Publications

To study human T cell suppression of immunoglobulin (Ig) synthesis with homogeneous populations of immunoregulatory cells, human suppressor T cell hybridomas were prepared by somatic cell fusion of concanavalin A-activated peripheral blood T cells with hypoxanthine-guanine phosphoribosyltransferase-(HGPRT, EC 2.4.2.8) deficient human leukemic CEM T cells. After selection in hypoxanthine-aminopterin-thymidine (HAT) medium and cloning by limiting cell dilution, two human T cell hybridomas were identified that produced 60 to 80% suppression of in vitro polyclonal immunoglobulin production when cocultured with pokeweed mitogen- (PWM) stimulated peripheral blood lymphocytes. Further, one of the suppressor T cell hybridomas constitutively secreted a soluble suppressor factor(s) (TsF) of m.w. 70,000 to 85,000 daltons, which produced reversible noncytotoxic inhibition of lectin-activated B cell Ig production. In contrast, this TsF did not inhibit lectin- or antigen-induced T cell proliferation, nor did it interfere with the generation or effector function of cytotoxic T cells. Additional studies indicated that this Tsf acts directly on B cells or monocytes rather than indirectly modulating the activity of immunoregulatory T cells. In summary, these studies suggest that techniques of somatic cell fusion may provide a valuable approach to further study human immunoregulatory cell-cell interactions as well as provide a source of sufficient quantities of important lymphokines for further purification and characterization.

We evaluated 29 uncomplicated post-myocardial infarction patients with heart rate-limited and symptom-limited modified Naughton treadmill exercise tests predischarge and 31 similar patients with symptom-limited modified Naughton and standard Bruce stress tests at 6 weeks following infarction to determine their comparative value for detecting unsuspected ischemic abnormalities. Predischarge, the symptom-limited modified Naughton test identified a significantly greater number of patients with ECG ST segment depression or angina than did the heart rate-limited test (21 vs 13 patients, p less than 0.05). This resulted from a significantly longer average maximal exercise duration (10.5 +/- 4.9 vs 7.9 +/- 4.2 minutes, P less than 0.001) and higher maximal rate-pressure product (21.9 +/- 5.8 vs 19.2 +/- 4.6 X 10(3), p less than 0.001) during the symptom-limited test. At 6 weeks following infarction, the standard Bruce stress test identified a significantly higher frequency of ischemic abnormalities than did the symptom-limited modified Naughton test (20 vs 13 patients, p less than 0.05). This resulted from a higher average maximal rate-pressure product (23.1 +/- 7.3 vs 21.0 +/- 6.2 X 10(3), p less than 0.02), despite a shorter maximal exercise duration (6.9 +/- 1.2 vs 10.7 +/- 4.4 minutes, p less than 0.001) during the Bruce stress test. We conclude that: (1) symptom-limited exercise is superior to heart rate-limited exercise predischarge and (2) the standard Bruce stress test is superior to the symptom-limited modified Naughton exercise test at 6 weeks following infarction for the detection of unsuspected ischemic abnormalities in uncomplicated postinfarction patients.

The relative ability of M-mode echocardiography (EC) and systolic time intervals (STIs) to quantify acute positive inotropic interventions (PI) concurrently validated by hemodynamic measurements is unknown. Thus we studied the response of eight patients with normal coronary arteriography and LV function to successive incremental infusions of dobutamine (D-1, D-2) during cardiac catheterization. During D-1 with heart rate, arterial pressure and LV end-diastolic pressure unchanged, dP/dt max increased 65% (p less than or equal to 0.001), QS2 decreased 12% (p less than or equal to 0.01), PEP decreased 24% (p less than or equal to 0.01), LVET and PEP/LVET were not significantly changed, while EC %delta D and mean Vcf increased by 22% and 33% (both p less than or equal to 0.01). During D-2 with heart rate increased (increases 33%, p less than or equal to 0.001), EC Vcf (increases 66%, p less than or equal to 0.01) and PEP (decreases 33%, p less than or equal to 0.001) exhibited the greatest changes of the noninvasive parameters. The observed decreases in QS2 and LVET but not PEP were considerably attenuated after normalization for heart rate. Our data suggest: (1) echo and STIs are complementary in assessing PI; (2) PEP is more sensitive than QS2 in quantitating PI, particularly when large increases in contractile enhancement have occurred; and (3) both noninvasive techniques are less sensitive than dP/dt in detecting positive inotropic action.