Russell body gastritis

A 63-year-old woman who presented with chest and back pain underwent an upper gastrointestinal endoscopy which revealed elevated legion in the antrum mucosa. Histologic examinations of gastric biopsies were showing monoclonal proliferation plasma cells containing Russell bodies. Differential diagnosis from B-cell lymphoma and plasmacytoma is difficult, because of monoclonality. Molecular analyses of immunoglobulin heavy chain (IgH) gene demonstrated that gene rearrangement was negative. Thus, diagnosis of Russell body gastritis was made. The Giemsa stains were also showing infection of Helicobacter pylori (H.pylori). After eradication therapy for H.pylori, follow-up upper gastrointestinal endoscopy was performed. She then recovered.     

Moderate-to-vigorous physical activity and the risk of stroke recurrence in patients with a history of minor ischemic stroke in Japan: a retrospective analysis

Background: Physical activity (PA) is beneficial for stroke prevention; in particular, moderate-to-vigorous physical activity (MVPA). However, few studies have investigated its relationship with recurrent ischemic stroke (RIS).

Objectives: To clarify the relationship between MVPA and RIS and the burden of risk factors after a first-ever ischemic stroke.

Methods: A total of 45 outpatients (mean age 67.1 ± 10.2 years) who had previously experienced a transient ischemic attack or a minor non-cardioembolic ischemic stroke at a single hospital in Japan (mean 6.4 ± 4.2 years previously), were enrolled between March and June 2016. All patients wore an accelerometer around their hips for 10 days, and their percentage body fat (%BF) and visceral fat level (VFL) were measured by bioelectrical impedance. Retrospective information about the history of RIS and risk factors (blood pressure, lipoprotein cholesterol and estimated glomerular filtration rate) were extracted from the clinical records. Binary logistic regression models were used to estimate the relevance of the RIS history to MVPA and potential risk factors such as sociodemographic and clinical variables (obesity, smoking and hypertension).

Results: RIS occurred in 9 patients; they had significantly higher VFL (p = 0.007) and %BF (p = 0.007) values and lower MVPA (p = 0.011) values than patients without recurrence. A multivariate analysis of these factors indicated that age, VFL and MVPA were signi?cant independent predictors of RIS.

Conclusions: Patients with a history of mild ischemic stroke had low MVPA and high VFL values, which together may be a risk factor for RIS.     

PD-1, but Not PD-L1, Expressed by Islet-Reactive CD4+ T Cells Suppresses Infiltration of the Pancreas During Type 1 Diabetes

