Determination of phospholipidosis potential based on gene expression analysis in HepG2 cells.

Phospholipidosis (PLD) is characterized by an intracellular accumulation of phospholipids in lysosomes and the concurrent development of concentric lamellar bodies. Recently, H. Sawada et al. (2005, Toxicol. Sci. 83, 282-292) identified 17 genes as potential biomarkers of PLD in HepG2 cells. The present study was undertaken to determine if this set of genes measured by quantitative PCR could be validated in the same cell line. The objective was also to investigate the dose-response relationship to further validate the assay and to select the concentrations to use for screening activities. In a first experiment (one concentration tested), out of the 17 genes, the best gene biomarkers of PLD (i.e., 11 genes) were selected for practical screening reasons. Based on these genes, 91.6% (i.e., 11 of 12) of the compounds known to induce PLD were identified as positive and all the negative compounds (i.e., five of five) were also confirmed. When the data obtained in the first experiment were compared to the data by Sawada et al., (2005) the coefficient of correlation calculated was slightly higher than 75%. In the second experiment (26 compounds [all 17 compounds from the first experiment plus 9 other compounds] tested at a minimum of three concentrations), 93.3% (14/15) of the compounds known to induce PLD were identified as such and all the negative controls (six compounds) were also confirmed. Three compounds likely to induce PLD were identified as positive in our assay. Finally, two compounds for which no data are available were also tested. When both experiments 1 and 2 were compared, the coefficient of correlation for 16 compounds tested at the same concentrations reached 87.7%. In conclusion, the present study further confirms the utility of gene expression in HepG2 cells to identify a potential to induce PLD. Finally, based on the data presented, researchers are encouraged to use a range of minimum three concentrations (e.g., 12.5, 25, and 50 microM) to screen for PLD in the human HepG2 cell line.     

Up-regulation of urinary UPIII mRNA levels in vesicoureteral reflux patients: Potential application as a screening test for vesicoureteral reflux

OBJECTIVES: Vesicoureteral reflux (VUR) is the most common congenital urinary tract anomaly. This disease can pose a major threat to the kidneys as twenty percent of patients with endstage renal disease are reported to have VUR. Although genetic studies for uroplakin III (UPIII) have been reported recently, no study has focused on UPIII gene expression in VUR patients. We describe here the up-regulation of UPIII mRNA in exfoliated urinary cells from primary VUR patients. METHODS: A real-time RT-PCR for UPIII mRNA was performed on exfoliated urothelial cells from 18 primary VUR and 38 control samples. UPIII mRNA copies were calculated for each sample. The statistical differences were assessed by the Mann-Whitney U test. Receiver operator characteristic curves were constructed for analysis of the diagnostic values. RESULTS: UPIII mRNA was found to be up-regulated to a greater extent in VUR than in control exfoliated urinary cells (mean +/- SE: 497.0 +/- 178.5 copies vs. 69.0 +/- 10.0 copies, respectively, P < 0.001). In evaluating the measurement of urinary UPIII mRNA as a screening test for VUR, the sensitivity was 77.8% and the specificity was 76.3% by the best diagnostic cutoff point. CONCLUSIONS: This is the first report demonstrating up-regulation of UPIII in mRNA levels in VUR patients. We submit that the quantitative measurement of urinary UPIII mRNA has a potential of developing into the first non-invasive screening test for VUR.     

