Histology and histopathology Vol.15, nº 4 (2000)
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- PublicationOpen AccessLiver fibrosis, the hepatic stellate cell and tissue inhibitors of metalloproteinases(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2000) McCrudden, R.; Iredale, J. P.Liver fibrosis occurs as a consequence of net accumulation of matrix proteins (especially collagen types I and III) in response to liver injury. The pathogenesis of liver fibrosis is underpinned by the activation of hepatic stellate cells (HSC) to a myofibroblast like phenotype with a consequent increase in their synthesis of matrix proteins such as interstitial collagens that characterise fibrosis. In addition to this there is increasing evidence that liver fibrosis is a dynamic pathologic process in which altered matrix degradation may also playa major role. Extracellular degradation of matrix proteins is regulated by matrix metalloproteinases (MMPS) - produced by HSC - which in turn are regulated by several mechanisms which include regulation at the level of the gene (transcription and proenzyme synthesis), cleavage of the proenzyme to an active form and specific inhibition of activated forms by tissue inhibitors of metalloproteinases (TIMPS). Insights gained into the molecular regulation of HSC activation will lead to therapeutic approaches in treatment of hepatic fibrosis in the future , and could lead to reduced morbidity and mortality in patients with chronic liver injury .
- PublicationOpen AccessSelective expression of lysyl oxidase (LOX) in the stromal reactions of broncho-pulmonary carcinomas(Murcia : F. Hernández, 2000) peyrol, S.; Galateau-Salle, F.; Raccurt, M.; Gleyzal, C.; Sommer, P.Lysyl oxidase (LOX) is the extracellular enzyme that initiates the main pathway of collagen and elastin cross-linking. LOX has also been correlated with the ras recision gene, a putative tumour suppressor isolated from revertants of ras-transformed fibroblasts. The present study investigates the potential correlation of LOX-dependent matrix protein cross-linking in the stromal reaction of lung carcinomas, with reference to the architecture of the main stromal reactions accompanying the neoplastic breast tissues. A strong LOX expression was associated with the hypertrophic scar-like stromal reaction found at the front of tumour progression in squamous carcinomas, adenocarcinomas, large cell carcinomas, or at sites of initial extense in bronchiolo-alveolar carcinomas. In contrast, little or no LOX expression was found within the stromal reaction of invasive carcinomas, small cell carcinomas, and neuro-endocrine carcinomas. The significance of LOX expression and of the stromal reaction are discussed, in light of data that associate LOX expression with tumours displaying a rather good prognosis.
- PublicationOpen AccessGlycogen autophagy in newborn rat hepatocytes(Murcia : F. Hernández, 2000) Kalamidas, Stefanos; Kotoulas, Othon B.Glycogen autophagy in newborn rat hepatocytes was studied by using enzyme determinations and electron microscopy. Cyclic AMP induced glycogen autophagy in these cells. Glycogen-hydrolyzing acid glucosidase activity increased whereas acid mannose 6- phosphatase activity decreased in the liver of these animals. Parenteral glucose, which prevents postnatal glucagon secretion and tissue cyclic AMP elevation, and propranolol which antagonizes cyclic AMP, inhibited glycogen autophagy. Glucosidase activity decreased and phosphatase activity increased. These findings raise the possibility that cyclic AMP-induced autophagic mechanisms in newborn rat hepatocytes are associated with changes in the activity of acid mannose 6- phosphatase.
- PublicationOpen Accesslmmunohistochemical detection of metallothionein in carcinomatous and normal human gastric mucosa(Murcia : F. Hernández, 2000) Tuccari, G.; Giuffre, G.; Arena, F.; Barresi, G.Utilising a specific monoclonal mouse antibody (E9), metallothionein (MT) expression has been immunohistochemically investigated in 112 formalin-fixed paraffin-embedded surgical gastric samples, 38 of which were early carcinomas (EGC) and 74 advanced ones (AGC); clinico-pathological details and follow-up data (ranging from 3 to 197 months, mean 60.5 months) were available. Eighty-nine portions of gastric mucosa adjacent to examined carcinomas (transitional mucosa) were also analysed; in addition, 22 biopsies of normal gastric mucosa were studied as tissue control. The MT immunoreactivity was evaluated by staining and intensity-distribution scores. A various MT positivity was appreciable in the cytoplasm and nucleus of antrum or body gastric epithelia1 cells in 100% of normal control biopsies. 751112 (67%) gastric carcinomas showed MT immunoreactivity with a significant lower expression in AGC. No relationships were encountered between MT immunostaining and clinico-pathological data; in addition, no difference in the Kaplan-Meier survival curves of patients with various MT expression was achieved. When the transitional mucosa was examined, 84/89 (94%) samples were stained although the immunoreaction was not always concordant with that encountered in adjacent carcinomatous elements. The significant statistical decrease of MT scores observed by us moving from normal to neoplastic gastric mucosa allows us to exclude the hypothesis of an overexpression of MT in gastric carcinomas.
- PublicationOpen AccessExpression of a neu,c-erbB-2-like product in neuroendocrine cells of mammals(Murcia : F. Hernández, 2000) Martin Lacave, Inés; Utrilla, J.C.The neulc-erbB-2 oncogen encodes a 185 kDa protein closely homologous to the epidermal growth factor receptor. The protein product (p185) is a glycoprotein with an external domain and an internal domain with tyrosine kinase activity. Amplification and/or overexpression of p185 is related to several human adenocarcinomas. Subsequent studies demonstrated its presence in certain neuroendocrine (NE) neoplasms, including phaeochromocytomas. insulinomas and medullary thyroid carcinomas. However, relatively little is known about its role in normal cell growth regulation and development. Therefore, our objetive was to determine whether neulc-erbB-2 was expressed in normal NE tissues of different mammals, specially in humans, as it was in their neoplasms. We have examined by immunohistochemistry different endocrine glands (thyroid, pancreas, suprarrenal and hypophysis) and the small intestine of human beings, rats and guinea pigs, using two polyclonal antibodies raised against the intracytoplasmic part of the protein, and specific antigen absorption controls. We have found that a neulc-erbB-2- like product occurs in all normal NE tissues examined: C cells of the thyroid gland, chromaffin cells of the adrenal medulla, pancreatic islets, enteroendocrine cells of the small intestine and, finally, scattered cells of the adenohypophysis, according to a typical granular immunohistochemical pattern. Our results indicate that normal NE cells share a new common antigen in their cytoplasms, a neulc-erbB-2-like product, with a similar immunostaining pattern to that presented by the neoplasms derived from them.