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- Antza, C., et al.
(författare)
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Prevention of cardiovascular disease in young adults: Focus on gender differences. A collaborative review from the EAS Young Fellows
- 2023
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Ingår i: Atherosclerosis. - 0021-9150. ; 384
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Tidskriftsartikel (refereegranskat)abstract
- A steady rise in cardiovascular morbidity and mortality has been observed in young adults within the last decades. This trend corresponds to an increasing prevalence of traditional cardiovascular risk factors such as obesity and diabetes mellitus type 2 among young adults living in developed countries. Moreover, age-specific risk factors, such as substance abuse, contraceptive medication, and pregnancy-related diseases also correlate with an increased incidence of cardiovascular diseases. In this review, we discuss the available data for young adults on the epidemiology and the rationale for the causality of traditional and newly emerging risk factors of atherosclerotic cardiovascular diseases. We focus on gender-related differences in the exposure to these risk factors, investigate the recent data regarding screening and risk stratification in the young adult population, and describe the current state of the art on lifestyle and therapeutic intervention strategies in the primary prevention setting.
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| 10. |
- Berggren, P, et al.
(författare)
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p53 mutations in urinary bladder cancer
- 2001
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Ingår i: British journal of cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 84:11, s. 1505-1511
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Tidskriftsartikel (refereegranskat)
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| 11. |
- Berglof, A, et al.
(författare)
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Association of bronchopneumonia with sinusitis due to Bordetella bronchiseptica in an experimental rabbit model
- 2000
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Ingår i: American journal of rhinology. - : SAGE Publications. - 1050-6586 .- 1539-6290. ; 14:2, s. 125-130
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Tidskriftsartikel (refereegranskat)abstract
- An animal model for rhinogenic sinusitis was developed in rabbits naturally colonized with Bordetella bronchiseptica. It was found that ostial occlusion predisposes the sinus to invasion with this opportunistic bacterium and subsequent sinusitis as a result of reduced local host defense. In addition to the inflammatory lesions in the sinus, bronchitis and pneumonia were found in 84% of the experimental rabbits, suggesting that ostial dysfunction can also contribute to infectious disease of the lower respiratory tract. In such a model it is possible to study the significance of asymptomatic carriage of potential pathogens after ostial occlusion.
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- Martinez-Monleon, Angela, et al.
(författare)
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Amplification of CDK4 and MDM2: a detailed study of a high-risk neuroblastoma subgroup
- 2022
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- In neuroblastoma, MYCN amplification and 11q-deletion are important, although incomplete, markers of high-risk disease. It is therefore relevant to characterize additional alterations that can function as prognostic and/or predictive markers. Using SNP-microarrays, a group of neuroblastoma patients showing amplification of one or multiple 12q loci was identified. Two loci containing CDK4 and MDM2 were commonly co-amplified, although amplification of either locus in the absence of the other was observed. Pharmacological inhibition of CDK4/6 with ribociclib or abemaciclib decreased proliferation in a broad set of neuroblastoma cell lines, including CDK4/MDM2-amplified, whereas MDM2 inhibition by Nutlin-3a was only effective in p53(wild-type) cells. Combined CDK4/MDM2 targeting had an additive effect in p53(wild-type) cell lines, while no or negative additive effect was observed in p53(mutated) cells. Most 12q-amplified primary tumors were of abdominal origin, including those of intrarenal origin initially suspected of being Wilms' tumor. An atypical metastatic pattern was also observed with low degree of bone marrow involvement, favoring other sites such as the lungs. Here we present detailed biological data of an aggressive neuroblastoma subgroup hallmarked by 12q amplification and atypical clinical presentation for which our in vitro studies indicate that CDK4 and/or MDM2 inhibition also could be beneficial.
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| 29. |
- Muth, Andreas, 1974, et al.
(författare)
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Genetic testing and surveillance guidelines in hereditary pheochromocytoma and paraganglioma
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:2, s. 187-204
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Tidskriftsartikel (refereegranskat)abstract
- Pheochromocytoma and paraganglioma (PPGL) are rare tumours and at least 30% are part of hereditary syndromes. Approximately 20% of hereditary PPGL are caused by pathogenic germ line variants in genes of the succinate dehydrogenase complex (SDHx), TMEM127 or MAX. Herein we present guidelines regarding genetic testing of family members and their surveillance based on a thorough literature review. All cases of PPGL are recommended genetic testing for germ line variants regardless of patient and family characteristics. At minimum, FH, NF1, RET, SDHB, SDHD and VHL should be tested. In addition, testing of MEN1, SDHA, SDHAF2, SDHC, TMEM127 and MAX is recommended. Healthy first-degree relatives (and second-degree relatives in the case of SDHD and SDHAF2 which are maternally imprinted) should be offered carrier testing. Carriers of pathogenic variants should be offered surveillance with annual biochemical measurements of methoxy-catecholamines and bi-annual rapid whole-body magnetic resonance imaging and clinical examination. Surveillance should start 5 years before the earliest age of onset in the family and thus only children eligible for surveillance should be offered pre-symptomatic genetic testing. The surveillance of children younger than 15 years needs to be individually designed. Our guidelines will provide a framework for patient management with the possibility to follow outcome via national registries and/or follow-up studies. Together with improved insights into the disease, this may enable optimisation of the surveillance scheme in order to minimise both anxiety and medical complications while ensuring early disease detection.
