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Biomedical subjects

I Olsson

Publications and source records attributed to I Olsson.

At least 73 records · Page 4Linked to original sources
PubMed1991

Epidemiology of absence epilepsy. II. Typical absences in children with encephalopathies.

A population-based study of absence epilepsy in Swedish children, aged 0-15 years, comprised cases selected on the basis of EEG criteria. Absence epilepsy was found in 119 of the 134 children with 3 Hz spike-and-wave discharges, and 12 of these 119 (10.1%) had typical absences in addition to other generalized seizures and slow irregular spike-and-wave activity on the EEG. The mean annual incidence of this type of absence epilepsy was 0.7/100,000. The median age at onset of absences was 6 years. Eight of the 12 patients had neurological abnormalities and/or severe mental retardation. The patients constitute a heterogeneous group of encephalopathies. They may have a genetic predisposition for absence epilepsy, causing it to appear during the course of a more severe, encephalopathy related, type of epilepsy.

Adolescent↗
PubMed1991

On the binding of tumor necrosis factor (TNF) to heparin and the release in vivo of the TNF-binding protein I by heparin.

Tumor necrosis factor (TNF), a protein released by activated macrophages, is a central mediator of the host response to infection and inflammation. The TNF-binding protein I (TNF-BP-I) is a soluble fragment of the p60 transmembrane TNF receptor and an antagonist to TNF. The level of serum TNF-BP-I was found to be increased in patients with renal insufficiency as a result of a decrease in the glomerular filtration rate. During hemodialysis of patients with renal failure there was a rapid but transient increase in serum TNF-BP-I. This increase was found to be caused by heparin given before dialysis and a similar dose-dependent response to heparin was observed also in healthy individuals. The finding of a repeated release of TNF-BP-I into the circulation with intermittent injections of heparin indicates that TNF-BP-I is present both in a storage pool and in a circulating pool. The mechanism for the heparin-mediated release of TNF-BP-I was not explained; TNF-BP did not show affinity for heparin. On the other hand, TNF was found to have affinity for heparin and it could also be dissociated from heparin by TNF-BP-I. It is suggested that heparin-like molecules of the extracellular matrix can retain TNF in physical proximity with target cells and restrict the actions of TNF and protect against systemic harmful manifestations.

Carrier Proteins↗
PubMed1991

Comparison of four different serological methods for detection of antibodies to Borrelia burgdorferi in erythema migrans.

Three different enzyme-linked immunosorbent assays (ELISA) and Western blot were compared in regard to the detection of antibodies to Borrelia burgdorferi in sera from 100 patients with erythema migrans and from 100 controls. For IgG detection, a commercial indirect ELISA kit with flagellum antigen (flagellum ELISA) was significantly more sensitive than the routinely-used indirect ELISA with sonicated whole-cell antigen (sonicate ELISA) (p = 0.008). The difference in positivity in the IgM test was of borderline significance (p = 0.058). An IgM antibody-capture ELISA with sonicated whole-cell antigen (capture ELISA) was significantly more sensitive than either the IgM sonicate ELISA (p less than 0.001) or IgM flagellum ELISA (p less than 0.001). With the Western blot pattern chosen as the criterion for positivity, IgM Western blot was at least equal to IgM capture ELISA in terms of the number of positive erythema migrans sera, but a frequent discrepancy between these two tests was noted as to positivity in individual sera. IgG Western blot was considered to be of less value for the diagnosis of current disease due to a high occurrence of positivity among controls.

Adolescent↗
PubMed1990

Biosynthesis and processing of cathepsin G and neutrophil elastase in the leukemic myeloid cell line U-937.

