View details for Web of Science ID A1989AU52300004. One secondary endpoint, measurements of the anti-inflammatory cytokine IL-10 in sinus fluid, was significantly (p < 0.03) increased in the tgAAVCF-treated sinus relative to the placebo-treated sinus at day 90 after vector instillation. A., Reynolds, T., Moran, M. L., Moss, R. B., Wine, J. J., Flotte, T. R., Gardner, P. A phase I/II study of tgAAV-CF for the treatment of chronic sinusitis in patients with cystic fibrosis. Assessing the biological activity and clinical efficacy of gene therapy is critically important in cystic fibrosis (CF). Their conflicting politics, and his conflicted feelings, led the . Intracellular administration of hydrolysis-resistant guanosine triphosphate (to persistently activate GTP-binding protein) and guanosine diphosphate (to competitively inhibit GTP-binding proteins) analogues mimicked and inhibited substance P-induced reduction of K+ conductance, respectively. About Phyllis Gardner, M.D. Deafness and hearing impairment have a genetic cause in at least half the cases. Dr. Phyllis Gardner, MD, is an Internal Medicine specialist practicing in Stanford, CA with 47 years of experience. To investigate this signal transduction, plasma membrane calcium-permeable channels were characterized in T-lymphocytes by means of whole cell or single channel patch-clamp recordings. Among the presbycusis group, these solely occurred within the GJB2 and SLC26A4 genes. She has served on the board of directors of several public and private companies, including . Leflunomide, a novel immunosuppressive drug, prolongs experimental graft survival effectively and has been well tolerated in patients with rheumatoid arthritis. We reexamined this hypothesis by use of whole-cell patch clamp recordings of three matched pairs of cell lines, which were either drug-sensitive or drug-resistant due to P-gp overexpression. Stimulation of T cells by externally applied PGE1 stimulated 125I efflux and activated a slowly developing membrane current. For each patient, a dose of 100,000 replication units of tgAAVCF was administered to one maxillary sinus, while the contralateral maxillary sinus received a placebo treatment, thereby establishing an inpatient control. The maximal effects were seen at concentrations of 25-50 microM. Phyllis Gardner, Stanford University professor of medicine and health care venture capital firm partner, on her early suspicions about disgraced Theranos founder Elizabeth Holmes, whom she . Spectrofluorescence of Indo/AM dye measured intracellular Ca2+ mobilization. You may use our global navigation in the heading bar or return to our home page using the buttons below. She has previously served as Dean of Education. Dr. Phyllis I. Gardner is an internist in Stanford, California. View details for Web of Science ID 000078432500017. Nghiem, P., OLLICK, T., Gardner, P., Schulman, H. ACTIVATION OF CA2+ CURRENT IN JURKAT T-CELLS FOLLOWING THE DEPLETION OF CA2+ STORES BY MICROSOMAL CA2+-ATPASE INHIBITORS. 2. With fluorescent cytometry, using the visible wavelength calcium probe, fluo-3, and patch clamping, we investigated whether TNF induces cytosolic free Ca2+ changes and Ca(2+)-activated Cl- current, respectively. 2. 1. Moss, R. B., BOCIAN, R. C., Hsu, Y. P., Dong, Y. J., Kemna, M., Wei, T., Gardner, P. Mechanism of the antiproliferative action of leflunomide - A77 1726, the active metabolite of leflunomide, does not block T-cell receptor-mediated signal transduction but its antiproliferative effects are antagonized by pyrimidine nucleosides. InsP3 may have its effect indirectly through depletion of Ca2+ stores, or directly with a plasma membrane-associated InsP3 receptor. After more than a decade in conceptualisation and experimentation, four systems that have commercial potential are discussed: i) implantable microchips with on-demand microdosage for one or more therapeutic agents under internal control or external control using a wireless link; ii) nanopore pumps, implantable titanium pumps, consisting of a drug reservoir with a nanopore-release membrane, capable of delivering potent small or macromolecules at constant serum levels for sustained periods of time; iii) nanocages, microfabricated nanopore immunoisolation chambers for cellular implants, capable of natural feedback-controlled delivery