雷公藤内酯醇对非霍奇金淋巴瘤基质细胞衍生因子-1及其特异性受体生物学轴效应的影响

目的研究雷公藤内酯醇对非霍奇金淋巴瘤（non—Hodgkin lymphoma，NHL）细胞系Raji增殖的抑制作用，并探讨雷公藤内酯醇体外抑制NHL肿瘤细胞通过淋巴结转移的作用及其分子机制。方法采用MTT法测定雷公藤内酯醇对Raji细胞增殖的影响；采用RT—PCR方法检测雷公藤内酯醇对NHL淋巴结基质细胞中基质细胞衍生因子-1α（SDF—1α）表达的影响；采用流式细胞术检测雷公藤内酯醇作用前后NHL淋巴结瘤细胞CXCR4受体表达水平的变化；采用Transwell微孔隔离室迁移实验观察雷公藤内酯醇对NHL淋巴结瘤细胞体外迁移的影响。结果MTT法表明低剂量雷公藤内酯醇（6．25～25nmol／L）即可以时间和剂量依赖方式明显抑制Raji细胞的生长；其作用24、36、48、60、72h的IC50值分别为43．06、25．08、7．32、2．66、0．58nmol／L。RT—PCR结果显示雷公藤内酯醇能抑制NHL淋巴结基质细胞SDF-1α的表达，其中较低剂量组（12．5nmol／L）与对照组相比有一定的降低，但差异无显著性（P〉0．05），而较高剂量组（25、50nmol／L）则可明显抑制SDF-1α的表达（P〈0．05），并具有量效关系。流式细胞术分析结果发现经不同浓度雷公藤内酯醇处理后，NHL淋巴结瘤细胞CXCR4表达率与对照组相比逐渐下降（P〈0．01），此抑制效应呈剂量依赖性。Transwell趋化活性分析显示雷公藤内酯醇既能抑制重组人SDF-1α对NHL淋巴结瘤细胞的趋化作用，也能阻断NHL淋巴结基质细胞对瘤细胞的体外迁移，且雷公藤内酯醇对趋化作用的抑制具有剂量依赖关系。结论雷公藤内酯醇具有抗淋巴瘤细胞增殖的效应，并能阻断NHL淋巴结瘤细胞通过淋巴结的转移。其抗肿瘤机制及其抗细胞增殖作用与对NHLSDF-1／CXCR4生物学轴的抑制效应有关。     

雷公藤内酯醇对匹罗卡品致痫大鼠海马神经元的保护性研究

目的研究雷公藤内酯醇对颞叶癫痫大鼠海马神经元的保护作用及其机制。方法随机将70只生后21 d的雄性Wistar大鼠分为空白对照组10只,癫痫组及雷公藤内酯醇干预组各30只。采用Nissl、FJB染色法观察海马神经元的损伤变化;采用免疫组化法检测海马组织中星形胶质细胞标志物胶质纤维酸性蛋白(GFAP)和小胶质细胞标志物钙离子结合适配器分子1(IBa-1)的表达状况。结果与空白对照组相比,癫痫组和药物干预组海马神经元损伤明显,GFAP、IBa-1呈高表达;与癫痫组相比,药物干预组海马神经元的损伤较小,GFAP及IBa-1表达较低。结论雷公藤内酯醇对癫痫持续状态后海马神经元的损伤有保护性作用,其作用机制可能与雷公藤内酯醇抑制胶质细胞活化抵抗脑内炎症反应有关。     

