Histology and histopathology Vol.24,nº11 (2009)

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  • Publication
    Open Access
    A role for monomeric C-reactive protein in regulation of angiogenesis, endothelial cell inflammation and thrombus formation in cardiovascular/cerebrovascular disease?
    (Murcia : F. Hernández, 2009) Slevin, M.; Krupinski, J.
    Native CRP (nCRP) is a pentameric oligoprotein composed of identical 23 KDa subunits which can be irreversibly dissociated to form free subunits or monomeric CRP (mCRP). mCRP has a reduced aqueous solubility and a tendency to aggregate into matrix-like lattices in various tissues, in particular, blood vessel walls. A dramatic increase in expression of mCRP occurs in angiogenic blood vessels derived from stroked brain regions, atherosclerotic arteries and active vessels from other angiogenic diseases such as Alzheimer’s. Furthermore, mCRP unlike the native molecule is highly angiogenic to vascular endothelial cells in vitro and therefore might impact on the processes of vascularization and re-modelling thus affecting tissue survival and development. In this mini-review, we will discuss the differences in the biological properties between nCRP and mCRP. We will provide a brief historical background to the importance of nCRP as a biomarker for cardiovascular disease. We will explain the mechanisms of conversion of nCRP to its monomeric form and describe evidence for the role of mCRP in modulation of endothelial cell activation, promotion of inflammatory status and thrombus formation in cardio/cerebrovascular disease. Finally, we will provide evidence for the accumulation of mCRP in angiogenic microvessels from diseased tissue, and demonstrate its highly pro-angiogenic capabilities. The discovery of the existence of this tissue-associated, highly angiogenic monomeric form of CRP capable of cellular binding and intra-cellular signal transduction activation may help in our understanding of the processes responsible for modulation of angiogenesis and inflammation in disease.
  • Publication
    Open Access
    Hepatocyte nuclear factor-1B(HNF-1B) in human urogenital organs, Its expression and role in embryogenesis and tumorigenesis
    (Murcia : F. Hernández, 2009) Kato, Noriko; Motoyama, Teiichi
    Molecules responsible for embryogenesis are often involved in tumorigenesis. Recent exhaustive cDNA microarray analyses in human neoplasms expanded knowledge of such molecules. Hepatocyte nuclear factor-1ß (HNF-1ß) is a homeobox transcription factor that functions as a homodimer or heterodimer with HNF-1a. In contrast to HNF-1a, HNF-1ß is very weakly expressed in the liver and is commonly expressed in the kidneys. During human embryonic stage, HNF-1ß plays an important role in organogenesis, especially of the urogenital system. In the human fetus, HNF-1ß expression is common in mesonephric duct derivatives and metanephros (permanent kidneys). HNF-1ß germline mutations cause malformations of these structures. Recent microarray analyses have disclosed that HNF-1ß is aberrantly up-regulated in clear cell carcinoma of the ovary, which is a carcinoma of müllerian nature, but which was initially misnamed “mesonephroma”. HNF-1ß is also expressed in ovarian endometriosis, which is a probable origin of clear cell carcinoma. On the other hand, HNF-1ß is downregulated in renal neoplasms, such as chromophobe cell carcinoma. In this review, we first summarize HNF-1ß expression in the developing urogenital system of the human embryo. Then, we describe the HNF-1ß status in human urogenital neoplasms and discuss its role in tumorigenesis.
  • Publication
    Open Access
    MUC-1-ESA+ progenitor cells in normal benign and malignant human breast epithelial cells
    (Murcia : F. Hernández, 2009) Lu, Xinquan; Li, Huixiang; Xu, Kejia; Nesland, Jahn M.; Suo, Zhenhe
    The existence of mammary epithelial stem/progenitor cells has been demonstrated in MUC-1-/ ESA+ subpopulations of breast epithelial cells. However, knowledge about the expression and localization in benign and malignant breast lesions is unknown. Using a double-staining immunohistochemistry method, we investigated MUC-1-/ESA+ cells in 10 normal breast tissues, 49 cases with fibrocystic disease, 40 fibroadenomas, 36 invasive ductal carcinomas and the breast cancer cell lines MCF-7 and MDA-MB-468. In normal breast tissues MUC-1-/ESA+ cells were mainly found in the suprabasal layer, but under the apical surface of the duct/alveolus. In the hyperplastic areas of fibrocystic disease, the number of this subpopulation of cells was higher than that in hypoplastic areas and in fibroadenomas. In invasive ductal carcinoma, the MMUC-1-/ESA+ cells were heterogeneously present in different carcinoma nests. In the MCF-7 cell line most cells were MUC-1-/ESA+, and in the MDA-MB-468 cell line MUC-1-/ESA+ cells and MUC-1-/ESA+ cells were almost equal. Our results show that the MUC-1-/ESA+ subpopulation increases in fibrocystic disease within the hyperplastic areas, and varies in benign and malignant breast tumours, indicating that breast carcinogenesis may develop from malignant changes of normal MUC-1-/ESA+ cells.
