Lipoprotein glomerulopathy: Significance of lipoprotein and ultrastructural features

Lipoprotein glomerulopathy: Significance of lipoprotein and ultrastructural features.BackgroundLipoprotein glomerulopathy (LPG) is a unique disease characterized by intraglomerular lipoprotein thrombi and type III hyperlipoproteinemia. Recently, we have demonstrated that LPG is associated with inherited apolipoprotein E (apoE) variants including apoE Sendai. On the other hand, electron microscopy shows that intraglomerular lipoprotein thrombi consist of lipid granules of various sizes. To elucidate the relationship between the peculiar histology and abnormal lipid metabolism related to apoE Sendai, we studied lipoprotein profiles and ultrastructural features.MethodsThe subjects were 11 patients with LPG. Four patients were nephrotic, and two others became nephrotic within six months following the biopsy. Eight patients underwent apoE gene analysis and showed apoE Sendai. The other three were presumed to have apoE Sendai because this mutation was demonstrated in their kindreds. Under electron microscopy, diameters of more than 1000 lipid granules were measured in several glomeruli, and a mean value was calculated in each case. Lipoprotein profiles were analyzed by the ultracentrifugation methods.ResultsThe mean diameter of intraglomerular lipid granules correlated inversely with the levels of plasma triglyceride (TG; rs = -0.73, P < 0.05), TG (rs = -0.77, P < 0.01) and cholesterol (Chol; rs = -0.75, P < 0.05) in very low-density lipoprotein (VLDL) fraction and TG in high-density lipoprotein (HDL) fraction (rs = -0.75, P < 0.05). The inverse correlation was also seen between the mean lipid diameter and TG/Chol ratios in whole plasma (rs = -0.80, P < 0.01) and in HDL (rs = -0.80, P < 0.01). In addition, the cases showing smaller lipid granules and higher TG/Chol ratios in plasma and in HDL were nephrotic or became nephrotic within six months.ConclusionThese results suggest that the size of lipid granules in LPG may become smaller under the influence of hypertriglyceridemia and particularly elevated plasma VLDL and HDL-TG, which may lead to heavy proteinuria

Long-term observation of fibrillation cycle length in patients under angiotensin II receptor blocker therapy for chronic atrial fibrillation

AbstractIntroductionThe long-term effect of angiotensin II receptor blockers (ARBs) on atrial fibrillation (AF) is unclear. In this study, we evaluated the change in the fibrillation cycle length (FCL) in patients under long-term ARB therapy for chronic AF.Methods and resultsThe study population consisted of 25 chronic AF patients who were prescribed the same medication for more than 6 years and in whom specific ECG recording for FCL evaluation could be performed before and after the 6-year observation period. The patients were divided into 2 groups: those with and without ARB (ARB group and non-ARB group and n=15 and 10, respectively). FCL was calculated by the spectral analysis of the fibrillation waves in the surface ECG. There was no significant difference in the clinical characteristics between the 2 groups. In the ARB group, the mean FCL was prolonged from 154±20ms to 187±37ms (p=0.005), whereas it remained unchanged in the non-ARB group (150±12ms vs. 149±10ms). In the comparison between patients with and those without FCL prolongation (>30ms; n=6 and 19, respectively), a significant difference was observed only in those prescribed ARBs.ConclusionIn cases of chronic AF, FCL might be prolonged under long-term ARB treatment

Blastocyst complementation using Prdm14-deficient rats enables efficient germline transmission and generation of functional mouse spermatids in rats.

Murine animal models from genetically modified pluripotent stem cells (PSCs) are essential for functional genomics and biomedical research, which require germline transmission for the establishment of colonies. However, the quality of PSCs, and donor-host cell competition in chimeras often present strong barriers for germline transmission. Here, we report efficient germline transmission of recalcitrant PSCs via blastocyst complementation, a method to compensate for missing tissues or organs in genetically modified animals via blastocyst injection of PSCs. We show that blastocysts from germline-deficient Prdm14 knockout rats provide a niche for the development of gametes originating entirely from the donor PSCs without any detriment to somatic development. We demonstrate the potential of this approach by creating PSC-derived Pax2/Pax8 double mutant anephric rats, and rescuing germline transmission of a PSC carrying a mouse artificial chromosome. Furthermore, we generate mouse PSC-derived functional spermatids in rats, which provides a proof-of-principle for the generation of xenogenic gametes in vivo. We believe this approach will become a useful system for generating PSC-derived germ cells in the future

