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  1. Article ; Online: Viruses in type 1 diabetes.

    Hyöty, Heikki

    Pediatric diabetes

    2016  Volume 17 Suppl 22, Page(s) 56–64

    Abstract: Environmental factors play an important role in the pathogenesis of type 1 diabetes and can determine if a genetically susceptible individual develops the disease. Increasing evidence suggest that among other exogenous agents certain virus infections can ...

    Abstract Environmental factors play an important role in the pathogenesis of type 1 diabetes and can determine if a genetically susceptible individual develops the disease. Increasing evidence suggest that among other exogenous agents certain virus infections can contribute to the beta-cell damaging process. Possible viral etiology of type 1 diabetes has been explored extensively but the final proof for causality is still lacking. Currently, the group of enteroviruses (EVs) is considered as the strongest candidate. These viruses have been found in the pancreas of type 1 diabetic patients, and epidemiological studies have shown more EV infections in diabetic patients than in controls. Prospective studies, such as the Type 1 Diabetes Prediction and Prevention (DIPP) study in Finland, are of fundamental importance in the evaluation viral effects as they can cover all stages of the beta-cell damaging process, including those preceding the initiation of the process. DIPP study has carried out the most comprehensive virological analyses ever done in prospective cohorts. This article summarizes the findings from these analyses and discuss them in the context of the existing other knowledge and the prospects for intervention studies with EV vaccines or antiviral drugs.
    MeSH term(s) Diabetes Mellitus, Type 1/virology ; Enterovirus ; Enterovirus Infections/complications ; Humans ; Prospective Studies
    Language English
    Publishing date 2016
    Publishing country Denmark
    Document type Journal Article ; Review
    ZDB-ID 1502504-4
    ISSN 1399-5448 ; 1745-1426 ; 1399-543X
    ISSN (online) 1399-5448
    ISSN 1745-1426 ; 1399-543X
    DOI 10.1111/pedi.12370
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Human intestinal organoid models for celiac disease research.

    Dotsenko, Valeriia / Sioofy-Khojine, Amir-Babak / Hyöty, Heikki / Viiri, Keijo

    Methods in cell biology

    2023  Volume 179, Page(s) 173–193

    Abstract: Celiac disease pathogenesis, in addition to immune cell component, encompasses pathogenic events also in the duodenal epithelium. In celiac disease patients, exposure to dietary gluten induces drastic changes in epithelial differentiation and elicit ... ...

    Abstract Celiac disease pathogenesis, in addition to immune cell component, encompasses pathogenic events also in the duodenal epithelium. In celiac disease patients, exposure to dietary gluten induces drastic changes in epithelial differentiation and elicit cellular response to inflammatory cytokines. The autoantigen in celiac disease, transglutaminase 2 (TG2) enzyme, has been also suggested to play its pathogenic gliadin deamidation event in the intestinal epithelium. Therefore in vitro epithelial cell-line models have been exploited in the past to study these pathogenic mechanisms, but they are hampered by their simplistic nature lacking proper cell-type composition and intestinal environ. Moreover, these cell models harbor many cancer-related mutations in tumor suppressor genes making them unsuitable for studying cell differentiation. Intestinal organoids provide a near-native epithelial cell model to study pathogenic agents and mechanisms related to celiac disease. Here we describe protocols to initiate and maintain celiac patient-derived organoid cultures and how to grow them in alternative ways allowing their exploitation in different kind of experiments.
    MeSH term(s) Humans ; Celiac Disease/genetics ; Intestines ; Organoids ; Cell Differentiation ; Cell Line
    Language English
    Publishing date 2023-02-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 0091-679X
    ISSN 0091-679X
    DOI 10.1016/bs.mcb.2023.01.008
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Editorial: The contribution of viruses and innate immune system in the pathogenesis of type 1 diabetes.

    Nigi, Laura / Laiho, Jutta E / Hyöty, Heikki / Dotta, Francesco

    Frontiers in endocrinology

    2023  Volume 14, Page(s) 1335716

    MeSH term(s) Humans ; Diabetes Mellitus, Type 1/pathology ; Immune System/pathology ; Immunity, Innate ; Viruses
    Language English
    Publishing date 2023-12-15
    Publishing country Switzerland
    Document type Editorial
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2023.1335716
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  4. Article ; Online: Urban indoor gardening enhances immune regulation and diversifies skin microbiota - A placebo-controlled double-blinded intervention study.

