STAT4基因敲除通过miR-9促进泡沫细胞形成及动脉粥样硬化

目的探究动脉粥样硬化斑块发生发展过程中信号转导与转录激活因子4(STAT4)信号通路在巨噬细胞分化及泡沫细胞形成中的作用及调控机制。方法将STAT4基因敲除(STAT4~(-/-))小鼠与载脂蛋白E基因敲除(ApoE~(-/-))小鼠进行杂交,筛选出ApoE/STAT4纯合子双基因敲除(DKO)小鼠,研究新型动脉粥样硬化相关小鼠模型的易感性和机制。将3月龄小鼠分为野生型(WT)、STAT4~(-/-)、ApoE~(-/-)、DKO共4组,经过12周高脂胆固醇饮食喂养,分别采用油红O染色及石蜡切片HE/Masson染色检测主动脉斑块形成情况。采用流式细胞术分析小鼠外周血、骨髓及脾脏髓系细胞各亚群比例。从小鼠骨髓分离CD11b~+髓系细胞进行体外培养,采用巨噬细胞集落刺激因子(M-CSF)进行诱导,流式分析巨噬细胞不同亚型分化情况。采用实时定量聚合酶链反应(PCR)及Western blot分别检测基因表达水平及蛋白水平。结果 ApoE~(-/-)小鼠动脉粥样硬化斑块局部的CD11b~+细胞中可检测到STAT4表达。ApoE~(-/-)及DKO小鼠经12周高脂喂养,油红O染色阳性的主动脉斑块主要分布在主动脉根部至髂动脉分叉处,DKO小鼠的斑块较ApoE~(-/-)小鼠明显增多;HE及Masson染色显示DKO小鼠的主动脉斑块较ApoE~(-/-)小鼠具有更薄的纤维帽及更大的脂质核心,且斑块中的纤维更稀疏,排列也相对更紊乱。体外细胞实验显示STAT4基因敲除可促进CD11b~+Gr-1~+未成熟髓系细胞的异常动员、巨噬细胞的M1极化以及泡沫化。STAT4基因缺失通过磷酸肌醇3激酶(PI3K)/丝氨酸苏氨酸激酶(Akt)/核因子κB(NF-κB)通路下调miR-9的表达,上调酰基辅酶A胆固醇酰基转移酶(ACAT-1)表达,进而促进巨噬细胞的脂质蓄积及泡沫细胞形成,最终加速动脉粥样硬化斑块的发生发展。结论 STAT4通过调控免疫炎症反应及脂质代谢,在巨噬细胞分化及泡沫细胞形成过程中发挥关键作用。STAT4相关信号通路可作为未来动脉粥样硬化性疾病的潜在治疗靶点。     

β3肾上腺素受体激动剂米拉贝隆对载脂蛋白E基因敲除小鼠动脉粥样硬化的影响

目的:探索米拉贝隆(mirabegron)对动脉粥样硬化(As)的作用。方法:建立载脂蛋白E基因敲除(ApoE~(-/-))小鼠As模型(n=16)并分为米拉贝隆组(n=8)、安慰剂组(n=8),同时设立空白对照组(n=8)。米拉贝隆干预6周后,采集小鼠心脏及主动脉标本,油红O及HE染色观察主动脉斑块面积,Masson染色观察主动脉根部胶原纤维含量,免疫组织化学染色检测主动脉根部平滑肌细胞,巨噬细胞表达水平。结果:与空白对照组相比,安慰剂组小鼠主动脉斑块表面积(P0.05)、横截面积(P0.05)显著增大,斑块中平滑肌数目(P0.05)、巨噬细胞数目(P0.05)、胶原纤维(P0.05)均明显升高;与安慰剂组相比,米拉贝隆组小鼠主动脉斑块表面积(P0.05)及横截面积(P0.05)显著减小,斑块中平滑肌数目(P0.05)、巨噬细胞数目(P0.05)及胶原纤维成分(P0.05)均显著下降。结论:米拉贝隆可延缓Apo E~(-/-)小鼠As的发展,具有潜在的防治As的临床价值。     