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- Sandstedt, Joakim, et al.
(författare)
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COMP (Cartilage Oligomeric Matrix Protein) Neoepitope: A Novel Biomarker to Identify Symptomatic Carotid Stenosis
- 2021
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Ingår i: Arteriosclerosis, thrombosis, and vascular biology. - 1524-4636 .- 1079-5642. ; 41:3, s. 1218-1228
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: COMP (cartilage oligomeric matrix protein) is abundantly expressed in the cardiovascular system, cartilage, and atherosclerotic plaques. We investigated if the total COMP (COMPtotal) and COMP neoepitope (COMPneo) with other cardiovascular markers and clinical parameters could identify symptomatic carotid stenosis. Approach and Results: Blood samples were collected from patients with symptomatic carotid stenosis (stenosis, n=50), patients with stroke without carotid stenosis but small plaques (plaque, n=50), and control subjects (n=50). COMPtotal and COMPneo were measured using an ELISA. Ninety-two cardiovascular disease markers were measured by the Olink CVD kit. The presence of native COMP and COMPneo was determined by immunohistochemistry. The concentration of COMPneo was higher and COMPtotal was lower in the stenosis group. When the concentration was compared between the stenosis and control groups, IL-1ra (interleukin-1 receptor antagonist protein), IL6 (interleukin-6), REN (Renin), MMP1 (matrix metalloproteinase-1), TRAIL-R2 (tumor necrosis factor-related apoptosis-inducing ligand receptor 2), ITGB1BP2 (integrin beta 1 binding protein 2), and COMPneo were predictive of stenosis. Conversely, KLK6 (kallikrein-6), COMPtotal, NEMO (nuclear factor-kappa-B essential modulator), SRC (Proto-oncogene tyrosine-protein kinase Src), SIRT2 (SIR2-like protein), CD40 (cluster of differentiation 40), TF (tissue factor), MP (myoglobin), and RAGE (receptor for advanced glycation end-products) were predictive of the control group. Model reproducibility was good with the receiver operating characteristic plot area under the curve being 0.86. When comparing the plaque group and stenosis group, COMPneo, GAL (galanin), and PTX3 (pentraxin-related protein PTX3) were predictive of stenosis. Model reproducibility was excellent (receiver operating characteristic plot area under the curve 0.92). COMPneo was detected in smooth muscle-, endothelial-, and foam-cells in carotid stenosis. CONCLUSIONS: Degradation of COMP may be associated with atherosclerosis progression and generation of a specific COMP fragment-COMPneo. This may represent a novel biomarker that together with COMPtotal and other risk-markers could be used to identify symptomatic carotid stenosis. Graphic Abstract: A graphic abstract is available for this article.
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| 35. |
- Sandstedt, K, et al.
(författare)
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Differential susceptibility to Mycoplasma pulmonis intranasal infection in X-linked immunodeficient (xid), severe combined immunodeficient (scid), and immunocompetent mice
- 1997
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Ingår i: Clinical and experimental immunology. - : Oxford University Press (OUP). - 0009-9104 .- 1365-2249. ; 108:3, s. 490-496
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Tidskriftsartikel (refereegranskat)abstract
- Mice with the scid mutation are highly susceptible to Mycoplasma pulmonis infection and develop a disseminated disease. In order to study the contribution of humoral immunity to the immune response, M. pulmonis was inoculated intranasally to X-linked immunodeficient (xid) mice. Severe combined immunodeficient (scid) and immunocompetent CBA mice were used as controls. The mice were killed and necropsied at day 30 or 37 post-infection. Samples from the nose, lungs and joints were taken for bacteriological and histological examination. Rhinitis was observed in all mouse strains. Chronic purulent bronchopneumonia was diagnosed in some of the CBA mice. Xid mice did not show severe lung lesions, despite the presence of numerous mycoplasma organisms in the lungs, in contrast to immunocompetent mice, which developed lung pathology. Scid mice showed less signs of pneumonia, but unlike in xid and CBA mice, there was spread of mycoplasmas from the respiratory tract and severe pathological changes in the joints. Our results indicate that B and/or T lymphocytes protect against dissemination of M. pulmonis from the airways. Innate immune reactions and/or bacterial virulence factors seem to contribute to the development of joint lesions, whereas IgG3 and IgM antibodies might be involved in lung pathology.
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| 38. |
- Skoglund, Karin, et al.
