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Biomedical subjects

I Olsson

Publications and source records attributed to I Olsson.

At least 55 records · Page 3Linked to original sources
PubMed1994

Adherence of neutrophils induces release of soluble tumor necrosis factor receptor forms.

TNF is a potent activator of neutrophil granulocytes which acts via two cell surface receptors: the p55-TNF receptor (TNF-R55) and the p75-TNF receptor (TNF-R75). The extracellular region of the receptors can be released by proteolytic cleavage and form soluble TNF-binding proteins, TNF-R55-BP and TNF-R75-BP, respectively. The phorbol ester PMA, the chemotactic peptide FMLP, and TNF were all found to induce release of TNF-R55-BP and TNF-R75-BP from neutrophils in suspension in a time- and dose-dependent manner as measured by ELISA. Exposure of neutrophils to 10 ng/ml of PMA for 60 min resulted in release of 900 pg of TNF-R55-BP and 350 pg of TNF-R75-BP per 5 million cells, corresponding to approximately 4800 receptors per cell. In addition, adherence by itself of neutrophils to fibrinogen-coated culture plates and other surfaces resulted in a release of TNF-R55-BP of the same magnitude as seen in response of neutrophils in suspension to 1 nM TNF, whereas the release of TNF-R75-BP was less pronounced. The protein kinase C inhibitors staurosporin and calphostin C inhibited both the TNF-, PMA-, and adherence-induced release of soluble forms of TNFRs. Ab to the common beta-chain of the leukocyte integrins (CD18) did not affect adherence-induced TNF-R55-BP release, indicating that non-integrin-dependent mechanisms are involved in receptor cleavage. However, cross-linking of anti-CD18 Ab (IB4) with a Fab2 fragment resulted in a decrease of specific binding of 125I-TNF to neutrophils indicating that the leukocyte integrins can modulate TNFR expression on neutrophils. Thus, adherence to a biological surface, without additional stimuli, induces release of soluble TNFR form from neutrophils. TNFR expression can be modulated by protein kinase C as well as both leukocyte integrins and non-integrin-dependent adherence mechanisms.

Antigens, CD↗
PubMed1994

Processing and intracellular transport of cathepsin G and neutrophil elastase in the leukemic myeloid cell line U-937-modulation by brefeldin A, ammonium chloride, and monensin.

The effects of brefeldin A, monensin, and the weak base NH4Cl on the biosynthesis and processing of cathepsin G and neutrophil elastase of myeloid cells were investigated. Monoblast-like U-937 cells were biosynthetically labeled with [35S]methionine, followed by subcellular fractionation, immunoprecipitation, and analysis by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and fluorography. Brefeldin A inhibited proteolytic processing, intracellular transport, and secretion. The effects were reversible inasmuch as removal of brefeldin A resulted in a normal pattern of processing and transfer to high-density organelles, corresponding to lysosomes, and restitution of constitutive secretion of precursor forms. Both cathepsin G and neutrophil elastase acquired resistance to endoglycosidase-H, suggesting that conversion to complex oligosaccharide side chains also occurs in the presence of brefeldin A. Monensin and NH4Cl inhibited final proteolytic processing, indicating either that acidification is necessary for directing cathepsin G and neutrophil elastase to lysosomal-like organelles or that the protease(s) responsible for processing requires an acid pH. We conclude that pH-dependent proteolytic processing of cathepsin G and neutrophil elastase occurs in post-Golgi structures and that transfer to lysosomes or an immediately prelysosomal compartment is mandatory for complete processing.

Ammonium Chloride↗
PubMed1994

Arylsulfatase B is present in crystalloid-containing granules of human eosinophil granulocytes.

Eosinophil granulocytes are characterized by large crystalloid-containing granules whose major contents of highly cationic proteins may play a role in allergic reactions and parasitic infections. Human eosinophils are also rich in arylsulfatase B whose enzymatic activity is localized to a population of small type cytoplasmic granules and used as a marker for such organelles. We utilized immunoelectron microscopy to investigate its subcellular distribution in human eosinophils. The arylsulfatase B antigen was found to be concentrated to both the crystalloid core and the matrix of crystalloid-containing granules as well as in small type granules. Therefore arylsulfatase seems to be present primarily in crystalloid-containing granules in a possibly inactive form (but detected by antibodies) that is converted to an enzymatically active form, e.g. during secretion and formation of small type granules which may derive from the former granules.

