Airway hyperresponsiveness was tested by provocation with increasing doses of MCh aerosol and according to ethics approval provocation was terminated once an animal had reached the ED200 or above. Dried aerosols were generated by a computer-controlled aerosol generator system (Bronchy III+feedback dose control system, Fraunhofer Institute, Hannover,

Germany). All values are expressed as mean+SEM. Statistical analysis was performed using one-way ANOVA (Bonferroni post hoc test) or Mann–Whitney U-test using PRISM 4 (GraphPad, La Jolla, CA, USA). A p-value <0.05 was considered as statistically significant. The authors thank Karin Westermann and Marion Hitzigrath for their excellent technical assistance. We acknowledge the excellent technical assistance of the members of the Hannover Medical School Core Facility for Cell Sorting and would like to thank

Shahzad N. Syed Selisistat concentration for providing the Fc RIV-specific RT-PCR primers. We especially thank Heinz-Gerd Hoymann for the lung function measurements. We thank Rachel Thomas for carefully editing and improving the manuscript. This work was supported by Deutsche Forschungsgemeinschaft SFB 587 (B5), a grant of StrucMed to M.M., a grant of GK1441 to J.K.K., and partially by a grant from the Excellence Cluster “From Regenerative Biology to Reconstructive buy AUY-922 Therapy” (German Research Foundation) to G.M.N.B. Conflict of interest: The authors declare no financial or commercial conflict on interest.

“
“A critical component of vaccine design is to generate and maintain antigen-specific memory lymphocytes of sufficient quantity and quality to give the host life-long protection against re-infection. Therefore, it is important to understand how memory T cells acquire the ability for self-renewal while retaining a potential for heightened recall of effector functions. During acute viral infection or following vaccination, antigen-specific T cells undergo extensive phenotypic and functional changes during differentiation to the effector and memory phases of the immune response. The changes in cell phenotype that accompany memory T-cell differentiation are predominantly Diflunisal mediated through acquired transcriptional regulatory mechanisms, in part achieved through epigenetic modifications of DNA and histones. Here we review our current understanding of epigenetic mechanisms regulating the off-on-off expression of CD8 and CD4 T-cell effector molecules at naive, effector and memory stages of differentiation, respectively, and how covalent modifications to the genome may serve as a mechanism to preserve ‘poised’ transcriptional states in homeostatically dividing memory cells. We discuss the potential of such mechanisms to control genes that undergo on-off-on patterns of expression including homing and pro-survival genes, and the implications on the development of effector-memory and central-memory T-cell differentiation.

We also developed a bioinformatics method to predict pMHC-I stability, which suggested that 30% of the nonimmunogenic binders hitherto classified as “holes in the T-cell repertoire” can be explained as being unstably

bound to MHC-I. Finally, we suggest that nonoptimal anchor residues in position 2 of the peptide are particularly prone to cause unstable interactions BGB324 mouse with MHC-I. We conclude that the availability of accurate predictors of pMHC-I stability might be helpful in the elucidation of MHC-I restricted antigen presentation, and might be instrumental in future search strategies for MHC-I epitopes. Major histocompatibility complex class I (MHC-I) plays a pivotal role in the generation of specific immune responses mediated

by cytotoxic T lymphocytes (CTLs). MHC-I molecules sample peptides derived from intracellular proteins, translocate them to the cell surface, and display them to CTLs, allowing immune scrutiny of the ongoing intracellular metabolism leading to the detection of the presence of any intracellular pathogens. To fulfill this crucial antigen presenting function, MHC-I molecules must be endowed with the ability to retain bound peptides at the cell surface while waiting for the arrival of rare circulating CTL clones of the appropriate specificity. Sustained presentation at the cell surface and induction of specific immune T-cell responses therefore requires

some LY294002 mouse degree of pMHC-I stability. Indeed, it has been claimed that stability, rather than affinity, of pMHC-I complexes is the better correlate of immunogenicity and immunodominance [[1-5]]. Experimentally, however, affinity remains the most frequently DNA ligase established correlate of immunogenicity. Thus, when Assarsson et al. [[6]] recently conducted a quantitative analysis of the variables affecting the repertoire of T-cell specificities recognized after vaccinia virus infection, they found that the vast majority of epitopes (85%) bound their restricting allele with an affinity of 500 nM or better, and most (75%) bound with an affinity of 100 nM or better. Investigating the stability of pMHC-I complexes for a small sample of immunogenic and nonimmunogenic peptides, they found a suggestive, but not statistically significant, trend for off-rates and immunodominance being correlated. The authors concluded that “in our hands, peptide stability did not correlate significantly better with immunodominance than did equilibrium binding measurements”. One reason why pMHC stability has not been addressed more extensively undoubtedly relates to the cumbersome and/or low-throughput nature of current biochemical methods used to measure the dissociation of pMHC complexes [[6-12]]. A particularly interesting dissociation assay developed by Parker et al.

