红霉素联合阿奇霉素短程治疗小儿支原体肺炎临床分析

目的探讨红霉素联合阿奇霉素短程治疗和红霉素、阿奇霉素常规治疗小儿支原体肺炎是否疗效相同;并作安全性比较.方法将56例患儿随机分为两组,对照组26例,观察组30例,并记录症状、体征及胸部X线、肝功能变化.结果两组治疗3 d后,症状均明显好转,且2周后复查X线阴影基本吸收,疗效无差异.结论红霉素联合阿奇霉素短程治疗与常规治疗疗效无差异,安全性相同.但前者可减少用药频率,缩短住院时间.     

多种siRNA的抗肿瘤作用研究

目的研究短干扰RNA(short interfering RNA,siRNA)的抗肿瘤作用.方法采用MTT法检测siR-NA的生长抑制作用,H&E染色法观察细胞形态变化,TUNEL标记法检测核DNA断裂,Western Blot法分析蛋白表达水平变化和流式细胞法检测细胞周期分布变化.结果siRNA-Bcl2,siRNA-MDM2,siRNA-CDK2和siRNA-HRas可以明显抑制人乳腺癌MCF-7等肿瘤细胞的生长;siRNA-MDM2和siRNA-Bcl2可以引起MCF-7细胞染色质凝集;siRNA-Bcl2,siRNA-MDM2,siRNA-CDK2和siRNA-HRas均可以明显降低靶基因的表达水平,同时诱导MCF-7细胞发生染色体DNA断裂;siRNA-MDM2还可以导致MCF-7细胞发生G1期阻滞.结论siRNA可以明显抑制肿瘤细胞的生长,降低靶基因的表达水平,并诱导肿瘤细胞凋亡和周期阻滞,提示siRNA可能发展成为一类高效特异的新型抗肿瘤药物.     

Practical population group assignment with selected informative markers: characteristics and properties of Bayesian clustering via STRUCTURE

Population stratification, which is caused by population genetic substructure (PGS), is a critical issue for the design and interpretation of genetic association studies. Methods to address this problem have been devised, but little is known at this point about practical genotyping requirements for resolving PGS based on different marker characteristics. In this report, we seek to (1) identify a small, practical marker set to differentiate African Americans (AAs) from European Americans (EAs), and (2) assess the impact of marker efficiency and sample size on clustering individuals into subgroups by the methods of STRUCTURE (Pritchard et al., [2000a] Genetics 155:945-959). A panel of 37 markers was genotyped for 865 individuals (640 EAs and 225 AAs) from the Northeastern United States. Among EAs, the assignment accuracy reached >99% using only the 4 most efficient markers. Among AAs, the assignment accuracy exceeded 95% when using the 6 most informative markers. Smaller sample size increased the variance in population differentiation, rather than degrading the results consistently. We conclude that the use of marker-efficiency measures for marker selection yielded a relatively small set of STR markers that were effective at differentiating EA and AA populations. The number of markers required is much lower than has been suggested in previous studies.     

SOS1 is the second most common Noonan gene but plays no major role in cardio-facio-cutaneous syndrome

Background

Heterozygous gain‐of‐function mutations in various genes encoding proteins of the Ras‐MAPK signalling cascade have been identified as the genetic basis of Noonan syndrome (NS) and cardio‐facio‐cutaneous syndrome (CFCS). Mutations of SOS1, the gene encoding a guanine nucleotide exchange factor for Ras, have been the most recent discoveries in patients with NS, but this gene has not been studied in patients with CFCS.

Methods and results

We investigated SOS1 in a large cohort of patients with disorders of the NS–CFCS spectrum, who had previously tested negative for mutations in PTPN11, KRAS, BRAF, MEK1 and MEK2. Missense mutations of SOS1 were discovered in 28% of patients with NS. In contrast, none of the patients classified as having CFCS was found to carry a pathogenic sequence change in this gene.

Conclusion

We have confirmed SOS1 as the second major gene for NS. Patients carrying mutations in this gene have a distinctive phenotype with frequent ectodermal anomalies such as keratosis pilaris and curly hair. However, the clinical picture associated with SOS1 mutations is different from that of CFCS. These findings corroborate that, despite being caused by gain‐of‐function mutations in molecules belonging to the same pathway, NS and CFCS scarcely overlap genotypically.     

