S H Jee

National Taiwan University, Taipei, Taipei, Taiwan

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Publications (29)77.06 Total impact

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    ABSTRACT: Psoriasis is a common inflammatory cutaneous disorder characterized by activated T-cell infiltration. T lymphocytes bearing natural killer cell receptors (NKRs) have been suggested to play an important role in the pathogenesis of psoriasis. However, the expression pattern of activating and inhibitory NKRs on T lymphocytes from psoriatic patients and its significance in psoriasis needs further study. To investigate the pathogenesis of NKR-expressing T cells in psoriasis. Thirty patients with chronic plaque psoriasis and 20 healthy controls were enrolled in this study. The immunophenotypic profiles of NKRs, including CD56, CD16 (activating NKRs), CD158a, CD158b, CD94 and NKG2A (inhibitory NKRs), were analysed in peripheral blood T lymphocytes, as well as psoriatic lesional infiltrating T cells, by triple-fluorescence flow cytometry. A significant increase of inhibitory CD8+ CD158b+, CD4 CD8 CD158b+ and CD8+ CD94/NKG2A+ T cells was found in the peripheral blood of patients with psoriasis when compared with controls. Tissue-infiltrating T lymphocytes expressing inhibitory receptors CD158b, CD94 and NKG2A were found in psoriatic lesions. There was a significant positive correlation between the increased percentage of circulating CD8+ CD94/NKG2A+ T cells and the Psoriasis Area and Severity Index. In the present study, we demonstrated increased proportions of particular subsets of inhibitory CD158b+ and/or CD94/NKG2A+ T cells in patients with psoriasis. The elevation of these inhibitory NKR-expressing T cells was correlated with disease severity, which may signify the possibility of chronic antigen-driven stimulation and dysregulated cytokine production in the pathogenesis of psoriasis.
    British Journal of Dermatology 09/2006; 155(2):318-24. · 3.76 Impact Factor
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    ABSTRACT: Breast tumour kinase (BRK) is a newly identified non-receptor protein tyrosine kinase from a metastatic breast tumour. Its biological functions are still under extensive investigation. The mouse homologue Sik (Src-related intestinal kinase) has been implicated in mouse keratinocyte differentiation; however, not much is known about the functions of BRK in human cutaneous biology. Using HaCaT cells as an experimental model, to explore the mutual relationships between BRK and differentiation of human keratinocytes. Archival paraffin blocks of normal and pathological skin were retrieved for examining the in vivo distribution of BRK. Its expression and subcellular localization were examined via indirect immunofluorescence, and quantitative changes were analysed by Northern and Western blots. The kinase activity of BRK was determined by its autophosphorylation and phosphorylation of exogenous substrate in the in vitro kinase assay. Using a retroviral infection method, we established stably transfected HaCaT cells expressing vector, wild-type BRK or a kinase-defective mutant (K219M). Expression of the differentiation marker keratin 10 (K10) was compared among these cells using semiquantitative reverse transcription-polymerase chain reaction. Results Histochemical examination showed that BRK was expressed exclusively in suprabasal keratinocytes. Its distribution was both cytoplasmic and intranuclear. An enhanced regional suprabasal expression pattern was observed in the confluent areas of cell cultures. The expression of BRK transcript and protein was up-regulated in prolonged confluence culture in a serum-dependent manner. Its kinase activity was activated shortly after the addition of calcium and ionomycin and returned to the basal level within 30 min. Overexpression of wild-type BRK moderately promoted the expression of K10 transcript while the kinase-defective BRK mutant exerted a prominent suppressive effect. The in vivo distribution of BRK and its up-regulation during in vitro differentiation of HaCaT cells, together with the activation of its kinase activity by calcium/ionomycin and its influence on K10 expression, all indicate a role for BRK in the complex process of keratinocyte differentiation.
