Inhibition of experimental autoimmune encephalomyelitis in Lewis rats by nasal administration of encephalitogenic MBP peptides: synergistic effects of MBP 68-86 and 87-99

Induction of mucosal tolerance by inhalation of soluble peptides with defined T cell epitopes is receiving much attention as a means of specifically down-regulating pathogenic T cell reactivities in autoimmune and allergic disorders. Experimental autoimmune encephalomyelitis (EAE) induced in the Lewis rat by immunization with myelin basic protein (MBP) and Freund's adjuvant (CFA) is mediated by CD4+ T cells specific for the MBP amino acid sequences 68-86 and 87-99. To further define the principles of nasal tolerance induction, we generated three different MBP peptides (MBP 68-86, 87-99 and the non- encephalitogenic peptide 110-128), and evaluated whether their nasal administration on day -11, -10, -9, -8 and -7 prior to immunization with guinea pig MBP (gp-MBP) + CFA confers protection to Lewis rat EAE. Protection was achieved with the encephalitogenic peptides MBP 68-86 and 87-99, MBP 68-86 being more potent, but not with MBP 110-128. Neither MBP 68-86 nor 87-99 at doses used conferred complete protection to gp-MBP-induced EAE. In contrast, nasal administration of a mixture of MBP 68-86 and 87-99 completely blocked gp-MBP-induced EAE even at lower dosage compared to that being used for individual peptides. Rats tolerized with MBP 68-86 + 87-99 nasally showed decreased T cell responses to MBP reflected by lymphocyte proliferation and IFN-gamma ELISPOT assays. Rats tolerized with MBP 68-86 + 87-99 also had abrogated MBP-reactive IFN-gamma and tumor necrosis factor-alpha mRNA expression in lymph node cells compared to rats receiving MBP 110-128 nasally, while similar low levels of MBP-reactive transforming growth factor-beta and IL-4 mRNA expressing cells were observed in the two groups. Nasal administration of MBP 68-86 + 87-99 only slightly inhibited guinea pig spinal cord homogenate-induced EAE, and passive transfer of spleen mononuclear cells from MBP 68-86 + 87-99-tolerized rats did not protect naive rats from EAE. Finally, we show that nasal administration of MBP 68-86 + 87-99 can reverse ongoing EAE induced with gp-MBP, although higher doses are required compared to the dosage needed for prevention. In conclusion, nasal administration of encephalitogenic MBP peptides can induce antigen-specific T cell tolerance and confer incomplete protection to gp-MBP-induced EAE, and MBP 68-86 and 87-99 have synergistic effects. Non-regulatory mechanisms are proposed to be responsible for tolerance development after nasal peptide administration.      

Apoptotic cell death in mouse models of GM2 gangliosidosis and observations on human Tay-Sachs and Sandhoff diseases

Tay-Sachs and Sandhoff diseases are autosomal recessive neurodegenerative diseases resulting from the inability to catabolize GM2 ganglioside by beta-hexosaminidase A (Hex A) due to mutations of the alpha subunit (Tay-Sachs disease) or beta subunit (Sandhoff disease) of Hex A. Hex B (beta beta homodimer) is also defective in Sandhoff disease. We previously developed mouse models of both diseases and showed that Hexa-/- (Tay-Sachs) mice remain asymptomatic to at least 1 year of age while Hexb-/- (Sandhoff) mice succumb to a profound neurodegenerative disease by 4-6 months of age. Here we find that neuron death in Hexb-/- mice is associated with apoptosis occurring throughout the CNS, while Hexa-/- mice were minimally involved at the same age. Studies of autopsy samples of brain and spinal cord from human Tay-Sachs and Sandhoff diseases revealed apoptosis in both instances, in keeping with the severe expression of both diseases. We suggest that neuron death is caused by unscheduled apoptosis, implicating accumulated GM2 ganglioside or a derivative in triggering of the apoptotic cascade.      

