Biomedical subjects

Derek Fine

Publications and source records attributed to Derek Fine.

3 recordsLinked to original sources

PubMed2005

A SAGE-based comparison between glomerular and aortic endothelial cells.

Endothelial cells have many characteristics in common, but significant morphological and functional differences exist between endothelial cells from different anatomic sites. The specific glomerular endothelial (GEn) cell transcript repertoire is unknown. We sought to determine whether endothelial cells derived from bovine glomeruli display a distinct transcriptional profile compared with bovine aortic endothelium (BAE) under identical conditions. Serial analysis of gene expression (SAGE), which includes known and unknown transcripts, was used to make the comparison. The GEn and BAE SAGE libraries contain 36,844 and 26,452 total tag sequences, respectively. Among 6,524 unique tag sequences represented at least 2 times in the 2 libraries, 2,094 (32%) were matched to well-characterized bovine cDNA sequences (358 tags) or expressed sequence tags (EST). Identification of the human homolog was achieved for 1,035 of these tags. Forty-two tags were differentially expressed in GEn. For 25 of these, the bovine cDNA or EST, and for 17 the human homolog was identified. Among all transcripts with a known bovine and human tag, seven were expressed at levels more than 10-fold higher in cultured GEn cells compared with all other SAGE libraries. The transcript "DKFZp564B076" was localized by in situ hybridization to glomerular endothelium in vivo and was shown by real-time RT-PCR to be highly abundant in glomeruli compared with aortic intima. This work supports the concept that differences in the transcriptional profile of endothelial cells from distinct origins are observed under otherwise equivalent conditions. Furthermore, we have identified the first known transcript predominant in glomerular endothelium in vivo.

Animals↗

PubMed2004

Urine protein-to-creatinine ratio is a reliable measure of proteinuria in lupus nephritis.

OBJECTIVE: To evaluate the 24-hour urine protein-to-creatinine (U pr:cr) ratio compared to 24-h urine total protein excretion as a measure of proteinuria in patients with lupus nephritis. METHODS: Proteinuria in 8 patients with lupus nephritis treated with cyclophosphamide was monitored by total protein excretion and U pr:cr ratio in 24-h urine collections. A median of 16 measurements per patient were collected over a median of 47 months. Adequacy of the 24-h collection was assessed by comparing total urine creatinine to the predicted creatinine. Collections in which the difference between the predicted 24-h urine creatinine and the measured 24-h urine creatinine was greater than or equal to 20% were defined as inadequate collections. RESULTS: Timed 24-h urine collections were frequently inadequate (30.2% of total collections were under-collections, while 14.3% were over-collections). We found 87.5% of patients had at least one under-collection whereas 75% had at least one over-collection. Correlations between total protein and U pr:cr ratio for individual patients ranged from 0.87 to 0.99 (mean 0.95). For the entire sample, the correlation (R2 = 0.89) of total urine protein to Upr:cr ratio was excellent. Excluding the 38 under-collections led to improvement in the overall correlation (0.94). Excluding the 18 over-collections led to a correlation of 0.89. Excluding both under-collections and over-collections led to a correlation of 0.94. CONCLUSION: In patients with lupus nephritis, the 24-h U pr:cr ratio is highly correlated with the 24-h urine protein excretion when the collections are adequate. The error of the estimate is higher when collections are poor.

Adult↗

PubMed2003

Renal function improves in liver transplant recipients when switched from a calcineurin inhibitor to sirolimus.

Sirolimus (Rapamune; Wyeth-Ayerst, Philadelphia, PA) is a newer immunosuppressive drug with no known acute or chronic nephrotoxic effects; however, limited data are available in liver transplant recipients. We prospectively evaluated changes in renal function in liver transplant recipients after conversion from a calcineurin inhibitor to sirolimus monotherapy. We measured serial serum creatinine levels in liver transplant recipients with chronic nephrotoxicity caused by calcineurin inhibitors before and after conversion to sirolimus therapy. Estimated glomerular filtration rate (eGFR) was calculated from the Modification of Diet in Renal Disease formula. Change in eGFR over time, incidence of acute hepatocellular rejection, and adverse events while being administered sirolimus monotherapy were recorded. Mean interval between liver transplantation and initiation of sirolimus therapy was 310 weeks (range, 9 to 780 weeks). Of 21 patients included in our study, 18 patients were converted to sirolimus monotherapy and 3 patients were switched to sirolimus and low-dose steroid therapy. Patients were followed up for a mean of 66.8 +/- 38.9 (SD) weeks after conversion. Renal function improved in 71% of patients (15 of 21 patients). Median eGFR improved significantly from 34 mL/min/1.73 m2 at the time of conversion to 43 mL/min/1.73 m2 at the last follow-up (27% increase in eGFR; P = 001). Median monthly change in eGFR was from -0.25 mL/min/1.73 m2 pre-sirolimus therapy to +1.28 mL/min/1.73 m2 post-sirolimus therapy (P =.09). Adverse events were mostly mild and self-limited. Only 1 patient developed biopsy-proven acute cellular rejection, which was treated with sirolimus and mycophenolate mofetil. Two patients discontinued sirolimus therapy because of toxicity (oral ulceration, 1 patient; interstitial pneumonitis, 1 patient). Renal function improved significantly in the majority of liver transplant recipients with renal insufficiency caused by calcineurin inhibitors when converted to sirolimus therapy. Sirolimus monotherapy provided adequate immunosuppression with a low incidence of acute cellular rejection and minimal adverse events.

Adult↗