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Biomedical subjects

S Im

Publications and source records attributed to S Im.

At least 19 recordsLinked to original sources
PubMed2002

Melasma: histopathological characteristics in 56 Korean patients.

BACKGROUND: Melasma is a common acquired symmetrical hypermelanosis characterized by irregular light to dark brown macules and patches on sun-exposed areas of the skin. Its histopathological characteristics are not fully understood. OBJECTIVES: To characterize the histopathological features of facial melasma skin in comparison with adjacent normal skin. METHODS: Biopsies were taken from both melasma lesional skin and adjacent perilesional normal skin in 56 Korean women with melasma. The sections were stained using haematoxylin and eosin, Fontana-Masson, diastase-resistant periodic acid-Schiff, Masson trichrome and Verhoeff-van Gieson stains, and immunostaining for melanocytes. Data on the changes in number of melanocytes and melanin contents of the epidermis were analysed by a computer-assisted image analysis program. The ultrastructure of the skin was also examined. RESULTS: The amount of melanin was significantly increased in all epidermal layers in melasma skin. The staining intensity and number of epidermal melanocytes increased in melasma lesions. Lesional skin showed more prominent solar elastosis compared with normal skin. Melanosomes increased in number and were more widely dispersed in the keratinocytes of the lesional skin. Lesional melanocytes had many more mitochondria, Golgi apparatus, rough endoplasmic reticulum and ribosomes in their cytoplasm. A dihydroxyphenylalanine reaction was apparent in the cisternae and vesicles of the trans-Golgi network in melanocytes from lesional skin. CONCLUSIONS: Melasma is characterized by epidermal hyperpigmentation, possibly caused both by an increased number of melanocytes and by an increased activity of melanogenic enzymes overlying dermal changes caused by solar radiation.

Adult↗
PubMed2001

Cloning of BNIP3h, a member of proapoptotic BNIP3 family genes.

Apoptosis is regulated by interaction of antiapoptotic Bcl-2 family proteins with various proapoptotic proteins, several of which are also members of the Bcl-2 family. BNIP3 (formerly NIP3) is a proapoptotic mitochondrial protein classified in the Bcl-2 family based on limited sequence homology-3 (BH3) domain and COOH-terminal transmembrane domain. Sequence comparison of BNIP3 has indicated that there are several BNIP3 human homologs of this protein, like BNIP3L, Nix and BNIP3. We have cloned a new member of BNIP3 family from the cDNA library prepared from human dermal papilla cells and designated as BNIP3h. BNIP3h shows substantial homology with other BNIP3 family proteins. BNIP3h induced apoptosis from 24 hours after transfection in MCF7 cell lines and its apoptosis inducing activity is extended until 72 hours after transfection.

Amino Acid Sequence↗
PubMed2001

Anti-tumor effects of human peripheral gammadelta T cells in a mouse tumor model.

Peripheral gammadelta T cells derived from healthy donors were found to exhibit cytotoxicity against a variety of tumor cell lines in vitro, including CNE2, which was established from nasopharyngeal carcinoma (NPC). The anti-tumor effects were further studied in a mouse model. Control nude mice inoculated s.c. with 5 x 10(6) CNE2 cells regularly developed hypodermal tumors, which progressively increased in size, and animals had a mean survival of 35 +/- 3.4 days. Tumor growth was arrested and tumor size was reduced after animals were infused with 5 x 10(7) gammadelta T cells derived from a healthy donor. The anti-tumor effects were temporary, however, and tumor growth was resumed after about 1 week in a group of the animals that had been given a single dose of gammadelta T cells. In another group of animals given 2 doses of gammadelta cells 1 week apart, resumption of tumor growth was delayed for a further week. Mean survival of the 2 groups was increased to 61 +/- 15.7 and 74 +/- 12.9 days, respectively. Immunohistology revealed an accumulation of infused cells in tumors attended by focal tumor necrosis in specimens taken 2 days after infusion. Infiltrative cells virtually disappeared from tumor tissues 6 days after infusion, accompanied by increased mitotic indices of tumor cells. These temporal relationships suggested that the accumulation of infused gammadelta T cells in hypodermal tumors was responsible for the observed anti-tumor effects.

