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Publications (206)
In mid-18th Century France, the cooking and serving of meat dishes had been in decline for many years. Household cooks were invariably male and were experienced professionals serving those who could afford their expertise. In 1746, Menon, a prolific food writer, published a cook-book, "La Cuisiniere Bourgeiose", which was specifically written for t...
Background:
Cell-based therapies aimed at replenishing renal parenchyma have been proposed as an approach for treating CKD. However, pathogenic mechanisms involved in CKD such as renal hypoxia result in loss of kidney function and limit engraftment and therapeutic effects of renal epithelial progenitors. Jointly administering vessel-forming cells...
The current proliferation of modern cookbooks targeted to the public at large makes it impossible to conceive of there being any that could have had an overriding influence on culinary practice or eating preferences, even at a local level. However, when there was a historical absence of cookbooks for a half-century, as there was in France in the fi...
The seminal experiments of Ivan Petrovich Pavlov set the stage for an understanding of the physiological concomitants of appetite and feeding behavior. His findings, from careful and creative experimentation, have been uncontested for over a century. One of Pavlov’s most fundamental observations was that activation of salivary, gastric and pancreat...
b> Background: A statement was made by Avicenna (980-1037) in his Canon of Medicine that the liver separates fluid from the blood. An explanation for this view has not been considered. Methods: Since the statement emerged from an existing English translation of the Canon (which was made from a prior Latin edition), an alternative English translatio...
Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
Around the turn of the 20th century, Ernest Henry Starling (1866-1927) made many fundamental contributions to the understanding of human physiology. With a deep interest in how fluid balance is regulated, he naturally turned to explore the intricacies of kidney function. Early in his career he focused upon the process of glomerular filtration and w...
Ernest Henry Starling laid the groundwork for our modern understanding of how the interstitial fluid, which he referred to as 'lymph', is regulated. Together with his colleague, William Bayliss, he provided the crucial insight into how fluid is driven out of the capillary to form interstitial fluid. That was to measure (estimate) the capillary pres...
Background:
Based upon observations which indicate that chronic intrarenal hypoxia and microvascular obliteration play an important role in the pathogenesis of renal scarring and loss of function, the idea is presented that restoration of kidney structure and function by arresting microvascular drop-out and restoring the interstitial capillary net...
Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
Chronic kidney disease is characterized by progressive loss of the renal microvasculature, which leads to local areas of hypoxia and induction of profibrotic responses, scarring and deterioration of renal function. Revascularization alone might be sufficient to restore kidney function and regenerate the structure of the diseased kidney. For revascu...
This commentary discusses the role of endothelial progenitor cells in injured kidney.
In chronic kidney disease, functional impairment correlates with tubulointerstitial fibrosis characterised by inflammation, accumulation of extracellular matrix, tubular atrophy and rarefaction of peritubular capillaries. Loss of the microvasculature implies a hypoxic milieu and suggested an important role for hypoxia when the "chronic hypoxia hypo...
A vast amount of evidence, based upon human renal biopsy material, indicates that the presence of tubular atrophy and interstitial fibrosis is a better indicator of outcome of renal function than is the extent of glomerular sclerosis. The pathophysiological basis for this surprising fact has not been adequately addressed. In this review we point ou...
Michael S. Goligorsky – Renal Research Institute, New York Medical College, Valhalla, NY, USA
Nature Clinical Practice Nephrology will deliver timely interpretations of key research developments, translating the latest findings into clinical practice. Our Editor-in-Chief and international Advisory Board will ensure comprehensive coverage of topical issues throughout the year, with the highest standards of editorial quality and integrity tha...
In chronic renal failure (CRF), renal impairment correlates with tubulointerstitial fibrosis characterized by inflammation, interstitial expansion with accumulation of extracellular matrix (ECM), tubular atrophy and vascular obliteration. Tubulointerstitial injury subsequent to glomerular sclerosis may be induced by proteinuria, leakage of glomerul...
The handwritten note of the post-mortem examination of Dr Samuel Johnson resides in the library of the Royal College of Physicians of London. Headed 'asthma' it suggests that he had only one functioning kidney, probably had hypertension, left ventricular hypertrophy and congestive heart failure. This article describes an imaginary presentation by D...
Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
Proteomics methods were used to characterize proteins that change their form or abundance in the nucleus of NRK49F rat kidney fibroblasts during prolonged hypoxia (1% O(2), 12 h). Of the 791 proteins that were monitored, about 20% showed detectable changes. The 51 most abundant proteins were identified by mass spectrometry. Changes in nuclear recep...
Retinoids, a family of vitamin A metabolites or analogs, play an important role in regulating cell proliferation, differentiation, and apoptosis.
The biological importance of retinoids in the kidney and the potential of retinoids in the treatment of renal diseases are reviewed.
Vitamin A deficiency and mutations of retinoid nuclear receptors cause...
Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) is an oxidative stress-inducible gene. In this study, we investigated signaling pathways involved in oxidative stress-induced MKP-1 expression and its role in apoptosis of rat mesangial cells. Northern and Western blot analyses showed that H(2)O(2) induced expression of MKP-1 mRNA and pro...
Charles Edward Isaacs (1811-1860), an anatomist working in New York, undertook a series of studies which attempted to define the microscopic structure of the nephrons in a variety of species. Given that he published his findings 15 years after William Bowman's seminal paper on the subject, he was able to add only a few of the finer details to the p...
The existence of tubulointerstitial damage in most cases of progressive human glomerular disease suggests that this compartment of the kidney is likely to be targeted by renoprotective agents which slow the progression of disease. Angiotensin-converting enzyme (ACE) inhibitors have become the cornerstone of renal protection. Since we have proposed...
To assess the quality and completeness of a database of clinical outcomes after cardiac surgery and to determine whether a process of validation, monitoring, and feedback could improve the quality of the database.
Stratified sampling of retrospective data followed by prospective re-sampling of database after intervention of monitoring, validation,...
All-trans-retinoic acid (t-RA) inhibits hydrogen peroxide (H(2)O(2))-induced apoptosis by inhibiting the c-Jun N-terminal kinase (JNK)-activator protein 1 (AP-1) pathway. In this report, we examined the involvement of mitogen-activated protein kinase phosphatase 1 (MKP-1) in suppression of JNK and the antiapoptotic effect of t-RA and the roles of n...
Development of micro- and macrovascular disease in diabetes mellitus (DM) warrants a thorough investigation into the repertoire of endothelial cell (EC) responses to diabetic environmental cues. Using human umbilical vein EC (HUVEC) cultured in three-dimensional (3-D) native collagen I (NC) or glycated collagen I (GC), we observed capillary cord fo...
glomerular inflammation, mesangial cells, platelet-derived growth factors (PDGF), caveolin-1
Is there a common mechanism for the progression of different types of renal diseases other than proteinuria? Towards the unifying theme of chronic hypoxia. The question of why chronic renal diseases progress is a topic only recently investigated. Putative causes such as proteinuria do not account for all aspects of progressive renal disease. An alt...
The mechanisms underlying the progressive fibrosis that characterises end-stage renal disease in vivo remain to be established but hypoxia, as a result of microvascular injury and loss, has been suggested to play an important role. In support of this hypothesis, in vitro studies show that hypoxia (1% O(2)) induces a fibrogenic phenotype in human re...
The balance between local offense factors and defense machinery determines the fate of tissue injury: progression or resolution. In glomerular research, the most interest has been on the offensive side, for example, the roles of leukocytes, platelets, complement, cytokines, eicosanoids, and oxygen radical intermediates. There has been little focus...
Progressive renal disease is characterized by expansion of the tubulo-interstitium and accumulation of extracellular matrix within this tissue compartment. Interstitial fibroblasts are the primary producers of the interstitial matrix, and in the evolution of tubulo-interstitial fibrosis these cells undergo changes, namely increased proliferation, d...
British contributions to renal physiology trace back to the seminal contribution of William Bowman, who defined the structure of mammalian nephron and its blood supply and pointed out its likely mode of function. A series of contributions followed, which stemmed from a distinguished lineage of physiologists based at University College London and wh...
