Using genetically-defined rodent strains for the identification of hippocampal traits relevant for two-way avoidance behavior: a non-invasive approach

Summary Genetically-defined rodent strains permit the identification of hippocampal traits which are of functional relevance for the performance of two-way avoidance behavior. This is exemplified here by analyzing the relationship between infrapyramidal mossy fibers (a tiny projection terminating upon the basal dendrites of hippocampal pyramidal neurons) and two-way avoidance learning in about 800 animals. The necessary steps include 1) identification of structural traits sensitive to selective breeding for extremes in two-way avoidance, 2) testing the robustness of the associations found by studying individual and genetical correlations between hippocampal traits and behavior, 3) establishing causal relationships by Mendelian crossing of strains with extreme structural traits and studying the behavioral consequences of such structural randomization, 4) confirming causal relationships by manipulating the structural variable in inbred (isogenic) strains, thereby eliminating the possibility of genetic linkage, and 5) ruling out the possibility of spurious associations by studying the correlations between the hippocampal trait and other behaviors known to depend on hippocampal functioning.In comparison with the classical lesion approach for identifying relationships between brain and behavior, the present procedure appears to be superior in two aspects: it is non-invasive, and it focuses automatically on those brain traits which are used by natural selection to shape behaviorally-defined animal populations, i.e., it reveals the natural regulators of behavior.     

甲状腺功能亢进226例外科治疗

对甲状腺功能亢进２２６ 例患者进行了手术治疗,结果显示：全部病例无手术死亡,无甲亢危象,无切口感染,疗效满意．认为做好充分的术前准备是手术成功和预防术后并发症的关键．     

骨化三醇不同治疗方法对尿毒症维持性血透患者SHPT远期疗效分析

目的探讨骨化三醇常规剂量治疗和冲击治疗对尿毒症维持性血透患者继发性甲状旁腺功能亢进(SHPT)的远期疗效.方法选取38例连续接受血液透析的尿毒症合并SHPT患者,将患者分为冲击治疗组(21例),常规治疗组(17例).常规治疗组给予三醇口服0.25~0.50μg,每晚1次;冲击治疗组根据患者甲状旁腺激素水平给予不同剂量骨化三醇.比较两组患者治疗前后的甲状旁腺激素、血钙、血磷、钙磷乘积水平以及临床症状变化.结果两组患者总有效率之间差异无统计学意义(P0.05);治疗后两组患者甲状旁腺激素水平均明显降低,与治疗前相比差异具有统计学意义(P0.05).结论两种治疗方法远期疗效无明显差异,但常规治疗可降低高血钙和高钙磷乘积的发生率,降低患者心血管事件的发生风险.因此,对尿毒症患者推荐选择骨化三醇常规剂量治疗.     

The specificity of binding of glycoprotein hormones to their receptors

The glycoprotein hormone receptor family is peculiar because, in contrast to other G protein-coupled receptors, a large N-terminal extracellular ectodomain is responsible for hormone recognition. Hormone-receptor pairs have evolved in such a manner that a limited number of positions both at the 'seat-belt' domain of the hormone and the leucine-rich repeats of the receptor, play attractive and repulsive interactions for binding and specificity, respectively. Surprisingly, the constitutive activity of the receptor, mostly modulated by highly conserved amino acids within the heptahelical domain of the receptor (i.e., outside the hormone binding region), also regulates effectiveness of hormone recognition by the extracellular part. In this review we analyze, at the molecular level, these important discriminating determinants for selective binding of glycoprotein hormones to their receptors, as well as natural mutations, observed in patients with gestational hyperthyroidism or ovarian hyperstimulation syndrome, that modify the selectivity of binding.     

甲亢患者尿β2微球蛋白,白蛋白和IgG水平的检测

采用放射免疫分析法测定了７１例甲亢患者尿β２微球蛋白（β２－Ｍ）、白蛋白（ＡＬｂ）和ＩｇＧ水平，以观察甲亢患者肾脏功能的变化。结果表明甲亢患者尿β２－Ｍ、ＡＬｂ和ＩｇＧ水平明显高于正常对照组，肾脏损害检出率６７．６％，肾小球或肾小管同时受损率为２６．８％。提示部分甲亢患者存在肾脏功能异常     

应用ROC曲线评价甲状腺功能相关指标对原发性甲亢的诊断价值

目的:探索原发性甲亢患者最适实验室诊断指标。方法:用放射免疫法测定不同人群中三碘甲状腺原氨酸(TT3)、甲状腺素(TT4)、促甲状腺素(TSH)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)浓度,并比较受试者工作特征曲线(ROC)下面积。结果:原发性甲亢诊断ROC值TSH:0.88±0.02,FT3:0.80±0.07,FT4:0.83±0.04,TT3:0.81±0.03,TT4:0.77±0.03,FT4/TSH比值:0.93±0.02。结论:放射免疫法测定FT4/TSH比值显示出最佳的诊断准确性;ROC曲线是一种科学、全面评价检验指标的检验方法。     

