Mustard-gas skin lesion and bullous pemphigoid antigen

1994 ◽  
Vol 52 ◽  
pp. 254-255
Author(s):  
John P. Petrali ◽  
Susan B. Oglesby ◽  
Tracey A. Hamilton
Keyword(s):  
Bullous Pemphigoid ◽  
Sulfur Mustard ◽  
Repair Process ◽  
Chemical Warfare Agent ◽  
Mustard Gas ◽  
Basal Cells ◽  
Immunochemical Study ◽  
Bullous Pemphigoid Antigen ◽  
Type Iv ◽  
Bullous Diseases

Human dermal exposure to the chemical warfare agent, sulfur mustard gas (HD), results in the delayed formation of fluid filled bullae which are incapacitating, persistent and slow to heal. In animal investigations, the pathology is typically described as that occurring during a prevesication period and that of a vesication period. During the first 24 hours, the pathology involves the latent lethal targeting of epidermal basal cells, a disabling of hemidesmosomes (prevesication) and a progressive inflammatory edema of the lamina lucida all contributing to the formation of characteristic lucidolytic microvesicles persisting at the dermal epidermal junction (vesication). We are now investigating possible primary or secondary HD-induced effects on extracellular adherent structural proteins of the basement membrane microenvironment which may contribute to vesication or may influence the repair process. Proteins selected for immunochemical study were laminin, type IV collagen, bullous pemphigoid antigen (BPA), fibronectin and desmosomal protein.Effects on BPA were of special interest. Its epitopes, BPA1 and BPA2, have been anatomically localized to basal cell hemidesmosomes and lamina lucida, and its role as an autoimmune antigen in the etiology of clinical bullous diseases such as bullous pemphigoid is well documented.

scholarly journals Bullous pemphigoid in a 3-month-old infant: case report and literature review of this dermatosis in childhood

2013 ◽  
Vol 88 (6) ◽  
pp. 961-965 ◽  
Author(s):  
Eugenio Galdino de Mendonça Reis-Filho ◽  
Tainah de Almeida Silva ◽  
Luiza Helena de Lima Aguirre ◽  
Carmelia Matos Santiago Reis
Keyword(s):  
Case Report ◽  
Bullous Pemphigoid ◽  
Immunohistochemical Staining ◽  
Collagen Type ◽  
Laboratory Data ◽  
Collagen Type Iv ◽  
Prognostic Features ◽  
Type Iv ◽  
Bullous Diseases ◽  
Infant Case

Bullous pemphigoid is an autoimmune subepidermal blistering dermatosis that is uncommon in childhood. We report a case of a female infant, 3 months old, which presented clinical and laboratory data for the confirmatory diagnosis of bullous pemphigoid. The authors used immunohistochemical staining for collagen type IV that allowed the differentiation of bullous pemphigoid from other subepidermal bullous diseases. Opportunely we review the clinical, immunological, therapeutic and prognostic features of this pathology in children.

Mustard Gas Inhalation Injury

2014 ◽  
Vol 33 (4) ◽  
pp. 271-281 ◽  
Author(s):  
Brian M. Keyser ◽  
Devon K. Andres ◽  
Wesley W. Holmes ◽  
Danielle Paradiso ◽  
Ashley Appell ◽  
...  
Keyword(s):  
Homeland Security ◽  
Sulfur Mustard ◽  
Chemical Warfare Agent ◽  
Inhalation Injury ◽  
Mustard Gas ◽  
Chemical Terrorism ◽  
Effective Therapeutic Strategy ◽  
Anti Inflammatory ◽  
Gas Inhalation ◽  
Inhibitor Compounds

Mustard gas (sulfur mustard [SM], bis-[2-chloroethyl] sulfide) is a vesicating chemical warfare agent and a potential chemical terrorism agent. Exposure of SM causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract; of these, the respiratory injury, if severe, may even be fatal. Therefore, developing an effective therapeutic strategy to protect against SM-induced respiratory injury is an urgent priority of not only the US military but also the civilian antiterrorism agencies, for example, the Homeland Security. Toward developing a respiratory medical countermeasure for SM, four different classes of therapeutic compounds have been evaluated in the past: anti-inflammatory compounds, antioxidants, protease inhibitors and antiapoptotic compounds. This review examines all of these different options; however, it suggests that preventing cell death by inhibiting apoptosis seems to be a compelling strategy but possibly dependent on adjunct therapies using the other drugs, that is, anti-inflammatory, antioxidant, and protease inhibitor compounds.

