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  • 11
    ISSN: 1432-0584
    Keywords: Hematopoietic progenitor cells ; Dog ; Monoclonal antibodies ; CFU-GM ; Autologous bone marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Canine hematopoietic progenitor cells were characterized by separation with monoclonal antibodies. Depleted and enriched fractions were studied for growth of CFU-GM in semisolid agar and for repopulating capacity of lethally irradiated dogs. CFU growth was not reduced by depletion of marrow using monoclonal antibodies F 3-20-7 (anti-dog Thy-1), MT606 (anti-human CD6), and IOT2a (anti-human DR). CFU growth was variable following treatment with the anti-canine T-cell antibody MdT-P1 and immunomagnetic bead separation. It was regularly enriched when MdT-P1 treatment was followed by immunorosetting with staphylococcal protein A-loaded sheep red blood cells and density gradient separation. Lethally irradiated dogs were reconstituted by autologous marrow depleted of MdT-P1-positive cells using immunorosetting and density gradient centrifugation, whereas immunomagnetic bead-depleted marrow was ineffective. Fluorescence-activated cell sorting showed enrichment of hematopoietic progenitor cells in the weakly MdT-P1-positive fraction.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1432-0584
    Keywords: Canine lymphocytes ; Monoclonal antibodies ; Mixed lymphocyte culture ; Cell-mediated lympholysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Functional characterization of subsets of T lymphocytes is essential for transplantation studies in dogs, as it is in other species. We studied the function of T cells separated by two mouse monoclonal antibodies recognizing complementary subsets — an antibody directed to canine T cells (MdT-P1) with an up-regulating function, and an antibody directed to human CD 8 (MT811) that cross-reacts with down-regulating canine T cells. Immunorosetting with sheep red blood cells and Percoll gradient allowed us to study depleted and enriched fractions. Their function was tested in mixed lymphocyte culture (MLC), cell-mediated cytotoxicity (CML), and coculture with B cells in a hemolytic plaque assay (PFC). In MLC, MdT-P1-positive cells showed a high proliferative response, and MT811-positive cells responded poorly to allogeneic cells. Vice versa, MT811-negative cells responded strongly, and MdT-P1-negative cells were poor responders but strong stimulators. Effector cells of CML were separated following 8 days of culture and prior to mixing with target cells. Enriched and depleted fractions with either antibody showed low cytotoxic activity as compared with unseparated cells. When added to unseparated effector cells MT811-positive cells suppressed cytotoxicity. B cells were obtained by resetting with staphylococcal protein A (SPA). Their immunoglobulin production was studied following 6 days of culture stimulated by pokeweed mitogen in a reverse hemolytic plaque assay. Again, MT811-positive cells added to the culture suppressed, and MT811-negative cells enhanced immunoglobulin production. In conclusion, immunorosetting with two monoclonal antibodies allowed us to distinguish subpopulations of canine T cells with up-regulating (helper/inducer) from those with down-regulating (suppressor) activity.
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1432-0584
    Keywords: Chronic myeloid leukemia ; Interferon ; Hydroxyurea ; Busulfan ; Bone marrow transplantation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The therapeutic efficacy of interferon-alpha (IFN-α) in the treatment of chronic myeloid leukemia is currently being tested in a number of institutional, interinstitutional, and international trials. There is no doubt that responses are achieved in many patients, and in a small subset complete eradication of clonogenic cells may be possible. However, it has not yet been shown that overall survival of patients treated with IFN-α is better than that of those treated with conventional cytoreductive drugs. There are still controversial opinions on problems such as dosages and duration of treatment, combination with cytostatic agents, definition of responses, and relevance of cytogenic and molecular data. An international workshop discussed the data on interferon therapy and attempted to define the role of interferon today in the management of chronic myeloid leukemia.
