丹参提取物F对幽门螺杆菌致敏小鼠的免疫调理作用研究

研究丹参提取物F（DanShenextractF,DSE－F）对幽门螺杆菌（Helicobacterpylori,HP）致敏胃粘膜固有层淋巴细胞有无免疫调理作用。经口给予小鼠HP全菌破碎抗原与DSE－F2周后,提取脾淋巴细胞和胃粘膜固有层T淋巴细胞（LPL）,检测对肿瘤细胞的细胞毒活性和IL－2诱生能力的改变。结果显示DSE－F与HP抗原协同能增强脾淋巴细胞和胃LPL细胞的抗肿瘤细胞的细胞毒性;对HP抗原致敏胃粘膜有免疫调理作用。     

斑点ELISA法检测幽门螺旋菌感染的研究

用幽门螺旋菌(HP)的超声粉碎物为抗原,建立了斑点ELISA法检测人血清中抗HP—IgG方法。该法敏感性为94.4％,特异性为87.5％,阳性预测值为97.1％,阴性预测值为77.8％。对271例儿童抗HP抗体调查,发现HP感染与儿童性别无关(P>0.05)。1月以内新生儿抗体检出率59.4％,1～12月婴儿抗体检出率最低(29.1％),1岁后开始逐渐上升,2岁后即可达到50％以上,接近成年人水平。结果表明,我国HP感染年龄早,感染率高。     

从人粪便中分离幽门螺旋菌

<正>人类幽门螺旋菌(HP)感染可能是最常见的慢性细菌性感染。如在非洲的部分地区,成年人几乎都有HP感染。在冈比亚,婴儿的HP感染将近50％,而5岁儿童的HP感染则高达90％。胃粘膜是HP定居的场所,HP最初也是从胃粘膜中分离出来的。后来有人从牙斑中也分离到HP,政提示HP感染可能是经口腔分泌物传播的。最近有人又证明在粪便中也有HP,从而说明HP感染的高度流行可能与不良的家庭生活有关。本研究则旨在从HP感染者的粪便中分离培养出HP。     

幽门螺旋杆菌与胃溃疡的致病关系

胃溃疡(gastric ulcer, GU)是世界上发病率和患病率不断上升的主要胃肠疾病之一,被认为是一个全球性的健康问题,即便有很多人研究,但其具体发病机制尚不完全清楚。幽门螺杆菌(Helicobacter pylori, HP)是定植于人类胃黏膜上皮细胞的微需氧型细菌。全世界近80%～90%的GU是由HP感染引起的,HP感染是造成GU发病率的最大危险因素。本文对HP与GU的致病关系进行综述,以便国内外的学者对其进行更深入的了解,同时也为进一步研究提供帮助。     

HP感染后Men1基因对非酒精性脂肪肝病及炎症反应的调控机制

为了研究HP感染后Men1基因对NAFLD小鼠的调控机理,本研究检测了Men1基因和蛋白在NAFLD+HP和NAFLD组小鼠中的表达,同时检测了炎症因子IL-6和IL-18基因以及含量的变化。结果表明,HP感染后NAFLD小鼠中Men1基因和蛋白的表达均显著下调,但是IL-6和IL-18基因和含量均显著上调和增加。结合前人的研究报道结果,本研究推断Men1基因可能会与小鼠体内的其它因子协同来影响IL-6和IL-18等炎症因子的表达,而Men1基因下调阻断了这种协同作用,从而使IL-6和IL-18等炎症因子表达上调,促进小鼠肝脏的损伤程度。因此本实验的结果表明,Men1基因可能会是治疗HP感染后NAFLD的一个有效的靶点,改变其表达量就能调节HP感染的非酒精性脂肪肝病的严重程度。     

日本血吸虫DNA疫苗的优化策略

血吸虫病严重危害人类及家畜健康,发展疫苗是防治血吸虫感染的有效措施。传统疫苗的发展因成本高、免疫原性低及安全隐患而受到限制。发展DNA疫苗成为近年的研究重点。为提高DNA疫苗的免疫保护力,候选抗原的筛选、CpG序列的优化、基因佐剂的选用、多价疫苗的构建等被认为是日本血吸虫DNA疫苗的优化策略。     

