Biomedical subjects

P Berglund

Publications and source records attributed to P Berglund.

At least 19 recordsLinked to original sources

PubMed2005

First measurement of the transverse spin asymmetries of the deuteron in semi-inclusive deep inelastic scattering.

First measurements of the Collins and Sivers asymmetries of charged hadrons produced in deep-inelastic scattering of muons on a transversely polarized 6LiD target are presented. The data were taken in 2002 with the COMPASS spectrometer using the muon beam of the CERN SPS at 160 GeV/c. The Collins asymmetry turns out to be compatible with zero, as does the measured Sivers asymmetry within the present statistical errors.

Journal Article↗

PubMed2001

Enhanced simian immunodeficiency virus-specific immune responses in macaques induced by priming with recombinant Semliki Forest virus and boosting with modified vaccinia virus Ankara.

The immunogenicity of two vector-based vaccines, either given alone or in a prime-boost regimen, was investigated. Cynomolgus macaques were immunised with modified vaccinia virus Ankara (MVA) expressing simian immunodeficiency virus (SIV)macJ5 env, gag-pol, nef, rev, and tat genes (MVA-SIVmac) or primed with a Semliki forest virus (SFV) vaccine expressing the same genes (SFV-SIVmac) and boosted with MVA-SIVmac. Generally, antibody responses, T-cell proliferative responses and cytotoxic T-cell responses remained low or undetectable in vaccinees receiving MVA-SIVmac or SFV-SIVmac alone. In contrast, monkeys who first received SFV-SIVmac twice and then were boosted with MVA-SIVmac showed increased antibody responses as well as high T-cell proliferative responses. Three of these vaccinees had cytotoxic T-lymphocytes directed against three or four of the gene products. No evidence of protection was seen against an intrarectal heterologous SIVsm challenge given 3 months after the last immunisation. The study demonstrates a prime-boost strategy that efficiently induces both humoral and cellular immune responses.

AIDS Vaccines↗

PubMed2001

Self-replicative RNA vaccines elicit protection against influenza A virus, respiratory syncytial virus, and a tickborne encephalitis virus.

In genetic vaccination, recipients are immunized with antigen-encoding nucleic acid, usually DNA. This study addressed the possibility of using the recombinant alpha virus RNA molecule, which replicates in the cytoplasm of transfected cells, as a novel approach for genetic vaccination. Mice were immunized with recombinant Semliki Forest virus RNA-encoding envelope proteins from one of 3 viruses: influenza A virus, a tickborne flavivirus (louping ill virus), or respiratory syncytial virus (RSV). Serologic analyses showed that antigen-specific antibody responses were elicited. IgG isotyping indicated that predominantly Th1 type immune responses were induced after immunization with RSV F protein-encoding RNA, which is relevant for protection against RSV infection. Challenge infection showed that RNA immunization had elicited significant levels of protection against the 3 model virus diseases.

Animals↗

PubMed2001

Pollen and mold exposure impairs the work performance of employees with allergic rhinitis.

BACKGROUND: Although quality of life studies suggest that allergic rhinitis has a substantial impact on work impairment, national survey estimates of the magnitude of this impairment have varied widely. Retrospective recall bias is likely to be a major cause of this variability. OBJECTIVE: This study used a nationally representative daily diary sample to obtain prospective data that improve on previous estimates of the work impairment because of allergic rhinitis. METHODS: The MacArthur Foundation National Survey of Daily Experience is a daily diary survey that included a nationally representative subsample of 739 employed people, each of whom provided daily reports on work performance for 1 randomly assigned week of the calendar year. National Allergy Bureau monitoring station data were merged with the survey data to study the association of time-space variation in pollen/mold exposure with impaired daily work quality and quantity. RESULTS: National Allergy Bureau pollen/mold counts are significantly related to work impairments only among respondents with self-reported allergic rhinitis. The average estimated monthly salary-equivalent work impairment costs associated with pollen/mold exposure for each allergy sufferer is between $109 and $156, with an annualized national projection of between $5.4 billion and $7.7 billion. CONCLUSIONS: The extent to which these costs can be recovered by increasing the proportion of allergy sufferers who are successfully treated remains unknown and can only be evaluated definitively in effectiveness trials.

