Medicine and Health Sciences Commons^™

Bcma Is Essential For The Survival Of Long-Lived Bone Marrow Plasma Cells, Brian P. O'Connor, Vanitha S. Raman, Loren D. Erickson, W. James Cook, Lehn K. Weaver, Cory Ahonen, Ling-Li Lin, George Mantchev, Richard J. Bram, Randolph J. Noelle

Dartmouth Scholarship

Long-lived humoral immunity is manifested by the ability of bone marrow plasma cells (PCs) to survive for extended periods of time. Recent studies have underscored the importance of BLyS and APRIL as factors that can support the survival of B lineage lymphocytes. We show that BLyS can sustain PC survival in vitro, and this survival can be further enhanced by inter- leukin 6. Selective up-regulation of Mcl-1 in PCs by BLyS suggests that this 􏰀-apoptotic gene product may play an important role in PC survival. Blockade of BLyS, via transmembrane activator and cyclophilin ligand interactor–immunoglobulin treatment, inhibited PC survival in …

Characterization Of Insulin-Like Growth Factor Binding Protein-2 Secretion In Mouse Mesangial Cells, Marianne Ellen Albert

MUSC Theses and Dissertations

Dysregulation of the insulin-like growth factor (IGF) system plays a key role in the hyperproliferative state seen in diabetic complications. Enhanced IGF-I activity plays a causal role in diabetic glomerulosclerosis (DG) by stimulating mesangial cell proliferation, secretion and hypertrophy. Other alterations of the IGF system may include increased IGF-I receptor (IGF-IR) and increased IGF binding protein (IGFBP) expression. The IGFBP family consists of six soluble binding proteins, IGFBP 1-6, which have higher affinities for the IGFs than the IGF-IR, resulting in blocking IGF access to the IGF-IR. Since the IGFBPs primarily function to inhibit IGF action, we hypothesize that overexpression …

Detection And Mapping Of Quantitative Trait Loci That Determine Responsiveness, Janet L. Mueller, E. A. Ellenberger, Linda K. Vaughn, John K. Belknap, Raymond M. Quock

Biomedical Sciences Faculty Research and Publications

Exposure to 70% N₂O evokes a robust antinociceptive effect in C57BL/6 (B6) but not in DBA/2 (D2) inbred mice. This study was conducted to identify quantitative trait loci (QTL) in the mouse genome that might determine responsiveness to N₂O. Offspring from the F₂ generation bred from B6 and D2 progenitors exhibited a broad range of responsiveness to N₂O antinociception as determined by the acetic acid-induced abdominal constriction test. QTL analysis was then used to dissect this continuous trait distribution into component loci, and to map them to broad chromosomal regions. To this end, …

Inactivation Of A Bacterial Virulence Pheromone By Phagocyte-Derived Oxidants: New Role For The Nadph Oxidase In Host Defense, Jacob M. Rothfork, Graham S. Timmins, Michael N. Harris, Xian Chen, Aldons J. Lusis, Michael Otto, Ambrose L. Cheung, Hattie D. Gresham

Dartmouth Scholarship

Quorum sensing triggers virulence factor expression in medically important bacterial pathogens in response to a density-dependent increase in one or more autoinducing pheromones. Here, we show that phagocyte-derived oxidants target these autoinducers for inactivation as an innate defense mechanism of the host. In a skin infection model, expression of phagocyte NADPH oxidase, myeloperoxidase, or inducible nitric oxide synthase was critical for defense against a quorum-sensing pathogen, Staphylococcus aureus, but not for defense against a quorum sensing-deficient mutant. A virulence-inducing peptide of S. aureus was inactivated in vitro and in vivo by reactive oxygen and nitrogen intermediates, including HOCl and ONOO(-). …

Slbp Is Associated With Histone Mrna On Polyribosomes As A Component Of The Histone Mrnp, Michael L. Whitfield, Handan Kaygun, Judith A. Erkmann, W. H. Davin Townley-Tilson, Zbig Dominski, William F. Marzluff

Dartmouth Scholarship

The stem–loop binding protein (SLBP) binds the 3′ end of histone mRNA and is present both in nucleus, and in the cytoplasm on the polyribosomes. SLBP participates in the processing of the histone pre-mRNA and in translation of the mature message. Histone mRNAs are rapidly degraded when cells are treated with inhibitors of DNA replication and are stabilized by inhibitors of translation, resulting in an increase in histone mRNA levels. Here, we show that SLBP is a component of the histone messenger ribonucleoprotein particle (mRNP). Histone mRNA from polyribosomes is immunoprecipitated with anti-SLBP. Most of the SLBP in cycloheximide-treated cells …