The inhibitory receptor programmed death-1 (PD-1) constrains type 1 diabetes (T1D) in the nonobese diabetic (NOD) mouse. However, how PD-1 influences diabetogenic CD4⁺ T cells during natural diabetes is not fully understood. To address this question, we developed a novel model to investigate antigen-specific CD4⁺ T cells under physiological conditions in vivo. We transferred a low number of naïve CD4⁺ T cells from the BDC2.5 mouse into prediabetic NOD mice to mimic a physiological precursor frequency and allowed the cells to become primed by endogenous autoantigen. Transferred BDC2.5 T cells became activated, differentiated into T-bet⁺ IFN-γ–producing cells, and infiltrated the pancreas. In this model, loss of PD-1, but not programmed death ligand-1 (PD-L1), on the antigen-specific CD4⁺ T cell resulted in increased cell numbers in the spleen, pancreas-draining lymph node, and pancreas. PD-1 deficiency also increased expression of the chemokine receptor CXCR3. Lastly, histological data showed that a loss of PD-1 caused BDC2.5 cells to penetrate deep into the islet core, resulting in conversion from peri-insulitis to destructive insulitis. These data support a model by which PD-1 regulates islet-reactive CD4⁺ T cells in a cell intrinsic manner by suppressing proliferation, inhibiting infiltration of the pancreas, and limiting diabetes.Type 1 diabetes (T1D) is an autoimmune disease mediated by T-cell destruction of the insulin-producing β-cells in the pancreatic islets of Langerhans (1). The nonobese diabetic (NOD) mouse is a classic model for studying T1D because it shares many similarities with human T1D, including the requirement of CD4⁺ T cells for disease (2–4). However, knowledge of how diabetogenic CD4⁺ T cells are regulated and how this regulation fails, causing T1D, is limited owing to a lack of tools to monitor endogenous diabetogetic CD4⁺ T cells.Common models used to study diabetogenic CD4⁺ T cells in NOD mice include adoptive transfer of high numbers of naïve or in vitro activated T-cell receptor (TCR) transgenic cells into wild-type (WT) or lymphopenic NOD recipients (5–10). While informative, these approaches fail to recapitulate the natural inflammatory environment present in NOD mice and the timing associated with T1D progression. Previous work in other systems showed that transferring lower numbers of naïve T cells allowed greater clonal expansion on a per cell basis and more efficient effector cell differentiation (11–14). Since we speculate that endogenous autoantigen in the NOD mouse is low, we predicted that limiting the diabetogenic precursor frequency would be essential for autoantigen encounter and activation. Therefore, in this study we developed a new model by transferring a small number of islet-specific BDC2.5 transgenic CD4⁺ T cells (15,16) into prediabetic NOD mice to mimic an endogenous preimmune repertoire.The inhibitory receptor programmed death-1 (PD-1) interacting with programmed death ligand-1 (PD-L1) is critical for suppressing diabetes, since disrupting PD-1/PD-L1 interactions accelerates T1D in NOD mice (7,17–19) and polymorphisms in PD-1 have been associated with human T1D (20). Previous studies demonstrated roles for the PD-1 pathway by inhibiting CD4⁺ T-cell survival, proliferation, and cytokine production using in vitro and in vivo systems (5,7,21–24). However, since many of the in vivo studies relied on adoptive transfer of nonphysiologically high numbers of TCR transgenic T cells, the cellular mechanisms by which PD-1 constrains diabetogenic CD4⁺ T cells in hosts with a normal T-cell repertoire remain unclear. We therefore reexamined the role of PD-1 in regulating CD4⁺ T cells in vivo using a new adoptive transfer model that more closely mimics the normal naïve preimmune repertoire. Our results show that PD-1 expressed by the BDC2.5 T cell is required to regulate proliferation, chemokine receptor CXCR3 expression, infiltration of the pancreas, and diabetes pathogenesis.     

Comparison of PPIs and H2-receptor antagonists plus prokinetics for dysmotility-like dyspepsia

AIM: To compare efficacy of proton pump inhibitors (PPIs) with H₂-receptor antagonists (H₂RAs) plus prokinetics (Proks) for dysmotility-like symptoms in functional dyspepsia (FD).METHODS: Subjects were randomized to receive open-label treatment with either rabeprazole 10 mg od (n = 57) or famotidine 10 mg bid plus mosapride 5 mg tid (n = 57) for 4 wk. The primary efficacy endpoint was change (%) from baseline in total dysmotility-like dyspepsia symptom score. The secondary efficacy endpoint was patient satisfaction with treatment.RESULTS: The improvement in dysmotility-like dyspepsia symptom score on day 28 was significantly greater in the rabeprazole group (22.5% ± 29.2% of baseline) than the famotidine + mosapride group (53.2% ± 58.6% of baseline, P < 0.0001). The superior benefit of rabeprazole treatment after 28 d was consistent regardless of Helicobacter pylori status. Significantly more subjects in the rabeprazole group were satisfied or very satisfied with treatment on day 28 than in the famotidine + mosapride group (87.7% vs 59.6%, P = 0.0012). Rabeprazole therapy was the only significant predictor of treatment response (P < 0.0001), defined as a total symptom score improvement ≥ 50%.CONCLUSION: PPI monotherapy improves dysmotility-like symptoms significantly better than H₂RAs plus Proks, and should be the treatment of first choice for Japanese FD.     

