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. Their conflicting politics, and his conflicted feelings, led the . View details for Web of Science ID A1991FH80200006. The precise functional role of the voltage-activated K+ channel remains to be determined. CF is one of the most extensively researched genetic diseases as a target for gene therapy development. 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. A., Daddona, P., Gardner, P., Huang, M. T. Efficient and persistent gene transfer of AAV-CFTR in maxillary sinus. 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. The effects of the dihydropyridine calcium channel agonist Bay K 8644 on indo-1-loaded Jurkat human leukemia T lymphocytes was assessed by flow cytometry. Stanford Hospital and Clinics. The known potent A2 adenosine receptor (A2AR) agonist, 5'-(N-cyclopropyl) carboxamidoadenosine (CPCA, 2 microM) but not the A1 adenosine receptor agonist, N6-phenyl adenosine (N6-phenyl ADO, 10 microM) markedly increased 125I efflux rate (baseline, 5.9 +/- 2.0% min-1, + CPCA, 10.9 +/- 0.6% min-1; P < 0.01). Specific attenuation of interleukin-2 transcriptional induction occurs in Jurkat T cells following pretreatment with a Ca2+ ionophore. This difference was independent of atopy. 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). 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. If you see your name among the Troy High School graduates, someone is looking for you! We show the cDNA structure of two variants of this human CaM kinase, gamma B and gamma C, which are predicted to translate to 518 and 495 amino acids, respectively. However, the absence of voltage-dependent activation, relative conductance sequence for divalent cations (Ca2+ > Ba2+ approximately Sr2+ > Mn2+), and lack of inhibition by nifedipine, D600, diltiazem, delta-conotoxin, or aga-IVa were unlike that of voltage-gated Ca2+ channels. Holmes forged ahead anyway. The maximal effects were seen at concentrations of 25-50 microM. The voltage-activated K+ channel is postulated to have a role in mitogenesis, based on studies that demonstrate an increase in K+ channel amplitude in the 24-48 hr following mitogen stimulation, and on studies that demonstrate that K+ channel blockers inhibit mitogenesis in a dose-dependent manner with the same potency sequence for ion channel block. The identity of the amplified products was confirmed by hybridization to CFTR-specific probes and DNA sequencing. Although CF occurs with the highest incidence in Caucasians, it also occurs in other ethnicities with variable frequency. Expression of beta-Gal did not differ substantially when the virus was administered to the duodenum, ileum, or colon. These results suggest that there is no relationship between P-gp and the chloride channel activated by cell swelling. We realize that a Troy High School year book may be hard to . About Phyllis Gardner, M.D. . The expression of the three K+ channel subtypes varies with the cell's developmental state and functional class. View details for Web of Science ID A1994NH08400029. View details for Web of Science ID A1991GP26900012. Wagner, J. 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. The arrayed primer extension genotyping microarray carries 59 sequence variant detection sites, of which 53 are detectable bi-directionally. @stanford: Currently teaching. 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. It is possible that disruption of IL-10-mediated anti-inflammatory homeostasis may contribute to early onset sustained inflammation in CF airways. 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. Addition of BAPTA (10 mM), a Ca2+ chelator, to the perfusion pipette also abolished the ADO-elicited Cl- current. Three channel types that may contribute to activation have also been described in B lymphocytes. Gardner recently opened up about her distrust and dislike . This pathway is defective in cystic fibrosis-derived human cloned T cells. It seems likely that rapid progress will be made in our understanding of these areas through a combination of immunological, biochemical, and electrophysiological approaches. It is widely accepted that clinical testing using surrogate markers including pulmonary function will be useful in assessing clinical efficacy. A., Nepomuceno, I. View details for Web of Science ID A1995RY95400014. 