Rapid mobilization of hematopoietic progenitor cells in rhesus monkeys by a single intravenous injection of interleukin-8

Interleukin-8 (IL-8) is a chemoattractant cytokine involved in chemotaxis and activation of neutrophils. Because in vivo administration of IL-8 induces mobilization of hematopoietic stem cells in mice, we assessed the mobilizing properties of IL-8 in rhesus monkeys. Recombinant human IL-8 was administered as a single intravenous injection at doses of 10, 30, and 100 micrograms/kg to rhesus monkeys (age, 2 to 3 years; weight, 2.5 to 4.5 kg). Venous blood samples were obtained at time intervals ranging from 1 to 480 minutes after IL-8 administration. Cell counts, colony-forming unit-Mix assays, and fluorescence-activated cell sorter analysis were performed. Plasma was harvested to assess IL-8 levels. A time-controlled bolus intravenous injection of 100 micrograms IL-8 per kilogram of body weight resulted in peak IL-8 plasma levels up to 5 micrograms/mL. The calculated half-time life of free IL-8 was 9.9 +/- 2.2 minutes. IL-8 injection resulted in instant neutropenia that was due to pulmonary sequestration, as shown using 99mTc-labeled leukocytes. Within 30 minutes after IL-8 injection, neutrophilia developed with counts up to 10-fold greater than baseline levels. The numbers of hematopoietic progenitor cells (HPCs) increased from 45 +/- 48/mL to 1,382 +/- 599/mL of blood at 30 minutes after injection of 100 micrograms IL-8 per kilogram of bodyweight (mean +/- SD, n = 8). Individual animals showed 10- to 100-fold increase in numbers of circulating HPCs that returned to almost pretreatment values (92 +/- 52 CFU/mL) at 240 minutes after the injection of IL-8. Immunophenotyping showed no significant changes in lymphocyte (sub)populations. A second bolus injection of IL-8 with an interval of 72 hours resulted in similar numbers of mobilized stem cells as observed after the first injection, showing that no tachyphylaxis had occurred. We conclude that IL-8 induces mobilization of HPCs from the bone marrow of rhesus monkeys in a rapid and reproducible fashion. Therefore, IL-8 may be a potentially useful cytokine in the setting of blood stem cell transplantation.     

Plasma dihydroxyphenylalanine and total body and regional noradrenergic activity in humans

Dihydroxyphenylalanine (DOPA) is the immediate product of the rate-limiting step in catecholamine biosynthesis, hydroxylation of tyrosine. This study examined whether plasma concentrations of DOPA are related to tyrosine hydroxylase activity. Plasma concentrations of DOPA, norepinephrine, and the norepinephrine metabolites 3,4-dihydroxyphenylglycol (DHPG) and 3-methoxy-4-hydroxyphenylglycol (MHPG) were measured in arterial blood and blood draining the heart, brain, and forearm of 21 patients undergoing cardiac catheterization. Rates of entry of norepinephrine into arterial plasma and plasma draining the heart were estimated using infusions of radioactive norepinephrine. Arterial plasma DOPA correlated positively with arterial plasma DHPG (r = 0.63), MHPG (r = 0.47), norepinephrine (r = 0.67), and the rate of entry of norepinephrine into arterial plasma (r = 0.62). There were significant arteriovenous increments in plasma DOPA: 28% across the heart, 18% across the brain, and 32% across the forearm. Arteriovenous increments in plasma DOPA across the brain correlated positively with increments in plasma DHPG (r = 0.83), but not with increments in norepinephrine or MHPG. In the arm, where MHPG was the major metabolite, arteriovenous increments in DOPA correlated positively with increments in MHPG (r = 0.52) and with the combined increments in MHPG, DHPG, and norepinephrine (r = 0.60). In the heart, where DHPG was the major metabolite, arteriovenous increments in DOPA correlated positively with increments in DHPG (r = 0.72) and the combined increments in DHPG, MHPG, and norepinephrine (r = 0.62). The rate at which norepinephrine entered the great cardiac venous plasma from tissues of the heart correlated positively with the rate at which DOPA overflowed from the heart into the systemic circulation (r = 0.56). The relationships between plasma DOPA and norepinephrine metabolism and the rates of norepinephrine entry into plasma support the view that plasma DOPA reflects tyrosine hydroxylase activity.     

