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Mucosal Surfaces (mucosal + surface)
Selected AbstractsNARROW BAND IMAGING IN THE DETECTION OF COLORECTAL POLYP: KOREAN EXPERIENCEDIGESTIVE ENDOSCOPY, Issue 2 2008Jeong-Sik Byeon Background:, Although white light (WL) colonoscopy is a gold standard to detect colorectal polyps, substantial polyps are missed. Narrow band imaging (NBI) is a new technology that enables a more detailed visualization of the mucosal surface. The aim of the present study was to determine whether NBI can improve the detection of colorectal polyps. Methods:, We prospectively enrolled 188 (M : F = 99:89, 21,80 years) subjects undergoing colonoscopy as a screening procedure in nine referral centers. After a careful WL examination of the whole colorectum, rectosigmoid colon (0,30 cm from the anal verge) was reobserved by NBI. Size, macroscopic morphology, and the histology of all the polyps detected during WL and NBI examination were analyzed. Results:, WL examination detected 162 polyps in 188 subjects, of which 106 lesions were neoplastic, while NBI of rectosigmoid colon detected an additional 61 polyps of which eight lesions were neoplastic. Only 10 (6.2%) of 162 polyps discovered during WL examination were flat polyps compared to 10 (16.4%) of 61 newly detected polyps during NBI being flat type (P = 0.002). The mean polyp size detected by NBI was smaller than that found by WL colonoscopy (2.8 ± 1.0 mm vs 6.5 ± 4.5 mm, P < 0.001). Conclusion:, Many additional colorectal polyps, especially flat type, could be detected by NBI examination for normal-looking rectosigmoid mucosa. The role of NBI in colorectal neoplasm screening needs to be further investigated in future studies. [source] MAGNIFYING ENDOSCOPY FOR THE DIAGNOSIS OF EARLY GASTRIC CANCERDIGESTIVE ENDOSCOPY, Issue 2002Yasumasa Niwa Magnifying endoscopy of stomach cancer requires observation of minute structure and minute vessel patterns of the mucosal surface. The small pits, various-sized pits, irregularly branched pits and irregular vessels were found to be characteristics as the surface structure of early gastric cancer. Small pits were commonly observed on the differentiated type of early gastric cancer (88%) compared with the undifferentiated type (50%). We found it important to analyze not only the minute vessel patterns, but also the minute surface structure to ensure magnifying endoscopic observation using 0.1% indigo-carmine and the binarized images would be effective in determining the margin of the lesion. The relationship between the findings of magnifying endoscopy in cancer and the histology should now be investigated. Applying the techniques mentioned above, more delicate observation in the regular endoscopy and prudent photographing to obtain clear images might be promoted. Thus, this would contribute to endoscopy with a concept similar to optical biopsy, and which can depend on the usual biopsy methods. [source] Evidence for surfactant contributing to the gastric mucosal barrier of the horseEQUINE VETERINARY JOURNAL, Issue 6 2000M. T. ETHELL Summary This study was undertaken to determine the hydrophobicity of the luminal surface of the equine stomach and to elucidate the ultrastructure of the lining imparting that property. Gastric and duodenal mucosal samples from 5 horses were collected immediately after euthanasia and subjected to surface contact angle measurement using a goniometer. Gastric mucosal samples from 4 horses and a foal were examined by electron microscopy following a fixation procedure known to preserve phospholipids and oligolamellar structures. Contact angles for the equine gastric glandular mucosal surface (mean ± s.e. 78.0 ± 11.0°) were greater than for the duodenum (33.4 ± 8.7°), (P = 0.003). The contact angles for gastric squamous tissue (50.4 ± 4.5°) tended to be greater than for duodenum (P = 0.15). Electron microscopy revealed the existence of surfactant as abundant osmiophilic phospholipid material within both squamous and glandular gastric mucosae. These results indicate the hydrophobic nature of the equine gastric mucosae. We propose that the water-repellent nature of the stomach contributes to the ,gastric mucosal barrier' and is imparted by surface-active phospholipid adsorbed to the surface. Phospholipids may also be utilised as a physical barrier to back-diffusion of acid by lining intracellular canaliculi and oxyntic ducts where other defence mechanisms are absent. [source] Paradox of simultaneous intestinal ischaemia and hyperaemia in inflammatory bowel diseaseEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 10 2005O. A. Hatoum Abstract This review has focused on evidence regarding intestinal perfusion of inflammatory bowel disease (IBD). Basic investigation has defined an altered microvascular anatomy in the affected IBD bowel, which corresponds with diminished mucosal perfusion in the setting of chronic, long-standing inflammation. Diminished perfusion is linked to impaired wound healing, and may contribute to the continued refractory mucosal damage, which characterizes IBD. Alterations in vascular anatomy and physiology in IBD suggests additional possible mechanisms by which micro-vessels may contribute to the initiation and perpetuation of IBD. This begs the following questions: will angiogenesis within the gut lead to sustained inflammation, does the growing vasculature generate factors that transform the surrounding tissue and does angiogenesis generate vascular anastomosis within the gut, with shunting of blood away from the mucosal surface, impairment of metabolism and potentiation of gut damage? Further studies are required to define the mechanisms that underlie the vascular dysfunction and its role in pathophysiology of IBD. [source] Oral hygiene of elderly people in long-term care institutions , a cross-sectional studyGERODONTOLOGY, Issue 4 2006Luc M. De Visschere Objective:, The aim of this cross-sectional study was to assess the level of oral hygiene in elderly people living in long-term care institutions