Such a hypothesis has limited theoretical immunological support

Such a hypothesis has limited theoretical immunological support. Transplant immunology is complex, and as our arsenal of highly specific immunosuppressant and immunomodulating medications integrated into clinical practice increase, the occurrence of unusual and seemingly paradoxical reactions, although uncommon, will likely continue to present management challenges. We emphasize the importance of careful clinical assessment, vigilance with exclusion of infection, R428 and wide consultation with specialist services and medical literatures when faced with unexpected and unexplained adverse

events after transplantation. “
“To report the kidney transplant activity and survival data during the past 25 years from the Thai Transplant Registry. By using the registry database that was collected and updated yearly by 26 transplant centres across the country, we Fulvestrant cost have reported the donor, recipient, and transplant characteristics during the past 25 years from 1987 to 2012. The primary outcome was graft loss

that was defined as return to dialysis, graft removal, retransplant, or patient death. 465 kidney transplants were performed in 2012, an 8.1 percent and 23.0 percent increase in living and deceased donor transplants compared to the previous year, respectively. Between 1987 and 2012 with the data of 3,808 recipients, patient survival and graft survival improved significantly. Traffic accident was the most common cause of death in brain-dead donors. Additionally, the most common cause of end-stage kidney disease was glomerulonephritis.

Infection has been among the most common causes of death in kidney transplant recipients. We have reported the total number, the graft and the patient survival data of kidney transplant recipients in Thailand for the period from 1987 to 2012. Although the number of patients is much lower than that in the developed countries, the patients and the graft survival rates are comparable. “
“Aim:  The percentage of people Anacetrapib in Australia who undertake home dialysis has steadily decreased over the past 40 years and varies within Australia. Consumer factors related to this decline have not previously been determined. Methods:  A 78-question survey was developed and piloted in 2008 and 2009. Survey forms were distributed to all adult routine dialysis patients in all Australian states and territories (except Northern Territory) between 2009 and 2010. Of 9223 distributed surveys, 3250 were completed and returned. Results:  49% of respondents indicated they had no choice in the type of dialysis and 48% had no choice in dialysis location. Respondents were twice as likely to receive information about haemodialysis (85%) than APD (39%) or CAPD (41%). The provision of education regarding home modalities differed significantly between states, and decreased with increasing patient age.

3E) These data indicated that the activated phenotype of NK cell

3E). These data indicated that the activated phenotype of NK cells was determined by MHC class I down-regulation

rather than by NKG2D-L levels expressed on early-stage tumors. Nevertheless, the higher MHC class I and lower NKG2D-L expression levels found in late tumor stages suggested that both, MHC class I MK-2206 cost recovery and loss of NKG2D-L, may provide mechanisms of immune escape. To directly test the role of NKG2D-L loss in immune escape, we established cell lines from lymphoma-bearing mice with reduced MHC class I expression and selected variants with different NKG2D-L levels. Cell line myc-E showed background levels of NKG2D-L. In contrast, cell line myc-B had a 20-fold enhanced expression of NKG2D-L (Fig. 4A). After transfer into naïve WT mice, the myc-B line grew out slowly PLX-4720 nmr and was even rejected in 50% of the animals. In contrast, all mice injected with myc-E cells rapidly succumbed to tumor growth (Fig. 4B). Importantly, when NKG2D-L on myc-B cells were blocked with NKG2D multimers

prior to injection, protection was lost, and mice died as rapidly as those receiving the myc-E line. Protection against myc-B was also abrogated by NK-cell depletion (Fig. 4B). The data show that in these cell lines showing low MHC class I levels, expression of NKG2D-L is a signal that is required for NK cell-mediated elimination of tumor cells. To test the hypothesis that tumor escape from NK-cell surveillance results from re-expression of MHC class I and from suppression of NKG2D-L, we analyzed the outgrowing lymphomas in mice having received cell line myc-B. Indeed, the tumor cells that grew out after challenge with MHC