  • Publication
    Open Access
    Temporal and spatial distribution of TGF-B isoforms and signaling intermediates in corneal regenerative wound repair
    (Murcia : F. Hernández, 2009) Huh, Man-IL; Chang, Yongmin; Jung, Jae-Chang
    The present study analyzed the temporal and spatial expression of TGF-ß isoforms and activated pSmad2 and p38MAPK during epithelial debridement wound repair, using chick cornea by immunohistochemistry. Normal corneas showed low-level TGFßs staining. Following wounding, TGF-ß1 expression was strong in the Bowman’s layer (BL). TGF-ß3 expression was confined to basal cells in the regenerating and unwounded regions, and was not detected in migrating epithelial, stromal or endothelial cells. In addition, TGF-ß3 treatment stimulated the proliferation of cultured epithelial cells. Our present findings seem to suggest that the TGF-ß3 signal may be required for epithelial cell proliferation. TGF-ß2 expression was strong in migrating and proliferating epithelial cells, many active migrating fibroblasts at the wound edge, endothelial cells and Descemet’s membrane (DM). Although both nuclear pSmad2 and p38MAPK staining was observed in many basal epithelial cells, pSmad2 positive cells were co-localized with PCNA positive cells. Therefore, it seems likely that the pSmad2 signal may affect epithelial cell proliferation in healing corneas. Both pSmad2 and p38MAPK expression were also observed in endothelial cells. Interestingly, many active fibroblasts over the whole stroma in early wound healing at day 2 expressed nuclear pSmad2, but little if any cytoplasmic p38MAPK. Collectively, temporal/spatial up-regulation and distribution of the three TGF-ß isoforms, as well as concerted activation of both Smad2 and p38MAPK, appears to be a key aspect of regenerative corneal wound healing in the chick.
  • Publication
    Open Access
    Effects of photo stimulation and nonstimulation of golden hamsters (Mesocricetus auratus) from birth to early puberty on testes structure and function
    (Murcia : F. Hernández, 2009) Hance, Michael W.; Mason, J.Ian; Chamindrani Mendis-Handagama, S.M.L.
    We tested whether puberty in golden hamsters is photoperiodically controlled. Hamsters were raised under 14:10 hours Light:Dark (14L) and 1:23 hours Light:Dark (1L) respectively, from birth to 28 days and tested for various parameters. Body weight, Leydig cell (LC) size and testicular testosterone secretion were greater and plasma thyroxin (T4), testicular androstenedione secretion and LC number were lower (P<0.05) in 1L than 14L hamsters. Volumes of testicular components were similar in the two groups. 3ß-hydroxy steroid dehydrogenase immunohistochemistry demonstrated LC progenitors and newly formed adult LC (ALC) in 14L hamsters, which were absent in 1L hamsters; they contained only fetal LC (FLC). Latter findings suggest the presence and absence of postnatally-differerentiated LC in 14L and 1L hamsters, respectively. Androgen results agreed with these findings, because FLC primarily secrete testosterone, and androstenedione is a major androgen secreted by the newly formed ALC. Reduced T4 in 1L hamsters is attributed to the inhibition of thyroid function by the increased duration of melatonin secretion due to non-photostimulatory conditions. The arrest in LC differentiation in 1L hamsters is attributed to low T4 levels. Although the testis size is unaltered under nonphotostimulatory conditions, postnatal LC differentiation is inhibited in golden hamsters, and therefore, it is logical to suggest that their puberty is photoperiodically controlled.