Histological examination of the kidney was well under way by the mid-19th century. Pathological changes noted to be present in Bright's disease gave rise to considerable debate in the literature of the time. Toynbee was perhaps the first to note medial hypertrophy and intimal narrowing of blood vessels in the kidney, while Johnson, around the same...
Insights into the pathogenesis of human disease must be based on an understanding of the molecular mechanisms that regulate the structure and function of individual organs. For this purpose, gene transfer technologies provide powerful and attractive tools. In principle, two different approaches are feasible to identify pathophysiological roles of c...
Transforming growth factor beta (TGF-beta) has been regarded as a 'blackguard molecule' that induces glomerular diseases. During the process of glomerulonephritis, upregulated TGF-beta stimulates the production of extracellular matrix and inhibits its degradation, leading to excessive matrix deposition. On the other hand, TGF-beta has the potential...
Successful gene transfer into specific renal structures allows for evaluation of in vivo effects of certain molecules on the structure and function of the kidney. It would also be useful for therapeutic intervention in renal diseases by introducing "beneficial" genes into the affected sites. Towards achieving these goals, several gene transfer appr...
Tubulointerstitial fibrosis is characterized by tubular basement membrane thickening and accumulation of interstitial extracellular matrix (ECM). Since chronic low-grade hypoxia has been implicated in the pathogenesis of fibrosis and proximal tubular epithelial cells (PTE) are sensitive to oxygen deprivation, we hypothesized that hypoxia may stimul...
Communication between resident glomerular cells and infiltrating macrophages plays a crucial role in the pathogenesis of glomerular disease. Using matrix metalloproteinase-9 (MMP-9) as an indicator molecule, we examined the interaction between mesangial cells and macrophages. Mesangial cells cocultured with activated macrophages or exposed to macro...
A modern understanding of oedema formation traditionally begins with Starling's description in 1898 of hydrostatic and oncotic forces acting on the capillary membrane. Clearly, hypotheses of oedema formation predating the knowledge of the existence of capillaries must have been incomplete. Marcello Malpighi first described capillaries in 1661, but...
1and probably a similar proportion in other industrialised countries, and therefore has a substantial economic impact. Most stones contain calcium, usually as calcium oxalate. The aims of treatment are to reduce urinary calcium excretion, by restriction of dietary protein and calcium and by use of thiazide diuretics, and to decrease intestinal calc...
Adhesion of macrophages is a crucial event that determines the number and function of macrophages at inflammatory sites. The aim of this study was to elucidate the role of mesangial cells in the regulation of macrophage adhesiveness. J774.2 macrophages were suspended in serial dilutions of mesangial cell conditioned medium (MC medium) and seeded on...
Cross-communication between glomerular cells and infiltrating mononuclear cells plays an important role in the generation of or recovery from glomerular diseases. We found that cultured mesangial cells secrete a factor that inhibits production of proinflammatory cytokines by activated macrophages. Treatment of J774.2 macrophages with conditioned me...
Kidney International aims to inform the renal researcher and practicing nephrologists on all aspects of renal research. Clinical and basic renal research, commentaries, The Renal Consult, Nephrology sans Frontieres, minireviews, reviews, Nephrology Images, Journal Club. Published weekly online and twice a month in print.
The hypertrophy and proliferation of renal cells underlies the progressive interstitial fibrosis which occurs in experimental and clinical renal failure. The effects of vasoactive factors on the growth of renal cells is reviewed. Evidence from in vitro studies indicates that vasoactive factors are capable of influencing the growth of renal cells an...
To obviate the problem of rejection in situations where cells are used as vectors for gene delivery, the feasibility of using autologous mesangial cells cultured from renal biopsy specimens was studied for the purpose of gene transfer into the glomerulus. Using the calcium-phosphate co-precipitation method, a reporter gene which encodes bacterial b...
Using in vivo gene transfer, we examined the anti-inflammatory potential of transforming growth factor-beta 1 (TGF-beta 1) in the renal glomerulus. TGF-beta 1 cDNA, modified to allow for secretion of the active form of TGF-beta 1, was introduced into cultured rat mesangial cells. The responses of the established transfectants were examined in cultu...
