Responses of tonically discharging neurons in the monkey striatum to primary rewards delivered during different behavioral states

In the primate striatum, the tonically discharging neurons respond to conditioned stimuli associated with reward. We investigated whether these neurons respond to the reward itself and how changes in the behavioral context in which the reward is delivered might influence their responsiveness. A total of 286 neurons in the caudate nucleus and putamen were studied in two awake macaque monkeys while liquid reward was delivered in three behavioral situations: (1) an instrumental task, in which reward was delivered upon execution of a visually triggered arm movement; (2) a classically conditioned task, in which reward was delivered 1 s after a visual signal; (3) a free reward situation, in which reward was delivered at irregular time intervals outside of any conditioning task. The monkeys′ uncertainty about the time at which reward will be delivered was assessed by monitoring their mouth movements. A larger proportion of neurons responsive to reward was observed in the free reward situation (86%) than in the classically conditioned (57%) and instrumental tasks (37%). Among the neurons tested in all situations (n = 78), 24% responded to reward regardless of the situation and 65% in only one or two situations. Responses selective for one particular situation occurred exclusively in the free reward situation. When the reward was delivered immediately after the visual signal in the classically conditioned task, most of the neurons reduced or completely lost their responses to reward, and other neurons remained responsive. Conversely, neuronal responses invariably persisted when reward was delivered later than 1 s after the visual signal. This is the first report that tonic striatal neurons might display responses directly to primary rewards. The neuronal responses were strongly influenced by the behavioral context in which the animals received the reward. An important factor appears to be the timing of reward. These neurons might therefore contribute to a general aspect of behavioral reactivity of the subject to relevant stimuli. Received: 16 September 1996 / Accepted: 1 April 1997     

电刺激大鼠下丘脑弓状核对中脑导水管周围灰质单位放电的影响

用玻璃微电极引导大鼠中脑导水管周围灰质（ＰＡＧ）单位放电。发现：电刺激弓状核（ＡＲＣ）后，在所观察的６４个ＰＡＧ单位中，表现为抑制的有３７个单位，其余单位分别表现为先抑制后兴奋、兴奋和无变化。结果表明，大鼠ＡＲＣ对ＰＡＧ单位活动的调制作用以抑制米。     

庚酸睾酮男性抗生育作用的临床研究

62名健康男性,自愿接受每周1次200mg庚酸睾酮(TE)肌肉注射的避孕方法研究。4人非医学原因中断试验,其余受试者先后实现无精子,自第1次注射TE到全部达到无精子的平均时间为108(58～232)天,在此后的连续12个月共592个妇女月避孕效果观察中,有1例怀孕,临床避孕率为98％(Pearl指数为2.02/100妇女年)。停药后,平均188(135～254)天全部受试者的精子密度恢复到用药前水平或高于20×10~6/ml。在用药期间,除预料的血清睾酮升高、促性腺激素(FSH、LH)受抑制、睾丸体积缩小、体重和血红蛋白轻度增加以及2例出现轻度痤疮外,其余检查,包括血脂代谢、肝肾功能、前列腺大小、血压和性功能等均无显著性改变。结果表明,由TE抑制生精作用的男性激素避孕方法具有效果好,可逆和毒副作用小的优点。     

Comparison of Two Formulations of Nifedipine During 24-Hour Ambulatory Blood Pressure Monitoring

Study Objective . To determine if one commercial extended-release formulation of nifedipine (Adalat CC) is as effective as another (Procardia XL) in controlling blood pressure over 24 hours. Design . Open-label, randomized, crossover study. Setting . University-affiliated family medicine clinic. Patients . Fifteen patients with stage 1–4 primary hypertension. Interventions . Procardia XL or Adalat CC once/day was titrated to achieve blood pressure control. The effective dose was continued for 4 weeks, washed out for 1 week, and reinstituted with other study drug. Measurements and Main Results . Twenty-four-hour ambulatory blood pressure was recorded the conclusion of each treatment phase. Treatment phases were compared for mean 24-hour blood pressure, mean daytime (6:00 a.m.–10:00 p.m.) and mean nighttime blood pressure, and mean blood pressure load (percentage of blood pressure measurements < 140/90 mm Hg daytime and > 120/80 mm Hg nighttime). Thirteen patients completed the study. No statistically significant difference was seen in mean 24-hour blood pressure (138/86 mm Hg for Procardia XL vs 137/85 mm Hg for Adalat CC), daytime or nighttime blood pressure, or blood pressure load. Two patients experienced clinically significant adverse effects while taking Adalat CC. Conclusions . In these patients with primary hypertension, Adalat CC was as effective as Procardia XL at controlling blood pressure for 24 hours. Blood pressure, heart rate, and adverse effects should be monitored 2–4 weeks after any exchange of Adalat CC for Procardia XL.     

