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Antigen Ki-67 and c-myc oncogene as related to histoclinical parameters in pigmented skin lesions.

121 cases of cutaneous melanomas, 82 lymph nodes with melanoma metastases and 62 naevi were stained immunohistochemically for presence of Ki-67 antigen and c-myc oncogene. A significant correlation between expression of investigated markers, and survival time as well as presence of metastases, in cutaneous melanomas was found (p < 0.05). The role of Ki-67 antigen for differential diagnosis between naevi and melanomas is also demonstrated.

Adult↗

[Effective removal of certain skin pigment spots (lentigines) using the Q-switched ruby laser].

OBJECTIVE: To determine the results of treatment of lentigines with the so-called Q-switched ruby laser (QSRL). DESIGN: Descriptive. SETTING: Netherlands Institute for Pigment Disorders. Amsterdam, the Netherlands. METHOD: In 15 patients (nine women and six men), QSRL treatment was applied to solar lentigines (to patients), labial lentigines (2), segmental lentigines (2) and lentigo simplex (1): The light energy ranged from 3 to 10 J/sq.cm. RESULTS: In 11 of 15 patients, one treatment session sufficed to remove the lesion completely. Acute side effects were slight and transient. Six months after the treatment, none of the patients showed recurrences or scar formation. No hypo- or depigmentations were seen. CONCLUSION: In the cases described. QSRL is a successful treatment for lentigines. For lesions of this nature. QSRL is to be preferred above conventional forms of therapy, such as cryotherapy, chemical peeling and abrasion.

Adolescent↗

A retrospective clinicopathologic study of 212 dogs with cutaneous hemangiomas and hemangiosarcomas.

The relationship between skin pigmentation and piliation and the development of hemangiomas and hemangiosarcomas in the dermis and subcutaneous tissue was studied in 212 dogs. These 212 dogs had a combined total of 306 tumors; 38 of these 212 dogs had two or more of the same tumor in a different location or a combination of hemangioma and hemangiosarcoma. The average age of the dogs at the time of excision of these tumors was greater than 10 years. There was no sex predilection for the presence or absence of tumors. Cutaneous hemangiomas (73%) were more common than cutaneous hemangiosarcomas (27%). Hemangiomas had no predilection for dermis (51%) or subcutaneous tissue (47%), but hemangiosarcomas had a marked predilection for dermis (73%) over subcutaneous tissue (7%). Dogs with short hair coats and lightly pigmented skin had more hemangiomas and hemangiosarcomas of the dermis (65%) than did dogs with variable length hair coats and pigmentation (28%). Dogs with short hair coats and lightly pigmented skin had fewer hemangiomas and hemangiosarcomas of the subcutaneous tissue (10%) than did dogs with variable length hair coats and pigmentation (22%). Dogs with short hair coats and lightly pigmented skin also had more hemangiomas and hemangiosarcomas of ventral glabrous skin (65%) than did dogs with variable length hair coats and pigmentation (22%). In addition, there was no predilection of subcutaneous hemangiosarcoma for haired (33%) versus glabrous (33%) skin, but dermal hemangiosarcoma had a marked predilection for the glabrous skin (63%) when compared with haired skin (10%). The increased incidence of dermal hemangiomas and hemangiosarcomas in ventral glabrous skin suggests an association between solar radiation and the biologic properties of glabrous skin in the genesis of these tumors.

Age Factors↗

Cutaneous side effects from laser treatment of the skin: skin cancer, scars, wounds, pigmentary changes, and purpura--use of pulsed dye laser, copper vapor laser, and argon laser.

