AIM： TO investigate the effect of interaction between enteric epithelial cells and lymphocytes of Peyer＇s patch on the release of nitric oxide （NO） and IL-6 in response to Shigella lipopolysaccharide （LPS）. METH...AIM： TO investigate the effect of interaction between enteric epithelial cells and lymphocytes of Peyer＇s patch on the release of nitric oxide （NO） and IL-6 in response to Shigella lipopolysaccharide （LPS）. METHODS： Human colonic epithelial cells （Caco-2） were mixed cocultured with lymphocytes of Peyer＇s patch from wild-type （C57 mice） and inducible NO synthase knockout mice, and challenged with Shigella F2a-12 LPS. Release of NO and raiL-6 was measured by Griess colorimetric assay and enzyme-linked immunosorbent assay （ELISA）, respectively. RESULTS： In the absence of LPS challenge, NO was detected in the culture medium of Caco-2 epithelial cells but not in lymphocytes of Peyer＇s patch, and the NO release was further up-regulated in both cocultures with lymphocytes from either the wild-type or iNOS knockout mice, with a significantly higher level observed in the coculture with iNOS knockout lymphocytes. After Shigella F2a-12 LPS challenge for 24-h, NO production was significantly increased in both Caco-2 alone and the coculture with lymphocytes of Peyer＇s patch from the wild-type mice but not from iNOS knockout mice. LPS was found to stimulate the release of mIL-6 from lymphocytes, which was suppressed by coculture with Caco-2 epithelial cells. The LPS-induced mIL-6 production in lymphocytes from iNOS knockout mice was significantly greater than that from the wild-type mice. CONCLUSION： Lymphocytes of Peyer＇s patch maintain a constitutive basal level of NO production from the enteric epithelial cell Caco-2. LPS-induced mIL-6 release from lymphocytes of Peyer＇s patch is suppressed by the cocultured epithelial cells. While no changes are detectable in NO production in lymphocytes from both wild-type and iNOS knockout mice before and after LPS challenge, NO from lymphocytes appears to play an inhibitory role in epithelial NO release and their own mIL-6 release in response to LPS.展开更多
Objective: To research the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha) on the apoptosis and number of T lymphocyte in Peyer’s patches after severe burn on plateau in rats. Methods: Wistar rats (n = 1...Objective: To research the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha) on the apoptosis and number of T lymphocyte in Peyer’s patches after severe burn on plateau in rats. Methods: Wistar rats (n = 130) were subjected to deep thickness burn injury (30% TBSA, III degree), at two different altitudes. 60 of them were given delayed fluid resuscitation (DFR, n = 30 at each altitude) 6 h after burn at different altitude;60 of them were carried out immediate fluid resuscitation (IFR, n = 30 at each altitude);10 rats were subjected to 37°C warm water as sham burn (SG, n = 10). The Peyer’s patches were harvested from the ileum of rats at different time point after burn respectively. The expression of HIF-1 alpha, CD3(+) and the apoptosis and number of T lymphocyte in Peyer’s patches were detected by tissue microarray technology and immunohistochemistry. Results: The apoptosis was higher in DFR group than that in IFR group. The increase in HIF-1 alpha expression was observed mainly on cell nucleus in T lymphocytes. The expression levels of HIF-1 alpha in Peyer’s patches were much higher in DFR group and IFR group than those in SG, and they were higher at high altitude (3848 metres) than those at lower altitude (1517 metres), and also higher in DFR group compared with IFR group (all P < 0.05). The expression levels of CD3<sup>+</sup> in Peyer’s patches were much lower in DFR group and IFR group than those in sham group, and the lowest value appeared at 12 hours after burn (all P < 0.05). Conclusion: High expression of HIF-1 alpha may induce the apoptosis of T lymphocytes in Peyer’s patches after severe burn with delayed fluid resuscitation in rats at plateau.展开更多
Suspension of formalized Campylobacter jejunt (2×10 CFU/ml)was injected into a bothend-ligated intestinal loop of ileum which contained some Peyer's patches from non-immunized adult mice after laparotomy unde...Suspension of formalized Campylobacter jejunt (2×10 CFU/ml)was injected into a bothend-ligated intestinal loop of ileum which contained some Peyer's patches from non-immunized adult mice after laparotomy under anesthesia.After 1-hour post inoculation, the specimen was taken out and prepared for TEM and SEM observation.The results showed that bacteria adhered specifically on the surface of M cells of Peyer's patches.The microvilli and microfolds of the M cells fused to capture the bacteria and to form a large endocytotic vesicle in the cytoplasm of the M cell,then transported inward,and, at last.released into the central cavity between lymphocytes.Occasionally, we found some of them were phagocytosed by lymphocytes.展开更多