Airway epithelial damage induced by sulfur mustard in uinea pigs, effects of glucocorticoids

1996 ◽  
Vol 15 (12) ◽  
pp. 964-971 ◽  
Author(s):  
JH Calvet ◽  
A. Coste ◽  
M. Levame ◽  
A. Harf ◽  
I. Macquin-Mavier ◽  
...  
Keyword(s):  
Cell Density ◽  
Guinea Pigs ◽  
Sulfur Mustard ◽  
Chemical Warfare Agent ◽  
Tracheal Epithelium ◽  
Basal Cells ◽  
Airway Epithelial ◽  
Epithelial Damage ◽  
Epithelium Regeneration ◽  
Cell Shedding

Sulfur mustard (SM) represents a potential chemical warfare agent. In order to characterize SM-induced airway epithelial damage, we studied the effects of an intratracheal injection of 0.3 mg/kg of SM in guinea pigs, 5 h, 24 h, 14 days and 35 days after exposure. During the acute period, lesions prevailed in tracheal epithelium exhibiting intra-epithelial blisters, inflammatory cell infiltration and columnar cell shedding with exposure of basal cells. Fourteen days after intoxication, tracheal epithelium appeared disorganized and showed a signifi cant decrease in height and cell density. Tracheal epithelium recovery was still not complete even 35 days after SM-intoxication. At day 14, in SM-intoxicated guinea pigs treated with betamethasone from day 7 to day 14, epithelium height, cell density and cell proliferation (evaluated by immunohistochemistry) were significantly increased compared to untreated guinea pigs. In conclu sion, the lesions observed in SM-intoxicated guinea pigs seem to be in accordance with clinical human observa tions and are relevant to the study of airway epithelial damage induced by SM. This animal model could be used to illustrate tracheal epithelium regeneration mainly derived from basal cells and to show glucocorticoid effects on airway epithelial recovery after chemical aggression.

scholarly journals Distinct functions for integrins alpha 3 beta 1 in focal adhesions and alpha 6 beta 4/bullous pemphigoid antigen in a new stable anchoring contact (SAC) of keratinocytes: relation to hemidesmosomes.

1990 ◽  
Vol 111 (6) ◽  
pp. 3141-3154 ◽  
Author(s):  
W G Carter ◽  
P Kaur ◽  
S G Gil ◽  
P J Gahr ◽  
E A Wayner
Keyword(s):  
Bullous Pemphigoid ◽  
Dominant Role ◽  
Focal Adhesions ◽  
Human Keratinocytes ◽  
Isolation Procedure ◽  
Basement Membrane Zone ◽  
Basal Cells ◽  
Bullous Pemphigoid Antigen ◽  
Insoluble Complex ◽  
Affinity Isolation

Basal cells of stratified epidermis are anchored to the basement membrane zone (BMZ) of skin via hemidesmosomes. We previously identified integrin alpha 3 beta 1, in focal adhesions (FAs), of cultured human keratinocytes (HFKs) as a mediator of HFK adhesion to secreted BMZ-like extracellular matrix (ECM; Carter, W.G., E.A. Wayner, T.S. Bouchard, and P. Kaur. 1990. J. Cell Biol. 110: 1387-1404). Here, we have examined the relation of integrins alpha 6 beta 4 and alpha 3 beta 1, to bullous pemphigoid antigen (BPA), a component of hemidesmosomes. We conclude that alpha 6 beta 4 in HFKs localizes in a new stable anchoring contact (SAC) that cooperates with alpha 3 beta 1-FAs to mediate adhesion to ECM, based on the following. (a) Comparison of secreted ECM, with exogenous laminin, fibronectin and collagen identified ECM as the preferred ligand for HFK adhesion and spreading and for formation of both alpha 6 beta 4-SACs and alpha 3 beta 1-FAs. (b) Inhibition of HFK adhesion with combined anti-alpha 3 beta 1 (P1B5) and anti-alpha 6 beta 4 (GoH3) antibodies indicated that both receptors were functional in adhesion to ECM while alpha 3 beta 1 played a dominant role in spreading. (c) alpha 6 beta 4 colocalized with BPA in SACs that were proximal to but excluded from FAs. Both alpha 6 beta 4-SACs and alpha 3 beta 1-FAs were in contact with the adhesion surface as indicated by antibody exclusion and interference reflection microscopy. (d) In contrast to alpha 3 beta 1-FAs, alpha 6 beta 4-SACs were present only in nonmotile cells, not associated with stress fibers, and were relatively stable to detergents and urea, suggesting a nonmotile, or anchoring function for SACs and motility functions for alpha 3 beta 1-FAs. (e) alpha 6 beta 4 formed a detergent-insoluble complex with exogenous ECM in an affinity isolation procedure, confirming the ability of an unidentified ECM ligand to interact with alpha 6 beta 4. (f) We suggest that alpha 6 beta 4/BPA-SACs in culture restrict migration of HFKs on ECM while alpha 3 beta 1-FAs form dynamic adhesions in spreading and migrating cells. alpha 6 beta 4/BPA-SACs in culture bear functional and compositional similarities to hemidesmosomes in skin.

scholarly journals Degradation of the epidermal-dermal junction by proteolytic enzymes from human skin and human polymorphonuclear leukocytes.

