bluuebunny/crossref_metadata_2025 huggingface dataset:
Perioperative collapse: prevalence of latex allergy in patients sensitive to anaesthetic agents
Authors: Tan B. B. , Lear J. T. , Watts J. , Jones P. , English S. C.
Published: April 2006

The evidence in the literature suggests that the prevalence of latex allergy in the general population is approximately 1%. With increasing awareness of transmission of HIV and other infections such as hepatitis B. the use of latex gloves and condoms has escalated in recent years. As cheaper latex gloves of variable and doubtful quality flood the market, health care workers and patients are being increasingly sensitized by these latex products, A retrospective study investigated the prevalence of latex allergy in a cohort of 26 patients who suffered perioperative anaphylactoid reactions. 84% of these patients were hypersensitive to at least 1 anaesthetic‐related agent. 7.7% were also allergic to latex (p= 0.028). Atopy is a strong predisposing factor (p= 0.006)). An accurate preoperative history of atopy and past reactions to latex will identify most at‐risk patient. Prick test and RAST to latex will confirm the latex allergy. Anaesthetists, surgeons, allergists and other health practitioner should be aware of this problem.
10 years of patch testing with the (meth)acrylate series
Authors: Kanerva Lasse , Jolanki Riitta , Estlander Tuula
Published: April 2006

Statistics on 10 years of patch testing with 30 (meth)acrylates were compiled. Altogether 275 patients were patch tested and 48 patients (17.5%) had an allergic reaction to at least 1 (meth)acrylate. The (meth)acrylates most often provoking an allergic patch test reaction were 2‐hydroxyethyl acrylate (2‐HEA; 12.1%), 2‐hydroxypropyl methacrylate (2‐HPMA; 12.0%) and 2‐hydroxyethyl methacrylate (2‐HEMA; 11.4%). No allergic reactions were caused by 2‐ethylhexyl acrylate (2‐EHA), 2,2‐bis[4‐(methacryloxy)phenyl]propane (BIS‐MA), trimethylolpropane triacrylate (TMPTA), oligotriacrylate 480 (OTA 480), N,N‐methylenebisacrylamide (MBAA), or ethyl cyanoacrylate (ECA). The frequency of allergic patch test reactions presented cannot be considered as a “ranking” list of the most sensitizing (meth)acrylate compounds. In order to be able to judge the sensitization capacity of various (meth)acrylate compounds in humans, it would be necessary to have detailed information on the exposure history of the patients studied, including the purity of the (meth)acrylate compounds. Currently, this is not possible because (meth)acrylate‐containing products regularly contain undeclared (meth)acrylate compounds.
The nature and distribution of daffodil pickers' rash
Authors: Julian C. G. , Bowers P. W.
Published: April 2006

The rash associated with picking daffodils has long been recognized, but the distribution and differing types of lesions have not been explained. This study, from observations in the field, attempts to clarify the position. The method of picking and then gathering the flowers explains the development of the rash at the points of contact of plant sap with skin. Crystals of calcium oxalate in the sap, in conjunction with alkaloids, act as an irritant, and also cause the characteristic sores.
Regional differences in stratum corneum reactivity to surfactants Quantitative assessment using the corneosurfametry bioassay
Authors: Henry F. , Goffin V. , Maibach H. I. , Piérard G. E.
Published: April 2006

The skin does not react similarly to the presence of xenobiotics over all anatomic sites. Distinct regional differences have been described for irritancy and percutaneous absorption. The present study assesses the regional variation of stratum corneum reactivity to surfactants using the corneosurfametry bioassay. Stratum corneum was harvested from 6 body sites in 20 young adults. Corneosurfametry was performed using water, 1% SLS and a 5% soap solution. Data show that the best variable to assess regional variability in irritancy is the overall difference in corneosurfametry (ODC), comparing the effect of a given surfactant with water. The dorsal hand and volar forearm were the least reactive, the neck, forehead, back and dorsal foot the most reactive, sites. It is concluded that the corneosurfametry bioassay, through the ODC variable, is a practically non invasive tool for the evaluation of regional variation in irritancy at the level of the stratum corneum.
Allergy to cocamidopropyl betaine may be due to amidoamine: a patch test and product use test study
Authors: Fowler Joseph F. , Fowler Lynn M. , Hunter J. Edward
Published: April 2006

Cocamidopropyl betaine (CAPB) is an amphoteric surfactant commonly used in personal care products and surface cleaners. Patch testing with commercially‐available CAPB has yielded occasional reactions indicative of allergic contact dermatitis. To determine if subjects with previous positive patch tests would react in provocative use tests of products containing CAPB, and to study various contaminants in commercial CAPB supplies for allergenicity in these subjects. 10 subjects previously positive to CAPB on patch testing used a hair shampoo, hand soap, and body wash containing CAPB for 1–6 weeks or until a reaction developed. Later, they were patch tested to 2 different purity grades of CAPB and 3 possible manufacturing contaminants (dimethylaminopropylamine, amidoamine, and sodium monochloroacetate). 7 of the 10 subject developed dermatitis from 1 or more CAPB‐containing products at some point during the study 9 of the 10 use‐test subjects were then patch tested, and 6 of these subjects showed a reaction to amidoamine, (0.1% aq.). None reacted to dimethylaminopropylamine (0.1% pet.). 1 subject reacted to CAPB but not to amidoamine. In the follow‐up patch testing with CAPB that was free of amidoamine, there were no positive reactions. Most subjects who were patch‐test‐positive showed a reaction when using CAPB‐containing skin and hair care products. The chemical amidoamine, which is used in the synthesis of CAPB and which is a known contaminant of CAPB preparations, is likely to be the actual sensitizer in most cases rather than CAPB itself. The results do not rule out the possibility shin CAPB itself may be an allergen in rare cases.
Allergy testing in serious cutaneous drug reactions – harmful or beneficial?
Authors: Gebhardt M. , Wollina U.
Published: April 2006

