Frequency selectivity in Old-World monkeys corroborates sharp cochlear tuning in humans

Frequency selectivity in the inner ear is fundamental to hearing and is traditionally thought to be similar across mammals. Although direct measurements are not possible in humans, estimates of frequency tuning based on noninvasive recordings of sound evoked from the cochlea (otoacoustic emissions) have suggested substantially sharper tuning in humans but remain controversial. We report measurements of frequency tuning in macaque monkeys, Old-World primates phylogenetically closer to humans than the laboratory animals often taken as models of human hearing (e.g., cats, guinea pigs, chinchillas). We find that measurements of tuning obtained directly from individual auditory-nerve fibers and indirectly using otoacoustic emissions both indicate that at characteristic frequencies above about 500 Hz, peripheral frequency selectivity in macaques is significantly sharper than in these common laboratory animals, matching that inferred for humans above 4-5 kHz. Compared with the macaque, the human otoacoustic estimates thus appear neither prohibitively sharp nor exceptional. Our results validate the use of otoacoustic emissions for noninvasive measurement of cochlear tuning and corroborate the finding of sharp tuning in humans. The results have important implications for understanding the mechanical and neural coding of sound in the human cochlea, and thus for developing strategies to compensate for the degradation of tuning in the hearing-impaired.     

Array comparative genomic hybridization identifies novel potential therapeutic targets in cholangiocarcinoma

Background

Cholangiocarcinoma (CC) is a rare tumour with a dismal prognosis. As conventional medical management offers minimal survival benefit, surgery currently represents the only chance of cure. We evaluated DNA copy number (CN) alterations in CC to identify novel therapeutic targets.

Methods

DNA was extracted from 32 CC samples. Bacterial artificial chromosome (BAC) array comparative genomic hybridization was performed using microarray slides containing 3400 BAC clones covering the whole human genome at distances of 1 Mb. Data were analysed within the R statistical environment.

Results

DNA CN gains (89 regions) occurred more frequently than DNA CN losses (55 regions). Six regions of gain were identified in all cases on chromosomes 16, 17, 19 and 22. Twenty regions were frequently gained on chromosomes 1, 5, 7, 9, 11, 12, 16, 17, 19, 20 and 21. The BAC clones covering ERBB2, MEK2 and PDGFB genes were gained in all cases. Regions covering MTOR, VEGFR 3, PDGFA, RAF1, VEGFA and EGFR genes were frequently gained.

Conclusions

We identified CN gains in the region of 11 useful molecular targets. Findings of variable gains in some regions in this and other studies support the argument for molecular stratification before treatment for CC so that treatment can be tailored to the individual patient.     

异种生物型骨钉植入骨折模型的组织学变化

摘要 背景：近年来,采用可吸收螺钉固定关节骨折的病例数越来越多,但还存在力学性能不稳定,过早吸收后导致固定失败等缺点。因此,研制性能稳定而又价格低廉的异种骨螺钉替代可吸收螺钉很有必要。 目的：观察异种生物型骨钉植入兔骨折模型后的组织学反应。 方法：成年新西兰兔制备股骨内髁骨折模型后随机抽签法分为实验组和对照组,实验组用异种生物型骨钉固定,对照组用可吸收螺钉固定。术后2,4,6,8,12,24周取骨钉及周围组织行组织学检测。 结果与结论：术后两组动物均在一两天后逐渐恢复活动,约10 d后活动基本正常,伤口局部均无红肿、破溃,渗出及坏死等,均在2周完全愈合。病理切片显示：术后2,4周时生物型骨钉与宿主骨界面间有炎性细胞浸润;6~12周,炎性细胞数逐渐减少,纤维化较前明显,纤维边缘出现少许破骨细胞;24周,纤维层厚度减低,破骨细胞数明显增加,与宿主骨间发生骨桥连接。可吸收钉在术后2,4周可见可吸收钉道表面有炎性细胞浸润;6~8周,钉道松质骨炎性细胞浸润数逐渐减少,纤维化明显,未见破骨细胞浸润;12~24周,钉道表面纤维结缔组织层的厚度较前增厚,宿主松质骨内少许破骨细胞浸润。提示生物型骨钉具有一定的诱导成骨作用,无明显的免疫排斥反应。 关键词：生物型骨钉;异种;移植;骨折模型;可吸收螺钉;病理 doi:10.3969/j.issn.1673-8225.2010.47.006     

Mixed micropapillary–ductal carcinomas of the breast: a genomic and immunohistochemical analysis of morphologically distinct components

