Sezary cell morphology induced in peripheral blood lymphocytes: re- evaluation

In this study we examined the effect of mitogens and epidermal cells in inducing a Sezary cell morphology in normal peripheral blood lymphocytes. Peripheral blood mononuclear cells from six healthy volunteers were stimulated with the mitogens phytohemaglutinin and concanavalin A, and also cocultivated with human epidermal cell cultures. Incubation times with mitogens and epidermal cells were four days and stimulation of the lymphocytes by mitogens was confirmed by standard 3H-thymidine uptake. Standard transmission electron microscopy showed that in the mitogen-driven system 20% to 60% (33 +/- 15%) and in the epidermal cell-driven system 5% to 15% (8 +/- 4%) of the lymphoid cells exhibited mild to moderate indentation of the nuclei with nuclear contour indices (NCI) of 4.6 to 6.5 but no Sezary cells were observed (cells with NCI greater than 6.5 and up to 19.2). In the mitogen- stimulated preparation 2% to 5% (3 +/- 1%) of the lymphoid cells showed nuclear multilobulation resembling the cells seen in adult T cell lymphoma/leukemia. Incubation of mononuclear cells for longer periods of up to 4 weeks with mitogens and exogenous IL-2 resulted in no further morphologic changes. Using an indirect immunogold technique at the electron microscopic level, the cells showing nuclear indentation or lobulation were shown to bear both T helper (CD4) and T suppressor (CD8) cell phenotypes in a similar ratio to the total numbers of T helper and T suppressor cells present. Mitogens and epidermal cells are thus not able to induce a morphologic change to Sezary cells in normal peripheral blood lymphocytes.     

Ventricular fibrillation causes sudden death in Southeast Asian immigrants

Young, male, Southeast Asian immigrants living in the United States have a high incidence of unexplained, sudden, nocturnal death. We report the cases of three patients, two Laotians and one Filipino, who were resuscitated and subsequently studied extensively. Each patient was having ventricular fibrillation when first examined by paramedics outside the hospital, and episodes of fibrillation recurred in the early hospital course. Clinical evaluation found no significant coronary atherosclerosis or structural cardiac disease. One patient is asymptomatic after 2 years; the second patient died suddenly at 4 months; and the third is asymptomatic but had inducible ventricular tachycardia on electrophysiologic testing 6 months after resuscitation. The mechanism of sudden death in young Southeast Asian men appears to be ventricular fibrillation. The cause of the arrhythmia is unclear, although in our patients the arrhythmia was not an isolated event; underlying predispositions to further cardiac arrest persisted.     

Alcohol Self-Administration: Further Examination of the Role of Dopamine Receptors in the Nucleus Accumbens

One of the functions of the mesolimbic dopamine (DA) system is to regulate the process of reinforcement, a process that is thought to influence drug self-administration. This study tested the effects of centrally administered DA receptor ligands on ethanol self-administration behavior. Long-Evans rats were trained to lever press on a fixed-ratio 4 schedule of ethanol (10% v/v) reinforcement. DA agonists and antagonists were then bilaterally microinjected (0.5 μ/side) into the nucleus accumbens (N Acc) 10-min before sessions to test for effects on the onset, maintenance, and termination of ethanol self-administration. Infusions of the D₁-like agonist SKF 38393 (0.03 to 3.0 μg) produced no effect on ethanol self-administration. The D₁-like antagonist SCH 23390 (0.5 to 2.0 μg) reduced total responding by decreasing the time course of self-administration without altering response rate. The D₂-like agonist quinpirole produced a biphasic effect on self-administration. Quinpirole (1.0 μg) increased total responses and response rate, whereas higher doses (4.0 to 10.0 μg) decreased total responding as a result of early termination. The D₂-like antagonist raclopride (0.1 to 1.0 μg) reduced total responding by decreasing time course and response rate. Co-administration of either SKF 38393 or SCH 23390 with quinpirole prevented the behavioral effects observed with the low doses of quinpirole. Thus, in the N ACC either increased activation of D₁-like receptors or their blockade can affect the expression of the behavioral effects of the D₂-like agonist. This suggests that some intermediate level of D₁ activation is required to observe the D₂ effect. The decreases in total responding produced by raclopride were enhanced by co-administration of SKF 38393, but not altered by SCH 23390, thus suggesting that D₁-like and D₂-like receptors in the N Acc interact in the regulation of ethanol self-administration in a manner similar to their interactive regulation of other behaviors.     

