NF1 mutations in neurofibromatosis 1 patients with plexiform neurofibromas

Neurofibromatosis 1 (NF1) is an autosomal dominant disorder caused by genetic alterations of the NF1 gene on 17q11.2. About 30% of NF1 patients develop plexiform neurofibromas (PNFs), which often cause severe clinical deficits. To determine whether there is a certain genotype underlying PNFs or subtypes of PNFs, we screened 42 NF1 patients from 41 families with PNFs for mutations in the NF1 gene. In 33 out of the 41 (80%) unrelated patients NF1 mutations were found, 24 are novel while the other 9 have been described in previous studies. The 33 mutations included 23 nonsense and frameshift, six splice and four missense mutations. The tumors in these patients had various sizes and features/growth characteristics. No correlation was found between the type or location of the NF1 mutations and size, location or feature of the PNFs, suggesting that many types of NF1 mutations can lead to development of PNFs.     

Computerized analysis of mammographic parenchymal patterns for assessing breast cancer risk: effect of ROI size and location

The long-term goal of our research is to develop computerized radiographic markers for assessing breast density and parenchymal patterns that may be used together with clinical measures for determining the risk of breast cancer and assessing the response to preventive treatment. In our earlier studies, we found that women at high risk tended to have dense breasts with mammographic patterns that were coarse and low in contrast. With our method, computerized texture analysis is performed on a region of interest (ROI) within the mammographic image. In our current study, we investigate the effect of ROI size and ROI location on the computerized texture features obtained from 90 subjects (30 BRCA1/BRCA2 gene-mutation carriers and 60 age-matched women deemed to be at low risk for breast cancer). Mammograms were digitized at 0.1 mm pixel size and various ROI sizes were extracted from different breast regions in the craniocaudal (CC) view. Seventeen features, which characterize the density and texture of the parenchymal patterns, were extracted from the ROIs on these digitized mammograms. Stepwise feature selection and linear discriminant analysis were applied to identify features that differentiate between the low-risk women and the BRCA1/BRCA2 gene-mutation carriers. ROC analysis was used to assess the performance of the features in the task of distinguishing between these two groups. Our results show that there was a statistically significant decrease in the performance of the computerized texture features, as the ROI location was varied from the central region behind the nipple. However, we failed to show a statistically significant decrease in the performance of the computerized texture features with decreasing ROI size for the range studied.     

Hindlimb suspension inhibits air-righting due to altered recruitment of neck and back muscles in rats

Effects of 9-week hindlimb suspension and 8-week recovery on air-righting reaction in response to drop from a supine position were studied in adult rats. The righting time in rats at the end of suspension (approximately 220 ms) was longer than the age-matched controls (approximately 120 ms, p <0.05). The unloading-related change in righting time was accompanied by lowered activities of electromyogram (EMG) and altered recruitment of both neck and back muscles at a specific stage of drop. After 8 weeks of reambulation, righting time recovered toward the control level (approximately 153 ms, p <0.05), but the EMG activity of back muscle was still less than controls. In contrast, the EMG of neck muscle during fall was even increased. The differences in the characteristics of the muscle fibers between two groups were minor. It is suggested that inhibition of recruitment, rather than the changes in the fiber characteristics, of neck and back muscles is one of the major causes of the slow air-righting.     

黄雀延髓层状核的传出纤维联系──HRP法研究

向４２只黄雀的延髓展状核加压注入或微电泳泳入ＨＲＰ后，在同侧的脑桥上橄榄核、对侧的脑桥外侧丘系腹核及中脑外侧核背侧部内见到密集的顺行标记终末或纤维；在双侧的延髓巨细胞核出现了大量的逆行标记细胞；在对侧的层状核内既有密集的标记终末又有一些标记细胞．结果表明：层状核的传出纤维投射到同侧上橄榄核，经外侧丘系走行至对侧的外侧丘系腹核和中脑外侧核背侧部，双侧的层状核之间也有交互投射。此外，层状核接受耳蜗亚核──双侧巨细胞核的传入投射．因此，层状核是听觉上行通路中的第二级中继站．     

糖尿病小鼠视网膜碱性成纤维细胞生长因子的表达及细胞损害的电镜观察

目的：为临床研究提供形态学资料。方法：用免疫组化方法，观察碱性成纤维细胞生长因子(bFGF)在糖尿病小鼠视网膜的分布及表达密度；用透射电镜观察不同病程视网膜细胞的损害情况。结果：糖尿病及正常小鼠视网膜各层细胞均表达bFGF，反应强度和密度不同。发病组自6月龄起，居于大血管周围的阳性节细胞密度增加；不同病程bFGF的表达有不同程度的增加。随糖尿病病程延长，细胞超微结构受到不同程度的损害。结论：糖尿病时增多的bFGF直接或间接作用于血管内皮细胞和平滑肌细胞，刺激二者增殖，促进微血管病变的发生；另一方面，减弱视细胞与双极细胞间的信息传递，对糖尿病性盲的发生起重要作用。同时，各种细胞的超微结构及相应的功能也受到不同程度的损害。     