class Ilow/NKG2D-Lhigh myc-B cells were converted to MHC class Ihigh/NKG2D-Llow cells (Fig. 4C). NK cells isolated upon growth of myc-B also showed an activated status and decreased NKG2D expression (data not shown). The data demonstrate that tumor progression is not only due to exhaustion or paralysis of NK cells following their initial activation, as described above. In addition, loss of NKG2D-L as well as recovery of MHC class I on tumor cells contribute to escape from NK-cell surveillance. Protection from NK-cell attack and the NKG2D modulation observed on NK cells from tumor-bearing mice 4��8C might be an effect of NKG2D-L shedded from tumor cells. In two different assay systems (See the Materials and methods section), there was no evidence for the presence of soluble NKG2D-L in sera from tumor mice (Supporting Information), but a clear NKG2D down-regulation was seen when WT NK cells were incubated with ligand-expressing lymphoma cells in vitro (Fig. 4D). If NKG2D-L expression is needed for tumor elimination (Fig. 4B, C) although it was not correlated with the expression of NK-cell activation markers (Fig.

Total melanoma tumor counts were obtained on day 22 by adding

Total melanoma tumor counts were obtained on day 22 by adding

the number of foci counted in the superior, middle, inferior, and postcaval lobes of the right lung to the number of foci counted in the left lung. The endpoint of the study was originally defined as 100 metastases per lung set. All procedures and analyses were performed blind, without knowledge of the test samples. Differences in sCTLA-4 levels between treatments were analyzed using the Wilcoxon Matched-Pairs Signed-Ranks Test, and differences in metastatic melanoma tumor load by Mann–Whitney U test. This work was funded by an endowment grant (04/50) from NHS Grampian, UK, and a Knowledge Transfer Grant from the University of Aberdeen. Dr. Lekh N. Dahal was supported by a studentship from the University of Aberdeen and by Arthritis Research UK (Grant no. 19282). The authors are grateful to Professors Selleck Enzalutamide John Todd and Linda Wicker (University of Cambridge, UK) for helpful discussions and provision of reagents. The authors thank Teva Pharmaceuticals, Tikva, Israel, for their collaborative support in the murine melanoma model. The authors also thank Drs Jennifer Niven and Isabel Crane for their help with the IRBP model of experimental autoimmune uveitis. The authors

(FJW, LND, and RNB) have filed a patent covering the use of the monoclonal Ab JMW-3B3 as a therapeutic. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or MTMR9 typeset. Technical selleck chemicals support issues arising from supporting information (other than missing files) should be addressed to the authors. “
“Intra-amniotic pathogens and by-products activate innate immune responses encompassing multitudes of signaling molecules and pathways that can result in spontaneous preterm birth (PTB). This study investigates fetal membrane response to bacterial stimulation using a bioinformatics approach. Dysregulated biomarker (IL1-β, IL-2, IL-8, IL-10, and TNF-α) data from fetal membranes at term stimulated with Ureaplasma urealyticum, Ureaplasma parvum, Mycoplasma

hominis, E. coli, Group B Streptococci, Polyporhans gingivalis, or Gardnerella vaginalis with 50% (v/v) amniotic fluid (AF) were analyzed by Ingenuity Pathway Analysis. In racially stratified analysis, networks representing late-stage immune inflammation were seen in African-Americans in AF absence. Inflammation was dominant in AF presence as well. In Caucasians, late-stage immune response was dominant with AF, but not in its absence. Fetal membrane biofunctions in response to bacteria reflect early- and late-stage innate immune defenses that vary based on the presence of AF and subject race. “
“Here construction of an attenuated mutant of an avian pathogenic Escherichia coli serovar O78 using an allelic exchange procedure is described.

Frequency of screening

Frequency of screening high throughput screening assay Screening frequency for targeted individuals should be yearly if no abnormality is detected on initial evaluation. 4. Who should perform the screening Doctors,

nurses, paramedical staff and other trained healthcare professionals 5. Intervention after screening Patients detected to have CKD should be referred to primary care physicians with experience in management of kidney disease for follow up. A management protocol should be provided to the primary care physicians. Further referral to nephrologists for management will be based on the protocol together with clinical judgment of the primary care physicians with their assessment of the severity of CKD and the likelihood of progression. find more 6. Screening for cardiovascular disease risk It is recommended that cardiovascular disease risk factors should be screened in all patients with CKD. “
“Date written: April 2009 Final submission: April 2009 Kidney status in people with type 2 diabetes should be assessed by: (Grade B)* a.  Annual screening for albuminuria by: AER 30–300 mg/24 h or AER 20–200 µg/min in timed collection Macroalbuminuria