奥曲肽治疗肝硬变食管静脉曲张破裂出血

0　引言　我院 1996 - 0 6 / 1998- 0 7用奥曲肽治疗肝硬变食管静脉曲张破裂出血 19例 ,并与垂体后叶素作了对照 .1　对象和方法1.1　对象　经内镜证实食管静脉曲张破裂出血 37例 ;男 32例 ,女 5例 ;年龄 42～ 6 9岁 .肝炎后肝硬变 32例 ,乙醇性肝硬变 3例 ,血吸虫性肝硬变 2例 .按就诊顺序随机分为治疗组19例 ,对照 18例 .估计出血量 :治疗组 (146 3.6± 375 .8) m L;对照组 (144 9.5± 36 8.4) m L .出血至治疗间隔时间 :治疗组(11.6± 3.5 ) h;对照组 (11.2± 3.6 ) h.两组的年龄、性别、肝功 Child分级、食管静脉曲张程度、出血量、出…     

五灵胶囊治疗慢性肝炎的临床随访观察

0　引言　五灵丸治疗慢性病毒性肝炎取得了较好的疗效 [1 ] ,但五灵丸为大蜜丸 ,不易被患者所接受 ,且其消化道副作用较明显 .为此 ,我们改进剂型 ,研制成五灵胶囊 ,为明确其能否保持远期疗效 ,我们对用该药治疗的患者进行随访观察 ,同时与五灵丸的疗效进行比较 .1　对象和方法1.1　病例选择　按慢性肝炎的诊断标准选择住院患者 10 0例 ,随机分为两组 .治疗组为五灵胶囊组 ,对照组为五灵丸组 .每组各 5 0例 .治疗组轻度 19例 ,中度 2 0例 ,重度 11例 .对照组轻度 2 0例 ,中度 18例 ,重度 12例 .两组均选择 18～5 8岁 ,病程 1～ 2 0 a.平均 4…     

激光生物效应及医学应用研究

激光作用于生物体会产生物理、化学或生物学的效应,激光正是通过这些效应达到医学基础研究、诊断和治疗疾病的目的.本文简介了激光与生物组织相互作用所产生的生物效应,概述了激光生物效应在生物学和医学研究中的应用.     

Risk of refracture through unicameral bone cysts of the proximal femur

The authors determined the results after traction or traction and hip spica treatment of the initial fractures through unicameral bone cysts of the proximal femur in 20 children. All of the eight displaced fractures healed, but with coxa vara and avascular necrosis in one, coxa vara in a second, and coxa breva in a third. Spontaneous healing of the cyst occurred in three of the eight children; satisfactory healing was achieved and maintained after intralesional corticosteroid injections in four of the eight children. In the remaining child with a displaced fracture, reactivation of the cyst and exercise-related pain, indicative of an incipient refracture, occurred 3 years after initial presentation. All of the 12 undisplaced fractures healed without deformity or avascular necrosis. Intralesional corticosteroids were used in all of the 12 children because none of them showed spontaneous healing of their cysts. Satisfactory radiographic healing was achieved 1 year after presentation in all of the 12 children. However, one or more refractures resulting from reactivation of the cyst occurred in 6 of the 12 children 2 to 5 years after initial presentation. The results of this study indicate that satisfactory radiographic healing needs to be achieved by the end of the first year and needs to be maintained thereafter to prevent refractures.     

N-(6,6-二甲基-2-庚烯-4-炔基)-N-甲基-α-取代-1-(4-取代)萘甲胺类的合成及抗真菌活性

根据氮唑类和烯丙胺类抗真菌化合物的构效关系、作用机理。设计合成了30个N-(6,6-二甲基-2-庚烯-4-炔基)-N-甲基-α-取代-1-(4-取代)萘甲胺类化合物。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物Ⅰ_1a的真菌活性大致与克霉唑相当,对白念珠菌的活性明显高于naftifine和terbinafine,但对其它七种菌株的活性均不及naftifine和terbinafine;化合物Ⅲ_1a对八种试验菌株的活性均与terbinafine相当。     

4-{[2-(1H-咪唑基)-1-(4-取代苯基)乙氧基]甲基}苯甲酸类化合物的合成及其抑制血小板聚集的作用

根据咪唑类和吡啶类TXA₂合成酶抑制剂的构效关系和作用机制,设计合成了20个4-{[2-(1H-咪唑基)-1-(4-取代苯基)乙氧基]甲基}苯甲酸类化合物。初步体外药理试验结果表明,所有化合物都有不同程度的抑制TXA₂合成酶能力,从而抑制花生四烯酸(AA)诱导的血小板聚集。化合物15的抑酶活性最强,以IC₅₀值相比,其活性为Dazoxiben的55.6%。并初步探讨了这类化合物的构效关系。