瓜蒌-薤白对ApoE－/－小鼠动脉粥样硬化过程中NLRP3炎症小体活化的影响

目的通过建立ApoE^-/-小鼠动脉粥样硬化(As)模型,探讨As病程不同时间点NOD样受体热蛋白结构域3(NLRP3)炎症小体表达水平的变化及瓜蒌-薤白的干预作用。方法将高脂饲养6、20、34周的ApoE^-/-小鼠均随机分为模型组(M1、M2、M3)和给药组[6 g/(kg·d)](GX1、GX2、GX3),每组10只;另设C57BL/6J小鼠为空白组(C1、C2、C3)。空白组及模型组小鼠给予生理盐水灌胃,给药组小鼠每日给予相应药物灌胃,共4周。实验结束后处死小鼠,油红O染色评估主动脉斑块面积及形态;HE染色观察主动脉病理形态学变化;免疫组织化学法检测主动脉NLRP3表达;ELISA法检测血清中白细胞介素1β(IL-1β)和白细胞介素18(IL-18)水平;Western blot法检测主动脉组织中NLRP3、凋亡相关斑点样蛋白(ASC)、含半胱氨酸的天冬氨酸蛋白水解酶1(Caspase-1)的蛋白表达;qRT-PCR检测主动脉组织中NLRP3、ASC、Caspase-1的mRNA表达。结果在As病程进展过程中,模型组小鼠主动脉脂质累积和斑块面积显著增加,血清中IL-1β和IL-18的表达不断升高,NLRP3和ASC的蛋白及mRNA的表达均不断上调。Caspase-1的蛋白表达也呈上升趋势,但M2与M3组间的比较无统计学差异。与模型组相比,给药组各时间点小鼠主动脉的脂质累积和斑块面积显著减少,血清中IL-1β和IL-18的水平降低;主动脉组织中N LRP3、ASC、Caspase-1蛋白和mRNA表达显著下调。结论NLRP3炎症小体参与了主动脉As的病变过程,瓜蒌-薤白可能通过调节As模型小鼠主动脉不同阶段NLRP3炎症小体的表达,从而发挥抗As的作用。     

姜黄素通过影响巨噬细胞的极性延缓动脉粥样硬化进展

目的研究姜黄素对ApoE基因敲除(ApoE~(-/-))小鼠动脉粥样硬化进展及斑块中巨噬细胞极性的影响。方法用高脂高胆固醇饮食饲养ApoE~(-/-)小鼠建立动脉粥样硬化模型,设立姜黄素治疗组、阿托伐他汀治疗组和高脂组;通过免疫组织化学(HE染色、油红O染色、Masson染色、苏木精染色)及免疫荧光染色检测主动脉斑块形态及不同亚型巨噬细胞的含量。通过实时荧光定量PCR检测主动脉组织中炎症因子的表达。结果姜黄素干预能减轻ApoE~(-/-)小鼠主动脉粥样硬化病变,并降低动脉粥样硬化斑块的易损指数。姜黄素降低动脉粥样硬化斑块内M1/M2巨噬细胞的比值,减少M1型巨噬细胞分泌的促炎因子白细胞介素1β(IL-1β)、诱导型一氧化氮合酶(iNOS)和肿瘤坏死因子α(TNF-α)的表达,促进M2型细胞因子IL-10、Ym1和Fizz1的表达。结论姜黄素可通过影响斑块中巨噬细胞的极性、抑制相关的炎症反应,从而延缓ApoE~(-/-)小鼠动脉粥样硬化的进展。     

霍山石斛对高脂诱导的LDLR基因敲除小鼠动脉粥样硬化和血管钙化的影响

目的 研究霍山石斛(DH)对高脂食物诱导的雄性低密度脂蛋白受体基因敲除(LDLR－/－)小鼠动脉粥样硬化(As)和血管钙化的影响,并初步探讨其作用机制。方法 LDLR－/－小鼠随机分为对照组和霍山石斛组(DH组)。喂养18周后对小鼠处以安乐死,收集血清、主动脉、肝脏等。分析血清中谷丙转氨酶(ALT)、谷草转氨酶(AST)、碱性磷酸酶(ALP)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC)和低密度脂蛋白胆固醇(LDLC)的水平;对全主动脉及其根部切片进行油红O染色,检测动脉粥样硬化斑块面积;主动脉根部切片分别做天狼猩红和茜素红S染色,分析斑块稳定性和血管钙化程度;再对肝脏及其冰冻切片进行检测,分析其脂质积累情况。结果 霍山石斛喂食LDLR－/－小鼠18周后,与对照组比较,DH组小鼠血清TG水平下降(P＜0.05),但不影响血清中转氨酶及其他脂质水平。与对照组比较,DH组小鼠全主动脉及主动脉根部的粥样硬化斑块面积均减少约20%(P＜0.05);斑块损伤区域的胶原纤维含量增加约70%(P＜0.05),从而提高斑块的稳定性,且斑块中坏死核心的发生发展也受到明显抑制;对主动脉根部切片的茜素红S染色发现,对照组主动脉根部钙化面积占比1.34%,而DH组主动脉根部钙化面积占比为0.88%,减少了约34%(P＜0.01)。结论 霍山石斛可以抑制动脉粥样硬化和血管钙化的发生发展。     

