33 results on '"SACHS D"'
Search Results
2. Surgical outcome in diffuse low-grade glioma – contemporary prospective data from the LoG-Glio registry
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Coburger, J, Rückriegel, S, Nadji-Ohl, M, von der Brelie, C, Roder, C, Faust, K, Sachs, D, Löhr, M, Grüninger, S, Vajkoczy, P, Tatagiba, M, Ernestus, RI, Rohde, V, Ganslandt, O, Wirtz, CR, and Pala, A more...
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ddc: 610 ,610 Medical sciences ,Medicine - Abstract
Objective: Level of evidence for surgical management in low grade glioma (LGG) is low and mainly relies on retrospective series. Hence prospective contemporary assessment of surgical outcome is important to assure surgical quality control and to evaluate surgical strategies. Methods: Prospective[for full text, please go to the a.m. URL], 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie more...
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- 2020
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Catalog
3. Genome-wide transposon mutagenesis of paramyxoviruses reveals constraints on genomic plasticity: implications for vaccine and gene therapy
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Ikegame, S., Beaty, S. M., Stevens, C., Won, S. T., Park, A., Sachs, D., Hong, P., Thibault, P. A., and Lee, B.
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viruses - Abstract
The antigenic and genomic stability of paramyxoviruses remains a mystery. Here, we evaluate the genetic plasticity of Sendai virus (SeV) and mumps virus (MuV), sialic acid-using paramyxoviruses that infect mammals from two Paramyxoviridae subfamilies ( Orthoparamyxovirinae and Rubulavirinae ). We performed saturating whole-genome transposon insertional mutagenesis, and identified important commonalities: disordered regions in the N and P genes near the 3’ genomic end were more tolerant to insertional disruptions; but the envelope glycoproteins were not, highlighting structural constraints that contribute to the restricted antigenic drift in paramyxoviruses. Nonetheless, when we applied our strategy to a fusion-defective Newcastle disease virus ( Avulavirinae subfamily), we could select for F-revertants and other insertants in the 5’ end of the genome. Our genome-wide interrogation of representative paramyxovirus genomes from all three Paramyxoviridae subfamilies provides a family-wide context in which to explore specific variations within and among paramyxovirus genera and species. more...
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- 2020
- Full Text
- View/download PDF
4. Durable intermediate- to long-term outcomes after minimally invasive transiliac sacroiliac joint fusion using triangular titanium implants
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Sachs D, Kovalsky D, Redmond A, Limoni R, Meyer SC, Harvey C, and Kondrashov D
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multicenter study ,chronic low back pain ,Medical technology ,sacroiliac joint fusion ,R855-855.5 - Abstract
Donald Sachs,1 Don Kovalsky,2 Andy Redmond,3 Robert Limoni,4 S Craig Meyer,5 Charles Harvey,6 Dimitriy Kondrashov7 1Center for Spinal Stenosis and Neurologic Care, Lakeland, FL, 2Orthopaedic Center of Southern Illinois, Mount Vernon, IL, 3Precision Spine Care, Tyler, TX, 4BayCare Clinic, Green Bay, WI, 5Columbia Orthopaedic Group, Columbia, MO, 6Riverside Medical Center, Kankakee, IL, 7SF Spine Group at St Mary’s Spine Center, San Francisco, CA, USA Background: Sacroiliac joint (SIJ) fusion (SIJF), first performed 95years ago, has become an increasingly accepted surgical option for chronic SIJ dysfunction. Few studies have reported intermediate- or long-term outcomes after SIJF.Objective: The objective of this study is to determine patient-based outcomes after SIJF for chronic SIJ dysfunction due to degenerative sacroiliitis or SIJ disruption at ≥3years of follow-up.Methods: Consecutive patients who underwent SIJF prior to December 2012 were contacted over phone or through email. Participants completed questionnaires in clinic, over phone or by email, regarding SIJ pain, activities related to SIJ dysfunction, and the Oswestry Disability Index. Charts were reviewed to extract baseline parameters and the clinical course of follow-up.Results: One hundred seven patients were eligible and participated in this study. Mean (standard deviation) preoperative SIJ pain score was 7.5 (1.7). At mean follow-up of 3.7years, the mean SIJ pain score was 2.6 (representing a 4.8-point improvement from baseline, P more...
- Published
- 2016
5. One-year outcomes after minimally invasive sacroiliac joint fusion with a series of triangular implants: a multicenter, patient-level analysis
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Sachs D, Capobianco R, Cher D, Holt T, Gundanna M, Graven T, Shamie AN, and Cummings Jr J
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Medical technology ,R855-855.5 - Abstract
Donald Sachs,1 Robyn Capobianco,2 Daniel Cher,2 Timothy Holt,3 Mukund Gundanna,4 Timothy Graven,5 A Nick Shamie,6 John Cummings Jr7 1Center for Spinal Stenosis and Neurologic Care, Lakeland, FL, 2SI-BONE, Inc., San Jose, CA, 3Montgomery Spine Center, Montgomery, AL, 4Brazos Spine, College Station, TX, 5SSM Orthopedics, Wentzville, MO, 6UCLA Spine Center, Santa Monica, CA, 7Community Neurosurgical Care, Indianapolis, IN, USA Background: Sacroiliac joint (SI) pain is an often-overlooked cause of lower-back pain, due in part to a lack of specific findings on radiographs and a symptom profile similar to other back-related disorders. A minimally invasive surgical (MIS) approach to SI joint fusion using a series of triangular, titanium plasma spray-coated implants has shown favorable outcomes in patients with SI joint pain refractory to conservative care. The aim of this study was to provide a multicenter experience of MIS SI joint fusion using a patient-level analysis. Patients and methods: We report a patient-level analysis from 144 patients with a mean of 16 months postoperative follow-up. Demographic information, perioperative measures, complications, and clinical outcomes using a visual analog scale for pain were collected prospectively. Random-effects regression models were used to account for intersite variability. Results: The mean age was 58 years, 71% of patients were female, and 62% had a history of lumbar spinal fusion. Mean (95% confidence interval [CI]) operative time was 73 minutes (25.4–118), blood loss was minimal, and hospital stay was 0.8 days (0.1–1.5). At follow-up, mean (95% CI) visual analog scale pain scores improved by 6.1 points (5.7–6.6). Substantial clinical benefit, defined as a decrease in pain by >2.5 points or a score of 3.5 or less, was achieved in 91.9% of patients (95% CI 83.9%–96.1%), and 96% (95% CI 86.3%–98.8%) of patients indicated they would have the same surgery again. Conclusion: When conservative measures fail to relieve symptoms resulting from degeneration or disruption of the SI joint, MIS SI joint fusion using a series of triangular, porous, titanium plasma spray-coated implants is a safe and effective treatment option. Keywords: minimally invasive surgery, sacroiliac joint, SI joint fusion, arthrodesis, previous spine surgery more...