We report on 3 cases of adverse cutaneous drug reactions of erythema multiforme type. Despite the serious previous clinical conditions, patch tests with the possible causative drugs have been performed in all our patients, because of multiple candidate drugs and the need of the patients for further treatment with at least some of the agents. We demonstrate that patch tests are a good and safe approach to initial evaluation of the nature of a cutaneous drug reaction. In the case of a positive patch lest reaction to one of the substances, re‐exposure to the non‐reactants in a clinical setting is recommended. If a one‐side‐blinded placebo‐controlled challenge test is well tolerated, then the clinician should be able to reintroduce drugs previously suspected as causing the allergy.
Patch test results in schoolchildren
Authors: Brasch Jochen , Geier Johannes
Published: April 2006

Our aim was to explore the current spectrum of contact allergens in schoolchildren, as a basis for diagnosis and prevention of allergic contact dermatitis. Results of patch tests in children 6–15 years old, performed in the years 1990–1995 by 22 centres of the German Contact Dermatitis Research Group and filed by the Information Network of Departments of Dermatology, were analysed and evaluated retrospectively, including epidemiologic data. Children with positive tests (62 out of 156 boys and 108 out of 260 girls tested) had a higher frequency of allergic contact dermatitis and a lower frequency of atopic dermatitis than patch test negative ones. 16 distinct allergens elicited positive reactions in ≥1% of the children tested. Reactions to nickel sulfate occurred in 15.9% of all children tested, but in 25.0% of girls 14/15 years old, and in only 4.5% of boys 6–13 years old. Double‐sensitizations with cobalt salts, potassium dichromate and palladium were seen. Mercury compounds were found in 2nd place (thimerosal: all children: 11.3%; 6–13 years old: 14.3%, 14/15 years old: 8.0%), followed by fragrance allergens. We conclude that contact allergy in children is related to their sex and age. Prophylaxis against nickel, mercury, and fragrance allergy needs to be improved. A shortened standard series may be sufficient for testing children.
Pathogenesis of mechanobullous disorders
Authors: Bruckner‐Tuderman Leena
Published: April 2006

Abstract Recent advances in the molecular biology of the dermo‐epidermal basement membrane zone have contributed greatly to our understanding of the etiopathogenetic pathways underlying mechanobullous disorders. Genetic linkage was established between the keratin gene clusters and epidermolysis bullosa simplex, and keratin mutations were identified in several patients. Anchoring filaments and the α6β4 integrin are likely to be affected in junctional EB. Genetic linkage was established between the collagen VII gene and both dominant and recessive subtypes of dystrophic epidermolysis bullosa. and different molecular abnormalities of collagen VII leading to formation of non‐functional, rudimentary anchoring fibrils were observed in several families. These discoveries that led to definition of mutations underlying EB also help us to understand the normal physiology and function of the affected structures. They may also point the way to new therapeutic strategies for common acquired blistering diseases and disturbances of epithelialization in general.
Evidence that filopodia outgrowth is a common final pathway for fibroblast growth inhibition in vitro
Authors: Stanulis‐Praegers Betzabe M. , Yaar Mina , Gilchrest Barbara A.
Published: April 2006

Abstract To identify events associated with fibroblast growth inhibition, the effect of two known inhibitors, interferon‐alpha and all‐trans retinoic acid, on the growth and surface morphology of cultured fibroblasts was examined. Interferon‐alpha administered at seeding reduced both growth rate and saturation density; all‐trans retinoic acid reduced only saturation density. However, both negative growth modulators were associated with an increase in filopodia outgrowth and an increase in intracellular filamentous actin in a time course corresponding to onset of growth inhibition by these agents. In combination with earlier findings, these data suggested that, regardless of ctiology, cultured fibroblast growth restriction is mediated in part by an actin‐dependent outgrowth of filopodia that augment intercellular contact.
Circulating immune complexes in patients with psoriasis: Do they exist?
Authors: Hunziker Thomas , Kolmár Agnes , Späth Peter J. , Braathen Lasse R.
Published: April 2006

Abstract Sera from 16 patients suffering from active psoriasis without arthropathy (2 guttate, 10 nummular, and 4 mixed type) were examined for the presence of circulating immune complexes. Five routine laboratory assay systems were used, based on C1q‐binding or detection of IgG‐coupled C1q and C3‐breakdown products. In l4 patients, no elevated levels of circulating immune complexes were detected. One patient, who additionally suffered from late‐phase HIV‐1 infection, showed C1q‐binding activities as well as levels of IgG‐coupled C1q and C3‐breakdown products in four of the assay systems, which indicated the presence of immune complexes in his serum. In another patient, with nummular psoriasis, slightly elevated levels of circulating immune complexes were measured by two of the assay systems. These results question the hypothesis of an essential pathogenic role of circulating immune complexes in psoriasis.
Effects of ultraviolet radiation on the pathogenesis of Mycobacterium lepraemurium infection in mice
Authors: Jeevan Amminikutty , Gilliam Kelly , Heard Hillary , Kripke Margaret L.
Published: April 2006