The processing of the neutral proteases cathepsin G and neutrophil elastase, normally synthesized in myeloid precursor cells and stored in azurophil granules, were investigated by biosynthetic labeling with 14C-leucine of the monoblastic cell line U-937. The proteases were precipitated with specific antibodies and the immunoprecipitates were analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) followed by fluorography. The transfer to lysosomes of newly synthesized proteases was demonstrated in pulse-chase labeling experiments followed by centrifugation of cell homogenates in a Percoll gradient. The presence of a closely spaced polypeptide band-doublet at intermediate gradient density suggested cleavage of the specific aminoterminal pro dipeptide extension before storage in lysosomes. The molecular heterogeneity observed for cathepsin G and neutrophil elastase seemed to be due to modifications occurring after sorting into lysosomes, most likely because of C-terminal processing. Modifications of the secreted enzymes were not detectable by SDS-PAGE. In contrast to other lysosomal enzymes, no phosphorylation was demonstrated. Newly synthesized cathepsin G and neutrophil elastase rapidly became resistant to endoglycosidase H, indicating transport through the medial and trans cisternae of the Golgi complex and conversion to "complex" oligosaccharide side chains. This conversion was inhibited by an agent swainsonine, but translocation from the Golgi complex and secretion were unaffected. The processing described may play a role in activation of the proteases.

Acetylglucosaminidase↗
PubMed1990

Modulation of the constitutive gene expression of the 55 kD tumor necrosis factor receptor in hematopoietic cells.

The expression of the 55 kD human tumor necrosis factor (TNF) receptor gene was investigated. By use of a 1.2 kb cDNA we demonstrated a constitutive expression of a single 2.3 kb transcript in cell lines and fresh blood cells. The TNF receptor gene expression was not affected by phorbol esters, dibutyryl cAMP (dbcAMP), interleukin-1 (IL-1), interferon-gamma (IFN-gamma) or by TNF, agents known to modulate functional TNF receptors. The phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX) showed a dose dependent inhibition of the TNF receptor gene expression. This inhibition is not mediated by cAMP, since neither dbcAMP nor forskolin had any effects on the expression of the 55 kD receptor gene. The results suggest that the effects of phorbol diesters, IL-1, IFN-gamma, TNF and dbcAMP previously observed on binding of TNF to cells are limited to posttranscriptional regulation of the 55 kD TNF receptor.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Correlation between spontaneous oscillations of cytosolic free Ca2+ and tumor necrosis factor-induced degranulation in adherent human neutrophils.

By using a hemolytic plaque assay to detect release of lactoferrin and myeloperoxidase, tumor necrosis factor (TNF) was shown previously to induce secretion of these granule proteins from single adherent neutrophils. Secretion was inhibited by loading neutrophils with calcium chelators, indicating a crucial role of cytosolic free [Ca2+] in the signal transduction mechanism of TNF. In the present study, using a microfluorometer technique to follow changes in the cytosolic free [Ca2+] in single adherent neutrophils, we were not able to detect any TNF-induced [Ca2+] transients. However, these adherent cells exhibited spontaneous oscillations of their cytosolic free [Ca2+], as previously reported (Jaconi, M.E.E., Rivest, R.W., Schlegel, W., Wollheim, C.B., Pittet, D., and Lew, P.D. (1988) J. Biol. Chem. 263, 10557-10560). A close correlation was found between a reduced oscillatory activity of cytosolic free [Ca2+] and a reduced ability of TNF to induce degranulation, by reducing the extracellular [Ca2+] or loading the cells with a calcium chelator (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). In addition, when the cells were incubated at 37 degrees C for 3 h there was a parallel decline in the spontaneous oscillatory activity of cytosolic free [Ca2+] and TNF-induced secretion of lactoferrin. Control experiments showed that phorbol 12-myristate 13-acetate-induced secretion was not affected under the same conditions, indicating that the secretory process per se was not disturbed. We conclude that TNF by itself does not give rise to any changes of the cytosolic free [Ca2+] but that the spontaneous oscillatory activity of cytosolic free [Ca2+] in adherent neutrophils is necessary for TNF-induced degranulation.

Calcium↗
PubMed1990

Cytokine and non-cytokine differentiating agents for myeloid leukemic cells.

