| 1. |
- Carlander, Christina, et al.
(författare)
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HPV Types in Cervical Precancer by HIV Status and Birth Region : A Population-Based Register Study
- 2020
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : AMER ASSOC CANCER RESEARCH. - 1055-9965 .- 1538-7755. ; 29:12, s. 2662-2668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Data are lacking regarding which human papillomavirus (HPV) types cause high-grade cervical neoplasia (CIN2+) in people with HIV in Europe. We assessed which HPV types are associated with CIN2+ in women living in Sweden by HIV status.Methods: The Swedish National HIV Registry, the Swedish Population Registry, and the Swedish National Cervical Screening Registry were linked. CIN2+ tissue blocks of 130 women living with HIV (WLWH) and 234 HIV-negative women, matched for country of birth (1:2), were retrieved from bio-banks and HPV genotyped. Adjusted ORs (adjOR), stratified by country of birth, were calculated using conditional logistic regression. Matching was broken for cross-group comparisons.Results: WLWH with CIN2 were less likely to have HPV16 [14% vs. 40%; adjOR 0.1; 95% confidence interval (CI), 0.04-0.56] than HIV-negative women, but among women with CIN3, there was no difference in HPV16 prevalence by HIV status (adjOR 0.9; 95% CI, 0.51-1.70). WLWH were six times more likely to have HPV35 in CIN3 than HIV-negative women (adjOR 6.2; 95% CI, 1.3-30.4). WLWH from sub-Saharan Africa (SSA) had less 9-valent vaccine types, compared with both HIV-negative women born in Sweden (adjOR 0.1; 95% CI, 0.02-0.44) and WLWH born in Sweden (adjOR 0.1; 95% CI, 0.01-0.73), mostly because of decreased HPV16 and increased HPV35.Conclusions: WLWH from SSA were less likely to be covered by the 9-valent vaccine, mostly due to less HPV16 and more HPV35. Impact: This could have implications for HPV vaccines, currently not including HPV35, and for HPV-screening algorithms in women with origin from SSA.
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| 2. |
- Carlander, Christina, et al.
(författare)
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Nonvaccine human papillomavirus genotype common in women with HIV failing cervical precancer treatment
- 2021
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Ingår i: AIDS. - : Wolters Kluwer. - 0269-9370 .- 1473-5571. ; 35:14, s. 2367-2374
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The aim of this study was to assess failure after treatment of high-grade cervical intraepithelial neoplasia (CIN2+) by HIV status and human papillomavirus (HPV) type.Design: A population-based register study.Methods: The Swedish National HIV Registry, the Swedish Population Registry and the Swedish National Cervical Screening Registry were linked to identify all women in Stockholm and Gothenburg counties (Sweden) living with HIV and diagnosed with CIN2+ sometime between 1983 and 2014 (n = 179). HIV-negative controls with CIN2+, were matched (2 : 1) for country of birth. CIN2+ biopsies were retrieved from biobanks and genotyped. Absolute risk and adjusted odds ratios (adjOR) of treatment failure by HIV status given HPV type (HPV16/18 vs. non-HPV16/18) were calculated.Results: HPV16 (32%) and HPV35 (24%) dominated in women living with HIV (WLWH) with failure, HPV35 mainly in women born in sub-Saharan Africa (67%). The absolute risk of failure in women with HPV16/18 was 26% [95% confidence interval (95% CI) 14-44] in WLWH and 12% in HIV-negative (95% CI 7-19). The absolute risk of failure in women with non-HPV16/18 was 20% (95% CI 12-31) in WLWH and 5% in HIV-negative (95% CI 2-11). WLWH with non-HPV16/18 were six times more likely to fail than HIV-negative (adjOR 6.1, 95% CI 2.0-18.6).Conclusion: HPV35, not included in current HPV vaccines, was the second most common type in WLWH with failure. WLWH with non-HPV16/18 were six times more likely to fail than HIV-negative. This could have implications for surveillance and vaccination post CIN2+ treatment, particularly in WLWH from sub-Saharan Africa.
