NDST-1 modulates BMPR and PTHrP signaling during endochondral bone formation in a gene knockout model

GlcNAc N-deacetylase/N-sulfotransferase-1 (NDST-1), a member of the enzyme family catalyzing the first modification step in the biosynthesis of heparan sulfate (HS), was knocked out in mice to investigate its role in embryonic development. NDST-1 null mice exhibited delayed endochondral bone formation including shortened calcified zones in limbs, delayed chondrocyte and osteogenetic differentiation, and increased chondrocyte proliferation. In situ HS binding assay revealed that the binding ability of bone morphogenetic protein (BMP) -2, -4, and -6 to endogenous HS was decreased in mutant phalanges, while that of fibroblast growth factor-1 (FGF-1) was not affected. Up-regulation of BMPR-IA, Phospho-Smad1 (P-Smad1) and parathyroid-hormone related protein (PTHrP), but not the Indian hedgehog, Gli1, Gli3, Patched, and FGFR-3, was observed. Furthermore, block of BMPR signaling with noggin rescued the delayed chondrocyte hypertrophic differentiation in NDST-1 (−/−) mice and recovered the expression of both P-Smad1 and PTHrP proteins. These results suggested that NDST-1-dependent heparan sulfate might negatively modulate BMP and its downstream PTHrP signaling, and thus affect endochondral bone development.     

A Rapid Effect of Caffeinated Beverages on Two Choice Reaction Time Tasks

Abstract

Though consumers of tea and coffee can report feeling beneficial subjective effects of consumption virtually immediately, tests for objective effects of caffeine immediately post-consumption have been rare. Two experiments examined caffeine's ability to influence reaction time in choice reaction time tasks, using a dose of caffeine typical of a cup of tea or instant coffee, and testing at short post-consumption delays. Two groups of participants were given 60 mg of caffeine, after overnight abstinence, either in a hot tea drink, or a hot water drink. Two control groups also received hot tea or water, but without caffeine. In Experiment 1, participants were given a keypress task before the drink (baseline), immediately after the drink, and 40 min after the drink. In Experiment 2, a touch-screen test was given either 1, 14, or 27 min post consumption. Caffeine was found to reduce the effect of a distracter on reaction time in the keypress test and to reduce reaction time in a component of the touch-screen task; however, in neither experiment were these effects significantly modulated by post-consumption delay length. Thus, the speed of caffeine's action on psychomotor performance was shown to be on the order of minutes.     

The Relationship Between Early Language Delay and Later Difficulties in Literacy

The relationship between early language delay and later literacy development is explored. The paper begins by considering a diagnostic model of early language delay, upon which subsequent definitions of language delay are based. The degree to which there is continuity between early language delay and later difficulties in literacy development is then explored. The findings of four longitudinal studies are considered in turn, and the degree to which they show evidence of continuity between early language delay and later literacy difficulties is evaluated. From these four studies, the author identifies two significant findings: (a) there is strong evidence of continuity between early language delay and later reading difficulties for all children with early language delay, although some of these reading difficulties may be residual and mild; and (b) the likelihood that children with early language delay will develop later difficulties in literacy depends largely on the age to which language impairment persists and the severity of the impairment. The author concludes that language delay in the early years is a key risk factor for later literacy difficulties. Implications for future research and practice are identified and discussed.     

Common cancer-related symptoms among GP patients Opportunistic screening in primary health care

Objective - To study the occurrence of symptoms related to the five most common forms of cancer among patients regularly visiting primary care. To estimate the proportion of symptoms needing GP examination, and the number of tumours thus diagnosed. Design - Patients with some form of non-malignant chronic disease received a letter with information about cancer-related symptoms along with an invitation to regular check-up. The letter described the most common symptoms of breast, colorectal, lung, prostate and skin cancers. Setting - 12 health centres in Kalmar County, Sweden. Subjects - 5200 patients aged over 40 years. Results - One patient in 13 reported cancer-related symptoms to the GP. Women reported more symptoms than men, and almost half of them had had symptoms at previous check-ups. The GP was able to explain 7 out of 10 patients' symptoms directly. When other symptoms were examined, 8 cancers were diagnosed as well as 6 pre-malignant tumours, corresponding to 3 tumour diagnoses per 1000 check-ups. Conclusion ? While attending regular check-ups, patients may not report symptoms which cause anxiety and sometimes indicate serious diseases. It is possible to widen the perspective and link both primary and secondary prevention of certain cancers to the check-up.     

不同情境对儿童延迟满足影响研究:团体与个体

目的探讨2种情境(个体和团体)对儿童延迟满足的影响。方法设定个体和团体2种情境,条件1为先个体后团体,条件2为先团体后个体。对120名5岁儿童和120名6岁儿童的延迟满足进行测试。结果条件1的个人决定的延迟满足率5岁组为53.0%,6岁组为53.3%,差异无统计学意义;条件2的团体决定的延迟满足率5岁组为55.6%,6岁组为55.0%;差异无统计学意义;6岁组在2种条件下延迟满足率女生均高于男生,差异有统计学意义,条件1的个人决定χ2=6.70,(P<0.05);条件2的团体决定χ2=15.15,P<0.01。在团体决定对其后的个人决定的影响中,2种条件下个人决定在5岁、6岁组的差异无统计学意义;6岁组在条件2的个人决定中女生延迟满足率高于男生,差异有统计学意义(χ2=24.30,P<0.01),女生在条件2的个人决定的延迟满足率高于条件1,差异有统计学意义(χ2=7.68,P<0.01);65.0%的5岁儿童和73.3%的6岁儿童在2种情境中的选择保持一致。5岁组团体意见与个人决定中多数人意见一致率为72.5%,6岁组为75.0%。结论5岁、6岁儿童2个年龄组的延迟满足无差异,但女生的延迟满足能力高于男生;...     