of proteins and peptides; and iv) nanobuckets, micromachined silicon porous particles with drug-loading capacity and targeting ligands for localised delivery. The regulation of the channels by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in transformed B cells from CF patients is defective. A., COZENS, A. L., Schulman, H., Gruenert, D. C., Stryer, L., Gardner, P. PATCH CLAMP STUDIES OF LYMPHOCYTE-ACTIVATION, MODULATION OF MEMBRANE K+ CONDUCTANCE IN LYMPHOCYTES-T BY SUBSTANCE-P VIA A GTP-BINDING PROTEIN, IDENTIFICATION OF A HEMOLYSIN FROM ACTINOBACILLUS-PLEUROPNEUMONIAE AND CHARACTERIZATION OF ITS CHANNEL PROPERTIES IN PLANAR PHOSPHOLIPID-BILAYERS. In addition, several other internal feedback controls on TCR/CD3 function, by CD4-induced tyrosine-specific phosphorylation of the CD3 zeta subunit, or on the Ca2+ signal, by extracellular Cl- or by GM1 gangliosides, are also postulated. SK&F 96365 has no effect on Ca2+ stores release or K+ channels. By use of whole-cell patch clamp recordings, we show that nitric oxide activates cystic fibrosis transmembrane conductance regulator CI- currents in normal human cloned T cells by a cGMP-dependent mechanism. 4. Gardner recently. Ligation of the extracellular domains of the T-cell receptor activates receptor-associated tyrosine kinases that can phosphorylate the gamma-isoform of phospholipase C, increasing its catalytic activity. Thus, DBHQ appears to enhance Cl- channel activity via a Ca(2+)-dependent mechanism involving CaMKII. Whether a physiological defect exists in the immune system of CF patients has remained controversial. Cao, W. W., Kao, P. N., Chao, A. C., Gardner, P., Ng, J., Morris, R. E. CALCIUM-DEPENDENT AND CAMKII-DEPENDENT CHLORIDE SECRETION INDUCED BY THE MICROSOMAL CA2+-ATPASE INHIBITOR 2,5-DI-(TERT-BUTYL)-1,4-HYDROQUINONE IN CYSTIC-FIBROSIS PANCREATIC EPITHELIAL-CELLS. B-lymphoblasts from CF-affected humans demonstrated defective Cl- conductance regulation by cAMP but preserved regulation by calcium-mediated and volume regulation mechanisms. In addition, voltage-gated K+ channels, which closely resemble the delayed rectifier K+ channel of nerve and muscle, can be classified into three subtypes, according to their voltage dependence of activation, inactivation kinetics, and pharmacological sensitivity. View details for Web of Science ID A1991GF80400001. Many of the critical T-cell signal transducing enzymes such as phospholipase C and protein kinase C contain intrinsic Ca-binding domains, but for the most part the rise in cytoplasmic Ca is transduced by specialized Ca-binding proteins that lack catalytic domains. View details for Web of Science ID A1994PH77400001. There have been major advances over the last several years in understanding the molecular basis of signaling by the T lymphocyte (T-cell) antigen receptor. The current was similarly activated by 1 microM ionomycin, a Ca2+ ionophore. A single test that encompasses the majority of population-specific mutations is not currently available. Neither the primary efficacy endpoint, defined as the rate of relapse of clinically defined, endoscopically diagnosed recurrent sinusitis, nor several secondary endpoints (sinus transepithelial potential difference [TEPD], histopathology, sinus fluid interleukin [IL]-8 measurements) achieved statistical significance when comparing treated to control sinuses within patients. It may also serve as an important model for gene therapy of other diseases. View details for Web of Science ID A1995RY95400014. View details for Web of Science ID A1997WQ51300045. The channel appeared to be identical to the previously described voltage-insensitive, messenger-mediated, calcium-permeable channel involved in T cell activation. The Ca-binding proteins found in T-cells include members of both the EF-hand and annexin families, as well as other types of Ca-binding proteins. Academic pgardner@stanford.edu Tel: (650) 387-9319 Fax: (650) 327-9755. A total of 183 mutations were identified, including 14 different amino acid-changing novel variants. Gardner, P., Oitmaa, E., Messner, A., Hoefsloot, L., Metspalu, A., Schrijver, I. Microfabricated nanochannel implantable drug delivery devices: trends, limitations and possibilities. We used RNase protection of this variable region to reveal the level of expression of gamma B and gamma C CaM kinase mRNAs in nine human tissues and cell lines. 