scholarly journals Epithelial expression of Gata4 and Sox2 regulates specification of the squamous–columnar junction via MAPK/ERK signaling in mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nao Sankoda ◽  
Wataru Tanabe ◽  
Akito Tanaka ◽  
Hirofumi Shibata ◽  
Knut Woltjen ◽  
...  
Keyword(s):  
Precancerous Lesions ◽  
Lineage Tracing ◽  
Mouse Genetics ◽  
Erk Signaling ◽  
Columnar Epithelium ◽  
Transitional Epithelium ◽  
Proximal Stomach ◽  
Distal Stomach ◽  
Organoid Culture ◽  
Physiological Properties

AbstractThe squamous–columnar junction (SCJ) is a boundary consisting of precisely positioned transitional epithelium between the squamous and columnar epithelium. Transitional epithelium is a hotspot for precancerous lesions, and is therefore clinically important; however, the origins and physiological properties of transitional epithelium have not been fully elucidated. Here, by using mouse genetics, lineage tracing, and organoid culture, we examine the development of the SCJ in the mouse stomach, and thus define the unique features of transitional epithelium. We find that two transcription factors, encoded by Sox2 and Gata4, specify primitive transitional epithelium into squamous and columnar epithelium. The proximal–distal segregation of Sox2 and Gata4 expression establishes the boundary of the unspecified transitional epithelium between committed squamous and columnar epithelium. Mechanistically, Gata4-mediated expression of the morphogen Fgf10 in the distal stomach and Sox2-mediated Fgfr2 expression in the proximal stomach induce the intermediate regional activation of MAPK/ERK, which prevents the differentiation of transitional epithelial cells within the SCJ boundary. Our results have implications for tissue regeneration and tumorigenesis, which are related to the SCJ.

Role of prostaglandins in regulating gastric motility

1984 ◽  
Vol 247 (2) ◽  
pp. G117-G126 ◽  
Author(s):  
K. M. Sanders
Keyword(s):  
Gastric Emptying ◽  
Gastric Motility ◽  
Motor Performance ◽  
Tonic Contraction ◽  
Frequency Effect ◽  
Dominant Effect ◽  
Proximal Stomach ◽  
Distal Stomach ◽  
Endogenous Prostaglandins

Muscles of the stomach possess the ability to synthesize several prostaglandins. These compounds function as local regulatory agents by influencing the motor performance of the muscle cells. In the distal stomach the dominant effect of endogenous prostaglandins is to decrease the amplitude of contractions and decrease the ability of the muscles to respond to excitatory stimuli. Prostaglandins also have a chronotropic role in the distal stomach, and they are responsible for the frequency effect of gastrin pentapeptide. In the proximal stomach prostaglandins have an opposite role; they promote tonic contraction. Because of the diverse effects of prostaglandins, they probably have complicated effects on gastric motility. In general, emptying of solids should be retarded by endogenous prostaglandins, whereas emptying of fluids may be facilitated by these compounds. Overproduction of prostaglandins may produce abnormal motility patterns and affect gastric emptying. A case of gastric pseudoobstruction apparently involving prostaglandins is discussed.

PS01.076: LAPAROSCOPIC REMOVAL OF A SLIPPED ANGELCHIK ANTIREFLUX PROSTHESIS

2018 ◽  
Vol 31 (Supplement_1) ◽  
pp. 70-71
Author(s):  
Takahiro Masuda ◽  
Sumeet Mittal
Keyword(s):  
Gastric Bypass ◽  
Conflicts Of Interest ◽  
Gastroesophageal Junction ◽  
Gastric Pouch ◽  
Acid Reflux ◽  
Barium Swallow ◽  
Upper Gastrointestinal Endoscopy ◽  
Proximal Stomach ◽  
Distal Stomach ◽  
Laparoscopic Removal

