Analysis of telomere length and thymic output in fast and slow/non-progressors with HIV infection.

There are two models for CD4+ T-cell depletion leading to AIDS: a kinetic model and an immune suppression model. In the kinetic model, direct cell killing due to viral replication results in a continuous demand for CD4+ T-cells, which eventually exhausts their capacity for renewal by proliferative mechanisms. In the immune suppression model, CD4+ T-cell decline is due to an indirect global inhibitory effect of the virus on uninfected immune cell function. In order to address differences in the two models, we investigated proliferative history and thymic output in PBMC from the GRIV cohort of fast (FP) and slow/non-progressors (S/NP), and uninfected controls. Proliferative history and thymic output were assessed by measurement of mean telomeric restriction fragment (TRF) length and T-cell receptor Rearrangement Excision Circles (TREC) levels, respectively. Mean TRF lengths were significantly shorter in S/NP (n = 93, 7.59 +/- 0.11 kb) and FP (n = 42, 7.25 +/- 0.15 kb) compared to controls (n = 35, 9.17 +/- 0.19 kb). Mean TRF length in PBMC (n = 9, 7.32 +/- 0.31 kb) and CD4+ enriched fractions (n = 9, 7.41 +/- 0.30 kb) from a subset of non-GRIV HIV-1 infected samples were also significantly smaller than PBMC (n = 8, 9.77 +/- 0.33 kb) and CD4+ fractions (n = 8, 9.41 +/- 0.32 kb) from uninfected controls. Rates of telomeric shortening, however, were similar among S/NP (n = 93, -45 +/- 20 bp/yr), FP (n = 42, -41 +/- 14 bp/yr) and controls (-29 +/- 17 bp/yr). Paralleling differences observed in mean TRF length, TREC levels were significantly reduced in S/NP (n = 10, 3,433 +/- 843 mol/mu and FP (n = 8, 1,193 +/- 413) compared to controls (n = 15, 22,706 +/- 5,089), indicative of a defect in thymopoiesis in HIV-1 infection. When evaluated in the context of reduced thymopoiesis, the difference in mean TRF length between S/NP and controls (1.58 +/- 0.30 kb) is similar to that observed between memory and na?ve T-cells (1.4 +/- 0.1 kb), and may reflect perturbations in the peripheral T-cell population due to a decline in thymic output of na?ve T-cells rather than increased turnover. Based on the different clinical criteria used to select S/NP and FP, the sight difference in TREC between these two groups suggests the threshold for pathogenesis as a result of na?ve T-cell depletion may be quite low, and incremental increases in thymic output may yield substantial clinical results. Future studies regarding therapeutic vaccination, specifically with HIV-1 Tat targeted anti-immunosuppressive vaccines, should address the defect in thymic output in HIV-1 infection by using TREC analysis as a rapid method for biological evaluation.     

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胆道系统恶性肿瘤包括胆管癌和胆囊癌 ,前者主要指原发于肝内、肝门部和远端肝外胆管的恶性肿瘤。至今胆系肿瘤仍依ＴＮＭ分类法分为 0～Ⅳ期。 0期 :为原位癌 ;Ⅰ期 :肿瘤局限于粘膜层、肌层 ;Ⅱ期 :出现局部浸润 ;Ⅲ期 :在Ⅰ或Ⅱ期基础上肿瘤累及邻近组织或肝十二指肠韧带上淋巴结 ;Ⅳ期 :出现肝脏等器官受累或远处转移或出现以下之一区域的淋巴结转移 ,如胰周、十二指肠周、肝门周、腹腔及肠系膜。1　诊断胆系恶性肿瘤的诊断 ,主要依靠临床表现、实验室检查以及影象学检查。临床表现特异性不强 ,其中最基本的表现为胆道梗阻症状 ,同时可…     

