摘要:

In this review we have summarized the large mass of information that has accumulated in recent years relative to the heterogeneous group of molecules known as the interleukins (IL), the lymphokines, and the cytokines that control the growth and differentiation of cells of the hematopoietic and lymphoid lineage and cells of other lineages. Our intent is to provide the informed generalist with a body of information with which to interpret and understand forthcoming studies of this important class of molecules, particularly those with clinical import.

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Acute hypoxic pulmonary vasoconstriction is attenuated by respiratory alkalosis. It is unknown if alkalosis similarly reduces pulmonary vasoconstriction produced by thromboxane A2. Respiratory alkalosis does not always attenuate persistent pulmonary hypertension in newborns, some of whom have elevated serum thromboxane B2 levels. We hypothesized that alkalosis attenuates thromboxane-induced pulmonary vasoconstriction less than it does hypoxic pulmonary vasoconstriction in infants. Hemodynamic responses to respiratory alkalosis during pulmonary vasoconstriction produced in random order by breathing 12% inspired oxygen and by infusing 0.1 μg/kg/ min of the thromboxane-mimetic U46,619 were compared in eight 2-wk-old piglets. Hypoxia increased mean pulmonary artery pressure from 12 ± 3 to 29 ± 2 mm Hg and pulmonary vascular resistance (PVR) from 11 ± 4 to 25 ± 8 mmHg/L/min; U46,619 increased pulmonary artery pressure from 16 ± 5 to 37 ± 6 mm Hg and PVR from 14 ± 5 to 51 ± 17 mm Hg/liter/min. U46,619 also decreased cardiac output accounting in part for the greater increase in PVR compared to hypoxia-induced vasoconstriction. Respiratory alkalosis decreased PVR to 14 ± 6 mm Hg/ liter/min during exposure to hypoxia and to 28 ± 9 mm Hg/liter/min during infusion of U46,619. In six additional piglets with U46,619-induced pulmonary vasoconstriction, the effects of lung stretch and hypocapnic alkalosis were separated by doubling tidal volume and then adding inspired CO2to return PaCO2to prehyperventilation levels. Respiratory alkalosis decreased PVR from 52 ± 36 to 35 ± 21 mm Hg/liter/min. Despite the increased tidal volume, PVR increased to 53 ± 35 Hg/liter/min when PaCO2returned to 44 ± 5 mm Hg. Respiratory alkalosis rather than lung stretch reduces thromboxane-induced and hypoxia-induced pulmonary vasoconstriction by equal proportions.

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Hydoxyeicosatetraenoic acids (HETE) are major arachidonic acid metabolites of a number of cells found in blood and blood vessels. These products have been implicated in physiologic responses as diverse as platelet aggregation, cell migration, and cell proliferation. Using a sensitive and specific assay, GC/selected ion monitoring after high-performance liquid chromatography separation, we have measured the levels of three HETE isomers of biologic significance 12-HETE, 15-HETE, and 5-HETE in plasma, serum and stimulated serum (formed in the presence of arachidonic acid and calcium ionophore), obtained from normal adults and cord blood from normal neonates. Whereas there were no significant differences between the two groups for 5− or 15-HETE in any of the samples, stimulated serum from adults produced 12 times as much 12-HETE when compared to cord blood. When platelets were isolated from adult and cord blood, 12-HETE production by neonatal platelets, stimulated with 10 μM arachidonic acid, was less than one-fourth that of adults. Although no role for 12-HETE in normal platelet responses has yet been established, it has been reported that those individuals with myeloproliferative syndromes who demonstrate a concomitant decrease in platelet 12-HETE synthetic ability have an increased bleeding tendency. It needs to be further evaluated if this already depressed level of 12-lipoxygenase in neonatal platelets may contribute to pathologic bleeding in those infants subjected to additional stress (such as prematurity or birth asphyxia).

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The use of therapeutic hyperoxia has greatly improved the survival of infants born prematurely. However, high concentrations of oxygen cause pulmonary injury, leading to decreased pulmonary compliance and decreased oxygen diffusion. This injury can result in chronic pulmonary insufficiency. It has been hypothesized that the adverse effects of hyperoxia are mediated, in part, through changes in the pulmonary surfactant system. We investigated the effects of hyperoxia on surfactant-associated protein A (SP-A), the abundant surfactant-specific glycoprotein. Adult male rats were exposed to 85% oxygen for 72 h. Total lung volume and pulmonary compliance were measured, and alveolar surfactant material recovered by lavage. Hyperoxia decreased total lung capacity, and altered inflation and deflation hysteresis patterns. Disaturated phosphatidylcholine and SP-A content were significantly increased in alveolar surfactant material isolated from oxygen-treated rats. SP-A content was also significantly increased in lung tissue from oxygen-treated rats. The SP-A in the lavage of oxygen-treated rats appeared to be intact protein as no proteolytic fragments were detected and the SP-A migrated identically to that recovered from room air animals when analyzed by two-dimensional isoe-lectric focusing. We conclude that the decreased pulmonary compliance associated with pulmonary oxygen injury is not due to quantitative decreases in two major surfactant components, disaturated phosphatidylcholine and SP-A.