Prevalence of the metabolic syndrome in elderly and middle-aged Japanese

AbstractBackground/PurposeDiagnosis and management of the metabolic syndrome (MetS) are beneficial for successful aging. In spite of several criteria for MetS, there is little information on cardiometabolic risk clustering in elderly Japanese. The purpose of this study was, therefore, to determine the relationship between age-associated changes in obesity and metabolic components in the Japanese.MethodsWe analyzed data from the nationwide survey conducted in 2000. Using Adult Treatment Panel III (ATP III) and Japanese diagnostic criteria for MetS, we analyzed 2366 people aged from 40 to 79 years (men, 1425 and women, 941) from the total participants.ResultsThe prevalence of MetS was almost three fold higher by modified ATP III, International Diabetes Federation, and Japanese criteria, in elderly women than in middle-aged women, whereas no difference was found between middle-aged and elderly men by the three criteria. A marked increase in the prevalence of MetS was found by modified ATP III and International Diabetes Federation criteria compared with that by the Japanese criteria in women. Among the risk factors, the prevalence of central obesity and dyslipidemia increased only in women and that of high fasting glucose and high blood pressure increased in both genders with aging. Among the MetS subjects who fulfilled the modified ATP III criteria, more clustering of risk was observed in elderly than in middle-aged subjects, especially in women. Blood pressure increased and triglyceride decreased in both genders, and non-high-density-lipoprotein cholesterol decreased in elderly men. The prevalence of dyslipidemia decreased in elderly men.ConclusionAging is an important factor that affects the metabolic abnormality, and aging of the population would lead to increase in the prevalence of MetS. Therefore, the development of better approaches to the prevention and management of MetS is necessary for successful aging in our society

[資料] 秋田県豪雨災害における日本赤十字秋田看護大学・日本赤十字秋田短期大学 赤十字防災ボランティアステーションの取り組みと課題

2017年7月22日から23日にかけての記録的な大雨によって発生した秋田県豪雨災害の被災者支援のため、日本赤十字秋田看護大学・日本赤十字短期大学では、赤十字防災ボランティアステーションに所属する学生が中心となり、被災地で家財の搬出入、泥よけ、ボランティアニーズ調査などの災害ボランティア活動を行った。本稿では、今回の災害ボランティア活動と学生の学びについて報告する。また、今後、同ステーションが防災・減災ボランティア活動の教育やそれを担う人材の育成といった「災害が起こる前の備え」に関する活動だけでなく、災害ボランティア活動のような「災害対応」に関する活動にも関与していく上で、本学には、①迅速な意思決定システムの確立、②予算の柔軟な運用、③支援の「公平性」の確保という課題を克服する必要があることも指摘する。The purpose of this article is to report on the volunteer service actions by the Red Cross Volunteer Station for Disaster Prevention（RCVS）at the Japanese Red Cross Akita College of Nursing and the Japanese Red Cross Junior College of Akita, which was provided for the aff ected local residents during the 2017 Akita flood. RCVS volunteer students helped to clean up the flood damage as well as conduct needs assessment of the devastated areas.This article also addresses problems to be solved for when the RCVS engages in disaster response in the future as well as suggestions for disaster prevention and reduction in the future

Sustained reduction of serum cholesterol in low-dose 6-year simvastatin treatment with minimum side effects in 51,321 Japanese hypercholesterolemic patients - Implication of the J-LIT study, a large scale nationwide cohort study

