骨髓间充质干细胞-支架复合体向软骨诱导分化的实验研究

目的:以骨髓间充质干细胞作为种子细胞,探索组织工程化软骨的构建.方法:分离、获取、扩增骨髓间充质干细胞,通过将扩增的骨髓间充质干细胞接种于聚羟基乙酸(PGA)上,在成软骨诱导因子作用下在体外诱导培养3周后,将实验组和对照组的标本转植入自体兔腹腔内,进行体内培养6～12周后,再进行检测,评估工程化软骨的形成.结果:骨髓间充质干细胞接种于PGA支架上后,经过体外诱导培养和体内培养后,获得标本(7/10)出现软骨组织外观,进行组织学切片可见软骨陷窝,进行Ⅱ型胶原蛋白的免疫组化、Ⅱ型胶原mRNA原位杂交均为阳性.结论:兔骨髓间充质干细胞在成软骨诱导剂作用下,经体外和体内培养后,可生成组织工程化类软骨.     

肝豆状核变性ATP7B基因Arg778Leu突变型与临床表现的相关性研究

目的:探讨肝豆状核变性(Hepatolenticular Degeneration,HLD)患者ATP7B基因Arg778Leu突变型与临床表现之间的相关性。方法:采用PCR和DNA测序技术检测91例HLD患者ATPTB基因8号外显子Arg778Leu突变,将91例患者分为纯合突变组、杂合突变组和无突变组,并与临床表现(性别、起病年龄、临床表型)进行相关分析。结果:在91例HLD患者中检出26例Arg778Leu纯合子和40例杂合子,其余25例无此突变。患者性别、起病年龄、临床表型与该突变型均无相关性。结论:Arg778Leu突变与患者性别、起病年龄及临床表型无关。     

Autosomal dominant juvenile vitreoretinal degeneration and retinal detachment

To study the inheritance and clinical picture of a new form of vitreoretinal dystrophy I examined 18 family members of a family with six generations. Seven patients, three male and four female, in three consecutive generations were observed to be affected indicating autosomal dominant inheritance. The disease was characterized by juvenile degeneration of the vitreous with detachment of the vitreous body and some floating vitreous opacities, cystoid degeneration of the peripheral retina with whitish glistening stippled areas of superficial retinal degeneration, spotty hyperpigmentation, patches of retinal atrophy with pigmentations, occasional atrophic retinal holes, and in four family members at the age of 4 to 12 years, unilateral or bilateral retinal detachment with breaks in the peripheral retina. Most patients had hyperopia with or without astigmatism. In eyes without detached retina, the disease did not show any marked progression, the lens was clear, the posterior fundus and the retinal and choroidal vessels were normal, and the visual acuity, visual fields, dark adaptation, colour vision, electroretinograms, and visually evoked response findings were normal.     

Long-term neuroretinal full-thickness transplants in a large animal model of severe retinitis pigmentosa

Background The purpose of this study was to explore neuroretinal transplantation in a large animal model of severe retinitis pigmentosa and to establish graft development, long-term survival, graft-host integration, and effects on the host retina. Methods Rhodopsin transgenic pigs, aged 6 months, received in one eye a fetal full-thickness neuroretinal sheet in the subretinal space by means of vitrectomy and retinotomy. Six months postoperatively, eyes were studied in the light microscope and with immunohistochemical markers. Full-field electroretinography (ERG) was performed at 4 and 6 months. Results Laminated grafts with well-organized photoreceptors, rod bipolar cells, and Müller cells were found in five of six eyes. Neuronal connections between graft and host retina were not seen. In the five eyes containing a graft, the number of surviving rods in the host retina was significantly higher compared with unoperated eyes. The ERG did not reveal any significant difference in b-wave amplitude between operated and control eyes, but the cone-derived response in operated eyes increased significantly from 4 to 6 months while the rod response in control eyes decreased significantly. Conclusions Fetal full-thickness neuroretina can be transplanted safely to an eye with severe retinal degeneration. In their major part, the transplants develop a normal laminated morphology and survive for at least 6 months. Graft and host retinal neurons do not form connections. Retinal function in the host is reduced initially by the surgical trauma, but the presence of a well-laminated graft counteracts this effect and rescues rods from degeneration. Supported by The Foundation Fighting Blindness (grant# C-NC02-798-0078), The Faculty of Medicine, University of Lund, The Swedish Research Council, The Princess Margaretas Foundation for Blind Children, The 2nd ONCE International Award for New Technologies for the Blind.     

Principles for reconstruction of traumatic ear defects

Summary Traumatic defects of the auricle are quite common. The eventual success of the repair is considerably influenced by the initial treatment. The different parts of the auricle require different approaches. This paper presents our methods for repairing damage to the cartilaginous frame using autologous ear cartilage grafts, and local flaps from the mastoid region to cover soft tissue defects.     