Existing data suggest that normal maturation can sometimes be re-established in leukemia. A number of differentiation-inducing substances have been reported; these include retinoic acid, vitamin D3 and cytokines such as differentiation-inducing factor, tumor necrosis factor and lymphotoxin. Different agents obviously act by separate mechanisms to provide terminal maturation.

Binding Sites↗
PubMed1990

Tumor associated myelopoiesis inhibiting factors.

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 to acid isoferritin and LAI is not identical to LIA. They act in different ways to inhibit normal stem cell growth. The over-production 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 therefore have potential therapeutic value in leukemia.

Bone Marrow↗
PubMed1990

Infusion of tumor necrosis factor (TNF) causes an increase in circulating TNF-binding protein in humans.

Serum samples from cancer patients receiving intravenous infusions of recombinant tumor necrosis factor (rTNF) and recombinant interferon-gamma (rIFN-gamma) were analyzed for TNF and the TNF-binding protein (TNF-BP). TNF-BP is a soluble fragment of the transmembrane TNF receptor with antagonistic effects to TNF and is released by proteolytic cleavage of the receptor. During a 60-min infusion of rTNF, peak serum levels of rTNF were observed after 30 to 60 min and a transient increase of circulating TNF-BP was observed with peak levels between 30 and 120 min. Injection of IFN-gamma alone did not affect the levels of TNF and TNF-BP. Thus administration of rTNF leads to release into the circulation of TNF-BP, which may modulate both systemic and local effects of TNF and influence its therapeutic efficacy.

Carrier Proteins↗
PubMed1990

Tumor necrosis factor-induced degranulation in adherent human neutrophils is dependent on CD11b/CD18-integrin-triggered oscillations of cytosolic free Ca2+.

We have recently been able to correlate closely the "spontaneous" oscillatory activity of cytosolic free Ca2+ in adherent human neutrophils with the ability of tumor necrosis factor (TNF) to induce secretion of granule proteins from these cells. In the present work we show with a single-cell technique that preincubation of human neutrophils with antibodies to CD18, the common beta chain of leukocyte adhesion proteins, inhibits TNF-induced secretion of lactoferrin in a time- and concentration-dependent manner. Similar effects of CD18 antibodies were found on chemotactic factor (fMet-Leu-Phe)- but not on phorbol 12-myristate 13-acetate-induced secretion, suggesting that cell-surface-receptor-mediated secretion is dependent on integrin-associated signals. Similarly, antibodies to CD11b (alpha chain of macrophage 1) also inhibited TNF- and fMet-Leu-Phe- but not phorbol 12-myristate 13-acetate-stimulated release of lactoferrin. Antibodies to CD11a (alpha chain of lymphocyte function-associated antigen 1) or CD11c (alpha chain of p150,95) had only a minimal effect on agonist-induced secretion. Data obtained in several laboratories, including our own, made us suspect that integrin interaction with the surface is responsible for the oscillatory activity of cytosolic free Ca2+ in adherent cells. Indeed, preincubation with antibodies to either CD18 or CD11b, but not to CD11c, inhibited the oscillations of cytosolic free Ca2+ in adherent neutrophils. This inhibitory effect was evident both as a reduction of the number of responding cells and as a reduction of the oscillatory activity in the cells. In conclusion, the oscillatory activity of cytosolic free Ca2+ in adherent neutrophils is mediated through the CD18/CD11b integrins. The generation of this Ca2+ signal may explain how adherence, by way of the integrins, changes the functional properties of the cell and enables TNF to induce secretion.

Antibodies, Monoclonal↗
PubMed1990

Molecular cloning and expression of human and rat tumor necrosis factor receptor chain (p60) and its soluble derivative, tumor necrosis factor-binding protein.