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). In conclusion, our results suggest that A2AR participates in regulation of airway C1 secretion via aCa2+-dependent signalling pathway, which involves CaMK and appears to be at least partially conserved in cystic fibrosis airway epithelial cells. Rodriguez-Paris, J., Ballay, C., Inserra, M., Stidham, K., Colen, T., Roberson, J., Gardner, P., Schrijver, I. View details for DOI 10.1586/14737159.6.3.375, View details for Web of Science ID 000237916000010. 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. Gardner recently. Cystic fibrosis (CF) is the most common lethal genetic disease among Caucasians, primarily affecting epithelial tissues of the lung and gut. In the series premiere episode of 'The Dropout,' actress Laurie Metcalf essays the role of Gardner. The site facilitates research and collaboration in academic endeavors. Phospholipid bilayers composed of 1:1 w/w phosphotidylserine:phosphotidylethanolamine exposed to this toxin display discrete current flow events typical of transmembrane channels and consistent with the interpretation that this toxin acts by forming pores in phospholipid membranes. Stimulation of T cells by externally applied PGE1 stimulated 125I efflux and activated a slowly developing membrane current. 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. Thus, DBHQ appears to enhance Cl- channel activity via a Ca(2+)-dependent mechanism involving CaMKII. B-lymphoblasts from CF-affected humans demonstrated defective Cl- conductance regulation by cAMP but preserved regulation by calcium-mediated and volume regulation mechanisms. We show here that Ca2+ ionophore activates Cl- currents in cell-attached and whole-cell patch-clamp recordings of Jurkat T lymphocytes, but this activation is not direct. 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. View details for Web of Science ID A1989T048300039. 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. View details for Web of Science ID 000260722000005. Gardner tried to. Overexpression of either P-gp or cystic fibrosis transmembrane conductance regulator, the protein product of the CF gene and another member of the ATP-dependent transporters, is associated with a hypotonicity-induced, rapid onset, transient current prior to onset of the volume-sensitive chloride-selective current, an apparent nonspecific effect related to the overexpression of an integral membrane protein. By use of whole cell patch-clamp and Indo-1 fluorescence studies of the Jurkat T leukaemic cell line, we show that the new organic antagonist of receptor-mediated Ca2+ entry, SK&F 96365, inhibits the T cell Ca2+ current in a dose-dependent fashion, with an IC50 of 12 microM. Traditional therapeutic modalities address these problems with pancreatic enzyme replacement, vitamins and nutritional supplementation, antibiotics, and respiratory therapy. Her research centered on cardiac arrhythmias, ion channel biophysiology, cell biology, cystic . 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). When the vector was directly administered to segments of the distal ileum containing a Peyer's patch, transgene expression was approximately 10-fold higher than in segments lacking a Peyer's patch. Phosphorylation of the cystic fibrosis transmembrane conductance regulator (CFTR) by cAMP-dependent protein kinase leads to chloride flux in epithelial cells. Dr. Phyllis Gardner, MD is an Internal Medicine Specialist in Stanford, CA and has over 47 years of experience in the medical field. It is shown here that a chloride channel with kinetic and regulatory properties similar to those described for secretory epithelial cells is present in both T and B lymphocyte cell lines. Thus, the control of [Ca2+]i remains coupled to TCR/CD3 function. Deafness and hearing impairment have a genetic cause in at least half the cases. We were unable to detect a statistically significant difference between our control and affected populations regarding the frequency of sequence variants detected with the APEX array. Professor of Medicine (Clinical Pharmacology) Medicine - Med/Clinical Pharmacology University - Faculty 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. CFTR is required for the cAMP pathway but not for the calcium pathway. A chloride ion transport defect has been described in human CF-derived lymphocytes; however, it has not been possible to detect CFTR mRNA in lymphocytes. 