| 1. |
- Alamidi, Daniel, et al.
(författare)
-
T1 Relaxation Time in Lungs of Asymptomatic Smokers.
- 2016
-
Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:3
-
Tidskriftsartikel (refereegranskat)abstract
- Interest in using T1 as a potential MRI biomarker of chronic obstructive pulmonary disease (COPD) has recently increased. Since tobacco smoking is the major risk factor for development of COPD, the aim for this study was to examine whether tobacco smoking, pack-years (PY), influenced T1 of the lung parenchyma in asymptomatic current smokers.
|
|
| 2. |
- Skrtic, Stanko, 1970, et al.
(författare)
-
Contemporary risk estimates of three HbA(1c) variables in relation to heart failure following diagnosis of type 2 diabetes
- 2017
-
Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 103:5, s. 355-360
-
Tidskriftsartikel (refereegranskat)abstract
- Background We evaluated the association between glycaemic control and the risk of heart failure (HF) in a contemporary cohort of persons followed after diagnosis of type 2 diabetes (T2D). Methods and results Persons with T2D diagnosed between 1998 and 2012 were retrieved from the Clinical Practice Research Data Link in the UK and followed from diagnosis until the event of HF, mortality, drop out from the database due to any other reason, or the end of the study on 1 July 2015. The association between each of three different haemoglobin A(1C) (HbA1c) metrics and HF was estimated using adjusted proportional hazard models. In the overall cohort (n= 94 332), the increased risk for HF per 1% (10 mmol/mol) increase in HbA(1c) was 1.15 (95% CI 1.13 to 1.18) for updated mean HbA(1c), and 1.06 (1.04 to 1.07) and 1.06 (1.04 to 1.08) for baseline HbA(1c) and updated latest HbA(1c), respectively. When categorised, the hazard risk (HR) for the updated mean HbA(1c) in relation to HF became higher than for baseline and updated latest HbA(1c) above HbA(1c) levels of 9%, but did not differ at lower HbA(1c) levels. The updated latest variable showed an increased risk for HbA(1c)
|
|
| 3. |
- Vestberg, Daniel, et al.
(författare)
-
Decreased eGFR as a Risk Factor for Heart Failure in 13 781 Individuals With Type 1 Diabetes.
- 2016
-
Ingår i: Journal of diabetes science and technology. - : SAGE Publications. - 1932-2968. ; 10:1, s. 131-136
-
Tidskriftsartikel (refereegranskat)abstract
- Impaired renal function is a well-known risk factor of cardiovascular disease, but its relation to heart failure in individuals with type 1 diabetes has been sparsely studied. The aim of our study was to quantify the risk increase for development of heart failure with decreasing kidney function in individuals with type 1 diabetes.
|
|
| 4. |
- Berg, Tove, et al.
(författare)
-
Gene expression analysis of membrane transporters and drug-metabolizing enzymes in the lung of healthy and COPD subjects.
- 2014
-
Ingår i: Pharmacology research & perspectives. - : Wiley. - 2052-1707. ; 2:4, s. e00054-
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes for the first time the expression levels of genes encoding membrane transporters and drug-metabolizing enzymes in the lungs of ex-smoking patients with chronic obstructive pulmonary disease (COPD). Membrane transporters and drug-metabolizing enzymes are key determinants of drug uptake, metabolism, and elimination for systemically administered as well as inhaled drugs, with consequent influence on clinical efficacy and patient safety. In this study, while no difference in gene expression was found between healthy and COPD subjects, we identified a significant regional difference in mRNA expression of both membrane transporters and drug-metabolizing enzymes between central and peripheral tissue in both healthy and COPD subjects. The majority of the differentially expressed genes were higher expressed in the central airways such as the transporters SLC2A1 (GLUT1), SLC28A3 (CNT3), and SLC22A4 (OCTN1) and the drug-metabolizing enzymes GSTZ1, GSTO2, and CYP2F1. Together, this increased knowledge of local pharmacokinetics in diseased and normal lung may improve modeling of clinical outcomes of new chemical entities intended for inhalation therapy delivered to COPD patients. In addition, based on the similarities between COPD and healthy subjects regarding gene expression of membrane transporters and drug-metabolizing enzymes, our results suggest that clinical pharmacological studies in healthy volunteers could be a valid model of COPD patients regarding drug disposition of inhaled drugs in terms of drug metabolism and drug transporters.
|
|
| 5. |
- Skrtic, Stanko, 1970, et al.
