Ki-67表达及幽门螺杆菌感染在阿司匹林相关性胃黏膜病变中的作用

目的探讨Ki-67表达及幽门螺杆菌(Helicobacter pylori,H.pylori)在阿司匹林相关性胃黏膜病变中的作用。方法本组阿司匹林相关性胃黏膜病变患者共136例,根据胃镜下表现分为出血组、溃疡组和胃炎组;所有患者均应用快速尿素酶试验检测、病理组织学Giemsa染色及13C尿素呼气试验将136例阿司匹林相关性胃黏膜病变患者分为H.pylori感染阳性组和阴性组,应用免疫组织化学染色对各组病变的增殖细胞核抗原Ki-67表达进行检测。结果在正常胃黏膜上皮组织Ki-67无表达或呈弱阳性表达,平均染色积分为0.125±0.354。在阿司匹林相关性胃黏膜病变中,出血组胃黏膜上皮组织Ki-67平均染色积分为3.916±1.676;溃疡组胃黏膜上皮组织Ki-67平均染色积分为2.174±1.527;胃炎组胃黏膜上皮组织Ki-67平均染色积分为1.394±0.899。出血组胃黏膜上皮组织Ki-67平均染色积分显著高于溃疡组及胃炎组(P<0.05)。H.pylori感染阳性组胃黏膜上皮组织Ki-67平均染色积分为2.275±1.511,H.pylori感染阴性组胃黏膜上皮组织Ki-67平均染色积分为1.588±1.698。H.pylori感染阳性组胃黏膜上皮组织Ki-67染色积分明显高于H.pylori感染阴性组(P<0.05)。结论阿司匹林相关性胃黏膜病变组织中,阿司匹林和H.py-lori均可导致胃黏膜的损伤,促进胃黏膜上皮细胞增殖。     

DEC205在幽门螺杆菌感染的巨噬细胞中的表达

目的:探讨幽门螺杆菌( H pylori)感染与巨噬细胞表面的胞吞受体DEC205的关系.方法:用蛋白纯化法提取得到H pylori-HSP60.分别用H pylori、H pylori-HSP60和E.coli-LPS刺激单核细胞(NOMO1)后提取蛋白进行免疫印迹法分析. 利用PMA将NOMO1细胞分化成巨噬细胞, 再用H pylori或H pylori-HSP60刺激细胞后提取RNA进行实时PCR分析; 细胞表面DEC205抗原的表达通过流式细胞术进行分析.结果:H pylori的刺激能明显引起DEC205蛋白的表达, 而H pylori-HSP60或E.coli-LPS的刺激只引起了少许DEC205蛋白的表达; 经PMA分化后的NOMO1细胞表面DEC205 mRNA的表达增强, 分化后的NOMO1细胞被H pylori或H p y l o r i-HSP60刺激后也增强了DEC205mRNA的表达; 流式细胞术结果表明NOMO1细胞在H pylori刺激后, 细胞表面DEC205抗原的表达明显增加(88.10% vs 7.84%, P<0.05), 而且当NOMO1细胞被PMA分化后, 经H pylori或H pylori-HSP60刺激后DEC205表达也有所增高(74.73%, 51.31% vs 43.77%, 均P<0.05).结论:H pylori感染与巨噬细胞表面的胞吞受体DEC205有着密切的联系.     