Abstract The purpose of this study was to determine whether exposing mice to ultraviolet radiation (UVR) would alter the pathogenesis of infection with Mycobacterium lepraemurium (MLM), which causes a chronic, progressive, lethal disease in susceptible mouse strains. BALB/c mice were irradiated on dorsal skin with various doses of UVR from FS40 sunlamps 3 days before infection with MLM in the hind footpad. The course of disease was followed by assessing the number of acid‐fast bacteria in the footpad, regional lymph node and spleen, and measuring the size of the lesion at the site of MLM infection at various times after infection. Mice were also tested periodically for a delayed‐type hypersensitivity (DTH) response by injecting MLM antigen into the uninfecled footpad and measuring footpad swelling 24 hours later. Mice treated with a single high dose of UVR (45 kJ/m2) had significantly more bacteria in the infected footpad, lymph node and spleen than unirradiated control animals. They also had larger lesions at the site of MLM infection and exhibited significant suppression of the DTH response at 3 and 6 months after infection. Injection of mice s.c. in the footpad with MLM 3 d after 45 kJ/m2 UVR reduced the median survival time from 391 to 305 d and after i.v. infection from 171 to 139 d. Dose‐response studies indicated that exposing mice to 2.3 kJ/m2 of UVR, which is approximately 1 minimal erythemal dose for this strain, suppressed the DTH response by 50% at 3 months alter infection. Significant increases in the number of bacteria in the footpad, spleen and lymph node were detected with doses of UVR≥5.6 kJ/m2. Mice exposed chronically to UV radiation also showed impaired responses to MLM. Thus, exposing mice to a single or multiple doses of UVR before infection increased the severity of a chronic mycobacterial infection and decreased the immune response to mycobacterial antigens.
Molecular biology and pathology of type VII collagen*
Authors: Uitto Jouni , Chung‐Honet Linda C. , Christiano Angela M.
Published: April 2006

Abstract Type VII collagen is a genetically distinct member of the collagen family of proteins. Type VII collagen has been shown to be the major component of anchoring fibrils, attachment complexes which secure the cutaneous basement membrance of the skin to the underlying dermis. Understanding of the structure of type VII collagen has been advanced by recent cloning of the corresponding gene. Chromosomal mapping of the gene to the short arm of chromosome 3 and identification of intragenic polymorphic markers have allowed demonstration of strong genetic linkage between the type VII collagen locus and the dystrophic forms of EB (epidermolysis bullosa). This overview summarizes the progress made in the molecular genetics of type VII collagen.
Human epidermal keratinocytes are a source of soluble ICAM‐1 molecules*
Authors: Budnik Anne , Trefzer Uwe , Parlow Frauke , Grewe Markus , Kapp Alexander , Schöpf Erwin , Krutmann Jean
Published: April 2006

Abstract A soluble form of the usually membrane‐bound adhesion molecule ICAM‐I was detected in supernatants derived from human epidermal keratinocytes. Specifically, supernatants harvested from long‐term cultured normal human keratinocytes, or from the spontaneously immortalized keratinocyte cell line HaCaT, did not contain significant amounts of sICAM‐l, but shedding of sICAM‐1 was found to be markedly induced upon stimulation of keratinocytes with rh IFNγ. In contrast, cells from the two epidermoid carcinoma cell lines. KB and A431, constitutively shed significant amounts of slCAM‐l even without cytokine stimulation, and sICAM‐l contents in supernatants harvested from these cells were further increased upon stimulation of cells with rh IFNγ. These studies indicate, that in addition to peripheral blood mononuclear cells and human melanoma cells, human epidermal keratinocytes constitute an important cellular source of sICAM‐l. By binding to leukocyte LFA‐1 molecules, keratinocyte‐derived sICAM‐l may influence inflammatory responses in the skin. In addition, constitutive shedding of sICAM‐l by transformed human keratinocytes may represent a possible mechanism by which neoplastic keratinocytes escape from cytotoxicity.
The 6/2 (AA3) polyclonal antibody identifying a 37 kD keratinocyte protein reacts also with BM‐600/nicein, the basement membrane component bound by the monoclonal antibody GB3
Authors: Verrando Patrick , Partouche Odile , Pisani Anne , Ortonne Jean Paul
Published: April 2006

Abstract An unexpected finding concerning our previously reported polyclonal antibody raised against an extract from human amnion (pAb 6/2, also termed AA3), and which recognizes an epidermal keratinocyte protein, is presented in this study. Using the immunoblot technique, pAb 6/2 binds to a 37 kD intracellular protein antigen. We have subsequently found that, by radioimmunoprecipitation performed after metabolic labelling with 35S‐methionine of cultured keratinocyles, pAb 6/2 recognizes the 600 kD epidermal basement membrane component (termed BM‐600/nicein) which was reported to be bound by the monoclonal antibody mAb GB3. Specifically, pAb 6/2 reacts with immunoaffinity chromatography‐isolated BM‐600/nicein blotted onto nitrocellulose. The data suggest the existence of two immunological reactivities borne by pAb 6/2, each of them being directed against, respectively, the 37 kD (seen in immunoblots) and the 600 kD protein (seen in immunoprecipitations). The data further suggest possible independent expression of these two proteins in cell culture. In comparison with the staining pattern of normal skin, immunofluorescence was previously noted to be impaired (pAb 6/2) or absent (mAb GB3) in lethal junctional epidermolysis bullosa. Thus, we conclude that mAb GB3, rather than pAb 6/2, is a more appropriate probe for the comprehensive biochemical study of this genodermatosis.
Signal transduction pathways in keratinocytes
Authors: Rosenbach Thomas , Czarnetzki Beate M.
Published: April 2006

Abstract Mammalian cells do not live as isolated organisms, but are instead organized into complex, highly specialized tissue organs composed of a homogeneous or a mixed cell population. In order to maintain tissue homeostasis in physiological and pathophysiological conditions, intercellular communication is an absolute requirement. This review will summarize our current knowledge as to how an extracellular signal is transduced via a specific receptor to the interior of the cell and how this signal will induce special cell functions. Attention will be paid to the major signal transduction pathways known to be active in keratinocytes, namely the adenylate cyclase, guanylate cyclase, tyrosine kinase, and phospholipase C systems. Finally, examples will be given of how interactions between these signal tranduction pathways can take place and how ‘signal cross‐talk’ might regulate keratinocyte function.
Studies and perspectives of signal transduction in the skin
Authors: Inohara Shinichi
Published: April 2006

