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Biomedical subjects

D Killander

Publications and source records attributed to D Killander.

At least 37 records · Page 2Linked to original sources
PubMed1986

Simultaneous immunofluorimetric quantitation of IgM and IgG in single splenic lymphoid cells after immunization.

The amount of IgM and IgG was determined in individual mouse spleen lymphocytes by double immunofluorimetry after "staining" with dimethylamino-naphthaline sulfonyl chloride-labeled anti-IgM and fluorescein isothiocyanate-labeled anti-IgG. During a single immune response against sheep erythrocytes there was an inverse relationship between the amounts of these two immunoglobulins in individual cells. There was an early steep increase of the cellular amount of IgM during the first 3 days after immunization. Subsequently IgG increased exceeding the initial IgG levels while IgM decreased. Most cells containing high amounts of IgM had a low IgG content and vice versa. The present results directly demonstrate a quantitative switch from IgM to IgG in individual cells on the single cell level after an antigenic stimulus. This indicates simultaneous active production of both immunoglobulins in these cells. For an explanation of this phenomenon differential mRNA splicing rather than DNA rearrangement as an underlying process for immunoglobulin expression may be proposed in these early B-cells.

Animals↗
PubMed1979

Interferon therapy in multiple myeloma.

A woman with multiple myeloma relapsed after 6 years of satisfactory tumor control with melphalan therapy. When progression then occurred, she was given exogenous human leukocyte interferon, 3 x 10(6) reference units twice daily i.m., as the sole therapy. Side-effects of the interferon therapy consisted of fever reactions and thrombocytopenia. One month after the initiation of interferon therapy there was 1) improvement of general health with less pain and tiredness, 2) reduction of the M-component, IgG-lambda, in the serum, and 3) a reduced plasma cell concentration in the bone marrow. After 5 months of interferon therapy tumor progression occurred despite continuous interferon treatment. At the same time, the tumor cells were less sensitive to interferon in in vitro tests than prior to interferon therapy. It is suggested that interferon therapy should be given as initial treatment to a few patients with multiple myeloma in a phase I trial.

Aged↗
PubMed1978

Prognostic factors in Hodgkin's disease. II. Role of the lymphocyte defect.

Purified blood lymphocytes from 81 consecutive and previously untreated patients with Hodgkin's disease were studied in vitro. The patients were evaluated 23 to 52 months after institution of therapy and were divided into two prognostic groups: 1. Complete remission with or without previous relapse/relapses. 2. Uncontrolled relapse or decreased from Hodgkin's disease. Lymphocyte activation by concanavalin A, pokeweed mitogen or phytohaemagglutinin was impaired and spontaneous DNA synthesis was high in patients with poor prognosis as compared to the good prognosis group. The prognostic information increased if the four lymphocyte tests were combined in a score (range 0-8). All 8 patients with pronounced lymphocyte defects (score 7-8), died, while all patients with score 0 and 1 were in complete remission. In contrast, total lymphocyte and T-lymphocyte counts and lymphocyte stimulation by PPD were of no prognostic value. The ability of certain lymphocyte functions to predict prognosis was equal or better than that of age and better than clinical staging, histopathology and symptoms.

Adolescent↗
PubMed1977

75Se-Selenite scrintigraphy in the clinical staging of malignant lymphomas.

The value of 75Se-selenite scintigraphy in clinical staging was investigated in 45 patients with Hodgkin's disease and in 28 patients with non-Hodgkin's lymphoma. Of these, 9 patients had recurrence of previously treated lymphomas. The scintigraphic results were compared with clinical, cytologic, histologic and radiographic findings in different anatomic regions. 75Se-selenite scintigraphy resulted in 6 to 20 per cent false negative findings, 15 to 43 per cent false positive and 12 to 20 per cent equivocal evaluations, the accuracy being least in the abdominal region. The relatively high rediation dose delivered by 75Se-selenite, furthermore, makes it less attractive for use in the primary diagnosis of malignant lymphomas.

Abdomen↗
PubMed1977

Bone marrow kinetic studies on three patients with myelomatosis. Indications for malignant proliferation within both the plasma cell and lymphoid cell compartments.