Heterotopic gastric mucosa of the proximal esophagus (HGMPE),also referred to as"inlet patch"or"cervical inlet patch",is a salmon colored patch that is usually located just distal to the upper esop...Heterotopic gastric mucosa of the proximal esophagus (HGMPE),also referred to as"inlet patch"or"cervical inlet patch",is a salmon colored patch that is usually located just distal to the upper esophageal sphincter. HGMPE is uncommon with endoscopic studies reporting a prevalence ranging from less than one percent to 18%.Most HGMPE are asymptomatic and are detected incidentally during endoscopy for evaluations of other gastrointestinal complaints.Most consider HGMPE as clinically irrelevant entity.The clinical significance of HGMPE is mainly acid related or neoplastic transformation.The reported prevalence of laryngopharyngeal reflux symptoms varies from less than 20%to as high as 73.1%.However,most of these symptoms are mild. Clinically significant acid related complications such as bleeding,ulcerations,structure and fistulization have been reported.Although rare,dysplastic changes and malignancies in association with HGMPE have also been reported.Associations with Barrett's esophagus have also been reported but the findings so far have been conflicting.There are still many areas that are unknown or not well understood and these include the natural history of HGMPE,risk factors for complications,role of Helicobacter pylori infection and factors associated with malignant transformations.Follow-up may need to be considered for patients with complications of HGMPE and surveillance if biopsies show intestinal metaplasia or dysplastic changes.Despite the overall low incidence of clinically relevant manifestations reported in the literature,HGMPE is a clinically significant entity but further researches are required to better understand its clinical significance.展开更多
AIM:To determine the association between Helicobacter pylori(H.pylori)and globus sensation(GS)in the patients with cervical inlet patch. METHODS:Sixty-eight patients with esophageal inlet patches were identified from ...AIM:To determine the association between Helicobacter pylori(H.pylori)and globus sensation(GS)in the patients with cervical inlet patch. METHODS:Sixty-eight patients with esophageal inlet patches were identified from 6760 consecutive patients undergoing upper gastrointestinal endoscopy prospectively.In these 68 patients with cervical inlet patches, symptoms of globus sensation(lump in the throat), hoarseness,sore throat,frequent clearing of the throat,cough,dysphagia,odynophagia of at least 3 mo duration was questioned prior to endoscopy. RESULTS:Cervical heterotopic gastric mucosa(CHGM) was found in 68 of 6760 patients.The endoscopic prevalence of CHGM was determined to be 1%.H.pylori was identified in 16(23.5%)of 68 patients with inlet patch.53 patients were classified as CHGMⅡ.This group included 48 patients with globus sensation,4 patients with chronic cough and 1 patient with hoarseness.All the patients who were H.pylori(+)in cervical inlet patches had globus sensation.CONCLUSION:Often patients with CHGM have a long history of troublesome throat symptoms.We speculate that disturbances in globus sensation are like non-ulcer dyspepsia.展开更多
The proximal esophagus is rarely examined,and its inspection is often inadequate.Optical chromoendoscopy techniques such as narrow band imaging improve the detection rate of inlet patches in the proximal esophagus,a r...The proximal esophagus is rarely examined,and its inspection is often inadequate.Optical chromoendoscopy techniques such as narrow band imaging improve the detection rate of inlet patches in the proximal esophagus,a region in which their prevalence is likely underestimated.Various studies have reported correlations between these esophageal marks with different issues such as Barrett’s esophagus,but these findings remain controversial.Conflicting reports complicate the process of interpreting the clinical features of esophageal inlet patches and underestimate their importance.Unfortunately,the limited clinical data and statistical analyses make reaching any conclusions difficult.It is hypothesized that inlet patches are correlated with various esophageal and extraesophageal symptoms,diagnoses and the personalized therapeutic management of patients with inlet patches as well as the differential diagnosis for premalignant lesions or early cancers.Due to its potential underdiagnosis,there are no consensus guidelines for the management and follow up of inlet patches.This review focuses on questions that were raised from published literature on esophageal inlet patches in adults.展开更多
