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Notes: Limiting molar conductances of the K+ and Cl− ions in heavy and light water have been determined at 45 °C as a function of pressure up to 2000 kgf cm−2 (1 kgf cm−2 =0.9807×105 Pa) from the measured conductances and transference numbers of KCl. The residual friction coefficients (Δζobs ) of the K+ and Cl− ions obtained by using their limiting molar conductances and the bulk viscosity of solvent are compared up to 1000 kgf cm−2 with the corresponding values (ΔζHO ) predicted by the Hubbard–Onsager dielectric friction theory. As predicted, Δζobs for the cation in H2 O is smaller than that in D2 O and slightly decreases with increasing pressure, while its value in D2 O is almost invariant in the pressure range studied. The failure of the continuum theory in D2 O indicates that the effect of the open structure of water on the cation migration cannot be neglected even at 45 °C because of stronger hydrogen bonds in D2 O than in H2 O. For the anion, on the other hand, the continuum theory shows more serious limitations: (i) Δζobs (Cl−) in H2 O is not smaller than that in D2 O even at 45 °C with a large difference at high pressures and (ii) Δζobs (Cl−) becomes negative in both types of water at high pressures. The difference in Δζ(Cl−) between theory and experiment at 45 °C, however, becomes much smaller than that at lower temperatures.

Notes: The purpose of the present study was to evaluate the role of angiotensinogen (AGT) gene polymorphisms in the progression of IgA nephropathy (IgAN). The association of the haplotypes defined by A-20C and M235T, which correspond to G-6 A polymorphisms, with the severity of glomerular or interstitial lesions and renal prognosis were investigated.Patients with histologically proven IgAN were recruited after informed consent was obtained for the genetic study, which was approved by the ethics committee of our institute. Genomic DNA from each patient was prepared from peripheral blood leucocytes using an automatic DNA isolation system (NA-100, Kurabo, Osaka, Japan). A–C transition at nucleotide −20, G–A transition at −6, C–T transition at +68 and M235T variant at exon two in the AGT gene were determined as described previously.1,2The renal survival rate was analysed for 114 IgAN patients with a creatinine clearance (Ccr) level of 70 mL/min or greater and followed up more than 24 months. The patients with haplotype T235 and C-20 (n = 63) were compared with those without T235 and C-20 (n = 51) for age, sex, blood pressure, proteinuria, serum Cr, Ccr at the time of renal biopsy, drugs administered, and severity of renal histopathologic lesion.Light microscopic evaluation of all specimens was performed in a double blind fashion according to the grading classification described previously, including glomerular cellular proliferation, mesangial matrix increase, global or segmental sclerosis, endocapillary proliferation, leucocyte exudation, duplication of glomerular basement membrane, crescent formation, and tufts adhesion to Bowman’s capsule as well as tubulointerstitial lesions.3The Kaplan-Meier method and the Cox proportional hazards regression model analysed the time course from renal biopsy to end point (initiation of dialysis or sCr level doubled after the time of diagnosis). Several covariates were selected by a stepwise backward method and the effects of these covariates were expressed by a hazard ratio. P 〈 0.05 was considered statistically significant.The genotype distributions in the present study were not different from that in Hardy–Weinberg equilibrium. The genotype and allele frequencies of AGT variants were compatible with previous studies for Japanese population.1,4 Haplotype analysis showed a complete linkage disequilibrium between M235T and A-20C alleles (linkage-disequilibrium coefficient: D′, 1.00). Because the AGT gene variant at −20 was observed only in a subset of the 235T alleles, the following haplotypes were determined: T235 and C-20; T235 and A-20; and M235 and A-20. The incidence of hypertension was not different between each haplotype of AGT.An association study of histopathological findings revealed that patients with haplotype T235 and C-20 had significantly higher grading scores in crescent formation (P = 0.017) than those without haplotype T235 and C-20. Renal survival rate was significantly lower in the patients with haplotype T235 and C-20 (〈link href="#f1"〉Fig. 1, P = 0.003). The Cox proportional hazards regression model showed an increased hazard ratio (HR) for haplotype T235 and C–20 of 5.9 from multivariate analysis (〈link href="#f2"〉Fig. 2; 95% CI, 2.1–16.7; P 〈 0.001). Furthermore, in IgAN patients without administration of angiotensin I converting enzyme inhibitors (n = 77), renal survival rate was significantly lower in those with haplotype T235 and C–20 (P = 0.011).〈figure xml:id="f1"〉1〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP19:NEP_19_f1"/〉Effect of AGT haplotype on the renal survival rate in IgAN patients. Solid and dashed lines represent the renal survival rate in the patients with and without haplotype T235 and C–20, respectively.〈figure xml:id="f2"〉2〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP19:NEP_19_f2"/〉Cox proportional hazards regression model to test the predictors for renal survival time in multivariate analysis. Covariates were selected by stepwise backward analysis. U-protein, urinary protein; HT at renal biopsy, hypertensives at the time of renal biopsy; ACEI, angiotensin I converting enzyme inhibitor. The bars represent the 95% confidence intervals of hazard ratio.This work provides the evidence that the C–20 gene polymorphism of AGT, a subset of 235T alleles, is associated with histopathological severity of glomerular injury, and progression of renal dysfunction in Japanese patient with IgAN.