Abstract Tumor‐promoting phorbol ester and epidermal growth factor (EGF) exert marked influences on the proliferation and differentiation of keratinocytes. These two agents bring their physiological functions into play via protein kinase C (PKC) activation (and/or down regulation) and protein tyrosine kinase, respectively. In this paper, the present situation in the studies on the signal transduction of keratinocytes centering around these two kinases is discussed. An outline of studies on signal transduction of cells other than keratinocytes in the skin is also given.
A non‐radiolabelled in situ hybridization method for the detection of epidermal cytokine mRNA
Authors: Howie S. E. M. , Aldridge R. D. , McVittie E. , Thornton E. , Ramage E. , Hunter J. A. A.
Published: April 2006

Abstract We describe a non‐radiolabelled method for the in situ detection of epidermal cytokine mRNA in paraffin sections of skin biopsies from sites of nickel contact sensitivity. The method uses fluorescein isothiocyan‐ate‐labelled oligonucleotide exon probe cocktails.
The ELAM‐1 ligand sialosyl‐Lex is present on Langerhans cells isolated from stratified epithelium
Authors: Nylander Karin , Larsen Jorgen K. , Larsen Jacob , Clausen Henrik , Bonding Nina , Dabelsteen Erik
Published: April 2006

Abstract In this study we show the expression of the newly identified carbohydrate ligand. sialosyl‐Lex on Langerhans cells. The receptor Tor sialosyl‐Lex is the endothelial leukocyte adhesion molecule‐1 (ELAM‐1) present on activated endothelial cells. Using How cytometry. Langerhans cells were selected due to positivity for an antibody against CD la and low orthogonal light scatter. The CD la antigen stained by the OK T6 antibody is considered a maturational marker of Langerhans cells in agreement with the specific labeling of dendritic cells in the epithelium only. Double immunostaining (OKT6/anti‐sialosyl‐Lex) using flow cytometry and immunohistochemistry demonstrated that almost all OKT6‐positive cells in normal stratified epithelium expressed sialosyl‐Lex. Conversely, by immunohistochemistry of oral epithelium with acute inflammation, additional dendritic cells negative for OKT6 were found to express sialosyl‐Lex In addition, sialosyl‐Lex‐positive but not OKT6‐positive dendritic cells were found in the submucosa. These findings indicate that the carbohydrate antigen sialosyl‐Lex is expressed earlier than the CD la antigen in the maturation of the Langerhans cell lineage. Future studies should aim at investigating the importance of adhesion between sialosyl Lex and ELAM‐1 in epithelial recruitment of Langerhans cells.
Comparison of skin changes induced on mice by either group A type 12 or group G streptococci
Authors: Reitmeyer James C. , Macdonald Etta , Tschen Eduardo H. , Thomas Danny , Head Cecile E.
Published: April 2006

Abstract Adult Swiss webster mice were injected with 3× 106 colony‐form inc units (cfu) of group G or 2. 5 × 106 cfu of group A streptococci at intradermal injection sites on the right and left paralumbar areas of the back. The mice were sacrificed at intervals between 4 hours and 14 days post‐injection (p. i.) and full thickness biopsies of skin 10 mm in diameter encompassing the sites of injection were taken. One tissue specimen was homogenized in PBS and plated to determine the number of cfu, while another was used for histopathological studies. The number of viable group A and group G streptotocci in the tissue increased to 3 × 109 cfu by 96 hours p. i. after 192 hours p. i. the group A cells had declined to 2. 7 × 106 cfu compared to 1. 1 × 108 cfu for group G cells. No streptococci of either group were detected at 336 hours (14 days p. i.). Gross edematous lesions induced by either streptococcus group were evident on all animals at 24 hours (p. i.). Group G streptococci lesions were larger and persisted longer than lesions induced by group A. Histological examination consistently revealed more inflammation and necrosis in tissue sections from mice injected with group G streptococci.
Increased expression of ICAM‐1, E‐selectin, and VCAM‐1 by cultured human endothelial cells upon exposure to haptens
Authors: Wildner O , Lipkow Th. , Knop J.
Published: April 2006

Abstract Contact allergens induce several accessory signals which promote the activation of antigen‐specific T cells. One of these signals is the increased expression of adhesion molecules on antigen‐presenting cells and endothelial cells. Epiculaneous application of non‐toxic doses of 2,4‐dinitrofluorobenzene (DNFB) onto the skin of non‐sensitized individuals elicited progressive staining for ICAM‐1 on dermal microvascular endothelial cells. To elucidate the question of whether contact allergens can act directly on endothelial cells to elevate their expression of surface structures that bind leukocytes, confluent monolayers of human umbilical vein endothelial cells were incubated with the contact allergens NiSO4, CoSO4 or DNFB. The ICAM‐1, E‐selectin and HLA‐DR expression were quantified by immunofiuorescence flow cytometric analysis. Furthermore VCAM‐1, E‐selectin and ICAM‐1 transcription were demonstrated by Northern blot hybridization. Constitutive ICAM‐1 expression on HUVEC increased similarly to that obtained after LPS (20 μg/ml) stimulation after 4 and 24 hours of incubation with 1 or 2 mM NiSO4 or CoSO4, respectively. Pulse‐stimulation with 100 or 500 nM DNFB resulted in a modest but significant increase of ICAM‐1‐positive cells. E‐selectin and VCAM‐I were not expressed on untreated HUVEC; 4 to 6 hours exposure to nickel sulfate and LPS resulted in a potent induction of E‐selectin and VCAM‐1 expression. DNFB and PMA had no significant influence on VCAM‐1 expression. None of the tested contact allergens was capable of inducing HLA‐DR expression on EC at 48 to 72 hours. Enhanced expression of adhesion molecules may be an important early unspecific mechanism for induction and elicitalion of a contact dermatitis.
Helium‐neon laser irradiation induces effects on cytokine production at the protein and the mRNA level
Authors: Funk Jens Oliver , Kruse Andrea , Neustock Petra , Kirchner Holger
Published: April 2006

