Differential effects of dopamine agonists on acoustically and electrically elicited startle response: Comparison to effects of strychnine

This study sought to determine where drugs that are known to alter sensorimotor reactivity measured with the acoustic startle reflex ultimately act within the acoustic startle pathway. To do this, startle was elicited either acoustically or electrically within various nuclei believed to comprise the acoustic startle pathway. Direct infusion of serotonin into the subarachnoid space of the lumbar spinal cord increased acoustic startle and startle elicited electrically through the ventral cochlear nucleus (VCN) to a comparable degree. Subconvulsant doses of strychnine increased startle elicited acoustically or electrically through either the VCN or the nucleus reticularis pontis caudalis (RPC), pointing to spinal locus of action of strychnine after systemic administration. In marked contrast, the dopamine agonists d-amphetamine and apomorphine consistently increased acoustic startle but actually depressed startle elicited electrically through the VCN or the RPC. These later results suggest that dopamine agonists increase sensorimotor reactivity measured with acoustic startle by acting on sensory rather than motor parts of the reflex arc.     

Pyruvate kinase isozyme (PK-Greenville) with defective allosteric activation by fructose-1,6-diphosphate: the role of F-1,6-P modulation in normal erythrocyte metabolism

A child with chronic hemolytic anemia since birth was found to have erythrocyte pyruvate kinase (PK) in a highly unusual form relative to other mutant isozymes when characterized by International Committee for Standardization in Hematology criteria. Most properties of the partially purified isozyme (designated PK-Greenville) were altered minimally, if at all, except for nearly total insensitivity to allosteric activation by fructose-1,6-diphosphate (F-1,6-P). One parent appeared to be heterozygous for a null gene and the other for an allele governing production of the mutant isozyme. Apparent restriction of the molecular defect to ineffective activation kinetics suggests that the F- 1,6-P binding site on erythrocyte PK is functionally as well as physically allosteric. The magnitude of the metabolic block at the PK step and the clinical severity indicate that allosteric modulation by F- 1,6-P is a crucial property of PK in normal erythrocyte metabolism.     

Pyruvate kinase Greensboro. A four-generation study of a high K0.5s (phosphoenolpyruvate) variant [published erratum appears in Blood 1988 Dec;72(6):2082]

The proband with lifelong hemolytic anemia has a high K0.5s phosphoenolypyruvate (PEP) erythrocyte pyruvate kinase (PK) variant substantially but incompletely normalized by the allosteric modifier fructose-1,6-diphosphate (F-1,6-P2) with conversion of sigmoidal to hyperbolic kinetics. Heterozygotes in four generations express qualitatively identical but less severely abnormal kinetics and lack overt hemolysis. Kinetic abnormalities are closely mimicked by sulfhydryl modification of normal PK. Three distinct clinical and metabolic phenotypes characterize the proband and two sisters: variant PK and hemolytic anemia, variant PK without clinical manifestations or hemolysis, and complete normality. Their mother, whose red cell PK is entirely normal except for a questionably slightly low Vmax, is postulated to express the gene products of nonidentical alleles, one encoding a product with mildly less favorable catalytic characteristics. At low PEP concentrations, the proband and heterozygotes for the PK mutant express only a very small fraction of normal PK activity despite apparent inheritance of one normal allele in the latter. Evidence suggests that disproportionately lowered PK activity may be a property of a heterotetrameric PK. Illusory abnormalities in nucleotide specificity are artifacts of diminished substrate affinity characterizing the mutant PK.     

Expression signature in peripheral blood cells for molecular diagnosis of head and neck squamous cell carcinoma

Patients with head and neck squamous cell carcinoma (HNSCC) have a poor prognosis due to the development of locoregional recurrences, distant metastases, and second primary tumors. There is an urgent need for biomarkers that enable detection and monitoring of the disease to provide adequate therapeutic strategies. In this study, we have investigated markers in peripheral blood cells (PBC) of 28 HNSCC patients who underwent surgery by means of expression profiling. Our hypothesis is that nucleated blood cells circulate continuously, also pass the tumor, and change their expression profile in response to tumor cell factors. For comparison, we enrolled a control group of 11 patients who underwent surgery in the head and neck region for non‐HNSCC reasons. A set of 2949 genes was found to be statistically different between the groups (P < 0.05, false discovery rate‐corrected) and the most prominently different pathways were EIF2, EIF4, and mTOR signaling. These preliminary results are promising and warrant further studies on the definitive role of PBC gene expression as a biomarker for HNSCC detection and monitoring.     

