Mesenteric lymph nodes contribute to proinflammatory Th17‐cell generation during inflammation of the small intestine in mice

T cells of the small intestine, including Th17 cells, are critically involved in host protection from microbial infection, and also contribute to the pathogenesis of small bowel inflammatory disorders. Accumulating evidence suggests that mesenteric lymph nodes (MLNs) play important roles in gut‐tropic T‐cell generation, although it is still unclear if MLNs are involved in the pathogenesis of small intestine inflammation. To address this issue, we analyzed the roles of both MLNs and Peyer's patches (PPs) by evaluating MLN‐ or PP‐deficient mice in an experimental model of small intestine inflammation, induced by CD3‐specific mAb injection. Interestingly, MLNs, but not PPs, were essential for the pathogenesis of intestinal inflammation, in particular the accumulation and infiltration of CD4⁺ T‐cell populations, including Th17 cells, from the blood. In addition, CD4⁺ T‐cell accumulation was dependent on the function of the α₄β₇ integrin. Furthermore, MLN removal led to a significantly reduced number of peripheral α₄β₇⁺ CD4⁺ effector memory T cells under normal conditions, suggesting that MLNs may play a role in maintaining the number of gut‐tropic CD4⁺ effector memory T cells circulating in the blood. Taken together, the present study highlights the important role of MLNs in contributing to the pathogenesis of small intestine inflammation.     

IL‐23 protection against Plasmodium berghei infection in mice is partially dependent on IL‐17 from macrophages

Although IL‐12 is believed to contribute to protective immune responses, the role played by IL‐23 (a member of the IL‐12 family) in malaria is elusive. Here, we show that IL‐23 is produced during infection with Plasmodium berghei NK65. Mice deficient in IL‐23 (p19KO) had higher parasitemia and died earlier than wild‐type (WT) controls. Interestingly, p19KO mice had lower numbers of IL‐17‐producing splenic cells than their WT counterparts. Furthermore, mice deficient in IL‐17 (17KO) suffered higher parasitemia than the WT controls, indicating that IL‐23‐mediated protection is dependent on induction of IL‐17 during infection. We found that macrophages were responsible for IL‐17 production in response to IL‐23. We observed a striking reduction in splenic macrophages in the p19KO and 17KO mice, both of which became highly susceptible to infection. Thus, IL‐17 appears to be crucial for maintenance of splenic macrophages. Adoptive transfer of macrophages into macrophage‐depleted mice confirmed that macrophage‐derived IL‐17 is required for macrophage accumulation and parasite eradication in the recipient mice. We also found that IL‐17 induces CCL2/7, which recruit macrophages. Our findings reveal a novel protective mechanism whereby IL‐23, IL‐17, and macrophages reduce the severity of infection with blood‐stage malaria parasites.     

Multi-Contrast Magnetic Resonance Imaging of Visual White Matter Pathways in Patients With Glaucoma

PurposeGlaucoma is a disorder that involves visual field loss caused by retinal ganglion cell damage. Previous diffusion magnetic resonance imaging (dMRI) studies have demonstrated that retinal ganglion cell damage affects tissues in the optic tract (OT) and optic radiation (OR). However, because previous studies have used a simple diffusion tensor model to analyze dMRI data, the microstructural interpretation of white matter tissue changes remains uncertain. In this study, we used a multi-contrast MRI approach to further clarify the type of microstructural damage that occurs in patients with glaucoma.MethodsWe collected dMRI data from 17 patients with glaucoma and 30 controls using 3-tesla (3T) MRI. Using the dMRI data, we estimated three types of tissue property metrics: intracellular volume fraction (ICVF), orientation dispersion index (ODI), and isotropic volume fraction (IsoV). Quantitative T1 (qT1) data, which may be relatively specific to myelin, were collected from all subjects.ResultsIn the OT, all four metrics showed significant differences between the glaucoma and control groups. In the OR, only the ICVF showed significant between-group differences. ICVF was significantly correlated with qT1 in the OR of the glaucoma group, although qT1 did not show any abnormality at the group level.ConclusionsOur results suggest that, at the group level, tissue changes in OR caused by glaucoma might be explained by axonal damage, which is reflected in the intracellular diffusion signals, rather than myelin damage. The significant correlation between ICVF and qT1 suggests that myelin damage might also occur in a smaller number of severe cases.     