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| 3. |
- Dzabic, Mensur
(författare)
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Cytomegalovirus infection in vascular diseases and transplant rejection
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Human cytomegalovirus (HCMV) infects 60-100% of the adult population. It belongs to the Herpesviridae family and establishes latency within its host post primary infection. HCMV reactivation is dependent on inflammation and the virus has evolved numerous mechanisms to sustain an inflammatory process and thus prolong its replication period. This has led to the hypothesis that HCMV may contribute to the pathogenesis of various inflammatory diseases. Our studies herein focus on further elucidating the role of HCMV in vascular diseases and transplant rejection. We found that: I) HCMV is present in a vast majority of abdominal aortic aneurysms where it predominantly infects the intimal smooth muscle cells. The infected cells showed an increased migratory capacity that was in part dependent on basic fibroblast growth factor. Furthermore, in the vascular lesions where HCMV was present there was an induced expression of 5-lipoxygenase, a key enzyme in the synthesis of the potent proinflammatory leukotriene B4. Thus, our study supports previous findings that HCMV is found in abdominal aortic aneurysm, and that it has the potential to contribute to the pathogenesis of abdominal aortic aneurysm. II) Native arteriovenous fistula (AVF) is the preferred form of haemodialysis vascular access however dysfunction due to neointimal hyperplasia, vascular stenosis and thrombosis is a major cause of morbidity in this patient population. In a prospective cohort study we sought to identify novel prognostic factors for failure of native AVF. Numerous biochemical and patient characteristics were analysed just prior to construction of the AVF. We identified white blood cell count, monocyte count and red blood cell distribution width as independent prognostic factors for AVF failure. Red blood cell distribution width is a novel prognostic factor and was also the most optimal. The mechanistic link between high red blood cell distribution width and AVF failure is yet to be elucidated. III) Using the patient cohort described in (II) we investigated the potential role of HCMV in the failure of AVF. In contrary to previous reports, high anti-HCMV IgG levels were not associated with reduced AVF patency in our study. HCMV proteins could be located in the vessels of 46% of patients at the time of AVF construction but presence of HCMV proteins was not associated with reduced AVF patency. Our study does not support the hypothesis that HCMV has a role in the failure of AVF. IV) HCMV has been associated with chronic transplant rejection however the virus has been difficult to detect in the affected organs and thus the effects of HCMV have been defined as indirect. In this retrospective cohort study we evaluated the presence of HCMV in chronic renal allograft dysfunction, in early as well as end-stage biopsies. We found that HCMV is present in a majority of grafts early post transplantation and that the HCMV levels increase as the graft deteriorates. Furthermore, high HCMV intragraft protein expression in the early biopsy is associated with reduced allograft survival. Our study provides further support for a role of HCMV in allograft rejection and suggests that direct effects of the virus are involved in chronic allograft dysfunction.
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| 4. |
- Dzabic, Mensur, et al.
(författare)
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Intragraft Cytomegalovirus Protein Expression Is Associated With Reduced Renal Allograft Survival
- 2011
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1058-4838 .- 1537-6591. ; 53:10, s. 969-976
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Tidskriftsartikel (refereegranskat)abstract
- Background: Cytomegalovirus (CMV) infection is a risk factor for acute and chronic rejection of transplanted organs and is thought to mediate rejection indirectly. Methods: In this retrospective observational cohort study, early- and end-stage biopsies from renal allografts lost because of chronic allograft dysfunction (n = 29) were examined for CMV antigens and DNA using immunohistochemistry, in situ hybridization, and real-time polymerase chain reaction. Results: CMV immediate-early and late proteins were present in 27 (93%) of 29 of the end-stage chronic allograft dysfunction biopsies and in 64% of the corresponding early biopsies but not in pretransplant biopsies from CMV-seronegative donors (n = 3). Graft survival time was reduced in patients with moderate or high CMV levels in the graft soon after transplantation compared with that in patients with no or low CMV levels in the graft. No significant difference was observed in serum creatinine obtained at the time of early biopsies. Conclusions: We provide evidence that intragraft CMV protein expression is associated with end-stage chronic renal allograft dysfunction, that intragraft CMV levels increase as graft function deteriorates, and that CMV protein expression in the grafts soon after transplant is associated with reduced graft survival. Thus, CMV may have a pathological role in chronic renal allograft dysfunction.
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| 5. |
- Gredmark-Russ, Sara, et al.