The proliferative activity has been studied in lymphocyte and plasma cell populations of purified bone marrow from three myeloma patients. In one of them, proliferation was also recorded in blood lymphocytes. Immunofluorescence studies, using idiotypic antisera against the M-component, were performed to identify lymphocytes and plasma cells belonging to the malignant cell clone. Pulse incubations with 3H-thymidine (3H-TdR) were made in vitro. Autoradiographic analyses revealed a higher overall 3H-TdR labelling index in the myeloma cell populations than in normal control cell populations. A few labelled plasma cells were observed in the myeloma cases (2.5-5%) but the major fraction (11.5-14%) and intensity of labelled cells were found among the lymphoid cells. This indicates that the proliferation of malignant cells in myeloma occurs not only within the plasma cell but also in the lymphoid cell population. The results provide additional support for the assumption that B-lymphocytes are part of the malignant cell clone in myelomatosis and most likely precursors to the myeloma plasma cells.

Autoradiography↗
PubMed1976

Hypersensitive reactions and antibody formation during L-asparaginase treatment of children and adults with acute leukemia.

One hundred and fourteen patients with acute leukemia, 57 children (10 AML and 47 ALL) and 57 adults (37 AML and 20 ALL) were treated with L-asparaginase (Asnase) 200 or 1000 IU/kg daily for 30 days unless withdrawn on account of side effects. Combinations with other cytotoxic drugs were used in all but eight patients. Hypersensitive reactions, decrease in Asnase activity in plasma, and bivalent antibodies to Asnase appeared more frequently in adults (28%, 46%, and 79%, respectively) than in children (16%, 17%, and 25% respectively). There was a clear association between these three parameters. Thus hypersensitive reactions generally developed at the time of or after the decrease in plasma Asnase activity. Antibodies were detected only where Asnase activity had disappeared from the plasma. This time sequence, and in vitro experiments, suggest the formation of antigen-antibody complexes which might be responsible for inactivation of Asnase and for the development of hypersensitive reactions. However in many cases antibodies were found without concomitant enzyme inactivation or hypersensitive reactions. Antibodies to Asnase of IgE type (reagins) were found in only 10 children and 6 adults. There was no correlation between hypersensitive reactions, decrease in Asnase activity, and IgE antibodies. The frequency of remission among patients developing bivalent antibodies to Asnase was 68% (13/19) in contrast to 27% (3/11) among patients whose sera contained no detectable antibodies to Asnase, but the difference was not statistically significant.

Adult↗
PubMed1976

Lymphocyte abnormalities in untreated patients with Hodgkin's disease.

The study comprises 38 unselected and untreated patients with Hodgkin's disease (HD) and 23 healthy persons. Highly purified blood lymphocytes were analyzed for cells forming rosettes with sheep red blood cells (T lymphocytes), and lymphocytes bearing surface immunoglobulin (B lymphocytes) and/or carrying receptors for complement. Their DNA synthesis, spontaneously, or after activation with mitogens (phytohemagglutinin, concanavallin A, poke weed mitogen) and purified protein derivative (PPD) was measured. Delayed skin hypersensitivity to PPD and mumps antigen was studied. Most HD patients had low numbers of T lymphocytes (50% of the cases below normal range) while the mean B-lymphocyte level was normal but with a greater variation than in the control group. Lymphocytes from most patients were poorly stimulated by T-cell mitogens. Two-thirds of the patients and one healthy control had negative skin reaction to 2 TU PPD and the DNA synthesis of their lymphocytes after activation with PPD was low. Large lymphoid cells (greater than 9-mm diameter) were commonly present in HD blood and the spontaneous DNA synthesis was high, particularly in lymphocytes from stage B patients. The percentage of T lymphocytes and the stimulation of lymphocytes by T-cell mitogens or by PPD, a T-lymphocyte function, did not correlate and each test only detected defects in about half the cases. Simultaneous application of all tests revealed abnormalities of blood T lymphocytes in 33 out of 38 patients. Although the defects were usually more pronounced in patients with advanced disease, the impairment of T lymphocytes and their functions is present in all stages of Hodgkin's disease.

B-Lymphocytes↗
PubMed1976

Relationship between the enhanced expression of histocompatibility antigens on interferon-treated L 1210 cells and their position in the cell cycle.

