Histology and histopathology Vol.16, nº 4 (2001)
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- PublicationOpen AccessTissue and molecular events in human conjunctival scarring in ocular cicatricial pemphigoid(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Razzaque, M. S.; Foster, C. S.; Ahmed, A. R.Detail ed histomo rph ometric analysis of human conjunctiva l biopsy specimens has convincingly demonstrated that tissue remodeling of the extracellular matri x (EC M) is an esse nti al and dy nami c process associated with conjuncti val sca rring in ocul ar cicatricial pemphi go id (OCP). The co njun cti va l sca rring ofte n eventuall y results in impaired vision and/or blindness. The molecul ar mechanisms of conjunctival scarring are not compl etely und erstood. Acc umulating evidence indicates that the earl y phase of conjunctival fibrosis is linked with an immuno-inflammatory process medi ated by cy tokines released by ac tiva ted conjunctiv al cells and/or by infiltrating cells. Fibrogenic cytokines secreted by infl ammatory cells and fibroblasts might acti vely be in vo lve d in remode lin g o f th e matri x within th e conjunctival stroma, possibly by regul ating the altered metabolism of matrix proteins.
- PublicationOpen AccessRecent progress in T-cadherin (CDH13, H-cadherin) research(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Takeuchi, T.; Ohtsuki, Y.T-cadherin is a un ique cadherin ce ll ad hesion molecul e that is anchored to the ce ll surface membrane th rough a glycosy l phosphat id yl inositol (G PI) moiety. The cy topl asmic domain , whi ch T-cad herin lacks. is be li eved to bc criti ca l fo r homophilic binding th ro ugh int erac ti on with subm cmbran e cy tos ke letal protc in s. Docs this mea n th at T- ca dh e rin is an un imp ortanl molec ul e? Howcvc r, th e T-cadherin amino ac id moti f has bee n we ll co nse rve d thro ug h evo luti o n in ve rt ebr ates, s uggestin g th a t T-c adh e rin may have biologica l signifi ca nce in higher animals. Co nsistent wi th this hypothesis, recent studies have thrown light on the re levance of T-cadh erin in the fie lds of oncology, neurology, respirology and ca rdiovascular ph ysiology. In this manu sc ript , we rev iew current adva nces in Tcad herin research.
- PublicationOpen AccessTight junctions and their role in cancer metastasis(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Martin, T. A.; Jiang, W. G.Tight Junctions gove rn the permeabili ty of endothelial and epithelial cells and are the most topical structures of these cell types. Tight junctions create an intercell ular ba rri er and in tramembrane diffusion fe nce. An important step in the fo rmation of ca ncer metastases is int e rac ti on and pe netrat io n o f th e vasc ula r endothelium by dissociated ca ncer cells. Ea rly studies demonstrated a correlation between the reduction of tight junctions and tumour diffe rent iati on and experimental evidence has emerged to pl ace tight junctions in the frontline as the structure that ca ncer cells must overcome in order to metastasise. Changes in tight juncti on function are thu s an ea rl y and key aspect in cancer metastasis. Further work is requ ired to fully realise the potent ial that this structure has in cancer invasion and metastasis in ord er to deve lop new and nove l th erapi es in th e prevention of tumour metastasis.
- PublicationOpen AccessVillous trophoblast of human placenta: a coherent view of its turnover, repair and contributions to villous development and maturation(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Mayhew, T. M.J\ coh e re nt vicw o f hum a n v illou s trophoblast as a continuously renewing epithelium is presented. Epithelia undergoing continuous rcnewal (e.g. intestinal mucosa, epidermis) display clonogenic ce lls which pass throug h sevc ral transit di visions be fore migrating out of proliferation zones and into zones of maturati on/differenti ati on. Quantitative relations (e.g. re lati ve numbers of cells) betwee n proliferati on and diffe rentiation zones help to define the steady state and this may va ry in res po nse to ph ysi o log ic al and pathological circumstances. From the differenti ati on compartment, ce lls or ce ll fr agments arc eve ntu all y extruded by mechanisms which may involve apoptosis. All these features are seen in trophoblastic epithelium. Cy totrophobl ast ce lls (CT, proliferation zone) divide continuously throughout gestation and post-mitotic cells are recruitcd into syncytiotrophoblast (ST, diffe rentiation zone) aft cr membrane fusion. Evidence of fu sion events includes localised confluence of CT and ST cytoplasms, and intrasy ncyti al plasma membrane segments bearing desmosomal remn ants. During diffe renti ati on, nu clei undergo changes in shape, chromatin condensation and packing densit y. Densely-clustered nuclei are associated with cy tokeratin intermed iate fil aments and annul ate lamellae . Both clustered and non-clustered nuclei show ultrastructural fea tures of pre-apoptosis and apoptosis. Normall y, apoptosis is triggered only when nuclei are in the syncytium. Some (pre-)apoptotic nuclear aggregates are se qu este red in sy nc yti a l knots, extrud ed as troph obl ast fr agments into the intervill ous space and th e n depo rt ed int o th e mate rn a l c irc ul ati o n to be ph agocytosed at extrapl acental sites. During gestation, there is some constancy in the numerical ratios between CT and ST nuclei pointing to a normal steady state. The steady state may be perturbed when the epithelium is damaged loca ll y. Whe re the epithelium is denud ed, fibrin-type fibrinoid from the intervillous space plugs the discontinuity and , with CT proliferation, facilitates reepitheli alisation. Features of normal villous development (e.g. sprouting, int ervillous bridge formati on, bridge abrupt ion, sy ncytial knot formation) arc explicable in the co nt ex t of tr o ph obl ast turn ove r with ea rl y CT pro li fe rati o n be in g ma inl y fo r g row th a nd la te r proliferation for renewa l and repair. Adaptive re-settings of the epithelial steady state may also occur in abnormal pregnancies.
- PublicationOpen AccessTGF-ß1 and IL-6 expression in rat pineal gland is regulated by norepinephrine and interleukin-1 ß(F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología, 2001) Tsai, S. Y.; Schluns, K. S.; Le, P. T.; McNulty, J. A.T he pineal g land is part of th e neur oendoc rin e system that modulat es immun e functions. Beca use the gland is outside the blood-brain barrier, il is accessibl e to dir ec t feedback from circul atin g cyto kin es that affec t th e sy nth esis and secreti on of melatonin . Recent studi es have suggested that intrinsic immunoregul atory cytokines med iate these neuro-immune int e ra cti o ns und er th e co ntr o l of sympathetic innervation to the pineal. This study focused on th e expression of transfo rmin g growt h factor-f3 1 (TGF-f3I) and interl eukin-6 (IL-6), two cy toki nes th at have important regula tory functions on both neurons and immune cells. Northern blot RNA analysis showed that TGF-f3l, but not IL-6, was expressed in freshly dissected rat pineal glands from neo natal age (l -day-o ld) into ad ults. Immun ocy toc hemistry for TGF-B1 in adult glands revealed localization of this protein in astrocy telik e cells. The sy mp ath e tic ne ur o tr ansmitt e r norepinephrine (NE) increased transcript levels for both TGF-f31 and IL-6 in adu lt pinea l organ cultures. The effect of NE o n I L-6 exp ressio n was not found in dispersed cell cultures established from neonatal pineal glands. The immunoregul atory molecule interleukin-l/3 (IL-l /3) up-regulat ed th e expression of both IL-6 and TGF-/31 in ad ult pineal organ cultures, but not in neonate pineal organ cultures. These findings suggest that TGF- /31 and IL-6 have intrinsic regul atory roles in the pinea l gland and that both neural and immune factors are important mechanisms of regulation.