Adult↗

PubMed2001

Controlling lipase enantioselectivity for organic synthesis.

Lipases are used frequently as chiral catalysts in the synthesis of various fine chemicals and intermediates. The increasing need of compounds with high stereochemical purity requires catalysts with an improved and controlled performance. This overview emphasizes some important aspects for the control of lipase enantioselectivity and some examples where the enantioselectivity has been altered or reversed are highlighted. However, in several of these cases the complete explanation for the altered or reversed enantioselectivity remains unclear and needs to be solved. Three different strategies (engineering of the reaction medium, the substrate molecule, and the enzyme) for exploring lipase enantioselectivity at a molecular level are discussed and summarized. These three different approaches represent powerful tools for understanding the molecular basis for lipase enantioselective catalysis and can guide the rational improvement and tailoring of catalyst performance. By combining approaches from chemistry and biology much is learnt about the most important parameters controlling lipase enantioselectivity for organic synthesis.

Chemistry, Organic↗

PubMed2001

Recombinant Semliki Forest virus vaccine vectors: the route of injection determines the localization of vector RNA and subsequent T cell response.

Vectors based on Semliki Forest virus (SFV) have been widely used in vitro and in vivo to express heterologous genes in animal cells. In particular, the ability of recombinant SFV (rSFV) to elicit specific, protective immune responses in animal models suggests that rSFV may be used as a vaccine vehicle. In this study, we examined the distribution of rSFV in vivo by immunohistochemistry and RT-PCR after intravenous, intramuscular and subcutaneous injection of rSFV particles and related this to the degree of cytotoxic T lymphocyte (CTL) responses and frequency of specific T cells detected by MHC-I tetramers. We found that after i.v. injection, rSFV-RNA was distributed to a variety of different tissues, whereas it was confined locally after i.m. and s.c. injections. The persistence of the rSFV vector was transient, and no viral RNA could be detected 10 days after inoculation. All tested routes of immunization generated significant levels of antigen-specific CTL responses and increased numbers of specific CD8+ T cells, as detected by tetramer binding. The distribution of antigen-specific CTLs correlated with the in vivo distribution pattern of rSFV, with a highest frequency in the spleen or local lymph node, depending on the injection route.

Animals↗

PubMed2000

Emergence of CD8+ T cells expressing NK cell receptors in influenza A virus-infected mice.

Both innate and adaptive immune responses play an important role in the recovery of the host from viral infections. In the present report, a subset of cells coexpressing CD8 and NKR-P1C (NK1.1) was found in the lungs of mice infected with influenza A virus. These cells were detected at low numbers in the lungs of uninfected mice, but represented up to 10% of the total CD8(+) T cell population at day 10 postinfection. Almost all of the CD8(+)NK1.1(+) cells were CD8alphabeta(+)CD3(+)TCRalphabeta(+) and a proportion of these cells also expressed the NK cell-associated Ly49 receptors. Interestingly, up to 30% of these cells were virus-specific T cells as determined by MHC class I tetramer staining and by intracellular staining of IFN-gamma after viral peptide stimulation. Moreover, these cells were distinct from conventional NKT cells as they were also found at increased numbers in influenza-infected CD1(-/-) mice. These results demonstrate that a significant proportion of CD8(+) T cells acquire NK1.1 and other NK cell-associated molecules, and suggests that these receptors may possibly regulate CD8(+) T cell effector functions during viral infection.

Animals↗

PubMed2000

A vaccine strategy utilizing a combination of three different chimeric vectors which share specific vaccine antigens.