We have determined the cell cycle position of individual mouse leukemia L 1210 cells by cytophotometric and autoradiographic techniques and simultaneously determined the amount of histocompatibility antigens expressed on the surface of individual cells by quantitative immunofluorescence. Interferon treatment of L 1210 cells was accompanied by an enhanced expression of histocompatibility surface antigens. The distribution of interferon-treated cells in the various phases of the cell cycle was similar to that for control cells and the enhanced expression of histocompatibility antigens was observed on interferon-treated cells in all phases of the cell cycle. We conclude, therefore, that this enhancement is not due to a preferential concentration of these cells in any one particular phase of the cell cycle.

Animals↗
PubMed1976

Simultaneous quantitation of two antigens in mixture in individual cells by microimmunofluorimetry.

Double immunofluorescence has so far only been used qualitatively. In present work the possibility of quantitative double immunofluorescence was evaluated in model systems with the ultimate goal to enable simultaneous measurements of different antigens in mixture in biological objects. In one test system a conjugate of fluorescein isothiocyanate (FITC) was studied in combination with conjugates of dimethyl-amino-naphthalene-sulphonyl-chloride (DANSC) or with tetramethyl-rhodamine-isothiocyanate (TRITC) in solutions. In another test system FITC + DANSC antibody conjugates were analyzed after reaction with antigen mixtures in insolubilized form. Fluorescence intensities were measured in a microspectrofluorimeter using narrow band excitation and emission filters of appropriate types for different fluorochromes. Fading was no problem in this system. A formula was developed to calculate the antibody proportions from the fluorescence contribution of either fluorochrome in the region of optimal fluorescence of other fluorochrome. Experimental values obtained from analyses of FITC + DANSC and FITC + TRITC combinations in solutions agreed excellently with theoretically expected values. In the second model system polyacrylic beads were coated with different proportions of two antigens, one labelled with 125I and the other with 131I. After radioactivity measurements the beads were stained with appropriate antisera conjugated with FITC and DANSC, respectively. "Double fluorescence" intensities of individual beads were measured and a very strong correlation was found between the radioactivity and the fluorescence values. The results indicate that quantiation of double fluorescence is possible and meaningful for measurements of two different antigens in mixture on individual particles.

Antigens↗
PubMed1976

Analysis of cell-surface markers with staphylococcal protein A: fluorescence studies on mammalian lymphoid determinants.

Membrane antigens including different classes of immunoglobulins, transplantation antigens, beta2-microglobulin, T lymphocyte specific antigens, and virally determined surface components were investigated using fluorescein-labeled Staphylococcal protein A in combination with cytofluorometric studies. Lymphocytes of seven species: mouse, rat, guinea pig, pig, cow, monkey, and human, and of ten human lymphoma-derived lines were tested. Analysis of the differential expression of surface markers revealed a reproducible reaction of protein A with cell-surface Fc of IgG actively produced by lymphoid cells from human, monkey, guinea pig, and pig, and with passively attached IgG molecules in the form of antibodies, directed against cell surface antigens of all lymphoid cells tested. No surface Ig was detected on so-called T lymphocytes. The distribution of cell-bound Ig density among surface Ig-positive cells was found to be different depending upon the origin of the cells with regard to lymphoid organ; it was parallel among the lymphoma lines tested and on peripheral blood cells from human, monkey, and pig, although large variations in fluorescence intensity among individual cells and among the different lines were recorded. Beta2-microglobulin determinants were found equally well on enriched human T and B cells. Transplantation, and T lymphocyte-specific antigens were detected on the majority of the lymphoid cells and on a restricted population respectively.

Animals↗
PubMed1976

Short-term tissue culture of two nonsecretory human myelomas. A morphological and functional study.

Bone marrow cells from two patients without detectable monoclonal immunoglobulin (Ig) in serum and urine but with the clinical picture of plasma cell myeloma were cultivated in vitro. Immunofluorescence studies of cultured living and fixed bone marrow cells showed no signs of Ig production in one of the cases, whereas in the other case cytoplasmic kappa chains were detected, which, however, were not expressed at the surface of living cells. Cells from the later patient were also subjected to kinetic, ultrastructural, and functional studies in vitro. The fraction of myeloma cells incorporating tritiated thymidine in vitro decreased gradually during prolonged culture, indicating a continuous cell death. The morphological characterization revealed many similarities between this nonsecretory myeloma and classical myeloma, although the frequency of cells with cisternae of endoplasmic reticulum distended by a granular material was unusually high, as was the frequency of "flaming" myeloma cells. "Flaming" cells were not labeled by tritiated thymidine, suggesting that they are nonproliferative end cells. Studies of the Ig synthesis by gel diffusion analyses of supernatant and cell lysates from [14C]leucine-labeled cultures agreed with the immunofluorescence studies that the myeloma cells were nonsecretory.

