Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twelve inbred rat strains were tested for their susceptibility to autologous immune complex glomerulonephritis (AIC) after a single injection of a primary tubular epithelial fraction emulsified in Freund's complete adjuvant. Six strains (Lewis, AS, BDV, L.BDV, AS2, L.AS2) showed high responsiveness in terms of proteinuria and immunohistological changes, which could be observed after 3 months. Strains BN, AVN and DA were completely resistant, even after 6 months of observation. An additional adjuvant (pertussis vaccine) did not break non-responsiveness in one of these strains (BN). Strains which share the Lewis strain genetic background (L.BN, L.AVN and L.WP) seemed to be at least weakly susceptible to AIC. A close association between susceptibility and the major histocompatibility haplotypes is demonstrated in segregation studies involving Lewis, L.BN and BN rats. A threshold model of AIC susceptibility, based on the action of major histocompatibility-linked genes and background genes, is suggested.
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PMID:Genetic control of susceptibility to autologous immune complex glomerulonephritis in inbred rat strains. 15 75

An immunological study in a case of nephrotic syndrome in early infancy with mesangioproliferative glomerulonephritis with focal crescents revealed deficiencies in humoral and cellular immunity. Serum Ig-G antibody levels such as pertussis-agglutinins, tetanus and diophtheria-antitoxing were decreased. A loss of tetanus antibodies in the urine could be observed. The production of tetanus-antibodies after immunogenic stimulation with tetanus-antigen was not diminished. The loss of Ig-A in the urine might have been compensated by a higher synthesis rate, which could also be the cause of the increased serum levels of Ig-M, since a loss of Ig-M in urine was not observed. The diminished serum levels of Ig-G antibodies were considered not only to be the result of loss, but possibly also of higher catabolism, and an insufficient compensation by a higher rate of synthesis. The percentage of T-cells in peripheral blood was found to be low. Stimulation of lymphocytes with PHA was at first normal, but in the last investigations diminished. Special experiments lead to the assumption, that this partial defect of cellular immunity might be the result of lacking or diminution of nutritive plasmafactors.
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PMID:[Immunological studies in a case of congenital nephrotic syndrome with focal extracapillary proliferative glomerulonephritis (author's transl)]. 30 66

Autoimmune glomerulonephritis was induced in chickens by immunization with human, bovine, turkey or chicken glomeruli in CFA. The influence of dose and of the pertussis vaccine was evaluated in two other separate experiments. The highest incidence of glomerulonephritis was observed in chickens immunized with human glomeruli, followed in descending order by bovine, chicken and turkey glomeruli. Capsular adhesions were seen in the last three groups. Epithelial crescents were seen only in the group immunized with chicken glomeruli. Interstitial lymphocytic infiltration was seen in 54% and 71% of chickens immunized with bovine and chicken glomeruli, respectively. The severity of the disease increased with time and the number of immunizations. IgG deposits on the GBM were seen in 92% (22/24), 54% (13/24), 50% (12/24) and 33% (8/24) of animals immunized with human, bovine, turkey and chicken glomeruli, respectively. Severity of disease was directly related to the amount of glomeruli injected. However, IgG deposits showed an inverse correlation with antigen dose. The disease was always less severe in chickens immunized with bovine glomeruli-CFA plus pertussis, as compared to bovine glomeruli-CFA immunized chickens. These studies demonstrate that the type of GBM antigen and immunization method play a significant role in the resultant histologic lesions in this model, and define conditions for optimal production of disease.
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PMID:Experimental autoimmune glomerulonephritis in chickens: I. Influence of source of antigen, dose and adjuvant. 297 15

A patient is described who developed renal failure due to a severe proliferative glomerulonephritis with hypocomplementaemia and cryoglobulinaemia while repeatedly injecting herself with diphtheria, pertussis, and tetanus vaccine (D.P.T. vaccine). After stopping the antigen administration there was recovery of renal function, complement values returned to normal, and cryoglobulin could no longer be recovered from the sera. The pathogenesis of the glomerulonephritis is discussed.
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PMID:Self-induced glomerulonephritis. 485 28

The skin window technic was utilized to determine the reactivity of patients with rheumatoid arthritis (RA) and acute poststreptococcal glomerulonephritis (APSGN) to human IgG (H-IgG). The response to H-IgG was compared in nine patients with RA, 20 patients with APSGN, and 10 normal individuals. All subjects were tested concomitantly with the saline solution used as solvent for H-IgG. The normal controls and five patients were challenged, in addition, with diphtheria-tetanus-pertussis antigen (DPT) to which they had previous prophylactic exposure. The following results were obtained: 1) Four patients with RA and nine patients with APSGN responded with increased lymphocyte migration (more than 2 SD above the normal mean level) at nine and 12 hours. 2) The mean estimated immunogenic lymphocytosis (calculated subtracting the lymphocyte counts of the saline skin windows) of both patient groups was significantly higher than that of controls at the same time intervals. 3) The response of normal individuals and patients to DPT was comparable in time of appearance and intensity to the response of patients to H-IgG. Our studies that patients with RA and APSGN respond to H-IgG in a manner comparable to that observed with a known antigenic stimulus and support a clinical role for antiglobulin reactivity.
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PMID:Skin window immune response to normal human IgG in patients with rheumatoid arthritis and acute poststreptococcal glomerulonephritis. 702 11