幽门螺杆菌感染对血清及胃组织核组蛋白2/nesfatin-1表达的影响

目的:研究幽门螺杆菌(Helicobacter pylori,H.pylori)感染对人血清及胃组织核组蛋白2(nucleobindin 2,NUCB2)/nesfatin-1表达的影响.方法:收集行胃镜检查的83例无症状体检者的空腹血清及胃窦黏膜,经13C呼气试验、快速尿素酶实验及组织切片Warth-Starry银染色三者共同确认分为H.pylori阳性组与H.pylori阴性组,采用酶联免疫吸附法及实时荧光定量PCR法分别测定血清NUCB2/nesfatin-1蛋白浓度及胃黏膜NUCB2 m RNA的表达量.结果:血清NUCB2/nesfatin-1蛋白浓度在H.pylori阳性组与H.pylori阴性组无明显差异(2.267 ng/m L±0.201 ng/m L vs 2.298 ng/m L±0.275 ng/m L,P0.05);胃黏膜NUCB2 m RNA相对表达量在H.pylori阳性组明显高于H.pylori阴性组(1.336±0.324 vs 0.914±0.171,P0.01).结论:H.pylori感染可导致胃黏膜NUCB2m R N A表达上调,但不影响感染者血清NUCB2/nesfatin-1浓度.     

幽门螺杆菌感染对老年人胃黏膜环氧合酶-2表达的影响及意义

目的:评估幽门螺杆菌(H pylori)感染对老年人胃黏膜COX-2表达的影响及意义.方法:取不同阶段的胃黏膜病变共200例,用速尿素酶试验结合组织学Giemsa染色或14C尿素呼气试验检测胃黏膜H pylori感染状况,应用免疫组织化学检测胃黏膜上皮细胞COX-2的表达.结果:不同组织类型H pylori检出率以胃癌最高,其次为不典型增生(AH)和肠上皮化生(IM).COX-2在慢性浅表性胃炎(CSG)、IM、AH和胃癌中的表达阳性率分别为8%、24%、46%和64%,呈递增趋势,其阳性率胃癌与非癌组织相比差异均有统计学意义(P<0.01).同一类型 H pylori 阳性组COX-2的表达高于H pylori 阴性组,2组比较有显著性差异(P＜0.05).结论:COX-2表达上调与H pylori感染的胃黏膜的癌变有关,可能在癌前病变早期阶段起作用.     

幽门螺杆菌感染患者胃癌及癌旁组织中p53、p16和bcl-2基因的表达

目的:研究幽门螺杆菌(H.pylori)感染胃癌患者胃粘膜病变中抑癌基因p53、p16和关键性凋亡调节基因bcl-2蛋白的表达,进一步探讨H.pylori在胃癌发生、发展过程中作用的分子机制.方法:胃镜检查及外科手术中取40例胃癌患者的癌组织和癌旁2 cm处组织各2块,石蜡包埋,切片HE染色作病理诊断及免疫组化检测p53、p16及bcl-2蛋白的表达.H.pylori阳性由快速尿素酶试验结合病理染色/14C-尿素呼气试验确定.结果:40例胃癌患者中,H.pylori阳性23例,阴性17例.p53阳性表达率在H.pylori阳性及阴性胃癌组织中无显著差异(P＞0.05).H.pylori阳性组慢性胃炎或肠化组织中p16的阳性表达率及表达强度均显著低于H.pylori阴性组(表达率:P＜0.05;表达强度:P＜0.001和P＜0.01).而H.pylori阳性组肠化组织中bcl-2的阳性表达率及表达强度均显著高于H.pylori阴性组(P＜0.05).结论:在胃癌发生的早期即存在较明显的p16基因表达低下与bcl-2基因过度表达,并与H.pylori感染有一定关系.p53基因过度表达是胃癌发展过程中较晚期的事件,与H.pylori感染无明显相关性.     