AIM:To demonstrate the feasibility of optical coherence tomography(OCT)imaging in differentiating cervical inlet patch(CIP)from normal esophagus,Barrett'sesophagus(BE),normal stomach and duodenum. METHODS:This stu...AIM:To demonstrate the feasibility of optical coherence tomography(OCT)imaging in differentiating cervical inlet patch(CIP)from normal esophagus,Barrett'sesophagus(BE),normal stomach and duodenum. METHODS:This study was conducted at the Veterans Affairs Boston Healthcare System(VABHS).Patients undergoing standard esophagogastroduodenoscopy at VABHS,including one patient with CIP,one representative patient with BE and three representative normal subjects were included.White light video endoscopy was performed and endoscopic 3D-OCT images were obtained in each patient using a prototype OCT system.The OCT imaging probe passes through the working channel of the endoscope to enable simultaneous video endoscopy and 3D-OCT examination of the human gastrointestinal(GI)tract.Standard hematoxylin and eosin(H and E)histology was performed on biopsy or endoscopic mucosal resection specimens in order to compare and validate the 3D-OCT data. RESULTS:CIP was observed from a 68-year old male with gastroesophageal reflux disease.The CIP region appeared as a pink circular lesion in the upper esophagus under white light endoscopy.OCT imaging over the CIP region showed columnar epithelium structure,which clearly contrasted the squamous epithelium structure from adjacent normal esophagus.3D-OCT images obtained from other representative patients demonstrated distinctive patterns of the normal esophagus,BE,normal stomach,and normal duodenum bulb.Microstructures,such as squamous epithelium,lamina propria, muscularis mucosa,muscularis propria,esophageal glands,Barrett's glands,gastric mucosa,gastric glands, and intestinal mucosal villi were clearly observed with OCT and matched with H and E histology.These results demonstrated the feasibility of using OCT to evaluate GI tissue morphology in situ and in real-time. CONCLUSION:We demonstrate in situ evaluation of CIP microstructures using 3D-OCT,which may be a useful tool for future diagnosis and follow-up of patients with CIP.展开更多
RIG-I （retinoid acid-inducible gene-I）, a putative RNA helicase with a cytoplasmic caspase-recrultment domain （CARD）, was identified as a pattem-recognition receptor （PRR） that mediates antiviral immunity by ind...RIG-I （retinoid acid-inducible gene-I）, a putative RNA helicase with a cytoplasmic caspase-recrultment domain （CARD）, was identified as a pattem-recognition receptor （PRR） that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I^-/- mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I^-/- mice are viable and fertile. Histological analysis shows that Rig-I^-/ mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer＇s patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation ofT-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein αi2 subunit （Gαi2） in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated Gαi2 expression. Moreover, Gαi2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of Gαi2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of Gαi2 and disturbed T-cell homeostasis.展开更多
基金Supported by Strategic Program of Chinese University of Hong KongDistinguished Young Investigator Fund of the National Natural Science Foundation of China, No. 30029002
文摘AIM： TO investigate the effect of interaction between enteric epithelial cells and lymphocytes of Peyer＇s patch on the release of nitric oxide （NO） and IL-6 in response to Shigella lipopolysaccharide （LPS）. METHODS： Human colonic epithelial cells （Caco-2） were mixed cocultured with lymphocytes of Peyer＇s patch from wild-type （C57 mice） and inducible NO synthase knockout mice, and challenged with Shigella F2a-12 LPS. Release of NO and raiL-6 was measured by Griess colorimetric assay and enzyme-linked immunosorbent assay （ELISA）, respectively. RESULTS： In the absence of LPS challenge, NO was detected in the culture medium of Caco-2 epithelial cells but not in lymphocytes of Peyer＇s patch, and the NO release was further up-regulated in both cocultures with lymphocytes from either the wild-type or iNOS knockout mice, with a significantly higher level observed in the coculture with iNOS knockout lymphocytes. After Shigella F2a-12 LPS challenge for 24-h, NO production was significantly increased in both Caco-2 alone and the coculture with lymphocytes of Peyer＇s patch from the wild-type mice but not from iNOS knockout mice. LPS was found to stimulate the release of mIL-6 from lymphocytes, which was suppressed by coculture with Caco-2 epithelial cells. The LPS-induced mIL-6 production in lymphocytes from iNOS knockout mice was significantly greater than that from the wild-type mice. CONCLUSION： Lymphocytes of Peyer＇s patch maintain a constitutive basal level of NO production from the enteric epithelial cell Caco-2. LPS-induced mIL-6 release from lymphocytes of Peyer＇s patch is suppressed by the cocultured epithelial cells. While no changes are detectable in NO production in lymphocytes from both wild-type and iNOS knockout mice before and after LPS challenge, NO from lymphocytes appears to play an inhibitory role in epithelial NO release and their own mIL-6 release in response to LPS.
