支气管哮喘患者IL-4、sICAM-1、IFNγ与IgE的相关性研究

目的　探讨支气管哮喘患者血清中白介素－ ４（ＩＬ－ ４）、可溶性细胞粘附因子－１（ｓＩＣＡＭ－ １）、γ干扰素在支气管哮喘发病中的作用及与ＩｇＥ水平的相关关系。方法　分别在支气管哮喘发作期、缓解期及口服强的松治疗后用ＥＬＩＳＡ双抗体夹心法分别测定血清中ＩＬ－４、ｓＩＣＡＭ－ １、ＩＦＮγ和ＩｇＥ水平。结果　在支气管哮喘发作期血清ＩＬ－４、ｓＩＣＡＭ－１、ＩｇＥ水平明显升高,ＩＦＮγ水平明显降低;在缓解期和经强的松治疗后,血清ＩＬ－４、ｓＩＣＡＭ－ １、ＩｇＥ水平明显降低。结论　ＩＬ－４ 可促进ｓＩＣＡＭ－１ 表达及ＩｇＥ分泌,并可抑制ＩＦＮγ的分泌,因此在支气管哮喘发病中起重要作用。     

弓形虫病诊断方法的对比研究

应用５种不同方法测定了６例弓形虫病人不同病期的血清标木。用ＩＨＡＴ和ＩＦＡＴ测定抗弓形虫总免疫球蛋白，ＩＨＡＴ在发病后第３周的２份血清标本中有１份已呈阳性，１４～１７周达高峰。滴度升高非常明显；ＩＦＡＴ第３周的标本都呈阳性，１７～２４周达高峰。用ＩｇＧ－ＥＬＩＳＡ和ＩｇＭ－ＥＬＩＳＡ，ＩｇＭ－ＩＦＡＴ分别测定抗弓形虫特异性抗体ＩｇＧ和ＩｇＭ，ＩｇＧ－ＥＬＩＳＡ从第６周呈阳性，随病情延长，滴度明显升高；ＩｇＭ－ＥＬＩＳＡ两份第３周的标本都呈阳性，至少第１７周仍保持较高水平，其中１人第２４周的标本仍呈阳性；但ＩｇＭ－ＩＦＡＴ仅２例（２／６）呈阳性且滴度不很高，在较短时间内就转阴。结果表明：病人的抗体类型相似；ＩｇＧ－ＥＬＩＳＡ，ＩｇＭ－ＥＬＩＳＡ和ＩＦＡＴ敏感特异，ＩＨＡＴ简便、快速；高滴度特异性ＩｇＧ易掩盖ＩｇＭ－ＩＦＡＴ；ＩｇＭ－ＥＬＩＳＡ可为早期诊断提供依据。     

IL-2、IL-6及其受体与多发性骨髓瘤的研究

采用固相放射免疫分析法（ＲＩＡ）和双抗体夹心酶联免疫法（ＥＬＩＳＡ）,对多发性骨髓瘤（ＭＭ）患者进行血清白细胞介素２（ＩＬ－２）（ｓＩＬ－２Ｒ）,白细胞介素６（ＩＬ－６）,白细胞介素８受体（ｓＩＬ－６Ｒ）检测,并进行长期随访。结果ＭＭ患者血清ＩＬ０２、ｓＩＬ－２Ｒ和ＩＬ－６、ｓＨ－６Ｒ水平明显升高,ＩＬ－２与２微球蛋白＊β２－ＭＧ）呈负相关,ＩＬ－６,ｗＩＬ－８Ｒ与β－ＭＧ呈正相关,初诊时血清ｓＩ     

