Epidermal growth factor receptor inhibition modulates the nuclear localization and cytotoxicity of the Auger electron emitting radiopharmaceutical 111In-DTPA human epidermal growth factor.

(111)In-DTPA-human epidermal growth factor ((111)In-DTPA-hEGF [DTPA is diethylenetriaminepentaacetic acid]) is an Auger electron-emitting radiopharmaceutical that targets EGF receptor (EGFR)-positive cancer. The purpose of this study was to determine the effect of EGFR inhibition by gefitinib on the internalization, nuclear translocation, and cytotoxicity of (111)In-DTPA-hEGF in EGFR-overexpressing MDA-MB-468 human breast cancer cells. METHODS: Western blot analysis was used to determine the optimum concentration of gefitinib to abolish EGFR activation. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled hEGF were evaluated by confocal microscopy in MDA-MB-468 cells (1.3 x 10(6) EGFRs/cell) in the presence or absence of 1 microM gefitinib. The proportion of radioactivity partitioning into the cytoplasm and nucleus of MDA-MB-468 cells after incubation with (111)In-DTPA-hEGF for 24 h at 37 degrees C in the presence or absence of 1 microM gefitinib was measured by cell fractionation. DNA double-strand breaks caused by (111)In were quantified using the gamma-H2AX assay, and radiation-absorbed doses were estimated. Clonogenic survival assays were used to measure the cytotoxicity of (111)In-DTPA-hEGF alone or in combination with gefitinib. RESULTS: Gefitinib (1 microM) completely abolished EGFR phosphorylation in MDA-MB-468 cells. Internalization and nuclear translocation of fluorescein isothiocyanate-labeled EGF were not diminished in gefitinib-treated cells compared with controls. The proportion of internalized (111)In that localized in the nucleus was statistically significantly greater when (111)In-DTPA-hEGF was combined with gefitinib compared with (111)In-DTPA-hEGF alone (mean +/- SD: 26.0% +/- 5.5% vs. 14.6% +/- 4.0%, respectively; P < 0.05). Induction of gamma-H2AX foci was greater in MDA-MB-468 cells that were treated with (111)In-DTPA-hEGF (250 ng/mL, 1.5 MBq/mL) plus gefitinib (1 microM ) compared with those treated with (111)In-DTPA-hEGF alone (mean +/- SD: 35 +/- 4 vs. 24 +/- 5 foci per nucleus, respectively). In clonogenic assays, a significant reduction in the surviving fraction was observed when (111)In-DTPA-hEGF (5 ng/mL, 6 MBq/microg) was combined with gefitinib (1 microM ) compared with (111)In-DTPA-hEGF alone (42.9% +/- 5.7% vs. 22.9% +/- 3.6%, respectively; P < 0.01). CONCLUSION: The efficacy of (111)In-DTPA-hEGF depends on internalization and nuclear uptake of the radionuclide. Nuclear uptake, DNA damage, and cytotoxicity are enhanced when (111)In-DTPA-hEGF is combined with gefitinib. These results suggest a potential therapeutic role for peptide receptor radionuclide therapy in combination with tyrosine kinase inhibitors.     

拉萨地区高原肺水肿经颅多普勒21例分析

目的:通过经颅多普勒(TCD)检测,了解高原肺水肿(HAPE)患者颅内脑底动脉环上的主要动脉血流动力学及各血流的生理参数,为高原肺水肿的诊断及治疗提供一些参考.方法:将已确诊的HAPE患者,与颞窗通过低频脉冲多普勒(2MHZ),获得颅内脑底动脉环上的主要动脉的多普勒超声频移信号,进行TCD检测.结果:TCD检测后了解到颅内脑底动脉环上的主要动脉:颈内动脉末梢、大脑中动脉、大脑前动脉血流速度(收缩期血流速度,平均血流速度,舒张末期血流速度)与正常人的TCD测值相比明显增快,但舒张末期血流速度(VE )增快较收缩期血流速度(VP )不明显,故频谱仍为低阻波形,搏动指数(PI)、收缩期血流速度与舒张末期血流速度的比值(S/D)正常,阻力指数有所降低.结论:经TCD检测可知高原肺水肿患者在高原(在低氧环境下),颅内主要脑血管扩张,脑血流量增加即颈内动脉系统的MCA,ACA,PICA血流速度(Vs,Vm,Vd)增快,通过TCD检查可为高原医生早期诊断及治疗提供参考.     

软组织扩张中扩张囊内外的细菌学分析

目的研究软组织扩张术患者扩张囊内、外的细菌数量及种类，为临床上防治扩张术感染提供依据。方法连续采集33例扩张术患者的51枚扩张囊内、外的液体标本，进行常规细菌培养和药敏试验，并将其结果进行统计学处理，采用Y0检验和Kappa检验。结果扩张囊内、外的细菌检出率分别为3．92％（2枚）、17．65％（9枚），囊外阳性率显著高于囊内（P〈0．05），囊内、外细菌的检出结果一致性较差（Kappa〈0．4）。细菌种类为金黄色葡萄球菌和凝固酶阴性葡萄球菌，对庆大霉素、去甲万古霉素、环丙沙星均敏感。33例患者（51枚）中，有10例患者（10枚）检出细菌，仅有1例患者（1枚）出现临床感染症状，致病菌为金黄色葡萄球菌。结论严格消毒后进行穿刺注水导致感染的几率很低，而感染后的细菌培养和药敏试验是治疗的关键。     

