Coexpression of CD40 and CD40 ligand in Epstein-Barr virus-infected T and NK cells and their role in cell survival

We investigated the role that CD40-CD40 ligand (CD40L) signaling plays in survival of Epstein-Barr virus (EBV)-infected T and NK cells. EBV-infected T and NK cell lines derived from patients with either chronic active EBV infection (CAEBV) or nasal T/NK cell lymphoma, as well as virus-infected peripheral T cells freshly isolated from a patient with CAEBV, were shown to express both CD40 and CD40L on their surface. Apoptosis of these cells was enhanced by blockade of CD40-CD40L signaling by a fusion protein of CD40 and immunoglobulin G (CD40Ig). Expression of CD40 was induced in human CD40L-positive Jurkat T cells after experimental EBV infection, and apoptosis of infected cells was enhanced by CD40Ig. These results suggest that CD40-CD40L signaling promotes survival of EBV-infected T and NK cells and, thus, plays an important role in the pathogenesis of T/NK lymphoproliferative disorders associated with the virus.     

Relationship between sleep bruxism and sleep respiratory events in patients with obstructive sleep apnea syndrome

Purpose

Both obstructive sleep apnea syndrome (OSAS) and sleep bruxism (SB) are commonly related to arousal events. In this study, we examined the effect of SB on the sleep architecture and investigated the relationship between SB and sleep respiratory events in patients with OSAS.

Methods

Patients with OSAS (n?=?67) in whom apnea/hypopnea occurred five or more times per hour were recruited to this study. Healthy volunteers (n?=?16) were recruited as controls. None of the healthy volunteers had any sleep disorders or medical disorders, nor had they taken any medication or alcohol. Data were collected by standard polysomnography during overnight sleep tests in a dark, quiet room.

Results

The frequency of SB was higher in the OSAS than in the control group. The risk of SB was significantly higher in the OSAS than in the control group (odds ratio, 3.96; 95 % confidence interval, 1.03–15.20; P?OSAS than in the control group.

Conclusions

We found that patients with OSAS have a high risk of SB. In particular, this is the first report relating phasic-type SB to obstructive apnea events. This relationship suggests that improvement in OSAS might prevent exacerbations of SB.     

Short telomeres in an oral precancerous lesion: Q-FISH analysis of leukoplakia

J Oral Pathol Med (2012) 41 : 372–378 Objectives: A precancerous condition is a lesion that, if left untreated, leads to cancer or can be induced to become malignant. In the oral region, leukoplakia is a lesion that has been regarded as precancerous. In cases of oral carcinoma, we have frequently noticed that a type of leukoplakia histologically demonstrating hyper‐orthokeratosis and mild atypia (ortho‐keratotic dysplasia; OKD) is often associated with carcinoma, either synchronously or metachronously. Therefore, we consider OKD‐type leukoplakia to be a true precancerous lesion. Materials and Methods: In an attempt to clarify the relationship between OKD as a precancerous condition in the oral mucosa and telomere length, we estimated telomere lengths in this type of leukoplakia using quantitative fluorescence in situ hybridization, and also quantified the frequency of anaphase–telophase bridges (ATBs) in comparison with squamous cell carcinoma in situ (CIS) and the background tissues of CIS and OKD. Results: Ortho‐keratotic dysplasia was frequently associated with squamous cell carcinoma (45.0%) and showed significantly shorter telomeres than normal control epithelium, CIS, or the background of CIS or OKD. The frequency of ATBs was much higher in OKD than in control epithelium or CIS. Conclusion: Ortho‐keratotic dysplasia appears to be frequently associated with carcinoma, chromosomal instability, and excessively shortened telomeres, not only in the lesion itself but also in the surrounding background. Therefore, when this type of leukoplakia is recognized in the oral region, strict follow‐up for oral squamous cell carcinoma is necessary, focusing not only on the areas of leukoplakia, but also the surrounding background.     