(författare)
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In vivo CYP3A activity and pharmacokinetics of imatinib in relation to therapeutic outcome in chronic myeloid leukemia patients
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: The hepatic enzymes CYP3A4 and CYP3A5 metabolize the tyrosine kinase inhibitor imatinib into a large number of metabolites including the pharmacologically active N-desmethyl imatinib (CGP74588). Because the metabolic activity of CYP3A varies considerably between individuals and a previous pilot study suggested an inverse association between in vivo CYP3A metabolic activity and therapeutic outcome of imatinib, the primary aim of this study was to investigate the influence of CYP3A metabolic activity on the outcome of imatinib therapy in chronic myeloid leukemia patients.Methods: Fifty-five patients were included and CYP3A activity was estimated in vivo using quinine as a probe drug. Imatinib and CGP74588 trough concentrations in the plasma were determined at steady state in 34 patients. Cytogenetic and molecular responses after 12 months of first-line imatinib were retrospectively collected from patients’ medical records.Results: Patients with optimal response to imatinib (complete cytogenetic response (CCgR) or molecular response of BCR-ABL <1%) did not have different levels of CYP3A activity compared to non-optimal responders. Similar results were found when analyzing the molecular response and CCgR separately. Neither the imatinib trough concentration nor the CGP74588/imatinib ratio were significantly associated with CYP3A activity.Conclusion: CYP3A enzyme activity, as measured by quinine metabolic ratio, does not correlate with the plasma concentrations of imatinib or CGP74588 and is not predictive of imatinib therapeutic outcome. These results indicate that even though imatinib is metabolized by CYP3A enzymes, this activity is not the ratelimiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes such as plasma protein binding or transport protein activity to look for the major contributor to patient variability in imatinib plasma concentration.
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| 41. |
- Stewénius, Ylva, et al.
(författare)
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Defective chromosome segregation and telomere dysfunction in aggressive Wilms' tumors
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 13:22, s. 6593-6602
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In many childhood neoplasms, prognostic subgroups have been defined based on specific chromosome changes. In Wilms' tumor (WT), such subclassification has been hampered by the diverse and relatively unspecific pattern of chromosomal imbalances present in these tumors. Unspecific patterns of cytogenetic imbalances in tumors are often caused by mitotic segregation errors due to short dysfunctional telomeres. As an alternative to cytogenetic classification, we therefore have evaluated whether the rate of telomere-dependent chromosomal instability could influence the clinical course inWT patients. Experimental Design: Telomere function and mitotic segregation errors were assessed in 12 cultured tumors and in tumor tissue sections from 41 WT patients. Results: Abnormal telomere shortening was found in cultured cells and in tissue sections from highly aggressive tumors. In vitro, dysfunctional telomeres were associated to specific cell division abnormalities, including anaphase bridges and multipolar mitoses. Assessment of mitotic figures in tissue sections revealed that anaphase bridges and multipolar mitoses were predominantly, but not exclusively, present in high-risk tumors and were predictors of poor event-free and overall survival. Conclusions: Telomere-dependent mitotic instability is present in a subgroup of WT predominately consisting of high-risk tumors.
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| 42. |
- Sundberg, Martin, et al.
(författare)
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Peripubertal moderate exercise increases bone mass in boys but not in girls: a population-based intervention study
- 2001
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Ingår i: Osteoporosis International. - : Springer Science and Business Media LLC. - 1433-2965 .- 0937-941X. ; 12:3, s. 230-238
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Tidskriftsartikel (refereegranskat)abstract
- On the basis of cross-sectional studies in elite athletes and longitudinal studies, physical activity in growing children has been suggested to enhance bone mineral acquisition and prevent osteoporosis later in life. The level of exercise in most of these studies is not applicable in a population on a day-to-day basis. The aim of this study was to determine whether moderate increased exercise within the school curriculum from age 12 to 16 years would have anabolic bone effects. In a population-based setting of 40 boys and 40 girls the school curriculum was enhanced to physical education 4 times per week for 3-4 years. Controls were 82 boys and 66 girls who had had physical education twice a week over a corresponding period. Both cases and controls were measured at age 16 years. Bone mineral content (BMC), areal bone mineral density (aBMD), bone size (femoral neck width) and volumetric BMD (vBMD) were measured in total body, spine and femoral neck (FN) by dual-energy X-ray absorptiometry. Data are presented as mean +/- SD. BMC (8 +/- 15%, p = 0.04), aBMD (9 +/- 13%, p = 0.002) and vBMD (9 +/- 15%, p = 0.001) were all higher in FN in the male intervention group compared with controls. FN bone size was no higher in the intervention group than in the controls. In girls, no differences were found when comparing the intervention group with controls. The results remained after adjusting for confounding factors such as weight, height, milk intake and activity after school. In summary, we report that increased bone mass can be achieved in a population-based cohort of boys (but not in girls) by moderate increased physical activity within the school curriculum from age 12 to 16 years. We speculate that the same results can be seen in girls if intervention starts at an earlier age. We conclude that increasing the physical education content of the Swedish school curriculum may improve bone mass in at least peripubertal boys.
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