Effect of topical application of fluoride gel NaF 2% on enzymatic and non-enzymatic antioxidant parameters of saliva

ObjectiveThe aim of the study was to evaluate the effect of topical fluoride gel NaF 2% application on antioxidant parameters of whole saliva from children.DesignThe saliva mechanically stimulated with parafilm was collected from 25 children (6–12 years) attending the Clinic of Paediatric Dentistry of Universidade Cruzeiro do Sul, São Paulo, Brazil, before (control group) and immediately after application of neutral fluoride gel NaF 2% (fluoride-gel group), according to the Standards for Research Using Human Subjects, Resolution 196/96 of the USA National Health Council of 10/10/1996. Afterwards, pre-post ferric-reducing antioxidant power (FRAP), trolox-equivalent antioxidant capacity (TEAC), uric acid, reduced/oxidised glutathione content (GSH/GSSG) and total peroxidase activity (TPO) were evaluated in whole saliva of both groups.ResultsAll non-enzymatic antioxidant parameters were augmented by fluoride-gel NaF 2% application, whereas a notable reduction (31%) of peroxidase activity was concomitantly observed in the children's saliva (p ≤ 0.05). Nevertheless, the reducing power of saliva was kept unaltered under these circumstances (p ≤ 0.05).ConclusionsDespite the reduced activity of peroxidase (an important antimicrobial and antioxidant enzyme), the topical fluoride gel NaF 2% favourably stimulated the release of non-enzymatic antioxidant components of saliva, sustaining the reducing power of saliva and the natural defences of the oral cavity.     

A comparison of error detection rates between the reading aloud method and the double data entry method

Data entry and its verification are important steps in the process of data management in clinical studies. In Japan, a kind of visual comparison called the reading aloud (RA) method is often used as an alternative to or in addition to the double data entry (DDE) method. In a typical RA method, one operator reads previously keyed data aloud while looking at a printed sheet or computer screen, and another operator compares the voice with the corresponding data recorded on case report forms (CRFs) to confirm whether the data are the same. We compared the efficiency of the RA method with that of the DDE method in the data management system of the Japanese Registry of Renal Transplantation. Efficiency was evaluated in terms of error detection rate and expended time. Five hundred sixty CRFs were randomly allocated to two operators for single data entry. Two types of DDE and RA methods were performed. Single data entry errors were detected in 358 of 104,720 fields (per-field error rate=0.34%). Error detection rates were 88.3% for the DDE method performed by a different operator, 69.0% for the DDE method performed by the same operator, 59.5% for the RA method performed by a different operator, and 39.9% for the RA method performed by the same operator. The differences in these rates were significant (p<0.001) between the two verification methods as well as between the types of operator (same or different). The total expended times were 74.8 hours for the DDE method and 57.9 hours for the RA method. These results suggest that in detecting errors of single data entry, the RA method is inferior to the DDE method, while its time cost is lower.     

Media conditioned by retinal pigment epithelial cells suppress the canonical Wnt pathway

Retinal pigment epithelial (RPE) cells play critical roles in the maintenance of visual function, partly by secreting various biologically active factors that modulate the intraocular environment. Recent studies suggest involvement of Wnt proteins secreted by RPE cells in the pathogenesis of photoreceptor degeneration. In the present study, we examined, via the luciferase assay, the effect of media conditioned by RPE cells (RPE-CM) on activity of the canonical Wnt pathway in vitro. We isolated primary RPE cells from Long-Evans rats at P6-P9. In culture, these cells formed a monolayer with polygonal cell morphology and demonstrated repigmentation at confluency and immunoreactivity for ZO-1, a marker for tight junctions. To evaluate the effect of RPE-CM on the canonical Wnt pathway, we replaced the culture media of COS-7 cells transfected with (Tcf)(7)LUC, a multimeric Tcf-responsive element luciferase reporter construct, with RPE-CM and measured luciferase activity with or without Wnt3a or SB216763, a specific GSK3 inhibitor. RPE-CM did not enhance basal or Wnt3a-induced (Tcf)(7)LUC activity; instead, this activity decreased by 60%. RPE-CM also reduced SB216763-induced (Tcf)(7)LUC activity by 65%, which suggests that the inhibitory effect of RPE-CM is probably due to intracellular crosstalk rather than extracellular antagonism. RPE cells may thus be able to modulate the intraocular environment by regulating the canonical Wnt pathway.