is indicated by: AER > 300 mg/24 h or AER > 200 µg/min in timed collection OR Albumin: Creatinine Ratio (ACR) – spot urine sample. Microalbuminuria is indicated by: ACR 2.5–25 mg/mmol in males ACR 3.5–35 mg/mmol in females Macroalbuminuria is indicated by: ACR > 25 mg/mmol in males ACR > 35 mg/mmol in females If AER or ACR screening is positive for microalbuminuria: Perform additional ACR or AER measurements one to two times within 3 months. Microalbuminuria is confirmed if at least two

of three tests (including the screening test) are positive. If AER or ACR screening is positive for macroalbuminuria: Perform a 24 h urine collection for quantitation Mirabegron of protein excretion. AND eGFR < 60 mL/min per 1.73 m2 indicates at least moderate kidney dysfunction (Stage 3–5 chronic kidney disease [CKD]). eGFR 60–90 mL/min per 1.73 m2 may indicate mild kidney dysfunction (Stage 2 CKD if albuminuria also present). Continue annual screening for albuminuria and eGFR in the event of negative screening tests. Screening for microalbuminuria and glomerular filtration rate (GFR) should be preformed on an annual basis from the time of diagnosis of type 2 diabetes. This guideline topic has been taken from the NHMRC ‘National Evidence Based Guidelines for Diagnosis, Prevention and Management of CKD in type 2 diabetes’ which can be found in full at the CARI website (http://www.cari.org.au). The NHMRC guideline covers issues related to the assessment and prevention of CKD in individuals with established type 2 diabetes.

We used antisense transfection, over-expression, or knock-down of

We used antisense transfection, over-expression, or knock-down of IL-32 to assess the effects of the HPV-16 E7 oncogene on IL-32 expression in

cervical cancer cells. Cyclo-oxygenase 2 (COX-2) inhibitor treatment PS-341 clinical trial was conducted, and the expression levels, as well as the promoter activities, of IL-32 and COX-2 were evaluated in human HPV-positive cervical cancer cell lines. E7 antisense treatment reduced the expression levels and promoter activities of COX-2, which is constitutively expressed in HPV-infected cells. Constitutively expressed IL-32 was also inhibited by E7 antisense treatment. Moreover, IL-32 expression was blocked by the application of the selective COX-2 inhibitor, NS398, whereas COX-2 over-expression resulted in increased IL-32 levels. These results show that the high-risk variant of HPV induces IL-32 expression via E7-mediated COX-2 stimulation. However, E7 and COX-2 were down-regulated in the IL-32γ over-expressing cells and recovered by IL-32 small interfering RNA, indicating that E7 and COX-2 were feedback-inhibited by IL-32γ selleck chemicals in cervical cancer cells. Cervical cancer is the second most frequent cause of cancer death in women worldwide, and molecular epidemiological studies

have demonstrated clearly that human papillomavirus (HPV) is a prerequisite for the development of cervical carcinoma.1,2 Approximately 200 different HPV types have been characterized, Carnitine palmitoyltransferase II and the two most frequent high-risk HPV genotypes, HPV-16 and HPV-18, account for at least 50% of cervical cancers worldwide.3,4 Several HPV-16 type oncoproteins expressed during the early stage of infection have been associated with oncogenicity; specifically, E5, E6 and E7 have been demonstrated to contribute to the maintenance

of malignant cervical cancer phenotypes.5 The function of the E5 oncoprotein-activating epidermal growth factor receptor remains to be clearly elucidated, and E6 promotes the degradation of p53 via its interaction with E6AP.6 The E7 oncoprotein binds to the pRb retinoblastoma protein, and disrupts its formation of a complex with the E2F transcription factor in the G1 phase of the cell cycle. E7 also binds to and activates cyclin complexes such as cyclin-dependent kinase cdk2 and cyclin A, which control cell cycle progression.7 The viral genes E6 and E7 found in a specific subset of HPVs are invariably expressed in HPV-positive cervical cancer cells.8 It has also been previously reported that the E7 gene of HPV-16 triggers a cellular immunosuppression and profoundly enhances the release of angiogenic cytokines by macrophages or dendritic cells.9 The E6 and E7 oncogenes also inhibit the IL-18-mediated immune response, which carries out crucial functions in host defence mechanisms against infection and cancer.

