bluuebunny/crossref_metadata_2025 huggingface dataset:
Concomitant contact dermatitis due to textile dyes and to colour film developers can be explained by the formation of the same hapten
Authors: Hansson C. , Ahlfors S. , Bergendorff O.
Published: April 2006

P‐phenylenediamine derivatives are widely used in industry and in cosmetics, and several of them are well‐known sensitizers. One group of allergenic p‐phenylenediamine derivatives are used as colour film developers. Cross‐reactivity between the colour film developers has been reported. In this paper, an occupational facial dermatitis due to colour Him developers is described. The patient reacted to colour film developers (CD‐1, CD‐2 CD‐3. and CD‐4), but not to other p‐phenylenediamine derivatives tested. He also showed allergic reactions to Disperse Blue 106 and Disperse Blue 124 and to Disperse Red 17, hut not to Disperse Orange 3. The activation of the colour film developers by oxidation al physiological pH was analysed with chemical methods, and the mechanism responsible for the concomitant reactivities to the colour film developers and the disperse dyes at a molecular level is discussed.
Contact allergy to dental restorative materials in patients with oral lichenoid lesions
Authors: Laine Juhani , Kalimo Kirsti , Happonen Risto‐Pekka
Published: April 2006

118 patients with oral lichenoid lesions (OLL) topographically related to dental fillings were patch tested (FT) to reveal contact allergy to restorative materials. 80 (67.8%) patients displayed positive PT reactions to metals of dental filling materials: 76 reactions were found to various mercury compounds. 4 to sodium aurothiosulphate, 3 to stannic chloride and 2 to silver nitrate. The positive patch lest reactions appeared more commonly in patients with restricted contact lesions (85.1%, type‐1 lesions) as compared to patients with lesions exceeding to the adjacent areas (38.6%, type‐2 lesions). The replacement of dental fillings was carried out in 62/80 PT‐positive and 15/38 PT‐negative patients. 28 out of 62 (45.2%) PT‐positive and 3/15(20%) PT‐negative patients showed complete healing of OLL after a mean follow‐up time of 16 months. Complete healing occurred in 29/54(54.0%) type‐1 and 2/23 (8.7%) type‐2 lesions. Topographical relation between the lesion and the filling material (restricted versus exceeding the contact area) indicated association of OLL lesion and the filling material, which could be further confirmed by patch testing in the majority of patients. The patch test series should include mercuric chloride (0.1%), mercury (0.5%) and mercury ammonium chloride (1.0%), each in pet.
Skin reactions to hydroxyzine
Authors: Michel M. , Dompmartin A. , Louvet S. , Szczurko C. , Castel B. , Leroy D.
Published: April 2006

Sensitivity to histamine H1‐antagonists has mainly been observed with phenothiazine and ethylenediamine, and is very rare with hydroxyzine. We report 3 cases of sensitization to hydroxyzine, which was prescribed to treat urticaria and atopic dermatitis. A generalized maculopapular eruption appeared shortly after taking the drug. Patch tests with Atarax® tablet were positive +++, and ++ or +++ with different dilutions of hydroxyzine. Patch tests with ethylenediamine, piperazrne and other antihistamines were negative: therefore, there is no cross‐allergy. We believe these rapid systemic reactions to hydroxyzine after the initial dose may have been due to prior systemic sensitivity to this drug, which cannot be used topically. Allergy to antihistamines must be considered when cutaneous lesions worsen on such therapy.
Dinitrohalobenzenes: evaluation of relative skin sensitization potential using the local lymph node assay
Authors: Basketter David A. , Dearman Rebecca J. , Hilton Jennifer , Kimber Ian
Published: April 2006

The dinitrohalobenzenes are known to cause skin sensitization and have been used in many seminal investigations of the relationships between physicochemical characteristic and sensitizing potential. The electrophilic theory of skin sensitization implies that contact allergic potential should correlate positively with the ability of chemicals to react with proteins to form immunogenic hapten‐protein conjugates. It is intriguing, therefore, that previous studies in guinea pigs and mice have suggested that such correlations do not apply to dinitrohalobenzenes. To address this, we have examined, using the murine local lymph node assay (LLNA), the sensitizing activity of 2,4‐dinitroiodobenzene (DNFB), 2,4‐dinitrochlorobenzene (DNCB), 2,4‐dinitrobromo‐bezene (DNBB) and 2,4‐dinitroiodobenzene (DNIB). In contrast to previous investigations, it was found that the ability of these chemicals to provoke responses in the LLNA correlated closely with their reported protein reactivity. On the basis of these data, it is proposed that dinitrohalobenzenes conform to the electrophilic theory of skin sensitization and that they should be regarded as direct acting haptens.
Threshold for occluded formaldehyde patch test in formaldehyde‐sensitive patients
Authors: Flyvholm Mari‐Ann , Hall Barbara M. , Agner Tove , Tiedemann Eva , Greenhill Peter , Vanderveken Walter , Freeberg Fred E. , Menné Torkil
Published: April 2006