金沢大学大学院医学系研究科　The Japan Lipid Intervention Trial (J-LIT) study, a nationwide cohort study utilizing the clinical practice of general physicians, was designed to clarify the relationship between the incidence of coronary heart disease and serum lipid concentrations during simvastatin therapy, as well as the safety of the therapy, in a large number of Japanese hypercholesterolemic patients. All the enrolled patients were treated with simvastatin. The current study analyzed the lipid lowering effect and safety of the low-dose simvastatin therapy used in the J-LIT study. Open-labeled simvastatin was given to 51,321 patients at an initial dose of mostly 5 mg/day. After 6 months of the treatment, the average serum total cholesterol (TC) and low density lipoprotein-cholesterol concentrations in all the patients followed up were reduced by 18.3% and 26.0%, respectively, and that of high density lipoprotein-cholesterol increased 2.3% on average. These concentrations were well maintained throughout the 6-year treatment period. A minority of patients (1.4%) unexpectedly had a remarkable reduction in TC concentration by more than 40%. Hyper-responders, even to low-dose statin, were found for the first time in this large-scale and long-term investigation. Overall adverse drug reactions occurred in 3.3% of subjects during the 6-year treatment, the major events being hepatic and musculoskeletal disorders, of which the incidence was less than 1%. Low-dose simvastatin therapy of 5 mg/day effectively controlled the serum TC concentration by reducing it by approximately 20% on average in hypercholesterolemic Japanese patients, a reduction that corresponds to the effect of simvastatin 20 mg/day in Western studies. In addition, the low incidence of drug-related adverse events in this study may. be also related to the low dosage of simvastatin

Large-scale cohort study on the relationship between serum lipid concentrations and risk of cerebrovascular disease under low-dose simvastatin in Japanese patients with hypercholesterolemia: Sub-analysis of the Japan Lipid Intervention Trial (J-LIT)

金沢大学大学院医学系研究科　Background: The Japan Lipid Intervention Trial was a nationwide cohort study of 52,421 hypercholesterolemic patients treated with open-labeled simvastatin for 6 years under standard clinical practices. Cerebrovascular disease (CVD) is one of the leading causes of death in Japan, but the effect of hypercholesterolemia on CVD has not been well established in Japanese patients. This study aimed to determine the relationship between the risk of CVD and serum lipid concentrations during treatment in Japan. Methods and Results: Patients were treated with 5-10 mg/day of simvastatin and all, including those who discontinued simvastatin for any reason, had their lipid concentrations and incidence of CVD monitored for 6 years. Data of 41,088 patients were analyzed in this study, excluding those who had a history of coronary heart disease or CVD. The risk of cerebral infarction was higher in patients whose mean total cholesterol concentrations during treatment were ≥240 mg/dl, low-density lipoprotein cholesterol concentrations ≥160 mg/dl, triglycerides ≥150 mg/dl and high-density lipoprotein cholesterol concentrations <40 mg/dl. There was no obvious correlation between cerebral hemorrhage and serum lipid concentrations. Conclusion: Improvement of serum lipid concentrations is important for reducing the incidence of cerebral infarction

Effects of daily aspirin on cancer incidence and mortality in the elderly Japanese

BackgroundLong‐term follow‐up of studies to investigate preventive effects of aspirin on arterial thrombosis indicate that aspirin reduces the incidence and mortality of some cancers in Western populations.ObjectivesTo explore the effects of aspirin on cancer incidence and mortality in the elderly Japanese.Patients/MethodsPatients aged 60 to 85 years, presenting with hypertension, dyslipidemia, or diabetes mellitus (n = 14 601, 7297 in the aspirin group and 7304 in the no‐aspirin group) participated the Japanese Primary Prevention Project (JPPP), a multicenter, open‐label, randomized, parallel‐group trial. A subanalysis of JPPP was performed to analyze the incidence of newly diagnosed cancer and death related to cancer.ResultsThe cumulative incidence of newly diagnosed cancer was 5.60% (4.65‐6.64%) in the aspirin group and 4.14% (3.67‐4.66%) in the no‐aspirin group. The hazard ratio for newly diagnosed cancer was 1.24 (1.06‐1.46), and the cancer incidence was significantly higher in the aspirin group. The cumulative cancer mortality was 1.96% (1.65‐2.31%) in the aspirin group and 1.87% (1.56‐2.22%) in the no‐aspirin group, with no statistically significant difference. The Fine and Gray model suggested that the difference in the incidence of newly diagnosed cancer between the two groups decreased year by year.ConclusionsLow‐dose aspirin use did not reduce the cancer incidence or cancer mortality during a 5‐year‐average study period in the elderly Japanese. The cancer incidence in the aspirin group might decrease, however, to less than that in the no‐aspirin group after the study period. Aspirin use might have led to earlier cancer diagnosis in our study