    Type of Medium: Electronic Resource
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  • 14
    ISSN: 1432-0584
    Keywords: Key words Blood stem cell transplantation ; Data management quality control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To improve the infrastructure of hemopoietic stem-cell transplantations in our country, the German Registry for Hemopoietic Stem-Cell Transplantations (DRST) was established in 1998. The present paper summarizes the current status of the DRST and gives a survey of transplant activities in Germany in 1998 in terms of transplant units, transplant types, transplant frequencies and underlying diseases.
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1432-0584
    Keywords: Knochenmarktransplantation ; Vermeidung von GvH ; T-Zell-Globulin ; Bone marrow transplantation ; Prevention of GvH ; Preincubation of donor bone marrow ; Specific anti-T-cell globulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary An in vitro incubation of incompatible donor bone marrow by xenogenic anti-T-cell globulin (ATG) suppressed an otherwise lethal GvH reaction in animal models. An application of this principle to clinical bone marrow transplantation was successfully tried in three patients with acute lymphoblastic leukemia. Preparation of the specific anti-human T-cell globulin (ATCG-H) was carried out by absorption of anti-human thymocyte globulin with liver-kidney homogenate, chronic lymphocytic leukemia cells of B-cell type, and erythrocytes. Subsequent testing revealed that the serum still reacted with human T-cells but no longer reduced the number of colony-forming units in culture (CFU-C). All three bone marrow recipients were treated by chemotherapeutic conditioning and total body irradiation followed by grafting of in vitro treated bone marrow from HLA-identical siblings. The transplantation of the bone marrow was well tolerated and no major side effects were encountered. No patient so far (24, 7, 6 months) has shown any signs of GvHD. The in vitro pretransplantation treatment of bone marrow with anti T-globulin may be a new approach to the prevention for GvHD in man.
    Notes: Zusammenfassung Tierexperimentelle Befunde ergaben den Hinweis, daß bei Knochenmarktransplantation mit inkompatiblem Spendermark eine Vorinkubation des Spendermarkes mit xenogenem Anti-T-Zell-Globulin eine sonst toxisch verlaufende Graft versus Host-(GvH)Erkrankung vermeidet. Bei drei Patienten mit akuter lymphatischer Leukämie wurde dieses Prinzip bei der Knochenmarktransplantation erfolgreich klinisch angewandt. Zur Anwendung gelangte ein spezifisches antihumanes Anti-T-Zell-Globulin (ATCG-H), das durch mehrere Absorptionsschritte aus rohem antihumanem Globulin (ATG) gewonnen wurde. Eine Vortestung des Serums ergab eine unveränderte Reaktion gegen menschliche T-Zell-Lymphozyten ohne toxische Nebenwirkungen auf in vitro nachweisbare Vorläuferzellen der Hämopoese (CFU-C). Die Knochenmarktransplantation wurde bei allen drei Patienten nach üblicher Chemotherapie („Konditionierung“) und Ganzkörperbestrahlung mittels vorinkubiertem Spendermark von HLA-identischen Geschwisterndurchgeführt. Toxische Nebenwirkungen durch die Vorinkubation traten nicht auf. Anzeichen einer GvH wurden bisher (24, 7, 6 Monate) bei den Empfängern nicht beobachtet. Die in vitro -Vorinkubation von Spenderknochenmark kann somit als ungefährlicher neuer Versuch zur Vermeidung einer GvH beim Menschen empfohlen werden.
    Type of Medium: Electronic Resource
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  • 16
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 42 (1981), S. 263-265 
    ISSN: 1432-0584
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 17
    ISSN: 1432-0584
    Keywords: Acute leukemia ; Bone marrow transplantation ; Anti-T-cell-globulin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Anti-human-thymocyte globulin (AHTZG) was applied to prevent GvHD in clinical bone marrow transplantation. AHTZG produced by absorption with several cell preparations reacted specifically with T-lymphocyte populations and was no longer inhibitory to human CFUc and bone marrow growth in diffusion chambers. Marrow grafts of 14 patients with ALL were incubated in vitro with AHTZG and transferred to the recipients conditioned with antileukemic chemotherapy and total body irradiation of 1000 rad. Ten patients were transplanted after relaps, four patients during remission. The patients tolerated the marrow without side effects and a hemopoietic engraftment was seen in 12 cases. Three patients showed signs of GvHD on the skin, two of them showed later on also manifestations in the liver. In the other cases no GvHD could be detected. Five out of 14 patients are still alive between 144 and 964 days post transplantation in remission.