A large number of recombinant of viral and bacterial systems have been engineered as vectors to express foreign genes for vaccination and/or gene therapy. A common problem is the immune response to the vector itself. The presence of anti-vector immune responses may preclude sufficient 'priming' or immunogenicity if pre-existing immune responses are present, or they may impair optimal 'boosting' upon repeated immunization or delivery with the same vector. To circumvent this problem we developed a strategy using different chimeric vectors which share only the expression of common specific antigens desired for immunization. This approach not only has the advantage of avoiding increased anti-vector responses, but allows the use of combinations of vectors which could subsequently present the same or related antigen differently to the immune system as well as at alternative sites to induce the optimal type of immunity against the pathogen of interest.

Animals↗

PubMed2000

Recent care of common mental disorders in the United States : prevalence and conformance with evidence-based recommendations.

OBJECTIVE: To relate the presence of recent mental disorders to use of mental health services. DESIGN: Cross-sectional survey. STUDY POPULATION: The study population was 3,032 respondents to the Midlife Development in the United States (MIDUS) survey, a nationally representative telephone-and-mail survey conducted in 1996. Twelve-month diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, Revised, Third Edition, of major depressive episode, panic disorder, generalized anxiety disorder, and serious mental illness were made using a structured assessment. Information was obtained on 12-month treatment for mental health problems in the general medical, mental health specialty, human services, and self-help sectors. Definitions of treatments consistent with evidence-based recommendations were developed using available practice guidelines. MEASUREMENTS AND MAIN RESULTS: Crude and adjusted likelihoods of receiving any mental health care and guideline-concordant care were measured. Although 53. 8% of respondents with at least one 12-month mental disorder received any mental health care in the previous year, only 14.3% received care that could be considered consistent with evidence-based treatment recommendations. Even among those with the most serious and impairing mental illness, only 25% received guideline-concordant treatment. Predictors of receiving guideline-concordant care included being white, female, severely ill, and having mental health insurance coverage. CONCLUSIONS: An epidemic of untreated and poorly treated mental disorders exists in the United States, especially among vulnerable groups such as African Americans and the underinsured. Cost-effective interventions are needed to improve both access to and quality of treatment.

Adult↗

PubMed1999

Creation of a synthetically useful lipase with higher than wild-type enantioselectivity and maintained catalytic activity.

[reaction: see text] We have found that two Geotrichum candidum lipase isozymes have remarkably different abilities to differentiate between enantiomers of ethyl 2-methyldecanoate. By rational recombination of selected portions of the two isozymes, we have created a novel lipase with an enantioselectivity superior to that of the best wild-type parent isozyme. Site-directed mutagenesis identified two key amino acid residues responsible for the improved enantioselectivity without compromised total activity of the reengineered enzyme.

Amino Acids↗

PubMed1999

Immunization with recombinant Semliki Forest virus induces protection against influenza challenge in mice.

The replicon of Semliki Forest virus (SFV) offers the possibility to direct high-level, transient expression of heterologous proteins in vivo. We initiated studies to determine the possibility of employing the SFV expression system for recombinant vaccine purposes. Mice immunized with recombinant SFV encoding Influenza A nucleoprotein (NP) or E. coli LacZ developed long-lasting antigen-specific IgG levels and induction of cytotoxic T-cell (CTL) memory that persisted for over one year. Predominantly type 1 T-helper cells were induced as shown by IgG subclass ELISA. Humoral and cell-mediated immune responses could be induced upon delivery by several administration routes and mucosal immunizations induced secretory IgA in the respiratory tract. Development of immune responses against the vector itself did not inhibit boost responses by subsequent immunizations with recombinant SFV. Immunization of mice with vectors encoding the Influenza A virus antigens nucleoprotein (NP) and hemagglutinin (HA) resulted in immune responses that were protective against challenge infection with Influenza virus.

Animals↗

PubMed1999

Impairment in pure and comorbid generalized anxiety disorder and major depression at 12 months in two national surveys.