    British Journal of Dermatology 09/2005; 153(2):282-9. · 3.76 Impact Factor
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    ABSTRACT: Atopic dermatitis (AD) is a complex disease with both a genetic background and environmental interactions. Although multiple linkage-analyses about AD have been studied, there have been only a few family aggregation tests of AD or perennial allergic rhinitis (AR) to date. The association of allergen-specific IgE in AD and atopic dermatitis with allergic perennial rhinitis (ADR) have also been seldom discussed. The purpose of this study was to evaluate family aggregation and assess allergen-specific IgE in patients with AD and ADR. We also planned to investigate the effect of family history of AD on the prevalence of allergen-specific antibodies. The serum levels of IgE, eosinophil cationic protein (ECP) and major basic protein (MBP) were measured and compared in patients with AD and those with ADR. Proportional analysis compared allergen-specific IgE between AD and ADR. The family aggregation was conducted to estimate the odds ratio for various atopic diseases in different family members. Total IgE and allergen-specific antibodies in serum were compared between those patients who had AD with AR and those without. The result revealed that allergic rhinitis is the most common concomitant atopic disease associated with AD. The ADR group was more likely to have serum mite-, cockroach-, and feather-specific IgE. The positive rates for wheat, peanut and soybean were higher in those AD without rhinitis. In the family aggregation of AD, the odds ratio for siblings was higher than for parents, the ratios for brother and sister were 9.91 and 8.75, respectively. However, the odds ratio for parents of ADR was higher than siblings; the ratios for father and mother of ADR were 8.22 and 2.94, respectively. AD patients with family histories of AD were more likely to have mite-, soybean-, and peanut-specific antibodies in their serum. We concluded that aeroallergens are the most important allergens aggravating atopic diseases in Taiwan. Food plays an important role in the pathogenesis of AD. Measurement of serum total IgE combined with the MAST-CLA test could be helpful in the diagnosis of atopic diseases. The differential aggregation tendency for AD and ADR implicated the complexity of the gene-environment interaction in these atopic diseases.
    J Dermatol. 01/2004; 31(10):784-93.
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    ABSTRACT: Dysregulation of interleukin-6 has been reported to be associated with various types of tumors, and interleukin-6 plays an important part in regulating apoptosis in many types of cells. Previously, Mcl-1 was shown to be significantly increased in interleukin-6-overexpressed basal cell carcinoma cells and conferred on them anti-apoptotic activity. The aim of this study was to investigate which signaling pathway is involved in the anti-apoptotic effect of interleukin-6 on basal cell carcinoma cells. Here we show that the addition of recombinant 100 ng per ml interleukin-6 to basal cell carcinoma cells induced a 2.3-fold increase in the level of Mcl-1 protein in basal cell carcinoma cells. Transfection with dominant-negative STAT3 (STAT3F) into inter-leukin-6-treated basal cell carcinoma cells caused a decrease of phosphotyrosyl STAT3 but did not alter Mcl-1 protein levels; however, AG490, a Janus tyrosine kinase inhibitor, was capable of inhibiting the interleukin-6-induced elevation of Mcl-1 protein. Next, interleukin-6 stimulation elicited extracellular signal-regulated kinase activation in basal cell carcinoma cells, and the mitogen-activated protein kinase inhibitor, PD98059, could affect this response without affecting the interleukin-6-medi-ated Mcl-1 upregulation. Use of the two phosphotidyl inositol 3-kinase inhibitors, LY294002 and wortmannin, to check whether this pathway is involved in Mcl-1 upregulation by interleukin-6, we found that the phosphotidyl inositol 3-kinase inhibitors completely attenuated the interleukin-6-induced Mcl-1 upregulation. Furthermore, in the interleukin-6-overexpressing basal cell carcinoma cell clone, dominant-negative Akt also significantly reduced the increased level of Mcl-1. Interestingly, Janus tyrosine kinase inhibitor, AG490, treatment strongly blocked the phosphotidyl inositol 3-kinase pathway activation, as evidenced by the decrease in phospho-Akt level. Blockage of phosphotidyl inositol 3-kinase/Akt pathway abolished the interleukin-6-mediated anti-apoptotic activity in ultraviolet B treated cells. Unexpectedly, without ultraviolet B irradiation, STAT3F transfection also induced a significant apoptosis in basal cell carcinoma/interleukin-6 cells. Taken together, our data suggest that both the phosphotidyl inositol 3-kinase/Akt and STAT3 pathways are potentially involved in interleukin-6-mediated cell survival activity in basal cell carcinoma cells; however, the upregulation of the anti-apoptotic Mcl-1 protein by interleukin-6 is mainly through the Janus tyrosine kinase/phosphotidyl inositol 3-kinase/Akt, but not the STAT3 pathway.
