石斛合剂对衰老糖尿病大鼠胰腺组织凋亡相关基因Bax,Bcl-2mRNA及蛋白表达的调控

目的观察石斛合剂对衰老及衰老糖尿病（DM）大鼠胰腺组织凋亡相关基因Bax、Bcl-2mRNA及蛋白表达的影响。方法采用D-半乳糖致衰，继而加高脂高糖及注射低剂量链脲佐菌素（STZ）制备衰老DM模型，测定血清中SOD、MDA浓度，并利用RT-PCR法和Western-Blot法检测大鼠胰腺组织凋亡相关基凼Bax、Bcl-2mRNA及蛋白表达水平。结果与衰老及衰老DM组相比，石斛合剂各治疗组MDA浓度明显降低（P〈0．05），SOD浓度明显升高（P〈0．05～0．01），衰老DM石斛合剂治疗组胰腺组织BaxmRNA及蛋白水平明显降低（P〈0.05～0．01），Bcl-2mRNA及蛋白水平明显升高（P〈0．05）。结论①衰老大鼠呈现Bax／Bcl-2比值显著升高，衰老DM大鼠Bax／Bcl-2比值升高更为显著，即衰老大鼠Bax和Bcl-2mRNA及蛋白表达失衡，且这种失衡在衰老DM大鼠显得更为突出；②石斛合剂降低血糖，显著升高衰老及衰老DM大鼠SOD水平，降低MDA水平，其分子机制之一与其降低衰老DM大鼠胰腺组织Bax、增加Bcl-2 mRNA及蛋白水平，即调整Bax和Bcl-2mRNA及蛋白表达的失衡有关。     

血液透析患者外周血淋巴细胞凋亡与Bax蛋白表达的临床意义

采用流式细胞术检测32例血液透析（HD）患者外周血淋巴细胞（PBLs）Bax蛋白表达水平和凋亡率。结果HD患者较正常组PBLs表达Bax蛋白水平明显增高（P〈0．01），PBLs凋亡率增加（P〈0．01）；PBLs Bax蛋白表达水平与凋亡率成正相关（r=0．7124，P〈0．05）。认为Bax蛋白表达增高促使PBLs凋亡增加。     

缬沙坦对大鼠缺血-再灌注心肌caspase-3活性及凋亡相关基因表达的影响

目的：观察缬沙坦对大鼠心肌缺血-再灌注(I/R)时心肌细胞天冬氨酸特异的半胱氨酸蛋白酶-3(caspase-3)活性、Bcl-2和Bax蛋白表达的影响。方法：以SD大鼠建立I/R模型,设立I/R组、缬沙坦组和假手术组。用分光光度法检测caspase-3活性,免疫组化法检测心肌组织Bcl-2和Bax蛋白表达,透射电镜观察心肌超微结构的变化。结果：同I/R组相比,缬沙坦组心肌组织caspase-3活性明显降低(P＜0．05),Bax蛋白表达显著降低(P＜0．01),而Bcl-2蛋白表达显著增高(P＜0．01),Bax/Bcl-2显著降低(P＜0．01),心肌细胞超微结构损伤明显减轻。结论：缬沙坦通过抑制caspase-3活性、调控Bax/Bcl-2表达而抑制心肌I/R所致细胞凋亡。     

缬沙坦对2型糖尿病大鼠肾脏细胞凋亡及调控基因Bcl-2、Bax的影响

目的：观察缬沙坦对2型糖尿病大鼠肾脏细胞凋亡及其调控基因Bcl-2、Bax的影响。方法：随机选择15只SD雄性大鼠，以高糖高脂饲料喂养6周后，腹腔注射STZ30mg／kg；2周后血糖升高≥16mmol／L者12只，随机又分为2型糖尿病组（n=6）和2型糖尿病缬沙坦治疗组（简称治疗组，n=6），治疗8周，另选6只健康SD雄性大鼠为空白对照组，查内生肌酐清除率（Ccr），24h尿白蛋白的排泄率（Uaer）。流式细胞术检测大鼠肾脏细胞凋亡率。免疫组化法检测Bcl-2、Bax的表达。结果：8周后，糖尿病组大鼠肾小球细胞外基质增生，部分肾小管轻度萎缩或管腔扩张，上皮细胞肿胀，胞浆内可见脂肪空泡变性，但治疗组较糖尿病组病变减轻。细胞凋亡率糖尿病组较治疗组高（26．54±2．67VS20．05±2．03，P〈0．05）；Ccr糖尿病组较治疗组低（O．021±0．001VS0．065±0．004ml／min，P〈0．05），Uaer糖尿病组高于对照组和治疗组（O．150±0．004VS0．081±0．001，0．086±0．002mg，P〈0．05）。治疗组和糖尿病组肾小管均较对照组的Bcl-2和Bax阳性表达高（P-40．05），治疗组肾小管Bcl-2较糖尿病组的阳性表达高，而Bax阳性表达低（P〈O．05）。结论：缬沙坦通过增加Bcl-2／Bax在肾小管的比例，使糖尿病大鼠肾脏细胞凋亡率减低，保护肾功能。     