It is envisaged that circulating IgA complexes play a primary role in the glomerular injury of IgA nephropathy, the most common glomerulonephritis worldwide. In this study, we examined the pathophysiological effects of IgA and IgG isolated from IgA-nephritic patients on the signal transduction of human neutrophils. Heat-aggregated forms and monomers of IgA and IgG were prepared from sera of 11 IgA-nephritic patients and 11 healthy controls. Signal transduction was studied by measuring the inositol triphosphate (IP3) production in neutrophils incubated with the immunoglobulin preparations. Different forms of IgA or IgG from IgA-nephritic patients failed to induce a significant increase in IP3 production directly as compared with control IgA or IgG. However, neutrophils preincubated with heat-aggregated IgA (HAA) from IgA-nephritic patients demonstrated a significant rise in IP3 production upon subsequent stimulation by a chemotactic peptide, FMet-Leu-Phe (FMLP); a similar finding was not observed with heat-aggregated IgG. HAA pretreatment of neutrophils increased FMLP-induced IP3 production in a dose-dependent manner. The raised IP3 production was not due to increased FMLP receptors, as HAA preincubation of neutrophils did not increase the binding of tritiated FMLP. The increased IP3 production upon FMLP stimulation in HAA-primed neutrophils was completely abolished by pertussis toxin in a dose-dependent manner. These findings tend to refute a direct stimulatory effect of HAA on phospholipase C, but, instead, may suggest that HAA prepared from IgA-nephritic patients upregulates the activation of G proteins in the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Heat-aggregated IgA prepared from patients with IgA nephropathy increases priming of human neutrophils to produce inositol triphosphate following FMet-Leu-Phe stimulation in vitro. 789 78

Ab-mediated mechanisms have been considered the major causes of glomerulonephritis (GN). However, recent studies suggest that T cells may be more important in mediating GN. To investigate the effects of antigen-specific CD4(+) T cells, we generated Th1 cell lines specific for this antigen from rats that had been immunized with a recombinant form of the glomerular basement membrane (GBM) antigen, Col4alpha3NC1. Upon the transfer of in vitro-activated T cell lines to pertussis toxin-primed, naive syngeneic rats, the recipients developed severe proteinuria/albuminuria, which plateaued after approximately 35 days. Although no IgG binding to GBM or C3 deposition could be detected by immunofluorescence, five out of eleven rats exhibited severe GN, as judged by the formation of characteristic crescent-shaped lesions in the glomeruli, whereas the others exhibited modest GN. Thus Col4alpha3NC1-specific T cells directly initiated glomerular injury in the recipients. One notable difference from GN induced by active immunization was a T cell infiltration in the renal interstitium, which affected some tubules. We therefore injected fluorescence-labeled Col4alpha3NC1-specific into naive rats, and we found that they were enriched 4.5-fold in the kidney cortex relative to nonspecific control T cells 24 hours later. Many of the T cells were located in the Bowman's space and had a flattened shape, suggesting that the primary target for the T cells was in or adjacent to the Bowman's capsule.
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PMID:CD4(+) T cells specific to a glomerular basement membrane antigen mediate glomerulonephritis. 1190 Nov 77

The lipoxygenase-derived leukotrienes (LTs) are important proinflammatory lipid mediators. Lipoxins (LXs), more recently described lipoxygenase products, modulate many proinflammatory actions of LTs and have impressive proresolution properties. Mesangial cell (MC) proliferation is a central event in the pathogenesis of glomerulonephritis. LTD4-induced proliferation of mesangial cells is modulated by LXA4. Here, we demonstrate that LXA4 inhibits PDGF- and LTD4-stimulated proliferation through modulation of platelet-derived growth factor receptor beta (PDGFRbeta) activation. Specifically, we demonstrate that LTD4 transactivates the PDGFRbeta, a process associated with c-src recruitment and ras activation. We demonstrate expression of cysLT1 and cysLT2 receptors in MCs. LTD4-induced c-src activation was insensitive to pertussis toxin and the cysLT1 receptor antagonist Zafirlukast but was blocked by the nonselective antagonist Pobilukast. We show that LXA4 inhibits LTD4-stimulated activation of the PDGFRbeta and that LXA4 modulates PDGF-BB-stimulated tyrosine phosphorylation of the PDGFRb and subsequent mitogenic events. Furthermore, expression of recombinant LXA4 receptor (ALXR) in CHOK1 cells was associated with an attenuation of serum-stimulated proliferation. These data demonstrate that LXA4 receptor (ALXR) activation is accompanied by antimitogenic effects coupled with inactivation of growth factor receptors, highlighting the complex cross-talk between G protein-coupled receptors and receptor tyrosine kinases in an inflammatory milieu. These data elaborate on the profile of cell signaling events that underpin the anti-inflammatory and proresolution bioactions of LX.
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PMID:Lipoxin, leukotriene, and PDGF receptors cross-talk to regulate mesangial cell proliferation. 1222 54