OBJECTIVE: Generalized anxiety disorder might be better conceptualized as a prodrome, residual, or severity marker of major depression or other comorbid disorders than as an independent diagnosis. The authors questioned whether generalized anxiety disorder itself is associated with role impairment or whether the impairment of patients with generalized anxiety disorder is due to depression or other comorbid disorders. METHOD: The authors assessed data from the National Comorbidity Survey and the Midlife Development in the United States Survey for generalized anxiety disorder and major depression at 12 months by using the DSM-III-R criteria with modified versions of the Composite International Diagnostic Interview. RESULTS: The prevalences of generalized anxiety disorder at 12 months were 3.1% and 3.3%, respectively, in the National Comorbidity Survey and the Midlife Development in the United States Survey; the prevalences of major depression at 12 months were 10.3% and 14.1%. The majority of respondents with generalized anxiety disorder at 12 months in the National Comorbidity Survey (58.1%) and the Midlife Development in the United States Survey (69.7%) also met the criteria for major depression at 12 months. Comparisons of respondents with one versus neither disorder showed that both disorders had statistically significant independent associations with impairment that were roughly equal in magnitude. These associations could not be explained by the other comorbid DSM-III-R disorders or by sociodemographic variables. CONCLUSIONS: These results show that a substantial amount of generalized anxiety disorder occurs independently of major depression and that the role impairment of generalized anxiety disorder is comparable to that of major depression.

Adolescent↗

PubMed1998

Site-directed mutagenesis combined with chemical modification as a strategy for altering the specificity of the S1 and S1' pockets of subtilisin Bacillus lentus.

By combining site-directed mutagenesis with chemical modification, we have altered the S1 and S1' pocket specificity of subtilisin Bacillus lentus (SBL) through the incorporation of unnatural amino acid moieties, in the following manner: WT --> Cysmutant + H3CSO2SR --> Cys-SR, where R may be infinitely variable. A paradigm between extent of activity changes and surface exposure of the modified residue has emerged. Modification of M222C, a buried residue in the S1' pocket of SBL, caused dramatic changes in kcat/KM, of an up to 122-fold decrease, while modification of S166C, which is located at the bottom of the S1 pocket and is partially surface exposed, effected more modest activity changes. Introduction of a positive charge at S166C does not alter kcat/KM, whereas the introduction of a negative charge results in lowered activity, possibly due to electrostatic interference with oxyanion stabilization. Activity is virtually unaltered upon modification of S156C, which is located toward the bottom of the S1 pocket and surface exposed and whose side chain is solvated. An unexpected structure-activity relationship was revealed for S166C-SR enzymes in that the pattern of activity changes observed with increasing steric size of R was not monotonic. Molecular modeling analysis was used to analyze this unprecedented structure-activity relationship and revealed that the position of the beta-carbon of Cys166 modulates binding of the P1 residue of the AAPF product inhibitor.

Amino Acid Substitution↗

PubMed1998

Enhancing immune responses using suicidal DNA vaccines.

We describe a DNA vaccine strategy that allows antigens to be produced in vivo in the context of an alphaviral replicon. Mice immunized with such vectors developed humoral and cellular immune responses at higher levels than mice that received a conventional DNA vaccine vector. Immunized animals acquired protective immunity to lethal influenza challenge. Compared with traditional DNA vaccine strategies in which vectors are persistent and the expression constitutive, the expression mediated by the alphaviral vector was transient and lytic. As a result, biosafety risks such as chromosomal integration, and the induction of immunological tolerance, could be circumvented.

Adjuvants, Immunologic↗

PubMed1998

Social phobia subtypes in the National Comorbidity Survey.

