salicylates and Lymphatic-Diseases

Activation and proliferation of lymphocytes requires the active signal transducer Ras. Activation of lymphocytes, associated with autoimmunity, may therefore be modified by S-farnesylthiosalicylic acid (FTS), a synthetic substance that detaches Ras from the inner cell membrane and induces its rapid degradation. The MRL/lpr mouse is a genetic model of a generalized autoimmune disease sharing many features and organ pathology with systemic lupus erythematosus (SLE) and the primary antiphospholipid syndrome (APS). The objective of the present study was to examine the effect of FTS on laboratory and clinical pathology in the MRL/lpr mouse. Female MRL/lpr (n = 50) and MRL/++ control (n = 35) mice were treated intraperitoneally with either FTS (5 mg/kg/day) or saline between 6 and 18 weeks of age. The mice were weighed, tested for proteinuria and lymphadenopathy, lymphocyte proliferation, antibodies, grip strength and behaviour in an open field. FTS treatment resulted in a 50% decrease in splenocyte proliferation to ConA, LPS and a disease specific antigen, beta(2)-glycoprotein-I, and in a significant decrease in serum antibody levels against cardiolipin and dsDNA. Proteinuria and grip strength were normalized and lymphadenopathy and postmortem lymph node and spleen weights were significantly reduced in FTS treated MRL/lpr mice. These findings indicate that modulation of Ras activation has a significant impact on the MRL/lpr model and may represent a new therapeutic approach for the treatment of systemic autoimmune diseases such as SLE and APS.

Topics: Animals; Antiphospholipid Syndrome; Autoantibodies; Autoimmune Diseases; Farnesol; Female; In Vitro Techniques; Lupus Erythematosus, Systemic; Lymphatic Diseases; Lymphocyte Activation; Lymphocytes; Mice; Mice, Inbred MRL lpr; ras Proteins; Salicylates

Kawasaki disease, mucocutaneous lymph node syndrome, thought to be rare in the continental United States, occurred in epidemic form in New York City and adjacent New York and New Jersey in November-December, 1977. Aspirin and corticosteroids, reported to be ineffective treatment, were found to completely control the illness in affected children, provided adequate doses to achieve therapeutic blood levels were administered. Patients were found to malabsorb aspirin (and perhaps also to destroy it) and so required extraordinarily high doses during the acute phase; during recovery, doses had to be lowered to the usual range to avoid toxicity. The need for hospitalization and morbidity were reduced and, hopefully, mortality will also be reduced. The importance of not judging a drug ineffective in a disease without demonstrating adequate serum levels was again shown.

Topics: Aging; Aspirin; Child; Child, Preschool; Disease Outbreaks; Feces; Humans; Infant; Lymphatic Diseases; Mucocutaneous Lymph Node Syndrome; New York City; Salicylates

Since October 1978, four cases of mucocutaneous lymph node syndrome, a disease previously not yet described in our country were observed in our childrens hospital. This particular disease has been described quite frequently in Japan since 1967. It has a characteristic manifestation being mostly benign and self limited. In a few cases however acute cardiac arrest has been described. The first case we observed expired as a result of acute coronary infarction on the twentyfifth day of illness although clinical improvement had been previously noted. At post mortem examination the coronary arteries showed changes consistent with arteriitis. The following three cases presented the more typical benign course of this disease one of them with deformities of the coronary arteries. The clinical synopsis describes the above mentioned cases.

Topics: Adrenal Cortex Hormones; Arteritis; Austria; Child, Preschool; Coronary Vessels; Electrocardiography; Humans; Infant; Lymphatic Diseases; Male; Mucocutaneous Lymph Node Syndrome; Myocardial Infarction; Salicylates

Topics: Cathartics; Cyclamates; Halogens; Haptens; Humans; Lymphatic Diseases; Nalidixic Acid; Phenothiazines; Photosensitivity Disorders; Salicylates; Stilbenes; Sulfonamides

Topics: Adolescent; Alanine Transaminase; Arthritis, Juvenile; Aspartate Aminotransferases; Bilirubin; Child; Child, Preschool; Clinical Enzyme Tests; Diagnosis, Differential; Female; Fever; Hepatomegaly; Humans; Infant; Leukocyte Count; Liver; Liver Function Tests; Lymphatic Diseases; Male; Pain; Pericarditis; Pleurisy; Salicylates; Sex Factors; Splenomegaly; Sulfobromophthalein