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J Andersson

Publications and source records attributed to J Andersson.

At least 145 records · Page 8Linked to original sources
PubMed1997

A systemic downregulation of gamma interferon production is associated with acute shigellosis.

Production of cytokines by peripheral blood mononuclear cells from Shigella-infected patients was assessed. The frequencies of tumor necrosis factor alpha (TNF-alpha), TNF-beta, and transforming growth factor beta mRNA-expressing cells were persistently upregulated during the course of shigellosis in comparison to those of healthy controls. In contrast, the frequency of gamma interferon (IFN-gamma) mRNA-expressing cells was significantly reduced during the acute stage compared to that during the convalescent stage and to that of healthy Bangladeshi controls (P < 0.01). Constitutive IFN-gamma production in Bangladeshi controls was significantly upregulated compared to that in Swedish controls.

Adult↗
PubMed1997

Positron emission tomography studies of healthy volunteers--no effects on the dopamine terminals and synthesis after short-term exposure to toluene.

Despite extensive research, the mechanisms for the effects of organic solvents on the central nervous system are still unknown. One mechanism proposed is that solvents interfere with the synthesis of neurotransmitters. In the present study 11 male healthy volunteers were exposed during 15 min to 100 p.p.m. toluene at light physical exercise, and the dopamine decarboxylase activity and number of terminals in putamen were measured before and after exposure by positron emission tomography. Two different tracers were used [beta-11C]L-DOPA for decarboxylase activity during the in vivo synthesis of dopamine, and [11C]nomifensine to estimate the number of terminals. Although there was a slight increase in the rate of dopamine synthesis in the putamen after the exposure, this difference was not statistically significant (P = 0.4). No effect was observed with regard to the uptake of nomifensine. There was no significant relationship between the dose of toluene and rate of dopamine synthesis, and no significant correlation between the time from end of exposure to start of the PET-camera and DOPA. Our findings indicate that short term exposure to 100 p.p.m. of toluene does not affect the rate of dopamine synthesis or the number of presynaptic terminals.

Adult↗
PubMed1997

Tumor therapy with an antibody-targeted superantigen generates a dichotomy between local and systemic immune responses.

Repeated injections of a fusion protein containing the superantigen staphylococcal enterotoxin A (SEA) combined with a Fab fragment of a tumor-specific antibody is a highly efficient immunotherapy for mice expressing lung melanoma micrometastasis. In the present study, the systemic and local immune responses generated by this therapy were analyzed at a cellular level. Two distinct but coupled immune reactions occurred after repeated therapy. Tumor necrosis factor and macrophage inflammatory protein-1 alpha and -1 beta were immediately synthesized, in the absence of T lymphocytes, at the local tumor site in the lung. This was followed by the induction of VCAM-1 adhesion molecule expression on pulmonary vascular endothelial cells. Concurrently, the early response in the spleen was characterized by the induction of selective T cells producing interleukin (IL)-2. The primed and expanded SEA-reactive V beta 3- and V beta 11-expressing T lymphocytes accumulated to the tumor area only after Fab-SEA therapy and were not present in the lung when SEA, Fab fragment, or recombinant IL-2 was injected. The tumor-infiltrating T cells produced large amounts of interferon-gamma, but no IL-2 or Th2 type of lymphokines were detected at the tumor site in the Fab-SEA-targeted antitumor immune response. These results emphasize the necessity to investigate several sites of antigen presentation to elucidate the effects of immunotherapy.

Animals↗
PubMed1996

B-CLL cells experimentally infected with EBV enter DNA synthesis, produce cytokines and stimulate T-lymphocytes.

Several B-chronic lymphocytic leukemia (B-CLL) clones, represented by different patients can be infected with EBV in vitro. A proportion of the cells becomes activated by the virus, but they rarely yield immortalized cell lines. We used cells from two B-CLL patients which differed in sensitivity to EBV infection. After 7 days in culture, we studied the CLL cells exposed to the B-cell activators Staphylococcus aureus, IL-2 and/or to EBV for expression of the activation markers CD23, CD39 and the adhesion and costimulatory molecules CD54 and CD80, for DNA synthesis, for production of various cytokines and for capacity to stimulate autologous and allogeneic T-lymphocytes. Generally the frequency of cells expressing cytokines in the cytoplasm correlated with the activation status of the populations and with their capacity to stimulate T-cells. It is likely that the difference between the clones with regard to sensitivity to the viral infection, is determined by the maturation state of the CLL cells. It may therefore reflect the variation in the response within a normal B-cell population. The results obtained in the present and in our earlier experiments with EBV provide information concerning the events after primary EBV infection in vivo. The T-lymphocyte stimulatory capacity of the infected CLL cells may be considered as an in vitro correlate to the syndrome of infectious mononucleosis. The detection of cytokines in the infected B-CLL cells suggests that their production by the B-blasts contributes to the level of T-lymphocytosis induced by the primary infection.