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. Phyllis Gardner (Professor) Manage my profile (650) 387-9319 pgardner. In this study we used 125I efflux and whole-cell patch-clamp studies to investigate whether prostaglandin E1 (PGE1), an agonist that generates intracellular cAMP in Jurkat T lymphocytes, activates a Cl- conductance. These findings not only delineate a novel transduction mechanism for nitric oxide but also support the hypothesis that an intrinsic immune defect may exist in cystic fibrosis. These results suggest that appropriate selective microsomal Ca(2+)-ATPase inhibitors may be therapeutically useful in improving Cl- secretion in CF epithelial cells. It may also serve as an important model for gene therapy of other diseases. Wagner, J. View details for Web of Science ID A1991GF80400001. View details for Web of Science ID 000074207900007, View details for Web of Science ID 000074088900015, View details for Web of Science ID 000073201700014. 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). Lifetime resident of Fullerton, passed away on 11/18/21 in her home. There is also an associated K+ efflux and membrane hyperpolarization. IL-8 concentration rose in sinus fluids from affected sinuses. A 48-h antisense treatment reduced the expression of CFTR protein as assayed by immunoprecipitation and autoradiography to 26% of the level in sense-treated T84 cells. This action was blocked by substituting Cs+ for K+ in the recording pipette and by the substance P antagonist. Dose-dependent changes in TEPD responses to pharmacologic intervention were observed following treatments. @Stanford #PhyllisGardner was a skeptic of #ElizabethHolmes from the time she met Holmes . A., Nepomuceno, I. 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. The regulation of the channels by adenosine 3',5'-monophosphate (cAMP)-dependent protein kinase in transformed B cells from CF patients is defective. These agents induce Cl- secretion only in cells expressing the wild-type CFTR, indicating that this molecule is the final common effector of the signaling pathway. 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. In this review, we discuss agents that increase Cl- secretion via preserved Cl- secretory pathways, such as uridine triphosphate, or that enhance Na+ resorption, such as amiloride, thereby correcting altered airway secretions. Bacterial cultures and increased sinus leukocytes corroborated recurrent sinusitis. 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. This cross-sectional study was performed at Stanford University with presbycusis samples from the California Ear Institute. Sinusitis recurred at a rate of 45% during one month of follow-up. 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. 300 Pasteur Dr Stanford, CA 94305. Dr. Phyllis I. Gardner is an internist in Stanford, California. 1. 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. While STa and guanylin bind to the same receptor guanylyl cyclase and raise cell cGMP, the signaling mechanism distal to cGMP remains controversial. Dr. Gardner has spent more than 35 years in academia, medicine and industry. The intestinal tract has many features that make it an attractive target for therapeutic gene transfer. 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. Microsomal Ca(2+)-ATPase inhibitors such as thapsigargin (THG), cyclopiazonic acid (CPA) and 2,5-di-(tert-butyl)-1,4-hydroquinone (DBHQ) have been shown to inhibit Ca2+ reuptake by the intracellular stores and increase cytosolic free Ca2+ ([Ca2+]i). 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. 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. Recently, guanylin, an endogenous peptide with properties similar to STa, was identified. View details for Web of Science ID A1996VQ33800028, View details for PubMedCentralID PMC2200601. In the presence of costimulation, Ca2+ influx in T cells leads to activation (transcription of interleukin-2; ref. PHYLLIS STANKO OBITUARY. You may use our global navigation in the heading bar or return to our home page using the buttons below. Phyllis I. Gardner, MD Director Dr. Phyllis Gardner has over 40 years of experience in academia, medicine and the healthcare industry. 5. She trained in Internal Medicine at Massachusetts General Hospital, followed by a Chief Residency at Stanford University Hospital. Beals, C. R., Sheridan, C. M., Turck, C. W., Gardner, P., Crabtree, G. R. Reduced IL-10 secretion by CD4(+) T lymphocytes expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR). Each of the systems, along with future trends in microfabrication manufacturing, limitations and possibilities, are discussed. We are interested in the general process of signal transduction, focusing on the role that ion channels play in this process. Support teaching, research, and patient care. These sites represent the most common variants in Tay-Sachs disease, Bloom syndrome, Canavan disease, Niemann-Pick A, familial dysautonomia, torsion dystonia, mucolipidosis type IV, Fanconi anemia, Gaucher disease, factor XI deficiency, glycogen storage disease type 1a, maple syrup urine disease, nonsyndromic sensorineural hearing loss, familial Mediterranean fever, and glycogen storage disease type III. We conclude that generation of InsP3 is sufficient to activate Ca(2+)-selective channels in the plasma membrane of T cells. 