Effect Of Culture Medium Volume On The Development And Viability Of Microinjected Or Noninjected One-Cell Hybrid And Cd-1 Strain Mouse Embryos, Haydar Bağiş, Hande Odaman Mercan

Turkish Journal of Veterinary & Animal Sciences

We investigated the effects of drop volume on the development of mouse presumptive zygotes to the completely hatched blastocyst stage. For this aim, we established 3 experimental groups. In the first group, we cultured hybrid presumptive zygotes to the hatched blastocyst stage in 10 presumptive zygotes per 5, 10, 20, 40 and 50 µl drops. In the second group, we used microinjected hybrid zygotes for culture. In the last group, we cultured CD-1 mouse presumptive zygotes to the hatched blastocyst stage. There was no statistical difference in the first group. In contrast, the data demonstrated that there were significant differences …

Pathological Findings In Acute Amitraz Intoxication In Mice, Ayhan Fi̇lazi̇, Tolga Güvenç, Cavi̇t Kum, Seli̇m Sekki̇n

Turkish Journal of Veterinary & Animal Sciences

This study examined the pathological changes in tissues and organs with acute intoxications with amitraz and its veterinary medicinal formulation. In total 312 healthy white English mice (Mus musculus), 156 female and 156 male, were used for this purpose. The solutions were given to the mice by gavage at the following dosages: 500, 1000, 1500, 1800, 2200 or 2500 mg of technical amitraz/kg and 50, 100, 250, 500, 750 or 1000 mg of amitraz/kg in a veterinary formulation. There was an interval of 1 week after the administration of the study medication. Necropsies were performed immediately on the mice that …

A Scanning Electron Microscope Examination Of Heligmosomum Costellatum, Kader Yildiz, Külti̇gi̇n Çavuşoğlu

Turkish Journal of Veterinary & Animal Sciences

The morphology of Heligmosomum costellatum, a nematode of field mice (Microtus epiraticus), was described by scanning electron microscope. The scanning electron microscopic view of this nematode revealed that the anterior end was surrounded by 2 cephalic vesicles. The 2 copulatory spicules of the male were enveloped in membrane and the male bursa was large. The female posterior end was characterized by a caudal spine. The body of this parasite had transverse ridges.

Impaired Antigen Receptor Induced Calcium Mobilization In A Phospholipase C-Gamma1 Deficient B Cell Line., Natarajan Muthusamy, Do Joon Park, Hei-Won Rho, Sue Goo Rhee, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B lymphocytes express phospholipase C-gamma(1) (PLC-gamma(1)) and phospholipase C-gamma(2) (PLC-gamma(2)) isozymes. However, the relative importance of these two isozymes in B cell signaling is not known. We report here the identification and analysis of a B cell line deficient in PLC-gamma(1). Mature splenic B lymphocytes and a panel of cell lines representing pre-B, immature and mature B cell stages expressed phospholipase C-gamma (PLC-gamma), but not the beta or delta isoforms of phospholipase C (PLC). While all the tested B cell lines and primary splenic B cells expressed PLC-gamma(1) and PLC-gamma(2) isozymes, the L1.2 B cell line exclusively expressed PLC-gamma(2), but …

Oncolog, Volume 48, Number 12, December 2003, Karen Stuyck, Dawn Chalaire, Martha A. Askins, Martha Aschenbrenner

OncoLog MD Anderson's Report to Physicians (All issues) Archives

• On the Move: Efforts Under Way to Improve Outcomes for Patients with Renal Cancer
• Protocols: Studies Examine Treatments for Renal Cell Carcinoma
• Art Therapy Helps Children Affected by Cancer Express Their Emotions
• Children's Art Project Has Been Improving the Lives of Children with Cancer for 30 Years
• DiaLog: When a Parent Is Sick: Talking to Children about Cancer, by Martha A. Askins, PhD, Division of Pediatrics, and Martha Aschenbrenner, Director, Child Life Services

Transcriptional Inhibition Of Type I Collagen Gene Expression In Scleroderma Fibroblasts By The Antineoplastic Drug Ecteinascidin 743., Natalia Louneva, Biagio Saitta, David J Herrick, Sergio A. Jimenez

