Assessment of F-MuLV-induced tumorigenesis reveals new candidate tumor genes including Pecam1, St7, and Prim2.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
C Galvao
Publications and source records attributed to C Galvao.
The phosphatidylinositol synthase of proximal tubule cells.
Phosphatidylinositol (PI) is a precursor for an important class of phospholipids, the phosphatidylinositol polyphosphates. Because renal myo-inositol levels may vary under both physiological (e.g., antidiuretic) and pathophysiological (e.g., diabetic) conditions, the formation of PI from CDP-diacylglycerol (CDP-DG) and myo-inositol via phosphatidylinositol synthase and the regulation of this enzyme have important implications for the cellular biology of renal epithelia. We sought to understand the role of PI synthase by determining its subcellular localization, kinetic properties and regulation in rabbit proximal tubule cells. Proximal tubule cells were isolated from New Zealand White rabbits. The subcellular synthesis of PI was assessed by [32P]orthophosphate labelling with subsequent subcellular fractionation. Labelling of PI was time-dependent and consistent with the rapid incorporation of 32PO4 into basolateral, brush-border, microsomal and nuclear fractions. Pulse-chase labelling of proximal tubule cells was consistent with the formation of PI in microsomal fraction of the proximal tubule cells in addition to both brush-border and basolateral membranes. Conversely, phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol displayed radiolabelling patterns consistent with microsomal synthesis alone. The in situ formation of phosphatidylinositol was substantiated by the direct measurement of phosphatidylinositol synthase activity in basolateral, brush-border and microsomal fractions. The apparent Km values for myo-inositol were 0.32 +/- 0.19, 0.39 +/- 0.21 and 0.23 +/- 0.05 mM, and for CDP-DG were 0.12 +/- 0.02, 0.14 +/- 0.05 and 0.12 +/- 0.02 mM in basolateral, brush-border and microsomal fractions, respectively. Vmax values for phosphatidylinositol formation were slightly, but not significantly greater, in microsomal than for plasma membrane fractions. Moreover, based on enzymatic enrichment data, plasma membrane PI synthase activity could not be explained by microsomal cross-contamination alone. PI synthase activity was inhibited by co-incubation with PI without differences among the cellular fractions. Intracellular myo-inositol concentration in the proximal tubule cells as measured by gas-liquid chromatography was 20.5 mM, significantly greater than the apparent Km values for myo-inositol. In conclusion, the in situ synthesis of phosphatidylinositol occurs in several membrane fractions; the kinetic properties of phosphatidylinositol synthase appear to be similar in each fraction; and phosphatidylinositol synthase in proximal tubule cells is inhibited by its own formation product. These data suggest that myo-inositol concentration alone is unlikely to be an important regulator of the chemical mass of phosphatidylinositol at the levels of this polyol observed in rabbit kidney.
Animals↗
Acinetobacter peritonitis during chronic peritoneal dialysis.
Among gram-negative bacilli isolated during peritonitis in chronic peritoneal dialysis (CPD), Pseudomonas species are most common but Acinetobacter species are nearly as frequent. A survey of more than 450 patient-years' experience with CPD revealed 23 episodes of Acinetobacter peritonitis (AP), making this the second most common form of gram-negative peritonitis. Concomitant break in sterile technique and exit-site/tunnel infection were infrequent. AP appeared as the first peritonitis episode in five cases and as the second in six cases, and the duration of CPD at the time of AP ranged from less than 1 to greater than 56 months. However, AP was noted to appear shortly after treatment of another peritonitis episode or shortly after CPD access placement, within 2 months in 11 cases (47%) and within 3 months in 14 cases (61%). Treatment with intraperitoneal antibiotics succeeded in 21 cases (91%) without CPD interruption or catheter removal, with tobramycin or gentamicin alone in 16 cases, and with combined aminoglycoside and penicillin or cephalosporin in six cases. In two cases intraperitoneal antibiotics alone were insufficient therapy: one case with concomitant tunnel infection and dialysate leak and one case with bacteremia while receiving corticosteroids. The time-dependent incidence of AP suggests opportunistic infection during a vulnerable period in the first 2 to 3 months following another peritonitis episode, but AP also appears amenable to intraperitoneal antibiotic therapy alone without interruption of the CPD routine in the majority of cases.
Acinetobacter Infections↗
Epidermal growth factor enhances renal tubule cell regeneration and repair and accelerates the recovery of renal function in postischemic acute renal failure.
To determine the timing and location of renal cell regeneration after ischemic injury to the kidney and to assess whether exogenous epidermal growth factor (EGF) enhances this regenerative repair process to accelerate recovery of renal function, experiments were undertaken in rats undergoing 30 min of bilateral renal artery clamp ischemia followed by reperfusion for varying time intervals. Renal cell regeneration, as reflected by incorporation of radiolabeled thymidine within the kidney, began between 24 to 48 h and reached a peak at 72 h after renal ischemia. As demonstrated by histoautoradiography, renal thymidine incorporation was essentially confined to tubule cells. Morphometric analysis of histoautoradiograph sections of renal tissue demonstrated that the majority of labeled cells were found in renal cortex, but some labeled cells were also located in the inner stripe of the outer medulla, suggesting that injury to medullary thick ascending limbs also occurs in this ischemic model. Exogenous EGF administration produced increases in renal thymidine incorporation compared with non-treated animals at 24, 48, and 72 h after ischemic injury. This accelerated DNA replicative process was associated with significantly lower peak blood urea nitrogen (BUN) and serum creatinine levels, averaging 63 +/- 20 and 3.1 +/- 0.4 mg/dl in EGF-treated ischemic rats compared with 149 +/- 20 and 5.1 +/- 0.1 mg/dl, respectively, in nontreated ischemic rats, and was also associated with a return to near normal BUN and serum creatinine levels in EGF-treated animals approximately 4 d earlier than that observed in nontreated animals. This report is the first demonstration that EGF accelerates the repair process of a visceral organ after an injurious insult.
Acute Kidney Injury↗