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- 2014
6. Characteristics of IgGs Produced in Neu5Gc and alpha 1-3 Gal Double Knock-Out Pigs
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Salama, A., Conchon, S., Perota, A., Martinet, B., Judor, J. -P., Evanno, G., Bernardet, S. Le-Bas, Le Berre, L., Hervouet, J., Minault, D., Concordet, J. -P., Dugast, E., Vanhove, B., Abadie, J., Gaide, N., Lagutina, I., Duchi, R., Lazzari, G., Sachs, D., Gauthier, O., Brouard, S., Cozzi, E., Blancho, G., Perreault, H., Bach, Jean-Marie, Galli, C., Soulillou, J. -P., ProdInra, Migration, Université de Nantes (UN), Société d'Accélération du Transfert de Technologies (SATT OUEST VALORISATION), Fondazione Avantea, Partenaires INRAE, Structure et Instabilité des Génomes (STRING), Muséum national d'Histoire naturelle (MNHN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Acides nucléiques : dynamique, ciblage, et fonctions biologiques - Régulation et dynamique des génomes (ANDCFB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Animaux modèles pour la recherche en oncologie comparée (AMaROC), Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Fondazione Avantea [Cremona, Italy], Massachusetts General Hospital, Massachusetts General Hospital [Boston], University Hospital of Padua, University of Manitoba, University of Manitoba [Winnipeg], Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Institut National de la Recherche Agronomique (INRA)-Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes, and American Society of Transplant Surgeons (ASTS). Arlington, USA. more...
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[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2015
7. HLA-Cw3 expression on porcine endothelial cells protects against xenogeneic cytotoxicity mediated by a subset of human NK cells
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Jörg Seebach, Comrack, C., Germana, S., Leguern, C., Sachs, D. H., and Dersimonian, H.
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Immunology ,Immunology and Allergy - Abstract
There is increasing evidence that NK cells make an important contribution to human anti-porcine xenogeneic cytotoxicity. Most allogeneic as well as autologous normal cells are not susceptible to NK cell-mediated cytotoxicity because they express inhibitory molecules encoded within the MHC class I loci. The protective signal is delivered to NK cells through killer cell-inhibitory receptors expressing different MHC class I specificities. It has been proposed that xenogeneic target cells may be susceptible to NK cell-mediated lysis because their MHC class I molecules fail to be recognized by human killer cell-inhibitory receptors. To explore this hypothesis, we examined the effect of human MHC class I expression on porcine target cell lysis by human NK cells. An immortalized porcine bone marrow-derived endothelial cell line (2A2) was transfected with three different human MHC class I allelic genes (HLA-A2, -B27, or -Cw3). The cytotoxic activity of several GL183+ NK clones, which lysed untransfected porcine cells effectively, was substantially blocked by the presence of HLA-Cw3. In contrast, HLA-Cw3-positive cells were not protected against lysis by GL183- EB6+ NK clones. The expression of HLA-B27 or HLA-A2 molecules on pig target cells did not provide substantial protection from lysis by any of the NK clones tested. In addition to confirming the hypothetical basis of NK cell-mediated killing of xenogeneic targets, these results have practical implications as an approach to overcoming NK cell-mediated cytotoxicity, which may be an obstacle to pig-to-human xenotransplantation. more...
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- 1997
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8. Generation of cloned CD55-CD39 transgenic alpha 1,3-galactosyltransferase depleted (GAL-/-) piglets
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Perota A., Brunetti D., Charreau B., Chatelais M., Lagutina I., LAZZARI, GIOVANNA, Anegon I., Sachs D. H., Cozzi E., Lucchini F., GALLI, CESARE, Perota A., Brunetti D., Charreau B., Chatelais M., Lagutina I., Lazzari G., Anegon I., Sachs D.H., Cozzi E., Lucchini F., and Galli C. more...
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GAL-/- piglet ,CD55-CD39 - Published
- 2010
9. The role of PKA and PKCε pathways in prostaglandin E2-mediated hypernociception
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Sachs, D, Villarreal, CF, Cunha, FQ, Parada, CA, and Ferreira, SH
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Male ,Pain ,Protein Kinase C-epsilon ,Research Papers ,Cyclic AMP-Dependent Protein Kinases ,Second Messenger Systems ,Dinoprostone ,Rats ,Enzyme Activation ,Isoenzymes ,Catalytic Domain ,Ganglia, Spinal ,Physical Stimulation ,Animals ,Neurons, Afferent ,Rats, Wistar ,Pain Measurement ,Signal Transduction - Abstract
Protein kinase (PK) A and the epsilon isoform of PKC (PKCepsilon) are involved in the development of hypernociception (increased sensitivity to noxious or innocuous stimuli) in several animal models of acute and persistent inflammatory pain. The present study evaluated the contribution of PKA and PKCepsilon to the development of prostaglandin E(2) (PGE(2))-induced mechanical hypernociception.Prostaglandin E(2)-induced mechanical hypernociception was assessed by constant pressure rat paw test. The activation of PKA or PKCepsilon was evaluated by radioactive enzymic assay in the dorsal root ganglia (DRG) of sensory neurons from the hind paws.Hypernociception induced by PGE(2) (100 ng) by intraplantar (i.pl.) injection, was reduced by i.pl. treatment with inhibitors of PKA [A-kinase-anchoring protein St-Ht31 inhibitor peptide (AKAPI)], PKCepsilon (PKCepsilonI) or adenylyl cyclase. PKA activity was essential in the early phase of the induction of hypernociception, whereas PKC activity was involved in the maintenance of the later phase of hypernociception. In the DRG (L4-L5), activity of PKA increased at 30 min after injection of PGE(2) but PKC activity increased only after 180 min. Moreover, i.pl. injection of the catalytic subunit of PKA induced hypernociception which was markedly reduced by pretreatment with an inhibitor of PKCepsilon, while the hypernociception induced by paw injection of PKCepsilon agonist was not affected by an inhibitor of PKA (AKAPI).Taken together, these findings are consistent with the suggestion that PKA activates PKCepsilon, which is a novel mechanism of interaction between these kinases during the development of PGE(2)-induced mechanical hypernociception. more...