    Type of Medium: Electronic Resource
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  • 18
    ISSN: 1432-0584
    Keywords: Key words P-Glycoprotein ; AML ; ALL ; CML ; Idarubicin
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of the study was to test whether fractionated (weekly) idarubicin administration to multiply pretreated leukemia patients is effective and tolerable for outpatient treatment, and whether idarubicin alone can overcome P-glycoprotein (P-gp)-related resistance. P-gp was assessed with an immunocytological technique using the monoclonal antibody 4E3.16. P-gp expression was characterized as a percentage of P-gp-positive blasts. Additionally, the function of P-gp was determined with the rhodamine-123 (R-123) accumulation test in combination with or without verapamil and expressed as the R123 accumulation ratio. Fractionated idarubicin (12 mg/m2/week) was given to 36 acute myelogenous leukemia (AML) patients, 12 acute lymphoblastic leukemia (ALL) patients, and eight chronic myelogenous leukemia (CML) patients in blast crisis. Furthermore, 11 AML and four ALL patients were treated with fractionated daunorubicin at a dose of 50 mg/m2/week. All patients had been pretreated with drugs inducing P-gp-related resistance including daunorubicin and/or doxorubicin or vindesine (CML patients). Of 71 pretreated patients, 51 (72%) had a P-gp value between 25 and 98%. Six of these patients with increased P-gp expression had a nonpumping P-gp; four of them were CD34 positive. Of 51 patients with increased P-gp expression, 30 (59%) were CD34 positive. With regard to idarubicin monotherapy, overall response was 33/56 (59%) patients, and 23/33 (70%) responding patients showed a P-gp expression between 25 and 95%. All idarubicin-responding patients with high P-gp expression before treatment showed a clear reduction of P-gp-positive blasts. No patients with P-gp expression between 34 and 85% treated with fractionated daunorubicin showed response or reduction of P-gp-positive blasts in bone marrow. This study demonstrates that P-gp-related resistance can be overcome in multiply pretreated leukemia patients with idarubicin alone, and that the protocol used here is tolerable for outpatient treatment.
    Type of Medium: Electronic Resource
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  • 19
    Electronic Resource
    Electronic Resource
    Springer
    Diabetologia 9 (1973), S. 461-466 
    ISSN: 1432-0428
    Keywords: Erythrocyte 2.3-DPG ; diabetes ; blood glucose variation ; islet cell tumor ; insulin ; tolbutamide ; microangiopathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary No significant differences were found in the erythrocyte 2.3-DPG concentration between 14 normals (16.82±0.66 μmoles 2.3-DPG/g Hb) and 44 diabetic patients (16.22±0.38 μmoles 2.3-DPG/g Hb). However, in diabetic patients we could demonstrate significant fluctuations determined by the metabolic control of their diabetes. Hyperglycaemic patients (n = 10) developed during treatment, concomitant with declining blood glucose, a significant decrease to 13.97± 0.64 [mioles 2.3-DPG/g Hb. After normalization of blood glucose the 2.3-DPG level rose again. Two patients with islet cell tumors had a fluctuation in the 2.3-DPG concentration of about 20%, when symptomatic hypoglycaemia occurred during an extended fast. This variation in 2.3-DPG dependent upon changes in blood glucose was also demonstrated in-vitro by a dialysis technique where glucose was kept constant at 400 or 80 mg/100 ml. Incubating hyperglycaemic blood (n = 6) of uncontrolled diabetics in a high glucose medium, 2.3-DPG was constant over 7 h, whereas at low glucose concentration 2.3-DPG dropped significantly (p 〈 0.001). Blood from nondiabetic subjects did not show this phenomenon. In-vitro additions of insulin and tolbutamide failed to produce an effect on 2.3-DPG. Our results suggest that pronounced fluctuations of blood glucose in diabetics influence 2.3-DPG levels in erythrocytes and thus might impair peripheral oxygen supply.
