Flt-3L、SCF在食管癌患者外周血细胞的诱导及树突细胞的培养

目的探讨从食管癌患者外周血分离、诱导与扩增树突细胞(DC)的有效方法。方法采用密度梯度离心法从食管癌患者外周血分离单个核细胞,分别加入GM-CSF(100 ng/ml)+IL-4(50 ng/ml)(作为对照组);GM-CSF(100 ng/ml)+IL-4(50 ng/ml)+Flt-3L(40 ng/ml)(作为实验1组);加入GM-CSF(100 ng/ml)+IL-4(50 ng/ml)+Flt-3L(40 ng/ml)+SCF(100 ng/ml)(作为实验2组)。于37℃、5%CO2环境下进行培养,动态观察细胞生长情况,流式细胞仪检测培养第6天时DC表面分子CD1a、CD83、CD80、CD86的表达水平。结果上述不同刺激物均能从外周血单个核细胞成功诱导出DC,与对照组相比,实验组诱导出更多数量的DC,其中以实验2组最多;培养至第6天时,两实验组DC细胞表型CD1a表达率与对照组无明显差别(P>0.05),CD83、CD80、CD86表达水平明显高于对照组(P<0.01),其中以实验2组表达水平最高(P<0.01)。结论联合应用GM-CSF、IL-4、flt-3L和SCF能有效地从食管癌患者外周血诱导培养出大量具有活性的DC,为进一步的临床研究奠定基础。     

直肠癌患者外周血单核细胞诱导为树突细胞

目的 用直肠癌患者外周血单核细胞通过体外培养的方法诱导为成熟树突细胞.方法 CS-3000血细胞分离机采集直肠癌患者外周血单核细胞悬液,Ficoll分离单个核细胞,用含10%FBS的RPMI-1640培养基培养,第0天加入GM-CSF 1 000 U/ml、IL-4 500 U/ml,第4天2/3量换液,补足GM-CSF、白介素(IL)-4,并加入肿瘤坏死因子(TNF)-α 500 U/ml诱导其成熟,以后每隔3天2/3量换液.结果 培养至第11天,收集培养的1×105～2×105个树突细胞经流式细胞仪检测表达CD83+(52.9±5.8)%,CD86+(79.2±8.1)%,HLA-DR(65.8±5.7)%,CD1a(51.3±6.4)%,及CD+14(4.72±2.16)%.结论 直肠癌患者外周血单核细胞经GM-CSF、IL-4及TNF-α联合培养能诱导出成熟树突细胞.为直肠癌的免疫治疗提供了临床应用基础.     

树突状细胞与冠状动脉严重狭窄的关系及辛伐他汀的干预作用

目的探讨冠状动脉严重狭窄患者动脉粥样硬化与树突状细胞关系及辛伐他汀免疫干预作用的可能机制。方法根据选择性冠状动脉造影结果,20例冠状动脉正常,无明显动脉粥样硬化斑块者为阴性对照组;20例冠状动脉严重狭窄,未服用他汀类药物者为动脉粥样硬化组;20例冠状动脉严重狭窄,服用辛伐他汀40mg/d,连续30天以上者为辛伐他汀组。分别抽取冠状动脉血20mL,采用密度梯度离心法分离单个核细胞,行树突状细胞体外培养扩增,采用流式细胞术检测树突状细胞免疫表型、平均荧光强度、刺激T淋巴细胞增殖能力的刺激指数;动脉粥样硬化组分为B1、B2两个亚组,B2组在树突状细胞培养第5天时加入100μmol/L辛伐他汀,其他培养与检测方法相同。结果冠状动脉血分离单个核细胞后经体外培养与扩增,均成功培养出典型树突状细胞,各组树突状细胞形态无差异;与阴性对照组比较,B1组CD1a阳性细胞比例、CD1a与CD80、CD83、CD86双阳性细胞比例、平均荧光强度、收获细胞总数、树突状细胞数量和刺激指数均明显增高(P<0.05);与B1组比较,B2组收获细胞总数无差异,但CD1a阳性细胞比例、CD1a与CD80、CD83、CD86双阳性细胞比例、平均荧...     

