Induction of cathepsin D protein during estrogen carcinogenesis: possible role in estrogen-mediated kidney tubular cell damage

We have proposed that an early step in estrogen carcinogenesis in the hamster kidney is tubular damage followed by reparative cell proliferation. This tubular injury is progressive and increases in severity with continued estrogen treatment; one pertinent feature is a marked rise in the number of both secondary and tertiary lysosomes. Data presented herein indicate that cathepsin D, an estrogen-responsive lysosomal proteolytic enzyme, is increased in the kidney following estrogen treatment in the hamster. Three isoforms of cathepsin D were detected in estrogen-treated kidneys, 52, 31, and 27 kDa, the major being 52 kDa. At 1 and 3 months of estrogen treatment, 52-kDa cathepsin D content increased 1.4- to 1.6-fold. These changes coincided with a rise in renal estrogen receptor levels during the same estrogen treatment periods. More pronounced rises in cathepsin D levels, 2.7- and 3.5-fold, were seen after 4 and 5 months of estrogen treatment, respectively. A concomitant, 3.0- to 4.0-fold rise in estrogen receptor content was also observed. At 5 months of estradiol or DES treatment, both 27- and 31-kDa isoforms were present in hamster kidneys, in addition to the 52-kDa form. Neither progesterone nor DHT treatment affected the untreated levels of cathepsin D. Interestingly, either concomitant tamoxifen or DHT and estrogen treatment prevented the rise in cathepsin D and estrogen receptor content observed after estrogen treatment alone. Primary estrogen-induced renal tumors and their metastases exhibited markedly elevated levels of all three isoforms of cathepsin D. Immunohistochemical analysis of cathepsin D in kidney sections confirmed the Western blot findings. These data suggest a novel role for estrogen-induced cathepsin D in the hamster kidney during tumorigenesis; that is, mediating renal tubular damage as a prelude to reparative cell proliferation, thus initiating a multi-step estrogen-driven process which leads to renal tumor formation.      

Enhanced levels in neonatal rat liver of 7,8-dihydro-8-oxo-2'- deoxyguanosine (8-hydroxydeoxyguanosine), a major mutagenic oxidative DNA lesion

The purpose of this study was to determine whether the level of 7,8- dihydro-8-oxo-2'-deoxyguanosine (8-hydroxy-2'-deoxyguanosine) (8-oxo- dG), a major mutagenic DNA oxidation product, is enhanced in newborn rat liver DNA as a consequence of oxidative stress incurred during the early postnatal period. 32P-postlabeling showed this adduct to increase approximately 2-fold from the 20th day of gestation (2 days before birth) to a peak level at 50-53 h after birth. Postnatal levels exceeded fetal levels at all time points investigated, i.e. 0.5-1, 8, 24, 50-53, 100, 216 and 432 h after birth. Increased formation of this mutagenic DNA lesion during the critical postnatal phase when there is rapid cell proliferation in all tissues is proposed to contribute to carcinogenesis in susceptible tissues later in life.      

Growth hormone deficiency in patients with 22q11.2 deletion: expanding the phenotype

The list of findings associated with the 22q11.2 deletion is quite long and varies from patient to patient. The hallmark features include: conoruncal cardiac anomalies, palatal defects, thymic aplasia or hypoplasia, T cell abnormalities, mild facial dysmorphia, and learning disabilities. The 22q11.2 deletion has been seen in association with the DiGeorge sequence, velocardiofacial syndrome (VCFS), conotruncal anomaly face syndrome, isolated conotruncal cardiac anomalies, and some cases of autosomal dominant Optiz G/BBB syndrome. Short stature has been seen in one to two thirds of children reported in the literature with a diagnosis of VCFS, but growth hormone deficiency (GHD) has not been described in conjunction with this diagnosis. We present 4 patients with a 22q11.2 deletion and short stature who were found to have abnormalities in the growth hormone-insulin-like growth factor I axis. All had growth factors less than -2 SD for age and failed provocative growth hormone testing. Two patients were found to have abnormal pituitary anatomy. In our population, the incidence of GHD in 4 or 95 children with 22q11 deletion is significantly greater than the estimated incidence of GHD in the general population. Children with a 22q11.2 deletion appear to be at a greater risk for pituitary abnormalities. Therefore, those children with the 22q11.2 deletion and short stature or poor growth should be evaluated for GHD, as replacement growth hormone therapy may improve their growth velocity and final height prediction.     

针灸防治炎症性肠病的研究进展

炎症性肠病是一种全球性疾病,其机制尚未完全清楚,当前的治疗也存在一些不足。针灸作为一种绿色、安全、有效的治疗方式,对于炎症性肠病的防治具有一定的积极作用。本文通过对相关文献进行分析总结,发现目前针灸作为一种单独的治疗方式或同药物一起对炎症性肠病均具有一定的疗效,主要通过调节基因表达及表观遗传、提高机体免疫功能及调节炎症因子、改善肠道菌群、调节机体代谢物水平等途径延缓炎症性肠病的发展。现总结目前针灸防治炎症性肠病的研究进展,为进一步的研究及临床工作提供参考和依据。     

微型单侧外固定支架治疗第一掌骨基底骨折

目的 总结微型单侧外固定支架治疗第一掌骨基底骨折的手术方法及其疗效经验。方法 将86例第一掌骨底基骨折患者拇指向桡远侧持续牵引,在骨折线远近端（第一掌骨远端及大多角骨和舟状骨）旋入4枚螺杆,在X线透上手法复位,通过调节侧方延长杆纠正短缩及分离,用万向球形关节纠正成角或旋转畸形。术后2h-2d即能活动拇指间关节,进行主动伸屈功能操练。 固定4－6周拆除支架锻炼活动。结果 86例患者随访80例,失访6例。去支架后随访半年至3年9个月,平均26个月。90％患者拇指外展、内收、内旋及对掌功能恢复良好。结论 微型单侧外固定支架结构简单,使用方便,固定可靠,临床效果满意。     

Pulse sequence extrapolation with MR image synthesis

Previous reports have presented validation studies of magnetic resonance (MR) image synthesis in which multiple spin-echo (MSE) source data were used to generate spin-echo images for various echo times and repetition times (TRs). A new method-"pulse sequence extrapolation" -synthesizes images for pulse sequences different from that of the acquisition. MSE data acquired in a time equivalent to a TR of 2,000 msec can be used to generate inversion-recovery (IR) images for arbitrarily chosen TI inversion times. Other combinations of pulse sequences were also studied, and synthetic images were compared visually and quantitatively to directly acquired images with corresponding parameters. Synthetic IR signals of the brain parenchyma consistently matched directly acquired signals to within 6%, with respect to the full magnetization signal. The noise level of synthetic signals was generally no more than twice that of direct acquisition signals, as predicted. This method can achieve selective fat suppression and enhancement in IR imaging.