Abstract The construction of an in vitro model allowed an investigation of the basic functions of immunocompetent cells after laser irradiation. Among low‐energy laser sources, the helium‐neon (He‐Ne) laser, with a wavelength of 632.8 nm, has often been found to produce photobiological effects including evidence of interference with immunological functions. Previous experiments revealed an influence of He‐Ne laser irradiation on concentrations of interleukin‐lα (IL‐lα. tumor necrosis factor‐α (TNF‐α, interleukin‐2 (IL‐2), and interferon‐γ (IFN‐γ) in supernatants of cultures of human peripheral blood mononuclear cells (PBMC) with increased cytokine concentrations after irradiation of 18.9 J/cm2 and decreased concentrations after irradiation of 37.8 J/cm2. Now, the mechanisms involved were studied. Results showed that cytokine production of cells stimulated with phytohemagglutinin (PHA), concanavalin A (Con A), or bacterial lipopolysaccharide (LPS) was altered significantly after laser irradiation but not after stimulation with staphylococcus aureus enterotoxin B (SEB). In situ hybridization of IFN‐γ mRNA producing PBMC revealed that the number of positive cells was modulated similarly. The results were identical in cultures of enriched monocytic (Mφ) or enriched T cells. Cells of the human monocytic cell line Mono Mac 6 were also influenced after LPS stimulation, whereas constitutively 1L‐2‐producing Jurkat cells were not influenced by laser irradiation at any energy density. Analysis of the IL‐2 receptor (IL‐2R) and intercellular adhesion molecule‐1 (ICAM‐I) expression in PBMC showed partial down‐regulation of both receptors at 37.8 J/cm2, but only after stimulation with PHA. Collected data demonstrated that He‐Ne laser irradiation induces functional changes of stimulated PBMC both on protein production and at the mRNA level.
Increased polymorphonuclear leukocyte Fc gamma‐dependent chemiluminescence in active psoriasis is not related to FcRIII (CD 16) receptor expression
Authors: De Simone C. , Guerriero C. , Venier A. , Rumi C. , Bussa S. , Fresu R. , De Sole P.
Published: April 2006

Abstract The role of the two main serum opsonins (IgG and C3b) in the induction of polymorphonuclear leukocyte chemiluminescence was studied in a group of psoriatic patients. Chemiluminescence was stimulated with zymosan opsonized by fresh plasma (IgG‐ and C3b‐dependent chemiluminescence) or by complement‐depleted plasma (IgG‐dependent chemiluminescence). While C3b‐dependent chemiluminescence was similar in patients with chronic or active forms of psoriasis. IgG‐dependent chemilumi‐nescence was significantly increased in patients with active disease. However, FcR‐III expression, evaluated by means of flow cytofluorimetry. was similar in the different groups of patients studied. The discrepancy between Fc‐receptor (CD 16) expression and IgG‐dependent chemilumi‐nescence is, therefore, indicative of modifications that occur in psoriatic neutrophils that do not involve FcIII‐receptor expression.
TP53 tumor‐suppressor gene and human carcinogenesis
Authors: Basset‐Séguin N. , Molès J. P. , Mils V. , Dereure O. , Guilhou J. J.
Published: April 2006

Abstract The wild‐type tumor‐suppressor TP53 gene encodes for a nuclear protein which has been shown to act as a transcriptional modulator. The cellular role of the p53 protein is the control of cell proliferation, particularly important in stressed cells. The TP53 gene is frequently mutated in sporadic and familial human cancers. Most transforming mutations localize in highly conserved domains of the gene and define hot‐spot regions that have a certain degree of tissue specificity. Moreover, most mutations are point mutations and the type and localization of the nucleotide substitution may sometimes help in recognizing the carcinogenic agent. This is the case for C to T transitions at dipyrimidine sites induced by UV radiation in cutaneous epitheliomas. Inactivation of p53 protein can also occur through mechanisms other than genetic alteration, such as binding to viral or cellular proteins. Loss of wild‐type TP53 function seems therefore to play a crucial role in cell transformation in human cancers, either during carcinogenesis or later in tumor progression.
Mode of release of interleukin‐8 from proliferating human epidermal keratinocytes in vitro
Authors: Takematsu Hideaki , Tagami Hachiro
Published: April 2006

Abstract Keratinocytes have been shown to express interleukin‐8 (IL‐8) mRNA on stimulation with IL‐1 and other substances. This has been assumed to account for the large amount of this neutrophil chemotaclic cytokine in psoriasis. We found that, without any added agents, commercially available normal human epidermal keratinocytes proliferating in Keratinocyte Growth Medium® (KGM) released a chemotactic peptide extracellularly, which was confirmed to be IL‐8. To determine whether most of the IL‐8 is secreted extracellularly from proliferating keratinocytes or is mainly stored to be released only on stimulation. We quantified cell‐associated and released immunoreactive IL‐8 from keratinocytes cultured in KGM for up to 11 days at the peptide level. The keratinocytes proliferated, taking a sigmoid growth curve, to reach a plateau at day 7. We found that the amounts of immunoreactive IL‐8 gradually increased in the culture supernatant with cell growth but its prominent release took place only after the cell growth reached a plateau. The cell‐associated IL‐8 was much smaller in amount than that noted in the supernatant. These results suggest that the IL‐8 constitutively produced by keratinocytes was mostly released extracellularly but that the production by actively proliferating cells seems to be far less than that by non‐proliferating cells that probably occurred in an autocrine fashion under the stimulation of keratinocyte‐derived cytokines accumulated in the culture medium. Neutrophil chemotactic activity assayed concomitantly showed a consistent increase during the culture period, indicating that, with their growth, the keratinocytes release substances other than IL‐8 that exert an influence on neutrophil chemotactic functions.
Epidermal growth factor induces ornithine decarboxylase in SV40‐immortalized human keratinocytes
Authors: Prystowsky Janet H. , Clevenger Charles V. , Zheng Zai‐Sheng
Published: April 2006