    Type of Medium: Electronic Resource
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  • 20
    ISSN: 1432-1440
    Keywords: Bone marrow transplantation ; Acute leukaemia ; Knochenmarktransplantation ; akute Leukämie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Im Rahmen der Arbeitsgemeinschaft Knochenmarktransplantation München wurden von August 1975 bis Juni 1980 insgesamt 17 Patienten mit rezidivierter, akuter Leukämie mit Knochenmark von HLA-identischen Geschwistern transplantiert. Die antileukämische und immunsuppressive Vorbehandlung bestand aus BCNU, Cytosin-Arabinosid, Cyclophosphamid in hoher Dosierung und Ganzkörperbestrahlung mit etwa 9 Gy Körpermitteldosis an einer60Co-Doppelbestrahlungsanlage. Die Prophylaxe einer Graft-versus-Host Krankheit (GvHK) wurde in allen Fällen mit Methotrexat durchgeführt, bei neun Patienten wurde als zusätzliche GvHK-Prophylaxe das Knochenmark mit Anti-T-Zell-Globulin inkubiert, von dem die Antikörper gegen hämopoetische Stammzellen absorbiert waren. Zwei von fünf auswertbaren Patienten, die unbehandeltes Knochenmark erhalten hatten, entwickelten chronische GvHK, während kein Patient nach ATCG-Inkubation des Knochenmarkes eindeutige GvH-Krankheit bekam. Sechs Patienten leben in Vollremission zwischen einem und 33 Monaten nach Knochenmarktransplantation (KMT). Fünf Patienten starben mit Rezidiven zwischen 3 1/2 und 24 Monaten nach KMT, drei Patienten mit interstitieller Pneumonie innerhalb von 3 Monaten nach KMT und drei Patienten innerhalb von 4 Wochen ohne ausreichende Knochenmarkfunktion. Vier von 13 Patienten, die vor mehr als 6 Monaten transplantiert wurden, überleben zur Zeit 11, 14, 19 und 33 Monate in Vollremission. Unsere Ergebnisse bestätigen, daß selbst in fortgeschrittenen Stadien akuter Leukämie durch KMT noch langfristige Remissionen erreichbar sind.
    Notes: Summary Seventeen patients with relapsed, acute leukemia were grafted with bone marrow from HLA-identical siblings by the ‘Munich Cooperative Group for Bone Marrow Transplantation’ during the period from August 1975 to June 1980. The antileukemic and immunosuppressive conditioning treatment consisted of high doses of Bischlorethyl nitrosourea, Cytosine-Arabinoside and Cyclophosphamide, as well as, total body irradiation of about 9 Gy (midline body dose) from dual60Cobalt sources. Methotrexate was given to all patients for prophylaxis of graft-versus-host disease (GvHD). Nine patients received marrow that was treated with anti-T-cell globulin (ATCG) “in vitro”. — Crossreacting antibodies against hemopoietic stem cells were removed by absorption. Two of 5 evaluable patients given untreated marrow developed chronic GvHD, while patients given ATCG-treated marrow did not show unequivocal symptoms of GvHD. Six patients are in complete remission one to 33 months following bone marrow transplantation (b.m.t.) Five patients died with relapses of leukemia between 3 1/2 and 24 months following b.m.t., 3 patients died with interstitial pneumonia within 3 months of b.m.t. and 3 patients died with insufficient graft function within 4 weeks of b.m.t. Four of thirteen patients that were grafted more than 6 months ago are presently alive and in continuous complete remission at 11, 14, 29 and 33 months following b.m.t. Our results confirm that longterm remissions can be obtained with b.m.t. in patients with acute leukemia in advanced stage.
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