Pathogenesis Of Ulcer Research Articles

CagA promotes proliferation and secretion of extracellular matrix by inhibiting signaling pathway of apoptosis in rat glomerular mesangial cells

Cytotoxin-associated antigen A (CagA), a major virulence factor of Helicobacter pylori (Hp), is associated with the pathogenesis of peptic ulcer and gastric cancer. Recent researches demonstrated that Hp exists in palatine tonsil in all studied IgA nephropathy (IgAN) patients, most of which were CagA-positive, suggesting that CagA may be a causative pathogenic factor of IgAN. However, the underlying molecular mechanisms and signaling pathway are still largely unclear. In the present study, CCK8 assay, enzyme-linked immunosorbent assay, and immunohistochemistry were performed to investigate the effect of CagA on cell proliferation and extracellular matrix secretion in rat glomerular mesangial cells. RT-PCR and western blotting were used to reveal the potential signaling pathway. Rat glomerular mesangial cells were treated with recombinant CagA protein for 72 h, in a dose- and time-dependent manner. We found that CagA promoted cell proliferation and extracellular matrix secretion by inhibiting signaling pathway of apoptosis. Taken together, these findings suggested that CagA induced cellular injury in glomerular mesangium by proliferation and secretion of extracellular matrix, and may play an important role in pathogenesis of IgAN.

Oral Ulceration: An Overview of Diagnosis and Management

Mouth ulcers are a common complaint by patients, with individuals regularly presenting to primary care practitioners for diagnosis and treatment. The aetiology and pathogenesis of oral ulceration is, however, both varied and complex. This article highlights the importance of differentiating recurrent aphthous stomatitis (RAS) in otherwise healthy individuals from recurrent oral ulceration (ROU) secondary to known or unknown systemic disease. An overview of the diagnosis and management of such patients is provided as a framework to guide general dental practitioners' with clinical decision making on whether to treat or refer to secondary care.

Assessment, Definition, and Classification of Lower Limb Ulcers in Systemic Sclerosis: A Challenge for the Rheumatologist.

To evaluate pathogenesis and clinical features of lower limb ulcers in systemic sclerosis (SSc) and to propose a classification that could be used in clinical practice. Charts of 60 patients with SSc who had lower limb cutaneous lesions were reviewed. All patients had videocapillaroscopy and arterial and venous lower limb color Doppler ultrasonography (US). Arteriography was performed if occlusive peripheral arterial disease was suspected. The 554 lesions were classified as hyperkeratosis, ulcers, and gangrenes. There were 341 (61.6%) hyperkeratoses, 208 (37.5%) ulcers, and 5 (0.9%) gangrenes. Ulcers were divided into pure ulcers, ulcers associated with hyperkeratosis, and ulcers secondary to calcinosis. Involvement of arterial and venous macrocirculation as determined by color Doppler US was observed in 17 (18.3%) and 18 (30%) patients, respectively. Seventeen out of 37 patients with pure ulcers (45.9%) presented neither venous insufficiency nor hemodynamically significant macrovascular arterial disease. In these patients, pure ulcers were most likely caused by isolated SSc-related microvascular involvement (pure microvascular ulcers). The only significant risk factor for development of pure microvascular ulcers in the multivariate analysis was the history of lower limb ulcers (OR 26.67, 95% CI 2.75-259.28; p < 0.001). Results of our study indicate that lower limb ulcers in SSc often have a multifactorial pathogenesis that may be difficult to manage. Further studies are needed to validate the proposed classification and to assess the most appropriate management of lower limb ulcers in SSc.

