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Biomedical subjects

U Bucher

Publications and source records attributed to U Bucher.

At least 19 recordsLinked to original sources

Biochemical identification of the antigen recognized by the monoclonal pan-B cell antibody Y29/55.

To examine the biochemical structure of the antigen recognized by the monoclonal pan-B cell antibody, Y29/55, the Daudi- and Jurkat-cell lines were labeled by two different methods and immunoprecipitation experiments were carried out. After surface labeling with iodine, two bands with molecular weights of about 38 and 42 kD were observed. The same two proteins were precipitated after biosynthetic labeling with (35S)-methionine from B cells and, to a lesser extent, from T cells. Therefore, it seems that the same proteins, or proteins with similar molecular weight, exist intracellularly in T cells as exist on the surface of, and possibly intracellularly, in B cells. It was confirmed that 80-90% of normal blood-derived B cells were stained with Y29/55 by indirect immunofluorescence. Double-labeling experiments with the pan-B cell antibodies Leu 16 (CD 20) and Leu 12 (CD 19) showed a B-cell population which could be stained with both antibodies (Y29/55 and Leu 16 or Y29/55 and Leu 12). A minor cell population was stained with the antibody Y29/55 alone. Our findings indicate that the antibody Y29/55 recognizes a B-cell antigen, which has not been described previously.

Antibodies, Monoclonal↗

[Severe hemolytic anemia following purse-string valvuloplasty of the mitral valve].

A patient who had undergone valvuloplasty for mitral insufficiency due to chordal rupture developed severe hemolytic anemia a few weeks after surgery. Progressive mitral regurgitation was noted at the same time. Extensive laboratory workup excluded other reasons for hemolytic anemia. In comparison with other cases in the literature it is assumed that the patient was suffering from cardiogenic mechanical hemolysis. Fourteen months later mitral valve replacement (St Jude) was performed and the hemolysis ceased promptly. A brief review of the literature is presented.

Aged↗

[Autologous bone marrow transfusion in the treatment of adults with hematologic neoplasms. Experiences from Bern].

21 patients with hematological neoplasias (8 ALL, 4 AML, 4 NHL, 5 HD) were treated with high dose therapy and autologous bone marrow rescue (ABMT). At the time of ABMT 12 patients were in CR, 6 in PR and 3 in relapse. 66% of the patients were at high risk at the time of diagnosis. Before ABMT patients received an ablative regimen such as cyclophosphamide or ARA-C, VP-16, DNR and 12 Gy TBI in 6 fractions. In 9 patients the bone marrow was treated in vitro with monoclonal antibodies and complement. The hospital stay was a median 33 (24-57) days and isolation 19 (9-49) days. Complications were septicemia (7), herpes stomatitis (7), infections (6), fungal sepsis (1) and hemorrhagic cystitis (2). Late complications (up to 6 months after ABMT) were pneumococcal sepsis (1), cerebral toxoplasmosis (1) and herpes zoster (3). 10 of 19 evaluable patients are alive and relapse-free 1-33 months (median 10) after ABTM, and 3 of 10 more than 2 years later: 4 of 5 were transplanted in 1. CR, 4 of 6 in greater than or equal to 2. CR and 2 of 8 in PR. 4 patients are living in therapy sensitive relapse 2, 11, 11 and 39 months after ABMT in 2. CR or PR. 5 patients died 1-13 (median 3.5) months on relapse, 2 of 21 from septicemia. The morbidity of ABMT is comparable with conventional high dose chemotherapy. Relapse-free survival was significantly influenced by the remission status at ABMT. Long-term survivors can be expected even in patients with high risk hematological malignancies. However, only wider trials will serve to establish the efficacy of ABMT.

Adolescent↗

[Positive direct Coombs' test in acute leukemias and other hemoblastoses: relation to clavulanic acid-containing antibiotics?].