Abstract The effect of epidermal growth factor (EGF) on the activity of ornithine decarboxylase (ODC) was evaluated and partially characterized in SV40‐transformed, immortalized cultured human keratinocytes. It was observed that the addition of fresh complete medium to confluent cultures resulted in a 10‐fold increase in ODC activity. Characterization of this activity using serum‐free medium revealed that the increase in ODC activity was primarily due to the presence of EGF (10 ng/ml). A dose‐dependent increase in ODC activity was observed when cultures were treated with EGF. Although near maximal induction occurred with EGF concentrations as low as 2.5–10 ng/ml, maximal induction of ODC (25‐fold) occurred with an EGF concentration of 50 ng/ml. The peak time for ODC induction was 10 hours following the addition of EGF to keratinocyte cultures. The induction of ODC by EGF was inhibited by pretreatment of cultures with either cycloheximide or actinomycin D, suggesting that both protein synthesis and gene transcription are important in the FGF induction of ODC. EGF significantly increased the steady stale levels of ODC mRNA with a peak at 4 hours, preceding the peak in observed enzyme activity as expected. Pretreatment of cultures with retinoic acid (10−5–10−7M) significantly inhibited the induction of ODC by EGF. Retinoic acid decreased the steady‐state levels of ODC mRNA. These data demonstrate that ODC is an enzyme that is induced by EGF in human keratinocytes; this induction probably involves both gene transcription and protein synthesis. Retinoic acid partially prevents the EGF induction of ornithine decarboxylase activity through a presently undefined mechanism(s), but appears to have effects that result in decreased ODC mRNA levels.
Basal cell carcinomas display extensive abnormalities in the hemidesmosome anchoring fibril complex
Authors: Korman Neil J. , Hrabovsky Sharon L.
Published: April 2006

Abstract We have employed a panel of antibodies directed against several newly‐defined and well‐characterized components of the epidermal basement membrane (BM) to investigate the biology of basal cell carcinoma (BCC) by indirect immunofluorescence and to determine whether alterations in BM components may play a significant role in BCC tumor invasion. We found that the 230 KD bullons pemphigoid antigen (BPA) was either not detected (13/16) or significantly diminished (3/16) in BCC tumor BM. While the 180 KD BPA revealed less intense staining of the normal overlying epidermal BM than did the 230 KD BPA, the 180 KD BPA was uniformly undetectable in BCC tumor BM (16/16). Epiligrin was either not detected (9/15) or minimally detected (6/15) in BCC tumor BM. α6 integrin was not detected (15/16) or minimally detected (1/16) in BCC tumor BM, whereas β4 integrin was uniformly undetectable in BCC tumor BM (16/16). Type VII collagen was also not detected (9/16) or was significantly diminished (4/16) in BCC tumor BM. Laminin and type IV collagen were both at least as strong in BCC tumor BM as in adjacent normal BM. All of these components were present both in the epidermis of normal skin as well as in the normal epidermal BM overlying BCC tumor nests. Our findings reveal extensive alterations in numerous components of the hemidesmosome anchoring fibril complex of BCC's. As this complex is thought to play an important part in epidermal cell adhesion to the BM, our findings suggest that these extensive BM abnormalities may facilitate or contribute to BCC tumor invasion.
Roles of CD4+ and CD8+ cells in UVB‐induced suppression of splenic alloantigen presenting function
Authors: Kitajima Toshiyuki , Imamura Sadao
Published: April 2006

Abstract Whole body ultraviolet light (UV) radiation causes systemic immunosuppression. Splenic antigen‐presenting cell (APC) activity is decreased by UV radiation. To determine whether splenic CD4+ or CD8+ cells are involved in the UV‐induced depression of splenic alloantigen presenting function, we investigated the effect of in vivo UV radiation on the splenic stimulatory function in allogeneic mixed lymphocyte reaction in mice after the elimination of CD4+ or CD8+ cells by administering anti‐CD8 or anti‐CD4 Ab. Ab‐treated and non‐treated mice were exposed to UVB radiation (2.5 k.J/m2) twice or eight times. Two exposures to UVB radiation significantly suppressed the splenic alloantigen‐presenting function of mice previously treated with anti‐CD4 Ab, but hardly affected that of anti‐CD8 Ab‐treated or non‐treated mice 2 days after the last radiation. On the other hand, eight exposures to UVB radiation suppressed this function in all mice. FACS analysis revealed that the UV induced suppression is not associated with a significant decrease in the number of IA+ cell, as stimulator cells. It is suggested that CD4+ cells are somewhat preventive of the UV‐induced depression of splenic alloantigen‐presenting function.
UVA does not photoreactivate pyrimidine dimers in cultured human fibroblasts
Authors: Tanew Adrian , Ortel Bernhard , Hönigsmann Herbert
Published: April 2006