两种麻醉方法对单双肺通气期间能量代谢和呼吸氧价及应激反应的影响

目的:观察胸段硬膜外复合全静脉麻醉和全静脉麻醉对单、双肺通气能量代谢、呼吸氧价和应激反应的影响,比较两者的差异。方法:选择2004-07/2005-01徐州医学院附属医院心胸外科择期行食管癌根治术且需要单肺通气的患者40例,按随机数字表法分为硬膜外复合全静脉麻醉组(n=20)和全静脉麻醉组(n=20),经患者同意并签字后进入试验。分别在单肺通气和双肺通气时进行氧耗量、二氧化碳排出量、能量代谢和呼吸商测定,同时测量肾上腺素、去甲肾上腺素、皮质醇和血糖水平。结果:40例患者全部进入结果分析,无脱落。①在单、双肺通气时硬膜外复合全静脉麻醉组的氧耗量、二氧化碳排出量、能量代谢均高于全静脉麻醉组(P<0.05);两组患者单肺通气时段氧耗量、二氧化碳排出量、能量代谢低于双肺通气时段,但差异无显著性意义(P>0.05)。②在单、双肺通气时硬膜外复合全静脉麻醉组的肾上腺素、去甲肾上腺素、皮质醇和血糖水平均低于全静脉麻醉组(P<0.05);单、双肺通气相比,两组患者肾上腺素、去甲肾上腺素变化差异无显著性意义(P>0.05)。结论:与全静脉麻醉相比,胸段硬膜外阻滞复合全静脉麻醉能够增加胸科手术的氧耗量、能量代谢,减轻应激反应。单、双肺通气期间没有明显差异。     

大学生静态平衡能力与运动及性别的关系:定量对比分析

目的:采用定量分析方法比较体育与非体育专业大学生静态平衡能力,分析运动及性别对大学生静态平衡功能的影响。方法:于2007-01/03选取首都体育学院在校大学生共78名为受试对象,其中体育(武术)专业学生40名,非体育(康复)专业学生38名。所有选取对象了解试验目的,并同意参与本实验。采用意大利PosturalEqua平静分析系统,对实验对象分别在睁眼60s、闭眼60s两种状态下测试其静态平衡的各项指标,包括压力中心,线形图总长度,最大摆幅,线形图面积,LFS指数,压力分布,稳定性图及隆伯格值。结果:78名为受试对象均进入结果分析。①两专业学生压力中心X轴短于Y轴、压力分布前(%)高于后(%)(P<0.01)。②在闭眼状态下,体育专业男大学生在指标LFS指数和额状面上大于非体育专业(P<0.05)。③非体育业大学生在睁眼状态下,Y值女性小于男性,额状面值女性大于男性。男、女生睁闭眼差值进行比较时,女性在线形图总长度、额状面和LFT指数均大于男性(P<0.01),而线形图面积小于男性(P<0.05)。④体育专业大学生在睁眼状态下,指标参数Y值女性小于男性,额状面值女性大于男性;闭眼状态下,指标参数Y值女性小于男性,额状面值和LFS值女性大于男性。男、女生睁闭眼差值比较,女性在线形图总长度、额状面和LFT指数均大于男性(P<0.05,P<0.01),而线形图面积小于男性(P<0.05)。结论:①运动训练对大学生静态平衡影响不大,但对男性大学生的某些平衡指标却有显著影响。②性别对大学生的静态平衡均产生影响,表现为男性平衡的微控制能力优于女性。     

苄基四氢巴马汀对α和β等受体的影响

苄基四氢巴马汀(BTHP)使苯福林对大鼠肛尾肌和兔主动脉条作用的累积量效曲线平行右移,最大反应不压低,pA₂值分别为5.86和5.8,但对甲氧明和B-HT920升高DP作用的量效曲线无明显影响。BTHP可使异丙肾上腺素和组胺正性频率作用的量效曲线非平行右移,最大反应压低。BTHP还能明显缩短大鼠再灌流所致心律失常的持续时间。结果提示,BTHP对α₁受体的阻断及对β和H₂受体的非竞争性拮抗作用可能与该药抗心律失常作用有部分关系但并非其主要机理。     