Our purpose was to investigate the eliciting threshold concentration of formaldehyde in formaldehyde‐sensitive individuals in the occluded and non‐occluded patch teat and to evaluate the relationship in repeated open application test (ROAT) with a product containing a formaldehyde releaser. 20 formaldehyde‐sensitive patients and a control group of 20 healthy volunteer were included in the study. Occluded and non‐occluded patch tests with formaldehyde solutions form 25 to 10,000 ppm. and ROAT for I week with a leave‐on cosmetic product containing on average 300 ppm formaldehyde. Were carried out simultaneously on each subject. In the occluded patch test. 1/2 of the 20 patients only reacted to 10,000 ppm formaldehyde. 9 reacted to 5,000 ppm. 3 reacted to 1.000 ppm. 2 reacted to 500 ppm and I reacted to 25 ppm. No definite positive reactions were observed in the non‐occluded patch test or in the ROAT No positive reactions were observed in the control group to any of the test procedures. We concluded that the threshold concentration for occluded patch test to formaldehyde in formaldehyde‐sensitive patients was 250 ppm. The threshold in occluded patch test corresponded to the degree of sensitivity Definite positive reactions in the ROAT were not seen, either indicating that they are unlikely to happen with the type of product used or that the exposure time was too short.
Managing the excited skin syndrome: patch testing hyperirritable skin
Authors: Mitchell John , Maibach Howard I.
Published: April 2006

Inflammation‐modulating phenomena (IMPs), humoral and cellular, fluctuate during the course of irritant and allergic contact dermatitis influencing irritability of the skin. The patch test procedure is a biological assay, a titration of responses to IMPs which can produce hypo reactivity or hyperirritability of the skin of patients who have dermatitis (PDs) and a single patch test is a “snapshot” of the tempo of an evolving process. The excited skin syndrome (ESS) refers lo hyperirritability from clinical and patch test dermatitis creating false‐positive patch test reactions which are not reproducible when dermatitis and IMPs have subsided. During ESS, the threshold for irritancy decreases and irritant reactions increase. Patch test concentrations should be determined and ESS investigated in PDs having enhanced IMPs, not in “normal” individuals, and if a patch test result is important to a patient the test should be performed more than once. Variable reproducibility is inherent in the patch test method, but ESS can be managed by appropriate testing and retesting, and search for relevance.
Contact and photocontact sensitivity to sunscreens
Authors: Schauder Silvia , Ippen Hellmut
Published: April 2006

This review summarizes published and unpublished data of our 15‐year experience with sunscreen allergy and photoallergy. From 1981–1996. 402 patients with suspected clinical photosensitivity were patch and photopatch tested with the commercial sunscreens and facial cosmetics (hat they had used and with chemical UV absorbers, fragrance materials, preservatives, and emollients. Mi patients (20%) (28 men, 52 women) demonstrated allergic and/or photoallergic contact dermatitis to 1 or more UV absorber(s). In 47 patients with photodermatoses or photo‐aggravated dermatoses and in 33 subjects with normal photosensitivity, 91 allergic and 84 photoallergic reactions to UV filters were observed. Over the years sunscreens were added lo the test series, which since 1989 comprised the following 10 UV absorbers and which induced allergic (a) and photoallergic (pa) reactions (number, type of reaction); 4 UVA absorbers – isopropyldibenzoylmethane (30a/32pa); butyl methoxydibenzoyl‐methane (15a/13pa); henzophenone‐3 (3a/9pa): benzophenone‐4 (0a/0pa); and 6 UVB absorbers – PABA (2a/2pa); octyl dimethyl PABA (1a/2pa); methylbenzylidene camphor (32a/5pa); octyl methoxycinnamate (3a/4pa); isoamyl p‐methoxycinnamate (4a/10pa); and phenylbenzimidazole sulfonic acid (1a/7pa). The frequent (photo)sensitization to isopropyldibenzoylmethane was the reason that its production was discontinued in 1993. 47 patients reacted to fragrance materials, 11 to preservatives and 2 to lanolin alcohol. These constituents were contained in the commercial sunscreens and cosmetics that they had used. Continuous revision of the UV absorber photopatch test series was necessary to be closer to the real frequency of exposure and of reported I photo (allergy to newer sunscreens. Clinicians should consider contact and photocontact allergy, especially in patients with photodermatoses and photo‐aggravated dermatoses and they should perform photopatch testing. Once the culprit has been identified, its INCI (International Nomenclature Cosmetic Ingredients) designation should be given to the patient, who must be warned to avoid products containing the (photo)allergen.
Substance P levels are decreased in lesional skin of atopic dermatitis
Authors: Fantini F. , Pincelli C. , Romualdi P. , Donatini A. , Giannetti A.
Published: April 2006

Abstract There is increasing evidence that neuropeptides (NP) such as substance P (SP) and vasoactive intestinal polypeptide (VIP) are involved in the pathogenesis of atopic dermatitis (AD). Vasoactive intestinal polypeptide levels were found to be significantly elevated in lesional skin of AD as compared to controls. We evaluated by radioimmunoassay the SP content in whole skin homogenates from chronic lichenified lesions of patients with AD. The levels of SP were significantly decreased in lesional skin from AD patients as compared to control skin (0.25 ± 0.03 vs. 0.97 ± 0.24 pmol/g tissue, p < 0.01). The diminished SP levels as opposed to increased VIP concentrations could be consistent with different roles of these NP as modulatory agents in the mechanisms associated with AD.
Lack of correlation between UV‐induced enhancement of melanoma development and local suppression of contact hypersensitivity
Authors: Donawho Cherrie K. , Kripke Margaret L.
Published: April 2006

