Fermented rice bran supplementation attenuates chronic colitis-associated extraintestinal manifestations in female C57BL/6N mice.

Patients with inflammatory bowel disease (IBD) have higher incidence of extraintestinal manifestations (EIM), including liver disorders, sarcopenia, and neuroinflammation. Fermented rice bran (FRB), generated from rice bran (RB), is rich in bioactive compounds, and exhibits anti-colitis activity. However, its role in EIM prevention is still unclear. Here, for the first time, we investigated whether EIM in female C57Bl/6N mice is attenuated by FRB supplementation. EIM was induced by repeated administration of 1.5% dextran sulfate sodium (DSS) in drinking water (4 d) followed by drinking water (12 d). Mice were divided into 3 groups-control (AIN93M), 10% RB, and 10% FRB. FRB ameliorated relapsing colitis and inflammation in muscle by significantly lowering proinflammatory cytokines Tnf-α and Il-6 in serum and advanced glycation end product-specific receptor (Ager) in serum and muscle when compared with the RB and control groups. As FRB reduced aspartate aminotransferase levels and oxidative stress, it might prevent liver disorders. FRB downregulated proinflammatory cytokine and chemokine transcripts responsible for neuroinflammation in the hippocampus and upregulated mRNA expression of G protein coupled receptors (GPRs), Gpr41 and Gpr43, in small and large intestines, which may explain the FRB-mediated protective mechanism. Hence, FRB can be used as a supplement to prevent IBD-associated EIM.

Elucidation of the Effects of a Current X-SCID Therapy on Intestinal Lymphoid Organogenesis Using an In Vivo Animal Model.

BACKGROUND & AIMS: Organ-level research using an animal model lacking Il2rg, the gene responsible for X-linked severe combined immunodeficiency (X-SCID), is clinically unavailable and would be a powerful tool to gain deeper insights into the symptoms of patients with X-SCID. METHODS: We used an X-SCID animal model, which was first established in our group by the deletion of Il2rg gene in pigs, to understand the clinical signs from multiple perspectives based on pathology, immunology, microbiology, and nutrition. We also treated the X-SCID pigs with bone marrow transplantation (BMT) for mimicking a current therapeutic treatment for patients with X-SCID and investigated the effect at the organ-level. Moreover, the results were confirmed using serum and fecal samples collected from patients with X-SCID. RESULTS: We demonstrated that X-SCID pigs completely lacked Peyer's patches (PPs) and IgA production in the small intestine, but possessed some dysfunctional intestinal T and B cells. Another novel discovery was that X-SCID pigs developed a heterogeneous intestinal microflora and possessed abnormal plasma metabolites, indicating that X-SCID could be an immune disorder that affects various in vivo functions. Importantly, the organogenesis of PPs in X-SCID pigs was not promoted by BMT. Although a few isolated lymphoid follicles developed in the small intestine of BMT-treated X-SCID pigs, there was no evidence that they contributed to IgA production and microflora formation. Consistently, most patients with X-SCID who received BMT possessed abnormal intestinal immune and microbial environments regardless of the presence of sufficient serum IgG. CONCLUSIONS: These results indicate that the current BMT therapies for patients with X-SCID may be insufficient to induce the organogenesis of intestinal lymphoid tissues that are associated with numerous functions in vivo.

Nickel-Catalyzed Asymmetric Propargylic Amination of Propargylic Carbonates Bearing an Internal Alkyne Group.

We have achieved the nickel-catalyzed asymmetric propargylic amination of propargylic carbonates bearing an internal alkyne group. A wide variety of propargylic carbonates and N-methylaniline derivatives were tolerated under the reaction conditions, providing the corresponding chiral propargylic amines in up to 97% yield with up to 97% ee.

Effects of a moderate-fat diet that is enriched with fish oil on intestinal lipid absorption in a senescence-accelerated prone mouse model.

