Histology and histopathology Vol.21, nº 5 (2006)

Ir a Estadísticas

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http://hdl.handle.net/10201/177492

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Open Access
Angiogenesis in rheumatoid arthritis
(Murcia : F. Hernández, 2006) Maruotti, Nicola; Cantatore, F.P.; Crivellato, E.; Vacca, A.; Ribatti, Doménico
There is much evidence that rheumatoid arthritis is closely linked to angiogenesis. Important angiogenic mediators have been demonstrated in synovium and tenosynovium of rheumatoid joints. VEGF (Vascular Endothelial Growth Factor), expressed in response to soluble mediators such as cytokines and growth factors and its receptors are the best characterized system in the angiogenesis regulation of rheumatoid joints. Moreover, other angiogenic mediators such as platelet-derived growth factor (PDGF), fibroblast growth factor-2 (FGF-2), epidermal growth factor (EGF), insulin-like growth factor (IGF), hepatocyte growth factor (HGF), transforming growth factor beta (TGF-ß), tumor necrosis factor alpha (TNF- a), interleukin-1 (IL-1), IL-6, IL-8, IL-13, IL-15, IL-18, angiogenin, platelet activating factor (PAF), angiopoietin, soluble adhesion molecules, endothelial mediator (endoglin) play an important role in angiogenesis in rheumatoid arthritis. On the other hand, endostatin, thrombospondin-1 and -2 are angiogenic inhibitors in rheumatoid arthritis. The persistence of inflammation in rheumatoid joints is a consequence of an imbalance between these inducers and inhibitors of angiogenesis.
Open Access
Genetics of pigment cells, lessons from the tyrosinase gene family
(Murcia : F. Hernández, 2006) Murisier, F.; Beermann, Friedrich
In mammals, the melanin pigment is produced in two cell types of distinct developmental origins. The melanocytes of the skin originate form the neural crest whereas the retinal pigment epithelium (RPE) of the eye originates from the optic cup. The genetic programs governing these two cell types are thus quite different but have evolved to allow the expression of pigment cell-specific genes such as the three members of the tyrosinase-related family. Tyrosinase, Tyrp1 and Dct promoters contain a motif termed E-box which is bound by the transcription factor Mitf. These E-boxes are also found in the promoters of the corresponding fish genes, thus highlighting the pivotal role of Mitf in pigment cell-specific gene regulation. Mitf, which displays cell type-specific isoforms, transactivates the promoters of the tyrosinase gene family in both pigment cell lineages. However, specific DNA motifs have been found in these promoters, and they correspond to binding sites for RPE-specific factors such as Otx2 or for melanocyte-specific factors such as Sox10 or Pax3. The regulation of pigment cell-specific expression is also controlled by genetic elements located outside of the promoter, such as the tyrosinase distal regulatory element located at -15 kb which acts as a melanocytespecific enhancer but also protects from spreading of condensed chromatin. Thus, by using the tyrosinase gene family as a model, it is possible to define the transcription factor networks that govern pigment production in either melanocytes or RPE.
Open Access
Matrix metalloproteinases in bone marrow: roles of gelatinases in physiological hematopoiesis and hematopoietic malignancies
(Murcia : F. Hernández, 2006) Yu, X.F.; Han, Z.C.
Turnover balance of extracellular matrix (ECM) is a prerequisite for the structural and functional homeostasis of bone marrow (BM) microenvironment. The role of ECM in physiologic hematopoiesis and its pathologic change in hematopoietic malignancies are very important and under extensive investigation. Accumulating evidence suggests that matrix metalloproteinases (MMPs), a family of zinc-dependent proteinases, take an active part in the physiological and pathological hematopoiesis through remodeling the ECM in BM hematopoietic microenvironment. In this review, we will focus on the roles of MMPs in physiological hematopoiesis, hematopoietic stem cells mobilization/transplantation, and hematological malignancies. Furthermore, the preclinical studies on the role of synthetic MMP inhibitors in the treatment of hematological malignancies will be discussed.
Open Access
Lewis y antigen (CD174) and apoptosis in gastric and colorectal carcinomas, Correlations with clinical and prognostic parameters
(Murcia : F. Hernández, 2006) Baldus, S.E.; Mönig, S.P.; Zirbes, T.K.; Thakran, J.; Köthe, D.; Köppel, M.; Hanisch, F.G.; Thiele, J.; Schneider, P.M.; Hölscher, A.H.; Dienes, H.P.
Lewisy (Ley), also designated CD174, represents a carbohydrate blood group antigen which is strongly expressed in neoplastic gastrointestinal tissues. Previous reports indicated an association between Ley expression and apoptosis. Therefore, we tried to elucidate its clinicopathological relevance in a series of 160 gastric and 215 colorectal carcinomas by immunohistochemical detection of Ley and visualization of apoptotic cells applying the in-situ-end labelling (ISEL) method, followed by semiquantitative scoring of the specimens. In both gastric as well as colorectal carcinomas, between 40 and 50% of the cases were Ley reactive. Signet-ring cell carcinomas of the stomach exhibited a significantly stronger Ley expression compared to other tumor types. In colorectal cancers, Ley was associated with increased tumor staging, showing the strongest positivity in stage IV. Further correlations with clinicopathological variables or prognosis were not observed. On the other hand, the amount of apoptotic cells was significantly reduced in mucinous adenocarcinomas of the colorectum compared to non-mucinous carcinomas. Scoring of apoptotic cells did not result in any other clinicopathologically relevant correlations. In addition, a significant association between Ley antigen expression and apoptosis score could not be established. Therefore, the hypothesis of a functional relationship between these two aspects of gastrointestinal tumor biology is not confirmed by our data.
Open Access
Naris occlusion alters transductory protein immunoreactivity in olfactory epithelium
(Murcia : F. Hernández, 2006) Coppola, D.M.; Waguespack, A.M.; Reems, M.R.; Butman, M.L.; Cherry, J.A.
We have recently shown that unilateral naris occlusion (UNO) causes an increase in olfactory marker protein (OMP) immunoreactivity (IR) in mouse olfactory sensory neurons (OSN) from the occluded side of the nasal cavity and a decrease in OMP-IR on the non-occluded side, relative to controls. Given OMP's demonstrated role in olfactory modulation, these OMPIR changes have been interpreted as a compensatory response by OSNs to odor deprivation on the occluded side and to supernormal exposure to odor on the nonoccluded side of the nasal cavity. In the current study, we examined the developmental timing and the regional distribution of this process throughout the nasal cavity using immunocytochemistry. Results demonstrate that OMP-IR diverges in OSNs from the occluded side relative to the non-occluded side of the nasal cavity within eleven days after UNO, with statistically significant differences measurable after 17 days (n=16). We also measured relative levels of the Type 4 phosphodiesterase (PDE4A), another potential olfactory modulator, in nasal cavity tissue from UNO (n=8) and untreated mice (n=9) using western blots and immunocytochemistry. Like OMP, PDE4A-IR increased on the occluded side of the nasal cavity after UNO. Finally, we used immunocytochemistry to assess relative levels of olfactory-specific adenylyl cyclase (ACIII, n=4) and G-protein (Golf, n=2) in OSNs from the occluded and non-occluded sides of the nasal cavity of UNO mice. Following UNO, ACIII but not Golf -IR levels diverged comparing the occluded to the non-occluded sides of the nasal cavity. Taken together, our findings provide support for the previously unknown phenomenon of compensatory responses by OSNs to odor environment.

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