Differential stimulatory requirements and regulation of naive and primed human lymphocytes

In these investigations, human lymphocytes primed in vitro in MLR have been employed as a model for human memory cells and have been compared to naive lymphocytes from the same donor. Both the stimulatory requirements and the regulation of these cells were found to differ significantly. The dose of stimulators giving a maximal primary (I°) response was < 10% the dose of restimulating cells giving a maximal secondary (II°) response, II° responses were further found to be inversely related to the original I° response. This was associated with at least two separate regulatory phenomena. Suppressor cell induction was enhanced at high priming doses while memory cell precursors were preferentially stimulated at very low priming doses. Priming of memory cells could also be demonstrated to occur in the absence of any detectable I° proliferation by utilizing platelets or heat treated stimulators. Memory cells were also a much more resistant than naive cells to both alloantigen induced suppressor cells and to culture activated monocyte suppressor cells. This in vitro model suggests that the human I° and II° responses to alloantigen have both distinct triggering requirements and differential sensitivity to regulatory cells. It is suggested that preferential formation of memory cells under conditions that require no proliferation and which are suboptimal for suppressor cell generation and the acquired resistance of memory cells to down regulation by suppressor cells may contribute to the poor graft prognois of sensitized renal transplant patients.     

Differential electrophysiological features of neuropathies associated with 17p11.2 deletion and duplication

Hereditary neuropathy with liability to pressure palsies (HNPP) and hereditary motor-sensory neuropathy type IA (HMSN IA) are quite distinct clinical entities recently associated to deletion and duplication, respectively, of the 17p11.2 segment including the gene for peripheral myelin protein 22 (PMP-22). We studied the electrophysiological features of 48 HNPP and 62 HMSN IA motor nerves. Conduction velocities (CV) and compound muscle action potential amplitudes were significantly reduced and distal latencies prolonged in HMSN IA compared to HNPP. CV was uniformly slowed in HMSN IA nerves whereas in HNPP it was focally slowed in 80% of ulnar and 12% of peroneal nerves at usual compression sites. Conduction block was present in 6% of HNPP nerves but in none of HMSN IA. In conclusion: (1) HMSN IA with 17p11.2 duplication presents marked, diffuse, and uniform slowing; (2) HNPP with 17p11.2 deletion presents focal electrophysiological abnormalities possibly correlated with the presence of tomaculae; and (3) under-and overexpression of PMP-22 in concurrence with environmental factors might be responsible for the distinctive features of HNPP and HMSN IA. © 1995 John Wiley & Sons, Inc.     

Treatment of unipolar depression following electroconvulsive therapy. Relapse rate comparisons between lithium and tricyclics therapies following ECT.

A restrospective chart study and follow-up telephone interviews were used to compare the relapse rates of unipolar depressives who had received either lithium or tricyclics following ECT. The results showed no difference between the two treatment groups. The literature on ECT was reviewed in the light of the results from the present study. We concluded that ECT followed by either lithium or a tricyclic antidepressant is a more effective treatment for unipolar depression than ECT alone.     

Adequate anticoagulation during cardiopulmonary bypass determined by activated clotting time and the appearance of fibrin monomer.

The adequacy of anticoagulation during 2 hours of cardiopulmonary bypass at 30 degrees C in 9 rhesus monkeys was determined by measuring the whole-blood activated clotting time (ACT) and by noting the appearance of thrombin-altered fibrin (fibrin monomer) and the relative consumption of clotting factors. Factor V and VIII, the heparin cofactor, antithrombin III, prothrombin time, partial thromboplastin time, ACT, platelets, hematocrit, fibrinogen, and fibrin monomer were determined prior to heparinization and after protamine. In 6 of 9 experiments, fibrin monomer became positive in the plasma during cardiopulmonary bypass (CPB), indicating that active coagulation was occurring. In 5 of the 6 animals, initial ACT was less than 400 seconds, and fibrin monomer appeared within the first 30 minutes of bypass. In 1 animal with an initial ACT of 439 seconds, fibrin monomer appeared after 60 minutes of bypass, at which time the ACT was less than 400 seconds. An abnormal level of fibrin monomer was not detected in 5 pediatric patients with an ACT greater than 450 seconds during CPB. Our experimental study and clinical data suggest that the lower limit, as measured by the ACT, for anticoagulant effect to provide coagulation-free CPB is at least 400 seconds.     