Abstract Injection of melanoma cells into the UV‐irradiated ear skin of syngeneic mice results in an increased incidence of melanomas compared with that in nonirradiated ear skin. This effect of UV is localized to the site of irradiation and appears to be immunoiogically mediated. In these studies we test the hypothesis that the effect of UV irradiation on melanoma development is related to its ability to alter epidermal Langerhans cells and impair the induction of contact hypersensitivity. A regimen of UV irradiation that altered epidermal immune cells and interfered with the generation of contact hypersensitivity was tested for its ability to increase the incidence of melanoma. Conversely, the ear skin of C3H mice treated with a regimen of UV radiation that enhanced melanoma development was examined for the number of appearance of ATPase+ and Thy‐1+ dendritic epidermal cells and tested for the ability to initiate a contact hypersensitivity response. No correlation between these effects of UV irradiation could be detected. Furthermore, implantation of melanoma cells into UV‐irradiated ear skin resulted in the generation of systemic immunity against subsequent tumor challenge. Therefore, we conclude that the ability of UV irradiation to modify melanoma development is unrelated to its effects on the afferent arm of the contact hypersensitivity response and that enhanced melanoma development is not due to an impairment in the induction of tumor immunity.
A reappraisal of the use of 5‐methoxypsoralen in the therapy of psoriasis
Authors: Calzavara‐Pinton Piergiacomo , Ortel Bernhard , Carlino Anna , Honigsmann Herbert , De Panfilis Giuseppe
Published: April 2006

Abstract 5‐methoxypsoralen (5‐MOP) is considered an alternative to 8‐methoxypsoralen (8‐MOP) for photochemotherapy of psoriasis. We have compared the clinical efficacy and tolerability of 5‐MOP (1.2 mg/kg)‐UVA versus 8‐MOP (0.6 mg/kg)‐UVA therapy in 25 patients of skin type III and IV, affected by relapsing plaque‐type psoriasis of similar body involvement; indeed, the same patients were given 8‐MOP during 1 year and 5‐MOP during the subsequent year after relapsing. Both treatments cleared psoriatic lesions with a comparable number of exposures, but 5‐MOP required significantly higher cumulative UVA doses. The difference was due to the lower phototoxicity of 5‐MOP, as assessed by the determination of the minimal phototoxic dose, and to its higher tanning activity, as assessed by the weekly grading of pigmentation. Nevertheless, therapy by 5‐MOP‐UVA seemed particularly interesting in that it showed a higher tolerability since only 1 patient experienced nausea, whereas during therapy with 8‐MOP‐UVA nausea and/or vomiting occurred in 7 patients, sunburn in 6 and itching in 3. Since we have treated the same patients with the two drugs, our results were not influenced by interindividual variations of phototoxic responses, tanning ability and susceptibility to develop psoraleninduced short‐term side‐effects. It was concluded that, although long‐term side‐effects of the 5‐MOP‐UVA treatment have still to be determined, such treatment of psoriasis should be reappraised due to its higher tolerability in comparison to 8‐MOP‐UVA treatment.
Kalinin is abnormally expressed in epithelial basement membranes of Herlitz's junctional epidermolysis bullosa patients
Authors: Meneguzzi G. , Marinkovich M. P. , Aberdam D. , Pisani A. , Burgeson R. , Ortonne J. P.
Published: April 2006

Abstract Kalinin is an extracellular adhesion molecule specific to epithelial basement membranes (BM) identified as a component of anchoring filaments of hemidesmosomes. This heterotrimeric protein is synthesized by cultured normal human keratinocytes and is involved in cell attachment. In indirect immunoriuorescence studies, the epidermal BM of patients with junctional epidermolysis bullosa (JEB) of Herlitz's type were found not to be reactive with the anti‐kalinin monoclonal antibodies ka146 and K140 and displayed a decreased immunoreactivity to two anti‐kalinin antibodies cross‐reacting with K‐laminin, an anchoring filament component recently described. The intrinsic defect of JEB keratinocytes in the synthesis of kalinin was further documented by indirect immunofiuorescence on in vitro cultures of these cells. In non‐Herlitz JEB patients, staining of BM was constantly detected. Impairment of expression of kalinin correlated with the lack of reactivity to the monoclonal antibody GB3, which delects the BM component nicein/BM600. These results clearly demonstrate a defect of kalinin expression in epithelial basement membranes of Herlitz JEB patients and suggest that kalinin may play a role in the pathogencsis of the disease. Further studies are in progress to define possible relationships between kalinin and nicein.
Enhanced antibody titers to an oxidized DNA base in inflammatory and neoplastic diseases
Authors: Frenkel K. , Khasak D. , Karkoszka J. , Shupack J. , Stiller M.
Published: April 2006

Abstract Reactive oxygen species (ROS) produced by phagocytic cells induce oxidative stress during chronic inflammation, ROS play a role in the pathogenesis of a broad range of diseases including autoimmune, cardiac and neoplastic abnormalities. We found that sera of patients with a variety of inflammatory dermatoses contain elevated levels of antibodies (Ab) binding to an oxidized DNA base derivative, 5‐hydroxyme‐thyl‐2′deoxyuridine (HMdU) coupled to bovine serum albumin, as determined by the enzyme‐linked immunosorbent assay. Patients with immune complex diseases and a history of neoplasm elaborated the highest titers of anti‐HMdU Ab. Titers from sera of psoriatic subjects were lower than from the aforementioned groups but were still significantly elevated (p<0. 001) above those of healthy controls. Treatment of inflammatory dermatoses with systemic antiinflammatory and cytotoxic drugs significantly lowered the titers [p<0. 005 (immune complex) or p<0. 001 (psoriasis and neoplastic) diseases], suggesting that this assay may be of value in monitoring the response to therapy in these diseases.
Adult T‐cell leukemia/lymphoma (ATL) –clinical, histopathological, immunological and immunohistochemical characteristics
Authors: Nagatani Tetsuo , Miyazawa Megumi , Matsuzaki Toshiko , Iemoto Gaijiro , Ishii Harumi , Kim Shu‐Taku , Baba Naoko , Miyamoto Hideaki , Minato Keisuke , Motomura Shigeki , Nakajima Hiroshi , Shimoyama Masanori , Shimoyama Kiyoshi
Published: April 2006

