Neck masses due to internal jugular vein phlebectasia: Frequency in Menkes disease and literature review of 85 pediatric subjects

Classic Menkes disease is a rare X‐linked recessive disorder of copper metabolism caused by pathogenic variants in the copper transporter gene, ATP7A. Untreated affected individuals suffer failure to thrive and neurodevelopmental delays that begin at 6–8 weeks of age and progress inexorably to death, often within 3 years. Subcutaneous injections of Copper Histidinate (US Food and Drug Administration IND #34,166, Orphan product designation #12‐3663) are associated with improved survival and neurological outcomes, especially when commenced within a month of birth. We previously identified internal jugular vein phlebectasia (IJP) in four Menkes disease subjects. This feature and other connective tissue abnormalities appear to be consequences of deficient activity of lysyl oxidase, a copper‐dependent enzyme. Here, we report results from a prospective study of IJP based on 178 neck ultrasounds in 66 Menkes subjects obtained between November 2007 and March 2018. Nine patients met the criterion for IJP (one or more cross‐sectional area measurements exceeding 2.2 cm²) and five subjects had clinically apparent neck masses that enlarged over time. Our prospective results suggest that IJP occurs in approximately 14% (9/66) of Menkes disease patients and appears to be clinically benign with no specific medical or surgical actionability. We surveyed the medical literature for prior reports of IJP in pediatric subjects and identified 85 individuals and reviewed the distribution of this abnormality by gender, sidedness, and underlying etiology. Taken together, Menkes disease accounts for 16% (15/94) of all reported IJP individuals. Neck masses from IJP represent underappreciated abnormalities in Menkes disease.     

A study on facial features of children with Williams syndrome in China based on three‐dimensional anthropometric measurement technology

To describe special facial features of children with Williams syndrome in China by using method of three‐dimensional craniofacial anthropometry. Using three‐dimensional stereo photogrammetric device, 14 craniofacial anthropometric measurements were performed and five indices were calculated in 52 children with Williams syndrome and 208 age and sex matched controls of Han Chinese ethnicity. Except intercanthal width, mouth breadth, morphological face height, nasal height‐breadth index, nasal breadth‐depth index, morphological ear index, the Williams syndrome group under 3 years old were smaller than the control group in the other 12 variables. Compared with the control group, the Williams syndrome group aged 3–5 years old had smaller biocular breadth, nasal length, nasorostral angle, bitragal breadth, ear width, morphological ear index and face depth. The Williams syndrome group aged above 6 years old had smaller biocular breadth, nasal breadth, bitragal breadth, ear width, ear length and face depth than the control group. The craniofacial variability index of the Williams syndrome group was greater than the control group. Greater variation was found among children with Williams syndrome than normal in China, specifically at eye, nose, ear and face shape, which demonstrate the usefulness of three‐dimensional stereo photogrammetric analysis in supporting accurate diagnose of the patient with Williams syndrome.     

健脾补肾药对脾虚大鼠细胞因子水平的影响

目的 :观察健脾补肾方药对实验性脾虚证大鼠细胞因子的影响 ,探讨脾虚证与细胞因子的关系及脏腑相关的意义。方法 :选用SD雄性大鼠 ,随机分为 :正常对照组 ,脾虚模型组 ,健脾补肾方高、低剂量组 ,通过大黄复制脾虚证动物模型 ,并用健脾补肾方药进行防治。采用放射免疫分析观察各组动物血清肿瘤坏死因子(TNF)、白细胞介素 - 6 (IL - 6 )、白细胞介素 - 2 (IL - 2 )水平的变化。结果 :脾虚模型组大鼠血清TNF、IL - 6、IL - 2含量均比正常对照组显著降低 (p <0 0 1) ,而健脾补肾方药能明显升高TNF、IL - 6、IL - 2含量 ,使体重增加 ,脾脏和胸腺组织的重量增加。结论 :脾虚证的发生与细胞因子网络调节系统的失衡有关 ,而健脾补肾中药对实验性脾虚证有较好的防治作用 ,脾肾相关理论对实践有指导意义。     

