Structural change in dopamine D2 receptor gene in a patient with neuroleptic malignant syndrome

Dysfunction of the dopaminergic system has been suggested as a pathogenic mechanism in neuroleptic malignant syndrome. Therefore, we examined the complete coding sequences of the dopamine D₂ receptor (DRD₂) gene for structural abnormalities in 12 patients with a history of NMS, including two cases of familial NMS. Mutational analysis was performed by denaturing gradient gel electrophoresis (DGGE), a highly sensitive technique for detecting sequence differences. We found in one patient with a history of NMS a nucleotide substitution at codon 310 (CCG→TCG) of exon 7 of the DRD₂ gene which predicts the replacement of proline to serine in the third cytoplasmic loop of the receptor, a part of the receptor that interacts with G-proteins. A larger series of patients with NMS needs to be investigated to establish whether this allele is associated with an increased susceptibility to NMS. © 1995 Wiley-Liss, Inc.     

Model of bicarbonate secretion by resting frog stomach fundus mucosa I. Transepithelial measurements

In the present in vitro experiments on gastric fundus mucosa of Rana esculenta we try to define the mechanism of alkaline secretion that is observed in summer frogs in the resting stomach (blockage of HCl secretion by ranitidine, 10^–5 mol/l). The transepithelial voltage and the rate of alkalinization (ASR) of an unbuffered gastric lumen perfusate was measured as a function of serosal (and mucosal) fluid composition. ASR was high (0.88±S.E. 0.09 Eq·cm^–2·h^–1, n=11) during serosal bath perfusion with HCO₃ ^–-Ringer solution, decreased slightly to 0.50±0.07 Eq·cm^–2·h^–1 (n=6) in HCO₃ ^–-free HEPES-buffered Ringer solution of the same pH, and decreased to approximately 20% when carbonic anhydrase was inhibited by acetazolamide. While replacement of mucosal or serosal Cl^– did not — within 1 h — significantly alter ASR, replacement of serosal Na⁺ in the presence or absence of HCO₃ ^– strongly reduced ASR, and a similar reduction was observed after serosal application of the anion transport inhibitor DIDS (4,4-diisomiocyanatostilbene-2,2-disulphonate, 2·10^–4 mol/l), the metabolic poison rotenone (10^–5 mol/l), the uncoupler dinitrophenol (10^–4 mol/l), and the Na⁺ pump inhibitor ouabain (10^–4 mol/l), while serosal amiloride (10^–4 mol/l) had no effect. These data can be accounted for by a model of alkaline secretion that consists of basolateral HCO₃ ^– uptake from the serosal fluid into the cell via a DIDS-inhibitable Na⁺(HCO₃ ^–)_n-cotransporter and HCO₃ ^– secretion from the cell to the gastric lumen via an anionic conductance pathway. Microelectrode experiments on oxyntopeptic cells reported in the subsequent paper suggest that these cells may also be involved in the resting state alkaline secretion.     

Activation of MAP kinases,pp90rsk and pp70-S6 kinases in mouse mast cells by signaling through the c-kit receptor tyrosine kinase or FcϵRI: rapamycin inhibits activation of pp70-S6 kinase and proliferation in mouse mast cells

The high-affinity receptor for IgE, Fc_?RI, represents the major cell surface structure through which mast cells express immunologically specific secretory function. By contrast, the stem cell factor receptor (SCFR), which is encoded by c-kit, is essential for normal mast cell development. The signaling pathways initiated by the stimulation of mast cells through the Fc_?RI, which lacks intrinsic kinase activity, and the SCFR, a member of the receptor tyrosine kinase family, generally have been regarded to be distinct. We report here that mouse mast cells stimulated either with SCF or with IgE and specific antigen exhibit a remarkably similar pattern of activation of mitogen-activated protein kinases (MAPK), 90 kDa-S6 kinases (pp90^rsk), and pp70-S6 kinases (pp70-S6K). These results indicate that all three families of protein kinases are associated with the cell surface receptor-dependent activation of secretion, as well as proliferation, in mast cells. We also show that the immunosuppressant rapamycin, but not FK506, can inhibit both SCF-dependent pp70-S6 kinase activation and SCF-dependent proliferation in mouse mast cells, without suppressing IgE- and antigen-dependent mediator release. These findings suggest that the activation of pp70-S6 kinase represents an important link in the stimulation of cell proliferation by SCF. Our results also indicate that the intracellular signaling pathways initiated by stimulation of mast cells through the Fc_?RI or the SCFR exhibit more overlap than has previously been appreciated.     

人外周血淋巴细胞激活与CD2mRNA表达

对 PHA、抗 CD3单克隆抗体 RW2—8C8、胸腺肽、抗 CD2与抗 CD3等对人 T 淋巴细胞的增殖现象及动力学进行了观察,除抗 CD3与抗 CD2单抗联合应用为抑制效应外,前三者均呈正效应且动力学完全一致.在此基础上,应用反义 CD2mRNA 探针检测了 mRNA 在激活24小时以后的变化,发现 T 细胞活化者均显示 mRNA 量呈上升;反之则不见变化或低于未激活 T 细胞对照组水平.本研究证明了小牛胸腺肽有激活 T 细胞和提高 mRNA 水平的作用,为首次报导.本文对上述在基因水平上观察的结果进行了讨论.     

