11 research outputs found
Genetics of Cutaneous Melanoma
A portion of melanoma is familial and has been associated with atypical mole syndrome. This review outlines the current understanding of the genetics of melanoma and the relationship to cutaneous nevus phenotypes. A review of genetic studies of melanoma is presented, including linkage studies. Data from a linkage study of 12 Utah kindreds and one Texas kindred are detailed.There is strong evidence both for a genetic component to melanoma and, to a lesser extent, for a genetic component to the atypical mole phenotype. Reports of linkage of melanoma/dysplastic nevus syndrome to chromosome 1p markers are now strongly in doubt. The Utah group has shown strong evidence of linkage of melanoma to chromosome 9p21 without evidence for heterogeneity. This is in the same region where chromosomal deletions are common in tumors of numerous tissues.We conclude that there is a specific melanoma susceptibility locus located on chromosome 9p. The combination of the results of linkage in families with multiple cases of melanoma and the deletion of this chromosomal region in sporadic cases of melanoma strongly suggests that this melanoma susceptibility locus acts as a tumor suppressor. J Invest Dermatol 103:112S-116S, 199
Su1459 Characterization of Celiac Disease Antibody Response Reveals Wheat Non-Gluten Proteins As Novel Target Antigens
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International Human Dimensions Programme on Global Environmental Change (IHDP) Report 18
Coastal zones play a key role in Earth System functioning, by contributing significantly to the life support systems of most societies. Human activities modifying riverine hydrology and riverine material fluxes to the coastal zone, have increased in both scale and rate of change in the last 200 years. The underlying processes that drive changes to coastal systems occur at a multiplicity of temporal and spatial scales. These changes alter the availability of ecosystem goods and services. However, disciplinary fragmentation impedes our ability to understand the regional and global changes that affect coastal systems, and thus limits our ability to guide management and decision making. Progress has been made in understanding the changes in Earth System processes that affect the coastal zone, and the role of coastal systems in global change. This includes identifying proxies that describe the state of coastal systems under existing conditions and change scenarios. Typologies have been developed to assist in the interpolation of results into areas where primary information is lacking. This has enabled a first-order up-scaling to a global synthesis
Specific Nongluten Proteins of Wheat Are Novel Target Antigens in Celiac Disease Humoral Response
While
the antigenic specificity and pathogenic relevance of immunologic
reactivity to gluten in celiac disease have been extensively researched,
the immune response to nongluten proteins of wheat has not been characterized.
We aimed to investigate the level and molecular specificity of antibody
response to wheat nongluten proteins in celiac disease. Serum samples
from patients and controls were screened for IgG and IgA antibody
reactivity to a nongluten protein extract from the wheat cultivar <i>Triticum aestivum</i> Butte 86. Antibodies were
further analyzed for reactivity to specific nongluten proteins by
two-dimensional gel electrophoresis and immunoblotting. Immunoreactive
molecules were identified by tandem mass spectrometry. Compared with
healthy controls, patients exhibited significantly higher levels of
antibody reactivity to nongluten proteins. The main immunoreactive
nongluten antibody target proteins were identified as serpins, purinins,
α-amylase/protease inhibitors, globulins, and farinins. Assessment
of reactivity toward purified recombinant proteins further confirmed
the presence of antibody response to specific antigens. The results
demonstrate that, in addition to the well-recognized immune reaction
to gluten, celiac disease is associated with a robust humoral response
directed at a specific subset of the nongluten proteins of wheat
Autoimmunity to Desmocollin 3 in Pemphigus Vulgaris
Pemphigus vulgaris is a blistering disease associated with autoantibodies to the desmosomal adhesion protein, desmoglein 3. Genetic deficiency of desmoglein 3 in mice mimics autoimmunity to desmoglein 3 in pemphigus vulgaris, with mucosal-dominant blistering in the suprabasal layer of the epidermis. Mice with an epidermal-specific deletion of desmocollin 3, the other major desmosomal cadherin isoform expressed in the basal epidermis, develop suprabasal blisters in skin that are histologically identical to those observed in pemphigus vulgaris, suggesting that desmocollin 3 might be a target of autoantibodies in some pemphigus vulgaris patients. We now demonstrate that desmocollin 3 is an autoantigen in pemphigus vulgaris, illustrated in a patient with mucosal-dominant blistering. Six of 38 pemphigus vulgaris and one of 85 normal serum samples immunoprecipitate desmocollin 3 (P = 0.003). Incubation of patient IgG with human keratinocytes causes loss of intercellular adhesion, and adsorption with recombinant desmocollin 3 specifically prevents this pathogenic effect. Additionally, anti-desmocollin 3 sera cause loss of keratinocyte cell surface desmocollin 3, but not desmoglein 3 by immunofluorescence, indicating distinct cellular pathogenic effects in anti-desmocollin and anti-desmoglein pemphigus, despite their identical clinical presentations. These data demonstrate that desmocollin 3 is a pathogenic autoantigen in pemphigus vulgaris and suggest that pemphigus vulgaris is a histological reaction pattern that may result from autoimmunity to desmoglein 3, desmocollin 3, or both desmosomal cadherins