雷公藤内酯醇抑制血管内皮细胞生长因子的表达与合成

目的 探讨雷公藤内酯醇对血管内皮细胞生长因子（VEGF）mRNA表达及VEGF合成与分泌的影响,进一步探讨雷公藤内酯醇降低肾小球肾炎患者尿蛋白的作用机制。方法 以人内皮细胞系ECV－304为研究对象,利用逆转录－聚合酶链反应（RT－PCR）、流式细胞仪、酶联免疫吸附法（ELISA）检测不同剂量雷公藤内酯醇对佛波脂（PMA）诱导的内皮细胞VEGF mRNA表达及VEGF合成与分泌的影响,并采用RT－PCR检测雷公藤内酯醇对内皮细胞c-jun/c-fos mRNA表达的影响。结果 雷公藤内酯醇可以抑制PMA诱导的内皮细胞VEGF mRNA表达及VEGF合成与分泌,并呈剂量依赖性。同样,雷公藤内酯醇剂量依赖性抑制PMA诱导的内皮细胞c-jun/c-fos mRNA的表达。结论 雷公藤内酯醇抑制内皮细胞VEGF mRNA表达及VEGF合成与分泌可能是其雷公藤内酯醇降低肾小球肾炎患者尿蛋白的作用机制之一。雷公藤内酯醇可能通过影响转录因子AP－1的形成而影响内皮细胞VEGF的表达与合成。     

雷公藤内脂醇在体外人脐静脉血管内皮细胞的c-fos基因mRNA的表达

目的 探讨雷公藤内酯醇对体外培养的血管内皮细胞c-fos基因mRNA表达的方式的作用及机理,为角膜碱烧伤后新生血管的增生抑制提供一种可能的理论依据.方法 人脐静脉获取血管内皮细胞,体外培养成功后,在细胞增殖的同时分别加入不同浓度的雷公藤内酯醇,以原位分子杂交方法检测不同浓度雷公藤内酯醇对血管内皮细胞c-fos基因mRNA表达的影响.结果 c-fos原位分子杂交染色结果表明正常HUVEC c-fos mRNA表达阳性,加入雷公藤内酯醇后呈剂量依赖性地抑制c-fos mRNA的表达.结论 ①雷公藤内酯醇可能通过抑制c-fos基因表达进而影响转录因子AP-1的形成.②雷公藤内酯醇通过抑制c-fos基因表达进而抑制血管内皮细胞的复制.     

雷公藤内酯醇抗肿瘤作用研究进展

雷公藤内酯醇是从卫矛科植物雷公藤中分离出的环氧化二萜内酯化合物，对多种肿瘤细胞均有很好的杀伤作用，其主要作用机制是通过抑制细胞增殖、干预细胞周期、诱导细胞凋亡、抑制核因子NF-κB、抑制基质金属蛋白酶（MMP）的表达、影响血管形成等多种途径来诱导肿瘤细胞凋亡。     

雷公藤内酯醇治疗常染色体显性多囊肾病的现状及前景

常染色体显性多囊肾病(autosomal dominant polycystic kidney disease,ADPKD)是人类最常见的单基因遗传性肾脏疾病,其特点是双肾无数囊肿形成并进行性增大,破坏肾脏正常结构和功能,最后进展至终末期肾脏疾病。目前临床上尚无有效抑制囊肿形成和增大的治疗措施。雷公藤内酯醇(triptolide,TL)是从中药雷公藤中提取的环氧二萜类化合物,具有抗炎、抗增殖等多种作用,多个动物实验研究显示其具有抑制囊肿形成以及保护肾功能的作用,为将来的临床应用奠定了基础。     

雷公藤内酯醇对TNFα诱导人肾小管上皮细胞补体C3的抑制

近年研究表明,肾脏局部固有细胞,尤其是肾小管上皮细胞在病理因素诱导下过度产生和激活的补体,在肾免疫损伤中发挥重要作用;阻断这一作用将对保护肾功能、延缓肾病恶化具有重要意义。雷公藤内酯醇(T_4)是雷公藤二萜化合物中免     