预变神经段修复神经缺损的实验研究

目的探讨不同预变时间组移植神经对神经再生的影响。方法以ＳＤ大鼠的不同预变时间组的尺神经作为移植神经，修复其正中神经的缺损。实验侧按移植神经预变时间的不同分为０、１、２、３、４、８周共６组，每组６只ＳＤ大鼠。移植后１２周，检测实验侧趾屈肌群的张力、最大收缩力、再生神经的形态及神经轴突的截面积。结果用预变１周的尺神经修复正中神经后，其趾屈肌群的张力及最大收缩力的恢复率达到正常对照组的８１．１％及８５．９％。显微镜下观察，预变１周组和其它各时间组相比，其再生的神经轴突最多，发育最成熟。结论用预变１周的神经段修复神经缺损，其神经再生能力最佳     

Conditions of Alzheimer-type dementia in the old-old and oldest-old patients with special reference to extreme conditions of brain aging

A neuropathological study on 1540 consecutive autopsy brains ranging from 60 to 107 years of age revealed the following points. (1) Of the of the demented cases of the plaque-predominant type, 93% were complicated with multiple tiny cortical infarcts. They showed a tendency for dementia to develop before or after the appearance or worsening of a systemic disorder such as cardiovascular disease, respiratory infection and cancer. However, there was no case showing Alzheimer-type dementia (ATD). (2) The plaque-predominant type might be an extreme condition of brain aging in terms of senile plaques (SP). It is likely that although the pathological appearance of SP alone is not responsible for dementia, its coexistence with multiple cortical infarcts could be the cause of dementia. Therefore, this type should be distinguished from ATD. (3) Primary hippocampal degeneration could also be an extreme condition of brain aging in terms of neurofibrillary tangles. This condition was different pathologically from the hippocampal lesion in ATD. (4) Several characteristics of old-old and oldest-old patients were clarified.     

锌指蛋白440在人膝关节OA软骨细胞损伤中的促进作用及机制

探讨锌指蛋白440（ZNF440）在膝关节（Knee）骨性关节炎（OA）软骨细胞损伤和退化变性病理生理学中的作用。方法 Knee软骨中分离人软骨细胞,分为对照组、Knee OA组、ZNF440-GFP（绿色荧光蛋白）组、ZNF440-siRNA组和Scriptaid组。通过免疫组化和Western blotting测定ZNF440在Knee OA软骨中的表达。用ZNF440-GFP过表达和ZNF440-siRNA转染细胞,并给予白细胞介素-1β(IL-1β)刺激。分别用qPCR和WB检测分解代谢、合成代谢和凋亡相关标志物的mRNA和蛋白表达水平。生物信息学分析有可能抑制ZNF440表达的化合物。结果 与对照组相比,ZNF440在Knee OA软骨中的表达有所增加(P＜0.05);ZNF440过表达明显增加基质金属蛋白酶（MMP）13和PARP p85的表达,并降低COL2A1表达(P＜0.05);siRNA敲除ZNF440可部分逆转IL-1β刺激诱导的人Knee OA软骨细胞的分解代谢和细胞凋亡(P＜0.05)。通过生物信息学分析和验证实验,确定Scriptaid是一种有可能下调ZNF440表达的化合物。Scriptaid处理可降低OA软骨细胞中ZNF440的表达,同时降低过表达ZNF440的人Knee OA软骨细胞中MMP13和PARP p85的表达(P＜0.05)。结论 ZNF440在人Knee OA软骨中的表达明显增加,可能通过调节细胞中炎症、分解代谢和凋亡标志物的表达参与软骨退行性机制。此外,Scriptaid可降低ZNF440的表达,并抑制其在OA软骨细胞中的破坏作用     

Amyotrophic lateral sclerosis with ophthalmoplegia and multisystem degeneration in patients on long-term use of respirators

Summary We describe two patients with sporadic amyotrophic lateral sclerosis (ALS), who had developed progressive external ophthalmoplegia of a predominantly supranuclear type while they survived on respirators, and displayed histopathological abnormalities both typical and atypical of ALS. Patient 1 was a 43-year-old man with ALS of 5-year duration, who had initially exhibited fulminant ALS, and remained on a respirator for 4 years. Patient 2 was a 51-year-old man with ALS of 13-year duration, who remained on a respirator for 8 years. Both patients died in a totally locked-in state. Autopsy of both patients revealed not only histopathological abnormalities consistent with ALS, but also multisystem degeneration which involved the pontine tegmentum, substantia nigra, Clarke's dorsal nuclei and spinocerebellar tracts. In addition, Patient 2 displayed intracyto-plasmic neuronal basophilic inclusion bodies which exhibited marked immunoreactivity to anti-ubiquitin antibodies. Our case reports indicate that the longer survival which is possible through the use of respirators may make one subgroup of ALS patients prone to develop atypical clinical and neuropathological features which are not observed during the natural cours of ALS.Supported by a Grant-in-Aid from the Research Committee of CNS Degenerative Diseases, the Ministry of Health and Welfare of Japan, and by a Grant from Nihon University School of Medicine, Tokyo