OBJECTIVES: We examined a moderate-fat (MF) diet that is enriched with fish oil (FO) and assessed whether lipid absorption was inhibited in senescence-accelerated prone mice (SAM-P8). METHODS: All mice (N = 70) were fed a normal diet that contained 4 g soybean oil/100 g of diet for 6 mo and then divided the mice into four groups (n = 10 or 20/group). Mice in the baseline group were euthanized at 6 mo old, those in the control group continued on a normal diet until 15 mo of age, those in the MF diet group switched to an MF diet (8 g soybean oil/100 g of diet) until 15 mo of age, and those in the MF + FO group switched to an MF diet that was enriched with FO (6.4 g soybean oil + 1.6 g FO/100 g of diet) until 15 mo of age. RESULTS: The area under the curve for lipid absorption decreased with age but lipid absorption tended to be less attenuated with an MF diet that contained FO. Messenger RNA (mRNA) levels of apolipoprotein B, fatty acid transport protein 4, and microsomal triacylglycerol transfer protein in the small intestine decreased with age but tended to be maintained with an MF diet with or without FO. A histologic analysis of the small intestine showed that villi degenerated with age but the decline was less in mice in the MF + FO group. CONCLUSIONS: The results of this study suggest that MF + FO diets can inhibit the attenuation of lipid absorption commensurate with aging in SAM-P8 via a delay of the natural degeneration that occurs in small intestinal villi over time.

Association between lifestyle factors assessed by standard question items of specific health checkup and the incidence of metabolic syndrome and hypertension in community dwellers: A five-year cohort study of National Health Insurance beneficiaries in Habikino City.

Objective　From April 2008, specific health checkups have been implemented to prevent metabolic syndrome (MetS) and related cardiovascular diseases based on assurance of medical care for the elderly in Japan. In its "Standard Health Checkup and Counseling Guidance Program," 22 standard question items are recommended to assess health conditions of Japanese citizens. However, there are few community-based studies to clarify the relationship between question items and new onset of high risk conditions for cardiovascular diseases such as MetS. Accordingly, we performed a 5-year follow-up study of community dwellers who participated in health checkups of National Health Insurance beneficiaries in Habikino City, Osaka.Method　Lifestyle factors assessed by standard question items in 2008 were defined as exposures at baseline survey. In the analysis of MetS, we followed-up 4,720 participants without MetS; and in the analysis of hypertension, we followed-up 3,326 participants without hypertension until the end of March in 2013. New-onset MetS or hypertension during follow-up were defined as outcomes. Cox proportional hazard model was used to evaluate the relationship between lifestyle factors and the incidence of MetS or hypertension after adjustment for age and waist circumference.Results　The median follow-up period for incidence of MetS was 3.1 years for men and 3.6 years for women. We observed 570 new cases of MetS during follow-up. For men, "taking dinner within 2 hours before going to sleep" and "body weight increase by 10 kg or greater from 20 years old" were significantly associated with MetS (hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.09-1.88 and HR, 1.33; 95% CI, 1.19-1.75, respectively). Occasional consumption of alcohol in men was negatively associated with MetS. For women, "increase or decrease of body weight by 3 kg or greater within 1 year" and "body weight increase by 10 kg or greater from age of 20" were significantly associated with MetS (HR, 1.83; 95% CI, 1.40-2.40 and HR, 2.02; 95% CI, 1.52-2.68, respectively). Daily alcohol consumption from 1 to less than 2 gou (about 23 to 45 g of ethanol) in women was positively associated with MetS (HR, 2.64; 95% CI, 1.51-4.64). We observed 1,045 new cases of hypertension; however, except for daily alcohol consumption for men, no lifestyle factors were associated with incidence of hypertension.Conclusion　Most standard question items of specific health checkups did not predict new-onset MetS or hypertension, at least within 5 years. Thus, development of more predictive question items is warranted.

Effects of mycoplasmal pneumonia of swine (MPS) lung lesion-selected Landrace pigs on MPS resistance and immune competence in three-way crossbred pigs.

To clarify the genetic influence of mycoplasmal pneumonia of swine (MPS) lesion-selected Landrace (La) on MPS resistance and immune characteristics in three-way crossbred pigs (LaWaDa), the LaWaDa pigs were compared with the non-selected crossbred (LbWbDb) and purebred (La) pigs. The MPS lesion score in the three lines was as follows: La line < LaWaDa line < LbWbDb line, with significant differences among the lines. The proportions of myeloid cells and T cells were lower and higher, respectively, in the LaWaDa pigs compared with those in the other two lines. Messenger RNA (mRNA) expression of interleukin (IL)-6, IL-10, transforming growth factor-ß, and interferon-γ in peripheral blood was significantly increased after vaccination in the La and LaWaDa lines. IL-4 mRNA expression in the LaWaDa line was intermediate to the La and LbWbDb lines. Furthermore, principal component analysis for immune traits and MPS lesions was executed to clarify the characteristics of each pig line. These findings suggest that the immune responses in the three pig lines are genetically distinct and that MPS resistance and some immunity characteristics from the La line were transmitted to the three-way crossbred pigs.