输尿管镜气压弹道碎石治疗输尿管结石110例

目的总结输尿管镜气压弹道碎石治疗输尿管结石的临床效果。方法采用F8/9.8 Wolf硬性输尿管镜、JUN—AIR气压弹道碎石机治疗110例输尿管结石。结果输尿管镜直视下一次碎石成功105例，成功率95．5％（105／110），1～6周内结石全部排净。2例因置镜失败改开放手术，3例输尿管上段结石上移至肾脏行ESWL2例，口服排石药物治疗1例。术后泌尿系感染5例，轻度肉眼血尿1～3d。结论输尿管镜气压弹道碎石是治疗输尿管中、下段结石的有效方法之一，具有碎石率高、安全、并发症少、操作简单的优点。     

对耳轮过度前突畸形的整复

对耳轮过度前突为对耳轮的角度过锐，致使耳轮的位置相应后移，表现为与招风耳完全相反的畸形。畸形虽不十分明显，但影响美观。自１９９２年４月开始应用患侧耳廓软骨和耳后皮瓣对５例患者８只外耳进行治疗得到满意效果。认为文中所述方法是矫正对耳轮过度前突畸形的良好方法。     

乙酰胆碱受体抗体量与眼型重症肌无力病情关系的实验观察

目的　观察血清乙酰胆碱受体抗体 (Ach Rab)含量与眼型重症肌无力患者病情程度和发展为全身型重症肌无力的关系。方法　 2 0例眼型重症肌无力患者按受累程度分为轻、中、重三组 ,采用固相酶免疫吸附法测定血清 Ach Rab含量 (P/ N值 )。结果　对照组和病情轻、中、重三组血清 P/ N值分别为 :0 .6 7± 0 .45、0 .78± 0 .30、1.16± 0 .18和 1.5 1± 0 .13。轻度组与对照组比较无显著差异 (P >0 .0 5 ) ,中度组与轻度组比较差异显著 (P <0 .0 5 ) ,重度组与中度组比较有非常显著差异 (P <0 .0 1)。3例 P/ N值明显高患者 (中度组 1例、重度组 2例 ) 2年后发展成全身型。结论　 P/ N值可反映患者病情程度和提供眼型重症肌无力发展为全身型重症肌无力的预兆信息。     

The Effect of Acupuncture on Bone Mineral Density in Postmenopausal Women

According to the TCM theory that the kidney is in charge of the bone, the authors carried out a study on the effect of acupuncture on bone mineral density in 40 postmenopausal women with osteoporosis treated by the method of reinforcing the kidney to strengthen the bone, with satisfactory therapeutic results reported as follows.     

EFFECTS OF ANGIOTENSINS II AND III ON GLOMERULOTUBULAR BALANCE IN RATS

1. The role of angiotensin as a modulator of proximal glomerulotubular (GT) balance was investigated in anaesthetized rats by examining the relationship between glomerular filtration rate (GFR) and absolute proximal reabsorption (APR) during removal of endogenous angiotensin II (AII) and III (AIII) with enalaprilat (CEI) and then during their subsequent replacement by intravenous infusions. 2. Enalaprilat lowered mean arterial blood pressure (MABP) and increased renal blood flow (RBF), GFR, urine flow rate and sodium excretion. Filtration fraction (FF) was not altered. Absolute proximal reabsorption, derived from fractional lithium clearance, increased by only 48% of the change expected for 'perfect' GT balance. 3. Angiotensin II replacement corrected MABP, GFR and plasma renin level, but reduced RBF and increased FF; APR was decreased and GT balance was restored. Urine flow and sodium excretion remained above control values with AII. 4. Replacement with AIII did not correct the hypotension but completely reversed the renal and renin responses to enalaprilat and restored GT balance without affecting FF. 5. It was concluded that the relation between proximal reabsorption and GFR is considerably modified by the intrarenal angiotensin concentration. The findings are best explained by a direct stimulation of proximal tubular sodium transport by angiotensin at the concentrations existing in anaesthetized rats.     

GREB1L基因突变致后天性单侧肾萎缩一例报道并文献复习

肾发育不良和肾发育不全（RAH）是先天性肾脏与尿路畸形（CAKUT）的主要表现之一,是导致儿童慢性肾脏病的重要原因。遗传因素与发病密切相关,随着全基因检测技术的发展,越来越多与RAH相关的基因突变被报道,GREB1L基因突变已被证实可导致RAH。本研究报道了1例后天性单侧肾萎缩GREB1L基因c.4688A>G杂合突变患儿,并复习相关文献。该患儿基因突变源自母亲,该变异为罕见变异,并且具有不完全外显特性,多种蛋白质危害预测软件预测该突变为有害变异。本文发现了新的GREB1L基因突变位点,可能拓展了与RAH相关的基因突变谱和临床谱。     

Aneuploidy induction by water extract from Tripterygium hypoglaucum (Level) Hutch in mouse bone marrow cells

Hie aneuploidy-inducing activity of a Chinese medicinal herb,Tripterygium hypoglaucum (level) Hutch (THH), was investigatedby means of three cytogenetic end-points, i.e. C-mitotic (CM)effects, micronuclei (MN) and parallel chromosome structuralaberration (CA) analyses in vivo. The CA analysis was expectedto reflect the origins of MN induced by clastogens or aneugens.The experiments were performed on mouse bone marrow cells. Theanimals were treated with the crude water extracts of THH (singlei.p. injection) in the dose range 120–686 mg/kg. Colchicine(COL) was taken as a positive control for its known aneuploidy-inducingeffects. THH showed similar genotoxic effects to COL in CM,MN and CA analyses: positive CM effects were observed accompaniedwith increases of mitotic index and frequencies of CM cellsas well as decreased frequencies of anaphase in all of the THH-treatedgroups. The compound showed a positive MN response in bone marrowpolychromatic erythrocytes but was negative in CA analyses.No sex differences were found in any treated group. The preliminaryresults suggested that THH is an aneuploidy inducer in mousebone marrow cells under the present experimental conditions.