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- 2009
10. The ZOOM Minimization Package
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Fischler, M and Sachs, D
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Computing and Computers - Published
- 2005
11. Pig hematopoietic cell chimerism in baboons conditioned with a nonmyeloablative regimen and CD154 blockade
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Buehler, Leo Hans, Awwad, M, Treter, S, Chang, Q, Basker, M, Alwayn, I P J, Teranishi, K, Ericsson, T, Moran, K, Harper, D, Kurilla-Mahon, B, Huang, C A, Sackstein, R, Sykes, M, White-Scharf, M E, Sachs, D H, Down, J D, and Cooper, D K more...
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Transplantation Chimera ,ddc:617 ,Swine ,Histocompatibility Testing ,Transplantation, Heterologous/immunology ,Haplotypes/genetics ,Molecular Sequence Data ,Hematopoietic Stem Cell Transplantation ,CD40 Ligand/immunology ,Colony-Forming Units Assay ,Carbohydrate Sequence ,Trisaccharides/blood/isolation & purification ,Interleukin-3/blood ,Animals ,Hematopoietic Stem Cell Mobilization/methods ,Swine, Miniature ,Leukapheresis ,Hematopoietic Cell Growth Factors/therapeutic use ,Papio - Abstract
In an attempt to induce mixed hematopoietic chimerism and transplantation tolerance in the pig-to-primate model, we have infused high-dose porcine peripheral blood progenitor cells (PBPC) into baboons pretreated with a nonmyeloablative regimen and anti-CD154 monoclonal antibody (mAb). more...
- Published
- 2002
12. Pig kidney transplantation in baboons: anti-Gal(alpha)1-3Gal IgM alone is associated with acute humoral xenograft rejection and disseminated intravascular coagulation
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Buehler, Leo Hans, Yamada, K, Kitamura, H, Alwayn, I P, Basker, M, Appel, J Z (3rd), Colvin, R B, White-Scharf, M E, Sachs, D H, Robson, S C, Awwad, M, Cooper, D K, and Surgery
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Graft Rejection ,Time Factors ,Swine ,Transplantation, Heterologous/immunology ,Transplantation, Heterologous ,Disaccharides ,Kidney ,Antibodies ,Animals, Genetically Modified ,Antigens, CD55/genetics ,Graft Rejection/immunology/pathology ,Kidney/pathology ,Disseminated Intravascular Coagulation/blood/immunology ,Animals ,Humans ,Blood Coagulation ,ddc:617 ,CD55 Antigens ,Kidney Transplantation/immunology ,Graft Survival ,Ureter/pathology/transplantation ,Antibodies/analysis ,Immunoglobulin M/analysis/immunology ,Disseminated Intravascular Coagulation ,Kidney Transplantation ,Disaccharides/immunology ,Immunoglobulin M ,Acute Disease ,Antibody Formation ,Animals, Genetically Modified/genetics ,Swine, Miniature ,Ureter ,Papio - Abstract
Kidneys harvested from miniature swine or pigs transgenic for human decay-accelerating factor (hDAF) were transplanted into baboons receiving an anti-CD154 monoclonal antibody (mAb) and either a whole body irradiation (WBI)- or cyclophosphamide (CPP)-based immunosuppressive regimen.Group 1 baboons (n=3) underwent induction therapy with WBI and thymic irradiation, pretransplantation antithymocyte globulin, and immunoadsorption of anti-Gal(alpha)1-3Gal (Gal) antibody (Ab). After transplantation of a miniature swine kidney, maintenance therapy comprised cobra venom factor, mycophenolate mofetil, and an anti-CD154 mAb (for 14-28 days). In group 2 (n=2), WBI was replaced by CPP in the induction protocol. Group 3 (n=3) animals received the group 2 regimen, but underwent transplantation with hDAF pig kidneys.Group 1 and 2 animals developed features of disseminated intravascular coagulation (DIC), with reductions of fibrinogen and platelets and increases of prothrombin time, partial thromboplastin time, and fibrin split products. Graft survival was for 6-13 days. Histology showed mild acute humoral xenograft rejection (AHXR) of the kidneys, but severe rejection of the ureters. Group 3 animals developed features of DIC in two of three cases during the fourth week, with AHXR in the third case. Graft survival was for 28 (n=1) or 29 (n=2) days. Histology of day 15 biopsy specimens showed minimal focal mononuclear cellular infiltrates, with predominantly CD3+ cells. By days 28 and 29, kidneys showed mild-to-moderate features of AHXR. In all groups, the humoral response was manifest by reappearance of anti-Gal IgM below baseline level, with no or low return of anti-Gal IgG. All excised kidneys showed IgM deposition, but no complement and no or minimal IgG deposition. No baboon showed a rebound of anti-Gal Ab immediately after excision of the graft, and anti-Gal Ab increased over pretransplantation levels only when anti-CD154 mAb was discontinued.DIC was observed with WBI- or CPP-based therapy, and after miniature swine or hDAF kidney transplantation. AHXR+/-DIC was observed in all recipients even in the absence of complement and no or low levels of anti-Gal IgG, but was significantly delayed in the hDAF recipients. These results confirm our earlier observation that CD154 blockade prevents T cell-dependent sensitization in baboons to pig antigens, but that baseline natural anti-Gal Ab production is not inhibited. We suggest that IgM deposition, even in the absence of IgG and complement, leads to endothelial cell activation with the development of DIC, even when there are only minimal histologic changes of AHXR. more...