1984 ◽  
Vol 160 (4) ◽  
pp. 1027-1042 ◽  
Author(s):  
R A Briggaman ◽  
N M Schechter ◽  
J Fraki ◽  
G S Lazarus
Keyword(s):  
Human Skin ◽  
Bullous Pemphigoid ◽  
Polymorphonuclear Leukocytes ◽  
Skin Diseases ◽  
Proteolytic Enzymes ◽  
Cathepsin G ◽  
Basal Cells ◽  
Lamina Densa ◽  
Normal Human Skin ◽  
Bullous Pemphigoid Antigen

The degradation of normal human skin by the human polymorphonuclear leukocyte proteinases cathepsin G and elastase, and by a human skin chymotrypsin-like proteinase that appears to be a mast cell constituent, was examined. Enzymes were incubated with fresh, split-thickness skin for up to 8 h; the tissue was examined ultrastructurally and immunohistochemically using antibodies to known basement membrane constituents. In all cases, the primary damage observed was at the epidermal-dermal junction. Elastase degraded the lamina densa leaving scattered and disorganized anchoring fibrils, dermal microfibril bundles, and normal-appearing collagen fibers. Immunohistochemically, type IV collagen, laminin, KF1 antigen, and EBA antigen were absent. The bullous pemphigoid antigen was present and localized on the basal cells. Epidermal-dermal separation produced by the chymotrypsin-like proteinases, cathepsin G, and the human skin proteinase, was confined to the lamina lucida. The lamina densa and sub-lamina densa fibrillar network remained intact. The human skin chymotrypsin-like proteinase produced extensive epidermal-dermal separation, while cathepsin G, at comparable concentrations, produced only focal separations. Immunohistochemically, all antigens were present after incubation with enzyme. The bullous pemphigoid antigen, however, was found on the epidermal side of the split, while laminin was found on the dermal side. These results show that the epidermal-dermal junction is highly susceptible to neutral serine proteinases located in mast cells and polymorphonuclear leukocytes. Although all the proteinases produce epidermal-dermal separation, the patterns and extent of degradation are different. The distinctive patterns of degradation may provide a clue to the involvement of these proteinases in skin diseases.

Acute Ocular Effects of Mustard Gas: Anatomic Pathology and Immunohistopathology of Exposed Cornea

1997 ◽  
Vol 3 (S2) ◽  
pp. 65-66
Author(s):  
J.P. Petrali ◽  
T.A. Hamilton ◽  
A.V. Finger ◽  
E. J. Dick
Keyword(s):  
Sulfur Mustard ◽  
Chemical Warfare Agent ◽  
Whole Body ◽  
Mustard Gas ◽  
World War ◽  
Clinical Observations ◽  
Corneal Damage ◽  
Major Chemical ◽  
The Right ◽  
Eye Lesions

Sulfur mustard gas (HD), a synthetic vesicating agent used effectively as a major chemical warfare agent during World War 1, continues to be a modern day threat agent. Unfortunately there is no specific pretreatment or antidotal therapy for those who may become exposed. Whole body exposure results in cutaneous, respiratory and ocular effects. of these, eye impairment leads to the most immediate incapacitation. However HD-induced eye lesions remain to be fully characterized. In the present study we explore histological, ultrastructural and immunopathological effects of a vesicating dose of HD in rabbit cornea occurring during the first 24 hours following exposure.A 0.4μl drop of liquid HD was placed on the left cornea of anesthetized rabbits. The right cornea served as an unexposed control. Following exposure animals were returned to their cages and given appropriate care by an attending veterinarian. Eye injury was evaluated by clinical observations and given scores of severity from simple conjunctival redness to apparent corneal damage.

The mucocutaneous manifestations of sulfur mustard gas on 1024 Iraqi victims: ISIS chemical attack in the South of Kirkuk

Toxin Reviews ◽  
2021 ◽  
pp. 1-6
Author(s):  
Seyed Naser Emadi ◽  
Bahareh Abtahi-Naeini ◽  
Ghasem Rahmat Pour Rokni ◽  
Seyed Emad Emadi ◽  
Shahin Hamzelou
Keyword(s):  
Sulfur Mustard ◽  
Mustard Gas ◽  
The South ◽  
Chemical Attack
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