胃黏膜TGF-β1在幽门螺杆菌感染中的表达及与外周血T细胞亚群变化的关系

目的:探讨幽门螺杆菌(H.pylori)感染、TGF-β1及T淋巴细胞亚群在胃黏膜癌变过程中的作用及相互关系.方法:选取不同胃黏膜病变组织的72例胃镜活检标本,采用快速尿素酶试验(rapid urease test,RUT)结合Giemsa染色判断H.pylori感染,免疫组织化学染色技术检测胃黏膜组织中TGF-β1表达,流式细胞术检测不同胃黏膜病变患者外周血T淋巴细胞亚群CD3+、CD4+、CD8+及CD4+/CD8+比值.结果:TGF-β1在慢性浅表性胃炎(CSG)、慢性萎缩性胃炎(CAG)、肠上皮化生及不典型增生(IM/Dy)和胃癌(GC)中表达的阳性率分别为39.1%,52.6%,62.3%和87.5%,CSG组与IM/Dy、GC组相比,差异有统计学意义(P<0.05);IM/Dy中H.pylori阳性者TGF-β1表达明显高于H.pylori阴性者(87.5% vs 33.3%,P<0.05).与CSG相比,GC中CD3+明显降低(P<0.05),CD4+及CD4+/CD8+明显降低(P<0.01);IM/Dy患者CD4+及CD4+/CD8+低于CSG,有显著性差异(均P<0.01).不同胃黏膜病变TGF-β1表达与CD3+、CD4+T细胞、CD4+/CD8+呈负相关.结论:在GC前病变中,AKCSG到GC,TGF-β1表达逐渐增加,细胞免疫功能降低,TGF-β1对细胞免疫功能的抑制作用是IM/Dy、GC患者细胞免疫功能低下的原因之一.     

唾液、牙斑与胃黏膜幽门螺杆菌感染关系的研究

背景幽门螺杆菌(H.pyloori)在人群中感染率高,但其传播途径仍不清楚.目前有关口腔中H.pylori感染与胃黏膜H.plori感染关系的研究不多.目的了解口腔中的H.pylori感染状况及其与胃黏膜H.pylori感染的关系.方法应用聚合酶链反应(PCR)技术同时检测60例非萎缩性胃炎患者唾液、牙斑和胃黏膜中的H.pylori.结果47例胃黏膜H.pylori阳性的胃炎患者中有31例(66.0%)唾液中检出H.pylori,17例(36.2%)牙斑中检出H.pylori;而13例胃黏膜H.pylori阴性的胃炎患者中仍有1例(7.7%)唾液中检出H.pylori,2例(15.4%)牙斑中检出H.pylori.胃黏膜H.pylori阳性与阴性胃炎患者唾液和牙斑中的H.pylori检出率有显著差异(P＜0.01).结论口腔中的H.pylori与胃黏膜中的H.pylori之间可能存在一定的病因学联系.     

H pylori感染在胃癌前病变中对端粒酶相关基因及细胞增殖与凋亡的影响

目的:分析胃癌前病变中端粒酶RNA(hTR)、端粒酶逆转录酶(Htert)、c-Myc、增殖细胞核抗原(PCNA)的表达及相互关系,并探讨H pylori感染致胃癌前病变的可能机制.方法:33例胃癌前病变中H pylori阳性19例,H pylori阴性14例.采用原位杂交法检测胃黏膜活检标本中hTR表达; 免疫组织化学SP法检测hTERT、c-Myc、PCNA表达; TUNEL法检测细胞凋亡.结果:H pylori阳性胃癌前病变组h TR、hTERT、c-Myc阳性率均显著高于H pylori阴性胃癌前病变组(63.2% vs 28.6%,68.4% vs21.4%,47.4% vs 7.1%,均P<0.01); 增殖指数及凋亡指数在H pylori阳性组分别为17.5±5.4、17.7±3.9,H pylori阴性组分别为8.3±3.6、9.2±5.2,两组相比均有显著性差异( P<0.01).胃癌前病变中hTERT与hTR、hTERT与c-Myc表达均呈显著正相关性( rs = 0.45,0.54,均P<0.01).结论:H pylori感染可诱导胃癌前病变中端粒酶相关基因及c-Myc过度表达,促进细胞增殖与凋亡,引起胃黏膜上皮细胞动力学紊乱.     