One of the factors limiting progress in this area is the inherent

One of the factors limiting progress in this area is the inherent complexity of the flora, but the advent of genomics-based approaches is rapidly plugging this technology gap and the increasing application of this technology will hopefully clarify the role of the flora to

a significant degree in the near future. More indirect human data are available from the relevant epidemiology literature concerning the role of microbial pathogens as opposed to commensal flora [28,29]. The original conceptualization of the hygiene hypothesis envisaged infection frequency as the key factor discriminating high-risk and low-risk populations, but it has become evident that qualitative aspects of MK-2206 mouse infection(s) may be of equivalent or even greater importance. In particular, there is strong evidence linking enteric infections with reduced risk for allergic sensitization

learn more [30], and similarly for mild–moderate respiratory infections (without wheeze/fever) which spread to the lower respiratory tract [31], whereas upper respiratory tract infections do not appear to play such a role [32]. In contrast to the above, one class of viral infections has been linked epidemiologically in multiple studies to risk for subsequent development of asthma in childhood, notably moderate–severe viral infections which spread to the lower respiratory tract and which are of sufficient

intensity to trigger wheeze and/or febrile responses [32–34]. These infections serve as independent risk factors for subsequent asthma development, but their asthma-promoting effects are much stronger against a background or respiratory allergy (reviewed in [35,36]). On the basis of these findings, we have proposed a ‘two-hit’ model for asthma aetiology in early childhood (Fig. 1) in which interactions between inflammatory pathways involved in host responses to aeroallergens and viruses infecting the airway epithelium synergize to perturb early postnatal lung growth and differentiation, resulting in later expression of the asthma phenotype [35,36]. These Isotretinoin interactions are most profound in children who are sensitized to aeroallergens early and who experience severe infections during the same period [32]. A key question remaining to be resolved fully relates to the nature of these interactions between the anti-viral and atopic pathways. We hypothesize that one important focus of these interactions is the network of airway mucosal dendritic cells (AMDC) first described in humans [37] and experimental animals [38,39] by our group, and which are now recognized generally to play an essential ‘gatekeeper’ role in control of immune responses in the respiratory tract to all classes of inhaled antigens and pathogens [40,41].

We questioned whether targeting DCs with OVA-3-sulfo-LeA or OVA-t

We questioned whether targeting DCs with OVA-3-sulfo-LeA or OVA-tri-GlcNAc influenced CD4+ T-cell polarization Acalabrutinib rather than proliferation. Thereto, naive OVA-specific CD4+CD62Lhigh T cells were co-cultured with neo-glycoprotein-pulsed CD11C+ splenic DCs and 1 wk later production of cytokines related to Th1-, Th2 and Th17-differentiation was analyzed using flow cytometry. We compared this with the profile of T cells differentiated by native OVA pulsed CD11C+ splenic DCs. DCs targeted with either neo-glycoconjugate

generated significantly higher frequencies of IFNγ-producing CD4+ T cells compared to native OVA-loaded DCs (Fig. 4, left panel). By contrast, OVA-3-sulfo-LeA and OVA-tri-GlcNAc either reduced or did not affect the frequency of IL4 or IL17-producing www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html T cells, respectively (Fig. 4, middle and right panel). These data imply that 3-sulfo-LeA- and tri-GlcNAc-glycosylated antigens that target efficiently to the MR on DCs result in induction

of IFNγ-producing effector T cells. As targeting of the MR with OVA-3-sulfo-LeA and OVA-tri-GlcNAc resulted in enhanced cross-presentation to CD8+ T cells, we investigated the intracellular routing of native OVA and OVA-3-sulfo-LeA into BMDCs derived from C57BL/6 and MR−/− mice. To this end, BMDCs were incubated with fluorescent-labeled OVA or OVA-3-sulfo-LeA. Two hours later, cells were washed and co-stained for MR, EEA-1 (endosomal marker) or LAMP-1 (lysosomal marker) and analyzed using confocal microscopy. We observed that OVA and OVA-3-sulfo-LeA Amino acid (red) that bind to the MR (green, co-localization with

