Strain‐dependent induction of allergic rhinitis without adjuvant in mice

BACKGROUND: To date, no murine models have been reported to show the induction of both antigen-specific IgE and nasal eosinophilia, two of the major hallmarks of allergic rhinitis, after local sensitization in the absence of adjuvants, a phenomenon which reflects natural exposure. In this report, we attempted to establish a murine model representing an initiation of allergic rhinitis. METHODS: BALB/c, CBA/J, and C57BL/6 mice were sensitized intranasally to Schistosoma mansoni egg antigen (SEA) solely. After repeated sensitization, serum Ab titers, nasal eosinophilia, and cytokine production by nasal lymphocytes were determined. RESULTS: BALB/c mice produced SEA-specific IgE after repeated sensitization. High-dose sensitization to SEA induced IgE production in CBA/J mice, while C57BL/6 mice did not show the production throughout the period observed, suggesting that IgE production was regulated genetically. BALB/c mice also exhibited nasal eosinophilia after the nasal challenge. In addition, nasal lymphocytes sensitized with SEA intranasally produced significant amount of IL-5 in vitro. CONCLUSIONS: These results suggest that intranasal sensitization with SEA in the absence of adjuvants induces a Th2 immune reaction, reflecting the hallmarks of the initiation of allergic rhinitis both in vivo and in vitro, which is genetically regulated.     

原发性肉碱缺乏致脂质沉积性肌病的临床与病理特点

目的 分析原发性肉碱缺乏致脂质沉积性肌病（LSM）的临床与病理特点。方法 回顾性分析4例可能LSM患者的临床资料。结果 本组患者为亚急性或慢性起病，主要表现为近端肌无力，疲劳不能耐受；血清肌酶有不同程度的升高；肌电图示肌源性损害；病理检查示肌纤维内可见大量细小空泡和裂隙形成；MGT染色无破碎红纤维，油红O染色显示空泡为大量脂滴充填；受累纤维以Ⅰ型纤维为主。电镜证实肌纤维内脂滴堆积，可伴有线粒体的轻度增多。改善能量和糖皮质激素治疗有效。结论原发性肉碱缺乏致LSM是一种以易疲劳和肌无力为主要临床表现的脂质代谢障碍性肌病，病理改变以肌纤维内脂滴堆积为主，一般不伴有线粒体结构的明显异常。糖皮质激素治疗可获得良好疗效。     

经皮肤活体组织检查确诊的Lafora病五例

目的 探讨Lafora病的临床、病理特点及诊断方法.方法 总结分析5例经腋窝皮肤活体组织检查确诊的Lafora病患者的临床和组织病理学特点.5例患者都进行了腋窝皮肤活体组织检查,常规行HE、糖原(PAS)和阿辛蓝-糖原(AB-PAS)染色.结果 5例患者中4例青少年发病,1例成年起病.所有患者均表现为进行性加重的强直阵挛发作、肌阵挛和智能损害,可早期出现性格改变,构音障碍和行走不稳.腋窝皮肤活体组织检查发现Lafora包涵体存在于大、小汗腺的肌上皮细胞和导管细胞内.结论 经皮肤活体组织检查发现PAS阳性圆形或卵圆形包涵体,结合Lafora病典型的临床表现可以确诊该病;皮肤活体组织检查的部位可选择腋窝或腋窝以外的部位.     

乳腺癌患者保乳术联合腔镜腋窝淋巴结清扫术的临床研究

目的 探讨保乳手术联合腔镜腋窝淋巴结清扫术(MALND)对乳腺癌患者上肢功能、应激反应及血管细胞黏附分子-1 (VCAM-1)、细胞间黏附分子-1(ICAM-1)水平的影响。方法 回顾性分析98例乳腺癌患者的临床资料,依据手术方式的不同分为研究组53例和对照组45例。对照组行保乳手术联合传统腋窝淋巴结清扫术(CALND),研究组行保乳手术联合MALND。比较2组术前、术后6个月上肢功能;收集2组患者术前、术后12 h焦虑自评量表(SAS)、抑郁自评量表(SDS)评分以及心率(HR)、平均动脉压(MAP)水平,并对比2组应激反应程度;比较2组患者术前、术后5 d VCAM-1、ICAM-1水平。结果 术后6个月,研究组前屈、后伸、内收、外展、内旋、外旋活动角度大于对照组,差异有统计学意义(P<0.05);术后12 h,研究组SAS、SDS评分及HR、MAP水平低于对照组,差异有统计学意义(P<0.05);术后5 d,研究组VCAM-1、ICAM-1水平低于对照组,差异有统计学意义(P<0.05)。结论 保乳手术联合MALND对乳腺癌患者上肢功能影响小,术后应激反应程度轻...     

Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis. Protein S Study Group

Protein S is a protein C-dependent and independent inhibitor of the coagulation cascade. Deficiency of protein S is an established risk factor for venous thromboembolism. We have used a strategy of specific amplification of the coding regions and intron/exon boundaries of the active protein S gene (PROS1) and direct single-strand solid phase sequencing, to seek mutations in 35 individuals with phenotypic protein S deficiency. Nineteen point mutations (16 novel) in 19 probands (or relatives of probands) with venous thromboembolism are reported here. Fifteen of the 19 mutations were expected to be causal and included 10 missense mutations (Lys9Glu, Glu26Ala, Gly54Glu, Cys145Tyr, Cys200Ser, Ser283Pro, Gly340Asp, Cys408Ser, Ser460Pro, and Cys625Arg). Three of the 15 mutations resulted in premature stop codons (delete T 635 producing a stop codon at position 126, Lys368stop and Tyr595stop) and two were at intron/exon boundaries (+1 G to A in intron d and +3 A to C in intron j). Of the remaining four mutations, three were within intronic sequence and one was a silent mutation within the coding region and did not alter amino acid composition. In two of the 10 missense mutations, reduced plasma protein S activity compared with antigen level suggested the presence of variant (type II) protein S.     

Naratriptan: biological profile in animal models relevant to migraine

The biological profile of naratriptan (N-methyl-3-(1-methyl-4-piperidinyl)-1H-indole-5-ethane-sulphona-mide), a novel 5HT_1B/1D receptor agonist, was investigated in a variety of experimental models of relevance to migraine. Naratriptan has high affinity for human recombinant 5HT_1B and 5HT_1D receptors (pKi = 8.70.03 and 8.30.1, respectively) and causes contractions of dog isolated basilar and middle cerebral artery (EC₅₀ values of 0.11 and 0.07 M, respectively). Naratriptan causes small contractions of human isolated coronary arteries (EC₅₀ value of 0.17 M; maximum contraction equivalent to 33% of 5HT maximum). In anaesthetized dogs, naratriptan causes selective vasoconstriction of the carotid arterial bed (CD₅₀ dose = 193 g kg⁻¹) and, in anaesthetized rats, naratriptan selectively inhibits neurogenic plasma protein extravasation in the dura (ID₅₀ = 4.1 g kg⁻¹). In a variety of antinociceptive tests, naratriptan has no effect even at high doses. In conscious rats and dogs, naratriptan has high oral bioavailability (71% and 95%, respectively). The data show that naratriptan is a selective agonist at 5HT_1B/1D receptors, with a pharmacological profile very similar to that of sumatriptan, albeit 2-3 fold more potent. These observations, coupled with high oral bioavailability in animals, suggest that naratriptan has the profile of an orally effective anti-migraine drug.     

化瘀通络方对局灶性脑缺血大鼠再灌注(MCAO)后脑组织氧自由基和NOS表达的影响

目的:观察化瘀通络方治疗大鼠局灶性脑缺血-再灌注损伤对脑组织自由基及一氧化氮合成酶(NOS)和iNOS变化的影响。方法:制备大鼠局灶性脑缺血再灌注损伤模型,给予化瘀通络方治疗后观察丙二醛(MDA)、超氧化物歧化酶(SOD)及一氧化氮合成酶(NOS)和诱导型一氧化氮合成酶(iNOS)的变化。结果:化瘀通络方可显著降低MDA含量以及iNOS和NOS活性,SOD含量升高。结论:在脑缺血再灌注损伤后,化瘀通络方能抑制脑缺血再灌注后脂质过氧化反应,促进自由基清除,对抗自由基损伤,提高脑组织自身抗氧化能力,降低NOS和iNOS介导脑缺血-再灌注时的神经损伤,保护脑细胞。     

1140919448CD200-dependent suppression of human NK activity by IVIG requires CD200 receptor type 2