雷公藤内酯醇对红白血病K562细胞株增殖和凋亡的影响

目的探讨雷公藤内酯醇对人类红白血病K562细胞株增殖和凋亡的影响。方法运用四甲基偶氮唑盐(MTT)法、流式细胞术(FCM)等检测雷公藤内酯醇对K562细胞株增殖和凋亡的影响。结果雷公藤内酯醇能明显抑制K562细胞的增殖,呈时间与剂量依赖性,作用24h时其半数抑制浓度IC50为25nmol/L。且经雷公藤内酯醇处理后K562细胞G1/S期所占的百分比较对照组上升(P<0.05)。雷公藤内酯醇作用48h,其浓度的变化与K562细胞凋亡率具有相关性(r=0.97,P<0.05),而作用24h时,则无明显诱导凋亡的作用。结论雷公藤内酯醇有明确的抗白血病细胞增殖的能力,干扰K562细胞周期,上调细胞G/S期检测点,并具有促进细胞凋亡的作用。     

雷公藤甲素新型给药系统研究进展

<正>雷公藤是卫茅科雷公藤属木质藤本植物,具有解毒散结、活血化瘀、扶正祛邪、抗炎、免疫抑制、抗肿瘤和抗生育等多种药理作用。雷公藤甲素(又称雷公藤内酯醇、雷公藤内酯)是从雷公藤中提取分离到的环氧化二萜内酯化合物,是我国临床上应用的各种雷公藤制剂的主要活性成分,但大剂量使用对胃肠     

雷公藤内酯醇抑制白血病干细胞自我更新的研究

目的:检测在雷公藤内酯醇作用下,白血病干细胞的NANOG、β-catenin和OCT-4蛋白表达的水平,从抑制白血病干细胞细胞自我更新方面探讨其机制。方法:首先使用免疫磁珠法进行分选白血病干细胞。实验共设4组,分为:对照组、雷公藤内酯醇3个浓度(低中高)组。4个组均加入K562/A02细胞悬液100μL,对照组加入RPMI1640培养液100μL,雷公藤内酯醇低中高浓度组终浓度分别为10、50、100ng/mL。进行各组细胞增殖率的检测、并采用蛋白印迹法检测各组细胞NANOG、β-catenin和OCT-4蛋白的表达水平。结果:对各组细胞增殖率检测结果显示,3个不同浓度雷公藤内酯醇组,处理24h后都可以观察到K562/A02干细胞增殖受抑,并呈浓度依赖性。与对照组比较,3个不同浓度雷公藤内酯醇度组的β-catenin蛋白表达水平降低,且与对照组间存在统计学差异(P0.05)。中剂量组中OCT-4蛋白表达水平较对照组有统计学差异,而NANOG蛋白的表达在这4个组中,没发现显著差异。结论:中剂量组的雷公藤内酯醇能够调控β-catenin/OCT-4蛋白表达水平,表明该浓度剂量对抑制白血病干细胞自我更新作用最强;而试验中发现的其具有抑制白血病干细胞增殖的浓度依赖性,表明白血病干细胞受到高浓度雷公藤内酯醇抑制可能存在其他机制。     

95例SARS患者T细胞及其亚群动态变化的观察

对 95例SARS患者的T淋巴细胞亚群动态变化进行分析。其中 85例痊愈 ,1 0例死亡。 85例痊愈患者 ,病程第 7天平均CD4 + ( 3 2 5± 1 90 )个 /μL ,CD8+ ( 3 1 9± 3 1 5 )个 /μL ,CD4 + /CD8+ 1 .2 5± 0 .71 ,与我国正常人相比〔平均CD4 + ( 72 7± 2 5 5 )个 /μL、CD8+ ( 5 3 9± 1 3 4)个 /μL ,CD4 + /CD8+ 1 .49〕 ,T淋巴细胞亚群明显下降 (P =0 .0 0 1 )。病程第1 4天左右免疫功能逐渐恢复 ,平均CD4 + ( 5 61± 5 2 2 )个 /μL ,CD8+ ( 3 70± 2 71 )个 /μL ,CD4 + /CD8+ 1 .68± 1 .1 1。 2 1d后免疫功能基本恢复正常 ,平均CD4 + ( 675± 448)个 /μL ,CD8+ ( 4 67± 2 41 )个 /μL ,CD4 + /CD8+ 1 .48± 0 .68。 1 0例死亡患者的T细胞亚群在入院后逐渐出现下降趋势 ,病程第 7天CD4 + ( 2 48± 82 )个 /μL ,CD8+ ( 2 3 3± 1 1 5 )个 /μL ,CD4 + /CD8+ 1 .2 1± 0 .40 ,第 1 4天T淋巴细胞继续下降 ,平均CD4 + ( 1 81± 1 2 8)个 /μL ,CD8+ ( 1 73± 1 0 9)个 /μL ,CD4 + /CD8+ 1 .1 7± 0 .45 ,2 1d后CD4 + 细胞继续下降 ,平均CD4 + ( 1 2 5± 46)个 /μL ,CD8+ ( 94± 3 8)个 /μL ,CD4 + /CD8+ 1 .44±0 .5 9。结果提示 :SARS患者早期可能存在异常的免疫反应 ,这种异常免疫反应可能是导?     