Loss of tumor-promoting activity of unleaded gasoline in N- nitrosodiethylamine-initiated ovariectomized B6C3F1 mouse liver

Unleaded gasoline (UG) vapor (2056 ppm) increased the incidence of liver tumors in a chronic bioassay and exhibited tumor-promoting activity in N-nitrosodiethylamine (DEN)-initiated female mouse liver. Estrogen inhibited mouse liver tumor development and the hepatocarcinogenic and tumor-promoting dose of UG produced uterine changes suggestive of estrogen antagonism. To directly test the hypothesis that UG-induced tumor-promoting ability is secondary to its interaction with the mouse liver tumor inhibitor, estrogen, we compared the tumor-promoting ability of UG in ovariectomized (Ovex) mice with the hepatic tumor-promoting ability of UG in intact mice. Ovaries were surgically removed at 4 weeks of age. Exposure to wholly vaporized UG (2018 ppm) under bioassay and tumor-promoting conditions began at 8 weeks of age. After 4 months of exposure, UG increased relative liver weight and hepatic microsomal cytochrome P450 pentoxyresourfin-O- dealkylase and ethoxyresorufin-O-deethylase activity to a similar extent in intact and Ovex mice. Non-focal hepatocyte proliferation, as measured by the incorporation of bromo-deoxyuridine, was not changed by UG exposure and was similar in all treatment groups. After 4 months of exposure to DEN-initiated mice, UG significantly increased the volume fraction of liver occupied by foci (three-fold) as compared to control intact mice. As expected, volume of foci was elevated in DEN/Ovex/control mice as compared to DEN/intact/control mice. In DEN/Ovex mice UG did not significantly increase the focal volume fraction. Thus, the tumor promoting activity of UG, as demonstrated by increased volume fraction of liver occupied by hepatic foci in intact mice, is greatly attenuated in Ovex mice. The volume fraction data in Ovex mice support the hypothesis that the tumor promoting activity of UG is dependent upon the interaction of UG with ovarian hormones. These data also indicate that hepatic microsomal cytochrome P450 PROD and EROD induction, hepatomegaly and non-focal hepatic LI are not specific markers of hepatic tumor promoting activity of UG.      

Prognostic indicators for breast cancer patients with one to three regional lymph node metastases, with special reference to alterations in expression levels of bcl-2, p53 and c-erbB-2 proteins

Patients with primary breast carcinoma with one to three axillary lymph node metastases but without distant metastases (n1-3) in Japan have been shown to have a 10-year disease-free survival rate of > 60%. It would be reasonable to divide n1-3 Japanese breast cancer patients into groups with high- or low-risk for recurrence and to consider post-operative adjuvant therapy. In the present study, we analyzed 228 consecutive Japanese patients with n1-3 breast cancer who underwent radical mastectomy and were followed up for a median time of 11.0 years. The expression of bcl-2, p53 and c-erbB-2 proteins in the primary tumors was examined immunohistochemically and their prognostic roles were also analyzed along with conventional clinicopathologic indicators. bcl-2 expression was correlated with positive estrogen receptor status and inversely correlated with p53, c-erbB-2 and histologic grade. Univariate analysis showed that bcl-2, p53 and c-erbB-2 expression were prognostic indicators of the patient's group as well as node status, histologic grade, tumor size, age at diagnosis, menopausal status and estrogen receptor status. Cox's regression analysis demonstrated that the number of nodes involved, menopausal status, p53 and bcl-2 were independent predictors for overall survival and that histologic grade and the number of nodes involved were independent predictors for disease-free survival. These results suggest that bcl-2 expression in combination with p53 and c-erbB-2 expression, the number of lymph node metastases, histologic grade and menopausal status are useful in selecting subgroups of n1-3 breast cancer patients with good or poor prognoses.