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Allison A Eddy - One of the best experts on this subject based on the ideXlab platform.
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vascular endothelial cadherin modulates renal Interstitial Fibrosis
Nephron Experimental Nephrology, 2012Co-Authors: Ikuyo Yamaguchi, Bie Nga Tchao, Megan L Burger, Muneharu Yamada, Toshitake Hyodo, Costanza Giampietro, Allison A EddyAbstract:Background/Aims: Renal Interstitial Fibrosis is a final common pathway of all chronic, progressive kidney diseases. Peritubular capillary rarefaction is strongly correlated with fib
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Interstitial Fibrosis in mice with overload proteinuria: Deficiency of TIMP-1 is not protective
Kidney international, 2000Co-Authors: Allison A Eddy, Heungsoo Kim, Jesus M. Lopez-guisa, Takashi Oda, Paul D. Soloway, Lori Mcculloch, Elaine Liu, Diane WingAbstract:Interstitial Fibrosis in mice with overload proteinuria: Deficiency of TIMP-1 is not protective. Background Progressive renal Interstitial Fibrosis is characterized by up-regulated expression of the gene that encodes the tissue inhibitor of metalloproteinases-1 (TIMP-1), a regulator of extracellular matrix remodeling, suggesting that impaired matrix turnover contributes to the fibrogenic process. The present study was designed to develop a murine model of renal Interstitial Fibrosis, and to determine the functional significance of up-regulated Timp-1 expression by comparing the severity of this renal disease in wild-type mice and mice genetically deficient in Timp-1. Methods Initial pilot studies developed and characterized a murine model of bovine serum albumin (BSA)-induced protein-overload proteinuria with respect to the degree of proteinuria, severity of Interstitial Fibrosis, and renal mRNA levels for genes encoding matrix proteins, transforming growth factor-β1 (TGF-β1), and TIMP-1, -2, -3, and -4. In the final study, the severity of Interstitial Fibrosis was compared in wild-type and Timp-1 –deficient mice after six weeks of proteinuria. Results Mice injected with large daily intraperitoneal doses of BSA developed proteinuria, Interstitial inflammation, and progressive Interstitial Fibrosis. A time course study based on measurements after one, two, and six weeks of BSA injections showed increased renal mRNA levels for the matrix genes procollagens α1(I), α1(III), and α2(IV) and TGF-β1 and Timp-1. Timp-2 and Timp-3 genes were constitutively expressed at high levels in the normal kidneys and showed little change in the proteinuric kidneys. Timp-4 transcripts were not detected in any of the kidneys. After six weeks of BSA overload-proteinuria, the groups ( N = 8 per group) of wild-type and Timp-1 –deficient mice developed significant Interstitial Fibrosis compared with the control saline-injected groups. The severity of the Interstitial Fibrosis was similar in both proteinuric groups based on an assessment of the final kidney weight, total kidney collagen content, and the number of Interstitial fields with increased fibronectin staining. Conclusions Results of the present study indicate that TIMP-1 deficiency does not alter the degree of Interstitial Fibrosis in the murine overload proteinuria model. Potential explanations include Timp-1 genetic redundancy, as suggested by the observation that, despite significant intrarenal induction of the Timp-1 gene expression, net renal metalloproteinase-9 (MMP-9) activity was not significantly altered. TIMP-1 is a multifunctional protein that may play a metalloproteinase-independent role in response to renal injury.
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molecular insights into renal Interstitial Fibrosis
Journal of The American Society of Nephrology, 1996Co-Authors: Allison A EddyAbstract:Progressive Interstitial Fibrosis accompanied by loss of renal tubules and Interstitial capillaries typifies all progressive renal diseases. Dynamic and complex, the process evidently overlaps with matrix remodeling; it may even be reversible. The Interstitial fibrous tissue comprises several normal and novel matrix proteins, proteoglycans, and glycoproteins. Interstitial myofibroblasts are a major site of matrix protein overproduction, although resident fibroblasts, tubular cells, and inflammatory cells may contribute. Inadequate matrix degradation also appears to contribute to the fibrogenic process. Two protease cascades, the metalloproteinases and the plasminogen activator/ plasmin family of serine proteases, are implicated in the turnover of Interstitial matrix proteins; upregulated expression of protease inhibitors has been observed in each. Increased tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 levels suggest that the intrinsic renal activity of the metalloproteinases and serine proteases are inhibited while matrix proteins accumulate in the interstitium. Several signals that may direct the Interstitial fibrogenic process have been identified, but not yet proved to cause it. Upregulated expression of transforming growth factor beta-1, the proteotypic fibrogenic cytokine, has been observed in experimental and human models; it probably does not act alone. There may be supportive roles for platelet-derived growth factor, interleukin-1, basic fibroblast growth factor, angiotensin II, and endothelin-1. Although it is not known why Interstitial Fibrosis compromises renal function, atrophy of renal tubules may be pivotal. Ischemic necrosis and/or apoptosis may generate nonfunctioning atubular and sclerotic glomeruli. Future studies must delineate the molecular basis of the differences between renal repair and renal destruction by Fibrosis, two processes that share many common features.