    Saarenpää, Mika / Roslund, Marja I / Nurminen, Noora / Puhakka, Riikka / Kummola, Laura / Laitinen, Olli H / Hyöty, Heikki / Sinkkonen, Aki

    Environment international

    2024  Volume 187, Page(s) 108705

    Abstract: According to the hygiene and biodiversity hypotheses, frequent exposure to environmental microbiota, especially through soil contact, diversifies commensal microbiota, enhances immune modulation, and ultimately lowers the risk of immune-mediated diseases. ...

    Abstract According to the hygiene and biodiversity hypotheses, frequent exposure to environmental microbiota, especially through soil contact, diversifies commensal microbiota, enhances immune modulation, and ultimately lowers the risk of immune-mediated diseases. Here we test the underlying assumption of the hygiene and biodiversity hypotheses by instructing volunteers to grow edible plants indoors during the winter season when natural exposure to environmental microbiota is low. The one-month randomized, placebo-controlled double-blind trial consisted of two treatments: participants received either microbially diverse growing medium or visually similar but microbially poor growing medium. Skin microbiota and a panel of seven immune markers were analyzed in the beginning of the trial and after one month. The diversity of five bacterial phyla (Bacteroidetes, Planctomycetes, Proteobacteria, Cyanobacteria, and Verrucomicrobia) and one class (Bacteroidia) increased on the skin of participants in the intervention group while no changes were observed in the placebo group. The number of nodes and edges in the co-occurrence networks of the skin bacteria increased on average three times more in the intervention group than in the placebo group. The plasma levels of the immunomodulatory cytokine interleukin 10 (IL-10) increased in the intervention group when compared with the placebo group. A similar trend was observed in the interleukin 17A (IL-17A) levels and in the IL-10:IL-17A ratios. Participants in both groups reported high satisfaction and adherence to the trial. The current study provides evidence in support of the core assumption of the hygiene and biodiversity hypotheses of immune-mediated diseases. Indoor urban gardening offers a meaningful and convenient approach for increasing year-round exposure to environmental microbiota, paving the way for other prophylactic practices that might help prevent immune-mediated diseases.
    Language English
    Publishing date 2024-04-26
    Publishing country Netherlands
    Document type Journal Article
    ZDB-ID 554791-x
    ISSN 1873-6750 ; 0160-4120
    ISSN (online) 1873-6750
    ISSN 0160-4120
    DOI 10.1016/j.envint.2024.108705
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Book ; Thesis: Viral and immunological markers reflecting the etiology of type 1 diabetes

    Hyöty, Heikki

    (Acta Universitatis Tamperensis : Ser. A ; 248)

    1988  

    Series title Acta Universitatis Tamperensis : Ser. A ; 248
    Acta Universitatis Tamperensis
    Acta Universitatis Tamperensis ; Ser. A
    Collection Acta Universitatis Tamperensis
    Acta Universitatis Tamperensis ; Ser. A
    Keywords Diabetes mellitus ; Typ 1 ; Immunkrankheit ; Virusinfektion
    Subject Virale Infektion ; Immunopathie ; Immunologische Krankheit ; Immunologische Erkrankung ; Typ I ; Diabetes verus ; Zuckerharnruhr ; Zuckerkrankheit
    Language English
    Size Getr. Zählung : Ill., graph. Darst.
    Publishing country Finland
    Document type Book ; Thesis
    Thesis / German Habilitation thesis Tampere, Univ., Diss., 1988
    HBZ-ID HT003278345
    ISBN 951-44-2319-4 ; 978-951-44-2319-2
    Database Catalogue ZB MED Medicine, Health

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    Shelf markLoan statusLocation
    89 E 593 order for loan Magazin

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  6. Article: CXADR polymorphism rs6517774 modifies islet autoimmunity characteristics and exhibits sex disparity.

    Nygård, Lucas / Valta, Milla / Laine, Antti-Pekka / Toppari, Jorma / Knip, Mikael / Veijola, Riitta / Hyöty, Heikki / Ilonen, Jorma / Lempainen, Johanna

    Frontiers in genetics

    2023  Volume 14, Page(s) 1248701

    Abstract: Enteroviral infections have been linked to the development of islet autoimmunity (IA) and type 1 diabetes (T1D), and the coxsackie and adenovirus receptor (CXADR) is one of the ligands used by adenoviruses and enteroviruses for cell internalization. ... ...