文摘Objective: To research the expression of hypoxia inducible factor-1 alpha (HIF-1 alpha) on the apoptosis and number of T lymphocyte in Peyer’s patches after severe burn on plateau in rats. Methods: Wistar rats (n = 130) were subjected to deep thickness burn injury (30% TBSA, III degree), at two different altitudes. 60 of them were given delayed fluid resuscitation (DFR, n = 30 at each altitude) 6 h after burn at different altitude;60 of them were carried out immediate fluid resuscitation (IFR, n = 30 at each altitude);10 rats were subjected to 37°C warm water as sham burn (SG, n = 10). The Peyer’s patches were harvested from the ileum of rats at different time point after burn respectively. The expression of HIF-1 alpha, CD3(+) and the apoptosis and number of T lymphocyte in Peyer’s patches were detected by tissue microarray technology and immunohistochemistry. Results: The apoptosis was higher in DFR group than that in IFR group. The increase in HIF-1 alpha expression was observed mainly on cell nucleus in T lymphocytes. The expression levels of HIF-1 alpha in Peyer’s patches were much higher in DFR group and IFR group than those in SG, and they were higher at high altitude (3848 metres) than those at lower altitude (1517 metres), and also higher in DFR group compared with IFR group (all P < 0.05). The expression levels of CD3<sup>+</sup> in Peyer’s patches were much lower in DFR group and IFR group than those in sham group, and the lowest value appeared at 12 hours after burn (all P < 0.05). Conclusion: High expression of HIF-1 alpha may induce the apoptosis of T lymphocytes in Peyer’s patches after severe burn with delayed fluid resuscitation in rats at plateau.
文摘Suspension of formalized Campylobacter jejunt (2×10 CFU/ml)was injected into a bothend-ligated intestinal loop of ileum which contained some Peyer's patches from non-immunized adult mice after laparotomy under anesthesia.After 1-hour post inoculation, the specimen was taken out and prepared for TEM and SEM observation.The results showed that bacteria adhered specifically on the surface of M cells of Peyer's patches.The microvilli and microfolds of the M cells fused to capture the bacteria and to form a large endocytotic vesicle in the cytoplasm of the M cell,then transported inward,and, at last.released into the central cavity between lymphocytes.Occasionally, we found some of them were phagocytosed by lymphocytes.
文摘Heterotopic gastric mucosa of the proximal esophagus (HGMPE),also referred to as"inlet patch"or"cervical inlet patch",is a salmon colored patch that is usually located just distal to the upper esophageal sphincter. HGMPE is uncommon with endoscopic studies reporting a prevalence ranging from less than one percent to 18%.Most HGMPE are asymptomatic and are detected incidentally during endoscopy for evaluations of other gastrointestinal complaints.Most consider HGMPE as clinically irrelevant entity.The clinical significance of HGMPE is mainly acid related or neoplastic transformation.The reported prevalence of laryngopharyngeal reflux symptoms varies from less than 20%to as high as 73.1%.However,most of these symptoms are mild. Clinically significant acid related complications such as bleeding,ulcerations,structure and fistulization have been reported.Although rare,dysplastic changes and malignancies in association with HGMPE have also been reported.Associations with Barrett's esophagus have also been reported but the findings so far have been conflicting.There are still many areas that are unknown or not well understood and these include the natural history of HGMPE,risk factors for complications,role of Helicobacter pylori infection and factors associated with malignant transformations.Follow-up may need to be considered for patients with complications of HGMPE and surveillance if biopsies show intestinal metaplasia or dysplastic changes.Despite the overall low incidence of clinically relevant manifestations reported in the literature,HGMPE is a clinically significant entity but further researches are required to better understand its clinical significance.
文摘AIM:To determine the association between Helicobacter pylori(H.pylori)and globus sensation(GS)in the patients with cervical inlet patch. METHODS:Sixty-eight patients with esophageal inlet patches were identified from 6760 consecutive patients undergoing upper gastrointestinal endoscopy prospectively.In these 68 patients with cervical inlet patches, symptoms of globus sensation(lump in the throat), hoarseness,sore throat,frequent clearing of the throat,cough,dysphagia,odynophagia of at least 3 mo duration was questioned prior to endoscopy. RESULTS:Cervical heterotopic gastric mucosa(CHGM) was found in 68 of 6760 patients.The endoscopic prevalence of CHGM was determined to be 1%.H.pylori was identified in 16(23.5%)of 68 patients with inlet patch.53 patients were classified as CHGMⅡ.This group included 48 patients with globus sensation,4 patients with chronic cough and 1 patient with hoarseness.All the patients who were H.pylori(+)in cervical inlet patches had globus sensation.CONCLUSION:Often patients with CHGM have a long history of troublesome throat symptoms.We speculate that disturbances in globus sensation are like non-ulcer dyspepsia.