By definition, the ACR is dependent on albumin and creatinine excretion rates. The influence of age and sex on 24 h

urinary creatinine is well established. For example, one large population-based Belgian study of over 4000 people (26–60 years) demonstrated significantly lower creatinine excretion in females and significant negative correlation of 24 h urinary creatinine excretion with age.11 Therefore, increases in ACR with age can be explained Small molecule library high throughput in part by the age related changes in AER and 24 h urinary creatinine excretion observed in both males and females. Normal ageing is characterized by a progressive decline in skeletal muscle mass and increase in body fat composition. Other age related factors that may influence ACR include the decline in skeletal muscle mass between the 20–80 years of age, which has been estimated to range from 22% to 40%,84,85 a decrease in the proportion of muscle in lean body mass85 and a lower meat intake in older subjects.81 Bakker71 has proposed the use of age-specific cut off values for ACR to help restrict the number of people selected for follow up with timed urine collections. In this large study (n > 2300) an increase in the ACR cut-off for each decade, from age group <50

to >70 years, was required to maintain equivalent sensitivities and specificities in each age subgroup. However, the use of both gender and age-specific cut off values for ACR may be confusing and impractical. The clinical importance of an age-related increase in ACR is an increased false positive rate in older patients (e.g. decreased specificity). Using the recommended cut off values, the age-related increase in false positive rates Sirolimus datasheet for spot ACR was approximately 30% for patients of either sex over 65 years limits.79 Table A4 presents a summary of studies (including those discussed above) that

provide evidence in relation to the use of AER and ACR PTK6 for the screening and diagnosis of albuminuria. Included in the table is a summary of the key components of the cross sectional studies relevant to assessment of diagnostic accuracy. Where reported the sensitivity and specificity is shown along with the key conclusions made by the authors. It should be noted that only a few of the studies provided PPV and NPV values. Estimation of GFR (eGFR) based on serum creatinine is a pragmatic, clinically relevant approach to assessing kidney function in people with type 2 diabetes (Level III – Diagnostic Accuracy). The CG and the MDRD formulas for the estimation of GFR were developed predominantly in individuals without diabetes. Studies involving people with type 2 diabetes, are summarized in Table A5 and are generally consistent with the findings for the large number of studies in non diabetes populations.46 Nonetheless, the study by Walser86 questioned the acceptability of the CG and MDRD equations for monitoring kidney function in individuals with type 2 diabetes.

The results of cytokine secretion (pg/mL) were statistically analyzed for significant differences between spontaneous secretion and secretion in response to various antigens using the Mann-Whitney U-test. P-values of <0.05 were considered significant. Spontaneous secretion of various cytokines by PBMCs of TB patients in the

absence of exogenously added mycobacterial antigens varied considerably, both with respect to the percentages of donors Selleck LDK378 secreting detectable concentrations of various cytokines, as well as their absolute concentrations. For example, detectable concentrations of IL-6 and IL-8 were secreted by PBMCs from all patients, whereas detectable concentrations of IL-2 and IL-10 were secreted by PBMCs from <50% of patients (Fig. 1a–c). With respect to the absolute concentrations of each cytokine secreted

into the culture supernatants, the median concentration was highest for IL-8 (5157 pg/mL), followed by IL-6 (225 pg/mL), IL-5 (157 pg/mL), TNF-α (112 pg/mL), IL-4 (51 pg/mL), IFN-γ (18 pg/mL), TNF-β (10 pg/mL), IL-1β (14 pg/mL), IL-10 (<6.9 pg/mL), and IL-2 (<8.9 pg/mL) (Fig. 1a–c). Spontaneous secretion of one or more Th1 and Th2 cytokines by PBMCs was observed in the majority (60% and 94%, respectively) of TB patients included in the study (Fig. 1b,c). Quantitation of proinflammatory cytokines in supernatants obtained from cultures with exogenously added mycobacterial antigens and pools of RD-peptides showed that only complex mycobacterial antigens induced secretion of IL1-β and TNF-α (Fig. 2a,c) (P < 0.05), and that relatively greater amounts of