Diabetic hindfoot problems

Diabetes prevalence is reaching pandemic proportions in the 21st century. Since the discovery of insulin physicians and surgeons have been challenged by the long term complications of diabetes. Foot and ankle complications consume a great proportion of healthcare resources. In recent times there have been great advances in understanding the basic science behind the aetiology of diabetic foot and ankle complications. The combination of abnormal biomechanics, neuropathy and vascularity is integral to the pathogenesis of ulceration and Charcot arthropathy. The article discusses the unique biomechanical properties of a diabetic neuropathic lower limb.Hindfoot and ankle ulcerations have a greater association with major lower limb amputation. Conservative treatment includes prescription of off-loading orthotics and local ulcer treatment. However heel ulcers can also be the result of overzealous surgical intervention.Mirroring the increased prevalence of diabetes, Charcot arthropathy incidence is rising. We discuss the conservative and surgical management of this devastating complication of a neuropathic hindfoot and ankle. Conservative management is the mainstay of the initial phase of this disease though evidence is appearing of the benefits of early surgical intervention. Surgical interventions aim at preserving the lower limb and producing a stable plantigrade foot.

下肢静脈疾患・静脈性うっ滞性潰瘍の病態，診断，治療

下肢静脈に多くの病変が起きやすいのは下肢静脈には安静時立位時に高い静脈圧がかかり，容易に静脈高血圧が起こることによる．臨床所見と超音波診断などから適切なCEAP分類に基づいた診断を行い，静脈高血圧の原因を明らかにする．治療は静脈高血圧の是正で，基本は下肢挙上など生活の改善，弾性包帯，弾性ストッキングによる圧迫療法である．両治療ともに患者に指示するだけでは成功率は低く，患者に受け入れられるように改変することが大切である．下肢静脈性潰瘍に対する表在静脈逆流遮断術（下肢静脈ストリッピング術あるいは血管内焼灼術）は基礎となる圧迫療法にくらべて潰瘍治癒効果は高いわけではないが，再発予防に有用である．特に一次性下肢静脈瘤が病因であるときは必須の手技となる．一次性下肢静脈瘤の治療は血管内焼灼術が広く使用されつつあるが，その長期成績，特に静脈性潰瘍例での成績は明らかではない点には注意を要する．

The calcium-regulating system and recurrent peptic ulcer

To elucidate the functional state and value of the calcium-regulating system, calcium and phosphorus metabolism in the pathogenesis and sanogenesis of peptic ulcer (PU); to define the possible ways to correct shifts found in the treatment of disease relapse, by affecting the different levels of their disorders. A total of 220 patients with recurrent PU were examined by determining the blood levels of parathyrin, calcitonin, calcium and phosphorus, as well as gastric secretory and motor functions. Recurrent PU was accompanied by a considerable increase in the blood concentration of parathyroid hormone and calcium, a slight rise in that of calcitonin, and a significant reduction in that of phosphorus. These changes were attended by a substantial increase in gastric acid- and pepsinogen-forming functions, a decrease in the production of gastric mucoproteins, and hypermotor dyskinesia. The use of calcitrin, nifedipine, and etidronic acid, which eliminate dysfunction of the calcium-regulating system at different levels of its impairments, leads to a significant reduction in the time of alleviation of the clinical and endoscopic manifestations of a recurrence. Recurrent PU runs in the presence of calcium-regulating system dysfunction. Incorporation of the thyroid C-cell hormone preparation calcitrin, the slow calcium-channel blocker nifedipine, and etidronic acid bisphosphonate into a complex of treatment for a disease recurrence is pathogenetically sound and clinically effective.

Silencing TNFα with lipidoid nanoparticles downregulates both TNFα and MCP-1 in an in vitro co-culture model of diabetic foot ulcers