Animals↗
PubMed2001

Distinct tumour specificity and IL-7 requirements of CD56(-)and CD56(+) subsets of human gamma delta T cells.

gamma delta T cells are believed to recognize tissue injury caused by infections, tumours, as well as chemical and physical agents. The present study was carried out to study the feasibility of the ex vivo expansion of gamma delta T cells from healthy individuals, and to determine their functional capacity against tumours. We selectively expanded the peripheral gamma delta T cells of five donors against a myeloma cell line, XG-7. Under optimal conditions, the resulting bulk cultures comprised about 82% of the gamma delta T cells, more than 90% of which showed the T-cell receptor (TCR)-V gamma 9 delta 2 rearrangement. These gamma delta T-cell cultures exhibited TCR-gamma delta dependent cytotoxicity against different tumour cell lines including Molt-4, BJAB, Epstein-Barr virus (EBV) transformed lymphoid cell lines (LCL), and the nasopharyngeal carcinoma (NPC) cell lines, CNE2 and 915, in addition to the stimulator XG-7. By competitive cytotoxicity assays, the gamma delta T cells demonstrated recognition of at least three distinct target specificities expressed by Molt-4, CNE2 and LCL, respectively, which were related to that expressed by the stimulator XG-7 cells. The recognition of the specificity expressed by XG-7 and Molt-4 was further shown to require the participation of heat shock protein (HSP). The specificity expressed by CNE2 and 915 was preferentially recognized by the CD56 subset of gamma delta T cells, which could be sustained in the presence of interleukin (IL)-7. These results suggested that gamma delta T-cell immunity against tumour cell lines may be acquired in response to other types of tissue injury and, hence, implicates a role for their use in the prevention and treatment of tumours.

Burkitt Lymphoma↗
PubMed2001

Application of computerized image analysis in pigmentary skin diseases.

BACKGROUND: Melanocyte number and the amount of melanin pigment are related to diagnosis and treatment of pigmentary skin diseases. Various histologic methods are used, such as Fontana-Masson stain for melanin pigment or immunohistochemical stain for melanocytes. Recently, computerized image analysis has been applied to many fields to avoid interobserver bias. In this study, we applied a computerized image analysis to assess the melanin content and melanocyte density of human epidermis. METHODS: We evaluated the skin biopsy specimens (paraffin blocks) from normal human skin (33 +/- 6.6, n = 11) and diseased skins; vitiligo (32 +/- 10.0, n = 8), melasma (35 +/- 8.6, n = 11), and lentigo senilis (40 +/- 7.2, n = 11) (mean age +/- SD). Each specimen was stained with Fontana-Masson for melanin pigments and immunohistochemical method for melanocytes. Quantitative analysis of melanin pigment and melanocyte number (density) were investigated through two methods: (1) two dermatologists measured the visual scales; and (2) computerized image analysis was used to measure melanin content indices (MCI). The data were evaluated using one-way ANOVA. RESULTS: The visual scale of the Fontana-Masson stain was the highest for lentigo senilis (3.8 +/- 0.40), followed by melasma (2.6 +/- 0.67), normal skin (1.8 +/- 0.60) and vitiligo (0) (P < 0.05). These findings were consistent with objective measurements made by computerized image analysis. MCI values were 120.3 +/- 20.74 for lentigo senilis, 81.1 +/- 19.27 for melasma, 45.5 +/- 16.92 for normal skin, and 0.3 +/- 0.30 for vitiligo in decreasing order (P < 0.05). MC/1E (melanocyte number per 1 mm epidermis) was about two fold larger in lentigo senilis (18.1 +/- 8.92) than melasma (9.7 +/- 2.40) or normal skin (9.3 +/- 2.67) (P < 0.05). MC/1B (melanocyte number per 1 mm basal layer) was about 1.5 fold higher in lentigo senilis (13.5 +/- 4.17), compared to normal skin (9.0 +/- 3.55) (P < 0.05). Melasma showed increased melanocyte numbers compared to normal skin, but it was not statistically significant (P > 0.05). CONCLUSION: We believe this computerized image analysis could be useful tool for diagnosis and comparison of interval changes in pigmentary diseases like melasma or lentigo senilis by quantifying melanin pigments or melanocytes in skin biopsy specimens.