Department of Medicine Faculty Papers

We previously showed that COL1A1 expression is up-regulated at the transcriptional level in systemic sclerosis (SSc) fibroblasts and that the CCAAT-binding factor (CBF) is involved in this increased expression. Ecteinascidin 743 (ET-743) is a chemotherapeutic agent that binds with sequence specificity to the minor groove of DNA and inhibits CBF-mediated transcriptional activation of numerous genes. Therefore, we examined the effects of ET-743 on the increased COL1A1 expression in SSc fibroblasts. The drug caused a potent and dose-dependent inhibition of type I collagen biosynthesis, which reached 70-90% at 700 pM without affecting cell viability. The same drug concentration caused 60-80% reduction …

Il-7 Enhances Peripheral T Cell Reconstitution After Allogeneic Hematopoietic Stem Cell Transplantation., Onder Alpdogan, Stephanie J Muriglan, Jeffrey M Eng, Lucy M Willis, Andrew S Greenberg, Barry J Kappel, Marcel R M Van Den Brink

Department of Medical Oncology Faculty Papers

We used clinically relevant murine allogeneic bone marrow transplantation (BMT) models to study the mechanisms by which IL-7 administration can improve posttransplant peripheral T cell reconstitution. After transplant we could distinguish two populations of mature donor T cells: (a) alloreactive T cells with decreased expression of CD127 (IL-7 receptor alpha chain) and (b) nonalloreactive T cells, which express CD127 and undergo homeostatic proliferation. IL-7 administration increased the homeostatic proliferation of nonalloreactive T cells, but had no effect on alloreactive T cells and the development of graft-versus-host disease. Allogeneic transplant of purified hematopoietic stem cells and adoptive transfer of thymocytes into …

A Null Mutation For Tissue Inhibitor Of Metalloproteinases-3 (Timp-3) Impairs Murine Bronchiole Branching Morphogenesis., Sean E Gill, M Cynthia Pape, Rama Khokha, Andrew J Watson, Kevin J Leco

Obstetrics & Gynaecology Publications

Tissue inhibitors of metalloproteinases (TIMPs) regulate extracellular matrix (ECM) degradation by matrix metalloproteinases (MMPs). We have examined the role of TIMP-3 on ECM homeostasis and bronchiole branching morphogenesis during murine embryogenesis. Employing an in vitro organ culture system, we found decreased bronchiolar branching in null lungs when compared with wild type (WT) counterparts after 2 days in culture. When a synthetic inhibitor of MMPs at low dose was added to the culture system, branching was augmented regardless of genotype. Gelatin and in situ zymography revealed that null lungs exhibited enhanced activation of MMPs throughout lung development. We analysed the impact …

Vegf164-Mediated Inflammation Is Required For Pathological, But Not Physiological, Ischemia-Induced Retinal Neovascularization, Susumu Ishida, Tomohiko Usui, Kenji Yamashiro, Yuichi Kaji, Shiro Amano, Yuichiro Ogura, Tetsuo Hida, Yoshihisa Oguchi, Jayakrishna Ambati, Joan W. Miller, Evangelos S. Gragoudas, Yin-Shan Ng, Patricia A. D'Amore, David T. Shima, Anthony P. Adamis

Ophthalmology and Visual Science Faculty Publications

Hypoxia-induced VEGF governs both physiological retinal vascular development and pathological retinal neovascularization. In the current paper, the mechanisms of physiological and pathological neovascularization are compared and contrasted. During pathological neovascularization, both the absolute and relative expression levels for VEGF₁₆₄ increased to a greater degree than during physiological neovascularization. Furthermore, extensive leukocyte adhesion was observed at the leading edge of pathological, but not physiological, neovascularization. When a VEGF₁₆₄-specific neutralizing aptamer was administered, it potently suppressed the leukocyte adhesion and pathological neovascularization, whereas it had little or no effect on physiological neovascularization. In parallel experiments, genetically altered VEGF_{164 …}

Probucol Prevents Early Coronary Heart Disease And Death In The High-Density Lipoprotein Receptor Sr-Bi/Apolipoprotein E Double Knockout Mouse, Anne Braun, Songwen Zhang, Helena E. Miettinen, Shamsah Ebrahim, Teresa M. Holm, Eliza Vasile, Mark J. Post

Dartmouth Scholarship

Mice with homozygous null mutations in the high-density lipoprotein receptor SR-BI (scavenger receptor class B, type I) and apolipoprotein E genes fed a low-fat diet exhibit a constellation of pathologies shared with human atherosclerotic coronary heart disease (CHD): hypercholesterolemia, occlusive coronary atherosclerosis, myocardial infarctions, cardiac dysfunction (heart enlargement, reduced systolic function and ejection fraction, and ECG abnormalities), and premature death (mean age 6 weeks). They also exhibit a block in RBC maturation and abnormally high plasma unesterified-to-total cholesterol ratio (0.8) with associated abnormal lipoprotein morphology (lamellar/vesicular and stacked discoidal particles reminiscent of those in lecithin/cholesterol acyltransferase deficiency and cholestasis). Treatment …

