Browsing by Subject "Stomach"

Now showing 1 - 6 of 6
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    Gastrokine-1, an anti-amyloidogenic protein secreted by the stomach, regulates diet-induced obesity
    (Springer Nature, 2021-05-04) Overstreet, Anne-Marie C.; Grayson, Bernadette E.; Boger, Antonia; Bakke, Danika; Carmody, Erin M.; Bales, Cayla E.; Paski, Shirley C.; Murphy, Stephen F.; Dethlefs, Christopher R.; Shannon, Kara J.; Adlaka, Katie R.; Wolford, Claire E.; Campiti, Vincent J.; Raghunandan, Christina V.; Seeley, Randy J.; Boone, David L.; Microbiology and Immunology, School of Medicine
    Obesity and its sequelae have a major impact on human health. The stomach contributes to obesity in ways that extend beyond its role in digestion, including through effects on the microbiome. Gastrokine-1 (GKN1) is an anti-amyloidogenic protein abundantly and specifically secreted into the stomach lumen. We examined whether GKN1 plays a role in the development of obesity and regulation of the gut microbiome. Gkn1−/− mice were resistant to diet-induced obesity and hepatic steatosis (high fat diet (HFD) fat mass (g) = 10.4 ± 3.0 (WT) versus 2.9 ± 2.3 (Gkn1−/−) p < 0.005; HFD liver mass (g) = 1.3 ± 0.11 (WT) versus 1.1 ± 0.07 (Gkn1−/−) p < 0.05). Gkn1−/− mice also exhibited increased expression of the lipid-regulating hormone ANGPTL4 in the small bowel. The microbiome of Gkn1−/− mice exhibited reduced populations of microbes implicated in obesity, namely Firmicutes of the class Erysipelotrichia. Altered metabolism consistent with use of fat as an energy source was evident in Gkn1−/− mice during the sleep period. GKN1 may contribute to the effects of the stomach on the microbiome and obesity. Inhibition of GKN1 may be a means to prevent obesity.
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    Global microRNA expression is essential for murine mast cell development in vivo
    (Elsevier, 2014-10) Oh, Sun Young; Brandal, Stephanie; Kapur, Reuben; Zhu, Zhou; Takemoto, Clifford; Department of Pediatrics, IU School of Medicine
    MicroRNAs (miRNAs) are small, noncoding RNAs that have been shown to play a critical role in normal physiology and disease, such as hematopoietic development and cancer. However, their role in mast-cell function and development is poorly understood. The major objective of this study was to determine how global miRNA expression affects mast-cell physiology. The RNase III endonuclease, Dicer, is required for the processing of pre-miRNAs into mature miRNAs. To investigate the effect of global miRNA depletion on mast cells in vivo, we generated a mast-cell-specific knock out of Dicer in mice. Transgenic mice (Mcpt5-Cre) that express Cre selectively in connective tissue mast cells were crossed with mice carrying the floxed conditional Dicer allele (Dicer fl/fl). Mcpt5-Cre × Dicer fl/fl mice with homozygous Dicer gene deletion in mast cells were found to have a profound mast-cell deficiency with near complete loss of peritoneal, gastrointestinal, and skin mast cells. We examined the in vivo functional consequence of mast-cell-specific Dicer deletion using an immunoglobulin-E-dependent passive systemic anaphylaxis murine model. Immunoglobulin-E-sensitized wild type Mcpt5-Cre × Dicer +/+ and heterozygous Mcpt5-Cre × Dicer fl/+ mice show marked hypothermia with antigen; however, homozygous Mcpt5-Cre × Dicer fl/fl mice were completely unresponsive to antigen challenge. These studies suggest a critical role for Dicer and miRNA expression for establishment of tissue compartments of functional mast cells in vivo
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    Intragastric botulinum toxin injection: Is it the solution to all gastric ailments?