一氧化氮合酶与重症肌无力中枢损害关系

研究表明 ,重症肌无力 (ＭＧ)患者乙酰胆碱受体抗体(ＡＣｈＲａｂ)的病理作用除累及神经肌接头处乙酰胆碱受体(ＡＣｈＲ)外 ,还可波及到中枢神经系统[1,2 ] 。据报道一氧化氮合酶 (ＮＯＳ)参与ＭＧ患者发病过程[3] 。本研究通过对ＭＧ中枢损害大鼠脑、胸腺及血中ＮＯＳ的测定 ,探讨其在ＭＧ患者中枢神经系统损害中的作用。1 材料和方法 :取 5例临床症状典型 ,血ＡＣｈＲａｂ阳性的全身型ＭＧ患者血清各 10ｍｌ,另取 2例健康人血清各 10ｍｌ,提取ＩｇＧ ;成年雄性ＳＤ大鼠 5 6只 ,体重 2 0 0～ 2 5 0ｇ。随机分为正常组、对照组及实验组 ,脑…     

快速酶联免疫吸附法检测血清脂阿拉伯甘露糖—IgG对肺结核的…

目的评估脂阿拉伯甘露糖－ＩｇＧ（ＬＡＭ－ＩｇＧ）检测对活动性肺结核的诊断价值，方法采用快速酶联免疫吸附法（ＥＬＩＳＡ）检测９０例肺结核，５３例肺癌患者及３０例正常人血清中的ＬＡＭ－ＩｇＧ。结果，肺结核组ＬＡＭ－ＩｇＧ阳性率为８２％，其中痰结核杆菌除（＋）培（＋）组达９６％，涂（－）培养（－）组为６９％，肺癌组４例阳性，正常组１例阳性，假阳性率分别为８％和３％，结论，提示血清ＬＡＭ－ＩｇＧ测量是肺结     

弓形虫病诊断方法的对比研究

应用５种不同方法测定了６例弓形虫病人不同病期的血清标本。用ＩＨＡＴ和ＩＦＡＴ测定弓形虫总免疫球蛋白，ＥＨＡＴ在发病后第３周的２份血清标本中有１份已呈阳性，１４－１７周达高峰。滴度升高非常明显；ＩＦＡＴ第３周的标本都呈阳性；１７－２４周达高峰。用ＩｇＧ－ＥＬＩＳＡ和ＩｇＭ－ＥＬＩＳＡ，ＩｇＭ－ＩＦＡＴ分别测定抗弓形虫特异性抗体ＩｇＧ和ＩｇＭ＜ＩｇＧ－ＥＬＩＳ从第６周呈阳性，随病情延长，滴度明显升高，     

扩张型心肌病TNF和IL－1的检测及意义

应用双抗体夹心法及ＣｏｎＡ小鼠胸腺细胞增殖法分别检测３０例扩张型心肌病（ＤＣＭ）及２０例正常人（ＮＣ）的血清肿瘤坏死因子（ＴＮＦ）和白细胞介素１（ＩＬ－１）的水平，结果发现ＤＣＭ病人ＴＮＦ及ＩＬ－１均明显高于ＮＣ组（Ｐ＜０．００１，Ｐ＜０．０１），提示ＴＮＦ与ＩＬ－１可能在ＤＣＭ的发病机理中起重要作用。     

过敏性哮喘患者细胞因子对IgE生成机制的探讨

对３０例过敏性哮喘患者发作期和缓解期及３０例健康成年人的外周血，采用ＥＬＩＳＡ双抗体夹心法，测定血清ＩｇＥ，可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）和白细胞介素－４（ＩＬ－４）水平，生物学方法测定血清ＩＬ－２水平和３Ｈ－ＴｄＲ掺入法定量测定血清ＩＬ－６。结果：过敏性哮喘患者发作期血清ＩｇＥ、ｓＩＬ－２Ｒ、ＩＬ－４和ＩＬ－６水平明显升高，与缓解期和对照组有明显差异（Ｐ＜０．０１），而发作期血清ＩＬ－２水平明显下降，与缓解期和对照组有明显差异（Ｐ＜０．０１），且血清ＩｇＥ分别与ｓＩＬ－２Ｒ和ＩＬ－４水平有明显正相关（Ｐ均＜０．０１），与ＩＬ－２水平有明显负相关（Ｐ＜０．０１）。说明ＩｇＥ合成增加是过敏性哮喘的关键，细胞因子有促进Ｂ细胞合成ＩｇＥ的作用，并且直接参与过敏性哮喘气道炎症的形成。     