    Abstract Enteroviral infections have been linked to the development of islet autoimmunity (IA) and type 1 diabetes (T1D), and the coxsackie and adenovirus receptor (CXADR) is one of the ligands used by adenoviruses and enteroviruses for cell internalization. Two
    Language English
    Publishing date 2023-11-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2606823-0
    ISSN 1664-8021
    ISSN 1664-8021
    DOI 10.3389/fgene.2023.1248701
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  7. Article ; Online: Atopic sensitization in childhood depends on the type of green area around the home in infancy.

    Voor, Tiia / Pärtel, Meelis / Peet, Aleksandr / Saare, Liisa / Hyöty, Heikki / Knip, Mikael / Davison, John / Zobel, Martin / Tillmann, Vallo

    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology

    2023  Volume 53, Issue 8, Page(s) 850–853

    MeSH term(s) Infant ; Humans ; Hypersensitivity, Immediate ; Allergens
    Chemical Substances Allergens
    Language English
    Publishing date 2023-04-11
    Publishing country England
    Document type Letter ; Research Support, Non-U.S. Gov't
    ZDB-ID 645204-8
    ISSN 1365-2222 ; 0954-7894 ; 0960-2178
    ISSN (online) 1365-2222
    ISSN 0954-7894 ; 0960-2178
    DOI 10.1111/cea.14317
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  8. Article ; Online: Safety, tolerability and immunogenicity of PRV-101, a multivalent vaccine targeting coxsackie B viruses (CVBs) associated with type 1 diabetes: a double-blind randomised placebo-controlled Phase I trial.

    Hyöty, Heikki / Kääriäinen, Susanna / Laiho, Jutta E / Comer, Gail M / Tian, Wei / Härkönen, Taina / Lehtonen, Jussi P / Oikarinen, Sami / Puustinen, Leena / Snyder, Michele / León, Francisco / Scheinin, Mika / Knip, Mikael / Sanjuan, Miguel

    Diabetologia

    2024  Volume 67, Issue 5, Page(s) 811–821

    Abstract: Aims/hypothesis: Infection with coxsackie B viruses (CVBs) can cause diseases ranging from mild common cold-type symptoms to severe life-threatening conditions. CVB infections are considered to be prime candidates for environmental triggers of type 1 ... ...

    Abstract Aims/hypothesis: Infection with coxsackie B viruses (CVBs) can cause diseases ranging from mild common cold-type symptoms to severe life-threatening conditions. CVB infections are considered to be prime candidates for environmental triggers of type 1 diabetes. This, together with the significant disease burden of acute CVB infections and their association with chronic diseases other than diabetes, has prompted the development of human CVB vaccines. The current study evaluated the safety and immunogenicity of the first human vaccine designed against CVBs associated with type 1 diabetes in a double-blind randomised placebo-controlled Phase I trial.
    Methods: The main eligibility criteria for participants were good general health, age between 18 and 45 years, provision of written informed consent and willingness to comply with all trial procedures. Treatment allocation (PRV-101 or placebo) was based on a computer-generated randomisation schedule and people assessing the outcomes were masked to group assignment. In total, 32 participants (17 men, 15 women) aged 18-44 years were randomised to receive a low (n=12) or high (n=12) dose of a multivalent, formalin-inactivated vaccine including CVB serotypes 1-5 (PRV-101), or placebo (n=8), given by intramuscular injections at weeks 0, 4 and 8 at a single study site in Finland. The participants were followed for another 24 weeks. Safety and tolerability were the primary endpoints. Anti-CVB IgG and virus-neutralising titres were analysed using an ELISA and neutralising plaque reduction assays, respectively.
    Results: Among the 32 participants (low dose, n=12; high dose, n=12; placebo, n=8) no serious adverse events or adverse events leading to study treatment discontinuation were observed. Treatment-emergent adverse events considered to be related to the study drug occurred in 37.5% of the participants in the placebo group and 62.5% in the PRV-101 group (injection site pain, headache, injection site discomfort and injection site pruritus being most common). PRV-101 induced dose-dependent neutralising antibody responses against all five CVB serotypes included in the vaccine in both the high- and low-dose groups. Protective titres ≥8 against all five serotypes were seen in >90% of participants over the entire follow-up period.
    Conclusions/interpretation: The results indicate that the tested multivalent CVB vaccine is well tolerated and immunogenic, supporting its further clinical development.
    Trial registration: ClinicalTrials.gov NCT04690426.
    Funding: This trial was funded by Provention Bio, a Sanofi company.
    MeSH term(s) Adolescent ; Adult ; Female ; Humans ; Male ; Young Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; Diabetes Mellitus, Type 1/drug therapy ; Double-Blind Method ; Vaccination ; Vaccines, Combined
    Chemical Substances Antibodies, Neutralizing ; Antibodies, Viral ; Vaccines, Combined
    Language English
    Publishing date 2024-02-19
    Publishing country Germany
    Document type Randomized Controlled Trial ; Clinical Trial, Phase I ; Journal Article
    ZDB-ID 1694-9
    ISSN 1432-0428 ; 0012-186X
    ISSN (online) 1432-0428
    ISSN 0012-186X
    DOI 10.1007/s00125-024-06092-w
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  9. Article: Primary Site of Coxsackievirus B Replication in the Small Intestines: No Proof of Peyer’s Patches Involvement

