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Volume 122, Issue 1, Pages (January 2002)

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Presentation on theme: "Volume 122, Issue 1, Pages (January 2002)"— Presentation transcript:

1 Volume 122, Issue 1, Pages 119-133 (January 2002)
Genetic or chemical hypochlorhydria is associated with inflammation that modulates parietal and G-cell populations in mice  Yana Zavros, Gabriele Rieder, Amy Ferguson, Linda C. Samuelson, Juanita L. Merchant  Gastroenterology  Volume 122, Issue 1, Pages (January 2002) DOI: /gast Copyright © 2002 American Gastroenterological Association Terms and Conditions

2 Fig. 1 Representative H&E and PAS/alcian blue stains from mouse stomachs. Representative H&E-stained sections of inflamed stomach from a 16-week-old (A) G+/+ and (B) G−/− mouse with severe inflammation (arrow) and (C) metaplasia (open arrow), (D) neutral (red arrowhead) and acid (black arrowhead) mucins were detected by using PAS/alcian blue in G−/− mice. Magnification: (A-C) 400×; (D) 600×. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

3 Fig. 2 Analysis of T and B lymphocytes by flow cytometry. The light scatter analysis and histograms showing the distribution of CD45-, CD3-, or CD19-positive cells and the percentage of gated cells in (A) G+/+ and (B) G−/− mouse gastric mucosa. The gated CD45 population is in panel 1 (circled) and the gated CD3 and CD19 populations are in panel 4 (circled) of the light scatter analyses. (C) T and B lymphocytes isolated from stomachs of G+/+ (2), G+/+ with antibiotics (▩), G−/− (■), and G−/− mice treated with antibiotics (▨) were analyzed by flow cytometry and expressed as the number of T and B lymphocytes in the gastric mucosa per mouse (CD3+ or CD19+). *P ≤ 0.05 versus G+/+ mice, n = 10 for G+/+ group, and n = 12 for G−/− group. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

4 Fig. 3 Histologic evaluation of G+/+ and G−/− mice treated with antibiotics. (A) Normal histology of G+/+ mouse untreated (panel a); G+/+ mouse plus antibiotics (panel b); G−/− untreated (panel c); G−/− treated with antibiotics (panel d). Resolution of inflammation in G−/− mice after antibiotic treatment. (B) Histologic grades according to the grading system for gastritis in mice. ● Represent the score for each mouse and—is the mean from the 12 mice analyzed. n = 10 for G+/+ group, n = 12 for G−/− group. *P < 0.05 compared with G+/+ without antibiotics. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

5 Fig. 4 Distribution of parietal cells and BrdU labeling in G+/+ and G−/− mice. Fundic distribution of H+,K+-ATPase positive cells in (A) G+/+ and (B) G−/− mice. BrdU incorporation in the fundus of (C) G+/+ and (D) G−/− mice. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

6 Fig. 5 Quantification of parietal cells by morphometric and flow cytometry. (A) The number of parietal cells/gland in both G+/+ (2), G+/+ mice treated with antibiotics (▩), G−/− (■), and G−/− mice treated with antibiotics (▨) were counted. (B) The percent of H+,K+-ATPaseNpositive cells per cytokeratin-18–positive cells was determined by flow cytometry and is shown for the G+/+ (2), G+/+ with antibiotics (▩), G−/− (■), and G−/− mice treated with antibiotics (▩). *P < 0.05 versus G+/+ mice, n = 10 for G+/+ group, n = 12 for G−/− group, number in parentheses = fold change relative to G+/+ mice. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

7 Fig. 6 Distribution of G cells and BrdU labeling in G+/+ and G−/− mice. Antral distribution of GRPr positive cells in (A) G+/+ and (B) G−/− mice. BrdU positive staining in the fundus of (C) G+/+ and (D) G−/− mice. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

8 Fig. 7 Quantification of G cells by morphometry and flow cytometry. (A) The number of G cells/gland in both G+/+ (2), G+/+ with antibiotics (▩), G−/− (■), and G−/− mice treated with antibiotics (▨) were counted. (B) The percent of G cells detected by fluorescently tagged bombesin per cytokeratin-18–positive cells was quantified by flow cytometry in G+/+ untreated mice (2), G+/+ mice treated with antibiotics (▩), G−/− mice untreated (■), and G−/− mice plus antibiotics (▨). *P < 0.05 versus G+/+ mice, n = 10 for G+/+ group, n = 12 for G−/− group. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

9 Fig. 8 Bacterial counts from stomachs of G+/+ and G−/− mice treated with antibiotics. (A) Fundus and (B) antrum. The number of CFU/g tissue is plotted on a log scale. Aerobic cultures (■), facultative cultures (▵), anaerobic cultures (●). Each point represents the culture results from a single animal. *P ≤ 0.05 versus untreated mice, #P ≤ 0.05 versus G+/+ untreated mice. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

10 Fig. 9 Representative H&E stains from G+/+ mice treated with omeprazole followed by antibiotic therapy. Representative normal H&E stains of (A) vehicle and (B) vehicle plus antibiotic-treated mouse stomachs. (C) Inflamed mouse stomach after 2 months of omeprazole treatment (arrow indicates inflammation), and (D) resolved inflammation in omeprazole-treated mice on antibiotics. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

11 Fig. 10 Quantification of neuroendocrine and epithelial cells in response to omeprazole treatment in G+/+ animals. The percent of (A) fundic H+,K+-ATPase and (B) antral bombesin-Cy3Npositive cells per cytokeratin-18–positive cells were quantified by flow cytometry, number in parentheses indicates fold change relative to vehicle-treated mice. 2, vehicle alone; ▩, vehicle plus antibiotics; ■, omeprazole alone; ▨, omeprazole plus antibiotics. *P < 0.05 compared with vehicle-treated mice, n = 8. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

12 Fig. 11 Bacterial counts from the stomachs of omeprazole-treated mice. (A) Fundus and (B) antrum of G+/+ mice treated with vehicle, vehicle plus antibiotics, omeprazole, or omeprazole plus antibiotics. The number of CFU/g tissue is plotted on a log scale. ■, Aerobic cultures; ▵, facultative cultures; ●, anaerobic cultures. Each point represents the result from a single animal. *P ≤ 0.05 compared with animals not treated with antibiotics, #P ≤ 0.05 compared with G+/+ vehicle-treated mice. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions

13 Fig. 12 A model proposed for the regulation of parietal and G cells in the hypochlorhydric stomach during inflammation and bacterial overgrowth. Colonization of the gastric mucosa by increased numbers of active bacteria trigger the recruitment of inflammatory cells and the release of cytokines and growth factors that in turn stimulate expansion of both the G and parietal cell compartments. Hypergastrinemia results, thus, increasing acid secretion presumably to promote the clearance of bacteria. Gastroenterology  , DOI: ( /gast ) Copyright © 2002 American Gastroenterological Association Terms and Conditions


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