胃黏膜病变演化过程中抗氧化蛋白Peroxiredoxin6的表达及其与幽门螺杆菌感染的关系

目的探讨胃黏膜病变演化过程中抗氧化蛋白Peroxiredoxin 6(Prx6)表达水平变化及其与幽门螺杆菌(H.pylori)感染的关系。方法根据组织形态学将104例临床内镜检查活检标本分为慢性浅表性胃炎(33例)、慢性萎缩性胃炎(25例)、肠上皮化生(32例)及异型增生(14例)4组。用免疫组织化学方法检测组织标本中Prx6的表达水平。用快速尿素酶试验及Warthin-Starry银染检测H.pylori感染。结果 Prx6在慢性浅表性胃炎、慢性萎缩性胃炎、肠上皮化生、异型增生组的阳性表达率分别为39.4%(13/33)、80.0%(20/25)、93.8%(30/32)、92.9%(13/14),过表达率分别为15.2%(5/33)、44.0%(11/25)、81.3%(26/32)、85.7%(12/14)。慢性浅表性胃炎、慢性萎缩性胃炎组H.pylori阳性者Prx6阳性表达率显著高于H.pylori阴性者(P<0.05),肠上皮化生组Prx6的表达在H.pylori阳性者和阴性者无显著差异(P>0.05)。结论在胃黏膜病变演化过程中,Prx6的表达随着胃黏膜病变的进展而增加,H.pylori在胃黏膜病变演化的早期阶段促进了Prx6的表达。     

Cdx2蛋白在不同亚型肠上皮化生中的表达及其与H.pylori感染的关系

目的探讨胃黏膜肠上皮化生（intestinal地metaplasia,IM）中尾型同源异型盒基因2（caudal type homeobox genes2,Cdx2）蛋白的表达及其与幽门螺杆菌（helicobacter pylori,H.pylori）感染的关系。方法选取内镜下活检的18例正常胃黏膜和53例IM胃黏膜。采用高铁二铵-爱先蓝-过碘酸雪夫反应（HID-AB-PAS）将胃黏膜IM分为Ⅰ、Ⅱ、Ⅲ型,然后用Cdx2单克隆抗体进行免疫组织化学染色,检测Cdx2在正常胃黏膜及不同亚型IM中的表达。采用一分钟快速尿素酶实验及甲苯胺蓝染色检测H．pylori感染。结果Cdx2蛋白在正常胃黏膜中不表达,IM中Cdx2阳性表达率为83．02％（44／53）,其中Ⅰ型IM阳性率为95．45％（21／22）。Ⅱ型为83．33％（15／18）,Ⅲ型为61．53％（8／13）,三者间Cdx2蛋白表达有显著性差异（P=0．036）。IM中H．pylori感染阳性率为47．17％（25／53）,其中Ⅰ型IM中H．pylori感染阳性率为27．27％（6／22）,Ⅱ型为55．56％（10／18）,Ⅲ型为69．23％（9／13）,三者间Mpylori感染率亦有显著性差异（P=0．038）。Cdx2蛋白表达主要集中于H．pylori感染阴性者,但H．pylori感染阳性者和阴性者Cdx2表达无统计学差异（P〉0．05）。结论Cdx2蛋白异常表达可能参与了胃黏膜IM向胃癌的转变,检测其表达有助于预测胃黏膜IM向胃癌转变的可能性。     

Eradication therapy of Helicobacter pylori directly induces apoptosis in inflammation-related immunocytes in the gastric mucosa--possible mechanism for cure of peptic ulcer disease and MALT lymphoma with a low-grade malignancy