It has been the intention of this thesis to increase the knowledge on the development of cutaneous side effects from treatment with the argon laser, the copper vapor laser, and the pulsed dye laser, which represent technical developments within laser systems used for treatment of vascular lesions. To reach that goal, the investigations focused on patient and lesional characteristics (skin pigmentation, skin redness, and epidermal thickness) and on the importance of UV irradiation before and after dermatological laser treatment. The aspect of UV irradiation was added because vascular lesions frequently involve the face and, therefore, may be exposed to sunlight in relation to laser treatment. Risk assessments were performed on clinically visible side effects in order to improve the preoperative information to the patients about their individual risks of obtaining side effects from dermatological laser treatment. The laser-induced side effects were evaluated by systematic clinical assessments, by histological and biochemical examinations, by skin reflectance measurements, optical profilometry, and ultrasonography. The term side effects is associated with both transient and permanent skin reactions such as purpura, wounds, textural changes, scars, pigmentary changes, and squamous cell carcinomas. Lightly pigmented, hairless hr/hr C3H/Tif mice, hairless, albino hr/hr MORO/Ibm mice, human, healthy volunteers, and children with port-wine stains were included in the studies. This thesis represents the first systematic and experimental approach to selected side effects from laser treatment of the skin. The argon laser (AL) and the copper vapor laser (CVL) The results from AL and CVL treatments are described together because these lasers are continuous/quasicontinuous lasers that do not meet the requirements for selective photothermolysis, which represents the most selective delivery of energy to cutaneous vessels. In normal-skinned human volunteers, the postoperative development of scars and pigmentary alterations depended on the preoperative constitutive skin pigmentation degree. Significant correlations were found between the preoperative skin pigmentation and the clinically scored pigmentary changes and scarring 1, 2, and 6 months postoperatively, indicating that dark-pigmented skin types respond with more heavy skin reactions than fair-pigmented skin types. Pigmentary changes occurred at lower intensity levels than scarring. No difference was seen between the AL and the CVL concerning the risk of inducing these side effects. In hairless, albino hr/hr MORO/Ibm mice increasing epidermal thicknesses reduced CVL-induced wounds and scars. Significant negative correlations were found between preoperative epidermal thicknesses and CVL-induced skin reactions. In lightly pigmented, hairless hr/hr C3H/Tif mice, CVL treatment induced an increase in skin pigmentation, evaluated by a semiquantitative technique. Postoperative UV irradiations with simulated solar UV increased the CVL-induced skin pigmentation additionally. The size of CVL-induced wounds and scars tended to enlarge by preoperative UV irradiations. In contrast, CVL-induced wounds were diminished and had a prolonged wound healing time when postoperative UV irradiations were given. This may indicate a deep constricted skin damage. Moreover, the histologically evaluated fibrosis and the frequency of bulging infiltration were increased by postoperative UV irradiation. When taking the liberty to extend the obtained results from the animal studies to humans, these results support the importance of pre- and postoperative sunprotection. Regarding skin cancer, in hairless mice it was found that one treatment with the CVL did not have a malignant potential itself. Pretreatment with the CVL at the highest intensity level (1.4W) delayed UV-induced photocarcinogenesis significantly. The pulsed dye laser (PDL) The PDL is described separately because it is the only laser in this thesis that fulf

Adult↗

Seeing the gene therapy: application of gene gun technique to transfect and decolour pigmented rat skin with human agouti signalling protein cDNA.

We developed a gene gun method for the transfer of human agouti signalling protein (ASP) cDNA to alter rat skin colour in vivo. Human ASP cDNA was cloned into a modified cytomegalovirus plasmid and delivered to the skin of Long-Evans rats by gene gun bombardment. Skin pigmentation, body weight and blood sugar of ASP cDNA-transfected rats were recorded against the control group, which were injected with plasmids encoding for green fluorescent protein. The treated skin showed lighter skin colour after 3 days of ASP gene transfection. This depigmentation effect was most prominent on day 14 and the skin gradually returned to its original pigmentation by day 28. Successful transfection of ASP gene in skin and hair follicles, as well as downregulation of melanocortin-1 receptor (MC1R) and tyrosinase expression upon treatment, was confirmed using immunohistochemistry and Western blot analysis. Body weight and blood sugar in the treated rats did not show statistically significant differences as compared to control groups. These observations demonstrate that gene transfer using the gene gun method can induce high cutaneous ASP production and facilitate a switch from dark to fair colour without systemic pleiotropic effects. Such a colour switch may be that ASP is acting in a paracrine fashion. In addition, this study verifies that ASP exerts its functions by acting as an independent ligand that downregulates the melanocyte MC1R and tyrosinase protein in an in vivo system. Our result offers new, interesting insights about the effect of ASP on pigmentation, providing a novel approach to study the molecular mechanisms underlying skin melanogenesis.

Agouti Signaling Protein↗

Analysis of localized erythema using clinical indicators and spectroscopy.

Localized erythema is regularly used as an indicator of post-ischemic events, including reactive hyperemia and Stage I pressure ulcers. The National Pressure Ulcer Advisory Panel definition of a Stage I ulcer includes both visual and nonvisual indicators in part to improve identification in darkly pigmented skin. A prospective, repeated-measures design was used to collect information on pressure-induced erythema that includes reactive hyperemia and Stage I pressure ulcers with an emphasis on distinguishing indicators in light and dark skin The relationships among clinical indicators (skin assessments) and results from tissue reflectance spectroscopy, as well as the clinical utility of spectroscopy for discerning tissue blanching status, were examined in a convenience sample of 76 inpatients and outpatients (95 test/control site pairs). Chi-square analysis and generalized logistic models were used to identify relationships and distinguishing characteristics of erythema. Analysis of variance was used to analyze blanching using spectroscopy. Nonblanching sites were more likely to be persistent erythema (c2=5.3; P = 0.021) but exhibited no relationships to temperature, tissue resilience, or disability. Erythema in subjects with dark skin was more likely to be nonblanching and have poor resilience. Spectrographic analysis of blanching found significant differences across skin pigmentation (P = 0.0001) and blanching status (P = 0.019). These results reinforce the belief that dark skin must be assessed differently than light skin and indicate that clinicians should use persistence of erythema rather than blanching status to judge incipient pressure ulcers. These results validate the use of visual and nonvisual indicators included in the National Pressure Ulcer Advisory Panel Stage I pressure ulcer definition.