- Published
- 2001
13. Clearance of mobilized porcine peripheral blood progenitor cells is delayed by depletion of the phagocytic reticuloendothelial system in baboons
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Basker, M, Alwayn, I P, Buehler, Leo Hans, Harper, D, Abraham, S, Kruger Gray, H, DeAngelis, H, Awwad, M, Down, J, Rieben, R, White-Scharf, M E, Sachs, D H, Thall, A, and Cooper, D K
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Time Factors ,Transplantation Conditioning ,Swine ,Transplantation, Heterologous ,Receptors, Fc ,Macrophages/cytology/drug effects ,Leukocyte Count ,Phagocytosis/physiology ,Phagocytosis ,Hematopoietic Stem Cells/physiology ,Animals ,Immunoglobulins, Intravenous/pharmacology ,Mononuclear Phagocyte System ,Transplantation Conditioning/methods ,ddc:617 ,Dose-Response Relationship, Drug ,Macrophages ,Receptors, Fc/antagonists & inhibitors ,Hematopoietic Stem Cell Transplantation ,Immunoglobulins, Intravenous ,Hematopoietic Stem Cells ,Blood Cell Count ,Liposomes ,Mononuclear Phagocyte System/physiology ,Papio - Abstract
Attempts to achieve immunological tolerance to porcine tissues in nonhuman primates through establishment of mixed hematopoietic chimerism are hindered by the rapid clearance of mobilized porcine leukocytes, containing progenitor cells (pPBPCs), from the circulation. Eighteen hours after infusing 1-2 x 10(10) pPBPC/kg into baboons that had been depleted of circulating anti-alphaGal and complement, these cells are almost undetectable by flow cytometry. The aim of the present study was to identify mechanisms that contribute to rapid clearance of pPBPCs in the baboon. This was achieved by depleting, or blocking the Fc-receptors of, cells of the phagocytic reticuloendothelial system (RES) using medronate liposomes (MLs) or intravenous immunoglobulin (IVIg), respectively.Baboons (preliminary studies, n=4) were used in a dose-finding and toxicity study to assess the effect of MLs on macrophage depletion in vivo. In another study, baboons (n=9) received a nonmyeloablative conditioning regimen (NMCR) aimed at inducing immunological tolerance, including splenectomy, whole body irradiation (300 cGy) or cyclophosphamide (80 mg/kg), thymic irradiation (700 cGy), T-cell depletion, complement depletion with cobra venom factor, mycophenolate mofetil, anti-CD154 monoclonal antibody, and multiple extracorporeal immunoadsorptions of anti-alphaGal antibodies. The baboons were divided into three groups: Group 1 (n=5) NMCR+pPBPC transplantation; Group 2 (n=2) NMCR+ML+pPBPC transplantation; and Group 3 (n=2) NMCR+IVIg+pPBPC transplantation. Detection of pig cells in the blood was assessed by fluorescence-activated cell sorter and polymerase chain reaction (PCR).ML effectively depleted macrophages from the circulation in a dose-dependent manner. Group 1: On average, 14% pig cells were detected 2 hr postinfusion of 1 x 10(10) pPBPC/kg. After 18 hr, there were generally less than 1.5% pig cells detectable. Group 2: Substantially higher levels of pig cell chimerism (55-78%) were detected 2 hr postinfusion, even when a smaller number (0.5-1 x 10(10)/kg) of pPBPCs had been infused, and these levels were better sustained 18 hr later (10-52%). Group 3: In one baboon, 4.4% pig cells were detected 2 hr after infusion of 1 x 10(10) pPBPC/kg. After 18 hr, however, 7.4% pig cells were detected. A second baboon died 2 hr after infusion of 4 x 10(10) pPBPC/kg, with a total white blood cell count of 90,000, of which 70% were pig cells. No differences in microchimerism could be detected between the groups as determined by PCR.This is the first study to report an efficient decrease of phagocytic function by depletion of macrophages with MLs in a large-animal model. Depletion of macrophages with MLs led to initial higher chimerism and prolonged the survival of circulating pig cells in baboons. Blockade of macrophage function with IVIg had a more modest effect. Cells of the RES, therefore, play a major role in clearing pPBPCs from the circulation in baboons. Depletion or blockade of the RES may contribute to achieving mixed hematopoietic chimerism and induction of tolerance to a discordant xenograft. more...
