. Prevalence of shoulder and upper-limb disorders among workers in the fish-processing industry. Scand J Work Environ Health 1993;19:12~31. A cross-sectional study was conducted among fish-processing workers to evaluate the prevalence of shoulder and upper-limb discomforts and to assess the associated ergonomic risk factors. A prestructured interview, a medical check-up, and job analyses were performed to determine musculoskeletal disorders among 207 workers in eight factories. The results showed shoulder girdle pain (30.9%), epicondylitis (14.5%), and carpal tunnel syndrome (15.0%) as the three most common soft-tissue disorders. The odds ratio of shoulder girdle pain was 1.6 (95% CI 1.1-2.5) among the workers who performed tasks with repetitive movement of their upper limbs, while it was 1.8 (95% CI 1.2-2.5) for the workers who sustainedforceful movement of their upper limbs during work. Women taking oral contraceptives had a 2.0 times higher odds ratio for carpal tunnel syndrome than did other women. It would appear that untrained or unskilled workers were prone to suffer from musculoskeletal disorders.

Previous reports have shown that cellular functions could be influenced by visual light (400-700 nm). Recent evidence indicates that cellular proliferation could be triggered by the interaction of a helium-neon laser (He-Ne laser, 632.8 nm) with the mitochondrial photoacceptor-cytochrome c oxidase. Our previous studies demonstrated that He-Ne irradiation induced an increase in cell proliferation, but not migration, in the melanoma cell line A2058 cell. The aim of this study was to investigate the underlying mechanisms involved in photostimulatory effects induced by an He-Ne laser. Using the A2058 cell as a model for cell proliferation, the photobiologic effects induced by an He-Ne laser were studied. He-Ne irradiation immediately induced an increase in mitochondrial membrane potential (delta psi(mt)), ATP, and cAMP via enhanced cytochrome c oxidase activity and promoted phosphorylation of Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) expressions. He-Ne irradiation-induced A2058 cell proliferation was significantly abrogated by the addition of delta psi(mt) and JNK inhibitors. Moreover, treatment with an He-Ne laser resulted in delayed effects on IL-8 and transforming growth factor-beta1 release from A2058 cells. These results suggest that He-Ne irradiation elicits photostimulatory effects in mitochondria processes, which involve JNK/AP-1 activation and enhanced growth factor release, and ultimately lead to A2058 cell proliferation.

Neutrophil extracellular traps (NETs) have been implicated in the development of certain immune-mediated diseases, but their role in psoriasis has not been clearly defined. Human β-defensin-2 (HBD-2) is an important antimicrobial peptide overexpressed in psoriasis epidermis. We evaluated whether the amount of NETs is increased in psoriasis and determined the effect of NETs on HBD-2 production in epidermal keratinocytes. Using fluorescent microscopy, we found that patients with psoriasis (n = 48) had higher amount of NETotic cells in their peripheral blood compared to healthy controls (n = 48) and patients with eczema (n = 35). Psoriasis sera showed increased ability to induce NET formation in control neutrophils but normal NET degradation ability. The amount of NETs in the peripheral blood correlated with psoriasis disease severity. NETosis was also observed in the majority (18 of 20) of psoriasis skin specimens. Furthermore, NETs induced HBD-2 mRNA and protein production in keratinocytes, and immunohistochemical analysis confirmed strong expression of HBD-2 in psoriasis lesional skin. In summary, NET formation is increased in peripheral blood and lesional skin of psoriasis patients and correlates with disease severity. Additionally, NET-induced HBD-2 production may provide a novel mechanism for the decreased susceptibility of psoriasis plaques to microbial infections.