    (Wolters Kluwer, 2022) AlLehibi, Abed H.; Al-Haddad, Mohammad; Medicine, School of Medicine
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    Mucosal Microbiota Associated With Eosinophilic Esophagitis and Eosinophilic Gastritis
    (Wiley, 2023) Furuta, Glenn T.; Fillon, Sophie A.; Williamson, Kayla M.; Robertson, Charles E.; Stevens, Mark J.; Aceves, Seema S.; Arva, Nicoleta C.; Chehade, Mirna; Collins, Margaret H.; Davis, Carla M.; Dellon, Evan S.; Falk, Gary W.; Gonsalves, Nirmala; Gupta, Sandeep K.; Hirano, Ikuo; Khoury, Paneez; Leung, John; Martin, Lisa J.; Menard-Katcher, Paul; Mukkada, Vincent A.; Peterson, Kathryn; Spergel, Jonathan M.; Wechsler, Joshua B.; Yang, Guang-Yu; Rothenberg, Marc E.; Harris, J. Kirk; Pediatrics, School of Medicine
    Objective: The aim of the study was to determine the mucosal microbiota associated with eosinophilic esophagitis (EoE) and eosinophilic gastritis (EoG) in a geographically diverse cohort of patients compared to controls. Methods: We conducted a prospective study of individuals with eosinophilic gastrointestinal disease (EGID) in the Consortium of Eosinophilic Gastrointestinal Disease Researchers, including pediatric and adult tertiary care centers. Eligible individuals had clinical data, mucosal biopsies, and stool collected. Total bacterial load was determined from mucosal biopsy samples by quantitative polymerase chain reaction (PCR). Community composition was determined by small subunit rRNA gene amplicons. Results: One hundred thirty-nine mucosal biopsies were evaluated corresponding to 93 EoE, 17 EoG, and 29 control specimens (18 esophageal) from 10 sites across the United States. Dominant community members across disease activity differed significantly. When comparing EoE and EoG with controls, the dominant taxa in individuals with EGIDs was increased ( Streptococcus in esophagus; Prevotella in stomach). Specific taxa were associated with active disease for both EoE ( Streptococcus , Gemella ) and EoG ( Leptotrichia ), although highly individualized communities likely impacted statistical testing. Alpha diversity metrics were similar across groups, but with high variability among individuals. Stool analyses did not correlate with bacterial communities found in mucosal biopsy samples and was similar in patients and controls. Conclusions: Dominant community members ( Streptococcus for EoE, Prevotella for EoG) were different in the mucosal biopsies but not stool of individuals with EGIDs compared to controls; taxa associated with EGIDs were highly variable across individuals. Further study is needed to determine if therapeutic interventions contribute to the observed community differences.
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    Primary lung sarcoma with gastric metastasis and morphological divergence presenting as melena
    (BMJ, 2021-08-12) Eiswerth, Michael J.; Pinter, Alexander; Reynolds, Samuel Benjamin; Guardiola, John; Medicine, School of Medicine
    A 61-year-old man was admitted to the medical intensive care unit following a 2-week history of weakness, lightheadedness and melena resulting in an acute anaemia. Upper endoscopy revealed multiple large gastric masses without evidence of active bleeding. CT of the chest revealed a large right upper lobe mass with bony destruction of the third rib and invasion into the anterior chest wall and mediastinum, as well as a soft-tissue density in the left kidney. Biopsy and histopathological review of both pulmonary and gastric masses revealed two distinct sarcomatous malignancies that, while both from a primary lung source, differed in their morphology. Natural history and behaviour are not well understood in sarcomas due to their rarity, but abdominal metastasis is considered an uncommon event in the progression of the disease. Gastrointestinal bleeding as the presenting symptom of a primary lung sarcoma is an atypical finding with no previously reported cases.
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    Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis
    (Biomed Central, 2019-06-20) Herring, B. Paul; Chen, Meng; Mihaylov, Plamen; Hoggatt, April M.; Gupta, Anita; Nakeeb, Attila; Choi, Jennifer N.; Wo, John M.; Cellular and Integrative Physiology, School of Medicine
    BACKGROUND: Gastric emptying is impaired in patients with gastroparesis whereas it is either unchanged or accelerated in obese individuals. The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in idiopathic gastroparesis and obesity. METHODS: Quantitative real time RT-PCR and whole transcriptome sequencing were used to compare the transcriptomes of lean individuals, obese individuals and either lean or obese individuals with idiopathic gastroparesis. RESULTS: Obesity leads to an increase in mRNAs associated with muscle contractility whereas idiopathic gastroparesis leads to a decrease in mRNAs associated with PDGF BB signaling. Both obesity and idiopathic gastroparesis were also associated with similar alterations in pathways associated with inflammation. CONCLUSIONS: Our findings show that obesity and idiopathic gastroparesis result in overlapping but distinct changes in the gastric muscularis transcriptome. Increased expression of mRNAs encoding smooth muscle contractile proteins may be contributing to the increased gastric motility observed in obese subjects, whereas decreased PDGF BB signaling may be contributing to the impaired motility seen in subjects with idiopathic gastroparesis.