Shin Goto

New Result in the Production and Decay of an Isotope, 278113, of the 113th Element

An isotope of the 113th element, i.e., 278 113, was produced in a nuclear reaction with a 70 Zn beam on a 209 Bi target. We observed six consecutive α-decays following the implantation of a heavy particle in nearly the same position in the semiconductor detector under an extremely low background condition. The fifth and sixth decays are fully consistent with the sequential decays of 262 Db and 258 Lr in both decay energies and decay times. This indicates that the present decay chain consisted of 278 113, 274 Rg ( Z =111), 270 Mt ( Z =109), 266 Bh ( Z =107), 262 Db ( Z =105), and 258 Lr ( Z =103) with firm connections. This result, together with previously reported results from 2004 and 2007, conclusively leads to the unambiguous production and identification of the isotope 278 113 of the 113th element.

Role of p38 Mitogen-Activated Protein Kinase on Cerebral Vasospasm After Subarachnoid Hemorrhage

Background and Purpose— Inflammatory cytokines are involved in the pathogenesis of cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to examine the role of p38 mitogen-activated protein kinase (MAPK) in the development of vasospasm and cytokine production. Methods— We measured the expression levels of genes and proteins related to inflammation in human vascular smooth muscle cells (hVSMCs) treated with hemolysate and FR167653 (FR) (1μmol/L), a selective p38MAPK inhibitor, for 48 hours by TaqMan real-time reverse transcription-polymerase chain reaction (RT-PCR) and ELISA. Twenty-one dogs were assigned to 3 groups of 7 animals: control, placebo, and FR-treated (1 mg/kg/d) groups in a double-hemorrhage model. The effects were assessed through the caliber of the basilar artery, and the changes in gene expressions and the activation of p38MAPK were assessed by Western blot analysis. Results— Treatment of hVSMCs with hemolysate induced significant upregulation of interleukin (IL)-1α, IL-1β, and IL-8 gene and protein expressions, which was suppressed significantly with FR. The mean vessel caliber on day 7, as a percentage of that of day 0, was 49% in the placebo, and 74% in the FR group (P = 0.0001). The gene expression levels of IL-1α, IL-1β, and IL-8 in the arterial wall were extremely elevated in the placebo, and significantly suppressed in the FR group (P = 0.0027, 0.0002, and 0.0073). p38MAPK phosphorylation was stimulated in the placebo and hemolysate in vitro, and suppressed in the FR group. Conclusions— These results suggest that p38MAPK is activated in the arterial wall after SAH, leading to the development of vasospasm, possibly through the upregulation of inflammatory cytokines.

Interaction Between ACE and ADD1 Gene Polymorphisms in the Progression of IgA Nephropathy in Japanese Patients

Abstract—An interaction effect between the angiotensin-converting enzyme insertion/deletion (ACE I/D) and &agr;-adducin (ADD1) Gly460Trp polymorphisms (G460W) on blood pressure regulation has recently been suggested, although its significance in the prognosis of renal function in IgA nephropathy (IgAN) has not been fully investigated. Therefore, we evaluated the clinical manifestations and renal prognosis in 276 Japanese patients with histologically proven IgAN with respect to their ACE I/D and ADD1 G460W polymorphisms. The prognosis of renal function was analyzed by Kaplan-Meier survival curves and multivariate Cox proportional-hazards regression models. Baseline data, including blood pressures, proteinuria, renal function, and incidence of hypertension, were similar for the different genotypes of ACE and ADD1. The individual genotypes taken alone were not associated with the progression of renal dysfunction. However, renal survival of patients with the 460WW polymorphism of ADD1 was significantly worse within the group with the II genotype of ACE (Kaplan-Meier, log rank test; &khgr;2=6.062, P =0.0138) but not for those with other ACE genotypes. In the Cox proportional-hazards regression model with adjustment for clinical risk factors, including hypertension, proteinuria, and no administration of an angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, the 460WW variant of ADD1 was a highly significant and independent risk factor only for patients with the ACE II genotype, with a hazard ratio of 3.65 (P =0.0016), but not for those with other ACE genotypes (hazard ratio=0.65, P =0.2902). These findings suggest an interaction between ACE and ADD1 polymorphisms not only on blood pressure regulation but also on the progression of renal dysfunction in patients with IgAN.