Micropapillary carcinomas (MPCs) can present as a rare histological special type of breast cancer; however, this histological type is more frequently found admixed with invasive ductal carcinomas of no special type (IDC‐NSTs). We have previously demonstrated that pure MPCs constitute a distinct entity at the morphological and genetic levels. Here, we sought to determine whether mixed MPCs have genomic aberrations similar to those found in pure MPCs, and to investigate whether the distinct morphological components of MPCs harbour different genetic aberrations. Using high‐resolution microarray comparative genomic hybridization (aCGH), we profiled a series of 10 MPCs of mixed histology and 20 IDC‐NSTs matched for grade and oestrogen receptor (ER) status. In addition, we generated tissue microarrays containing a series of 24 pure and 40 mixed MPCs and performed immunohistochemical analysis with ER, progesterone receptor (PR), Ki‐67, HER2, cytokeratin (CK) 5/6, CK14, CK17, EGFR, topoisomerase‐IIα, cyclin D1, caveolin‐1 and E‐cadherin antibodies. In situ hybridization was employed to evaluate the prevalence of HER2, TOP2A, EGFR, CCND1, MYC and FGFR1 gene amplification. Our results demonstrate that mixed MPCs harbour similar patterns of genomic aberrations and phenotype (82.5% luminal and 17.5% HER2) compared to pure MPCs. A comparison between the distinct morphological components of mixed MPCs in a pairwise fashion revealed that both components harbour strikingly similar genomic profiles. When compared to grade‐ and ER‐matched IDC‐NSTs, mixed MPCs significantly more frequently harboured amplification of multiple regions on 8q (adjusted Fisher's p value < 0.05). Furthermore, mixed MPCs displayed higher proliferative rates than grade‐ and ER‐matched IDC‐NSTs. Our results suggest that micropapillary differentiation in breast cancer may identify a subgroup of more aggressive ER‐positive breast carcinomas, even in those featuring a mixed histology, and that mixed MPCs are more closely related to pure MPCs than to IDC‐NSTs. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Glyceraldehyde-3-phosphate dehydrogenase versus toluidine blue as a marker for infarct volume estimation following permanent middle cerebral artery occlusion in mice

Infarct size is a good predictor of the neurological outcome following stroke. Estimation of infarct size in the early phase following experimental stroke depends on the availability of reliable techniques that can distinguish ischemic from nonischemic tissue. The objective of this study was to provide a simple and robust method for reliable delineation of the ischemic infarct area in fresh frozen cryosections from mice subjected to focal cerebral ischemia. Mice were subjected to permanent middle cerebral artery (MCA) occlusion and euthanised after 30 min, 1, 2, 4, 6, 12 and 24 h. The size of the developing infarct was compared in parallel series of sections in situ hybridized for mRNA encoding the enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or stained with toluidine blue (TB). The infarct was clearly delineated in GAPDH mRNA in situ hybridized sections as soon as 4 h after MCA occlusion. Infarct size was similar at 4 and 6 h in GAPDH mRNA in situ hybridized sections. Sections hybridized for GAPDH mRNA showed significantly larger infarcts than sections stained with TB after 6 h but not after 24 h of ischemia. Analysis of in situ hybridized sections revealed changes in neuronal GAPDH mRNA in areas prone to undergo degeneration 30 min to 1 h after MCA occlusion, thereby preceding visible pycnosis in TB-stained sections. The results showed that in situ hybridization for GAPDH mRNA was a reliable method and superior to TB staining for precise infarct delineation prior to 6 h of permanent MCA occlusion.     

小鼠急性细菌性鼻及鼻窦炎模型

目的建立小鼠急性细菌性鼻及鼻窦炎模型。方法 179只BALB/c/小鼠,随机分为4组。A、B组BALB/c小鼠右侧鼻腔中塞入棉条。A组,以耐甲氧西林金黄色葡萄球菌（methicillin resistant Staphylococcus aureus,MRSA）COL菌悬液浸润棉条;B组,以无菌生理盐水浸润棉条;C组,只在小鼠鼻腔中滴入MRSA COL菌悬液;D组,对照组。动物分别于1、4、7、14 d处死。对鼻部组织做细菌培养和病理切片研究。死亡的3只小鼠（A组）未计人数据统计中。结果 A组小鼠全部诱导出急性细菌性鼻及鼻窦炎,B组小鼠可诱导出鼻腔炎症反应。炎症程度经统计学分析,A、B组有明显统计学差异。C、D组小鼠没有出现炎症反应。结论以植入膨胀海绵并滴入菌液的方式成功建立小鼠急性细菌性鼻及鼻窦炎模型。     

中医药对乳腺癌患者生存质量影响的Meta分析

目的:系统评价中医药对乳腺癌患者生存质量的影响.方法:检索2005年以来发表的,运用随机对照试验研究方法评估中医药联合化疗对乳腺癌患者生存质量影响的有关文献,采用Jadad质量评分表对文献进行评价,用Rev Man 4.2软件包进行统计分析.结果:共有4篇随机对照试验文献(共839名病例)满足纳入标准.生存质量改善率:异质性检验P=0.80,合并效应量OR =3.06,95％ C1(2.18,4.30);合并效应量的检验Z=6.49,P＜0.000 01,表明中医药联合化疗与单纯化疗比较,生存质量显著提高.结论:现有临床研究证据表明中医药能改善乳腺癌患者的生存质量.但由于纳入研究的文献数量有限,本次评价的效度尚需进一步的验证.