Renal tubules have the capacity to regenerate following injury. We have investigated the possibility that tubular-derived endothelins, acting as autocrine growth factors, may be involved in this response in human kidney. ET-1 immunoreactivity was demonstrated by immunohistochemical staining in proximal tubules, distal cortical tubules and medullary...
Several lines of evidence suggest that hepatocyte growth factor/scatter factor (HGF/SF), a soluble protein secreted by embryo fibroblasts and several fibroblast lines, may elicit morphogenesis in adjacent epithelial cells. We investigated the role of HGF/SF and its membrane receptor, the product of the c-met protooncogene, in the early development...
To evaluate the pathophysiological function of specific molecules in the renal glomerulus, selective, sustained, and modifiable expression of such molecules will be required. Towards achieving this end, we devised a gene transfer system using the glomerular mesangial cell as a vector for gene delivery. A reporter gene which encodes bacterial beta-g...
Detailed histomorphometric analysis of human biopsy tissue over the last 30 years has convincingly demonstrated that preservation of the tubulointerstitial compartment of the kidney is the major determinant of renal outcome in a variety of human renal diseases. Nevertheless, the pathophysiology of tubulointerstitial disease remains obscure. In part...
The relentless progression of many renal diseases to end-stage renal failure after an apparently transient initial insult remains an enigma that continues to fascinate nephrologists. The "hyperfiltration" hypothesis based on the rat remnant kidney model of nephron ablation provided much of the intellectual stimulus to the study of glomerular injury...
Despite his success in publishing a book which was widely read and which drew attention to the fact that some cases of dropsy are associated with coagulable urine, John Blackall failed to make the link between this phenomenon and disease of the kidneys. Thus, to Richard Bright must go the credit for providing the critical understanding of the pheno...
We review the available methods of creating genetically engineered kidneys. These include transgenic technology to introduce novel genes or delete existing genes and methods of gene transfer into the post-natal or adult kidney. The use of such technology has provided insights into renal development and growth and created new animal models of human...
A vast amount of evidence, based upon human renal biopsy material, indicates that the presence of tubular atrophy and interstitial fibrosis is a better indicator of outcome of renal function than is the extent of glomerular sclerosis. The pathophysiological basis for this surprising fact has not been adequately addressed. In this review we point ou...
In this review we discuss two strategies for successful retrovirally-mediated transfer (transduction) of a reporter gene (bacterial beta-galactosidase) into the mammalian kidney. Retroviruses only integrate into dividing cells, but the adult kidney has a very low cell turnover. One approach used is the rapidly-dividing metanephros, or precursor of...
Our previous observation that embryonic kidney tissue can develop and differentiate when transplanted into the parenchyma of mouse kidneys in the postnatal period provided an avenue for transferring novel genes into the mammalian kidney in vivo. Mouse metanephric tissue was infected ex vivo with a replication defective retrovirus which transduces t...
Gene transfer using retroviral vectors requires cell replication for insertion of the DNA provirus. Since the mitotic index of the mammalian kidney is very low, renal tubular cell replication was induced in adult rats as part of a regenerative response to the nephrotoxic injury induced by an intraperitoneal injection of folic acid. At 48 h, at the...
Hypertrophy of renal proximal tubular cells is associated with an early increase in Na+/H+ antiport activity both in vivo and in vitro. The purpose of the study presented here was to determine whether functioning Na+/H+ antiport activity is required for hypertrophy to occur. LLC-PK1 cells deficient in Na+/H+ antiport activity were prepared by the "...
Knowledge of the control of cell growth and extracellular matrix deposition has assumed center stage in the understanding of how the diseased kidney responds to injury. After acute tubular injury, there may be reversible, partial depolarization of renal cells or cell necrosis. The latter requires a regenerative response, which could be under the co...
Purpose:
We reviewed the evidence that links altered levels of circulating and intrarenal growth factors with the genesis of renal glomerular hypertrophy, microvascular disease and interstitial fibrosis as seen in diabetes mellitus.
Animal data:
Insulin-like growth factor 1 (IGF-1) appears to be a hypertrophic factor in experimental renal diseas...