严重急性呼吸综合征死亡原因分析

为分析导致SARS患者死亡的危险因素 ,对 2 0 0 3年 3月至 6月在佑安医院死亡的 1 5例SARS患者的死亡原因进行分析。结果 :1 5例患者年龄 2 3～ 81岁 ,平均 ( 5 0 .7± 1 8.8)岁 ,其中年龄大于 5 0岁的 7例。基础病 :合并糖尿病 5例 ,高血压病 5例 ,慢性肾功能不全、尿毒症期 2例。T细胞亚群 :病程第 1周CD4 + T淋巴细胞明显降低 ,平均CD4 + ( 2 48± 82 )个 /μL ,第 2和第 3周继续下降 ,分别为 ( 1 81± 1 2 8)个 /μL和 ( 1 2 5± 46)个 /μL ,与痊愈组患者比较差异具有显著性 (P <0 .0 5 )。胸部影像学变化 :1 5例中 7例患者胸部影像学显示均在 7d内进展到双肺广泛磨玻璃样变或实变。CK及CK MB :平均CK( 2 69.3± 3 99.9)U/L ,CK MB( 3 1 .1± 2 6.1 )U/L。提示 :SARS患者若伴有高龄、多合并症、T细胞亚群进行性下降、快速进展的双肺广泛实变、CK及CKMB升高等情况时 ,预后极差     

调节性CD4~+T细胞及非调节性CD4~+T细胞与HIV/AIDS患者疾病进展关系的研究

目的分析比较中国HIV感染者CD4+CD25+Foxp3+调节性T细胞(CD4+regulatory T cells,Treg)及非Treg细胞与疾病进展的关系,探讨Treg细胞在HIV感染过程中的作用。方法选取76例HIV/AIDS患者,根据其CD4+T细胞计数水平不同分为3组,A组CD4<200个/μL,B组CD4200～400个/μL,C组CD4>400个/μL。采用流式细胞仪胞内染色技术检测CD4+CD25+Foxp3+调节性T细胞的水平,并分析其与CD4计数及病毒载量的相关性。结果随着疾病的进展,Treg细胞百分比逐渐升高,各组间差异有统计学意义;Treg细胞及非Treg细胞的绝对计数均明显下降,且以非Treg细胞下降为主;Treg绝对计数与病毒载量呈负相关(P<0.05)。结论中国HIV感染者随着疾病进展,辅助性T细胞等非Treg细胞的数量下降,对机体免疫保护能力降低,而Treg细胞数量及功能的下降使其对机体的过度免疫活化的抑制作用减弱,病毒复制,加剧病情进展。     

Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause

Context  The timing of initiation of hormone therapy may influence its effect on cardiovascular disease. Objective  To explore whether the effects of hormone therapy on risk of cardiovascular disease vary by age or years since menopause began. Design, Setting, and Participants  Secondary analysis of the Women's Health Initiative (WHI) randomized controlled trials of hormone therapy in which 10 739 postmenopausal women who had undergone a hysterectomy were randomized to conjugated equine estrogens (CEE) or placebo and 16 608 postmenopausal women who had not had a hysterectomy were randomized to CEE plus medroxyprogesterone acetate (CEE + MPA) or placebo. Women aged 50 to 79 years were recruited to the study from 40 US clinical centers between September 1993 and October 1998. Main Outcome Measures  Statistical test for trend of the effect of hormone therapy on coronary heart disease (CHD) and stroke across categories of age and years since menopause in the combined trials. Results  In the combined trials, there were 396 cases of CHD and 327 cases of stroke in the hormone therapy group vs 379 cases of CHD and 239 cases of stroke in the placebo group. For women with less than 10 years since menopause began, the hazard ratio (HR) for CHD was 0.76 (95% confidence interval [CI], 0.50-1.16); 10 to 19 years, 1.10 (95% CI, 0.84-1.45); and 20 or more years, 1.28 (95% CI, 1.03-1.58) (P for trend = .02). The estimated absolute excess risk for CHD for women within 10 years of menopause was –6 per 10 000 person-years; for women 10 to 19 years since menopause began, 4 per 10 000 person-years; and for women 20 or more years from menopause onset, 17 per 10 000 person-years. For the age group of 50 to 59 years, the HR for CHD was 0.93 (95% CI, 0.65-1.33) and the absolute excess risk was –2 per 10 000 person-years; 60 to 69 years, 0.98 (95% CI, 0.79-1.21) and –1 per 10 000 person-years; and 70 to 79 years, 1.26 (95% CI, 1.00-1.59) and 19 per 10 000 person-years (P for trend = .16). Hormone therapy increased the risk of stroke (HR, 1.32; 95% CI, 1.12-1.56). Risk did not vary significantly by age or time since menopause. There was a nonsignificant tendency for the effects of hormone therapy on total mortality to be more favorable in younger than older women (HR of 0.70 for 50-59 years; 1.05 for 60-69 years, and 1.14 for 70-79 years; P for trend = .06). Conclusions  Women who initiated hormone therapy closer to menopause tended to have reduced CHD risk compared with the increase in CHD risk among women more distant from menopause, but this trend test did not meet our criterion for statistical significance. A similar nonsignificant trend was observed for total mortality but the risk of stroke was elevated regardless of years since menopause. These data should be considered in regard to the short-term treatment of menopausal symptoms. Trial Registration  clinicaltrials.gov Identifier: NCT00000611      

NIH peer review of grant applications for clinical research

Context  Support of research to facilitate translation of scientific discoveries to the prevention and treatment of human disease is a high priority for the US National Institutes of Health (NIH). Nevertheless, a perception exists among clinical investigators that the NIH peer review process may discriminate against clinical research. Objective  To describe recent trends and outcomes of peer review of grant applications to NIH requesting support for clinical research. Design and Setting  Peer review outcomes of grant applications submitted to NIH by MDs were compared with those of non-MDs, and outcomes of applications involving inclusion of human subjects were compared with those not involving human subjects. Analyses were carried out using an inclusive definition of clinical research and after stratifying clinical research into specific categories. Main Outcome Measures  Median priority scores and funding rates. Results  Between 1997 and 2002, on average, 25.2% of total grant applications (ranging from 27 607 to 34 422 per year) were submitted by MDs, and 27.5% of awards (ranging from 8495 to 10 769 awards per year) were made to MDs. Median priority scores (239.0 vs 250.0) and funding rates (31.4% vs 29.1%) reviewed in 2 grant cycles in 2002 were more favorable for MDs than for non-MDs (P<.001). However, median priority scores (254.0 vs 244.0) and funding rates (23.9% vs 28.1%) were less favorable (P<.001) for R01 applications for clinical research (n = 7227 applications) than for nonclinical research (n = 10 209). This trend was most convincingly observed for clinical research categorized as mechanisms of disease (P = .006) or clinical trials and interventions (P = .001). Similar trends were observed for grant mechanisms other than R01. Concerns about safety and privacy of human subjects may have contributed to the less favorable outcomes of clinical research applications. Conclusion  Although physicians compete favorably in the peer review process, review outcomes are modestly less favorable for grant applications for clinical research than for laboratory research.      