BACKGROUND/AIMS: A possibility that the eradication therapy not only eliminates Helicobacter pylori (H. pylori) but also influences some factors regulating pathological changes in the gastric mucosa should be taken into consideration from some phenomena. Such as non-recurrent cases of peptic ulcer long-term in spite of unsuccessful anti-H. pylori eradication therapy and the effectiveness of eradication therapy for mucosa-associated lymphoid tissue with a low-grade malignancy except stomach. We hypothesized and investigated that antibiotic treatment for elimination of H. pylori might directly affect inflammatory cells to induce apoptosis in them and protect against pathological changes of gastric mucosa. METHODOLOGY: Subjects consisted of twenty-one patients with chronic gastritis. All were H. pylori positive and we investigated the effects of eradication therapy of H. pylori on inflammation-related immunocytes in the gastric mucosa of patients with chronic gastritis caused by H. pylori isolated mononuclear leukocytes which were taken from the patients and were examined for apoptosis-related morphological changes and DNA fragmentation before and after the therapy. Eradication therapy of H. pylori was performed by lansoprazole 30 mg/day, amoxicillin 1500 mg/day and clarithromycin 400 mg/day for one week. RESULTS: After the H. pylori eradication therapy, regardless of its effect on H. pylori status, marked vacuolation and degeneration were observed in mononuclear leukocytes in the gastric mucosa with a concomitant enhancement of nuclear DNA fragmentation. CONCLUSIONS: This observation suggests that H. pylori eradication therapy itself induces apoptosis in mononuclear leukocytes in the gastric mucosa.     

Effect of Helicobacter pylori infection on ghrelin expression in human gastric mucosa

OBJECTIVES: One of the counter-effects of Helicobacter pylori eradication therapy is subsequent obesity. Ghrelin is a recently discovered growth hormone releasing peptide. This endogenous secretagogue increases appetite and facilitates fat storage. The majority of circulating ghrelin is produced in the gastric mucosa. Therefore, we aimed at investigating changes in ghrelin immunoreactivity in gastric mucosa tissues of patients infected with H. pylori. METHODS: Sixty-one patients with H. pylori infection (25 cases each of duodenal and gastric ulcer, and 11 cases of gastritis) and 22 healthy controls without H. pylori infection were included in the study. H. pylori-infected patients received standard proton pump-based triple therapy followed by histological examination and (13)C-urea breath test to confirm H. pylori eradication. H. pylori was eradicated in 50 out of 61 patients. Biopsy specimens were obtained from antrum and corpus before and 3 months following eradication. Ghrelin expression was evaluated immunohistochemically with an anti-ghrelin antibody, and the number of ghrelin-positive cells determined per 1 mm(2) of the lamina propria mucosa. RESULTS: There was no relationship between ghrelin immunoreactivity and body weight or body mass index for healthy controls. The number of ghrelin-positive cells was significantly lower for H. pylori-infected patients than for healthy controls. However, the ghrelin-positive cell number increased significantly following H. pylori eradication without significant change in severity of atrophy. CONCLUSIONS: These data indicated that H. pylori infection affected ghrelin expression. After H. pylori eradication, gastric tissue ghrelin concentration increased significantly. This could lead to the increased appetite and weight gain seen following H. pylori eradication.     

萎缩性胃炎患者幽门螺杆菌根除后表皮生长因子及其受体的变化

目的　研究幽门螺杆菌 (Helicobacterpylori,H .pylori)感染对胃黏膜表皮生长因子受体 (epidermalgrowthfactorreceptor ,EGFR)、血清表皮生长因子 (epidermalgrowthfactor,EGF)水平的影响。方法　对 60例H pylori检测阳性的慢性萎缩性胃炎患者进行根除治疗 ,在治疗前及疗程结束 3个月后分别进行胃镜检查 ,并采用免疫组化及放射免疫法测定H pylori根除前后胃黏膜EGFR和血清EGF含量。 3 0例H pylori检测阴性且胃镜检查无明显异常者作为正常对照组。结果　 60例H pylori检测阳性的CAG患者的胃黏膜EGFR阳性率及血清EGF水平均高于正常对照 ,其差异有显著性 (P <0 0 5 ,P <0 0 1)。有 3 1例在根除治疗 3个月后进行了复查 ,其中 2 4例H pylori得到成功根除。 2 4例H pylori得到根除的CAG患者 ,根除后血清EGF水平明显下降 (P <0 0 1) ,而EGFR阳性率无改变 (P >0 0 5 )。结论　H pylori感染引起胃黏膜EGFR阳性率及血清EGF水平增加 ,根除H pylori后血清EGF可恢复至正常水平 ,而胃黏膜EGFR阳性率在短期内没有明显改变     

