Effect of ischaemia on somatosensory evoked potentials in diabetic patients.

The nerve action potential at the elbow and somatosensory evoked potentials (SEPs) at the scalp were recorded over 30 minutes of tourniquet-induced limb ischaemia in 10 diabetic patients and 10 controls. According to the SEP changes, an increased resistance to nerve ischaemia in diabetic patients was observed. The pathways involved in SEP conduction are discussed.     

颈内动脉接近完全闭塞时的处理

目的由于卒中风险随着狭窄严重程度的增加而升高，因此认为颈内动脉（ICA）接近闭塞患者的卒中风险很高。在现有的随机试验中，还没有专门针对这种情况进行探讨，因此其处理尚存在争汶。方法：对相关文献进行系统评价。结果：对ICA接近闭塞患者的处理还存在争议：一些学者支持进行干预，而另一些学者则认为存在风险或没有益处而反对进行干预。在ICA接近闭塞的有症状患者中进行一项比较外科治疗与最佳内科治疗的多中心前瞻性随机试验似乎非常困难，因为这类研究需要大量的患者。尽管如此，基于目前的证据，似乎很难拒绝手术治疗。结论：由于目前对ICA接近闭塞患者的最佳处理方案仍存在着争议，因此需要前瞻性观察性研究以证实其在有症状和无症状人群中的患病率以及相关的卒中风险。基于目前的证据，大多数医疗中心选择手术治疗，但它相对干内科治疗的特粱尚右待证章．     

Renal transplant patients show variations in their self-reactive repertoires: a serial study

We addressed the question of whether allo-transplantation (Tx) induces breakdown of tolerance to self-antigens or alteration of the autoreactive T cell repertoire in humans. The serial variation of T cell autoreactivity was studied in the peripheral blood of 12 renal transplant patients, by autologous limiting dilution assay and autologous mixed lymphocyte reaction. Ten of 12 patients presented a positive response in autologous peripheral blood mononuclear cells in the post-Tx period, in contrast to four of 12 patients before Tx (P = 0.038). Multi-hit kinetics was found in 57% of the assays analyzed, indicating frequent regulatory control of the autologous response. Quantitative analysis performed in eight patients showed an increase in precursor frequency at >1 year post-Tx in five patients. These data indicate that autoreactivity increases or develops following Tx, in humans. Post-Tx events such as alloreactivity, infections or immunosuppression could interfere with the balance of autoreactive and regulatory cells, leading to changes in the T cell repertoires to self-antigens and eventually breakdown of self-tolerance. Further investigation is needed to elucidate whether post-Tx autoreactivity contributes to rejection, plays a regulatory role over alloreactivity or both, at separate times.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.