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Biomedical subjects

C Persson

Publications and source records attributed to C Persson.

At least 55 records · Page 3Linked to original sources
PubMed1996

Analyses of functional antibody responses in HIV-1-infected individuals after vaccination with rgp160.

BACKGROUND: The immune response to HIV infection has been extensively studied and the antibody response against the virus has been characterized in detail. It is, however, still unclear which immune function it is most important to stimulate when administering a vaccine against HIV. OBJECTIVES: To analyze the functional antibody responses in asymptomatic HIV-1-infected individuals after vaccination with rgp160. STUDY DESIGN: Forty-nine asymptomatic HIV-1-infected individuals were followed for 9 months and analyzed for changes in functional antibody responses. Forty of them received HIV-1 envelope rgp160 injections and nine did not. RESULTS: Increased levels of antibodies mediating neutralization and cellular cytotoxicity (ADCC) could be seen in subjects who also showed a better CD4 development compared with the patients without increased levels of functional antibodies. Out of nine matched HIV-infected and influenza-immunized controls, none had increased neutralizing activity and only one had an increased ADCC titer. An increased capacity to block soluble CD4 binding to gp120 occurred in 10 immunized patients. Seroreactivity and avidity maturation were detectable to peptides representing consensus HIV-1 envelope regions, indicating an anamnestic response to the patients own virus. CONCLUSIONS: The humoral immune response in HIV-1-infected individuals was moderately influenced by repeated gp160 immunizations, while previous studies have shown that HIV-specific T-cell reactivity was strongly increased.

Journal Article↗
PubMed1996

YopH of Yersinia pseudotuberculosis interrupts early phosphotyrosine signalling associated with phagocytosis.

The PTPase YopH of Yersinia is essential to the ability of these bacteria to block phagocytosis. Wild-type Yersinia pseudotuberculosis, but not the yopH mutant strain, resisted phagocytosis by J774 cells. Ingestion of a yopH mutant was dependent on tyrosine kinase activity. Transcomplementation with wild-type yopH restored the anti-phagocytic effect, whereas introduction of the gene encoding the catalytically inactive yopHC403A was without effect. The PTPase inhibitor orthovanadate impaired the anti-phagocytic effect of the wild-type strain, further demonstrating the importance of bacteria-derived PTPase activity for this event. The ability to resist phagocytosis indicates that the effect of the bacterium is immediately exerted when it becomes associated with the phagocyte. Within 30 s after the onset of infection, wild-type Y. pseudotuberculosis caused a YopH-dependent dephosphorylation of phosphotyrosine proteins in J774 cells. Furthermore, interaction of the cells with phagocytosable strains led to a rapid and transient increase in tyrosine phosphorylation of paxillin and some other proteins, an event dependent on the presence of the bacterial surface-located protein invasin. Co-infection with the phagocytosable strain and the wild-type strain abolished the induction of tyrosine phosphorylation. Taken together, the present findings demonstrate an immediate YopH-mediated dephosphorylation of macrophage phosphotyrosine proteins, suggesting that this PTPase acts by preventing early phagocytosis-linked signalling in the phagocyte.

Animals↗
PubMed1995

Increased mRNA expression of IL-6, IL-10, TNF-alpha, and perforin in blood mononuclear cells in human HIV infection.

Evidence has been presented for the involvement of various cytokines, including interleukin (IL)-6, IL-10, and tumor necrosis factor (TNF)-alpha, in the pathogenesis of human immunodeficiency virus (HIV) infection. Since measured plasma levels may poorly reflect in vivo production of cytokines, we adopted in situ hybridization with cDNA oligonucleotide probes to enumerate blood mononuclear cells (MNCs) expressing mRNA for IL-6, IL-10, TNF-alpha, and perforin. The HIV-infected patients had elevated levels of MNCs expressing mRNA for all four cytokines compared to healthy controls. Numbers of IL-6 mRNA-expressing cells were higher in patients with clinical AIDS than in asymptomatic seropositive patients, and correlated inversely with CD4+ cell counts in blood, reflecting the involvement of IL-6 in later stages of HIV infection. The described approach could be an alternative way to study cytokines in HIV infection.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Mechanisms of nasal hyper-reactivity.

Hyper-reactivity to non-specific challenges has been considered a hallmark of asthma and is defined as an abnormal responsiveness of the bronchial airways to a variety of provocative agents. The mechanisms underlying hyper-reactivity in the upper and lower airways are not known. By using the nose to study the inflammatory response possible abnormalities can be investigated carefully and pathophysiology of specific airway hyper-reactivities can be better understood. Other factors than merely constriction of the bronchial smooth muscles can cause narrowing of the free lumen to airflow. Functionally different and very distinct mucosal end-organ reactivities may also be increased. If these reactivities can be well assessed, specific airway hyper-reactivity can be defined. In the present report, specific mucosal end-organ hyper-reactivities in the allergic nasal mucosa are presented. Certain widespread hypotheses, such as the role of the eosinophil and the "increased absorption permeability theory", are disputed.

