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  • 1
    Electronic Resource
    Electronic Resource
    s.l. : American Chemical Society
    Biochemistry 21 (1982), S. 301-308 
    ISSN: 1520-4995
    Source: ACS Legacy Archives
    Topics: Biology , Chemistry and Pharmacology
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Knowing when and where a gene is expressed in a cell often provides a strong clue as to its physiological role. It is estimated the human genome contains 80 000–100 000 genes. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed experimental strategy to expand the scope of biological investigation from a single gene to studying all genes at once in a systematic way. Capitalizing on the recently developed methodology of cDNA array hybridization, we monitored the simultaneous expression of thousands of genes in primary human mesangial cells. Complex α-33P-labelled cDNA probes were prepared from cultured mesangial cells. The probe was hybridized to a high-density array of 18 326 paired target genes. The radioactive hybridization signals were analysed by phosphorimager. Bioinformatics from public genomic databases was utilized to assign a chromosomal location of each expressed transcript. Approximately 7460 different gene transcripts were detected in mesangial cells. Close to 13% (957 genes) were full-length mRNA human transcripts (HTs), the remainder 6503 being expressed sequence tags (ESTs). Using special imaging computer software, the transcriptional level of the 957 HTs was compared with the expression of the ribosomal protein S28 (housekeeping gene). The HTs were also classified by function of the gene product and listed with information on their chromosomal loci. To allow comparison between clinical and experimental studies of gene expression, the detected human gene transcripts were cross-referenced to orthologous mouse genes. Thus, the presented data constitute a quantitative preliminary blueprint of the transcriptional map of the human mesangial cell. The information may serve as a resource for speeding up the discovery of genes underlying human glomerular diseases. The complete listing of the full-length expressed genes is available upon request via E-mail: (Abdalla_Rifai@Brown.edu).
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY: It is well established that mesangial cell proliferation plays a major role in glomerular injury and progressive renal injury. The expression of a number of different genes has been reported in proliferative mesangial cells in culture. However, the relevance of these genes to renal injury in general and IgA nephropathy (IgAN) remains to be established. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed molecular strategy to expand the scope of clinical investigation from a single gene to studying all genes at once in a systematic pattern. Capitalizing on the recently developed methodology of high cDNA array hybridization, the simultaneous expression of thousands of genes in primary human proliferating mesangial cells was monitored and compared with renal tissue of IgAN. Complex [α-33P]-labelled cDNA targets were prepared from cultured mesangial cells, remnant tissue from five IgAN renal biopsies and four nephrectomies (controls). Each target was hybridized to a high-density array of 18 326 paired target genes. The radioactive hybridization signals were analysed by phosphorimager. Approximately 8212 ± 530 different gene transcripts were detected per target. Close to 5% (386 ± 90 genes) were full-length mRNA human transcripts (HT) and the remainder were expressed sequence tags (EST). Using a relational database, electronic subtraction was performed and matching was carried out to allow identification of 203 HT with shared expression in proliferative mesangial cells and IgAN renal biopsies. In addition hierarchical clustering analysis was performed on the HT of IgAN and controls to establish differential expression profiles of mesangial HT in IgAN and controls. Collectively the presented data constitutes a preliminary renal bioinformatics database of the transcriptional profiles in IgAN. More importantly, the information may help to speed up the discovery of genes underlying human IgAN.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY: A comprehensive profile of genes expressed at the mRNA level (transcriptome) in human renal tissue is important for elucidating the pathogenesis and treatment of IgA nephropathy (IgAN). The recent development of complementary DNA (cDNA) array hybridization allows the parallel monitoring of thousands of genes expressed in renal tissue. High-density cDNA containing 18 326 paired unique human cDNA gene probes were used to quantitatively analyse the expression of genes in renal biopsies of IgAN and controls. Computational analysis was used to cluster genes according to similarity in pattern of gene expression. Through relational database analysis, we determined 1901 genes that were commonly expressed in four selected IgAN renal biopsies and four controls. Further analysis of the expressed genes by self-organizing maps and hierarchical clustering revealed a genomic profile unique to severely affected IgAN patients. These findings represent a comprehensive preliminary molecular index of genes transcribed in IgAN. More importantly, this molecular approach may accelerate the discovery of pathogenic mechanisms underlying the most common form of glomerulonephritis worldwide.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY: A comprehensive profile of genes expressed at the mRNA level (transcriptome) in human renal tissue is important for elucidating the pathogenesis and treatment of IgA nephropathy (IgAN). the recent development of complementary DNA (cDNA) array hybridization allows the parallel monitoring of thousands of genes expressed in renal tissue. High-density cDNA containing 18326 paired unique human cDNA gene probes were used to quantitatively analyse the expression of genes in renal biopsies of IgAN and controls. Computational analysis was used to cluster genes according to similarity in pattern of gene expression. Through relational database analysis, we determined 1901 genes that were commonly expressed in four selected IgAN renal biopsies and four controls. Further analysis of the expressed genes by self-organizing maps and hierarchical clustering revealed a genomic profile unique to severely affected IgAN patients. These findings represent a comprehensive preliminary molecular index of genes transcribed in IgAN. More importantly, this molecular approach may accelerate the discovery of pathogenic mechanisms underlying the most common form of glomerulonephritis worldwide.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1440-1797
