Association study of human MTH1 gene polymorphisms with type 1 diabetes mellitus

Reactive oxygen species are considered to play a role in the development of diabetes mellitus and its complications. Human MTH1 (mutT homologue 1) has 8-oxo-7,8-dihydrodeoxyguanosine triphosphatase activity, which repairs oxidized forms of dGTP. This enzyme is known to have a thermolabile Met83 variant. We examined whether Val83Met polymorphism of human MTH1 gene is associated with type 1 diabetes mellitus. We recruited 156 type 1 diabetic patients (59 males and 97 females). The polymorphism was analyzed by restriction fragment length polymorphism analysis with Nsi I. The Met/Met genotype at codon 83 was very rare in both control and patient groups. Val/Met genotype tended to be more frequent in the whole type 1 diabetic patients than in controls. When subjects were divided into subgroups according to gender, there were no differences in the genotype and allele frequencies between patients and controls in males. On the other hand, in female type 1 diabetic patients, the Val/Met genotype was more frequent than in female controls (corrected P = 0.102). The Met allele was significantly more frequent in female type 1 diabetic patients than in female controls (corrected P = 0.022). Our results suggested that the Met allele at codon 83 of MTH1 gene might be involved in the development of type 1 diabetes mellitus in the Japanese female population.     

Quantitative Monitoring of Circulating Epstein-Barr Virus DNA for Predicting the Development of Posttransplantation Lymphoproliferative Disease

Epstein-Barr virus (EBV)-DNA was quantitatively measured to assess posttransplantation virus reactivation by real-time polymerase chain reaction (PCR). In the first retrospective analysis of a 7-year-old boy with lymphoproliferative disease (LPD) after an unrelated cord blood transplantation, serum EBV-DNA progressively increased to 4 x 10(5) copies/mL. EBV load was then prospectively monitored in peripheral blood from posttransplantation patients. The second case was an 8 year-old boy with aplastic anemia who received a CD34+ cell transplantation. This patient died of LPD with the progression of pulmonary nodules. EBV-DNA increased to 4 x 10(4) copies/mL after the control of cytomegalovirus reactivation. On the other hand, EBV-DNA was undetectable (<200 copies/mL) in the series of all 58 samples from 10 patients who did not develop LPD after hematopoietic stem cell transplantation. Sequential monitoring of circulating EBV-DNA by quantitative PCR may be a useful indicator for predicting the development of posttransplantation LPD.     

Cytotoxic T-Cell Lymphoma Arising in Behçet Disease

The case of a 49-year-old man with peripheral T-cell lymphoma arising in Behçet disease (BD) is reported. A diagnosis of incomplete BD was made, and the patient was treated with immunosuppressive agents for 9 months. A left perirenal mass emerged, and a computed tomography-guided needle biopsy of the tumor revealed the infiltration of small- and medium-sized lymphoma cells.The cells were positive for CD3, CD8, CD45RO, CD43, granzyme B, and T-cell intracellular antigen-1.A diagnosis of non-Hodgkin’s lymphoma (diffuse medium, T-cell) was made.A left orbital mass also appeared. Standard combination chemotherapy diminished the perirenal and orbital lesions.Lymphoma cell infiltration in the esophagus was detected after chemotherapy, and the patient died of massive bleeding from the gastrointestinal tract. Non-Hodgkin’s lymphoma is rarely associated with BD, and only 7 cases have been reported in the literature.We have summarized the published case reports of malignant lymphoma arising in BD.To our knowledge, this case report is the first to describe cytotoxic T-cell lymphoma arising in Behçet disease.     

Alberta Stroke Program Early CT Score Calculation Using the Deep Learning-Based Brain Hemisphere Comparison Algorithm

ObjectivesThe Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is a promising tool for the evaluation of stroke expansion to determine suitability for reperfusion therapy. The aim of this study was to validate deep learning-based ASPECTS calculation software that utilizes a three-dimensional fully convolutional network-based brain hemisphere comparison algorithm (3D-BHCA).Materials and MethodsWe retrospectively collected head non-contrast computed tomography (CT) data from 71 patients with acute ischemic stroke and 80 non-stroke patients. The results for ASPECTS on CT assessed by 5 stroke neurologists and by the 3D-BHCA model were compared with the ground truth by means of region-based and score-based analyses.ResultsIn total, 151 patients and 3020 (151 × 20) ASPECTS regions were investigated. Median time from onset to CT was 195 min in the stroke patients. In region-based analysis, the sensitivity (0.80), specificity (0.97), and accuracy (0.96) of the 3D-BHCA model were superior to those of stroke neurologists. The sensitivity (0.98), specificity (0.92), and accuracy (0.97) of dichotomized ASPECTS > 5 analysis and the intraclass correlation coefficient (0.90) in total score-based analysis of the 3D-BHCA model were superior to those of stroke neurologists overall. When patients with stroke were stratified by onset-to-CT time, the 3D-BHCA model exhibited the highest performance to calculate ASPECTS, even in the earliest time period.ConclusionsThe automated ASPECTS calculation software we developed using a deep learning-based algorithm was superior or equal to stroke neurologists in performing ASPECTS calculation in patients with acute stroke and non-stroke patients.     

