- Browse by Date
Bonnie Blazer-Yost
Permanent URI for this collection
Dr. Bonnie Blazer-Yost’s primary interest is in epithelial cell biology as it relates to ion transport. Recently she has been investigating treatments for polycystic kidney disease. These studies resulted from a serendipitous finding regarding the potential use of Pioglitazone, a commonly used diabetes drug, in polycystic kidney disease patients. This research has progressed from tissue culture, through preclinical animal models and is currently funded as an initial clinical trial in polycystic kidney disease patients.
Dr. Blazer-Yost and her team are also researching potential treatments for hydrocephalus or “water on the brain.” Hydrocephalus may develop as a consequence of trauma, infection, tumors, intracranial hemorrhage or as a result of a congenital birth defect. Elderly patients may suffer from a poorly understood and underdiagnosed form called “normal pressure hydrocephalus,” characterized by urinary incontinence, gait instability, and dementia. Post-traumatic hydrocephalus occurs as the result of traumatic brain injury. Regardless of the form, brain surgery is currently the only effective long-term treatment. Dr. Blazer-Yost and her collaborators recently obtained a three-year Department of Defense grant to conduct translational studies in animal models with a goal of developing a drug treatment for hydrocephalus.
Dr. Blazer-Yost’s work to treat polycystic kidney disease and hydrocephalus is another example of how IUPUI faculty are TRANSLATING RESEARCH INTO PRACTICE.
Browse
Browsing Bonnie Blazer-Yost by Issue Date
Results Per Page
Sort Options
Item Prenatal diagnosis of cystinosis(1975-10) States, Beatrice; Blazer, Bonnie; Harris, Dorothy; Segal, StantonCystinosis was diagnosed in a small quantity of cultured amniotic cells from a 22-week-old fetus by a modified pulse-labeling technique in which intracellular 55Sl-cystine retention was measured. As a result of the above finding, the pregnancy was terminated by administration of prostaglandin. The diagnosis was confirmed when the nonprotien-free cystine cystine content of the kidney, liver, placenta, spleen, thymus, and gut, as well as that of a large amount of cultured amniotic cells, was found to be 100-fold higher than normal levels.Item Late-onset nonketotic hyperglycinemia and spinocerebellar degeneration(1979-06-01) Steiman, Gerald S.; Yudkoff, Marc; Berman, Peter H.; Blazer-Yost, Bonnie; Segal, StantonInvestigation of a 15-year old boy with progressive optic atrophy and spinocerebellar degeneration revealed elevated plasma, cerebrospinal fluid, and urine glycine concentrations. During an oral glycine loading test, the patient's plasma glycine concentration rose to a higher level than control values, although the initial rate of rise was slower; there was no concomitant rise in the plasma serine concentration. An oral serine loading test resulted in a prompt rise of both glycine and serine serum concentrations. The renal glycine clearance was elevated, and the renal tubular glycine reabsorption was diminished. These findings of decreased intestinal uptake and increased renal tubular glycine clearance suggest that a generalized derangement of glycine entry into cells may account for the phenotypic manifestations of the disorder.Item Acetylation of albumin by low doses of aspirin(1981-08) Burch, John W.; Blazer-Yost, BonnieAspirin has a variety of pharmacologic actions, which are expressed at different doses of the drug. An effect on platelet function occurs at very low doses of aspirin (1,2). Indeed, a large number of clinical trials have been carried out to assess whether low to moderate doses of aspirin (180 to 1500 mg per day) taken prophylactically will affect the natural history of a variety of diseases in which thrombosis is thought to play a role (3).Item Aldosterone-induced proteins in renal epithelia(1982-10-28) Blazer-Yost, Bonnie; Geheb, Michael A.; Preston, Alan; Handler, Joel; Cox, MalcolmSimilar aldosterone-induced proteins have been demonstrated in two renal epithelia, the urinary bladder of the toad, Bufo marinus, and epithelia formed by cells of the A6 line derived from the kidney of the toad, Xenopus laevis. The proteins are induced along with the stimulation of Na+ transport but their synthesis is not dependent on Na+ transport per se. In view of the similar characteristics of the aldosterone-induced proteins in these two different epithelia, we suggest that they may have an important role in aldosterone-induced Na+ transport.Item Role of insulin and IGF1 receptors in proliferation of cultured renal proximal tubule cells(1992-02-03) Blazer-Yost, Bonnie; Watanabe, Melanie; Haverty, Thomas P.; Ziyadeh, Fuad N.We have used a murine proximal tubule cell line (MCT cells) to determine the presence and binding characteristics of insulin and IGF1 receptors and to correlate these parameters with the concentration-response relationships for ligand-induced cellular proliferation. Separate insulin and IGF1 receptors were identified by equilibrium binding assays. Half-maximal displacement of either peptide occurred at 3-10 nM; crossover binding to the alternate receptor occurred with a 10- to 100-fold lower affinity. Peptide effects on cellular proliferation were determined by measuring [3H]thymidine incorporation. Both insulin and IGF1 stimulate thymidine incorporation in a dose-dependent manner with similar increases above the basal level. The estimated half-maximal stimulation (EC50) occurred at 4 nM for IGF1 and 8 nM for insulin. A comparison of the receptor binding affinities with the dose-response relationships for [3H]thymidine incorporation reveals that each growth factor appears to be exerting its effect via binding to its own receptor. Therefore, in this cell line, physiologic concentrations of either insulin or IGF1 can modulate cellular growth. To our knowledge this is the first demonstration of a mitogenic effect which may be modulated by ligand binding to the insulin receptor in proximal tubule epithelia.Item Differential effects of brefeldin A on hormonally regulated Na + transport in a model renal epithelial cell