    Journal of Investigative Dermatology 12/2002; 119(5):1121-7. · 6.19 Impact Factor
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    ABSTRACT: This presentation focuses on the four most important skin diseases in Taiwan thought to be of environmental and/or occupational origin. The majority of work-related dermatoses are contact dermatitis patients. Among occupational contact dermatitis patients, 58.5% involved irritant and 41.5%, allergic dermatitis. Electronics, hairdressing, medical practice, and construction were the most important occupations causing contact dermatitis. An endemic occurrence of chronic arsenism causing hyperpigmentation, keratosis, and cancer has been reported in Taiwan. Arsenical skin cancers present as multiple lesions at different disease stages. The skin cancers are usually found in non-sun-exposed areas. UVB exerts an inhibitory effect on the proliferation of arsenical cancers; this may explain its non-sun-exposed nature. An outbreak of premalignant and malignant skin lesions was reported among paraquat manufacturers in 1985. The skin lesions were mainly distributed over the sun-exposed areas. Photodamage and photocarcinogenesis revealed a strong association with exposure to bipyridines among paraquat manufacturers. In 1979, a mass poisoning occurred in Taiwan from cooking oil contaminated by polychlorinated biphenyls (PCBs). Over 60% of patients were in grades O-II by the Japanese classification. The blood PCB levels of the Taiwanese patients were found to be higher than those of the Yusho subjects.
    The Journal of Dermatology 12/2001; 28(11):628-31. · 1.77 Impact Factor
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    ABSTRACT: Interleukin-6 (IL-6) is a pleiotropic cytokine that is capable of modulating the diverse functions of cells such as acute phase responses and inflammation. Excessive or insufficient production of IL-6 may contribute to certain diseases of the skin. The aim of this study was to investigate the possible role of IL-6 in the tumorigenesis of basal cell carcinoma (BCC). Initially, we transfected IL-6 expression vector, under the control of a CMV promoter, into human BCC cells and successfully obtained IL-6-overexpressing clones (BCC/IL-6-c1 and BCC/IL-6-c2) and a mixture (BCC/IL-6). DNA synthesis assay determined using (3)H-thymidine pulse incorporation revealed that IL-6-expressing BCC cells exhibited a much higher DNA synthesis rate than the neo control or parental BCC cells. We also detected a greater abundance of IL-6-expressing cell colonies formed in soft agar than in the vector control cells. Furthermore, BCC/IL-6 cells, but not vector control cells, were resistant to UV and photodynamic therapy (PDT)-induced apoptosis, as confirmed using DNA fragmentation and morphologic change analyses. Immunoblot analysis showed that Mcl-1, an anti-apoptotic protein, was specifically up-regulated IL-6 transfectants but not in the control cells. Transient transfection of IL-6 transfectants with antisense mcl-1 greatly enhanced their apoptosis frequency by UV treatment. In tumorigenesis assay, IL-6 transfected clones formed tumors in nude mice more rapidly than the control cells. These tumors appeared to be highly vascularized using pathological examination. Supportive of this finding, we found that IL-6 transfected cells expressed elevated levels of two angiogenic factors, cyclooxygenase (Cox)-2 and vascular endothelial growth factor (VEGF). These results suggest that overexpression of IL-6 enhances the tumorigenic activity of BCC cells by both suppressing apoptosis and actively promoting angiogenesis.