高浓度胰岛素对人树突状细胞分化、成熟及免疫功能的影响

目的:研究高浓度胰岛素对树突状细胞(Dendritic Cell,DC)分化、成熟及免疫功能的影响。方法:采用连续贴壁法分离正常人外周血单核细胞,在含重组人粒-巨噬细胞集落刺激因子(GM-CSF,100ng/ml)和重组人白细胞介素-4(IL-4,100ng/ml)的完全培养基中培养。5天后收集细胞,重新铺板后继续在胰岛素浓度分别为0nmol/L、10nmol/L及100nmol/L的培养基中培养48小时,收集细胞和上清液,采用流式细胞术检测细胞表面CD40、CD80和CD83的表达;用ELISA法检测上清液中细胞因子IL-12、IL-10、TNF-α的浓度;用倒置显微镜动态观察DC形态变化。结果:胰岛素浓度为10nmol/L、100nmol/L组的DC表面标成CD40、CD80和CD83阳性表达率较含胰岛素0nmol/L的对照组升高,培养上清液中细胞因子IL-12、TNF-α的浓度也较对照组升高,而细胞因子IL-10的浓度则较对照组降低。结论:高浓度胰岛素促进了树突状细胞表型CD40、CD80和CD83的表达;促进了DC对细胞因子IL-12和TNF-α的分泌;对IL-10的分泌则起抑制作用。高浓度胰岛素通过促进树突状细胞免疫功能的成熟,可能是其参与动脉粥样硬化免疫炎症反应的发生、发展的机制之一。     

体外诱导白血病源性树突状细胞及其对T细胞杀伤活性影响的研究

目的 :探讨体外培养白血病源性树突状细胞 (DC)及其对T细胞杀伤活性的影响。方法 :从慢性髓细胞性白血病 (CML)患者外周血中分离单个核细胞 ,加入 1× 10 6U/L粒 巨噬细胞集落刺激因子 (GM CSF)、1×10 6U/L白细胞介素 (IL) 4和 5 0× 10 3 U/L肿瘤坏死因子 (TNF α) ,每 3～ 4天换液 1次 ,连续培养 14天 ,获得DC。取外周血单个核细胞加入 5 0 0× 10 3 U/LIL 2 ,培养至第 7天 ,把细胞分成两组 ,其中一组加入培养的DC ,两组细胞继续培养 3～ 4天 ,然后测定T细胞杀伤活性。结果 :DC具有典型的树状突起 ,高表达CD1a,具有慢粒特异性染色体t(9;2 2 ) ,能增强T细胞对白血病细胞的杀伤活性。结论 :在体外利用细胞因子可以把CML细胞诱导分化成具有刺激T细胞产生细胞毒性反应的白血病源性DC。     

高浓度胰岛素对急性冠状动脉综合征患者外周单核细胞源树突状细胞分化成熟及免疫功能的影响

目的 研究高浓度胰岛素对急性冠状动脉综合征患者外周单核细胞源树突状细胞分化、成熟及免疫功能的影响.方法 采用贴壁法分离急性冠状动脉综合征患者(ACS组)和正常人(正常组)外周血单核细胞,在含粒-巨噬细胞集落刺激因子(100 μg/L)和白细胞介素4(100 μg/L)的RPMI 1640完全培养基中培养.5天后收集细胞,作为未成熟树突状细胞,重新铺板后继续在胰岛素浓度分别为1、10 nmol/L和100 nmol/L的RPMI1640完全培养基中培养48 h后,收集细胞和上清液,此时细胞作为成熟树突状细胞,采用流式细胞术检测成熟树突状细胞表面 CD40、CD80和CD83的表达;用酶联免疫吸附法测定检测上清液中细胞因子白细胞介素12、白细胞介素10和肿瘤坏死因子α的浓度;用倒置显微镜动态观察树突状细胞形态变化.结果 树突状细胞表型CD40、CD80和CD83随着胰岛素浓度升高而升高(P＜0.05),培养上清液中细胞因子白细胞介素12、肿瘤坏死因子α的浓度也随着胰岛素浓度升高而升高(P＜0.05),而细胞因子白细胞介素10的浓度则随着胰岛素浓度升高而降低(P＜0.05).同等胰岛素浓度下,急性冠状动脉综合征患者较正常组的树突状细胞表面CD40、CD80和CD83的阳性表达率升高(P＜0.05),培养上清液中细胞因子白细胞介素12、肿瘤坏死因子α的浓度升高(P＜0.05),而细胞因子白细胞介素10的浓度则降低(P＜0.05).结论 高浓度胰岛素促进了急性冠状动脉综合征患者的树突状细胞表面标志物CD40、CD80和CD83的表达;促进了树突状细胞对细胞因子白细胞介素12和肿瘤坏死因子α的分泌;对白细胞介素10的分泌则起抑制作用.高浓度胰岛素通过促进树突状细胞免疫功能成熟,参与动脉粥样硬化免疫炎症反应的发生和发展,是急性冠状动脉综合征发生的可能机制之一.     