Relationship between interleukin-1β gene expression in epicardial adipose tissue and coronary atherosclerosis based on computed tomographic analysis

BackgroundAnti-inflammatory therapy targeting interleukin (IL)-1β reduced cardiovascular events in a randomized trial. We evaluated the relationship between IL-1β mRNA expression in epicardial adipose tissue (EAT) and clinically-assessed coronary atherosclerosis on computed tomography (CT).MethodsWe studied 45 patients before cardiac surgery (coronary artery bypass grafting [CABG], n ?= ?18; non-CABG, n ?= ?27). EAT volume, the coronary calcium score (CCS), and the presence of non- and/or partially-calcified coronary plaques (NCPs) and high-risk coronary plaques (HRPs; minimum CT density <30 Hounsfield units and vascular remodeling index >1.1) on CT angiography were assessed. EAT samples were obtained during cardiac surgery. IL-1β mRNA expression in EAT was measured using quantitative real-time PCR and normalized to that of β-actin in each patient.ResultsThere was no difference in IL-1β mRNA levels between patients who were scheduled for CABG and non-CABG surgery or among subgroups based on the CCS. However, patients with NCPs (median [interquartile range], 4.1[2.0-11.6]E-4 versus 1.8[0.6-4.5]E-4, p ?= ?0.024) and HRP (7.6[3.0-20.4]E-4 versus 1.9[0.7-4.3]E-4, p ?= ?0.0023) had higher IL-1β mRNA levels than those without these plaques. On multivariate analysis adjusted for age, sex, coronary risk factors, statin therapy, CCS, and EAT volume, the presence of HRPs was significantly correlated with elevated IL-1β mRNA levels in EAT (β ?= ?0.39, p ?= ?0.047).ConclusionOur data suggest a contribution of EAT to coronary atherosclerosis through molecular behavior, such as IL-1β gene expression, which may be a new therapeutic target.     

Clinicopathologic Characteristics and Prognosis of Advanced Gastric Cancer Simulating Early Gastric Cancer

Background

Although the clinicopathologic features and prognosis of Borrmann type advanced gastric cancer has been well characterized, those of advanced gastric cancer simulating early gastric cancer (AGC simulating EGC) still remains unclear.

Methods

We reviewed 1985 gastric cancer patients who had undergone gastrectomy at our hospital to determine the clinicopathologic characteristics, susceptible sites for lymph node metastasis, and prognosis of AGC simulating EGC in comparison with Borrmann type advanced gastric cancer.

Results

Among 102 patients with AGC simulating EGC, 100 patients (98%) had tumors with depressed type appearance. The frequencies of serosal invasion, lymph node metastasis, lymphatic vessel invasion, blood vessel invasion, and liver metastasis were significantly lower in AGC simulating EGC than in Borrmann type tumors. The prognosis of AGC simulating EGC was significantly better than that of the Borrmann type tumors. Multivariate analysis indicated that the gross appearance was an independent prognostic factor. In patients with AGC simulating EGC which invaded to the the muscularis propria (MP), most lymph node metastasis was restricted with the perigastric lymph nodes (1st-titer lymph nodes) and lymph node metastasis to 2nd-titer lymph nodes was only observed at station 8a.

Conclusion

AGC simulating EGC is less advanced in comparison with Borrmann type advanced gastric cancer. Based on the results of susceptible sites for lymph node metastasis in the current study, limited lymph node dissection could be indicated for AGC simulating EGC whose depth of invasion is MP.     

Clinical characteristics of patients with ischemic stroke after the 2016 Kumamoto earthquake,a multi-center study

Objective

To investigate the clinical characteristics of patients with ischemic stroke following the 2016 Kumamoto earthquake.