    Oncogene 02/2001; 20(2):198-208. · 7.36 Impact Factor
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    ABSTRACT: Topical use of alpha-hydroxy acid (AHA) may increase skin photosensitivity, as demonstrated by increased numbers of sunburst cells. However, effects of AHA on tanning have not been studied. Our purpose was to study whether short-term use of glycolic acid hastens resolution of pre-existing light-induced pigmentation and whether the skin becomes tan more easily in Asian and Caucasian subjects after such treatment. Six Asian and six Caucasian volunteers received separate irradiations of UVB and UVA to both sides of the lower back. In a double-blind fashion, patients then applied a 10% glycolic acid gel, pH 3.52, to one side of the back, including the irradiated area, and the contralateral extensor forearms once daily for 7 days and then twice daily for 2 weeks. A placebo gel, pH 5.75, was applied to the opposite sides. The subjects returned for measurement of residual tanning with a colorimeter and received additional irradiation to forearms and a second site on the back. Resulting pigmentation was measured immediately after irradiation, at 2 hours, and at 1 week. Increased UVB-induced skin tanning occurred on the forearm and the lower back in both races in areas pretreated with glycolic acid. UVA also caused increased tanning, but only on the extensor forearms in Asian subjects. Treatment with glycolic acid for 3 weeks had no effect on pre-existing light-induced pigmentation. Short-term topical treatment of glycolic acid caused an increase in UVB tanning as well as in UVA tanning in some subjects, even in the absence of overt irritation. The inclusion of UVB, and even UVA, sunscreen in AHA products may be warranted.
    Journal of the American Academy of Dermatology 09/2000; 43(2 Pt 1):238-43. · 4.91 Impact Factor
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    ABSTRACT: Curcumin, a potent antioxidant and chemopreventive agent, has recently been found to be capable of inducing apoptosis in human hepatoma and leukemia cells by way of an elusive mechanism. Here, we demonstrate that curcumin also induces apoptosis in human basal cell carcinoma cells in a dose- and time-dependent manner, as evidenced by internucleosomal DNA fragmentation and morphologic change. In our study, consistent with the occurrence of DNA fragmentation, nuclear p53 protein initially increased at 12 h and peaked at 48 h after curcumin treatment. Prior treatment of cells with cycloheximide or actinomycin D abolished the p53 increase and apoptosis induced by curcumin, suggesting that either de novo p53 protein synthesis or some proteins synthesis for stabilization of p53 is required for apoptosis. In electrophoretic mobility gel-shift assays, nuclear extracts of cells treated with curcumin displayed distinct patterns of binding between p53 and its consensus binding site. Supportive of these findings, p53 downstream targets, including p21(CIP1/WAF1) and Gadd45, could be induced to localize on the nucleus by curcumin with similar p53 kinetics. Moreover, we immunoprecipitated extracts from basal cell carcinoma cells with different anti-p53 antibodies, which are known to be specific for wild-type or mutant p53 protein. The results reveal that basal cell carcinoma cells contain exclusively wild-type p53; however, curcumin treatment did not interfere with cell cycling. Similarly, the apoptosis suppressor Bcl-2 and promoter Bax were not changed with the curcumin treatment. Finally, treatment of cells with p53 antisense oligonucleotide could effectively prevent curcumin-induced intracellular p53 protein increase and apoptosis, but sense p53 oligonucleotide could not. Thus, our data suggest that the p53-associated signaling pathway is critically involved in curcumin-mediated apoptotic cell death. This evidence also suggests that curcumin may be a potent agent for skin cancer prevention or therapy.
