Corticotropin releasing hormone is a proangiogenic cytokine

ESDR I JSID I SID Abstracts

0271

0274

DESCRIPTION OF AN UNUSUAL FOCUS OF ENDEMlC PEMPHIGUS FOLlACEUS IN A RURAL AREA OF THE MUNlClPALlTY OF EL BAGRE, COLOMBIA, SOUTH AMERICA. Ma M. AbrereVelez’. Juan G. Maldonado.” Andres Jaramillo. * Joma Botero’snd Fernando M&ova” BiomediGYl Basic Science Corporaboi~n~, School oF Veteribary’and Medicine, Ubiv&ty ofAnlbqu!a, Medeffin, CoFunbia. A casecontrol study of an endemic focus of pemphigus foliaceus (EPF) m the rural area of El Eagre, Cdombia was canfed out. Forty-two EPF patients diagnosed by clinical, histopathological and immunological crftwta. and 27 controls from the same area were tested. According to our data, the prevalence of EPF in El Bagre, in the risk group (men among 30 to 70 Mng in rural area) was 1.4 %. All subiects were lvtno in the n&-al area and oerfotmed outdoor ackvlties as rnlnin~ and fan&. Senior m& were the mostly afF&ted (93.3%) with mean age of 50 );ears, which are&v differs from the Brazilian foao selvaae fFS) and the Tunisia EPF foci. Fimilia;cases were detected in t9%ot the EFF ‘pattents. The predominant dnical form @I%) simulate a &near Usher-like syndrome. Sun expo& was the most imoortant environmental factor assodated unth lW% of the EPF oatfents. The El Bagre area has been subjected to forest destructkm with’consequent increases in the average temperature of the area. The heavy metal mercury. is rouknelly used in large cuantities. in El Bagre for gold extraction. We tested for mercury levels in hair by mass spectrcecopy in the subjects of this study and we found htgher levels in EPF patients compared with co&ok (~~0.05). Higher IgE levels were found In the EPF pattents compared with the controls (vO.05) and no association with atopy or parasNc diseases wis detected by clinical and familiar Nstoty and by several coprology test. Based on these results and in the occupational exposure of PF patients (sun and mercury), we suggest that the combination of these factors couid bigger PF in people that is genetically predsposed.

A CASE

OF

PSORIASIS

ASSOCIATED WITH BULLOUS PEMPHIGOID AND D EXANTHEMATOUS PUSTULOSIS (AGEP). EJ&o!& CDurrieu. JJ&_ax. Department of Dermatology Purpan

A 7cyear-old woman was treated by acitretin since 1995 For psortasis. In October 1995, numsrous pruritic tense bullae on a erythematous base developed on safe skin and psoriasis lesions. Microscopic examination of a biopsy specimen disclosed a subepidermal bullae containing neutrophils and eosinophils. cutaneous direct immunofluorescence showed linear deposits of IgG and complement at the dermoepidermal junction, indirect immunofluorescence revealed circulatin basal membrane zone antibodies (l/256) staining the epidermal side of split skin. 8 estem immunoblottin analysis showed circulating antibodies to a 230 kDa epidermal antigen of similar werg,9, than major BP antigen. We conclude to bullous pemphigoid occuring in extensive psoriasis and the patient was treated with topical corticosteroids. During hospitalisation, she was treated with pristinamycine For cutaneous infection: 5 da s later. she develooed a oeneralized emotion with ervthema and numerous non-follicu Ysr and ‘aseptic pusiulosii Laboratory a’nalysis shohed a high ranuloc e count and ervthrocvte sedimentation rate. Histolooic Features were tvoica 9 of AGE $ and the skin ertptionbomplete disappeared withinone week when the treatment was stopped. The association o ? psorrasrs ‘. and bullous pemphigoid is described as a coincidental event but, recently. bullous eruptions occuring on psoriasis with circulating antibodies to a 200 kDa and/or s 230kDa anti en have been rs.p, orted. In our csss, the diagnosis of bullous pemphigoid and AGE 8, associated wt psonasrs has s solid clmical, histologic and immunologic basis and the occurencs of thess three diseases saems to be rare.

t

0272

0275

LARYNGEAL AND NASAL INVOLVEMENT IN PEMPHIGUS VULGARIS. Elizabeth A. Ksufmann and Jean-Claude Bvstrvn, Ronald 0. Perelman Dept. of Dermatology, NYU School of Medicine. New York NY. Laryngeal and nasal lesions have been described in pemphigus vulgaris, but the Frequency with which these sites are involved in the disease is not known. To address this issue, we studied the presence of laryngeal and nasal lesions in 53 sequential patients with pemphigus vulgaris diagnosed by dmical, histological, and immunofluorescencecriteria. Twentysix(49%)oFthepatientscomplainedoFlaryngeal and/or nasal symptoms at some time during the course of their disease. Twenty one had laryngeal symptoms (pain in the throat or on swallowing, hoarseness) and 12 nasal symptoms (stuFfmesa. crusting, blood tinged mucus discharge). Over90% of the ptswithsuch symptoms had evidence of pemphigus based on direct ENT examination and/or rapid resolution of svmptoms with increasing doses of corticosteroids. Two had candidiasis confirmed by Fun& culture. These observations indicate that laryngeal and nasal symptoms are common in patients wtth pemphigus vulgaris. In the majority of csses these symptoms appear to be due to involvement with pemphigus. and occasionally to candidiasis.