and to investigate the relationship between institutional and individual characteristics, and the observed oral cleanliness. Materials and methods:, Clinical outcome variables, denture plaque and dental plaque were gathered from 359 older people (14%) living in 19 nursing homes. Additional data were collected by a questionnaire filled out by all health care workers employed in the nursing homes. Results:, Only 128 (36%) residents had teeth present in one or both dental arches. About half of the residents (47%) wore complete dentures. The mean dental plaque score was 2.17 (maximum possible score = 3) and the mean denture plaque score was 2.13 (maximum possible score = 4). Significantly more plaque was observed on the mucosal surface of the denture with a mean plaque score of 2.33 vs. 1.93 on the buccal surface (p < 0.001). In the multiple analyses only the degree of dependency on an individual level was found to be significantly correlated with the outcome dental plaque (odds ratio: 3.09) and only the management of the institution with denture plaque (odds ratio: 0.43). Conclusion:, Oral hygiene was poor, both for dentures and remaining teeth in residents in long-term care institutions and only the degree of dependency of the residents and the management of the institutions was associated with the presence of dental plaque and denture plaque respectively. [source] Nuclear factor-,B contributes to interleukin-4- and interferon-dependent polymeric immunoglobulin receptor expression in human intestinal epithelial cellsIMMUNOLOGY, Issue 1 2004Laynez W. Ackermann Summary Polymeric immunoglobulins (pIgs) that are present at mucosal surfaces play key roles in both the innate and adaptive immune responses. These pIgs are delivered to the mucosal surface via transcytosis across the epithelium, a process mediated by the polymeric immunoglobulin receptor (pIgR). Previous studies demonstrate that expression of the pIgR is regulated by multiple immunomodulatory factors including interleukin-4 (IL-4) and interferon-, (IFN-,). In studies using human intestinal epithelial cells (HT29), multiple inhibitors of the transcription factor nuclear factor-,B (NF-,B), including a dominant negative I,B,-serine mutant, inhibited both IL-4- and IFN-dependent increases in pIgR expression. Under identical conditions, NF-,B inhibitors had no effect on cytokine-dependent increases in expression of the transcription factor interferon regulatory factor-1. Over-expression of the I,B,-serine mutant also inhibited reporter gene expression in response to IL-4, TNF-,, IL-1,, and in some cases IFN-, using constructs with sequences from the pIgR promoter. Reduced levels of pIgR were observed even when inhibitors were added ,24 hr after cytokines suggesting that prolonged activation of NF-,B is required. Finally, reporter gene studies with NF-,B enhancer elements indicated that IFN-, alone and IL-4 in combination with other cytokines activated NF-,B in HT29 cells. Together, these studies provide additional insight into the signalling pathways that contribute to expression of the pIgR, a critical player in mucosal immunity. [source] Effect of the anti-tumor necrosis factor-, antibody infliximab on the ex vivo mucosal matrix metalloproteinase,proteolytic phenotype in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 2 2007Martin J. Meijer MSc Abstract Background: Previous studies have shown an upregulation of matrix metalloproteinases (MMPs) in intestinal tissue of patients with inflammatory bowel disease (IBD) and significant clinical improvement after administration of the anti-TNF-, antibody infliximab. The aims of our study were to determine expression and secretion of MMP-1, -2, -3, -9, and their inhibitors TIMP-1, -2 by IBD versus control intestinal mucosa ex vivo and to assess the regulatory capacity by infliximab of the proteolytic phenotype. Methods: Intestinal mucosal explants from 20 IBD and 15 control patients were cultured with or without infliximab and/or the T-cell activator pokeweed mitogen (PWM). Explants and culture supernatants were analyzed for MMPs, TIMPs, and TNF-, protein, activity and/or mRNA levels. All patients were genotyped for functional TNF-,, MMP, and TIMP single nucleotide polymorphism (SNP) loci. Results: Expression of MMP and TIMP protein/activity in basal medium was higher in IBD versus control explants. Dependent on genotype at SNP loci, infliximab downregulated MMP-1, -3, and -9 relative to TIMP-1 and -2 and also decreased MMP-1 and -3 activities, while PWM enhanced these levels, partly counteracted again by infliximab. The expression of MMP-2 relative to TIMP did not change by treatment with infliximab and/or PWM. Conclusions: The high expression of MMPs in patients with IBD suggests a role for these proteinases in the pathogenesis of this disease. Infliximab seems to induce a genotype-associated matrix protective phenotype, which may contribute to the observed therapeutic efficacy of this drug in IBD, particularly at the mucosal surface. (Inflamm Bowel Dis 2007) [source] A novel immunotherapy for superficial bladder cancer by intravesical immobilization of GM-CSFJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 6b 2010Zhiming Hu Abstract In situ gene therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF) was demonstrated to successfully inhibit tumour cell growth in a mouse orthotopic bladder cancer model, but suffered from several disadvantages, such as limited efficiency for gene delivery, low expression efficiency of the transgene and the safety concern resulting from viral vector. In order to address the limits, a novel immunotherapy was developed attentively through immobilization of streptavidin-tagged bioactive GM-CSF on the biotinylated mucosal surface of bladder wall on the basis of both the unique property of streptavidin (SA) to bind rapidly and almost irreversibly to any biotin-linked molecule and the outstanding ability of biotin to be incorporated easily into the proteins on the cell surface. The mouse orthotopic model of MB49 bladder