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Biomedical subjects

I Olsson

Publications and source records attributed to I Olsson.

At least 109 records · Page 6Linked to original sources
PubMed1986

Effects of recombinant tumor necrosis factor on proliferation and differentiation of leukemic and normal hemopoietic cells in vitro. Relationship to cell surface receptor.

The clonogenic growth of myeloid leukemia cell lines was inhibited by recombinant tumor necrosis factor (rTNF) at 1-15 pM concentration. However, wild type (promyelocytic) HL-60 cells were highly resistant to growth inhibition, but responded with differentiation into monocyte-like cells at 100 pM rTNF. The clonogenic growth of fresh acute myeloid leukemia cells was inhibited by 50% at approximately 15 pM rTNF. The growth of normal granulocyte-macrophage progenitors (CFU-GM) was also inhibited (by 50 pM rTNF), as was the growth of erythroid progenitors (BFU-E) (by 150 pM rTNF). A synergistic antiproliferative effect was demonstrated between rTNF and recombinant interferon-gamma. Use of radioiodinated rTNF enabled us to detect 1,500-2,100 binding sites on myeloid cell lines at 4 degrees C with Kd of approximately 300 pM. At 37 degrees C, the transfer of bound ligand to lysosomes was followed by degradation, inhibited by NH4+. No correlation was observed between the number of binding sites or affinity at 4 degrees C and antiproliferative response to the addition of rTNF.

Cell Differentiation↗
PubMed1986

Localization of eosinophil cationic protein, major basic protein, and eosinophil peroxidase in human eosinophils by immunoelectron microscopic technique.

An immunoelectron microscopic technique using protein A-gold as a specific marker was used for precise intracellular localization of eosinophil granule proteins. Eosinophils from healthy individuals were isolated in metrizamide gradients. Eosinophil cationic protein (ECP) and eosinophil peroxidase (EPO) were clearly located in the matrix of the large crystalloid-containing granules. In addition, ECP was probably present in the small granules of eosinophils. Major basic protein (MBP) was present in the crystalloid structure of specific granules. This method can be applied in studies of eosinophil degranulation to trace the release of biological effector molecules.

Blood Proteins↗
PubMed1986

The spirochetal etiology of lymphadenosis benigna cutis solitaria.

Ten patients with a clinical diagnosis of lymphadenosis benigna cutis (LABC) solitaria were investigated. Four of the patients knew that they had received a tick bite during the year prior to the appearance of the LABC lesion. Five patients had had a migrating erythema, indicating a previous erythema chronicum migrans Afzelius, near the site where the LABC lesion had developed. In one patient meningitis and a facial palsy occurred. Elevated titers of antibodies against Borrelia spirochetes were found in sera from six of nine patients. Spirochetes were cultivated from one out of two biopsies from LABC lesions. The clinical findings, the results of the serologic tests and the successful cultivation of spirochetes show that Ixodes ricinus-transmitted Borrelia spirochetes can cause LABC solitaria.

Adult↗
PubMed1986

The processing and intracellular transport of myeloperoxidase. Modulation by lysosomotropic agents and monensin.

Myeloperoxidase, stored in azurophil granules of neutrophils, is synthesized in promyelocytes as a larger molecular weight precursor, which is processed to yield a transient Mr 82 000 intermediate and mature polypeptides with molecular weights of 62 000 and 12 000. We have tried to define subcellular sites for processing using metabolic labelling of the promyelocytic leukemia cell line HL-60 in combination with subcellular fractionation on a Percoll gradient. A reasonable separation was achieved between azurophil granules, Golgi elements and endoplasmic reticulum. The finding of almost exclusively fully processed myeloperoxidase in granules and a mixture of unprocessed and processed polypeptide in fractions enriched in Golgi elements suggests that processing occurred mainly in pregranular structures. Monensin, which exchanges protons for Na+, and the base chloroquine blocked processing probably by inhibition of transport through the Golgi apparatus. However, the lysosomotropic NH4+ cation did not inhibit processing or transport indicating that processing is not necessarily influenced by pH-dependent mechanisms. Results from digestion with endoglycosidase H, incubation with tunicamycin and metabolic labelling with [3H]mannose indicated that myeloperoxidase contained high mannose oligosaccharide side chains. Also [32P]phosphate incorporated into Mr 90 000 and Mr 62 000 myeloperoxidase was susceptible to endoglycosidase H indicating that oligosaccharide side chains are modified by phosphorylation as in lysosomal enzymes. Thus, even if myeloperoxidase contained mannose 6-phosphate residues, these may not necessarily be involved in directing transport to the azurophil granules.