these FK506 datasheet cytokines were secreted in response to whole-cell mycobacteria and MT-CW than MT-CF (P < 0.05). Moreover, all the complex mycobacterial antigens and peptide pools of RDs stimulated secretion of IL-6 (Fig. 3a,b), whereas, none of the mycobacterial antigens or RD peptides induced secretion of IL-8 (Fig. 3c,d). With respect to Th1 and Th2 cytokines, none of the mycobacterial antigens or peptide pools showed antigen-induced secretion of Th1 cytokine IL-2 (E/C < 2, P > 0.05) (Fig. 4a,b), whereas TNF-β was secreted in response to whole-cell M. tuberculosis, to MT-CF and MT-CW and peptide pools of RD1, RD6 and RD13 (Fig. 4c,d). Secretion of Th2 cytokines IL-4 and IL-5 was not detected in response to any of the complex mycobacterial antigens and RD peptides (E/C < 2, P > 0.05) (Fig. 5), except for weak IL-5 secretion (E/C = 2.6) in response to RD13 (Fig. 5d). Furthermore, antigen-induced secretion by PBMCs of IFN-γ and IL-10 was observed in response to all the preparations of complex mycobacterial antigens (E/C = 15 to 251, P < 0.05, Fig. 6a,c). However, variations in the concentrations of secreted IFN-γ and IL-10 were observed, MT-CF inducing the highest concentration of IFN-γ and the lowest concentration of IL-10 (P < 0.05), with an IFN-γ:IL-10 ratio of 14.5.

While G4-stimulated cells showed high Akt inhibitor expression, R848-APC had a reduced number of MHC class II molecules, which could explain their low stimulatory potency. However, since PD-L1 is correlated with tolerance induction 32, we also tested, whether

PD-L1-dependent signaling contributes to the weak T-cell proliferation observed. Blockade of PD-L1 was effective to enhance T-cell proliferation in the presence of R848-APCs (Fig. 3C). Thus, reduced MHC class II expression and upregulation of PD-L1 are characteristics for TLR-APCs and their changed functional capacities. To further analyze the mechanisms of induction of the tolerogenic APC phenotype, we next analyzed release of cytokines upon initial TLR trigger. APCs generated in the presence of R848 secreted high amounts of pro-inflammatory cytokines (IL-6, TNF and IL-12p40) as well as immunosuppressive cytokines (IL-10) (Fig. 4A–D). Secretion of IL-6 was remarkably high (Fig. 4A). In order to determine whether auto- or paracrine active cytokines directly mimic the effect of R848 we added cytokines alone or cytokine mixtures to G4-stimulated cell cultures. While single addition of cytokines (IL-6 or IL-10) only partially induced the TLR-APC phenotype, a combination of both was almost similar effective to stimulation

with R848 (Supporting Information Fig. 4). In order ABT737 to further define the signal requirement for induction of TLR-APCs, we analyzed the pattern of MAPKs, known to be involved in TLR-mediated cytokine release 33. MAPKs are in addition important for differentiation processes. It was striking that the pattern of MAPK activation was clearly different between R848-APCs and conventional iDCs. Each MAPK exhibited a special pattern of activation (Fig. 5A): differentiation of monocytes in the presence of G4 and R848 showed an early

and prolonged phosphorylation of p38, whereas in G4-generated cells p38 phosphorylation was only detectable within the first 30 min. The activation pattern of p44/42 differed completely from p38 phosphorylation. p44/42 phosphorylation was only visible during the initial 15 min in R848-APCs and in contrast for 24 h in iDCs. Phosphorylation of SAPK/JNK was only detectable in R848-APCs and only for a short period. Inhibition of the two MAPK pathways (p38, p44/42) with pharmacological p38 (SB203580, SB) and p44/42 inhibitors all (UO126, UO) resulted in markedly reduced secretion of IL-6 (Fig. 5B) and IL-10 (Fig. 5C), at least when both MAPKs p38 and p44/p42 were blocked. Similar results were obtained when the cells were stimulated with LPS plus G4 (data not shown). IL-12p40 release in contrast was not diminished (Fig. 5D) but even slightly increased. The reduced cytokine release after MAPK inhibition correlated with reduced surface expression of CD14 and PD-L1. FACS analyses revealed that preservation of CD14 expression was blocked almost completely by the addition of SB and UO (Fig. 6A).