Monocyte chemoattractant protein-1 A-2518G gene polymorphism and renal survival of Japanese patients with immunoglobulin A nephropathy.

BackgroundMonocyte chemoattractant protein (MCP)-1 is closely related to the pathogenesis of the progression of various chronic renal diseases, including IgA nephropathy (IgAN), through its chemoattractant effect on macrophages. However, the correlation of MCP-1 gene polymorphism with the long-term prognosis of Japanese patients with IgAN has not been clearly determined yet.MethodsWe investigated 277 Japanese patients diagnosed with IgAN based on renal biopsy to clarify the association between the progression of IgAN and MCP-1 gene polymorphism at position A-2518G, which regulates the transcription of the MCP-1 gene.ResultsThe incidence of endstage renal disease was significantly higher in patients with the AA genotype (47.1%) compared to those with the AG (24.1%) or GG (27.4%) genotype (P = 0.024). Moreover, Kaplan-Meier analysis revealed that the AA genotype significantly facilitated the progression of renal disease (log rank; P = 0.0029), and Cox proportional hazards regression model analysis showed that the AA genotype represented a 2.058-fold risk for the progression of renal disease (P = 0.026) compared to the AG/GG genotype. However, when the patients were treated with angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker, or corticosteroid, homozygosity for the -2518A allele was not associated with a higher rate of incidence of endstage renal disease. Serum MCP-1 levels were higher although not significantly so, in the patients with IgAN possessing the AA genotype.ConclusionsThe AA genotype at MCP-1 -2518 was an independent risk factor for the progression of renal disease in Japanese patients with IgAN, and was closely associated with renal survival.

Requiring Higher Doses of Erythropoietin Suggests Pregnancy in Hemodialysis Patients

Background/Aims: Pregnancy in hemodialysis (HD) patients tends to be diagnosed late because of its infrequency and the lack of validity of urine pregnancy tests, and because these patients tend to have menstrual irregularities. The outcome is influenced by pregnancy-related anemia. We investigated the characteristics of pregnancy-related anemia and whether it is a useful diagnostic clue to pregnancy in HD patients. Methods: We retrospectively investigated six pregnancies of 5 HD patients (mean age 30 years), including 4 patients treated with recombinant human erythropoietin (rHuEpo) and a transfusion-dependent patient with two pregnancies in the pre-rHuEpo era. Results: The mean duration of HD was 6 years, the mean duration of the patients’ marriages at the time of pregnancy was 6 years, and the mean gestational age at diagnosis was 11 weeks and 4 days. The progression of anemia (an 8% decrease in the hematocrit) was detected by 8 weeks of gestation in all patients. The prepregnancy hematocrit was stable in 5 pregnancies, facilitating the detection of changes, but during one of the pregnancies of the transfusion-dependent patient the hematocrit was low and was influenced by the transfusions. The amount of rHuEpo required to attain a target hematocrit of 30% increased gradually or rapidly until delivery. Conclusions: The progression of anemia or hyporesponsiveness to rHuEpo was a useful early diagnostic clue to pregnancy in HD patients. However, the prepregnancy hematocrit should be stabilized with rHuEpo, so that decreases can be easily detected. The precise mechanisms of hyporesponsiveness to rHuEpo, which progressed during pregnancy and subsided after delivery, remain to be clarified.

Gender specific association of aldosterone synthase gene polymorphism with renal survival in patients with IgA nephropathy.

Immunoglobulin A nephropathy (IgAN), which is the most prevalent form of primary glomerulonephritis and one of the major causes of end stage renal disease (ESRD), has a variable clinical course.1–3 Poor prognostic factors for the progression of renal dysfunction in IgAN have been identified as high blood pressure, heavy proteinuria, and a severe histopathological appearance of the renal biopsy.4,5 In addition to these prognostic factors, it has been proposed that several genetic backgrounds are associated with a susceptibility to ESRD in patients with IgAN.6,7 The renin-angiotensin-aldosterone system is an important regulator of blood pressure and plays a central role in the development and progression of end organ damage. Polymorphisms in genes that encode components of this system have been reported to be associated with physiological risk factors for progressive renal dysfunction in IgAN. The most consistent of these is the angiotensinogen ( AGT ) gene, which is associated with essential hypertension and with an increased risk of cardiovascular diseases and renal failure.8–10 A deletion polymorphism in the angiotensin converting enzyme ( ACE ) gene influences the circulating ACE levels, and although it has little effect on blood pressure, it has been associated with an increased risk of cardiovascular diseases in some but not all studies.11–13 Aldosterone is one of the main effectors of the renin-angiotensin system14 and has classically been thought to act as a regulator for the absorption of Na and water, as well as the excretion of K in normal physiology, and as a mediator of oedema in numerous disease states. However, it is now well recognised that the actions of aldosterone are not limited to effects on ion transport in epithelial tissue, and its important role in cardiovascular disease involves non-epithelial tissues.15,16 Recently, it has been shown that …