Alerted by a high incidence of positive autologous controls in pretransfusion compatibility testing for patients with acute leukemia, we retrospectively analysed 59 cases of severe hemoblastoses undergoing myelosuppressive treatment. Seventeen (29%) of these patients had a positive direct antiglobulin test (DAT) with the following characteristics: the test was of the IgG and/or C3d type in all but two cases, which reacted with polyvalent antiglobulin sera only; the reaction was very weak throughout; very high concentrations of monospecific sera were needed to elicit positive reactions; free antibodies were never detected in the patients' serum; the eluates of the patients' red cells were non-reactive against a very large panel of test erythrocytes. All these criteria suggested a non-immunologic absorption of proteins under the influence of drugs such as cephalosporins and clavulanic acid. Timenten (ticarcillin and clavulanic acid) was found to be the only common drug which had been administered to the majority of the patients with a positive DAT: 15 of the 17 patients with a positive DAT (88%) had received Timenten against 19 of 42 patients (45%) with negative DAT. 44% of all the patients receiving Timenten thus had a positive DAT, whereas only 8% of the patients without this drug reacted in this way. These data document the role of clavulanic acid in the development of a positive DAT. The literature and our experience show that this kind of unspecific binding of proteins to the red cell membrane is not associated with increased hemolysis. Knowledge of the phenomenon, however, is important for differential diagnosis of anemias and interpretation of difficulties arising during pretransfusional compatibility testing.

Acute Disease↗

[Unusual features in Glanzmann thrombasthenia; proliferation of B-lymphocytes, lead poisoning].

Four case histories are reported: 1. A 37-year-old woman suffering from Glanzmann's thrombasthenia has been regularly seen since 1955. Characteristically (and in contrast to the first description by Glanzmann!) persistently prolonged bleeding times were noted. Clot retraction is severely diminished and the platelets fail to aggregate upon various stimuli. (Platelet agglutination upon addition of ristocetin to platelet rich plasma is normal.) The diagnosis of thrombasthenia was confirmed by demonstration of a deficiency of the membrane glycoprotein IIb/IIIa complex. In recent years the patient has become refractory to platelet transfusion therapy, a response shown to be due to antibodies against GPIIb/IIIa in the plasma. Spontaneous bleeding tendency has appeared to improve over the years. 2. Two patients with proliferation of B-lymphocytes are presented. a) Splenomegaly and an increase of B-lymphocytes in the peripheral blood were detected in a 45-year-old asymptomatic man. DNA analysis suggested that polyclonal proliferation of B-lymphocytes was present. Diagnostic considerations are discussed. b) In a 46-year-old male patient with subacute aleukemic leukemia of a pre-B-cell type diagnosed in 1981, the disease showed an unexpectedly benign course: after initial mild chemotherapy the patient has remained in a stable condition while off cytotoxic treatment for the last two years. Nevertheless, besides anemia necessitating regular transfusions, persistent agranulocytosis is present which is not explained by bone marrow infiltration. In vitro experiments suggest suppression of myelopoiesis by cellular interaction with leukemic cells or a deficiency of growth factors causing agranulocytosis. 3. An 81-year-old man showed signs and symptoms of lead intoxication which proved to be due to oral ingestion of a lead-containing ointment.

Adult↗

Humoral immune function in pediatric patients treated with autologous bone marrow transplantation for B cell non-Hodgkin's lymphoma. The influence of ex vivo marrow decontamination with anti-Y 29/55 monoclonal antibody and complement.

Elimination of neoplastic B cell populations from autologous bone marrow grafts also removes normal B lymphocytes. This is potentially hazardous for the reconstitution of the immune system in patients undergoing high-dose chemotherapy and total body irradiation followed by autologous marrow rescue. Five pediatric patients with B cell non-Hodgkin's lymphoma in first remission undergoing such a regimen were studied. They received bone marrow pretreated with anti-Y 29/55 monoclonal antibody and complement. B and T lymphocyte subpopulations reached normal levels within 6 months after autologous bone marrow transplantation (ABMT), and serum immunoglobulin levels became normal within 4 to 9 months. Vaccination with diphtheria and tetanus toxoid, trivalent poliomyelitis vaccine of the Salk type, and pneumococcal capsular antigens (38 to 54 months after transplantation) gave rise to specific antibody production. ABO isoagglutinins could be demonstrated in all patients. The response pattern was similar to that of patients who received unmanipulated autologous bone marrow. It is concluded that ex vivo anti-Y 29/55 depletion of the marrow graft does not induce relevant disturbances of humoral immune functions.