红霉素对肺纤维化大鼠核因子κB活性及细胞因子mRNA表达的影响

目的　探讨红霉素治疗肺纤维化的机制和疗效。方法　实验用Ｗｉｓｔａｒ 大鼠８１ 只，分成三组：正常对照组、博莱霉素模型组和红霉素治疗组， 每组２７ 只。气管内注入单剂量博莱霉素制备大鼠肺纤维化模型，于博莱霉素气管内注入后每日给予口服红霉素（１００ ｍｇ／ｋｇ）治疗，各组动物分别于气管内用药后第４、７ 和２８ 天处死动物。用凝胶电泳迁移实验测定肺泡巨噬细胞（ＡＭ） 的核因子（ＮＦ）κＢ活性；用Ｎｏｒｔｈｅｒｎ 杂交测定肺组织的白细胞介素１（ＩＬ１）β和转化生长因子（ＴＧＦ）βｍＲＮＡ表达。结果红霉素治疗组第４ 和第７ 天时，ＡＭ 的ＮＦκＢ活性与博莱霉素模型组比较，差异有显著性（Ｐ＜０－０５） ，第７ 天时肺组织的ＩＬ１β和ＴＧＦβｍＲＮＡ表达与博莱霉素模型组比较，差异有显著性（ Ｐ＜０－０５）。在病理上，红霉素减轻了肺泡炎及后续的肺纤维化。结论　在肺纤维化中，红霉素可能通过抑制ＮＦκＢ活性、ＩＬ１β和ＴＧＦβｍＲＮＡ表达起抗炎和抗纤维化作用。     

地塞米松对哮喘患者IL—4,IL—5及IgE合成的抑制作用观察

观察了地塞米松（Ｄｅｘ）对哮喘患考外周血单个核细胞（ＰＢＭＣ）合成白介素－４（ＩＬ－４）、白介素－５（ＩＬ－５）和免疫球蛋白Ｅ（ＩｇＥ）的抑制作用。结果证明，哮喘１组（仅用植物血凝素，简称ＰＨＡ）ＰＢＭＣ合成ＩＬ－４、ＩＬ－５、ＩｇＥ较对照组（仅用ＰＨＡ）明显增高（Ｐ＜０．０１），哮喘２组（ＰＨＡ＋Ｄｅｘ）ＰＢＭＣ合成ＩＬ－４、ＩＬ－５、ＩｇＥ较哮喘１组显著下降（Ｐ＜０．０５）。认为Ｄｅｘ治疗哮喘的机理，部分是通过减少ＩＬ－４ＩＬ－５、ＩｇＥ的合成而达到抗炎的目的。     

糖皮质激素对重症肌无力患者细胞和体液免疫功能影响的研究

目的　探讨糖皮质激素对重症肌无力 (MG )患者细胞和体液免疫功能的影响。方法　ELISA法检测 3 2例MG患者在糖皮质激素治疗前和治疗 3个月后的血清白细胞介素 (IL) 6和乙酰胆碱受体抗体 (AChRab)水平。结果　MG患者血清IL 6和AChRab均显著高于对照组(P <0 .0 1) ,而糖皮质激素治疗后均明显降低 (P <0 .0 5或P <0 .0 1)。血清IL 6在AChRab阳性MG患者高于AChRab阴性患者 (P <0 .0 5 ) ,且与AChRab滴度呈正相关 (r =0 .710 ,P <0 .0 1)。结论　糖皮质激素可通过抑制MG患者体内IL 6和AChRab的产生 ,有效调节机体细胞和体液免疫功能。     

Further Studies on the Noradrenergic and the Renin Angiotensin Systems in the Brain of the Rat

