In this study, replication-defective adenoviral vectors were used to explore parameters that may be important in administering gene therapy vectors to the intestine. View details for Web of Science ID A1988Q219900001, Department: Medicine - Med/Clinical Pharmacology, Genetic Analysis of Presbycusis by Arrayed Primer Extension. Ca2+ influx induced by inositol 1,4,5-triphosphate (IP3)-coupled surface receptors (either the TCR or a heterologous muscarinic receptor) was compared with Ca2+ influx induced by inhibitors of the microsomal Ca(2+)-ATPase (thapsigargin, cyclopiazonic acid, di-tert-butylhydroquinone), which release stored Ca2+ without production of IP3. In T-cells, a number of important kinases, phosphatases, and cytoskeleton-modulating enzymes are functionally Ca dependent but have no Ca-binding domains and therefore must sense changes in the cytoplasmic Ca level through interactions with Ca-binding proteins. 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. Recently, guanylin, an endogenous peptide with properties similar to STa, was identified. Sustained elevation of intracellular Ca2+ by cell surface receptors is often dependent on influx of Ca2+ across the plasma membrane through routes not involving voltage-gated Ca2+ channels. The expression of the three K+ channel subtypes varies with the cell's developmental state and functional class. Phyllis Gardner (6 October 1890 - 16 February 1939) was a writer, artist, and noted breeder of Irish Wolfhounds. Dr. Phyllis Gardner Despite Holmes' ability to charm older white businessman, assembling an impressive all-male board of directors at Theranos, there was one person who told her what she was. Each of the systems, along with future trends in microfabrication manufacturing, limitations and possibilities, are discussed. We report here that normal human B-lymphoblasts display whole cell Cl- conductances induced by calcium-mediated pathways, volume regulation, and cAMP which are equivalent to currents described in epithelial cells. The Ca2+ current was reversibly blocked by > 90% with 0.3 mM Cd2+, whereas the same concentration of Ni2+ or Co2+ blocked only 50 to 60% of the current. 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. Leflunomide, a novel immunosuppressive drug, prolongs experimental graft survival effectively and has been well tolerated in patients with rheumatoid arthritis. Calcineurin dephosphorylates conserved serine residues in the amino terminus of NF-AT, resulting in nuclear import. Phyllis Gardner was a skeptic of Elizabeth Holmes dating back to when she met Holmes, nearly 20 years ago. These results suggest that PGE1, acting through PKA, activates a Cl- current in Jurkat T cells. Dr. Phyllis Gardner, MD - Stanford, CA | Internal Medicine Hence, the cAMP and calcium pathways are separate. The precise functional role of the voltage-activated K+ channel remains to be determined. The effect of Ca2+ ionophore on whole-cell Cl- currents is inhibited by a specific peptide inhibitor of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase). Is CFTR also required for the calcium-dependent activation of chloride channels? It may also serve as an important model for gene therapy of other diseases. Jan 18, 2022 Updated Mar 17, 2022, 5:09pm PDT Years before Theranos founder Elizabeth Holmes was prosecuted for fraud, Dr. Phyllis Gardner saw right through her. Wagner, J. A > 90% block of inducible interleukin-2 reporter gene activity was initiated by transfection of a constitutively active mutant of multifunctional Ca2+/calmodulin-dependent protein kinase (CaM kinase or CaM kinase II), but not by constitutive mutants of CaM kinase IV, calcineurin or protein kinase C. The block was complete six hours after kinase transfection and showed specificity for interleukin-2; there was no change in beta-actin transcription or in c-fos transcription induced by phorbol myristyl acetate, and a Rous sarcoma virus promoter was stimulated threefold. View details for DOI 10.2353/jmoldx.2007.060100, View details for Web of Science ID 000245427600013, View details for PubMedCentralID PMC1867437. 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. Addition of adenosine (ADO; 0.1-1 mM) markedly increased 125I efflux rate. Whether a physiological defect exists in the immune system of CF patients has remained controversial. 