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. These results are consistent with the activation of Cl- secretion via a P1 purinoceptor. The transcription factor NF-AT responds to Ca2+-calcineurin signals by translocating to the nucleus, where it participates in the activation of early immune response genes. In this article we discuss the early phases of T-cell activation with an emphasis on receptor-associated signaling molecules, mobilization of Ca, and on the possible roles of Ca in signal transduction. 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. We also discuss agents, including deoxyribonuclease (DNase), that directly reduce sputum viscosity. Chao, A. C., ZIFFERBLATT, J. View details for Web of Science ID A1994NA28800008, View details for Web of Science ID A1994BB86U00010. 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. View details for Web of Science ID A1995RF90000002, View details for PubMedCentralID PMC398388. Learn how we are healing patients through science & compassion, Stanford team stimulates neurons to induce particular perceptions in mice's minds, Students from far and near begin medical studies at Stanford. Patch clamp studies in T and B cells have revealed the presence of several types of ion channels that apparently contribute to the ion fluxes and to the membrane potential changes associated with lymphocyte activation. Assessing the biological activity and clinical efficacy of gene therapy is critically important in cystic fibrosis (CF). MED 299: Directed Reading in Medicine (Autumn, Winter, Spring, Summer) MED 280: Early Clinical Experience in Medicine (Autumn, Winter, Spring, Summer) Gardner is played by actress Laurie Metcalf in the series premiere episode of 'The Dropout.' The wider application of patch-clamp and microfluorimetry techniques to lymphocytes has helped to clarify some issues and raised many more. 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. 3. The involvement of CFTR suggests a possible cystic fibrosis heterozygote advantage against STa-induced diarrhea. The current was similarly activated by 1 microM ionomycin, a Ca2+ ionophore. This cost-effective array is based on a diversely applied platform technology and is suitable for both carrier screening and disease detection in Ashkenazi and Sephardic Jewish populations. 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. A significant proportion (78/85) of the different mutations identified would not have been detected by the ACMG/ACOG-recommended 25-mutation screening panel. Phase I/II AAV-CFTR gene therapy trials.3. She's a professor of medicine at Stanford and a former partner in a health care venture capital firm. The same Ca2+ influx pathway could be activated by IP3-dependent or IP3-independent means, and therefore appeared to be regulated by the fullness of the microsomal Ca2+ stores rather than by the direct action of IP3. Wagner, J. However, chronic respiratory inflammation and infection remain unexplained phenomena in disease pathogenesis. She has served on the board of directors of several public and private companies, including . Significant transduction of the tissue was observed and histochemical staining was used to identify enterocytes as the primary targets of gene transfer. Ca2+/calmodulin activation of Cl- channels presents a pathway with therapeutic potential for circumventing defective regulation of Cl- channels in cystic fibrosis. Phyllis Gardner knew from the moment the 19-year-old student started talking about her "brilliant" idea that it wouldn't work. Phyllis I. Gardner (born July 7, 1950) is a Professor of Medicine at the Stanford University School of Medicine. The effects of purinoceptor agonists on Cl- secretion were examined in a transformed cystic fibrosis airway phenotype epithelial cell line, CFPEo-. Heat-stable enterotoxins (STa) produced by pathogenic bacteria induce profound salt and water secretion in the gut, leading to diarrhea. Purification of the NF-AT kinase revealed that it is composed of a priming kinase activity and glycogen synthase kinase-3 (GSK-3). The Ca2+ permeable channel also undergoes a Ca2(+)-dependent inactivation process in an autoregulatory fashion. View details for DOI 10.1542/peds.2005-2519, View details for Web of Science ID 000240959100016. Who Is Phyllis Gardner? Gardner was one of the first people to be publicly skeptical of Elizabeth Holmes, the founder of blood testing company Theranos, who was later found guilty of investor fraud. The initial technical evaluation of this microarray demonstrates that it is comprehensive, robust, sensitive, specific, and easily modifiable. 