摘要:

AbstractRecent progress in understanding the molecular organization of the cutaneous basement membrane zone (BMZ) has revealed an intricate network of structural proteins necessary for stable association of the epidermis to the underlying dermis. Molecular genetics of the cutaneous BMZ has also revealed that defects in as many as nine distinct genes within the dermal‐epidermal junction which result in different forms of epidermolysis bullosa (EB). a group of heritable mechano‐bullous disorders. We have recently demonstrated that a variant of EB associated with late‐onset development of muscular dystrophy (EB‐MD. MIM no. 226670) results from mutations in the gene encoding plectin (PLEC1). a cytoskeleton associated attachment protein present in the hemidesmosomal inner plaque and the sarcolemma of the muscle. Consequently, mutations in this multi‐functional gene/protein system can result in phenotypic manifestations of EB‐MD both in the skin and the muscle. In this overview, we will summarize the domain organization of plectin and the structure of the corresponding gene (PLEC1). as well as the genetic basis of EB‐MD in families studied thus far. Elucidation of the molecular basis of this subtype of EB adds to our understanding of the structural and functional complexity of the

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1996.tb00124.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractReactive oxygen species (ROS) are potentially cytotoxic and several mechanisms have evolved to protect against their damaging effects. In melanocytes, tyrosinase may have such a role by utilising the superoxide anion (O2−)in the production of melanin. In the present study, we have examined the cytotoxic effects of O2−and hydrogen peroxide (H2O2) in human melanocytes both before and following the activation of tyrosinase. Xanthine oxidase (XO, 5–150 mU · ml−1) and glucose oxidase (GO, 0.1‐20 mU · ml−1) were used to generate the O2−and H2O2respectively, and the cytotoxic effects assessed by measuring cell survival using the 3‐[4,5‐dimethylthiazol‐2‐yl]‐2.5 diphenyltetrazolium (MTT) assay. 3 h later, dose related decreases in melanocyte survival were seen. Similar experiments with keratinocytes and libroblasts showed that these cells were more resistant to the cytotoxic effects of O2−than were the melanocytes. The effect of increasing tyrosinase activity was examined by growing the melanocytes in the presence of an analogue of melano‐cyte‐stimulating hormone (MSH) Nle4DPhe7α‐MSH (10−8M), for 48 h. This increased tyrosinase activity, melanin content, the ability to trap O2−and the resistance of the melanocytes to the cytoloxic effects of this ROS. but failed to alter their susceptibility to the damaging effects of H2O. Nle4DPhe7α‐MSH had no effect on the resistance of keratinocytes and libroblasts to either O2−or H202. After 3 h, XO. as opposed to GO. also increased the melanin content of human melanocytes; this effect was not accompanied by an increase in tyrosinase activity. The present results suggest that tyrosinase may utilise O2−to produce melanin and that this process may protect melanocytes from

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1996.tb00125.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractTo verify if the counter‐ion Cl−permits the same interactions between nickel and divalent metals with physicochemical similarities as the counter‐ion SO4−does, 50 sensitive subjects to nickel sulfate 5% pet. who previously gave positive patch test reactions either to 8 μl of aq. nickel sulfate 0.1 M or to 8 μl of aq. nickel chloride 0.1 M, or to both, were patch retested simultaneously to 8 μl of respectively, aq. nickel sulfate 0.1 M and aq. nickel chloride 0.1 M, and to 8 (il of aq. mixed solutions containing, respectively, nickel chloride 0.1 M +magnesium chloride 0.3 M, nickel chloride 0.1 M+ zinc chloride 0.3 M, nickel chloride 0.1 M+zinc chloride 0.5 M, nickel chloride 0.1 M + manganese chloride 0.3 M, and nickel chloride 0.1 M + manganese chloride O.5 M. Whilst 4 subjects gave a positive patch test response to only nickel sulphate. 8 gave a positive response to nickel chloride alone and the remaining 38 gave a concomitant positive response to both. In all subjects who gave positive responses to nickel chloride, the chlorides of divalent metals were not able to inhibit or reduce the positive reaction. 25 healthy subjects patch tested to both single salts and mixed solutions, and all gave negative responses. 9 of the 50 subjects, 4 who previously gave positive reactions to only nickel chloride 0.1 M, and 5 with concomitant reactions of equal intensity to both nickel chloride and nickel sulfate 0.1 M, were patch retested simultaneously to 8 μ1 of, respectively, aq. nickel sulfate 0.1 M, aq. nickel chloride 0.1 M and aq. mixed solutions containing nickel sulfate (0.1 M) mixed with sulfates (0.3 M) and nickel chloride (0.1 M) mixed with chlorides of Mg, Zn, Mn (0.3 M). Whilst the mixed sulfate solutions were able to reduce nickel sulfale, 0.1 M patch test positive reactions, those containing chlorides, at all concentrations tested, did not inhibit the nickel chloride reactions in any of the subjects. The results of the tests to chlorides, compared to those reached on testing to sulfates of the same metals, lead us to hypothesize that the anion probably affects the uptake and local tissue distribution of the metal, modulating in this way, together with the individual cutaneous ligands,

