Effects of Dihydrotestosterone and Estradiol on Experimental IgA Nephropathy Induced by Vomitoxin

Ingestion of the trichothecene vomitoxin (VT) by mice induceseffects that mimic the common human glomerulonephritis, IgAnephropathy (IgAN). These include elevation of serum IgA, IgAimmune complexes, and mesangial IgA deposition. Based on previousobservations that male mice are more prone to VT-induced IgAN,the effects of castration of male and female B6C3F1 mice andsex hormone supplementation on several immunopathologic indicatorsof the disease were compared. In the first study, castratedand intact male and female mice were fed control AIN-76A dietor the same diet containing 10 ppm VT for 12 weeks. At Week12, all but the intact female group fed VT exhibited increasedserum IgA, with castrated female mice having greater levelsthan intact females. When microscopic hematuria was used asan indicator of disease severity in intact VT-fed mice, erythrocytecounts for males exceeded those for females at weeks 4 and 12.VT-fed, castrated females exhibited greater hematuria than intactcounterparts, whereas VT-fed, castrated males had lower urinaryerythrocyte counts than intact counterparts. In a second study,castrated male and female mice were implanted with controlledrelease pellets of placebo, 5-dihydrotestosterone (DHT), or17ß-estradiol (E₂) and then were fed either controldiet or a 10 ppm VT diet for 8 weeks. Castrated male and femalemice treated with VT and DHT pellet exhibited more severe hematuria,higher IgA levels, and greater mesangial IgA deposition thanmice exposed to the same diet with placebo or E₂ pellet at Week8. While VT-fed animals with an E₂ pellet exhibited greaterhematuria and mesangial IgA deposition at Week 8 than the placebogroups, their IgA levels were not significantly elevated overthose for VT-fed mice with a placebo pellet. Relative to twoother pathologic markers for IgAN, the aforementioned effectsin both studies were generally consistent with mesangial depositionof complement component C₃ but not IgG. The results suggestthat (1) enhanced male susceptibility to VT-induced IgAN maybe related to modulation by the biologically active androgenDHT and (2) while castration of females increased severity ofVT-induced IgAN, supplementation of castrated male or femalemice with E₂ did not reverse this effect but rather increaseddisease severity.     

Problems in the Measurement of Putative Serum Immune Complexes by the Method of Beaumont

ABSTRACT: A methodological investigation of the procedure used by Beaumont et al for measuring a “serum immune complex” precipitated by 25% ammonium sulfate and alleged to contain an ethynyl-estradiol binding immunoglobulin has found major problems with reproducibility and with the correlation of total protein as measured by the Lowry method and the IgG content as determined by a specific nephelometric procedure.     

IgE binding studies with large peptides expressed from Der p II cDNA constructs

The major mite allergen Der p II shows marked resistance to denaturation and is expressed from cDNA in bacteria with almost all of its IgE binding activity. Despite these properties, the IgE binding activity appears to be dependent on maintaining the complete primary structure. Random fragment libraries of cDNA, able to code for up to 93 of the 129 amino acid residue protein, did not express IgE binding peptides. Large overlapping peptides 1-69, 69-129 and 42-117 expressed as the fusions from the glutathione transferase of pGEX vectors only had binding activity with IgE in 15 out of 57 sera, and this was typically weak. Sera from children with atopic dermatitis bound IgE in seven out of eight cases but this was also weak compared with their strong reactivity to intact recombinant Der p II. The inability of such large peptides to form IgE binding structures suggests that the antigenic determinants of Der p II are highly conformational and restricted.     

Acute Pericarditis Resulting From an Endocardial Active Fixation Screw-In Atrial Lead

We examined the occurrence of acute pericarditis after pacemaker implantation in 123 consecutive patients (61 males, 62 females, ages 17–87 years) in whom a newer atrial active fixation bipolar lead was inserted endocardially in the right atrium for dual chamber pacing. The atrial leads were positioned to obtain the best possible pacing and sensing thresholds, after an initial attempt was made for insertion into the right atrial appendage or medially into the right atrial septum. Six patients (4.9%) developed acute symptomatic pericarditis with effusion within 24 hours of implantation. Of these six patients, four had leads screwed into the lateral waH. and the other two had leads placed in the anterolateral wall. The lead implantation parameters between patients with pericarditis and those without did not show any significant difference in the atrial P wave amplitude (2.3 ± 0.4 vs 2.9 ± 0.9 mV), pacing threshold (1.1 ± 0.2 vs 1.1 ± 0.4 V), or resistance (524 ± 112 vs 480 ± 94 ohms). All symptomatic patients were treated with nonsteroidal anti-inflammatory drugs with symptoms resolving in 1–2 weeks. We condude that: (1) a significant number of patients (4.9%) developed acute symptomatic pericarditis after insertion of this type of atrial fixation lead: (2) because of the lead design, the implantation parameters coud not be taken to predict the occurrence of pericarditis: and (3) caution should be taken for the insertion of this lead into the thin atrial wall.