Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

MRL-lpr/lpr (MRL/l) mice spontaneously develop a disease that is characterized by glomerulonephritis, diffuse vasculitis, and arthritis associated with high levels of autoantibodies that include IgG rheumatoid factor (RF). To define the immunopathogenic mechanisms that lead to the development of extravascular lesions such as arthritis, we implanted a tissue cage subcutaneously in arthritic MRL/l mice and compared components of the tissue cage fluid, which resembles the extravascular fluid, with those of sera. When compared with those of sera, tissue cage fluids from arthritic MRL/l mice had similar levels of RF and one-third the amount of C1q immune complexes. In contrast, anti-DNA activities in tissue cage fluids corresponded to only 10% of the serum activities and, most strikingly, nephritogenic retroviral gp70-anti-gp70 immune complexes were almost undetectable in tissue cage fluids. This was also the case for another strain of autoimmune mice, (New Zealand black X New Zealand white)F1 mice, although they did not produce RF. The absence of gp70 immune complexes in tissue cage fluids could be due to markedly limited diffusion of gp70 antigen in these fluids. These results strongly suggest that serum proteins, including autoantigen and autoantibodies, appear in extravascular fluid in a selective manner, depending on their size and charge. Their specific properties in sera or extravascular fluid could partly account for the different manifestations of vascular and extravascular lesions observed in autoimmune mice.
 ...
PMID:Quantitation of retroviral gp70 antigen, autoantibodies, and immune complexes in extravascular space in arthritic MRL-lpr/lpr mice. Use of a subcutaneously implanted tissue cage model. 368 61

Viable group A, M56 streptococci were inoculated into subcutaneously implanted steel net cages in rabbits, thereby establishing a local infection. The infectious process was monitored by quantitating the number of bacteria in the cage fluids. Functional signs of renal lesion were followed by urine analysis and measurement of serum creatinine. All animals were sacrificed 2-8 weeks after the inoculation and showed histological and immunological signs of kidney lesions. The morphological and functional abnormalities observed closely mimic those of post-streptococcal glomerulonephritis in man.
 ...
PMID:Experimental poststreptococcal glomerulonephritis in rabbits. 635 81

F1 hybrid offspring of New Zealand Black mothers and New Zealand White fathers [(NZB X NZW)F1] female mice develop antibodies to single-stranded (ss) and native DNA, immune complex glomerulonephritis, massive proteinuria, and premature death with renal failure. By a series of matings, congenic (NZB X NZW)F1 . xid/xid mice were prepared. These mice were different from (NZB X NZW)F1 mice in having the X chromosome-linked immune deficiency gene, xid, in homozygous form. Such congenic (NZB X NZW)F1 . xid/xid females failed to develop antibodies to single-stranded or native DNA. They also failed to develop fatal renal disease as measured by proteinuria, glomerular histology, glomerular immunofluorescence, and survival. To control for unknown genetic factors, studies were performed with littermates that were derived by mating NZB . xid/+ females with NZW . xid/Y males such that the resulting offspring were either (NZB X NZW)F1 . xid/xid (and therefore "defective") or (NZB X NZW)F1 . xid/+ [phenotypically like (NZB X NZW)F1]. In these and in additional studies, mice were housed in the same cages and identified by ear tagging so as to avoid possible environmental variations from cage to cage. In these studies, xid/xid mice failed to develop the characteristic signs of autoimmunity, whereas the controls did. Similar results were also obtained with (NZW X NZB)F1 xid/xid mice compared with (NZW X NZB)F1 xid/+ mice. The effect of xid/xid upon (NZB X NZW)F1 mice was further investigated by assessing responses to immunization and polyclonal B cell activation in vivo. The xid/xid mice failed to produce anti-ssDNA following immunization with ssDNA complexed to a protein carrier in fluid form or even emulsified in adjuvant. Finally, the xid/xid mice failed to produce antiDNA in response to multiple injections of the polyclonal activator, bacterial lipopolysaccharide (LPS), or the polyclonal activator, polyribose inosinic acid . polyribose cytidylic acid. However, the xid/xid mice were neither generally hyporesponsive nor unable to recognize LPS because they made normal antibody responses following immunization with LPS to which multiple trinitrophenyl groups were chemically attached. We conclude from these studies that xid/xid, which is known to cause the deletion of a B cell subset, has a profound affect upon (NZB X NZW)F1 mice, rendering them insusceptible to the naturally occurring autoimmune disease characteristic of (NZB X NZW)F1 mice, and preventing them from producing antibodies to DNA despite purposeful immunization and polyclonal B cell activation. These results force a reevaluation of previous concepts regarding the mechanisms by which xid/xid might interfere with the development of autoimmunity, and a consideration of therapeutic implications.
 ...
PMID:Ability of the xid gene to prevent autoimmunity in (NZB X NZW)F1 mice during the course of their natural history, after polyclonal stimulation, or following immunization with DNA. 698 Sep

