Histology and histopathology Vol.17, nº 2 (2002)
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- PublicationOpen AccessTumor-associated fibroblasts (Part I): active stromal participants in tumor development and progression?(Murcia: F. Hernández, 2002) Kunz-Schughart, L.A.; Knuechel, R.Phenotypic and functional characteristics of tumor associated fibroblasts (TAF) in contrast to normal fibroblasts are re v i e wed in this first synopsis (part I). Terms as tumor stroma, desmo-plasia, T A F , myofibroblast, and fetal-type fibroblast are defined, and experimental systems to study heterologous cell interactions are presented. While we only start to gather information on the genotype of T A F , a broad range of data deals with the e xpression profile of these cells, co v ering e.g. ECM and ECM-modulating molecules, growth factors and cytokines. Summarizing the recent state of kno w l e d g e indicates that TAF provide sources for tumor diagnosis and therap y , that ha v e to be further defined in an or g an- s p e c i f ic approach in terms of the functional impact on the tumor cell and its environment (see part II).
- PublicationOpen AccessEffect of heparin and antivenom on skeletal muscle damage produced by Bothrops jararacussu venom(Murcia : F. Hernández, 2002) Calil-Elias, S.; Martinez, A.M.B.; Melo, P.A.We examined the effect of treatment with heparin and polyvalent antivenom on mice muscle Extensor digitorum longus (EDL) regeneration, after damage induced by injection of B o t h rops jara ra c u s s u crude venom over the muscle of the right posterior limb. The mice were separated into groups and each group received treatment, by intravenous route with either high molecular weight heparin (H), low molecular weight heparin (LMWH), polyvalent antivenom (PAV) or with the combination of PAV plus H or PAV plus LMWH at 15 minutes and 4 hours after the injection of the venom. Myotoxicity was measured by the increase in plasma creatine kinase (CK) activity at two hours after the injection of the venom. The histological changes in EDL at 1, 3, 7 and 21 days after the injection of the ve n o m were analyzed by light microscopy. In each group the normal and regenerated muscle fibers were quantifi e d using Scion Image computer program. We also evaluated in vitro, the influence of these substances in the proteolytic and phospholipase activities of the ve n o m . Heparins decreased the proteolytic activity of the venom but did not affect its phospholipase activity. However the PAV antagonized both activities. PAV and its combinations showed antimyotoxic activity, according to the magnitude of CK plasma levels. At 21 days the r egeneration was observed in all animals, also in those that received only the venom. All treatments, ex c e p t LMWH, promote a significant increase in the number of muscle fibers.
- PublicationOpen AccessIntergenic mRNAs. Minor gene products or tools of diversity?(Murcia : F. Hernández, 2002) Finta, C.; Warner, S.C.; Zaphiropoulos, P.G.The general model of gene e x p r e s s i o n implies that the units of genetic information, the genes, constitute the basis of the mRNA and protein products detected in living organisms. It is well known that in eukaryotic cells a single gene may give rise to va r i o u s gene products due to alternative splicing and/or different positions of transcriptional start and termination. H ow eve r, recent experimental results suggest that in addition to this variation in gene expression, another l evel of complexity may also exist as evidence for the presence of mRNAs that combine sequence information ( exons) from distinct genes is accumulating. Moreove r, the mechanisms that allow this production of intergenic mRNAs are starting to unravel and it appears that these f o l l ow two general pathways: (a) bypass of transcriptional termination, resulting in the generation of bicistronic pre-mRNAs; and (b) authentic trans-splicing events between pre-mRNAs of distinct genes.
- PublicationOpen AccessLow density lipoproteins and mitogenic signal transduction processes: Role in the pathogenesis of renal disease(Murcia : F. Hernández, 2002) Kamanna, V.S.Abnormalities in lipid and lipoprotein metabolism are commonly observed in patients with chronic renal disease. Specifi c a l l y, hyperlipidemia and the glomerular deposition of atherogenic lipoproteins (e.g., Low density lipoprotein, LDL; and its oxidized variants) are implicated in key pathobiological processes i nvo l ved in the development of glomerular disease, including stimulation of monocyte infiltration into the mesangial space, mesangial cell hy p e r c e l l u l a r i t y, and mesangial extracellular matrix deposition. This rev i ew discusses recent understanding of glomerular mitogenic responses, intracellular signaling events associated with mesangial hypercellularity in renal diseases, and the participation of cholesterol and atherogenic lipoproteins in intracellular signaling pathways involved in mesangial cell proliferation. G e n e r a l l y, the mitogenic intracellular signaling p a t h ways are regulated by the activation of series of transmembrane and cytoplasmic protein tyrosine kinases that converge into the activation of Ras and down-stream m i t o g e n - a c t ivated protein kinase (MAP kinase). A c t ivated MAP kinase, through translocating into the nucleus and the activation of various transcription factors and protooncogenes, regulate cell proliferation. The importance of mitogenic intracellular signaling in mesangial proliferative disease has only recently been recognized and showed that the activation of MAP kinase and/or cy c l i n / cyclin-dependent kinases play crucial role in different phases of cell growth cycle and hypercellularity of glomerular cells in va r i o u s experimental renal diseases. Using glomerular mesangial cells as an in-vitro model system, studies from our laboratory indicated that the accumulation of LDL and more potently its oxidized forms within the glomerulus, through the activation of membrane receptor tyrosine kinases (e.g., EGF receptor), activate Ras and MAP kinase signaling cascade leading to DNA synthesis and subsequent mesangial cell proliferation. These data suggest that atherogenic lipoproteins may act as one of the major endogenous modulators for mitogenic signaling response and cell proliferation within the glomerulus. It is reasonable to speculate that the correction or reduction of hy p e r l i p i d e m i a , glomerular lipid deposition, and the pro-oxidative milieu within the glomerulus, through the inhibition of mitogenic signaling events, may provide protective e nvironment against mesangial hypercellularity and subsequent matrix deposition, and the progression of renal disease.
- PublicationOpen AccessEffects of cigarette smoke exposure on the utlrastructure of the golden hamster parathyroid gland(Murcia : F. Hernández, 2002) Yano, R.; Hayakawa, D.; Emura, S.; chen, H.; Ozawa, Y.; Taguchi, H.; Shoumura, S.Cigarette smoking has been identified as one of the risk factors to induce osteoporosis. However, we find no study on the morphology of the parathy r o i d gland under smoking exposure. We studied the ultrastructure of the parathyroid gland, lung and femur of the golden hamster exposed to cigarette smoke. Fourweek- old male hamsters were housed in a plastic case (48x31x30 cm) and were exposed to cigarette smoke for 12 weeks, 5 minutes exposure, 4 times a day, 4 days a week. There were no differences in serum calcium level and the whole bone mineral density between the control and the smoke-exposed groups. In the parathyroid gland of the smoke - exposed animals, the Golgi complexe s associated with many prosecretory granules were well d eveloped and many secretory granules were located near the plasma membrane. Large lipid-like inclusion bodies were observed in the alveolar macrophages of the smoke-exposed animals. The femur morphology showed a wider area of resorbing surface in the smoke-exposed group than in the control group. From these findings, it is conceivable that the secretory activity of the p a r a t hyroid gland was stimulated with cigarette smoke exposure.