| 41. |
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| 42. |
- Akhiani, Aliasghar, 1957
(författare)
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The role of type-specific antibodies in colonization and infection by Helicobacter pylori
- 2005
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Ingår i: Curr Opin Infect Dis. ; 18:3, s. 223-7
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Forskningsöversikt (refereegranskat)abstract
- PURPOSE OF REVIEW: Helicobacter pylori is a Gram-negative spiral bacterium that colonizes the stomach of humans, causing gastritis, peptic ulcer disease, or gastric cancer. H. pylori infection accounts for a high percentage of mortality and morbidity rates in developing as well as developed countries. H. pylori bacteria reside in the mucus layer covering the gastric epithelium, and therefore the type of protective measures that could confer resistance appear to be limited. Although H. pylori infection stimulates strong local and systemic specific IgA and IgG antibody production, the influence of antibodies on bacterial colonization and gastric inflammation is still controversial. RECENT FINDINGS: Recent studies in experimental animal models have indicated a non-essential role of specific antibodies for host resistance against H. pylori infection. Recent data show that protection is mediated by T cells, CD4 T helper type 1 cells, in particular. Antibodies are not only dispensable for protection, but they impair both the elimination of bacteria and the development of gastritis. This effect appears to be IgA-dependent and is not a function of specific IgM or IgG antibodies. SUMMARY: This review highlights the recent advances in our understanding of how antibodies may influence the development of gastric inflammation and bacterial colonization. Such information can significantly increase our basic knowledge of immune regulation and protection against H. pylori infection, but can also indicate new strategies for vaccine development.
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| 43. |
- Akhiani, Aliasghar, 1957, et al.
(författare)
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Vaccine-induced immunity against Helicobacter pylori infection is impaired in IL-18-deficient mice.
- 2004
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Ingår i: Journal of immunology. - 0022-1767. ; 173:5, s. 3348-56
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Forskningsöversikt (refereegranskat)abstract
- Protective immunity against Helicobacter pylori infection in mice has been associated with a strong Th1 response, involving IL-12 as well as IFN-gamma, but recent studies have also demonstrated prominent eosinophilic infiltration, possibly linked to local Th2 activity in the gastric mucosa. In this study we investigated the role of IL-18, because this cytokine has been found to be a coregulator of Th1 development as well as involved in Th2-type responses with local eotaxin production that could influence gastric eosinophilia and resistance to infection. We found that IL-18(-/-) mice failed to develop protection after oral immunization with H. pylori lysate and cholera toxin adjuvant, indicating an important role of IL-18 in protection. Well-protected C57BL/6 wild-type (WT) mice demonstrated substantial influx of CD4(+) T cells and eosinophilic cells in the gastric mucosa, whereas IL-18(-/-) mice had less gastritis, few CD4(+) T cells, and significantly reduced numbers of eosinophilic cells. T cells in well-protected WT mice produced increased levels of IFN-gamma and IL-18 to recall Ag. By contrast, unprotected IL-18(-/-) mice exhibited significantly reduced gastric IFN-gamma and specific IgG2a Ab levels. Despite differences in gastric eosinophilic cell infiltration, protected WT and unprotected IL-18(-/-) mice had comparable levels of local eotaxin, suggesting that IL-18 influences protection via Th1 development and IFN-gamma production rather than through promoting local production of eotaxin and eosinophilic cell infiltration.
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| 44. |
- Al-Haddad, Benjamin J S, et al.
(författare)
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The fetal origins of mental illness.
