Antimelanoma antibodies in swine with spontaneously regressing melanoma.

Sinclair swine provide a unique model for studying mechanisms of tumor regression because they are born with melanomas that spontaneously regress approximately 10 weeks after birth. To examine whether an antitumor immune response is present in these animals, and, if so, to study its relation to tumor regression, 38 sera specimens collected at different times from 13 swine born with melanomas were tested for melanoma antibodies by immunoprecipitation and SDS-PAGE analysis of 125I labelled swine melanoma macromolecules. Antibodies to melanoma were present in 13 (100%) of the swine versus 1 of 3 control swine. The antibodies were directed to antigens of approximately 45, 68-75, or 100 kDa. These antigens were also expressed on human melanomas and normal melanocytes but on only one of five unrelated tumors. The incidence and level of these antibodies increased with time. Antibodies to the 45, 68-75, and 100 kDa antigens were present in 36%, 55%, and 9%, respectively, of sera collected prior to 7 weeks of age, but in 80%, 100%, and 37% of sera collected between 7 and 20 weeks (P < 0.05). The rise in melanoma antibodies usually preceded or appeared together with tumor regression and loss of pigmentation. These findings indicate that Sinclair swine with melanomas have antibodies to antigens preferentially expressed on pigment cells, and support the hypothesis that the regression phenomenon and the vitiligo-like skin depigmentation result from immune responses to common antigens shared by normal and malignant swine pigment cells.

Chronic mineralocorticoid excess and cardiovascular remodeling.

Chronic mineralocorticoid (MC) excess, whether due to elevated plasma aldosterone (ALDO) or deoxycorticosterone (DOC), is associated with a perivascular fibrosis of systemic and coronary arterioles. This remodeling of resistance vessels contributes to the appearance of hypertension. Chronic MC excess is also accompanied by cardiac myocyte necrosis, secondary to myocardial potassium depletion, and a subsequent reparative fibrosis that appears in the normotensive, nonhypertrophied right and hypertensive, hypertrophied left ventricles. Fibrosis contributes to the appearance of ventricular arrhythmias and dysfunction. Herein, clinical and experimental evidence linking chronic, inappropriate (relative to dietary sodium) elevations in circulating ALDO and DOC with these reactive and reparative forms of fibrous tissue formation in the heart and other tissues is presented.

Collagen vascular disease.

The iatrogenic L-tryptophan-induced eosinophilia-myalgia syndrome, often considered to be a "new" disease, has proven to be a remarkable mimic of the classic sclerosing rheumatologic disorders. Although subacute cutaneous lupus erythematosus remains a clinically defined entity, supportive histologic and immunopathologic findings have recently been proposed. Rheumatoid neutrophilic dermatitis needs to be added to our usual differential diagnosis of a neutrophilic dermatosis without leukocytoclastic vasculitis. The antiphospholipid syndrome is associated with noninflammatory vascular thrombosis and often has recognizable cutaneous findings. Finally, ANCA are a valuable adjunct in the systemic evaluation of patients with vasculitis syndromes and suggest a common pathogenesis for several of the systemic vasculitides.