cancer was used to evaluate the feasibility and efficacy of the novel immunotherapy performed twice a week for 3 weeks. Briefly, 1 day after intravesical implantation of 1 × 106 MB49 tumour cells in C57BL/6 mouse, 100 ,l of 1 mg/ml NHS-PEO4-biotin was instilled and allowed to incubate in the bladder for 30 min., followed by intravesical instillation of 100 ,l of 0.15 mg/ml SA-GM-CSF bifunctional fusion protein and incubation for 1 hr. SA-GM-CSF fusion protein was shown to be immobilized efficiently and durably on the biotinylated mucosal surface of bladder wall. The bladder cancer incidence was dramatically decreased from 100% in the control group to 37.5% in the SA-GM-CSF group. Importantly, 70% of the SA-GM-CSF-cured mice were protected against a second intravesical wild-type MB49 tumour challenge, indicating that an effective anti-tumour immunity was generated against MB49 bladder cancer. Thus, the novel immunotherapy may be an attractive therapeutic alternative and should be evaluated in bladder cancer patients. [source] Effect of ursodeoxycholic acid treatment on the expression and function of multidrug resistance-associated protein 2 in rat intestineJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 8 2009Ryoko Yumoto Abstract Effect of ursodeoxycholic acid (UDCA) treatment on the expression and function of intestinal multidrug resistance-associated protein (Mrp) 2 was examined in rats. When rats were orally administered 0.5% UDCA solution for 6 days, mRNA and protein levels of Mrp2 in the intestine were increased about twofold compared with those in untreated rats. In in vitro everted sac study, Mrp2-mediated efflux of 2,4-dinitrophenyl-S-glutathione (DNP-SG) to the mucosal surface was shown to be increased by UDCA treatment. In vivo intestinal exsorption clearance of DNP-SG was also increased by UDCA treatment. In addition, in situ intestinal absorption of methotrexate, a substrate of Mrp2, was decreased by the treatment. These results indicate that the expression and function of intestinal Mrp2 is up-regulated by oral administration of UDCA. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2822,2831, 2009 [source] The use of simple dynamic mucosal models and confocal microscopy for the evaluation of lyophilised nasal formulationsJOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 6 2007Fiona McInnes A range of methods is reported in the literature for assessing hydration and adhesion parameters in the performance of nasal bioadhesive formulations; however, these tests do not always represent the dynamic conditions in the nasal cavity. Lyophilised formulations intended for nasal administration were evaluated using in-vitro tests designed in an attempt to mimic relevant processes in the nasal cavity, and intended to discriminate between different formulations. Initial investigative studies using scanning electron microscopy revealed that the lyophilisate had a highly porous internal structure, expected to provide an ideal porous pathway for re-hydration. Vapour sorption analysis demonstrated substantial weight gain of the lyophilisates on exposure to 95% relative humidity, ranging from 38% to 66%. Agar was used as a synthetic mucosal model designed to provide a standardised quantity of water available for rehydration of the formulations in in-vitro tests. A dynamic adhesion test and a texture analyser sliding test were designed to quantify different aspects of the spreading and adhesion of the hydrating formulations on the synthetic mucosal surface. Examination of the lyophilised formulations using confocal microscopy allowed visualisation and quantification of the initial rate of water ingress into the lyophilisates, which was found to consist of an initial rapid phase, followed by a slower steady-state phase. The results demonstrated that the use of a combination of methods representing the dynamic conditions of the nasal cavity is advisable in order to evaluate a formulation fully and to avoid misleading conclusions. [source] Simultaneous measurement of serotonin and melatonin from the intestine of old mice: the effects of daily melatonin supplementationJOURNAL OF PINEAL RESEARCH, Issue 1 2010P. P. Bertrand Abstract:, Ageing is associated with important changes in gastrointestinal function and in the levels of intestinal hormones secreted. Enterochromaffin (EC) cells containing serotonin (5-HT) and melatonin may play a major role in maintaining gut function during ageing. Our aim was to characterise the mucosal availability of 5-HT and melatonin in the ileum and colon of a mouse model of ageing. Female young mice (2,5 month; n = 6), aged mice (22,24 months; n = 6) and aged mice treated with melatonin (n = 6; 10 mg/kg/day) were examined. Electrochemical methods were used to measure 5-HT and melatonin concentrations near the mucosal surface of ileum and distal colon. Amperometry studies showed that steady state levels of 5-HT from ileum and colon were decreased in aged mice treated with melatonin when compared to aged mice, while compression-evoked 5-HT release was unchanged. Differential pulse voltammetry studies showed that young mice had concentrations of 5-HT of 4.8 ± 0.8 ,m in the ileum and 4.9 ± 1.0 ,m in the colon. Concentrations of melatonin were 5.7 ± 1.4 ,m in the ileum and 5.6 ± 1.9 ,m in the colon. Compared to young mice, the levels of 5-HT and melatonin were increased in aged mice (combined ileum and colon: 5-HT = 130% and melatonin = 126% of young mice) and decreased in melatonin-treated mice (5-HT = 94% and melatonin = 82%). In conclusion, our data show that the availability of gut 5-HT and melatonin is increased in aged mice and melatonin treatment suppresses natural gastrointestinal production of 5-HT and melatonin in the aged mouse intestine. [source] Oesophageal morphometry and residual strain in a mouse model of osteogenesis imperfectaNEUROGASTROENTEROLOGY & MOTILITY, Issue 5 2001H. Gregersen Recently, it was demonstrated in the oesophagus that the zero-stress state is not a closed cylinder but an open circular cylindrical