Antigens, CD↗
PubMed1996

Bacteriophage T4 anaerobic ribonucleotide reductase contains a stable glycyl radical at position 580.

It has been recently recognized that the class III anaerobic ribonucleotide reductase requires the presence of a second activating gene product, NrdG. We have proposed that the role for NrdG involves the generation of an oxygen sensitive glycyl free radical within the NrdD enzyme. In this article we present the generation of such a glycyl free radical within the T4 NrdD subunit and its dependence upon the phage NrdG subunit. Initially, an overexpression system was created that allowed the joint production of T4 NrdD and T4 NrdG. With this system and in the presence of T4 NrdG, an oxygen-sensitive cleavage of NrdD was observed that mimicked the cleavage observed in phage infected Escherichia coli extracts. Under anaerobic conditions the presence of T4 NrdD with NrdG revealed a strong doublet EPR signal (g = 2.0039). Isotope labeling of the NrdD with [2H]glycine and [13C]glycine, respectively, confirmed the presence of a stabilized glycine radical. The unpaired electron is strongly coupled to C-2 in glycine and the doublet splitting originates from one of the alpha-protons. The glycine residue at position 580 was determined to be the radical containing residue through site-directed mutagenesis studies involving a G580A NrdD mutant. The glycyl radical generation was specific for the T4 NrdG, and the host E. coli NrdG was found to be unable to activate the phage reductase. Finally, anaerobic purification revealed the holoenzyme complex to contain iron, whereas the NrdD polypeptide was found to lack the metal. Our results suggest a tetrameric structure for the T4 anaerobic ribonucleotide reductase containing one homodimer each of NrdD and NrdG, with a single glycyl radical present.

Anaerobiosis↗
PubMed1996

Regional activation of human cerebral cortex upon an adaptation in mirror drawing.

To elucidate cerebral regions involved in adaptation to mirror drawing, changes in regional cerebral blood flow were measured using positron emission tomography at different levels of adaptation. A significant signal in subtraction images was localized in left Brodmann's area 45 (ventral sub-region of Broca's area) in the initial phase of the mirror drawing. This activity decreased as adaptation proceeded, and a small cluster in area 19 of the medial extrastriate cortex became significantly active. An after-effect of ca. 30 min of mirror-drawing was also detected in the right area 21 of the temporal association cortex. The results first demonstrated visuo-cortical regions where neurons might change their activity to evoke plastic response to the inverted vision.

Adaptation, Psychological↗
PubMed1996

Plasma from patients with severe invasive group A streptococcal infections treated with normal polyspecific IgG inhibits streptococcal superantigen-induced T cell proliferation and cytokine production.

Previous studies have suggested a central role for superantigen-induced immune responses in the pathogenesis of streptococcal toxic shock syndrome. The production of streptococcal superantigens by clinical group A streptococcal (GAS) isolates was studied, and the ability of plasma collected from patients with severe invasive GAS infections to neutralize the proliferative- and cytokine-inducing activities of these superantigens was investigated. Overnight culture supernatants from all GAS isolates obtained from patients with invasive disease were found to contain superantigenic activity, as evident from their ability to drive potent T cell proliferation, induce high production of cytokines, and stimulate T cells in a V beta-specific manner. Twelve patients with severe invasive GAS infections, including 11 streptococcal toxic shock syndrome cases and one necrotizing fasciitis without shock, were treated with i.v. infusions of normal polyspecific Ig (IVIG). Plasma samples collected from each patient before and after IVIG administration were analyzed for their ability to neutralize the activity of streptococcal superantigens produced by the GAS isolate that caused their disease. In all IVIG-treated patients, the capacity to neutralize the superantigenic activity, produced by their respective GAS isolate or by purified streptococcal pyrogenic exotoxins, increased in plasma following IVIG administration. Of particular clinical relevance, post-IVIG plasma from each patient completely blocked cytokine production elicited by their respective GAS culture supernatants or by purified streptococcal pyrogenic exotoxins. This study shows that IVIG treatment confers in vivo inhibitory activity against a large array of streptococcal superantigens and suggests that IVIG may be useful in the treatment of severe invasive streptococcal infections.