(författare)
-
Impact of CKD Progression on Cardiovascular Disease Risk in a Contemporary UK Cohort of Individuals With Diabetes
- 2020
-
Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 5:10, s. 1651-1660
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: It remains unclear whether an increased progression rate of chronic kidney disease (CKD) adds predictive information regarding cardiovascular disease (CVD) risk. The aim of this study was to evaluate the association between CKD progression, based on estimated glomerular filtration rate (eGFR) slope estimates and the risk for CVD. Methods: We compared the updated eGFR slope calculated over multiple overlapping 2-year periods and the updated mean eGFR. Incident CKD subjects were selected from a prevalent population with diabetes (T2DM). Subjects from the UK Clinical Practice Research Data Link GOLD (CPRD) were followed from CKD diagnosis (n = 30,222) until heart failure (HF), myocardial infarction (MI), ischemic stroke (IS), or a composite end point including all 3 event types (MACE plus), mortality, database dropout, or end of study follow-up. Results: Both the updated eGFR slope and updated mean eGFR were associated with MACE plus and HF. Updated eGFR slope decline of > -3 ml/min/1.73 m(2) increased the risk for MACE plus (adjusted hazard ratio [HR] = 1.45; 95% confidence interval [CI], 1.26-1.67), HF (HR = 1.50; 95% CI, 1.27-1.76), and MI (HR = 1.39; 95% CI, 1.01-1.91). Conclusions: This study strongly supports current evidence that CKD is an independent risk factor for CVD. From a clinical perspective, both rate of progression and cumulative status of CKD describe distinct aspects of the cardiorenal risk among persons with diabetes. This evidence is essential to enable more timely and improved use of treatments in this population.
|
|
| 6. |
|
|
| 7. |
- Tiikkaja, S., et al.
(författare)
-
Familial risk of premature cardiovascular mortality and the impact of intergenerational occupational class mobility
- 2012
-
Ingår i: Social Science & Medicine. - : Elsevier BV. - 0277-9536 .- 1873-5347. ; 75:10, s. 1883-1890
-
Tidskriftsartikel (refereegranskat)abstract
- The negative impact of low social class on cardiovascular disease (CVD) and mortality has been consistently documented. However, less scientific consistency exists in terms of whether a unique health effect of social mobility from childhood to adulthood prevails. This study explored how childhood and adult social class and the transition between them (social mobility), are related to premature CVD mortality when familial aggregation of CVD among siblings is also considered. The study includes nearly 1.9 million Swedish residents born 1939-1959 distributed over 1,044,725 families, of whom 14,667 died prematurely from CVD in 1990-2003. Information on parental class (1960) and own mid-life occupational class (1990) was retrieved from the respective censuses. Odds ratios for premature CVD mortality according to trajectory-specific social mobility, along with pairwise mean odds ratios for sibling resemblance of premature CVD mortality, were calculated by means of alternating logistic regression. This model calculates the remaining dependency of CVD mortality within sibships after accounting for available risk factors (like parental and adult social class) in the population mean model. Results showed that premature CVD mortality was associated with both parental and own adult social class. A clear tendency for the downwardly mobile to have increased, and for the upwardly mobile to experience a decreased risk of premature DID mortality was found, as well as a corresponding unique effect of social mobility per se among the manual and non-manual classes. This effect was verified for men, but not for women, when they were analysed separately. The pairwise mean odds ratios for premature CVD mortality among full siblings were 1.78 (95% CI: 1.52-2.08), and were independent of parental CVD mortality and parental or adult occupational class.
|
|
| 8. |
- Elgqvist, Jörgen, 1963, et al.
(författare)
-
Fractionated radioimmunotherapy of intraperitoneally growing ovarian cancer in nude mice with 211At-MX35 F(ab')2: therapeutic efficacy and myelotoxicity
- 2006
-
Ingår i: Nucl Med Biol. - : Elsevier BV. - 0969-8051. ; 33:8, s. 1065-72
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The aim of this study was to investigate the therapeutic efficacy and myelotoxicity during fractionated radioimmunotherapy of ovarian cancer in mice. The study was performed using the monoclonal antibody MX35 F(ab')(2) labeled with the alpha-particle emitter (211)At. METHODS: Animals were intraperitoneally inoculated with approximately 1x10(7) cells of the cell line NIH:OVCAR-3. Four weeks later, the mice were given the first treatment. Six groups of animals were intraperitoneally injected with approximately 800, 3x approximately 267, approximately 400, 3x approximately 133, approximately 50 or 3x approximately 17 kBq (211)At-MX35 F(ab')(2) (n=18 in each group). The second and third injections for Groups 2, 4 and 6 were given 4 and 8 days after the first injection, respectively. As controls, animals were treated with unlabeled MX35 F(ab')(2) (n=12). Eight weeks after the last injection, the animals were sacrificed and the presence