Evidence for a physiological role for oxytocin in the control of prolactin secretion

The presence of oxytocin (OT) in neuronal elements of the external layer of the median eminence and in hypophysial portal plasma suggests a role for the peptide in the control of anterior pituitary function. We have reported previously that OT stimulates PRL release in vitro; therefore, we attempted to establish evidence for a physiological PRL-releasing role for OT. Plasma OT levels rose significantly just before the PRL surges occurring during a suckling stimulus in lactating rats (10 min after pup reinstatement vs. 15 min for PRL) and 48 h after estrogen injection in ovariectomized (OVX) rats (at 1200 h vs. 1300 h). Dispersed anterior pituitary cells harvested from lactating female rats and OVX estrogen-primed rats released PRL in a specific, significant, and dose-related fashion when perifused in vitro with incubation medium containing 10(-7)-10(-9) M OT, doses similar to levels found previously in hypophysial portal plasma. Infusion of antiserum specific for OT into lactating females before pup reinstatement and into estrogen-primed OVX rats 2 h before the expected release of endogenous OT delayed and significantly reduced subsequent PRL surges compared to levels in saline-or normal rabbit serum-infused rats; however, PRL release was not completely abolished. These data indicate that OT plays a physiological role in the hypothalamic control of PRL secretion and further suggest the importance of multiple factors in coordinated regulation of PRL release.     

Prolactin-releasing peptide and its homolog RFRP-1 act in hypothalamus but not in anterior pituitary gland to stimulate stress hormone secretion

The RF-amide peptides (RFRPs), including prolactin (PRL)-releasing peptide-31 (PrRP-31) and RFRP-1, have been reported to stimulate stress hormone secretion by either direct pituitary or indirect hypothalamic actions. We examined the possible direct effects of these peptides on PRL and adrenocorticotropin (adrenocorticotropic hormone [ACTH]) release from dispersed anterior pituitary cells in culture and on PRL and ACTH secretion following intracerebroventricular (icv) administration in vivo. Neither peptide significantly altered PRL or ACTH release from cultured pituitary cells (male rat donors). Central administration of 1.0 and 3.0 nmol of PrRP-31, but only the higher dose of RFRP-1, significantly elevated serum corticosterone levels in conscious male rats. The effect of PrRP-31 was not blocked by pretreatment (iv) with the corticotropin-releasing hormone (CRH) antagonist, α-helical CRH 9–41; however, pretreatment of the animals (iv) with an antiserum to CRH significantly lowered the hypothalamic-pituitary-adrenal axis response to central administration of PrRP-31. On the other hand, the release of PRL was significantly elevated by 3.0 nmol of RFRP-1, but not PrRP-31, in similarly treated, conscious male rats. Pretreatment with the catecholamine synthesis inhibitor, α-methyl-para-tyrosine, prevented the stimulation of PRL secretion observed following central administration of RFRP-1. RFRP-1 similarly did not alter PRL secretion in rats pretreated with the dopamine, D₂ receptor blocker, domperidone. These results suggest that the RF-amide peptides are not true neuroendocrine regulators of stress hormone secretion in the rat but, instead, act centrally to alter the release of neuroendocrine factors that do act in the pituitary gland to control PRL and ACTH release. In the case of RFRP-1, stimulation of PRL secretion is potentially owing to an action of the peptide to inhibit dopamine release into the median eminence. The corticosterone secretion observed following central administration of PrRP-31 does not appear, based on our current results, to be solely owing to an action of the peptide on CRH-producing neurons but, instead, may be a result of the ability of PrRP-31 to increase as well the exposure of the corticotrophs in vivo to other ACTH secretagogues, such as oxytocin or vasopressin.