    Journal of Investigative Dermatology 11/1998; 111(4):656-61. · 6.19 Impact Factor
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    ABSTRACT: We report a 28-year-old young male with MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes) presenting with two previous episodes of stroke-like manifestation, lactic acidosis and mitochondrial cardiomyopathy. He was also affected with insulin-dependent diabetes mellitus (IDDM), as diagnosed by the experience of diabetic ketoacidosis (DKA), and dependence on insulin therapy. On admission, the serum lactate level was found to be increased to 5.4 mmol/l, and plasma glucose level to 7.9 mmol/l with haemoglobin A1c 8.4%, while he was using insulin 26-30 units per day. Physical examination revealed a short stature male of height of 150 cm and weight of 49 kg. Mild mental retardation with bilateral sensorineural hearing impairment was observed. After glucagon stimulation, C-peptide levels rose from 0.46 nmol/l to 0.53 nmol/l, indicative of impaired insulin secretion. Anti-glutamate decarboxylase (anti-GAD) antibody was positive. In addition, human leucocyte associated antigen (HLA) typing showed DR3 and DR4, suggesting the strong contribution of autoimmunity to the pathogenesis of IDDM in this patient. Moreover, the result of a treadmill exercise test was positive due to inferior wall myocardial ischaemia. Cardiac catheterization and endomyocardial biopsy disclosed a normal coronary angiogram and confirmed the diagnosis of mitochondrial cardiomyopathy. Molecular genetic analysis of his family revealed a sporadic occurrence of mitochondrial DNA (mtDNA) mutation at base pair (bp) 3243. The degree of heteroplasmy of mtDNA mutation from a total of 19 passages of skin-derived fibroblasts from this patient showed a slightly downward trend. This extremely rare case of sporadic MELAS syndrome with autoimmune IDDM harbouring mtDNA mutation highlights the possible pathogenetic role of mtDNA mutations in autoimmune disease.
    Clinical Endocrinology 09/1998; 49(2):265-70. · 3.40 Impact Factor
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    ABSTRACT: In this study, we investigated the involvement of reactive oxygen species (ROS) in the motorcycle exhaust particle (MEP)-induced genotoxic and non-genotoxic activity in mammalian cell systems. Initially, the capability of MEP to induce ROS was evaluated by using 2',7'-dichlorofluorescin diacetate (DCFH-DA) to detect hydrogen peroxide (H2O2). A five-fold increase in H2O2 was observed in Chinese hamster lung V79 and human lung carcinoma Calu-1 cells treated with 100 microg/ml MEP for 2 h. Under the same experimental conditions, only a two-fold elevation in H2O2 was detected in hepatic cell systems such as BNL.Cl.2, HepG2, and Hep3B. Treatment of the V79 cells with varying concentrations of MEP caused a dose-dependent increase in sister chromatid exchanges (SCEs), which are effectively inhibited by addition of antioxidants, N-acetyl-l-cysteine (NAC) and ascorbic acid. Furthermore, we determined the oxidized bases in the V79 cells after exposure to MEP. The result showed that 500 microg/ml MEP induced a 3.7-fold increase in thymine glycol (TG) and a seven-fold increase in 8-hydroxy-guanosine (8-OHGua) as compared to untreated cells. We subsequently examined whether MEP would affect gap junctional intercellular communication (GJIC), a tumor promotion process, in V79 cells. We found that MEP inhibited GJIC in a dose-response fashion. Maximal inhibition occurred at 500 microg/ml. The concentration that inhibited at 0.5 of the fraction of the control was 200 microg/ml. Interestingly, when cells were pretreated with NAC or ascorbic acid, they could abolish the MEP-mediated inhibition of GJIC. In addition, a moderate decrease of glutathione was observed in the V79 cells during exposure to MEP. Taken together, our findings suggest that MEP can induce oxidative stress in a broad range of cell lines, especially in lung cell systems. The MEP-induced oxidative stress was critically involved in both genotoxic and non-genotoxic activity.
    Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 04/1998; 413(2):143-50. · 3.90 Impact Factor
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    ABSTRACT: The p34cdc2 kinase is a highly regulated serine-threonine kinase that, when complexed with cyclins A and B, controls cell entry into mitosis. Recently, premature activation of p34cdc2 was shown to be required for apoptosis induced by a wide variety of agents. Here, we show that Taxol induced p34cdc2 kinase activity with a peak at 6 h in human breast carcinoma MCF-7 cells. We subsequently observed that the activation of CPP32/Yama protease as well as the cleavage of its substrate poly(ADP-ribose) polymerase occurred 9 h after Taxol treatment. Olomoucine, a potent p34cdc2 inhibitor, effectively prevented Taxol-induced p34cdc2 kinase activation and subsequent apoptosis. Furthermore, the treatment of cells with cyclin B1-specific antisense oligonucleotide also blocked Taxol-induced apoptosis, suggesting that cyclin B1-associated p34cdc2 kinase plays an important role in the induction of apoptosis by Taxol. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a protein kinase C activator, was found to exert strong protection against Taxol-induced cell death in MCF-7 cells. TPA inhibited Taxol-mediated activation of p34cdc2 kinase by preventing the dephosphorylation of the Tyr-15 residue on p34cdc2 without altering the levels of Cdc2 and cyclin B1. In contrast, the ability of Taxol to enhance tubulin polymerization was not inhibited by TPA. These findings suggest that modulation of protein kinase C signaling can protect against Taxol-induced cell death by inhibiting p34cdc2 kinase activation.
