Apolipoprotein E4 enhances brain inflammation by modulation of the NF-κB signaling cascade

Apolipoprotein E4 (apoE4), the major genetic risk factor of Alzheimer's disease (AD), is associated with enhanced brain inflammation. Genome-wide gene expression profiling was employed to study the effects of apoE genotype on hippocampal gene expression in LPS-treated mice, transgenic for either apoE4 or the AD benign allele, apoE3. This revealed that the expression of inflammation-related genes following intracerebroventricular injection of LPS was significantly higher and more prolonged in apoE4 than in apoE3 transgenic mice. Clustering analysis revealed gene clusters which responded differently in apoE4 and apoE3 mice and were significantly enriched in NF-kappaB response elements. Direct measurement of NF-kappaB-regulated genes revealed that their extent of activation was greater in the apoE4 mice. Immunohistochemistry experiments revealed that microglial and NF-kappaB activation were more pronounced in apoE4 than in apoE3 mice. These findings suggest that the increased brain inflammation in apoE4 mice is related to disregulation of NF-kappaB signaling pathway.     

斯奇康联合丝裂霉素顺铂胸腔内注射治疗肺癌恶性胸水的疗效观察

目的　探讨斯奇康联合丝裂霉素、顺铂胸腔内注射治疗肺癌恶性胸水的有效性和安全性。方法　对我科1999年以来确诊为肺癌恶性胸水的 5 3例患者 ,随机分为斯奇康组 ( 2 7例 )和对照组 ( 2 6例 ) ,进行胸腔内注药 ,观察治疗的有效率、Karnofsky评分及不良反应。结果　斯奇康组与对照组治疗有效率分别为 88 8%和 5 3 9%,两组比较有显著性差异 (P <0 0 1) ;两组治疗后生存质量均有改善 ,但Karnofsky评分 70分以上治疗组为 66 7%,对照组为 3 0 8%,两组比较差异显著 (P <0 0 1) ;两组均出现不同程度的白细胞、血小板减少 ,但治疗组与对照组相比反应明显较轻 ,有显著性差异 (P <0 0 5 )。结论　斯奇康联合丝裂霉素、顺铂胸腔内注射治疗肺癌恶性胸水疗效较好 ,毒副反应较轻。     

腹腔注射细菌脂多糖加重大鼠的应激性抑郁症

目的 观察腹腔注射细菌脂多糖对大鼠应激性抑郁症的影响。方法 制备大鼠应激性抑郁症模型，采用开场实验检测大鼠的行为性抑郁，用MTT法测定淋巴细胞转化。结果 慢性应激16d，大鼠出现自主活动时间和中区逗留时间缩短、活动路程减少等抑郁性行为。腹腔注射细菌脂多糖加重大鼠的行为性抑郁，并加强应激大鼠血清对正常淋巴细胞转化的抑制作用。结论 腹腔注射细菌脂多糖加重大鼠的行为性抑郁，其原因可能与脂多糖引起的脑内炎性细胞因子的释放有关。     

All-trans retinoic acid suppresses liver injury induced by Propionibacterium acnes and lipopolysaccharide in rats

All-trans retinoic acid (ATRA) has been reported to exert major effects on the immune system, including monocytes/macrophages. The present study was designed to determine whether ATRA would modulate macrophage-associated liver injury induced by Propionibacterium acnes and lipopolysaccharide (LPS) in rats. All-trans retinoic acid administration alleviated the liver injury and reduced the incidence of death following hepatic failure. Serum alanine aminotransferase (ALT) levels 5 h after, and survival rates within 12 h after the administration of LPS were significantly lower in the ATRA-treated group (134 ± 119 IU/L and 72.7%) compared with the control group (713 ± 411 IU/L and 18.2%; P < 0.05). Histological findings supported these results. These effects may be due to suppression of tumour necrosis factor-α (TNF-α) and superoxide anions produced by activated macrophages. Serum levels of TNF-α 1 h after LPS administration were significantly lower in the ATRA-treated group (60.5 ± 7.0 ng/mL) as compared with the control group (105.2 ± 39.3 ng/mL; P < 0.05). Formazan deposition that was generated by the perfusion of the liver with nitroblue tetrazolium, also suggested suppression of the release of superoxide anions from hepatic macrophages. These results suggest that ATRA acts as an immunomodulator in liver injury by suppressing the activation of liver macrophages.     

大鼠腹腔巨噬细胞表达促肾上腺皮质激素释放激素的实验研究

目的 观察促肾上腺皮质激素释放激素(CRH)在大鼠腹腔巨噬细胞的表达变化规律.方法 体外培养大鼠腹腔巨噬细胞,采用RT-PCR及ELISA技术检测正常及脂多糖(LPS)、佛波脂(PMA)刺激后,细胞CRH mRNA转录水平及CRH多肽合成水平.结果 RT-PCR结果显示,正常大鼠腹腔巨噬细胞内有一定水平的CRH mRNA,LPS及PMA刺激后,细胞内CRH mRNA水平均显著增高(P＜0.01).在多肽水平,正常大鼠腹腔巨噬细胞可表达低水平的CRH[约(0.07±0.01)ng/107cells],LPS及PMA促进了CRH多肽的合成(P＜0.01).结论 正常大鼠腹腔巨噬细胞可合成表达CRH,其水平在活化后大鼠腹腔巨噬细胞显著上调.     

