Library

Notes: The effects of hydrogen annealing on capacitance–voltage (C–V) characteristics and interface-state density (Dit) of 4H–SiC metal–oxide–semiconductor (MOS) structures have been investigated. The Dit was reduced to as low as 1×1011 eV−1 cm−2 at Ec−E=0.6 eV using hydrogen annealing above 800 °C, where Ec−E is the energy level from the conduction-band edge. Secondary ion mass spectroscopy and Dit analysis revealed that Dit decreased with the increase of hydrogen concentration accumulated at the SiO2/4H–SiC interface. The interface states at SiO2/4H–SiC are thought to be originated from the dangling bonds of C atoms as well as Si atoms, because Dit decreases as the hydrogen annealing temperature increases and saturates around 800 °C. This high-temperature hydrogen annealing is useful for accumulation-type SiC metal–oxide–semiconductor field-effect transistors, which have n-type MOS structures to reduce the Dit. © 2000 American Institute of Physics.

Notes: Background Regulated on activation, normal T cells expressed and secreted (RANTES) is a member of the CC chemokine family and contributes to viral-induced airway inflammation including exacerbations of asthma. Double-stranded RNA (dsRNA) is known to be synthesized during replication of many viruses and a ligand of Toll-like receptor 3. We hypothesized that dsRNA may mimic viral infection and induce RANTES expression in airway epithelial cells.Objective We first confirmed that dsRNA up-regulated RANTES mRNA and protein synthesis in the airway epithelial cells. We next focused our studies on the transcriptional regulation of RANTES.Methods Airway epithelial cell line BEAS-2B and normal human bronchial epithelial cells were used in vitro study. Levels of RANTES mRNA and protein expression were determined with RT-PCR and ELISA. Mechanisms of transcriptional regulation were assessed by electrophoretic mobility shift assay and dual luciferase assay using RANTES promoter-luciferase reporter plasmids.Results Activation of nuclear factor-κB (NF-κB) was confirmed by nuclear protein binding to a DNA probe derived from the RANTES promoter. Activity of the RANTES promoter was increased by dsRNA. The stimulation with dsRNA was partially inhibited in plasmids mutated at either of the binding sites for NF-κB or IFN regulatory factors (IRFs). When both sites were mutated, the activation was totally abrogated.Conclusion These results imply that dsRNA activates NF-κB and IRFs and these transcription factors activate transcription of the RANTES promoter and its protein expression in airway epithelial cells.

Notes: IgA nephropathy (IgAN) is characterized by the presence of IgA deposits, predominantly in the glomerular mesangium, and by mesangial proliferative glomerulonephritis (GN). Concerning its pathogenesis, several investigators have suggested that the glomerular IgA deposits in IgAN are antibodies (Ab) to viral, bacterial or dietary antigens. Thus, the Ab are probably produced as part of the specific host immune response to various environmental antigens. Such reports strengthen the possibility of a relationship between mucosal immunity and the pathogenesis of IgAN. Nevertheless, attempts to isolate a specific IgA circulating immune complex-associated antigen in patients with IgAN have been unsuccessful.We have shown that mucosal infections such as pharyngitis are often associated with the acute onset of IgAN.1 IgAN is, then, an immune complex disease that is caused by a poor mucosal immune response to environmental antigens to which the patient has been chronically exposed. We have observed previously that Haemophilus parainfluenzae (HP) is more commonly isolated from the pharynx of patients with IgAN than from those with other glomerular diseases.2 We have also identified the glomerular deposition of outer membranes of HP