• Journal of Periodontal and Implant Science
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• 제49권3호
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• pp.138-147
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• 2019

Purpose: Several studies have shown that the oral cavity is a secondary location for Helicobacter pylori colonization and that H. pylori is associated with the severity of periodontitis. This study investigated whether H. pylori had an effect on the periodontium. We established an invasion model of a standard strain of H. pylori in human periodontal ligament fibroblasts (hPDLFs), and evaluated the effects of H. pylori on cell proliferation and cell cycle progression. Methods: Different concentrations of H. pylori were used to infect hPDLFs, with 6 hours of co-culture. The multiplicity of infection in the low- and high-concentration groups was 10:1 and 100:1, respectively. The Cell Counting Kit-8 method and Ki-67 immunofluorescence were used to detect cell proliferation. Flow cytometry, quantitative real-time polymerase chain reaction, and western blots were used to detect cell cycle progression. In the high-concentration group, the invasion of H. pylori was observed by transmission electron microscopy. Results: It was found that H. pylori invaded the fibroblasts, with cytoplasmic localization. Analyses of cell proliferation and flow cytometry showed that H. pylori inhibited the proliferation of periodontal fibroblasts by causing G2 phase arrest. The inhibition of proliferation and G2 phase arrest were more obvious in the high-concentration group. In the low-concentration group, the G2 phase regulatory factors cyclin dependent kinase 1 (CDK1) and cell division cycle 25C (Cdc25C) were upregulated, while cyclin B1 was inhibited. However, in the high-concentration group, cyclin B1 was upregulated and CDK1 was inhibited. Furthermore, the deactivated states of tyrosine phosphorylation of CDK1 (CDK1-Y15) and serine phosphorylation of Cdc25C (Cdc25C-S216) were upregulated after H. pylori infection. Conclusions: In our model, H. pylori inhibited the proliferation of hPDLFs and exerted an invasive effect, causing G2 phase arrest via the Cdc25C/CDK1/cyclin B1 signaling cascade. Its inhibitory effect on proliferation was stronger in the high-concentration group.

• Journal of Microbiology and Biotechnology
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• 제11권2호
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• pp.317-325
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• 2001

For heuristic purposes, the relative ratio of urease contents inside and outside cells was surveyed using nine ureB+ strains of Helicobacter pylori. the ratio of the enzyme specific activity appeared to vary greatly between the various H. pylori strains, ranging from 0.5 to 2.5. Besides the above compartment, urease was also richly found in the membrane fraction, especially in either peripheral or integral form. The urease distribution across the H. pylori membrane was significantly influenced by the ambient pH; the specific activity of external urease was highest at pH 5.5 with a narrow plateau, whereas the internal specific activity was highest within a pH range of 4.5 to 6.5 with a broad plateau. These finding strongly suggest that H. pylori urease is secretory and responded to the external pH. However, at pH 4.0 or below, no urease activity was detected in either the internal or external compartment, although an increase in the color development with 2,4,6-trinitrobenzene sulfonate (TNBS) was observed. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) demonstrated that these phenomena may be related to a specific proteolysis in certain proteins, including urease or ${\gamma}$-glutamyl transpeptidase. Interestingly, the effect of ammonium ions n alleviating the enzyme inactivation inside the H. pylori cells was remarkably similar to that of D-glucose. In addition, it would appear that the cation acted as a surrogate of not only $Na^+$ but also $K^+$ thereby increasing the H. pylori P-type ATPase activity. This is of great interest, as it implies that the urease action in H. pylori is indispensible at any locus.