Cytokines↗
PubMed1996

A subpopulation of B220+ cells in murine bone marrow does not express CD19 and contains natural killer cell progenitors.

Bone marrow of both normal and rearrangement-deficient mice contains a small population of B220(CD45R)+ cells, which do not express the B lineage marker CD19. Instead, part of this population coexpresses the surface marker CD43 and lacks or expresses very low levels of heat stable antigen (HSA) and BP-1, thus representing a part of Hardy's fraction A (B220(+)-CD43+HSA-, BP-1-) of B lineage development. However, some 20-40% of these B220(+)-CD19- cells also coexpress the NK1.1 surface molecule and do not express genes like VpreB or B29 restricted to the B cell lineage. These cells respond to recombinant interleukin 2 in vitro, and develop into killer cells that can lyse the prototypic NK target tumor cell, YAC-1, as well as syngeneic normal lipopolysaccharide or concanavalin A blasts, providing they lack the surface expression of major histocompatibility complex class I molecules. The implications of these findings for studies on B lymphopoiesis are discussed. It is suggested that the CD19-specific monoclonal antibody is more reliable, as in humans, than B220(CD45R) to detect B lineage cells in mice.

Animals↗
PubMed1996

Antibody-targeted superantigen therapy induces tumor-infiltrating lymphocytes, excessive cytokine production, and apoptosis in human colon carcinoma.

Bacterial superantigens are the most potent known activators of human T lymphocytes. To engineer superantigens for immunotherapy of human colon carcinoma, the superantigen, staphylococcal enterotoxin A (SEA) was genetically fused to the Fab region of the colon carcinoma-reactive monoclonal antibody C242. In the present study the effector mechanisms involved in the anti-tumor response to C242 Fab-SEA were characterized. Immunohistochemistry and computer-aided image analysis were used in studies of cryopreserved tumor tissue to evaluate the phenotype of infiltrating cells and their cytokine profiles in response to therapy. Human T cells and monocytes were recruited to the tumor area and penetrated the entire tumor mass within hours after injection of C242 Fab-SEA. The production of cytokines at the single-cell level was found to be dominated by tumor necrosis factor (TNF)-alpha, interleukin (IL)-2, IL-4, IL-5, IL-10, IL-12, interferon (IFN)-gamma, granulocyte-macrophage colony-stimulating factor, and transforming growth factor-beta, whereas IL-1-alpha, IL-1ra, IL-1 beta, TNF-beta, IL-3, IL-6, and IL-8 were undetectable. Most of the TNF-alpha, IL-2, IL-12, and IFN-gamma were made by the infiltrating human leukocytes, while the colon carcinoma cells were induced to produce IL-4, IL-10, and TNF-alpha. Up-regulation of IFN-gamma receptors and TNF R p60 receptors was found, while the TNF R p80 receptor was absent. The cytokine production, T cell infiltration, and CD95 Fas receptor expression concomitantly occurred to induce programmed cell death in the tumor cells. This was followed by a strong reduction of the tumor mass that was seen within 24 h after C242 Fab-SEA infusion. These findings demonstrate that antibody-superantigen proteins efficiently recruit tumor-infiltrating lymphocytes actively producing a variety of cytokines likely to be essential for the therapeutic effects observed in the model. Although the humanized SCID model has obvious limitations in its predictive value for treatment of human cancer, we believe that these results encourage clinical evaluation of antibody-targeted superantigens.

Animals↗
PubMed1996

Dissociation between cytokine mRNA expression and protein production in shigellosis.