基于血凝素(HA)的新型流感疫苗研究进展

新型广谱流感疫苗是预防和控制不断变异的流感病毒的重要手段。血凝素(HA)是流感病毒表面的糖蛋白,具有免疫原性,但其变异性强,是A型流感病毒发生抗原变异的主要原因。近年来研究发现,HA存在保守的恒定区,可诱导机体产生流感病毒特异性广谱中和抗体,拮抗多种流感病毒的感染。因此,如何采取不同策略和方法,研发基于HA的新型疫苗成为流感防治研究的重点。就基于HA的新型流感疫苗研究进展作一综述。     

2型糖尿病患者幽门螺杆菌感染与超敏c反应蛋白、血脂情况的关系

目的：探讨2型糖尿病（T2DM）患者幽门螺杆菌（HP）感染与超敏c反应蛋白（hs-CRP）、血脂水平的关系。方法：以2009年1月1日至2009年12月31日在我院体检的683例2型糖尿病患者为研究对象,根据HP感染情况分成HP阳性组（n=306）和HP阴性组（n=377）,采用单因素和多因素Logistic回归分析方法,分析HP感染与hs-CRP、血脂水平的关系。结果：（1）HP阳性组的hs-CRP水平高于HP阴性组（1.14mg/L vs 0.96mg/L）,差异有统计学意义（P〈0.05）。（2）HP阳性组的血脂异常率（59.8%vs 50.7%）和hs-CRP异常率（20.9%vs 14.3%）均高于HP阴性组,差异均有统计学意义（均P〈0.05）。（3）单因素Logistic回归分析显示,血脂异常和hs-CRP异常对HP阳性的OR值及分别为1.449和1.582,均有统计学意义（均P〈0.05）,多因素Logistic回归分析显示,hs-CRP异常对HP阳性的OR值为1.509,有统计学意义（P〈0.05）。结论：2型糖尿病患者,HP感染可能通过增高hs-CRP水平,影响脂质代谢,触发一系列生物、生物化学级联反应,可使患者并发心血管病变的风险性增高。     

2 型糖尿病患者幽门螺杆菌感染与超敏c 反应蛋白、血脂情况的关系

目的:探讨2型糖尿病(T2DM)患者幽门螺杆菌(HP)感染与超敏c反应蛋白(hs-CRP)、血脂水平的关系。方法:以2009年1月1日至2009年12月31日在我院体检的683例2型糖尿病患者为研究对象,根据HP感染情况分成HP阳性组(n=306)和HP阴性组(n=377),采用单因素和多因素Logistic回归分析方法,分析HP感染与hs-CRP、血脂水平的关系。结果:(1)HP阳性组的hs-CRP水平高于HP阴性组(1.14mg/L vs 0.96mg/L),差异有统计学意义(P<0.05)。(2)HP阳性组的血脂异常率(59.8%vs 50.7%)和hs-CRP异常率(20.9%vs 14.3%)均高于HP阴性组,差异均有统计学意义(均P<0.05)。(3)单因素Logistic回归分析显示,血脂异常和hs-CRP异常对HP阳性的OR值及分别为1.449和1.582,均有统计学意义(均P<0.05),多因素Logistic回归分析显示,hs-CRP异常对HP阳性的OR值为1.509,有统计学意义(P<0.05)。结论:2型糖尿病患者,HP感染可能通过增高hs-CRP水平,影响脂质代谢,触发一系列生物、生物化学级联反应,可使患者并发心血管病变的风险性增高。     

胃癌病理特征改变与幽门螺旋杆菌感染的相关性分析

目的:探究HP感染与胃癌患者病理特征性改变的相关性。方法:选取我院消化内科收治并确诊为胃癌的患者50例,作为胃癌组;确诊为慢性浅表性胃炎的患者50例,作为胃炎组;选取同期进行健康体检未发现胃部异常的患者50例,作为对照组。对三组患者进行快速尿素氮试验、13C尿素呼气试验以及血清抗HPCag A等检查,比较患者HP感染等情况。结果:胃癌组及胃炎组患者HP感染阳性率及抗HPCag A阳性率显著高于对照组,且胃癌组较胃炎组明显增高,差异有统计学意义(P0.05)。胃癌早期及进展期患者HP感染率高于对照组,差异有统计学意义(P0.05)。胃癌组患者非贲门部HP感染率显著高于贲门部及对照组,差异有统计学意义(P0.05)。结论:HP感染是导致胃癌的主要因素,明确HP感染与胃癌病理分期及病变部位的相关性对胃癌的治疗及预防有重要的临床意义。     

Expression of histo-blood group antigens by lipopolysaccharides of Helicobacter pylori strains from asian hosts: the propensity to express type 1 blood-group antigens