肝脏螺旋CT增强扫描的最佳延时时间

目的 探讨肝脏螺旋CT增强扫描的最佳延时时间。方法 随机选取100例肝脏增强扫描的特例，采用不同的造影剂总量、注射速率和延时时间，观察肝脏的强化程度结果采用3ml／s和4ml／s的注射速率和120ml～l50ml的造影剂总量，肝脏的强化程度最高。注射速率越高，到达强化峰值的时间也越短。结论 肝脏螺旋CT增强扫描的合理的技术方案为采用120ml～150m1的造影剂总量，注射速率3ml／s～4ml／s，动脉期延时20s—26s，门脉期延时70s～80s。     

股骨干骨折合并同侧股骨颈骨折的漏诊分析与对策

目的 分析同侧股骨干骨折合并股骨颈骨折出现漏诊的原因及治疗。方法 回顾性分析7例同侧股骨干骨折合并股骨颈骨折的治疗方法、结果和漏诊原因。结果 漏诊病例与入院时未重视髋部损伤及X线片未明确显示骨折有关,但经正确治疗后效果满意。结论 提高对股骨干骨折合并同侧股骨颈骨折损伤的注意并行相应的查体及影像学检查可避免股骨颈骨折的漏诊,出现漏诊后如果采取正确及时的治疗仍可得到较满意的效果。     

Serotonin and tolerance to delay of reward in rats

Rationale: Tolerance to delay of gratification, taken to reflect impulsiveness, has been proposed to be under the preferential control of central serotonin (5-HT) processes. Objective: The present study further examined the effects of drugs which directly or indirectly alter 5-HT transmission, on behaviour controlled by a delayed positive reinforcer. Methods: Rats were given the choice in a T-maze between two magnitudes of reward: small (two food pellets) and immediate versus large (ten pellets) but delayed. When a 15-s waiting period was imposed in the arm leading to the large reward, rats selected this arm on 65–70% of the trials. This frequency was reduced to less than 40% when the large reward was delayed by 25 s. Results: In rats whose ascending 5-HT pathways had been lesioned by infusion of 5,7-dihydroxytryptamine (5,7-DHT) into the dorsal raphe, the introduction of the 15-s delay contingency resulted in a transient larger reduction of the frequency of choice of the now-delayed reward, compared to sham operated controls. In contrast, choice behaviour of rats given 5,7-DHT into the substantia nigra did not differ from controls. para-Chlorophenylalanine (pCPA, 150 mg/kg IP, daily for 3 days), a 5-HT synthesis inhibitor, bretazenil (0.5-8 mg/kg IP), a benzodiazepine (BZD) receptor partial agonist, and muscimol (0.25-1 mg/kg IP), a GABA_A receptor agonist, induced a shift toward immediate reward. In contrast to the other BZDs, alprazolam (1–2 mg/kg IP) enhanced the frequency of choice of the large-but-25 s-delayed reward. Similar increased preference for the large-but-delayed reward was induced by the selective 5-HT reuptake inhibitors, fluoxetine (4–8 mg/kg IP) and fluvoxamine (4 mg/kg IP). The full 5-HT_1A receptor agonist, 8-OH-DPAT (0.015–0.5 mg/kg IP) enhanced the frequency of choice of the large reward delayed by 25 s, whereas the partial agonists, buspirone (1–4 mg/kg IP), ipsapirone (0.5–1 mg/kg IP) and MDL 73005EF (1–2 mg/kg SC), and the antagonist, WAY 100635 (4 mg/kg SC), reduced the number of choices of the large reward delayed by 15 s. Unexpectedly, WAY 100635 (2 mg/kg), which had no effect on choice whatever the delay, did not counteract the increased tolerance to delay induced by 8-OH-DPAT (0.06 mg/kg) and further reduced the frequency of choice of the large-but- 15 s-delayed reward induced by ipsapirone (0.5 mg/kg). Conclusions: These effects on tolerance to delay may be accounted for by a subtle balance between the opposing functional consequences of pre- versus post-synaptic 5-HT_1A receptor activation or blockade. Overall, the present results provide further support to the idea that 5-HT processes participate in the control of impulsive-related behaviour, as assessed from tolerance to delay of reward in this particular T-maze procedure. Received: 26 April 1999 / Final version: 20 May 1999     

磁共振增强血管成像检测扫描延迟时间的探讨

目的 探讨磁共振增强血管成像(CEMRA)检测扫描延迟时间的可行性及其临床应用价值.方法 20例健康成人志愿者行循环时间(TT)和主动脉强化峰值持续时间(DPE)血管成像扫描时间测试,对注射速度时间TT.主动脉峰值信号(SPE)和DPE与延迟注射时间(TI)的差值(△T),分别获取不同注射速度及延迟注射时间CEMRA原始图信噪比及CEMRA影像.同时对18例主动脉病变患者行三维稳态快速激发序列(3DFISP)CEMRA.结果 20例健康成人组CEMRA图像清晰.主动脉走向显示清楚.18例主动脉病变组CEMRA图像清晰,对大动脉炎.颈动脉变窄,腹主动脉管腔扩张,走行扭曲,主动脉弓和胸主动脉内膜撕裂,胸腹主动瘤,主动脉病变大小,范围及主动脉各大分支动脉显示清楚.结论 磁共振灌注血管成像检测扫描延迟时间在理论、技术上有较高价值,充分满足影像诊断及临床应用.