antigens (OMHP) and an increased serum concentration of IgA-Ab against OMHP in patients with IgAN.2 Furthermore, we have shown that patients with IgAN have a specific increase in the production of IgA-Ab against OMHP via polyclonal activation against these, with switching of production from one isotype to another (e.g. from IgM to IgA3), and that a significant relationship between IgA-Ab against OMHP and renal lesions exists in patients with IgAN,4 and that OMHP stimulate tonsillar B-lymphocytes to produce specific IgA1-Ab against OMHP and tonsillar T-lymphocytes in patients with IgAN.5,6Our objective was to investigate the production of IgA and several cytokines by tonsillar lymphocytes from patients with IgAN induced by stimulation with OMHP. We used tonsillar lymphocytes from the palatine tonsils of 18 patients with IgAN and 25 patients with chronic tonsillitis but without renal diseases as controls. There were no significant differences in the backgrounds of the two groups. Haemophilus parainfluenzae was detected in the tonsils of all 43 patients before tonsillectomy. We examined production of total IgA, IgA-Ab against OMHP, IL-4, IL-6, IL-10, and TGF-β in the culture supernatants after lymphocyte incubation with OMHP. The spontaneous production of total IgA and TGF-β by tonsillar lymphocytes from patients with IgAN was higher than that by tonsillar lymphocytes from controls (P 〈 0.05). Stimulation with OMHP in vitro enhanced the production of HP-specific IgA by tonsillar lymphocytes from patients with IgAN (P 〈 0.01), but not by tonsillar lymphocytes from controls. Outer membranes of HP stimulation also enhanced the production of TGF-β and IL-10 by tonsillar lymphocytes from patients with IgAN (P 〈 0.001).Our results suggest that the infection of HP in the tonsil may be involved in the aetiology of IgAN.

Notes: Application criteria of steroid therapy for the patients of IgA nephropathy (IgAN) have not yet been established. The purpose of the present study was to establish retrospectively the clinical and pathological criteria for the steroid therapy by using a histological scoring on 104 adult patients of IgAN. Steroid therapy was designated as an administration of prednisolone in the amount of more than 30 mg per day in the period of more than 4 weeks within 1 year of kidney biopsy.We developed our own scoring system for the following main glomerular and tubulointerstitial changes as shown in 〈link href="#t1"〉Table 1. The histological scoring was expressed by evaluating semiquantitatively the extent of glomerular and tubulointerstitial lesions in terms of activity index (AI) and chronicity index (CI). Activity index is the sum of graded score according to the extent of glomeruli with mesangial hypercellularity, intracapillary macrophagic infiltration and cellular crescent as well as to the extent of interstitial inflammation and tubulitis. Chronicity index is the sum of graded score according to the extent of glomeruli with global sclerosis, increase of extracellular matrices or periglomerular fibrosis, and tuft adhesion or fibrous (or fibrocellular) crescent as well as to the extent of interstitial fibrosis (〈link href="#t1"〉Table 1).〈tabular xml:id="t1"〉1〈title type="main"〉 Histological scoring 〈table frame="topbot"〉〈tgroup cols="5" align="left"〉〈colspec colnum="1" colname="col1" align="left"/〉〈colspec colnum="2" colname="col2" align="center"/〉〈colspec colnum="3" colname="col3" align="center"/〉〈colspec colnum="4" colname="col4" align="center"/〉〈colspec colnum="5" colname="col5" align="center"/〉〈thead valign="bottom"〉〈row rowsep="1"〉Score0123〈tbody valign="top"〉〈entry namest="col1" nameend="col5" align="left"〉AI: Activity Index〈entry namest="col1" nameend="col5" align="left"〉G: glomerularm: mesangial hypercellularity−〈 40%〈 80%≥ 80%i: intracapillary macrophage infiltration−+++e: cellular crescent0〈 30%≥ 30%〈entry namest="col1" nameend="col5" align="left"〉I: tubulointerstitiali: interstitial inflammation−+++t: tubulitis−+++〈entry namest="col1" nameend="col5" align="left"〉CI: Chronicity Index〈entry namest="col1" nameend="col5" align="left"〉G: glomerulars: global sclerosis〈 10%〈 30%〈 50%≥ 50%i: increase of extracellular matrix〈 10%〈 30%〈 50%≥ 50%e: fibrous (or fibrocellular) crescent, adhesion〈 10%〈 30%〈 50%≥ 50% I: tubulointerstitial
