Biomedical subjects

B Pittet

Publications and source records attributed to B Pittet.

21 records · Page 2Linked to original sources

PubMed1994

Effect of gamma-interferon on the clinical and biologic evolution of hypertrophic scars and Dupuytren's disease: an open pilot study.

Hypertrophic scars and Dupuytren's disease are characterized by the presence of modified fibroblasts or myofibroblasts which are allegedly responsible for tissue retraction and excessive connective tissue production. gamma-Interferon, a cytokine produced by T-helper lymphocytes, has been shown to decrease fibroblast replication, alpha-smooth-muscle actin (the actin isoform characterizing myofibroblasts) expression, and collagen production. We have investigated in an open pilot study the possibility that intralesional injections of gamma-interferon exert a beneficial effect on the evolution of hypertrophic scars and Dupuytren's disease. In the 14 selected patients, gamma-interferon decreased the symptoms and the size of the lesions of both diseases; in hypertrophic scars, immunofluorescence examination showed that alpha-smooth-muscle actin expression also was decreased in myofibroblasts. Moreover, in fibroblasts cultured from 4 patients with hypertrophic scars, gamma-interferon decreased replication and alpha-smooth-muscle actin expression in vitro. Our results suggest that gamma-interferon could represent a useful adjunct to the nonsurgical therapy of hypertrophic scars and Dupuytren's disease. Larger controlled clinical studies, however, should test the validity of these preliminary observations.

Actins↗

PubMed1989

Myofibroblasts from diverse pathologic settings are heterogeneous in their content of actin isoforms and intermediate filament proteins.

We examined by immunofluorescence the distribution of vimentin, desmin, alpha-smooth muscle actin and alpha-sarcomeric actin in normal human soft tissues and in pathologic tissues containing myofibroblasts, including normally healing granulation tissue, hypertrophic scar, and fibromatosis. The pattern of actin isoforms was also documented biochemically by two-dimensional gel electrophoresis. Fibroblastic and/or myofibroblastic cells in each setting always expressed vimentin and never alpha-sarcomeric actin. Moreover, these cells showed an heterogeneous cytoskeletal composition which defined four phenotypes: (a) cells expressing only vimentin; (b) cells expressing vimentin, alpha-smooth muscle actin and desmin; (c) cells expressing vimentin and alpha-smooth muscle actin; and (d) cells expressing vimentin and desmin. Given this, two groups of lesions are distinguished: the first contains only vimentin cells and consists of normally healing granulation tissue, eschars and normally healed scars; the second contains vimentin cells admixed with variable proportions of vimentin, alpha-smooth muscle actin and desmin, vimentin and alpha-smooth muscle actin, and vimentin and desmin cells and consists of hypertrophic scars and fibromatoses. Immunogold electron microscopy showed that alpha-smooth muscle actin was present in a proportion of cells with ultrastructural features of myofibroblasts. Our findings suggest that contrary to myofibroblasts of normally healing granulation tissue and normally healed scars, myofibroblasts of pathologic conditions characterized by chronic retraction express always immunochemical features indicative of smooth muscle differentiation.

Actins↗

PubMedDate not supplied

Covering by a flap induces apoptosis of granulation tissue myofibroblasts and vascular cells.

It has recently been shown that during the healing of an open wound, apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Because reduced contraction and a decrease in the number of fibroblastic cells have been described in wounds covered with a successful skin graft, we hypothesized that apoptosis could be responsible for these phenomena. Using in situ labeling of fragmented DNA, immunohistochemistry for alpha-smooth muscle actin, and electron microscopy, we have studied in rats the evolution of 10-day-old wound tissue covered with a total skin flap (containing epidermis, dermis, and the cutaneous muscle). In 10-day-old wound tissue, few apoptotic vascular cells and rare apoptotic myofibroblasts were present; the number of apoptotic cells increased slightly 72 hours later. In wounds covered with total skin flaps, the number of apoptotic vascular and myofibroblastic cells increased drastically 6 hours after flap application with a maximum at 24 and 48 hours, respectively. A decrease of apoptotic cell number was noted at 72 hours; at this time, the size of the granulation tissue was greatly reduced and showed extracellular matrix remodeling. Total flaps were more efficient in the induction of granulation tissue cell apoptosis compared with dermo-epidermal flaps. Moreover, the control application of full-thickness skin autografts, which were not viable 7 days later, did not induce apoptosis 24 hours after implantation. Our results indicate that covering granulation tissue with a skin flap results in a massive apoptotic process, possibly by means of a (some) locally released substance(s).

Journal Article↗