Diabetes is one of the most formidable diseases facing the world today, with the number of patients growing every year. Poor glycemic control yields a host of complications, such as impaired wound healing. This often results in the formation of diabetic foot ulcers, which carry a poor prognosis because they are notoriously difficult to treat. Current therapies do not address the increased number of infiltrating macrophages to the wound bed that overproduce tumor necrosis factor α (TNFα), which increases fibroblast apoptosis and collagen dismantling and decreases angiogenesis. In this study, we investigated the potential of RNA interference therapy to reduce the inappropriately high levels of TNFα in the wound bed. Although TNFα is a challenging gene silencing target, our lipidoid nanoparticles potently silence TNFα mRNA and protein expression at siRNA doses of 5–100nM without inducing vehicle-related gene silencing or cell death. We also describe the creation of an in vitro macrophage–fibroblast co-culture model, which reflects the TNFα and monocyte chemotactant protein-1 (MCP-1/CCL2) cross-talk that exists in diabetic wounds. Because TNFα induces fibroblasts to produce MCP-1, we show that silencing TNFα results in a downregulation of MCP-1, which should inhibit the recruitment of additional macrophages to the wound. In co-culture experiments, a single lipidoid nanoparticle dose of 100nM siTNFα downregulated TNFα and MCP-1 by 64% and 32%, respectively. These data underscore the potential of lipidoid nanoparticle RNAi treatment to inhibit a positive feedback cycle that fuels the pathogenesis of diabetic foot ulcers. Statement of significanceDiabetic foot ulcers are a rapidly growing issue worldwide, with current ulcer treatments not as effective as desired. RNA interference therapy represents a largely untapped possible solution to impaired wound healing. We show that siRNA-loaded lipidoid nanoparticles silence the overexpression of tumor necrosis factor α (TNFα) in inflammatory macrophages which leads to a subsequent downregulation of fibroblast-produced macrophage chemotactant protein-1 (MCP-1). Both TNFα and MCP-1 are critical components of the inflammatory feedback loop that exists in chronic wounds. In contrast to the majority of wound drug delivery studies, our study utilizes macrophage/fibroblast co-culture experiments to recapitulate a multicellular wound environment in which cytokine signaling influences inflammation. Results underscore the therapeutic potential of siRNA nanoparticles directed against TNFα in inhibiting two key inflammatory targets in chronic wounds.

Peptic Ulcer Disease Different Pathogenesis of Duodenal and Gastric Ulcer

Despite decrease frequency of Helicobacter pylori (H. pylori) due to eradication therapy, peptic ulcer disease as a manifestation of this infection is still remain a health burden. Understanding the physiology of gastric acid secretion and its alteration by H. pylori induced inflammation will aid physician in differentiating peptic ulcer disease based on its location. Duodenal ulcer and gastric ulcer disease are two common condition that usually found in peptic ulcer. Recognition of symptoms and its pathogenesis may lead physician to understand the fate of each condition in the future. This article reviews concept of peptic ulcer pathogenesis according to ulcer etiology.

Metabolomic profiles delineate mycolactone signature in Buruli ulcer disease.

Infection of human skin with Mycobacterium ulcerans, the causative agent of Buruli ulcer, is associated with the systemic diffusion of a bacterial macrolide named mycolactone. Patients with progressive disease show alterations in their serum proteome, likely reflecting the inhibition of secreted protein production by mycolactone at the cellular level. Here, we used semi-quantitative metabolomics to characterize metabolic perturbations in serum samples of infected individuals, and human cells exposed to mycolactone. Among the 430 metabolites profiled across 20 patients and 20 healthy endemic controls, there were significant differences in the serum levels of hexoses, steroid hormones, acylcarnitines, purine, heme, bile acids, riboflavin and lysolipids. In parallel, analysis of 292 metabolites in human T cells treated or not with mycolactone showed alterations in hexoses, lysolipids and purine catabolites. Together, these data demonstrate that M. ulcerans infection causes systemic perturbations in the serum metabolome that can be ascribed to mycolactone. Of particular importance to Buruli ulcer pathogenesis is that changes in blood sugar homeostasis in infected patients are mirrored by alterations in hexose metabolism in mycolactone-exposed cells.