Adolescent↗

Comparison of posttransfusion recoveries achieved with either fresh or stored platelet concentrates.

The effectiveness of platelet concentrate transfusion depends on such variables as blood bag material, donor--recipient compatibility, and time elapsed between donation and transfusion. To study the latter a corrected thrombocyte increment for recovery in the recipients was evaluated with 108 platelet transfusions in 31 patients. In 83 treatment programs, the mean recovery at the one-hour post-transfusion time point was 8.6 X 10(9) platelets/l with fresh platelets and 5.9 X 10(9) platelets/l with stored platelets. Significantly better recovery was achieved with freshly prepared platelet over the total of platelet concentrates stored for up to 96 hours; however, if the recoveries in different patient groups given stored platelets were considered separately in terms of storage times of up to 48 h or 48-96 h, the good recovery with fresh platelets was significantly better only when compared to the older (p = 0.034) but not to the younger group of stored platelets. In patients with signs indicating enhanced platelet destruction (fever, splenomegaly, disseminated intravascular coagulation) the transfusion with fresh platelet concentrates gave a significantly better recovery compared to stored platelet concentrates (p = 0.028), whereas in the absence of such signs the recovery produced by fresh concentrates was not significantly higher than with stored concentrates. These findings may be relevant for the logistics in blood banking.

Adult↗

[Is 1,25(OH)2D3 effective in chronic osteomyelofibrosis?].

1,25-dihydroxycholecalciferol (1,25[OH]2D3) is the most important active metabolite of vitamin D3 and has a remarkable antiproliferative effect on megakaryocytes in vitro. It may have a favorable influence on collagen formation and degradation by a megakaryocyte/monocyte dependent modulation. We evaluated the clinical effect of 1,25(OH)2D3 in four patients suffering from idiopathic myelofibrosis. The daily dose ranged from 0.006 to 0.016 microgram/kg. One patient died from asthenia 2.5 months after starting treatment and three were observed for more than a year. Despite treatment with 1,25(OH)2D3, they all needed regular transfusions. During follow-up bone marrow biopsies did not reveal a decrease in fibrosis.

Blood Transfusion↗

Hereditary leaky red cell syndrome in a Swiss family.

A Swiss family was found to have a hereditary hemolytic disorder associated with excessively leaky red cell membranes. Hemolysis was mild and fully compensated. Membrane lipid analysis revealed an increased phosphatidylcholine:phosphatidylethanolamine ratio. Membrane leaks included an increased permeability to sodium, potassium, calcium and, possibly, creatine. It is suggested that in hemolytic states, the combined finding of reticulocytosis and normal red cell creatine might be an easily obtainable clue to the presence of a leaky red cell syndrome.

Adult↗

[Autologous bone marrow transplantation--clinical experience in Berne].

Autologous bone marrow transplantation was performed in 28 pediatric and adult patients with various neoplasias. Long-term remissions were obtained in one patient with yolk sac tumor and in 9 patients with B-cell non-Hodgkin's lymphoma. The relapse rate was decreased in patients receiving in-vitro decontaminated marrow (anti-Y 29/55 and complement).

Adolescent↗

[How long will preserved blood and bone marrow films give reliable cytochemical staining?].

We tested how long unstained and unfixed films of blood and aspirated bone marrow could be kept before special cytochemical staining. To exclude influences other than time on the outcome of the reactions, all the material was taken from hematologically normal persons. A simple score was used to evaluate the results. These may be summarized as follows: in most cells Naphthol-AS-acetate-esterase first shows a progressive decline in reactivity after a delay of 6 weeks, the reaction becoming very weak after 10 +/- 1 weeks. This does not hold for monocytes, megakaryocytes and platelets, which maintain reactivity (and susceptibility to NaF) for more than three months. With PAS staining, a slight decrease in reactivity after 8 +/- 2 weeks could be observed, whereas all other stainings tested (POX, Sudan black B and Naphthol-AS-D-esterase) were unaffected even by a delay of up to 16 weeks.

Adolescent↗

[Acute graft-versus-host disease following a single transfusion of erythrocytes].