'the Dropout': What's Real and Fake in Elizabeth Holmes Miniseries View details for Web of Science ID A1991GF80400001. Here we show that STa, guanylin and cGMP each activate intestinal Cl- secretion, and that this is abolished by inhibitors of cAMP-dependent protein kinase (PKA), suggesting that PKA is a major mediator of this effect. By contrast, N6-phenyl ADO did not affect [Ca2+]i. Chao, A. C., deSauvage, F. J., Dong, Y. J., Wagner, J. These findings suggest that two Ca2+/calmodulin-responsive enzymes, multifunctional CaM kinase and calcineurin, could mediate the divergent effects of Ca2+ signals in T-lymphocyte regulation. 0 (0 ratings) Leave a review. To study the mechanism by which rhTNF alpha induced Ca(2+)-activated Cl- current, we examined the involvement of calcium/calmodulin-dependent protein kinase (CaM kinase). Previous work with excised inside-out patches suggests that inositol 1,4,5-trisphosphate is the activating second messenger of the voltage-insensitive T-cell Ca2+-permeable channel. Academic pgardner@stanford.edu Tel: (650) 387-9319 Fax: (650) 327-9755. SK&F 96365 also inhibits [3H]-thymidine incorporation and interleukin-2 (IL-2) synthesis in peripheral blood lymphocytes. T cell clones (TCC) from controls and CF patients displayed equivalent Ca(2+)-mediated Cl- current; however, TCC from patients with CF but not controls displayed defective cAMP-mediated Cl-current. The data demonstrate a modulation of T-lymphocyte K+ channels by substance P and substantiate a possible role for GTP-binding proteins in this modulation. These assays suggest a pore diameter in the order of 2 nm. Homozygous and compound heterozygous pathogenic mutations were exclusively seen in affected individuals. Stimulation of human T-lymphocytes via either the surface T3-Ti antigen-major histocompatibility complex receptor complex or the T11 molecule results in clonal proliferation through a calcium-dependent mechanism. 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. One of the best moments happens early in the series during a heated exchange between then-Stanford student Holmes and Stanford professor of medicine Phyllis Gardner (Laurie Metcalf,. 4. This page may have moved, does not exist, or we may be experiencing a temporary issue. In contrast, the calcium-activated chloride current was not affected by antisense treatment. Although great strides have been made in the treatment of CF, it remains lethal, often by early adulthood. But Cl- flux in cystic fibrosis cells, as in normal cells, can be activated by raising intracellular Ca2+ (refs 5-10). In the absence of costimulation, Ca2+ influx results in anergy (interleukin-2 transcriptional block) through an unknown mechanism. 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. Schrijver, I., Oitmaa, E., Metspalu, A., Gardner, P. Diagnostic testing by CFTR gene mutation analysis in a large group of Hispanics novel mutations and assessment of a population-specific mutation spectrum. In the present study, we investigated whether P1 agonist-induced Cl- secretion is preserved in cystic fibrosis airway epithelium and which signalling mechanism is involved. This is the first account of an organic inhibitor of the T cell Ca2+ current. Clinical studies have identified the host immune response and low vector efficiency as key impediments to effective CF gene therapy. Ca2+ currents induced by receptor stimulation and Ca(2+)-ATPase inhibition were not additive. Contact. Cystic fibrosis (CF), which is due to mutations in the cystic fibrosis transmembrane conductance regulator gene, is a common life-shortening disease. What Stanford professor Dr. Phyllis Gardner thinks about Theranos Multifunctional CaM kinase also attenuated interleukin-2 activation by calcineurin plus phorbol ester. Academic pgardner@stanford.edu Tel: (650) 387-9319 Fax: (650) 327-9755 Current Research and Scholarly Interests We are interested in the general process of signal transduction, focusing on the role that ion channels play in this process. Patch clamp studies have identified an InsP3-activated, Ca2+ permeable channel in the plasma membrane of T lymphocytes that may be responsible for the sustained elevation of [Ca2+]i during continuous TCR/CD3 occupancy. Theranos: Stanford prof never trusted Elizabeth Holmes - The Mercury News In the series premiere episode of 'The Dropout,' actress Laurie Metcalf essays the role of Gardner. Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasians, primarily affecting epithelial tissues of the lung and gut. Gardner, P., Oitmaa, E., Messner, A., Hoefsloot, L., Metspalu, A., Schrijver, I. Microfabricated nanochannel implantable drug delivery devices: trends, limitations and possibilities. It is possible that disruption of IL-10-mediated anti-inflammatory homeostasis may contribute to early onset sustained inflammation in CF airways. [1] [2] [3] Support Lucile Packard Children's Hospital Stanford and child and maternal health. Dr. Phyllis Gardner, MD is a board certified internist in Stanford, California. In the futuristic ideal, these systems would involve the implantation of precisely microfabricated drug delivery systems with nanopores, nanochannels and/or nanoreservoirs fabricated from silicon, coupled with electronic sensing and actuator systems, for the precise, timed and/or targeted delivery of drugs. Her research centered on cardiac arrhythmias, ion channel biophysiology, cell biology, cystic . 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. In addition, the current was blocked by 10 microM 5-nitro-2(3-phenylpropylamino) benzoic acid (NPPB), a potent Cl- channel blocker. A., Messner, A. H., Moran, M. L., DAIFUKU, R., Kouyama, K., Desch, J. K., Manley, S., Norbash, A. M., Conrad, C. K., Friborg, S., Reynolds, T., Guggino, W. B., Moss, R. B., Carter, B. J., Wine, J. J., Flotte, T. R., Gardner, P. Maxillary sinusitis as a surrogate model for CF gene therapy clinical trials in patients with antrostomies. The universal newborn hearing screening program, together with remarkable recent progress in the characterization of genes associated with the function of hearing, have resulted in increased demand and exciting possibilities of detecting the molecular basis of hereditary hearing loss through DNA testing. The regulation of the channels by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in transformed B cells from CF patients is defective. MiMedx Announces Appointment of Phyllis Gardner, M.D. to Thus, the control of [Ca2+]i remains coupled to TCR/CD3 function. While the function of nitric oxide as a direct cytotoxic effector molecule is well established, its function as a transducer molecule in immune cells is not. View details for Web of Science ID 000177015400009. Phyllis Gardner | Stanford Medicine A membrane-permeable cAMP analog mimicked the effect of PGE1, whereas intracellular application of a cAMP antagonist Rp-cAMP blocked the effect of PGE1. NFAT mediated gene transcription; modulations by kinases and phosphatases. 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). These data provide evidence for a novel in vitro mechanism of the antiproliferative action of this immunosuppressant. The linear relationship of current amplitude to holding potential when examined over the -60 to +60 mV range indicates that this pore has a constant mean single channel conductance level of 350-400 pS. View details for Web of Science ID 000260722000005. View details for Web of Science ID A1994PH77400001. Dr. Phyllis Gardner, MD, is an Internal Medicine specialist practicing in Stanford, CA with 47 years of experience. ADO (0.1-mM) and CPCA (2 microM) both induced a marked increase in intracellular [Ca2+] ([Ca2+]i); the effect of the latter was again abolished by pretreatment of the cells with DMPX. About Dr. Phyllis Gardner. It is unclear whether or not this type of Ca2+ channel is present in straight B-cell lines. Preclinical and clinical research has lead to the rapid development of a variety of vectors designed to correct the basic defect in CF, including adenovirus, adeno-associated virus, and liposomes. Three types of T-cell channels are described in this review. CFTR is required for the cAMP pathway but not for the calcium pathway. The identity of the amplified products was confirmed by hybridization to CFTR-specific probes and DNA sequencing. Furthermore, currents flowing through Ca2+-permeable channels are apparently autoregulated, as inward conductance is abolished by elevation of Ca2+ concentration in the bathing solution. Phyllis Gardner Age: 68 Position: Professor of medicine at Stanford, board member at Revance Therapeutics and CohBar. The Stanford professor was one of the first people to doubt Holmes' credentials and products, dismissing Holmes' patch idea when she was a 19-year-old student at the university. Among the presbycusis group, these solely occurred within the GJB2 and SLC26A4 