Apocynin protects against ethanol-induced gastric ulcer in rats by attenuating the upregulation of NADPH oxidases 1 and 4

Gastric ulcer is a common gastrointestinal disorder affecting many people all over the world. Absolute ethanol (5 ml/kg) was used to induce gastric ulceration in rats. Apocynin (50 mg/kg) was given orally one hour before the administration of absolute ethanol. Omeprazole (20 mg/kg) was used as a standard. Interestingly, apocynin pre-treatment provided 93.5% gastroprotection against ethanol-induced ulceration. Biochemically, gastric mucin content was significantly increased with apocynin pre-treatment. This finding was further supported by alcian blue staining of stomach sections obtained from the different treated groups. Also, gastric juice volume and acidity were significantly reduced. Apocynin significantly ameliorated ethanol-induced oxidative stress by replenishing reduced glutathione and superoxide dismutase levels as well as reducing elevated malondialdehyde levels in gastric tissues. Besides, ethanol-induced pro-inflammatory response was significantly decreased by apocynin pre-treatment via reducing elevated levels of pro-inflammatory markers; interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2 and inducible nitric oxide synthase. Additionally, caspase-3 tissue level was significantly reduced in apocynin pre-treated group. Interestingly, NADPH oxidase-1 (NOX-1) and NOX-4 up-regulation was shown to be partially involved in the pathogenesis of ethanol-induced gastric ulceration and was significantly reversed by apocynin pre-treatment. Gastroprotective properties of apocynin were confirmed by histopathological examination. It is worth mentioning that apocynin was superior in all aspects except gastric mucin content parameter where it was significantly increased by 13.5 folds in the omeprazole pre-treated group. This study was the first to show that apocynin is a promising gastroprotective agent against ethanol-induced gastric ulceration, partially via its anti-oxidant, anti-inflammatory, anti-apoptotic effects as well as down-regulating NOX-1 and NOX-4 expression.

REDOX-SENSITIVE TRANSCRIPTION FACTORS EGR-1 AND SP1 IN THE PATHOGENESIS OF EXPERIMENTAL GASTRIC ULCER.

Changes in redox status of gastric mucosa cells are the main pathogenic factor of gastric erosion and gastric ulcer development. Pro-oxidants can affect cell transcription activity via changes in redox-sensitive transcription factors. Egr-1 and Sp-1 may regulate the transcription of genes that are associated with the pathogenesis of gastric ulcer (growthfactors, cell cycle regulators, etc.). The aim of the present study was to reveal the possible involvement of zinc-finger transcriptionfactors Egr-1 & Sp-1 in the molecular mechanisms underlying gastric lesions caused by aspirin administration and stress. Gastric ulcer was induced in male rats (180-220 g) by immobilization stress combined with water-immersion (IMO-WI) or aspirin gavage (10 mg/100 g). The rats were euthanized 20 min, 1 hour, or 3 hours following the ulcerogenic factor exposure. Protein expression was determined by Western blot analysis and RT-PCR; levels of SH-groups of proteins were determined by method of Ellman et al. Development of gastric ulcer lesions was associated with twofold (P < 0.05) decrease in concentration of protein SH-groups in the rat gastric mucosa. These changes were accompanied by significant (P < 0.05) increase in the expression of Egr-1 mRNA and protein in both gastric ulcer models, and the changes in IMO-WI were more profound. Increased levels of Egr-1 were associated with the decrease in SpI protein levels. We showed for the first time the competitive interaction between redox-sensitive transcription factors Egr-1 and Sp1 in the early phases of gastric ulcer development, which might facilitate inducible transcriptional activity of Egr-1 at the expense of reduction in Sp1 activity.