Chemokines play pivotal roles in the recruitment of inflammatory cells into the kidney. The chemokine receptors CXCR3 and CCR5 are expressed on activated T lymphocytes, and expression of CXCR3 by mesangial cells has been suggested. Detailed description of CXCR3 expression might form a rational basis for use as a diagnostic marker and for therapeutic CXCR3 targeting in human glomerulonephritis. We studied the expression of CXCR3 in renal biopsies by immunohistochemistry (n = 45), and real time RT-PCR (n = 78). Biopsies were from patients with IgA nephropathy, lupus nephritis, and membranoproliferative glomerulonephritis. Furthermore, cultured human mesangial cells (HMC) were studied for CXCR3 expression, and for functional responses to the ligands CXCL10/IP-10 and CXCL9/Mig. CXCR3-positive cells were rarely found in glomerular tufts, but formed a major part of the tubulointerstitial infiltrates. Consistently, CXCR3 mRNA expression was too low to be quantified in glomerular compartments, and was not detectable in HMC. The published staining for CXCR3 of mesangial cells could be traced to cross-reactivity of an antibody for CXCR3 with a potentially related chemokine receptor as revealed by FACS analysis. Despite an absence of CXCR3 expression, mesangial cells reacted to CXCR3 ligands by proliferation and migration, which was blocked by pertussis toxin but not by an anti-CXCR3 antibody. These results indicate that HMC do not express the classical CXCR3, but may potentially express a related receptor with shared ligand specificity. By immunohistochemistry the number of CXCR3-positive cells, mainly interstitial T cells, correlated with renal function, proteinuria, and percentage of globally sclerosed glomeruli. A significant morphological and numerical correlation between CD3, CXCR3, and CCR5-positive cells indicated a CXCR3/CCR5 double-positive T cell population. No apparent difference in the CXCR3 expression pattern was found between disease entities. CXCR3 expression was localized to interstitial T cells, and these cells correlated strongly with important prognostic markers. Therefore interstitial CXCR3, as well as CCR5-positive T cells might play an important role during progressive loss of renal function, and are potential therapeutic targets in human glomerular diseases.
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PMID:CXCR3 is involved in tubulointerstitial injury in human glomerulonephritis. 1474 68

The morbidity burden associated with anti-neutrophil cytoplasmic autoantibody-associated vasculitis is increasing, and many novel biological therapies are now entering the drug development pipeline. There is thus an urgent need to develop a representative animal model to facilitate testing of these agents. We previously examined the effect of antineutrophil cytoplasmic autoantibody on leukocyte-endothelial interactions in WKY rats via immunization with human myeloperoxidase. We now seek to extend this model so that all animals reliably develop crescentic glomerulonephritis and lung hemorrhage. We also wish to investigate whether there is a genetic contribution to vasculitis development in this rat strain. Using escalating doses of human myeloperoxidase, we found that a dose of 1600 microg/kg induced pauci-immune crescentic glomerulonephritis and lung hemorrhage in all immunized animals. We also found that the addition of pertussis toxin and killed Mycobacterium tuberculosis to the adjuvant when immunizing with 400 microg/kg of myeloperoxidase resulted in crescentic glomerulonephritis and lung hemorrhage in all animals. However, when Lewis, Wistar Furth, or Brown Norway rats were immunized using a similar protocol, no animals developed hematuria or glomerulonephritis, despite having identical levels of anti-human myeloperoxidase antibodies. We conclude that, by adjusting the immunization regimen, all WKY rats immunized with myeloperoxidase develop experimental autoimmune vasculitis, thus facilitating future therapeutic studies. The resistance of Lewis rats to experimental autoimmune vasculitis provides a genetic basis for future studies of anti-myeloperoxidase antibody-associated vasculitis.
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PMID:Experimental autoimmune vasculitis: an animal model of anti-neutrophil cytoplasmic autoantibody-associated systemic vasculitis. 1926 5


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