The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice

Objective: To determine whether the pharmacokinetics and electrocardiographic pharmacodynamics of terfenadine are affected by the concomitant administration of grapefruit juice. Methods: Six healthy volunteers were recruited for a balanced cross-over study. Each volunteer received 120 mg terfenadine 30 min after drinking 300 ml of either water or freshly squeezed grapefruit juice. The alternative treatment was administered on the second study day 2 weeks later. Measurements of the area under the terfenadine plasma concentration-time curve (AUC), maximum terfenadine concentration (C_max) and the time to maximum concentration (t_max) were made, and the corrected QT (QTc) interval was measured from the surface electrocardiogram. Results: Terfenadine was quantifiable in plasma in all 6 subjects on both study days for up to 24 h post-dosing. The AUC of terfenadine was significantly increased by concomitant grapefruit administration (median values 40.6 vs 16.3 ng · ml⁻¹ · h), as was the C_max (median values 7.2 vs 2.1 ng · ml⁻¹). The t_max was not significantly increased and there was no significant change in the median QTc interval despite the increased terfenadine levels. The 95% confidence interval for the difference in the change in QTc interval at C_max was −13 to +38 ms. Conclusion: Administration of grapefruit juice concomitantly with terfenadine may lead to an increase in terfenadine bioavailability, but the increase observed in this study did not lead to significant cardiotoxicity in normal subjects. However, this does not exclude the risk of cardiotoxicity in high-risk subjects given greater doses of grapefruit juice over longer periods of time. Received: 14 October 1996 / Accepted in revised form: 10 December 1996     

在就诊患者和健康体检者中筛检人胃螺杆菌

目的：通过几种不同的检查方法调查人胃螺杆菌在人群中的感染情况及在慢性胃炎中的致病作用。方法：３８０例行消化道症状的就诊患者和４３２名健康体检者的胃粘膜活检标本分别行涂片、尿素酶试验、１４Ｃ－尿素呼吸试验和组织学检查。结果：人胃螺杆菌在上述两类人群中的感染率分别为２．１１％和１．１６％。涂片Ｇｒａｍ染色和切片ＷＳ银染是目前诊断该菌感染较理想的手段，不论有无症状，患者在组织学上均伴有慢性炎症改变，根据形态学特点该菌可大致分为两型，分别与某些动物胃内的螺旋菌相似。结论：人胃螺杆菌在人群中感染率较低，可能是一种源自动物的慢性胃炎相关性病原菌。     

Tests of autonomic dysfunction in patients with multiple sclerosis

Autonomic dysfunction is frequent in patients with multiple sclerosis (MS). The sympathetic skin response (SSR) and the R-R interval variation (RRIV) are simple electrophysiologic tests for the assessment of central and peripheral autonomic disturbances. Both tests were performed in 60 patients with clinically definite MS and 30 controls. The SSR was recorded simultaneously from both upper and both lower limbs. In all volunteers normal responses were recorded from the four limbs, but 39 patients (65%) showed abnormal responses in at least one limb. The reduction in amplitude of the response was correlated with patients' EDSS. In individual limbs, the SSR amplitude correlated with weakness, spasticity and cerebellar dysfunction, but was not sufficiently related to the deep sensory loss. The RRIV was abnormal in 48 MS patients (80%), as compared to the controls, but showed no significant relationship either to the EDSS or to the SSR. The sensitivity of SSR and RRIV is high and comparable with that of visual and somatosensory evoked potentials.     

房室折返性心动过速RP‘时距的特征及对旁道定位的意义

应用食管调搏，检测６４例旁道参与的房室折返性心速患者Ⅰ、Ⅱ、Ⅴ１和食管导联的室房时距、Ｐ＇ｖ，Ｐｅｔ时距。发现左侧ＡＰ者ＲＰ＇１较ＲＰ＇Ｖ１短（Ｐ＜０．０１），而右侧ＡＰ时较ＲＰ＇ｖ１长（Ｐ＜０．０１）。     

Kindergarten and first grade: A time for developing and nurturing gifted behaviors in young children

This article concludes that there is a tremendous need for gifted programs at the kindergarten and first grade levels. A review of the literature suggests that it is difficult to identify young gifted children through traditional screening techniques. The author concludes that Renzulli's Enrichment Triad Model may prove useful for identifying young gifted children.     

奥美拉唑静脉给药治疗上消化道大出血的疗效观察

本文阐述了奥美拉唑（Ｏｍｅｐｒａｚｏｌｅ）治疗急性上消化道大出血８０例与法莫替丁（Ｆａｍｏｔｉｄｉｎｅ）治疗上消化道大出血５０例比较，前者有效率明显高于后者。提示奥美拉唑治疗急性上消化道大出血效果好，无副作用，减少了手术率、死亡率，是一种有效的止血药物。