Abstract Background The Angelchik prosthesis is c-shaped silicone ring designed to prevent acid reflux. The device, which is fitted around the gastroesophageal junction, was popular in 1980s and over 25,000 devices were placed in patients worldwide. However, follow-up showed a high frequency of undesirable results, including device migration and esophageal erosion. The use of this device was therefore abandoned in the early 1990s. Methods A 70-year-old man with a body mass index of 36 kg/m2 presented to us with persistent dysphagia and progressively increasing heartburn. He had undergone placement of an Angelchik prosthesis 37 years earlier. He said that he had experienced dysphagia since it was implanted, but had accepted it. His past medical history included hypertension, hyperlipidemia, sleep apnea, atrial fibrillation, cerebrovascular accident, and benign prostatic hypertrophy. Upper gastrointestinal endoscopy, contrast esophagram, and high-resolution manometry showed a slipped Angelchik device on the stomach with moderately impaired esophageal body motility. Results The patient underwent laparoscopic removal of the Angelchik prosthesis, followed by a Roux-en-Y gastric bypass for antireflux. After laparoscopic access, adhesions from previous laparotomy were taken down and standard laparoscopic foregut surgery ports were placed. A fibrous calcified capsule encircling the Angelchik prosthesis was noted around the proximal stomach. The anterior wall of the capsule was peeled off using a Harmonic scalpel, and the Angelchik prosthesis was removed in one piece. Given the patient's esophageal dysmotility and scarring around the fundus, we proceeded with Roux-en-Y gastric bypass. The alimentary and biliary limbs were tailored to 80 cm and 30 cm in length, respectively. Using linear staplers, the gastric pouch was created by dividing the proximal stomach just below the level of the scarred tissue created by the Angelchik device. The distal stomach was left in situ. The operation lasted 160 minutes, and the intraoperative blood loss was 150 mL. Barium swallow on postoperative day 1 showed no leakage, and a liquid diet was initiated. The patient was discharged on postoperative day 2. The patient now reports resolved dysphagia and reflux. Conclusion Laparoscopic removal of the Angelchik prosthesis and Roux-en-Y gastric bypass was performed safely with good outcomes. Disclosure All authors have declared no conflicts of interest.

scholarly journals Fbxw7 is a driver of uterine carcinosarcoma by promoting epithelial-mesenchymal transition

2019 ◽  
Vol 116 (51) ◽  
pp. 25880-25890 ◽  
Author(s):  
Ileana C. Cuevas ◽  
Subhransu S. Sahoo ◽  
Ashwani Kumar ◽  
He Zhang ◽  
Jill Westcott ◽  
...  
Keyword(s):  
Endometrial Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Genetic Model ◽  
Precancerous Lesions ◽  
Lineage Tracing ◽  
Model Systems ◽  
Cancer Type ◽  
Cell Of Origin ◽  
Uterine Carcinosarcoma ◽  
Mesenchymal Transition

Uterine carcinosarcoma is an aggressive variant of endometrial carcinoma characterized by unusual histologic features including discrete malignant epithelial and mesenchymal components (carcinoma and sarcoma). Recent studies have confirmed a monoclonal origin, and comprehensive genomic characterizations have identified mutations such asTp53andPten. However, the biological origins and specific combination of driver events underpinning uterine carcinosarcoma have remained mysterious. Here, we explored the role of the tumor suppressorFbxw7in endometrial cancer through defined genetic model systems. Inactivation ofFbxw7andPtenresulted in the formation of precancerous lesions (endometrioid intraepithelial neoplasia) and well-differentiated endometrioid adenocarcinomas. Surprisingly, all adenocarcinomas eventually developed into definitive uterine carcinosarcomas with carcinomatous and sarcomatous elements including heterologous differentiation, yielding a faithful genetically engineered model of this cancer type. Genomic analysis showed that most tumors spontaneously acquiredTrp53mutations, pointing to a triad of pathways (p53, PI3K, and Fbxw7) as the critical combination underpinning uterine carcinosarcoma, and to Fbxw7 as a key driver of this enigmatic endometrial cancer type. Lineage tracing provided formal genetic proof that the uterine carcinosarcoma cell of origin is an endometrial epithelial cell that subsequently undergoes a prominent epithelial–mesenchymal transition underlying the attainment of a highly invasive phenotype specifically driven by Fbxw7.

Water stimulation of the posterior oral cavity induces inhibition of gastric motility

2000 ◽  
Vol 279 (3) ◽  
pp. R778-R785 ◽  
Author(s):  
Motoi Kobashi ◽  
Masatoshi Mizutani ◽  
Ryuji Matsuo
Keyword(s):  
Gastric Motility ◽  
Superior Laryngeal Nerve ◽  
Sodium Concentration ◽  
Inhibitory Response ◽  
Afferent Neurons ◽  
Proximal Stomach ◽  
Distal Stomach ◽  
Efferent Nerve ◽  
Vagal Efferent Nerve ◽  
Stimulation Of

The response of gastric motility to the administration of water and saline in the larynx and epiglottis was investigated in urethan-chloralose anesthetized rats. Administration of water inhibited motility of the distal stomach, but 0.15 M NaCl did not induce the inhibitory response. Bilateral sectioning of the superior laryngeal nerve (SLN) abolished the inhibitory response induced by water. Bilateral cervical vagotomies abolished the inhibitory responses, although spinal transection did not affect the inhibitory response. These inhibitory responses have been observed in immobilized animals. The degree of inhibition by water and hypotonic saline was negatively correlated with the sodium concentration. In contrast, the degree of inhibition to hypertonic saline was positively correlated with the sodium concentration. The proximal stomach also showed a reduction in intragastric pressure in response to the administration of water. These findings suggest that water-responsive afferent neurons in the SLN suppress gastric motility via the vagal efferent nerve.