 interstitial fibrosis〈 10%〈 30%〈 50%≥ 50%〈note xml:id="t1_note5" numbered="no"〉AI: AGm + AGi + AGe*2 + AIi + Ait, CI: CGS + CGi + CGe + CIFor the applicability of steroid therapy, three groups were categorized by evaluating the statistical significance for the correlation of AI, CI and daily amount of urine protein to the outcome of the patients as follows (〈link href="#t2"〉Table 2). In group A (inappropriate indication of steroid therapy) which showed CI ≥ 5 alone, 10 out of 11 cases revealed decline of renal function (Cr ≥ 1.2 mg/dL and Ccr 〈 80 mL/min) within 2.2–19.3 years (mean 9.0 ± 6.4 years) without respect to steroid therapy. In group B (unnecessary indication of steroid therapy) which showed CI 〈 5, AI 〈 5, and UP 〈 1 g/day, 58 out of 60 cases showed normal renal function (Cr 〈 1.2 mg/dL and Ccr ≥ 80 mL/min) within 4.2–21.6 years (mean 10.1 ± 4.7 years). In group C (necessary indication of steroid therapy) which showed CI 〈 5 and AI ≥ 5 or UP ≥ 1 g/day, patients with steroid therapy revealed significantly higher incidence of outcome with normal renal function (12 out of 13 patients, final evaluation of renal function in 6.8 ± 2.3 years after renal biopsy) than that of the patient without steroid therapy (seven out of 20 cases, evaluation of renal function in 9.2 ± 4.0 years after renal biopsy) (P 〈 0.01) (〈link href="#t3"〉Table 3). In the 13 patients with steroid therapy in group C (steroid pulse in four patients, prednisolone 40 mg/day internally in three patients, predonisolone 30 mg/day internally in six patients) showed a significant decrease of proteinuria and remained until final evaluation time (〈link href="#t4"〉Table 4).〈tabular xml:id="t2"〉2〈title type="main"〉 Application criteria of steroid therapy 〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP15:NEP_15_t2"/〉〈tabular xml:id="t3"〉3〈title type="main"〉 Comparison of steroid (−) with steroid (+) in the group of ‘necessary’ 〈table frame="topbot"〉〈tgroup cols="4" align="left"〉〈colspec colnum="1" colname="col1" align="left"/〉〈colspec colnum="2" colname="col2" align="center"/〉〈colspec colnum="3" colname="col3" align="center"/〉〈colspec colnum="4" colname="col4" align="center"/〉〈thead valign="bottom"〉〈row rowsep="1"〉steroid therapy+− P 〈row rowsep="1"〉no.1320〈tbody valign="top"〉〈entry namest="col1" nameend="col4" align="left"〉At Renal Biopsyage (years)〈entry align="char" char="[plusmn]"〉31.5 ± 12.936.3 ± 13.0nsUP (g/day)〈entry align="char" char="[plusmn]"〉2.3 ± 1.91.3 ± 0.5〈 0.05Cr (mg/dL)〈entry align="char" char="[plusmn]"〉0.8 ± 0.30.9 ± 0.1nsCCr (mL/min)〈entry align="char" char="[plusmn]"〉111 ± 4392 ± 34nsHypertension (n)19ns+ ACEI (n)410nsFollow-up years from
 renal biopsy〈entry align="char" char="[plusmn]"〉6.8 ± 2.39.2 ± 4.0ns〈entry namest="col1" nameend="col4" align="left"〉End of follow-upCr (mg/dL)〈entry align="char" char="[plusmn]"〉0.8 ± 0.35.5 ± 6.6〈 0.01 Normal renal function
 (n)127 Renal insufficiency (n)16〈 0.01 Dialysis (n)07〈tabular xml:id="t4"〉4〈title type="main"〉 Change of urine protein in the 13 cases with steroid treatment in the group of 'necessary' 〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP15:NEP_15_t4"/〉From the results above, our evaluation system using histological scoring together with grading proteinuria was proven to be useful in estimating the applicability of steroid therapy for adult IgAN patients.