Biopsy↗
PubMed2000

The melanocortin-1 receptor is a key regulator of human cutaneous pigmentation.

The cloning and characterization of the human melanocortin-1 receptor (MC1R) and the demonstration that normal human melanocytes respond to the melanocortins, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotrophic hormone (ACTH), with increased proliferation and eumelanogenesis had put an end to a long-standing controversy about the role of melanocortins in regulating human cutaneous pigmentation. We have shown that alpha-MSH and ACTH bind the human MC1R with equal affinity, and are equipotent in their mitogenic and melanogenic effects on human melanocytes. We also showed that the activation of the MC1R is important for the melanogenic response of human melanocytes to ultraviolet radiation (UVR). The MC1R is also the principal mediator of the inhibitory effects of agouti signaling protein (ASP) on melanogenesis. Expression of the MC1R is subject to regulation by its own ligands alpha-MSH and ACTH, as well as by UVR and endothelin-1. Recent studies that we conducted on the expression of MC1R variants by human melanocytes and the implications of these variants on the function of the MC1R revealed the following. Human melanocytes homozygous for Arg160Trp mutation in the MC1R demonstrated a significantly reduced response to alpha-MSH. Also, this culture responded poorly to ASP and exhibited an exaggerated cytotoxic response to UVR. Another culture, which was homozygous for Val92Met mutation in the MC1R, demonstrated a normal response to alpha-MSH. Heterozygous mutations that are frequently expressed in various melanocyte cultures did not disrupt MC1R function. These results begin to elucidate the significance of MC1R variants in the function of the receptor. Our data emphasize the significance of a normally functioning MC1R in the response of melanocytes to melanocortins, ASP, and UVR.

Agouti Signaling Protein↗
PubMed2000

Expression of progesterone receptor in human keratinocytes.

Despite the various responses of human skin to female sex hormones, cellular and subcellular targets and the mechanisms of action of estrogen and progesterone in human skin are not well understood. The detection of estrogen receptor (ER) and progesterone receptor (PR) in the skin is of great importance to understand the effect of estrogen and progesterone. In primary cultures of human keratinocytes, expression of ER and PR was monitored by immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Paraffin embedded skin tissues were stained with monoclonal antibodies to human ER and PR by immunohistochemistry. Cultured human keratinocytes expressed cytoplasmic PR protein and PR mRNA transcripts. By contrast, ER was detected only at the mRNA level. Suprabasal keratinocytes from samples of pruritic urticarial papules, plaques of pregnancy (PUPPP) and psoriasis were stained positively only for PR, while those from samples of erythema nodosum were negative for both ER and PR. Lesional epidermis of PUPPP showed positive PR immunoreactivity, while nonlesional epidermis did not. No other cells in the normal human skin were stained with ER and PR. The present study suggests that by expressing PR human keratinocytes act as targets for progesterone action.

Adolescent↗
PubMed2000

Assignments of the tyrosinase related protein-1 and -2 genes to human chromosome bands 9p23 and 13q32.1 by in situ hybridization.