EKSPRESI ANTI-HELICOBACTER PYLORI PADA GASTRITIS KRONIS, LESI PRAKANKER, DAN KARSINOMA GASTER

Prevalence of Helicobacter pylori infection in Indonesia was 36-46%. In Jakarta and Surabaya, the prevalence were 85,7%-93,9%. Helicobacter pylori infection play role in pathogenesis of pectic ulcers, chronic gastritis, carcinoma of gaster and gastric lymphoma. Epidemiologic study showed 80% of carcinoma of gaster related with H pylori infection.This study analyzed expression of anti-Helicobacter pylori in chronic gastritis, precancer lesion , and carcinoma of gaster. This study was a observational descriptive study with case control design. Thirty (30) samples from paraffin bloc that were diagnosed with chronic gastritis, precancer lesion, and carcinoma of gaster at Dokter Kariadi hospital in 2013 was stained by hematoxylin eosin, giemsa and immunohistochemistry of anti-helicobacter pylori. Data was analyzed by descriptive analysis. Thirty (30) samples were diagnosed as gastritis chronis 13 (43,3% ), pra cancer lesion(36.6%), and carcinoma(20.1%). Chronic gastritis can be occurred at all age and no distinct difference on sex, while gastric carcinoma predominant in male older than 40 years. Expresion of Helicobacter pylori on chronic gastritis was 84.6%, precancer lesion was 54.5%, and gastric carcinoma was 83.3%. The Giemsa stain gave 23.3% false positive and 20% false negative. Helicobacter pylori expression can be showed in chronic gastritis, precancer lesion, and gastric carcinoma.Keywords: Chronic gastritis, gastric carcinoma, Helicobacter pylori

Using ultrasound elastography to monitor human soft tissue behaviour during prolonged loading: A clinical explorative study

PurposePressure ulcers are localized injuries to the skin or underlying tissues over a bony prominence, as a result of pressure, or pressure in combination with shear. Ultrasound imaging techniques are widely applied to detect and to investigate pressure ulcer pathogenesis and healing, but due to missing structural alterations, very early signs of tissue alterations are not detectable. Ultrasound elastography was proposed as a new method to measure very early signs of pressure ulcer development but this was not investigated in humans so far. The aim of this study was to investigate for the first time whether US elastography is able to measure potential changes in dermal and subcutaneous tissue stiffness during prolonged loading. Materials and methodsAn exploratory study including nine healthy volunteers (mean age 70.1 (SD 4.8) years) was conducted. Study participants were requested to follow a standardized lying protocol, consisting of two loading phases of 90 and 150 min in supine position on a standard hospital mattress. Three pressure ulcer predilection sites (lateral heel over the calcaneus, sacral, and upper back area) were measured using B-mode and elastographic ultrasound system at baseline – immediately, after 90 min, and after 150 min loading. ResultsMean baseline shear wave velocities were highest in the heel skin (2.7 m/s) and lowest in the upper back skin (1.9 m/s) indicating that heel skin was stiffest. Also the subcutaneous soft tissue stiffness was highest for the heel (2.7 m/s) and lowest for the upper back region (1.3 m/s). After 90 and 150 min loading there was a mean stiffness increase of the skin layers and a pronounced stiffness decrease of subcutaneous heel and sacral tissues. ConclusionsContinuous loading of skin and underlying subcutaneous soft tissues leads to dynamic changes of tissue stiffness which are considered to play key roles in pressure ulcer development. Superficial skin and deep tissues seem to react differently. Elastography is able to quantify the dynamic of skin and subcutaneous soft tissue stiffness changes non-invasively in vivo. Shear wave velocity might serve as a new parameter for quantifying pressure ulcer damage risk in superficial and deeper tissues prone to pressure ulcer development.

Potential humoral markers of gastric and duodenal stress ulcers accompanied by concomitant head injury