Cyclophilin A is a new M cell marker of bovine intestinal epithelium.

Microfold (M) cells in the follicle-associated epithelium (FAE) of Peyer's patches contribute to the mucosal immune response by the transcytosis of microorganisms. The mechanism by which M cells take up microorganisms, and the functional proteins by which they do this, are not clear. In order to explore one such protein, we developed a 2H5-F3 monoclonal antibody (2H5-F3 mAb) through its binding to bovine M cells, and identified the antibody reactive molecule as cyclophilin A (Cyp-A). The localization patterns of Cyp-A were very similar to the localization pattern of cytokeratin (CK) 18-positive M cells. Cyp-A was identified at the luminal surface of CK18-positive M cells in bovine jejunal and ileal FAE. The membranous localization of Cyp-A in the bovine intestinal cell line (BIE cells) increased as cells differentiated toward M cells, as determined by flow cytometry analysis. Additionally, BIE cells released Cyp-A to the extracellular space and the differentiation of BIE cells to M cells increased the secretion of Cyp-A, as determined by western blotting. Accordingly, Cyp-A may be localized in M cells in the small intestinal epithelium of cattle. The rise of the membranous localization and secretion of Cyp-A by differentiation toward M cells indicates that Cyp-A has an important role in the function of M cells. While Cyp-A of the M cell membrane may contribute to the uptake of viruses with peptidyl-prolyl cis-trans isomerase activity, in the extracellular space Cyp-A may work as a chemokine and contribute to the distribution of immuno-competent cells.

Immunogenic properties and mycoplasmal pneumonia of swine (MPS) lung lesions in Large White pigs selected for higher peripheral blood immune capacity.

Immunogenic properties and mycoplasmal pneumonia of swine (MPS) lung lesions were compared between the immunity-selected Large White line and the non-selected Large White line. The selected Large White line showed a higher level of pulmonary MPS lesions compared with the non-selected Large White line. Subsequent to vaccination, the percentage of natural killer cells and T cells (CD3(+) CD4(+) CD8(-) and CD3(+) CD4(-) CD8(+) T cells) were significantly increased in the non-selected line but remained unchanged in the immunity-selected Large White line. Secretion of Mycoplasma hyopneumoniae vaccine-specific immunoblogulin G and phagocyte activity in peripheral blood were significantly higher in the immunity-selected Large White line than in the non-selected line. Expression of interleukin (IL)-4 and IL-6 messenger RNA in hilar lymph nodes was significantly lower in the immunity-selected Large White line than in the non-selected line. However, expression of IL-10 in all immune tissues was significantly higher in the immunity-selected Large White line. These results suggest that the selection for high immunity was not effective in increasing resistance to MPS lung lesions.

Coffee consumption delays the hepatitis and suppresses the inflammation related gene expression in the Long-Evans Cinnamon rat.

BACKGROUND AND AIMS: Large-scale epidemiological studies have shown that drinking more than two cups of coffee per day reduces the risks of hepatitis and liver cancer. However, the heterogeneity of the human genome requires studies of experimental animal models with defined genetic backgrounds to evaluate the coffee effects on liver diseases. We evaluated the efficacy of coffee consumption with one of experimental animal models for human disease. METHOD: We used the Long Evans Cinnamon (LEC) rat, which onsets severe hepatitis and high incidence of liver cancer, due to the accumulation of copper and iron in livers caused by the genetic mutation in Atp7B gene, and leading to the continuous oxidative stress. We determined the expression of inflammation related genes, and amounts of copper and iron in livers, and incidence of the pre-neoplastic foci in the liver tissue of LEC rats. RESULTS: Coffee administration for 25 weeks delayed the occurrence of hepatitis by two weeks, significantly improved survival, reduced the expression of inflammatory cytokines, and reduced the incidence of small pre-neoplastic liver foci in LEC rats. There was no significant difference in the accumulation of copper and iron in livers, indicating that coffee administration does not affect to the metabolism of these metals. These findings indicate that drinking coffee potentially prevents hepatitis and liver carcinogenesis through its anti-inflammatory effects. CONCLUSION: This study showed the efficacy of coffee in the prevention of hepatitis and liver carcinogenesis in the LEC model.

