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.      

Hydrogen peroxide Modulates Ca2+-Activation of Single permeabilized Fibres from Fast- and Slow-twitch Skeletal Muscles of Rats

We examined the effects of redox modulation on single membrane-permeabilized fibre segments from the fast-twitch extensor digitorum longus (EDL) and slow-twitch soleus muscles of adult rats to determine whether the contractile apparatus was the redox target responsible for the increased contractility of muscles exposed to low concentrations of H₂O₂. The effects of H₂O₂ on maximum Ca²⁺-activated force were dose-dependent with 30 min exposure to 5 mM H₂O₂ causing a progressive decrease by 22 ± 3 and 13 ± 2% in soleus and EDL permeabilized muscle fibres, respectively. Lower concentrations of exogenous H₂O₂ (100 M and 1 mM) had no effect on maximum Ca²⁺-activated force. Subsequent exposure to the reductant dithiothreitol (DTT, 10 mM, 10 min) fully reversed the H₂O₂-induced depression of force in EDL, but not in soleus muscle fibres. Incubation with DTT alone for 10 min did not alter Ca²⁺-activated force in either soleus or EDL muscle fibres. The sensitivity of the contractile filaments to Ca²⁺ (pCa₅₀) was not altered by exposure to any concentration of exogenous H₂O₂. However, all concentrations of H₂O₂ diminished the Hill coefficient in permeabilized fibres from the EDL muscle, indicating that the cooperativity of Ca²⁺ binding to troponin is altered. H₂O₂ (5 mM) did not affect rigor force, which indicates that the number of crossbridges participating in contraction was not reduced. In conclusion, H₂O₂ may reduce the maximum Ca²⁺ activated force production in skinned muscle fibres by decreasing the force per crossbridge.     

Neuroendocrine mechanisms that delay and initiate puberty in higher primates

This paper highlights a series of studies using the male rhesus monkey that has led to a model for the control of the onset of puberty in higher primates. The model proposes that the timing of puberty in these species is governed by the duration of a central brake that, during juvenile development, holds in check the hypothalamic network of gonadotropin-releasing hormone (GnRH) neurons, which, in the adult, drive the pituitary-gonadal axis. The neurobiology of this hypothalamic brake, and the physiological mechanisms that time its application and removal, are incompletely understood. Nevertheless, the pubertal resurgence of pulsatile GnRH release, which terminates the juvenile phase of primate development and triggers the initiation of puberty in man and monkeys, is associated with structural and molecular remodeling of the hypothalamus. A major component of this developmental plasticity appears to involve neuropeptide Y (NPY). NPY inhibits GnRH release, and NPY gene expression in the hypothalamus is elevated during juvenile development when GnRH release is restrained. Since the changes in hypothalamic function and morphology that trigger primate puberty unfold in the absence of gonadal steroid feedback, the possibility is raised that, in addition to activating the pituitary-gonadal axis at this stage of development, they may also contribute directly to the causation of behaviors and affective states that emerge at adolescence.     

中西医结合治疗小儿脑性瘫痪流涎症

探讨小儿脑性瘫痪流涎症的有效治疗方法。方法:46例小儿脑性瘫痪流涎症患儿随机分为两组,观察组采用口操、针灸、经络导平及东莨菪碱治疗;对照组采用东莨菪碱治疗,治疗后用TDS进行疗效评定。结果:观察组总有效率为56.92％,对照组17.39％。观察组明显优于对照组(x~2=7.558,P<0.01)。结论:中西医结合治疗小儿脑性瘫痪流涎症是行之有效的方法。     

Viatical settlements: what case managers should know

Culturally we are taught not to discuss money and other people's financial circumstances, particularly if financial hardship exists. The reluctance is even greater if that hardship involves dire circumstances like a serious illness. Added to this reticence is anecdotal evidence that case managers (and other professionals who may be called to interact with clients regarding a broad range of stressful issues during ill health) are hesitant to discuss financial matters other than those directly pertaining to payment for specific, predetermined medical treatment.     

足反射疗法对前列腺增生效果分析

目的　前列腺增生是男性中老年的常见病、多发病。单纯药物治疗效果不明显 ,手术治疗会给患者造成痛苦和不便。了解足反射疗法对此病的疗效。方法　对 90例前列腺增生患者进行了分组对比 ,A组 3 0例 ,采用足反射疗法。B组 3 0例 ,采用药物疗法。C组 3 0例 ,采用足反射疗法与口服药物双重治疗。三组均以B超声诊断仪测定。结果　治疗前与第一疗程后 ,前列腺三径之差进行比较。显效 :两次差≥ 1 5cm。有效二两次差≥ 1 0cm。结果 :A组显效率 3 6 60 % ,有效率 5 3 3 3 % ,总有效率 89 99%。B组 :显效率 3 3 3 %。有效率 10 % ,总有效率 13 3 3 %。C组 :显效率 5 6 66%、有效率 3 6 66% ,总有效率 93 3 2 %。结论　证实了足反射疗法可作为治疗前列腺增生及前列腺炎的首选方法。如与药物疗法配合使用 ,效果更好 ,并可解除有手术禁忌患者的痛苦。     

The effect of temporal frequency variation on threshold contrast sensitivity deficits in optic neuritis.

The effect of increasing temporal frequency on contrast sensitivity anomalies in unilateral optic neuritis has been investigated. For 4 c/deg gratings no change in the deficit was observed at any temporal frequency whereas there was a tendency for the deficit to decrease with increase in temporal frequency for 0-5 c/deg gratings. The latter effect was not observed in a case of optic neuritis with severe deficit and not in two cases of other optic nerve pathology. An explanation based on the assumption that "threshold scotomata" might be present in cases of demyelinating optic nerve disease is proposed.