative components of the glucose sensing apparatus in chondrocytes. Recent studies have shown that GLUT1 and GLUT3 are both expressed in chondrocytes and their HIF-1a-mediated transcription may be dually stimulated in response to hypoxia and low glucose conditions which in turn promote anaerobic glycolysis in favor of oxidative phosphorylation. This working model provides, for the first time, a unifying hypothesis to explain how chondrocytes might sense and respond to low oxygen tensions and alterations in extracellular glucose.
- PublicationOpen AccessIs mitotic chromatid segregation random?(Murcia : F. Hernández, 2005) Bell, C.D.The question of whether mitotic segregation of chromatids is random or programmed assumes great significance for cellular differentiation if one recognizes that sister chromatids may have epigenetic differences and carry them from one generation into the next. The literature was examined for evidence of nonrandom chromosomal and chromatid segregation. Many organisms were described as undergoing non-random homologue segregation in meiosis I. The explanations for these phenomena were attributed in some instances, to peculiarities of the meiotic spindle, though in some convincing experiments, the epigenetic heterochromatin of the kinetochores was implicated. The few existing descriptions of non-random mitotic segregation were also described. Existing literature on ultrastructural, immunohistochemical, and physiological features of the chromatid kinetochores during the mitotic process was searched for evidence of asymmetry or structural differences between sister chromatids, which is presented. Also reported are descriptions of how epigenetic changes and cell differentiation can influence centromeric function and ultimately, kinetochore function. Fundamental to the hypothesis of gene regulation presented here, is the assumption that genetic foci on different chromosomes interact, and must be proximate to each other and stereologically compatible for interactions to occur. Also described are spatial changes in chromosomal territories associated with function and differentiation. These territories can be in varying nuclear locations depending on gene function, and may show asymmetry between daughter cells. Despite evidence presented for the possibility of non-random chromatid segregation at mitosis, this question will remain unanswered until the matter is specifically addressed by experiment.
- PublicationOpen AccessDEC1 expression in 1p-aberrant oligodendroglial neoplasms(Murcia : F. Hernández, 2005) Preusser, Matthias; Birner, P.; Ambros, I.M.; Ambros, P.F.; Budka, H.; Harris, A.L.; Hainfellner, J.A.Background. Expression of hypoxia-related tissue factors in 1p-aberrant oligodendroglial neoplasms diminishes patient outcome. Differentiated embryochondrocyte expressed gene 1 (DEC1) has been described as novel hypoxia-related tissue factor. In our study, we assessed the expression of DEC1 in 1p aberrant oligodendroglial neoplasms and its association with necrosis and expression of hypoxia-inducible factor 1a (HIF-1a), carbonic anhydrase-9 (CA9), and vascular endothelial growth factor-mRNA (VEGF). Materials and methods. 44 primary and 16 recurrent oligodendroglial neoplasms with 1p-aberrations were investigated immunohistochemically for the expression of DEC1, HIF-1a, and CA9. Expression of VEGF was investigated using in situ hybridization. DEC1 expression was correlated with necrosis and with expression of HIF-1a, CA9, and VEGF. Results. DEC1 was expressed in tumor cell nuclei, and occasionally in nuclei of endothelial cells, and glial and neuronal cells of surrounding brain tissue. High expression (>10% of tumor cells immunolabeled) of DEC1 was found in 56 cases, low expression (<10% of tumor cells immunolabeled) was found in 3 cases. In 1 case no expression of DEC1 was evident. DEC1 expression showed no topographical association with necrosis or expression of HIF-1a, CA9, or VEGF. Conclusion. DEC1 expression is found in the majority of 1p-aberrant oligodendroglial neoplasms and does not correlate with necrosis or expression of HIF-1a, CA9, VEGF. Thus, immunohistochemical analysis of DEC1 expression is in our hands not suitable for detection of tissue hypoxia in this type of primary brain tumor.