Chondro-4-Sulfatase↗
PubMed1994

No association with HLA class II alleles in Swedish patients with cutaneous manifestations of Lyme borreliosis.

The possibility of an association between manifestations of Lyme borreliosis and HLA class II alleles has been investigated with varying results. In the present study, we used genomic typing techniques to determine the DR, DQ and DP allele frequencies in 29 patients with erythema migrans and 36 patients with acrodermatitis chronica atrophicans. We did not find a significant deviation from controls in the distribution of the HLA class II alleles in any of these disease manifestations, nor in the subgroup of 8 patients with acrodermatitis chronica atrophicans and long-standing arthritis. With the additional information obtained by the typing techniques used, our results are thus in accord with those studies where no association between the development of the late disease manifestation acrodermatitis chronica atrophicans and HLA class II alleles has been found.

Acrodermatitis↗
PubMed1994

Changes in Borrelia burgdorferi-specific serum IgG antibody levels in patients treated for acrodermatitis chronica atrophicans.

The kinetics of Borrelia burgdorferi-specific serum IgG antibody values in 74 patients treated for acrodermatitis chronica atrophicans was analysed by means of enzyme-linked immunosorbent assay. At the last clinical control, there had been no clinical signs of active infection. The serological follow-up time ranged from 12 months to 5 1/2 years (median 2 years and 1 month). In 68 (92%) of the 74 patients, a significant decrease of the specific antibody values was found within 3 years after the initiation of therapy. In 53 (72%) of the patients, this decrease was found within 15 months. Most of the patients remained seropositive during the follow-up period. The results show that a significant decline of the levels of serum IgG antibodies to Borrelia burgdorferi can be expected in the majority of patients who do not exhibit clinical evidence of persistent infection after antibiotic treatment of acrodermatitis chronica atrophicans.

Acrodermatitis↗
PubMed1994

Mechanisms involved in the processing of the p55 and the p75 tumor necrosis factor (TNF) receptors to soluble receptor forms.

The two tumor necrosis factor (TNF) receptors (TNF-R55 and TNF-R75) can release soluble TNF-binding proteins (TNF-R55-BP and TNF-R75-BP) by proteolytic cleavage. The proteolytic processing of the TNF receptors was investigated in monoblastic THP-1 and promyelocytic HL-60-10 leukemic cell lines. The release of soluble forms of both receptors was rapidly stimulated by staurosporine-sensitive protein kinase C activation by phorbol myristate acetate (PMA) and more slowly stimulated by TNF. No receptor release was seen below a temperature of 16 degrees C. NH4Cl (10 mmol/liter) and monensin (1 mumol/liter), known to increase intracellular pH, inhibited to some extent PMA- and TNF-induced release of both TNF-R55-BP and TNF-R75-BP. The inhibitory effect of monensin might be explained by a diminished translocation of newly synthesized receptor to the plasma membrane. The weak inhibitory effect of NH4Cl on PMA-induced release of soluble receptor forms could be due to effects on a pH-sensitive compartment. PMA-induced down-regulation of receptors was not dependent on acidity as it occurred also in the presence of monensin and NH4Cl when the release of TNF-BPs is partially blocked. Dibutyryl cAMP inhibited the PMA-induced release of TNF-R55-BP but not of TNF-R75-BP in both cell lines investigated. In addition, dibutyryl cAMP alone stimulated the release of both receptors but only in THP-1 cells. Our data show that the generation of soluble forms of both TNF receptors can be regulated by both PKC and PKA.

Alkaloids↗
PubMed1993

Interleukin-1 beta induces interleukin-1 receptor antagonist and tumor necrosis factor binding protein in humans.

