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Michael J Ross

Publications and source records attributed to Michael J Ross.

10 recordsLinked to original sources
PubMed2006

Dual tropism of HIV-1 envelopes derived from renal tubular epithelial cells of patients with HIV-associated nephropathy.

The phenotype of HIV-1 gp120 envelope derived from renal epithelium and peripheral blood mononuclear cells (PBMC) of patients with HIV-associated nephropathy was investigated in vitro. Chimeric viruses were derived from kidney or blood and used to infect primary CD4+T cells, cell lines expressing single co-receptors and a renal epithelial cell line HPT-1. HIV-1 variants derived from renal epithelium were dual tropic whereas simultaneously derived viruses from PBMC were R5-tropic. Utilization of alternative co-receptors CCR3, BONZO and BOB, also differed.

AIDS-Associated Nephropathy↗
PubMed2006

Role of ubiquitin-like protein FAT10 in epithelial apoptosis in renal disease.

Dysregulated apoptosis of renal tubular epithelial cells (RTEC) is an important component of the pathogenesis of several renal diseases, including HIV-associated nephropathy (HIVAN), the most common cause of chronic kidney failure in HIV-infected patients. In HIVAN, RTEC become infected by HIV-1 in a focal distribution, and HIV-1 infection has been shown to induce apoptosis in vitro. In microarray studies that used a novel renal tubular epithelial cell line from a patient with HIVAN, it was found that the ubiquitin-like protein FAT10 is one of the most upregulated genes in HIV-infected cells. Previously, FAT10 was shown to induce apoptosis in murine fibroblasts. The expression of FAT10 in HIVAN and the ability of FAT10 to induce apoptosis in human RTEC therefore were studied. This study revealed that FAT10 expression is induced after infection of RTEC by HIV-1 and that expression of FAT10 induces apoptosis in RTEC in vitro. Moreover, it was found that inhibition of endogenous FAT10 expression abrogated HIV-induced apoptosis of RTEC. Immunohistochemical studies demonstrated increased FAT10 expression in a murine model of HIVAN, in HIVAN biopsy samples, and in autosomal dominant polycystic kidney disease, another renal disease that is characterized by cystic tubular enlargement and epithelial apoptosis. These results suggest a novel role for FAT10 in epithelial apoptosis, which is an important component of the pathogenesis of many renal diseases.

AIDS-Associated Nephropathy↗
PubMed2006

HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells.

HIV-associated nephropathy (HIVAN) is the most common cause of chronic renal failure in HIV-infected patients. Tubulointerstitial inflammation is a prominent component of the histopathology of HIVAN. The pathogenesis of HIVAN is a result of infection of renal epithelial cells, but the cellular response to this infection remains poorly defined. In these studies, we used oligonucleotide microarrays to identify differentially expressed genes in renal tubular epithelial cells from a patient with HIVAN at three time points after infection with vesicular stomatitis virus-pseudotyped gag/pol-deleted HIV-1. Very few genes were differentially expressed 12 and 24 hours after infection. Three days after infection, however, 47 genes were upregulated by at least 1.8-fold. The most prominent response of these cells to HIV-1 expression was production of proinflammatory mediators, including chemokines, cytokines, and adhesion molecules. Many of the upregulated genes are targets of interleukin 6 and nuclear factor kappa B regulation, suggesting a central role for these proteins in the response of tubular epithelial cells to HIV-1 infection. Analysis of kidneys from HIV-1 transgenic mice revealed upregulation of many of the proinflammatory genes identified in the microarray studies. These studies provide novel insights into the mechanisms by which HIV-1 infection of tubular epithelial cells leads to tubulointerstitial inflammation and progressive renal injury.

AIDS-Associated Nephropathy↗
PubMed2005

Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal disease.

The rise in the number of patients with HIV-associated nephropathy and HIV-infection with end-stage renal disease (HIV+ ESRD) continues to be a substantial concern for the ESRD program. In order to assess the impact of highly active antiretroviral therapy (HAART) on the progression of patients with AIDS to the development of ESRD and to project the prevalence of HIV+ ESRD through 2020, a mathematical model of the dynamics of HIV+ infection in the ESRD population was developed. Epidemiologic data on AIDS and HIV+ ESRD among black individuals in the United States were obtained since 1991 from the Centers for Disease Control and Prevention and US Renal Data System, respectively. The model was constructed to predict the prevalence of HIV+ ESRD incorporating the current rate of growth in AIDS prevalence. Two possible trends were considered: linear AIDS growth and exponential AIDS growth. The likely effectiveness of HAART in slowing progression to HIV+ ESRD was estimated from the best fit of the model to the data after 1995, when HAART was introduced. The model was then used to evaluate recent data and to project the prevalence of HIV+ ESRD through 2020. The model suggested that HAART has reduced the rate of progression from AIDS to HIV+ ESRD by 38%. The model projected an increase in HIV+ ESRD prevalence in the future as a result of the increase in the AIDS population among black individuals. This increase was predicted even assuming a 95% reduction in the progression from AIDS to HIV+ ESRD. Despite the potential benefit of HAART, the prevalence of HIV+ ESRD in the United States is expected to rise in the future as a result of the expansion of the AIDS population among black individuals. It is concluded that prevention of progression to ESRD should focus on early antiretroviral treatment of HIV-infected patients who have evidence of HIV-associated nephropathy.

AIDS-Associated Nephropathy↗
PubMed2005

NF-kappaB regulates Fas-mediated apoptosis in HIV-associated nephropathy.