The association of a spondyloepiphyseal dysplasia tarda (SED-T) with the nephrotic syndrome (NS) was found in three siblings. They have counsaguineous (first cousins) healthy parents. Patient 1 was a boy who was admitted to hospital for oedema at the age of 8 years; NS was diagnosed, renal biopsy revealed mesangioproliferative glomerulonephritis. After 4 years he developed end-stage renal failure and died whilst on haemodialysis. Combined therapy with cyclophosphamide and prednisone was of no benefit. At the age of 11 years his height was 122 cm (< 3rd percentile -3.2 SD); he had a short neck, broad and prominent chest and a short wide trunk. Patient 2, another male, had non-nephrotic proteinuria in a 24-h urinary sample at the age of 11 years; this was confirmed in a later analysis; mild lymphopenia and a reduction of helper T cell (OKT4)/suppressor T cell (OKT8) ratio was also detected. At 22 years of age he was admitted to hospital with end-stage renal failure. He was on haemodialysis for a few months until his mother donated a kidney. At the age of 22 years his height was 157 cm (< 3rd percentile), he had a short trunk with the thoracic cage increased in anteroposterior diameter and shoulder elevation. Roentgenograms revealed a disostosis of the spinal column and pelvis and a slight lombar platyspondylia. Patient 3, a girl, was admitted to hospital at 12.5 years for pain and restricted mobility of the right hip. X-rays showed deep acetabula and short femoral necks and mild dysplastic changes, especially in the right hip.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Spondyloepiphyseal dysplasia tarda and nephrotic syndrome in three siblings. 774 15

A number of factors have been implicated in the pathogenesis of acute poststreptococcal glomerulonephritis (APSGN). The lack of a reliable animal model has made it difficult to further examine the role of these factors in the pathogenetic process. In this report, we present a tissue cage model in mice for the study of APSGN. Morphological and immunohistological changes in the kidney, resembling those of APSGN in man, were induced at high frequency in the experimental model after infection with group A streptococcal nephritis isolates. Nephritis-associated strain induced hypercellularity, occlusion of capillaries, and C3 deposition at high frequencies compared to the changes induced in animals infected with a non-nephritis-associated strain and non-infected controls. In animals infected with a nephritis isolate, hematuria and proteinuria were also detected. If penicillin treatment was initiated on the third day of infection, the development of the nephritis process was prevented. Streptokinase, as well as preabsorbing antigen and streptococcal pyrogenic exotoxin B (SpeB), have been implicated in the pathogenesis of APSGN. These proteins, as well as SpeA and SpeF, were detected in the fluids of the infectious focus, regardless of the origin of the strains and whether or not glomerulonephritis was seen. Antibodies to streptokinase were evoked in the majority of the infected animals. This immune response did not correlate with the nephritic process since hypercellularity was also seen in animals which lacked detectable streptokinase antibodies. The results show that the mouse tissue cage model can be used to study APSGN and to evaluate factors involved in the pathogenesis of the disease.
 ...
PMID:An experimental model for acute poststreptococcal glomerulonephritis in mice. 898 44