Sustained release or high levels of interleukin-1 (IL-1) and/or tumor necrosis factor (TNF), as observed after endotoxin challenge, can produce a variety of toxicities. Naturally occurring inhibitors to IL-1 and TNF, IL-1 receptor antagonist (IL-1ra) and soluble TNF receptor forms, have been detected. These proteins may function to buffer or limit the effects of these cytokines as part of a regulatory network. As part of a clinical trial of recombinant human interleukin-1 beta (rhIL-1 beta), serial plasma samples were obtained from 6 patients with metastatic melanoma treated with 30-min infusions of rhIL-1 beta for 5 consecutive days. The presence of circulating IL-1 receptor antagonist and soluble TNF binding proteins (TNF-R55-BP and TNF-R75-BP) were assessed. A maximum 86-fold increase for IL-1ra, a 7-8-fold increase for TNF-R55-BP, and a 2-3-fold increase for TNF-R75-BP were seen 2-4 h, 1 h, and 4 h, respectively, after rhIL-1 beta infusion. On each day of the treatment, the secretion of IL-1ra and release of TNF-R55-BP was observed, but there was no accumulation above baseline value for IL-1ra before each of the 5 daily infusions. Although there was a steady decrease of the 6-h postinfusion plasma levels for IL-1ra and TNF-R55-BP over the 5 treatment days, no increase of clinical side effects was noted. Two patients had measurable levels of TNF-alpha, but no correlation to TNF-binding proteins was observed. Our data show that early after rhIL-1 beta infusion the induction of IL-1ra secretion, as well as TNF-binding protein release, is observed.

Adult↗
PubMed1993

Subcutaneous sterile water injections for chronic neck and shoulder pain following whiplash injuries.

In many cases of whiplash injury symptoms persist and do not respond to treatment. There is uncontrolled evidence to suggest that intracutaneous injections of sterile water might help. Since that route may be unacceptable to patients the subcutaneous route is used in the randomised trial reported here. 40 patients with whiplash syndrome, mean age 46 years (24-73) were given subcutaneous injections of 0.3-0.5 ml sterile water or saline over tender and trigger points in the neck and shoulder. A maximum of three treatments were given during the first two months of the study and the patients were followed up for 8 months. The accidents had occurred 4-6 years previously. X-ray examinations revealed no traumatic spinal lesions. Neck mobility and pain levels were evaluated by a physiotherapist immediately before and after the first treatment and after 1, 3, and 8 months. After 3 months, the mean total mobility of the cervical spine had increased by 39 degrees in the sterile water group and 6 degrees in the saline group (p < 0.05). Minimum and maximum levels of pain in the weeks just before treatment were evaluated by a visual analogue scale from 0 to 10. After 3 months the minimum pain level had fallen from 2.2 to 1.4 in the sterile water group but was not reduced in the saline group (p < 0.02); the maximum had fallen from 8.1 to 3.8 in the sterile water group and from 8.3 to 7.5 in the saline group (p < 0.001). After 3 months, 19 of 20 patients in the sterile water group assessed their condition as generally improved but only 6 in the saline group felt that they had got better. After 8 months there were still significant differences for minimum pain score and for mobility but not for maximum pain or for self-assessment of improvement.

Adult↗
PubMed1993

Phorbol ester-induced degranulation in adherent human eosinophil granulocytes is dependent on CD11/CD18 leukocyte integrins.

Secretion of unique eosinophil granule constituents may play a role in allergic and parasitic reactions. Therefore we have investigated possible mechanisms for regulation of secretion in eosinophils. A hemolytic plaque assay and an enzyme-linked immunospot (ELISPOT) assay were developed for detection of secreted eosinophil cationic protein (ECP) from single adherent eosinophils. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA) induced release of ECP in a dose-dependent fashion but 4-alpha-PMA, an analogue that does not activate protein kinase C, did not cause degranulation. Staurosporine and K252a, inhibitors of protein kinase C, decreased PMA-induced ECP secretion. Low concentrations of cytochalasin B enhanced PMA-induced secretion but high concentrations had an inhibitory effect. The calcium ionophores A23187 and ionomycin were weaker secretagogues than PMA. Tumor necrosis factor, granulocyte-macrophage colony-stimulating factor, interleukin-3, interleukin-5, N-formylmethionyl-leucyl-phenylalanine, and lipopolysaccharide caused little or no degranulation in adherent eosinophils. Preincubation of eosinophils with antibodies to CD18, the common beta chain of leukocyte adhesion proteins, resulted in inhibition of PMA-induced ECP release from adherent cells. 1,2-Bis(O-aminophenyl)-ethane-ethane-N,N,N',N'-tetraacetic acid (BAPTA), an agent that acts intracellularly by chelation of calcium, also inhibited PMA-mediated ECP release. In conclusion, PMA induces release of ECP from single adherent eosinophils and the effect appears to be mediated via protein kinase C and, in contrast to that in neutrophils, to be dependent on CD11/CD18 leukocyte integrins.