Novel Brugada syndrome‐causing mutation in ion‐conducting pore of cardiac Na+ channel does not affect ion selectivity properties

Aim: Brugada syndrome is an inherited cardiac disease with an increased risk of sudden cardiac death. Thus far Brugada syndrome has been linked only to mutations in SCN5A, the gene encoding the α‐subunit of cardiac Na⁺ channel. In this study, a novel SCN5A gene mutation (D1714G) is reported, which has been found in a 57‐year‐old male patient. Since the mutation is located in a segment of the ion‐conducting pore of the cardiac Na⁺ channel, which putatively determines ion selectivity, it may affect ion selectivity properties. Methods: HEK‐293 cells were transfected with wild‐type (WT) or D1714G α‐subunit and β‐subunit cDNA. Whole‐cell configuration of the patch‐clamp technique was used to study biophysical properties at room temperature (21 °C) and physiological temperature (36 °C). This study represents the first measurements of human Na⁺ channel kinetics at 36 °C. Ion selectivity, current density, and gating properties of WT and D1714G channel were studied. Results: D1714G channel yielded nearly 80% reduction of Na⁺ current density at 21 and 36 °C. At both temperatures, no significant changes were observed in V_1/2 values and slope factors for voltage‐dependent activation and inactivation. At 36 °C, but not at 21 °C, D1714G channel exhibited more slow inactivation compared with WT channel. Ion selectivity properties were not affected by the mutation at both temperatures, as assessed by either current or permeability ratio. Conclusion: This study shows no changes in ion selectivity properties of D1714G channel. However, the profoundly decreased current density associated with the D1714G mutation may explain the Brugada syndrome phenotype in our patient.     

衰老大鼠急性肺损伤诱导肾功能受损

目的:观察衰老大鼠的急性肺损伤(ALI)是否可进一步诱导肾功能受损。方法:Wistar雄性大鼠40只, 复制成衰老模型, 然后再随机分成对照组(静脉注射生理盐水), ALI组(静脉注射脂多糖, LPS)及LPS组(左心室内注射LPS), 后两组再分2h及6h组。每组8只。注LPS后2h或6h收集血并取肺、肾。制备肺、肾组织匀浆待测。结果:ALI组在注LPS后仅至6h时血中肌酐(Cr)、尿素氮(BUN)含量才有显著升高(均P＜0.01)。而LPS组Cr、BUN含量均无显著升高。ALI组血中乳酸(LD)、丙二醛(MDA)及一氧化氮(NO)含量在注LPS后2h时均显著升高(P＜0.05, P＜0.01);而肺组织中谷胱甘肽过氧化物酶(GSH-P_X)及Na⁺-K⁺-ATPase活性均显著下降(均P＜0.01);上述变化持续至观察的6h时。ALI组在注LPS后仅至6h时, 肾组织中MDA、NO含量才有显著升高(均P＜0.01)及GSH-P_X、Na⁺-K⁺-ATPase活性显著下降(P＜0.01)。而在LPS组, 除注LPS后2h时的血中和2h、6h的肺组织中NO含量显著升高(均P＜0.05)及2h时的肺组织中Na⁺-K⁺-ATPase活性显著下降(P＜0.05)外, 其它均无显著变化。结论:给衰老大鼠静脉内注射5mg/kg的LPS可致ALI, 并可进一步诱导肾功能受损。     

vWF在MODS中表达的免疫组化研究

目的 探讨血管性血友病因子(von willbrand factor,vWF)在多器官功能不全综合征(MODS)中的表达及其意义。方法 应用免疫组化技术,对MODS死亡标本的心、肺、肾组织vWF进行检测。结果 MODS组心、肺、肾组织vWF抗原表达多为弱阳性及阳性,对照组多为阳性及强阳性,两者间差异显著(P<0.01)。结论 MODS存在vWF抗原表达减少,vWF减少导致的凝血功能障碍可能是MODS的重要发病机制之一。     