Genetic Polymorphism of NPHS1 Modifies the Clinical Manifestations of Ig A Nephropathy

Nephrin, the molecule responsible for congenital nephrotic syndrome of Finnish type, is crucial in maintaining the glomerular filtration barrier. Recently, its complete gene structure and common gene polymorphisms in its exons have been reported, although the functional and clinical significance of these polymorphisms has not yet been elucidated. We investigated a possible association of the NPHS1 polymorphisms with the development of Ig A nephropathy (IgAN), as well as the clinical and histologic manifestations in IgAN. A total of 464 Japanese subjects, including 267 patients with histologically proven IgAN and 197 healthy controls with normal urinalysis, were genotyped for the NPHS1 G349A, G2289A, and T3315C polymorphisms. The frequencies of the genotypes, alleles, and estimated haplotypes of NPHS1 polymorphisms were no different between patients with IgAN and the controls. Within the IgAN group, patients carrying at least one G allele of G349A tended to present with more proteinuria, lower renal function, and more severe histopathologic injury than those with the AA genotype, although the time from the first urinary abnormality to the renal biopsy was no different between both groups. The logistic regression analysis indicated that even after adjusting for the effect of proteinuria and hypertension the GG genotype of NPHS1 G349A was an independent risk factor for the deteriorated renal function at the time of diagnosis. This study suggests that the NPHS1 G349A polymorphism may be associated with heavy proteinuria and a decline in renal function in patients with IgAN.

Genetic polymorphisms in the promoter and 5′ UTR region of the Fc α receptor (CD89) are not associated with a risk of IgA nephropathy

AbstractThe molecular mechanisms of immunoglobulin A glomerulonephritis (IgAN), the most prevalent form of primary glomerulonephritis, remain poorly understood. Recently, the essential role of soluble Fc α receptor (FcαR) in the formation of the pathogenic immune complex has been revealed. We screened genomic DNA samples from patients with IgAN and those with other glomerular diseases for polymorphisms in the promoter and the 5′-untranslated region region of the FcαR gene by direct nucleotide sequencing. We found three common polymorphisms in this region, T-114C, T-27C, and T+56C from the putative transcription initiation site. Each genotype was determined in 151 patients with IgAN and 163 patients with other glomerular diseases shown to have no mesangial IgA deposition by renal biopsy. The haplotype analysis revealed tight linkage disequilibrium among them. An association study for the genotype, allele, and haplotype frequencies of the polymorphisms between the patients with histologically proven IgAN and those with other glomerular diseases showed no significant difference in the genotype, allele, and haplotype distributions between the two groups. The present study indicates that the analyzed polymorphisms of the FcαR gene do not appear to be primarily involved in the susceptibility to IgAN.

Peroxisome proliferator-activated receptor γ C161T polymorphisms and survival of Japanese patients with immunoglobulin A nephropathy

Peroxisome proliferator‐activated receptor γ (PPARγ) plays an important role in lipid metabolism, insulin sensitivity, atherogenesis, and immune regulation. A genetic polymorphism (C161T) at exon 6 of PPARγ gene (PPARG) was reported to be associated with the onset of coronary artery disease. However, there has been no report of an association with renal disease. Genomic DNAs were isolated from 225 Japanese patients with histologically confirmed immunoglobulin A nephropathy (IgAN). The PPARG C161T genotype was determined by polymerase chain reaction‐restriction fragment length polymorphism. The association of the polymorphism with renal prognosis in IgAN patients was analyzed using the Kaplan–Meier method and Cox proportional hazard regression model. The PPARG polymorphism was not associated with the renal survival rate. However, when patients were stratified into those either with or without hypertension at the time of diagnosis, the renal survival of the CT/TT genotypes was significantly better in those without hypertension than those with the CC genotype. We report that the PPARG C161T polymorphism is associated with the survival of IgAN patients without hypertension. The T allele of the polymorphism might have a protective effect on the progression of IgAN.