55例艾滋病合并结核病临床分析

目的探讨艾滋病(AIDS)合并结核病的临床特点、诊断和治疗。方法对1995—2005年期间在北京佑安医院诊治的55例艾滋病合并结核病的患者进行临床资料分析。结果最常见临床表现为发热55例(100%),咳嗽34例(61.8%)、盗汗29例(52.7%)、体质量下降28例(50.9%)、呼吸困难13例(23.6%)、胸痛11例(20%)。临床类型:单纯肺结核8例,结核性胸膜炎3例,单部位淋巴结核12例,播散型肺结核25例,其他部位结核7例。常见影像表现:肺中下叶的局灶性或弥散性渗出病变、淋巴结肿大、胸膜炎、弥散性粟粒或结节影。免疫功能:CD4+0.002×109~0.164×109/L,平均(0.049±0.043)×109/L。治疗:23例未同时抗结核和抗病毒治疗组中,2年后因结核死亡12例;27例同时抗结核和抗病毒治疗组中,2年后因结核死亡5例。结论艾滋病合并结核病的患者中播散型结核多、临床和影像表现复杂多样、诊断困难,及时抗结核治疗和联合高效抗逆转录病毒治疗能缩短病程,改善预后。     

外周血CD4~+T淋巴细胞表面CCR5受体表达水平与HIV感染关系的研究

目的研究人外周血中CD4+T淋巴细胞表面趋化因子受体5(chemokine receptor5,CCR5)的表达,比较健康人群、HIV急性期患者和HIV慢性期患者之间CCR5表达的差异,明确CCR5表达在正常人和HIV感染者之间的差异,以及CCR5表达与HIV病情进展的关系,以明确CCR5在HIV患者外周血CD4+T淋巴细胞表面表达的意义,并为CCR5拮抗剂在HIV临床治疗中的作用提供临床标本依据。方法收集来自首都医科大学附属北京佑安医院的260例HIV感染者和60例健康人的外周血标本,其中急性期感染者98例、慢性期感染者162例,利用淋巴细胞分离液分离外周血中PBMC,在显微镜下进行淋巴细胞计数,应用直接荧光标记的单克隆抗体对外周血单个核细胞(peripheral blood mononuclear cells,PBMC)表面CD4分子及CCR5进行染色,利用流式细胞术分析CD4+T淋巴细胞表面CCR5表达;对流式细胞术所得检测结果进行统计学分析。结果检测结果表明:(1)HIV急性期患者和HIV慢性期患者外周血中CD4+T淋巴细胞表面CCR5的表达显著高于正常人,差异有统计学意义(P<0.01);(2)HIV慢性期患者外周血中CD4+T淋巴细胞表面CCR5的表达显著高于HIV急性期患者,差异有统计学意义(P<0.01)。结论此项研究表明外周血中CD4+T淋巴细胞表面CCR5表达的差异与HIV的易感性、疾病进展情况密切相关。外周血中CD4+T淋巴细胞表面CCR5表达的检测,将对HIV患者的早期诊断、治疗和判断预后具有一定的临床意义。     