The value of pleural fluid anti-A60 IgM in BCG-vaccinated tuberculous pleurisy patients

Objectives   To determine if detection of IgM and IgG antibodies against mycobacterial antigen A60, together with the Mantoux tuberculin skin test (TST), could be used in the diagnosis of tuberculous pleurisy (TP) in BCG-vaccinated cases.
Methods   We investigated 125 BCG-vaccinated patients with pleural effusion. Of these, 88 had TP and 37 had non-tuberculous pleurisy (NTP). TST and anti-A60 IgM and IgG measurements by ELISA were performed in the sera and pleural effusions of both groups.
Results   Cut-off values, in optical density, for serum anti-A60 IgM, pleural fluid anti-A60 IgM, serum anti-A60 IgG and pleural fluid anti-A60 IgG were defined as 0.624, 0.614, 0.464, and 0.613, respectively. TP patients had higher IgG and IgM levels in the serum ( P  < 0.001 and P  < 0.05, respectively) and pleural effusion ( P  < 0.001 and P  < 0.001, respectively). Regardless of the diagnosis, IgG and IgM levels were higher in the sera ( P  < 0.001 and P  < 0.05, respectively) and pleural effusions ( P  < 0.001 and P  < 0.001, respectively) of TST-positive cases, and serum and pleural fluid IgM levels were higher ( P  < 0.001 and P  < 0.001, respectively) in the TST-positive TP cases. Sensitivity and specificity of TST were 65% and 68%, respectively. As a single parameter, pleural fluid anti-A60 IgM had the highest sensitivity (77%) and specificity (94%) in patients with negative TST.
Conclusion   We suggest that in populations where tuberculosis prevalence is high and BCG vaccination is common, pleural fluid anti-A60 IgM can facilitate the diagnosis of TP.     

Cytologic features of disseminated bacillus Calmette-Guérin (BCG) infection

Disseminated bacillus Calmette-Guérin (BCG) infection is an unusual complication of immunization against Mycobacterium tuberculosis with the bacillus Calmette-Guérin. We report on 4 such cases in which the diagnosis was suspected at the fine-needle aspiration biopsy (FNAB) procedure. Participants were 4 males (mean age, 21.5 mo; range, 8-36 mo) in good general condition, in whom epidemiology data favoring tuberculosis and presence of pulmonary tuberculosis were lacking. Cases 1 and 2 presented with a deep-seated subcutaneous nodule located near the left mamilla and lower aspect of the left scapula, respectively, resulting from lymph node involvement by BCG. Cases 3 and 4 presented as an osteolytic lesion of the ninth right rib and right iliac bone, respectively. FNAB findings showed poorly to moderately cellular smears. Epithelioid histiocytes in a granuloma pattern with occasional multinucleated Langerhans-type giant cells, lymphocytes, and polymorphonuclear leukocytes in a finely granular background with necrotic debris were found in all cases. The presence of isolated calcified spherules interspersed among the cells was found to be a useful finding for diagnosis. When dealing with disseminated BCG infections, clinical and cytological pictures must be evaluated as a whole in order to arrive at an accurate diagnosis.     

Histopathological studies on the local reactions induced by complete Freund's adjuvant (CFA), bacterial lipopolysaccharide (LPS), and synthetic lipopeptide (P3C) conjugates

The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage.     

Immune biology of macaque lymphocyte populations during mycobacterial infection

Immune responses of lymphocyte populations during early phases of mycobacterial infection and reinfection have not been well characterized in humans. A non-human primate model of Mycobacterium bovis bacille Calmette-Guerin (BCG) infection was employed to characterize optimally the immune responses of mycobacteria-specific T cells. Primary BCG infection induced biphasic immune responses, characterized by initial lymphocytopenia and subsequent expansion of CD4+, CD8+ and gammadelta T cell populations in the blood, lymph nodes and the pulmonary compartment. The potency of detectable T cell immune responses appears to be influenced by the timing and route of infection as well as challenge doses of BCG organisms. Systemic BCG infection introduced by intravenous challenge induced a dose-dependent expansion of circulating CD4+, CD8+ and gammadelta T cells whereas, in the pulmonary compartment, the systemic infection resulted in a predominant increase in numbers of gammadelta T cells. In contrast, pulmonary exposure to BCG through the bronchial route induced detectable expansions of CD4+, CD8+ and gammadelta T cell populations in only the lung but not in the blood. A rapid recall expansion of these T cell populations was seen in the macaques reinfected intravenously and bronchially with BCG. The expanded alphabeta and gammadelta T cell populations exhibited their antigen specificity for mycobacterial peptides and non-peptide phospholigands, respectively. Finally, the major expansion of T cells was associated with a resolution of active BCG infection and reinfection. The patterns and kinetics of CD4+, CD8+ and gammadelta T cell immune responses during BCG infection might contribute to characterizing immune protection against tuberculosis and testing new tuberculosis vaccines in primates.