Protective role of IL‐1β against post‐arthroplasty Staphylococcus aureus infection

MyD88 is an adapter molecule that is used by both IL‐1R and TLR family members to initiate downstream signaling and promote immune responses. Given that IL‐1β is induced after Staphylococcus aureus infections and TLR2 is activated by S. aureus lipopeptides, we hypothesized that IL‐1β and TLR2 contribute to MyD88‐dependent protective immune responses against post‐arthroplasty S. aureus infections. To test this hypothesis, we used a mouse model of a post‐arthroplasty S. aureus infection to compare the bacterial burden, biofilm formation and neutrophil recruitment in IL‐1β‐deficient, TLR2‐deficient and wild‐type (wt) mice. By using in vivo bioluminescence imaging, we found that the bacterial burden in IL‐1β‐deficient mice was 26‐fold higher at 1 day after infection and remained 3‐ to 10‐fold greater than wt mice through day 42. In contrast, the bacterial burden in TLR2‐deficient mice did not differ from wt mice. In addition, implants harvested from IL‐1β‐deficient mice had more biofilm formation and 14‐fold higher adherent bacteria compared with those from wt mice. Finally, IL‐1β‐deficient mice had ～50% decreased neutrophil recruitment to the infected postoperative joints than wt mice. Taken together, these findings suggest a mechanism by which IL‐1β induces neutrophil recruitment to help control the bacterial burden and the ensuing biofilm formation in a post‐surgical joint. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29: 1621–1626, 2011     

Laparoscopic choledochotomy in management of choledocholithiasis

PURPOSE: Laparoscopic choledochotomy on patients indicated for common bile duct exploration was carried out according to an algorithm for managing choledocholithiasis. This study describes retrospectively our method and evaluates a new cystic duct biliary decompression cannula (J-tube) as an alternative to the T-tube. METHODS: Patients with confirmed choledocholithiasis (n=46) underwent laparoscopic choledochotomy. The T-tube was inserted in cases with suspected retained stones after common bile duct clearance, and the J-tube (950-mm long, 4 Fr) with a tapered and J-shaped segment at the distal end was inserted in other cases. RESULTS: Only 1 case was converted to open surgery (success rate, 97.8%); the J-tube was inserted in 30 patients and the T-tube in 15. The median operation time, hospital stay, and the interval until removal of the tube were significantly shorter with J-tube than with T-tube cases. Bile leakage after surgery occurred in 4 J-tube and 2 T-tube cases with one residual stone in each case. CONCLUSIONS: The transcystic decompression tube is easily and safely inserted with the J-kit. Among several strategies currently available for the management of choledocholithiasis, laparoscopic choledochotomy with the use of the J-tube is one of the safest and most feasible methods.     

Adenocarcinoma arising in a colonic interposition following a total gastrectomy: Report of a case

A segment of the transverse colon can be used for gastric reconstruction after a total gastrectomy. This report presents the case of a 68-year-old woman with primary adenocarcinoma of the colon in a segment used for reconstruction after a total gastrectomy. The interposed colon developed colon carcinoma 9 years after the gastric reconstruction. The possibility of a primary carcinoma arising in a gastric colon interposition must be considered when employing the transverse colon as a gastric substitute.     