8% in 2008).[16] In the Australian dialysis population, infection accounted for 11% of mortality, the third most common cause of death following dialysis withdrawal (35%) and cardiac disease (43%)[17] Of the 11% (n = 148), approximately 25% was secondary to bacterial septicaemia. Similarly, 17% of mortality was attributed to infection in the New Zealand dialysis population. CRI has an enormous adverse impact, not only at individual level of increased morbidity and mortality, but also financial implications with the costs of hospital admissions, antibiotics use and catheter change. Cost-per-infective-episode has been estimated to be between US$3703 and US$29 000 in the USA from non-tunnelled catheters in intensive care

units.[18] With the high incidence of catheter use in incident haemodialysis patients, it is imperative to develop strategies to prevent Selleckchem 5-Fluoracil and treat CRI. There have been studies examining the application of topical agents to the exit site to prevent both local and systemic infections. Intense interests have been concentrating on the use of antimicrobial lock solutions (ALS) to reduce CRI in recent years. Once bacteraemia has occurred, catheter removal, with or without delay in insertion of a new vascular catheter, is often indicated. Alternative therapy such as combining systemic antibiotics and ALS, without changing the catheter, has been evaluated in the literature. The objective of this guideline is to identify appropriate recommendations for central Opaganib in vitro venous catheter insertion and catheter care, as well as prevention and treatment of CRI in dialysis patients with tunnelled catheters in-situ. Dressing type, frequency of dressing changes and cleansing solutions will be addressed. The use of topical agents or intraluminal lock solutions will be investigated as will be the various treatment strategies for CRI. The use of real-time ultrasound guidance is strongly recommended for the placement of haemodialysis catheters and results in improved rates of successful catheter

placement, and reduced rates of both haematoma formation and inadvertent arterial puncture. (Level 1 evidence) (Suggestions are based on Level III and IV evidence) The adherence to strict aseptic technique is proven to reduce the catheter related bacteraemia rate and all units should therefore audit this practise. Tunnelled haemodialysis DCLK1 catheters should be used as they are associated with lower rates of catheter related bacteraemia, catheter dysfunction and vascular damage (venous trauma, and stenosis) compared with temporary non-tunnelled catheters. The right internal jugular vein is the preferred insertion site with respect to ease of access and lower rates of short and long-term complications. In ICU settings, subclavian catheter placement has excellent short-term outcomes compared with jugular and femoral approaches but has significant long-term sequelae recommending against their use.

Other indirect evidence also supports the concept that the in vivo effect of insulin is determined, at least in part, by insulin’s own effect to reach metabolically active tissues by changing local blood flow distribution

patterns. Recently, the effects of systemic insulin infusion on transport and distribution kinetics of the extracellular marker, [14C]inulin, were studied in an animal model that allowed access to hindlimb lymph, a surrogate for interstitial fluid [27]. Insulin, at physiological concentrations, augments the access of the labeled inulin to insulin-sensitive tissues. In addition, access of macromolecules to insulin-sensitive tissues is impaired during diet-induced insulin resistance [26]. The presented data suggest that insulin redirects blood flow from non-nutritive vessels to nutritive capillary beds, resulting in an increased and more homogeneous overall capillary selleck chemicals llc perfusion termed “functional capillary recruitment.” The latter would enhance the access of insulin and glucose to a greater mass of muscle for metabolism. Consistent with such a mechanism in humans, insulin increases microvascular blood volume as measured with CEU or positron emission tomography, and concomitantly enhances the distribution

volume of glucose in human muscle [6,7,14]. Subsequently, capillary recruitment selleck kinase inhibitor was reported in the forearm of healthy humans following a mixed meal and was found to follow closely the time-dependent rise in plasma insulin [112]. In addition, insulin-mediated microvascular recruitment in the forearm was shown to be impaired in obese women when they were exposed to a physiological insulin clamp [16]. By directly visualizing capillaries in human skin, it has been demonstrated that systemic hyperinsulinemia is capable of increasing the number of perfused capillaries [22,100]. Comparable to insulin-mediated microvascular recruitment in the forearm [16], the action of insulin on capillary recruitment is impaired in obese subjects [21,22]. Further insight

