重组人EPO真核表达质粒在大鼠骨骼肌中的表达及其对贫血的治疗作用

目的和方法构建ＥＰＯ真核细胞表达载体（ｐｃＤ２ＥＰＯ）,用缝线法和注射法将其直接导入肾性贫血大鼠股四头肌,观察ＥＰＯ在骨骼肌细胞中的表达及其对贫血的治疗作用。结果：ｐｃＤ２ＥＰＯ导入股四头肌２周后,骨骼肌细胞内出现ＥＰＯｍＲＮＡ,提示被导入的ＥＰＯ基因在肌细胞内得到表达。贫血动物被治疗１周后,缝线组和注射组动物的ＨＧＢ和ＲＢＣ均显著升高;在第３周,缝线组的ＨＧＢ和ＲＢＣ接近健康大鼠的水平;至第４周,两个治疗组的ＨＧＢ和ＲＢＣ仍显著高于对照组。结论：经缝线法导入的ｐｃＤ２ＥＰＯ在骨骼肌中的表达效率及对贫血的治疗效果明显高于直接注射法,而两种治疗方法对改善肾性贫血动物肾脏清除ＢＵＮ的功能无明显差异     

基于视差敏感复杂细胞的聚散式眼动的生理模型

根据心理物理实验和电生理实验的结果,选用对非零视差有选择性反应的视差敏感复杂细胞来检测视差信息,并把所提取的视差信息直接投射到聚散式眼动细胞（ｖｅｒｇｅｎｃｅｃｅｌ）以控制聚散式眼动。同时,综合考虑了复杂细胞编码范围的限制、近细胞和远细胞的相位关系以及跳跃式眼动后增强效应（ｐｏｓｔ－ｓａｃｃａｄｉｃｅｎｈａｎｃｅｍｅｎｔ）等因素。得到的模拟结果与心理物理实验结果定性地符合     

壳聚糖金属离子配合物吸附尿素性能研究

由于尿素吸附剂存在吸附容量低、吸附选择性差、生物相容性和血液相容性差等缺点,使人工肾和口服尿素吸附剂的应用受到限制．近几年,尿素吸附材料方面的研究进展较快,主要有：１９９０年,藤田良枝用活性炭作尿素吸附剂,吸附量为９０ｍｇ／ｇ（尿素初始浓度为２１００ｍｇ／Ｌ）,吸附容量低,且微炭粒易脱落,有造成栓塞的危险,不宜作人工肾材料［１］;１９９３年,何炳林等用交联聚丙烯酸固载化氧化β环糊精作尿素吸附材料,吸附容量较高,为８２１ｍｇ／ｇ（尿素的初始浓度为１３００ｍｇ／Ｌ）．由于其利用的是Ｓｃｈｉｆｆ…     

Decrease of rotenone inhibition is a sensitive parameter of complex I damage in brain non-synaptic mitochondria of aged rats

We investigated NADH oxidation in non-synaptic and synaptic mitochondria from brain cortex of 4- and 24-month-old rats. The NADH oxidase activity was significantly lower in non-synaptic mitochondria from aged rats; we also found a significant decrease of sensitivity of NADH oxidation to the specific Complex I inhibitor, rotenone. Since the rotenone-binding site encompasses Complex I subunits encoded by mtDNA, these results are in accordance with the mitochondrial theory of aging, whereby somatic mtDNA mutations are at the basis of cellular senescence. Accordingly, a 5 kb deletion was detected only in the cortex of the aged animals.     

Quantitative genetic dissection of complex traits in a QTL-mapping pedigree

This paper summarizes and modifies quantitative genetic analyses on a pedigree used to map genetic factors (i.e., QTLs) underlying a complex trait. The total genetic variance can be exactly estimated based on the F₂ family derived from two homozygous parents for alternative alleles at all QTLs of interest. The parents, F₁ hybrids, and two backcrosses are combined to each parent, and the total number of QTLs and the number of dominant QTLs are estimated under the assumptions of gene association with the two parents, equal gene effect, no linkage, and no epistasis among QTLs. Further relaxation for each of the assumptions are made in detail. The biometric estimator for the QTL number and action mode averaged over the entire genome could provide some basic and complementary information to QTL mapping designed to detect the effect and location of specific genetic factors.     

The influence of aging on renal response to cadmium in Syrian hamsters

To determine the renal effects of cadmium (Cd) in older animals, we administered subcutaneously a single dose of cadmium, 3.0 mg/kg/BW, to Syrian hamsters aged 16 wk (“young”) and 60 wk (“old”). Marked morphologic changes in the kidney and renal dysfunction were observed, especially in the older animals. The concentration of MDA in the renal cortex was significantly increased only in young hamsters treated with cadmium. Concentrations of glutathione (GSH) in the renal cortex were increased in the old hamsters on d 6. Increased levels of renal MDA after cadmium treatment may induce the production of GSH in the kidney thus preventing renal damage. Aging can increase the susceptibility to the renal effects of cadmium.     

Inactivation of complex I of the respiratory chain of maize mitochondria incubated in vitro by elevated temperature

The functional stability of the ‘external’ NADH dehydrogenase and complexes I–IV of the respiratory chain of maize mitochondria was studied during mitochondria incubation in vitro at elevated temperatures. The increase in the incubation temperature from 0°C to 37°C significantly changed the stability of the respiratory chain. At 27°C and higher, the rate of oxidation of NAD-depended substrates decreased drastically, which is related to inactivation of complex I. Complexes II, III and IV of the respiratory chain and the ‘external’ NADH dehydrogenase were functionally stable at elevated temperatures. Moreover, the possibility of electron transport during oxidation of NAD-dependent substrates, in particular malate, bypasses complex I using rotenon insensitive NADH dehydrogenase.     