Expression of myostatin in neural cells of the olfactory system.

Recent studies show that myostatin mRNA expression is found in some regions of the brain. However, the functional significance of this is currently unknown. We therefore investigated myostatin expression and function in the brain. In this study, we used immunohistochemistry, in situ hybridization, and RT-PCR analysis to reveal that myostatin is expressed in the mitral cells in the olfactory bulb (OB) and in neurons in the olfactory cortex (OC). Using 3D reconstruction, mitral cells positive for myostatin were positioned in the lateral and ventral regions of the OB. In contrast, myostatin-positive mitral cells were detected in mice at 2 weeks of age, but not on days 0 and 7 after birth. Activin receptor IIB, a myostatin receptor, was expressed in the OB, OC, hippocampus, and paraventricular thalamic nucleus. Moreover, c-Fos immunostaining in granule cells in the OB was augmented after intracerebroventricular injection of myostatin. These findings suggest that myostatin is localized in specific cells associated with the olfactory system of the brain and may act as a key inhibitor in cell and/or signal development of the olfactory system.

Distribution of myofiber types in the crural musculature of sheep.

In domestic animals, the legs function in both postural maintenance and propulsion. The crural muscles participate in actions of the tarsal and toe joints. Mammalian skeletal muscles consist of myofibers, which are histochemically classified into three myofiber types, slow-twitch/oxidative (SO) or type I, fast-twitch/oxidative/glycolytic (FOG) or type IIA, and fast-twitch/glycolytic (FG) or type IIB myofibers. The histochemical characteristics of myofiber types reflect an aspect of function that myofibers possess. In the present study, we investigated the composition and average diameter of myofiber types of each muscle in crus of sheep and determined their roles in the movement of tarsal and toe joints. The tibialis cranialis muscle was a flat unipennate muscle and not capable to generate a large tension; however, it could function primarily in posture maintenance and play a cooperative role in adjusting standing posture. The flexor hallucis longus and flexor digitorum superficialis muscles were the major muscles that contributed to posture maintenance in leg musculature. These muscles were capable to generate a large tension and participate primarily in standing posture maintenance. The composition and diameter of myofiber types in ovine crural musculature reflected the role of each muscle in posture maintenance and locomotion.

Morpho-functional relationship between muscular architecture and proportion of myofiber types in ovine antebrachial musculature.

The antebrachium of domestic animals supports the trunk against gravity and generates propulsive force. The antigravity action of antebrachium is attributed to the contraction of flexor muscles of the carpal and digital joints. Mammalian skeletal muscles consist of myofibers, which are histochemically classified into type I, type IIA, and type IIB myofibers, of which composition reflects the proportional involvement of the muscle in varying function, such as posture maintenance and locomotion. The physiological cross-sectional area (PCSA), which are calculated from muscle volume, myofiber length, and pennation angle, reflects the maximum force of muscle. In the present study, we evaluated the PCSA of myofiber types in the antebrachial musculature and determined the magnitude of contribution from individual muscles toward varying actions of carpal and digital joints. The extensor carpi ulnaris and flexor digitorum superficialis muscles possessed a large proportional PCSA of type I myofibers, indicating the role for these muscles in maintaining a standing posture. The additional force required for walking/running was primarily provided by the flexor digitorum profundus caput humerale and extensor carpi radialis muscles. The proportional PCSA of myofiber types reflected the force generated for varying muscular function and provided insights into the dynamics of carpal and digital joints.

Orally administered prion protein is incorporated by m cells and spreads into lymphoid tissues with macrophages in prion protein knockout mice.

Transmissible spongiform encephalopathies are fatal neurodegenerative diseases. Infection by the oral route is assumed to be important, although its pathogenesis is not understood. Using prion protein (PrP) knockout mice, we investigated the sequence of events during the invasion of orally administered PrPs through the intestinal mucosa and the spread into lymphoid tissues and the peripheral nervous system. Orally administered PrPs were incorporated by intestinal epitheliocytes in the follicle-associated epithelium and villi within 1 hour. PrP-positive cells accumulated in the subfollicle region of Peyer's patches a few hours thereafter. PrP-positive cells spread toward the mesenteric lymph nodes and spleen after the accumulation of PrPs in the Peyer's patches. The number of PrP molecules in the mesenteric lymph nodes and spleen peaked at 2 days and 6 days after inoculation, respectively. The epitheliocytes in the follicle-associated epithelium incorporating PrPs were annexin V-positive microfold cells and PrP-positive cells in Peyer's patches and spleen were CD11b-positive and CD14-positive macrophages. Additionally, PrP-positive cells in Peyer's patches and spleen were detected in the vicinity of peripheral nerve fibers in the early stages of infection. These results indicate that orally delivered PrPs were incorporated by microfold cells promptly after challenge and that macrophages might act as a transporter of incorporated PrPs from the Peyer's patches to other lymphoid tissues and the peripheral nervous system.