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Central cholinergic mechanisms mediate release of growth hormone (GH) as well as peripheral secretion of pancreatic polypeptide (PP). To determine if impaired ability to secrete GH is associated with defective PP response, we studied the PP, epinephrine, and norepi-nephrine responses to insulin-induced hypoglycemia in 31 children evaluated for GH deficiency by insulin-arginine stimulation (IATT) and 24-h integrated concentrations of GH (IC-GH). Eleven patients had normal GH by IATT and IC-GH (controls), 10 patients had normal GH by IATT but subnormal IC-GH, 10 patients had GH deficiency by both IATT and IC-GH. PP levels peaked at the time of glucose nadir, and remained elevated for 20 min thereafter. The peak PP and incremental PP change from baseline were not significantly different among the three groups. The log peak PP response was inversely correlated with the glucose nadir (r = −0.5, p < 0.005). Peak PP levels were also significantly correlated with the peak epinephrine levels (r = 0.6, p < 0.001) but not with norepinephrine. Our findings suggest that 1) GH deficiency disorders are not associated with impaired vagal cholinergic response to hypoglycemia; 2) in children the magnitude of PP response is inversely related to the degree of hypoglycemia; and 3) the peripheral hormonal manifestation of autonomic nervous system responses to hypoglycemia as measured by PP and epinephrine levels are closely correlated.

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

To determine the factors regulating cardiac output in newborn lambs and to examine the effects of age after birth, we altered heart rate, afterload, preload, and myocardial contractility in eight younger lambs, 5 to 13 days old, and seven older lambs, 15 to 36 days old. To control heart rate, we ablated the atrioventricular node by injecting formalin into the region of the node, and paced the right ventricle at a baseline heart rate of 200 beats/ min. After the lambs recovered from surgery, we performed two protocols. In the first protocol we assessed the effects of changing heart rate by pacing the ventricle at various rates. We also examined the effect of altering afterload and preload at a fixed heart rate: afterload was increased by infusing phenylephrine and decreased by infusing nitroprusside. Preload was increased by infusing blood or 0.9% NaCl solution over 2 min. In the second protocol, we increased myocardial contractility by infusing isoproterenol at a fixed heart rate. Increasing heart rate above baseline levels caused no significant increase in cardiac output in the younger lambs (3.9 ± 4.0%, mean ± SD), and only small increases in the older lambs (11.4 ± 6.7%). Decreasing heart rate, however, resulted in a progressive decrease in cardiac output in both groups of lambs. Decreasing afterload caused no significant increase in cardiac output in the younger lambs (1.4 ± 14.0%) and only a small increase in the older Iambs (11.1 ± 1.9%). However, increasing afterload resulted in a fall in cardiac output in both groups of lambs, but this was significant only in the younger group (-14.4 ± 8.2%). Volume infusion caused a modest increase in cardiac output in the younger lambs (19.9 ± 13.8%) and a more variable but not significant response in the older lambs (15.8 ± 18.2%). Isoproterenol infusion caused the largest increases in cardiac output of 33.5 ± 10.8% in the younger lambs and 64.0 ± 20.0% in the older lambs at a dose of 0.3 μg/kg/min. We conclude that 1) resting heart rates are near optimal in lambs such that increasing heart rate by ventricular pacing does not markedly increase cardiac output, whereas decreasing heart rate significantly decreases output; 2) afterload is near optimal as well since decreasing afterload minimally increases cardiac output, whereas increasing it markedly reduces output; 3) the response to volume loading is limited in the lamb during ventricular pacing; and 4) there is a significant response to β-adrenoreceptor stimulation with out changes in heart rate, and this response is more pronounced in the older lamb. This supports the concept that there is a postnatal change in β-adrenoreceptor stimulation of myocardial performance.