Mo1555 Small Carcinomas in the Proximal Stomach Show Clinicopathologic Features Dissimilar to Those in the Distal Stomach

2012 ◽  
Vol 142 (5) ◽  
pp. S-627 ◽  
Author(s):  
Qin Huang ◽  
Jason S. Gold ◽  
Qi Sun ◽  
Hongyan Wu ◽  
Hiroshi Mashimo ◽  
...  
Keyword(s):  
Clinicopathologic Features ◽  
Proximal Stomach ◽  
Distal Stomach

scholarly journals Dorso-ventral heterogeneity in tracheal basal stem cells

Biology Open ◽  
2021 ◽  
Author(s):  
Tomomi Tadokoro ◽  
Keisuke Tanaka ◽  
Shun Osakabe ◽  
Mimoko Kato ◽  
Hisato Kobayashi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Gene Ontology ◽  
Smooth Muscle ◽  
Three Dimensional ◽  
Lineage Tracing ◽  
Basal Cells ◽  
Gene Ontology Analysis ◽  
Organoid Culture

The tracheal basal cells (BCs) function as stem cells to maintain the epithelium in steady state and repair it after injury. The airway is surrounded by cartilage ventrolaterally and smooth muscle dorsally. Lineage tracing using Krt5-CreER shows dorsal BCs produce more, larger, clones than ventral BCs. Large clones were found between cartilage and smooth muscle where subpopulation of dorsal BCs exists. Three-dimensional organoid culture of BCs demonstrated that dorsal BCs show higher colony forming efficacy to ventral BCs. Gene ontology analysis revealed that genes expressed in dorsal BCs are enriched in wound healing while ventral BCs are enriched in response to external stimulus and immune response. Significantly, ventral BCs express Myostatin, which inhibits the growth of smooth muscle cells, and HGF, which facilitates cartilage repair. The results support the hypothesis that BCs from the dorso-ventral airways have intrinsic molecular and behavioural differences relevant to their in vivo function.

Organization of fasting and postprandial myoelectric activity in stomach and duodenum of conscious dogs

1985 ◽  
Vol 249 (6) ◽  
pp. G655-G661 ◽  
Author(s):  
R. C. Gill ◽  
M. A. Pilot ◽  
P. A. Thomas ◽  
D. L. Wingate
Keyword(s):  
Phase Locking ◽  
Oral Feeding ◽  
Slow Waves ◽  
Conscious Dogs ◽  
Necessary Condition ◽  
Myoelectric Activity ◽  
Periodic Activity ◽  
Proximal Stomach ◽  
Distal Stomach ◽  
Spike Bursts

In conscious dogs, contractile and myoelectric activity was recorded from force transducers and monopolar electrodes chronically implanted in the serosal surface of the proximal and distal stomach. Periodic activity during fasting was characterized at each site. Proximally, activity fronts consisted of a series of regular large-amplitude contractions, without correlated myoelectric changes, occurring at 50-s intervals. The distal activity front comprised a series of bursts of two to three contractions 11 s apart, with each burst in phase with a proximal contraction. Only during the burst sequence was each electrical slow wave associated with a spike burst (1:1 phase locking). In contrast, 1:1 phase locking characterized the electrical correlates of the duodenal activity front. Oral feeding abolished periodic activity for at least 3 h. Postprandially, the proximal stomach remained electrically silent; in the duodenum spike bursts were intermittently associated with regular slow waves, but in the distal stomach regular low-amplitude contractions were characterized electrically by 1:1 phase-locked spike bursts and slow waves. These observations suggest that the proximal stomach regulates the canine fasting activity front and require modification of the concept that 1:1 phase locking is a necessary condition of the activity front.

Gastric emptying of liquids and solids: roles of proximal and distal stomach

1980 ◽  
Vol 239 (2) ◽  
pp. G71-G76 ◽  
Author(s):  
K. A. Kelly
Keyword(s):  
Gastric Emptying ◽  
Proximal Stomach ◽  
Distal Stomach

The objective was to explore the hypothesis that the proximal stomach has a major role in gastric emptying of liquids and the distal stomach a major role in gastric emptying of solids. The results of experiments on the intact stomach and on the stomach after selective resections, denervations, and during hormonal infusions are, in general, consistent with the hypothesis.

scholarly journals Endocardium-to-coronary artery differentiation during heart development and regeneration involves sequential roles of Bmp2 and Cxcl12/Cxcr4.