sector. The closed cylinder with no external loads applied is called the no-load state and residual strain is the difference in strain between the no-load state and the zero-stress state. To understand the physiology and pathology of the oesophagus, it is necessary to know the zero-stress state and the stress,strain relationships of the tissues in the oesophagus, and the changes of these states and relationships due to biological remodelling of the tissues under stress. The aim of this study was to investigate the morphological and biomechanical remodelling at the no-load and zero-stress states in mutant osteogenesis imperfecta murine (oim) mice with collagen deficiency. The oesophagi of seven oim and seven normal wild-type mice were excised, cleaned, and sectioned into rings in an organ bath containing calcium-free Krebs solution with dextran and EGTA. The rings were photographed in the no-load state and cut radially to obtain the zero-stress state. Equilibrium was awaited for 30 min and the specimens were photographed again. Circumferences, submucosa and muscle layer thicknesses and areas, and the opening angle were measured from the digitized images. The oesophagi in oim mice had smaller layer thicknesses and areas compared to the wild types. The largest reduction in layer thickness in oim mice was found in the submucosa (approximately 36%). Oim mice had significantly larger opening angles (120.2 ± 4.5°) than wild-type mice (93.0 ± 11.2°). The residual strain was compressive at the mucosal surface and tensile at the serosal surface in both oim and wild types. In the oim mice, the residual strains at the serosal and mucosal surfaces and the mucosa-submucosal,muscle layer interface were higher than in the wild types (P < 0.05). The gradient of residual strain per unit thickness was higher in oim mice than in wild-type mice, and was highest in submucosa (P < 0.05). The only morphometric measure that was similar in oim and wild-type mice was the inner circumference in the no-load state. In conclusion, our data show significant differences in the residual strain distribution and morphometry between oim mice and wild-type mice. The data suggest that the residual stress in oesophagus is caused by the tension in the muscle layer rather than the stiffness of the submucosa in compression and that the remodelling process in the oim oesophagus is due mainly to morphometric and biomechanical alterations in the submucosa. [source] Comparison of the composition of oral mucosal residual saliva with whole salivaORAL DISEASES, Issue 6 2007J-Y Lee Objective:, Compared with whole saliva, residual saliva comprising the oral mucosal film shows a high protein concentration. The purpose of this study was to compare the composition of residual saliva with unstimulated and stimulated whole saliva in normosalivators. Materials and methods:, The composition of oral mucosal residual saliva in 30 healthy individuals was investigated and compared with that of whole saliva. The concentrations of total protein, secretory immunoglobin A (sIgA), lactoferrin, total carbohydrate, and sialic acid were examined. The activities of peroxidase, lysozyme and , -amylase were determined. Results:, Residual saliva had higher levels of total protein and carbohydrate than whole saliva, with a higher carbohydrate to protein ratio in the residual saliva suggesting that salivary glycoproteins are concentrated on the oral mucosal surface. sIgA, lactoferrin and sialic acid were present as highly concentrated forms in residual saliva. The enzymatic activity of peroxidase in residual saliva was higher than that of whole saliva. Conclusions:, These concentrated carbohydrate and antimicrobials on the oral mucosal surface work for mucosal defence and could be used for targeting sites for the delivery of therapeutic agents. [source] Ciliary assessment in bronchiectasisRESPIROLOGY, Issue 2 2000Kenneth Wt Tsang Objective: Bronchiectasis is a common condition among the Oriental population and affected patients suffer from chronic sputum production punctuated by recurrent infective exacerbations. Cilia are minute structures present on the surface of respiratory and other epithelial cells that beat continuously to maintain a sterile mucosal surface in the respiratory tract. Patients with primary ciliary dyskinesia could potentially develop recurrent sinotrachrobronchitis, bronchiectasis, serous otitis media, hydrocephalus, and male infertility. The assessment of cilia has, however, received little attention until recently and generally involves elaborate methods that require complex and expensive technology. This brief article discusses application of the saccharine test, light microscopy assessment of ciliary beat, and transmission electron microscopy assessment of the ultrastructure of cilia. The rationale and indications for ciliary assessment are also listed along with illustrations showing ciliary structure, equipment required for sampling and assessment of cilia, and transmission electron micrographs of ciliary ultrastructural abnormalities. [source] How to outwit the enemy: dendritic cells face Salmonella,APMIS, Issue 9 2006Review article Salmonella enterica serovar Typhi causes typhoid fever, a serious life-threatening systemic infection. In mice, a similar disease is caused by Salmonella enterica serovar Typhimurium. During typhoid fever, soon after attachment to the mucosal surface of the gut, bacteria come into contact with the dendritic cells (DCs). The ability to sample antigens, process and present them to na,Đve and mature T cells, in the context of major histocompatibility complex molecules, makes DCs indispensable for mounting a specific and efficient immune response to invading pathogens. These bacteria, however, have evolved a number of mechanisms to interfere with or subvert DC functions. This review aims to describe how Salmonella clashes with dendritic cells at different stages of infection as well as the war strategies of these two opposing sides. [source] Involvement of Iron (Ferric) Reduction