These results suggested that the peptide epitope of the IgA1 hinge region which was aberrantly exposed by underglycosylation could induce the humoral immune response in IgAN.
Two-dimensional gel electrophoretic display of polypeptides labeled in vivo and those synthesized in vitro from poly(A)(+)-RNA indicated that treatment of cultured cells of tobacco (Nicotiana tabacum) BY-2 with methyl jasmonate (MeJA) induces accumulation of a limited number of specific mRNAs within a few hours. The MeJA-induction of most of these mRNAs was inhibited by cycloheximide (CHX). Six MeJA-inducible cDNAs identified by differential screening were classified into three groups based on the sensitivity of their induction to CHX. Induction of group I mRNAs by MeJA occurred earlier than the induction of other mRNAs and it was not inhibited by CHX. The induction of group II mRNAs by MeJA was blocked by CHX, while group III mRNAs were induced by CHX alone. One group I cDNA was found to encode a putative protein, JIGT, homologous to UDP-sugar glycosyltransferases previously characterized from several plant species. JIGT was structurally different from a putative glycosyltransferase that is rapidly inducible by salycylic acid (SA) in BY-2 cells. JIGT mRNA was not induced by SA. In addition to MeJA, as little as 10(-9) M coronatine induced JIGT mRNA. A sequence highly homologous to JIGT is present as a single copy in the genomes of Nicotiana sylvestris and N. tomentosiformis. The MeJA-inducible production of JIGT may be involved in sugar-conjugation of an unknown substrate in a defensive response and expression of the gene for JIGT in BY-2 cells might serve as a good model system for disecting molecular events occurring in JA-inducible gene expression.
A cDNA of tobacco BY-2 cells corresponding to an mRNA species which was rapidly induced by methyl jasmonate (MeJA) in the presence of cycloheximide (CHX) was found to encode ornithine decarboxylase (ODC). Another cDNA from a MeJA-inducible mRNA encoded S-adenosylmethionine synthase (SAMS). Although these enzymes could be involved in the biosynthesis of polyamines, the level of putrescine, a reaction product of ODC, increased slowly and while the levels of spermidine and spermine did not change following treatment of cells with MeJA. However, N-methylputrescine, which is a precursor of pyrrolidine ring of nicotine, started to increase shortly after MeJA-treatment of cells and the production of nicotine occured thereafter. The levels of mRNA for arginine decarboxylase (ADC), an alternative enzyme for putrescine synthesis, and that for S-adenosylmethionine decarboxylase (SAMDC), required for polyamine synthesis, were not affected by MeJA. In addition to mRNAs for ODC and SAMS, mRNA for putrescine N-methyltransferase (PMT) was also induced by MeJA. Unlike the MeJA-induction of ODC mRNA, MeJA-induction of SAMS and PMT mRNAs were blocked by CHX. The level of ODC mRNA declined after 1 to 4 h following MeJA treatment, while the levels of mRNAs for SAMS and PMT continued to increase. Auxin significantly reduced the MeJA-inducible accumulation of mRNAs for ODC, SAMS and PMT. These results indicate that MeJA sequentially induces expression of a series of genes involved in nicotine biosynthesis by multiple regulatory mechanisms.
This study was undertaken to clarify prognostic indices of a long‐term clinical course in IgA nephropathy in large series. PATIENTS From 1972 to 1990, a total of 603 patients were diagnosed to have primary IgA nephropathy in our renal unit. Of these patients 366 patients were continuously followed up for 10 years or more. These patients were the subjects of this study. METHODS As predictive factors, several parameters were evaluated as follows: initial proteinuria; initial creatinine clearance (Ccr) values; initial hypertension; histological severity (eight parameters and total score); % duration of massive proteinuria (%DP); % duration of hypertension (%DH). %DP was defined as [(duration of proteinuria of 1.0g/day or more ÷ total duration of follow‐up observation) × 100]. %DH was defined as [duration of hypertension ÷ total duration of follow‐up observation] × 100]. As histological severity, eight parameters were evaluated according to the semiquantitative method of Pirani et al. Each of these lesions was graded from 0 to 3. A total score was defined as a total of all eight scores, graded from 0 to 24. During the 10‐year follow‐up observation, corticosteroid treatment was conducted in 112 patients. Most of the patients received antiplatelet drugs. Hypertensive patients were treated with antihypertensive therapy. Final outcome at 10 years since the initial renal biopsy was divided into three clinical courses as follows: a stable course was defined as no decrease of renal function for 10 years; a progressive course was defined as a decrease of 15% or more of initial Ccr values without going into HD; and haemodialysis (HD). Univariate analysis for these predictive factors was performed by using one‐factor ANOVA corrected by Bonferroni/Dunn or Kruskal‐Wallis test to determine the final outcome. A multivariate analysis was done by using a logistic model. RESULTS The age of the 366 patients was 33 ± 10 (range: 13–61); gender (M/F) 181/185; initial proteinuria 1.0 ± 1.0g/day (range: 0–6.6); initial Ccr values 85 ± 21 mL/min (range: 25–139); initial hypertension 63 cases (17%); total score as histological severity 7.7 ± 4.6. The final proteinuria was 0.9 ± 1.0 g/day (range: 0–5.7); final Ccr values 58 ± 38 mL/min (0–128); final hypertension 94 cases (25%); %DP 33 ± 39; %DH 18 ± 30. Numbers of patients having a stable course, a progressive course and haemodialysis were 192 (52%), 89 (25%) and 85 (23%), respectively. Clinical prognostic indices showed significant differences in age, initial proteinuria, initial Ccr, initial hypertension, %DO and %DH, respectively (P < 0.0001). Treatment with corticosteroids was significantly frequent in progressive and haemodialysis groups than a stable group (P < 0.0003). Histological prognostic indices showed significant differences in hypercellularity, active crescent, tuft adhesion, mesangial sclerosis, global sclerosis, tubular atrophy, interstitial fibrosis, vascular sclerosis and total score (P < 0.005). Multivariate analysis of clinical prognostic indices showed the highest releva...
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