Aim. To evaluate the significance of a number of humoral indicators in gastrointestinal bleeding at various stages of severe concomitant head injury.Methods. The study included 347 patients with severe head injuries (brain contusion, intracerebral hemorrhage) associated with fractures of the extremities and pelvis (215 patients), abdominal organs injuries (75 patients), chest and lung injuries (57 patients). Samples of blood and stomach contents were taken on the 1st, 3rd, 5th, 8th, 9th, 12th, 15th and 18th days after the injury. Esophagogastroduodenoscopy was performed on the 3rd, 5th, 7th and 10th day after the trauma. Anti-streptolysin O, antihyaluronidase, C-reactive protein, sialic acids levels were determined by serum titration and precipitate formation.Results. On the 1st day, anti-streptolysin O level exceeded normal values (by 4.1±1.3 IU/ml), reaching a maximum value by 8-10th day (exceeding the normal range by 61.3±1.7 IU/ml) with further decrease after the 15th day. Antihyaluronidase level was permanently increased from the 5th day of observation. C-reactive protein level was higher than normal from the first day of study (0.1±0.17 mg/l), with further upward trend, reaching its peak on day 9, indicating continuous inflammation. Sialic acids level in the first days was twice as high as the normal level, and remained almost at the same level until the end of the study. Endoscopic examinations in 21 patients with gastrointestinal bleeding showed that in 11 (52.4%) cases, the source of bleeding were acute gastric and duodenal erosions and ulcers, in 5 (23.8%) cases - chronic gastric and duodenal ulcers, in 5 (23.8%) cases bleeding occurred due to exacerbation of chronic duodenal ulcer.Conclusion. Changes in serum anti-streptolysin O, antihyaluronidase, sialic acids levels in patients with severe head injuries, combined with other injuries may reflect the pathogenesis of acute gastroduodenal erosions and ulcers and be considered as the markers for their development.

Impacts of H. pylori mixed-infection and heteroresistance on clinical outcomes.

Helicobacter pylori infection is recognized as a major factor in the pathogenesis of chronic gastritis, peptic ulcer and gastric cancer (1, 2). Although treatment regimens containing a proton pump inhibitor (PPI) and combination of two or more antibiotics (amoxicillin, clarithromycin, metronidazole, or tetracycline) are considered to be the most efficacious, current antibiotic regimens show only 60–85% cure rates in clinical practices (3). The treatment failure was due to a pre-existing antibiotic resistant H. pylori strain or emergence of a new resistant strain from a susceptible ancestor. H. pylori resistance to amoxicillin, clarithromycin, metronidazole and tetracycline has been reported from Iran and other countries (4-6). Although H. pylori strains from individual patients typically have either an antibiotic susceptible or resistant phenotype, both antibiotic susceptible and resistant strains could exist among a single population of H. pylori in each patient. Heteroresistance represents infection with variants of H. pylori strains that were evolved during long-time chronic infection. Heteroresistance is believed to be as a cause of treatment failure of conventional therapeutic regimens against this infection (7-10). In a study in Iran, high frequency of mixed-type infection (77%) and also quasispecies development (15.4%) was reported, which suggests inefficacy of common therapeutic regimens in the infected patients due to co-existence of the resistant strains (11). Susceptible or heteroresistance strains could simultaneously present in the same region of the stomach (7), while their presence in different regions (antrum compared to corpus) was also reported (12, 13).

Small-Fiber Neuropathy: A Diabetic Microvascular Complication of Special Clinical, Diagnostic, and Prognostic Importance.

Damage of small nerve fibers may lead to a large variety of clinical symptoms. Small-fiber neuropathy underlies the symptoms of painful diabetic neuropathy, which may decrease quality of life. It also contributes to the poor prognosis of diabetic neuropathy because it plays a key role in the pathogenesis of foot ulceration and autonomic neuropathy. Impairment of small nerve fibers is considered the earliest alteration in the course of diabetic neuropathy. Therefore, assessment of functional and morphological abnormalities of small nerve fibers may enable timely diagnosis. The definition, symptoms, and clinical significance of small-fiber neuropathy are considered in the present review. An apparently more complex interaction between small-fiber impairment and microcirculation is extensively discussed. Diagnostic modalities include morphometric and functional methods. Corneal confocal microscopy and punch skin biopsy are considered gold standards, but noninvasive functional tests are also diagnostically useful. However, in routine clinical practice, small-fiber neuropathy is diagnosed by its typical clinical presentation. Finally, prompt treatment should be initiated following diagnosis.

Pathogenesis and management of diabetic foot ulcers.

