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…     

Köbberling type of familial partial lipodystrophy: an underrecognized syndrome

OBJECTIVE: The phenotypic expression of partial lipodystrophy is present in two familial syndromes: familial partial lipodystrophy type 1 (FPLD1), with fat loss from the extremities, and central obesity and FPLD type 2, with fat loss from the extremities, abdomen, and thorax. The latter disorder is associated with mutations in the LMNA gene. FPLD1 is thought to be rare. Here, we report 13 subjects with FPLD1, suggesting that this syndrome is more common than previously thought. RESEARCH DESIGN AND METHODS: Fasting glucose, plasma lipids, leptin, HbA(1c), and anthropomorphic measurements were evaluated in 13 subjects with clinical features of FPLD1 and are compared with two age-matched control groups, with and without diabetes. RESULTS: Only women with clinical features of FPLD1 have been identified. Although they lack extremity and gluteal subcutaneous fat, they do have truncal obesity. Skinfold thickness on the arm and leg was significantly less than that in control subjects. The ratio of skinfold thickness from abdomen to thigh was significantly higher in subjects, suggesting an easy method for identifying affected patients. FPLD1 subjects also had components of the metabolic syndrome, including hypertension, insulin resistance, and severe hypertriglyceridemia resulting in pancreatitis. Premature coronary artery disease was present in 31% of subjects. None of the subjects had coding mutations in the LMNA gene or in the gene coding for peroxisome proliferator-activated receptor (PPAR)-gamma. CONCLUSIONS: FPLD1 is more common than previously described, but the diagnosis is often missed. Early recognition and intensive treatment of hyperlipidemia and diabetes in FPLD1 is important for prevention of pancreatitis and early cardiovascular disease.     

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.     

Microglandular adenosis or microglandular adenoma? A molecular genetic analysis of a case associated with atypia and invasive carcinoma

Aims: Microglandular adenosis (MGA) is a rare breast lesion, which has long been considered to be hyperplastic. However, atypical forms of MGA (AMGA) and invasive carcinomas arising in the background of MGA are recorded. Recent studies have suggested that MGA may be a non‐obligate precursor of invasive carcinomas that are negative for hormone receptors and lack HER‐2 overexpression (triple‐negative phenotype). The aim of this study was to determine whether MGA is clonal and whether it harbours chromosomal aberrations similar to those found in matched invasive ductal carcinoma of no special type (IDC‐NST). Methods and results: We report on a case comprising MGA, AMGA and a high‐grade IDC‐NST. The three components were separately microdissected and subjected to genetic analysis with high‐resolution microarray comparative genomic hybridisation. Identical genetic changes were detected in all components with subsequent acquisition of additional genetic aberrations in the invasive component, suggesting that MGA was the substrate for the development of the invasive carcinoma. Immunohistochemistry revealed concordant profiles across all components, characterized by triple‐negative phenotype and variable positivity for basal markers. Conclusions: Similar to adenomas, MGA is, at least in some cases, a clonal lesion and may be a non‐obligate precursor of a subgroup of high‐grade triple‐negative and basal‐like breast carcinomas.