- Published
- 2001
14. Effects of specific anti-B and/or anti-plasma cell immunotherapy on antibody production in baboons: depletion of CD20- and CD22-positive B cells does not result in significantly decreased production of anti-alphaGal antibody
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Alwayn, I P, Xu, Y, Basker, M, Wu, C, Buehler, Leo Hans, Lambrigts, D, Treter, S, Harper, D, Kitamura, H, Vitetta, E S, Abraham, S, Awwad, M, White-Scharf, M E, Sachs, D H, Thall, A, and Cooper, D K
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Graft Rejection ,Transplantation, Heterologous/immunology ,Sialic Acid Binding Ig-like Lectin 2 ,Plasma Cells ,Transplantation, Heterologous ,Antigens, CD/immunology ,Epitopes/immunology ,Enzyme-Linked Immunosorbent Assay ,Ricin ,Ricin/immunology ,Disaccharides ,Antigens, Differentiation, B-Lymphocyte/immunology ,Graft Rejection/immunology/prevention & control ,Lymphocyte Depletion ,Epitopes ,Mice ,immune system diseases ,Antigens, CD ,hemic and lymphatic diseases ,Lectins ,Animals ,Humans ,B-Lymphocytes ,ddc:617 ,Antibodies, Monoclonal ,B-Lymphocytes/immunology ,Antigens, CD20 ,Antibodies, Monoclonal/pharmacology ,Antigens, Differentiation, B-Lymphocyte ,Disaccharides/immunology ,Plasma Cells/immunology ,Antibody Formation ,Immunotherapy ,Cell Adhesion Molecules ,Antigens, CD20/immunology ,Papio - Abstract
Anti-Galalpha1-3Gal antibodies (antialphaGal Ab) are a major barrier to clinical xenotransplantation as they are believed to initiate both hyperacute and acute humoral rejection. Extracorporeal immunoadsorption (EIA) with alphaGal oligosaccharide columns temporarily depletes antialphaGal Ab, but their return is ultimately associated with graft destruction. We therefore assessed the ability of two immunotoxins (IT) and two monoclonal antibodies (mAb) to deplete B and/or plasma cells both in vitro and in vivo in baboons, and to observe the rate of return of antialphaGal Ab following EIA. The effects of the mouse anti-human IT anti-CD22-ricin A (proportional to CD22-IT, directed against a B cell determinant) and anti-CD38-ricin A (proportional to CD38-IT, B and plasma cell determinant) and the mouse anti-human anti-CD38 mAb (proportional to CD38 mAb) and mouse/human chimeric anti-human anti-CD20 mAb (proportional to CD20 mAb, Rituximab, B cell determinant) on B and plasma cell depletion and antialphaGal Ab production were assessed both in vitro and in vivo in baboons (n = 9) that had previously undergone splenectomy. For comparison, two baboons received nonmyeloablative whole body irradiation (WBI) (300 cGy), and one received myeloablative WBI (900 cGy). Depletion of B cells was monitored by flow cytometry of blood, bone marrow (BM) and lymph nodes (LN), staining with anti-CD20 and/or anti-CD22 mAbs, and by histology of LN. EIA was carried out after the therapy and antialphaGal Ab levels were measured daily. In vitro proportional to CD22-IT inhibited protein synthesis in the human Daudi B cell line more effectively than proportional to CD38-IT. Upon differentiation of B cells into plasma cells, however, less inhibition of protein synthesis after proportional to CD22-IT treatment was observed. Depleting CD20-positive cells in vitro from a baboon spleen cell population already depleted of granulocytes, monocytes, and T cells led to a relative enrichment of CD20-negative cells, that is plasma cells, and consequently resulted in a significant increase in antialphaGal Ab production by the remaining cells, whereas depleting CD38-positive cells resulted in a significant decrease in antialphaGal Ab production. In vivo, WBI (300 or 900 cGy) resulted in 100% B cell depletion in blood and BM, > 80% depletion in LN, with substantial recovery of B cells after 21 days and only transient reduction in antialphaGal Ab after EIA. Proportional to CD22-IT depleted B cells by > 97% in blood and BM, and by 60% in LN, but a rebound of B cells was observed after 14 and 62 days in LN and blood, respectively. At 7 days, serum antialphaGal IgG and IgM Ab levels were reduced by a maximum of 40-45% followed by a rebound to levels up to 12-fold that of baseline antialphaGal Ab by day 83 in one baboon. The results obtained with proportional to CD38-IT were inconclusive. This may have been, in part, due to inadequate conjugation of the toxin. Cell coating was 100% with proportional to CD38 mAb, but no changes in antialphaGal Ab production were observed. Proportional to CD20 mAb resulted in 100% depletion of B cells in blood and BM, and 80% in LN, with recovery of B cells starting at day 42. Adding 150cGy WBI at this time led to 100% depletion of B cells in the BM and LN. Although B cell depletion in blood and BM persisted for > 3 months, the reduction of serum antialphaGal IgG or IgM Ab levels was not sustained beyond 2 days. Proportional to CD20 mAb + WBI totally and efficiently depleted CD20- and CD22-positive B cells in blood, BM, and LN for > 3 months in vivo, but there was no sustained clinically significant reduction in serum antialphaGal Ab. The majority of antibody secretors are CD38-positive cells, but targeting these cells in vitro or in vivo with proportional to CD38-IT was not very effective. These observations suggest that CD20-and CD22-positive B cells are not the major source of antialphaGal Ab production. Future efforts will be directed towards suppression of plasma cell function. more...
- Published
- 2001
15. Peripheral blood progenitor cell mobilization and leukapheresis in pigs
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Nash, K, Chang, Q, Watts, A, Treter, S, Oravec, G, Ferrara, V, Buehler, Leo Hans, Basker, M, Gojo, S, Sachs, D H, White-Scharf, M, Down, J D, and Cooper, D K
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Male ,Swine ,Swine, Miniature/physiology ,Leukocyte Count/drug effects/veterinary ,Leukocyte Count ,Stem Cell Factor/pharmacology ,Leukapheresis/methods/veterinary ,Granulocyte Colony-Stimulating Factor ,Leukocytes ,Animals ,Humans ,Leukapheresis ,Hematopoietic Stem Cell Mobilization/methods/veterinary ,Stem Cell Factor ,ddc:617 ,Hematopoietic Stem Cells/drug effects ,Hematopoietic Stem Cells ,Hematopoietic Stem Cell Mobilization ,Hematopoiesis ,Swine, Miniature ,Female ,Interleukin-3 ,Interleukin-3/pharmacology ,Leukocytes/drug effects ,Granulocyte Colony-Stimulating Factor/pharmacology ,Hematopoiesis/drug effects - Abstract
The pig is being investigated as an organ donor for humans. Induction of immunologic tolerance to pig tissues in primates would overcome the major immunologic barriers to xenotransplantation. A proven method of inducing tolerance to allografts is by the induction of mixed hematopoietic chimerism by bone marrow transplantation. We are therefore investigating induction of mixed hematopoietic chimerism in the pig-to-baboon model.To obtain large numbers of pig hematopoietic cells, leukapheresis was used to collect blood cell products in miniature swine (n = 5) after progenitor cell mobilization by use of a course of hematopoietic growth factors (cytokines), consisting of porcine interleukin 3, porcine stem cell factor, and human granulocyte colony-stimulating factor.Cytokine therapy and leukapheresis were well tolerated. Cytokine therapy increased the total white blood cell count and allowed large numbers of leukocytes (60 x 10(10)) to be obtained by apheresis, of which approximately 0.1% were granulocyte-erythrocyte-monocyte-megakaryocyte colony-forming units (CFU-GEMMs), which are considered to be representative of hematopoietic progenitors with multi-lineage potential.The combination of cytokine therapy and leukapheresis enables hematopoietic progenitor cells to be obtained safely from miniature swine. more...