Past studies have shown that the cell surface lipopolysaccharides (LPSs) of the ubiquitous human gastric pathogen Helicobacter pylori (a type 1 carcinogen) isolated from people residing in Europe and North America express predominantly type 2 Lewis x (Le(x)) and Le(y) epitopes and, infrequently, type 1 Le(a), Le(b), and Le(d) antigens. This production of Lewis blood-group structures by H. pylori LPSs, similar to those found in the surfaces of human gastric cells, allows the bacterium to mimic its human niche. In this study, LPSs of H.pylori strains extracted from patients living in China, Japan, and Singapore were chemically and serologically analyzed. When compared with Western H.pylori LPSs, these Asian strains showed a stronger tendency to produce type 1 blood groups. Of particular interest, and novel observations in H.pylori, the O-chain regions of strains F-58C and R-58A carried type 1 Le(a) without the presence of type 2 Le(x), strains R-7A and H607 were shown to have the capability of producing the type 1 blood group A antigen, and strains CA2, H507, and H428 expressed simultaneously the difucosyl isomeric antigens, type 1 Le(b) and type 2 Le(y). The apparent proclivity for the production of type 1 histo-blood group antigens in Asian H.pylori LPSs, as compared with Western strains, may be an adaptive evolutionary effect in that differences in the gastric cell surfaces of the respective hosts might be significantly dissimilar to select for the formation of different LPS structures on the resident H.pylori strain.     

Helicobacter pylori lipopolysaccharide-mediated gastric and extragastric pathology.

Lipopolysaccharides (LPS) are a family of toxic phosphorylated glycolipids in the outer membrane of Gram-negative bacteria, including Helicobacter pylori, and are composed of a lipid moiety (termed lipid A), a core oligosaccharide, and a polymeric O-specific polysaccharide chain. Compared with LPS of other bacteria, H. pylori LPS and lipid A induce low immunological activities in a range of test systems. Nevertheless, these reduced levels of LPS-induced cytokines and toxic oxygen radicals can contribute, with those induced by bacterial proteins, to the H. pylori-associated inflammatory response. Whether the ability of H. pylori LPS to induce low production of both procoagulant activity and plasminogen activator inhibitor type 2 by human mononuclear cells contributes to localized inflammatory responses alone and, in addition, play a role in extragastric pathology remains an open question. The core oligosaccharide of H. pylori LPS, in part with a 25 kDa protein adhesin, mediates the binding of the bacterium to the host glycoprotein laminin, and hence interferes with gastric cell receptor-laminin interaction in the basement membrane. Also affecting mucosal integrity, the core sugars of certain H. pylori strains, particularly those associated with gastric ulceration, have been implicated in pepsinogen induction, but this is a strain-dependent phenomenon. Of particular interest, the O-chains of a large proportion of H. pylori strains mimic Lewis (Le) antigens. Although investigations have focussed on the role of these antigens in H. pylori-associated autoimmunity, which remains to be unequivocally established, other pathogenic consequences of Lewis mimicry are becoming apparent. Expression of Lewis antigens may be crucial for H. pylori colonization and adherence and, by aiding bacterial interaction with the gastric mucosa, thereby aid delivery of secreted products, and hence influence the inflammatory response.     

Lewis antigens in Helicobacter pylori: biosynthesis and phase variation

The lipopolysaccharides (LPS) of most Helicobacter pylori strains contain complex carbohydrates known as Lewis antigens that are structurally related to the human blood group antigens. Investigations on the genetic determinants involved in the biosynthesis of Lewis antigens have led to the identification of the fucosyltransferases of H. pylori, which have substrate specificities distinct from the mammalian fucosyltransferases. Compared with its human host, H. pylori utilizes a different pathway to synthesize the difucosylated Lewis antigens, Lewis y. and Lewis b. Unique features in the H. pylori fucosyltransferase genes, including homopolymeric tracts mediating slipped-strand mispairing and the elements regulating translational frameshifting, enable H. pylori to produce variable LPS epitopes on its surface. These new findings have provided us with a basis to further examine the roles of molecular mimicry and phase variation of H. pylori Lewis antigen expression in both persistent infection and pathogenesis of this important human gastric pathogen.     

