A slow-cycling subpopulation of melanoma cells with highly invasive properties.

Melanoma is a heterogeneous tumor with different subpopulations showing different proliferation rates. Slow-cycling cells were previously identified in melanoma, but not fully biologically characterized. Using the label-retention method, we identified a subpopulation of slow-cycling cells, defined as label-retaining cells (LRC), with strong invasive properties. We demonstrate through live imaging that LRC are leaving the primary tumor mass at a very early stage and disseminate to peripheral organs. Through global proteome analyses, we identified the secreted protein SerpinE2/protease nexin-1 as causative for the highly invasive potential of LRC in melanomas.

Variability of the N-protein and the intergenic region of the S RNA of tomato spotted wilt tospovirus (TSWV).

The genetic heterogeneity of the N protein gene and the intergenic region (IGR) of the S RNA from tomato spotted wilt virus (TSWV) isolates, collected in Bulgaria, were compared with isolates from other parts of the world. The results substantiated the highly conserved nature of the N protein. Twenty six independent sequences revealed only seven variable amino acid positions, common to all isolates. The type of amino acids present in these positions seems to be independent of the geographical origin. In contrast to the structural N protein, comparisons of the related IGR-sequences led to clusters correlated with the geographical origin of the isolates. Although the overall sequence homology in the IGRs was much lower than for the N proteins, three conserved parts within this region were identified. The outstanding part was a central area of 31 nucleotides with a significantly increased GC-content. This was located in both viral- and viral-complement RNA at structures with similar foldings, which led to the assumption that this stabilised structure, rather than a sequence motive, might serve as a transcription terminator during the synthesis of the two mRNAs from the ambisense segments.

[Morphologic changes in the walls of the internal saphenous vein used as an arterial bypass]. / Les altérations morphologiques de la paroi de la saphène interne utilisée comme by-pass artériel.

Long saphenous vein (LSV) is considered an optimal plastic material for arterial reconstructions in revascularization of the myocardium and in the femoral-popliteal segment. The authors analyze the results from the investigation of the operation material from 12 patients with obliterating atherosclerosis of the lower limbs in which reversed LSV has been previously used for arterial bypass grafts. Material is taken during the second operation performed between two days and 18 months after the first reconstruction. In the early period after LSV implantation into the arterial blood flow there is a prevalence of destructive alterations which are mainly manifested in the intima and internal layers of the media. In later periods a massive layer is formed growing into the venous vascular lumen designated as "néo-intima". Investigations of its structure and of mechanisms of its formation could enable the regulation of this process by clinicists.

Immunohistological localization of regenerating protein in ocular structures.

PURPOSE: To investigate the presence of pancreatic stone protein (PSP)/reg (regenerating) protein in eyes and extraocular structures of rabbits, monkeys and man, according to species and age. METHODS: Rabbit eyes, with normal or de-epithelialized corneas, were taken from albino and pigmented animals. Monkey eyes were taken from cynomolgus monkeys, 2 years old. Stillborn and adult human eyes were obtained after autopsy. They were studied by immunohistochemistry methods, using a monoclonal antibody raised against human PSP. RESULTS: On rabbit ocular structures, the anti-PSP monoclonal antibody showed a strong reactivity at the level of basement membranes and basal poles of the cells of corneal and conjunctival epithelia and on basement membranes of skin and palpebral conjunctiva in eyelids. On de-epithelialized rabbit eyes, the remaining basement membrane was labeled while, along the re-epithelialization, the anti-PSP reactivity appeared with the migrating cells which cover the denuded cornea. On young monkeys, the whole corneal epithelium was reactive. Similar results were obtained from stillborn eyes, whereas no reactivity was detected on autopsy specimens from aged persons. CONCLUSIONS: As in other tissues and organs, the reg protein, in the eye, is found in structures known for their continuous and rapid renewal. This protein seems not to exist (or persist) in eyes from aged donors while it is strongly expressed in young donor eyes (monkey, stillborn baby) as well as in regenerating corneal epithelium. These findings enforce the hypothesis about the involvement of reg protein in cell proliferation and differentiation phenomena and its probable correlation with aging.

CMDBS, functional analogue of heparin sulfate as a new class of corneal ulcer healing agents.

Soluble dextran polymer derivatives (CMDBSs) are originally synthesized as heparin-like plasma substitutes. Some of them mimic heparin in its interactions and stabilize, protect and facilitate actions of heparin binding growth factors. The wound healing activity of one specific CMDBS was studied in a model of corneal ulcer on the rabbit eye and compared with the activity of basic fibroblast growth factors (bFGF) added alone or in association with CMDBS. Total reepithelization was observed with bFGF + CMDBS, bFGF alone and CMDBS alone after, respectively, 3.8 +/- 0.78, 4.3 +/- 0.67 and 4.4 +/- 0.51 days. All treatments were efficient if compared with eyes treated with saline (p < 0.0001). The grade of significance of the applied treatments was as follows: bFGF + CMDBS > bFGF > CMDBS > saline. Our study pinpoints that some specific CMDBS are as potent agents as bFGF for corneal ulcer healing, and can therefore be proposed for therapeutic use.