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Expression of genes that promote renal Interstitial Fibrosis in rats with proteinuria.
Kidney international. Supplement, 1996Co-Authors: Allison A EddyAbstract:The development of progressive tubular atrophy and Interstitial Fibrosis represents a final common pathway leading to renal insufficiency. My laboratory has been investigating several rat models of primary glomerular disease in an effort to determine cellular and molecular mechanisms of renal Interstitial Fibrosis. These models include puromycin aminonucleoside nephrosis (PAN), protein-overload proteinuria, passive Heymann nephritis, and diet-induced hypercholesterolemia. From a functional perspective, it is likely that the associated loss of tubules accounts for the decline in renal function. Four recurrent themes are emerging from our studies.
Robert B. Colvin - One of the best experts on this subject based on the ideXlab platform.
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Renal Interstitial Fibrosis: mechanisms and evaluation.
Current opinion in nephrology and hypertension, 2012Co-Authors: Alton B. Farris, Robert B. ColvinAbstract:Purpose of reviewTubuloInterstitial injury in the kidney is complex, involving a number of independent and overlapping cellular and molecular pathways, with renal Interstitial Fibrosis and tubular atrophy (IFTA) as the final common pathway. Furthermore, there are multiple ways to assess IFTA.Recent
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Persistent rejection of peritubular capillaries and tubules is associated with progressive Interstitial Fibrosis
Kidney International, 2002Co-Authors: Akira Shimizu, Kazuhiko Yamada, David H. Sachs, Robert B. ColvinAbstract:Persistent rejection of peritubular capillaries and tubules is associated with progressive Interstitial Fibrosis Background We have reported that a 12-day course of high dose cyclosporine A treatment in thymectomized miniature swine with major histocompatibility complex (MHC) class I-mismatched renal allografts results in transient acute rejection followed by either in chronic rejection (progression group) or graft acceptance (recovery group). Here, we examined the differential features between both groups in the peritubular capillaries (PTCs) and tubules to clarify the pathogenesis of the progressive Interstitial Fibrosis in chronic rejection. Methods Morphometric and immunohistochemical studies were performed on serial renal biopsies (days 0 to 100) obtained from both groups, focusing on the cellular infiltrate, rejection of PTCs and tubules, myofibroblast accumulation, and progressive Interstitial Fibrosis. Results In the progression group, acute rejection occurred by day 8 and progressed to chronic rejection by day 100, with the development of Interstitial Fibrosis. PTC endothelial cell and tubular epithelial cell death associated with CD3+ cell infiltration was evident, confirmed by nick end-labeling (TUNEL), commencing by day 8 and continuing thereafter. In acute rejection, destruction of PTCs and tubules accompanied by disruption of basement membrane (BM) occurred with capillaritis or tubulitis in areas with a severe cellular infiltrate. During the development of chronic rejection, capillaritis of PTCs and tubulitis continued by day 100, accompanied by persistent T cell infiltration, and the remaining PTCs and tubules exhibited progressive atrophy with thickening and/or lamination of BM. On day 100, identifiable PTCs and tubules were lost in areas of Interstitial Fibrosis. Proliferating (PCNA+) α-actin+ myofibroblasts accumulated around PTCs, tubules and in interstitium, and widespread Interstitial Fibrosis developed by day 100. In contrast, in the recovery group, injured PTCs and tubules recovered by day 100 based on the resolution of acute rejection, and minimal loss of PTCs and tubules was evident by day 100 with minimal Interstitial Fibrosis. Conclusions Persistent rejection directed at PTCs and tubules, and proliferation of myofibroblasts are prominent features in the progressive Interstitial Fibrosis in chronic rejection, and are probably key events in its pathogenesis.
Katsusuke Naito - One of the best experts on this subject based on the ideXlab platform.
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Quantitative analysis of testicular Interstitial Fibrosis after vasectomy in humans.