Previous investigations have shown that depletion of brain norepinephrine (NE) induced by chemical sympa thectomy resulted in significant changes in the central renin-angiotensin system. The purpose of the present work was to increase the NE concentration in the central nervous system (CNS) in order to analyze its effect on the peptidergic complex and on the blood pressure (BP) levels. Treated rats were given the following drugs in the drinking water: 1-dopa (12 mg/rat/day), carbidopa (6 mg/rat/day) and pargyline (10 mg/rat/day) during 25 days. BP was determined, blood and cerebrospinal fluid (CSF) samples were obtained. The CNS was dissected into several areas. NE, angiotensinogen (AoC) and renin concentration (RC) were determined in the brain parenchyma; AoC was evaluated in CSF and plasma samples. Pharmaco-logical treatment resulted in an hypotensive effect and, at the same time, an increase of NE in the CNS (about 100 %; pCO .0005). These changes were accompanied by a significant decrease in the peripheral and central AoC. These results add new evidence to the postulated relationship between these two important regulatory systems involved in cardiovascular control.     

Production of tumor necrosis factor and other cytokines by astrocytes stimulated with lipopolysaccharide or a neurotropic virus.

Rat astrocytes, immunologically competent glial cells of the central nervous system (CNS), released a variety of cytokines after activation. Lipopolysaccharide-stimulated astrocytes produced tumor necrosis factor (TNF) as demonstrated by Northern blot analysis using a mouse TNF probe and by functional assay. Biological activity of rat astrocyte-derived TNF was neutralized by rabbit antiserum against recombinant murine TNF. Stimulation of astrocytes by lipopolysaccharide also activated the interleukin 1 and interleukin 6 genes. We have also investigated whether a neurotropic paramyxovirus, Newcastle disease virus, triggers cytokine production by astrocytes. This virus induced astrocytes to produce TNF, lymphotoxin, interleukin 6, and alpha- and beta-interferons. Thus, stimulation by endotoxin and virus activated distinct, yet overlapping, sets of cytokine genes. We propose that astrocytes and the cytokines they produce may play a significant role in the pathogenesis of immunologically and/or virally mediated CNS disease, in CNS intercellular communication, and in the interactions between the nervous and immune systems.     

Synergistic interaction between insulin-like growth factors-I and -II in central regulation of pulsatile growth hormone secretion.

Insulin-like growth factor (IGF)-I and -II peptides, receptors, mRNAs, and binding proteins are widely distributed in the central nervous system (CNS), yet their physiological role in the brain remains largely unknown. While earlier in vivo studies in the rat suggested that IGF-I may participate in feedback regulation of GH secretion at a CNS level, the preparations used were only partially pure. The recent availability of purified recombinant IGF-I and -II peptides prompted us to reexamine the involvement of the IGFs in vivo in central regulation of pulsatile GH secretion. Five groups of free-moving adult male rats bearing chronic intracerebroventricular (icv) and intracardiac venous cannulae were icv administered IGF-I (in doses of 0.5, 2, 3, and 10 micrograms) or the acid-saline vehicle; an additional group received 1 microgram of the potent IGF-I analog, long R3 IGF-I. Spontaneous 6-h plasma GH secretory profiles were obtained from all groups. Vehicle-injected control animals exhibited the typical pulsatile pattern of GH secretion, with most peak GH values above 150 ng/ml and trough levels below 1.2 ng/ml. Central administration of IGF-I alone or long R3 IGF-I at all doses tested failed to alter the pulsatile pattern of GH release; there were no significant differences in GH peak amplitude, GH trough level, GH interpeak interval, or mean 6-h plasma GH level compared to those in vehicle-injected controls. In a second study, designed to determine the effects of central administration of IGF-I and IGF-II, in combination, icv injection of 1 microgram IGF-I and 1 microgram IGF-II resulted in a marked suppression in the amplitude of spontaneous GH secretory bursts approximately 3 h after injection; both GH pulse amplitude (43.5 +/- 5.6 vs. 130.6 +/- 14.6 ng/ml; P less than 0.001) and mean plasma GH level (16.3 +/- 1.9 vs. 35.2 +/- 1.8 ng/ml; P less than 0.001) were severely reduced 3-6 h after injection compared to those in vehicle-injected controls. These results demonstrate that IGF-I alone does not play a physiologically important role in feedback regulation of GH secretion at the level of the CNS. Our findings suggest a synergistic interaction between IGF-I and -II in the brain for central control of pulsatile GH secretion.     