Ammonium Chloride↗
PubMed1986

The biosynthesis of neutrophil and eosinophil granule proteins.

Composition of azurophil and specific granules from human polymorphonuclear neutrophils and granules from eosinophils is presented. Biosynthesis of the granule proteins is discussed in detail with particular emphasis on neutrophil myeloperoxidase (MPO) and eosinophil cationic protein (ECP).

Blood Proteins↗
PubMed1986

T lymphocyte-derived differentiation-inducing factor inhibits proliferation of leukemic and normal hemopoietic cells.

A differentiation-inducing factor (DIF) for the promyelocytic HL-60 cell line is constitutively produced by the malignant T lymphocyte line HUT-102. DIF was highly purified from HUT-102-conditioned media by means of diethylaminoethanol (DEAE)-chromatography, gel chromatography, and high-resolution, ion-exchange chromatography on a MonoQ column and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In addition to inducing differentiation of wild-type HL-60 cells, resulting in secondary inhibition of growth, DIF, at a tenfold lower concentration, inhibited the growth of some clones of the monoblastic U-937 cell line as well as that of subclones of HL-60. The latter effect was most likely a primary growth inhibition and not secondary to differentiation; 50% inhibition of clonogenic growth in agar was seen at approximately 1.0 pmol/L of DIF. In addition, the clonogenic growth of fresh leukemia cells from 10 of 12 patients with acute myeloid leukemia (AML) was inhibited with 50% inhibition at approximately 10 pmol/L of DIF. The growth of normal granulocyte-macrophage colonies was inhibited at a similar concentration, whereas early erythroid colonies were much more resistant. DIF and interferon-gamma (gamma-IFN) were shown to be separate molecules inasmuch as a neutralizing antibody for gamma-IFN did not abolish the DIF effect. The differentiation effect on wild-type HL-60 and the proliferation inhibitory effect on leukemic and normal myeloid cells cochromatographed through all purification steps suggest that both activities are exhibited by identical polypeptides. DIF may have a role in regulating normal hemopoiesis. The growth inhibitory effect of DIF and the ability to induce differentiation of some leukemia cells may suggest a clinical utility in the treatment of leukemia.

Cell Differentiation↗
PubMed1986

Biochemical properties of the eosinophil cationic protein and demonstration of its biosynthesis in vitro in marrow cells from patients with an eosinophilia.

The eosinophil cationic protein (ECP), which has been shown to be secreted both in vitro and in vivo, is a cytotoxic unique constituent of eosinophil granules. To increase the understanding of the mechanisms behind the role of the eosinophil as a cytotoxic effector in disease, a detailed biochemical characterization of ECP was performed. A considerable molecular heterogeneity was revealed when purified ECP was eluted isocratically from a high-resolution cation exchange resin; the separation, reproducibly achieved, of five components was probably due to hydrophobic interaction with the resin. These polypeptides, which reacted quantitatively with anti-ECP antiserum, showed molecular weights (mol wt) of 19,500 and 16,700 and showed almost identical amino acid compositions. The amino-terminal sequence for one of the polypeptides was (in the standard one-letter code) (R-P-X-Q-F-T-R-A-Q-W-F-A-I-Q-H-I-S-L-N-P-R-R-C-T-I-A-M-R-A-I-N-N-Y-). The biosynthesis of ECP was demonstrated in marrow cells from patients with eosinophilia using labeling with (14C)-leucine, followed by immunoprecipitation with anti-ECP, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography for visualization of labeled ECP. Biosynthesis was demonstrated of mol wt 22,000 ECP, which may represent precursor ECP, since with time some of it was processed into ECP with a mol wt of 18,000 to 19,000. Monensin, a proton ionophore, blocked the processing of mol wt 22,000 ECP. This study shows that ECP consists of a family of similar polypeptides. These may, however, have different biological activities.