On the calculation of binding free energies using continuum methods: Application to MHC class I protein-peptide interactions

This paper describes a methodology to calculate the binding free energy (ΔG) of a protein-ligand complex using a continuum model of the solvent. A formal thermodynamic cycle is used to decompose the binding free energy into electrostatic and non-electrostatic contributions. In this cycle, the reactants are discharged in water, associated as purely nonpolar entities, and the final complex is then recharged. The total electrostatic free energies of the protein, the ligand, and the complex in water are calculated with the finite difference Poisson-Boltzmann (FDPB) method. The nonpolar (hydrophobic) binding free energy is calculated using a free energy-surface area relationship, with a single alkane/water surface tension coefficient (γ_aw). The loss in backbone and side-chain configurational entropy upon binding is estimated and added to the electrostatic and the nonpolar components of ΔG. The methodology is applied to the binding of the murine MHC class I protein H-2K^b with three distinct peptides, and to the human MHC class I protein HLA-A2 in complex with five different peptides. Despite significant differences in the amino acid sequences of the different peptides, the experimental binding free energy differences (ΔΔG_exp) are quite small (<0.3 and <2.7 kcal/mol for the H-2K^b and HLA-A2 complexes, respectively). For each protein, the calculations are successful in reproducing a fairly small range of values for ΔΔG_calc (<4.4 and <5.2 kcal/mol, respectively) although the relative peptide binding affinities of H-2K^b and HLA-A2 are not reproduced. For all protein-peptide complexes that were treated, it was found that electrostatic interactions oppose binding whereas nonpolar interactions drive complex formation. The two types of interactions appear to be correlated in that larger nonpolar contributions to binding are generally opposed by increased electrostatic contributions favoring dissociation. The factors that drive the binding of peptides to MHC proteins are discussed in light of our results.     

Regucalcin increases Ca2+-ATPase activity and ATP-dependent calcium uptake in the microsomes of rat kidney cortex

The effect of regucalcin, a Ca²⁺-binding protein, on Ca²⁺ transport system in rat renal cortex microsomes was investigated. The presence of regucalcin (10^-8 to 10^-6 M) in the reaction mixture caused a significant increase in Ca²⁺-ATPase activity and ATP-dependent⁴⁵ Ca²⁺ uptake in the microsomes. Regucalcin (10^-7 M) increased Ca²⁺-ATPase activity independently of increasing concentrations of CaCl_{_2}. The microsomal Ca²⁺-ATPase activity and⁴⁵ Ca²⁺ uptake were markedly decreased by the presence of vanadate (0.1 mM) or N-ethylmaleimide (NEM; 5 mM) in the absence or presence of regucalcin. Dithiothreitol (DTT; 5 mM) markedly elevated Ca²⁺-ATPase activity and ⁴⁵Ca²⁺ uptake in the microsomes. The DTT effects were not further enhanced by regucalcin (10^-7 M). Meanwhile, the microsomal Ca²⁺-ATPase activity and ⁴⁵Ca²⁺ uptake were significantly decreased by the presence of dibutyryl cyclic AMP (DcAMP; 10^-5 and 10^-3 M) or inositol 1,4, 5-trisphosphate (IP3; 10^-7 and 10^-5 M). The effect of regucalcin (10^-7 M) on Ca²⁺ ATPase activity and ⁴⁵Ca²⁺ uptake was weakened in the presence of DcAMP or IP₃. The present results demonstrate that regucalcin has a stimulatory effect on ATP-dependent Ca²⁺ uptake in the microsomes of rat renal cortex due to acting on the thiol groups of Ca²⁺-ATPase.     

心室内注射腺苷对肾交感神经传出活动的影响

在切断两侧缓冲神经和迷走神经的麻醉大鼠,观察心室内注射腺苷及其同系物对肾交感神经传出活动的影响。心室内冲击注射腺昔（0．5μmol／kg,0．1ml）时,肾交感神经传出放电（RSNA）增加41．9±6．08％（P＜0．001）,并引起平均动脉血压（MAP）先短暂升高1．39±0．19kPS（P＜0．001）和随后下降3．74±0．64kPa（P＜0．001）,以及心率（HR）减慢95±14bpm（P＜0．001）。为了确定何种受体亚型介导腺苷所致RSNA增加,又分别应用了选择性腺昔A1受体激动剂[（-）-N6－（2－Phenylisopropyl）adenosine,R－PIA]和A2受体激动剂[5＇－（N－ethylcarboxamido）adenosine,NECA]。无论R－PIA（0．05μmol／kg,0．1ml）或NECA（0．05μmol／kg,0．1ml）均使MAP下降和HR减慢,且作用持续时间较腺苷的明显延长;R－PIA使RSNA增加31．6±5．21％（P＜0．001）,但NECA对RSNA无明显影响。选择性腺苷A1受体拮抗剂（8－cyclopentyl－1,3－dipropylxanthine,DPCPX）可完全抑制腺苷对RSNA的兴奋效应。切除双侧星状神经节后,腺苷兴奋RSNA的效应消失。以上结果提示,腺苷可通过A1受体激活心交感神经传入纤维,反射地增强肾交感神经的传出活动。