    Bopegamage, Shubhada / Berakova, Katarina / Gomocak, Pavol / Baksova, Renata / Galama, Jochem / Hyoty, Heikki / Tauriainen, Sisko

    Microorganisms. 2021 Dec. 16, v. 9, no. 12

    2021  

    Abstract: Background: Enterovirus (EV) infections are associated with a broad range of diseases. Since the first experimental infection of primates with poliovirus (PV), tonsils and the Peyer’s patches (PPs) have been believed to be the primary replication sites ... ...

    Abstract Background: Enterovirus (EV) infections are associated with a broad range of diseases. Since the first experimental infection of primates with poliovirus (PV), tonsils and the Peyer’s patches (PPs) have been believed to be the primary replication sites of EVs. Our aim was to localize different viral markers in the small intestines (SI) of coxsackievirus B (CVB) orally and intraperitoneally (i.p.) infected mice. Methods: Transverse sections of SIs of both infected and control male outbred mice were collected at different intervals post-infection (p.i) and analyzed for presence of interferon-alpha (IFN-α) and viral protein VP1 by immunohistochemistry and in situ hybridization (ISH). Fluorescent marker, eGFP, was identified in cryosections of mice infected with eGFP-CVB3. Results: In the infected SIs, we observed enlarged germinating centers (GCs) in the PPs; IFN-α was detected in the PPs and mucosal layer of the SIs. However, VP1, viral RNA and the eGFP were absent in the GCs of PPs at all stages of infection irrespective of the virus strains used. Conclusions: Virus was present in the epithelial cells but not in GCs of the PPs of the murine SIs. Our results do not support the hypothesis of EV replication in the PP especially in the GCs.
    Keywords RNA ; epithelium ; fluorescence ; hybridization ; immunohistochemistry ; interferon-alpha ; males ; mice ; viruses
    Language English
    Dates of publication 2021-1216
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9122600
    Database NAL-Catalogue (AGRICOLA)

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  10. Article: Primary Site of Coxsackievirus B Replication in the Small Intestines: No Proof of Peyer's Patches Involvement.

    Bopegamage, Shubhada / Berakova, Katarina / Gomocak, Pavol / Baksova, Renata / Galama, Jochem / Hyoty, Heikki / Tauriainen, Sisko

    Microorganisms

    2021  Volume 9, Issue 12

    Abstract: Background: Enterovirus (EV) infections are associated with a broad range of diseases. Since the first experimental infection of primates with poliovirus (PV), tonsils and the Peyer's patches (PPs) have been believed to be the primary replication sites ... ...

    Abstract Background: Enterovirus (EV) infections are associated with a broad range of diseases. Since the first experimental infection of primates with poliovirus (PV), tonsils and the Peyer's patches (PPs) have been believed to be the primary replication sites of EVs. Our aim was to localize different viral markers in the small intestines (SI) of coxsackievirus B (CVB) orally and intraperitoneally (i.p.) infected mice.
    Methods: Transverse sections of SIs of both infected and control male outbred mice were collected at different intervals post-infection (p.i) and analyzed for presence of interferon-alpha (IFN-α) and viral protein VP1 by immunohistochemistry and in situ hybridization (ISH). Fluorescent marker, eGFP, was identified in cryosections of mice infected with eGFP-CVB3.
    Results: In the infected SIs, we observed enlarged germinating centers (GCs) in the PPs; IFN-α was detected in the PPs and mucosal layer of the SIs. However, VP1, viral RNA and the eGFP were absent in the GCs of PPs at all stages of infection irrespective of the virus strains used.
    Conclusions: Virus was present in the epithelial cells but not in GCs of the PPs of the murine SIs. Our results do not support the hypothesis of EV replication in the PP especially in the GCs.
    Language English
    Publishing date 2021-12-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2720891-6
    ISSN 2076-2607
    ISSN 2076-2607
    DOI 10.3390/microorganisms9122600
    Database MEDical Literature Analysis and Retrieval System OnLINE

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