line(1994) Blazer-Yost, Bonnie; Coupaye-Gerard, Brigitte; Kim, Hyun Jin; Singh, AnupNa+ transport in renal epithelia is regulated by a wide variety of endogenous and exogenous cellular factors. Although most natriferic agents have an action on the amiloride-sensitive Na+ channel, the biochemical pathways which precede activation of the channel remain incompletely defined. One approach to dissecting such intricate pathways is to perturb a specific cellular process and determine its importance in the postulated mechanism. The current studies examine the effect of brefeldin A (BFA), an inhibitor of the central vacuolar system, on basal as well as aldosterone-, insulin-, and forskolin-stimulated Na+ transport. In the A6 cell line, BFA had a time-dependent effect on basal transport. Aldosterone-induced Na+ transport was sensitive to BFA while insulin's action was only partially blocked and forskolin-stimulated Na+ transport was relatively resistant to the action of the inhibitor. These studies highlight differences as well as points of convergence in the natriferic pathways.Item Characterization of hormone-stimulated Na+ transport in a high-resistance clone of the MDCK cell line(1996-08) Blazer-Yost, Bonnie; Record, Rae D.; Oberleithner, HansThe Madin-Darby canine kidney (MDCK) cell line forms an epithelial monolayer which expresses many of the morphological and functional properties of the renal collecting duct. The C7 subclone of the parent line forms an epithelium which expresses many of the characteristics of principal cells. The MDCK-C7 subclone forms a high-resistance epithelium that is capable of vectorial ion transport. We have found that this epithelium responds to aldosterone, antidiuretic hormone (ADH) and insulin like growth factor 1 (IGF1) with increases in amiloride-sensitive Na+ transport. The responses to aldosterone and ADH follow time-courses that are consistent with the action of these hormones in vivo. This is the first demonstration of IGF1-induced Na+ reabsorption in a mammalian model system. Interestingly, a maximal response to any one of these natriferic factors does not inhibit a subsequent response to another hormone. These studies indicate that the C7 subclone retains many of the natriferic responses of the native principal cells and is an ideal model for studying hormonal modulation of Na+ transport.Item Aldosterone-induced proteins in primary cultures of rabbit renal cortical collecting system(1996-10) Bindels, Rend J.M.; Engbersen, A.M.T.; Hartog, A.; Blazer-Yost, BonniePrimary cultures of immunodissected cells from rabbit kidney connecting tubule and cortical collecting duct were used to study aldosterone's action on transcellular Na+ flux. Incubation with 10(-7) M aldosterone stimulated transcellular Na+ transport which was detected as an increase in benzamil-sensitive short-circuit current. The stimulatory response was consistently noted after 2 h of incubation and stabilized after 6 h. 2D-PAGE was used to identify proteins which were induced concurrently with the increase in transcellular Na+ flux after an aldosterone incubation of 15 h. Three aldosterone-induced proteins (AIPs; M(r) = 100, 70-77 and 46-50 kDa) were found in the membrane and microsomal fractions. Two of these appeared to have more than one isoform. A single heterogeneous AIP (M(r) = 77 kDa) was detected in the soluble fraction.Item Time-dependent stimulation by aldosterone of blocker-sensitive ENaCs in A6 epithelia(1998-04) Helman, Sandy I.; Liu, Xuehong; Baldwin, Kieron; Blazer-Yost, Bonnie; Els, Willem J.To study and define the early time-dependent response (< or = 6 h) of blocker-sensitive epithelial Na+ channels (ENaCs) to stimulation of Na+ transport by aldosterone, we used a new modified method of blocker-induced noise analysis to determine the changes of single-channel current (iNa) channel open probability (Po), and channel density (NT) under transient conditions of transport as measured by macroscopic short-circuit currents (Isc). In three groups of experiments in which spontaneous baseline rates of transport averaged 1.06, 5.40, and 15.14 microA/cm2, stimulation of transport occurred due to increase of blocker-sensitive channels. NT varied linearly over a 70-fold range of transport (0.5-35 microA/cm2). Relatively small and slow time-dependent but aldosterone-independent decreases of Po occurred during control (10-20% over 2 h) and aldosterone experimental periods (10-30% over 6 h). When the Po of control and aldosterone-treated tissues was examined over the 70-fold extended range of Na+ transport, Po was observed to vary inversely with Isc, falling from approximately 0.5 to approximately 0.15 at the highest rates of Na+ transport or approximately 25% per 3-fold increase of transport. Because decreases of Po from any source cannot explain stimulation of transport by aldosterone, it is concluded that the early time-dependent stimulation of Na+ transport in A6 epithelia is due exclusively to increase of apical membrane NT.Item Phosphatidylinositol 3-kinase activation is required for insulin-stimulated sodium transport in A6 cells(1998-04) Record, Rae D.; Froelich, Larry L.; Vlahos, Chris J.; Blazer-Yost, BonnieInsulin stimulates amiloride-sensitive sodium transport in models of the distal nephron. Here we demonstrate that, in the A6 cell line, this action is mediated by the insulin receptor tyrosine kinase and that activation of phosphatidylinositol 3-kinase (PI 3-kinase) lies downstream of the receptor tyrosine kinase. Functionally, a specific inhibitor of PI 3-kinase, LY-294002, blocks basal as well as insulin-stimulated sodium transport in a dose-dependent manner (IC50 approximately 6 microM). Biochemically, PI 3-kinase is present in A6 cells and is inhibited both in vivo and in vitro by LY-294002. Furthermore, a subsequent potential downstream signaling element, pp70 S6 kinase, is activated in response to insulin but does not appear to be part of the pathway involved in insulin-stimulated sodium transport. Together with previous reports, these results suggest that insulin may induce the exocytotic insertion of sodium channels into the apical membrane of A6 cells in a PI 3-kinase-mediated manner.