Aktuelle Urologie, 2003Co-Authors: Koji Shiraishi, Hiroshi Takihara, Katsusuke NaitoAbstract:PURPOSE Germ cell differentiation, DNA synthesis, and apoptosis can be evaluated quantitatively. On the other hand, an Interstitial lesion is difficult to examine. We have focused on the quantitative analysis of testicular Interstitial Fibrosis after vasectomy. MATERIALS AND METHODS Forty testicular biopsy specimens from twenty consecutive men were obtained at vasovasostomy. Johnsen's mean score was calculated from testicular biopsy specimens. Percent of Interstitial Fibrosis was determined quantitatively by the NIH-Image after Masson-trichrome staining. RESULTS A significant increase in Interstitial Fibrosis was observed along with the obstructive interval (p < 0.001). Johnsen's mean score count did not associate with the obstructive interval. CONCLUSION Interstitial lesions of testicular physiology and pathophysiology can be evaluated using the NIH-Image. Interstitial Fibrosis, but not the intraseminiferous status, reflects the irreversible damage of vasectomized testes.
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Influence of Interstitial Fibrosis on spermatogenesis after vasectomy and vasovasostomy.
Contraception, 2002Co-Authors: Koji Shiraishi, Hiroshi Takihara, Katsusuke NaitoAbstract:This study focused on the testicular Interstitial Fibrosis after vasectomy and the intraseminiferous status [i.e., Johnsen's score, proliferative cell nuclear antigen (PCNA) expression] following vasectomy reversal. Testicular biopsy specimens from 21 consecutive men were obtained at vasovasostomy. Percent of Interstitial Fibrosis was determined quantitatively by NIH-image after Masson Trichrome staining. PCNA-labeling index (LI) was calculated on each testis. The associations between the obstructive interval and each parameter were examined. These parameters were also analyzed on whether patency or pregnancy was achieved or not. Significant decrease in PCNA-LI and increase in Interstitial Fibrosis were observed along with the obstructive interval (p
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Original research article Influence of Interstitial Fibrosis on spermatogenesis after vasectomy and vasovasostomy
2002Co-Authors: Koji Shiraishi, Hiroshi Takihara, Katsusuke NaitoAbstract:This study focused on the testicular Interstitial Fibrosis after vasectomy and the intraseminiferous status [i.e., Johnsen’s score, proliferative cell nuclear antigen (PCNA) expression] following vasectomy reversal. Testicular biopsy specimens from 21 consecutive men were obtained at vasovasostomy. Percent of Interstitial Fibrosis was determined quantitatively by NIH-image after Masson Trichrome staining. PCNA-labeling index (LI) was calculated on each testis. The associations between the obstructive interval and each parameter were examined. These parameters were also analyzed on whether patency or pregnancy was achieved or not. Significant decrease in PCNA-LI and increase in Interstitial Fibrosis were observed along with the obstructive interval (p 0.0001, p 0.0005, respectively). Interstitial Fibrosis of the patients without patency/fertility was significantly greater than that of the patients with patency/fertility (47.5%/39.0% versus 33.4%/32.3%, p 0.02/0.04, respectively). PCNA-LI and Johnsen’s score did not predict the treatment outcome. Interstistial Fibrosis, but not the extent of germ cell differentiation or DNA synthesis, reflects the treatment outcome after vasectomy reversal. Interstistial Fibrosis contributes to the irreversible damage of vasectomized testes. © 2002 Elsevier Science Inc. All rights reserved.
Koji Shiraishi - One of the best experts on this subject based on the ideXlab platform.
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Quantitative analysis of testicular Interstitial Fibrosis after vasectomy in humans.
Aktuelle Urologie, 2003Co-Authors: Koji Shiraishi, Hiroshi Takihara, Katsusuke NaitoAbstract:PURPOSE Germ cell differentiation, DNA synthesis, and apoptosis can be evaluated quantitatively. On the other hand, an Interstitial lesion is difficult to examine. We have focused on the quantitative analysis of testicular Interstitial Fibrosis after vasectomy. MATERIALS AND METHODS Forty testicular biopsy specimens from twenty consecutive men were obtained at vasovasostomy. Johnsen's mean score was calculated from testicular biopsy specimens. Percent of Interstitial Fibrosis was determined quantitatively by the NIH-Image after Masson-trichrome staining. RESULTS A significant increase in Interstitial Fibrosis was observed along with the obstructive interval (p < 0.001). Johnsen's mean score count did not associate with the obstructive interval. CONCLUSION Interstitial lesions of testicular physiology and pathophysiology can be evaluated using the NIH-Image. Interstitial Fibrosis, but not the intraseminiferous status, reflects the irreversible damage of vasectomized testes.