Sequential monitoring of serum IL-6, TNF-α, and IFN-γ levels in a CAEBV patient treated by plasma exchange and immunochemotherapy

We report the case of a female patient with chronic active Epstein?CBarr virus infection (CAEBV) accompanied by hemophagocytic syndrome (HPS). On admission, she presented with severe liver dysfunction and disseminated intravascular coagulation with elevation of serum IL-6, TNF-??, and IFN-?? levels. Plasma exchange (PE) followed by immunochemotherapy with prednisolone, cyclosporine A, and VP16 was performed. PE decreased serum cytokine levels dramatically and improved liver function. Following immunochemotherapy, CAEBV became inactive. Four months after discharge, however, CAEBV relapsed with HPS, and serum cytokine levels were extremely elevated again. There was no response to immunochemotherapy, and the patient died 1?day after admission. We examined the cytokines in five additional untreated-CAEBV patients and determined that they were elevated above the normal level in all patients. These results suggest that inflammatory cytokines may have roles in the development of CAEBV, and that their depletion can be an effective treatment for this disease.     

Effects of bile-acid-binding resin (colestimide) on blood glucose and visceral fat in Japanese patients with type 2 diabetes mellitus and hypercholesterolemia: an open-label, randomized, case-control, crossover study

ObjectiveThe objective was to examine the effects of colestimide on blood glucose, visceral fat, adipocytokines, and bile acid conjugate fractions in Japanese patients.MethodsThis study was an open-label, randomized, case–control, crossover study of colestimide 3 g/day in 40 Japanese patients with type 2 diabetes mellitus (T2D) and hypercholesterolemia. Patients were assigned to the colestimide group in which pravastatin and colestimide were administered orally and to the statin group in which pravastatin alone was administered orally. The principal outcome measures were serum lipid levels, fasting plasma glucose level in the early morning, hemoglobin A1c (HbA_1c), visceral fat area (VFA), and serum 1,5-anhydroglucitol (1,5-AG) level.ResultsSerum low-density lipoprotein cholesterol levels significantly decreased from 113±38 mg/dl at baseline to 90±20 mg/dl (P=.009) at week 12 of colestimide administration. HbA_1c significantly decreased from 7.4%±0.9% at baseline to 6.9%±0.9% (P=.001) at week 12 of colestimide administration. Serum 1,5-AG levels increased from 9.4±10.1 μg/ml to 12.4±9.5 μg/ml (P=.05) at week 12 of colestimide administration. The statin group showed no significant changes in lipids and 1,5-AG. However, ΔVFA was inversely correlated with Δcholic acid, and multivariate analysis revealed that ΔVFA was a significant explanatory variable.ConclusionsColestimide holds promise not only for the treatment of hypercholesterolemia but also for the possible improvement of T2D and visceral fat obesity.     

Estimation of salt intake from spot urine samples in patients with chronic kidney disease

ABSTRACT: BACKGROUND: High salt intake in patients with chronic kidney disease (CKD) may cause high blood pressure and increased albuminuria. Although, the estimation of salt intake is essential, there are no easy methods to estimate real salt intake. METHODS: Salt intake was assessed by determining urinary sodium excretion from the collected urine samples. Estimation of salt intake by spot urine was calculated by Tanaka's formula. The correlation between estimated and measured sodium excretion was evaluated by Pearson's correlation coefficients. Performance of equation was estimated by median bias, interquartile range (IQR), proportion of estimates within 30 % deviation of measured sodium excretion (P30) and root mean square error (RMSE).The sensitivity and specificity of estimated against measured sodium excretion were separately assessed by receiver-operating characteristic (ROC) curves. RESULTS: A total of 334 urine samples from 96 patients were examined. Mean age was 58 +/- 16 years, and estimated glomerular filtration rate (eGFR) was 53 +/- 27 mL/min. Among these patients, 35 had CKD stage 1 or 2, 39 had stage 3, and 22 had stage 4 or 5. Estimated sodium excretion significantly correlated with measured sodium excretion (R = 0.52, P < 0.01). There was apparent correlation in patients with eGFR <30 mL/min (R = 0.60, P < 0.01). Moreover, IQR was lower and P30 was higher in patients with eGFR < 30 mL/min. Estimated sodium excretion had high accuracy to predict measured sodium excretion, especially when the cutoff point was >170 mEq/day (AUC 0.835). CONCLUSIONS: The present study demonstrated that spot urine can be used to estimate sodium excretion, especially in patients with low eGFR.