Antigenic Mimicry Between Helicobacter pylori and Gastric Mucosa: Failure to Implicate Heat-Shock Protein Hsp60 Using Immunoelectron Microscopy

Background. Helicobacter pylori infection induces autoantibodies that cross-react with human gastric mucosa from infected individuals. Candidates for the antigens responsible for molecular mimicry causing autoreactivity include the heat-shock protein HspB (Hsp60, sometimes called Hsp54) or Lewis x and Lewis y carbohydrate antigens.
Objective. Our goal was to investigate the involvement of HspB (Hsp60) in autoreactivity between H. pylori and gastric biopsy tissue.
Materials and Methods. Immunoelectron microscopy was used to study cross-reactivity among biopsy tissues from a patient with gastritis, gastric ulcer, and duodenal ulcer and his own serum as well as reactivity with serum raised against HspB from H. pylori and monoclonal antibodies against Lewis antigens.
Results. The patient serum reacted with gastric mucosa, and the antibodies involved were predominantly IgG. Antibody raised to H. pylori HspB (Hsp60) reacted only with H. pylori cells but not with gastric mucosal tissue. In contrast, monoclonal antibodies specific for Lewis x and Lewis y antigens reacted with both H. pylori and human gastric epithelial tissue.
Conclusions. Hsp60 (Hsp54) is unlikely to be involved in autoreactivity seen in individuals infected with H. pylori. In contrast, we could not rule out the role of Lewis x and Lewis y carbohydrate antigens, expressed as a component of H. pylori lipopolysaccharides, in molecular mimicry and autoantibody production.     

Evaluation of ribotyping for characterization and identification of Enterococcus haemoperoxidus and Enterococcus moraviensis strains

Periodontopathic Campylobacter rectus strains possess 41- and 68-kDa proteinaceous antigens which share antigenicity with antigens of Helicobacter pylori strains. H. pylori strains have a 54-kDa antigen which reacts with C. rectus strains. We found that the salivary IgA levels against H. pylori were correlated with those against C. rectus. These cross-reactive antigens of C. rectus may affect the serological diagnosis of H. pylori infections, especially when saliva is used. It is possible that these cross-reacting antigens may relate to the induction of immunopathological responses against both microorganisms.     

No correlation of babA2 with vacA and cagA genotypes of Helicobacter pylori and grading of gastritis from peptic ulcer disease patients in Brazil

BACKGROUND: The babA2 gene, which encodes a blood-group antigen-binding adhesin that mediates attachment of Helicobacter pylori to human Lewis(b) antigens on gastric epithelial cells, has been associated with a higher risk of peptic ulcer and gastric cancer. The purpose of this study was to ascertain the frequency of babA2 genotype in H. pylori strains of patients with peptic ulcer and to correlate with other virulence factors. MATERIALS AND METHODS: vacA, cagA, and babA2 genotypes of H. pylori were determined by using polymerase chain reaction (PCR). DNA was extracted from positive urease test gastric samples of 150 patients with peptic ulcer. Antrum and corpus biopsies were taken for histologic examination according to the updated Sydney system classification. RESULTS: babA2 genotype was present in 104 (69.3%) and cagA in 113 (75.3%) gastric samples. No significant correlation was observed between babA2 and vacAs1 genotype or between babA2 and cagA status. The correlation of vacAs1 genotype with positive cagA was statistically significant ( p < .001). The babA2-positive strain was more frequently found from the gastric samples of men, than of women (p = .01). Strains harboring cagA, vacAs1, and babA2 genotypes had no association to the grading of gastritis, presence of glandular atrophy, or intestinal metaplasia. The simultaneous presence of cagA, vacAs1, and babA2 was found in 32.6% of the H. pylori strains. CONCLUSIONS: babA2 genotype is frequently found in H. pylori strains from peptic ulcer disease in Brazil, although it has no significant correlation to the worsening of the gastritis and to other virulence markers such as vacAs1 and cagA.     

Progress in vaccine development against Helicobacter pylori

Based on the very high prevalence of diseases caused by Helicobacter pylori, particularly in the developing world, and the rapid emergence of antibiotic resistance among clinical isolates, there is a strong rationale for an effective vaccine against H. pylori. In this review we describe recent promising candidate vaccines and prophylactic or therapeutic immunization strategies for use against H. pylori, as well as studies to identify immune responses that are related to protection in experimental animals. We also describe identification of different types of immune responses that may be related to protection against symptoms based on comparisons of H. pylori-infected patients with duodenal ulcers or gastric cancer and asymptomatic carriers. We conclude that there is still a strong need to clarify the main protective immune mechanisms against H. pylori as well as to identify a cocktail of strong protective antigens, or recombinant bacterial strains that express such antigens, that could be administered by a regimen that gives rise to effective immune responses in humans.     