- 2019
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Ingår i: American journal of obstetrics and gynecology. - : Elsevier BV. - 1097-6868 .- 0002-9378. ; 221:6, s. 549-562
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Forskningsöversikt (refereegranskat)abstract
- The impact of infections and inflammation during pregnancy on the developing fetal brain remains incompletely defined, with important clinical and research gaps. Although the classic infectious TORCH pathogens (ie, Toxoplasma gondii, rubella virus, cytomegalovirus [CMV], herpes simplex virus) are known to be directly teratogenic, emerging evidence suggests that these infections represent the most extreme end of a much larger spectrum of injury. We present the accumulating evidence that prenatal exposure to a wide variety of viral and bacterial infections-or simply inflammation-may subtly alter fetal brain development, leading to neuropsychiatric consequences for the child later in life. The link between influenza infections in pregnant women and an increased risk for development of schizophrenia in their children was first described more than 30 years ago. Since then, evidence suggests that a range of infections during pregnancy may also increase risk for autism spectrum disorder and depression in the child. Subsequent studies in animal models demonstrated that both pregnancy infections and inflammation can result in direct injury to neurons and neural progenitor cells or indirect injury through activation of microglia and astrocytes, which can trigger cytokine production and oxidative stress. Infectious exposures can also alter placental serotonin production, which can perturb neurotransmitter signaling in the developing brain. Clinically, detection of these subtle injuries to the fetal brain is difficult. As the neuropsychiatric impact of perinatal infections or inflammation may not be known for decades after birth, our construct for defining teratogenic infections in pregnancy (eg, TORCH) based on congenital anomalies is insufficient to capture the full adverse impact on the child. We discuss the clinical implications of this body of evidence and how we might place greater emphasis on prevention of prenatal infections. For example, increasing uptake of the seasonal influenza vaccine is a key strategy to reduce perinatal infections and the risk for fetal brain injury. An important research gap exists in understanding how antibiotic therapy during pregnancy affects the fetal inflammatory load and how to avoid inflammation-mediated injury to the fetal brain. In summary, we discuss the current evidence and mechanisms linking infections and inflammation with the increased lifelong risk of neuropsychiatric disorders in the child, and how we might improve prenatal care to protect the fetal brain.
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| 45. |
- Alao, John Patrick, 1973, et al.
(författare)
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Caffeine as a tool for investigating the integration of Cdc25 phosphorylation, activity and ubiquitin-dependent degradation in Schizosaccharomyces pombe.
- 2020
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Ingår i: Cell Division. - : Springer Science and Business Media LLC. - 1747-1028. ; 15
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Forskningsöversikt (refereegranskat)abstract
- The evolutionarily conserved Cdc25 phosphatase is an essential protein that removes inhibitory phosphorylation moieties on the mitotic regulator Cdc2. Together with the Wee1 kinase, a negative regulator of Cdc2 activity, Cdc25 is thus a central regulator of cell cycle progression in Schizosaccharomyces pombe. The expression and activity of Cdc25 is dependent on the activity of the Target of Rapamycin Complex 1 (TORC1). TORC1 inhibition leads to the activation of Cdc25 and repression of Wee1, leading to advanced entry into mitosis. Withdrawal of nitrogen leads to rapid Cdc25 degradation via the ubiquitin- dependent degradation pathway by the Pub1 E3- ligase. Caffeine is believed to mediate the override of DNA damage checkpoint signalling, by inhibiting the activity of the ataxia telangiectasia mutated (ATM)/Rad3 homologues. This model remains controversial, as TORC1 appears to be the preferred target of caffeine in vivo. Recent studies suggest that caffeine induces DNA damage checkpoint override by inducing the nuclear accumulation of Cdc25 in S. pombe. Caffeine may thus modulate Cdc25 activity and stability via inhibition of TORC1. A clearer understanding of the mechanisms by which caffeine stabilises Cdc25, may provide novel insights into how TORC1 and DNA damage signalling is integrated.
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| 46. |
- Alao, John Patrick, 1973, et al.
(författare)
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Rad3 and Sty1 function in S. pombe: an integrated response to DNA damage and environmental stress?