Eradication of Helicobacter pylori reduced the immunohistochemical detection of p53 and MDM2 in gastric mucosa

BACKGROUND: Although Helicobacter pylori has been regarded as a pathogen of gastric cancer, the mechanism by which H. pylori is involved in gastric carcinogenesis remains unknown. To clarify the role of H. pylori in carcinogenesis, the expression of tumor suppressor p53 and its regulator multiple double minute 2 (MDM2) in gastric mucosa were examined before and after H. pylori eradication. METHODS: Biopsy specimens were obtained from 31 patients with H. pylori-infected gastric mucosa. Endoscopic biopsies were repeated 6 months after successful eradication. In addition, biopsy specimens from 12 patients with non-infected gastric mucosa were obtained. Immunohistochemical analysis was performed on the specimens using primary antibodies specific for p53 and MDM2. RESULTS: Six months after H. pylori eradication, labeling indices for p53 were significantly reduced in the gastric corpus (2.3-fold; P < 0.01), and in the gastric antrum (2.0-fold; P < 0.01). Similarly, labeling indices for MDM2 were significantly reduced in the corpus (1.7-fold; P < 0.01), and in the antrum (3.5-fold; P < 0.01). In the non-infected group, labeling indices for p53 and MDM2 in the gastric mucosa were significantly lower (P < 0.01) than those of the H. pylori-infected group. CONCLUSION: A significant increase is shown in p53 and MDM2 expression in H. pylori-infected gastric mucosa as compared to normal gastric mucosa; but successful eradication of H. pylori dramatically reduced the p53 and MDM2 levels. Therefore, H. pylori infection may be associated with alteration of cell proliferation and apoptosis.     

根除幽门螺杆菌对胃黏膜肠化的影响

目的　幽门螺杆菌 (Hp)感染可导致慢性活动性胃炎进一步发展为慢性萎缩性胃炎、胃黏膜肠化、最终发展成肠型胃癌。通过 5年随访 ,探讨根除Hp是否对胃黏膜肠化逆转、发生及发展有影响。方法　将 1996年快速尿素酶试验及组织学方法检测Hp均为阳性的 398例病人随机分为治疗组和对照组。治疗组 2 0 1例 ,进行根除Hp治疗 ;对照组 197例 ,给予安慰剂 ;服药前及 5年后分别从胃窦部及胃体部取材检测胃炎、胃炎活动性及肠化。结果　 5年后治疗组中 15 1/2 0 1例Hp为阴性 ,对照组中 16 1/197例Hp为阳性 ;治疗组中Hp被根除的病人胃炎活动性的检出率明显减少 ,与对照组持续Hp感染者比较 ,差异有显著性 (P <0 .0 0 0 1) ;对照组中持续Hp感染者 5年后肠化检出率与自身 5年前、治疗组成功根除Hp者 5年前和 5年后比较均增高 ,差异有显著性 (P均 <0 .0 0 1) ,治疗组根除Hp的病人 5年前后比较差异无显著性 ;对照组中持续Hp感染者胃窦部 5年后肠化检出率与自身 5年前、治疗组根除Hp者 5年前和 5年后比较均增高 ,差异有显著性 (分别为P <0 .0 0 1,P <0 .0 0 1和P<0 .0 1) ,治疗组根除Hp感染的病人 5年前后比较差异无显著性 ;对照组持续Hp感染的病人与治疗组根除Hp感染的病人胃窦部肠化新增及新减情况比较无差异。 结论　 5年     