Learned helplessness decreases [3H]imipramine binding in rat cortex

Specific binding of [3H]imipramine decreased in frontal neocortex from rats demonstrating learned helplessness, an animal model of depression. The decrease was in maximal binding but not in affinity for the receptor site. No change in [3H]imipramine binding was found in septum or hippocampus. The receptor changes found in frontal neocortex parallel behavioral and neurochemical changes produced by learned helplessness in this region. These changes are also similar to those found in the frontal neocortex from suicides and in platelets of patients with depression.     

Biochemical indices of cholinergic and adrenergic autonomic innervation in dog heart: disparate alterations in chronic right heart failure

Abnormal reflex sympathetic and parasympathetic control of heart rate occurs in canine right heart failure. Therefore, we investigated the activities of enzymes catalyzing synthesis of acetylcholine (choline acetyltransferase) and norepinephrine (tyrosine hydroxylase and dopamine-β-hydroxylase) to assess possible mechanisms of altered parasympathetic and sympathetic function respectively in hearts of dogs with chronic (greater than 2 years) right heart failure produced by tricuspid avulsion and pulmonary artery constriction (n = 7) and sham animals (n = 7). In dogs with tricuspid avulsion and pulmonary artery constriction there was a reduction in sympathetic neuroenzymes in both the stressed right ventricle and non-stressed left ventricle without any alteration in the parasympathetic neuroenzymes in these regions. There were no detectable changes in any enzyme activities within the left atrium. In the right atrium, however, significant reductions occurred in both sympathetic and parasympathetic neurochemical indices in the region of the sinoatrial node. The variable pattern of cardiac sympathetic and parasympathetic changes in dogs with tricuspid avulsion and pulmonary artery constriction suggests the possbility of non-uniform alterations in autonomic neural control of the chronically diseased heart.     

The influence of smoker status, smoking history, sex, and situational variables on smokers'' self-efficacy

Recent work in smoking cessation has focused on cognitive factors related to relapse and maintenance. The present investigation utilized an established self-efficacy-based questionnaire to determine whether sex, length of smoking history, successful quitting attempts, and environmental events affected subjects' perceived confidence of resisting smoking urges. It was hypothesized that: (a) subjects with fewer years smoking would have higher self-efficacy than those smoking for longer periods; (b) reported self-efficacy would be lowest for those situations involving negative moods; and (c) successful quitters would report higher self-efficacy than unsuccessful quitters. The second and third hypotheses were strongly confirmed, and a nonsignificant tendency in the expected direction was found for the first hypothesis. The results were generally consistent with the self-efficacy and the Abstinence Violation Effect (AVE) models.     

Effects of carvedilol on delayed rectifier and transient inactivating potassium currents in rat hippocampal CA1 neurons

1. The aims of the present study were to investigate the mechanism(s) underlying the protective effect of carvedilol against neural damage. 2. The transient inactivating potassium current (I_A) and the delayed rectifier potassium current (I_K) in rat hippocampal CA1 pyramidal neurons were recorded using whole‐cell patch‐clamp techniques. 3. Carvedilol (0.1–3 μmol/L) significantly inhibited I_K with an IC₅₀ of 1.3 μmol/L and the inhibition was voltage independent. Over the same concentration range, carvedilol had no effect on the amplitude of I_A. At 1 μmol/L, carvedilol did not significantly change the steady state activation curves of I_A and I_K, but did negatively shift their steady state inactivation curves. Recovery from inactivation was slowed for both I_A and I_K. The inhibitory effect of carvedilol on I_K was not affected by the adrenoceptor agonists phenylephrine and prazosin or the adrenoceptor antagonist isoproterenol, but propranolol was able to shift the dose–response curve of carvedilol for I_K to the right. 4. Because I_K is the main pathway for loss of intracellular potassium from depolarized neurons, selective obstruction of I_K by carvedilol could be useful for neuroprotection.