Aged↗
PubMed1976

Specific chromosomal aberrations in polycythemia vera.

The chromosomes of bone marrow cells from ten patients with polycythemia vera (PV) were identified by Q-, G-, and C-banding techniques. Four of the patients had received no treatment with cytotoxic drugs, while three had received 32P only and the other three, in addition, had received busulfan or busulfan and procarbazine. One 73-yr-old male patient treated with venesection only for 4 yr lacked the Y chromosome and had a deletion of the long arm of chromosome 20 (20q-) in all cells investigated. One of the other three patients who had received no drugs had a chromosome abnormality, but only in 1 of 19 identifiable metaphases. However, the abnormality was the same (+9) as the most common one in treated patients. In the group of treated patients, an extra chromosome 9 (+9) was found in three patients, an extra chromosome 8 (+8) in one, and a deletion of the long arm of one chromosome 20 (20q-) in one patient. Multiple aberrations in addition to the extra chromosome 9 were found in one patient in whom the disease had transformed into acute myeloblastic leukemia. The finding of identical chromosomal aberrations (20q- and +9, respectively) in two patients who had received no drugs and in four patients who had received 32P and busulfan or procarbazine favors the view that these aberrations are specifically associated with the disease and not induced by the drugs. With the exception of the patient with acute myeloblastic leukemia, all other patients are alive 1-11 mo after chromosome analyses and 1-229 mo after diagnosis.

Aged↗
PubMed1975

L-asparaginase and prednisolone pretreatment followed by rubidomycin and cytosine arabinoside for induction of remission in adult patients with acute myeloblastic leukaemia.

77 unselected adult patients with acute myeloblastic leukaemia (AML), including practically all AML patients from an area with 1.9 million inhabitants, were randomized for either (1) 5 days pretreatment with 1-asparaginase and prednisolone followed by a combination of rubidomycin and cytosine arabinoside (ARAP), or (2) treatment with a combination of rubidomycin, cytosine arabinoside and prednisolone without 1-asparaginase pretreatment (RAP). Complete remission was induced with ARAP in 12 patients (31%) and with RAP in 13 patients (34%). Thus pretreatment with 1-asparaginase did not improve the therapeutic response. The overall remission frequency was significantly higher below the age of 60; 50% compared to 13% above this age. Side-effects such as liver dysfunction, nausea and vomiting were more common in patients pretreated with 1-asparaginase. Sterilization of the gut did not improve the remission frequency with either regime.

Adolescent↗
PubMed1975

Epstein-Barr virus (EBV)-associated antibody patterns in relation to the deficiency of cell-mediated immunity in patients with Hodgkin's disease.

Sera from unselected and untreated patients with Hodgkin's disease (HD) were examined for antibodies to Epstein-Barr viral (EBV) capsid antigens (VCA). Delayed cutaneous hypersensitivity reactions were carried out with purified tuberculoprotein (PPD). Highly purified blood lymphocytes of the same patients were studied morphologically and classified for cell surface markers. Incorporation of 14C-thymidine was used as a measure of spontaneous DNA synthesis and DNA synthesis after exposure to different concentrations of three mitogens (PHA, Conconavalin A and pokeweed mitogen) and PPD. The distribution of EBV titres was in good agreement with previous reports. Most patients were lymphopenic, due to subnormal levels of T lymphocytes. The lymphocyte stimulation and skin tests showed different degrees of impairment in a considerable number of the patients. The results in 43 patients indicated that a relation exists between the immune defect and the anti-VCA titres. High serological anti-VCA reactivity was related to a poor cutaneous response to PPD, a decreased level of T lymphocytes in the blood and a depression of mitogen-induced DNA synthesis.

Antibodies, Viral↗