OKADAIC ACID AND PERVANADATE REGULATE EGFRFERK, MKK3/p39 AND JNK SIGNALING PATHWAYS IN KERATINOCYTES. A Mews, D Pew and MR IPittelkow Depts of Dermstology. and Molecular Biology, Mayo Clinic, Rochester, MN. Okadaic acid (OA) is a known skin tumor promoter and a widely used inhibitor of protein phosphatasas (PTP) type 1 and type 2A. Pervanadate-(PV) is a broad inhibitor of PTPs. PTPs serve important regulatory Functions For a wide range of signal transduction pathways in many cell types, some of which we have characterbed in kerstinocytes. We have shown these pathways sre also activated by oxidative stress. Speckically. EGF receptor (EGFR)/ERK pathway activation is rapidly activated by extra- and intra-cellular hydrogen peroxide (H,Oz) generated by csllular stress including UVB irradiation. Extracellular H102 levels released by keratinocytes. measured using A6550 are not increased by OA. Hcwever, PV signiF!csntly increases H202 levels dose-dependently. Dose- and time-dependent diQerential activation of EGFRIERK, MKK3Ip35 and JNK was observed after treatment with OA or PV. Activation of all these pathways by PTP inhibitors was blocked by N-acetylcysteine and enhanced bv buthionine suifoximine. Marked inhibition of OA-induced JNK activation by adeioviral overexpressed catalase indicates that basal H,Ozlevels play a critical role in mediating kerstinocyte signaling responses following PTP inhibition. In contrast. adenaviral overexpression of CuRn superoxide dismutase exerted only a minimal effect. Specific EGFR inhibition by PD153035 afler OA and PV treatment also blocked ERK pathway activation. Modulation of the intracellularredox state and inhibition of keratinwyte PTPs represents a pivotal regulatory mechanisms in the activation of EGFWERK, MKK3Ip38 and JNK signal transduction pathways Following cellular stresses such as H2020F UVB irradiation.

0276

0273 APPLICATION OP IL? GOLD Pas TF2mnDSo ntlummm BULBOUSSKIN DISKASES. Tsutomu Wmmatsu, Toshihiko

Shirai

University.

of Wdicine,

Chiang

In autoimum precise

tissues

Ccmceming gold

expensive

TO dwelop

equi-t

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which wa’e fixed

polymerized

with W light.

sem

and then

Stained

mjugated

gold.

but also

preserves

pemphigoid

This

method.

Ultrathin

by using

method not only

method

the LR Gold

were prepared

were incubated anti-human

from mm1

in LR Gold and with patients’

IgC and streptavidin

shows ~ltrastructwal

of @tapes

using of the

this

and emkedd&

wctins

biotinylated

(ID!)

to perform.

we performed blocks

the

patients’

and cryosubstitutian hmever.

not easy

in parafomldehyde

the antigenicity

autoantibcdies.

method.

En. LR Gold tissue

human skin

microscoW

cryofimtim

is a superior

ard easy

by these

af the ultrastructure

and is technically

mope convenient

posterbedded

Faculty

and pemphigoid,

by immumxlectron

of epitopes,

IEM system

of Demtolagy, of Pathology,

recognized

the preservation

and the mtigenicity

postembsdding requires

such as @igus

of autoantigens

has been examined

gold.

Departmmt

and *DapWment

Katsmi,

Chiacg Mei. Thailand.

diseases

of epitopes

autoantibodies

Japan

Mai University.

bullous

location

colloidal

Sara.

Sachiko

recognized

presemtim. by pmphigus

RRLEABINC HORMONE IS A PROANGIOCBNIC CITOKINE Jack L Arbiser, Kafia Karalis, Akila Viswanathan, Cheko Koike, Bela Anand-Apte, Bruce Zetter, Joseph Majzoub Dept of DemtoloSy, Harvard Medical School. Divi&ons of Surgical Research and EndocrinoloSy, Childrena Aospital. Rarvard Medical School Corticotropin releasing hormone (CRH) mediates the proximal end of the hypothalamic-pituitary-adrenal axis. and is found peripherally in sites of inflamatian, such as in arthritis. The role of peripheral CM is unknown, A genomic CRH clone was transfected info 293 cells, a human tumor cell line. and a CW seeretina clone was obtained. The CKS secreting cells demonstrated a Sro”thvadvantsSe in viva when Cransplanted subcutaneously info nude mice, compared with 293 cells transfeceed with eoncral vecfor, despite similar arovth rates in “itro. Grossly, the CRH producing tumors appeared hemorrhagic, suSSesting that CKS may sfimulate an&genesis. CKS potently stimulated endathelial chemotaxis in a dose-dependent fashion in a Boyden chamber assay. with a maximal effecr at SOnS/ml. This effect could be blocked by alpha-helical CR”, a CKH receptor antagonist. This effect was specific for endothelium, aa CRH had no effect on chemoraxis of vascular smooth muscle. The effect of CKS was shown to be true chemotaxis, and not random chemokinesis using a Checkerboard assay. CRH had no effect on endothelial

CORTICOTROPIN

TO MfmIrmRlE

Kmilio Hmoki.

and Prrunote Variittamka*.

Sara Medical

TmzSNIW

and

mitogenesis. Mice bearing CRH-producing tumors demonstrated an enhanced inflammatory reaction to subcutaneous carrageenan. These results demonsCrate that CR” is a potent endothelial chemoartracrant synthesized at sites of peripheral inf,,amarion. CRA may be an important mediator of inflammatory angiogenesis and inhibition of CRH may result in enhanced treatment of infla.matory disorders.