- 2008
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Ingår i: Molecular Microbiology. - : Wiley. - 0950-382X. ; 68, s. 246-254
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Forskningsöversikt (refereegranskat)abstract
- In Schizosaccharomyces pombe, the Ataxia Telangiectasia-mutated (Atm)/Atm and Rad 3 Related (Atr) homologue Rad3 is an essential regulator of the response to DNA damage and stalled replication forks. Rad3 activates the downstream kinases Chk1 and Cds1. These kinases in turn inhibit cell cycle progression by mediating Cdc2 phosphorylation. Studies in both yeast and mammalian cells suggest additional roles for Rad3 in regulating cellular responses to environmental stress. In S. pombe, cellular responses to various environmental stresses are regulated primarily through the stress-activated MAP kinase p38 homologue Sty1. An important function of Sty1 is to drive cells rapidly through mitosis by facilitating the accumulation of Cdc25. Interestingly, Sty1 is activated simultaneously with Rad3 following exposure to UV radiation or ionizing radiation (IR). Similarly, exposure to environmental stresses induces the expression of rad3+, cds1+ and other checkpoint regulator genes. It is currently unclear how the pathways regulated by Sty1 and Rad3 and their opposing effects on mitosis are integrated. Recent studies suggest that Sty1 and Rad3 function together to regulate the expression of several stress response genes following exposure to IR. In this review, we discuss current knowledge on the interaction of Rad3/Atm and Sty1/p38 in regulating cellular responses to environmental stress and DNA damage.
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| 47. |
- Alao, John Patrick, 1973
(författare)
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The ATM regulated DNA damage response pathway as a chemo- and radiosensitisation target
- 2009
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Ingår i: Expert Opinion on Drug Discovery. - : Informa Healthcare. - 1746-0441 .- 1746-045X. ; 4:5, s. 495-505
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Forskningsöversikt (refereegranskat)abstract
- Background: Ataxia telangiectasia mutated (ATM) kinase plays a central role in maintaining genomic stability and regulating the response of cells exposed to agents that induce DNA damage. ATM regulated pathways also enable cancer cells to resist the lethal effects of genotoxic cancer treatments. The pharmacological inhibition of these pathways may thus sensitise cancer cells to chemo- and radiotherapy. Objectives: This review outlines the role of ATM in regulating components of the DNA damage response pathway. The potential of inhibitors that target ATM regulated pathways to act as chemo- and radiosensitising agents is also discussed. Results/conclusions: Inhibitors that target ATM and its downstream targets are likely to be effective as chemo- and/ or radiosensitising agents. Their effective use will, however, require a better understanding of when and how ATM influences the sensitivity of cancer cells to particular genotoxic agents.
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| 48. |
- Alao, John Patrick, 1973
(författare)
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The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention
- 2007
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Ingår i: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 6
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Forskningsöversikt (refereegranskat)abstract
- Cyclin D1 is an important regulator of cell cycle progression and can function as a transcriptionl co-regulator. The overexpression of cyclin D1 has been linked to the development and progression of cancer. Deregulated cyclin D1 degradation appears to be responsible for the increased levels of cyclin D1 in several cancers. Recent findings have identified novel mechanisms involved in the regulation of cyclin D1 stability. A number of therapeutic agents have been shown to induce cyclin D1 degradation. The therapeutic ablation of cyclin D1 may be useful for the prevention and treatment of cancer. In this review, current knowledge on the regulation of cyclin D1 degradation is discussed. Novel insights into cyclin D1 degradation are also discussed in the context of ablative therapy. A number of unresolved questions regarding the regulation of cellular cyclin D1 levels are also addressed.
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| 49. |
- Albertsson, Per, 1964, et al.
(författare)
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Positron emission tomography and computed tomographic (PET/CT) imaging for radiation therapy planning in anal cancer: A systematic review and meta-analysis
- 2018
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Ingår i: Critical reviews in oncology/hematology. - : Elsevier BV. - 1040-8428. ; 126, s. 6-12
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Forskningsöversikt (refereegranskat)abstract
- To improve the accuracy of chemoradiation therapy in anal cancer patients PET/CT is frequently used in the planning of radiation therapy. A systematic review was performed to assess impact on survival, quality of life, symptom score, change in target definition and treatment intention. Systematic literature searches were conducted in Medline, EMBASE, the Cochrane Library, and Centre for Reviews and Dissemination. Ten cross-sectional studies were identified. No data were available on survival or quality of life. The summary estimate of the proportion of patients in which PET/CT had an impact on the target definition, was 23% (95% CI 16;33). The corresponding summary estimate of a change in treatment intent from curative to palliative was 3% (95% CI 2;6). Almost one in four patients had a change in target definition, which supports the use of PET/CT in radiation therapy planning, but the consequence regarding survival and quality of life is still uncertain.
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| 50. |
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