Adult↗

Melanogenesis: a photoprotective response to DNA damage?

Exposure to ultra violet radiation (UVR) is associated with significant long-term deleterious effects such as skin cancer. A well-recognised short-term consequence of UVR is increased skin pigmentation. Pigmentation, whether constitutive or facultative, has widely been viewed as photoprotective, largely because darkly pigmented skin is at a lower risk of photocarcinogenesis than fair skin. Research is increasingly suggesting that the relationship between pigmentation and photoprotection may be far more complex than previously assumed. For example, photoprotection against erythema and DNA damage has been shown to be independent of level of induced pigmentation in human white skin types. Growing evidence now suggests that UVR induced DNA photodamage, and its repair is one of the signals that stimulates melanogenesis and studies suggest that repeated exposure in skin type IV results in faster DNA repair in comparison to skin type II. These findings suggest that tanning may be a measure of inducible DNA repair capacity, and it is this rather than pigment per se which results in the lower incidence skin cancer observed in darker skinned individuals. This evokes the notion that epidermal pigmentation may in fact be the mammalian equivalent of a bacterial SOS response. Skin colour is one of most conspicuous ways in which humans vary yet the function of melanin remains controversial. Greater understanding of the role of pigmentation in skin is vital if one is to be able to give accurate advice to the general public about both the population at risk of skin carcinogenesis and also public perceptions of a tan as being healthy.

DNA↗

Pigmentation dependent, short time skin reactions to copper vapour laser and argon laser treatment.

Thirteen human volunteers selected to have a varying degree of epidermal skin pigmentation were laser treated on the inside of the brachium in six hexagonal areas; three areas with an argon laser (AL, 488, 514.5 nm) and three corresponding areas with a copper vapour laser (CVL, 578 nm). The lasers were connected to a Hexascan device and the physical settings were identical for the two laser types, except for the wavelengths. Beam diameter was 1 mm, pulse duration 200 ms, intensities 0.7, 1.0 and 1.3 W/spot, corresponding to 14.1, 20.2 and 26.2J/cm2 per treated skin area. The skin pigmentation was objectified by skin reflectance. A correlation was demonstrated between skin pigmentation and wound healing time, maximum wound area, and the acute clinical response at days 0, 1, 4, 7, 11 and 17 after laser treatment. An increased skin pigmentation resulted in increased acute and subacute skin reactions. Comparison of the AL and the CVL demonstrated that the CVL on day 0 (0.7 and 1.0 W/spot) and on day 1 (0.7 W/spot) induced a significantly higher degree of skin reactions as compared with the AL. At 0.7 W/spot the CVL induced a significantly higher maximum wound area and a significantly prolonged wound healing time as compared with the AL. An inverse reaction existed between pigmentation and the threshold intensity required to induce wound formation.

Adult↗

Albinism in Nigeria with delineation of new recessive oculocutaneous type.

Seventy-nine Nigerian oculocutaneous albinos were investigated. Fifty-six had typical tyrosinase-positive albinism (TPA) and 23 had brown albinism (BA), a new oculocutaneous type. The TPA were characterized by localized but no generalized skin pigment, yellow hair, blue to brown irides, nystagmus, and reduced or absent retinal pigment. Localized skin pigment included freckles and lentigines. The iris and skin pigment were the result of the slow accumulation of pigment with age as both were found in older individuals. The most severe skin changes were premalignant keratoses and squamous cell carcinoma of the skin, and the skin malignancies were the major factor in limiting the lifespan for TPA. The BA were characterized by generalized light brown skin pigment, light brown hair, blue to brown irides, nystagmus, and reduced retinal pigment. There was little accumulation or change of pigment in the eyes or skin with age. The generalized light skin pigment was effective in reducing sensitivity to solar radiation and very few BA had premalignant keratoses. Pedigree analysis for BA suggested on autosomal recessive inheritance pattern.

Adolescent↗

Carney complex--an unexpected finding during puerperium.