    Cell growth & differentiation: the molecular biology journal of the American Association for Cancer Research 02/1998; 9(1):23-9.
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    ABSTRACT: Ceramide, a product of sphingomyelin turnover, is a novel lipid second messenger that mediates important cellular functions including proliferation, differentiation and apoptosis. This study demonstrates that the CPP32/Yama protease was activated during apoptosis induced by the membrane-permeable second messenger C2-ceramide in HL-60 cells. We also found that the addition of a specific tetrapeptide inhibitor of CPP32/Yama, Ac-DEVD-CHO, provided an effective protection against ceramide-induced cell death. These results suggested that CPP32/Yama has a central role in ceramide-mediated apoptosis. Furthermore a wide variety of cytokines were examined for their effect on ceramide-induced apoptosis. Only transforming growth factor beta1 (TGF-beta1) (1 ng/ml) exerted significant prevention of apoptosis induced by C2-ceramide, or by sphingomyelinase (increases intracellular ceramide). Consistently, TGF-beta1 abrogated the cleavage of poly(ADP-ribose) polymerase and the production of the CPP32/Yama active subunit, p17. However, TGF-beta1 treatment did not cause growth inhibition or alter the level of cyclin-dependent kinase inhibitor p27. It suggests that the preventive effect of TGF-beta1 is not mediated by growth arrest. Interestingly, we found that TGF-beta1 prevented the C2-ceramide-caused decrease of Bcl-2 protein. We thus propose that TGF-beta1 rescues ceramide-induced cell death, possibly by maintaining the constant level of Bcl-2, thereby abolishing CPP32/Yama protease activation.
    Biochemical Journal 12/1997; 327 ( Pt 3):663-7. · 4.65 Impact Factor
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    ABSTRACT: The morphologic and functional characteristics of cultured hair follicle dermal papilla (DP) cells, dermal sheath (DS) cells and interstitial dermal fibroblasts (DF cells) derived from human scalp tissue are compared. DP and DS cells, but not DF cells, showed aggregative behavior at a preconfluent density. All three types of cells stained positive for type I collagen, type IV collagen, laminin and heparan sulfate proteoglycan. Only DP and DS cells expressed smooth muscle alpha-actin. DP and DS cells also synthesized more glycosaminoglycans (GAG) than DF cells, while there was no significant difference between DP and DS cells in GAG synthesis. Ultrastructurally, 7 out of 10 strains of DP and 2 out of 10 strains of DS cells were found to form intranuclear rodlets, while none of the 10 strains of DF cells examined formed intranuclear rodlets. The conditioned medium of the three types of cells was collected and tested for the presence of interleukin (IL)-1 beta, tumor necrosis factor (TGF)-beta 2, IL-6, platelet-derived growth factor-AB, epidermal growth factor, b-FGF, GM-CSF, insulin-like growth factor (IGF)-1 and HGF (hepatocyte growth factor) by ELISA or RIA. Among the tested cytokines and growth factors, TGF-beta 2, IL-6 and IGF-I were detectable in at least some conditioned media. The others were undetectable. There was no significant difference in the production of IL-6 and IGF-I among the three types of cells. In contrast, DP cells produced the highest levels of TGF-beta 2, DS cells produced intermediate levels of TGF-beta 2, and DF cells produced the lowest levels of TGF-beta 2. DP and DS cells are morphologically and functionally different from the nonfollicular, interstitial DF cells. Moreover, the presence of some minor biologic differences between DP and DS cells suggests that they represent follicular mesenchymal cells in different functional or differentiation states.
