Cellular immunity and hypersensitivity as components of periodontal destruction

BACKGROUND: Cellular immunity has been implicated in periodontal destruction for over 25 years. Studies in the 1970s used lymphocyte transformation and lympho-kine assays to establish a role for cell-mediated mechanisms in periodontal disease. lmmunohistological studies subsequently showed that the formation of gingivitis followed a similar pattern to the formation of a delayed type hypersensitivity reaction. Further functional studies suggested that a T cell/macrophage immunoregulatory imbalance may exist locally in the periodontitis lesion and that this imbalance may be antigen specific. RECENT EVIDENCE: More recently, T cell subsets have been dichotomised on the basis of their cytokine profiles. In general, Thl cells produce IL-2 and IFN-gamma while Th2 cells produce IL-4, IL-5 and IL-6. The major function of Th l cells is to mediate delayed type hypersensitivity. In contrast the major function of Th2 cells is to provide B cell help.
HYPOTHESIS: A model for periodontal disease has now been developed based on this functional dichotomy which provides a framework for the study of cytokine profiles in periodontal disease. Early studies in this context have demonstrated a higher proportion of IL-4 producing cells in periodontitis tissues suggesting a role for Th2 cells in the progressive lesion. Clonal studies have shown that the selection of a particular cytokine profile is not antigen dependent and that differences may be due to the host susceptibility although this remains to be determined.
CONCLUSION: These emerging data clearly establish a role for cell-mediated mechanisms in the control of periodontal destruction and raise the possibility that in the future cytokine therapy for the treatment of periodontal disease in susceptible subjects may become a viable option.     

The lipoprotein-associated coagulation inhibitor that inhibits the factor VII-tissue factor complex also inhibits factor Xa: insight into its possible mechanism of action

Blood coagulation is initiated when plasma factor VII(a) binds to its essential cofactor tissue factor (TF) and proteolytically activates factors X and IX. Progressive inhibition of TF activity occurs upon its addition to plasma. This process is reversible and requires the presence of VII(a), catalytically active Xa, Ca2+, and another component that appears to be associated with the lipoproteins in plasma, a lipoprotein-associated coagulation inhibitor (LACI). A protein, LACI(HG2), possessing the same inhibitory properties as LACI, has recently been isolated from the conditioned media of cultured human liver cells (HepG2). Rabbit antisera raised against a synthetic peptide based on the N-terminal sequence of LACI(HG2) and purified IgG from a rabbit immunized with intact LACI(HG2) inhibit the LACI activity in human serum. In a reaction mixture containing VIIa, Xa, Ca2+, and purified LACI(HG2), the apparent half-life (t1/2) for TF activity was 20 seconds. The presence of heparin accelerated the initial rate of inhibition threefold. Antithrombin III alpha alone had no effect, but antithrombin III alpha with heparin abrogated the TF inhibition. LACI(HG2) also inhibited Xa with an apparent t1/2 of 50 seconds. Heparin enhanced the rate of Xa inhibition 2.5-fold, whereas phospholipids and Ca2+ slowed the reaction 2.5-fold. Xa inhibition was demonstrable with both chromogenic substrate (S-2222) and bioassays, but no complex between Xa and LACI(HG2) could be visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Nondenaturing PAGE, however, showed that LACI(HG2) bound to Xa but not to X or Xa inactivated by diisopropyl fluorophosphate. Thus, LACI(HG2) appears to bind to Xa at or near its active site. Bovine factor Xa lacking its gamma-carboxyglutamic acid-containing domain, BXa(-GD), through treatment with alpha-chymotrypsin, was used to further investigate the Xa requirement for VIIa/TF inhibition by LACI(HG2). LACI(HG2) bound to BXa(-GD) and inhibited its catalytic activity against a small molecular substrate (Spectrozyme Xa), though at a rate approximately sevenfold slower than native BXa. Preincubation of LACI(HG2) with saturating concentrations of BXa(-GD) markedly retarded the subsequent inhibition of BXa. The VII(a)/TF complex was not inhibited by LACI(HG2) in the presence of BXa(-GD), and further, preincubation of LACI(HG2) with BXa(-GD) slowed the inhibition of VIIa/TF after the addition of native Xa. The results are consistent with the hypothesis that inhibition of VII(a)/TF involves the formation of a VIIa-TF-XA-LACI complex that requires the GD of XA.(ABSTRACT TRUNCATED AT 400 WORDS)     

Clinical significance of anti-Yt(b). Report of a case using a 51chromium red cell survival study

Several published reports have documented the variable survival of Yt(a+) red cells (RBC) in patients with anti-Yt(a) as measured by 51Chromium (Cr)-labeled RBC survival studies. Similar studies with anti-Yt(b) have not been reported. A 51Cr-labeled RBC survival study was performed using Yt(b+) RBCs and a monocyte monolayer assay in a young hemodialysis patient who required chronic transfusion therapy and who had developed anti-Yt(b). The survival of the transfused RBCs was 100 and 93 percent at 1 and 24 hours, respectively, with a half life of 21 days at termination of the study (normal, 28 to 32 days). These results showed no evidence of rapid destruction of the Yt(b+) RBCs, indicating that this patient could be transfused safely with blood from Yt(b+) donors. Long-term survival of the 51Cr-labeled Yt(b+) RBCs was shortened moderately, however, a finding that correlated with a slightly abnormal monocyte monolayer assay test.     