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. Wagner, J. View details for Web of Science ID A1989AX58900003. 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. She worked within the hospitality management industry for well over 30 years. 0 (0 ratings) Leave a review. In contrast, the calcium-activated chloride current was not affected by antisense treatment. She was 78 years old. 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. 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. Since there is a significant increase in phosphoinositide turnover after stimulation via either the T3-Ti or T11 pathway, it is suggested that triggering of either structure opens a common set of channels through this mechanism. Sequence changes were identified in 11.7% and 10% of presbycusis and control alleles, respectively. First, patch clamp studies have revealed the presence of a nonvoltage-gated, Ca2+ permeable channel, the probability of whose opening increases upon exposure of the T cell to activating ligands. 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. View details for Web of Science ID A1994NM61500008. 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 . It is unclear whether or not this type of Ca2+ channel is present in straight B-cell lines. SCHUMANN, M. A., Gardner, P., Raffin, T. A. View details for Web of Science ID A1989AK17900033. 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. Gardner, a medical professor at Stanford University, told Holmes that her idea for a microfluidic patch that tested blood and delivered medicine was not possible. A., McDonald, T. V., Gardner, P. STIMULATION OF CHLORIDE SECRETION BY P-1 PURINOCEPTOR AGONISTS IN CYSTIC-FIBROSIS PHENOTYPE AIRWAY EPITHELIAL-CELL LINE CFPEO-. 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. Phyllis Gardner Professor of Medicine (Clinical Pharmacology) Medicine - Clinical Pharmacology Bio ACADEMIC APPOINTMENTS Professor, Medicine - Clinical Pharmacology Research & Scholarship CURRENT RESEARCH AND SCHOLARLY INTERESTS A similar order of potency was seen in transformed cystic fibrosis nasal polyp cells, CFNPEo- (ADO > ATP > AMP > ADP). 3. Chao, A. C., deSauvage, F. J., Dong, Y. J., Wagner, J. 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. Ion channels, and ion fluxes in general, appear to regulate a wide variety of processes important to lymphocyte function in normal and disease states. 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. She attended the Slade School of Fine Art and was a suffragette when they met. The Ca2+ signal can be separated into an early transient peak due to InsP3-released Ca2+ from intracellular stores, and a sustained plateau due to altered transmembrane Ca2+ flux. We conclude that expression of mutant CFTR in human TCC is accompanied by ion channel dysfunction characteristic of the CF phenotype, and is accompanied by a reduction in IL-10 secretion after polyclonal activation. About Phyllis Gardner, M.D. 6. SK&F 96365 also inhibits [3H]-thymidine incorporation and interleukin-2 (IL-2) synthesis in peripheral blood lymphocytes. 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. It was 2002, and the student was a Stanford University sophomore. Ca2+ currents induced by receptor stimulation and Ca(2+)-ATPase inhibition were not additive. These include resting ionic homeostasis and the more complex signaling events involved in activation, proliferation, cytotoxic function, and volume regulation. The conductance saturated when external Ca2+ was raised (Kd approximately 2 mM) and became highly permeable to monovalent cations when external Ca2+ was lowered to below 100 nM, much as has been observed for some voltage-gated Ca2+ channels. 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. Cystic fibrosis C1-channels in epithelial cells and lymphocytes; associated signal transduction pathways and cell biological coupling mechanisms.
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