into the complex relationships among vasodilatation, blood flow velocity, and capillary recruitment was gained through measurement of the capillary permeability-surface area PS for glucose and insulin. PS for a substance describes its capacity to reach the interstitial fluid. This depends on the permeability and the capillary surface of area, of which the latter in turn partly depends on the amount of perfused capillaries. A recent investigation employing direct measurements of muscle capillary permeability showed that PS for glucose increased after an oral glucose load, and a further increase was demonstrated during an insulin infusion [38]. Importantly, the increase of PS was exerted without any concomitant change in total blood flow. It was concluded that the insulin-mediated increase in PS seen after oral glucose is important for the glucose uptake rate in normal muscle [38].

At each survey, a single blood sample was obtained by finger prick (approximately 0·3 mL) for thick and thin blood films, filter paper blood collection (Whatman 3, Maidstone, UK), Haemoglobin test (HemoCue photometer) and for a Rapid Diagnostic Tests (RDT; Orchid Biomedical Systems, Goa, India) for malaria.

Filter papers were air-dried and stored in plastic bags with silica desiccant (silica gel type III; Sigma, Dorset, UK) and stored at −20°C. Plasma was see more diluted 1 : 1 in 0·1% sodium azide in PBS (reaching a final concentration of 0·05%). Individuals were followed up for 6 months by passive case detection with those who experienced a clinical malaria attack (temperature >37·5°C with parasites at any density) treated according to national treatment guidelines. Parasites were detected using three methods; microscopy, RDT and PCR. For microscopy, 100 fields of a Giemsa stained thick blood film were examined during the surveys, and at

all occasions, when a clinical malaria episode was suspected, RDTs (RDT; Orchid Biomedical Systems) were used for immediate detection of infection in the field. For PCR, DNA was extracted from filter paper samples using the QIAamp DNA mini kit (QIAGEN, Hilden, Germany), parasite detection carried out by nested-PCR amplification of the small subunit ribosomal RNA (rRNA) gene [16]. Immunoglobulin G (IgG) antibodies Quizartinib in vivo were assayed by ELISA, as described previously [14, 17]. Recombinant P. falciparum apical membrane antigen (AMA-1 FVO, provided by Takafumi Tusboi, Ehime PJ34 HCl University, Japan), merozoite surface protein 119 (MSP-119 Wellcome allele,

provided by Patrick Corran, London School of Hygiene & Tropical Medicine with permission of Tony Holder), merozoite surface protein 2 (MSP-2, Dd2 allele provided by David Cavanagh, Institute of Immunology and Infection Research, Edinburgh, UK), circumsporozoite protein (CSP; NANP16 peptide, provided by Patrick Corran, London School of Hygiene & Tropical Medicine) and Anopheles gambiae salivary antigen (gSG6 provided by Bruno Arcà, Sapienza University, Rome, Italy) were coated onto ELISA plates overnight at 4°C at a concentration of 1.25 ug/mL for AMA1, 5 μg/mL for gSG6 and 0.5 μg/mL for all the other antigens. Plates were washed using PBS plus 0·05% Tween 20 (PBS/T) and blocked with 1% (w/v) skimmed milk powder (Marvel, UK) in PBS/T. Serum samples were added in duplicate to each plate at a serum dilution of 1 : 400 for CSP, 1 : 2000 for AMA-1, 1 : 1000 for MSP-2 and MSP-119, and 1 : 100 for gSG6 in 1% bovine serum albumin (BSA) in PBS/T. A positive control of pooled hyperimmune serum collected from adults resident in a malaria endemic area was included in duplicates on each plate in a 4-fold serial dilution from 1 : 50 to 1/51 200 (6 concentrations in total) to allow standardization of day-to-day and plate-to-plate variation.