Antibodies↗
PubMed1993

Independent transcriptional and posttranscriptional regulation of the two tumor necrosis factor receptors in promyelocytic HL-60 cells.

Two separate tumor necrosis factor (TNF) receptors of approximately 55 kDa (TNF-R55) and 75 kDa (TNF-R75) have been identified. The role of protein kinase A activation by dibutyryl cAMP (dbcAMP) and of protein kinase C activation with phorbol myristate acetate (PMA) for transcriptional and posttranscriptional regulation of the two receptors was investigated in promyelocytic HL-60 cells. Incubation with dbcAMP or the adenylate cyclase agonist forskolin caused an increase in the level of TNF-R75 mRNA while TNF-R55 mRNA was unaffected. The half-life of transcripts for both TNF-R55 and TNF-R75 was unaffected as judged by disappearance of mRNA after inhibition of transcription with actinomycin D. Thus the transcription of the TNF-R75 gene seemed to be enhanced by activation of protein kinase A. This enhancement was not dependent on de novo protein synthesis. Incubation with PMA did not affect the mRNA level of any of the TNF receptors. Both TNF-R55 and TNF-R75 mRNA showed a prolonged half-life after incubation with the inhibitor of protein synthesis cycloheximide, indicating superinduction of the genes. Our results demonstrate that the two TNF receptors can be regulated differently at the transcriptional level and that both transcriptional and posttranscriptional regulation occurs.

Base Sequence↗
PubMed1992

The receptors for regulatory molecules of hematopoiesis.

Proliferation and differentiation of hematopoietic cells are controlled by pleiotropic regulatory molecules. While the sequences of these factors are not related, their membrane receptors are restricted to two gene families with homologous domains. The members of the hematopoietic (or cytokine) receptor family (for erythropoietin, interleukins-2, -3, -4, -6 andu-7, granulocyte-macrophage and granulocyte colony-stimulating factor) are composed of multiple subunits necessary for high-affinity binding and cell signalling. Signal transducing mechanisms are largely unknown. The occurrence of variant signal transducers in different tissues could explain the pleiotropy of these regulatory molecules. Members of the receptor tyrosine kinase family bind dimeric forms of macrophage colony-stimulating factor, stem cell factor and platelet-derived growth factor leading to kinase activation and phosphorylation of many substrates involved in production of second messengers. Soluble forms (binding proteins) exist for members of both families. These may be proteolytic cleavage products of transmembrane receptors or naturally secreted products. Such binding proteins can potentially function as inhibitors in feedback regulation and in protection and transport of cytokines and would provide a rational therapy when cytokines are produced in excess. Knowledge of signal transduction mechanisms and of the three-dimensional structure of ligands and receptors can lead to the design of drugs with cell-specific effects.

Animals↗
PubMed1992

Roxithromycin in Lyme borreliosis: discrepant results of an in vitro and in vivo animal susceptibility study and a clinical trial in patients with erythema migrans.