• Journal of Microbiology and Biotechnology
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• 제15권4호
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• pp.866-872
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• 2005

H. pylori is known to cause severe gastric diseases, including peptic ulcers and gastric cancers, and a link has also been suggested with iron-deficiency anemia (IDA). However, little is known about the pathogenesis of H. pylori-associated IDA. In the present study, to determine whether H. pylori strains are correlated with the prevalence of IDA, we analyzed and compared the sequences of the napA genes encoding a bacterioferritin-like protein in H. pylori strains. A total of 20 H. pylori strains were isolated from antral biopsies of patients with and without IDA, and the napA genes amplified from the genomic DNA were sequenced. A comparison of the deduced amino acid sequences for NapA revealed two sites with major variations. At residue 70, five out of the 12 non-IDA strains ($41.7\%$) contained serine, while only one of the 8 IDA strains ($12.5\%$) contained serine, indicating a significantly higher frequency of serine in the non-IDA strains. In addition, the NapA proteins from all 17 Western strains available on Web sites were found to contain serine residues at this position. Meanwhile, the other major variation was located at residue 73, where all eight IDA strains ($100\%$) contained leucine, while this was only true for eight of the 12 non-IDA strains ($66.7\%$). Therefore, these results indicated that the strains within each group were more genetically related to each other than to strains in the other group. When the expression level of the napA genes in the H. pylori strains was measured using RT-PCR, no significant difference was observed between the two groups, suggesting a similar intensity for the inflammatory responses induced by the NapA protein among the strains. Consequently, when taken together, the present data suggest that the occurrence of H. pylori-associated IDA may be partly determined by the infecting H. pylori strain, and the non-IDA strains are more closely related to Western strains than the IDA strains.

• Preventive Nutrition and Food Science
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• 제18권2호
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• pp.104-110
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• 2013

Presence of Helicobacter pylori is associated with an increased risk of developing upper gastrointestinal tract diseases. Antibiotic therapy and a combination of two or three drugs have been widely used to eradicate H. pylori infections. Due to antibiotic resistant drugs, new drug resources are needed such as plants which contain antibacterial compounds. The aim of this study was to investigate the ability of GutGard$^{TM}$ to inhibit H. pylori growth both in Mongolian gerbils and C57BL/6 mouse models. Male Mongolian gerbils were infected with the bacteria by intragastric inoculation ($2{\times}10^9$ CFU/gerbil) 3 times over 5 days and then orally treated once daily 6 times/week for 8 weeks with 15, 30 and 60 mg/kg GutGard$^{TM}$. After the final administration, biopsy samples of the gastric mucosa were assayed for bacterial identification via urease, catalase and ELISA assays as well as immunohistochemistry (IHC). In the Mongolian gerbil model, IHC and ELISA assays revealed that GutGard$^{TM}$ inhibited H. pylori colonization in gastric mucosa in a dose dependent manner. The anti-H. pylori effects of GutGard$^{TM}$ in H. pylori-infected C57BL/6 mice were also examined. We found that treatment with 25 mg/kg GutGard$^{TM}$ significantly reduced H. pylori colonization in mice gastric mucosa. Our results suggest that GutGard$^{TM}$ may be useful as an agent to prevent H. pylori infection.

• Preventive Nutrition and Food Science
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• 제8권1호
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• pp.70-74
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• 2003

This study investigated the relationship of Helicobacter pylori (H. pylori) infection to iron-deficiency anemia in high school girls. Four hundred and fourty-five subjects resided in Ulsan City in Korea were evaluated by questionnaire or blood analysis for serum indicators of iron status, daily nutrient intakes, symptoms of anemia, and H. pylori IgG antibody status. In H. pylori infected subjects, total energy intake of was 1534.14±350.81 kcal (73.0% of the Korean RDA), the iron intake of subjects was 11.38±3.90 mg (71.1% of Korean RDA) and calcium intake was 467.63±175.96 mg (58.3% of the Korean RDA). Carbohydrate (p < 0.05), vitamin A (p < 0.05), vitamin C (p < 0.01) intakes were significantly lower in infected subjects than in non-infected subjects. The prevalence of anemia (hemoglobin (Hb) < 12 g/dL.) in H. pylori infected subjects was 22.7% as compared to 14.7% in non-infected subjects. The mean serum ferritin of infected subjects (21.71±21.50 ng/mL) was significantly lower than in non-infected subjects (p < 0.05) (as was the mean Hb concentration (12.54±1.51 g/dL) and hematocrit (37.99±3.64%)). Total iron binding capacity (TIBC) of H. pylori infected subjects (449.09±78.23 ㎍/dL) was significantly higher than that of non-infected subjects (432.99＋76.15 ㎍/dL) (P < 0.05). The levels of iron, red blood cell (RBC) and transferrin saturation were similar in infected and non-infected subjects. Two symptoms of anemia, 'pale face (p < 0.01)' and 'decreased ability to concentrate (p < 0.005)', were significantly higher in H. pylori infected subjects than in non-infected subjects. High school girls are known to be more vulnerable to iron deficiency than other age groups, and this research demonstrates that infection with H. pylori increases their risk of iron-deficiency anemia.