1. Over one third of the mutations (27/85) occurred with a relative frequency >1%, which illustrates that the identified mutations are not all rare. About Dr. Phyllis Gardner. Stimulation of T-lymphocytes via either structure results in opening of an identical set of voltage-insensitive plasma membrane Ca2+-permeable channels through the action of a diffusible second messenger. Phyllis Gardner (Professor) Manage my profile (650) 387-9319 pgardner. Each of the systems, along with future trends in microfabrication manufacturing, limitations and possibilities, are discussed. Chao, A. C., ZIFFERBLATT, J. Single channel recordings by the extracellular patch-clamp technique indicated that Bay K 8644 activated an 8-pS, barium-permeable channel that opened as bursts of brief events. About Phyllis Gardner, M.D. We realize that a Troy High School year book may be hard to . 3. Phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR) by cAMP-dependent protein kinase leads to chloride flux in epithelial cells. When tested, persistence was observed in one patient for 41 days and in another for 10 weeks. This channel presumably underlies the K+ efflux and membrane hyperpolarization that accompany the mitogen-induced increase in [Ca2+]i. The stimulant effect of CPCA (10 microM) was abolished by addition of the A2AR antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) (100 microM; reported K(i) = 11 +/- 3 microM). Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasians, primarily affecting epithelial tissues of the lung and gut. Recently, guanylin, an endogenous peptide with properties similar to STa, was identified. The host immune response and low vector efficiency have been key impediments to effective cystic fibrosis transmembrane regulator (CFTR) gene transfer for cystic fibrosis (CF). View details for Web of Science ID A1988Q219900001, Department: Medicine - Med/Clinical Pharmacology, Genetic Analysis of Presbycusis by Arrayed Primer Extension. P1 purinoceptor agonists like adenosine have been shown to stimulate Cl- transport in secretory epithelia. It has been suggested that P-glycoprotein (P-gp), an ATP-dependent transporter responsible for classical multidrug resistance, is also a volume-regulated chloride channel. This study was conducted in Jurkat T cells to investigate the effects of A77 1726 on signal transduction pathways initiated by ligands of the T-cell receptor CD3 complex and to evaluate the effects of A77 1726 on nucleotide biosynthesis.Tritiated thymidine incorporation and cell counts quantitated cell proliferation. Clinical studies have identified the host immune response and low vector efficiency as key impediments to effective CF gene therapy. This is a review of the application of microfabrication technologies, borrowed from the semiconductor industry, to drug delivery implants incorporating structures in the nanometer dimension. These results suggest that CaM kinase mediates the Ca2+ pathway of Cl- channel activation. Chao, A. C., Kouyama, K., Heist, E. K., Dong, Y. J., Gardner, P. ACTIVATION OF CFTR CHLORIDE CURRENT BY NITRIC-OXIDE IN HUMAN T-LYMPHOCYTES. Nghiem, P., SAATI, S. M., Martens, C. L., Gardner, P., Schulman, H. FLASH-PHOTOLYSIS OF CAGED INOSITOL 1,4,5-TRISPHOSPHATE ACTIVATES PLASMA-MEMBRANE CALCIUM CURRENT IN HUMAN T-CELLS. Raising intracellular free calcium concentration from 2 to 200 nM reversed the reduction, induced by substance P, in current peak amplitude and disclosed an apparent desensitization towards the neuropeptide action. Simultaneous multigene mutation detection in patients with sensorineural hearing loss through a novel diagnostic microarray: A new approach for newborn screening follow-up. View details for Web of Science ID A1989T048300039. A., Nepomuceno, I. A., Dong, Y. J., Gruenert, D. C., Gardner, P. ACTIVATION OF INTESTINAL CFTR CL- CHANNEL BY HEAT-STABLE ENTEROTOXIN AND GUANYLIN VIA CAMP-DEPENDENT PROTEIN-KINASE. The tgAAVCF administration was well tolerated, without adverse respiratory events, and there was no evidence of enhanced inflammation in sinus histopathology or alterations in serum-neutralizing antibody titer to adeno-associated virus (AAV) capsid protein after vector administration.
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