Humoral and Cellular Responses to Influenza Vaccination in Human Recipients Naturally Tolerant to a Kidney Allograft

Rare kidney allograft recipients enjoy unaltered graft function years after interruption of their immunosuppressive treatment. To assess the extent to which this state of 'operational tolerance' (TOL) is specific to the graft and not the result of a global immunodeficiency, we analyzed the response of such patients following influenza vaccination. Hemagglutination inhibition titers and frequency of IFNgamma-secreting T cells were measured before 1 and 3 months after vaccination. The proportion of healthy volunteers (HV) responding to vaccine was significantly higher than that of immunosuppressed (IS) patients. Three 'TOL' patients presented a humoral response similar to that of HV, whereas the two others had a poor response, like the IS recipients. Although the small number of patients does not allow for definitive conclusions to be made, these data suggest that the status of tolerance may be heterogeneous, with some patients with a global immunodeficiency and others with an adapted response to vaccination.     

Gamma-hydroxybutyric Acid Tolerance and Withdrawal in a Rat Model

Long-term daily use of gamma-hydroxybutyrate (GHB) and related compounds has recently been associated with a withdrawal syndrome. To the best of the authors' knowledge, there are currently no animal models of GHB withdrawal. OBJECTIVES: The authors studied and described the effect of chronic dosing of GHB (3-6 days) on tolerance and withdrawal in a rat model. METHODS: Rats were administered GHB every three hours via intraperitoneal catheter. Groups of rats (2 per group) were dosed with GHB for either 3 (24 doses), 4 (32 doses), 5 (40 doses), or 6 (48 doses) days. The GHB dose was 0.25 g/kg for doses 1-8, 0.75 g/kg for doses 9-12, 1 g/kg for doses 13-16, 1.25 g/kg for doses 17-24, 1.5 g/kg for doses 25-32, 1.75 g/kg for doses 33-40, and 2 g/kg for doses 41-48. Following the last dose of GHB, the rats were scored using a 16-point ethanol intoxication-withdrawal scale rating spontaneous behaviors, response to handling, grooming, and neurological signs. Lower scores indicate intoxication, while higher scores indicate withdrawal. Scores were recorded at hours 0, 1, 2, 3, 4, 5, 6, 9, 12, and 24. RESULTS: Tolerance: Rats dosed with GHB for more days were less intoxicated one hour after their last GHB dose despite receiving higher doses. WITHDRAWAL: The scores for all rats dosed with GHB increased at hours 4 (p = 0.028), 5 (p = 0.037), 6 (p = 0.007), and 9 (p = 0.024) after the last dose, indicating withdrawal. The scores demonstrated a linear increase dependent upon the number of days of GHB dosing at hours 3 (p < 0.000), 4 (p = 0.004), 5 (p = 0.002), and 12 (p = 0.039) as well as prior to the last dose at hour 0 (p = 0.000). No rats developed seizures. CONCLUSIONS: Tolerance and mild withdrawal in rats can be induced by administering intraperitoneal GHB every three hours for 3-6 days. More prolonged dosing and higher doses of GHB may be necessary to induce severe withdrawal.     

头皮冠状切口的并发症及其防治

目的：对采用头皮冠状切口所引发的并发症进行分析，探讨防治策略。方法：对我科2003-01～2006—07应用头皮冠状切口行颅颌面骨折修复重建、颌面部肿瘤切除与缺损修复、先天性颅颌面畸形矫正的221例中发生并发症的40例进行分析总结。结果：18例出现头皮麻木及感觉异常，9例有较宽切口瘢痕，6例出现脱发，4例发生颞窝凹陷，2例发生头皮下血肿，2例出现单侧面神经颞支损伤，1例发生鼻眶区肥厚。结论：头皮冠状切口具有切口隐蔽、面部疤痕不明显，显露充分的优点，但对其并发症也不容忽视。应根据具体情况选择合适的切口类型，术中精细的解剖、神经血管的良好保护以及正确的缝合方法可减少并发症的发生。     