genes. Premack, B. Young, W., Chen, J., Jung, F., Gardner, P. Freeman Spogli Institute for International Studies, Institute for Computational and Mathematical Engineering (ICME), Institute for Human-Centered Artificial Intelligence (HAI), Institute for Stem Cell Biology and Regenerative Medicine, Stanford Institute for Economic Policy Research (SIEPR), Stanford Woods Institute for the Environment, Office of VP for University Human Resources, Office of Vice President for Business Affairs and Chief Financial Officer. (ABSTRACT TRUNCATED AT 400 WORDS), View details for Web of Science ID A1990DA09800009. This difference was independent of atopy. DBHQ (25 microM) caused a short-term rise in [Ca2+]i in the absence of ambient Ca2+, and a sustained elevation of [Ca2+]i in cell monolayers bathed in the efflux solution (1.2 mM Ca2+), which was largely attenuated by Ni2+ (5 mM). Ion channels, and ion fluxes in general, appear to regulate a wide variety of processes important to lymphocyte function in normal and disease states. View details for Web of Science ID A1992JF85600026. She attended Stanford University, where she first came up with the idea for her company, Theranos. You may use our global navigation in the heading bar or return to our home page using the buttons below. By means of arrayed primer extension technology, we have designed a genotyping microarray with 204 probe sites for CF transmembrane conductance regulator gene mutation detection. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis. Gardner and. Nishimoto, I., Wagner, J. This panel, developed on a microarray, is capable of simultaneous evaluation of multiple mutations in 8 genes (GJB2, GJB6, GJB3, GJA1, SLC26A4, SLC26A5 and the mitochondrial genes encoding 12S rRNA and tRNA-Ser[UCN]).The arrayed primer extension array for sensorineural hearing loss is based on a versatile platform technology and is a robust, cost-effective, and easily modifiable assay. The question of whether a G protein couples TCR/CD3 to PI hydrolysis and to Ca2+ mobilization is unresolved, although some indirect evidence for the involvement of GTP binding proteins in T cell activation has recently been obtained with cholera toxin. To characterize the CaM kinase present in these tissues we have cloned an isoform of this kinase from human T lymphocytes. This hemolysin produces pores in membranes as demonstrated by osmotic protection studies using red blood cells and carbohydrate compounds of various molecular weights. View details for Web of Science ID A1995RF90000002, View details for PubMedCentralID PMC398388. Specialties. A., Goeddel, D. V., Gardner, P. PROPERTIES OF CA CURRENTS ACTIVATED BY T-CELL RECEPTOR SIGNALING, CLONING AND ANALYSIS OF 2 NEW ISOFORMS OF MULTIFUNCTIONAL CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE - EXPRESSION IN MULTIPLE HUMAN TISSUES. View details for Web of Science ID A1997WH48600017. She graduated from Harvard University / School Of Medicine in 1976. Phyllis Stanko Obituary (1943 - 2021) - Fullerton, CA - Orange County Stanford Medicine Alumni Association presents Women in - YouTube Expression of the CFTR protein is thought to be physiologically important only in exocrine epithelial cells. Hometown: Her father was a professor, so she grew up in college towns. Enhanced opening probability appears to be mediated by the second messenger InsP3, implying that InsP3 is responsible for both intracellular Ca2+ stores release and enhanced transmembrane Ca2+ influx. In this study, we tested the feasibility of utilizing DBHQ to improve Cl- secretion via the Ca(2+)-dependent pathway, in the cystic fibrosis (CF)-derived pancreatic epithelial cell line CFPAC-1. STANFORD, CA - MAY 24: Stanford University professor Phyllis Gardner poses for a portrait on May 24, 2019, in Stanford, Calif. Gardner's blunt criticism of Theranos and its disgraced founder . Phyllis Gardner - Wikipedia Register to let other graduates of Troy High School find and contact you. Foreman, P. K., Wainwright, M. J., Alicke, B., Kovesdi, I., Wickham, T. J., Smith, J. G., Meier-Davis, S., Fix, J. These channels in normal cells are activated by cyclic AMP-dependent protein kinase and protein kinase C. In cystic fibrosis these kinases fail to activate otherwise normal Cl- channels. A group of 257 self-identified Hispanics with clinical manifestations consistent with CF were studied by temporal temperature gradient electrophoresis and/or DNA