Evidence-based clinical practice guidelines for nephrotic syndrome 2014

Nephrotic syndrome is a clinical syndrome showing specific features of heavy proteinuria and hypoalbuminemia or hypoproteinemia as its consequence. It is caused by increased permeability of serum protein through the damaged basement membrane in the renal glomerulus. The definition of nephrotic syndrome includes both massive proteinuria (≥3.5 g/day) and hypoalbuminemia (serum albumin ≤3.0 g/dL) (Tables 1, 4). Primary nephrotic syndrome has no background diseases, whereas secondary nephrotic syndrome has any background diseases. As a result of massive proteinuria and hypoalbuminemia, this syndrome is frequently accompanied by edema, dyslipidemia, abnormalities in coagulation/fibrinolysis, reduced renal function, and immunological disorders. The effect of treatment is determined by the urinary protein level after treatment (Tables 2, 3). Table 1 Clinical definition of adult nephrotic syndrome 1. Proteinuria: ≥3.5 g/day and continuous (comparable to ≥3.5 g/gCr at spot urine) 2. Hypoalbuminemia: Serum albumin ≤ 3.0 g/dL Serum total protein ≤ 6.0 g/dL is helpful 3. Edema 4. Dyslipidemia (Hyper LDL cholesterolemia) The above urine protein and hypoalbuminemia are indispensable prerequisites for the clinical diagnosis of nephrotic syndrome Edema is not an indispensable prerequisite but an important finding for nephrotic syndrome Dyslipidemia is not an indispensable prerequisite for nephrotic syndrome Oval fat body is helpful for diagnosis of nephrotic syndrome Table 2 Therapeutic evaluation for nephrotic syndrome The therapeutic evaluation is done by the amount of urine protein at 1 and 6 months after the initiation of treatment Complete remission: urine protein <3.0 g/day Incomplete remission I: 0.3 g/day ≤ urine protein <1.0 g/day Incomplete remission II: 1.0 g/day ≤ urine protein <3.5 g/day Non-response: urine protein ≥3.5 g/day The diagnosis of nephrotic syndrome and therapeutic evaluation should be done by 24-hour urine collection. If to collect 24-hour urine is impossible, the ratio of urine protein and urine creatinine (g/gCr) at spot urine is available for the diagnosis of nephrotic syndrome and therapeutic evaluation In principle, the evaluation of complete remission or incomplete remission at 6 months after the initiation of treatment includes the improvement of clinical finings and serum albumin The evaluation of relapse is the condition that urine protein ≥ 1 g/gCr (1g/gCr) runs or ≥(2+) continues 2–3 times in a row In Europe and the United States partial remission defines 50% or more of the reduction of urine protein, while the Japanese evaluation does not use this definition Table 3 The classification by the response to treatment of nephrotic syndrome Steroid resistant nephrotic syndrome: The enough dose of steroid treatment fails to achieve complete remission or incomplete remission I at 1 month after the initiation of treatment Refractory nephrotic syndrome: The various treatments including steroid and immunosuppressive agents fail to achieve complete remission or incomplete remission I at 6 months after the initiation of treatment Steroid dependent nephrotic syndrome: Steroid treatment is impossible to discontinue, because repeated over 2 times relapses appear after the reduction or discontinuation of steroid Frequent relapse nephrotic syndrome: Over 2 times relapses appear in 6 months Nephrotic syndrome requiring chronic treatment: Nephrotic syndrome to be treated by steroid or immunosuppressive agents over 2 years Table 4 The definition of nephrotic syndrome in children 1. Nephrotic syndrome: Massive proteinuria (40 ≥ mg/h/m2) + hypoalbuminemia (serum albumin ≤ 2.5 g/dL) 2. Steroid sensitive nephrotic syndrome: Daily administrated prednisolone treatment attains the remission within 4 weeks 3. Relapse: After the remission urine protein of 40 ≥ mg/h/m2 or morning urine 100 mg/dL or more by dip stick continues for 3 days