The TSH receptor and its role in thyroid disease

The thyrotropin (TSH) receptor plays a preeminent role in thyroid physiology and disease. TSH, acting through the TSH receptor, is the major stimulator of thyroid cell growth, differentiation and function. In Graves' disease, the TSH receptor is the target of stimulating antibodies that cause hyperthyroidism. Although still a topic of debate, the TSH receptor has been implicated in the pathogenesis of the endocrine ophthalmopathy associated with Graves' disease. Blocking antibodies against the TSH receptor are involved in the development of hypothyroidism in a subset of patients with autoimmune hypothyroidism. Transplacental passage of stimulating or blocking TSH receptor antibodies from a mother with autoimmune thyroid disease may result in transient hyper- or hypothyroidism in early infancy. During pregnancy, the placental hormone human choriogonadotropin (hCG) can cause gestational hyperthyroidism through cross-reaction with the TSH receptor. Gestational hyperthyroidism may also be involved in the pathogenesis of hyperemesis gravidarum. Trophoblast tumors secreting hCG are a rare cause of hyperthyroidism. Somatic activating mutations of the TSH receptor have been identified as a molecular cause of toxic adenomas, whereas activating mutations in the germline give rise to nonautoimmune familial hyperthyroidism or sporadic congenital hyperthyroidism. These gain-of-function mutations are dominant, and one mutated allele is sufficient to result in disease. Inactivating germline mutations of both TSH receptor alleles lead to variable degrees of resistance to TSH, encompassing a spectrum ranging from euthyroid hyperthyrotropinemia to overt hypothyroidism with thyroid hypoplasia. Received 31 January 2001; received after revision 3 April 2001; accepted 3 April 2001     

Role of nitric oxide in the functional response to ischemia-reperfusion of heart mitochondria from hyperthyroid rats

We investigated the role of nitric oxide (NO) in the mitochondrial derangement associated with the functional response to ischemia-reperfusion of hyperthyroid rat hearts. Mitochondria were isolated at 3000 g from hearts subjected to ischemia-reperfusion, with or without N-nitro-L-arginine (L-NNA, an NO synthase inhibitor). During reperfusion, hyperthyroid hearts displayed tachycardia and low functional recovery. Their mitochondria exhibited O₂ consumption similar to euthyroid controls, while H₂O₂ production, hydroperoxide, protein-bound carbonyl and nitrotyrosine levels, and susceptibility to swelling were higher. L-NNA blocked the reperfusion tachycardic response and increased inotropic recovery in hyperthyroid hearts. L-NNA decreased mitochondrial H₂O₂ production and oxidative damage, and increased respiration and tolerance to swelling. Such effects were higher in hyperthyroid preparations. These results confirm the role of mitochondria in ischemia-reperfusion damage, and strongly suggest that NO overproduction is involved in the high mitochondrial dysfunction and the low recovery of hyperthyroid hearts from ischemia-reperfusion. L-NNA also decreased protein content and cytochrome oxidase activity of a mitochondrial fraction isolated at 8000 g. This and previous results suggest that the above fraction contains, together with light mitochondria, damaged mitochondria coming from the heaviest fraction, which has the highest cytochrome oxidase activity and capacity to produce H₂O₂. Therefore, we propose that the high mitochondrial susceptibility to swelling, favoring mitochondrial population purification from H₂O₂-overproducing mitochondria, limits hyperthyroid heart oxidative stress.Received 24 March 2004; received after revision 9 June 2004; accepted 5 July 2004     

女性甲亢患者血清瘦素水平与身体成分的相关性

目的:探讨女性甲亢患者血清瘦素水平的变化与其身体成分的相关关系.方法:采用放射免疫分析法(RIA)检测33例女性甲亢患者和12例女性正常对照者血清瘦素水平,同时应用双能X线吸收法(DXA)测量全身的骨矿盐含量(简称骨量)、脂肪量和肌肉量.结果:女性甲亢组血清瘦素水平与正常对照组比较差异无显著意义(P＞0.05).血清瘦素水平与全身骨量呈显著正相关(r=0.447,n=33,P＜0.01),与全身脂肪量(r=0.501,n=33,P＜0.01)呈显著正相关,与全身肌肉量无明显相关性(r=0.101,n=33,P＞0.05).结论:女性甲亢患者身体骨量和脂肪量的变化与血清瘦素水平明显相关.     

高频彩色多普勒超声对甲亢的诊断价值

目的:探讨高频彩色多普勒超声对原发性甲状腺机能亢进(Graves病)的诊断价值。方法:对30例Graves病患者及30例正常人行高频彩色多普勒超声检查,并结合T3,T4结果进行分析。结果:甲亢患者甲状腺三径值显著增大,与对照组比差异显著(P<0.01),腺体回声增粗增强,血流信号增多,甲状腺上动脉收缩期峰值流速及阻力指数增高,与T3T4升高呈正相关(r=0.703,P<0.01)。结论:高频彩色多普勒超声在原发性甲亢诊断中有较高价值。