复方普洱茶饮料对动脉粥样硬化小鼠主动脉斑块的干预作用及血清TXA2/PGI2比值和DNA甲基化水平的影响

目的探讨复方普洱茶饮料对高脂喂养的Apo E基因敲除(ApoE~(-/-))小鼠动脉粥样硬化(As)斑块的干预作用及血清血栓素(TX)A2/前列环素(PG)I2比值和DNA甲基化水平的影响。方法将30只8周龄雄性ApoE~(-/-)小鼠高脂饲料喂养6 w后随机分为模型组、立普妥(阳性对照组)和茶饮料组(n=10),给予药物干预6 w,另设正常组同品系小鼠(C57BL/6J家系)6只。检测其血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、胰岛素、TXA2、PGI2、DNA甲基化转移酶(DNMT)水平和DNA甲基化水平。HE染色和VG染色,图像分析测量小鼠主动脉As斑块面积、斑块内细胞外脂质成分和胶原成分。结果与模型组相比,茶饮料组和立普妥组小鼠血清TC和TG水平明显降低,HDL-C水平明显升高(均P0.01),校正后主动脉As斑块面积、斑块内细胞外脂质成分显著降低(P0.05);小鼠血清DNA甲基化、DNMT及胰岛素水平、小鼠血清TXA2水平显著降低而血清PGI2水平显著升高(均P0.01)。结论复方普洱茶饮料可以降低血清TXA2/PGI2比值和DNA甲基化水平,从而达到抗ApoE~(-/-)小鼠主动脉As斑块的作用。     

多不饱和脂肪酸不同构成及配比对ApoE－/－小鼠动脉粥样硬化的影响

目的观察多不饱和脂肪酸不同构成及其配比对ApoE~(-/-)小鼠动脉粥样硬化(As)的预防作用,为合理使用脂肪酸预防As提供科学依据。方法设置对照组、模型组、3组实验油组,按饱和脂肪酸(SFA)∶单不饱和脂肪酸(MUFA)∶多不饱和脂肪酸(PUFA)=0.25∶1∶1比例配制3种实验油定制饲料。设计实验油1和油2中ω-6/ω-3 PUFA比例为2.5∶1,实验油3中ω-6/ω-3 PUFA比例为10∶1。其中实验油1中ω-3 PUFA来源为α-亚麻酸(ALA),实验油2及实验油3中ω-3 PUFA来源为二十碳五烯酸(EPA)、二十二碳六烯酸(DHA)和α-亚麻酸(ALA)。记录小鼠体质量变化,主动脉大体油红O染色及主动脉窦HE染色观察主动脉内膜斑块形成情况;肝脏油红O染色观察肝脏脂质蓄积情况;酶法检测肝脏甘油三酯(TG)和总胆固醇(TC)水平;酶法检测血清TG、TC、低密度脂蛋白胆固醇(LDLC)和高密度脂蛋白胆固醇(HDLC)水平。结果与模型组比较,3组实验油均能减少主动脉As斑块形成(P0.05),降低肝脏TG、TC(P0.05),降低血清TG、TC、 LDLC(P0.05),改善肝脏脂质蓄积。与实验油1组及实验油3组比较,实验油2组更能有效抑制主动脉As斑块形成(P0.05),显著降低肝脏TG、TC(P0.05),降低血清TG、TC、LDLC,升高血清HDLC(P0.05),改善肝脏脂质蓄积。结论减少SFA摄入,增加MUFA和PUFA摄入具有抗动脉粥样硬化的作用,EPA、DHA和ALA共同作为ω-3 PUFA的供体比ALA单独提供ω-3 PUFA抗动脉粥样硬化效果更好,低比例ω-6/ω-3PUFA比高比例ω-6/ω-3PUFA抗动脉粥样硬化效果更好。     