Abstract Pyrimidine dimers were induced in duplicates of cultured human skin fibroblasts by irradiation with various doses of UVB radiation. Subsequently, one set of cells was further exposed to either 5 or 10 J/cm2 of UVA radiation to assess the photoreactivating activity of this spectral range in a human cell system. Following irradiation, pyrimidine dimers were quantified in all cells by determining the number of endonuclease‐sensitive sites (ESS). No difference in the yield of ESS was observed between cells which had been irradiated with UVB only as compared to cells which subsequently had been exposed to 5 or 10 J/cm2 UVA. In contrast, subsequent exposure of UVB‐irradiated cells of Monodelphis domestica to 10 J/cm2 UVA resulted in an almost 50% reduction of UVB‐induced pyrimidine dimers. These data indicate that UVA does not induce photoenzymatic repair in human fibroblasts.
ETH615, a synthetic inhibitor of leukotriene biosynthesis and function, also inhibits the production of and biological responses towards interleukin‐8
Authors: Kristensen Mette , Jinquan Tan , Thomsen Mads K. , Zachariae Claus , Paludan Kirsten , Ahnfelt‐Ronne Ian , Matsushima Kouki , Thestrup‐Pedersen Kristian , Larsen Christian G.
Published: April 2006

Abstract ETH6I5 (4‐(2‐quinolylmethoxy)‐N‐(3‐fluorobenzyl‐phenyl‐amino‐methyl‐4‐benzoic‐acid), a synthetic inhibitor of leukotriene B4 production and activities, was tested for its effect on the production of and biological responses towards human interleukin‐8. We found that ETH615 inhibits lipopolysaccharide‐induced (LPS‐induced) expression of interleukin‐8 messenger‐RNA (mRNA) and interleukin‐8 production in human peripheral blood mononuclear cells. We also observed that ETH615 completely inhibited interleukin‐8 as well as leukotriene B4 directed chemotaxis of human neutrophils in a dose‐dependent manner. A moderate effect on fMLP‐directed neutrophil chemotaxis was observed. Further, no significant effect on either interleukin‐8. leukotriene B4 or fMLP‐directed T‐cell migration was observed. These results further support the concept of a cytokine‐leukotriene regulatory circuit and encourage the establishment of clinical trials testing the effect of ETH615 on inflammatory skin diseases, which are characterized by high levels of interleukin‐8 and leukotriene B4 in lesional skin.
Influence of staphylococcal lipoteichoic acid on the frustrated phagocytosis of neutrophils against opsonized corneocytes
Authors: Kato Taizo , Terui Tadashi , Zhen Ya‐Xian , Tagami Hachiro
Published: April 2006

Abstract Stratum corneum (SC) exerts a proinflammatory effect in the presence of complement. When Staphylococcus aureus (S. aureus) invades the skin through damaged SC. neutrophils accumulate at the sub‐corneal portion of epidermis to phagocytize the S. aureus as noted in impetigo. Besides the phagocytosis of bacteria. neutrophils interact with opsonized SC in a form of frustrated phagocytosis, increasing a damage of the surrounding tissues. Based on our previous finding that staphylococcal protein A promotes the interaction between SC and neutrophils. we investigated whether lipoteichoic acid (LTA), another cell wall component of S. aureus, also shows similar properties. We found that LTA significantly promoted the binding of neutrophils to opsonized SC, resulting in an increase in SC‐induced respiratory burst of neutrophils assessed by chemiluminescence (CL). The binding of neutrophils to the SC was almost completely inhibited by the blocking of CR3 with anti‐CD11b antibody, suggesting that the binding between SC and neutrophils is mediated by interaction between C3bi and CR3 (Mac‐1). Such enhanced interaction seems to function in the primary host defence mechanism against the invading S. aureus through the skin such as in impetigo.
Production of multiple cytokines by cultured human melanomas*
Authors: Bennicelli Jeannette L. , Guerry DuPont
Published: April 2006

Abstract We screened a panel of 8 primary and 21 metastatic melanoma cell lines for constitutive secretion of cytokines. Melanomas expressed bioactivity for TGF‐β (8/25 lines) and IFN (7/12), but not IL‐2. Immu‐noassays detected IL‐1α (4/25), IL‐1β (12/25), 1L‐6 (13/29), IL‐8 (29/ 29), TGF‐β2, (5/12) and GM‐CSF (11 /29). but not IL‐3, IL‐4, TNF‐α, or IFN‐γ. There was no preferential association of cytokine production with cells cultured from primary versus metastatic disease, and only IL‐8 was produced by all lines tested. These data demonstrate that cultured melanomas produce a variety of cytokines which are potentially capable of influencing tumor growth in vivo.
Cellular and molecular composition of human skin in long‐term xenografts on SCID mice
Authors: Kaufmann Roland , Mielke Volker , Reimann Jörg , Klein C. Eberhard , Sterry Wolfram
Published: April 2006

Abstract We report on the immunophenotypical characterization of adult human skin transplanted onto severe combined immunodeficienl (SCID) mice. Thirty animals were followed for up to 12 months after receiving split‐thickness xenografts. of which 28 were tolerated for the whole test period. Antigen mapping revealed an almost complete preservation of human cellular and extracellular tissue components in long‐term trans‐plants including skin immune cells (Langerhans‐cells, macrophages. lymphocytes) and also parts of the engrafted endolhelium. Hence, xeno‐grafts on SCID mice offer a versatile experimental tool for the in vivo study of both human skin immune cell function and endothelial cell‐mediated interactions in an environment completely devoid of inter‐ferences by adoptive host immune response.
Expression of growth factor receptors on human melanoma cells: Comparison of modulating effects of interferons and retinoids
Authors: Worm Margitta , Reichert Uwe , Dippel Edgar , Czarnetzki Beatc M. , Schadcndorf Dirk
Published: April 2006