To determine the precise chromosomal localization of tyrosine related protein-1 and -2 (TRP-1 and TRP-2) genes by fluorescence in situ hybridization, we used DNAs isolated from human bacterial artificial chromosome clones. They contain genomic sequences with approximately 120 kb inserts for TRP-1 and TRP-2. The TRP-1 and TRP-2 genes were assigned to human chromosome bands 9p23 and 13q32.1, respectively. These results confirmed the previously mapped location for the TRP-1 gene and more precisely located the TRP-2 gene, which had previously been mapped to chromosome 13q31-q32.

Chromosomes, Human, Pair 13↗
PubMed1999

Inhibition of interleukin-12 production in lipopolysaccharide-activated macrophages by curcumin.

Pharmacological control of interleukin-12 production may be a key therapeutic strategy for modulating immunological diseases dominated by type-1 cytokine responses. In this study we investigated the effects of curcumin (1,7-bis[4-hydroxy-3-methoxyphenyl]-1, 6-heptadiene-3,5-dione) on the production of interleukin-12 from mouse macrophages stimulated with lipopolysaccharide. Curcumin potently inhibited the production of interleukin-12 in a dose-dependent manner. The effect of curcumin on interleukin-12 p40 promoter activation was analyzed by transfecting RAW264.7 monocytic cells with p40 promoter/reporter constructs. The repressive effect mapped to a region in the p40 promoter containing a binding site for nuclear factor kappaB (p40-kappaB). Furthermore, activation of macrophages by lipopolysaccharide resulted in markedly enhanced binding activity to the kappaB site, which significantly decreased upon addition of curcumin. These results suggest that curcumin-induced inhibition of interleukin-12 production in macrophages may explain some of the biological effects of curcumin including its anti-inflammatory activity.

Animals↗
PubMed1999

The melanocortin-1 receptor and human pigmentation.

alpha-Melanocyte stimulating hormone (alpha-MSH) is known to be the main physiologic regulator for integumental pigmentation of various vertebrate species. However, the role of alpha-MSH and related melanocortins in the regulation of human cutaneous pigmentation is only beginning to be understood. Cloning of the melanocortin-1 receptor (MC1R), and the feasibility of establishing normal human epidermal melanocyte cultures have made it possible to demonstrate direct and specific biological effects of alpha-MSH on these cells. It is now recognized that both alpha-MSH and ACTH have similar mitogenic and melanogenic effects on human epidermal melanocytes. These effects are mediated by binding of these hormones to the specific MC1R that recognizes them both with similar affinity. Human MC1R is homologous to its mouse counterpart in that its activation leads to stimulation of eumelanin synthesis. MC1R is also the binding site for agouti signaling protein (ASP), the product of the agouti locus. Human epidermal melanocytes respond to purified recombinant mouse or human ASP, with a reduction in basal tyrosinase activity, and complete abrogation of the mitogenic and melanogenic effects of alpha-MSH. These results suggest that ASP induces pheomelanin synthesis by competing with alpha-MSH for binding to the MC1R. This receptor seems to be subject to regulation by a variety of paracrine and/or autocrine factors that are synthesized in response to exposure of the skin to ultraviolet radiation (UVR). Activation of MC1R seems to be pivotal for UV-induced melanogenesis, since stimulation of the cAMP pathway plays a key role in the melanogenic response of human epidermal melanocytes. The melanogenic response to UVR might be influenced by the presence of allelic variants of the MC1R gene. Allelic variants have been identified and shown to be associated with red hair, poor tanning ability, and possibly melanoma. The possible influence of these variants on the function of the MC1R needs to be investigated, in order to understand the physiological consequence of these mutations. Also, the interaction of alpha-MSH with other factors that are known to affect pigmentation needs to be better understood in order to define the role possible of this hormone and its receptor in acquired human cutaneous hyper- or hypopigmentation.

Agouti Signaling Protein↗
PubMed1999

Participation of the melanocortin-1 receptor in the UV control of pigmentation.