OVA appears yellow) co-localized with the endosomal marker EEA-1 (blue, co-localization OVA-MR-EEA-1=cyan) (Fig. 5A and B). This co-localization is also clearly observed when fluorescence images are converted into histograms (indicated by arrows). Surprisingly, we observed that co-localization of the MR-bound OVA-3-sulfo-LeA with EEA-1 was higher compared to native OVA. In addition, we assessed that the internalized OVA-3-sulfo-LeA did not co-localize with the lysosomal marker LAMP-1, but only with the MR (data not shown). The uptake of OVA and OVA-3-sulfo-LeA in BMDCs derived from MR−/− was dramatically decreased (Fig. 5C and D). These data correlate with the data on binding and antigen presentation demonstrating that OVA-3-sulfo-LeA targeted to the MR results in increased internalization of antigen to the endosomal compartment to facilitate loading of antigen to MHC class I molecules leading to enhanced cross-presentation to CD8+ T cells. Here, we show that DC-expressed MR is capable of binding sulfated glycans such as 3-sulfo-LeA or GlcNAc besides mannose glycans, present on native OVA.

Thus, it is very likely that local GCs contribute to the generati

Thus, it is very likely that local GCs contribute to the generation of both memory B cells and plasma cells. In light of the reviewed data, what can be concluded about

memory B cells? Are there five different subsets, four layers or two layers? It would appear that the model system used to study mouse memory B cells is important for the outcome as they elicit different responses with regard to the duration of the primary (and secondary) response, persistence Panobinostat ic50 of GCs and memory subsets. It is also dependent on the dose and type of antigen, the time interval between immunizations, as well as the markers used to define memory B cells. Nevertheless, the reviewed data would argue that there are two pathways to formation of memory B cells, one that is GC-dependent and one that is not, as discussed Daporinad mw under (3). Both these pathways require T cell help and give rise to IgM as well as isotype-switched memory B cells. Whether these two

pathways give rise to the multiple layers as discussed under (2) is a possibility but presently unclear. Even five subsets of switched and non-switched memory B cells, as discussed under (1), could fit in with two pathways, perhaps representing different phases of the immune response. Along one of the pathways, memory B cells would be generated that express unmutated antibodies that protects the host against variants of the invader, whereas the other pathway would generate memory B cells that rapidly respond with high affinity, mutated and isotype-switched antibodies and provides a defense against rechallange with the same antigen. Ti antigens can also mount a memory response with both isotype-switched and unswitched B cells. Under autoimmune conditions, the autoreactive immune response might initially follow the same pathways as those find more driven by exogenous antigens. However, as

the disease-causing autoantibodies mainly are mutated and isotype-switched, this may indicate that the constant presence of autoantigens skews the response towards chronic GCs and perpetual production of GC-dependent memory B cells and autoantibody-producing plasma cells [60, 64, 65]. The mechanisms determining the fate of the B cell, that is, what makes the cell go down the early memory B versus the GC B cell pathway, and what makes a GC B cell differentiate into a memory B rather than a plasma cell, are still unclear [3, 10, 11, 32, 66, 67]. Whether a single signal, or several, directs a B cell down a certain path is not fully understood, perhaps it is under the influence of both intrinsic and external signals, for instance antibody feedback mechanisms [3, 10, 11, 67-69].

Animal studies have demonstrated a linear association between FGF

Animal studies have demonstrated a linear association between FGF-23 and phosphate; however, human trials have reported a variable rise in FGF-23 levels following phosphate-loading.31–33 This highlights the complexity of phosphate regulation in humans. It is likely that FGF-23 is not the only mediator of increasing Y-27632 in vitro phosphate excretion, and that other phosphatonins (frizzled-related protein-4, fibroblast growth factor-7, matrix extracellular phosphoglycoprotein)34 play an additional role which is currently

poorly understood. The stimulation of FGF-23 by phosphate may be dependent on its dose, duration of exposure, bone derived co-factors and the severity and chronicity of CKD. It is also unclear as to whether serum or local phosphate concentrations provide the primary stimulus for FGF-23 secretion. FGF-23 has an inhibitory effect on PTH secretion; however, FGF-23 secretion may also occur in response to PTH levels. It is not known whether this occurs through a negative feedback loop mechanism or is conferred by the effects of PTH on calcitriol and serum phosphate (Fig. 1).26 The interaction between FGF-23 and Klotho may be selleckchem necessary for normal phosphate metabolism. However, it is possible that high levels of FGF-23, as seen in CKD patients can exert a Klotho-independent effect, and bind to FGF-R with low affinity.13 This is supported by decreased expression

