ABSTRACT
Cell motility consists of repeating cycles of protrusion of a leading edge in the direction of migration, attachment of the advancing membrane to the matrix, and pulling of the trailing edge forward. In this dynamic process there is a major role for the cytoskeleton, which drives the protrusive events via polymerisation of actin in the lamellipodium, followed by actomyosin contractility. To study the transition of the actin cytoskeleton from a 'protrusive' to 'retractive' form, we have monitored the formation of focal adhesions and stress fibres during cell migration on a micro-patterned surface. This surface consisted of parallel arrays of 2 microm-wide, fibronectin-coated gold stripes, separated by non-adhesive (poly(ethylene glycol)-coated) glass areas with variable width, ranging from 4-12 microm. Monitoring the spreading of motile cells indicated that cell spreading was equally effective along and across the adhesive stripes, as long as the non-adhesive spaces between them did not exceed 6 microm. When the width of the PEG region was 8 microm or more, cells became highly polarised upon spreading, and failed to reach the neighboring adhesive stripes. It was also noted that as soon as the protruding lamella successfully crossed the PEG-coated area and reached an adhesive region, the organisation of actin in that area was transformed from a diffuse meshwork into a bundle, oriented perpendicularly to the stripes and anchored at its ends in focal adhesions. This transition depends on actomyosin-based contractility and is apparently triggered by the adhesion to the rigid fibronectin surface.
ABSTRACT
The present study is a retrospective search on the actual use of systemic retinoids in the treatment of psoriasis. The design of the study was inclusion of the patients in whom retinoid treatment was initiated from 1981 up to 1989. The analysis was carried out in 1999, after at least 10 years of follow up. In total 94 patients were included, who were treated with etretinate or acitretin, out of a cohort of 2,000 patients with psoriasis at the Nijmegen Department of Dermatology. The majority of the patients were older than 40 years, 31% were suffering from pustular psoriasis, 6% from erythrodermic psoriasis and 17% from psoriasis arthropatica. Most patients had had psoriasis for more than 5 years and in 56% of them retinoids were the first systemic treatment. Continuous treatment for more than one year was recorded in 33% of the patients. During long-term follow up of at least 10 years, 25% of them were included again for acitretin treatment. Therefore, prolonged treatment actually had occurred in approximately half of the patients. In contrast to the common belief, erythrodermic psoriasis proved to be not the typically "low-dose" - and pustular psoriasis was not the typically "high dose" indication. The present study, however, reconfirmed the high efficacy of systemic retinoids in pustular- and erythrodermic psoriasis. It was also reconfirmed that systemic retinoids are not effective in arthropathic psoriasis. The occurrence of side effects largely followed the controlled investigations. At least 10 years' follow up had not revealed serious side effects. In those patients (n = 30) who completed the entire survey in the Nijmegen centre 19 patients were treated with at least one course of photo(chemo)therapy and 9 patients were treated subsequently with methotrexate.