Vascular smooth muscle sensitivity to noradrenaline is reduced during an infection with trypanosoma brucei in rats and rabbits

α₁-adrenoceptor sensitivity to noradrenaline has been studied in some arterial smooth muscles of rats and rabbits infected with T. brucei. In rabbits, a decrease in sensitivity of the arterial smooth muscles to noradrenaline was observed in the thoracic aorta, central ear but not renal arteries. No change in the sensitivity of the smooth muscles to histamine was observed. In rats, noradrenaline potency was reduced in the aorta, renal but not tail arteries. In both species, affinity of noradrenaline for a,-adrenoceptors was significantly (P < 0.05) reduced in arteries where the potency of noradrenaline was reduced. Prazosin K_B values in infected animals were significantly (P < 0.05) lower than controls. These results are interpreted to suggest either an alteration in the structure of a,-adrenoceptors during an infection, or accumulation of some factor(s) in the receptor microenvironment that modulated binding of agonists and antagonists to the receptors during an infection with T. brucei. The possible role of reduced α₁-adrenoceptor affinity in the hypotension observed during an infection with T. brucei is discussed.     

Sodium bicarbonate secretion indicated by ultrastructural cytochemical localization of HCO3 −, Cl−, and Na+ ions on rat bile duct brush cells

Brush cells are widely distributed in the digestive and respiratory apparatus, but their function is still unknown. Because brush cells (BC) are found in organs secreting NaHCO₃, it was hypothesized that these cells may secrete NaHCO₃. To test this possibility, rat common bile duct epithelia were examined by ultrastructural cytochemical methods for localizing HCO₃⁻, Cl⁻, and Na⁺ ions. All three ion precipitates were few in or on BCs of rats without stimulation. Lead carbonate precipitates, which localized HCO₃⁻ ions by the lead nitrate-osmium method, increased markedly on the surface of the microvilli (MV) of BCs after secretin or meal stimulation, but similar precipitates were few on the luminal surface of principal cells (PCs). Silver chloride precipitates, which indicate the presence of Cl⁻ ions by the silver-osmium method, increased in the apical cytoplasm and in MV of BCs after secretin or meal stimulation, but they were few in PCs. Sodium pyroantimonate precipitates, which localize Na⁺ ions by the potassium pyroantimonate-osmium method, increased on the surface of the MV, along the basolateral membrane, and in the apical cytoplasm of BCs after secretin or meal stimulation, but they were few in PCs. These results strongly suggest that BCs may be a significant source of NaHCO₃ secretion.     

红藻氨酸癫痫大鼠前额叶皮层多巴胺D2受体的变化及意义

利用红藻氨酸颈部皮下注射 ,诱发大鼠癫痫发作 ,用免疫组化和原位杂交方法 ,观察前额叶皮层多巴胺 D2 受体蛋白和m RNA的变化。在诱发 4,5级癫痫发作后 4周 ,模型大鼠前额叶皮层 层细胞多巴胺 D2 受体免疫反应活性及其 m RNA明显下降 ,而在 、 层则有明显上升。多巴胺 D2 受体蛋白及其 m RNA在 层的下调可能导致该层锥体细胞的脱抑制 ,从而导致其往皮层下核团如尾壳核和伏隔核的谷氨酸能输入增加。而 层的上调则可能导致该层输出信息的障碍 ,引起皮层间信息联系的改变 ,这种变化对于探讨癫痫并发的认知障碍可能具有一定的意义。     

脊柱三维运动实验加载方式的改进

目的:改进三维运动实验的加载方式。方法:新鲜羊腰椎标本6例(L1~5),置于脊柱三维运动实验机上进行六个自由度的运动。两次预加载后依次对标本进行3、0、0.3Nm的加载,并采集三种加载时的运动图像。3Nm加载及0加载的图像作为传统加载方式计算出脊柱的运动范围及中性区,3Nm加载及0.3Nm加载的图像作为新的加载方式计算出新的脊柱运动范围及中性区,再对两种计算方法得出的运动范围及中性区进行配对t检验,计算两种方法各自的变异率,并进行配对t检验。结果:两种方法得到的运动范围之间不存在差异(P=0.105),但中性区之间存在显著性差异(P=0.013)。采用新的加载方式得到的运动范围的变异系数比以往的方法要小得多(P<0.001)。结论:采用新的加载方式可以得到较为准确的脊柱运动的运动范围。     

一种快速有效的医学图像灰度插值算法

介绍一种用于快速有效的医学图像灰度插值算法。通过在两幅已知图像上寻找对应点，有效地解决了线性插值边界模糊的问题，同时避免了基于形状的插值算法中图像分割的问题，具有较强的适用范围。实验结果表明此算法能得到令人满意的插值结果。