实验性小鼠动脉粥样硬化斑块易损指数计算方法的优化

目的通过对Shiomi等提出的以脂质堆积为核心的斑块易损指数计算方法进行优化,以期更全面、客观地对实验性动脉粥样硬化斑块不稳定性进行评估。方法实验分为对照组(C57BL/6小鼠)和模型组(LDLR~(-/-)和ApoE~(-/-)小鼠),每组6只动物。对照组给予正常饲料,模型组给予高脂饲料,25周后处死动物,分离主动脉根部和主动脉弓,经OCT包埋后连续切片,分别进行HE、苦味酸-天狼猩红、油红O、阿利新蓝染色,内皮细胞及平滑肌细胞免疫荧光染色、基质金属蛋白酶及巨噬细胞免疫组织化学染色。对Shiomi等提出的斑块易损指数公式进行改良,在计算公式分子中增加影响斑块不稳定性因素,同时在分母中增加影响斑块稳定性指标,优化动脉粥样硬化斑块易损指数计算公式。通过对比两个公式对LDLR~(-/-)小鼠主动脉根部和无名动脉斑块稳定性的判断,考察评估优化后计算公式的可靠性。之后采用优化公式对高脂饮食ApoE~(-/-)小鼠和LDLR~(-/-)小鼠主动脉不同部位斑块稳定性进行评价,对比两种小鼠动脉粥样硬化进展的差异。结果模型组小鼠主动脉不同部位斑块破损面积,脂质沉积,胶原蛋白、蛋白多糖和基质金属蛋白酶分布,巨噬细胞浸润,纤维帽内皮细胞覆盖率和平滑肌细胞覆盖率与对照组相比发生明显改变。在此基础上优化了基于多指标病理染色的斑块不稳定性计算公式。通过计算发现,ApoE~(-/-)小鼠和LDLR~(-/-)小鼠无名动脉斑块易损指数明显大于主动脉根部;而在相同部位,ApoE~(-/-)小鼠斑块易损指数明显高于LDLR~(-/-)小鼠。结论本研究所优化的基于多指标组织病理学染色的斑块易损指数计算公式,涵盖多种影响斑块不稳定性的重要因素,可对斑块不稳定性进行准确评估。该方法简单、全面、可靠,具有较大实用价值。     

BCG-CpG-DNA对支气管哮喘小鼠肺组织STAT4、STAT6表达的影响

目的 观察BCG-CpG-DNA干预对支气管哮喘(简称哮喘)小鼠信号转导和转录激活因子4(STAT4)、STAT6的影响,探讨其对小鼠哮喘的作用机制.方法 将30只BALB/c小鼠随机分为3组:正常对照组(A组)、哮喘模型组(B组)、BCG-CpG-DNA治疗组(C组).其中B、C组小鼠于第0天、第13天分别给予卵清白蛋白(OVA)和佐剂液态铝混悬液致敏,于第25天至第30天每天给予雾化OVA建立哮喘模型,C组于致敏后以BCG-CpG-DNA腹腔注射,A组以生理盐水代替OVA致敏和激发.所有动物于第31天处死,采用Western blot技术检测小鼠肺组织中STAT4、STAT6的蛋白表达水平.结果 与A组比较,B组STAT4、pSTAT4表达降低(P值均＜0.01),STAT6、pSTAT6的表达升高(P值均＜0.01);与B组比较,BCG-CpG-DNA治疗后小鼠哮喘症状和肺组织的炎症病理变化减轻,STAT4、pSTAT4表达增加,STAT6、pSTAT6表达降低,差异具有统计学意义(P值均＜0.01).结论 BCG-CpG-DNA可能通过抑制STAT6、促进STAT4的表达,调节Th1/Th2细胞因子平衡,从而起到抑制气道炎症的作用.     

西洋参茎叶总皂苷对载脂蛋白E基因敲除小鼠血脂及脂质代谢相关基因周脂素和CD36表达的影响

目的观察西洋参茎叶总皂苷对载脂蛋白E基因敲除小鼠斑块成分及脂质代谢相关基因周脂素和清道夫受体CD36表达的影响,探讨西洋参茎叶总皂苷稳定动脉粥样硬化斑块的作用及可能机制。方法33只6~8周龄小鼠载脂蛋白E基因敲除小鼠予高脂饮食喂养13周后,待其形成成熟的动脉粥样硬化斑块后,随机分为3组:模型组、西洋参茎叶总皂苷组、辛伐他汀组(阳性对照组),每组11只。继续高脂喂养,并按体重比折算给予小鼠临床推荐剂量的相应药物治疗13周,处死动物,检测血脂,取心脏和主动脉,每只小鼠均取主动脉根部的4个切面,分别行HE染色和Movat染色,观察并计算各组小鼠主动脉粥样斑块内脂质核心大小,脂质成分与胶原成分比值。实时荧光定量PCR法检测主动脉内周脂素和CD36 mRNA的表达。结果给药13周后,与模型组比较西洋参茎叶总皂苷组小鼠主动脉斑块内脂质核心面积以及脂质成分与胶原成分比值明显减小(P<0.01),血清高密度脂蛋白显著升高(P<0.01)。而主动脉内周脂素和CD36 mRNA的表达与模型组比较均显著降低(P<0.05)。结论在临床推荐剂量上,西洋参茎叶总皂苷可通过改善载脂蛋白E基因敲除小鼠主动脉斑块内部成分,尤其是减少斑块内脂质含量来起到稳定动脉硬化斑块的作用,其机制可能与抑制脂质代谢相关基因周脂素和清道夫受体CD36 mRNA的表达有关。     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.     