in the Iron Absorption Mechanism of a Trivalent Iron-Protein Complex (Iron Protein SuccinylateBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 3 2000Kishor B. Raja Iron protein succinylate is a non-toxic therapeutic iron compound. We set out to characterise the structure of this compound and investigate the importance of digestion and intestinal reduction in determining absorption of the compound. The structure of the compound was investigated by variable temperature Mössbauer spectroscopy, molecular size determinations and kinetics of iron release by chelators. Intestinal uptake was determined with radioactive compound force fed to mice. Reduction of the compound was determined by in vitro incubation with intestinal fragments. The compound was found to contain only ferric iron, present as small particles including sizes below 10 nm. The iron was released rapidly to chelators. Digestion with trypsin reduced the molecular size of the compound. Intestinal absorption of the compound was inhibited by a ferrous chelator (ferrozine), indicating that reduction to ferrous iron may be important for absorption. The native compound was a poor substrate for duodenal reduction activity, but digestion with pepsin, followed by pancreatin, released soluble iron complexes with an increased reduction rate. We conclude that iron protein succinylate is absorbed by a mechanism involving digestion to release soluble, available ferric species which may be reduced at the mucosal surface to provide ferrous iron for membrane transport into enterocytes. [source] Systemically administered trefoil factors are secreted into the gastric lumen and increase the viscosity of gastric contentsBRITISH JOURNAL OF PHARMACOLOGY, Issue 1 2006S Kjellev Background and purpose: Trefoil factors (TFFs) secreted by mucus-producing cells are essential for the defence of the gastrointestinal mucosa. TFFs probably influence the viscoelastic properties of mucus, but this has not been demonstrated in vivo. We therefore studied the gastric secretion of systemically administered TFF2 and TFF3, and their influence on the viscosity of the secretions. Experimental approach: Mice and rats under general anaesthesia were injected intravenously with human (h) TFF2, hTFF3 (5 mg kg,1 to mice and 25 mg kg,1 to rats), murine (m) 125I-TFF3, or 125I-hTFF3 (300 000 cpm, mice only). The appearance of TFFs in the gastric mucosa and luminal secretions was analysed by autoradiography, gamma-counting, and ELISA, and the viscosity by rheometry. Key results: 125I-mTFF3 and 125I-hTFF3 were taken up by secretory cells of the gastrointestinal tract and detected at the gastric mucosal surface 15 min after injection. Stressing the stomach by carbachol (3.5 ,g kg,1) and pyloric ligation significantly increased the uptake. Injected hTFF2, hTFF3, and mTFF3 were retrieved from the gastric contents after 4 h. In rats, an approximately seven-fold increase in the viscosity was detected after injection of TFF2 compared to the controls, whereas TFF3 did not increase the viscosity. In mice, TFF2 increased the viscosity approximately 4-fold. Conclusions: These data indicate that systemically administered TFFs are transferred to the gastric lumen in a biologically active form. British Journal of Pharmacology (2006) 149, 92,99. doi:10.1038/sj.bjp.0706840 [source] A major role for intestinal epithelial nucleotide oligomerization domain 1 (NOD1) in eliciting host bactericidal immune responses to Campylobacter jejuniCELLULAR MICROBIOLOGY, Issue 10 2007Matthias Zilbauer Summary Campylobacter jejuni is the foremost cause of bacterial-induced diarrhoeal disease worldwide. Although it is well established that C. jejuni infection of intestinal epithelia triggers host innate immune responses, the mechanism(s) involved remain poorly defined. Innate immunity can be initiated by families of structurally related pattern-recognition receptors (PRRs) that recognize specific microbial signature motifs. Here, we demonstrated maximal induction of epithelial innate responses during infection with live C. jejuni cells. In contrast when intestinal epithelial cells (IECs) were exposed to paraformaldehyde-fixed bacteria, host responses were minimal and a marked reduction in the number of intracellular bacteria was noted in parallel. These findings suggested a role for intracellular host,C. jejuni interactions in eliciting early innate immunity. We therefore investigated the potential involvement of a family of intracellular, cytoplasmic PRRs, the nucleotide-binding oligomerization domain (NOD) proteins in C. jejuni recognition. We identified NOD1, but not NOD2, as a major PRR for C. jejuni in IEC. We also found that targeting intestinal epithelial NOD1 with small interfering RNA resulted in an increase in number of intracellular C. jejuni, thus highlighting a critical role for NOD1-mediated antimicrobial defence mechanism(s) in combating this infection at the gastrointestinal mucosal surface. [source] Modulation of dendritic cell phenotype and functionin an in vitro model of the intestinal epitheliumEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2006Matt Butler Abstract A network of dendritic cells (DC) can be detected in close proximity to the epithelial cells overlying Peyer's patches in the gut. Intestinal DC show distinct phenotypes as compared to DC from the systemic lymph nodes (relatively low MHC and costimulatory molecules and high IL-10 and TGF,) and may play a role in maintaining tolerance to enteric antigens. We show that a similar phenotype is induced in the presence of a polarised epithelial cell monolayer in vitro. Monocyte-derived DC were co-cultured with Caco-2 intestinal epithelial monolayers for 24,h. Co-culture resulted in DC with reduced expression of MHC class,II, CD86, and CD80, and poor T,cell stimulatory capacity. Cytokine profiles showed reduced levels of inflammatory cytokine production, and co-cultured DC were less sensitive to stimulation via Toll-like receptors (TLR2, 4, and 6) as a result of increased levels of autocrine