In our study, infection with Shigella dysenteriae type 1 (n = 16) or Shigella flexneri in adults (n = 5) was associated with a gradual accumulation of mRNA for interleukin (IL)-1 beta, tumor necrosis factor (TNF)-alpha, IL-6, transforming growth factor-beta, IL-10, IL-4, TNF-beta, interferon (IFN)-gamma and perforin in the rectal biopsy samples during the convalescent stage of the disease demonstrated by in situ hybridization. In contrast, immunohistochemical staining in rectal tissues of cytokine protein-producing cells at the single-cell level exhibited a steady-state expression during 2-36 days after the onset of the disease. The frequency of cytokine mRNA-expressing cells varied in the range of 3-100-fold higher than that of the corresponding protein-synthesizing cells. The accumulation of cytokine mRNA in vivo during shigellosis represented a long-lasting phenomenon throughout the disease course, and may be linked to its immunopathogenesis. The results also indicate that assessment of both protein and mRNA in vivo may provide complementary information. Stimulation in vitro of peripheral blood mononuclear cells from normal healthy donors with Shigella-derived lipopolysaccharide or shiga toxin was carried out to elucidate the role of Shigella antigens in the regulation of translation of cytokine-specific mRNA. The incidence of cytokine (IFN-gamma, IL-6 and TNF-alpha) mRNA- and cytokine protein-expressing cells was very similar and congruent after both these Shigella-derived stimuli. We could, thus, not find evidence for shiga toxin-induced down-regulation of cytokine mRNA translation as the explanation for the observed discrepancy between cytokine mRNA and protein levels in the tissue biopsies.

Acute Disease↗
PubMed1996

Computerized assessment of production of multiple human cytokines at the single-cell level using image analysis.

A technique using a computerized image analysis system was developed for evaluating and quantifying human cytokine production. This system registered single cells as positive or negative cytokine producers based on a specific juxtanuclear staining pattern generated by accumulation of the proteins in the Golgi-endoplasmatic reticulum compartment. The characteristic morphology of the immunocytochemical staining offered the opportunity to register individual producer cells within multicomponent cell populations. A color camera was then adapted to transfer on-line images directly into the computer-controlled operating system. In this study cultured human peripheral blood mononuclear cells were polyclonally stimulated and then analyzed for interleukin-1alpha (IL-1alpha), IL-1beta, IL-1ra, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor-alpha (TNF-alpha), TNF-beta, interferon-gamma, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor production. The image-analyzing system detected cytokine-producing cells in a sensitive and reproducible manner, which was in total congruence with enumeration by conventional microscopy. Furthermore, accurate assessments of cell distributions by signal intensity and cell area were applied at the single-cell level. The image-analyzing system allowed the detection of at least 1 in 1,000 events by using unique cytokine-associated morphometric criteria. The results of kinetic studies measuring cytokine production following activation and cell transformation provided data supporting increases in intensity of intracellular localized specific immunostaining and in cell size within the cytokine-producing cells.

Adult↗
PubMed1996

Activation PET scanning in pretreatment evaluation of patients with cerebral tumours or vascular lesions in or close to the sensorimotor cortex.

Treatment of tumours and vascular lesions in or close to eloquent cortex may inflict neurological deficits. Intra-operative mapping procedures have been used for many decades in efforts to minimize neurological sequelae. The possibility for non-invasive pre-operative brain mapping has emerged with the advent of positron emission tomography (PET). In this paper we report on 11 patients with a tumour or vascular lesion in or close to the sensorimotor (10 patients) or visual cortex (one patient). The patients were subjected to activation PET scanning by means of vibrotactile or visual stimulation. The results show that in most of the patients the important relation between the lesion and the sensorimotor cortex could be determined. The patient with a lesion in the occipital lobe had involvement of the entire visual cortex as judged by comparison with activated areas on the nonlesion side.

Adult↗
PubMed1996

Valvular function of peripheral veins after hyperemic dilation.

PURPOSE: We wanted to answer the question of whether physiological dilation of normal extremity veins can induce temporary valvular leakage and reflux. METHODS: Directional flow was recorded in 22 forearm and popliteal veins by Doppler duplex scanning after distal compression. Reflux was assessed by valve closure time and calculation of a "reflux index," the ratio of backward to forward flow areas. RESULTS: Hyperemia and enhanced flow did not increase but lowered reflux. During control conditions the mean reflux ratio (backward/forward flow area) of 21 veins was 0.058 and decrease to 0.028 (p < 0.05). Reflux was slightly longer in patients in the erect position in the popliteal vein, compared to forearm veins (with the patients in the sitting position). Significantly increased reflux occurred during hyperemia in only one deep forearm vein (valve closure time 0.92 seconds). CONCLUSIONS: Most veins of the upper (forearm) and lower extremity (popliteal vein) were competent even after a maneuver that induced venodilation and an increase in blood flow (exercise hyperemia or postocclusion reactive hyperemia). Veins with an inherent valvular weakness can be identified by a hyperemia test with duplex flow analysis.