乙型肝炎病毒感染对造血干细胞活性的影响

目的 了解HBV感染对脐血来源的造血干细胞活性的影响.方法 将分离纯化的健康脐血CD34+细胞,在含有干细胞生长因子(SCF)、酪氨酸激酶受体家族Ⅲ配体(FL)、促血小板生成素(TPO)、IL-3和10%FBS的IMDM培养基中扩增,同时加入高拷贝HBV,观察干细胞扩增与病毒复制规律;干细胞扩增后,在巨细胞集落刺激因子(GM-CSF)和IL-4作用下诱生树突状细胞,对干细胞及树突细胞进行形态学观察,并检测其表面分子的表达.两组间比较采用独立t检验,多组间比较采用方差分析.结果 感染HBV的造血干细胞自然增殖能力明显低于正常干细胞(P<0.01);加入细胞因子后细胞增殖增加(P<0.01),细胞内HBV DNA复制也增加(P<0.01),但其干细胞增殖仍低于正常干细胞加细胞因子组(P<0.05).电子显微镜观察发现HBV感染干细胞后胞质内出现Dane颗粒;HBV感染的干细胞经诱导为树突状细胞后,其免疫表型CD80、CD86、CD1a、HLA-DR的表达均低于未感染组(P<0.01).结论 HBV可以感染CD34+造血干细胞,并随干细胞增殖而复制增加,HBV不仅抑制造血干细胞增殖,而且下调干细胞分化来源的树突状细胞免疫表型的表达.     

三氧化二砷对炎症细胞的影响及其分子机制

目的观察三氧化二砷(As2O3)对人T淋巴细胞和人树突状细胞(DCs)凋亡以及对树突状细胞表型、细胞因子分泌的影响,探索As2O3洗脱支架局部抗炎作用的有关机制。方法分离培养人T淋巴细胞,用rhGM-CSF和rhIL-4诱导单个核细胞分化为树突状细胞,流式细胞仪检测As2O3对T淋巴细胞和树突状细胞凋亡的影响;用LPS诱导树突状细胞分化成熟,流式细胞仪检测As2O3干预对树突状细胞成熟表型的影响,ELISA检测As2O3对树突状细胞分泌细胞因子的影响。结果 As2O3在1umol/L浓度时即可明显诱导人T淋巴细胞凋亡,在5umol/L浓度时可诱导树突状细胞凋亡,且均呈剂量依赖性;As2O3在低于凋亡诱导剂量时即可抑制LPS诱导的树突状细胞成熟,下调树突状细胞表面分子CD83和CD86的表达率,并减少树突状细胞IL-10、IL-12和IFN-γ等细胞因子的释放。结论 As2O3具有诱导T淋巴细胞、树突状细胞凋亡以及抑制树突状细胞的免疫成熟的作用,As2O3洗脱支架的局部抗炎作用和As2O3的上述作用有关。     

分化抑制培养体系体外扩增脐血造血细胞的研究

目的:探讨分化抑制培养体系对脐血造血细胞体外扩增效应。方法:分化抑制培养体系与脐血单个核细胞(MNC)体外共同培养7 d,检测MNC细胞总数、CFC、CD34 细胞反应扩增效果,并检测CD34 细胞表面归巢相关黏附分子VLA-4(CD49d)、VLA-5(CD49e)、LFA-1(CD11a)、HCAM(CD44)、L-selectin(CD62L)的表达率。结果:分化抑制培养体系组明显扩增脐血MNC细胞总数、CFC、CD34 细胞(均P<0．05),对照组培养脐血MNC细胞总数明显下降,CFC和CD34 细胞完全死亡(均P<0．01)。CD34 细胞表面各黏附分子CD49d、CD44和C1362L表达与扩增前相当(均P>0．05),而CD49e和CD11a表达明显高于扩增前(均P<0．05)。结论:分化抑制培养体系体外显著扩增脐血造血细胞,并且扩增后的造血干(祖)细胞总体上保持其表面归巢相关黏附分子的表达,归巢功能不会减低,是一种安全有效的扩增体系。     