• Journal of Digestive Cancer Research
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• 제8권2호
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• pp.81-90
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• 2020

배경 및 목적: Helicobacter pylori (H. pylori) 제균 치료는 위암 발병률을 줄이는 것으로 알려져 있다. 그러나 만성 위축성 위염, 장상피화생 및 이형성증이 있는 일반 집단에서도 위암의 발생 위험을 예방할 수 있는지에 대해서는 여전히 논란의 여지가 있다. 우리는 포괄적인 메타분석을 통해 이에 대한 연구를 수행해 보고자 한다. 방법: 2019년 12월까지 H. pylori 제균 치료가 위암에 미치는 영향을 평가한 논문들을 PubMed, KoreaMed, EMBASE 및 Cochrane Library에서 검색하였다. 전암성 병변(만성 위축성 위염/장상피화생/이형성증), 지역(아시아/비아시아) 및 추적관찰기간에 따라 하위 집단 분석을 수행하였다. 모든 데이터는 Review Manager 5.3으로 분석하였다. 결과: 본 연구에서는 총 6편의 전향적 무작위 연구가 최종 분석에 포함되었다. 전체 집단에서 H. pylori 제균 치료는 위암 발생 위험을 유의하게 감소시켰다(위험비[RR]=0.56; 95% 신뢰구간[CI]: 0.41-0.77, p<0.01). 또한, 하위 집단 분석을 보면, H. pylori 제균 치료는 아시아 지역과 10년 이상의 추적관찰을 시행한 집단에서 위암 발생 위험을 현저하게 감소시키는 것을 보여주었다(RR=0.54, 95% CI: 0.39-0.75, p<0.01 및 RR=0.51; 95% CI: 0.35-0.73, p<0.01). 그러나, 전암성 병변 유무에 따른 하위 집단 분석에서는 유의한 결과가 도출되지 않았다(전암성 병변이 있는 군, RR=0.86, 95% CI: 0.47-1.59, p=0.63; 전암성 병변이 없는 군, RR=0.42, 95% CI: 0.02-7.69, p=0.56). 결론: H. pylori 제균 치료는 일반 집단, 특히 아시아 지역에서 위암 발생 위험을 낮춘다. 제균 치료의 위암 예방 효과는 10년 이상 장기간 추적관찰 하였을 때 유의하다. 한편, 전암성 병변이 있는 일반 집단에서 위암 예방을 위해 H. pylori 제균 치료를 시행하는 것은 아직 근거가 명확하지 않아 권고하기 어렵다. 따라서 앞으로 이에 대한 더 많은 연구가 필요하다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.9005-9008
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• 2014