N-甲基-N-(α-取代萘甲基)取代苄胺类化合物的合成及抗真菌活性

报道25个N-甲基-N-(α-取代萘甲基)取代苄胺类化合物的合成及抗真菌活性。抑菌测试结果表明,目标化合物对于8种试验菌种均有不同程度的抑菌活性,化合物6,7,8,10,11和21等活性为naftifine的4～20倍,化合物8,10,11和21等活性为butenafine的2～10倍,化合物8,9,10,11和21等对Sporotrichum schencki及Aspergilus fumigatus的活性为clotrimazole的8～15倍,化合物7,8,9和21等对Cryptococus neoformans亦表现出较高活性,MIC为0.31～1.25μg·ml^-1。     

微波直接接触辐射器临床应用的生物学效能

目的:评定微波直接接触辐射器临床应用的生物学效能。方法:动物实验于2004-09/2005-01在武汉市武昌铁路医院动物实验室完成。选择健康大耳白兔30只,按随机数字表法分为3组:对照组、直接接触辐射组、近场辐射组,每组10只。对照组:不做任何处理。直接接触辐射组:采用自制圆盘形直接辐射器(直径10.3m,频率915MHz,功率0～10W,天线为微带型,单元结构,驻波系数<3,专利号zl00324703.1)紧贴皮毛照射左侧桡骨骨折处,设定时间10min,功率5W,温度5～10℃,1次/d,10次为1个疗程,休息3d,再进行下一疗程,共3个疗程。近场辐射组:采用WR-Ⅱ型微波治癌机配备的圆柱形近场辐射器,距皮毛5cm,功率50W,时间为30min,温度5～10℃,1次/d,10次为1个疗程,休息3d,再进行下一疗程,共3个疗程。每周拍摄左前肢桡骨X射线片。每天进行临床一般检查,定期测定血清总蛋白、球蛋白、补体C3,观察全身状态。临床观察于2005-02/07选择武汉市武昌铁路医院门诊及住院患者402例,接受体表圆盘形直接辐射器理疗患者300例,为实验组,接受体表圆柱形近场辐射理疗患者102例,为对照组。实验组颈椎病患者:5min/次,功率2～6W,隔日1次,5次为1个疗程;急性创伤患者:骨折需固定术后24h方可进行理疗,8～10min/次,功率10W,10次为1个疗程;慢性腰腿痛患者:10～15min/次,功率10～15W,10次为1个疗程。对照组患者:治疗时间30min/次,治疗功率50～100W,治疗方法:距患部3～5cm。结果:动物实验结果:①直接接触辐射组、近场辐射组兔骨折愈合过程明显缩短。②X射线片显示直接接触辐射组、近场辐射组骨痂生成较对照组提前14d。③组织学观察直接接触辐射组、近场辐射组镜下见大片软骨组织及成骨细胞明显增生活跃,大片状骨小梁排列成网架状;对照组镜下见软骨组织成成骨细胞增生不活跃。④直接接触辐射组、近场辐射组疗效比较无差异,与对照组比较差异显著。⑤直接接触辐射组出现的副作用少于近场辐射组。⑥直接接触辐射组血清总蛋白、γ-球蛋白、补体C3含量高于近场辐射组和对照组。临床观察结果:①临床观察:急性期一期愈合患者占90%,慢性期患者症状减轻、缓解好转占80%。②疗效比较:实验组、对照组患者功能部分恢复,主要体征消失,症状缓解分别为284,96例,功能症状、体征与治疗前无好转变化分别为16,6例,治疗有效率分别为94.74%,93.75%。③副作用:实验组、对照组患者出现头昏症状分别为5,0例,出现胸闷症状分别为0,8例,出现失眠症状分别为0,2例,出现月经不调症状为0,2例,反应率分别为1.6%,21.5%。结论:微波直接接触辐射器临床使用的生物学效能优于近场辐射器,减少副作用、提高效率、节能、省时。