Abstract Twenty‐one patients with ATL were assessed. The predominant physical findings were lymph node and bone marrow involvement, skin involvement, hepatosplenomegaly and leukemic manifestations. The predominant histopathological findings in both skin and lymph node specimens were the diffuse medium‐sized cell type and the diffuse mixed cell type. Some phenotypic discrepancy was found between the neoplastic cells in the peripheral blood, lymph nodes and skin of patients with ATL with respect to CD45RA and CD45RO, and CD7, CD29, CD25 and HLA‐DR. That is, the predominant neoplastic cell phenotype was the helper T‐cell, which was CD3+, CD4+, CD7+, CD25+, CD45RA+ and HLA‐DR+, and CD29− and CD45RO− in peripheral blood and lymph nodes, and CD3+, CD4+, CD7+, CD29+, CD45RO+ and HLA‐DR+, and CD45RA− in the skin. In other words, we have described the phenotypic heterogeneity of ATL cells and demonstrated the heterogeneity of CD45R isoform expression on ATL cells in different organs – the skin, peripheral blood and lymph nodes – of the same patient.
Sensitivity of diagnosis of malignant melanoma: A clinicopathologic study with a critical assessment of biopsy techniques
Authors: Witheiler Daniel D. , Cockerell Clay J.
Published: April 2006

Abstract Although most examples of cutaneous malignant melanoma are easily recognized by their clinical appearances, in some cases this serious neoplasm may clinically simulate other less serious forms of skin cancer or benign processes. This study was undertaken to assess both the sensitivity of clinical diagnosis of cutaneous malignant melanoma and the efficacy of biopsies of clinically unsuspected melanomas in yielding specimens on which complete and accurate histologic assessments could be made. A retrospective analysis of 1784 cases of histologically proven melanomas diagnosed between 1985 and 1990 was performed in search of lesions not clinically suspected. Biopsy techniques used to sample these lesions were subjected to critique of their efficacy in yielding specimens that could be accurately diagnosed and completely assessed histologically. Of 1784 histologically proven primary cutaneous melanomas, 583 were not clinically suspected, yielding a sensitivity of 61%. Clinical diagnosis included nevi (33%), no diagnosis (17%), multiple diagnoses (13%.), basal cell carcinoma (12%), keratosis (9%), and lentigo (9%) among others. The biopsy methods used to sample these lesions were shave (56%), excisional (24%), punch (11%), curettage (2%), and undetermined (6%). Eighty‐six percent of shave biopsies could be accurately assessed while only 32% of punches and no curettages provided sufficient material for both definitive and complete evaluation of melanomas. Eighteen percent of specimens histologically reviewed were considered inadequate for complete evaluation. In 34%, the actual diagnosis of melanoma was uncertain because of inability to assess diagnostic features as a consequence of the biopsy technique. Melanoma may be unsuspected clinically in a significant number of cases and may be mistaken for less serious cutaneous neoplasms. Biopsy material that is not representative of the entire process may lead to misdiagnosis. Biopsy specimens measuring 5–6 mm in breadth and extending to at least the mid‐reticular dermis for 4–5 mm will provide representative sections in most cases and should allow for detection of clinically occult melanoma.
Percutaneous absorption of azelaic acid in humans
Authors: Tauber U. , Weiss C. , Matthes H.
Published: April 2006

Abstract Six healthy male volunteers received a single topical treatment with 5 g of an anti‐acne cream containing 20% azelaic acid (AzA) onto the face, the chest and the upper back. One week later 1 g of AzA was given orally to the same subjects as aqueous microcrystalline suspension. Following the two treatments the renal excretion of the unchanged compound was measured. Analysis included ether extraction of the urine, derivatization of extract and HPLC with UV detection. After topical application 2.2 ± 0.7%, and after oral administration 61.2 ± 8.8% of the dose had been excreted unchanged with the urine. By comparing both amounts, the percutaneous absorption of AzA from the cream was assessed to 3.6% of the dermally applied dose.
Diet‐induced dermatitis response of hairless rats to systemic treatment with cyclosporin A (Sandimmun®), cyclosporin H and FK506
Authors: Bavandi A. , Meingassner J. G. , Becker S.
Published: April 2006

Abstract Weaned hairless rats were fed a diet deficient in fat, magnesium and folacin. After approximately 1 week, an erythematous dermatitis developed which was associated with extreme generalized pruritus. Scratching led to excoriations and hemorrhagic crusting. The acute stage (pruritic rash) resolved after several days and was followed by sporadic non‐itching relapses. Subsequent to the onset of symptoms, rats were treated orally, once daily for 3 days with CyA, CyH or FK506. The immunosuppressants CyA and FK506 caused a dose‐dependent inhibition of symptoms in contrast to CyH. The immediate clinical response was associated with changes in blood histamine, white blood cell counts and histological parameters. Since CyH is known to lack immunosuppressive activity, these results may indicate that the cutaneous changes induced by the nutritional deficiency are associated with immunological abnormalities. The results may also indicate mechanisms influenced by CyA and FK506 but not by CyH; for example, release of chemical mediators from inflammatory cells.
Enhancing effect of protein A on the interaction between opsonized corneocytes and neutrophils in Staphylococcal infection
Authors: Kato Taizo , Terui Tadashi , Hara Masahiro , Iizawa Osamu , Tagami Hachiro
Published: April 2006