体外诱导人骨髓单个核细胞生成树突状细胞的实验研究

目的通过体外诱导人骨髓单个核细胞（MNC）生成大量树突状细胞（DC）,为抗肿瘤免疫提供效应细胞。方法使用淋巴细胞分层液密度梯度离心技术从人骨髓中分离大量的MNC,利用几种细胞因子GM-CSF、TNF-a、SCF、FL进行配伍的方法诱导MNC生成DC,利用光镜和电镜观察细胞形态并用流式细胞仪检测细胞表型。结果MNC经细胞因子组合诱导后定向分化为DC,DC由未成熟状态过渡到成熟状态,DC细胞表型发生改变。结论经细胞因子配伍可诱导MNC生成大量DC。     

胰岛素瘤的解剖分布特点分析

目的胰岛素瘤是最常见的胰腺神经内分泌肿瘤，因其临床表现多样，导致诊断困难。影像学诊断尤其是超声内镜(EUS)在胰岛素瘤的诊断中起着重要作用，拥有较高的敏感性和特异性。本研究拟通过明确胰岛素瘤的解剖分布特点，以期有助于提高影像学的诊断准确率和降低漏诊率，尤其是在教育和培训实践中对于EUS的学习者更具有指导价值。 方法回顾性分析解放军总医院第一医学中心病案资料数据库1993年1月至2019年11月经外科手术、病理确诊为胰岛素瘤的患者的临床资料，检索方法采取搜索术后病理诊断为"胰岛素瘤"的病例，通过查阅病例的方法，提取出胰岛素瘤的大小和解剖分布等数据，进一步分析其特点。 结果共检索到确诊为胰岛素瘤的患者116例，其中，男45例、女71例，年龄13～76岁，平均年龄(44.4±14.85)岁。胰岛素瘤单发110例(94.8%)、多发6例(5.2%)。位置分布：头颈部46例(39.7%)，单发45例、多发1例；体尾部68例(58.6%)，单发65例、多发3例；全胰腺多发2例(1.7%)。病变大小特点：最大径0.4～3.4 cm，平均大小(1.53±0.58)cm。≤1 cm 29例、>1 cm而≤1.5 cm41例、>1.5 cm而≤2.0 cm28例，≤3 cm 15例，>3 cm 3例。年龄与肿瘤的大小相关，≤44岁患者肿瘤平均大小为(1.36±0.51)cm、>44岁患者肿瘤平均大小为(1.70±0.60)cm，P<0.05。头颈部的肿瘤大于体尾部的肿瘤，头颈部肿瘤平均大小(1.66±0.63)cm，体尾部(1.42±0.52)cm，P<0.05。 结论胰岛素瘤在胰腺体尾部较头颈部更好发；绝大多数单发，但可以全胰腺多发；多数小于1.5 cm，肿瘤的大小与患者年龄和肿瘤的解剖分布相关。     

Pathogenesis of carcinoma of the papilla of Vater

Most adenomas and carcinomas of the small intestine and extrahepatic bile ducts arise in the region of the papilla of Vater. In familial adenomatous polyposis (FAP) it is the main location for carcinomas after proctocolectomy. In many cases symptoms due to stenosis lead to diagnosis at an early tumor stage. In about 80%, curative intended resection is possible. Operability is the most relevant prognostic factor. Most ampullary carcinomas resp. carcinomas of the papilla of Vater develop from adenomatous or flat dysplastic precursor lesions. They can be sited in the ampulloduodenal part of the papilla of Vater, which is lined by intestinal mucosa. They also can develop in deeper parts of the ampulla, which are lined by pancreaticobiliary duct mucosa. Intestinal-type adenocarcinoma and pancreaticobiliary-type adenocarcinoma represent the main histological types of ampullary carcinoma. Furthermore, there exist unusual types and undifferentiated carcinomas. Many carcinomas of intestinal type express the immunohistochemical marker profile of intestinal mucosa (keratin 7?, keratin 20+, MUC2+). Carcinomas of pancreaticobiliary type usually show the immunohistochemical profile of pancreaticobiliary duct mucosa (keratin 7+, keratin 20?, MUC2?). Even poorly differentiated carcinomas, as well as unusual histological types, may conserve the marker profile of the mucosa they developed from. These findings underline the concept of histogenetically different carcinomas of the papilla of Vater which develop either from intestinal- or from pancreaticobiliary-type mucosa of the papilla of Vater. Molecular alterations in ampullary carcinomas are similar to those of colorectal as well as pancreatic carcinomas, although they appear at different frequencies. In future studies, molecular alterations in ampullary carcinomas should be correlated closely with the different histologic tumor types. Consequently, the histologic classification should reflect the histogenesis of ampullary tumors from the two different types of papillary mucosa.     