of Klotho in renal biopsies from CKD patients.35 The expression of Klotho occurs predominantly in the distal tubules, and the signalling sequence that leads to decreased phosphate absorption in the proximal tubules remains unclear.36 FGF-23 levels are increased early in CKD and cross-sectional studies involving patients with a wide range of glomerular filtration rates (GFR), demonstrate an inverse relationship with renal function.37–39 The increase in FGF-23 levels observed in CKD may in part be a physiological response to restore normal serum phosphate levels.

Proposed mechanisms include reducing renal tubular phosphate re-absorption, as well as decreasing circulating calcitriol levels (by downregulation of 1α-hydroxylase Baricitinib and upregulation of 24-hydroxylase) with resultant decreased intestinal phosphate absorption.40 Calcitriol is involved in a feedback loop, via liganded vitamin D receptor (VDR) binding to the FGF-23 promoter.41 It is therefore increasingly likely that early FGF-23 release, rather than decreasing renal mass and subsequent reduced 1α-hydroxylase function, constitutes the main mechanism leading to the biochemical changes that characterize SHPT. Recently reported clinical studies support a phosphate-centric, FGF-23-mediated pathogenesis of SHPT (Fig. 2). One study involving 125 CKD stage 1–3 patients reported elevated FGF-23 and PTH levels inversely associated with estimated GFR (eGFR), and positively associated with increased urinary fractional excretion of phosphate.

In this study we have addressed the potential utility of immunoth

In this study we have addressed the potential utility of immunotherapy Cisplatin using regulatory T cells (Treg) to treat murine autoimmune cholangitis. In particular, we have taken advantage of our ability to produce portal inflammation and bile duct cell loss by transfer of CD8+ T cells from the dominant negative form of transforming growth factor beta receptor type II (dnTGF-βRII) mice to recombination-activating gene (Rag)1–/– recipients. We then used this robust established adoptive transfer system and co-transferred CD8+ T cells from dnTGF-βRII mice with either C57BL/6 or dnTGF-βRII forkhead box protein 3 (FoxP3+) T cells. Recipient mice were monitored for histology,

including portal inflammation and intralobular biliary cell damage, and also included a study of the phenotypical changes in recipient lymphoid populations and local and systemic cytokine production. Importantly, we report herein that adoptive transfer of Treg from C57BL/6 but not dnTGF-βRII

mice significantly reduced the pathology of autoimmune cholangitis, including decreased portal inflammation and bile duct damage as well as down-regulation of the secondary inflammatory response. Further, to define the mechanism of check details action that explains the differential ability of C57BL/6 Treg versus dnTGF-βRII Treg on the ability to down-regulate autoimmune cholangitis, we noted significant differential expression of glycoprotein A repetitions predominant (GARP), CD73, CD101 and CD103 and a functionally significant increase in interleukin (IL)-10 in Treg from C57BL/6 compared to dnTGF-βRII mice. Our data reflect the therapeutic potential of wild-type CD4+ FoxP3+ Treg in reducing the excessive T cell responses of autoimmune cholangitis, which has significance for the potential immunotherapy of PBC. “
“Cryptosporidium parvum infects intestinal Celecoxib epithelial cells and is commonly the parasite

species involved in mammalian cryptosporidiosis, a major health problem for humans and neonatal livestock. In mice, immunologically mediated elimination of C. parvum requires CD4+ T cells and IFN-γ. However, innate immune responses also have a significant protective role in both adult and neonatal mice. NK cells and IFN-γ have been shown to be important components in immunity in T and B cell-deficient mice, but IFN-γ-dependent resistance has also been demonstrated in alymphocytic mice. Epithelial cells may play a vital role in immunity as once infected these cells have increased expression of inflammatory chemokines and cytokines and demonstrate antimicrobial killing mechanisms, including production of NO and antimicrobial peptides. Toll-like receptors facilitate the establishment of immunity in mice and are involved in the development of inflammatory responses of infected epithelial cells and also dendritic cells. Around 20 recognized species of the apicomplexan Cryptosporidium infect the gastro-intestinal tract of vertebrates.