Background: Gastric cancer is the second leading course of cancer death worldwide and H. pylori infection is an important risk factor for gastric cancer development. This study was design to evaluate the clinical, pathological features, survival rate and prevalence of H. pylori infection in gastric cancer in Thailand. Materials and Methods: Clinical information, histological features, endoscopic findings and H. pylori status were collected from gastric cancer patients from Thammasat university hospital during June 1996-December 2011. H. pylori infection was assessed by histological evaluation, rapid urease test and serological test. Clinical information, endoscopic findings and histopathology of all patients were recorded and compared between patients with active or non-active H. pylori infection. Results: A total of 100 gastric cancer patients (55 men and 45 women with mean age of $55{\pm}16.8years$) were enrolled in this study. Common presenting symptoms were dyspepsia (74%), weight loss (66%), anemia (63%) and anorexia (38%). Mean duration of symptoms prior to diagnosis was 98 days. Overall prevalence of H. pylori infection was 83% and active H. pylori infection was 40%. 1-year and 5-year survival rates were 43% and 0%. There was no significant difference between active H. pylori infection in different locations (proximal vs non-proximal: 47.1% vs 48.5%; P-value = 0.9, OR=0.9; 95%CI=0.3-3.1) and histology of gastric cancer (diffuse type vs intestinal type: 47.4% vs 50%; P-value = 0.8, OR=0.9, 95%CI=0.3-2.7). However, linitis plastica was significantly more common in non-active than active H. pylori infection (27.9% vs 0%; P-value<0.0001, OR=13.3, 95%CI=3.2-64.5). Moreover, gastric cancer stage 4 was higher in non-active than active H. pylori infection (93% vs 50%, P-value<0.001). Conclusions: Prevalence of H. pylori infection in Thai gastric cancer patients was high but active infection was low. Most gastric cancer patients presented in advance stage and had a grave prognosis. Screening for gastric cancer in high risk individuals might be an appropriate tool for early detection and improve the treatment outcome for this particular disease in Thailand.

• Journal of Microbiology and Biotechnology
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• 제11권1호
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• pp.35-39
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• 2001

A simple method for studying the lectin-like interactions between Helicobacter pylori and cultured human epithelial cell lines was developed using an enzyme-linked, biotin-streptavidin bacterial-adhesion assay. The present study suggests that this method is suitable for evaluating the participation of lectin interactions in the adhesion of H. pylori to cultured HeLa S3 and Kato III cells, both fixed and glycosidase-treated cells, as well as assessing glycoconjugated binding inhibition studies. The time-course and dose-dependent kinetics of the biotin-labeled H. pylori adhesion th the formaldehyde-fixed Hela S3 and Kato III cell lines exhibited saturation. In addition, the binding of the biotin-labeled H. pylori to the formaldehyde-fixed cultured cells was partially blocked by pre-incubation with glycoconjugates and polyclonal antibodies against a heparan sulfate binding protein from H. pylori.

• Clinical and Experimental Pediatrics
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• 제64권1호
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• pp.21-25
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• 2021

Helicobacter pylori infection has declined over recent decades. However, its prevalence remains high, and nearly 50% of the global population has been infected. In Korea, seroprevalence has steadily decreased in adults, but the status of H. pylori infection in children is unknown. The current status or trend of H. pylori infection in children is important because it can help estimate H. pylori-related diseases including gastric cancer in later life. In this review, the authors discuss the change in H. pylori infection rate among children and adolescents based on literature reviews and our research.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제8권1호
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• pp.12-20
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• 2005