(författare)
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Active cytomegalovirus infection in aortic smooth muscle cells from patients with abdominal aortic aneurysm
- 2009
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Ingår i: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 0946-2716 .- 1432-1440. ; 87:4, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- Cytomegalovirus (CMV) is associated with atherosclerosis and transplant vascular sclerosis. The aim of this study was to explore the hypothesis that active CMV infection in the vessel wall could be associated with abdominal aortic aneurysm (AAA). We examined the prevalence of CMV in AAA specimens from 22 patients undergoing surgery and, in five cases, characterized the function of smooth muscle cells (SMCs) from the aneurysm in vitro. Twenty-one (95%) of the 22 AAA specimens were CMV positive by a polymerase chain reaction assay, in situ hybridization, or a highly sensitive immunohistochemical staining technique. No positive cells were found in aortas from three CMV-seronegative organ donor cadavers. CMV immediate-early and late antigens were expressed in SMCs in the lesions and were associated with 5-lipoxygenase (5-LO) expression. CMV-positive intimal SMCs migrated 6.6 +/- 1.5 times more efficiently than CMV-negative medial SMCs (p < 0.05). In vitro CMV infection of medial SMCs resulted in a 3.2 +/- 1.2 times increase in migration (p < 0.05). The intimal migration was significantly inhibited by antibodies against basic fibroblast growth factor (bFGF; p < 0.05) in a dose-dependent fashion. Antibodies against platelet-derived growth factor (PDGF)-AB, insulin-like growth factor 1, vascular endothelial growth factor (VEGF), RANTES, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, or interleukin-1beta did not significantly affect intimal SMC migration. However, intimal and medial SMCs secreted similar amounts of bFGF, MCP-1, MIP-1alpha, RANTES, PDGF-AB, PDGF-BB, epidermal growth factor, and VEGF. CMV infection in vitro of intimal and medial cells did not result in significant changes of bFGF or MCP-1 secretion. Since CMV infection can affect several functional parameters in SMCs, including several key factors in infected SMCs, our findings provide support for the hypothesis that CMV contributes to the pathogenesis of abdominal aortic aneurysm.
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| 6. |
- Gustafsson, Amanda Jabin, et al.
(författare)
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Ryanodine receptor-operated activation of TRP-like channels can trigger critical Ca2+ signaling events in pancreatic beta-cells
- 2005
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Ingår i: The FASEB Journal. - : Wiley. - 0892-6638 .- 1530-6860. ; 19:2, s. 301-303
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Tidskriftsartikel (refereegranskat)abstract
- There is little information available concerning the link between the ryanodine (RY) receptors and the downstream Ca(2+) signaling events in beta-cells. In fura-2 loaded INS-1E cells, activation of RY receptors by 9-methyl 5,7-dibromoeudistomin D (MBED) caused a rapid rise of [Ca(2+)]i followed by a plateau and repetitive [Ca(2+)]i spikes on the plateau. The [Ca(2+)]i plateau was abolished by omission of extracellular Ca(2+) and by SKF 96365. In the presence of SKF 96365, MBED produced a transient increase of [Ca(2+)]i, which was abolished by thapsigargin. Activation of RY receptors caused Ca(2+) entry even when the ER Ca(2+) pool was depleted by thapsigargin. The [Ca(2+)]i plateau was not inhibited by nimodipine or ruthenium red, but was inhibited by membrane depolarization, La(3+), Gd(3+), niflumic acid, and 2-aminoethoxydiphenyl borate, agents that inhibit the transient receptor potential channels. The [Ca(2+)]i spikes were inhibited by nimodipine and ryanodine, indicating that they were due to Ca(2+) influx through the voltage-gated Ca(2+) channels and Ca(2+)-induced Ca(2+) release (CICR). Activation of RY receptors depolarized membrane potential as measured by patch clamp. Thus, activation of RY receptors leads to coherent changes in Ca(2+) signaling, which includes activation of TRP-like channels, membrane depolarization, activation of the voltage-gated Ca(2+) channels and CICR.
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| 7. |
- Woolcott, Orison O, et al.
(författare)
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Arachidonic acid is a physiological activator of the ryanodine receptor in pancreatic beta-cells.
- 2006
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Ingår i: Cell Calcium. - : Elsevier BV. - 0143-4160 .- 1532-1991. ; 39:6, s. 529-37
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic beta-cells have ryanodine receptors but little is known about their physiological regulation. Previous studies have shown that arachidonic acid releases Ca(2+) from intracellular stores in beta-cells but the identity of the channels involved in the Ca(2+) release has not been elucidated. We studied the mechanism by which arachidonic acid induces Ca(2+) concentration changes in pancreatic beta-cells. Cytosolic free Ca(2+) concentration was measured in fura-2-loaded INS-1E cells and in primary beta-cells from Wistar rats. The increase of cytosolic Ca(2+) concentration induced by arachidonic acid (150microM) was due to both Ca(2+) release from intracellular stores and influx of Ca(2+) from extracellular medium. 5,8,11,14-Eicosatetraynoic acid, a non-metabolizable analogue of arachidonic acid, mimicked the effect of arachidonic acid, indicating that arachidonic acid itself mediated Ca(2+) increase. The Ca(2+) release induced by arachidonic acid was from the endoplasmic reticulum since it was blocked by thapsigargin. 2-Aminoethyl diphenylborinate (50microM), which is known to inhibit 1,4,5-inositol-triphosphate-receptors, did not block Ca(2+) release by arachidonic acid. However, ryanodine (100microM), a blocker of ryanodine receptors, abolished the effect of arachidonic acid on Ca(2+) release in both types of cells. These observations indicate that arachidonic acid is a physiological activator of ryanodine receptors in beta-cells.
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