Aquaporin Proteins In Murine Trophectoderm Mediate Transepithelial Water Movements During Cavitation., Lisa C Barcroft, Hanne Offenberg, Preben Thomsen, Andrew J Watson

Obstetrics & Gynaecology Publications

Mammalian blastocyst formation is dependent on establishment of trophectoderm (TE) ion and fluid transport mechanisms. We have examined the expression and function of aquaporin (AQP) water channels during murine preimplantation development. AQP 3, 8, and 9 proteins demonstrated cell margin-associated staining starting at the 8-cell (AQP 9) or compacted morula (AQP 3 and 8) stages. In blastocysts, AQP 3 and 8 were detected in the basolateral membrane domains of the trophectoderm, while AQP3 was also observed in cell margins of all inner cell mass (ICM) cells. In contrast, AQP 9 was predominantly observed within the apical membrane domains of the …

Mammalian Erv46 Localizes To The Endoplasmic Reticulum–Golgi Intermediate Compartment And To Cis-Golgi Cisternae, Lelio Orci, Mariella Ravazzola, Gary J. Mack, Charles Barlowe, Stefan Otte

Dartmouth Scholarship

Yeast endoplasmic reticulum (ER) vesicle protein Erv46p is a novel membrane protein involved in transport through the early secretory pathway. Investigation of mammalian Erv46 (mErv46) reveals that it is broadly expressed in tissues and protein-secreting cells. By immunofluorescence microscopy, mErv46 displays a crescent-shaped perinuclear staining pattern that is characteristic of the Golgi complex. Quantitative immunoelectron microscopy indicates that mErv46 is restricted to the cis face of the Golgi apparatus and to vesicular tubular structures between the transitional ER and cis-Golgi. Minor amounts of mErv46 reside in ER membranes and later Golgi cisternae. On Brefeldin A treatment, mErv46 redistributes to punctate …

Promoters Of The Murine Embryonic Β-Like Globin Genes Ey And Βh1 Do Not Compete For Interaction With The Β-Globin Locus Control Region, Xiao Hu, Michael Bulger, Julia N. Roach, Susan K. Eszterhas, Emmanuel Olivier, Eric Bouhassira, Mark Groudine, Steven Fiering

Dartmouth Scholarship

Mammalian β-globin loci contain multiple β-like genes that are expressed at different times during development. The murine β-globin locus contains two genes expressed during the embryo stage, Ey and βh1, and two genes expressed at both the fetal and postnatal stages, β-major and β-minor. Studies of transgenic human β-like globin loci in mice have suggested that expression of one gene at the locus will suppress expression of other genes at the locus. To test this hypothesis we produced mouse lines with deletions of either the Ey or βh1 promoter in the endogenous murine β-globin locus. Promoter deletion eliminated expression of …

Regulation Of Human Col9a1 Gene Expression. Activation Of The Proximal Promoter Region By Sox9., Ping Zhang, Sergio A. Jimenez, David G Stokes

Department of Medicine Faculty Papers

The COL9A1 gene contains two promoter regions, one driving expression of a long alpha1(IX) chain in cartilage (upstream) and one driving expression of a shorter chain in the cornea and vitreous (downstream). To determine how the chondrocyte-specific expression of the COL9A1 gene is regulated, we have begun to characterize the upstream chondrocyte-specific promoter region of the human COL9A1 gene. Transient-transfection analyses performed in rat chondrosarcoma (RCS) cells, human chondrosarcoma (HTB) cells, and NIH/3T3 cells showed that the COL9A1 promoter was active in RCS cells but not HTB or NIH/3T3 cells. Inclusion of the first intron had no effect on promoter …

A Genetic Lesion That Arrests Plasma Cell Homing To The Bone Marrow, Loren D. Erickson, Ling-Li Lin, Biyan Duan, Laurence Morel, Randolph J. Noelle