The cloning of the melanocortin-1 receptor (MC1R) gene from human melanocytes and the demonstration that these cells respond to the melanocortins alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH) with increased proliferation and melanogenesis have renewed the interest in investigation the physiological role of these hormones in regulating human pigmentation. Alpha-melanocyte stimulating hormone and ACTH are both synthesized in the human epidermis, and their synthesis is upregulated by exposure to ultraviolet radiation (UVR). Activation of the MC1R by ligand binding results in stimulation of cAMP formation, which is a principal mechanism for inducing melanogenesis. The increase in cAMP is required for the pigmentary response of human melanocytes to UVR, and for allowing them to overcome the UVR-induced G1 arrest. Treatment of human melanocytes with alpha-MSH increases eumelanin synthesis, an effect that is expected to enhance photoprotection of the skin. Population studies have revealed more than 20 allelic variants of the MC1R gene. Some of these variants are overexpressed in individuals with skin type I or II, red hair, and poor tanning ability. Future studies will aim at further exploration of the role of these variants in MC1R function, and in determining constitutive human pigmentation, the response to sun exposure, and possibly the susceptibility to skin cancer.

Alleles↗
PubMed1998

Activation of the cyclic AMP pathway by alpha-melanotropin mediates the response of human melanocytes to ultraviolet B radiation.

A hallmark of sun exposure is increased melanin synthesis by cutaneous melanocytes which protects against photodamage and photocarcinogenesis. Irradiation of human keratinocytes or melanocytes with ultraviolet (UV) rays stimulates the synthesis and release of alpha-melanotropin (alpha-MSH) and adrenocorticotropic hormone (ACTH), which induce cyclic AMP (cAMP) formation and increase the proliferation and melanogenesis of human melanocytes. We report that stimulation of cAMP formation is obligatory for the melanogenic response of cultured normal human melanocytes to UVB radiation. In the absence of cAMP inducers, UVB radiation inhibited, rather than stimulated, melanogenesis. UVB radiation (28 mJ/cm2) arrested melanocytes in the G1 phase of the cell cycle, and concomitant treatment with 0.1 microM alpha-MSH enhanced their proliferation but did not increase the surviving fraction. Irradiation with UVB, with or without alpha-MSH, caused prolonged expression of p53 and p21(waf-1, cip-1), maintained pRB in a hypophosphorylated state, and reduced the expression of Bcl2. However, alpha-MSH allowed UVB-irradiated melanocytes to enter S phase, suggesting that alpha-MSH acts as a mitogen rather than a survival factor, and that overexpression of p53 is mainly a signal for cell death. Our results underscore the importance of the cAMP pathway and its physiological inducers in mediating the response of human melanocytes to UV radiation.

Cyclic AMP↗
PubMed1998

Abdominal incision tumor implantation following pneumoperitoneum laparoscopic procedure vs. standard open incision in a syngeneic rat model.

INTRODUCTION: A recent hamster model study suggests that the abdominal wall wound implantation rate increases following laparoscopic colon cancer surgery compared with the traditional open technique. However, results of that study were confounded by several factors, including a midline incision in the laparoscopy group, an unclear definition of wound implantation, significant age variations in study subjects, and cell line use with low viability. The aim of this study was to compare the abdominal incision implantation rates following a pneumoperitoneum-laparoscopic-type procedure with a standard open incision using a syngeneic host/colon cancer rat model. METHODS: Viable DHD/K12 rat colon carcinoma cells (2 x 10(5) cells/rat) were injected intraperitoneally via 18G angiocath into anesthetized, immunocompetent BD-IX rats (syngeneic host rats). Rats were then randomly divided into open incision and laparoscopy groups. At three weeks post-operatively, tumor growth at the injection, incision, and port sites was measured. RESULTS: Following standard midline incision, 50 percent of rats (26/50 rats) developed wound implantations, whereas only 25 percent of rats (14/57 rats) developed at least one trocar site wound implantation after laparoscopy with pneumoperitoneum. Fourteen percent of trocar sites (16/114 port sites) developed wound implantations. No tumor growth was noted on the peritoneal surfaces other than in the incisional sites. CONCLUSION: Laparoscopic-type procedure with pneumoperitoneum did not increase wound implantation in a syngeneic host/colon carcinoma rat model compared with the standard open incision technique.

