Histology and histopathology Vol.19, nº 3 (2004)
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- PublicationOpen AccessImmuno-histochemical expression of a1, a2 and a3 integrin subunits during angiogenesis in vitro(Murcia: F. Hernández, 2004) Suda, H.; Asami, Y.; Murata, E.; Fujita, K.; Akita, M.Aortic explants were obtained from mouse fetuses and cultured in collagen gels. Immuno-fluorescence microscopy, antibodies (anti a1, a2 and a3 integrin subunits) were used. Fibroblastic cells migrated from the aortic explant after one day of cultivation. The migrating cells located in the peripheral part of the aortic explant were positive for a1 and a2 integrin subunit antibodies. Immuno-fluorescence-positive staining for the a3 integrin subunit antibody was clearly seen in the migrating cells located near the aortic explant and surrounding tube-like structures. In an immuno-electron microscope study performed by pre-embedding immuno labeling, gold particles associated with the a3 integrin subunit were found to reside on the membranes of the cells surrounding the capillary-like tubes. Two synthetic peptides, GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro) and KDGEA (Lys-Asp-Gly-Glu-Ala), were added to the growth medium to study their effects on cell migration. KDGEA, a compound containing the recognition sequence for a2ß1 integrin, decreased cell migration, while GRGDSP exhibited no effect. The migration of fibroblastic cells is an important phenomenon for tube formation. The present study suggested that the a1 and a2 integrin subunits are both involved in the cell migration, and more specifically, that the a2 integrin subunit participates in cell migration through the KDGEA sequence. The a3 integrin subunit played a role in tube formation.
- PublicationOpen AccessEffect of telmisartan on preexistent cardiac and renal lesions in spontaneously hypertensive mature rats(Murcia : F. Hernández, 2004) Mandarim-de-Lacerda, Carlos A.; Pereira, L.M.M.Fifteen adult male spontaneously hypertensive rats (one year old) (SHR) were separated into three groups (n=5 each) during 15 weeks as follows: initial control group (IC); final control group (FC); and telmisartan group (T) (1.2 mg/kg/day of telmisartan). Serum and urinary creatinine and proteinuria were not different comparing untreated and telmisartan-treated SHRs. FC rats showed a continuous BP increase during the study while T rats reached the 15th week with a significantly low BP. The LV mass index was significantly smaller in the T group than in the FC group, as was the glomerular hypertrophy. The cardiomyocyte nuclei density per area and the cardiomyocyte mean cross-sectional area were smaller in the T group than in both the IC and FC groups. Intramyocardial artery densities (per area and per volume) were greater in the T group than in untreated SHRs, but myocardial fibrosis was reduced. In conclusion, telmisartan monotherapy effects on BP and also on the hypertension target organs, heart and kidney, are favorable. Telmisartan is able to attenuate SHR cardiomyocyte and glomerular hypertrophies, and myocardial reactive fibrosis as well. It also is favorable to the intramyocardial microcirculation.
- PublicationOpen AccessTransgenic mice overexpressing both amyloid ß-protein and perlecan in pancreatic acinar cells(Murcia : F. Hernández, 2004) Fukuchi, K.; Hart, M.; Yan, Z.; Hassell, J.R.; Li, L.Heparan sulfate proteoglycans such as perlecan are thought to facilitate amyloid fibril formation. Tg3695 mice overexpress perlecan core protein in many tissues including the brain and pancreas. Tg13592 mice overexpress the signal plus 99-amino acid carboxyl terminal sequences (C99) of amyloid ß-protein precursor in multiple tissues and develop amyloid deposits in the pancreas. To investigate a role of perlecan in ß-amyloidosis, we established doubly transgenic mice by crossing the two lines of transgenic mice. The expression levels of the two transgenes remained unchanged in the brain and pancreas and the doubly transgenic mice did not develop amyloid deposits in the brain up to 19-months of age. Amyloid load detected by thioflavine S in the pancreas of the doubly transgenic mice was not significantly different from that in the transgenic littermates expressing only C99. Amyloid load in the pancreas increased during aging. We found a positive correlation between the Aß-immunoreactive (non-fibrillar and fibrillar) and thioflavine S-positive (fibrillar) Aß deposits in the single (C99) but not doubly transgenic mice. Our results suggest that perlecan does not independently influence amyloid formation in the pancreas of the transgenic mice and that there may be other factors that may modulate amyloid formation together with perlecan.
- PublicationOpen AccessAberrant expression of a fetal glycoprotein 68 in hepatocellular carcinoma: a comparative study on the expression of alpha-fetoprotein and carcinoembryonic antigen(Murcia : F. Hernández, 2004) Kato, Massuo J.; Shinozawa, T.; Kato, S.; Terada, T.A rat IgG2a monoclonal antibody against a stage-specific fetal glycoprotein with a molecular mass of 68 kDa (FGP68) was produced and applied to paraffin sections. This monoclonal antibody was used to compare the expression of FGP68 with that of both alphafetoprotein (AFP) and carcinoembryonic antigen (CEA) in 75 hepatocellular carcinomas (HCCs). Seventy-five primary HCCs from patients aged 36 to 77 years were examined. Formalin-fixed, paraffin-embedded tissue sections were used for immunohistochemical analyses. Histologically, 6 cases of HCC were classified as type I according to the Edmondson and Steiner criteria, 57 cases as type II, and 12 cases as type III. The cancer tissues showed positive reactions with the antibody against FGP68. Approximately one-third of the HCCs (26/75) contained tumor cells that expressed FGP68 - (21/57 for Edmondson and Steiner type II; 4/12 for type III; and 1/6 for type I) - and positive immunoreactivity was observed in the cytoplasm of the cancer cells. Twenty-five of the 75 HCCs had tumor cells that expressed AFP and there was a significant correlation between FGP68 expression and AFP expression. Twenty-three of the 75 HCCs had tumor cells that expressed CEA and there was no significant correlation between FGP68 expression and CEA expression. No positive reactions for FGP68, AFP and CEA were observed in samples of non-neoplastic liver tissues. Based on the possibility that stage-specific FGP68 plays an important role in liver embryogenesis, FGP68- expressing tumor cells might ontogenetically revert to more primitive cells.
- PublicationOpen AccessCorticosterone 21-acetate in vivo induces acute stress in chicken thymus: cell proliferation, apoptosis and cytokine responses(Murcia : F. Hernández, 2004) Franchini, A.; Marchesini, E.; Ottaviani, E.In vivo effects of acute stress induced by corticosterone 21-acetate in male Gallus domesticus thymus are studied and the steroid actions are evaluated in terms of cell proliferation, apoptosis and cytokine response in 10- and 21-day-old chickens. Steroid treatment induced thymocyte apoptosis and cell death decreased in the cortical-medullar direction and was more evident in younger animals. 24 h after treatment, the observed effect was reversed. The mitotic activity and thymic cells containing cytokine-like molecules were also affected. Indeed, the acute stress stimulated cytokine immunoreactivity to anti-IL-1a, IL-6 and TNF- a antibodies both in epithelial cells and interdigitating cells located in medullar and cortical-medullar regions. The increased cytokine expression observed after 12 h was maintained after 24 h. The comparison between 10- and 21-day-old chickens showed a lower number of cells containing cytokine-like molecules in younger specimens. The present findings suggest that cytokines activated by acute stress in vivo could contribute to restoring immunological homeostasis and influence thymic glucocorticoid-mediated functions.