Dartmouth Scholarship

The coordinated regulation of chemokine responsiveness plays a critical role in the development of humoral immunity. After antigen challenge and B cell activation, the emerging plasma cells (PCs) undergo CXCL12-induced chemotaxis to the bone marrow, where they produce Ab and persist. Here we show that PCs, but not B cells or T cells from lupus-prone NZM mice, are deficient in CXCL12-induced migration. PC unresponsiveness to CXCL12 results in a marked accumulation of PCs in the spleen of mice, and a concordant decrease in bone marrow PCs. Unlike normal mice, in NZM mice, a majority of the splenic PCs are long-lived. …

Comparison Of Ifat And Elisa Results In Mice Experimentally Infected With Toxocara Canis, Hasan Ayçi̇çek, Mehmet Tanyüksel

Turkish Journal of Veterinary & Animal Sciences

Toxocariasis is a disease which indicates a wide symptomatic spectrum and occurs usually by the ingestion of infective Toxocara canis (rarely Toxocara cati) eggs by humans as a paratenic host. In this study, the sera samples of experimentally infected mice were evaluated on different days by IFAT and ELISA. Regarding the sera samples obtained on the 15^{th} and following days of the study, the groups seropositivity in IFAT by adult and larval sectional antigens and in TES-ELISA were 70, 73.3 and 96.7%, respectively. In the control group, seronegativity in IFAT by adult and larval sectional antigens, and in T. canis …

Rac-1 And Iqgap Are Potential Regulators Of E-Cadherin-Catenin Interactions During Murine Preimplantation Development., David R Natale, Andrew J Watson

Obstetrics & Gynaecology Publications

Adherens junction formation is fundamental for compaction and trophectoderm differentiation during mammalian preimplantation development. We recently isolated an IQGAP-2 cDNA from a differential display-polymerase chain reaction screen of bovine preimplantation developmental stages. IQGAP-1 and -2 proteins mediate E-cadherin-based cell-to-cell adhesion through interactions with beta-catenin and the Rho GTPases, rac1 and cdc42. Our study demonstrates IQGAP-1,-2, rac-1 and cdc42 mRNAs are present throughout murine preimplantation development. IQGAP-1 and rac-1 protein distribution changes from predominantly plasma membrane associated to predominantly cytoplasmic as the embryo progresses through cleavage divisions and compaction to the blastocyst stage.

The Cd154/Cd40 Interaction Required For Retrovirus-Induced Murine Immunodeficiency Syndrome Is Not Mediated By Upregulation Of The Cd80/Cd86 Costimulatory Molecules, Kathy A. Green, W. James Cook, Arlene H. Sharpe, William R. Green

Dartmouth Scholarship

C57BL/6 (B6) mice infected with LP-BM5 retroviruses develop disease, including an immunodeficiency similar to AIDS. This disease, murine AIDS (MAIDS), is inhibited by in vivo anti-CD154 monoclonal antibody treatment. The similar levels of insusceptibility of CD40^−/− and CD154^−/− B6 mice indicate that CD154/CD40 molecular interactions are required for MAIDS. CD4⁺ T and B cells, respectively, provide the CD154 and CD40 expression needed for MAIDS induction. Here, the required CD154/CD40 interaction is shown to be independent of CD80 and CD86 expression: CD80/CD86^−/− B6 mice develop MAIDS after LP-BM5 infection.

Histological Evaluation Of Cryopreserved Ovaries In Autologous Abdominal Transplant To NaïVe, Outbred, Cd1, Mice, Wentia Elissa Ford

Biological Sciences Theses & Dissertations

This study showed that fresh and frozen-thawed mouse ovaries would maintain viable primordial or primary follicles post-autologous transplantation. Furthermore, with appropriate hormonal stimulation, these early-stage follicles were shown to develop into Graafian follicles containing a metaphase II antral ovum. Partially sliced ovaries were transplanted into the abdominal cavity of naive, outbred, CD1, white mice. Hormonal stimulation with pregnant mare serum gonadotropin (PMSG) and human chorionic gonadotropin (hCG) one week after the autologous transplantation stimulated variable degrees of follicle and ovum maturation within the ovarian tissue. There were no major morphological differences observed between the four groups, three treatment and one …

Defective Cd19-Dependent Signaling In B-1a And B-1b B Lymphocyte Subpopulations., Goutam Sen, Hsin-Jung Wu, Gabriel Bikah, Chandrasekar Venkataraman, Darrell A Robertson, E Charles Snow, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Peritoneal and pleural cavities in mice and humans contain a unique population of B-lymphocytes called B-1 cells that are defective in B cell antigen receptor (BCR) signaling but have an increased propensity to produce autoantibodies. Several molecules such as Btk, Vav, and CD19 known to be important for BCR signaling have been shown to be critical for the development of B-1 cells from undefined precursors. Here we demonstrate that B-1 cell unresponsiveness to BCR cross-linking is in part due to defective signaling through CD19, a molecule known to modulate signaling thresholds in B cells. The defective CD19 signaling is manifested …

