Characterization of a new melanosomal structural component--the vesiculoglobular body--by conventional transmission, high-voltage, and scanning electron microscopy.
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Biomedical subjects
Publications and source records attributed to K Jimbow.
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Brown hyperpigmented disorders may be melanotic in which there is a normal number of epidermal melanocytes but melanin pigment is increased in the epidermis (eg, melasma), melanocytotic, in which melanocytes are increased (eg, café-au-lait macules), and nonmelanotic hyperpigmentation (eg, minocycline pigmentation). Blue hyperpigmented disorders may also be melanotic in which there is a normal number of epidermal melanocytes, but melanin pigment is present in the upper dermis (eg, gray/slate pigmentation in Riehl's melanosis), melanocytotic in which melanocytes are present in both the epidermis and dermis (eg, blue pigmentation in Nevus Ota and Mongolian spot), and nonmelanotic hyperpigmentation in which pigment is present in the deep dermis (eg, blue pigmentation in tattoos). Hypomelanosis (leukoderma) may be divided histopathologically into melanocytopenic disorders on which melanocytes are absent (eg, Vogt-Koyanagi-Harada syndrome and vitiligo), melanopenic disorders in which melanocytes are present but melanin is reduced (eg, nevus depigmentosus and incontinentia pigmenti achromians), and nonmelanotic disorders in which melanin pigmentation is unaffected (nevus anemicus) and the pigmentary abnormality is caused by something other than melanin. There are numerous pigmentary disorders in the oriental skin, and some of them are either characteristic to or established in the orientals. Importantly, a number of congenital hypermelanotic and hypomelanotic diseases (eg, nevus depigmentosus, incontinentia pigmenti, and incontinentia pigmenti achromians, take a distribution following to the Blaschko's line.
INTRODUCTION: We synthesized sulfo-glycolipid, beta-SQAG9 (designate square beta-SQAG9 liposome, because it efficiently forms a liposome structure) that possessed immunosuppressive effects such as inhibition of T-cell responses in human allogeneic MLR and skin allograft survival in rats, and bound to CD62L (L-selectin) in vitro. In this study, we further investigated the immunosuppressive mechanism in vivo by beta-SQAG9 liposome in a skin-allografted rat model. METHODS: ACI rats (RT1(a)) were grafted skin of LEW rats (RT1(1)) treated with PBS or beta-SQAG9 liposome IV once a day for 7 days. Subsequently, we investigated the population of T cells and CD62L(+) T-cell subset in the spleen, axillary lymph nodes (ALNs), and peripheral blood of skin-allografted rats by two-color flow cytometry. RESULTS: Five of 11 (45.5%) rats that were treated with 50 mg/kg beta-SQAG9 liposome showed graft survival and another showed moderate rejection in graft. The CD62L(+) T-cell subset population in ALNs of beta-SQAG9 liposome-treated rats decreased in a dose-dependent manner. No significant difference in the T-cell population was observed between the beta-SQAG9 and control groups. These data suggest that beta-SQAG9 could bind to the CD62L(+) T-cell subset in vivo as well as in vitro and affect T-cell migration, which might lead to T-cell tolerance in vivo.
The vitrification technique was applied to the preservation of human skin. This technique was simple, and no expensive equipment was needed. Split-thickness human skins from 8 patients were immersed in vitrification solution for 10 minutes at room temperature, immediately plunged into a liquid nitrogen tank, and cryopreserved for 3 weeks. The vitrification solution consisted of 40% ethylene glycol (vol/vol) and phosphate buffered saline solution that contained 30% Ficoll 70 (vol/vol; Wako Junyaku, Co, Tokyo, Japan) and 0.5 mol/L sucrose. The viability of vitrified and cryopreserved skin was evaluated with the trypan blue dye exclusion test, the methyl-thiazoldiphenyl-tetrazolium (MTT) colorimetric assay, and a culture test of the keratinocytes obtained from vitrified skin. The results of the trypan blue dye exclusion test showed 87.4% of viable cells, and MTT developed an average 0.817 absorbance. When vitrified skin was compared with 4 degrees C refrigerated skins after 3 weeks of storage, the difference of viability was significant both on the trypan blue dye exclusion test (P < .05) and on the MTT assay (P < .01). However, there was no significant difference in the viability of vitrified skins compared with fresh skin. Furthermore, keratinocytes from vitrified skin grew uneventfully in culture test. We used these vitrified skin allografts for patients with flame burns and electric burns. These allografts took well in both cases and promoted wound healing. We concluded that the vitrification method for skin preservation is simple and reliable, and this method could contribute to skin banking.
Systemically administered 4-S-cysteaminylphenol (4-S-CAP) and N-acetyl-4-S-CAP inhibited the growth of xenografts of a human melanoma cell line but not of an ovarian tumour cell line. No selective cytotoxicity for melanoma cells was observed in culture, however. Further study of the in vitro mechanism of 4-S-CAP toxicity showed minimal inhibition of tyrosinase activity or DNA, RNA and protein synthesis, and there was no phase-specific arrest of the cell cycle. However, expression of an 80 kD melanosomal antigen was decreased. Cytotoxicity of 4-S-CAP in culture was decreased by simultaneous treatment with a monoamine oxidase inhibitor. An affinity column prepared from 4-S-CAP retained several proteins from a melanoma cell lysate. One protein, found also in HeLa cells, was identified by N-terminal sequencing as protein disulphide isomerase, a molecule which has multiple roles in the modification of secretory proteins. These results identify a protein target for 4-S-CAP as one possible mechanism of cytotoxicity.
A unique biological property of the melanocyte, melanin synthesis may permit a rational approach to design agents for better management of malignant melanoma. This in vivo and in vitro study examined the selective melanocytotoxicity and antimelanoma effects of phenolic compounds, cysteinylphenol (CP), cysteaminylphenol (CAP), and related compounds, and found (1) that both 4-S-CP and 4-S-CAP are melanin precursors, (2) that 4-S-CAP possesses a marked depigmenting potency with selective destruction of melanocytes in black follicles, and (3) a significant inhibition in the protein synthesis and tumor growth of B16 melanoma. Importantly, a whole body autoradiography indicated that these phenolic melanin precursors are selectively incorporated into melanoma tissues after i.p. administration.
Using two methods (continuous monotherapy and intermittent therapy) for the treatment of psoriasis with cyclosporine, we observed the clinical efficacy and adverse reactions of each treatment method for more than 36 months to evaluate the clinical usefulness of both methods. Thirty-seven cases were analyzed and the following results were obtained: 1) The PASI score evaluated at each visit was maintained between 5 and 10 by both treatment methods and the improvement rate was more than 70%, while there was no difference in the daily dose between the two treatment methods; 2) The period required to achieve remission tended to be prolonged by intermittent therapy, while no change was observed with continuous monotherapy; 3) The period up to relapse tended to become shorter with both treatment methods but this tendency was more marked with intermittent therapy; 4) E-PAP(evaluation for prognosis with averaged PASI) was lower in the continuous monotherapy group and the patients were more satisfied; 5) The incidence of adverse reactions was similar to that reported in previous studies, with no difference between the two treatment methods in this regard; 6) A significant increase in BUN levels was observed in elderly patients; 7) There were only three cases in which the drug was discontinued due to exacerbation and adverse reactions. Based on the above findings, continuous monotherapy seems to be of greater clinical usefulness than intermittent therapy.