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Biomedical subjects

S Im

Publications and source records attributed to S Im.

At least 37 records · Page 2Linked to original sources
PubMed1996

Identification of autoantibody to melanocytes and characterization of vitiligo antigen in vitiligo patients.

Patients with vitiligo have circulating antibodies to melanocytes. To identify vitiligo antibodies and characterize the antigens by vitiligo antibodies, sera of 18 patients with vitiligo, 18 with Behcet's disease, 22 with syphilis and 14 normal control subjects were analyzed by indirect immunofluorescence, live cell ELISA, and immunoblotting. In indirect immunofluorescent microscopy and live cell ELISA, most vitiligo sera showed positive immunofluorescence and high optical density on the surface of melanocytes cultured from normal and vitiligo patients, indicating that autoantibodies in the vitiligo sera may react with vitiligo antigens on the surface of melanocytes. When the same experiments were performed with malignant melanoma cell lines and fibroblasts, no significant differences in the immunofluorescence and optical density were observed between normal and vitiligo sera. And the sera of patients with Behcet's disease or syphilis showed no significant difference in the reaction of live cell ELISA to fibroblasts, IGR-3 and melanocytes. The antibody titers of vitiligo patients in live cell ELISA decreased following systemic steroid treatments. Immunoblot analysis demonstrated that 44% of vitiligo sera was directed to melanocyte antigen with a molecular weight of 65 kDa. Inhibition assay using rabbit anti-melanocyte antibody showed inhibition of reaction between vitiligo sera and melanocytes in ELISA and immunoblotting. These findings support the hypothesis that the sera of vitiligo patients have autoantibodies mostly directed to the 65-kDa antigen and this antigen may originate mostly from the melanocyte surface.

Animals↗
PubMed1996

Binding of melanotropic hormones to the melanocortin receptor MC1R on human melanocytes stimulates proliferation and melanogenesis.

alpha-Melanocyte stimulating hormone (alpha-MSH) and ACTH increase the proliferation and melanogenesis of cultured human melanocytes. To further analyze how melanotropins produce these biological effects, we investigated the regulation of the melanocortin receptor MC1R expression by alpha-MSH and ACTH using Northern blot analysis and determine the relative affinity of the receptor for the structurally similar peptides alpha-MSH, ACTH, beta-MSH, and gamma-MSH. We also determined the relative potencies of these hormones to stimulate cAMP formation, tyrosinase activity, and melanocyte proliferation. The order of affinity and potency of the noted melanotropins in these assays were alpha-MSH = ACTH > beta-MSH > gamma-MSH. Because the binding affinity of each of these melanotropins for the MC1R correlated with its ability to stimulate human melanocyte proliferation and melanogenesis, we conclude that these effects are mediated specifically by binding to and activation of the MC1R. gamma-MSH stimulated cAMP formation without affecting proliferation or melanogenesis. However, we found that relative to alpha-MSH, the effect of gamma-MSH on cAMP formation was transient. Our results suggest that alpha-MSH, ACTH, and possibly beta-MSH, but not gamma-MSH, are capable of a physiological role in regulating human pigmentation, and that melanocytes in human skin are a specific target for these hormones.

Adrenocorticotropic Hormone↗
PubMed1995

Comparison of the responses of human melanocytes with different melanin contents to ultraviolet B irradiation.

Melanin is thought to serve in photoprotection. To investigate this, we have compared the responses of cultured human melanocytes derived from different pigmentary phenotypes (skin types I-VI) to a single irradiation with different doses of UVB light, ranging between 11.7 and 70.1 mJ/cm2. After UVB irradiation, heavily pigmented melanocytes had the same percent survival but a greater capacity to resume proliferation than their lightly pigmented counterparts. A significant increase in melanin content was observed in heavily pigmented but not in lightly pigmented melanocytes. Irradiation with UVB light blocked melanocytes, regardless of their melanin content, in G1, and induced the expression of the tumor suppressor p53 protein within 4 h. This induction steadily increased up to 48 h in lightly pigmented melanocytes; however, in heavily pigmented melanocytes, p53 level peaked at 24 h after UVB treatment and declined thereafter. Additionally, DNA from lightly pigmented melanocytes contained significantly higher numbers of cyclobutane pyrimidine dimers than did DNA from heavily pigmented melanocytes after irradiation with increasing doses of UVB light. We speculate that the prolonged induction of p53 in lightly pigmented melanocytes arrests them in G1 for a long time period in order to repair extensive DNA damage. The above described differences might partially explain the increased susceptibility of individuals with lightly pigmented skin compared to individuals with dark skin to the photodamaging and photocarcinogenic effects of sun exposure.