Carney complex is an extremely rare, autosomal dominant, multi-system disorder characterized by multiple neoplasias and lentiginosis. The genetic defect responsible for this complex has been localized to the short arm of chromosome 2 (2p16). The most prevalent clinical manifestations in patients with Carney complex are spotty skin pigmentation, skin and cardiac myxomas, Cushing's syndrome and acromegaly. Here we report the case of a 31-year-old woman with a spontaneous pregnancy. At 32 weeks of gestation, she was admitted to our Department of Obstetrics with hypertension and severe back pain. In addition, she had unusual pigmentation and typical cushingoid features. One day after admission, the pregnancy was terminated by emergency cesarian section because of preeclampsia and pathological CTG. During the postoperative period the severe back pain persisted, and radiographic evaluation revealed a collapse of L(2)/L(3) with severe osteopenia. A CT scan showed a mass in the right suprarenal area. Histopathological examination revealed a primary pigmented nodular adrenocortical disease. After biochemical confirmation of the diagnosis of Cushing's syndrome, it was recognized that the patient met the diagnostic criteria for Carney complex.

Acromegaly↗

Expression of galectin-3 in primary and metastatic melanoma: immunohistochemical studies on human lesions and nude mice xenograft tumors.

Galectins are a large family of proteins which bind galactoside-containing glycans. Their role in cancer seems to be important since members of the family may mediate cell adhesion and modulate cell growth. Galectin-3 (Gal-3) is expressed in the nucleus, in the cytoplasm and on the cell surface, and can also be secreted into the extracellular matrix. A series of experimental and clinical data have been reported which indicate that Gal-3 may play a putative role in carcinogenesis, cancer progression and the process of metastasis. To study the possible correlation between Gal-3 expression and malignant potential in primary melanoma lesions, we conducted an immunohistochemical study with monoclonal anti-Gal-3 antibody in a series of primary and metastatic melanoma lesions as well as benign skin pigmented lesions. We also developed a xenograft melanoma model in nude mice with two melanoma cell lines (ATCC G-361 and ATCC HT-144) and assessed staining with the Gal-3 antibody in the xenografts and the metastases. The expression of anti-Gal-3 staining was determined semiquantitatively. The expression of Gal-3 was higher in thin primary melanoma lesions than in benign pigmented skin lesions or metastases and seemed to correlate inversely with the aggressiveness as estimated by the Breslow index which is recognized as the main prognostic factor in melanoma. We propose Gal-3 expression in melanoma as a diagnostic and/or a prognostic parameter and suggest that further studies of such a role for Gal-3 are warranted.

Animals↗

Contradiction of clinical expectations in lymphoscintigraphy sentinel node mapping in detecting microscopic melanoma metastasis.

A 51-year-old man presented with lower back skin pigmentation tag that he had had for 2 years. Physical examination showed a 10 x 10 mm ulcerated, protruding pigmented skin mass at the midline of back at the 4th lumbar spine level. Skin biopsy disclosed a 5 mm thickness nodular melanoma, which had invaded the reticular dermis. In addition, a 20 x 20 mm lymph node in the right inguinal region was noted. A pelvic computed tomography scan revealed no definite evidence of lymph node enlargement in the left inguinal, bilateral iliac or para-aortic region. However, the 99mTc-sulfurcolloid dynamic lymphoscintigraphy revealed a sentinel lymph node (SLN) in the left inguinal area. The histological examination of the 4-mm SLN demonstrated a small cluster of metastatic melanoma, which was confirmed using HMB-45 immunohistochemical stain. Meanwhile, no melanoma cells were seen in the right enlarged inguinal lymph node. Subsequently, complete left inguinal lymph node dissection was performed, which confirmed that there was no melanoma metastasis in any of remaining 14 nodes. The patient underwent regular follow-up for 9 months and had no evidence of malignancy recurrence to date.

Humans↗

Expression and transmission of wild-type pigmentation in the skin of transgenic orange-colored variants of medaka (Oryzias latipes) bearing the gene for mouse tyrosinase.

Transgenic fish carrying a reconstructed mouse tyrosinase gene, mg-Tyrs-J, were produced by microinjecting the gene into the oocyte nucleus of an orange-colored variant of medaka (Oryzias latipes). Of 64 oocytes microinjected and subsequently inseminated, 13 embryos developed normally beyond hatching and three of them exhibited brown skin pigmentation in the adult as was commonly observed in the wild type of this species. Light and electron microscopic examination disclosed a ubiquitous distribution of typical melanophores in the skin of these transgenic fish. Judging from their population density and distribution pattern, it was presumed that melanogenesis in these fish was elicited in amelanotic melanophores that resided in the skin of the orange-colored fish of this variant. Immunofluorescence with use of the anti-mouse tyrosinase antiserum lacking reactivity to medaka tyrosinase clearly disclosed that the gene introduced was expressed in the melanophores of transgenic fish. Crosses of female transgenic fish and males from an orange-colored variant yielded offspring exhibiting wild-type or orange-colored pigmentation in a ratio of 1:1, thus implying that mg-Tyrs-J integrated into the medaka genome behaves like a dominant gene. Little melanogenesis was observed in xanthophores, leucophores and iridophores in transgenic fish, suggesting possible specificity in recognition of teleostean cell types (i.e., melanophores) by the regulatory region of the mouse tyrosinase gene.

Animals↗