sequencing. STANFORD, CA - MAY 24: Stanford University professor Phyllis Gardner poses for a portrait on May 24, 2019, in Stanford, Calif. Gardner's blunt criticism of Theranos and its disgraced founder, Elizabeth Holmes, have made her a favorite among those who have closely followed the blood testing company's downfall. MiMedx Announces Appointment of Phyllis Gardner, M.D. to Phyllis Gardner | Stanford Medicine - CAP Profiles The Sunday Times' tech correspondent brings on Dr Phyllis Gardner, the Standord medical professor who came across Elizabeth Holmes before she started Theranos and then worked behind the scenes to expose her, to talk about her background at Stanford (4:00), and in industry (5:00), meeting a young Elizabeth Holmes (6:55), rejecting her first idea Clinical manifestations include both pancreatic and pulmonary insufficiency. Stanford Professor Phyllis Gardner on Theranos and Elizabeth Holmes 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. Ca2+ is generally thought to be an essential second messenger for early activation, but the precise molecular events contingent upon the Ca2+ signal remain to be determined. The site facilitates research and collaboration in academic endeavors. Who Is Phyllis Gardner? Photolytic release of caged 1-(alpha-glycerophosphoryl)-inositol 4,5-bisphosphate, an analog of InsP3 which activates InsP3 receptors but is not readily metabolized to InsP4, also activates the current. Gardner tried to. This review addresses the genetics of hearing loss, discusses the most commonly offered genetic assays for nonsyndromic hearing loss, with advantages and limitations, proposes a practical testing algorithm, and highlights current developments. Pyrimidine and purine nucleosides were used to assess antagonism of the antiproliferative activity of A77 1726. Wagner, J. When external and internal Cl- were about equal, the current reversed at about zero mV, but when external Cl- was lowered from 157 to 7 mM the reversal potential shifted 75 mV in the positive direction, demonstrating that the current carrier was Cl-. Phyllis Gardner's Profile | Stanford Profiles Specific attenuation of interleukin-2 transcriptional induction occurs in Jurkat T cells following pretreatment with a Ca2+ ionophore. Support teaching, research, and patient care. Wagner, J. Born on July 7, 1950, Phyllis Gardner is an American biologist who is known for being one of the first people to oppose and criticize the ideas of Elizabeth Holmes. Dong, Y. J., Chao, A. C., Kouyama, K., Hsu, Y. P., BOCIAN, R. C., Moss, R. B., Gardner, P. MOLECULAR STRATEGIES FOR THERAPY OF CYSTIC-FIBROSIS, INHIBITION BY SK-AND-F-96365 OF CA2+ CURRENT, IL-2 PRODUCTION AND ACTIVATION IN T-LYMPHOCYTES. 1. The Ca2+ permeable channel also undergoes a Ca2(+)-dependent inactivation process in an autoregulatory fashion. This cross-sectional study was performed at Stanford University with presbycusis samples from the California Ear Institute. In the presence of costimulation, Ca2+ influx in T cells leads to activation (transcription of interleukin-2; ref. Traditional therapeutic modalities address these problems with pancreatic enzyme replacement, vitamins and nutritional supplementation, antibiotics, and respiratory therapy. In particular, the steady-state rise in interleukin-2 (T-cell growth factor) mRNA is dependent on the rise of [Ca2+]i resulting from ion movement across this channel. Rodriguez-Paris, J., Ballay, C., Inserra, M., Stidham, K., Colen, T., Roberson, J., Gardner, P., Schrijver, I. She is currently licensed to practice medicine in California. When transfected into Jurkat T cells, the gamma B cDNA encoded a functional kinase which cosedimented on sucrose gradients with endogenous T cell CaM kinase activity and formed a large multimeric enzyme. View details for Web of Science ID A1994PH25400057. About Phyllis Gardner, M.D. Thus, DBHQ appears to enhance Cl- channel activity via a Ca(2+)-dependent mechanism involving CaMKII. The rank order of potency of purinoceptor agonists in stimulating 125I efflux was ADO > AMP > ADP approximately equal to ATP. The page you requested cannot be found. Maldonado, D., Schumann, M., Nghiem, P., Dong, Y., Gardner, P. REGULATION OF CL- CHANNELS BY MULTIFUNCTIONAL CAM KINASE. She and Rupert Brooke had, on her side at least, a passionate relationship. Further research promises to refine vector technology and bring CF gene therapy to the bedside. She