Low-energy helium-neon lasers (632.8 nm) have been employed in a variety of clinical treatments including vitiligo management. Light-mediated reaction to low-energy laser irradiation is referred to as biostimulation rather than a thermal effect. This study sought to determine the theoretical basis and clinical evidence for the effectiveness of helium-neon lasers in treating vitiligo. Cultured keratinocytes and fibroblasts were irradiated with 0.5-1.5 J per cm2 helium-neon laser radiation. The effects of the helium-neon laser on melanocyte growth and proliferation were investigated. The results of this in vitro study revealed a significant increase in basic fibroblast growth factor release from both keratinocytes and fibroblasts and a significant increase in nerve growth factor release from keratinocytes. Medium from helium-neon laser irradiated keratinocytes stimulated [3H]thymidine uptake and proliferation of cultured melanocytes. Furthermore, melanocyte migration was enhanced either directly by helium-neon laser irradiation or indirectly by the medium derived from helium-neon laser treated keratinocytes. Thirty patients with segmental-type vitiligo on the head and/or neck were enrolled in this study. Helium-neon laser light was administered locally at 3.0 J per cm2 with point stimulation once or twice weekly. The percentage of repigmented area was used for clinical evaluation of effectiveness. After an average of 16 treatment sessions, initial repigmentation was noticed. Marked repigmentation (>50%) was observed in 60% of patients with successive treatments. Basic fibroblast growth factor is a putative melanocyte growth factor, whereas nerve growth factor is a paracrine factor for melanocyte survival in the skin. Both nerve growth factor and basic fibroblast growth factor stimulate melanocyte migration. It is reasonable to propose that helium-neon laser irradiation clearly stimulates melanocyte migration and proliferation and mitogen release for melanocyte growth and may also rescue damaged melanocytes, therefore providing a microenvironment for inducing repigmentation in vitiligo.

Although numerous epidemiological studies have shown that inorganic arsenicals cause skin cancers and hyperkeratoses in humans , there are currently no established mechanisms for their action or animal models. Previous studies in our laboratory using primary human keratinocyte cultures demonstrated that micromolar concentrations of inorganic arsenite increased cell proliferation via the production of keratinocyte-derived growth factors. As recent reports demonstrate that overexpression of keratinocyte-derived growth factors , such as transforming growth factor (TGF)-␣, promote the formation of skin tumors , we hypothesized that similar events may be responsible for those associated with arsenic skin diseases. Thus , the influence of arsenic in humans with arsenic skin disease and on mouse skin tumor development in transgenic mice was studied. After low-dose application of tetradecanoyl phorbol acetate (TPA) , a marked increase in the number of skin papillomas occurred in Tg.AC mice , which carry the v-Haras oncogene , that received arsenic in the drinking water as compared with control drinking water, whereas no papillomas developed in arsenic-treated transgenic mice that did not receive TPA or arsenic/ TPA-treated wild-type FVB/N mice. Consistent with earlier in vitro findings , increases in granulocyte/ macrophage colony-stimulating factor (GM-CSF) and TGF-␣ mRNA transcripts were found in the epidermis at clinically normal sites within 10 weeks after arsenic treatment. Immunohistochemical staining localized TGF-␣ overexpression to the hair follicles. Injection of neutralizing antibodies to GM-CSF after TPA application reduced the number of papillomas in Tg.AC mice. Analysis of gene expression in samples of skin lesions obtained from humans chronically exposed to arsenic via their drinking water also showed similar alterations in growth factor expression. Although confirmation will be required in nontransgenic mice, these results suggest that arsenic enhances development of skin neoplasias via the chronic stimulation of keratinocyte-derived growth factors and may be a rare example of a chemical carcinogen that acts as a co-promoter. (Am J Pathol 1998, 153:1775-1785) Arsenic, a ubiquitous element, represents a human health concern when concentrated in the environment from natural or anthropogenic processes. Arsenic contamination of water supplies has resulted in a very high incidence of skin lesions and cancers in exposed populations from Taiwan, China, Eastern Europe, India, Southwestern United States, and Cental and South America. The U.S. Environmental Protection Agency (EPA) estimates that over 350,000 people in the U.S. consume drinking water containing over 50 g/L arsenic, the current EPA standard, 1 and there is significant regulatory pressure to lower the acceptable levels. Chronic exposure to inorganic arsenic in drinking water is most often associated with increased mortality from skin cancer, but recent studies have also linked arsenic exposure to neoplasias in internal organs, including the lung, liv...

Our study provides in vitro evidence demonstrating that direct interaction between FK506 and KCs creates a favourable milieu for MC growth and migration. Furthermore, our findings provide a possible mechanism explaining how tacrolimus ointment induces repigmentation in patients with vitiligo.