Abdominal Muscles↗
PubMed1998

Endothelin-1 is a paracrine growth factor that modulates melanogenesis of human melanocytes and participates in their responses to ultraviolet radiation.

Endothelin (ET)-1, alpha-melanocyte stimulating hormone (alpha-melanotropin; alpha-MSH), and basic fibroblast growth factor (bFGF) are keratinocyte-derived factors that interact synergistically to stimulate human melanocyte proliferation. ET-1 has a dose-dependent mitogenic effect on human melanocytes and a biphasic effect on melanogenesis: a stimulatory effect at subnanomolar concentrations, and an inhibitory effect at concentrations equal to or higher than 1 nM. Human melanocytes express ET B receptors. Brief treatment of melanocytes with ET-1 caused up-regulation of alpha-MSH receptor mRNA but did not alter ET B receptor mRNA level. ET-1 modulates the response of human melanocytes to UV rays (UVRs). Treatment of melanocytes with 10 nM ET-1 immediately after exposure to UVRs enabled them to overcome the G1 growth arrest. However, ET-1 did not inhibit p53 accumulation or p21(Waf-1/SDI-1/Cip-1) overexpression, nor did it reverse the hypophosphorylated state of pRb or the reduction in Bcl2 level in irradiated melanocytes. These results substantiate the role of ET-1 as a paracrine regulator that modulates the response of human melanocytes to UVRs.

Cell Division↗
PubMed1997

Agouti signaling protein inhibits melanogenesis and the response of human melanocytes to alpha-melanotropin.

In mouse follicular melanocytes, the switch between eumelanin and pheomelanin synthesis is regulated by the extension locus, which encodes the melanocortin-1 receptor (MC1R) and the agouti locus, which encodes a novel paracrine-signaling molecule that inhibits binding of melanocortins to the MC1R. Human melanocytes express the MC1R and respond to melanotropins with increased proliferation and eumelanogenesis, but a potential role for the human homolog of agouti-signaling protein, ASIP, in human pigmentation has not been investigated. Here we report that ASIP blocked the binding of alpha-melanocyte-stimulating hormone (alpha-MSH) to the MC1R and inhibited the effects of alpha-MSH on human melanocytes. Treatment of human melanocytes with 1 nM-10 nM recombinant mouse or human ASIP blocked the stimulatory effects of alpha-MSH on cAMP accumulation, tyrosinase activity, and cell proliferation. In the absence of exogenous alpha-MSH, ASIP inhibited basal levels of tyrosinase activity and cell proliferation and reduced the level of immunoreactive tyrosinase-related protein-1 (TRP-1) without significantly altering the level of immunoreactive tyrosinase. In addition, ASIP blocked the stimulatory effects of forskolin or dibutyryl cAMP, agents that act downstream from the MC1R, on tyrosinase activity and cell proliferation. These results demonstrate that the functional relationship between the agouti and MC1R gene products is similar in mice and humans and suggest a potential physiologic role for ASIP in regulation of human pigmentation.

Agouti Signaling Protein↗
PubMed1997

Dyschromatosis universalis hereditaria: an electron microscopic examination.

We report electron microscopic findings from both hyperchromic and achromic macules of dyschromatosis universalis hereditaria (DUH). The keratinocytes of the hyperchromic macules contained numerous, fully melanized melanosomes; almost all of them were aggregated to form the melanosome complex. In contrast, the melanosomes were absent from both keratinocytes and melanocytes of achromic macules, even though intact melanocytes were found. Our results suggest that DUH may be a disorder of melanosome production and distribution in epidermal melanin units rather than a a disorder of melanocyte number.

Aged↗