26 research outputs found

    The Helicobacter pylori Genome Project : insights into H. pylori population structure from analysis of a worldwide collection of complete genomes

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    Helicobacter pylori, a dominant member of the gastric microbiota, shares co-evolutionary history with humans. This has led to the development of genetically distinct H. pylori subpopulations associated with the geographic origin of the host and with differential gastric disease risk. Here, we provide insights into H. pylori population structure as a part of the Helicobacter pylori Genome Project (HpGP), a multi-disciplinary initiative aimed at elucidating H. pylori pathogenesis and identifying new therapeutic targets. We collected 1011 well-characterized clinical strains from 50 countries and generated high-quality genome sequences. We analysed core genome diversity and population structure of the HpGP dataset and 255 worldwide reference genomes to outline the ancestral contribution to Eurasian, African, and American populations. We found evidence of substantial contribution of population hpNorthAsia and subpopulation hspUral in Northern European H. pylori. The genomes of H. pylori isolated from northern and southern Indigenous Americans differed in that bacteria isolated in northern Indigenous communities were more similar to North Asian H. pylori while the southern had higher relatedness to hpEastAsia. Notably, we also found a highly clonal yet geographically dispersed North American subpopulation, which is negative for the cag pathogenicity island, and present in 7% of sequenced US genomes. We expect the HpGP dataset and the corresponding strains to become a major asset for H. pylori genomics

    The impact of trastuzumab on radiation-induced pulmonary fibrosis: results of an experimental study

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    There are no data regarding the late toxicity of trastuzumab (T) administration with radiotherapy (RT). In this experimental study, we aimed to asses if concurrent or sequential administration of T has any impact for the development of radiation-induced pulmonary fibrosis in rats. Fifty-four female Wistar-albino rats were divided into 6 groups. First group of rats (Group 1; concurrent T) had irradiation to whole thoracic region concurrently with T. Second group (Group 2: sequential T-RT) received thoracic irradiation, 1 week after T. Third group (Group 3: sequential RT-T) had thoracic irradiation first and they had T injection 1 week after RT. Fourth group (Group 4: T only) had only T application. Fifth group (Group 5: RT) had only RT. The last group (Group 6: sham) of rats were observed without any application. A single dose of 12 Gy was given to both lungs with an anterior field at 2 cm depth. T dose which was equivalent to 6 mg/kg adult dose was calculated for each rat, and injected by the tail vein. As an end point the extent of pulmonary fibrosis for each field was graded on a scale from 0 (normal lung or minimal fibrous thickening) to 4 (total fibrous obliteration of the field) at histopathological examination. The mean value of fibrosis scores were 1.44, 1.77, 1.75 and 1.62 for Group 1, 2, 3 and 5, respectively, without any statistically significant differences among them (P > 0.05). The mean value of fibrosis scores for Group 4 and 6 were 0.25 and 0.33, respectively (P > 0.05). When the mean value of fibrosis scores of the groups which had RT with or without T, compared with the observation and the T only groups, the difference was significant (P < 0.05) (one-way ANOVA and Tukey HSD post hoc tests) As a conclusion: addition of T to thoracic irradiation either sequentially or concomitantly did not increase radiation-induced pulmonary fibrosis in rats
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