Problem: IVIG prepared from plasma of stored human blood can be efficacious in improving pregnancy success in a selected subgroup of patients but RCTs using an IVIG showing inferior suppression of NK activity in vitro have been negative (J Assist Reprod Genet 2006). A significant component of NK suppression by IVIG appears to be due to CD200 released into plasma from PBL during storage at 4C. CD200 receptors (CD200R) are expressed at the fetomaternal interface prior to onset of abortion; CD200R1 mediates direct effects on gamma‐delta T cell development and suppresses alpha‐beta T cell responses in vitro, whereas CD200R2 alters DC so as to facilitate development of alpha‐beta Treg cells. Which receptor(s) mediate NK cell suppression? Methods: Purified human PBL or the CD56⁺ NK cell subset of PBL were used to lyse 51Cr‐labeled K562 cells in vitro. Different IVIG preparations were tested for suppressive ability, and suppression was blocked by either anti‐huCD200 mAb or rabbit anti‐huCD200R1 or R2 antibodies. Results: CD200‐dependent IVIG NK suppressive potency differed among IVIG types (Gammagard>Gamunex>>Gamimmune). CD200‐dependent suppression was blocked by anti‐CD200R antibody able to react with the type 2 receptor. K562 cells did not express receptor, and purified CD56⁺ NK cells were suppressed effectively without the need for non‐NK cells. Conclusions: IVIG may directly express NK cell activity via CD200 binding to CD200R2.     

VEGF-C表达和微淋巴管密度与胃癌淋巴转移的关系及意义

目的探讨胃癌组织血管内皮生长因子C(VEGF-C)表达和微淋巴管密度(MLVD)及两者与胃癌淋巴转移的关系。方法应用免疫组织化学方法检测208例人胃癌组织、40例癌浸润前缘组织及139例人胃正常粘膜组织中VEGF-C、D2-40的表达,对D2-40阳性脉管进行MLVD计数,并结合病理资料进行统计学分析。结果胃癌组织VEGF-C的表达明显高于正常胃粘膜组织(χ2=109.199,P<0.01);胃癌组织中有淋巴结转移(χ2=14.496,P<0.01)或浸润透浆膜(χ2=11.586,P<0.01)组VEGF-C表达水平分别较无转移或浸润未及浆膜组增高。癌浸润前缘组织中MLVD(18.36±15.60个/mm2)明显高于胃癌组(9.41±9.32个/mm2,t=-3.681,P<0.01)和胃正常粘膜组织(7.70±7.69个/mm2,t=-4.180,P<0.01);胃癌淋巴结转移组MLVD(9.81±9.97个/mm2)高于无转移组(6.41±7.85个/mm2,t=2.516,P<0.01),而在浸润透浆膜组(11.20±10.55个/mm2)和未及浆膜组(8.54±9.36个/mm2)MLVD无差别(t=1.467,P=0.472)。另外,在胃癌组织中VEGF-C表达与MLVD呈正相关(F=2.910,P<0.05)。结论VEGF-C在胃癌中的高表达与胃癌浸润深度、淋巴转移密切相关。     

Reciprocal effect of Waardenburg syndrome mutations on DNA binding by the Pax-3 paired domain and homeodomain

The Pax-3 protein contains two DNA-binding domains, a paired domain and a homeodomain. Mutations in Pax-3 cause Waardenburg syndrome (WS) in humans and the mouse Splotch (Sp) phenotype. In the Sp-delayed mouse, a mutation in the Pax-3 paired domain (G9R) abrogates the DNA-binding activity of both the paired domain and the homeodomain, suggesting that they may functionally interact. To investigate this possibility further, we have analyzed the DNA-binding properties of additional point mutants in the Pax-3 paired domain and homeodomain that occur in WS patients (F12L, N14H, G15S, P17L, R23L, G48A, S51F and G66D in the paired domain, V47F and R53G in the homeodomain), the Pax-1 un mutation (G15A) and a substitution associated with Peters' anomaly in the PAX-6 gene (R23G). Within the paired domain, seven of 10 mutations were found to abrogate DNA-binding by the paired domain. Remarkably, these seven mutations also affected DNA binding by the homeodomain, causing either a complete loss (P17L and G66D), a reduction (R23G, R23L, G15S and G15A) or an increase in DNA-binding activity (N14H). In addition, the effect of paired domain mutations occurred at the level of monomer formation by the homeodomain, while the dimerization potential of this domain seemed unaffected in mutants where it could be analyzed. Furthermore, while both homeodomain mutations were found to abolish DNA binding by this domain, the R53G mutation also abrogated DNA binding by the paired domain. The important observation that independent mutations in either domain can affect DNA binding by the other in the intact Pax- 3 protein strongly suggests that the two domains are not functionally independent but bind DNA through cooperative interactions. Modeling the deleterlous mutations on the three-dimensional structure of the paired domain of Drosophila Prd shows that these mutations cluster at the DNA interface, thus suggesting that a series of DNA contacts are essential for DNA binding by both the paired domain and the homeodomain of Pax-3.