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Multiple skin nodules in a recreational gardener from New York

Balcacer-Estevez, D; Paniz Mondolfi, A E; Zivin-Tutela, T; Zappi, E; Sordillo, E M; Polsky, B
PMID: 21564187
ISSN: 1365-2230
CID: 132584

Delayed type hypersensitivity to intralesional triamcinolone acetonide [Case Report]

Brancaccio RR; Zappi EG
Corticosteroids are the most widely used class of drugs in dermatology. In the past, allergic contact dermatitis to topical corticosteriods was rarely reported. In this article, we present a case of delayed type hypersensitivity to triamcinolone acetonide
PMID: 10664873
ISSN: 0011-4162
CID: 57564

The systemic lupus erythematosus (SLE) disease autoantigen-calreticulin can inhibit C1q association with immune complexes

Kishore U; Sontheimer RD; Sastry KN; Zappi EG; Hughes GR; Khamashta MA; Reid KB; Eggleton P
Following its release from cells during infection and inflammation, calreticulin (CRT) can act as an autoantigen in diseases such as SLE. Why CRT is a target of protective immunity and whether it may interfere with innate immunity once released from cells during inflammation is unclear. In the present study, we found that CRT was detected more frequently in SLE sera and in higher amounts than found in control sera. Approximately 40% of SLE sera tested contained autoantibodies against CRT as detected by ELISA and immunoblotting. CRT was found to be predominantly in the sera of SLE patients associated with immune complexes and C1q, and only bound to the surfaces of neutrophils in the presence of low levels of calcium and magnesium. In order to further investigate the C1q-CRT interaction, recombinant CRT and its discrete domains (N-, P-, and C-domains) were produced in Escherichia coli. CRT binds to globular head region of C1q primarily via its N- and P-domains. The N-domain was shown to be the most autoantigenic region of CRT, as the anti-CRT autoantibodies from most patients reacted against this region. CRT also altered C1q-mediated immune functions. The P-domain of CRT bound to C1q and reduced the binding of immune complexes in SLE sera to immobilized C1q. Full length CRT and its N- and P-domains were able to reduce the C1q-dependent binding of immune complexes to neutrophils and solid-phase bound C1q. We conclude that CRT, once released from leucocytes during inflammation, may not only induce an antigenic reaction, but also interfere with C1q-mediated inflammatory processes
PMID: 9158084
ISSN: 0009-9104
CID: 17074

Release of calreticulin from neutrophils may alter C1q-mediated immune functions

Kishore U; Sontheimer RD; Sastry KN; Zaner KS; Zappi EG; Hughes GR; Khamashta MA; Strong P; Reid KB; Eggleton P
Calreticulin is an abundant intracellular protein which is involved in a number of cellular functions. During cytomegalovirus infection, as well as inflammatory episodes in autoimmune disease, calreticulin can be released from cells and detected in the circulation, where it may act as an immunodominant autoantigen in diseases such as systemic lupus erythematosus. Calreticulin is known to bind to the molecules of innate immunity, such as C1q, the first subcomponent of complement. However, the functional implications of C1q-calreticulin interactions are unknown. In the present study we sought to investigate, in greater detail, the interaction between these two proteins following the release of calreticulin from neutrophils upon stimulation. In order to pinpoint the regions of interaction, recombinant calreticulin and its discrete domains (N-, P- and C-domains) were produced in Escherichia coli. Both the N- and P-domains of calreticulin were shown to bind to the globular head regions of C1q. Calreticulin also appeared to alter C1q-mediated immune functions. Binding of calreticulin to C1q inhibited haemolysis of IgM-sensitized erythrocytes. Both the N- and P-domains of calreticulin were found to contain sites involved in the inhibition of C1q-induced haemolysis. Full-length calreticulin, and its N- and P-domains, were also able to reduce the C1q-dependent binding of immune complexes to neutrophils. We conclude that calreticulin, once released from neutrophils during inflammation, may not only induce an antigenic reaction, but, under defined conditions, may also interfere with C1q-mediated inflammatory processes
PMID: 9065775
ISSN: 0264-6021
CID: 17075

Allergic contact dermatitis from mupirocin ointment

Zappi EG; Brancaccio RR
PMID: 9039185
ISSN: 0190-9622
CID: 12387

Sclerotic primary cutaneous leiomyosarcoma [Case Report]

Karroum JE; Zappi EG; Cockerell CJ
We describe the case of a painful primary cutaneous leiomyosarcoma that developed on the back of a 54-year-old white male over a 6-year period. The lesion had been sampled by punch technique and had been originally diagnosed as cutaneous sclerosis. Histologic examination of excisional tissue revealed a diffuse spindle cell neoplasm in the dermis that extended into the subcutis. There was extensive sclerosis and sparse cellularity in the deep portion and in several zones throughout the tumor. Immunostaining for desmin was negative, although stains for vimentin and smooth muscle actin were both strongly positive. Sclerotic cutaneous leiomyosarcoma should be recognized as a distinct but unusual variant of leiomyosarcoma that may be difficult to diagnose because of extensive sclerosis. Lesions may be painful and should be considered in the differential diagnosis of painful cutaneous neoplasms of the skin
PMID: 8599440
ISSN: 0193-1091
CID: 17076