Notes: Summary We correlated monoamine concentrations in the cerebrospinal fluid from de novo (untreated) patients with Parkinson's disease with their clinical symptoms and therapeutic outcome after two years of L-dopa with/without other anti-parkinson medication. A significant correlation was found between the severity of some parkinsonian symptoms and the reduction in particular monoamines: Hoehn and Yahr's stage with dopamine, norepinephrine, and homovanillic acid: rigidity with dopamine; akinesia with dopamine and norepinephrine; freezing of gait with norepinephrine; and dementia with dopamine and homovanillic acid. Tremor had no correlations with the concentrations of the monoamines measured. Patients with dementia had a significantly increased level of epinephrine concentrations. Insufficient therapeutic responses of invidividual symptoms were associated with significantly decreased concentrations of particular monoamines before treatment: Hoehn and Yahr's stage with norepinephrine and epinephrine; akinesia with homovanillic acid and 5-hydroxyindoleacetic acid; and freezing of gait with dopamine, norepinephrine, homovanillic acid, and 5-hydroxyindoleacetic acid. These results suggest a significant correlation between the reduction in particular monoamines and the severity of some parkinsonian symptoms and their subsequent responses to L-dopa.

Notes: Abstract Background. Interleukin-1 (IL-1) has been reported to play a major role in the initiation and progression of several glomerulonephritis, and inhibition of IL-1 by the blockade of IL-1β-converting enzyme (ICE) has been suggested to be an ideal therapeutic strategy. Methods. To examine the effect of ICE inhibition on glomerulonephritis, we examined the susceptibility of ICE-deficient mice (ICE−/−) to anti-glomerular base-ment membrane antibody-induced glomerulonephritis (antiGBMGN), which has been previously reported to be mediated by IL-1β. Results. After the injection of antiGBM antibody to ICE−/− and wild type mice, albuminuria rose progressively and both groups of mice died within 7–9 days. Laboratory analysis of proteinuria, serum creatinine, and glomerular histology revealed no significant difference between the two groups. To pursue the mechanism of this result, bone marrow-derived monocyte/macrophage lineage cells (Mo/Mq cells) were established from both groups and the potency of IL-1β production in response to lipopolysaccharide was examined. An enzyme-linked immunosorbent assay (ELISA) of IL-1β revealed that, Mo/Mq cells from ICE−/− mice secreted IL-1β in response to lipopolysaccharide, although to a lesser extent than the Mo/Mq cells from ICE+/+ mice, suggesting that other protease(s) may process proIL-1β to generate the mature form. In fact, as was seen in the wild type mice, serum from antiGBM-injected ICE−/− mice contained IL-1β. Conclusions. These data suggest a limited effectiveness of ICE inhibition as a therapeutic strategy for glomerulonephritis.