Donor levels of serum alanine aminotransferase activity and antibody to hepatitis B core antigen associated with recipient hepatitis C and non- B, non-C outcomes

BACKGROUND: Hepatitis virus(es) that are neither hepatitis B (HBV) nor hepatitis C (HCV) (non-B, non-C [NBNC]) may be transmitted by transfusion. The present study assessed donor values for alanine aminotransferase (ALT) and antibody to hepatitis B core antigen (anti- HBc) for their association with HCV and NBNC hepatitis outcomes among allogeneic blood recipients. STUDY DESIGN AND METHODS: Data on blood donors and recipients enrolled in the Transfusion- Transmitted Viruses Study in four United States cities from 1974 through 1980 were supplemented by anti-HBc testing of donors and anti-HCV evaluation of recipients. Two statistical approaches estimated the value of these indirect tests in detecting donors associated with HCV seroconversion and NBNC hepatitis in recipients. RESULTS: For HCV cases, donor ALT alone (at > or = 60 IU/L) had a sensitivity and a specificity of 30 and 96 percent, respectively, and anti-HBc alone (at > or = 60% inhibition) had a sensitivity and specificity of 53 and 86 percent, respectively. The two markers combined had a sensitivity and a specificity of 69 and 83 percent. For NBNC hepatitis cases, each measure had low sensitivity (20%) that was not improved by using both (28%) [corrected]. CONCLUSION: The indirect tests proved to be equal in sensitivity to the first-generation anti-HCV tests. The positive predictive power of these indirect tests in the 1980s was sufficient to affect HCV incidence in studies during that period. Improved anti-HCV assays, however, replaced the need for indirect tests. The sensitivity of indirect tests for NBNC hepatitis contributed little.     

鸡胚胎素对小鼠红细胞数量及免疫器官质量的影响

目的:建立血虚和免疫抑制动物模型,观察鸡胚胎低温提取物对其红细胞造血以及免疫器官质量的影响。方法:实验于2001-04/2002-09在新乡医学院药物研究室完成。①实验材料:健康昆明种小鼠50只,雌雄各半。鸡胚胎素[中国发明专利公开(公告)号:CN1748713],符合研究者申报专利时提出的质量检验标准。②鸡胚胎素对血虚模型小鼠红细胞数值及血红蛋白含量的影响:取20只小鼠,随机排列表法分为鸡胚胎素组、模型对照组,10只/组,建立失血性血虚动物模型。失血后24h当红细胞数<3.2×1012L-1、血红蛋白含量<84g/L,且小鼠外观出现皮色苍白、食欲不振等现象时,代表造模成功。次日,鸡胚胎素组给予鸡胚胎素5g/(kg·d)灌胃,模型对照组给予生理盐水20mL/(kg·d)灌胃,连续14d。分别于失血前、失血后24h、末次给鸡胚胎素后2h尾部采血测定两组红细胞数量及血红蛋白含量的变化。③鸡胚胎素对免疫抑制模型小鼠免疫器官质量的影响:取30只小鼠,随机排列表法分为鸡胚胎素组、模型对照组、正常对照组,10只/组。鸡胚胎素组给予鸡胚胎素5g/(kg·d)灌胃,模型对照组和正常对照组均灌服等量生理盐水,连续14d。在第11天上午鸡胚胎素灌胃2h后,鸡胚胎素组、模型对照组腹腔注射环磷酰胺60mg/(kg·d),连续4d,复制免疫抑制动物模型。末次给予环磷酰胺2h后颈椎脱位法处死小鼠,计算胸腺、脾脏质量指数。结果:50只小鼠均进入结果分析。①失血前及失血后24h鸡胚胎素组与模型对照组的红细胞数值、血红蛋白含量基本相似(P>0.05)。末次给鸡胚胎素后2h与模型对照组比较,鸡胚胎素组红细胞数值、血红蛋白含量均明显升高(t=3.39,P<0.01;t=2.52,P<0.05)。②末次给环磷酰胺2h后与模型对照组比较,鸡胚胎素组、正常对照组的胸腺质量指数和脾脏质量指数均明显升高(t=6.62,P<0.01;t=2.47,P<0.05)。结论:鸡胚胎素灌胃对血虚小鼠具有较好的促红细胞造血功能,同时对环磷酰胺造成的免疫器官质量下降具有明显的增重作用。     