Lack of effect of various endocrine manipulations on tryptophan hydroxylase activity of individual nuclei of the hypothalamus, limbic system, and midbrain of the rat.

The tryptophan hydroxylase activity of individual nuclei of the limbic system, hypothalamus, and midbrain was determined after various endocrine manipulations in an attempt to identify specific endocrine-responsive serotonergic structures in the rat brain. Following adrenalectomy, thyroidectomy, castration, or treatment with pharmacological doses of dexamethasone, testosterone, or thyroxine, no changes in tryptophan hydroxylase activity occurred in any of the areas of brain examined. Furthermore, in large sections of the hypothalamus and midbrain, total tryptophan hydroxylase activity was unaltered, and no changes in Km for substrate or co-factor were found after adrenalectomy. This study, therefore, has failed to detect any hormonally responsive tryptophan hydroxylase activity in the rat brain. These findings suggest that endocrine-induced alterations in serotonin turnover, if they occur, do so without measurable changes in the activity or kinetic properties of tryptophan hydroxylase.     

The cholecystokinin-A receptor mediates inhibition of food intake yet is not essential for the maintenance of body weight

Food intake and body weight are determined by a complex interaction of regulatory pathways. To elucidate the contribution of the endogenous peptide cholecystokinin, mice lacking functional cholecystokinin-A receptors were generated by targeted gene disruption. To explore the role of the cholecystokinin-A receptor in mediating satiety, food intake of cholecystokinin-A receptor^–/– mice was compared with the corresponding intakes of wild-type animals and mice lacking the other known cholecystokinin receptor subtype, cholecystokinin-B/gastrin. Intraperitoneal administration of cholecystokinin failed to decrease food intake in mice lacking cholecystokinin-A receptors. In contrast, cholecystokinin diminished food intake by up to 90% in wild-type and cholecystokinin-B/gastrin receptor^–/– mice. Together, these findings indicate that cholecystokinin-induced inhibition of food intake is mediated by the cholecystokinin-A receptor. To explore the long-term consequences of either cholecystokinin-A or cholecystokinin-B/gastrin receptor absence, body weight as a function of age was compared between freely fed wild-type and mutant animals. Both cholecystokinin-A and cholecystokinin-B/gastrin receptor^–/– mice maintained normal body weight well into adult life. In addition, each of the two receptor^–/– strains had normal pancreatic morphology and were normoglycemic. Our results suggest that although cholecystokinin plays a role in the short-term inhibition of food intake, this pathway is not essential for the long-term maintenance of body weight.     

纤维蛋白原检测的指南

英国血液学界通常通过纤维蛋白原的测定来判断纤维蛋白量的降低和质的异常,评估出血危险性。纤维蛋白原的升高通常预示各种缺血性事件的存在,建议进行纤维蛋白原检测就是基于这种观点。 纤维蛋白原的测定方法有多种,其中Clauss检测法(以凝血酶时间为基础)是英国医院最常采用的,它可选用多种检测试剂和测定方法。许多实验室配置了自动凝集仪,其中许多是根据光散射变化的差异或凝血酶原时问(PT-Fg)检测时光密度的变化来计算纤维蛋白原的量。PT-Fg法检测中还存在一系列的问题,     

Autoimmunity-associated autonomic failure with sympathetic denervation

We report a case of autoimmunity-associated autonomic failure in a young adult woman who developed arthritis followed 3 years later by pandysautonomia. There was early recovery of parasympathetic functions but persistent neurogenic orthostatic hypotension from post-ganglionic sympathetic denervation. Clinical laboratory testing indicated variable amounts of sympathetic neuronal re-sprouting in the heart, kidneys, eyes, and body as a whole upon follow-up evaluation after 1.5 years.     

有症状门诊病人深静脉血栓形成的诊断,临床评价和D-二聚体分析可能减少对影像学诊断的需要

深静脉血栓形成(DVT)的年发病率为48-182／10万,一般估计为1／1000。DVT病死率为1%-5%,发病率和病死率与年龄密切相关。慢性疼痛、肿胀、偶尔腿部皮肤溃疡等血栓后综合征见于1／3发生过DVT的患者。血栓后综合征可出现较早,也可迟至10年才出现,总的发病率为2年23%,5年28%。患者如使用弹力加压袜至少2年以上,腿部病变的发生率可