Repeated antigen painting and sublingual immunotherapy in mice convert sublingual dendritic cell subsets

The sublingual mucosa (SLM) is utilized as the site for sublingual immunotherapy (SLIT) to induce tolerance against allergens. The contribution of SLM-dendritic cells (SLM-DCs) has not been clarified. The aim of this study was to examine the dynamics and phenotype of SLM-DCs after topical antigen painting and SLIT. SLM-DCs were histologically evaluated after FITC painting. A novel murine Japanese cedar pollinosis (JCP) model was generated and change in SLM-DCs after SLIT was examined. The density of SLM-DCs was clearly lower compared with the buccal mucosa and dorsal surface of the tongue. Topical FITC painting on the SLM induced maximal recruitment of submucosal DCs (smDCs) at 6 h, but most smDCs had vanished at 24 h. Repeated painting on the SLM induced exhaustion and conversion of the smDC phenotype. CD206^highCD11c^low round-type cells with fewer dendrites and less lymph node migration capacity became dominant. In the murine model of JCP, SLIT efficiently inhibited clinical symptoms and allergen-mediated immunological responses. SLIT markedly reduced the number of SLM-DCs, converted to the round-type dominant phenotype and inhibited the activation of regional lymph node DCs. Topical antigen painting on the SLM induced rapid exhaustion and conversion of smDCs. The unique dynamics of SLM-DCs may contribute to tolerance induction in SLIT.     

Therapeutic strategy using extracorporeal life support,including appropriate indication,management, limitation and timing of switch to ventricular assist device in patients with acute myocardial infarction

The appropriate indication for, management of and limitations to extracorporeal life support (ECLS) and the timing of a switch to a ventricular assist device (VAD) remain controversial issues in patients with acute myocardial infarction (AMI) complicated with cardiogenic shock or cardiopulmonary arrest. To evaluate and discuss these issues, we studied patients with AMI treated with ECLS and compared deceased and discharged patients. Thirty-eight patients with AMI who needed ECLS [35 men (92.1 %), aged 59.9 ± 13.5 years] were enrolled in this study. Of these 38 patients, 34 subsequently underwent percutaneous coronary intervention (PCI), and four subsequently received coronary artery bypass grafting (CABG). Fourteen patients (36.8 %) were discharged from the hospital. The outcome was not favorable for those patients with deteriorating low output syndrome (LOS) and the development of leg ischemia, hemolysis and multiple organ failure during ECLS. Levels of creatine kinase, creatine kinase-MB (CK-MB), lactate dehydrogenase, serum creatinine (Cr) and amylase after the patient had been put on ECLS and fluctuation of the cardiac index, blood pressure, arterial blood gas analysis and CK-MB and Cr levels during ECLS were indicators to switch from the ECLS to VAD. In the case of patients with no complication associated with ECLS, 4.6–5.6 days after initiation of ECLS was assumed to be the threshold to decide whether to switch from ECLS to VAD. Patients with AMI who suddenly developed refractory pulseless ventricular tachycardia or ventricular fibrillation without deteriorating LOS and who underwent successful PCI or CABG, and who prevented the complications associated with ECLS, showed a high probability of recovering with ECLS.     

Association between magnetic resonance imaging characteristics and pathological findings in entire posterior cruciate ligament with mucoid degeneration

Magnetic resonance imaging (MRI) findings of a tram-track appearance and celery stalk appearance in mucoid degeneration of the cruciate ligament are valuable; however, their pathological basis is unclear. Because these appearances are generally seen throughout the entire ligament, the association between MRI findings and pathological findings must be verified in specimens of the whole degenerated ligament, including the ligamentous attachments to bone. We herein report two cases of mucoid degeneration of the posterior cruciate ligament with osteoarthritis of the knee requiring total knee arthroplasty. The entire degenerated ligament, including the ligamentous attachments to bone, was removed and pathologically evaluated. On pathological examination, the central portion of the lesion showed typical mucoid degeneration, whereas the marginal and adherent portions showed normal ligament tissue, consistent with a tram-track appearance on T2-weighted MRI. The fibrous normal ligament tissues in the longitudinal direction in regions of mucoid degeneration were consistent with a celery stalk appearance on T2-weighted MRI. No mucoid degeneration was found in the attachment area. The tram-track appearance and celery stalk appearance of mucoid degeneration on MRI can be explained by the pathological findings.     

Amelioration of dextran sulfate sodium-induced colitis by anti-macrophage migration inhibitory factor antibody in mice

BACKGROUND & AIMS: We investigated the effects of macrophage migration inhibitory factor (MIF) antibodies in experimental colitis-induced dextran sulfate sodium (DSS) and trinitrobenzenesulfonic acid (TNBS) and examined whether plasma levels of MIF were elevated in patients with inflammatory bowel disease (IBD). METHODS: BALB/c or C57BL/6 mice were fed 4% DSS in their drinking water for up to 7 days with and without administration of an anti-MIF antibody every 2 days. The severity of inflammation in the cecum and colon was assessed by clinical signs and histologic scoring. Tissue levels of MIF, tumor necrosis factor (TNF)-alpha, interferon gamma (IFN-gamma), interleukin (IL)-4, and matrix metalloproteinase (MMP)-13 messenger RNA (mRNA) were measured. The effects of anti-MIF antibody on chronic colitis induced by TNBS was assessed in BALB/c mice. Plasma MIF concentrations were assayed in patients with Crohn's disease, ulcerative colitis, and healthy controls. RESULTS: During DSS-induced colitis, colonic MIF mRNA expression was increased. Clinical signs and histopathologic features were significantly improved in animals given anti-MIF antibody. DSS-induced up-regulation of colonic TNF-alpha and IFN-gamma were significantly suppressed in animals given the anti-MIF antibody. Colonic IL-4 was decreased during DSS but restored to baseline by the anti-MIF antibody. The anti-MIF antibody prevented MMP-13 up-regulation by DSS and ameliorated TNBS colitis. Plasma MIF was elevated in patients with Crohn's disease or ulcerative colitis compared with healthy controls. CONCLUSIONS: We conclude that anti-MIF antibodies reduce the severity of experimental colitis and limit the up-regulation of Th1-type cytokines. Anti-MIF antibodies are of potential therapeutic use in IBD.     