A 50-year-old severely immunodeficient woman with malignant non-Hodgkin lymphoma died from graft-versus-host disease due to transfusion of a single unit of packed red cells. Three days after this transfusion a maculo-papular rash appeared, followed by generalized erythroderma refractory to therapy and eventually progressing into generalized ulcero-squamous dermatitis. This case, and a review of other similar cases published elsewhere, prompt the authors to recommend prophylactic irradiation of blood products prior to their administration to patients with cellular immunodeficiency, particularly in cases of acute leukaemia or malignant lymphoma where patients receive intensive radio- and/or chemotherapy regimens. To appreciate the degree of cellular immunodeficiency in such risk patients, simple criteria should be developed to assess the efficiency of the cellular immune system.

Erythrocyte Transfusion↗

Autologous bone-marrow transplantation for Burkitt's lymphoma: marrow purging with anti-Y 29/55 monoclonal antibody and complement.

Reinfusion of undetected tumour cells is a possible cause of relapse after autologous bone-marrow transplantation. In this paper, a system for in-vitro purging of bone marrow is presented which involves the B-cell neoplasia-associated monoclonal antibody anti-Y 29/55 and complement. Five patients with Burkitt's lymphoma were transplanted with purged marrow, demonstrating the clinical feasibility of the method. The pretransplant regimen included vincristine 2 mg/m2, adriamycin 60 mg/m2, four doses of cyclophosphamide 45 mg/kg and total body irradiation with 6 Gy. Tumour control appears to be better in patients with purged bone marrow as compared to an earlier patient group with unpurged marrow.

Adolescent↗

[Effect of hypobaric hypoxia on motor behavior in rats].

Hypobaric hypoxic exposure for 18 h (pO2 8.7 kPa) effects characteristic changes of motoric behaviour in adult rats. We observed a posthypoxic increase of spontaneous locomotion and of open-field activity. 24 h after hypoxic exposure the locomotion stimulated by dopaminergic agonists apomorphine or amphetamine was strengthened. Dopaminergic nuclei showed a different sensitivity to unilaterally applied dopamine after hypoxic exposure. Rotational behaviour was facilitated in the nucleus accumbens but significantly decreased in the substantia nigra. In the nucleus caudatoputamen we could not prove changes in comparison to controls. These results indicate that central dopaminergic processes are influenced by hypobaric hypoxic exposure. Besides the sensitization of dopaminergic receptor populations these changes of motoric behaviour may be connected with interactions between different transmitter systems or displacement of central regulation systems.

Amphetamine↗

Autologous bone marrow transplantation in the treatment of children and adolescents with advanced malignant tumors.

Nineteen patients with advanced malignant tumors, less than 20 years old were treated with intensive chemotherapy (vincristine 2 mg/m2 i.v. and adriamycin 60 mg/m2 i.v. on day - 7; cyclophosphamide 45 mg/kg i.v. on days -6 to -3), total body irradiation (TBI, 600 rads on day -1) and autologous bone marrow transplantation (ABMT, day 0). Prior to this procedure induction of complete or partial remission by conventional therapy was attempted. Ten patients had intra-abdominal non-Hodgkin's lymphoma (NHL); three, yolk sac tumor; three, Ewing's sarcoma; and three, neuroblastoma. The supportive care included reverse isolation, immunoglobulin 400 mg/kg i.v. q 2 weeks, cotrimoxazole per os, and cell support as needed. No correlation between the bone marrow dose and the time of hematological reconstitution could be established. Five of seven patients with intra-abdominal NHL stage III (transplanted in first remission) are surviving disease-free for 5+, 5+, 20+, 23+, and 35+ months after ABMT. None of three patients with intra-abdominal NHL stage IV is surviving (two of them were transplanted in second remission). One of three patients with yolk sac tumor is surviving disease-free for 27+ months. There are no survivors among the patients with Ewing's sarcoma and neuroblastoma. Only one of 19 patients was lost due to therapeutic complications, while 12 died due to tumor. Regarding treatment results for advanced intra-abdominal NHL, the procedure described here is comparable to the best conventional regimens. In vitro methods for tumor cell eradication in the collected bone marrow might further improve the results of ABMT.

Adolescent↗