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Neurotransmitter systems in the developing brain are generally protected from growth retardation associated with nutritional deprivation. To investigate if such protective mechanisms extend to similar tissues in the peripheral sympathetic system, maturation of the chromaffin cells of the adrenal medulla and development of their centrally derived splanchnic innervation were evaluated in rats whose nutritional status had been altered during the neonatal period by increasing (16–17 pups/ litter) or decreasing (five to six pups/litter) the litter size from the standard (11–12 pups/litter). Ontogeny of adrenal catecholamine stores and activities of catecholamine-biosynthetic enzymes tyrosine hydroxylase and phenylethanolamine N-methyltransferase were monitored, along with activity of choline acetyltransferase, a marker enzyme for the preganglionic neurons innervating the chromaffin cells. Neonatal nutritional deprivation slowed body weight gain and retarded development of the chromaffin cells, as evidenced by subnormal catecholamine stores, tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities. The effects persisted despite the complete recovery of body weights postweaning. The developmental alterations were not caused by overcrowding stress, as plasma corticosterone levels were not elevated in the large litter group. Neonatal nutritional enrichment promoted body weight gain but failed to enhance development of adrenal catecholamines; tyrosine hydroxylase and phenylethanolamine N-methyltransferase activities were elevated only in the preweaning period. In contrast to effects on the chromaffin cells, altered neonatal nutritional status had only minor, transient effects on the development of the centrally derived cholinergic innervation of the adrenal and produced only small changes (<10%) in brain tyrosine hydroxylase activity. These results suggest that, unlike central transmitter systems, maturation of chromaffin cells is adversely affected by neonatal nutritional deprivation; ontogenetic gains may already be close to optimum at normal nutritional status.

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

We have studied the ontogenesis of 5′-deiodinase (5′D) activity in rat brain during fetal life, its capacity to respond to maternal or fetal hypothyroidism, and its regulation by maternal thyroid hormones. Type II 5′D (5′ D-II) activity increases 4-fold during the period studied (17 to 22 days of gestation), mainly between days 19 and 21. Fetal brain T4 concentrations increase in parallel with fetal plasma T4, whereas fetal brain T3 concentrations increase 18 times (days 17–21), six times more than would have been expected from the small increase in fetal plasma T3 levels. Maternal thyroidectomy did not affect 5′D-II activity or thyroid hormone concentrations in fetal brain (except brain T4 at 18 days of gestation). Fetal hypothyroidism, induced by giving a goitrogen (methimazole) to the mothers, depleted all fetal tissues studied, including the fetal thyroid, from thyroid hormones. By 19 days of gestation, the fetal brain was able to respond to hypothyroidism with a 3− to 5-fold increase in 5′D-II activity. Earlier onset of treatment with methimazole led to 2− to 3-fold increases in 5′D already at 17 and 18 days of gestation, showing that when fetal thyroid secretion starts the fetal brain 5′D-II is able to respond to hypothyroidism. Replacement of methimazole-treated mothers with physiological doses of T4, given by constant infusion, increased T4 and T3 concentrations in fetal brain, and inhibited fetal, as well as maternal, brain 5′D-II activity. But treatment of the mothers with T3 did not change T3 concentrations in the fetal brain, despite the increase in fetal plasma T3, and actually increased 5′D-II in fetal brain. Maternal cerebral 5′D-II was not inhibited by T3 treatment. Inverse relationships were found between the 5′D-II and thyroid hormone concentrations in the fetal brain. These correlations were not identical for fetuses from thyroidectomized and control mothers. In fetuses from thyroidectomized dams, brain 5′D-II is more sensitive to a decrease in brain T4 than in the progeny of control dams. The present results describe the developmental changes in rat cerebral 5′D-II activity and its regulation by thyroid hormones. Although fetal plasma T3 is 10% of adult levels, T3 concentrations in fetal brain increase almost to adult levels, suggesting an important role of local T3 production from T4, and thus, of 5′D-II in fetal brain. In addition, brain 5′D-II responds to thyroid hormone deficiency and can be modulated by maternal thyroid hormones when the fetus is hypothyroid.

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Corticosterone plays an important role in the regulation of postnatal development in the rat. Basal concentrations of plasma corticosterone increase markedly during the 3rd wk of life. To date, however, the physiologic bases of this increase have remained unclear. To understand the determinants of circulating concentrations of corticosterone during this period, the plasma half-life of disappearance at steady state (t1/2), the apparent volume of distribution, and metabolic clearance rate were determined after injection of a tracer dose of3H-corticosterone in rats at 12, 16, and 22 days of age. The t1/2for total plasma corticosterone decreased with increasing age. The volume of distribution decreased even more steeply and, consequently, the MCR displayed a highly significant decline between 12 and 22 days of age. As plasma concentrations of corticosteroid-binding globulin are known to increase markedly during this period, the t1/2of protein-bound corticosterone was measured and that of free corticosterone was computed. At all ages the t1/2of bound corticosterone was less than that of free corticosterone. Protein binding of the injected3H-corticosterone increased significantly with development. Thus, increased binding of corticosterone is associated with decreased t1/2. The increasing association of corticosterone with corticosteroid-binding globulin during this developmental period is the most likely explanation for the steep decline of volume of distribution and thus of the metabolic clearance rate for corticosterone. The latter provides, for the first time, an understanding of the basis of the developmental increase in plasma concentrations of corticosterone.

ISSN:0031-3998    

出版商:OVID    

年代:1988

数据来源: OVID