Stimulatory and inhibitory epitopes in the T cell responses of mice to Der p 1

BACKGROUND: The responses of mice to the mite allergen Der p 1 have been used to study the mechanisms of allergic sensitization and the development of new types of immunotherapy. Many of the studies require a knowledge of the T cell epitopes, and because Der p 1 is polymorphic, the effect of natural amino acid substitution in the allergen. The intranasal administration of peptides containing T cell epitopes can induce a mucosal tolerance but it is not known if the major activity is limited to stimulatory peptides and if, as found for autoimmunity, some epitopes are not inhibitory. OBJECTIVE: To determine and compare the sequences of Der p 1 which contain stimulatory epitopes for the high responding H-2(b) and H-2(q) mice and the sequences which induce tolerance by intranasal administration of peptides. METHODS: T cell responses of mice immunized with Der p 1 were measured by in vitro T cell stimulation assays so an extensive study of epitope recognition and intranasal tolerance could be made. Synthetic peptides were used to examine the stimulatory and inhibitory ability of all Der p 1 sequences and to map the major H-2(b) epitope in detail. This included the effect of the common polymorphic amino acid 124 substitution found within this epitope. RESULTS: Three and two regions, respectively, were found to contain stimulatory T cell epitopes for H-2(b) and H-2(q) mice. The peptides in these regions were also the most active at inducing intranasal tolerance for the responding haplotype. The correspondence between inhibitory and stimulatory peptides was maintained for the fine mapping of the major H-2(b) epitope. This was found about a core region of 118-126 which was overlapping but separate to a consensus sequence for the binding of endogeneous peptides. Peptides with alanine at the naturally polymorphic residue 124 stimulated and inhibited responses to Der p 1 more effectively, while peptides with the valine 124 variant were immunogenic but poorly cross-reactive. CONCLUSIONS: The intranasal administration of peptides representing each of five epitopes recognized by two strains of mice were able to induce mucosal tolerance and the major tolerizing activity was limited to these epitopes. The position of the core major epitope for C57 mice, which differs from a previously predicted epitope, and its specificity for the natural alanine 124 variant is described.     

Effects of d-amphetamine injected into the nucleus accumbens on ethanol reinforced behavior

Rats, initiated to self-administer 10% (v/v) ethanol in an operant situation using the sucrose-fading procedure, received bilateral n. accumbens microinjections of d-amphetamine prior to operant sessions. Doses of 4 micrograms, 10 micrograms and 20 micrograms/brain were administered and some animals also received a 4 microgram/brain dose of LY171555. Three different effects were observed: increased, decreased and no change in total session responding. There was no clear relation between injection area in the n. accumbens and type of effect observed. For either an increase or decrease in total session responding, momentary response rates were decreased. Both d-amphetamine and LY171555 produced similar results. The data support the hypothesis that dopamine in the n. accumbens is involved with ethanol reinforced operant responding but in a complex manner.     

转hCTLA4Ig树突状细胞诱导T细胞免疫耐受的实验研究

目的　通过逆转录病毒载体将人CTLA4Ig转染DCs ,探讨转人CTLA4Ig(hCTLA4Ig)树突状细胞 (DCsRev)诱导T细胞免疫耐受的可能性。方法　通过重组逆转录病毒将目的基因hCTLA4Ig转染到大鼠骨髓来源的DCs中 ,通过流式细胞检测目的基因hCTLA4Ig表达及DCs表面分子的改变 ;通过混合淋巴细胞反应 (MLR)检测DCsRev抑制T细胞免疫反应的能力。 结果　重组逆转录病毒转染DCs的最大效率为 91 2 5 % ;在功能上 ,DCsRev不但丧失了刺激MLR的能力 ,并且能够强烈抑制MLR中反应T细胞的增殖 ,而且抑制率与加入DCsRev的数量和DCsRev预处理反应T细胞的时间长短有关。具体来说 ,DCsRev数量在 10 3 ～ 10 4之间时 ,抑制率与剂量呈正相关 ,最高为 71 96%。而当DCsRev数量达到 5× 10 4抑制率下降为 5 9 2 %。在 12～ 48h之间 ,随着预处理时间的延长 ,抑制率却不断下降 ,预处理 12h抑制率最高 ,为 99 6%。但不做预处理 ,在反应开始时同时加入DCsRev ,则抑制率明显降低 ,仅为 5 9 2 %。对腹腔注射DCsRev大鼠脾T淋巴细胞体外分析表明 ,DCsRev也能在动物体内诱导耐受 ,但这种免疫耐受状态不能维持终身。结论　通过逆转录病毒载体将人CTLA4Ig转染DCs,不但DCs表面CD86分子被CTLA4Ig有效的封闭 ,并且能够诱导抗原特异性T细胞的免疫耐受     