of macro- and microscopic tumors and ascites was determined. Blood counts were determined for each mouse in Groups 1 and 2 before the first injection and 3, 7, 11, 15 and 23 days after the first injection. The calculation of the mean absorbed dose to the bone marrow was based on the ratio between the (211)At-activity concentration in bone and blood [i.e., the bone-to-blood ratio (BBLR)] as well as that between the (211)At-activity concentration in bone marrow and blood [i.e., the bone-marrow-to-blood ratio (BMBLR)] and the cumulated activity and absorbed fraction of the alpha-particles emitted by (211)At in the bone marrow. RESULTS: The tumor-free fractions of animals were 56% and 41% when treated with approximately 800 kBq and 3x approximately 267 kBq (211)At-MX35 F(ab')(2), respectively; 39% and 28% when treated with approximately 400 kBq and 3x approximately 133 kBq (211)At-MX35 F(ab')(2), respectively; and 17% and 22% when treated with approximately 50 kBq or 3x approximately 17 kBq (211)At-MX35 F(ab')(2), respectively. The nadir of the white blood cell (WBC) counts was decreased (from 46% to 19%, compared with the baseline WBC counts) and delayed (from Day 4 to Day 11 after the first injection) during the fractionated treatment compared with the single-dose treatment. The percentage of injected activity per gram (%IA/g) for blood, bone and bone marrow all peaked 6 h after injection at 13.80+/-1.34%IA/g, 4.00+/-0.69%IA/g and 8.28+/-1.38%IA/g, respectively. The BBLR and BMBLR were 0.20+/-0.04 and 0.58+/-0.01, respectively. The mean absorbed dose to bone marrow was approximately 0.4 Gy after intraperitoneally injecting approximately 800 kBq (211)At-MX35 F(ab')(2). CONCLUSION: No advantage was observed in the therapeutic efficacy of using a fractionated regimen compared with a single administration, with the same total amount of administered activity. Alleviation of the myelotoxicity was observed during the fractionated regimen in terms of decreased suppression and delayed nadir of the WBC counts. No thrombocytopenia was observed during either regimen.
|
|
| 9. |
- Haag, Petra, et al.
(författare)
-
Caspase-2 is a mediator of apoptotic signaling in response to gemtuzumab ozogamicin in acute myeloid leukemia
- 2022
-
Ingår i: Cell Death Discovery. - : Springer Nature. - 2058-7716. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- The antibody conjugate gemtuzumab ozogamicin (GO; Mylotarg((R))) provides targeted therapy of acute myeloid leukemia (AML), with recent approvals for patients with CD33-positive disease at diagnosis or relapse, as monotherapy or combined with chemotherapeutics. While its clinical efficacy is well documented, the molecular routes by which GO induces AML cell death warrant further analyses. We have earlier reported that this process is initiated via mitochondria-mediated caspase activation. Here we provide additional data, focusing on the involvement of caspase-2 in this mechanism. We show that this enzyme plays an important role in triggering apoptotic death of human AML cells after exposure to GO or its active moiety calicheamicin. Accordingly, the caspase-2 inhibitor z-VDVAD-fmk reduced GO-induced caspase-3 activation. This finding was validated with shRNA and siRNA targeting caspase-2, resulting in reduced caspase-3 activation and cleavage of poly [ADP-ribose] polymerase 1 (PARP-1). We previously demonstrated that GO-induced apoptosis included a conformational change of Bax into a pro-apoptotic state. Present data reveal that GO-treatment also induced Bid cleavage, which was partially reduced by caspase-2 specific inhibition while the effect on GO-induced Bax conformational change remained unaltered. In mononuclear cells isolated from AML patients that responded to GO treatment in vitro, processing of caspase-2 was evident, whereas in cells from an AML patient refractory to treatment no such processing was seen. When assessing diagnostic samples from 22 AML patients, who all entered complete remission (CR) following anthracycline-based induction therapy, and comparing patients with long versus those with short CR duration no significant differences in baseline caspase-2 or caspase-3 full-length protein expression levels were found. In summary, we demonstrate that GO triggers caspase-2 cleavage in human AML cells and that the subsequent apoptosis of these cells in part relies on caspase-2. These findings may have future clinical implications.
|
|
| 10. |
- Kondori, Nahid, 1967, et al.
(författare)
-
Development of IgG antibodies to Exophiala dermatitidis is associated with inflammatory responses in patients with cystic fibrosis.
- 2014
-
Ingår i: Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. - : Elsevier BV. - 1873-5010. ; 13:4, s. 391-399
-
Tidskriftsartikel (refereegranskat)abstract
- The clinical importance of airway colonisation by the fungus Exophiala dermatitidis in patients with cystic fibrosis (CF) is unclear. We have previously shown that E. dermatitidis frequently colonises the airways of patients with CF. The aims of the present study were to determine whether patients who are colonised by E. dermatitidis have detectable fungal antigens in the circulation, develop anti-fungal antibodies, and show signs of inflammation and impaired respiratory function.
|
|