Increase in apoptosis and decrease in ornithine decarboxylase activity of the gastric mucosa in patients with atrophic gastritis and gastric ulcer after successful eradication of Helicobacter pylori

OBJECTIVE: Recent reports have shown that patients infected with Helicobacter pylori (H. pylori) have a higher risk of gastric cancer. However, the mechanism of this increased risk is still unclear. In the gastric mucosa, the size of a continuously renewed population of cells is determined by the rates of cell production and of cell loss. Ornithine decarboxylase (ODC) activity is elevated in various gastrointestinal cancers and serves as a marker of mucosal proliferative activity. Apoptosis occurs throughout the gut and is associated with cell loss. Both cell proliferation and cell loss have important roles in H. pylori-associated gastric carcinogenesis. Therefore, we investigated the effect of H. pylori eradication on ODC activity and apoptosis in the gastric mucosa of patients with atrophic gastritis and gastric ulcers. METHODS: Biopsy specimens of the gastric antrum were obtained at endoscopy from 17 H. pylori-positive gastric ulcers patients and 15 H. pylori-positive gastritis patients before and 4 wk after eradication therapy with amoxicillin, omeprazole, and a new anti-ulcer agent, ecabet sodium, and from 10 gastric ulcer patients in whom ulcer healed but H. pylori was left untreated. ODC activity and induction of apoptosis were determined immunohistochemically. RESULTS: H. pylori was successfully eradicated with the triple therapy in 12 (80%) of 15 gastritis patients and 13 (76%) of 17 gastric ulcer patients. ODC activity was present in the gastric mucosa in 21 (84%) patients before eradication but in only four (16%) patients after successful eradication (p = 0.0005). The apoptotic index increased significantly (p = 0.0006) from 4.2% +/- 0.4% before treatment to 7.4% +/- 0.5% after successful eradication. CONCLUSIONS: Successful eradication of H. pylori decreases mucosal ODC activity and increases apoptosis in the gastric mucosa. These findings indicate that by decreasing mucosal cell proliferation and increasing epithelial cell loss, H. pylori eradication may help decrease the subsequent risk of gastric cancer.     

Decreased expression of epidermal growth factor receptor and mRNA of its ligands in Helicobacter pylori-infected gastric mucosa

BACKGROUND: Epidermal growth factor (EGF) and TGF-alpha play a central role in maintaining gastric mucosal integrity. Little is known about the regulative role of the four other widely expressed epidermal growth factor receptor ligands, heparin-binding EGF, amphiregulin, betacellulin and cripto in the gastric mucosa. METHODS: Nineteen patients with Helicobacter pylori-positive gastritis and 32 healthy controls were investigated. Mucosal mRNA expression of EGF receptor ligands was determined by quantitative PCR before and after H. pylori eradication. PCR products were analyzed by soft laser scanning densitometry. Moreover, the effect of chronic active gastritis on EGF receptor expression was assessed by [125I] EGF receptor autoradiography. Immunohistochemistry was performed for TGF-alpha to localize growth factor expression. RESULTS: Antral and oxyntic biopsies showed strong mRNA expressions for TGF-alpha, amphiregulin and heparin binding EGF, but not for EGF, cripto and betacellulin. mRNA expression was significantly reduced down to 50% in H. pylori infection, significantly lower compared to normal gastric mucosa, and increased after eradication therapy. Moreover, chronic gastritis was associated with decreased antral EGF receptor binding compared to healthy controls, possibly reflecting reduced autoinduction. Immunohistochemical analyses localized TGF-alpha in the cytoplasma of gastric epithelial cells and revealed its increased expression after H. pylori eradication. CONCLUSIONS: The data presented suggest that amphiregulin, heparin binding EGF and TGF-alpha are important EGF receptor ligands in the gastric mucosa. H. pylori infection apparently suppresses their mRNA as well as receptor expression that is reversed by H. pylori eradication. This deficiency of the gastroprotective EGF system may contribute to the gastric pathogenicity of H. pylori infection.