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Influence of Interstitial Fibrosis on spermatogenesis after vasectomy and vasovasostomy.
Contraception, 2002Co-Authors: Koji Shiraishi, Hiroshi Takihara, Katsusuke NaitoAbstract:This study focused on the testicular Interstitial Fibrosis after vasectomy and the intraseminiferous status [i.e., Johnsen's score, proliferative cell nuclear antigen (PCNA) expression] following vasectomy reversal. Testicular biopsy specimens from 21 consecutive men were obtained at vasovasostomy. Percent of Interstitial Fibrosis was determined quantitatively by NIH-image after Masson Trichrome staining. PCNA-labeling index (LI) was calculated on each testis. The associations between the obstructive interval and each parameter were examined. These parameters were also analyzed on whether patency or pregnancy was achieved or not. Significant decrease in PCNA-LI and increase in Interstitial Fibrosis were observed along with the obstructive interval (p
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Original research article Influence of Interstitial Fibrosis on spermatogenesis after vasectomy and vasovasostomy
2002Co-Authors: Koji Shiraishi, Hiroshi Takihara, Katsusuke NaitoAbstract:This study focused on the testicular Interstitial Fibrosis after vasectomy and the intraseminiferous status [i.e., Johnsen’s score, proliferative cell nuclear antigen (PCNA) expression] following vasectomy reversal. Testicular biopsy specimens from 21 consecutive men were obtained at vasovasostomy. Percent of Interstitial Fibrosis was determined quantitatively by NIH-image after Masson Trichrome staining. PCNA-labeling index (LI) was calculated on each testis. The associations between the obstructive interval and each parameter were examined. These parameters were also analyzed on whether patency or pregnancy was achieved or not. Significant decrease in PCNA-LI and increase in Interstitial Fibrosis were observed along with the obstructive interval (p 0.0001, p 0.0005, respectively). Interstitial Fibrosis of the patients without patency/fertility was significantly greater than that of the patients with patency/fertility (47.5%/39.0% versus 33.4%/32.3%, p 0.02/0.04, respectively). PCNA-LI and Johnsen’s score did not predict the treatment outcome. Interstistial Fibrosis, but not the extent of germ cell differentiation or DNA synthesis, reflects the treatment outcome after vasectomy reversal. Interstistial Fibrosis contributes to the irreversible damage of vasectomized testes. © 2002 Elsevier Science Inc. All rights reserved.
Mark Haas - One of the best experts on this subject based on the ideXlab platform.
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chronic allograft nephropathy or Interstitial Fibrosis and tubular atrophy what is in a name
Current Opinion in Nephrology and Hypertension, 2014Co-Authors: Mark HaasAbstract:Purpose of review Chronic allograft nephropathy has fallen into disfavor as a morphologic term to describe parenchymal scarring in the renal allograft, with a recommendation that this be replaced by the more descriptive term 'Interstitial Fibrosis and tubular atrophy'. However, neither term addresses the underlying cause of the scarring. This review focuses on whether all Interstitial Fibrosis and tubular atrophy in the renal allograft has the same implications for long-term graft survival, and whether there are specific features of Interstitial Fibrosis and tubular atrophy that can be used to identify its underlying cause. Recent findings Results from a number of studies indicate that Interstitial Fibrosis and tubular atrophy, when associated with Interstitial inflammation, is a strong predictor of graft loss, much more so than Interstitial Fibrosis and tubular atrophy alone. Most notably, findings from the multicenter Long-Term Deterioration of Kidney Allograft Function study, designed to identify the causes of late allograft dysfunction, showed Interstitial inflammation in the areas of Interstitial Fibrosis and tubular atrophy (i-IF/TA) was predictive of reduced time to graft failure, even after adjustment for serum creatinine. In addition, the presence of i-IF/TA correlates with increased acute kidney injury gene transcripts. However, neither Interstitial Fibrosis and tubular atrophy nor i-IF/TA is associated with any specific cause of chronic graft injury. Summary Although (i-IF/TA), especially when widespread, is clearly associated with reduced renal allograft survival and molecular markers of active graft injury and repair, there is presently no reliable way, using either morphology alone, immunohistochemistry, or molecular techniques, to differentiate i-IF/TA (or Interstitial Fibrosis and tubular atrophy alone) resulting from different causes.