Allergens↗
PubMed1995

Plasma concentrations of morphine, morphine-3-glucuronide, and morphine-6-glucuronide after intravenous and oral administration to healthy volunteers: relationship to nonanalgesic actions.

Healthy volunteers were given morphine as an i.v. infusion (10 mg), immediate release (IR) tablets (3 x 10 mg), and as a new controlled release (CR) tablet (30 mg) on separate occasions. Venous blood samples were analyzed for morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) using high-performance liquid chromatography (HPLC). Pupil size, salivation, and central nervous system (CNS) effects were evaluated serially. Pharmacokinetic parameters, calculated using a two-compartment model, were in accordance with previous results for i.v. administration of morphine. The absolute bioavailability of morphine in both IR and in CR tablets was, 32%, and the relative bioavailability of the CR tablet versus the IR tablets was 103% (91-115%, 95% confidence interval). Pupil size and unstimulated saliva production were significantly reduced and CNS effects most pronounced following i.v. infusion of morphine, but were only moderately affected after oral administration with IR or CR tablets. Miosis and reduction of salivation were observed at moderate concentrations of morphine and M6G. A pharmacokinetic/pharmacodynamic model based on previous studies of receptor binding and potency of morphine and its metabolites was used to assess the concentration-effect relationships. According to this model, M6G was four and eight times more potent than morphine in producing miosis and reduction of saliva production, respectively. The same model indicated that intrinsic activities of M6G and morphine were similar for both effect parameters, whereas M3G was either inactive or even opposed the effects of morphine and M6G.

Administration, Oral↗
PubMed1995

Cell-surface-bound Yersinia translocate the protein tyrosine phosphatase YopH by a polarized mechanism into the target cell.

YopH is translocated by cell-surface-bound bacteria through the plasma membrane to the cytosol of the HeLa cell. The transfer mechanism is contact dependent and polarizes the translocation to only occur at the contact zone between the bacterium and the target cell. More than 99% of the PTPase activity is associated with the HeLa cells. In contrast to the wild-type strain, the yopBD mutant cannot deliver YopH to the cytosol. Instead YopH is deposited in localized areas in the proximity of cell-associated bacteria. A yopN mutant secretes 40% of the total amount of YopH to the culture medium, suggesting a critical role of YopN in regulation of the polarized translocation. Evidence for a region in YopH important for its translocation through the plasma membrane of the target cell but not for secretion from the pathogen is provided.

Animals↗
PubMed1995

Various methods for testing nasal responses in vivo: a critical review.

Mucosal responses in the airway can ideally be studied in the nose. It is a readily accessible organ and can be provoked repeatedly. Likewise, mucosal responses to certain provocations can be easily monitored. Different methods for the provocation and measurement of nasal responses have been used in recent years. Each technique has its own advantage and restrictions. In order to make a correct interpretation of the results achieved, however, it is important that the investigator is familiar and comfortable with the methods used. For clinical purposes, techniques for qualitative measurements may be appropriate, but for experimental research, quantitative measurements with high reproducibility are essential. The present paper critically discusses current techniques for provocation and assessment of nasal responses, which may improve both the techniques used and the understanding of nasal physiology.

Alkaloids↗
PubMed1995

[Astute in vivo observations discover anti-asthma medication].

Will the new reductive biology write the book of revelation of all progress as concerns the pathophysiology and pharmacology of asthma? The early and recent medical history of anti-asthma drugs supports the possibility that exploratory in vivo research involving patients and disease-like test systems may "unexpectedly" provide leap discoveries in pathophysiology and pharmacology. New treatments based on defined molecular disease mechanisms will no doubt emerge. However, the future may also hold novel important anti-asthma drugs where the exact mode of action remains a challenge. Indeed, many aspects of the efficacies of the already long established anti-asthma drug principles have yet to be explained at the end-organ, cellular and molecular levels.

Adrenal Cortex Hormones↗
PubMed1994

Enzyme immunoassay (ELISA) for the evaluation of antibodies directed to the CD4 receptor-binding site of the HIV gp120 molecule.

The interaction between the HIV envelope glycoprotein gp120 and the CD4 molecule is probably the most important primary event determining HIV infection. Reactivity with the native viral envelope has been difficult to measure due to the lack of gp120 ligand purified directly from primary virus cultures. We have developed an ELISA, utilizing Galanthus nivalis agglutinin (GNA) which selectively binds native HIV envelope gp120 in culture medium. The GNA-based ELISA eliminates the need for isotope-labelled reagents, live cells and recombinant non-natively glycosylated envelope proteins and offers an easy way of using gp120 directly from crude HIV culture medium. The reactivities of sera from several categories of HIV infected individuals were assayed for inhibition of the HIV-1 gp120-CD4 binding. 19/32 (59.3%) sera from asymptomatic individuals and 7/10 (70%) sera from ARC/AIDS patients blocked the CD4-gp120 binding. 20 serum samples from uninfected individuals showed a gp120-CD4 interaction blocking capacity of 0-15%. Two monoclonal antibodies, T4.2 directed to CD4 and 1171 directed to the CD4 binding site of gp120 were used as positive controls. Both Mabs inhibited CD4-gp120 binding by 66-90%.