Cell Cycle↗
PubMed1995

Ultraviolet B light induces G1 arrest in human melanocytes by prolonged inhibition of retinoblastoma protein phosphorylation associated with long-term expression of the p21Waf-1/SDI-1/Cip-1 protein.

UVB irradiation inhibits melanocyte proliferation by causing arrest in G1 (D. Barker, K. Dixon, E. E. Medrano, D. Smalara, S. Im, D. Mitchell, G. Babcock, and Z. A. Abdel-Malek. Cancer Res., 55: 4041-4046, 1995). To determine how, after UVB irradiation, signal transduction pathways, DNA damage, and cell cycle arrest interact in the human melanocyte, we analyzed here the possible activation of tyrosine kinases, the serine-threonine kinases Baf-1 and ERK2, the status of the transcription factor c-fos, and the activation of cell cycle checkpoints induced by expression of p53 protein. We found that in contrast to the UVC response, exposure to UVB irradiation did not stimulate the above kinases. UVB light induced a prolonged c-fos expression, suggesting a mechanism of induction different from the transient expression elicited by growth factors. The tumor suppressor p53 and the p53-inducible cyclin-dependent kinase inhibitor protein p21Waf-1/SDI-1/Cip-1 were expressed at high levels for at least 2 days after UV-irradiation. In parallel, phosphorylation of Rb, the retinoblastoma tumor suppressor gene product, was halted in UVB-irradiated cells and correlated with the expression of the protein p21Waf-1/SDI-1/Cip-1. Our data define for the first time how UVB irradiation affects the expression of crucial regulatory events needed for cell cycle progression in the human melanocyte.

Cells, Cultured↗
PubMed1995

Treatment of stable vitiligo with autologous epidermal grafting and PUVA.

BACKGROUND: Previous reports have shown the benefits of epidermal grafting for vitiligo. OBJECTIVE: Our purpose was to evaluate the effectiveness and complications of epidermal grafting in combination with PUVA on stable vitiligo refractory to conventional treatments. METHODS: In 100 patients with stable refractory vitiligo we performed epidermal grafting with suction blisters followed by PUVA treatment. The grafted sites were examined for repigmentation for up to 5 years. RESULTS: Excellent repigmentation was observed at all grafted sites, especially on the face except for the lip and the alae nasae. PUVA treatment resulted in spreading of the pigmentation. Poor results were observed on the neck, axillae, and overlying bony prominences. Hyperpigmentation of the recipient and donor sites was frequently observed. Only six patients had recurrence and/or adjacent new lesions. Depigmentation developed at the donor site in only one patient with generalized vitiligo. Long-term observation in these patients indicates that repigmentation obtained by this method is permanent. CONCLUSION: Although epidermal grafting in combination with PUVA has some limitations, it is an easy, safe, inexpensive, and effective treatment for various types of stable refractory vitiligo.

Adolescent↗
PubMed1994

Biologic characteristics of cultured human vitiligo melanocytes.

BACKGROUND: Vitiligo is a pigmentary disorder of unknown cause characterized by depigmented patches due to destruction of melanocytes. Recently, the inherent cellular defect theory has been discussed. To investigate the biologic characteristics of cultured melanocytes from normal and vitiligo subjects, this study had the purpose to examine the functional and ultrastructural characteristics of these melanocytes and to observe the morphologic and functional changes of melanocytes in response to ultraviolet B irradiation. METHODS: Melanocytes were isolated and cultured from foreskin and arm skin of normal and vitiligo subjects. The DNA synthesis, tyrosinase activity assay, transmission and scanning electron microscopic examination, and the effects of ultraviolet B(UVB)-irradiation on cultured melanocytes were studied. RESULTS: Vitiligo melanocytes showed no significant differences in DNA synthesis and tyrosinase activity compared with normal melanocytes, but the vitiligo melanocytes contained dilated and/or circular rough endoplasmic reticulum (RER) on transmission electron microscopic examination. Exposure of the cultured melanocytes to UVB resulted in increased protein synthesis and tyrosinase activity. Morphologic alterations and changes in DNA synthesis were also noted. Compared with normal melanocytes, the responses of vitiligo melanocyte to UVB showed no significant difference. CONCLUSIONS: Normal and vitiligo melanocytes showed similar biologic characteristics except in the changes of RERs in the vitiligo melanocytes. The ultrastructural aberrations in vitiligo subjects do not seem to be directly related to the biologic characteristics and the responses to UVB irradiation in vitiligo melanocytes.

Cell Division↗
PubMed1993

The change of melanocyte cytotoxicity after systemic steroid treatment in vitiligo patients.

