PubMed · 13970043
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P BECHTEL. 1962. [Alveolo-capillary diffusion].. https://pubmed.ncbi.nlm.nih.gov/13970043/
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c-kit receptor tyrosine kinase is a marker of progenitor cells, which differentiate into blood and/or vascular endothelial cells, and has an important role in the amplification/mobilization of progenitor cells. c-kit is expressed in mature endothelial cells, but its role there is unclear. Stem cell factor, a c-kit ligand, dose-dependently promoted survival, migration, and capillary tube formation of human umbilical vein endothelial cells. These effects mimicked those of vascular endothelial growth factor, except that stem cell factor did not sufficiently support proliferation of these cells. After exposing cells to this factor, Akt, Erk1/2, and c-kit were immediately (</=5 min) and dose-dependently tyrosinephosphorylated. STI-571, a c-kit inhibitor, dose-dependently attenuated these phosphorylations and inhibited stem cell factor-promoted survival and capillary tube formation over the same dose range. Wortmannin and LY294002, inhibitors of phosphoinositide 3-kinase, and PD98059, an inhibitor of MEK, abrogated survival and capillary tube formation, indicating that Akt and Erk1/2 should promote survival and capillary tube formation of these endothelial cells at a locus downstream to stem cell factor/c-kit signaling. Akt was more strongly phosphorylated, whereas Erk1/2 and p38 were more weakly phosphorylated with stem cell factor than with vascular endothelial growth factor. Phospholipase Cgamma was phosphorylated only with the latter, indicating that stem cell factor/c-kit signaling is somewhat different.
BACKGROUND: Hypoplastic left heart syndrome is a condition characterized by a constellation of morphological malformations affecting the left side of the heart. We studied the capillary network, and quantified the capillarization of the ventricular myocardium, which, if different from normal, may have implications for the success of surgical reconstruction. METHODS: The capillaries were detected by immunohistochemistry using a monoclonal antibody (von Willebrand's factor) against the endothelium. Hearts with hypoplastic left heart syndrome have higher mean and maximal diffusion distances from any arbitrary point to the nearest capillary than normal hearts. RESULTS: There was no significant difference in the heterogeneity of capillary distribution between the hearts with hypoplastic left heart syndrome and the control heart. Increase in distance was found in both the right and left ventricles. CONCLUSIONS: Hearts with hypoplastic left heart syndrome show a reduction in the capillarization of both the right and left ventricles compared with age-matched controls. We believe this may be an inherent abnormality of hypoplastic left heart syndrome that may have implications for ventricular development.
PURPOSE: This paper discusses the lack of complete selectivity in the photodynamic closure of choroidal neovasculature (CNV) associated with age-related macular degeneration. The arguments presented are supported by examples of clinical observations and may be useful for the design of the next generation of photosensitizers. RESULTS AND CONCLUSION: Based on worldwide patient follow-up, it can be concluded that a substantial number of the more than 200000 treatments that have been dispensed so far could have resulted in stabilization of the disease for at least a number of years. Clinical observations also indicate that, in addition to the effective closure of the CNV observed 1 week after PDT, a significant closure (or at least reduced leakage) of normal choriocapillaries is observed in the treated area. Some of the concepts associated with the selectivity of Visudyne photodynamic therapy of choroidal neovascularization in age-related macular degeneration are also discussed. DISCUSSION: Novel approaches to improving selectivity could include attaching a photosensitizer to a targeting moiety such as a monoclonal antibody or a peptide. The undesirable closure of normal choriocapillaries in the treated area is one area of possible improvement to be sought for the next generation of drugs.