Adolescent↗
PubMed1996

The SCID but not the RAG-2 gene product is required for S mu-S epsilon heavy chain class switching.

We have investigated the capacity of precursor B cells from normal (BDF1) and V(D)J recombinase-deficient (RAG-27) or defective (SCID) mice to be induced by a CD40-specific monoclonal antibody and IL-4 to epsilon H chain gene transcription and to S mu-S epsilon switch recombination. In differentiating precursor B cells from all three strains of mice, the development of similar numbers of CD19+, CD23+, CD40+, and MHC class II+ expressing B lineage cells and similar levels of epsilon H chain gene transcription were induced. Efficient S mu-S epsilon switching occurred in normal and RAG-2-deficient, but not in SCID, precursor B cells. Thus, the transcription of the epsilon H chain is independent of the RAG-2 and the SCID gene product, while the S mu-S epsilon switch recombination requires the SCID gene-encoded DNA-dependent protein kinase, but not the RAG-2 protein.

Animals↗
PubMed1996

Sendai virus-induced IFN-alpha production analysed by immunocytochemistry and computerized image analysis.

IFN-alpha production in Sendai virus-stimulated human buffy coat cultures could readily be demonstrated in individual cells at a protein level by the use of a novel immuno-enzymatic staining procedure. A distinctive rounded, juxtanuclear staining pattern was generated in producer cells by the accumulation of the intracellularly synthesized IFN-alpha in the Golgi stacks. The technology is based upon acquiring a video image of stained monolayers of cells, viewed in a microscope by a colour camera, which then transfers binary images directly into a computer-controlled operating system. The characteristic appearance of the immunocytochemical staining enabled a computerized image-analysis system to measure IFN-alpha producing cells based on defined criteria set for morphology, intensity, colour and size. The automated system could accurately and reproducibly register a range of 0.1-7.0% of the total cell population as IFN-alpha producing cells during the kinetic studies of the response. Congruent results were obtained with manual microscopy and image analysis concerning the assessment of the incidence of IFN-alpha producing cells in the total cell populations. All IFN-alpha producing cells expressed surface HLA-DR molecules and 95% of these cells belonged to the myelomonocytic lineage. The image analysis system provided, in contrast to conventional microscopy, an opportunity to assess and document differences of signal intensity and cell size of individual IFN-alpha producing as well as non-producing cells.

Cell Size↗
PubMed1996

Oral ribavirin for prevention of severe liver disease caused by hepatitis C virus during allogeneic bone marrow transplantation.

Four allogeneic bone marrow transplant patients who were infected with hepatitis C virus (HCV) before bone marrow transplantation (BMT) were treated with oral ribavirin during and after transplantation. None of the patients had severe liver complications. One patient died early. Polymerase chain reaction analysis revealed that two patients who were HCV RNA-positive before BMT became HCV RNA-negative during therapy and remained HCV RNA-negative during 6 and 12 months of follow-up, respectively. No severe side effects of ribavirin were documented. Ribavirin therapy can be given safely to patients undergoing BMT and can result in clearance of HCV RNA.

Administration, Oral↗
PubMed1996

Acyclovir and prednisolone treatment of acute infectious mononucleosis: a multicenter, double-blind, placebo-controlled study.

Ninety-four patients with infectious mononucleosis and symptoms < or = 7 days were randomized to treatment with oral acyclovir (800 mg 5 times/day) and prednisolone (0.7 mg/kg for the first 4 days, which was reduced by 0.1 mg/kg on consecutive days for another 6 days; n = 48), or placebo (n = 46) for 10 days. Oropharyngeal Epstein-Barr virus (EBV) shedding was significantly inhibited during the treatment period (P = .02, Mann-Whitney rank test). No significant effect was observed for duration of general illness, sore throat, weight loss, or absence from school or work. The frequency of latent EBV-infected B lymphocytes in peripheral blood and the HLA-restricted EBV-specific cellular immunity, measured 6 months after onset of disease, was not affected by treatment. Thus, acyclovir combined with prednisolone inhibited oropharyngeal EBV replication without affecting duration of clinical symptoms or development of EBV-specific cellular immunity.

Acyclovir↗