Abstract Amocrine and paracrine growth factors are important mediators in malignant transformation. Interferons (IFN) and retinoids (RX) are well‐known differentiative and immunomodulating agents with effects on subsets of different human tumors including malignant melanoma. In this study, we examined the modulating effects of three IFN and seven different RX on human melanoma cell lines regarding growth factor receptor expression. Growth factor receptor expression, including PDGF‐R, NGF‐R, EGF‐R, IR, IGF‐l‐R, TFR and c‐kil. was studied by immunhislochemistry and FACSsean analysis. Both groups of sub‐stances modulated the expression of some growth factor receptors. Upre‐gulation of PDGF‐R was seen after treatment with IFN as well as with RX. In contrast, EGF‐R was found to be downregulated in two EGF‐R‐positive cell lines by IFN and. on the other hand, induced by RX in two EGF‐R‐negalive cell lines. The expression of NGF‐R was modulated am‐biguously by these substances but demonstrated a cell line specificity in the different melanoma cell lines tested. Additionally, some of the tested growth factor receptors were not markedly changed regarding their ex‐pression by treatment with IFN and RX (IR. 1GF‐I‐R, e‐kit, TFR).
Normal response to tumor necrosis factor‐alpha and transforming growth factor‐beta by keratinocytes in psoriasis
Authors: Malkani Angeli K. , Baker Barbara S. , Garioch Jennifer J. , Powles Anne V. , Lewis Helen M. , Valdimarsson Helgi , Fry Lionel
Published: April 2006

Abstract Normal and chronic plaque psoriatic keralinocyte cultures were tested for their in vitro response to 2–200 ng/nil TNF‐α and 0.1–10 ng/ml TGF‐β in a serum‐free culture system. All normal and lesional psoriatic epidermal cell cultures showed a dose‐ and lime‐dependent inhibition of growth in response to TNF‐α and TGF‐β. Inhibition in individual cultures was first seen at a concentration of 2 ng/ml for TNF‐α and 0.1 ng/ml for TGF‐β at day 2, but became significant at 20 ng/ml and 1 ng/ ml for TNF‐α and TGF‐β respectively at days 2‐6. This effect was statistically significant at days 3–4 for the group of normal (TNF‐α and TGF‐β, n = 10, p<0.01 and psoriatic cultures (TNF‐α. n = 9, p<0.0l; TGF‐β, n = 7, p<0.05). Epidermal cells from normal and psoriatic skin were inhibited to the same extent at the same optimal concentrations by each cytokine. Inhibition was abolished by the addition of specific antibody to each cytokine, whilst antibody to a different cytokine had no effect. Nuclear and/or nuclear membrane staining was observed with antibody to the p55 TNF receptor both in cultured keralinocyles and in the tipper epidermal layers of both normal and psoriatic skin. In contrast, plasma membrane and cytoplasmic expression of the p55 TNF receptor was observed on macrophages and lymphocytes infiltrating psoriatic der‐mis. This study has shown that the growth of normal and psoriatic keratinocytes was equally inhibited by TNF‐α and TGF‐βin vitro. The expression of TNF receptor by psoriatic keratinocytes in vivo may permit regulation of epidermal growth by administration of TNF‐α in this disease.
Inhibitory effect of azelastine, a potent antiallergic agent, on release of tumor necrosis factor‐α from activated human peripheral blood mononuclear cells and U937 cells
Authors: Hamamoto Yoshiaki , Nagai Kou , Muto Masahiko , Asagami Chidori
Published: April 2006

Abstract It is generally accepted that tumor necrosis factor‐α (TNF‐α) is a multifunctional cytokine which is involved in the regulation of inflammation as well as immunity. In the present study, we investigated whether azelastine, a potent antiallergic agent, affects release of TNF‐α from peripheral blood mononuclear cells (PBMC) and U937 cell line in vitro. When human PBMC and U937 cells were stimulated by phytohemagglulinin (PHA) and 12‐0‐letradecanoyl‐phorbol‐13‐acetate (TPA). respectively, the cells released significant amounts of TNF‐α as determined by TNF‐α‐specific enzyme immunoassay. TNF‐α levels in the culture supernatant of PHA‐stimulated human PBMC and TPA‐activated U937 cells decreased in a dose‐dependent manner when these cells were cultured in the presence of azelastine. This inhibitory effect of azelastine was obtained at concentrations where the drug produced no toxicity. Moreover, azelastine also inhibited release of TNF‐α from U937 cells which were already activated by TPA. These results suggest that the inhibitory effect of azelastine on TNF‐α release plays an important role in its antiallergic action in addition to inhibition and/or antagonism of histamine and leukolriens, which has been previously reported.
Phenotype of Langerhans cells in human afferent skin lymph derived from allergic contact dermatitis
Authors: Brand Ch. U. , Gerber H. A. , Hunziker Th. , Schaffner Th. , Limat A. , Brathen L. R.
Published: April 2006

Abstract By means of microsurgical lymph cannulation human skin lymph derived from the late phase of an elicitation reaction to diphenylcyclopropenone was sampled. Cells were isolated by centrifugation and then treated with mouse anti‐CDl a mnonoclonal antibodies and sheep antimouse antibody‐coated Dynabeads. Ultrastructural and immunocytochemical analyses revlaled anti‐CDl a/Dynabead‐rosetted CDl a‐ and protein S‐100‐positive cells which did not express monocyte surface markers, but surface antigens such as HLA‐DR, ICAM‐I and, in part, LFA‐3. In comparison to freshly prepared human epidermal Langerhns cells (LC), a large fraction of these cells contained no or markedly fewer Birbeck granules and exhibited extensive ruffling of the surface. These data suggest that the phenotype of LC in skin lymph derived from the elicitation phase of allergic contact dermatitis is similar to LC cultured in vitro. In the functional concept or LC or our time, these cells correspond to the dendritic cells designated as “veiled”.