Abstract Formation of subcorneal pustules characterizes skin lesions infected by Staphyloeoccus aureus. To elucidate the mechanism underlying the subcorneal pustule formation as well as that of anti‐bacterial host defence, we studied the effect of Staphylococcal protein A on the interaction between the stratum corneum (SC) and neutrophils. We found that protein A significantly promoted opsonized SC‐induced chemiluminescence (CL) in neulrophils. This was specific to SC because no enhancement was observed with opsonized zymosan. It look place even with the serum obtained from a patient with agammaglobulinemia, ruling out the possibility of the involvement of Fc‐receptors of neutrophils in this phenomenon. Microscopic observation of such SC revealed an increase in the number of neutrophils adhering to the surface of the protein A‐coated corneocytes. Ultrastructural observation showed a distinct deformation of the neutrophils adhering to the surface of thc corneocytes, suggesting that they are in an activated stale. Such an enhanced interaction between protein A‐attached SC and neutrophils seems lo play an important role in the host defence mechanism against the invading S. aureus and in the production of the characteristic pustules by the neutrophil‐mediated damage of the surrounding epidermal tissue.
Chemical carcinogens increase IL‐1α and IL‐6 gene transcripts in human keratinocytes
Authors: Khan Islam U. , Mukhtar Hasan , Haqqi Tariq M.
Published: April 2006

Abstract Using reverse transcriptase‐linked polymerase chain reaction, the effect of polycyclic aromatic hydrocarbons (PAHs) on IL‐lα, IL‐lβ and IL‐6 gene expression in cultured human keratinocytes was studied. Exposure to β‐naphthoflavone and benz(a)anthracene resulted in a higher copy number of IL‐lα and IL‐6 mRNA while lower level of IL‐1β mRNA was detected in these cells. These data suggest that, like ultraviolet B (UVB) radiation, ubiquitous environmental carcinogenic PAHs are potent inducers of lL‐lα and IL‐6 cytokines and, unlike UVB, they downregulate IL‐1β in human keratinocytes.
UVA irradiation stimulates the synthesis of various matrix‐metalloproteinases (MMPs) in cultured human fibroblasts
Authors: Herrmann Gernot , Wlaschek Meinhard , Lange T. Sascha , Prenzel Klaus , Goerz Günter , Scharffetter‐Kochanek Karin
Published: April 2006

Abstract UVA irradiation leads to photoaging including clinical features such as wrinkle formation, reduced recoil capacity and blister formation of the skin. Besides synthesis of the extracellular matrix, its regulated degradation by various matrix‐metalloproteinases (MMPs) determines the amount and the composition of the extracellular matrix within the dermis and the basement membrane of the dermo‐epidermal junction. In this study we therefore ascertained whether UV irradiation could modulate the synthesis of MMPs with substrate specifities for dermal (collagen I, III, V) and basement membrane compounds (collagen IV, VII, proteoglycans, laminin) and whether synthesis of the counteracting tissue inhibitor of metalloproteinases (TIMP‐I) was also affected. Following UVA irradiation specific mRNAs of MMPs 1, 2 and 3 were induced concomitantly up to 5‐fold compared to mock irradiated controls. In contrast, TIMP‐1 mRNA levels remained unaltered. Immunoprecipitation indicated that after UVA irradiation synthesis and secretion of MMPs 1, 2 and 3 into the supernatant increased. Taken together, our data show that UVA irradiation coordinately induced MMPs 1, 2 and 3 implying similar mechanisms in their regulatory pathways, while TIMP‐I synthesis was not altered. Hence, unbalanced synthesis of MMPs potentially contributes to the dissolution of dermal and basement membrane compounds finally leading to blister formation and cutaneous photoaging.
Review of the etiopathomechanism of vitiligo: A convergence theory
Authors: Le Poole I. C. , Das P. K. , van den Wijngaard R. M. J. G. J. , Bos J. D. , Westerhof W.
Published: April 2006

Abstract Vitiligo is an acquired melanin pigmentary disorder manifesting itself by expanding depigmented lesions of the skin. To date, the etiopathomechanism of vitiligo has not been convincingly elucidated and a number of seemingly mutually opposed hypotheses with equal likelihood still coexist. Concurrent theories on vitiligo etiology, together with supportive evidence, are reviewed here. Due to the observed variation in clinical manifestations of the disease, it seems likely that the etiology of vitiligo may differ among patients. Therefore several theories on vitiligo etiopathogenesis have been combined to formulate a convergence theory for vitiligo. also presented in this article. This theory stales that stress, accumulation of toxic compounds, infection, autoimmunity. mutations, altered cellular environment and impaired melanocyte migration and or proliferation can all contribute to vitiligo etiopathogenesis in varying proportions.
Cultured skin fibroblasts derived from three patients with disseminated superficial actinic porokeratosis (DSAP) are hypersensitive to the lethal effects of X‐radiation but not to those of ultraviolet (UV) light
Authors: Watanabe Ryoji , Otsuka Fujio
Published: April 2006

Abstract Disseminated superficial actinic porokeratosis (DSAP), skin lesions of which are known to be induced by ultraviolet (UV) light, does not develop into skin cancer as frequently as other types of porokeratosis (PK) To establish the cellular basis of this characteristic of DSAP. we examined the colony‐forming ability of UVC light‐ or X‐ray‐irradiated cultured fibroblasts derived from DSAP patients' skin. Sensitivity to the lethal effects of UV light was not significantly different between 3 DSAP and 5 control cell strains. In contrast, DSAP cell strains were significantly hypersensitive to the lethal effects of X‐radiation, although the sensitivity was less than that of cell strains from other types of PK patients. The results indicate that the actinic character of DSAP is not reflected in the cellular response to the lethal effects of UV light, but suggest that DSAP shares X‐ray sensitivity, which is probably associated with the cancer‐prone nature of PK.
Proteolytic activity in leg ulcer exudate
Authors: Palolahti Miina , Lauharanta Jorma , Stephens Ross W. , Kuusela Pentti , Vaheri Antti
Published: April 2006