- Published
- 2000
16. SORTIE: a resource mediated, spatially-explicit and individual-tree model that simulates stand dynamics in both natural and managed forest ecosystems
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Messier, Christian, Coates, K., Beaudet, M., Canham, C., and Sachs, D.
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Forest ecosystems ,Stand dynamics ,Modelling - Abstract
Working Paper 2001-10
- Published
- 1999
17. Analyses of monoclonal antibodies reacting with porcine wCD6 Results from the Second International Swine CD Workshop
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Pescovitz, M. D., Book, B. K., Aasted, B., Dominguez, J., Bullido, R., Trebichavsky, I., Novikov, B., Valpotic, I., Nielsen, J., Arn, S., Sachs, D. H., Lunney, J. K., Boyd, P. C., Walker, J., Lee, R., Petrinec, N., and Saalmüller, A. more...
- Subjects
Antigens, Differentiation, T-Lymphocyte ,General Veterinary ,Swine ,T-cells ,Immunology ,Antibodies, Monoclonal ,Flow Cytometry ,Antigen-Antibody Reactions ,Porcine wCD6 ,Antigens, CD ,T-Lymphocyte Subsets ,Monoclonal antibodies ,porcine wCD6 ,Animals - Abstract
Among the 57 monoclonal antibodies analyzed within the T-cell group of the Second International Swine CD Workshop, one mAb fell within cluster T14a that included the CD6 standard a38b2 (No. 175). The new mAb MIL8 (No. 082) and a38b2 both precipitated from activated T-cells a 150 kDa monomeric protein. Staining patterns on the various cell types were similar. There was no inhibition of binding of either mAb to peripheral blood T-cells with the opposite mAb. The new mAb, MIL8, reacts with a separate epitope on porcine wCD6. more...
- Published
- 1998
18. Development of a Solar Powered Aircraft for High Altitude Long Endurance Flight
- Author
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Keidel, B. and Sachs, D. (1)
- Published
- 1997
19. [Mixed chimerism and immune tolerance induction by low-stress pretreatment before kidney transplantation in monkeys]
- Author
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T, Kawai, T, Hoshino, S, Fujioka, K, Shimuzu, K, Tanabe, T, Okawa, K, Ota, B, Cosimi A, and H, Sachs D
- Subjects
Mice ,Transplantation Chimera ,Transplantation Immunology ,Radiation Chimera ,Cyclosporine ,Immune Tolerance ,Animals ,Humans ,Haplorhini ,Kidney Transplantation ,Immunosuppressive Agents ,Bone Marrow Transplantation - Published
- 1995
20. Editorial
- Author
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Sachs D
- Subjects
Transplantation ,Philosophy ,Art history ,Surgery - Published
- 1999
- Full Text
- View/download PDF
21. Effect of selective T cell depletion of host and/or donor bone marrow on lymphopoietic repopulation, tolerance, and graft-vs-host disease in mixed allogeneic chimeras (B10 + B10.D2----B10)
- Author
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Ildstad, S. T., Sherry Wren, Bluestone, J. A., Barbieri, S. A., Stephany, D., and Sachs, D. H.
- Subjects
Immunology ,Immunology and Allergy - Abstract
Reconstitution of lethally irradiated mice with a mixture of T cell-depleted syngeneic plus T cell-depleted allogeneic bone marrow (B10 + B10.D2----B10) leads to the induction of mixed lymphopoietic chimerism, excellent survivals, specific in vivo transplantation tolerance to subsequent donor strain skin grafts, and specific in vitro unresponsiveness to allogeneic donor lymphoid elements as assessed by mixed lymphocyte reaction (MLR) proliferative and cell-mediated lympholysis (CML) cytotoxicity assays. When B10 recipient mice received mixed marrow inocula in which the syngeneic component had not been T cell depleted, whether or not the allogeneic donor marrow was treated, they repopulated exclusively with host-type cells, promptly rejected donor-type skin allografts, and were reactive in vitro to the allogeneic donor by CML and MLR assays. In contrast, T cell depletion of the syngeneic component of the mixed marrow inocula resulted in specific acceptance of allogeneic donor strain skin grafts, whether or not the allogeneic bone marrow was T cell depleted. Such animals were specifically unreactive to allogeneic donor lymphoid elements in vitro by CML and MLR, but were reactive to third party. When both the syngeneic and allogeneic marrow were T cell depleted, variable percentages of host- and donor-type lymphoid elements were detected in the mixed reconstituted host. When only the syngeneic bone marrow was T cell depleted, animals repopulated exclusively with donor-type cells. Although these animals had detectable in vitro anti-host (B10) reactivity by CML and MLR and reconstituted as fully allogeneic chimeras, they exhibited excellent survival and had no in vivo evidence for graft-vs-host disease. In addition, experiments in which untreated donor spleen cells were added to the inocula in this last group suggest that the presence of T cell-depleted syngeneic bone marrow cells diminishes graft-vs-host disease and the mortality from it. This system may be helpful as a model for the study of alloresistance and for the identification of syngeneic cell phenotypes, which when present prevent engraftment of allogeneic marrow. more...
- Published
- 1986
- Full Text
- View/download PDF
22. Blocking of allogeneic cell-mediated lympholysis by monoclonal antibodies to H-2 antigens
- Author
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Suzanne Epstein, Ozato, K., and Sachs, D. H.