목 적: 급성 및 만성 복통 혹은 상부 위장관 출혈로 병원에 와서 상부 위장관 내시경술을 시행하여 H. pylori 감염이 확인된 환아의 내시경적 소견에 대해 알아보고 H. pylori 박멸 치료를 위해 사용한 omeprazole, amoxicillin, clarithromycin의 삼제 병합 요법을 1주 및 2주 투여군으로 나누어 그 제균 효과를 비교해 보고자 하였다. 방 법: H. pylori 감염의 진단은 상부위장관 내시경술(GIF-XQ240, Olympus, Tokyo, Japan)을 시행하여 위전정부와 위체부에서 2개씩의 조직을 얻어 CLO (Delta West, Bentley, Australia)검사와 조직학적 검사를 하여 양성이면 H. pylori에 감염된 것으로 판정하였다. 요소 분해 효소 검사는 실온 상태에서 CLO 키트에 생검 조직을 넣고 24시간까지 관찰하여 색이 노란색에서 적색으로 변하면 양성, 조직학적 검사는 Hematoxylin & Eosin 염색 표본을 시행 후 내시경 검사 결과를 모르는 한 명의 병리의가 현미경상 위 점막 조직에서 균이 관찰되면 양성으로 판정하였으며 이 중 하나 이상에서 양성인 경우 H. pylori 양성으로 진단하였다. H. pylori 감염이 확인된 환아들을 치료기간에 따라 두 개의 군으로 구분하여 제I군은 omeprazole (1 mg/kg/day, 최대 20 mg, bid), amoxicillin (50 mg/kg/day, 최대 1g, bid), clarithromycin (15 mg/kg/day, 최대 500 mg, bid)의 삼제 병합요법으로 1주간, 제II군은 같은 약제로 2주간 치료하였다. 치료 종료 4주 후에 4시간 이상 금식 후에 100 mg $^{13}C$-요소분말을 사용한 $^{13}C$-요소 호기 검사(IR300, OTSUKA electronics, Osaka, Japan)를 시행하여 음성인 경우 박멸이 성공한 것으로 하였고 요소 호기 검사에서 양성인 경우에는 같은 약제 또는 bismuth, metronidazole과 amoxicillin으로 추가 치료를 하였다. 결 과: H. pylori 양성 환아의 내시경 소견은 결절성 위염이 26명(43.3%)으로 가장 많았고 미란성 위염 10명(16.7%), 출혈성 위염 7명(11.7%), 위궤양 2명(3.3%), 정상 소견 15명(25.0%)이었다. Omeprazole, amoxicillin, clarithromycin (OAC) 삼제요법으로 1주간 치료한 제I군에서 치료 종료 4주 후 시행한 $^{13}C$-요소 호기 검사에서 30명 중 26명(86.7%)에서 음성 반응을, 4명(13.7%)에서 양성 반응을 보였다. 2주간 치료한 제II군에서도 치료 종료 4주 후 시행한 $^{13}C$-요소 호기 검사에서 30명 중 26명(86.7%)에서 음성 반응을, 4명(13.7%)에서 양성 반응을 보였다. 두 군 모두에서 H. pylori 박멸률은 86.7%였으며 두 군 사이에서 통계적으로 유의한 차이는 없었다. H. pylori 제균에 실패한 경우 제 I군에서 $^{13}C$-요소 호기 검사에서 양성 반응을 보인 4명의 환아를 bismuth, amoxicillin, metronidazole로 1주간 추가 치료를 하였고 4주 후 시행한 $^{13}C$-요소 호기 검사에서 모두 음성 반응을 보였다. 제II군에서 $^{13}C$-요소 호기 검사에서 양성 반응을 보인 4명의 환아 중 1명은 같은 약제로, 3명은 bismuth, amoxicillin, metronidazole로 1주간 추가 치료를 하였고 4주 후 시행한 $^{13}C$-요소호기 검사에서 모두 음성 반응을 보였다. $^{13}C$-요소호기검사에서 음성 반응을 보인 모든 환아에서 임상 증상은 완전히 소실되거나 호전되었다. 결 론: 소아에서 급성 및 만성 복통, 위장관 출혈과 H. pylori 감염간의 연관관계에 대하여는 논 란이 많으나 H. pylori 감염이 원인이 될 수 있으며 균 박멸을 위한 치료가 필요하다고 생각한다. 저자들의 연구에서 상부 위장관 증세를 가진 H. pylori 감염 환아에 대한 내시경 소견은 결절성 위염이 43.3%로 가장 많이 관찰되었으며 이것은 다른 연구들에서와 마차가지로 H. pylori 양성 환아들의 특징적인 소견으로 생각된다. 소아 H. pylori 감염의 치료에 있어서 omeprazole, amoxicillin, clarithromycin의 삼제 병합 요법의 1주간 치료와 2주간 치료 결과를 비교한 결과, 박멸률은 두 군 모두 86.7%로 두 군 간의 유의한 차이는 없었으며 이것은 성인에서의 85~95%와 유사하였다. 저자들의 연구에서는 omeprazole, amoxicillin, clarithromycin의 1주 치료가 박멸율, 순응도 및 비용면에서 일차 치료로 바람직하리라 생각된다. 향후 H. pylori 감염의 적절한 치료 방법 및 치료 기간에 대한 좀 더 체계적인 연구가 필요할 것이다.