Abstract Twenty‐five leg ulcer exudate samples from 17 patients with chronic non‐healing venous leg ulcer were analyzed for proteolytic activity using radial caseinolysis procedures and zymographic analysis, and for fibronectin fragmentation using immunoblotting technology. Caseinolytic activity was detected in 21 of the 25 samples. A minority of them were inhibited (3 were totally, 6 partially inhibited) by aprotinin, a serine proteinase inhibitor, suggesting that proteinase(s) other than plasmin were also responsible for the caseinolysis. In zymographic analysis, 23 of the 25 samples showed positive reactions for enzyme activities comigrating with plasmin and urokinase‐type plasminogen activator. Fibronectin fragmentation, another sign of proteolytic activity, was seen in all but 2 ulcers. No correlation was seen between bacterial infection or inflammatory cells and the above parameters in the wound fluid. Acute wound fluid collected from the donor sites of patients undergoing split skin grafting was used as a control. In the control specimens no proteolytic activity was found during the days following operation. These results show that there is proteolytic activity in the chronic ulcer exudate and support the possibility that the proteolytic activity and consequent fibronectin fragmentation may be related to the retarded epithelization and ulcer healing.
Single‐step purification of recombinant melanoma growth‐stimulating activity by anion‐exchange high‐performance liquid chromatography
Authors: Norgauer Johannes , Metzner Beatrix , Parlow Frauke , Elsner Jörn , Kownatzki Eckhard , Schraufstätter Ingrid U.
Published: April 2006

Abstract The cytokine melanoma growth‐stimulating activity (MGSA) is a growth factor for melanoma cells and a chemolaxin for neutrophils. Known purification procedures of MGSA from human sources or expression systems give a low yield and require multiple chromatography steps. Here, a fast and high‐yield method for the purification of recombinant MGSA is described. Approximately 500 μg MGSA were recovered from the bacterial lysate of a 10 liter culture within a day. For this purpose, total mRNA of Hs294T melanoma cells was isolated and cDNA of MGSA was obtained by reverse transcription and polymerase chain reaction. The cDNA of MGSA was subcloned into the expression vector pGEX‐2T, generating a fusion with the Schistosoma japonicum glutathione S‐transferase gene. The fusion protein was expressed in E. coli DH5a and purified from the bacterial lysale using glulalhione‐sepharose beads. MGSA was cleaved from the complex of fusion protein and glutathione scpharose beads with thrombin and purified to homogeneity by anion‐exchange high‐performance liquid chromatography with a Mono‐S‐column. The bioactivity of the recombinant MGSA was assessed by chemotactic migration and triggered [Ca2+]i‐transients in human neulro‐phils. In addition, [125I]MGSA bound specifically to undifferentiated human leukemia cells HL‐60 transfected with the cDNA of the interleukin‐8 (IL‐8) receptor β with similar properties as [125I]IL‐8. Thus, this described method might be a powerful tool to generate large amounts of cytokines in a short time.
Calcium modulates the expression of urokinase plasminogen activator and plasminogen activator inhibitor 2 by human keratinocytes
Authors: Lyons‐Giordano B. , Lazarus G. S.
Published: April 2006

Abstract Keratinocytes propagated in low calcium (30 μM CaCl2) serum‐free media grow in a monolayer and exhibit morphologic and biosynthetic phenolypes most similar to those of keratinocytes in the basal layer of the normal epidermis. When the calcium in the media is elevated to 1 mM. the cells stratify and differentiate. The effects of calcium on human foreskin keratinocyte expression of urokinase type (uPA) and tissue type (tPA) plasminogen activator enzymes and plasminogen activator inhibitor 1 and 2 (PAI‐1, PAI‐2) were assessed by Northern analyses. Our data show that keratinocytes, cultured in the presence of low and high CaCl2 concentrations, express transcripts for uPA and PAI‐2. Message levels for uPA were dramatically reduced in cultures stimulated with calcium, whereas those for PA 1–2 were only slightly decreased. Little PAI‐1 mRNA and no tPA mRNA were detected, independent of calcium levels. Aclin mRNA levels were not modulated consequent to calcium stimulation. Hybridizations to 28S ribosomal RNA confirmed that equal amounts of RNA were analyzed from cells grown under low and high calcium conditions. These data demonstrate that keratinocytes. propagated in serum‐free media under low and high calcium conditions, are similar to normal human epidermis with respect to their expression of regulators of plasminogen activation. Additionally, they suggest that the ratio of PAI‐2 to uPA increases with keratinocyte differentiation.
Cytokine system as potential target for antipsoriatic therapy
Authors: Kemény L. , Michel G. , Dobozy A. , Ruzicka T.
Published: April 2006

Abstract Cytokines are produced by a variety of cells and have numerous of overlapping activities. There is increasing evidence that cytokines play a crucial role in the pathogenesis of psoriasis and of other dermatologic diseases. This review summarizes current knowledge as to how the altered cytokine network is involved in the accumulation of inflammatory cells in lesional skin, and how the cytokines are involved in epidermal hyper‐proliferation. The actions of the most important therapeutic compounds, such as corticosteroids, dithranol, cyclosporine, retinoids, vitamin D3 analogues and ultraviolet radiation, on the cytokine system are also discussed. Consideration is given as to how the effects on the production of cytokines and/or cytokine receptors contribute to their therapeutic action.
Differential modulation of interleukin‐1α (IL‐1α) and interleukin‐1β(IL‐1β in human epidermal keratinocytes by UVB
Authors: Kondo Seiji , Sauder Daniel N. , Kono Takeshi , Galley Kevin A. , McKenzie Roderick C.
Published: April 2006