自体与异体移植重建膝关节前交叉韧带的关键技术

目的:探索膝关节前交叉韧带重建术的各个关键技术环节,为提高前交叉韧带修复的临床效果提供理论和实践依据。方法:通过分析与总结与前交叉韧带重建相关的文献资料,包括其手术方式、移植物的选择、骨道定位、髁间窝成形、移植物预张与张力、移植物固定等,同时结合作者的工作经验旨在进一步提高前交叉韧带重建技术。结果:①手术方式选择:膝关节镜下生物材料移植重建前交叉韧带取得比以往优良的临床效果,已得到广泛认可。多数采用单束重建,部分学者正在尝试双束重建以改善移植物生物力学性能。②移植材料的选择:包括自体和同种异体材料,其中自体骨-髌腱-骨与腘绳肌腱最为常用。骨-髌腱-骨由于两端带有骨块,固定牢靠,允许早期重返运动场,颇受年轻运动员青睐。腘绳肌腱取材切口小,术后很少出现膝前痛,但其稳定性不如骨-髌腱-骨,且术后相对容易出现骨隧道扩大。异体移植物在体内结合、重塑速度较自体移植慢,但若经过严格的供体筛选、合理的组织取材、消毒和保存,而不减弱移植物强度,仍可取得与自体移植相当的效果。③骨道位置:正确的骨道定位非常重要,骨道位置太靠前会造成髁间窝撞击和伸直受限。研究表明,术中采用骨性标志定位法要比采用软组织标志定位法准确,术中摄片有助于骨道位置的正确定位。④髁间窝成形术:髁间窝成形的目的是为了便于更清楚的观察髁间窝后侧,同时也是为了避免髁间窝撞击综合征的发生,由于髁间窝过度成形会增加关节出血、疼痛、肿胀以及骨赘生长,所以一般不主张广泛的髁间窝成形,除非术中确有必要时才进行。⑤移植物预张与张力:移植物初始张力不够会导致膝关节持续松弛,而张力过高会限制关节活动并加速关节退变。目前对于最佳的初始张力尚无确切说法。⑥固定:现在已经研制出许多不同类型的固定材料。对于骨-髌腱-骨而言,界面挤压螺钉单切口重建前交叉韧带时,股骨侧靠近关节腔侧固定,胫骨侧远离关节腔侧固定,双切口技术时胫骨侧靠近关节腔侧固定,股骨侧远离关节腔侧固定。股骨侧固定完毕后,膝关节取何角度对胫骨侧进行固定尚存争议。膝关节稍屈曲状态下固定不容易发生松弛,但正常的膝关节在前后方向上是允许有一定松弛度的。有些学者认为在膝关节完全伸直状态下固定可以避免屈曲挛缩畸形的发生并允许前后方向有轻度松弛。而有些学者认为在膝关节稍微屈曲状态下固定会更紧。结论:要真正做到解剖、生物力学、生理功能全方位重建,前交叉韧带重建技术,仍需不断完善,分子生物学、基因工程和组织工程技术的发展以及计算机辅助机器人手术的开展会使前交叉韧带重建技术日臻完善。     

Analysis of IGG and IGG4 in HIV-1 seropositive patients and correlation with biological and genetic markers.

We have compared the levels of immunoglobulins G (IgG) and G4 (IgG4) in extreme seropositive patients from the GRIV cohort consisting of 168 patients with slow progression (SP) and 60 with rapid progression (RP) as well as in 173 healthy controls. IgG levels were significantly higher in SP patients than in RP patients (P = 0.008), both higher than in seronegative individuals. IgG4 levels were significantly lower in SP patients than in RP patients (P = 0.001), both lower than in seronegative individuals. We tried to correlate these levels with biological parameters (CD4(+) and CD8(+) cells, total lymphocytes, white blood cell counts, percentage of CD4(+) cells, and viral load) as well as with genetic markers from Th1/Th2 cytokines (IL2, IL4, IL6, IL10, IL13, and IFNgamma). IgG levels were correlated with the percentage of CD4(+) cells in SP while IgG4 levels were correlated with CD8(+) cell count in SP and with percentage of CD4(+) cells in RP patients. Among the parameters measured in SP patients at the time of inclusion in the study, the best predictor of progression towards AIDS was the viral load, the best predictor for stability was CD4(+) cell count, but overall, the best predictor for SP evolution (stability vs. progression) appeared to be the percentage of CD4(+) cells. Interestingly, correlations between the levels of IgG or IgG4 and the cytokine gene polymorphisms were found, notably in the IL10 gene.     

Taking refuge from modernity: 21st century hermits

Idiopathic environmental intolerances, such as ‘multiple chemical sensitivity’ and ‘electrosensitivity,’ can drastically affect the quality of life of those affected. A proportion of severely affected patients remove themselves from modern society, to live in isolation away from the purported causal agent of their ill health. This is not a new phenomenon; reports of hermits extend back to the 3^rd century AD. We conducted a literature review of case reports relating to ancient hermits and modern day reclusion resulting from idiopathic environmental intolerance, in order to explore whether there are similarities between these two groups and whether the symptoms of these ‘illnesses of modernity’ are simply a present-day way of reaching the end-point of reclusion. Whilst there were some differences between the cases, recurring themes in ancient and modern cases included: dissatisfaction with society, a compulsion to flee, reports of a constant struggle and a feeling of fighting against the establishment. The similarities which exist between the modern-day cases and the historical hermits may provide some insight into the extreme behaviours exhibited by this population. The desire to retreat from society in order to escape from harm has existed for many centuries, but in different guises.