虫草菌丝对非酒精性脂肪肝病大鼠肝细胞凋亡的作用及其相关机制

目的（1）证实肝细胞凋亡的异常增多存在于非酒精性脂肪性肝病中。（2）观察虫草菌丝对肝细胞凋亡异常增多的影响，并探讨可能的分子机制。方法通过高脂饮食建立大鼠非酒精性脂肪性肝病（NAFLD）的模型，同时设立正常饮食对照组，病理对照组（NASH组），虫草菌丝干预组（CS组）。肝组织切片HE染色观察肝脏病理改变；检测肝组织超氧化物歧化酶（SOD）活性；TUNEL检测肝组织肝细胞凋亡情况；免疫组织化学染色观察肝组织Bax、Bcl-2、Caspase-3、NF-κB P65蛋白表达情况。结果（1）与正常对照组相比，病理对照组大鼠肝组织广泛弥漫肝细胞脂肪变性，炎性细胞浸润、坏死、局部有纤维组织增生；肝脏SOD活性显著降低（P〈0．01）；TUNEL法检测肝细胞凋亡显著增多（P〈0．01）；免疫组化染色显示Bax、Caspase-3蛋白表达增加（P〈0．01），而Bcl-2无显著变化（P〉0．05）；（2）与病理对照组相比，虫草菌丝组大鼠肝组织有广泛肝细胞脂肪变性，炎性细胞浸润，可见灶性及点状坏死，未见纤维组织增生；肝组织SOD活性高于病理对照组（P〈0．05）；TUNEL法检测凋亡的肝细胞显著减少（P〈0．01）；免疫组化染色显示Bax、Caspase-3蛋白表达也明显降低（分别为P〈0．05、P〈0．01），而Bcl-2、NF-κB P65蛋白表达增加（P〈0．01）。结论（1）NASH时肝细胞凋亡异常增多。（2）虫草菌丝可以通过增加超氧化物歧化酶（SOD）活性来减少活性氧含量，降低Bax表达，增加Bcl-2表达和活化NF-κB P65减轻NAFLD中肝细胞凋亡从而在一定程度上具有保护肝脏功能的作用，对延缓或阻止脂肪肝病变的进展起到一定的作用。     

衰老大鼠动脉顺应性与凋亡相关指标变化及缬纱坦对其影响

目的探讨衰老大鼠动脉顺应性与凋亡相关指标变化及缬纱坦对其影响,为阐明血管衰老对动脉硬化诊治的重要意义。方法Wistar大鼠分为青年组、衰老组及缬纱坦组,测定血浆丙二醛、超氧化物歧化酶水平,同时采用恒速注入流体方法测定大鼠颈动脉血管的顺应性,并利用免疫组织化学染色法、反转录—聚合酶链式反应和蛋白免疫印迹法分析各组凋亡相关基因Bcl-2 mRNA及蛋白表达、半胱氨酸天门冬氨酸蛋白酶3活性变化水平。结果与衰老组相比,缬纱坦组血浆丙二醛浓度明显降低(P<0.05),超氧化物歧化酶浓度明显升高(P<0.05);颈动脉血管的顺应性增高,其中弹性面积差异有显著性(P<0.05);主动脉血管Bcl-2阳性内皮细胞百分率增高(P<0.05),半胱氨酸天门冬氨酸蛋白酶3表达降低(P<0.05);Bcl-2 mRNA及蛋白表达水平明显增高(P<0.05),半胱氨酸天门冬氨酸蛋白酶3活性水平降低(P<0.01)。结论血管衰老有其特征性生理改变,凋亡相关基因Bcl-2表达下调、半胱氨酸天门冬氨酸蛋白酶3活性增高可能是血管衰老的重要分子机制之一,缬纱坦对血管衰老有一定保护作用,为延缓血管衰老以及防治动脉硬化开辟新途径。     