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: SUMMARY: It is well established that mesangial cell proliferation plays a major role in glomerular injury and progressive renal injury. the expression of a number of different genes has been reported in proliferative mesangial cells in culture. However, the relevance of these genes to renal injury in general and IgA nephropathy (IgAN) remains to be established. Assessment of gene activity on a global genome-wide scale is a fundamental and newly developed molecular strategy to expand the scope of clinical investigation from a single gene to studying all genes at once in a systematic pattern. Capitalizing on the recently developed methodology of high cDNA array hybridization, the simultaneous expression of thousands of genes in primary human proliferating mesangial cells was monitored and compared with renal tissue of IgAN. Complex [α-33P]-labelled cDNA targets were prepared from cultured mesangial cells, remnant tissue from five IgAN renal biopsies and four nephrectomies (controls). Each target was hybridized to a high-density array of 18 326 paired target genes. the radioactive hybridization signals were analysed by phosphorimager. Approximately 8212±530 different gene transcripts were detected per target. Close to 5% (386±90 genes) were full-length mRNA human transcripts (HT) and the remainder were expressed sequence tags (EST). Using a relational database, electronic subtraction was performed and matching was carried out to allow identification of 203 HT with shared expression in proliferative mesangial cells and IgAN renal biopsies. In addition hierarchical clustering analysis was performed on the HT of IgAN and controls to establish differential expression profiles of mesangial HT in IgAN and controls. Collectively the presented data constitutes a preliminary renal bioinformatics database of the transcriptional profiles in IgAN. More importantly, the information may help to speed up the discovery of genes underlying human IgAN.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 409 (1983), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Springer seminars in immunopathology 16 (1994), S. 81-95 
    ISSN: 1432-2196
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Conclusions The ultimate purpose of this review of experimental IgA nephropathy has been to identify the important immunopathogenetic factors that need to be elucidated en route to clear understanding of clinical IgA nephropathy. Summarizing from the discussion above, key experimental findings include the following. All the experimental models propound glomerular IgA-IC deposits as an end product of IC formation. The molecular form of IgA plays an important role in causing IC formation. Monomer IgA can only form small-sized complexes without any propensity for glomerular deposition. In contrast, polymeric IgA can form large-sized complexes that get entrapped in the mesangium. Free antigenic determinants in the deposited polymeric IgA complexes may serve as a binding site for circulating monomer IgA. Hence IgA-IC deposits may represent a continuous process of entrapped circulating macromolecules and in situ formed complexes. The liver has a major responsibility of maintaining the circulation free of IgA-IC. Under normal conditions, IgA-specific receptor on sinusoidal cells removes rapidly large-sized complexes. Hepatobiliary dysfunction or saturation of the elimination process may induce or contribute to glomerular IgA-IC deposition. Exacerbating factors under these conditions may also include heightened IgA immune response to alimentary and microbial antigens due to celiac disease or alcohol consumption. Macromolecules of purified human or murine IgA, free in solution or insolublized as renal deposits, lack the ability to activate the complement system. Glomerular C3 deposits that parallel the IgA pattern are due to complement activation by the antigen component of the IgA-IC deposits. Experimental and clinical evidence does not support the assumption that the complement system is essential for renal injury. The search for the inductor of tissue injury in the glomerular IgA-IC deposits revealed the antigen as the main proponent of damage. Comparative and correlative studies demonstrated the antigen as an elicitor of mesangial cell proliferation, inflammatory cell infiltration, fibrin deposition, and proteinuria production. This inflammatory process may also culminate from a cascade of engendered cytokines and eicosanoids. Although the extrapolation of experimental findings to IgA nephropathy is still in a developmental stage, astonishing progress has been made. In some instances, experimental investigations blazed the way for human studies that mutually reciprocated with seminal clinical observations providing essential clues and guides for the research to follow. Comparative analysis of the clinical and experimental literature on IgA nephropathy reveals parallel and complementary tracks that are converging on the preeminent objective of understanding and treatment of human renal disease.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1573-2592
    Keywords: IgA nephropathy ; cytokines ; interferon type II ; reverse transcription–polymerase chain reaction ; human clinical studies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To identify the cytokines that play a relevant role in the pathogenesis of IgA nephropathy, we analyzed and compared the gene expression of proinflammatory cytokines, immuno-regulatory cytokines, and growth factors in peripheral blood mononuclear cells (PBMC). Expression of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IFN-γ, TGF-β, TNF-α, and PDGF was examined in 28 patients with IgA nephropathy (IgAN), 20 patients with non-IgA mesangial proliferative glomerulo-nephritis (mesPGN), and 19 healthy controls. Compared with healthy controls, a significant number of IgAN and mesPGN patients showed increased expression of IL-1β, IL-4, IL-10, IL-12, and IFN-γ. The cytokine profile of renal tissue of 10 IgAN and 5 mesPGN biopsies was simultaneously analyzed and compared with that of PBMC. The proinflammatory IL-1α and growth factor PDGF-B were expressed more in renal tissues than in PBMC. Furthermore, the renal profile of IL-α, IFN-γ, and TNF-α expression was associated with the expression of IFN-γ PBMC. The serum level of IFN-γ of IgAN correlated significantly (P = 0.0003) with that of IL-12, suggesting a potential role for cross-stimulation. More importantly, expression of IFN-γ in PBMC and the elevated serum level correlated with the decline in glomerular filtration rate (P = 0.0012) and severity of renal histopathologic grade. To elucidate the role of leukocytes in renal cytokine expression, surface markers of T cells (CD3), monocytes (CD14), natural killer cells (CD16), and B cells (CD19) were also examined in renal tissues. The prominent renal expression of CD3, CD14, and CD16 implicates the leukocytes as the major source of proinflammatory cytokines in IgAN. Collectively, these findings indicate that IFN-γ plays a prominent role in an interactive network of cytokines that contribute to the pathogenesis and progression of IgA nephropathy.
    Type of Medium: Electronic Resource
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