Group A streptococcal infections are sometimes followed by the inflammatory kidney disease acute post-streptococcal glomerulonephritis (APSGN). To test the importance of streptokinase in the pathogenesis of this disease, isogenic strains of the nephritis isolate NZ131, differing only in the ability to produce streptokinase of the nephritis-associated ska1 genotype, were used for infection in a mouse tissue cage model for APSGN. Streptokinase production was found to be a prerequisite for the capacity of the strain to induce APSGN in mice. In addition, streptokinase was demonstrated in the kidneys of mice infected with the nephritogenic NZ131 and EF514 strains. After infection with the nonnephritogenic strain S84, neither streptokinase nor C3 deposition were observed. Deposition of streptokinase in the glomeruli was detected as soon as 4 days after infection. These findings provide support for the hypothesis that streptokinase initiates the nephritis process by glomerular deposition, which leads to local activation of the complement cascade. Detection of streptokinase in kidney tissue increased with the degree of glomerular hypercellularity. Thus, the severity of the pathological process may be a reflection of the degree of streptokinase deposition.
 ...
PMID:Streptokinase as a mediator of acute post-streptococcal glomerulonephritis in an experimental mouse model. 942 73

The effects of prolonged oral administration of aflatoxin B1 (AFB1) and fumonisin B1 (FB1) mycotoxins were evaluated in broiler chickens from 21 to 42 d of age. A total of 192 birds were housed in experimental batteries and assigned to 32 cages, 6 birds per cage. The following treatments were applied: 1) 0 mycotoxins (control), 2) 10 mg of FB1, 3) 50 microg of AFB1, 4) 50 microg of AFB1 + 10 mg of FB1, 5) 350 microg of AFB1, 6) 350 microg of AFB1 + 10 mg of FB1, 7) 2,450 microg of AFB1, 8) 2,450 microg of AFB1 + 10 mg of FB1/kg of feed. Each treatment consisted of 4 replicates of 6 birds each. At the end of the trial, blood samples from 12 birds per treatment were collected, and the birds were necropsied. Compared with controls, the percentage of heterophils was lower (P < 0.05) in birds from groups receiving 50 microg of AFB1/kg + 10 mg of FB1/ kg and 2450 microg of AFB1/kg alone or in combination with FB1. A higher percentage of lymphocytes (P < 0.05) was observed in birds fed 50 microg of AFB1/kg + 10 mg of FB1/ kg, 350 microg of AFB1/kg, and 2,450 microg of AFB1/kg. A decrease in plasma albumin was observed only in birds fed 2,450 microg of AFB1/kg + 10 mg of FB1/kg. The liver of AFB1-treated birds had focal areas of necrosis and inflammatory infiltrates. In birds fed rations containing only 10 mg of FB1/kg, bile duct hyperplasia with fibrosis and a mononuclear infiltrate accompanied by trabecular derangement were observed. In contrast, in treatments in which FB1 was administered in combination, hepatic vacuolar degeneration was observed, and renal tissue presented corpuscles with increased cellular agglomeration, characterizing glomerulonephritis, and a clearly visible tubular epithelium with areas of degeneration and necrosis. The FB1 residues were detected in liver and in excreta of all FB1-treated groups, at levels that ranged from 0.013 to 0.051 mg/kg and from 1.19 to 2.79 mg/kg, respectively. Results indicated that FB1 and AFB1, singly or in combination at the levels evaluated, do not change markedly the hematological and serological parameters of broiler chickens, but may cause relevant lesions in liver and in kidneys.
 ...
PMID:Effects of prolonged oral administration of aflatoxin B1 and fumonisin B1 in broiler chickens. 1647 38