Tumor necrosis factor-alpha (TNF-alpha), a protein released by activated macrophages, is involved in a wide variety of human diseases including septic shock, cachexia, and chronic inflammation. TNF binding protein (TNF-BP), a glycoprotein with high affinity to TNF-alpha isolated from urine, acts as an inhibitor of TNF-alpha by competing with the cell-surface TNF receptor. We report here the partial amino acid sequencing of human TNF-BP as well as the isolation, sequence, and expression of cDNA clones encoding a human and rat TNF receptor. The calculated Mr of the mature human and rat TNF receptor chains is 47,526 and 48,072, respectively. The extracellular ligand binding domain represents the soluble TNF-BP which is released by proteolytic cleavage. TNF-BP contains 24 cysteine residues and three potential N-glycosylation sites and shows sequence homology to the extracellular portions of TNF-R p80 chain and nerve growth factor receptor. Transfection of the human TNF receptor cDNA into mammalian cells resulted in increased binding capacity for TNF-alpha and increased reactivity with a monoclonal antibody directed against the human TNF receptor chain p60. When a stop codon was introduced into the cDNA at the site corresponding to the carboxyl terminus of TNF-BP, transfected cells secreted a protein that reacted with antibodies raised against natural TNF-BP.

Amino Acid Sequence↗
PubMed1990

Isoenzyme pattern of lactate dehydrogenase associated with human prostasomes.

Lactate dehydrogenase (LD, EC 1.1.1.27) activity was determined in serum, seminal plasma and prostasomes from normozoospermic and azoospermic (due to vasectomy) men. A 10-fold higher activity was noted in seminal plasma as compared with serum. LD activity was enriched in prostasomes although a fairly large amount of enzyme activity seemed to be free in solution. Isoenzymes LD1, LD2 and LD3, present in prostasomes in about equal amounts, gave rise to a characteristic isoenzyme pattern that differed distinctly from that found in seminal plasma of normozoospermic men, the main isoenzyme of which was LD-X.

Body Fluids↗
PubMed1990

Characterization in vitro of a human tumor necrosis factor-binding protein. A soluble form of a tumor necrosis factor receptor.

Tumor necrosis factor (TNF) is a pleiotropic mediator of inflammatory responses. A cysteine-rich, highly glycosylated 30-kD TNF-binding protein (TNF-BP) purified from urine may have a role in regulation because it protects in vitro against the biological effects of TNF. The cytotoxic effect of TNF on the fibrosarcoma cell line WEHI 164 was inhibited by 50% at a 10-fold excess of TNF-BP. The binding of TNF to the receptor was partially reversed after the addition of TNF-BP. Results from biosynthetic labeling of cells with 35S-cysteine followed by immunoprecipitation with anti-TNF-BP indicated that TNF-BP is formed and released at the cell surface by cleavage because no corresponding cellular polypeptide was observed. A cellular 60-kD polypeptide, which was immunoprecipitated with anti-TNF-BP, may correspond to the transmembrane TNF-receptor molecule and be the precursor of TNF-BP. Thus, TNF-BP appears to be a soluble form of a transmembrane TNF-receptor. Moreover our results demonstrate that the production of TNF-BP is increased when the TNF receptor is downregulated in cells by treatment with TNF or by activation of protein kinase C with phorbol esters. TNF-BP may be an important agent that blocks harmful effects of TNF, and, therefore, useful in clinical applications.

Cell Survival↗
PubMed1990

Nucleic acid association to human prostasomes.

Human prostasomes isolated from seminal plasma were subjected to phenol extraction and then to absorbance (A) measurements at 260 nm (A260) and 280 nm (A280). The A260/A280 ratio was about 2 for prostasome extract and lower for seminal plasma extract, indicative of the presence of nucleic acid. The ratio of nucleic acid to protein in prostasomes was about 1:100, and the ratio in seminal plasma was 1:1,000. Hence nucleic acid is enriched in prostasomes (compared to seminal plasma of 10). Treatment of prostasome samples with 2% sodium dodecyl sulfate resulted in an efficient dissociation of nucleic acid from prostasomes as demonstrated by electrophoresis. The association of nucleic acids of various sizes (range; 200 to 20,000 base pairs) to prostasome membranes was most probably genuine and not the result of contamination from spermatozoa, erythrocytes, leukocytes, or bacteria. The results of experiments employing nucleic acid-degrading enzymes favored the concept that double-stranded DNA but not RNA is present at the prostasome membrane surface.