Alu-LTR PCR方法检测HAART治疗系列各细胞亚群的整合型HIV-1 DNA

目的应用Alu-LTR PCR方法对高效抗反转录病毒治疗(highly active antiretroviral therapy,HAART)系列的CD4+T,CD8+T及B细胞进行检测,明确不同细胞亚群及HAART治疗的不同阶段是否存在整合的HIV-1 DNA。方法收集20例HIV-1感染患者HAART治疗过程中0、4、12周及10例健康对照的抗凝血标本,纯化CD4+T,CD8+T及B细胞并提取DNA,应用Alu-LTR PCR方法进行检测。结果 20例HIV-1感染者HAART治疗系列中CD4+T细胞及CD8+T细胞成功扩出目的片段,CD8+T细胞所扩条带亮度均低于CD4+T细胞,HAART治疗系列0、4、12周标本所扩条带亮度没有明显差异。B细胞及10例健康者均为阴性。结论 CD4+T及CD8+T细胞存在整合型HIV-1 DNA,HIV储藏库主要存在于CD4+T细胞内。B细胞内不存在整合型HIV-1 DNA。随着HAART治疗的进程,整合型HIV-1 DNA仍然存在,进一步证明HAART不能根除HIV储藏库。     

肺癌患者外周血CD4~+T淋巴细胞Th1/Th2分化情况检测与分析

目的观察肺癌患者外周血CD4+T淋巴细胞中Th1/Th2分化情况与反应状态,为肺癌的诊断和免疫治疗研究提供依据。方法以干扰素-γ(IFN-γ)和白细胞介素-4(IL-4)代表Th1和Th2细胞功能,应用细胞因子诱生技术和流式细胞仪,检测25例肺癌患者及25例健康志愿者外周血CD4+T淋巴细胞诱生的IFN-γ和IL-4水平。结果肺癌患者外周血CD4+T淋巴细胞诱生的IFN-γ水平与健康对照组比较明显降低,差异有统计学意义(P<0.05),IL-4水平在2组间差异无统计学意义(P>0.05)。结论肺癌患者外周血CD4+T淋巴细胞向Th1细胞的分化明显减少,向Th2细胞的分化无明显变化,Th1向Th2方向的漂移可能是肺癌细胞生长和免疫逃避的机制之一。     

Cannabis smoking and periodontal disease among young adults

Context  Tobacco smoking is a recognized behavioral risk factor for periodontal disease (through its systemic effects), and cannabis smoking may contribute in a similar way. Objective  To determine whether cannabis smoking is a risk factor for periodontal disease. Design and Setting  Prospective cohort study of the general population, with cannabis use determined at ages 18, 21, 26, and 32 years and dental examinations conducted at ages 26 and 32 years. The most recent data collection (at age 32 years) was completed in June 2005. Participants  A complete birth cohort born in 1972 and 1973 in Dunedin, New Zealand, and assessed periodically (with a 96% follow-up rate of the 1015 participants who survived to age 32 years). Complete data for this analysis were available from 903 participants (comprising 89.0% of the surviving birth cohort). Main Outcome Measure  Periodontal disease status at age 32 years (and changes from ages 26 to 32 years) determined from periodontal combined attachment loss (CAL) measured at 3 sites per tooth. Results  Three cannabis exposure groups were determined: no exposure (293 individuals, or 32.3%), some exposure (428; 47.4%), and high exposure (182; 20.2%). At age 32 years, 265 participants (29.3%) had 1 or more sites with 4 mm or greater CAL, and 111 participants (12.3%) had 1 or more sites with 5 mm or greater CAL. Incident attachment loss between the ages of 26 and 32 years in the none, some, and high cannabis exposure groups was 6.5%, 11.2%, and 23.6%, respectively. After controlling for tobacco smoking (measured in pack-years), sex, irregular use of dental services, and dental plaque, the relative risk estimates for the highest cannabis exposure group were as follows: 1.6 (95% confidence interval [CI], 1.2-2.2) for having 1 or more sites with 4 mm or greater CAL; 3.1 (95% CI, 1.5-6.4) for having 1 or more sites with 5 mm or greater CAL; and 2.2 (95% CI, 1.2-3.9) for having incident attachment loss (in comparison with those who had never smoked cannabis). Tobacco smoking was strongly associated with periodontal disease experience, but there was no interaction between cannabis use and tobacco smoking in predicting the condition's occurrence. Conclusion  Cannabis smoking may be a risk factor for periodontal disease that is independent of the use of tobacco.