TGF, production. However, phenotypic changes in co-cultured DC could not be blocked by removal of apoptotic cells or addition of anti-TGF, antibodies, suggesting that other soluble factors are involved in DC modulation. Thus, polarised epithelial cell monolayers create a ,tolerogenic' environment which modulates the activity of DC. These results highlight the regulatory importance of the epithelial microenvironment at mucosal surfaces. [source] Ultrastructural localization of salivary mucins MUC5B and MUC7 in human labial glandsEUROPEAN JOURNAL OF ORAL SCIENCES, Issue 1 2010Monica Piras Piras M, Hand AR, Tore G, Ledda GP, Piludu M. Ultrastructural localization of salivary mucins MUC5B and MUC7 in human labial glands. Eur J Oral Sci 2010; 118: 14,18. © 2010 The Authors. Journal compilation © 2010 Eur J Oral Sci As a result of their presence throughout the mouth in the submucosa or between muscle fibers, minor salivary glands secrete directly and continuously into the oral cavity, providing mucosal surfaces with highly glycosylated proteins that are active in bacterial aggregation and in oral tissue lubrication. In this study, we investigated the ultrastructural localization of the MUC5B and MUC7 mucins in human labial glands by means of a postembedding immunogold technique. Thin sections of normal human labial glands, obtained during surgery, were incubated with polyclonal antibodies to human salivary mucins MUC5B and MUC7, and then with gold-labeled secondary antibodies. Specific MUC5B reactivity was found in the secretory granules of mucous cells of all glands examined, and was associated with the luminal membrane of duct cells. MUC7 labeling was observed in the granules of both mucous and seromucous secretory cells of the glandular parenchyma. Quantitative analyses demonstrated that seromucous granules have higher immunogold labeling densities for MUC7 than mucous granules. Our immunohistochemical data extend the results of previous light microscopic studies of MUC5B and MUC7 localizations, pointing out the significant contribution of human labial glands in the secretion process of these two mucins. [source] Mapping of the 45M1 epitope to the C-terminal cysteine-rich part of the human MUC5AC mucinFEBS JOURNAL, Issue 3 2008Martin E. Lidell Mucins are large glycoproteins protecting mucosal surfaces throughout the body. Their expressions are tissue-specific, but in disease states such as cystic fibrosis, inflammation and cancer, this specificity can be disturbed. MUC5AC is normally expressed in the mucous cells of the epithelia lining the stomach and the trachea, where it constitutes a major component of the gastric and respiratory mucus. A number of mAbs have been raised against the gastric M1 antigen, an early marker for colonic carcinogenesis. Several of these mAbs recognize epitopes present on MUC5AC, suggesting that MUC5AC is the antigen. However, some of the mAbs raised against the gastric M1 antigen are widely used as antibodies against MUC5AC, despite the fact that their specificity for MUC5AC has not been clearly shown. In this study, we have tested the reactivity of the latter antibodies against a recombinantly expressed C-terminal cysteine-rich part of human MUC5AC. We demonstrate for the first time that the widely used mAb 45M1, as well as 2-12M1 and 166M1, are true antibodies against MUC5AC, with epitopes located in the C-terminal cysteine-rich part of the mucin. [source] Antimicrobial peptides and proteins, exercise and innate mucosal immunityFEMS IMMUNOLOGY & MEDICAL MICROBIOLOGY, Issue 3 2006Nicholas P. West Abstract This review examines the question of whether exercise can be used as an experimental model to further our understanding of innate antimicrobial peptides and proteins (AMPs) and their role in susceptibility to infection at mucosal surfaces. There is strong evidence to suggest that AMPs, in combination with cellular and physical factors, play an important role in preventing infection. Although AMPs act directly on microorganisms, there is increasing recognition that they also exert their protective effect via immunomodulatory mechanisms, especially in noninflammatory conditions. Further studies that manipulate physiologically relevant concentrations of AMPs are required to shed light on the role they play in reducing susceptibility to infection. Evidence shows that in various form prolonged and/or exhaustive exercise is a potent modulator of the immune system, which can either sharpen or blunt the immune response to pathogens. The intensity and duration of exercise can be readily controlled in experimental settings to manipulate the degree of physical stress. This would allow for an investigation into a potential dose,response effect between exercise and AMPs. In addition, the use of controlled exercise could provide an experimental model by which to examine whether changes in the concentration of AMPs alters susceptibility to illness. [source] Protection of the oral mucosa by salivary histatin-5 against Candida albicans in an ex vivo murine model of oral infectionFEMS YEAST RESEARCH, Issue 5 2010Brian M. Peters Abstract The oral cavity is a primary target for opportunistic infections, particularly oral candidiasis caused by Candida albicans. A commensal fungus commonly colonizing mucosal surfaces, under conditions of immune dysfunction, C. albicans can become a pathogen causing recurrent infections. Yet, the role of host oral innate immunity in the development of candidiasis is not fully elucidated. Specifically, the host salivary antimicrobial peptide histatin-5 (Hst-5) has been proposed to play a protective role in the oral cavity against C. albicans. However, investigations demonstrating its efficacy on oral tissue have been lacking. To this end, in this study, an ex vivo murine model of oral infection was developed. Viable C. albicans counts and histopathological analyses demonstrated a significant protective effect for Hst-5 on mouse oral tissue against C. albicans. More importantly, host saliva exerted a comparable anticandidal