Amino Acid Sequence↗
PubMed1985

Facial palsy.

Explore the source record for details and available documents.

Erythema↗
PubMed1985

The pathogenesis of eosinophilic endomyocardial disease in patients with carcinomas of the lung.

Studies were done on a patient with a carcinoma of the lung induced by hypereosinophilia who was thought to be at risk from developing eosinophilic endomyocardial disease to see whether the development of heart disease could be related to abnormalities in the morphology or kinetics of blood eosinophils. The patient was a 61-year-old man who had a partial resection of a squamous cell bronchial carcinoma of anaplastic large cell type which has spread locally. Seven months later, he developed a blood eosinophil count of 33.9 x 10(9)/1. There were only transient responses to treatment with steroids and tumor irradiation, and he died 15 weeks later. Up to 3 x 10(9)/1 blood eosinophils were degranulated, correlating with serum levels of eosinophil cationic protein. The blood half-life of 111indium-labeled eosinophils was prolonged to 53 h, but their distribution was normal. Although an unsuccessful search was made during life for the development of endomyocardial damage, at postmortem the left ventricle had features of eosinophilic endomyocardial disease in the acute necrotic stage. Among 13 other reported patients with carcinoma of the lung and hypereosinophilia, three also had endomyocardial disease or myocardial lesions. These findings confirm the suggestion that the presence in the blood of greater than 1 x 10(9)/1 degranulated eosinophils can be used to predict the development of eosinophilic endomyocardial disease before it becomes apparent clinically, and they also add weight to the hypothesis that blood eosinophil degranulation causes this complication of hypereosinophilic states.

Blood Proteins↗
PubMed1985

Production, characteristics and mode of action of hemopoietic growth inhibitors in myeloid leukemias.

The best characterized hemopoietic growth inhibitors in myeloid leukemias are leukemia associated inhibitor (LAI) and leukemia inhibitory activity (LIA). Both are normal cell products overproduced in leukemia. LIA is identical with acid isoferritins and LAI is not identical with LIA. They act in different ways to inhibit normal stem cell growth. The overproduction of these putative normal regulators may explain the suppression of normal hemopoiesis typical of myeloid leukemias. Modulation of the production and the action of LAI and LIA may have potential therapeutic value in leukemia.

Colony-Forming Units Assay↗
PubMed1985

Tick-borne spirochetes as a cause of facial palsy.

Twenty consecutive patients visiting an otolaryngological department in Sweden with a facial palsy were investigated for serological signs of tick-borne spirochete infection. Four patients showed serological evidence of and had a medical history compatible with a tick-borne spirochetosis. Spinal fluid analyses were performed in 3 of these patients and showed elevated specific antispirochetal antibody titres and an increase in mononuclear cells. The importance of a correct diagnosis and of antibiotic therapy in patients with spirochete-induced facial palsy is emphasized.

Adolescent↗
PubMed1985

Mechanisms for adherence of eosinophils to an antibody-coated surface.

Eosinophils may act by degranulation after attachment to a surface. As the mechanisms of adherence are not understood, we have investigated the dependency on Fc(IgG) receptors and other mechanisms by studying the adherence of human eosinophils to albumin-Sepharose beads coated with either specific rabbit IgG antibody, F(ab')2 antibody fragments or serum under different conditions. Adherence to Sephadex beads and albumin-coated microtitration plates was also investigated. 50% of the eosinophils adhered spontaneously to all 3 different surfaces not coated with the antibody, whereas only 25% of neutrophils and less than 10% of mononuclear cells adhered. A small but significant increase in adherence to albumin-Sepharose or albumin-coated plastic occurred after addition of the IgG-antibody, but not after addition of F(ab')2 fragments, indicating that the Fc region was responsible for some increase in adherence. Incubation of eosinophils with IgG-Fc fragments prevented the additional antibody-mediated adherence. As Fc receptor-negative eosinophils adhered almost as well as Fc receptor-positive cells, it appears that the Fc receptors are of minor importance and instead, a nonspecific adherence mechanism, possibly unique for the eosinophil, seems to be the most important in eosinophil adherence to antibody-coated surfaces.