Impact of ultraviolet irradiation on expression of SSA/Ro autoantigenic polypeptides in transformed human epidermal keratinocytes

Kawashima T; Zappi EG; Lieu TS; Sontheimer RD
SSA/Ro autoantibodies are frequently found in various autoimmune disorders including subacute cutaneous and neonatal lupus erythematosus. SSA/Ro patient sera precipitate a ribonucleoprotein complex consisting of multiple polypeptides and small RNA molecules (hY RNA). Such sera react in Western blot with at least four antigenically distinct proteins having molecular weights of 52-60 kD. Several laboratories have reported increased binding of anti-SSA/Ro patient serum to viable cultured human epidermal keratinocytes following UVB irradiation. However, it is currently unknown which SSA/Ro molecule(s) might be responsible for this increased antibody binding to UVB irradiated keratinocytes. To address this question, we studied the effect of UVB irradiation on the expression of three different polypeptide components of the SSA/Roautoantigen complex (60 kD SSA/Ro, 52 kD SSA/Ro, and 46 kD SSA/Ro (calreticulin) in A431 cells, a transformed human epidermal keratinocytes cell line. Total cellular and cell surface expression of each SSA/Ro antigenic polypeptide was examined by a whole cell ELISA and FACS using rabbit anti-synthetic peptide antisera as probes. Our results suggest that both total cellular and cell surface calreticulin, but not the 60 and 52 kD SSA/Ro polypeptides, is increased after 100 J/M2 of UVB irradiation, indicating that perturbed calreticulin expression may be primarily responsible for the UVB-induced increased binding of anti-SSA/Ro to keratinocytes. These results suggest that calreticulin could be a critical component of the SSA/Ro ribonucleoprotein complex that is involved in the pathogenesis of anti-SSA/Ro-associated photosensitive LE skin lesions
PMID: 7704007
ISSN: 0961-2033
CID: 17077

Calreticulin is released from activated neutrophils and binds to C1q and mannan-binding protein

Eggleton P; Lieu TS; Zappi EG; Sastry K; Coburn J; Zaner KS; Sontheimer RD; Capra JD; Ghebrehiwet B; Tauber AI
The Ca2+ storage protein calreticulin is associated with the endoplasmic reticulum and shares a high degree of amino acid homology with the surface receptor C1q-R. In this study, flow cytometric analysis detected calreticulin on the neutrophil surface, which decreased during stimulation probably as a consequence of shedding, as calreticulin was found by ELISA in the cell supernatants of stimulated cells. Antibodies raised against C1q-R and calreticulin demonstrated a high degree of immunological cross-reactivity for purified calreticulin as determined by dot blot analysis. Western blots of neutrophil subcellular fractions located calreticulin in both the cytosol and cell membrane fractions; C1q-R was largely confined to the cell membrane. Calreticulin and C1q-R both bind to C1q and mannan-binding protein. Therefore, calreticulin may be shed on cell activation and may be associated with the cell membrane, where it can potentially interact with C1q and serum lectins. The implications of this are discussed
PMID: 8062452
ISSN: 0090-1229
CID: 17078

Impact of ultraviolet radiation on the cellular expression of Ro/SS-A-autoantigenic polypeptides

Kawashima T; Zappi EG; Lieu TS; Sontheimer RD
Modulation of Ro/SS-A autoantigens in epidermal keratinocytes has been implicated in the pathogenesis of photosensitive forms of Ro/SS-A-antibody-associated cutaneous lupus erythematosus (LE) such as subacute cutaneous LE and neonatal LE. Since Ro/SS-A ribonucleoprotein particles have recently been shown to be very complex molecular structures, we have performed studies to determine whether the expression of three of the Ro/SS-A antigenic polypeptides might be differentially regulated in transformed human epidermal keratinocytes following UVB radiation. Our findings indicate that both total cellular and cell surface levels of calreticulin are upregulated by UVB exposure more so than are either the 52- or 60-kD Ro/SS-A antigens. These results suggest that calreticulin could be a critical component of the Ro/SS-A ribonucleoprotein complex involved in the pathogenesis of Ro/SS-A-antibody-associated LE skin lesions
PMID: 8049566
ISSN: 1018-8665
CID: 17079

The confined space-hypoxia syndrome [Case Report]

Zugibe, F T; Costello, J T; Breithaupt, M K; Zappi, E; Allyn, B
Two meter readers of a local water company were found dead in an underground water meter pit. Studies revealed a decrease in oxygen and an increase in carbon dioxide in the pit as a result of aerobic microorganisms present in the pit. Such an atmosphere may be rapidly fatal to the unwary worker who frequents such an environment. It is of paramount importance that this occupational hazard be recognized so that preventative measures may be established. We propose that the term "Confined Space-Hypoxia Syndrome" be adopted to all such confined space accidents occurring in water meter pits, tanks, holds of ships, mines, underground storage bins, and so forth, resulting from oxygen-deficient atmospheres. A series of recommended preventative procedures is included.
PMID: 3572347
ISSN: 0022-1198
CID: 633602