2021 ◽  
Author(s):  
Gaetano D'Amato ◽  
Ragini Phansalkar ◽  
Jeffrey A. Naftaly ◽  
Pamela E Coronado Rios ◽  
Dale O. Cowley ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heart Development ◽  
Molecular Mechanisms ◽  
Lineage Tracing ◽  
Mouse Genetics ◽  
Late Gestation ◽  
Small Subset ◽  
Angiogenic Potential ◽  
Coronary Endothelial Cells

Regenerating coronary blood vessels has the potential to ameliorate ischemic heart disease, yet there is currently no method of stimulating clinically effective cardiac angiogenesisis. Endocardial cells, a particularly plastic cell type during development, line the heart lumen and are natural coronary vessel progenitors. Their intrinsic angiogenic potential is lost in adults, but studying the endocardial-to-coronary developmental pathway could identify methods of re-instating this process in diseased hearts. Here, we use a combination of mouse genetics and scRNAseq of lineage-traced endothelial cells to identify novel regulators of endocardial angiogenesis and precisely assess the role of Cxcl12/Cxcr4 signaling. Time-specific lineage tracing demonstrated that endocardial cells differentiated earlier than previously thought, largely at mid-gestation. A new mouse line reporting the activity of Cxcr4 revealed that, despite widespread Cxcl12 and Cxcr4 expression, only a small subset of these coronary endothelial cells activated the receptor, which were mostly in arteries. In accordance with these two findings, Cxcr4 deletion in the endocardial lineage only affected artery formation and only when deleted before mid-gestation. Integrating scRNAseq data of coronary endothelial cells from the endocardial lineage at both mid- and late-gestation identified a transitioning population that was specific to the earlier timepoint that specifically expressed Bmp2. Recombinant Bmp2 stimulated endocardial angiogenesis in an in vitro explant assay and in neonatal mouse hearts upon myocardial infarction. Our data shed light on how understanding the molecular mechanisms underlying endocardial-to-coronary transitions can identify new potential therapeutic targets that could promote revascularization of the injured heart.

p53 and its influence in adenocarcinoma stomach

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15685-e15685
Author(s):  
C. M. Servarayan ◽  
A. Chandramohan ◽  
D. Datta ◽  
K. Manickavasagam
Keyword(s):  
Gastric Adenocarcinoma ◽  
Immunohistochemical Method ◽  
Proximal Stomach ◽  
Distal Stomach ◽  
Tissue Samples ◽  
P53 Expression ◽  
Study Results ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
P53 Immunoreactivity

e15685 Background: Gastric cancer is the second most common cause of the malignancy in the world after lung cancer. Various pathogenesis have been given for the adenocarcinoma, like mutation in the E-catherin gene, amplification of COX-2, HGF/ SF, VEGF; deletion of FHIT, APC, p53 but none have provided a definite target for treatment. Methods: This is a immunohistochemical prospective experiment study done on 76 cases of Gastric Adenocarcinoma.The location of the tumors were recorded as in the proximal stomach (fundus and body) and distal stomach (antrum, prepylorus, and pylorus). PAb1801 clonewas obtained from the ZYMED LABORATRIES, San Franscisco. A standardised immunohistochemical method was followed in this study. Results: p53 mutations were seen 41 out of 76 cases(53.95%). And 23 out of 41(56.09%) cases of p53 expression of the total mutated cases expressed p53 100%. 20 out of 36 cases (55.55%) of age below 60 yrs and 21 out of 40 cases (52.55%) of age above 60 yrs were p53 positive. 33 out of 60 (55%)of the males and 8 out of 16 (50%) females were reported of having gastric adenocarcinoma with p53expression. The histology of the tissue samples from the gastric adenocarcinoma patients had following relationship with the p53 immunoreactivity, 20 out of 37 cases(54.05%) of the well differentiated,7 out of 17 cases (41.18% )of the moderately differentiated, and and 13 out of 21 cases(61.90%) of the poorly differentiated gastric adenocarcinoma showed positive immunoreactivity. 15 out of 33 cases (45.45%)were localized to the proximal stomach and 30 out of 52 cases (57.69%)were localized to the distal stomach. 52.63 % of the non-mucinous type of gastric adenocarcinoma showed positive p53 immunoreactivity. Conclusions: The TP53 mutation is slightly more common in males than females, with greater occurrence in the late years of life. The mutation is more marked in the poorly differentiated gastric adenocarcinoma. The antral, pylorus,and the prepyloric parts of the stomach( the distal stomach) are more prone for mutated p53 induced adenocarcinoma. No significant financial relationships to disclose.

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