Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP)

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.      

Band-pass response properties of rat SI neurons

Rats typically employ 4- to 12-Hz "whisking" movements of their vibrissae during tactile exploration. The intentional sampling of signals in this frequency range suggests that neural processing of tactile information may be differentially engaged in this bandwidth. We examined action potential responses in rat primary somatosensory cortex (SI) to a range of frequencies of vibrissa motion. Single vibrissae were mechanically deflected with 5-s pulse trains at rates /=3 Hz. In contrast with this low-pass feature of the response, several other characteristics of the response revealed bandpass response properties. While average evoked response amplitudes measured 0-35 ms after stimulus onset typically decreased with increasing frequency, the later components of the response (>15 ms post stimulus) were augmented at frequencies between 3 and 10 Hz. Further, during the steady state, both rate and temporal measures of neural activity, measured as total spike rate or vector strength (a measure of temporal fidelity of spike timing across cycles), showed peak signal values at 5-10 Hz. A minimal biophysical network model of SI layer IV, consisting of an excitatory and inhibitory neuron and thalamocortical input, captured the spike rate and vector strength band-pass characteristics. Further analyses in which specific elements were selectively removed from the model suggest that slow inhibitory influences give rise to the band-pass peak in temporal precision, while thalamocortical adaptation can account for the band-pass peak in spike rate. The presence of these band-pass characteristics may be a general property of thalamocortical circuits that lead rodents to target this frequency range with their whisking behavior.     

Modulation of systolic and diastolic function by endothelin-1: relation to coronary flow

Different conclusions have been reached with regard to the effect of endothelin (ET-1) on cardiac contractility. We examined systolic and diastolic function in response to constant known concentrations of ET-1 with or without ET-1 induced reductions in coronary flow (CF). Rat hearts (n= 21) were buffer-perfused using constant coronary flow (cCF) or constant perfusion pressure (cPP). Left ventricular function was assessed isovolumically. Addition of ET-1 (10^-9 M) in the cCF group caused a gradual increase in PP from 61 ± 2 to 165±6mmHg (mean±SE) (P < 0.01). Within 10 min left ventricular systolic pressure (LVSP) increased from 111 ± 2 to a maximum of 134±4mmHg (P < 0.01) and [L\dP/dt] increased from 1640 ± 81 to a maximum of 2020 ± 92 mmHg s“¹ (P < 0.01). After 15 min left ventricular end diastolic pressure (LVEDP), a measure of diastolic stiffness (DS), also increased. With ET-1 (10 ⁸ M), similar haemodynamic alterations appeared more rapidly. In the cPP group, ET-1 (10”⁹ M) caused a sharp decrease in CF and LVSP fell from 115 ± 8 to 62±12 mmHg at 10 min (P < 0.001). Systolic function remained stable at a reduced level for 1 h. DS did not change. Thus, ET-1 possesses positive inotropic effects and increases diastolic stiffness. Both effects may be masked by vasoconstriction-induced ischaemia.     

HL-A Antigens in a Chinese Population

The HL-A antigens of a Chinese population now living on the island of Taiwan have been investigated with reagents obtained from and characterized in Caucasian populations and with antisera obtained from Chinese multiparous women. Both HL-A2, the most frequent specificity found, and HL-A9 appear highly heterogeneous in this Chinese population since groups of antisera used to define HL-A2 or 9 in Caucasians gave discordant reactions. Moreover, new associations were found using chi-square and cluster analyses, further demonstrating the complexity of HL-A in this Taiwanese population. Fourteen % of 1183 Chinese multipara sera and 237 sera from multiple tranfused individuals were lymphocytotoxic and could be placed by cluster analysis into three major groups.     

Clinical evidence of the nonpathogenic nature of the M34T variant in the connexin 26 gene

Mutations in GJB2 are the most common cause of congenital nonsyndromic hearing loss. The controversial allele variant M34T has been hypothesized to cause autosomal dominant or recessive nonsyndromic hearing impairment and some in vitro data has been consistent with this hypothesis. In this report, we present the clinical and genotypic study of 11 families (seven familial forms of nonsyndromic sensorineural hearing loss (NSSNHL) and four sporadic cases) in which the M34T GJB2 variant has been identified. The M34T mutation did not segregate with the deafness in six of the seven familial forms of NSSNH. Eight persons with normal audiogram presented a heterozygous M34T variation and five normal hearing individuals were composite heterozygous for M34T and another GJB2 mutation. Four normal hearing individuals with a documented audiogram were M34T/35delG and one was M34T/(GJB6-D13S1830)del. Screening a French control population of 116 subjects we have found an M34T allele frequency of 1.72%. This percentage was not significatively different from the prevalence of the M34T allele in the deaf population, which was 2.12%. All these data suggest that the M34T variant is not clinically significant in human and is a frequent polymorphism in France.     

