Publications

Forty-three consecutive patients with acute inferior transmural myocardial infarction but no history or electrocardiographic evidence of prior myocardial infarction were evaluated prospectively to assess the clinical and prognostic importance of persistent precordial (V1-V4) ST segment depression. Patients were evaluated within 24 hr of admission by history, physical examination, cardiac enzyme levels, right heart catheterization, and radionuclide angiography; all were followed for 1 year. Ten of the 43 patients (group I) had persistent anterior precordial ST segment depression, defined as 1 mm or greater in one or more precordial leads (V1-V4) 24 hr after admission to the coronary care unit, and 33 patients (group II) did not. Clinical variables that differed between groups I and II, respectively, included mean age (67 +/- 9 [+/- 1 SD] vs 59 +/- 8 years; p less than .01), incidence of Killip class II to IV (100% vs 33%; p less than .001), and average peak creatine kinase concentration (2878 +/- 1139 vs 1511 +/- 1034 IU/liter; p less than .001). Hemodynamic differences between groups I and II included a higher pulmonary arterial wedge pressure (19 +/- 4 vs 11 +/- 5 mm Hg; p less than .001) and a lower cardiac index (2.0 +/- 0.5 vs 2.6 +/- 0.7 liters/min/m2; p less than .05). An evaluation of left ventricular ejection fraction and wall motion index by radionuclide angiography showed that group I had a lower ejection fraction (44 +/- 11% vs 53 +/- 10%; p less than .05) and higher wall motion index (1.7 +/- 0.4 vs 1.4 +/- 0.3; p less than .05) compared with group II.(ABSTRACT TRUNCATED AT 250 WORDS)

Murine lupus in BXSB mice is associated with B cell hyperactivity, monocyte proliferation, and impaired T cell function. However, the significance of these abnormalities, and the relationship among them, has not been clearly established. To examine the role of T cells in the pathogenesis of autoimmune disease in BXSB mice, we depleted specific T cell subsets from BXSB males by using rat IgG2b monoclonal antibodies (MAb) to either Thy-1.2 (on all T cells) or L3T4 (on "helper/inducer" T cells). A single injection of anti-Thy-1.2 (6 mg i.v.) at age 3 mo produced a sustained 40 to 50% reduction in circulating T cells for 6 mo. Treatment prevented monocytosis, reduced anti-DNA antibody concentration, and retarded renal disease, but it did not prolong life. Repeated injections of rat MAb to Thy-1.2 were precluded by the development of a host immune response to rat immunoglobulin (Ig) that can cause anaphylaxis in BXSB mice. In contrast, rat MAb to L3T4 stimulated little or no immune response to rat Ig. We therefore were able to treat BXSB mice weekly with anti-L3T4 (2 mg i.p.) from age 3 to 12 mo. Treatment reduced circulating L3T4+ cells beneath the level of detection by fluorescence analysis. It also significantly reduced monocytosis, anti-DNA antibody production, renal disease, and mortality. These findings establish that monocytosis and autoimmunity in BXSB mice are promoted by T cells. They extend our previous observation that MAb to L3T4 retard autoimmunity in NZB/NZW F1 mice. Our finding that treatment with MAb to L3T4 is effective in two strains of lupus-prone mice suggests that treatment with MAb to Leu-3/T4, the human homologue for L3T4, may be effective in people with systemic lupus erythematosus.