Demonstration of the mechanism of action of biguanides

Summary Palmitic acid oxidation in rat diaphragm homogenate is depressed by biguanide concentrations that are still incapable of inhibiting oxidative phosphorylation. Glucose oxidation is not directly effected by the same biguanide concentrations: however, the inhibitory effect of palmitic acid on glucose oxidation is partly removed by biguanides. Inhibition of fatty acid oxidation, which accounts for most of the metabolic effects caused by these drugs, can be regarded as the fundamental mechanism of action of biguanides. There is some evidence suggesting that these drugs might interact with carnitine, thus preventing long-chain fatty acids from being transported across the mitochondrial membrane to the site of oxidation. Traduzione a cura degli AA.     

Lack of correlation of degree of villous atrophy with severity of clinical presentation of coeliac disease

BACKGROUND AND AIM: Both the clinical presentation and the degree of mucosal damage in coeliac disease vary greatly. In view of conflicting information as to whether the mode of presentation correlates with the degree of villous atrophy, we reviewed a large cohort of patients with coeliac disease. PATIENTS AND METHODS: We correlated mode of presentation (classical, diarrhoea predominant or atypical/silent) with histology of duodenal biopsies and examined their trends over time. RESULTS: The cohort consisted of 499 adults, mean age 44.1 years, 68% females. The majority had silent coeliac disease (56%) and total villous atrophy (65%). There was no correlation of mode of presentation with the degree of villous atrophy (p=0.25). Sixty-eight percent of females and 58% of males had a severe villous atrophy (p=0.052). There was a significant trend over time for a greater proportion of patients presenting as atypical/silent coeliac disease and having partial villous atrophy, though the majority still had total villous atrophy. CONCLUSIONS: Among our patients the degree of villous atrophy in duodenal biopsies did not correlate with the mode of presentation, indicating that factors other than the degree of villous atrophy must account for diarrhoea in coeliac disease.     

血吸虫童虫生长发育及其机制的研究进展

血吸虫童虫是宿主免疫系统攻击的重要靶标,包括皮肤型、肺型和肝门型童虫。宿主分子对童虫生长发育具有重要作用。童虫生长发育机制包括免疫调节、信号转导、性别发育及凋亡等。肌动蛋白、组织蛋白酶、烯醇化酶和葡萄糖基转移酶等分子为血吸虫童虫生长发育的重要分子。本文对血吸虫童虫生长发育及其机制的研究进展做一综述。     

124例耐多药结核分枝杆菌基因突变特征分析

目的对临床分离的耐多药结核分枝杆菌相关基因的突变特征进行分析。方法对124例耐多药结核分枝杆菌以及50株敏感株的耐药相关基因(包括异烟肼inh A、kat G、oxyR-ahp C间隔区以及利福平rpo B)进行序列测定,分析其基因突变情况。结果异烟肼耐药inh A基因突变率为14.5%;kat G基因突变率为70.2%(87/124),主要位于315位;oxyR-ahp C间隔区突变率为15.3%;inh A、kat G两种基因同时突变率75.0%,三种基因同时突变率为89.5%。利福平rpo B基因突变的检出率高达95.2%,突变主要发生在531、526、516位点。结论我省耐多药菌异烟肼耐药相关基因最常见突变为kat G 315、inh A C-T(-15)、axyR-ahp C间隔区(-10)C-T,利福平为rpo B531、526、516。结合MDR-TB耐药相关基因的特征分析,可以建立一种快速、准确、特异的适合于我省的检测结核菌耐多药性的新方法。     