- Subjects
Immunology ,Immunology and Allergy - Published
- 1980
- Full Text
- View/download PDF
23. Cross-reactive idiotypes of monoclonal anti-Iak antibodies: characterization with xenogeneic anti-idiotypic reagents and expression in anti-H-2 humoral responses
- Author
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Devaux, C., Suzanne Epstein, Sachs, D. H., and Pierres, M.
- Subjects
Immunology ,Immunology and Allergy - Published
- 1982
- Full Text
- View/download PDF
24. Idiotypes of anti-Ia antibodies. II. Effects of in vivo treatment with xenogeneic anti-idiotype
- Author
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Suzanne Epstein, Masakowski, V. R., Sharrow, S. O., Bluestone, J. A., Ozato, K., and Sachs, D. H.
- Subjects
Immunology ,Immunology and Allergy - Abstract
The effects of in vivo treatment with xenogeneic anti-idiotypic antibodies were examined in an anti-Ia idiotypic system. Monoclonal antibody 14-4-4S, specific for Ia.7, has been shown to bear idiotopes that are expressed at readily detectable levels in conventional alloantibody responses. Sera from mice treated with purified anti-idiotypic antibodies (anti-Id) were found to contain inhibitory activity in an ELISA specific for the 14-4-4S Id, whereas sera from control mice treated with heterologous normal Ig did not. In addition, sera of anti-Id-treated C3H.SW mice contained specific anti-I-E activity, shown by binding to B10.A(2R) but not B10.A(4R) LPS blasts in flow microfluorometry. The anti-I-E induced by anti-Id included more IgG1 than IgG2. Even though a significant amount of anti-I-E activity was present in the serum, absorption analysis showed that most of the idiotope-positive antibody was not I-Ek-specific. Penetrance of induction of anti-I-E by anti-Id was 100% in the C3H.SW mice tested, and activity persisted in the serum for at least 8 to 9 mo in some cases. B10 mice produced only marginal anti-I-E activity after treatment, suggesting that induction is due to specific triggering rather than due entirely to a resemblance of anti-Id to the I-E antigen. The results thus indicate long-lasting alterations in an anti-Ia idiotypic system in the absence of exposure to conventional antigen, and represent specific manipulation of anti-Ia immunity. more...
- Published
- 1982
- Full Text
- View/download PDF
25. Idiotypic and fluorometric analysis of the antibodies that distinguish the lesion of the I-A mutant B6.C-H-2bm12
- Author
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Melino, M. R., Suzanne Epstein, Sachs, D. H., and Hansen, T. H.
- Subjects
Immunology ,Immunology and Allergy - Abstract
The serologic lesion of the I-A mutant mouse strain, bm12, was investigated with the use of monoclonal anti-Iab antibodies and anti-idiotypic (Id) reagents produced against these antibodies. In a fluorometric analysis, three different monoclonal anti-Iab antibodies (25-9-17, 34-5-3, 28-16-8) failed to bind bm12 cells, whereas two anti-Iab antibodies (25-5-16 and 17/227), which bound bm12 cells, showed about one-half the fluorescence intensity that they showed in binding to Iab antigens. Of the three monoclonal antibodies that failed to react with bm12 cells, two antibodies (25-9-17 and 34-5-3) were found to bind the same steric site on Iab molecules (cluster I). In contrast, the antibodies (25-5-16 and 17/227) that reacted with both Iab and Iabm12 antigens were found to bind a second distinct site (cluster II). The binding of antibody 28-16-8 to Iab antigens inhibited reciprocally the binding of cluster I and II anti-Iab antibodies, suggesting a possible third site, sterically located intermediate between the other two sites. To assess the relatedness of the antibodies defining the serologic lesion of bm12 mice, xenogeneic and syngeneic anti-Id reagents were produced against antibodies 25-9-17 and 28-16-8. By using these anti-Ids in a binding site-related inhibition assay, a cross-reactive idiotype was detected that is shared by 25-9-17 and 34-5-3 antibodies; thus these two monoclonal antibodies share several features, including 1) idiotypic determinants, 2) failure to bind bm12 cells, 3) binding the same spatial Iab site, and 4) having indistinguishable serologic fine specificity that corresponds with a previously defined predominant alloantigenic determinant recognized in the bm12 anti-Iab humoral response. Therefore, several parameters of antibody recognition of Ia can now be correlated with structural changes in Ia molecules. These findings will potentiate future studies of the T cell recognition of these same Ia epitopes. more...
- Published
- 1983
- Full Text
- View/download PDF
26. Effects of in vivo administration of anti-T3 monoclonal antibody on T cell function in mice. I. Immunosuppression of transplantation responses
- Author
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Raphael Hirsch, Eckhaus, M., Auchincloss Jr, H., Sachs, D. H., and Bluestone, J. A.
- Subjects
Immunology ,Immunology and Allergy - Abstract
Anti-T3 mAb are being increasingly used clinically in the treatment of organ graft rejection. However, there has not previously been a murine model in which the effects of these mAb on the immune system could be studied in vivo. We have established such a model using the anti-murine-T3 mAb, 145-2C11. Administration of 145-2C11 led to rapid depletion of T cells from peripheral blood and suppression of skin graft rejection. However, depletion of T cells from spleen and lymph node was both delayed and incomplete. Full recovery of T cell number was dependent on the presence of a thymus, but treatment of thymectomized animals revealed that depletion was not the mechanism by which the mAb induced immunosuppression. Rather, alterations in TCR expression may play a more important role. TCR had modulated from T cells in spleen and lymph node early after treatment, and TCR expression remained subnormal for at least 51 days posttreatment. However, subnormal TCR expression alone could not fully explain the observed T cell dysfunction, inasmuch as a period of time existed after TCR re-expression during which T cells appeared to be anergic to CTL and MLR reactivity. These findings implicate T cell dysfunction as an important element in the induction of immunosuppression after anti-T3 administration. more...
- Published
- 1988
- Full Text
- View/download PDF
27. Inheritance of idiotype expression unlinked to the H chain allotype locus. Novel features of genetic control in the Ia.7 system
- Author
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Suzanne Epstein, Misplon, J. A., Arn, J. S., Max, E. E., Johnson-Leva, R., Harvath, L., and Sachs, D. H.