Although there is evidence of a strong association between antimelanocyte autoantibodies and vitiligo, the etiology of vitiligo is still unclear. To elucidate the biological significance of antimelanocyte autoantibodies in vitiligo, we measured the percent cytotoxicity of melanocyte mediated by autoantibody and complement in normal controls (n = 31) and in the patients with active, progressive vitiligo (n = 37). Significant differences in percent cytotoxicity of melanocyte were seen between the control and vitiligo groups (P = 0.0001). There were no significant differences in the percent cytotoxicity of melanocyte between the patients (n = 24) with more than 1 year duration and those (n = 13) with less than 1 year duration. The change of percent cytotoxicity between pre- and post-treatment groups (n = 29) with systemic steroid showed significant differences (P = 0.0243). These findings support the hypothesis that a decrease in the antibody-mediated cytotoxicity against melanocytes may play a role in the improvement of vitiliginous lesions after systemic steroid treatment.

Adolescent↗
PubMed1993

Skin concentration of 8-methoxypsoralen, 5-methoxypsoralen and 4,5,8-trimethylpsoralen in guinea pigs.

The skin concentrations of 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5,8-trimethylpsoralen (TMP) were studied in the albino guinea pig following oral administration and intraperitoneal injection. The skin concentration of phototoxic drugs after oral administration peaked at 1.5 h, and the concentration of 8-MOP was 3.5 times greater than that of 5-MOP. The skin concentration of TMP was not detected in our study (limit of sensitivity 5 ng/ml). The highest skin concentrations of 8-MOP and 5-MOP after intraperitoneal injection were achieved for both drugs at 0.5 h, with the level of 8-MOP approximately 1.3 times higher than that of 5-MOP. The level of TMP could not be measured even in the case of intraperitoneal injection.

5-Methoxypsoralen↗
PubMed1993

Increased incidence of antismooth muscle antibody in Korean vitiligo patients.

To evaluate the incidence of autoimmune disorders and organ-specific autoantibodies in Korean vitiligo patients, antibodies to nuclear, mitochondrial, smooth muscle, gastric parietal cell, thyroglobulin, and microsomal antigens were screened in 226 vitiligo patients and 120 controls. Of the 226 vitiligo patients, three (1.3%) had thyrotoxicosis and two (0.8%) had diabetes mellitus. The vitiligo patients had an increased incidence of antinuclear (12.4%), antimicrosomal (7.1%), and antismooth muscle antibodies (25.7%). The increased incidence of antismooth muscle antibody was correlated with early onset (less than 15 years), a positive family history of vitiligo, and long duration of vitiligo. These results support an autoimmune origin of vitiligo and suggest that the high incidence of antismooth muscle antibody is a distinctive feature of laboratory findings in Korean vitiligo patients.

Adolescent↗
PubMed1993

Peripheral blood lymphocyte imbalance in Koreans with active vitiligo.

BACKGROUND: An immune-mediated destruction of melanocytes is the most popular current theory of vitiligo. There have been a few published reports on the assessment of lymphocyte population in vitiligo, and they showed mixed results. The purpose of our investigation was to assess peripheral lymphocyte subpopulations in Koreans with actively spreading vitiligo. METHODS: Fifty patients with actively spreading vitiligo and 30 normal persons were studied for peripheral blood lymphocyte imbalance using flow cytometry. The percentages of total T-lymphocytes, B-lymphocytes, helper T cells, suppressor T cells, and natural killer cells were evaluated with the use of CD3, CD19, CD4, CD8, and CD16 monoclonal antibodies, respectively. RESULTS: The mean value of helper T cells showed a significant difference between the two groups with the value being 38.2% in patients and 43.5% in control subjects. Seventeen of the 50 patients showed reversed helper/suppressor T cell ratio, whereas only 1 of 30 control subjects showed reversed ratio. There was a statistically significant difference in the mean percentage of helper T cells and suppressor T cells between generalized vitiligo patients and control subjects. The percentage of B cells in patients with recent onset less than 1 year was higher than control subjects and patients with late onset. The mean percentage of natural killer cells was increased significantly in patients with negative autoantibody test. CONCLUSIONS: The present data show that immunologic abnormalities, both cellular and humoral, are involved in the pathogenesis of vitiligo.

Adolescent↗
PubMed1992

Epidermal changes in active vitiligo.