Methods

We retrospectively studied patients with ischemic stroke admitted to 5 stroke centers for 1 year after the earthquake. We compared clinical characteristics in these patients (the post-earthquake group) to those in the patients with ischemic stroke admitted during the same period from the previous 3 years (the pre-earthquake group). Additionally, we analyzed the trend of the incidence rate of stroke before and after the earthquake.

Results

A total of 1979 patients were admitted after the earthquake; 5670 (1,890/year on average) patients were admitted before the earthquake. A first-ever ischemic stroke (71 vs. 75%) and premorbid modified Rankin Scale > 1 (26 vs. 29%) were found significantly more frequently in patients after the earthquake. National Institutes of Health Stroke Scale score ≤ 2 at discharge (60 vs. 65%) was found more frequently in patients after the earthquake, although non-discharge to home (65 vs. 70%) was more frequent in patients after the earthquake. Trend analysis revealed a decrease of small vessel occlusion and large artery atherosclerosis in the month after the earthquake.

Conclusions

The 2016 Kumamoto earthquake may have affected the characteristics of stroke during the early phase of the earthquake and increased the difficulty in returning home.

     

Evaluation of bioartificial renal tubule device prepared with human renal proximal tubular epithelial cells cultured in serum-free medium

Bioartificial renal tubule devices (BTD) use cell therapy to improve conditions commonly observed in recipients of artificial kidneys for treatment of kidney diseases. We previously reported significant improvement of the condition of acute kidney injury (AKI) animals after treatment with BTD prepared with lifespan-extended human renal proximal tubular cells (hRPTEC). However, a major obstacle to use of BTD for patients is their biological safety, because hRPTEC are cultured in medium containing fetal calf serum. To establish the biological safety of BTD, we prepared BTD with lifespan-extended hRPTEC cultured in a newly developed serum-free medium and compared these with BTD prepared with hRPTEC cultured in serum-containing conventional medium. Lifespan-extended hRPTEC cultured in serum-free medium (hRPTEC-SFM) can proliferate similar to hRPTEC cultured in serum-containing conventional medium (hRPTEC-CM). Comparison of leakage and of reabsorption of small molecules for BTD prepared with hRPTEC-SFM (BTD-SFM) with those for our previous BTD prepared with hRPTEC-CM (BTD-CM) showed transportation in these two types of BTD was almost identical. When AKI goats were treated with BTD-SFM for 26 h, increase of survival time and reduction of cytokine expression in blood cells were almost same as for AKI goats treated with BTD-CM. Quantification of the expression of some genes of hRPTEC in BTD revealed significant changes during BTD treatment for AKI goats. In conclusion, lifespan-extended hRPTEC-SFM work as well as hRPTEC-CM, and the biological safety of BTD for patients could be elevated without loss of function by preparation from hRPTEC-SFM.     

Genetic analysis of ESBL-producing Klebsiella pneumoniae isolated from UTI patients in Indonesia

IntroductionExtended spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae is a serious concern for nosocomial infection and the emergence rate in Indonesia is higher than that in developed countries. The purpose of this study was to investigate the genetic characteristics of ESBL-producing K. pneumoniae isolated from UTI patients in Indonesia.Materials and methodsWe collected K. pneumoniae resistant to ceftazidime or cefotaxime isolated from UTI patients in Dr. Soetomo's Academic Hospital in Surabaya, Indonesia in 2015. Ninety-four strains were identified as ESBL-producing bacteria by confirmation tests. The isolates were investigated by antimicrobial susceptibility testing with 20 drugs and ESBL gene detection, plasmid replicon typing and virulence genes as hypermucoviscous (HMV) strains were tested by the string test.ResultsHigh rates of resistance to ciprofloxacin (86.2%), tetracycline (80.9%) and nalidixic acid (78.7%) were observed. CTX-M-15 was the most common ESBL gene (89.4%), 33 of which also carried SHV-type ESBL. IncF was the most prevalent plasmid replicon typing (47.6%). Sixteen (17.0%) strains were judged as HMV, all of which had rmpA and more than half of which had fimH, uge, and wab. IncL/M was the most common replicon plasmid in the HMV strains, and the difference in the positive rate was statistically significant (p = 0.0024).ConclusionThis study showed the high prevalence of multiple-drug resistant and predominately CTX-M-15-positive ESBL-producing K. pneumoniae in Indonesia. There was a correlation between IncL/M and the HMV phenotype in this study. As such hypervirulent strains continue to emerge, studying their dissemination with resistance determinants is an urgent priority.