- Subjects
Immunology ,Immunology and Allergy - Abstract
We have observed a pattern of inherited idiotype expression in three mouse strains that is unexpected from the genetics of the strains: a dominant idiotype that was expressed at high levels in two parental strains was expressed only at low levels in a heavy chain allotype congenic strain derived from them. In the C3H.SW strain, the antibody response to the class II MHC Ag I-E is of limited diversity, with dominant expression of an idiotype and the V kappa 21 L chain. The C57BL/10 strain expresses the same idiotype at high levels, whereas the CWB/12 strain, which was derived by replacing the Ig H chain Igh-Cj allele of C3H.SW with the Igh-Cb allele derived from C57B1/10, has been found to express little of this dominant idiotype. CWB/12 responds, with titers equal to those of the parental strains, to the I-E epitope responsible for dominant idiotype expression, and it expresses normal V kappa 21 levels; thus deficiencies in epitope-specific responsiveness or in V kappa 21 expression cannot explain the low Id expression in CWB/12. Furthermore, Southern blot analysis of three VH families gave no evidence of recombination within the the VH locus of CWB/12, which was Igh-Vb throughout. Black-cross analysis demonstrated that expression of the dominant idiotype segregated independently of Ig allotype, and was therefore due to genes unlinked to the H chain gene locus. To our knowledge, this pattern of Id expression is unprecedented, and indicates the need for caution in the interpretation of studies using allotype congenic strains. It also demonstrates a role for genes outside the Igh locus in the control of Id expression. more...
- Published
- 1989
- Full Text
- View/download PDF
28. Iatrogenic Pneumothorax
- Author
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Sachs D, Stern Mb, and Lane Cs
- Subjects
Iatrogenic pneumothorax ,medicine.medical_specialty ,business.industry ,General surgery ,Medicine ,Orthopedics and Sports Medicine ,Surgery ,General Medicine ,business - Published
- 1972
- Full Text
- View/download PDF
29. Expression of T-cell associated antigens by porcine natural killer cells
- Author
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Pescovitz, M D, Lowman, M A, and Sachs, D H
- Subjects
Antigens, Differentiation, T-Lymphocyte ,Killer Cells, Natural ,Swine ,Animals ,Antibodies, Monoclonal ,chemical and pharmacologic phenomena ,Complement System Proteins ,Cytotoxicity Tests, Immunologic ,Research Article ,T-Lymphocytes, Cytotoxic - Abstract
We have examined the cell surface phenotype of porcine natural killer (NK) cells and compared them with classic porcine cytotoxic T lymphocytes (CTL). NK cells were susceptible to treatment with monoclonal antibodies to CD2 (PT11), CD8 (PT8) and Ia plus complement (C), as well as with antiserum to asialo-GM1 (ASGM1) plus C. In addition, monoclonal antibodies to leucocyte function antigen 1 (LFA-1) but not to CD8 blocked NK-mediated lysis in the absence of C. This is in contrast to porcine CTL, which were eliminated by antibodies to CD2, CD8 and Ia plus C, but not by anti-ASGMI plus C, and which were blocked by anti-CD8 in the absence of C. Therefore, although porcine NK cells are similar to porcine CTL, they are distinguished by several important differences. more...
- Published
- 1988
30. Effects of T cell depletion in radiation bone marrow chimeras: I. Evidence for a donor cell population which increases allogeneic chimerism but which lacks the potential to produce GVHD
- Author
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Sykes, M., Michael Sheard, and Sachs, D. H.
- Subjects
Immunology ,Immunology and Allergy - Abstract
The opposing problems of graft-vs-host disease (GVHD) and failure of alloengraftment present major obstacles to the application of bone marrow transplantation (BMT) across complete MHC barriers. The addition of syngeneic T-cell-depleted (TCD) bone marrow (BM) to untreated fully allogeneic marrow inocula in lethally irradiated mice has been previously shown to provide protection from GVHD. We have used this model to study the effects of allogeneic T cells on levels of chimerism in recipients of mixed marrow inocula. The results indicate that T cells in allogeneic BM inocula eliminate both coadministered recipient-strain and radioresistant host hematopoietic elements to produce complete allogeneic chimerism without clinical GVHD. To determine the role of GVH reactivity in this phenomenon, we performed similar studies in an F1 into parent combination, in which the genetic potential for GVHD is lacking. The presence of T cells in F1 marrow inocula led to predominant repopulation with F1 lymphocytes in such chimeras, even when coadministered with TCD-recipient-strain BM. These results imply that the ability of allogeneic BM cells removed by T cell depletion to increase levels of allochimerism may be mediated by a population which is distinct from that which produces GVHD. These results may have implications for clinical BM transplantation. more...
31. Stability analysis of stochastic sensor networks
- Author
-
Chao Zhang, Wong, P. K., Sachs, D. G., Koetter, R., and Jones, D. L.
32. Die Wirkung von Strophanthin und Strophinos auf die Anspannungs- und Austreibungszeit des Herzens
- Author
-
Muller H, Sachs D, and Friese G
- Subjects
medicine.medical_specialty ,Cardiac cycle ,business.industry ,Internal medicine ,Cardiology ,Diastole ,Medicine ,Strophanthin ,General Medicine ,business ,End-systolic volume - Published
- 1956
- Full Text
- View/download PDF
33. PIN3 Factors Associated With Failure Of Telaprevir- And Boceprevir-Based Hcv Triple Therapy
- Author
-
Bichoupan, K., Tandon, N., Martel-Laferriere, V., Sachs, D., Ng, M., Schonfeld, E.A., Pappas, A., Crismale, J., Stivala, A., Khaitova, V., Gardenier, D., Linderman, M., Olson, W., Perumalswami, P., Schiano, T.D., Odin, J.A., Liu, L.U., Dieterich, D.T., and Branch, A.D. more...
- Full Text
- View/download PDF
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