Hypoglycemia normally promotes increases in plasma epinephrine (E) and norepinephrine (NE), tachycardia, and a widened pulse pressure; these responses can be modified by β-adrenoceptor-blocking agents. We assessed the catechola-mine and cardiovascular responses to a standard insulin tolerance test in 18 hyperthyroid patients before and during treatment with selective β-l (metoprolol; n = 9) or nonselective (propranolol; n = 9) β-blocking agents. During hypoglycemia, metoprolol as well as propranolol treatment caused an augmented increase in plasma E, while the increase in NE remained unaltered during β-blockade compared to pretreatment changes. Treatment with metoprolol reduced the supine basal heart rate (HR), although the HR rose significantly during hypoglycemia. Blood pressure (BP) changes were similar to pretreatment values. Propranolol not only lowered basal HR but also totally blocked hypoglycemia-induced tachycardia. Compared to pre-treatment, an increase in diastolic BP and a further rise in systolic BP were recorded. Eleven subjects were reexamined when they were made eu-thyroid by conventional antithyroid therapy. During hypogly-cemia, NE concentrations reached a similar maximum value in the hyperthyroid and euthyroid states, although basal concentrations were lower during hyperthyroidism. No differences were seen between plasma levels of E, and the cardiovascular changes were similar in hyper- and euthyroidism, except for lower basal diastolic BP in hyperthyroidism. Our data demonstrate that stress-induced increases in plasma catecholamines are not suppressed in hyperthyroidism. During β-adrenoceptor blockade, hypoglycemia provokes an enhanced response in plasma E. This increment in plasma E induces changes in the cardiovascular response which are quite different during selective β-l or nonselective β-blockade. The difference is probably due to a coexisting and unopposed change in the a-adrenergic tone during nonselective β-blockade. (J Clin Endo-crinol Metab50: 906, 1980)
Abstract The development of mature B cells in cultures of early B cell precursors depends on the presence of a confluent adherent bone marrow (aBM) cell layer. Adherent and sIgM+ cell-depleted bone marrow (BM) from untreated or 5-fluorouracil-pretreated donors or day 12 fetal liver cells were used as precursor cell populations. When adherent cells from thymus or highly enriched BM-derived macrophages were co-cultured with precursor cells, mature B cells were not developed. Similarly, aBM cell layers generated in the presence of hydrocortisone and horse serum were unable to support aBM cell-dependent precursor differentiation, even though cortisone was removed before the addition of precursor cells. In contrast, this type of microenvironment promoted the differentiation of precursor of myeloid cell lineages. Repeated treatment of established aBM cell populations with a monoclonal anti-macrophage antibody (31.3, known to recognize a surface marker on a subset of BM macrophages) and complement abolished the capacity of otherwise functional aBM cells to sustain the development of B cell precursors. Macrophage-depleted aBM cells regained their function after supplementation with highly enriched BM-derived macrophages grown in vitro. Limiting dilution analysis of aBM cells in microcultures containing saturating numbers of early B cell progenitors also suggests the participation of more than one cell type in the BM cell population. In conclusion, differentiation of early B cell progenitors requires macrophages in addition to at least one additional cell type contained in the aBM cell population.
T cells primed in mixed lymphocyte culture exert both positive and negative allogeneic effects on B cells expressing the appropriate alloantigens. The positive and negative effects can be separated by limiting dilution analysis: positive effects, measured by production of anti-sheep erythrocyte antibody, are revealed when low numbers of primed T cells are added to cultures of B cells and sheep erythrocytes, while suppression of the response occurs at higher T-cell inputs. In the present report, these negative allogeneic effects have been analysed in detail. Suppression was qualitatively and quantitatively similar when helper T cell activity was provided from any of several sources. Helper T cells in the alloantigen-primed population gave rise to active T-cell replacing factors even under conditions in which all microcultures were suppressed and suppressor cells were present at a high multiplicity in every well. The degree of suppression was influenced by the multiplicity of B cells in culture; as the number of B cells increased, more suppressor cells were required to inactivate a microculture. Taken together, these data indicate that the targets of the suppressor cells are B cells and not helper T cells or T-cell replacing factors. Although suppressor cells can prevent the activation of B cells by the more frequent helper cells in the primed T-cell population, detailed analysis of the stoichiometry of the suppression demonstrated that a single suppressor cell is capable of inactivating only a limited number of B cells, suggesting that a 'ratio-dominance' model of suppression is operative in this system.
The hormonal responses to the stimulus of changing from resting supine to sitting upright for 15 minutes were assessed in 20 patients with hypertension, divided into 2 groups. 8 patients had essential hypertension (EH) and 12 unilateral renal artery stenosis (URS). The prostaglandin E2(PGE2) concentration, plasma renin activity (PRA), angiotensin II (A-II) concentration, and norepinephrine (NE) concentration were measured in renal vein blood using specific methods. The PGE2concentration increased after sitting for 15 minutes in all patients (p < 0.001), but the increment was significant only in those with URS. The PRA was lower both at rest and after sitting up in the EH group than in the URS group. After sitting up the A-II concentration increased more in patients with URS than in those with EH (p < 0.05). NE levels rose significantly when all patients were included (p < 0.01), rainly owing tcj changes in the EH group. Supine and sitting PRA and A-I1 were correlated (r = 0.47 and r = 0.52; both p < 0.05), and also sitting PGE2 and A-II (r = 0.46, p < 0.05). The inverse relation between PGE2 and NE for the difference in hormone concentrations between supine and sitting (r = -0.44, p < 0.05) may be explained by an inhibitory effect of PGE2 on renal NE release, earlier observed in experiments in vitro. Similar changes in PGE2 and the measured components of the renin-angiotensin system i n response to change in posture may indicate these factors are .interrelated.