effect. However, this effect was neutralized upon treatment of saliva with proteases and C. albicans, previously shown to degrade Hst-5, indicating that Hst-5 is likely the salivary component responsible for the observed protection. Combined, the findings from this study demonstrate for the first time the efficacy of salivary Hst-5 in protecting host oral tissue against C. albicans infection, thereby affirming the therapeutic potential of this natural host peptide. [source] Factor V deficiency: a concise reviewHAEMOPHILIA, Issue 6 2008J. N. HUANG Summary., Factor V (FV; proaccelerin or labile factor) is the plasma cofactor for the prothrombinase complex that activates prothrombin to thrombin. FV deficiency can be caused by mutations in the FV gene or in genes encoding components of a putative cargo receptor that transports FV (and factor VIII) from the endoplasmic reticulum to the Golgi. Because FV is present in platelet ,-granules as well as in plasma, low FV levels are also seen in disorders of platelet granules. Additionally, acquired FV deficiencies can occur in the setting of rheumatologic disorders, malignancies, and antibiotic use and, most frequently, with the use of topical bovine thrombin. FV levels have limited correlation with the risk of bleeding, but overall, FV-deficient patients appear to have a less severe phenotype than patients with haemophilia A or B. The most commonly reported symptoms are bleeding from mucosal surfaces and postoperative haemorrhage. However, haemarthroses and intramuscular and intracranial haemorrhages can also occur. Because no FV-specific concentrate is available, fresh frozen plasma remains the mainstay of treatment. Antifibrinolytics can also provide benefit, especially for mucosal bleeding. In refractory cases, or for patients with inhibitors, prothrombin complex concentrates, recombinant activated FVIIa, and platelet transfusions have been successfully used. Some patients with inhibitors may also require immunosuppression. [source] Four Modes of Adhesion are Used During Helicobacter pylori Binding to Human Mucins in the Oral and Gastric NichesHELICOBACTER, Issue 2 2008Sara K. Lindén Abstract Background:,Helicobacter pylori causes peptic ulcer disease and gastric cancer, and the oral cavity is likely to serve as a reservoir for this pathogen. We investigated the binding of H. pylori to the mucins covering the mucosal surfaces in the niches along the oral to gastric infection route and during gastric disease and modeled the outcome of these interactions. Materials and Methods:, A panel of seven H. pylori strains with defined binding properties was used to identify binding to human mucins from saliva, gastric juice, cardia, corpus, and antrum of healthy stomachs and of stomachs affected by gastritis at pH 7.4 and 3.0 using a microtiter-based method. Results:,H. pylori binding to mucins differed substantially with the anatomic site, mucin type, pH, gastritis status, and H. pylori strain all having effect on binding. Mucins from saliva and gastric juice displayed the most diverse binding patterns, involving four modes of H. pylori adhesion and the MUC5B, MUC7, and MUC5AC mucins as well as the salivary agglutinin. Binding occurred via the blood-group antigen-binding adhesin (BabA), the sialic acid-binding adhesin (SabA), a charge/low pH-dependent mechanism, and a novel saliva-binding adhesin. In the healthy gastric mucus layer only BabA and acid/charge affect binding to the mucins, whereas in gastritis, the BabA/Leb -dependent binding to MUC5AC remained, and SabA and low pH binding increased. Conclusions:, The four H. pylori adhesion modes binding to mucins are likely to play different roles during colonization of the oral to gastric niches and during long-term infection. [source] Peptide antibiotic human beta-defensin-1 and ,2 contribute to antimicrobial defense of the intrahepatic biliary treeHEPATOLOGY, Issue 4 2004Kenichi Harada Human beta-defensins (hBDs) are important antimicrobial peptides that contribute to innate immunity at mucosal surfaces. This study was undertaken to investigate the expression of hBD-1 and hBD-2 in intrahepatic biliary epithelial cells in specimens of human liver, and 4 cultured cell lines (2 consisting of biliary epithelial cells and 2 cholangiocarcinoma cells). In addition, hBD-1 and hBD-2 were assayed in specimens of bile. hBD-1 was nonspecifically expressed immunohistochemically in intrahepatic biliary epithelium and hepatocytes in all patients studied, but expression of hBD-2 was restricted to large intrahepatic bile ducts in 8 of 10 patients with extrahepatic biliary obstruction (EBO), 7 of 11 with hepatolithiasis, 1 of 6 with primary biliary cirrhosis (PBC), 1 of 5 with primary sclerosing cholangitis (PSC), 0 of 6 with chronic hepatitis C (CH-C), and 0 of 11 with normal hepatic histology. hBD-2 expression was evident in bile ducts exhibiting active inflammation. Serum C reactive protein levels correlated with biliary epithelial expression of hBD-2. Real-time PCR revealed that in all of 28 specimens of fresh liver, including specimens from patients with hepatolithiasis, PBC, PSC, CH-C and normal hepatic histology, hBD-1 messenger RNA was consistently expressed, whereas hBD-2 messenger RNA was selectively expressed in biliary epithelium of patients with hepatolithiasis. Immunobloting analysis revealed hBD-2 protein in bile in 1 of 3 patients with PSC, 1 of 3 with PBC, and each of 6 with hepatolithiasis; in contrast, hBD-1 was detectable in all bile samples examined. Four cultured biliary epithelial cell lines consistently expressed hBD-1; in contrast these cell lines did not express hBD-2 spontaneously but were induced to express hBD-2 by treatment with Eschericia coli, lipopolysaccharide, interleukin-1, or tumor necrosis factor-,. In conclusion, these findings suggest that in the intrahepatic biliary tree, hBD-2 is expressed in response to local infection and/or active inflammation, whereas hBD-1 may constitute a preexisting component of the biliary antimicrobial defense system. Supplementary