Light and electron-microscopic studies were performed on the vitiligo and adjacent, normal appearing skin from 97 patients with actively spreading vitiligo and 19 patients with stable vitiligo. The vitiliginous skin revealed complete loss of pigment and melanocytes. In addition to degenerative changes in melanocytes, vacuolar changes of basal cells, epidermal infiltration of lymphocytes, dermal infiltration of lymphocytes, and melanophages in the upper dermis were also seen in the normal appearing skin adjacent to vitiliginous skin. These epidermal and dermal changes are more prominent in the skin of actively spreading vitiligo than in stable vitiligo. These findings suggest that the adjacent, normal appearing skin of actively spreading vitiligo shows some characteristic histopathologic findings, especially in the epidermis, indicating that cellular immunity could be involved in the pathogenesis of vitiligo.

Acute Disease↗
PubMed1992

Culture of melanocytes obtained from normal and vitiligo subjects.

The development of human melanocyte culture in vitro from normal adult skin and uninvolved skin of vitiligo patients is essential to investigate the mechanism of depigmentation in vitiligo and other pigmentary dermatoses. By using selective growth and long-term maintenance conditions, we selectively cultured melanocytes derived from normal foreskins and arm skins, and uninvolved foreskins and arm skins of vitiligo patients. The melanocytes of the arm skins were successfully cultured from the roofs of suction blisters. Melanocyte Growth Media (MGM) consisting of MCDB-153 formulation with basic fibroblast growth factor (bFGF), bovine pituitary extract (BPE), insulin, hydrocortisone, phorbol 12-myristate 13-acetate (PMA) and 10% human AB serum was sufficient to grow the melanocytes from normal and vitiligo donors. Melanocytes from uninvolved skin of vitiligo donors showed no different morphologic features, initial seeding capacity and population doubling time compared with those from normal skin. Melanocytes from both cell types grew without any lag period for more than 6 months (6-11 passages). Melanocytes obtained from foreskins had higher initial seeding capacity and shorter population doubling time than those obtained from arm skins using suction-blistered roofs. Our results suggest that the culture method using suction blisters may be a simple and easy way to obtain melanocytes. In addition, vitiligo melanocytes can be successfully cultured with appropriate growth conditions and may show no defective growth patterns. This culture system will be applied to investigate the basic pathophysiology of vitiligo and other various pigmentary dermatoses.

Cells, Cultured↗
PubMed1991

Hydroa vacciniforme with unusually severe scar formation: diagnosis by repetitive UVA phototesting.

Hydroa vacciniforme is a rare, chronic, photosensitive disorder manifested in childhood by recurrent vesicles that heal with scarring. Reproduction of vesicles with repetitive UVA phototesting may be an important diagnostic aid. Recurrent eruption resulted in severe scarring of the face and a flexion contracture of the finger in our patient. The clinical features and laboratory evaluation of hydroa vacciniforme are reviewed.

Adolescent↗
PubMed1991

Treatment of vitiligo with oral 5-methoxypsoralen.

Thirty-six patients with vitiligo were treated with oral 5-methoxypsoralen (5-MOP) and subsequently exposed to UVA irradiation. The patients were treated once or twice weekly over a period of 2-10 months, taking 40-60 mg of 5-MOP 2 hours before exposure to UVA light. The amount of exposure to UVA light was slowly increased according to the patient's tolerance. Eleven (31%) patients showed remarkable repigmentation of the areas of vitiligo within six months. Overall, 78% of the patients showed effective repigmentation. Areas of vitiligo on the face and trunk were more responsive to treatment than those on the distal part of limbs. Adverse effects due to the drug included 2 patients with nausea and 1 patient with headache. It is suggested that treatment with systemic 5-MOP is effective, safe, and useful in selected cases of vitiligo.

Administration, Oral↗
PubMed1991

The ultraviolet B protection effects of topically applied melanosomes onto human skin.

Melanosome is a cellular organelle that is composed of a melanosomal matrix and a brown biochrome, melanin which is formed by tyrosine-tyrosinase reactions. The melanosome is formed within the melanocyte and transferred to the surrounding keratinocytes through dendritic processes. Human skin color is related to the number, size, type and distribution of melanosomes, and the major role of melanosomes is to prevent skin from injurious nonionizing ultraviolet radiation. Controlled NaOH hydrolysis and centrifugation of human hair make it possible to isolate large amounts of melanosomes which are synthesized within the follicular melanocytes and transferred to hair matrix cells. In this study, the sun protection factors of topically applied melanosomes isolated from human hair were evaluated using ultraviolet B phototesting. Topically applied melanosomes increased the minimal erythemal doses. And the sun protection factors of each 50% and 25% melanosomal preparation were 12.3 +/- 5.5 and 3.1 +/- 1.3 respectively, and these ultraviolet B protection effects showed statistically significant differences from 10%, 5% and 1% melanosomal preparations and vehicle. Form these results, the dose-related photoprotective role of melanosomes was confirmed.

Humans↗