Helicobacter pylori infects more than half of the world's population, and is known to be involved in several diseases including gastric cancer. Its close interactions with the stomach and host immune system serves as a good model to study the co-adaptation and co-evolution of the organisms in the stomach micro-environment. In this project, we utilized RNA-seq and data analysis tools to investigate differentially expressed genes by H. pylori in patients at different stages of early gastric cancer development. We also investigated the abundance and diversity of bacterial genera other than H. pylori, and looked for correlations with H. pylori presence and number. For differential gene expression of H. pylori, one gene was differentially expressed between samples of corpus atrophy without metaplasia vs. samples of antrum gastritis, and eight genes were found to be differentially expressed between samples of corpus atrophy with metaplasia vs. samples with pan-gastritis. When samples were clustered into different groups based on the expression data, 52 genes (shared or unique to the specific comparison groups) were found to be differentially expressed, but no apparent patterns were observed that could be explained by medical or sample collection data. For bacterial diversity and abundances, we found several genera colonizing the stomach, of which some have been previously identified. While most of these bacteria colonize regardless of the presence of H. pylori, the abundance of three genera, Wolinella, Campylobacter, and Veillonella, seem to be correlated with the presence of H. pylori.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Despite earlier indirect evidence that an antral chalone exists, no such inhibitor has been found in antral extract. Recently, interest in the question of an antral inhibitory mechanism has been revived by studies that showed that for a given rise in serum gastrin caused by antral distension, the response of both the innervated and denervated stomach is greatly enhanced by vagal denervation of the antrum. While this study suggested a neuro-humoral character of the antral inhibitory mechanism, it gave no indication as to the source of the inhibitor. Subsequent studies, however, suggested that neither the antrum nor the CNS was the source for this inhibitor. The initial aim of this study was to investigate the fundus as a possible source of the inhibitor by studying the effect of proximal gastric vagotomy on the antral inhibitory mechanism initiated by distension. The results gave clear indication that the inhibitor was indeed released from the fundus; indeed, the antral inhibitory mechanism was in reality a fundic one. Once the fundus was shown to be the source of the inhibitor, it was necessary to establish whether this inhibitor did in fact reside in the fundic mucosa. Four dogs were prepared with a denervated fundic pouch (or Heidenhain pouch, HP), and a fistula of the main, innervated stomach (gastric fistula, GF). The acid secretory responses of both the HP and GF to graded doses of pentagastrin and histamine was studied. In addition both the secretion of acid and the response of immunoreactive gastrin in the blood in response to a standard meal of 15% liver extract was studied. All these experiments were repeated after excision of the fundic mucosa of the main stomach. The results show that excision of the fundic mucosa reduced the GF acid secretion to the stimuli by 85-100%. By contrast, the maximal HP acid secretion increased by 247% in response to pentagastrin and 200% in response to histamine. The increase in the response to submaximal doses of these exogenous stimuli was even greater. Similarly, the peak 30 minutes HP output in response to feeding increased by 418%. Fundic mucosal excision also resulted in the increase in both basal (from 36±3 to 248±37 pg/ml) and food-stimulated response (from 168±12 preoperatively to 392±49 pg/ml postoperatively). Since the intragastric pH was held constant at 5.5 during the meal tests both before and after the operation, the augmented gastrin response could not be attributed to reduced acid secretion caused by excision of the fundic mucosa. From these studies it can be concluded that: (1) antral distension releases an inhibitor from the fundus; (2) excision of the fundic mucosa results in increased response of the HP to both submaximal and maximal doses of pentagastrin and histamine indicating that both the sensitivity of the oxyntic cell and parietal cell mass has increased; (3) excision of the fundic mucosa results in increased basal and food-stimulated gastrin response independent of the pH of the meal suggesting removal of an inhibitor of gastrin release. / Surgery, Department of / Medicine, Faculty of / Graduate

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21994号 / 医博第4508号 / 新制||医||1037(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 羽賀 博典, 教授 武藤 学, 教授 山下 潤 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Bakgrund: Enligt forskning finns en ökad risk att utveckla alkoholbrukssyndrom efter en gastric bypass operation. Detta har även uppmärksammats inom den beroendemedicinska vården. För att få en ökad förståelse för dessa patienter och kunna utveckla vården behöver patienternas egna upplevelser lyftas. Syfte: Syftet med denna studie är att beskriva hur personer med alkoholbrukssyndrom som genomgått gastric bypass upplever skillnader i sitt alkoholbruk före och efter det kirurgiska ingreppet och deras beskrivning av behov av stöd. Metod: Semistrukturerade intervjuer genomfördes med tio personer som genomgått en gastric bypass-operation och även fått behandling för alkoholbrukssyndrom. En kvalitativ innehållsanalys med manifest inriktning användes. Resultat: I analysen av insamlat intervjumaterial framkom åtta underteman som resulterade i två huvudteman, Operationens påverkan på alkoholkonsumtion och Önskan om förbättrad eftervård. Resultatet visade att det är skillnader för patienter före och efter operation gällande sin alkoholkonsumtion. Det framkom även tydligt att uppföljningar efter operation var bristande. Slutsats: Det beskrivs skillnad i alkoholens effekter efter en genomgången gastric bypass operation, många upplever snabbare berusning av en mindre mängd alkohol som i sin tur ökar suget efter mer. Många upplever att det faller mellan stolarna efter operationen. De få uppföljningar som blir av är inte vad patienterna önskar, de berör ingen del av det psykiska måendet eller den identitetskris denna kroppsliga förändring innebär. Det efterfrågas även ett bättre samarbete mellan olika vårdinstanser som kan bidra med tydligare information, där sjuksköterskan kan identifiera omvårdnadsåtgärder för varje unik patient. / Background: According to research, there is an increased risk of developing alcohol use syndrome after gastric bypass surgery. This has also been noticed in addiction medicine care. To gain an increased understanding of these patients and be able to develop care, the patients' own experiences need to be highlighted. Aim: The purpose of this study is to describe how people with alcohol use syndrome who have undergone gastric bypass experience differences in their alcohol use before and after the surgical intervention and their description of the need for support. Method: Semi-structured interviews were conducted with ten persons who underwent gastric bypass surgery and received treatment for alcohol use syndrome. A qualitative content analysis with manifest orientation was used. Results: In the analysis of collected interview material, eight subthemes emerged that resulted in two main themes, the operation's impact on alcohol consumption and the desire for improved aftercare. The results showed that there are differences for patients before and after surgery regarding their alcohol consumption. It also became clear that follow-ups after surgery were lacking. Conclusion: There is a difference in the effects of alcohol after gastric bypass surgery, several persons experience faster intoxication from a smaller amount of alcohol, which increases the desire for more. Several persons feel neglected after the operation. The few follow-ups that do occur are not what the patients desire, due to the lack of interest regarding the mental state or the identity crisis this bodily change entails. There is also a demand for better collaboration between different care agencies that can contribute with clearer information, where the nurse can identify nursing measures for each unique patient.

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