拟除虫菊酯浸泡大网孔门窗帘毒杀侵入实验小屋蚊虫的研究

本研究采用牛房实验小屋，加装不透光百叶窗和透光门廊，从而全面观察药帘对侵入实验小屋蚊虫毒杀情况，包括蚊虫入屋前接触药帘时和屋内蚊虫外逸出屋外后的死亡情况。结果表明，澳氰菊酯、二氯苯醚菊酯毒效强和持效长，浸泡门窗帘后６个月１８次试验，对侵入屋内蚊虫毒杀，平均死亡率分别为８９．４％和９０．６％。两药对入屋内蚊虫的吸血率均没有明显减少，可能与诱饵动物的吸引力有关。二氯苯醚菊酯有明显驱避作用，其减少蚊虫入屋率，按蚊为７０．６％，库蚊为７５．２％均没有明显减少，阿蚊却没有效应。     

宫颈病变程度与人类乳头瘤病毒(16、18型)负荷的关系

目的探讨宫颈病变程度与人类乳头状瘤病毒(HPV)16、18型负荷的关系。方法采用实时荧光定量聚合酶链反应(FQ-PCR)方法,检测宫颈不同病变活检组织及石蜡包埋标本中HPV16、18型感染状况。结果正常宫颈上皮感染HPV16、18型阳性率为3%,CINⅠ、Ⅱ、Ⅲ级和宫颈癌感染HPV16、18阳性率分别为45.7%,69.5%,72.2%和74.6%。正常宫颈与CIN,宫颈癌HPV16、18阳性率差异有极显著性(P<0.0001)。宫颈糜烂(Ⅰ°、Ⅱ°、Ⅲ°),CIN(Ⅰ、Ⅱ、Ⅲ级)及鳞癌HPV16、18阳性标本平均拷贝数分别为:3.58×103、1.80×105、1.19×107,随着病变程度加重而逐渐增加,差异有极显著性(P<0.0001)。结论宫颈病变程度与HPV16、18型负荷呈正相关。对宫颈病变组织标本行HPV16、18型检测,对判断宫颈病变发展趋势,积极处理癌前病变,阻断病程、预防宫颈癌的发生将起到重要作用。     

抗人喉癌/抗VEGF双功能抗体制备及应用研究

目的：研制抗人喉癌／抗血管内皮因子（VEGF）双功能克隆抗体，用于喉癌抗血管生成治疗。方法：采用二次杂交瘤技术制备抗人喉癌／抗VEGF双功能抗体。经酶联免疫吸附试验法和SP法检测喉癌及癌前病患者血清及癌组织中VEGF的含量表达。结果：获得6株分泌抗人喉癌／抗VEGF双功能抗体的杂交瘤，经免疫组化证实与喉癌细胞特异性结合率为93％，而与血管内皮细胞结合率为89％。血清中VEGF含量表达，喉癌组与癌前病组及正常对照组相比差异均显著。IgG亚型鉴定为IgG2aBSAb抗体效价为1：25 600倍（ELISA法）。结论：二次杂交瘤法制备的双功能抗体具有均匀性、可控性、效价高、稳定性好，可用于喉癌抗血管生成治疗，动态检测可作为判断喉癌预后的客观指标。     

Additive Antinociception between Intrathecal Sildenafil and Morphine in the Rat Formalin Test

The possible characteristics of spinal interaction between sildenafil (phosphodiesterase 5 inhibitor) and morphine on formalin-induced nociception in rats was examined. Then the role of the opioid receptor in the effect of sildenafil was further investigated. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. For induction of pain, 50 µL of 5% formalin solution was applied to the hind-paw. Isobolographic analysis was used for the evaluation of drug interaction between sildenafil and morphine. Furthermore, naloxone was intrathecally given to verify the involvement of the opioid receptor in the antinociception of sildenafil. Both sildenafil and morphine produced an antinociceptive effect during phase 1 and phase 2 in the formalin test. The isobolographic analysis revealed an additive interaction after intrathecal delivery of the sildenafil-morphine mixture in both phases. Intrathecal naloxone reversed the antinociception of sildenafil in both phases. These results suggest that sildenafil, morphine, and the mixture of the two drugs are effective against acute pain and facilitated pain state at the spinal level. Thus, the spinal combination of sildenafil with morphine may be useful in the management of the same state. Furthermore, the opioid receptor is contributable to the antinocieptive mechanism of sildenafil at the spinal level.     

hCG对JEG-3滋养细胞系表达细胞因子的影响

目的：揭示人类绒毛膜促性腺激素（hCG)是否通过改变细胞因子的生成而影响滋养细胞的侵袭性。方法：以永生化的滋养细胞系JEG－3为研究对象，采用逆转录多聚酶链反应（RT－PCR）方法观察了hCG对JEG－3细胞与细胞侵袭力调节有关的多种因素因子表达的影响，结果：JEG－3细胞表达HGF，IGF－II，VEGF和TGF－β3，且VEGF的表达以VEGF121和VEGF165为主，而不表达IGF，TGF－1β，TGF－β2，IL－β1，25U／mL hCG处理50h可显著降低JEG－3细胞中HGF的表达，同时强烈诱导VEGF121和VEGF165的表达，而其它基因的表达未发生明显变化，结论：HGF对滋养细胞的侵入起促进作用，而VEGF则具有抑制效应，说明，高浓度的hCG可能通过两种细胞因子的自分泌机制对滋养细胞的侵入起抑制作用。