Organization, 1980; IARC, 1987). Exposures to inorganic arsenic from medicinal (Sommers and McManus, 1953;Frost, 1967), environmental (Neubauor, 1947;Tseng et al.. 1968;Yeh et al., 1968;Yeh, 1973; Cebnran et al., 1983) and occupational (Roth, 1957;Nelson et al., 1973;Brown and Rabinowitz, 1979) sources have been found to be associated with the development of skin cancer. Blackfoot disease (BFD) is a unique peripheral vascular disorder confined to an area on the south-west coast of Taiwan (Wu et al., 1961). The prevalence of BFD has been found to increase with the arsenic content of drinking water in a dose-response relation (Chen and Wu, 1962). The prevalence of skin cancer, hyperkeratosis and hyperpigmentation in the BFD endemic area was as high as 10.6, 71.0 and 183.5 per 1000 respectively (Tseng et al., 1968). A dose-response relation was also observed between the occurrence of skin cancer and the arsenic concentration in drinking water (Tseng et al., 1968;Tseng, 1977;Chen et al., 1985 Chen et al., , 1988Wu et al., 1989;Chen et al., 1992). Furthermore, a significant ecological correlation beween the arsenic level in well water and ageadjusted mortality from skin cancer in 314 townships all over Taiwan island was reported in a recent study (Chen and Wang, 1990). All these findings were obtained in ecological correlation studies on the association between arsenic exposure and skin cancer prevalence studies at the village level. They might be subject to the bias of ecological fallacy, i.e. the association observed at the village level may not hold at the individual level.Artesian wells have been used in the BFD endemic area since the decade 1900-10. In the 1960s a tap water supply Correspondence: C-J Chen Received 31 January 1994; revised 26 July 1994: accepted 16 August 1994 system was implemented in the endemic area, but the coverage was not high until the 1970s. This study was camred out at the individual level to assess the prevalence of skin cancer among residents in the BFD-endemic area who had not drunk high-arsenic artesian well water for more than 15 years.Despite a large number of residents having consumed higharsenic artesian well water, only a small fraction were affected with skin cancer (Tseng et al., 1968). Furthermore, residents with the same exposure to high-arsenic artesian well water were of different ages at the onset of skin cancer. Such discrepancies in individual susceptibility suggest the existence of some other co-factors in the induction of arsenic-related skin cancer. Multiple risk factors other than chronic arsenic exposure were also explored in this study. Material and methodsStud} area Three villages, Homei, Fuhsin and Hsinming of Putai Township on the south-western coast of Taiwan island, were selected as the study area. These three villages include approximately 5% of the total population of the BFD endemic area. BFD was hyperendemic in this area with a prevalence as high as 13.6% in Homei, 9.6% in Fuhsin and 10.3% in Hsinming (Wu et al., 1961). Residents in the area ha...

Narrow-band ultraviolet-B (UVB) radiation is an effective treatment for vitiligo vulgaris. However, the mechanisms of narrow-band UVB in inducing repigmentation of vitiligo lesions are not thoroughly clarified. The purpose of our study was to investigate the effects of narrow-band UVB irradiation on melanocyte proliferation and migration in vitro. Our results showed that the cell counts as well as [3H]thymidine uptake of melanocytes were significantly enhanced by narrow-band UVB-irradiated keratinocyte supernatants. In these supernatants, a significant increase in basic fibroblast growth factor (bFGF) and in endothelin-1 (ET-1) release was observed. bFGF is a natural mitogen for melanocytes, whereas ET-1 can stimulate DNA synthesis in melanocytes. This stimulatory effect of melanocyte proliferation by supernatants derived from narrow-band UVB-irradiated keratinocytes was significantly reduced by a selective endothelin-B (ET-B) receptor antagonist (BQ788), suggesting an essential role of ET-1 on melanocyte proliferation. Our results of time-lapse microphotography revealed a stimulatory effect of narrow-band UVB irradiation on melanocyte migration. Focal adhesion kinase (FAK) plays a pivotal role in cell migration. Phosphorylated FAK (p125(FAK)) expression on melanocyte was enhanced by narrow-band UVB irradiation. In this study, narrow-band UVB irradiation stimulated a significant increase in matrix metalloproteinase-2 (MMP-2) activity in melanocyte supernatants. Narrow-band UVB-irradiation-induced migration of melanocytes was significantly annihilated by the addition of p125(FAK) inhibitor (herbimycin-A) or MMP-2 inhibitor (GM6001). These results suggest that p125(FAK) and MMP-2 activity play important roles in narrow-band UVB-induced migration of melanocytes. Our results provide a theoretical basis for the effectiveness of narrow-band UVB irradiation in treating vitiligo.