Anterior pituitary progenitor cells express costimulatory molecule 4Ig-B7-H3.

Stem/Progenitor cells in the postnatal pituitary gland are embedded in a marginal cell layer around Rathke's pouch. However, the nature and behavior of anterior pituitary progenitor cells remain unclear. We established bovine anterior pituitary progenitor cell line (BAPC)-1 from the anterior pituitary gland, which expressed stem/progenitor cell-related genes and several inflammatory cytokines. To characterize and localize these pituitary progenitor cells, we produced a mAb (12B mAb) against BAPC-1. The 12B mAb recognized the 4Ig-B7-H3 molecule, which is a costimulatory molecule and negative regulator in T cell activation. WC1(+) gammadelta T cells in young bovine PBMC express the 4Ig-B7-H3 molecule, but few or no 4Ig-B7-H3-immunoreactive cells are expressed in PBMC in adult cattle. The 12B-immunoreactive cells in the bovine anterior pituitary gland were localized around Rathke's pouch and expressed IL-18 and MHC class II. However, the number of 12B-immunoreactive cells was lower in adult than in young cattle. BAPC-1 expressed IL-18 and MHC class II, and demonstrated phagocytotic activity. BAPC-1 also had the ability to promote CD25 expression in PBMC after 5 days of coculture, and blocking 4Ig-B7-H3 x 12B mAb enhanced their expression of CD25. In addition, the 12B-immunoreactive cells were observed around the pars tuberalis closely bordering the median eminence and in the blood vessels of the primary portal plexus in the anterior pituitary gland. These results suggest that an established BAPC-1 may originate from these progenitor cells, and that the progenitor cells with 4Ig-B7-H3 may play a critical role in the immunoendocrine network.

Presence of neuropeptide Y in somatotrophs of cattle.

Neuropeptide Y (NPY), a 36-amino acid member of the pancreatic polypeptide family, was found to be present by immunohistochemistry in the bovine adenohypophysis. NPY mRNA expression was confirmed in the adenohypophysis by RT-PCR. NPY immunoreactivity was present in about 38% of adenohypophyseal cells in the pars distalis. However, NPY immunoreactive cells (NPY-ir cells) were scarce in the zona tuberalis. Immunohistochemistry of NPY and specific hormones using mirror sections revealed that NPY was colocalized in GH immunoreactive cells. Over 90% of somatotrophs corresponded to NPY-ir cells. These results indicate that endogenous NPY is present in the bovine somatotroph and may act as an endocrine intercellular mediator in the adenohypophysis.

Expression of inflammatory-related factors in porcine anterior pituitary-derived cell line.

Recent studies have shown that undifferentiated stem cells act as immunomodulators. To investigate the immunomodulatory function of the progenitor cells of the anterior pituitary gland, we attempted to establish a stem/progenitor cell line from the porcine anterior pituitary gland, and to detail its inflammatory cytokine expression. A cloned cell line from the porcine anterior pituitary gland was established and was designated as the porcine anterior pituitary-derived cell line (PAPC). PAPC expressed the mRNA of Nanog and Oct-4, and showed positive immunoreactivity for beta-catenin and Hes1 in its nucleus. PAPC grew stably by repeated passage and rapidly in the EGF and bFGF containing medium. RT-PCR showed that PAPC expressed mRNA of IL-1alpha, IL-6, IL-12, IL-15, IL-18 and TLR4. PAPC expressed S100alpha and IL-18 protein, which was localized in the marginal epithelial cells of Rathke's pouch. These results suggest that PAPC is a stem/progenitor cell and may regulate anterior pituitary cell function through an immuno-endocrine pathway.

Localization of leptin and leptin receptor in the bovine adenohypophysis.