Circulating coupling factor 6 in human hypertension: role of reactive oxygen species

OBJECTIVE: Coupling factor 6 is an endogenous inhibitor of prostacyclin synthesis and might function as an endogenous vasoconstrictor in the fashion of a circulating hormone in rats. We investigated the role of coupling factor 6 in human hypertension. METHODS AND RESULTS: The patients with essential hypertension (EH) (n = 30) received a series of normal salt diet (12 g salt/day) for 3 days, low salt diet (2 g salt/day) for 7 days, and high salt diet (20-23 g salt/day) for 7 days. Normotensive control subjects (n = 27) received normal and low salt diets. The plasma level of coupling factor 6, measured by radioimmunoassay, during normal salt diet was higher in patients with EH than in normotensive subjects (17.6 +/- 1.7 versus 12.8 +/- 0.5 ng/ml, P < 0.01). Whereas the plasma level of coupling factor 6 was unchanged after salt restriction in normotensive subjects, it was decreased after salt restriction (from 12 g/day to 2 g/day) and was increased after salt loading (from 2 g/day to 20-23 g/day) in patients with EH. This increase in plasma level of coupling factor 6 was abolished by oral administration of ascorbic acid, but the level of blood pressure was unaffected. The percentage changes in plasma coupling factor 6 level after salt restriction and loading were positively correlated with those in mean blood pressure (r = 0.57, P < 0.01), and negatively correlated with those in plasma nitric oxide level (r = -0.51, P < 0.05). CONCLUSION: These indicate that circulating coupling factor 6 is elevated in human hypertension and modulated by salt intake presumably via reactive oxygen species.     

Vector potential of cockroaches for Helicobacter pylori infection

OBJECTIVES: The routes of human infection with Helicobacter pylori remain unclear. In the present study, we examined cockroaches as possible vectors for transmission of H. pylori. METHODS: We used a common species of cockroach (Periplaneta fuliginosa). After a 3-day fast, cockroaches were placed on agar plates containing freshly grown H. pylori (Sydney strain) (challenge group) or on sterile agar plates without H. pylori (control group). After 24 h of challenge, cockroaches were moved to disinfected containers, and sterile food and water were provided. The external surfaces (legs and body) and excreta of the cockroaches were sampled for culture, rapid urease test, and polymerase chain reaction (PCR). RESULTS: H. pylori were culturable from the excreta of the challenge group for 24 h postchallenge. Positive rapid urease test results were obtained up to day 3, and PCR analysis was positive for H. pylori DNA up to day 7 from the excreta. In contrast, H. pylori were not culturable from the external surfaces of the cockroaches. The rapid urease test was positive for only 8 h, and PCR analysis was positive for H. pylori DNA for 1 day from the external surface. CONCLUSIONS: Cockroaches usually live in unsanitary environments and may contaminate foods and food containment areas such as pantries. Transmission of H. pylori infection could be achieved via inadvertent ingestion of foods contaminated with cockroach excreta containing viable H. pylori.     

Silver-Russell syndrome in a girl born after <Emphasis Type="Italic">in vitro</Emphasis> fertilization: partial hypermethylation at the differentially methylated region of <Emphasis Type="Italic">PEG1</Emphasis>/<Emphasis Type="Italic">MEST</Emphasis>

Purpose: The prevalence of low birth weight (LBW) is increased in subjects born after assisted reproduction technology (ART), and defective imprinting has frequently been identified in patients with Beckwith-Wiedermann and Angelman syndromes conceived by ART. Thus, we examined methylation pattern in a girl born after ART who had Silver-Russell syndrome (SRS) which can be caused by maternal uniparental disomy for chromosome 7 and by hypomethylation of the differentially methylated region (DMR) of H19. Methods: We examined methylation status of 31 cytosines at the CpG dinucleotides in the DMR of PEG1/MEST on 7q32.2 and 23 cytosines at the CpG dinucleotides in the DMR of H19 on 11p15, using leukocyte genomic DNA. Results: Eight of the 31 cytosines in the patient and four of the 31 cytosines in the father were hypermethylated in the PEG1/MEST-DMR. In the H19-DMR, no abnormal methylation pattern was identified in the patient. Conclusion: The results suggest that hypermethylation of paternally expressed genes including PEG1/MEST, which usually have growth-promoting effects, may be relevant to LBW in subjects conceived by ART. Partial hypermethylation was identified at the differentially methylated region of paternally expressed PEG1/MEST in a girl with Silver-Russell syndrome born after in vitro fertilization.