Animals↗
PubMed1985

Combinations of interferon-gamma and retinoic acid or 1 alpha, 25-dihydroxycholecalciferol induce differentiation of the human monoblast leukemia cell line U-937.

The monoblastlike leukemia cell line, U-937, is induced to differentiate into monocytelike cells by incubation with 200-500 U/ml of recombinant human immune interferon (IFN-gamma) judging from capacity to reduce nitroblue tetrazolium. At least an additive differentiation-inducing effect was found between IFN-gamma and 1-100 nM retinoic acid (RA). A marked synergistic differentiation-inducing effect was found between IFN-gamma and 0.1-1.0 nM 1 alpha,25-dihydroxycholecalciferol (1,25[OH]2D3). It is also shown that U-937 can be primed for differentiation by treatment for approximately one day with 1,25(OH)2D3 followed by exposure to IFN-gamma. Priming of these cells does not depend on the normal rate of RNA synthesis, as it occurs even better in the presence of cordycepin, suggesting that a decrease in RNA synthesis favors IFN-induced differentiation. Actually, the addition of cordycepin during initial incubation with IFN increased the subsequent response to IFN-gamma (and also to RA and 1,25[OH]2D3). These results, indicating that combinations of IFN-gamma and either RA or 1,25(OH)2D3 induce differentiation of U-937, may be of importance in combination biotherapy of leukemia.

Calcitriol↗
PubMed1985

Clinical manifestations of erythema chronicum migrans Afzelius in 161 patients. A comparison with Lyme disease.

Clinical symptoms were studied in 161 consecutive patients with erythema chronicum migrans Afzelius and in a follow-up study signs of late manifestations were investigated. General symptoms such as headache, fever, myalgia and/or arthralgia were found in about half of the patients with a disease duration of less than or equal to 3 weeks. Three patients had coexisting lymphadenosis benigna cutis. Two untreated patients developed meningitis/meningoradiculitis and one untreated patient arthritis. The importance of a sufficient antibiotic therapy to prevent late manifestations is stressed. Although there are many similarities between erythema chronicum migrans Afzelius and Lyme disease, the results of the present study also point to differences. Multiple skin lesions, pronounced general symptoms, laboratory abnormalities and major symptoms from the joints were less common in patients with erythema chronicum migrans Afzelius than reported in patients with Lyme disease, but a prolonged course of the skin eruption was more common.

Adolescent↗
PubMed1985

Purification of eosinophil peroxidase and studies of biosynthesis and processing in human marrow cells.

Human eosinophil peroxidase (EPO) was purified from leukocytes obtained from a patient with hypereosinophilia. EPO was extracted from the granule fraction using 0.2 mol/L sodium acetate pH 4.0, and the extract was subjected to gel chromatography on Sephadex G-75 and ion exchange chromatography on Biorex 70. The mol wt calculated from gel chromatography was approximately 50,000. However, under reducing and denaturing conditions, polyacrylamide gel electrophoresis revealed two subunits with mol wt of 50,000 and 15,000. The biosynthesis of EPO was studied in marrow cells from patients with eosinophilia using labeling with (14C)-leucine, followed by immunoprecipitation with anti-EPO, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and fluorography for visualization of labeled EPO. Biosynthesis of an Mr 53,000 subunit was demonstrated. Biosynthetic labeling of the Mr 15,000 subunit was not demonstrated. A labeled Mr 25,000 chain was detected and may represent a degradation product or a chain that, after further modification, produces the Mr 15,000 subunit. Labeling was also detected in two polypeptides with mol wt of 78,000 and 72,000. These forms of EPO seem to represent precursor polypeptides subjected to proteolytic processing in a similar manner as has been reported for myeloperoxidase (MPO). However, Monensin, a proton ionophore, which blocks the processing of MPO, did not inhibit processing of EPO, indicating separate mechanisms by which MPO and EPO are directed to granules.

Antibodies, Monoclonal↗