Heterozygous Mutations in Natriuretic Peptide Receptor‐B (NPR2) Gene as a Cause of Short Stature

Based on the observation of reduced stature in relatives of patients with acromesomelic dysplasia, Maroteaux type (AMDM), caused by homozygous or compound heterozygous mutations in natriuretic peptide receptor‐B gene (NPR2), it has been suggested that heterozygous mutations in this gene could be responsible for the growth impairment observed in some cases of idiopathic short stature (ISS). We enrolled 192 unrelated patients with short stature and 192 controls of normal height and identified seven heterozygous NPR2 missense or splice site mutations all in the short stature patients, including one de novo splice site variant. Three of the six inherited variants segregated with short stature in the family. Nine additional rare nonsynonymous NPR2 variants were found in three additional cohorts. Functional studies identified eight loss‐of‐function mutations in short individuals and one gain‐of‐function mutation in tall individuals. With these data, we were able to rigorously verify that NPR2 functional haploinsufficiency contributes to short stature. We estimate a prevalence of NPR2 haploinsufficiency of between 0 and 1/26 in people with ISS. We suggest that NPR2 gain of function may be a more common cause of tall stature than previously recognized.     

声诱发的短潜伏期负反应与前庭诱发的肌源性电位关系初步研究

目的研究声诱发的短潜伏期负反应(acoustically evoked short latency negative response,ASNR)的特点,并初步证实该电位的前庭源性,即与前庭诱发的肌源性电位(vestibular evoked myogenic potentials,VEMP)同源。方法分别检测28例健康成人、16例前庭疾病和1例全聋患者的VEMP和ASNR,比较ASNR与VEMP之间的关系。结果ASNR正常引出率为87.5%,潜伏期正常值为3.50±0.25ms;2倍标准差作为正常值的上、下限,ASNR潜伏期的范围为3~4ms,阈值为80~90dB nHL。16例前庭疾病患者均行双侧检查,在VEMP消失的9耳(9例)中,ASNR均未引出;VEMP低振幅的8例(8耳)中,5例(5耳)未引出ASNR,3例(3耳)ASNR正常引出。5例梅尼埃病患者接受甘油试验,1例(2耳)甘油试验前后VEMP与ASNR均正常,2例(4耳)双侧VEMP与ASNR甘油试验前异常,甘油试验后正常,1例(1耳)患侧VEMP正常,甘油试验前后无变化,ASNR由异常变为正常;1例(2耳)VEMP甘油试验前双侧异常,甘油试验后正常,但ASNR均未引出。1例听力正常的前庭神经炎患者,患侧VEMP未引出,ASNR电位也未引出。1例先天性全聋患者人工耳蜗植入前,VEMP、ASNR正常引出;植入后,术侧VEMP振幅降低,ASNR未引出。结论ASNR与VEMP可能均源于球囊。鉴于目前的结果,在不便进行VEMP检测时可用ASNR替代。     

Oligodontia, short stature and small head circumference with normal intelligence

Complete absence of third molars and mandibular permanent second molars is reported in a 19-year-old female, with occipito-frontal head circumference and height at the 3rd centile. The patient's intelligence, appearance and physical examination were normal. Direct count of the patient's sweat pores in different areas of the palms and digits was normal. Microcephaly, short stature and normal intelligence have been reported in two families as a distinct autosomal dominant syndrome. To the best of our knowledge, oligodontia, in addition to these findings, has not been previously reported.     

Short rib-polydactyly syndrome and pericentric inversion of chromosome 4

We report on a newborn infant with clinical and radiological manifestations of some type of short rib-polydactyly syndrome who died soon after birth. Chromosomal studies on peripheral blood lymphocytes and chondrocytes demonstrated an apparently balanced pericentric inversion of chromosome 4 (present in the mother also). This association may have occurred by chance but, if not, the chromosomal breakpoints could interrupt the gene responsible for short rib-polydactyly syndromes, or else be related to the mechanism of short rib-polydactyly syndromes. © 1994 Wiley-Liss, Inc.