Biomedical subjects

E Nylander-Lundqvist

Publications and source records attributed to E Nylander-Lundqvist.

3 recordsLinked to original sources

PubMed1999

PUVA and cancer risk: the Swedish follow-up study.

There is concern about the long-term carcinogenic effects of psoralen and ultraviolet A radiation (PUVA) for treatment of skin disorders. Many authors have found an increased risk for cutaneous squamous cell carcinoma (SCC). Except in anecdotal reports, malignant melanoma had not been observed in patients treated with PUVA until recently. In the U.S.A., a 16-centre prospective study of 1380 patients showed for the first time that there might also be an increased risk for malignant melanoma in patients treated with high cumulative dosages of PUVA. We have therefore followed up the Swedish PUVA cohort until 1994. This cohort had previously been followed up until 1985. Information from 4799 Swedish patients (2343 men, 2456 women) who had received PUVA between 1974 and 1985 was linked to the compulsory Swedish Cancer Registry in order to identify individuals with cancer. The average follow-up period was 15.9 years for men and 16.2 for women. We did not find any increased risk for malignant melanoma in our total cohort of 4799 patients treated with PUVA or in a subcohort comprising 1867 patients followed for 15-21 years. For cutaneous SCC there was an increase in the risk: the relative risk was 5.6 (95% confidence interval, CI 4. 4-7.1) for men and 3.6 (95% CI 2.1-5.8) for women. Significant (P < 0.05) increases were also found in the incidence of respiratory cancer in men and women and of kidney cancer in women. In conclusion, we did not find any increased risk for malignant melanoma in our patients treated with high doses of PUVA and followed up for a long time. We confirm previous reports of an increase in the incidence of cutaneous SCC in patients treated with PUVA, and recommend that patients should be carefully selected for PUVA and rigorously followed up.

Adolescent↗

PubMed1997

Formation of active IL-1 beta from pro-IL-1 beta catalyzed by stratum corneum chymotryptic enzyme in vitro.

Interleukin 1 beta (IL-1 beta) is produced as a biologically inactive 31 kD precursor, which is converted to the active 18 kD form by proteolytic processing. Keratinocytes express IL-1 beta but not the active form of the specific IL-1 beta converting enzyme (ICE). We have recently presented evidence that IL-1 beta activation in human epidermis occurs via an alternative mechanism involving hitherto unknown proteases. We asked whether stratum corneum chymotryptic enzyme (SCCE), which is a serine protease specifically expressed in keratinizing squamous epithelia, can act as an IL-1 beta activator in vitro. Recombinant human pro-IL-1 beta was incubated with recombinant SCCE, and the reaction products were characterized as regards molecular size and ability to induce expression of E-Selectin in human umbilical cord endothelial cells. SCCE caused degradation of pro-IL-1 beta and the accumulation of a component with electrophoretic mobility slightly lower than recombination mature IL-1 beta. Whereas incubation mixtures with pro-IL-1 beta which had been incubated in the absence of SCCE, or with SCCE, which had been incubated in the absence of pro-Il-1 beta, did not induce expression above baseline levels of E-Selectin, pro-Il1 beta which had been incubated with SCCE induced a significant increase in E-Selectin expression. This effect could be abolished by neutralizing antibodies to IL-1 beta, but not by antibodies to IL-1 alpha. In addition to IL-1 beta activation, SCCE also prepared to be able to catalyze a further degradation of IL-1 beta, leading to a loss of biological activity. We conclude that SCCE is a potential candidate for being responsible for IL-1 beta activation in human epidermis.

Humans↗

PubMed1996

IL-1 beta activation in human epidermis.

IL-1 beta is produced as an inactive 31-kDa precursor processed to active 18-kDa IL-1 beta by proteolytic cleavage, catalyzed by the highly specific IL-1-converting enzyme (ICE). In vitro activation of IL-1 beta can also be obtained by other proteases. Human keratinocytes express IL-1 beta, but not active ICE. The role played by IL-1 beta produced by keratinocytes has therefore been unclear. We asked whether normal human plantar stratum corneum contains biologically active IL-1 beta and, if so, by which mechanism this IL-1 beta is activated. Crude extracts and partially purified preparations from which IL-1 alpha had been removed were used. Biologic IL-1 activity was measured as the ability to induce expression of E-selectin in HUVEC. The crude extract contained IL-1-like activity that could be partially abolished with Abs to IL-1 alpha or IL-1 beta and totally inhibited with a mixture of the two Abs. IL-1 activity in the partially purified preparation was totally inhibited by Abs to IL-1 beta. The specific IL-1 beta activity in the two preparations was 60 to 85% of the sp. act. of recombinant human IL-1 beta. IL-1 beta from plantar stratum corneum had a slightly higher molecular mass than recombinant mature IL-1 beta. Its isoelectric point was approximately 6.1 compared with 6.9 for rIL-1 beta. We conclude that human plantar stratum corneum contains biologically active IL-1 beta that has been activated by an alternative mechanism that does not involve ICE. This is, to our knowledge, the first report of an alternative mechanism of IL-1 beta activation occurring in vivo.

Amino Acid Sequence↗