Antigen-specific t lymphocyte clones. II. Purifcation and biological characterization of an antigen-specific suppressive protein synthesized by cloned T cells

We have generated an antigen-specific T suppressor clone that synthesizes 70,000-mol wt peptides that have antigen-specific-binding activity. Although these data also indicated that antigen-binding peptides completely inhibited the in vitro primary response to a complex antigen, suppression might reflect the combined biologic activities of many different 70-mol wt polypeptides or polypeptides associated with the 70,000-mol wt material by noncovalent interactions. The protein responsible for antigen-specific suppression was therefore purified to virtual homogeneity after sequential separation of internally labeled supernate peptides on Sephacryl S-200 and DEAE-cellulose columns followed by isoeleetrofocusing. The resulting protein is greater than 95 percent homogeneous according to sodium dodeeyl sulfate-polyacrylamide electrophoresis and represents two peptides having two very close but distinguishable isoelectric point values of approximately 5.0. The purified molecules are retained by columns coated with lentil lectin or antigen but not by columns coated with antisera specific for immunoglobulins, the I region of the major histocompatibility complex or Ly-1 or Ly-2 antigens. Less than 50 pg of the purified glycoprotein specifically and completely suppresses production of anti-sheep erythrocyte plaque-forming cell by mixtures of 10(6) Ly-1 cells and B cells and this is a result of inactivation of Ly-l-mediated helper function. Specific inactivation of T (Th) cells by the 70,000-mol wt molecule is rapid, specific, and requires the presence of antigen. The mechanism of specific suppression of Th function may depend upon two functionally distinct regions of the 70,000-mol wt molecule: one that binds antigen and a second that mediates suppression.     

Catheter problems in the use of ventricular cardiovascular assist systems

The prerequisite for efficient assist-ventricles and impulses in the pulsatile pumping function are sufficiently dimensioned afflux and flowing off connections. In systematic investigations on the hydraulic circulation model the cannulas from an internal parameter of 12 mm with a total length of the connection distance to the inflow and outflow valve, respectively, at the bypass ventricle of 30 cm proved sufficient for performing a volume of output of 5-6 l/min in clinic-relevant filling pressures in a hypodynamic circulatory situation. Connection cannulas for the heart-lung machine used in routine work are not sufficient in periodic filling and ejection processes in the pulsatile pumping function for an effective decompression and effective increase of the cardiac output. In case of an ECG-triggered mode of action of the ventricular assist-system an increase of frequency up to 130/min in after that incomplete filling of the assist-ventricle does not remarkably restrict the effectiveness of the assist-system.     

Effects of dosing intervals on the development of tolerance to high dose transdermal nitroglycerin

To investigate the antiischemic efficacy and development of tolerance to transdermal nitroglycerin, 14 patients with chronic, stable angina pectoris were studied using continuous ambulatory electrocardiographic monitoring. Patients demonstrated initial hemodynamic responsiveness to sublingual nitroglycerin and were titrated to a maximally tolerated dose of 30 to 60 mg/24 hours (52 +/- 5 mg). Two crossover phases were use in a randomized, double-blind, placebo-controlled manner: continuous nitroglycerin therapy (patches containing active drug worn for 24 hours) and intermittent nitroglycerin therapy (12-hour active drug followed by a 12-hour nitrate-free period). There were no differences in frequency or duration of ischemic episodes between the placebo days of each phase. A significant effect in frequency of episodes was observed between placebo and treatment days of continuous therapy (p less than 0.05). Nonsignificant reductions in frequency and duration of ischemic episodes also occurred during intermittent therapy. The major antiischemic effect of transdermal nitroglycerin therapy occurred during the first day of treatment but was lost by 48 hours. Reductions in frequency and duration of ischemic episodes (p less than 0.05) were present on day 1 of continuous therapy but ischemic episodes returned to placebo levels by day 2, suggesting the development of tolerance. Intermittent therapy did not prevent the development of tolerance on day 2 of treatment. The results demonstrate that the use of high doses of transdermal nitroglycerin in patients with chronic, stable coronary artery disease produced a beneficial reduction in the frequency and duration of ischemia. However, the antiischemic benefit was lost between 24 nd 48 hours after the onset of continuous and intermittent therapy, presumably due to tolerance.(ABSTRACT TRUNCATED AT 250 WORDS)