延髓后角脑啡肽超微结构定位和非突触部位释放——脑啡肽突触前抑制痛觉传递的形态学基础

阿片肽在后角镇痛的作用机理,被认为是通过突触前抑制一级传入纤维P物质释放的结果,然而始终未获得形态学的证实。鉴于一级传入纤维存在大量阿片受体的事实,曾提出阿片肽突触前抑制可能是通过非突触的轴-轴作用。为了验证这一设想,本文用免疫组化方法,详细观察了大鼠延髓后角浅层亮氨酸脑啡肽(L-ENK)轴突终末的突触结构和胞吐释放。电镜观察显示,延髓后角ENK终末可分为两类,第一类终末除了含圆形小清亮囊泡外,还有较多的大颗粒小泡(一般7个以上),主要分布于Ⅰ层,很少看到此类终末形成突触;第二类终末,一般含较多圆形清亮小泡和少量大颗粒小泡(一般不超过3个),它们分布于Ⅰ层和Ⅱ层,此类终末主要形成轴-树突触和少量的轴-体突触。只见到一例轴-轴突触,其突触后成分为未标记的R型终末,此外还见到ENK阳性树突成为中央终末的突触后成分。在去传入神经条件下,上述各类终末皆可见到ENK阳性大颗粒小泡的胞吐形成,它们皆位于非突触区,而在突触部位可见到清亮小泡胞吐像,上述结果提示后角ENK非突触部位释放可能是哭触后抑制一级传入纤维P物质释放的形态学基础。     

氧分压在体监测仪的研制

作者报道一种稳定性较高的氧分压在体监测，为医学研究、临床诊断提供一种新的可靠的测试方法及设备，具有较大的应用价值。     

Analysis of false negative results in the immunoassay for anti-acetylcholine receptor antibodies in myasthenia gravis

Possible causes for the failure of immunoassays to detect anti-acetylcholine receptor activity in serum from confirmed myasthenia gravis (MG) patients were investigated. A more sensitive assay, using Protein A to trap immune complexes (ARIA), was applied to 65 MG sera which were negative in the usual assay and to 42 normal human sera. Normal and negative MG sera had antibody (Ab) activity in the same range (50-70 pM). Titers present in 70% of normal sera appeared to be specific antireceptor antibodies as defined by tests for antigen specificity. Thus, higher sensitivity assays did not improve discrimination of MG from normals. In a second group of 108 MG sera studied, 48 were negative by the usual assay criteria in a rat acetylcholine receptor immunoassay. Further detailed analysis of this negative group showed that 3/48 had IgG3 antibody not detectable in the test, 14/48 had Ab's recognizing human receptor determinants exclusively, 29/48 had toxin blocking Ab's not determined by immunoassays, and 6/48 were negative in all tests. The results indicate that the exclusive occurrence of toxin-blocking antibodies in MG subjects is a major factor contributing to false negatives in the ARIA test. Estimates of the amount of Ab's with this functionality indicated that they are present in very much smaller amounts than other classes of anti-receptor Ab's. Degree of blocking activity in patient serum showed a fair correlation with severity of disease. Thus, blocking antibodies appear capable of causing all degrees of disease severity in the absence of other types of antireceptor Ab's. The development of a sensitive and quantitative in vitro assay for blocking antibodies combined with the usual immunoassay would be a major improvement for a MG diagnostic test, with greater than 94% positivity predicted.     

Pre-exposure of murine macrophages to lipopolysaccharide inhibits the induction of nitric oxide synthase and reduces leishmanicidal activity

Murine macrophages produce nitric oxide (NO) from L-arginine on stimulation with lipopolysaccharide (LPS), alone or with interferon-γ (IFN-γ). The effect of incubation of macrophages with low concentrations of LPS on NO synthesis on subsequent stimulation was investigated, using a murine macrophage cell line, J774, and peritoneal macrophages from CBA mice. Cells which had been incubated with LPS produced significantly lower amounts of NO, and expressed lower levels of NO synthase activity, following stimulation with IFN-γ and LPS, or with a high concentration of LPS. This effect was not reversed by tumor necrosis factor-α. The ability of CBA macrophages to kill the intracellular parasite Leishmania major was markedly reduced by pre-incubation with LPS. Reduced NO production by macrophages previously exposed to LPS is a manifestation of endotoxin tolerance, and may represent an important means of regulation of NO synthesis and thus a survival mechanism for intracellular parasites.     

A novel negative regulator for IL-1 receptor and Toll-like receptor 4

The Toll-IL-1 receptor (TIR) superfamily, defined by the presence of an intracellular TIR domain, initiates innate immunity via NF-kappaB activation, leading to production of proinflammatory cytokines. ST2 is a member of the TIR family that does not activate NF-kappaB and has been suggested as an important effector molecule of type 2 T helper cell responses. We have recently demonstrated that the membrane bound form of ST2 (ST2L) negatively regulated IL-1RI and TLR4 but not TLR3 signaling by sequestrating the adaptors MyD88 and Mal. In contrast to wild-type mice, ST2 deficient mice failed to develop endotoxin tolerance. Thus, ST2 suppresses IL-1R and TLR4 signaling via MyD88- and Mal-dependent pathways and modulates innate immunity. The results provide a molecular explanation for the role of ST2 in T(H)2 responses since inhibition of TLRs will promote a T(H)2 response and also identify ST2 as a key regulator of endotoxin tolerance.     