Central nervous system radiation syndrome in mice from preferential 10B(n, alpha)7Li irradiation of brain vasculature.

Ionizing radiations were directed at the heads of anesthetized mice in doses that evoked the acute central nervous system (CNS) radiation syndrome. Irradiations were done using either a predominantly thermal neutron field at a nuclear reactor after intraperitoneal injection of 10B-enriched boric acid or 250-kilovolt-peak x-rays with and without previous intraperitoneal injection of equivalent unenriched boric acid. Since 10B concentrations were approximately equal to 3-fold higher in blood than in cerebral parenchyma during the reactor irradiations, more radiation from alpha and 7Li particles was absorbed by brain endothelial cells than by brain parenchymal cells. Comparison of the LD50 dose for CNS radiation lethality from the reactor experiments with the LD50 dose from the x-ray experiments gives results compatible with morphologic evidence that endothelial cell damage is a major determinant of acute lethality from the CNS radiation syndrome. It was also observed that boric acid is a low linear energy transfer radiation-enhancement agent in vivo.     

Brain-selective overexpression of angiotensin (AT1) receptors causes enhanced cardiovascular sensitivity in transgenic mice

To examine the physiological importance of brain angiotensin II type 1 (AT1) receptors, we developed a novel transgenic mouse model with rat AT1a receptors targeted selectively to neurons of the central nervous system (CNS). A transgene consisting of 2.8 kb of the rat neuron-specific enolase (NSE) 5' flanking region fused to a cDNA encoding the full open-reading frame of the rat AT1a receptor was constructed and transgenic mice (NSE-AT1a) were generated. Two of six transgenic founder lines exhibited brain-selective expression of the transgene at either moderate or high levels. Immunohistochemistry revealed widespread distribution of AT1 receptors in neurons throughout the CNS. This neuron-targeted overexpression of AT1a receptors resulted in enhanced cardiovascular responsiveness to intracerebroventricular (ICV) angiotensin II (Ang II) injection but not to other central pressor agents, demonstrating functional overexpression of the transgene in NSE-AT1a mice. Interestingly, baseline blood pressure (BP) was not elevated in either transgenic line. However, blockade of central AT1 receptors with ICV losartan caused significant falls in basal BP in NSE-AT1a mice but had no effect in nontransgenic controls. These results suggest that whereas there is an enhanced contribution of central AT1 receptors to the maintenance of baseline BP in NSE-AT1a mice, particularly effective baroreflex buffering prevents hypertension in this model. Used both independently, and in conjunction with mice harboring gene-targeted deletions of AT1a receptors, this new model will permit quantitative and relevant investigations of the role of central AT1a receptors in cardiovascular homeostasis in health and disease.     

Superoxide mediates the actions of angiotensin II in the central nervous system

Angiotensin II (Ang II) has profound effects in the central nervous system (CNS), including promotion of thirst, regulation of vasopressin secretion, and modulation of sympathetic outflow. Despite its importance in cardiovascular and volume homeostasis, angiotensinergic mechanisms are incompletely understood in the CNS. Recently, a novel signaling mechanism for Ang II involving reactive oxygen species (ROS) has been identified in a variety of peripheral tissues, but the involvement of ROS as second messengers in Ang II-mediated signaling in the CNS has not been reported. The hypothesis that superoxide is a key mediator of the actions of Ang II in the CNS was tested in mice using adenoviral vector-mediated expression of superoxide dismutase (AdSOD). Changes in blood pressure, heart rate, and drinking elicited by injection of Ang II in the CNS were abolished by prior treatment with AdSOD in the brain, whereas the cardiovascular responses to carbachol, another central vasopressor agent, were unaffected. In addition, Ang II stimulated superoxide generation in primary CNS cell cultures, and this was prevented by the Ang II receptor (Ang II type 1 subtype) antagonist losartan or AdSOD. These results identify a novel signaling mechanism mediating the actions of Ang II in the CNS. Dysregulation of this signaling cascade may be important in hypertension and heart failure triggered by Ang II acting in the CNS.     