双特异抗体介导的人单核—巨噬细胞对荷人肝癌裸鼠的抑制作用

观察双特异性单克隆抗体介导的人单核－巨噬细胞在裸鼠体内对肝癌生长的抑制作用。用化学交联法制备双特异性单克隆抗体ＨＡｂ１８－ＭＡｂ７及ＨＡｂ１８Ｆ（ａｂ）２－ＭＡｂ７Ｆ（ａｂ＇＿２，并将其与单核－巨噬细胞－同注入荷人肝癌裸鼠体内，观察肿瘤体积的变化。     

中国人D13S301位点的微卫星多态及其应用价值

率先在国内应用ＰＣＲ技术扩增Ｗｉｌｓｏｎ病（ＷＤ）基因内部Ｄ１３Ｓ３０１位点的微卫星多态，通过变性聚丙烯酰胺凝胶电泳检测扩增产物，对８０名正常中国人进行了检测，结果具有１２种不同长度的等位片段，多态信息含量（ＰＩＣ值）为０．８８３，表明该位点在中国人群中具有长度多态性及较高的应用价值。应用该位点对１０个ＷＤ家系进行连锁分析，在２４名无症状个体中检出１２名基因携带者，７名正常纯合子及２名症状前患者，进一步证实该位点可用于ＷＤ的症状前诊断及杂合子筛选。     

Protein kinase C agonist and antagonist effects in normal human epidermal keratinocytes

Abstract Several lines of evidence implicate protein kinase C (PKC) in the development of basal cell and squamous cell carcinomas, tumors which originate from epidermal keratinocytes. To examine PKC in a model relevant to human skin, we exposed normal human epidermal keratinocytes (NHEK) in serum-free media to a variety of PKC agonists and antagonists. NHEK PKC activity increased up to 10-fold within the 1st hour of exposure to tetradecanoyl phorbol acetate (TPA), and gradually returned to control values within 72 h. TPA-induced PKC activity was enhanced by pretreatment of cultures with protein and RNA synthesis inhibitors. TPA-induced growth arrest and differentiation was antagonized by staurosporine. Down-regulation by bryostatin pretreatment blocked TPA-stimulated differentiation. Our overall conclusion is that activation of PKC in cultured human keratinocytes is required for differentiation. These results are crucial to the analysis of compounds suspected of promoting or inhibiting epidermal tumors.     

汞对人体必需元素干扰的研究

对42例汞吸收、2例汞中毒者(尿汞>99.7nmol/L),采用原子吸收光谱法,检测了汞对人体必需五种金属元素代谢的干扰。研究发现,汞时人体必需元素镁、铜具有拮抗作用。汞吸收者血清镁极显著低于对照组(P>0.01)。经驱汞治疗后,血清镁、铜自然上升与对照组无统计学差异(P>0.05),镁离子低下,可出现神经肌纤维兴奋性增高。由此推测,汞引起肌肉震颤的毒理,可能由汞拮抗镁离子低下引起。设想,对汞中毒者采用补镁制剂治疗,是否具有驱汞作用值得探讨。     

妇科腹腔镜手术几种激光对兔子宫壁损伤的实验研究

为掌握妇科腹腔镜手术所应用的激光器的治疗剂量，对几种激光引起的兔子宫壁热损伤进行观察。实验研究证实：所有激光产生的损伤程度与所用的剂量呈正相关。术后４８ｈ与即刻损伤程度相比，半导体激光的损伤程度明显加深、加宽；但ＣＯ２激光和ＮｄＹＡＧ激光接触式光刀无显著变化。说明应用激光行妇科腹腔镜手术治疗时，所产生的损伤与应用的功率密度有关，为临床合理选用腹腔镜下的激光治疗提供依据