Factors Associated with Pneumocystis jirovecii Pneumonia in Patients with Rheumatoid Arthritis Receiving Methotrexate: A Single-center Retrospective Study

Objective To investigate the risk factors for the development of Pneumocystis jirovecii pneumonia (PCP) in patients with rheumatoid arthritis (RA) undergoing methotrexate (MTX) therapy. Methods This single-center retrospective cohort study included consecutive patients with RA who received MTX for at least one year. The study population was divided into PCP and non-PCP groups, depending on the development of PCP, and their characteristics were compared. We excluded patients who received biologic disease-modifying anti-rheumatic drugs (DMARDs), Janus kinase inhibitors, and anti-PCP drugs for prophylaxis. Results Thirteen patients developed PCP, and 333 did not develop PCP. At the initiation of MTX therapy, the PCP group had lower serum albumin levels, a higher frequency of pulmonary disease and administration of DMARDs, and received a higher dosage of prednisolone (PSL) than the non-PCP group. A multivariate Cox regression analysis revealed that the concomitant use of PSL [hazard ratio (HR) 5.50, p=0.003], other DMARDs (HR 5.98, p=0.002), and serum albumin <3.5 mg/dL (HR 4.30, p=0.01) were risk factors for the development of PCP during MTX therapy. Patients with these risk factors had a significantly higher cumulative probability of developing PCP than patients who lacked these risk factors. Conclusion Clinicians should pay close attention to patients with RA who possess risk factors for the development of PCP during MTX therapy.     

A Rare Case of Rheumatoid Arthritis with Tocilizumab-induced Intestinal Mucosal Injury

Intestinal mucosal injury that develops as a complication of tocilizumab (TCZ) is usually associated with diverticulosis. We herein report a rare case of TCZ-induced intestinal mucosal injury in the absence of diverticulosis. A 74-year-old woman suffering from rheumatoid arthritis started taking TCZ. Six months later, she complained of hematochezia and abdominal pain. Colonoscopy revealed multiple ulcers spreading from the cecum to the transverse colon but no diverticulosis. These lesions were cured at three months after the discontinuation of TCZ. We should consider TCZ as a risk factor for intestinal mucosal injury, even if patients have no history of intestinal disease associated with diverticulosis.     

ENDOSCOPIC DIAGNOSIS OF INTRADUCTAL PAPILLARY‐MUCINOUS NEOPLASM OF THE PANCREAS BY MEANS OF PERORAL PANCREATOSCOPY USING A SMALL‐DIAMETER VIDEOSCOPE AND NARROW‐BAND IMAGING

Background: Intraductal papillary‐mucinous neoplasm (IPMN) is an intraductal tumor in which the mucin‐producing epithelium shows proliferated papillary and a wide variety of pathological changes ranging from hyperplasia to adenocarcinoma. Therefore, it is important to determine whether an IPMN is benign or malignant. In the present study of patients with IPMN, the protrusion was observed by a peroral pancreatoscopy (PPS) using a small‐diameter videoscope and narrow‐band imaging (NBI). We carried out the differential diagnosis of benign lesion to malignant lesion. Methods: Between April 2003 and May 2009, PPS using a small‐diameter videoscope by means of NBI was carried out on 21 hospitalized patients with IPMN (10 cases of adenocarcinoma, 11 cases of adenoma or hyperplasia; 14 males and seven females, with a mean age of 69.4 years). Results: Fifteen focal lesions of the 16 cases in the head of the pancreas (93.7%) and four focal lesions of the five cases in the pancreatic body (80%) were observable, whereas two lesions (adenocarcinoma in the pancreatic body, and adenoma in the uncus of pancreas) were not observable. Endoscopically, seven cases were classified as villous type and two cases as vegetative type, and nine cases were diagnosed as adenocarcinoma. Ten cases with sessile type or semipedunculated type were diagnosed as adenoma or hyperplasia. Vascular patterns and protrusions were detected more clearly in the NBI images than under white light observation. Conclusions: When combined with a videoscope and NBI, pancreatoscopy provided a clear image and was useful for evaluating whether the IPMN was benign or malignant.