A new semisynthetic macrolide roxithromycin was evaluated for its potential use in the treatment of Lyme borreliosis. Using a macro-dilution broth technique, Borrelia burgdorferi was shown to be susceptible to roxithromycin with a minimal bactericidal concentration (MBC) of 0.06-0.25 microgram/ml. A systemic B. burgdorferi infection was established in gerbils; a dosage of greater than or equal to 25 mg/kg/day roxithromycin for 10 days eliminated the infection. A single blind, randomized multicenter study was performed to evaluate the efficacy of roxithromycin 150 mg b.i.d. versus phenoxymethyl-penicillin 1 g b.i.d. for 10 days in patients with uncomplicated erythema migrans. The study was interrupted when 19 patients had enrolled because of five treatment failures. All 5 patients had received roxithromycin; three patients had persisting or recurrent erythema migrans, one developed a secondary erythema migrans-like lesion and severe arthralgia and one developed neuroborreliosis. B. burgdorferi was isolated from skin biopsies after roxithromycin therapy from two patients with persistent erythema migrans and both isolates were still highly susceptible to roxithromycin (MBC = 0.03 microgram/ml). No treatment failures were seen in 10 patients treated with phenoxymethyl-penicillin. Roxithromycin is thus not recommended for treatment of Lyme borreliosis.

Adult↗
PubMed1992

Involvement of an Asn/Val cleavage site in the production of a soluble form of a human tumor necrosis factor (TNF) receptor. Site-directed mutagenesis of a putative cleavage site in the p55 TNF receptor chain.

Soluble forms of receptors for tumor necrosis factor (TNF) might be important for regulating the actions of TNF. Site-directed in vitro mutagenesis was employed to examine the processing of the p55 tumor necrosis factor receptor chain (TNF-R55) into soluble TNF-binding protein (TNF-R55-BP). An Asn/Val sequence close to the transmembrane region in TNF-R55 was indicated as a putative cleavage site for proteolytic processing. By mutagenesis, Asn and Val were replaced with Gly and Ala, respectively. Expression in Chinese hamster ovary (CHO) cells resulted in identical binding of ligand to mutated receptors as compared to receptors not subjected to mutagenesis. Turnover rates of receptors as judged by disappearance of TNF binding capacity after inhibition of de novo protein synthesis and downregulation in response to incubation with phorbol esters were also identical between wild-type and mutated receptors. However, mutations of the cleavage site resulted in a decreased spontaneous and phorbol ester-induced release of soluble receptor (TNF-R55-BP) which was almost abolished when both Asn and Val were mutated. Our results clearly demonstrate the importance of an Asn/Val sequence for proteolytic processing of the TNF-R55 into soluble TNF-R55-BP and indicate that phorbol ester-induced downregulation of the TNF-R55 may be dissociated from proteolytic cleavage of the receptor.

Animals↗
PubMed1991

An alloimmunized, thrombocytopenic patient successfully transfused with acid-treated, random-donor platelets.

Alloimmunized, thrombocytopenic patients, refractory to random-donor platelet transfusion, often respond to HLA-identical single-donor platelets. HLA-compatible platelets are expensive, take time to prepare, and donors are sometimes not to be found. We have used random-donor platelets and 'peeled' the HLA-antigen off the platelets, using a modified laboratory method (incubation of platelets with citric acid solution at 0 degrees C). Platelet recovery in two healthy subjects was 72.0% for acid-treated platelets, and 73.5% for untreated control platelets, using 111In-labelled autologous platelets. Survival time (multiple hit) was 6.25 and 7.95 d, respectively. Random-donor platelets that were strongly positive in the crossmatch with serum from a patient became negative after treatment with the acid solution. Furthermore, transfusion of these platelets gave a post-transfusion, platelet-count increment comparable with transfusion of HLA-compatible single-donor platelets.

Blood Component Transfusion↗
PubMed1991

Epidemiology of absence epilepsy. III. Clinical aspects.

Absence epilepsy was studied in a Swedish population, aged 0-15 years, in 1978-1982. Cases were selected by electroencephalographic criteria. In the 134 children with 3 Hz spike-and-wave discharges, 97 (72.4%) had absences alone or in combination with generalized tonic-clonic seizures (grand mal): 56 had absences alone, 31 absences followed by grand mal, and 10 started with initial grand mal. Two distinct groups could be discerned: 1) childhood absence epilepsy: onset before the age of 12, with a quick response to therapy, little or no risk of grand mal, and a high remission rate; 2) juvenile absence epilepsy: onset at the age of 12 or later, a very high risk of grand mal, and usually a good response to therapy, but a high risk of relapses at withdrawal. This classification of absence epilepsy into subgroups may be useful for prognostic guidelines.

Adolescent↗