Experimental Autoimmune Encephalitis And Inflammation In The Absence Of Interleukin-12, Burkhard Becher, Brigit G. Durell, Randolph J. Noelle

Dartmouth Scholarship

IL-12 is considered a critical proinflammatory cytokine for autoimmune diseases such as multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). IL-12 is a heterodimer composed of a p35 subunit and a common p40 subunit shared by other cytokines. Both IL-12 p40^–/– and p35^–/– mice fail to produce IL-12 p70 heterodimer. However, in contrast to p40^–/– mice, p35^–/– mice are highly susceptible to the induction of EAE, establishing that IL-12 p70 is not essential for the development of EAE. When compared with wild-type mice, both p40^–/– and p35^–/– mice show deficiencies in primary …

Place Conditioning: What Does It Add To Our Understanding Of Ethanol Reward ?, Fred O. Risinger, Christopher L. Cunningham, Rick A. Bevins, Frank A. Holloway

Department of Psychology: Faculty Publications

This article describes the proceedings of a symposium at the 2001 RSA annual meeting in Montreal, Quebec, Canada. The cochairs were Fred O. Risinger and Christopher L. Cunningham. Presentations were as follows: (1) Place conditioning: understanding the motivational impact of stimuli, by Rick A. Bevins; (2) Role of historical factors in ethanol place conditioning, by Frank A. Holloway; (3) Ethanol place conditioning in mice: genetic and environmental infl uences, by Christopher L. Cunningham; and (4) Utilization of place conditioning for understanding the neuropharmacology of the rewarding effects of ethanol, by Fred O. Risinger.

Identification Of The Vibrio Cholerae Enterobactin Receptors Vcta And Irga: Irga Is Not Required For Virulence, Alexandra R. Mey, Elizabeth E. Wyckoff, Amanda G. Oglesby, Eva Rab, Ronald K. Taylor, Shelley M. Payne

Dartmouth Scholarship

The gram-negative enteric pathogen Vibrio cholerae requires iron for growth. V. cholerae has multiple iron acquisition systems, including utilization of heme and hemoglobin, synthesis and transport of the catechol siderophore vibriobactin, and transport of several siderophores that it does not itself make. One siderophore that V. cholerae transports, but does not make, is enterobactin. Enterobactin transport requires TonB and is independent of the vibriobactin receptor ViuA. In this study, two candidate enterobactin receptor genes, irgA (VC0475) and vctA (VCA0232), were identified by analysis of the V. cholerae genomic sequence. A single mutation in either of these genes did not significantly …

Treatment With Soluble Interleukin-15ralpha Exacerbates Intracellular Parasitic Infection By Blocking The Development Of Memory Cd8+ T Cell Response, Imtiaz A. Khan, Magali Moretto, Xiao-Qing Wei, Martha Williams, Joseph D. Schwartzman, F Y. Liew

Dartmouth Scholarship

Interferon (IFN)-γ–producing CD8⁺ T cells are important for the successful resolution of the obligate intracellular parasite Toxoplasma gondii by preventing the reactivation or controlling a repeat infection. Previous reports from our laboratory have shown that exogenous interleukin (IL)-15 treatment augments the CD8⁺ T cell response against the parasite. However, the role of endogenous IL-15 in the proliferation of activated/memory CD8⁺ T cells during toxoplasma or any other infection is unknown. In this study, we treated T. gondii immune mice with soluble IL-15 receptor α (sIL-15Rα) to block the host endogenous IL-15. The treatment markedly reduced the ability …

Stretch-Induced Calcium Release In Smooth Muscle., Guangju Ji, Robert J Barsotti, Morris E Feldman, Michael I Kotlikoff

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Smooth muscle cells undergo substantial increases in length, passively stretching during increases in intraluminal pressure in vessels and hollow organs. Active contractile responses to counteract increased transmural pressure were first described almost a century ago (Bayliss, 1902) and several mechanisms have been advanced to explain this phenomenon. We report here that elongation of smooth muscle cells results in ryanodine receptor-mediated Ca(2+) release in individual myocytes. Mechanical elongation of isolated, single urinary bladder myocytes to approximately 120% of slack length (DeltaL = 20) evoked Ca(2+) release from intracellular stores in the form of single Ca(2+) sparks and propagated Ca(2+) waves. Ca(2+) …