has served on the board of directors of several public and private companies, including Revance Therapeutics, Corium International, Inc. and CohBar, Inc. Dr. Gardner has also served as an advisor to Change Health Care, Inc.. In human lymphocytes and epithelial tissues, CaM kinase activates a chloride channel via a Ca(2+)-dependent pathway which is preserved in cystic fibrosis. The arrayed primer extension array, based on a platform technology for disease detection with multiple applications, is a robust, cost-effective, and easily modifiable assay suitable for CF carrier screening and disease detection. These results suggest that there is no relationship between P-gp and the chloride channel activated by cell swelling. The current was similarly activated by 1 microM ionomycin, a Ca2+ ionophore. View details for Web of Science ID A1996VQ33800028, View details for PubMedCentralID PMC2200601. T-cell receptor signalling activates multifunctional CaM kinase. An adeno-associated virus vector (AAV-CFTR) was used in a phase I dose-escalation study to transfer CFTR cDNA into respiratory epithelial cells of the maxillary sinus of 10 CF patients.A prospective, randomized, unblinded, dose-escalation, within-subjects, phase I clinical trial of AAV-CFTR was conducted.Ten patients with previous bilateral maxillary antrostomies were treated.Safety, gene transfer as measured by semiquantitative polymerase chain reaction (PCR), and sinus transepithelial potential difference (TEPD) were measured.The highest level of gene transfer was observed in the range of 0.1-1 AAV-CFTR vector copy per cell in biopsy specimens obtained 2 weeks after treatment. @Stanford #PhyllisGardner was a skeptic of #ElizabethHolmes from the time she met Holmes . Phyllis I Gardner | Departments | Stanford Directory Bacterial cultures and increased sinus leukocytes corroborated recurrent sinusitis. Characterization of CFTR mutations in the U.S. Hispanic population is vital to early diagnosis, genetic counseling, patient-specific treatment, and the understanding of cystic fibrosis (CF) pathogenesis. A prospective, randomized, double-blind, placebo-controlled, within-subjects, phase II clinical trial of the effect AAV-CFTR on clinical recurrence of sinusitis will determine the clinical efficacy of AAV gene therapy for CF. After surgically accessing the intestine, an E1-, E3-deleted adenoviral vector encoding beta-galactosidase (beta-Gal) was directly injected into various regions of the small and large intestine of rats and rabbits. View details for Web of Science ID 000228736900018. tgAAVCF, an adeno-associated cystic fibrosis transmembrane conductance regulator (CFTR) viral vector/gene construct, was administered to 23 patients in a Phase II, double-blind, randomized, placebo-controlled clinical trial. Addition of purified catalytic subunit of cAMP-dependent protein kinase (PKA) plus ATP to the recording pipette also activated a similar current, whereas internally applied Walsh inhibitor, the synthetic peptide inhibitor of PKA, blocked the PGE1 effect. Dr. Gardner has spent more than 35 years in academia, medicine and industry. Bath-application of DBHQ induced an outwardly-rectifying whole-cell Cl- current, which was abolished by pipette addition of BAPTA (5 mM) or CaMK [273-302] (20 microM), an inhibitory peptide of multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII). When tested, persistence was observed in one patient for 41 days and in another for 10 weeks. Phyllis Gardner (pictured), a professor of medicine at Stanford, criticized Elizabeth Holmes' blood testing company long before fraud charges were brought against her. Dr. Phyllis I. Gardner, MD | Stanford, CA | Internist | US News Doctors 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. We report here whole-cell patch clamp studies of normal and cystic fibrosis-derived airway epithelial cells showing that Cl- channel activation by Ca2+ is mediated by multifunctional Ca2+/calmodulin-dependent protein kinase. Addition of rhTNF alpha activated Cl- current in 80% of tested cells; the activated current was blocked by 10 microM 5-nitro-2-3-phenylpropylamino)benzoic acid, a Cl- channel blocker. These results suggest that CaM kinase mediates the Ca2+ pathway of Cl- channel activation. Gardner is played by actress Laurie Metcalf in the series premiere episode of 'The Dropout.'
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