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1996.tb00126.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractIntraepidermal nerve fibers were studied by electron microscopy in chronically photodamaged preauricular skin and in paired sun‐protected postauricular sites of 20 Caucasian women aged 56–70 years. As previously reported, basal keratinocytes in the sun‐exposed skin showed various degrees of degenerative changes including intracellular vacuolar structures and widened intercellular spaces. Neurites were frequently closely apposed to basal keratinocytes in preauricular sun‐exposed skin, but were observed less than 10% as often in sun‐protected postauricular skin. When degree of epidermal photodamage was quantified by means of the number of degenerated keratinocytes per 100 keratinocytes in the basal layer, the number of intraepidermal nerve libers was significantly correlated by linear regression analysis to the severity of epidermal photodamage (r=0.913) independent of anatomical sites. These results demonstrate for the first time a correlation between degree of epidermal innervation and chronic photodamage and suggest the possibility of neural involvement in the pathophysiology and/or repair of photodam

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1996.tb00127.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractWe have previously shown that retinaldehyde (RAL), a natural metabolite of (β‐carotene and retinol (ROL), can be used topically in human skin and exerts biological activity: it may be a convenient way to deliver multipotential vitamin A activity in epidermis. RAL can be converted enzymatically into 2 pathways: one leads to ROL (and then retinyl esters), the other to retin‐oic acid (RA). The aim of the present study was 2‐fold: (i) to see if RAL is metabolisedin vivowhen topically applied on mouse skin, and (ii) if so. to an‐alyse the occurrence and relative importance of the 2 metabolic pathways as compared to ROL. We studied by HPLC the metabolites detectable in mouse tail skin upon topical application of RAL and ROL. As compared to vehicle‐treated controls, RAL‐treated mouse skin contained low amounts of all‐trans RA and 13‐cis‐RA, whereas ROL content increased 10‐fold and retinyl esters 30‐fold after RAL application. As compared to RAL. ROL‐treated mouse skin showed no detectable RA, slightly less retinyl esters but a significant amount of 14‐hydroxy‐4, 14‐retro‐ROL (14‐HRR). a metabolite not previously reported in the skin. 14‐HRR was the predominant polar metabolite of ROL. These data indicate that keratinocytes metabolise topical RAL. thus confirming the concept of using RAL as a precursor. Both pathways are used but in significantly different proportions. Thus, only a low proportion of RAL is metabolised into all‐trans‐RA, which may explain the low irritancy profile of topical RAL and supports the concept of a controlled delivery of ligands. That keratinocytes predominantly channel RAL into storage forms indicates that RAL, should also be considered as a convenient way to load the epidermis with vitamin A. The detection of 14‐HRR. a metabolite not previously reported in skin, that promotes growth of B lymphocytes and activation of T lymphocytes, suggests