Renal parenchymal injury in HIV-associated nephropathy (HIVAN) is characterized by epithelial proliferation, dedifferentiation, and apoptosis along the entire length of the nephron. Although apoptotic cell death in HIVAN has been well documented, the mechanism for HIV-induced apoptosis is poorly understood. Whether the epithelial apoptosis in HIVAN is mediated by NF-kappaB-activated Fas ligand expression was investigated here. In human HIVAN and HIV-1 transgenic mouse kidney specimens, the expression of Fas receptor and ligand proteins were markedly upregulated on epithelium in diseased glomerular and tubulointerstitial compartments when compared with normal. Podocyte cell lines that were derived from HIV-1 transgenic mice showed a similar upregulation of Fas receptor expression and de novo expression of Fas ligand by semiquantitative reverse transcription-PCR and Western blotting. In cultured podocytes, cross-linking of the Fas receptor to mimic ligand binding induced caspase 8 activity and apoptosis in both normal and HIVAN podocytes. Because constitutive NF-kappaB activity has been demonstrated in HIVAN epithelia, evidence for transcriptional control of the Fas ligand expression by NF-kappaB was sought. With the use of cultured podocytes, expression of a Fas ligand promoter reporter plasmid was higher in HIVAN podocytes, indicating increased transcriptional activity. In addition, chromatin immunoprecipitation assays were performed to demonstrate that p65-containing (RelA) complexes bound the Fas ligand promoter and that suppression of activated NF-kappaB with a peptide inhibitor could reduce the expression of Fas ligand mRNA in HIVAN podocytes. These results suggest that NF-kappaB may regulate Fas-mediated apoptosis in HIVAN by controlling the expression of Fas ligand in renal epithelium.

AIDS-Associated Nephropathy↗
PubMed2005

Geriatric depression, medical diagnosis, and functional recovery during acute rehabilitation.

OBJECTIVE: To examine and compare the prevalence and functional impact of depressive symptoms for older adult stroke and nonstroke rehabilitation inpatients. DESIGN: Case-control study examining functional outcome using a 2 (stroke, nonstroke) by 2 (depression, no depression) design. SETTING: Urban hospital rehabilitation unit. PARTICIPANTS: A total of 509 rehabilitation inpatients (age, > or = 60 y) were included and grouped by diagnosis of stroke (n=207) and nonstroke (n=302). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Geriatric Depression Scale and FIM instrument. Analysis of covariance procedures examined the impact of depressive symptoms on discharge functional ability controlling for age, sex, admission functional ability, and hospital length of stay. RESULTS: Prevalence of depressive symptoms was similar for stroke (31.8%) and nonstroke (31.5%) and negatively associated with functional ability at discharge for both groups. Overall, the stroke and nonstroke groups did not differ significantly with respect to functional recovery. CONCLUSIONS: Depression, and its impact on acute rehabilitation, is significantly related to functional recovery but does not differ in its frequency or impact for stroke patients. Because depressive symptoms do not appear to discriminate across diagnostic groups, routine screening for depression is recommended for all rehabilitation inpatients.

Aged↗
PubMed2004

Sidekick-1 is upregulated in glomeruli in HIV-associated nephropathy.

Infection of podocytes by HIV-1 induces unique changes in phenotype, which contribute to the pathogenesis of glomerular disease in HIV-associated nephropathy (HIVAN). The host genetic pathways altered by HIV-1 infection that are responsible for these phenotypic changes are largely unknown. For identifying such pathways, representational difference analysis was performed comparing cDNA from HIV-1 transgenic podocytes with nontransgenic controls. In this way, a gene named sidekick-1 (sdk-1) was cloned, a transmembrane protein of the Ig superfamily that is highly upregulated in HIV-1 transgenic podocytes. Sdk-1 and its ortholog, sidekick-2 (sdk-2), were recently shown to guide axonal terminals to specific synapses in developing neurons. Their presence and role in other organs, including the kidney, has not been described. The current study demonstrates developmental expression of both sdk-1 and sdk-2 and a tight spatial and temporal regulation of these genes in kidney. During nephrogenesis, sidekick expression was observed first in ureteric bud and ureteric bud-derived tissues in a pattern similar to other genes known to play important roles in branching morphogenesis. In adult murine renal tissue, sidekick proteins were seen in glomeruli at low levels, and expression of sdk-1 was greatly upregulated in diseased HIV-1 transgenic mouse kidneys. In a human HIVAN kidney biopsy, sidekick expression was increased in glomeruli in a pattern consistent with the mouse model. It is proposed that the dysregulation of sdk-1 protein may play an important role in HIVAN pathogenesis.

AIDS-Associated Nephropathy↗
PubMed2001

Microcyst formation and HIV-1 gene expression occur in multiple nephron segments in HIV-associated nephropathy.

Tubular microcyst formation is a prominent histopathologic feature of HIV-associated nephropathy (HIVAN), but its pathogenesis is unknown. HIV-1 has recently been shown to infect renal tubular epithelial cells in patients with HIVAN. In addition, HIV-1 gene expression in renal epithelial cells has been shown to cause a renal disease that is identical to HIVAN in HIV-1 transgenic mice. In these studies, immunohistochemistry for tubular segment-specific markers and mRNA in situ hybridization for HIV-1 was used to determine which tubular segments develop microcysts and which segments express HIV-1 in the kidneys of transgenic mice and patients with HIVAN. It was found that microcysts involve multiple nephron segments in both patients with HIVAN and HIV-1 transgenic mice. Furthermore, HIV-1 infection in HIVAN and HIV-1 transgene expression also occurs in multiple segments of the nephron. These data support a direct role for HIV-1 infection of renal epithelial cells in the pathogenesis of microcyst formation in patients with HIVAN.

AIDS-Associated Nephropathy↗