    Journal of the Formosan Medical Association 10/1996; 95(9):667-74. · 1.00 Impact Factor
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    ABSTRACT: Paraquat manufacturers in Taiwan have been found to develop solar lentigo, actinic keratosis, as well as skin cancer in sun-exposed areas. Bipyridine has been found to be the responsible agent. At present, the mechanism for the pathogenesis of bipyridine-induced skin cancer is not known and it may be multifactorial. We investigated possible alterations in tumor necrosis factor (TNF)-alpha secretion in keratinocytes treated with 4,4'-bipyridyl dihydrochloride in vitro. Normal human keratinocytes were cultured and treated with bipyridine (10 micrograms/mL) or ultraviolet B (UVB) light (10 mJ/cm2), or with a combination of both. Bipyridine treatment alone resulted in a significant reduction in constitutive TNF-alpha secretion. Furthermore, in contrast to the finding in normal keratinocytes, UVB irradiation failed to promote TNF-alpha secretion in bipyridine-primed keratinocytes.
    Journal of the Formosan Medical Association 10/1996; 95(9):706-8. · 1.00 Impact Factor
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    ABSTRACT: An outbreak of severe itching, erythematous and edematous dermatitis over the extremities and upper back developed in 8 of 17 workers in the raw-materials department of a paint manufacturing factory. The outbreak occurred during a 2-month period when Acticide EP paste (Thor Chemical, Cheshire, UK) was used in place of Metatin as a microbiocide (Acima Chemical, Buchs, Switzerland). To evaluate the frequency and the etiologic agent of this outbreak, a plant walk-through, examination and review of photographs of skin lesions followed by statistical analysis for association between the development of dermatitis and exposure to Acticide paste were performed. Three guinea pigs were subjected to patch tests comparing the dermatotoxicity of Acticide EP and Metatin. The results showed that 8 out of 17 workers (47%) suffered from contact dermatitis during the 2-month period. Stratification by occupational exposure further confirmed the association between the development of dermatitis and exposure to the Acticide paste. The dermatotoxicity test on guinea pigs revealed the marked corrosive effect of the paste and the absence of dermatotoxicity of Metatin. After the removal of the paste from the raw material, there were no new cases of contact dermatitis at the 6 month follow-up. We conclude that Acticide EP paste was the responsible offending agent. Because isothiazolinone derivatives are well-known antigens and 2-n-octyl-4-isothiazolin-3-one is the active ingredient in Acticide EP paste, 2-n-octyl-4-isothiazolin-3-one is the likely cause of the dermatitis.
    Journal of the Formosan Medical Association 09/1996; 95(8):628-31. · 1.00 Impact Factor
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    ABSTRACT: Topical silicone gel or silicone cream with occlusive dressing has proved to be an efficacious method for the treatment and prevention of hypertrophic scars and keloids, but how this action is triggered remains unknown. Hydration of the epidermis and/or the cellular effects of the released low-molecular-weight silicone oil have been suggested as possible mechanisms. In order to further elucidate the mechanism, we used an in vitro keratinocyte-fibroblast coculture model to investigate the cellular effects of silicone and hydration. In this model, the condition of clinical usage of topical silicone gel or cream or the condition of hydration exerted by occlusive dressing could be mimicked. The model consisted of two chambers separated by a semipermeable membrane, in which a fully differentiated stratified epithelium is present in the upper chamber and medium and monolayer fibroblasts are located in the lower chamber. The keratinocytes were nourished from the basal side only, while the apical surface was submerged in silicone oil, paraffin, Hanks' balanced salt solution, or medium (hydration); or it was exposed to air (control). In the hydration-treated group, the proliferation of fibroblasts measured as [3H]thymidine incorporation and their collagen, glycosaminoglycan production was significantly inhibited when compared with the controls, but exposure of the keratinocyters to silicone oil or paraffin did not influence fibroblast behavior. The results suggest that hydration, not silicone, modulates the in vitro keratinocyte-fibroblast interaction. This may be one possible mechanism by which topical silicone or occlusive dressing treatment may affect the development of hypertrophic scars and keloids.