OBJECTIVE: This article presents epidemiologic data on the distinction between social phobia characterized by pure speaking fears and that characterized by other social fears. METHOD: The data come from the National Comorbidity Survey (N = 8,098). Social phobia was assessed with a revised version of the Composite International Diagnostic Interview. RESULTS: Latent class analysis showed that the brief set of social fears assessed in the survey can be disaggregated into a class characterized largely by speaking fears and a second class characterized by a broader range of social fears. One-third of the people with lifetime social phobia exclusively reported speaking fears, while the other two-thirds also had at least one of the other social fears assessed. The vast majority of the latter had multiple social fears including, in most cases, both performance and interactional fears. The two subtypes were similar in age at onset distribution, family history, and certain sociodemographic correlates. However, the social phobia characterized by pure speaking fears was less persistent, less impairing, and less highly comorbid with other DSM-III-R disorders than was social phobia characterized by other social fears. CONCLUSIONS: Further general population research assessing more performance and interaction fears is needed to determine whether social phobia subtypes can be refined and whether the subtypes are better conceptualized as distinct disorders. In the meantime, people who have social phobia with multiple fears, some of which are nonspeaking fears, appear to have the most impairment and should be the main focus of prevention and intervention efforts.

Adolescent↗

PubMed1997

Outcome of immunization of cynomolgus monkeys with recombinant Semliki Forest virus encoding human immunodeficiency virus type 1 envelope protein and challenge with a high dose of SHIV-4 virus.

Infection of macaques with chimeric simian-human immunodeficiency viruses (SHIVs) allows evaluation of HIV-1 envelope vaccines. SHIV-4 is based on SIVmac239 but carries the env, tat, and rev genes of HIV-1IIIB. In this study we used Semliki Forest virus (SFV) RNA vectors to express the envelope protein gp160 of HIV-1IIIB in cynomolgus macaques. Monkeys were immunized four times with recombinant suicide SFV. Whereas two of four monkeys showed T cell-proliferative responses, only one monkey had demonstrable levels of antibodies to HIV-1 gp41 and gp120 as shown by enzyme-linked immunosorbent assay (ELISA) and Western blot. The vaccinated monkeys and four control animals were challenged with 10,000 MID100 (100% minimum infectious doses) of cell-free monkey cell-grown SHIV-4 virus. As demonstrated by virus isolation, all macaques became infected after challenge. All vaccinated monkeys showed an HIV-1-specific anamnestic T cell-proliferative response. Three of four vaccines had developed HIV-1-Env-specific antibodies 2 weeks after challenge whereas none of the four controls showed any detectable immune response at this time point. Furthermore, three of four vaccinated monkeys had no demonstrable viral antigenemia and low viral load as opposed to one of the four naive control animals.

AIDS Vaccines↗

PubMed1997

Alphavirus expression vectors and their use as recombinant vaccines: a minireview.

Alphavirus vectors have become widely used in basic research to study the structure and function of proteins and for protein production purposes. Development of a variety of vectors has made it possible to deliver foreign sequences as naked RNA or DNA, or as suicide virus particles produced using helper vector strategies. Preliminary reports also suggest that these vectors may be useful for in vivo applications where transient, high-level protein expression is desired, such as recombinant vaccines. The initial studies have already shown that alphavirus vaccines can induce strong humoral and cellular immune responses with good immunological memory and protective effects.

Alphavirus↗

PubMed1997

Cloning of human IL-12 p40 and p35 DNA into the Semliki Forest virus vector: expression of IL-12 in human tumor cells.

IL-12 can enhance the development of effective immune responses against tumors as well as against certain infectious agents. It is therefore a potential candidate for therapeutic use in cancer therapy and in the design of vaccines against several infectious diseases. Several studies have demonstrated that IL-12 could efficiently induce tumor regression in animal models. To investigate the antitumor effect of direct gene transfer of human IL-12 into tumors, human IL-12 p35 and p40 cDNAs were cloned into the Semliki Forest virus (SFV) vector pSFV1. In order to express the two subunits from the same vector, the p35 and the p40 cDNAs were cloned into pSFV1, each under the control of a subgenomic SFV promoter. Recombinant RNA produced by in vitro transcription of SFV-IL-12 construct, was packaged into SFV viral particles with the use of a non-packageable helper RNA. We show that human tumor cell lines infected in vitro in vivo with recombinant SFV-IL-12 viral particles secrete high levels of biologically active heterodimeric p35/p40 IL-12, as demonstrated using ELISA and biological assays.

Gene Expression↗