DNA↗
PubMed1989

Effect of tumor necrosis factor and granulocyte/macrophage colony-stimulating factor on neutrophil degranulation.

Both TNF and and granulocyte/macrophage CSF (GM-CSF) can activate neutrophils. The aim of this work was to determine the effect of these cytokines on neutrophil degranulation. The secretion of lactoferrin of secondary granules and myeloperoxidase (MPO) of primary granules from single adherent human neutrophils was assayed by use of a reverse hemolytic plaque assay. Both rTNF and rGM-CSF caused secretion of lactoferrin in a dose-dependent manner. Both agents also caused secretion of MPO, but only in the presence of cytochalasin B. Preincubation with pertussis toxin inhibited rGM-CSF-induced secretion of both lactoferrin and MPO. rTNF-induced MPO secretion was also blocked by pertussis toxin, whereas lactoferrin secretion was only slightly affected. Neither rTNF nor rGM-CSF caused any detectable changes in the concentration of cytoplasmic free Ca2+ in fura-2-loaded cells. However, when neutrophils were loaded with increasing concentrations of quin-2 to buffer any local, not detectable, changes in the concentration of cytoplasmic Ca2+, both rTNF- and rGM-CSF-induced secretion of lactoferrin and MPO were almost totally abolished at a relatively low quin-2 concentration. These results suggest a role of a regulatory G-protein and minute local changes in the concentration of cytoplasmic Ca2+ in TNF- and GM-CSF-induced neutrophil degranulation.

Buffers↗
PubMed1989

Isolation and characterization of a tumor necrosis factor binding protein from urine.

Tumor necrosis factor (TNF)/cachectin can produce both beneficial and harmful manifestations. Mechanisms may operate to counteract potentially harmful effects such as shock and cachexia. The TNF binding protein (TNF-BP), which is found at increased levels in serum and urine of patients with chronic renal failure, may play such a role. TNF-BP was purified 1,000,000-fold to homogeneity from urine of patients with chronic renal failure by use of ion exchange chromatography, affinity chromatography on TNF-Sepharose and reverse phase chromatography. The purified protein contained only one chain with an apparent Mr on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of 30,000. The aminoterminal amino acid sequence D-S-V-X-P-Q-G-K-Y-I-H-P-Q-V-N-S-I-X-K-T revealed no significant homologies with previously described protein sequences. TNF-BP may act as a regulator of the bioactivities of TNF/cachectin.

Amino Acid Sequence↗
PubMed1989

Characterization of the receptor for lymphotoxin; a spontaneous internalization without recycling and ligand-induced downregulation in HL-60 cells.

The receptor system for lymphotoxin (LT) was investigated by use of the human promyelocytic HL-60 cell line. Utilizing subcellular fractionation, internalization of cell surface bound recombinant LT (rLT) and transfer to lysosomes followed by degradation was demonstrated. Binding of rLT to its cell surface receptor induced a downregulation of the receptor which was persistent for at least 6 h. Downregulation of the receptors from the cell surface by activation of protein kinase C with the diacylglycerol OAG was completely reversible but the recovery of the binding capacity was dependent on protein synthesis as it was inhibited by cycloheximide. Treatment with cycloheximide alone resulted in a loss of binding capacity with a half life of approximately 2 h, suggesting a spontaneous consumption of receptors. Affinity cross-linking revealed three ligand-receptor complexes with Mr of 85, 105 and 125 kDa. Because of a strong tendency for ligand polymerization these results suggest oligomer binding of the ligand to a single receptor molecule with an apparent Mr of 70 kDa. N-linked glycosylation constituted 4 to 5 kDa of the total molecular weight. In conclusion, we demonstrated a spontaneous internalization of the receptor for LT without recycling, and that ligand binding resulted in an irreversible downregulation of the receptor.

Asparagine↗