    Journal of Surgical Research 01/1996; 59(6):705-11. · 2.02 Impact Factor
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    ABSTRACT: We report familial acanthosis nigricans affecting a 35-year-old woman, her 7-year-old son and 5-year-old daughter. Absence of the eyebrows and eyelashes was noted in this family. The mother had no axillary hair and her pubic hair was sparse. The boy also suffered from congenital heart disease and a congenital cataract in the left eye. The combination of acanthosis nigricans and ectodermal defects in this family may represent a distinct nosological entity.
    British Journal of Dermatology 08/1995; 133(1):104-8. · 3.76 Impact Factor
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    ABSTRACT: Some workers in paraquat manufacturing, exposed to bipyridines, have developed pigmentation and keratosis on sun-exposed skin. This condition has been described as skin-malignancy or premalignancy. This study was designed to clarify the pathologic features of these lesions and to explore the etiologic role played by bipyridine. Twenty-three biopsy specimens, obtained from the affected skin of 10 workers, were scrutinized by a dermatopathologist. A total of 242 exposed workers from 28 paraquat factories were examined and interviewed during the period from 1983 to 1991. The severity of the characteristic skin lesions was graded from the lowest to the highest response to analyze the data by Mantel extension for a trend that focused on the heavy exposure to bipyridines as risk factor. All pathology specimens showed various degrees of solar damage: early actinic change, solar lentigo, actinic keratosis (AK), AK coexisting with squamous cell carcinoma (scc), and scc. Six specimens from four workers were scc or scc in situ. Three of six scc showed the coexistence of AK. Of the workers, 133 had skin lesions ranging in severity from grade 1 to grade 3 on sun-exposed areas. The severity of skin changes is strongly associated with heavy exposure to bipyridines (P < 0.0001). This pathologic study proves that all the lesions showed either photodamage or skin cancer. The strong trend in the correlation between severity of photodamage and exposure to bipyridine leads to the speculation about the synergistic role of bipyridine exposure and the solar effect in causing these malignant and premalignant skin lesions.
    International Journal of Dermatology 08/1995; 34(7):466-9. · 1.34 Impact Factor
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    ABSTRACT: We have investigated point mutations of codons 12, 13, and 61 in H-, K-, and N-ras oncogenes as well as p53 tumour suppressor gene exon 5 through exon 9 by PCR-SSCP analysis in 26 skin biopsy tissues from 16 arsenic-related Bowen's disease patients and 6 skin samples from 4 paraquat manufacturing workers. No mutation was found. These results are different from findings with UV associated skin cancers. Interestingly, a silent change at codon 27 of H-ras in one allele was detected in all 4 paraquat manufacturing workers and in 2 of 16 arsenic-related Bowen's disease patients. It is likely that the molecular mechanisms involved in arsenic and paraquat induced skin cancers differ from sunlight-related skin malignancies.
    Cancer Letters 11/1994; 86(1):59-65. · 4.26 Impact Factor
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    ABSTRACT: Human scalp specimens were incubated in 5 U/ml dispase solution at 4 degrees C overnight before the isolation of dermal papillae and follicle epithelium. This pretreatment not only facilitated the attachment and cell outgrowth of dermal papillae but also made it easier to pluck out hairs with intact follicle epithelium. The outer root sheath cells were released from the follicle epithelium and grown on a feeder layer of mitomycin C-treated human dermal fibroblasts. The subcultured outer root sheath cells were grown in a serum-free medium. When the mixtures of early-passage dermal papilla cells and outer root sheath cells were injected into the subcutis of nude mice, an epidermal cyst surrounded by layers of fibrous tissue was found in three weeks. No hair follicles were found when the mixtures were implanted onto the chorioallantoic membrane of nine-day-old chicken embryos. A keratinized mass lying on the chorionic epithelium with or without smaller similar masses in the chorioallantoic membrane was found in eight days. No hair follicle-like structure could be found. Possible factors contributing to the failure to undergo follicular differentiation in this study are discussed.
    Journal of the Formosan Medical Association 10/1994; 93(9):770-5. · 1.00 Impact Factor