Mutation screening and CAG repeat length analysis of the androgen receptor gene in Klinefelter's syndrome patients with and without spermatogenesis

BACKGROUND: Mutations of the androgen receptor (AR) gene give rise to a wide array of phenotypic abnormalities. A systematic analysis of the AR gene in patients with 47,XXY has not previously been performed. METHODS: Mutations of the AR gene and expansion of the CAG repeats in exon 1 of the AR gene were studied in 13 patients with Klinefelter's syndrome either with (n = 1) or without (n = 12) spermatogenesis. RESULTS: No abnormalities in the AR gene were detected by single strand conformational polymorphism analysis. The CAG lengths ranged from 17 to 27 (mean +/- SD 22.8 +/- 3.3, median 23) for Klinefelter patients or from 17 to 28 (mean +/- SD 23.2 +/- 2.6, median 23) for control subjects. X-inactivation analysis for the methylation status of the AR gene was performed in seven patients who were heterozygous for CAG repeats of different length, showing that the longer CAG repeat alleles underwent random but more frequent inactivation in five patients and skewed inactivation in two. CONCLUSIONS: An AR gene abnormality does not constitute an important factor for impaired spermatogenesis in patients with Klinefelter's syndrome.     

马凡综合征微纤维蛋白1基因突变检测及单倍型连锁分析

目的：检测中国人马凡综合征（Marfan syndrome,MFS)患者微纤维蛋白1（fibillin-1,FBN1)基因的突变及对马凡综合征患者的家系成员进行症状前诊断。方法：应用聚合酶链反应－单链构象多态性技术和测序方法，对汉族9个家系中共17个MFS患者进行基因突变检测；运用FBN1基因内4个内含子中的可变串联重复序列构建染色体单倍型，进行家系单倍型连锁分析和基因诊断。结果：发现MFS（A）家系Ⅱ1患者有单链构象改变，测序证实为位于FBN1基因第25号外显子3243－3256核苷酸之间有I个13bp的小片段缺失，为新位点基因移码突变，其序列为gcctctgcaccca;单倍型连锁分析发现MFS（B）家系Ⅲ1是1个无症状期患者。结论：中国人FBN1基因突变可以引起马凡综合征，应用突变检测与单倍型连锁分析方法能为马凡综合征基因诊断提供依据。     

甘肃省SARS抗体血清流行病学调查

目的 了解甘肃省严重急性呼吸综合征(SARS)患者、密切接触者和正常人群血清SARS冠状病毒特异性IgG抗体水平。方法 利用酶联免疫吸附试验(ELISA)法检测SARS病毒IgG抗体水平。检测对象包括甘肃省9例SARS患者的急性期和(或)恢复期系列血清，l109例直接护理SARS患者的医生、护士、实验室检测人员、疾控人员和曾与患者有接触的人员以及978例正常人血清。结果 9例临床诊断病例SARS冠状病毒特异性IgG抗体中6例为阳性，疾病恢复后12个月血清抗体仍为阳性；密切接触者1例特异性IgG抗体阳性；正常人3例特异性IgG抗体阳性。结论 病例抗体阳性符合临床诊断，密切接触者和正常人的抗体阳性数较低，提示可能不存在隐性感染。     

人染色体11p15.5 BWS致病位点新基因C11orf21的初步功能分析

目的研究人染色体11p15.5Beckwith-Wiedemann综合征致病位点新基因C11orf21的生物学功能。方法用RT-PCR和Northern印记方法分析C11orf21基因的表达;研究C11orf21蛋白功能用Western印记和细胞培养方法。结果检测到C11orf21基因在成人和胎儿心脏和肝脏等组织转录,在心脏有较强的表达并有0.9和3.1kb两个转录物。C11orf21蛋白在COS-1和Hela细胞细胞质表达,蛋白相对分子质量为14kDa。结论初步分析显示C11orf21是11p15.5Beckwith-Wiedemann综合征致病位点的一个非印记基因,在成人心脏有较强表达的局限细胞质蛋白。