Interactions between epidermal keratinocytes and dermal fibroblasts play an important role in regulating tissue homeostasis and repair. Nevertheless, little is known about the role of keratinocytes in the pathogenesis of keloid. In this study, we investigated the influence of normal skin- and keloid-derived keratinocytes on normal skin- and keloid-derived fibroblasts utilizing a serum-free indirect coculture system. The keloid-derived fibroblasts showed a greater proliferation and minimal apoptosis when cocultured with normal skin- or keloid-derived keratinocytes, and the results were most significant in the latter. This difference was not observed when the fibroblasts were treated with conditioned medium obtained from normal skin- and keloid-derived keratinocytes. Nevertheless, conditioned medium-treated groups showed more proliferation and less apoptosis compared to the nonconditioned medium-treated control groups. We also analyzed the profile of factors involved in cell growth and apoptosis in fibroblasts cocultured with keratinocytes. Extracellular signal-regulated kinase and c-Jun N-terminal kinase phosphorylations and expression of Bcl-2 and transforming growth factor-beta1 were all significantly upregulated in the fibroblasts cocultured with keloid-derived keratinocytes. Together, these results strongly suggest that the overlying keratinocytes of the keloid lesion play an important role in keloidogenesis by promoting more proliferation and less apoptosis in the underlying fibroblasts through paracrine and double paracrine effects.

The pathogenesis of keloid remains poorly understood. As no effective therapy for keloid is as yet available, an insight into its pathogenesis may lead to novel approaches. Apoptosis has been found to mediate the decrease in cellularity during the transition between granulation tissue and scar. Here, we report that in contrast to hypertrophic scar-derived and normal skin-derived fibroblasts, keloid-derived fibroblasts are significantly resistant to both Fas-mediated and staurosporine-induced apoptosis. The caspases-3, -8, and -9 were not activated indicating that the block in the apoptotic pathway in keloid is upstream of the caspases. There were no significant differences in the level of expression of Fas, Bcl-2, and Bax between the three groups but addition of transforming growth factor (TGF)-beta1 significantly inhibited Fas-mediated apoptosis in hypertrophic scar-derived and normal skin-derived fibroblasts and neutralization of autocrine TGF-beta1 with anti-TGF-beta1 antibody abrogated the resistance of keloid-derived fibroblasts. Anti-apoptotic activity was not observed with TGF-beta2. This is the first study linking refractory Fas-mediated apoptosis to cellular phenotype in keloids and indicating a pivotal role for the anti-apoptotic effect of TGF-beta1 in this resistance. Hence, it becomes important to treat keloids as a separate entity different from hypertrophic scars and enhancement of Fas-sensitivity could be a promising therapeutic target.

Background-Vascular abnormalities are a major cause of postoperative complications in irradiated tissues. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in irradiated human cervical arteries. Methods and Results-Irradiated arteries were taken from the neck region of patients who had radiation therapy. Arteries from patients who did not receive radiation therapy were used as controls. Endothelium-dependent relaxation to acetylcholine and A23187 was impaired in irradiated arteries. Norepinephrine-induced contraction and sodium nitroprusside-induced relaxation were unchanged. In control arteries, N

In the treatment of extramammary Paget's disease, indications of lymph node dissection are an important issue as well as wide local excision. From this prospective study, we have developed an algorithm for indications of lymph node dissection.

This article provides our experience with 45 ischial sores and 24 sacral sores in 53 paraplegic patients between 1990 and 1995. Data were evaluated as to the sites of sores and types of the transferred flaps. Types of the transferred flaps were categorized into the fasciocutaneous flap and the myocutaneous or muscle flap. In the treatment of 45 ischial sores, 18 were reconstructed with the fasciocutaneous flaps and 27 with the myocutaneous or muscle flaps. In the treatment of 24 sacral sores, 23 were reconstructed with the fasciocutaneous flaps and 1 with the myocutaneous flap. The recurrence rate was analyzed by percent pressure sore free survival (%PSFS) by the Kaplan-Meier method. Overall, the ischial sores provided a higher recurrence rate than sacral sores; however, there was no significant difference in the %PSFS between the sites of sores. The group of the sores reconstructed with the fasciocutaneous flap demonstrated significant or marginally significant better results in the %PSFS (total of ischial and sacral, p = 0.0155; ischial, p = 0.0555) compared with the group of the sores reconstructed with the myocutaneous or muscle flap. These findings indicated that the use of the fasciocutaneous flap is expected to provide a better long-term result in surgical reconstruction of pressure sores than the myocutaneous or muscle flap.