The present study was carried out to detail the cellular localization of leptin (Lep) and the leptin receptor (LepR) in the bovine adenohypophysis. Lep immunoreactivity (Lep-ir) was found in about 30% of adenohypophysial cells in the gland. Immunochemistry of Lep and specific hormones using serial sections revealed that Lep-ir was present in 60.4% of somatotrophs, 15.9% of gonadotrophs, 6.5% of mammotrophs, 6.5% of thyrotrophs and 2.4% of corticotrophs. Both the common short isoform (OBRa) and the long isoform (OBRb) of LepR mRNA were expressed in the bovine adenohypophysis. LepR immunoreactivity (LepR-ir) was found in only 2.8% of the adenohypophysial cells and over 50% of LepR-ir cells were gonadotrophs, in which most of the cells were distributed in the zona tuberalis. The findings on Lep and LepR in the adenohypophysial cells indicate that Lep may regulate gonadotroph function through autocrine/paracrine pathway in the bovine adenohypophysis.

[A case of limited form of Wegener's granulomatosis showing repeated occurrence and disappearance of nodules in chest X ray with no medication].

A 69-year-old woman was admitted to because of bloody sputum. Chest CT showed some nodules. The patient was seronegative for PR3-ANCA. One month after the admission, these shadows vanished with no medication. She was asymptomatic for one and a half years, and then she complained of cough again. Multiple nodules were seen on chest CT again. She was admitted, and surgical biopsy by video-assisted thoracoscopic surgery was performed. She was diagnosed to have a limited form of Wegener's granulomatosis. Multiple shadows vanished without medication, again. Administration of sulfamethoxazole-trimethoprim was started and there has been no relapse.

Two-dimensional analysis of elements and mononuclear cells in hard metal lung disease.

RATIONALE: Hard metal lung disease is caused by exposure to hard metal, a synthetic compound that combines tungsten carbide with cobalt as well as a number of other metals. Interstitial lung disease caused by hard metal is uniquely characterized by giant cell interstitial pneumonia. The pathogenesis of hard metal lung disease is unclear. OBJECTIVES: To elucidate the distribution of inhaled hard metal and reactive inflammatory cells in biopsy lung tissue from patients with hard metal lung disease. METHODS: Seventeen patients with interstitial lung disease in which tungsten was detected and five control subjects were studied. Detection and mapping of elements were performed with an electron probe microanalyzer equipped with a wavelength dispersive spectrometer. We immunohistochemically stained mononuclear cells, in tissue samples available from five patients, with anti-human CD4, CD8, CD20, CD68, and CD163 antibodies, and compared the distribution of positive cells with hard metal elements. MEASUREMENTS AND MAIN RESULTS: Thirteen of 17 patients were pathologically diagnosed as having giant cell interstitial pneumonia. Tungsten and cobalt were accumulated in the centrilobular fibrotic lesions, but were never found in the control lungs. CD8+ lymphocytes and CD163+ monocyte-macrophages were distributed predominantly in centrilobular fibrotic lesions around the hard metal elements. CD163+ colocalized with tungsten. Small numbers of CD8+ and CD163+ cells were also immunohistochemically shown in peribronchiolar areas and alveolar walls. CONCLUSIONS: Macrophages may phagocytose inhaled tungsten via CD163 and play an important role in forming the fibrotic lesion of hard metal lung disease with cytotoxic T lymphocytes.

Immunohistochemical characterization of cell types expressing the cellular prion protein in the small intestine of cattle and mice.

The gastrointestinal tract is thought to be the main site of entry for the pathological isoform of the prion protein (PrP(Sc)). Prion diseases are believed to result from a conformational change of the cellular prion protein (PrP(c)) to PrP(Sc). Therefore, PrP(c) expression is a prerequisite for the infection and spread of the disease to the central nervous system. However, the distribution of PrP(c) in the gut is still a matter of controversy. We therefore investigated the localization of PrP(c) in the bovine and murine small intestine. In cattle, most PrP(c) positive epithelial cells were detected in the duodenum, while a few positive cells were found in the jejunum. PrP(c) was expressed in serotonin producing cells. In bovine Peyer's patches, PrP(c) was distributed in extrafollicular areas, but not in the germinal centre of the jejunum and ileum. PrP(c) was expressed in myeloid lineage cells such as myeloid dendritic cells and macrophages. In mice, PrP(c) was expressed in some epithelial cells throughout the small intestine as well as in cells such as follicular dendritic cell in the germinal centre of Peyer's patches. In this study, we demonstrate that there are a number of differences in the localization of PrP(c) between the murine and bovine small intestines.