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1996.tb00128.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractIn atopic dermatitis (AD) patients, IgE molecules are demonstrated on the surface of Langerhans cells (LC). FcεRI molecules, which are present on the surface of LC in AD patients as well as normal individuals, are responsible for this binding. In this study, we have investigated phenotypic and functional characteristics of FcεRI on epidermal and dermal cell populations. Epidermal and dermal cell suspensions were prepared enzymatically with dispase followed by either trypsin or collagenase treatment, respectively. Peripheral blood basophils were negatively selected by excluding other leukocytes with surface marker staining. Consistent with previous reports, both peripheral blood basophils and epidermal LC were positively stained with anti FcεRI monoclonal antibody. In addition, an FcεRI positive population was demon‐strated among dermal HLA‐DR positive cells. These cells express significant amounts of HLA‐DR molecules (DRHi) and co‐express CD la molecules, which identifies them as LC‐like dendritie APC of the dermis. No other FcεRI positive population was found in the other dermal DRMidor DR populations, except for a minor DRlopopulation, presumably mast cells. To analyze whether these FcεRI molecules are signal transducing for LC, intracellular calcium mobilization after crosslinking of FcεRI was measured with How cytometry. Following crosslinking, peripheral blood basophils clearly increased intracellular calcium. On the other hand, neither normal epidermal LC nor dermal DRHiCD Ia+cells changed their intracellular calcium level after FcεRI crosslinking. These data indicate that normal epidermal and dermal LC, but not basophils, are resistant to calcium flux following

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1996.tb00129.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractIn the present study, facial skin from so‐called “screen dermatitis” patients were compared with corresponding material from normal healthy volunteers. The aim of the study was to evaluate possible markers to be used for future double blind or blind provocation investigations. Differences were found for the biological markers calcitonin generelated peptide (CGRP), somatostatin (SOM), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine amide (PHI), neuropeptide tyrosine (NPY). protein S‐100 (S‐100). neuron‐specific enolase (NSR), protein gene product (PGP) 9.5 and phenyl‐ethanolamine N‐methyltransferase (PNMT). The overall impression in the blind‐coded material was such that it turned out easy to blindly separate the two groups from each other. However, no single marker was 100% able to pin‐point the difference, although some were quite powerful in doing so (CGRP, SOM. S‐100). However, it has to be pointed out that we cannot, based upon the present results, draw any definitive conclusions about the cause of the changes observed. Whether this is due to electric or magnetic fields, a surrounding airborne chemical, humidity, healing, stress factors, or something else, still remains an open question. Blind or double‐blind provocations in a controlled environment are necessary to elucidate possible underlying causes for the changes reporte

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1996.tb00130.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

摘要:

AbstractFollowing the application of sensitizing chemicals to the skin, hapten‐bearing Langerhans cells (LC) and possibly other cutaneous dendritie‐cells (DC) migrate to the draining lymph nodes (DLN) of mice and induce the proliferation of antigen specific effector T cells. This migration of DC to the DLN is required for the induction of primary immune responses. In certain strains of mice, irradiation with ultraviolet‐B light (UVB) before sensitization results in the suppression of contact hypersensitivity responses.in vitroinvestigations have suggested that one influence of UVB is to modify the ability of Langerhans cells (LC) to present antigen. In the present investigation, putative UVB‐induced alterations in lymph node DC in vivo were examined. Lymph node DC were analysed following exposure of C3H/HeN mice to an immunosuppressive dose of UVB (1440 J/m2) 48 and 24 h prior to skin painting with the sensitizers fluorescein isothiocyanate or oxazolone. In functional studies. DC prepared from the DLN of contact sensitized mice were examined for their ability to induce hapten‐specific secondary T‐lymphocyte proliferative responses or mixed lymphocyte reactions in vitro. It neither case was the activity of DC influenced by local exposure to an immunosuppressive dose of UVB. The migration of LC from the epidermis to the draining lymph node in response to contact sensitization is associated with increased expression of several membrane determinants necessary for effective antigen presentation, including intercellular adhesion molecule‐1 (ICAM‐I: CD54), B7‐2 (CD86) and la antigen. The expression of these molecules was identical on DC isolated from the DLN of UVB‐irradiated and from control, unirradiated mice. Thus, the immunosuppressive effect of UVB on Ihe cutaneous immune system may not necessarily reflect changes in the antigen‐presenting DC that accumulate in the DLN followi

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1996.tb00131.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY

ISSN:0906-6705    

DOI:10.1111/j.1600-0625.1996.tb00132.x

出版商:Blackwell Publishing Ltd    

年代:1996

数据来源: WILEY