Abstract Conflicting reports exist concerning ultraviolet‐B (UVB) effects on keralinocyte (KC) interleukin‐l (IL‐1) expression. To clarify the modulatery effects of UVB on IL‐1, the following study was undertaken. Normal human epidermal KCs cultured in a standard low Ca2+ and serum‐free medium were irradiated in quiescent phase with UVB. In this study, we used semiquantitative reverse transcriptase‐polymerase chain reaction (RT‐PCR) to determine the mRNA level of interleukin‐1α (IL‐1α) and interleukin‐1β (IL‐β). After exposure to 100 or 300 J/m2 UVB, a transient increase in mRNA levels was observed within I hour for IL‐1α and 3 to 6 h for IL‐β Following this transient induction, mRNA levels for both IL‐1α and IL‐1β returned to steady‐state levels after 100 J/m2. After 300 J/m2 irradiation, IL‐1α and IL‐1β levels were downregulated compared to unirradiated cultures at 24‐h post‐irradiation. The half‐life for IL‐1α and IL‐1β was estimated using actinomycin D treatment. Both IL‐1α and IL‐1β mRNAs half‐lives (t1/2) decreased faster in irradiated cells (t1/2 = 30 minutes for IL‐1α and 2 h for IL‐1β) compared to unirradiated cells (t1/2= 1 h and 4 h, respectively). These results suggest that IL‐1α and IL‐1β mRNA expression are differentially regulated by UVB. In contrast to down‐regulation of mRNA levels, a significant increase in IL‐1α protein levels, measured by ELISA. was observed in culture supernatant from 6 h to 24 h after 300 J/m2 UVB irradiation. Cycloheximide treatment did not abrogate this increase in IL‐1α protein level. Since this dose of UVB irradiation decreased the stability of IL‐1α and IL‐1β mRNA, this suggests that the release of IL‐1α after UVB irradiation was due to leakage from UVB‐damaged cells and not from de novo protein synthesis.
Substance P induces inositol 1,4,5‐trisphosphate and intracellular free calcium increase in cultured normal human epidermal keratinocytes
Authors: Koizumi Hiroko , Yasui Chikako , Fukaya Torn , Ueda Tetsuo , Ohkawara Akira
Published: April 2006

Abstract Substance P is a neuropeptide which is present in peripheral C nerve endings and released from them. Free nerve endings of C nerve are present in human epidermis. The effects of substance P on the transmembrane signaling system of pig epidermal sheets were previously reported. In these studies, a small amount of cells other than keratinocytes contaminated the epidermal sheets and the species difference from human was also noticed. Therefore we investigated the effects of substance P on cultured normal human epidermal keratinocytes. Alteration of intracellular free calcium (Ca2+) in single living keratinocytes was studied using an inverted fluorescence microscope and Ca2+ ‐sensitive dye, Fura 2‐AM. Treatment of normal human epidermal kertinocytes with substance P resulted in an increase in inositol 1,4,5‐trisphosphate and in intracellular Ca2+. Substance P inhibited DNA synthesis of the keratinocytes in a dose‐dependent manner. These results are consistent with the view that substance P stimulates phosphatidylinositol‐4,5‐bisphosphate hydrolysis of human keratinocytes, resulting in inositol 1,4,5‐trisphosphate‐Ca2+ signal.
Murine skin as a target for melatonin bioregulation
Authors: Slominski Andrzej , Chassalevris Nikolaos , Mazurkiewicz Joseph , Maurer Marcus , Paus Ralf
Published: April 2006

Abstract Specific binding sites for 3H‐melatonin were delected in membrane fractions prepared from C57 BL‐6 mouse skin, and were localized to the epidermis and the epithelial bulb of the hair follicle by in situ autoradiography. In skin organ culture, melatonin stimulated DNA synthesis by the epidermal keratinocytes at concentration 0.1‐10 nM, while at ≥1 μM it inhibited tyrosinase activity. We concluded that murine skin is a target for melatonin bioregulation.
Effects of prostaglandin E1 on human keratinocytes and dermal fibroblasts: A possible mechanism for the healing of skin ulcers
Authors: Zhang Jian‐Zhong , Maruyama Kohji , Iwatsuki Keiji , Ono Ichiro , Kaneko Fumio
Published: April 2006

Abstract The effects of prostaglandin E, (PGE) on cell growth, cytokine production and interaction of cultured normal human keratinocytes (NHKs) and human dermal fibroblasts (HDFs) were investigated. When NHKs were treated with PGE, directly, only a slight increase in cell growth and a transient decrease in interleukin 1 alpha (IL‐lα) secretion were observed. No IL‐6 was detected either before or after PGE, treatment. In addition, IL‐8 and transforming growth factor alpha (TGFα) production were uninfluenced by PGE. The response of HDFs to PGE, differed from that of NHKs. Following PGE1, treatment, IL‐lα and TGFα. from HDFs remained undetectable while IL‐6 production was enhanced markedly. IL‐8 production was also slightly enhanced. Exposure of HDFs to PGE, for 96 hours significantly promoted cell proliferation. Two kinds of conditioned media (CM) were prepared by a brief feeding of HDFs with keratinocyte basic medium or Dulbecco's modified Eagle's medium supplemented with 5% PCS with or without PGE. NHKs proliferated more rapidly in CM than in corresponding basic medium. Moreover, CM prepared with PGE, treatment showed a stronger effect in promoting NHK proliferation than CM without PGE, treatment. This promoting effect was inhibited by anti‐human IL‐6 monoclonal antibody dose‐dependently. These results indicate that fibroblasts are more sensitive than keratinocytes in response to PGE, and that, upon PGE, stimulation. HDF‐derived IL‐6 may play an essential role in NHK cell proliferation which may at least partly account for the beneficial effects of PGE, in the treatment of cutaneous liberations.
All‐trans retinoic acid induces functional maturation of epidermal Langerhans cells and protects their accessory function from ultraviolet radiation
Authors: Dunlop Katharine J. , Halliday Gary M. , Barnetson Ross St. C.
Published: April 2006