顺铂对胃癌细胞Bax和Bcl-2表达的影响

目的通过研究顺铂对人胃癌BGC-823细胞Bax和Bcl-2的影响,探讨顺铂对人胃癌BGC-823细胞增殖和凋亡的影响及可能的机制。方法用化疗药物顺铂以不同浓度、不同时间处理对数期生长的人胃癌BGC-823细胞,采用MTT法检测顺铂对BGC-823细胞增殖抑制率的影响,采用免疫印迹和逆转录聚合酶链反应（RT-PCR）法检测Bax及Bcl-2蛋白和mRNA的表达。结果顺铂对人胃癌细胞BGC-823生长增殖具有明显抑制作用,其效应成浓度和时间依赖性（P〈0．05）。不同浓度的顺铂处理BGC-823细胞24小时后,Bax蛋白和mRNA水平成浓度依赖性增加（P〈0．05）,而Bcl-2蛋白和mRNA水平成浓度依赖性减少。结论经顺铂处理的人胃癌BGC一823细胞,不论是在转录水平还是在翻译水平均上调了Bax的表达,同时使Bcl-2表达下调,此途径可能为顺铂所诱导肿瘤细胞凋亡的机制之一。     

洛沙坦对高血压大鼠血管平滑肌细胞凋亡及凋亡基因Bax和Bcl-2的影响

目的研究血管紧张素Ⅱ ATI-R阻滞剂洛沙坦对自发性高血压大鼠（SHR）血管平滑肌细胞（VSMC）凋亡及凋亡基因Bax、Bcl-2的影响。方法末端标记法（TUNEL）检测细胞凋亡及RT—PCR、免疫组化方法分别检测Bax、Bcl-2基因及其蛋白的表达。结果从（12～24）周龄，SHR VSMC凋亡逐渐减低，24周龄时，凋亡指数（APOI）低于同周龄正常血压大鼠（WKY）（P〈0.05）；洛沙坦应用8周和12周。使APOI增加71％、35％（P〈0．05）。随大鼠周龄增加，SHR胸主动脉Bax基因表达逐渐下调。与APOI变化趋势一致。洛沙坦降压治疗可使SHR胸主动脉Bax蛋白表达上调。Bcl-2蛋白下调。结论洛沙坦长期降压治疗促进Bax蛋白表达和／或抑制Bcl-2蛋白表达，其机制可促进VSMC凋亡。     

BDNF基因修饰神经干细胞移植对大鼠脊髓损伤后神经细胞凋亡的影响

采用电控大鼠脊髓损伤打击装置致大鼠脊髓损伤模型。将120只SD大鼠随机分为假手术组（Sham组）、脊髓损伤组（SCI组）、神经干细胞组（NSC组）、BDNF基因修饰神经干细胞组（NSC—BDNF组）。免疫组织化学法检测各组脊髓BDNF、Bax、Bcl-2的表达，流式细胞仪检测脊髓细胞凋亡率。结果 NSC—BDNF组BDNF免疫阳性细胞光密度值较NSC、SCI组明显增加（P〈0．05），表达时间及高峰延长；且Bcl-2蛋白表达较其他组在各时点均增高（P均〈0．05）。而Bax蛋白表达较其他组在各时点均降低（P均〈0．01）。凋亡率亦降低（P均〈0．01）。提示BDNF基因修饰NSC可在损伤脊髓内有效表达。且明显促进脊髓损伤后Bcl-2的高表达，抑制Bax的表达，从而降低神经细胞的凋亡率。     

IGF-1对MC3T3-E1细胞凋亡及凋亡调控蛋白Bax、Bcl-2表达的影响

目的 探讨胰岛素样生长因子-1（IGF-1）对小鼠前成骨样MC3T3-E1细胞凋亡基因相关蛋白Bax／Bcl-2表达的影响。方法 MC3T3-E1细胞分组培养，应用4个浓度的IGF-1（1ng／mL、10ng／mL、30ng／mL、50ng／mL）干预24h。观察MC3T3-E1细胞动态生长状况：流式细胞技术检测细胞凋亡率；免疫组织化学法检测凋亡蛋白Pax／Bcl-2的表达水平。结果 与正常血清对照组相比，无血清对照组MC3T3-E1细胞凋亡率增加（P〈0．05）；与无血清组相比，IGF-1组MC3T3-E1细胞凋亡率降低（P〈0．05），Bax表达减弱（P〈0．05），Bcl-2表达增强（P〈0．05）；各浓度组间比较，（1～50）ng／mL浓度范围内MC3T3-E1细胞凋亡率随IGF-1浓度加大而逐渐降低（P〈0．05），Bax表达逐渐减弱（P〈0．05），50ng／mL浓度组Bcl-2表达明显增强（P〈0．01），Bcl-2／Bax灰度比与细胞凋亡率呈显著正相关（r=0.917，P〈0．01）。结论 一定浓度的IGF-1同时调节Bax和Bcl-2表达，抑制无血清培养诱导的细胞凋亡。并存在剂量依赖性效应。     

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.