延续性护理在心脏瓣膜置换术患者中的应用效果分析

目的 探讨延续性护理在心脏瓣膜置换术患者中的应用效果.方法 选取2017年1月—2019年1月在四川省德阳市人民医院接受心脏瓣膜置换术治疗的80例瓣膜性心脏病患者作为研究对象,随机分为观察组和对照组各40例.出院后对照组不进行主动护理,观察组采用延续性护理,对两组患者干预前后服药依从性、生活质量及心功能进行比较分析.结果 出院时两组服药依从性、生活质量及心功能比较差异无统计学意义(P>0.05),出院后6个月观察组服药依从性、生活质量及心功能均优于对照组,差异有统计学意义(P<0.05).结论 延续性护理应用于心脏瓣膜置换术出院患者中可提高患者服药依从性,提升患者生活质量及心功能恢复,值得临床借鉴推广.     

Feasibility and benefits of the ewe as a model for vaginal surgery training

Introduction and hypothesis

The objective was to evaluate the ewe as an animal model for teaching and training in vaginal surgery.

Methods

Twenty-nine postgraduate surgeons attended a training course on vaginal prolapse surgery. After a review of human and sheep anatomy, the participants performed transvaginal meshes, vaginal hysterectomy, SSLF (Richter), and OAS repair in ewes and human cadavers. Participants completed questionnaires on the whole course.

Results

Questionnaires showed the significant superiority of ewes over human cadavers for all items evaluated regarding surgical dissections. Only identification of the sacrospinous ligament and the spine were judged to be similar in ewes and human cadavers. Participants noticed that ewe model is appropriate for vaginal prolapse surgery training for resident and for postgraduate surgeons. Two vaginal hysterectomies were also performed. Operating time, surgery, and anatomy were nearly identical to that of humans. The same conclusions were made while performing sacrospinous ligament fixation (Richter) and obstetric anal sphincter injury repair.

Conclusion

This series indicates that the ewe is a useful animal model for teaching vaginal surgery.

     

腓骨高位截骨在膝关节骨性关节炎的应用

目的:探讨腓骨高位截骨术对膝关节骨性关节炎的短中期疗效。方法:2014年10月至2016年7月,采用腓骨高位截骨治疗膝关节骨性关节炎76例,男22例,女54例;年龄47~82岁,平均61.62岁。术前查体膝关节内侧压痛,内侧麦氏征阳性,摄膝关节负重正侧位X线片显示内侧间隙变窄,术后行膝内侧间隙、股骨胫骨角、VAS疼痛评分及AKS评分进行评价。结果:术后随访10~18个月,平均8.9个月。与术前相比,术后膝内侧间隙明显变宽,股骨胫骨角度变大。术前VAS疼痛评分5.70±1.56,术后1周3.70±1.03,1个月3.20±0.95,3个月2.35±0.99,1年2.10±0.97。膝关节功能AKS评分术前疼痛14.45±1.76,活动度12.60±1.98,稳定性12.15±1.72;末次随访疼痛42.60±2.28,活动度21.80±2.14,稳定性20.85±2.16。VAS评分术前与术后各时间段相比差异有统计学意义,AKS评分术前与术后差异均有统计学意义。结论:腓骨高位截骨操作简单,并发症少,能有效减轻膝关节疼痛,改善膝关节功能,临床效果满意。     

Effects of malnutrition on the erythrocyte fatty acid composition and plasma vitamin E levels of Pakistani children

Abstract Erythrocyte fatty acids and plasma vitamin E concentrations were determined in 47 grade 2 and 21 grade 3 malnourished Pakistani children (ages 4–56 months). Data were compared with those of 26 age- and sex-matched apparently healthy controls. Evaluation with three statistical approaches revealed that both grade 2 and grade 3 malnourished children had decreased erythrocyte ω6 fatty acids and to a lesser extent decreased ω3 fatty acids. These decreases were compensated for by increased ω9 fatty acids. The patients tended to have lower plasma vitamin E concentrations. We conclude that malnourished Pakistani children have low essential fatty acid status, notably those of the ω6 series. The combination of low erythrocyte 22:6ω3 and a low 22:5ω6/22:4ω6 ratio in grade 2 patients suggests low Δ4-desaturation activity, which may be due to impaired peroxisomal β-oxidation.