Mice lacking the norepinephrine transporter are supersensitive to psychostimulants

The action of norepinephrine (NE) is terminated, in part, by its uptake into presynaptic noradrenergic neurons by the plasma-membrane NE transporter (NET), which is a target for antidepressants and psychostimulants. Disruption of the NET gene in mice prolonged the clearance of NE and elevated extracellular levels of this catecholamine. In a classical test for antidepressant drugs, the NET-deficient (NET-/-) animals behaved like antidepressant-treated wild-type mice. Mutants were hyper-responsive to locomotor stimulation by cocaine or amphetamine. These responses were accompanied by dopamine D2/D3 receptor supersensitivity. Thus altering NET expression significantly modulates midbrain dopaminergic function, an effect that may be an important component of the actions of antidepressants and psychostimulants.     

Clinical and cytogenetics studies on acute myeloid leukemia with abnormality of chromosome 11

OBJECTIVE: To investigate the incidence of chromosome 11 abnormality in acute myeloid leukemia and its relationship with the clinical aspects and prognosis. METHODS:Conventional cytogenetic analysis of R-band was used to detect the abnormalities of chromosome 11 in 356 acute myeloid leukemia patients. RESULTS: Thirty-four out of 356 patients (9.55%) had abnormalities of chromosome 11, of which 20 (58.8%) involved in 11q23, 7 (19.9%) had translocations involving 11p15, 5 (14.7%) had-11, and the rest had other abnormalities such as +11, and t(11;14). The incidence of 11q23 involvement in M4 and M5 was higher than other subtypes of acute myeloid leukemia (AML). Ten cases with 11q23 abnormality had additional cytogenetic aberrations. In 30 cases treated with chemotherapy, 13 cases acquired complete remission (CR). The CR rate was lower than that of whole cases of acute myeloid leukemia(34.3% versus 64.0%). The CR rate of AML with 11q23 abnormality was lower than that of AML with normal karyotype (25% versus 55.6%). In other 10 patients with additional chromosome aberrations, the CR rate was lower than that of AML with 11q23 alone. In 7 patients with translocations at 11p15, only 3 patients acquired CR, and 2 patients relapsed early. Only 2 patients acquired CR in 5 patients with-11. CONCLUSION: 11q23 was a frequent aberration in chromosome 11 anomaly, which was often detected in M4 and M5. It might be associated with the pathogenesis of acute monolytic leukemia. The patients with chromosome 11 anomaly had poorer prognosis.     

组织金属蛋白酶抑制剂TIMP—2基因转染对胃癌细胞体内外侵袭能 …

了解ＴＩＭＰ－２基因转地胃癌细胞侵袭行为的影响，进行阻断肿瘤细胞侵转移的筛选尝试。     

脑康复冲剂对大鼠软脑膜微循环作用的实验研究

目的：脑康复冲剂临床用于治疗脑血栓血瘀证患者，本实验观察其对在大鼠实验性软脑膜微循环障碍的影响。方法：大鼠预防性给药，用高分子右旋糖酐水溶液静脉注射形成大鼠软脑膜的微循环障碍，观察脑康复冲剂对大鼠微循环的影响。结果：用高分子右旋糖酐造模后，大鼠软脑膜的微循环发生障碍，表现为血液流速减慢、血细胞聚集等，脑康复冲剂组血流速度开始减慢的时间明显比生理盐水对照组延长，且分级数也明显优于生理盐水组，对高分子右旋糖酐造成的血液流态障碍，脑康复组明显好于生理盐水组（P＜0．05），毛细血管网交叉点数开始减少的时间也比生理盐水对照组延长，差异显著（P＜0．01）。结论：脑康复冲剂使大鼠血流速度和血液流态得到改善，具有预防和改善动物脑微循环障碍的作用。     

Kv11.1 channel subunit composition includes MinK and varies developmentally in mouse cardiac muscle

The Kv11.1 (also ERG1) K(+) channel underlies cardiac I(Kr), a current that contributes to repolarization in mammalian heart. In mice, I(Kr) current density decreases with development and studies suggest that changes in the structure and/or properties of the heteromultimeric I(Kr)/Kv11.1 channel are responsible. Here, using immunohistochemistry, we report that total Kv11.1 alpha subunit protein is more abundant in neonatal heart and is distributed throughout both adult and neonatal ventricles with greater abundance in epicardia. Immunoblots reveal that the alpha subunit alternative splice variant, Kv11.1a, is more abundant in adult heart while the Kv11.1b variant is more abundant in neonatal heart. Additionally, MinK channel subunit protein is shown to co-assemble with Kv11.1 protein and is more abundant in neonatal heart. In summary, Kv11.1/I(Kr) channel composition varies developmentally and the higher I(Kr) current density in neonatal heart is likely attributable to higher abundance of Kv11.1/I(Kr) channels, more specifically, the Kv11.1b splice variant.