Diabetic foot ulcers are a devastating component of diabetes progression and are caused by loss of glycemic control, peripheral neuropathy, peripheral vascular disease, and immunosuppression. An estimated 15% of patients with diabetes have diabetic foot ulcers. This article describes the pathogenesis, diagnosis, clinical management, and advances in wound treatment for diabetic foot ulcers.

Cytomegalovirus Identification and Quantification from the Saliva of Human Immunodeficiency Virus Seropositive and Seronegative Patients Using Real Time Polymerase Chain Reaction

Cytomegalovirus Identification and Quantification from the Saliva of Human Immunodeficiency Virus Seropositive and Seronegative Patients Using Real Time Polymerase Chain Reaction

Novel topical formulation for ischemic chronic wounds. Technological design, quality control and safety evaluation

Ulceration of the foot in diabetes is common and disabling, and frequently leads to amputation of the leg. The pathogenesis of foot ulceration is complex, clinical presentation variable and management requires early expert assessment. Despite treatment, ulcers readily become chronic wounds. Chronic wounds are those that remain in a chronic inflammatory state failing a normal healing process patterns. This is partially caused by inefficient eradication of opportunistic pathogens like Pseudomonas aeruginosa. We propose its control or eradication will promote wound healing. Lactobacillus plantarum cultures supernatants (LAPS) shows antipathogenic and pro-healing properties. The main objective was to design two pharmaceutical dosage forms by using LAPS as active pharmaceutical ingredient and to perform its quality control, in vitro activity conservation tests and human trials (safety evaluation). Both selected formulations reach the technological quality expected for 120 days, shows adequate occlusive characteristics and proper adhesion to human skin. From the in vitro release assays were found that LAPS shows adequate release from matrix and maintain its antimicrobial and anti-biofilm activity. First human trials were developed and neither edema nor erythema on healthy skin voluntaries was found. We conclude that C80 and C100 are adequate for their use in future clinical trials to demonstrate a comprehensive therapeutic effectiveness in ischemic chronic wounds.

Influence of prostate stem cell antigen gene polymorphisms on susceptibility to Helicobacter pylori-associated diseases: a case-control study.

Patients with duodenal ulcer have a reduced risk of developing gastric cancer compared to those without. Recently, the prostate stem cell antigen (PSCA) rs2294008 C>T polymorphism was found to be associated with different pathogenesis of duodenal ulcer and gastric cancer developments. However, whether PSCA rs2294008 C>T polymorphism is associated with severity of gastric mucosal atrophy is unclear. We examined the influence of the PSCA rs2294008 C>T polymorphism on susceptibility to H. pylori-related diseases and the relationships between PSCA polymorphism and gastric mucosal atrophy. PSCA rs2294008 C>T polymorphism was assessed in H. pylori-positive Japanese patients (n = 488) with noncardia gastric cancer (n = 193), gastric ulcer (n = 84), duodenal ulcer (n = 61), and atrophic gastritis (n = 150), as well as in H. pylori-negatives (n = 266). Frequency of PSCA rs2294008 C/C genotype in duodenal ulcer was 36.1%, which was significantly higher than those with gastric cancer (12.4%), gastric ulcer (19.0%), gastritis (10.7%), and H. pylori-negatives (19.5%) (p < .001). Compared with duodenal ulcer, having the T allele significantly increased the risk of gastric cancer (OR: 3.97, 95% CI: 2.02-7.80; p < .001), gastric ulcer (2.40, 1.13-5.10; p = .023), and gastritis (4.72, 2.26-9.86; p < .001). Mean pepsinogen (PG) I/PG II ratio in T allele carriers (2.17 ± 0.75) was significantly lower than that in C/C genotype (3.39 ± 1.27, p < .001). The PSCA rs2294008 C>T polymorphism is associated with differing susceptibilities to H. pylori-associated diseases. The PSCA rs2294008 C>T polymorphism may be acting through induction of gastric mucosal atrophy, finally leading to development of gastric ulcer and gastric cancer in PSCA rs2294008 T allele carriers, but not duodenal ulcer.