谷胱苷肽S转移酶在口腔鳞癌中的表达

目的　研究异型增生程度不同的口腔白斑和不同分级的鳞癌中谷胱苷肽S转移酶π(GST π)的表达 ,探讨GST π在口腔鳞癌发生发展中的作用。　方法　采用免疫S -P法 ,对 5 4例轻、中、重度异型增生 ,4 7例高、中、低分化的口腔鳞癌 ,7例口腔粘膜上皮单纯增生患者组织进行GST π检测。　结果　口腔粘膜上皮单纯增生组织中未见GST π的表达 ,轻、中、重度异型增生病例中的GST π阳性率分别为4 7.8%、5 2 .9%和 6 4 .2 % ,高于单纯增生组 (P <0 .0 1) ;高分化鳞癌GST π阳性率为 6 4 .7% ,中、低分化鳞癌组分别为 2 8.5 %及 2 2 .2 % ,中、低分化鳞癌组表达均低于高分化鳞癌组及异型增生组 (P <0 .0 5 )。　结论　GST π表达的变化与口腔鳞癌早期的发生发展密切相关     

CD80mAb协同imDC诱导同种异体大鼠胰十二指肠移植免疫耐受

目的 观察共刺激分子阻断剂CD80单克隆抗体（CD80mAb）在协同未成熟树突细胞（imDC）诱导同种异体大鼠胰十二指肠移植免疫耐受中的作用。方法 建立糖尿病大鼠胰十二指肠移植动物模型；4E5杂交瘤细胞株BABIMC小鼠腹腔注射，抽取腹水，分离纯化后获得CD80mAb；分离供体大鼠骨髓来源DC细胞前体，经GM—CSF、IL-4体外刺激后。再加入IL-10共培养，鉴定为imDC；移植前7d，将2×10^6imDC经静脉途径注射至受体体内，同时分别给予生理盐水1ml、CD80mAb5mg连续14d。结果 四组受体大鼠移植后中位生存时间分别为12．7d、32．4d、50．2d、92．0d，实验组存活时间明显延长；组织学观察发现移植后7dCD80mAb＋imDC组移植物形态尚完整，淋巴细胞浸润减少；混合淋巴细胞反应证实移植后7dCD80mAb＋imDC组供受体间呈低反应性。结论 共刺激分子阻断剂CD80mAb能够协同imDC诱导受体T细胞对移植物的免疫耐受，降低宿主对移植物的急、慢性排斥反应，延长移植物的存活时间。     

包含颈外静脉的颈阔肌肌皮瓣修复口腔癌切除后缺损

目的探讨将颈外静脉包含在颈阔肌肌皮瓣内修复口腔癌切除后缺损的手术方法。方法先形成蒂在颌缘下包含颈外静脉的颈阔肌肌皮瓣，待口腔肿瘤切除后，将肌皮瓣经口底隧道引入口腔修复缺损。结果临床应用17例，肌皮瓣均无血运障碍，100％存活，其中有2例发生口面痿，经换药后痿口完全闭合。结论将颈外静脉包含在颈阔肌肌皮瓣内有助于肌皮瓣血循环的改善和存活率的提高。