Presence of immunoreactive growth hormone and prolactin in the ovine pineal gland

Abstract: The use of antisera raised against bovine growth hormone (GH) and ovine prolactin (PRL) enabled the detection of related immunoreactive (ir) sequences of proteins in ovine pineal tissue. The isolation of PRL-like ir-material was accomplished using a 0.25 M ammonium sulphate (pH 5.5) extraction followed by ethanol precipitation, whereas the resulting 2.0 M ammonium sulphate (pH 7.0) precipitate contained a GH-like immunoreactivity. Gel chromatography of the GH-like immunoreactivity (Sephadex G-100) indicated the presence of several GH-like fragments ranging in the M_r range of 7,000 to 55,000. Analyses of the PRL-like ir-material found in pineal tissue on HPLC using a TSK 545-DEAE column led to the resolution into a single peak of immunoreactivity. A single peak of activity was also observed following chromatofocusing and hydrophobic interaction chromatography of the ir-peak from the TSK 545-DEAE column. The PRL-like ir-material inhibited the binding of [¹²⁵I]ovine PRL-S14 to anti-ovine PRL antibodies without showing an affinity for binding to anti-rat PRL or anti-bovine GH antibodies. Scatchard analysis of the binding of pineal PRL-like ir-material and pituitary ovine PRL-S14 to liver membranes from day-20 pregnant rats revealed similar affinity constants (K_a of 4.7 ± 0.2 × 10⁹ M^-1). In addition, the replication of Nb 2 Node rat lymphoma cells was stimulated by pineal PRL-like ir-material, an effect known to be specific for lactogenic hormones. The pineal PRL-like immunoreactivity appeared on sodium dodecyl sulfate polyacrylamide gels as a single major band of M_r 24,000. The functional status of PRL-and GH-like ir-material in the ovine pineal remains to be determined, but evidence is presented that the overall protein synthesis rate of the rat pineal responded to circulating concentrations of PRL.     

Microbiology of human immunodeficiency virus anorectal disease

PURPOSE: Individuals who are seropositive for the human immunodeficiency virus are at high risk for opportunistic infection and anorectal disorders. Little prospective information is available regarding anorectal pathogens in these patients. METHODS: One hundred sixty-three HIV-seropositive patients presented to the colorectal clinic between 1989 and 1992. Forty-seven (29 percent) patients were thought to have an infectious process and were prospectively studied using a standardized multiculture protocol. RESULTS: Mean age was 33 (range, 19–59) years. All were male; high-risk behavior accounted for 87 percent of HIV transmissions. Presenting complaints included anorectal pain (79 percent), pus per anum (28 percent), and blood per anum (26 percent). Examination revealed perianal tenderness (60 percent), condyloma (38 percent), perianal ulcers (38 percent), and anal fissures (34 percent). Sixty-six sets of cultures were performed; 28 patients had one set, 15 had two sets, and 4 had three sets. Thirty-two of these 47 patients (68 percent) had positive cultures including herpes (50 percent), cytomegalovirus (25 percent),Neisseria gonorrhoeae (16 percent), chlamydia (16 percent), acidfast bacilli (2 percent), and others (9 percent). Six of 32 patients with positive cultures had more than one organism cultured. Sixteen (50 percent) patients with positive cultures were treated medically, 8 (25 percent) were treated surgically and 8 (25 percent) were treated with both modalities. Sixty-one procedures were performed on 17 patients for condylomata. Eighteen patients had 20 procedures for abscesses, 50 percent of whom had positive cultures for other than common bowel flora; all improved. Fourteen patients underwent 33 procedures for perianal fistulas.Mycobacterium fortuitum was cultured from one patient who required 13 procedures for abscesses and fistulas. Forty-five (96 percent) patients were followed for an average of 12.5 months ±2.9 SEM (range, 1–94 months). Symptoms were improved or resolved in 22 of 32 (69 percent) patients with positive cultures and in 11 of 13 (84 percent) with negative cultures. CONCLUSIONS: Specific pathogens may often be identified in human immunodeficiency virus-seropositive patients with anorectal disorders if aggressively sought. Although patients without specific pathogens identified may be expected to improve with planned empiric treatment, positive identification allows more directed therapy.