Genotypic and phenotypic variation of Lewis antigen expression in geographically diverse Helicobacter pylori isolates

Background: Helicobacter pylori are a persistent colonizer of the human gastric mucosa, which can lead to the development of peptic ulcer disease and gastric adenocarcinomas. However, H. pylori can asymptomatically colonize a host for years. One factor that has been hypothesized to contribute to such persistence is the production of Lewis (Le) antigens in the lipopolysaccharide layer of the bacterial outer membrane as a form of molecular mimicry, because humans also express these antigens on their gastric mucosa. Humans and H. pylori both are polymorphic for Le expression, which is driven in H. pylori by variation at the Le synthesis loci. In this report, we sought to characterize Le genotypic and phenotypic variation in geographically diverse H. pylori isolates. Materials and Methods: From patients undergoing endoscopy in 29 countries, we determined Le phenotypes of 78 H. pylori strains and performed genotyping of the galT and β‐(1,3)galT loci in 113 H. pylori strains. Results: Le antigen phenotyping revealed a significant (p < .0001) association between type 1 (Le^a and Le^b) expression and strains of East Asian origin. Genotyping revealed a significant correlation between strain origin and the size of the promoter region upstream of the Le synthesis gene, galT (p < .0001). Conclusion: These results indicate that the heterogeneity of human Le phenotypes is reflected in their H. pylori colonizing strains and suggest new loci that can be studied to assess the variation of Le expression.     

Relevance of fucosylation and Lewis antigen expression in the bacterial gastroduodenal pathogen Helicobacter pylori

Helicobacter pylori is a prevalent bacterial, gastroduodenal pathogen of humans that can express Lewis (Le) and related antigens in the O-chains of its surface lipopolysaccharide. The O-chains of H. pylori are commonly composed of internal Le(x) units with terminal Le(x) or Le(y) units or, in some strains, with additional units of Le(a), Le(b), Le(c), sialyl-Le(x) and H-1 antigens, as well as blood groups A and B, thereby producing a mosaicism of antigenic units expressed. The genetic determination of the Le antigen biosynthetic pathways in H. pylori has been studied, and despite striking functional similarity, low sequence homology occurs between the bacterial and mammalian alpha(1,3/4)- and alpha(1,2)-fucosyltransferases. Factors affecting Le antigen expression in H. pylori, that can influence the biological impact of this molecular mimicry, include regulation of fucosyltransferase genes through slipped-strand mispairing, the activity and expression levels of the functional enzymes, the preferences of the expressed enzyme for distinctive acceptor molecules and the availability of activated sugar intermediates. Le mimicry was initially implicated in immune evasion and gastric adaptation by the bacterium, but more recent studies show a role in gastric colonization and bacterial adhesion with galectin-3 identified as the gastric receptor for polymeric Le(x) on the bacterium. From the host defence aspect, innate immune recognition of H. pylori by surfactant protein D is influenced by the extent of LPS fucosylation. Furthermore, Le antigen expression affects both the inflammatory response and T-cell polarization that develops after infection. Although controversial, evidence suggests that long-term H. pylori infection can induce autoreactive anti-Le antibodies cross-reacting with the gastric mucosa, in part leading to the development of gastric atrophy. Thus, Le antigen expression and fucosylation in H. pylori have multiple biological effects on pathogenesis and disease outcome.     

Occurrence of a nontypable Helicobacter pylori strain lacking Lewis blood group O antigens and DD-heptoglycan: evidence for the role of the core alpha1,6-glucan chain in colonization

The cell envelope of Helicobacter pylori contains a lipopolysaccharide (LPS) essential for the physical integrity and functioning of the bacterial cell membrane. The O-chain of this LPS frequently expresses type 2 Lewis x (Lex) and Lewis y (Ley) blood group antigens that mimic human gastric mucosal cell-surface glycoconjugates. This article describes the isolation and structural analysis of the LPS from a clinical isolate of H. pylori strain PJ2 that lacks Le antigens but is still capable of colonization. Subsequent composition, methylation, and CE-ESMS analyses of LPS revealed its core oligosaccharide structure to be consistent with the previously proposed structural model for H. pylori LPS. In addition, it carries an unusually long side branch alpha1,6-glucan and was devoid of Le O-chain polysaccharide. Its ability to colonize the mouse stomach was essentially identical to that of DD-heptoglycan- and Le antigen- producing H. pylori strains.