Abstract-The effect of mechanical strain on transcription and expression of the immediate-early genes, early growth response gene-1 (Egr-1), c-jun, and c-fos, was investigated in neonatal rat aortic vascular smooth muscle (VSM) cells. Cells grown on silicone elastomer plates were subjected to cyclic mechanical strain (1 Hz) at various durations and magnitudes. Egr-1 mRNA increased rapidly in response to cyclic strain, reached a maximum of 10-fold after 30 minutes, and returned to baseline after 4 hours. c-jun exhibited a similar pattern, whereas c-fos mRNA expression was unaffected by strain. Cycloheximide prolonged the increase in Egr-1 and c-jun mRNA and caused superinduction of both. The threshold level of continuous cyclic strain needed to induce expression was 5% for Egr-1 and c-jun. Even a single cycle of mechanical strain that lasted 1 second was sufficient to induce Egr-1 and c-jun mRNA. Strain also increased expression of a transiently transfected Egr-1 promoter-reporter construct. The effect of varying extracellular matrices on strain-induced Egr-1 and c-jun mRNA was examined. In contrast to collagen type 1-and pronectin-coated plates, strain did not significantly alter expression of Egr-1 and c-jun was less induced on laminin-coated plates. On collagen type 1, strain increased Egr-1 protein levels by 2.1-fold at 60 minutes. Immunofluorescence microscopy revealed translocation of Egr-1 to the nucleus in response to strain. These observations indicate that Egr-1 expression and translocation are sensitive to mechanical perturbation of the cell. c-jun is also induced by strain, but c-fos is not. The signal for this induction may involve specific cell-matrix interactions. (Circ Res. 1999;84:678-687.)

FcR nonbinding anti-CD3ε mAbs elicit partial TCR signaling that leads to T cell unresponsiveness and tolerance in vivo. In this study, the membrane-proximal events that promote T cell inactivation by FcR nonbinding anti-CD3 mAbs were examined. In the context of FcR nonbinding anti-CD3, TCR complexes did not aggregate and failed to translocate into glycolipid-enriched membrane microdomains. Furthermore, FcR nonbinding anti-CD3 mAbs induced tyrosine phosphorylation of the Fyn substrate Cbl, but not the ZAP-70 substrate linker for activation of T cells. Overexpression of Fyn, but not Lck, restored the mitogenicity of FcR nonbinding anti-CD3 in primary T cells. Taken together, these results suggest that Fyn mediates the partial signaling induced by TCR antagonists.

Lymphedema of the penis and scrotum is a rare entity characterized by enlargement of the skin and subcutaneous tissue of the genital region due to lymphatic drainage impairment. This clinical condition is more frequent in tropical countries due to a higher incidence of filariasis, which, in turn, is the main etiology. We describe the case of a 33-year-old man with large lymphedema of the scrotum and penis due to an acute and chronic inflammatory process, foreign body granuloma, and marked hyalinization. Four consecutive surgical interventions were necessary to remove the great part of the affected tissue, which enabled satisfactory results and improved the patient's quality of life.

Abstract-Prohferatlon of cultured neonatal vascular smooth muscle (VSM) cells 1~ enhanced by exposure to cychc mechanical strain, m part through autocrme action of secreted platelet-denved growth factor (PDGF) We examined transcrlptlon factors and DNA response elements that may participate m the mductlon of PDGF-A gene transcnptlon by mechanical strain. PDGF-A mRNA increased gradually over 4 to 24 hours exposure to cychc (1Hz) strain This was due, at least m part, to increased transcnptlon smce a full length (890bp) PDGF-A promoter reporter construct was induced 3 5-fold m transfected VSM cells exposed to strain for 24 hours A series of PDGF-A promoter truncation reporter constructs was used to ldentl@ potential regons of the promoter involved m regulation by strain Strain-responsive regions were found between -262bp and -92bp and between -92bp and -4lbp of the promoter Since these regions are GC-rich and contain response elements for Egr-1 and Sp-1, we exammed expression of these transcnptlon factors m response to strain mRNA for both factors increased over 0 5 to 4 hours of stram, while protein expression for both increased gradually over a 24 hours penod Gel shift assays with a probe specific for Egr-1 demonstrated at least 1 promment new shifted band after 4 to 12 hours exposure to strain An Sp-1 probe demonstrated constltutlve shifted bands that did not change m response to strain Thus, GC-rich regons m the proximal 92bp of the PDGF-A promoter contam mechanical strain-responsive elements that bmd Egr-1 and possibly Sp-1 (Hypertension. 1998;31[part 2]:170-175.)Key Words: vascular smooth muscle w mechanical strain n transcrlptlon factors n reporter genes n growth factors T he artenal wall 1s exposed to significant mechanical strain during the cardiac cycle ' Mechanical forces may partlclpate m the normal development of blood vessels' and m the pathological changes observed m hypertension '-' Recently, mechanical forces have been found to elicit a wide range of phenotyplc responses both m intact tissues and m cultured cells ' 6Our laboratory has previously shown that the apphcatlon of cychc (1 Hz) mechanical strains of 10% to 20% to neonatal VSM cells cultured on deformable &one elastomer membranes leads to increased prohferatlon, most likely via autocnne action of secreted PDGF' The magnitude of cychc strain necessary to induce PDGF m this m vitro system 1s comparable to the strain found m many vessels m situ ' Both PDGF-A and -B appear m the medium after 24 hours exposure to strain, PDGF-A' and -B8 RNAs are also increased by strain This response to mechanical stram observed m vitro may be relevant to the pathophyslology of hypertension, as several mvestlgators have demonstrated increased expression of PDGF m blood vessels of hypertensive animals 9 Negoro et al showed that antlhypertenslve drugs reduce expression of PDGF-A m vessel walls of hypertensive SHR rats 4The PDGF-A promoter has been cloned "I'~ and many of its regulatory elements have been identified 4 'z-l5 These studies suggest that a GC rich regio...