27 Accordingly, monocytes/macrophages should be considered as an important source of increased levels of CGRP in serum during sepsis and in inflamed tissues (in addition to CGRP containing sensory nerve terminals innervating inflamed tissues and blood vessels). Increased CGRP levels in inflamed tissues play an important role in neurogenic inflammation as well

as in immune responses initiated by immune cells.2 Based on the literature, the role of CGRP in the development of immune and inflammatory responses could be either facilitating or suppressing depending on the dynamics of immune and inflammatory process. Concentration-dependent regulation of the production of pro-inflammatory and anti-inflammatory mediators by CGRP might underlie the positive or negative role of CGRP in immune and inflammatory ABT-263 manufacturer responses (see discussion below). In the present study, we explored further the inflammatory mediators that LDK378 in vivo are possibly involved in LPS-induced CGRP synthesis in RAW macrophages. We found that the NGF sequester (NGF receptor Fc chimera) is able to suppress LPS-induced CGRP release from RAW macrophages, suggesting a role for this neurotrophin in the up-regulation

of CGRP induced by LPS. This hypothesis is consistent with previous reports showing that NGF is involved in LPS-induced synthesis of CGRP in human B lymphocytes and monocytes.7,9 Moreover, NGF and its receptors are induced in human monocytes28 and rat microglia29 following LPS treatments. As shown earlier,11–13 and in the current study as well, LPS (1 μg/ml) dramatically increased the release of IL-1β and IL-6 from RAW macrophages. It has previously been shown that IL-1β acts as a potent inducer of CGRP in various types of cells16,17 and IL-6 facilitates the release Protein kinase N1 of CGRP from nociceptive sensory terminals in the skin.18 We observed here that neutralizing antisera against IL-1β and IL-6 are able to suppress

LPS-induced CGRP release, suggesting that these two cytokines can regulate the synthesis of CGRP in RAW macrophages. Although here we did not explore the role of TNFα in LPS-induced CGRP release, this cytokine is also likely to be involved because it has been shown to stimulate the synthesis of CGRP in trigeminal ganglion neuron cultures.19 Exogenous CGRP enhanced LPS-induced release of IL-1β, IL-6 and TNFα concentration-dependently (the present study). Accordingly, the three cytokines and CGRP may have reciprocal facilitating effects on their synthesis. Such a mechanism would enable the rapid establishment of networks of inflammatory mediators required during inflammatory responses. A selective COX2 inhibitor NS-398 was also able to suppress LPS-induced CGRP release, suggesting a role for COX2-derived prostanoids in our model.

This discovery transformed the management of two chronic relapsing conditions from maintenance symptomatic therapies, and in some cases surgery, to curative treatment with targeted antibiotics. The possibility

that infections by other organisms from the genus Helicobacter are implicated in the pathogenesis of other human diseases is a tantalizing one. The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), demonstrate many similarities to gastric and duodenal ulceration before the discovery of H. pylori, including unexplained onset in previously healthy hosts, a chronic relapsing disease course with no curative treatments, chronic gastrointestinal inflammation ALK inhibitor and predisposition to malignant change. In this review, we shall consider the evidence supporting Helicobacter spp. as the pathogenic agents in IBD. We will discuss the relative incompatibility of H. pylori disease MAPK Inhibitor Library supplier and IBD, highlighted by the apparent protective effect of prior H. pylori infection on IBD disease risk. We shall review animal variants of IBD, which are both initiated by and associated with Helicobacter spp. infection. We will then review

the Helicobacter organisms associated with human gastrointestinal disease and the molecular evidence for Helicobacter organisms in human IBD. For the purpose of clarity, Helicobacter organisms associated primarily with gastritis or Methamphetamine biliary disease are not covered within this article. More than 30 Helicobacter organisms have been described to date (see Fig. 1), but only H. pylori has been

proven to cause human disease. It is inconceivable that H. pylori is the only human pathogen within such a broad genus, and as described below, other candidates are already being investigated. IBD comprises two main conditions: CD and UC. The onset of both conditions occurs at all ages, but with a bimodal distribution with peaks in the late teenage/early adult years (particularly CD) and in late adulthood (particularly UC) (Koehoorn et al., 2006). CD is characterized by transmural inflammation of the gastrointestinal tract at any site from mouth to anus. The disease can affect the mucosa in continuity or include healthy areas between affected sites leading to so-called ‘skip lesions’. Such skip lesions are characteristic of CD and, in addition to the hallmark granuloma on biopsy, they are utilized in differentiating CD from UC. UC affects only the mucosal layer of the gastrointestinal tract and extends in continuity proximally from the rectum (Lennard-Jones, 1989). In UC, the colon is involved exclusively, although ‘backwash’ ileitis can be a feature of extensive disease. The aetiology of both conditions is poorly understood, but genetic, immunological and environmental factors all play a role.