Adolescent↗
PubMed1994

Increased levels of interferon-gamma (IFN-gamma), IL-4 and transforming growth factor-beta (TGF-beta) mRNA expressing blood mononuclear cells in human HIV infection.

Evidence has been presented for the involvement of IFN-gamma, IL-4 and TGF-beta in AIDS. Measured plasma levels may, however, poorly reflect in vivo production, since cytokines act auto- and paracrinally and have very short half life in plasma. In situ hybridization with complementary DNA oligonucleotide probes was used to enumerate blood mononuclear cells expressing cytokine messenger RNA (mRNA). HIV-infected patients had elevated blood levels of cells expressing each of the cytokines, with predominance for cells expressing TGF-beta mRNA. All AIDS patients included had elevated numbers of IL-4 mRNA-expressing cells, and levels of cells expressing this cytokine correlated inversely with counts of CD4+ cells in blood, reflecting the involvement of Th2-like cells in later stages of HIV infection. The described approach should be useful in further studies of cytokines in HIV infection and other diseases.

Adult↗
PubMed1994

The lcrB (yscN/U) gene cluster of Yersinia pseudotuberculosis is involved in Yop secretion and shows high homology to the spa gene clusters of Shigella flexneri and Salmonella typhimurium.

Virulent bacteria of the genus Yersinia secrete a number of virulence determinants called Yops. These proteins lack typical signal sequences and are not posttranslationally processed. Two gene loci have been identified as being involved in the specific Yop secretion system (G. Cornelis, p. 231-265, In C. E. Hormache, C. W. Penn, and C. J. Smythe, ed., Molecular Biology of Bacterial Infection, 1992; S. C. Straley, G. V. Plano, E. Skrzypek, P. L. Haddix, and K. A. Fields, Mol. Microbiol. 8:1005-1010, 1993). Here, we have shown that the lcrB/virB locus (yscN to yscU) encodes gene products essential for Yop secretion. As in previously described secretion apparatus mutants, expression of the Yop proteins was decreased in the yscN/U mutants. An lcrH yscR double mutant expressed the Yops at an increased level but did not secrete Yops into the culture supernatant. The block in Yop expression of the ysc mutants was also circumvented by overexpression of the activator LcrF in trans. Although the Yops were expressed in elevated amounts, the Yops were still not exported. This analysis showed that the ysc mutants were unable to secrete Yops and that they were also affected in the negative Ca(2+)-regulated loop. The yscN/U genes showed remarkably high homology to the spa genes of Shigella flexneri and Salmonella typhimurium with respect to both individual genes and gene organization. These findings indicate that the genes originated from a common ancestor.

Adenosine Triphosphatases↗
PubMed1994

Improved cell-mediated immune responses in HIV-1-infected asymptomatic individuals after immunization with envelope glycoprotein gp160.

Strong specific T-cell responses to human immunodeficiency virus type 1 (HIV-1) gp160 were induced by immunization with recombinant gp160 (rgp160). It was given as postinfection vaccination to 40 asymptomatic HIV-1 seropositive patients. The participants received 6 doses of 160 micrograms rgp160 administered intramuscularly at 0, 1, 4, 8, 17, and 26 weeks and were monitored for 1 year. Lymphocyte proliferation was performed by cultivating lymphoid cells in vitro with specific antigens and mitogens. After immunization with gp160, specific T-cell proliferative responses were induced in all 40 patients. One week after the sixth immunization at day 180, a substantially increased response was detected in 98% of the patients, with a mean stimulation index value of 195. Furthermore, proliferative responses were also identified, after immunization, against native gp120 and against a peptide representing the V3 region of gp120. In addition to the HIV-specific T-cell responses, increased reactivity to several other non-HIV antigens, including tetanus toxoid, influenza, measles, and cytomegalovirus, were seen after gp160 vaccination. The responses to CMV and measles were interpreted to represent an improved recall antigen response. Such recall antigen responses were few in matched HIV-infected controls immunized with influenza virus only. All patients initially and repeatedly showed a normal capacity of total T-cell activation, evaluated by the mitogen phytohemagglutinin (PHA). The trend in CD4 counts improved in 30 of 40 patients during the year of follow-up. The frequency of increases of proliferative responses to antigens was associated with a better CD4 trend. Addition of zidovudine for 2 weeks after each immunization had no beneficial effects nor did it prevent induction of immune responses. All patients tolerated the immunizations well, and no systemic adverse effects were noted. This is a phase I trial, and no definitive conclusions regarding clinical efficacy can be reached.

Adult↗