Abstract Retinoids provide some protection against ultraviolet radiation‐induced skin damage. We have previously shown that topical all‐trans retinoic acid prevents ultraviolet light from reducing the density of epidermal Langerhans cells in the epidermis but does not inhibit the development of immunosuppression to a locally applied contact sensitizer. We therefore investigated the ability of all‐trans retinoic acid to modulate Langerhans cell induction of allogeneic T‐cell proliferation in the mixed epidermal cell lymphocyte reaction. Langerhans cells isolated from all‐trans retinoic acid‐treated mice induced an enhanced mixed epidermal cell lymphocyte reaction. This is similar to Langerhans cells cultured with granulocyte‐macrophage colony stimulating factor. Retinoic acid treatment also enhanced the allogeneic cell‐stimulating capability of Langerhans cells isolated from ultraviolet‐irradiated mice. Langerhans cells from all‐trans relinoic acid‐treated, ultraviolet‐irradiated mice which were “matured” by 3 days in culture induced a larger mixed epidermal cell lymphocyte reaction than mice treated with solvent and ultraviolet irradiation. Thus all‐trans retinoic acid treatment of mice causes Langerhans cell maturation and inhibits ultraviolet light from reducing their density or impairing their allogeneic cell‐stimulating capacity. However, these mice remained immuno‐suppresscd upon application of a contact sensitizer to irradiated or unirradiated skin. It is thus likely that, whereas all‐trans relinoic acid protects local Langerhans cell numbers and function, it does not inhibit the production of an ultraviolet radiation‐induced photoproduct which causes immunosuppression.
Quantitative assessment of melanoma single‐cell motility in vitro
Authors: Hofmann‐Wellenhof Rainer , Smolle Josef , Helige Christine , Gottlieb Gerhard , Tritthart Helmut A. , Kerl Helmut
Published: April 2006

Abstract Cell motility is a crucial property of tumor cells during invasion and metastasis. In this study we developed a computer assisted system to measure translocation and stationary motility of single cells and used this procedure to evaluate the influence of cytochalasin A (CA) on single‐cell motility parameters of K1735‐M2 mouse melanoma cells. The cells were seeded at low density into a microincubator. Time lapse microcine‐malography was performed every 20 seconds from a high power field to assess stationary motility and every 10 minutes with a screening objective to measure translocalion. 1 μMol CA was added to the medium 48 hours before measurement. Calculation of stationary motility was performed by subtraction of subsequent images and the resulting image difference was used for quantitative evaluation. Three different measuring windows were drawn to discriminate between membrane ruffling, intra‐cellular organelle transport and overall stationary motility. For each cell we measured change of density (CD), area of change (AC), perimeter of area of change (PC), area of ruffling (AR), number of ruffling sites (NR), change of inlracellular organelles (CIO) and number of changing intraccllular organelles (NIO). In order to quantify translocation, the center of gravity of each cell was assessed subsequently and the velocity was calculated by connecting the centers of gravity. CA‐treated cells showed a significantly lower stationary motility and membrane ruffling compared to the untreated cells (U‐test: p ≤ 0.01). but there was not significant difference concerning the intracellular organelle transport. The velocity of cells grown in the presence of CA (11.56, ±14.68 μm/h) was significantly lower (U‐test: p< = 0.01) than that of the control group (37.96, ±14.6 μm/h). In conclusion, our study shows that the techniques applied yield quantitative assessment of different characteristic parameters of single‐cell motility in vitro. Cytochalasin A significantly inhibited both membrane ruffling and translocative single‐cell motility of melanoma cells without impairing intracellular organelle transport.
Characterization of cutaneous antigen presentation in partially inbred miniature swine
Authors: Grabbe S. , Fishbein J. M. , Sachs D. H. , Flotte T. J. , Granstein R. D.
Published: April 2006

Abstract MHC class I and II‐defined, partially inbred miniature swine have recently become available as a large animal model in transplantation immunology. To investigate cutaneous immunocompetence in this model, cutaneous antigen presenting cell (ARC) function was assessed. For morphologic analysis, punch biopsies were examined by electron microscopy. By this technique, epidermal Langerhans cells bearing typical Birbeck granules could be detected. For functional studies, epidermal cell (EC) suspensions were prepared from split thickness skin specimens. Using FACS analysis, freshly prepared epidermal cell suspensions contained 1.8‐4.7% MHC class II‐positive cells. These EC potently stimulated allogeneic nylon wool‐enriched peripheral blood T cells in the primary mixed EC‐lymphocyte reaction. For in vivo assessment of cutaneous APC function. EC suspensions enriched for or depleted of class II‐positive EC were generated by panning of class II‐positive EC using mouse anti‐MHC class II antibodies and anti‐mouse IgG‐coatcd petri dishes. EC were then coupled to the hapten trinitrophenol (TNP) and injected s.c. into autologous or MHC‐mismatched pigs twice at a one week interval. One week later, pigs were challenged by s.c.‐injection of 0.5‐1 × 107 TNP‐coupled or uncoupled EC. Autologous unseparated EC as well as EC enriched for MHC class II‐positive cells were able to sensitize naive animals against TNP, whereas neither TNP‐coupled EC depleted of class II‐positive APC, MHC‐mismatched EC coupled to TNP, nor uncoupled EC induced immunity to TNP. Our data indicate that inbred miniature swine possess competent cutaneous APC which are able to induce cutaneous immunity in a manner similar to Langerhans cells in murine or human skin.