Effect of nicotine on type 2 deiodinase activity in cultured rat glial cells.

Intracellular generation of triiodothyronine (T3) from thyroxine (T4) by type 2 deiodinase (D2) in the mammalian brain, plays a key role in thyroid hormone action. The presence of D2 in rat astrocytes suggests the importance of glial cells in the regulation of intracellular T3 levels in the rat central nervous system (CNS). To analyze further the factors that regulate D2 activity in the CNS, we investigated the effects of nicotine and of mecamylamine, which inhibits the binding of nicotine with nicotinic acetylcholine receptors, on D2 activity in cultured mixed glial cells of the rat brain. We incubated cultured mixed glial cells obtained from neonatal Wistar rats in the presence of 10 mM dithiothreitol, 2 nM [125I] reverse T3 and 1 mM 6-N-propyl-2-thiouracil for 2 h at 37 degrees C, and the released 125I- was counted in a gamma counter. D2 activity of cultured cells was dependent on the temperature and the amount of protein. The basal D2 activity of rat mixed glial cells was 1.9 +/- 0.2 fmol of I- released/mg protein/h (mean +/- SEM). The addition of 10(-11), 2 x 10(-11), 10(-10), and 10(-9) M nicotine significantly increased D2 activity to approximately 2.2-, 2.4, 3.5- and 2.9-fold the basal level, respectively. D2 activity stimulated by 10(-8) M nicotine (2.5-fold) reached a peak after 9 h incubation. The stimulatory effect of nicotine was completely blocked by 10(-6) M mecamylamine. In conclusion, nicotine increases D2 activity probably via nicotinic acetylcholine receptors, and may influence brain function, at least in part, by affecting thyroid hormone metabolism.     

MRI analysis on a patient with the V30M mutation is characteristic of leptomeningeal amyloid

We report a characteristic finding in gadolinium-enhanced magnetic resonance images (MRIs) of the central nervous system (CNS) in a 61-year-old man with a homozygous transthyretin (TTR) Val30Met mutation. Although he presented with polyneuropathy accompanied by autonomic dysfunction and vitreous opacities in both eyes, he has shown no overt signs or symptoms of CNS involvement. Total protein level in the cerebrospinal fluid was moderately elevated. In the gadolinium-enhanced T₁-weighted MRIs of the brain and spinal cord, leptomeningeal enhancement was seen along the surfaces of the brain stem and more clearly in the spinal cord, suggesting leptomeningeal TTR-related amyloid deposition. Our result indicates that gadolinium-enhanced MRI of the CNS may be a very sensitive and useful method for detecting leptomeningeal amyloid deposition, since abnormal findings can be detected even at a presymptomatic stage of CNS involvement.     

MRI analysis on a patient with the V30M mutation is characteristic of leptomeningeal amyloid.

We report a characteristic finding in gadolinium-enhanced magnetic resonance images (MRIs) of the central nervous system (CNS) in a 61-year-old man with a homozygous transthyretin (TTR) Val30Met mutation. Although he presented with polyneuropathy accompanied by autonomic dysfunction and vitreous opacities in both eyes, he has shown no overt signs or symptoms of CNS involvement. Total protein level in the cerebrospinal fluid was moderately elevated. In the gadolinium-enhanced T1-weighted MRIs of the brain and spinal cord, leptomeningeal enhancement was seen along the surfaces of the brain stem and more clearly in the spinal cord, suggesting leptomeningeal TTR-related amyloid deposition. Our result indicates that gadolinium-enhanced MRI of the CNS may be a very sensitive and useful method for detecting leptomeningeal amyloid deposition, since abnormal findings can be detected even at a presymptomatic stage of CNS involvement.