氯硝柳胺悬浮剂的毒性评价

目的评价氯硝柳胺悬浮剂的毒性，为现场大规模应用灭螺提供依据。方法按照中华人民共和国国家标准GB 15670-1995《农药登记毒理学试验方法》和鱼类毒性试验方法进行。结果经口、经皮肤的LDso雌、雄性大鼠均>5 000 mg/kg，经呼吸道的LCso雌、雄性大鼠均>5 000mg/m3，该药经口、经皮肤、经呼吸道毒性均属微毒类药物；兔眼用药后，观察期内无不良反应，对眼无刺激性；皮肤用药后对皮肤无刺激性。与氯硝柳胺原药、氯硝柳胺乙醇胺盐原药和氯硝柳胺乙醇胺盐可湿性粉剂相比，氯硝柳胺悬浮剂对鱼急性毒性最低。结论氯硝柳胺悬浮剂属微毒类药物，对鱼的毒性低于其乙醇胺盐可湿性粉剂，适合于现场应用。     

Assessment of quality of life of parents of children with juvenile chronic arthritis

The aim of the study was to assess the quality of life (QOL) and the psychological status of parents of children with juvenile chronic arthritis (JCA). The QOL, anxiety and depression of the parents of 28 children with JCA were evaluated and compared to those of the parents of 28 healthy children. Mothers of JCA children and mothers of healthy children reported similar QOL. The reported anxiety and depression levels were similar for mothers and fathers in both groups. The parents of children with pauciarticular-type JCA reported lower QOL and higher levels of anxiety and depression than the parents of children with other types, namely polyarticular and systemic JCA. These findings may be explained by the fact that the pauciarticular patients had shorter disease duration and were less frequently seen in the outpatient clinic. The QOL of mothers of children with JCA was found to be slightly impaired in the group of children with pauciarticular JCA. Future larger studies are needed to confirm these results, as the number of subjects in the three groups was rather low. Received: 26 September 2001 / Accepted: 8 February 2002     

Numerical Simulation of the Effect of Rate of Change of Glucose on Measurement Error of Continuous Glucose Monitors

Background

A 5-day in-patient study designed to assess the accuracy of the FreeStyle Navigator® Continuous Glucose Monitoring System revealed that the level of accuracy of the continuous sensor measurements was dependent on the rate of glucose change. When the absolute rate of change was less than 1 mg•dl⁻¹•min⁻¹ (75% of the time), the median absolute relative difference (ARD) was 8.5%, with 85% of all points falling within the A zone of the Clarke error grid. When the absolute rate of change was greater than 2 mg•dl⁻¹•min⁻¹ (8% of the time), the median ARD was 17.5%, with 59% of all points falling within the Clarke A zone.

Method

Numerical simulations were performed to investigate effects of the rate of change of glucose on sensor measurement error. This approach enabled physiologically relevant distributions of glucose values to be reordered to explore the effect of different glucose rate-of-change distributions on apparent sensor accuracy.

Results

The physiological lag between blood and interstitial fluid glucose levels is sufficient to account for the observed difference in sensor accuracy between periods of stable glucose and periods of rapidly changing glucose.

Conclusions

The role of physiological lag on the apparent decrease in sensor accuracy at high glucose rates of change has implications for clinical study design, regulatory review of continuous glucose sensors, and development of performance standards for this new technology. This work demonstrates the difficulty in comparing accuracy measures between different clinical studies and highlights the need for studies to include both relevant glucose distributions and relevant glucose rate-of-change distributions.     

Study of constancy of hydrogen-consuming flora of human colon

The constancy of the hydrogen consuming flora of the human colon was studied in 15 healthy subjects via two measurements obtained 18 to 36 months apart. Hydrogen disappearance rate and the major products of H₂-consuming bacteria, methane and sulfide, were measured during incubation of fecal homogenates with excess hydrogen and sulfate. In 11/15, the hydrogen consumption rate and the predominant hydrogen-consuming pathway (methanogenesis, sulfate reduction, or neither) remained constant. However, major shifts in these pathways were observed in four subjects, with two losing and two gaining the ability to produce methane. Methanogenesis was associated with the highest hydrogen consumption rate. This study demonstrates that clinically unrecognizable, major alterations of the colonic flora occur in healthy subjects. Understanding of the factors responsible for these alterations might allow for therapeutic manipulation of the colonic flora.Supported in part by the Department of Veterans Affairs and NIDDKD RO1 DK 13309-25.