material for this article can be found on the Hepatology website (http:/interscience.wley.com/jpages/0270,9139/suppmat/index.html). (Hepatology 2004;40:925-932). [source] Session 7: Innate and adaptive immune responses to microbes at mucosal surfacesIMMUNOLOGY, Issue 2007Article first published online: 8 FEB 200 First page of article [source] Lactoferrin decreases pollen antigen-induced allergic airway inflammation in a murine model of asthmaIMMUNOLOGY, Issue 2 2006Marian L. Kruzel Summary Pollen grains contain reduced nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidases and in contact with mucosal surfaces generate superoxide anion (O2,,). In the presence of iron, O2,, may be converted to more reactive oxygen radicals, such as to H2O2 and/or ,OH, which may augment antigen-induced airway inflammation. The aim of the study was to examine the impact of lactoferrin (LF), an iron-binding protein, on ragweed (Ambrosia artemisiifolia) pollen extract (RWE)-induced cellular oxidative stress levels in cultured bronchial epithelial cells and accumulation of inflammatory and mucin-producing cells in airways in a mouse model of allergic airway inflammation. Results show that LF lowered RWE-induced increase in cellular reactive oxygen species (ROS) levels in bronchial epithelial cells. Most importantly, LF significantly decreased accumulation of eosinophils into airways and subepithelium of intranasally challenged, sensitized mice. LF also prevented development of mucin-producing cells. Amb a 1, the major allergenic ragweed pollen antigen lacking NAD(P)H oxidase activity, induced low-grade airway inflammation. When administered along with glucose oxidase (G-ox), a superoxide-generating enzyme, Amb a 1 induced robust airway inflammation, which was significantly lowered by LF. Surprisingly, LF decreased also inflammation caused by Amb a 1 alone. Iron-saturated hololactoferrin had only a marginal effect on RWE-induced cellular ROS levels and RWE- or Amb a 1 plus G-ox-induced inflammation. We postulate that free iron in the airways chemically reduces O2,, to more reactive species which augment antigen-induced inflammation in a mouse model of asthma. Our results suggest the utility of LF in human allergic inflammatory disorders. [source] Characterization of cells of the B lineage in the human adult greater omentumIMMUNOLOGY, Issue 1 2006Laurent Boursier Summary Peritoneal B cells and their omental precursors play an important role in the immune response of the peritoneal cavity and mucosal surfaces in mice. We have previously shown that peritoneal and mucosal B lineage cells are unlikely to be significantly linked in humans. However, the status of the omentum remains unknown. Here, using immunohistochemistry, we observed that sparse, quiescent B cells and occasional clusters of B cells were present in the omentum and that plasma cells, predominantly with cytoplasmic immunoglobulin G (IgG), were present. We analysed sequences of immunoglobulin genes amplified using reverse transcriptase,polymerase chain reaction (RT-PCR) from the normal human greater omentum, and describe the characteristics of variable region genes used by IgG, IgA and IgM. We focused on the properties of IgVH4 and IgVH5 families to allow comparisons of like with like between different Ig isotypes and cells from different immune compartments. We observed that the IgM genes were derived from a mixed population with mutated and unmutated immunoglobulin sequences. All IgVH4 and IgVH5 genes used by IgA and IgG from omental cells showed evidence of somatic hypermutation but the load of mutations was not significantly different to that seen in either the systemic or the mucosal compartments. The trends observed, including the dominance of IgG plasma cells, the IgA1/IgA2 ratio being biased towards IgA1, JH1 usage, and a moderate level of somatic mutations, link omental B lineage cells with the systemic compartment. These observations reinforce previous studies highlighting the difference between human and murine B-cell compartments and their relationship to the mucosal immune system. [source] Hereditary benign telangiectasia: first case in IranINTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 7 2006Zari Javidi A 14-year-old boy was referred to the Dermatology Clinic of the Medical University of Mashhad, Iran, with numerous cutaneous telangiectasias on the face, ears, lips, and back of the hands, with lesions in the temporal region being the first to appear (Figs 1,3). His mother stated that the lesions had been present for 10 years with an increase in the past 6 months. He had no history of bleeding from the nose, mouth, gastrointestinal tract, and other mucosal surfaces, and there was no sign of organ involvement. On inspection, no lesions were detected on the nasal mucosa, external ear, over the tympanic membrane, or mouth. Figure 1. Numerous telangiectasias affecting the cheeks, nose, and perioral areas Figure 2. Lateral view of Fig. 1 Figure 3. Telangiectasias affecting the dorsal aspect of the hands The patient is one member of a family of six. His mother is healthy, but similar lesions were seen in his father, sister and one of his brothers with similar distributions. Lesions were also seen in his aunt and paternal grandmother, showing disease distribution in six members of this family from three generations. The oldest brother is 20 years of age and mentioned the onset of disease from the age of 10 years. The sister is 18 years of age and lesions started to appear 7 years ago; she claims that the lesions regress during her menstrual period. The youngest brother is 4 years of age and shows no sign of cutaneous lesions as yet. The parents are not consanguineous. Generalized telangiectasia with a predominant distribution on light-exposed skin, an autosomal dominant inheritance, and no sign of systemic or mucosal involvement and bleeding disorders indicates a diagnosis of hereditary benign telangiectasia. Our patient did not consent to biopsy. [source] | ||||||||||||||||||||||||||||||||||