文摘The proximal esophagus is rarely examined,and its inspection is often inadequate.Optical chromoendoscopy techniques such as narrow band imaging improve the detection rate of inlet patches in the proximal esophagus,a region in which their prevalence is likely underestimated.Various studies have reported correlations between these esophageal marks with different issues such as Barrett’s esophagus,but these findings remain controversial.Conflicting reports complicate the process of interpreting the clinical features of esophageal inlet patches and underestimate their importance.Unfortunately,the limited clinical data and statistical analyses make reaching any conclusions difficult.It is hypothesized that inlet patches are correlated with various esophageal and extraesophageal symptoms,diagnoses and the personalized therapeutic management of patients with inlet patches as well as the differential diagnosis for premalignant lesions or early cancers.Due to its potential underdiagnosis,there are no consensus guidelines for the management and follow up of inlet patches.This review focuses on questions that were raised from published literature on esophageal inlet patches in adults.
基金Supported by The VA Boston Healthcare System and NIH grants R01-CA75289-14,to Fujimoto JG and Mashimo HK99-EB010071-01A1,to Zhou C+2 种基金Air Force Office of Scientific Research contract FA9550-10-1-0063,to Fujimoto JGMedical Free Electron Laser Program contract FA9550-10-1-0551,to Fujimoto JGthe MIT/CIMIT Medical Engineering Fellowship,to Tsai TH
文摘AIM:To demonstrate the feasibility of optical coherence tomography(OCT)imaging in differentiating cervical inlet patch(CIP)from normal esophagus,Barrett'sesophagus(BE),normal stomach and duodenum. METHODS:This study was conducted at the Veterans Affairs Boston Healthcare System(VABHS).Patients undergoing standard esophagogastroduodenoscopy at VABHS,including one patient with CIP,one representative patient with BE and three representative normal subjects were included.White light video endoscopy was performed and endoscopic 3D-OCT images were obtained in each patient using a prototype OCT system.The OCT imaging probe passes through the working channel of the endoscope to enable simultaneous video endoscopy and 3D-OCT examination of the human gastrointestinal(GI)tract.Standard hematoxylin and eosin(H and E)histology was performed on biopsy or endoscopic mucosal resection specimens in order to compare and validate the 3D-OCT data. RESULTS:CIP was observed from a 68-year old male with gastroesophageal reflux disease.The CIP region appeared as a pink circular lesion in the upper esophagus under white light endoscopy.OCT imaging over the CIP region showed columnar epithelium structure,which clearly contrasted the squamous epithelium structure from adjacent normal esophagus.3D-OCT images obtained from other representative patients demonstrated distinctive patterns of the normal esophagus,BE,normal stomach,and normal duodenum bulb.Microstructures,such as squamous epithelium,lamina propria, muscularis mucosa,muscularis propria,esophageal glands,Barrett's glands,gastric mucosa,gastric glands, and intestinal mucosal villi were clearly observed with OCT and matched with H and E histology.These results demonstrated the feasibility of using OCT to evaluate GI tissue morphology in situ and in real-time. CONCLUSION:We demonstrate in situ evaluation of CIP microstructures using 3D-OCT,which may be a useful tool for future diagnosis and follow-up of patients with CIP.
文摘RIG-I （retinoid acid-inducible gene-I）, a putative RNA helicase with a cytoplasmic caspase-recrultment domain （CARD）, was identified as a pattem-recognition receptor （PRR） that mediates antiviral immunity by inducing type I interferon production. To further study the biological function of RIG-I, we generated Rig-I^-/- mice through homologous recombination, taking a different strategy to the previously reported strategy. Our Rig-I^-/- mice are viable and fertile. Histological analysis shows that Rig-I^-/ mice develop a colitis-like phenotype and increased susceptibility to dextran sulfate sodium-induced colitis. Accordingly, the size and number of Peyer＇s patches dramatically decreased in mutant mice. The peripheral T-cell subsets in mutant mice are characterized by an increase in effector T cells and a decrease in naive T cells, indicating an important role for Rig-I in the regulation ofT-cell activation. It was further found that Rig-I deficiency leads to the downregulation of G protein αi2 subunit （Gαi2） in various tissues, including T and B lymphocytes. By contrast, upregulation of Rig-I in NB4 cells that are treated with ATRA is accompanied by elevated Gαi2 expression. Moreover, Gαi2 promoter activity is increased in co-transfected NIH3T3 cells in a Rig-I dose-dependent manner. All these findings suggest that Rig-I has crucial roles in the regulation of Gαi2 expression and T-cell activation. The development of colitis may be, at least in part, associated with downregulation of Gαi2 and disturbed T-cell homeostasis.
