The influence of some non-steroidal anti-inflammatory drugs on the retraction of collagen lattices.

The effects of some antirheumatics on the formation and retraction of collagen lattices seeded with fibroblasts have been studied. Among the antirheumatics, diclofenac was the most active inhibitor of lattice retraction, then tropesin and to a lesser extent indomethacin. Ibuprofen which is known as a very slight inhibitor of protein synthesis was able to significantly enhance lattice retraction when 10 micrograms/ml (48.5 microM) and 50 micrograms/ml (242 microM) were used.     

Primary chemotherapy in the treatment of breast cancer]

Between 1980 and 1992, 457 consecutive patients with initial breast cancer entered two successive protocols combining neoadjuvant chemotherapy, hormonotherapy (tamoxifen) and locoregional radiotherapy (teleradiotherapy and boost by iridium) as exclusive locoregional treatment. Cytological diagnosis, hormone receptors, cytological grading were provided by fine needle aspiration. Both protocols included velbe, thiotepa, methotrexate, 5FU and adriamycin with some minor differences regarding the schedule of doses and their number during induction and during the consolidation phase. In both studies, over 50% patients had locally advanced breast cancer (IIb, IIIa or IIIb). Chemotherapy induced tumor regression over 50% in 91% patients of the first protocol (30% complete clinical remission CR) and in 94% patients of the 2nd protocol (40% CR): in this protocol 20 poor responders were given a rescue protocol (2 CR; 9 partial remissions). The 5 year actuarial rate of breast preservation is 94% and the 5 year actuarial rate of local relapses is 15%. The cosmetic results according to Danoff are excellent 20%, good 55%, mean 35%. Disease free survival and overall survival compare favorably to published data: they depend on TNM stages, tumor differentiation and chemotherapy induced early tumor regression.     

Adhesion of human neutrophils to and activation by type-I collagen involving a beta 2 integrin.

We previously demonstrated that the alpha 1(I) polypeptide chain of collagen can bind and activate polymorphonuclear neutrophils (PMN). In the present experiments, performed in culture grade 96-well plastic plates coated with collagen, fibronectin, or other proteins, adhesion was assessed by staining the adhering cells after 30 min with crystal violet and measuring absorbance at 560 nm, and activation of PMNs was assessed by measuring the amount of O2-formed. Adhesion occurred at 17 and 37 degrees C but activation at 37 degrees C only. Monoclonal antibody anti-CD 18 inhibited adhesion, showing that the receptor of collagen I on PMNs is a beta 2 integrin. On the other hand, adhesion of PMNs to fibronectin was inhibited by monoclonal antibodies to CD18 and to CD11b.     

Acute management of intracranial hemorrhage in patients receiving thrombolytic therapy: case reports

Intracranial hemorrhage is an uncommon complication of antithrombotic therapy. We present two patients who suffered life-threatening intracranial bleeding as a complication of thrombolytic/anticoagulant treatment. Early diagnosis and treatment appear to be crucial factors for survival. We suggest an approach to perioperative management for intracranial hemorrhage resulting from antithrombotic therapy.     

Spontaneous increase of DNA turnover in murine systemic lupus erythematosus

DNA synthesis and release was studied in unstimulated splenocytes of strains of mice known to develop spontaneous systemic lupus erythematosus (SLE)-like disease and in non-SLE age- and sex-matched strains as well. Newly synthesized DNA was measured as total acid-insoluble radioactive material present in cell pellet plus supernatant of unstimulated 0–72 h cell cultures [³H]thymidine-pulsed, whereas DNA release was measured as amount of acid-precipitable radioactivity found in supernatant of those cultures. In all strains known to develop spontaneous murine SLE the amount of newly synthesized DNA was 1.3–2.1-fold increased when compared to normal strains studied concomitantly. Furthermore, a significant increase in DNA release into medium, unrelated to cell viability, was observed in those strains as well. These observations clearly demonstrate different metabolic rates of synthesis and release of DNA in murine SLE. This difference suggests the existance of an underlying mechanism responsible for extracellular DNA abundancy, which may be important for the formation of circulating DNA-anti-DNA immune complexes.     

Biological effects of cyclosporin A: A new antilymphocytic agent

The fungus metabolite cyclosporin A is a small peptide acting as a novel antilymphocytic agent. It strongly depressed appearance of both direct and indirect plaque-forming cells and produced a clear dose-dependent inhibition of haemagglutinin formation in mice upon oral administration. Skin graft rejection in mice and graft-versus-host disease in mice and rats were considerably delayed by cyclosporin A which also prevented the occurrence of paralysis in rats with experimental allergic encephalomyelitis. This compound was not only highly effective in preventing development of Freund's adjuvant arthritis, but in addition improved the symptoms in rats with established arthritis, although it is inactive in acute inflammation. This new agent contrasts with other immunosuppressives and cytostatic drugs in its weak myelotoxicity. Experimental evidence suggests that cyclosporin A, rather than being cytostatic or lympholytic, affects an early stage of mitogenic triggering of the immunocompetent lymphoid cell.     

Gammadelta T cells and interleukin-6 levels could provide information regarding the progression of human renal allograft

We have determined the percentage of alphabeta and gammadelta T cells by flow cytometry as well as serum interleukin-6 (IL-6) and soluble interleukin-6 receptor (sIL-6R) levels by enzyme-linked immunosorbent assay in kidney allograft recipients with acute, chronic or stable graft evolution. The percentage of CD4 and CD8 T cells in transplanted patients was lower than in the control group (P < 0.001) with the exception of CD8 gammadelta T cells from patients with stable evolution (P > 0.05). The serum levels of IL-6 and sIL-6R in acute and chronic rejection were higher than in the controls (P < 0.05). No differences in IL-6 levels were observed between the stable evolution and the control groups (P > 0.05). The levels of sIL-6R were higher in stable evolution patients than in the controls (P < 0.05) and no differences were observed between the chronic and stable evolution patients (P > 0.05). IL-6 decreased in patients with a favourable evolution, increased in those with an increased renal dysfunction and was maintained when the renal dysfunction was not modified. These results suggest that gammadelta T cells could participate in renal allograft maintenance and that IL-6 but not sIL-6R serum levels may provide a prognostic marker for measuring the evolution of kidney allograft.