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Sökning: LAR1:lu > Karolinska Institutet

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1.
  • Aaltonen, Kirsimari, et al. (författare)
  • Cyclin D1 expression is associated with poor prognostic features in estrogen receptor positive breast cancer
  • 2009
  • Ingår i: Breast Cancer Research and Treatment. - Springer. - 1573-7217. ; 113:1, s. 75-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Cyclins D1 and E play an important role in breast carcinogenesis. High cyclin E expression is common in hormone receptor negative and high grade aggressive breast cancer, whereas cyclin D1 in hormone receptor positive and low grade breast cancer. Experimental data has suggested that cyclin D1 and E mediate cell proliferation by different mechanisms in estrogen receptor (ER) positive and negative breast cancer. To test this hypotheses in large breast cancer material and to clarify the histopathological correlations of cyclin E and D1, especially the association with proliferation, we analyzed cyclin E and D1 immunohistochemical expression on breast tumour microarrays consisting of 1348 invasive breast cancers. High cyclin D1 expression was associated with high grade (P < 0.0005), high cyclin A (P < 0.0005) and Ki67 (P < 0.0005) expression among ER positive but with low grade (P = 0.05) and low Ki67 (P = 0.01) expression among ER negative breast cancers. Cyclin E and D1 expression correlated positively in ER positive (P < 0.0005) but had a negative correlation in ER negative tumours (P = 0.004). Cyclin E associated with high grade among all tumours (P < 0.0005). In conclusion, the findings of this study show that cyclin D1 has separate roles, and proliferation is driven by different mechanisms in ER positive and negative breast cancers.
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2.
  • Aase, K, et al. (författare)
  • Vascular endothelial growth factor-B-deficient mice display an atrial conduction defect
  • 2001
  • Ingår i: Circulation. - Lippincott Williams and Wilkins. - 1524-4539. ; 104:3, s. 358-358
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Vascular endothelial growth factors (VEGFs) and their receptors are essential regulators of vasculogenesis and angiogenesis in both embryos and adults. One of the factors with a still unknown physiological function is VEGF-B, which is expressed in many tissues, including the heart. METHODS AND RESULTS: Mice carrying a targeted deletion in the VEGF-B gene were developed. In VEGF-B(-/-) animals, no gross abnormalities were observed in organs that normally show high expression of VEGF-B, such as the heart, muscle, and kidney. Analysis of heart function by ECG showed that adult VEGF-B(-/-) mice have an atrial conduction abnormality characterized by a prolonged PQ interval. VEGF- or basic fibroblast growth factor-induced corneal angiogenesis was similar in normal and VEGF-B(-/-) mice. CONCLUSIONS: VEGF-B seems to be required for normal heart function in adult animals but is not required for proper development of the cardiovascular system either during development or for angiogenesis in adults.
3.
  • Abate, G, et al. (författare)
  • Characterization of isoniazid-resistant strains of Mycobacterium tuberculosis on the basis of phenotypic properties and mutations in katG
  • 2001
  • Ingår i: European Journal of Clinical Microbiology & Infectious Diseases. - Springer. - 1435-4373. ; 20:5, s. 329-333
  • Tidskriftsartikel (refereegranskat)abstract
    • Forty isoniazid-resistant Mycobacterium tuberculosis isolates were characterized on the basis of phenotypic properties (i.e., catalase activity, MIC of isoniazid, and growth pattern in the presence of 7 different concentrations of isoniazid) and alterations in the katG gene (codons 315 and 463). Three different growth patterns could be distinguished: concentration-dependent inhibition of growth was observed in 29 strains, similar growth at all concentrations was seen in 7 strains, and enhanced growth at low concentrations of isoniazid was evident in 4 strains. The MIC of isoniazid was < or = microg/ml for 29 of 40 strains. Mutation at codon 315 of the katG was detected in 28 of 40 strains. However, only one of the seven strains for which the MIC of isoniazid was > or = 16 microg/ml had mutation at this codon. Five of these seven strains for which the MIC was > or = 16 microg/ml had no catalase activity. The results indicate that the MIC of isoniazid for a majority of strains is below the level achievable in serum. Therefore, isoniazid may be beneficial for the treatment of some cases of multidrug-resistant tuberculosis. Determination of catalase activity aids in the detection of isolates for which MICs are high and could, in conjunction with molecular methods, provide rapid detection of most isoniazid-resistant strains.
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4.
  • Abate, G, et al. (författare)
  • Drug resistance in Mycobacterium tuberculosis strains isolated from re-treatment cases of pulmonary tuberculosis in Ethiopia: susceptibility to first-line and alternative drugs
  • 1998
  • Ingår i: The International Journal of Tuberculosis and Lung Disease. - International Union against Tuberculosis and Lung Disease. - 1815-7920. ; 2:7, s. 580-584
  • Tidskriftsartikel (refereegranskat)abstract
    • SETTING: Addis Ababa Tuberculosis Demonstration and Training Center, Ethiopia. OBJECTIVES: To determine the pattern of drug resistance among re-treatment cases of pulmonary tuberculosis (TB), to determine the risk factors associated with multi-drug resistant (MDR) TB, and to propose re-treatment regimens based on the patterns of susceptibility to first-line and alternative drugs. DESIGN: One hundred and seven Mycobacterium tuberculosis strains isolated from an equal number of re-treatment cases of pulmonary TB were included in the study. Drug susceptibility was determined by the Bactec method. RESULTS: About 50% of the strains were resistant to one or more of the first-line drugs and 12% of the strains were multi-drug resistant, i.e., resistant to both isoniazid and rifampicin. Previous treatment with rifampicin was the most important predictor of MDR-TB. All MDR strains were susceptible to amikacin, ciprofloxacin, ethambutol, ethionamide and clofazimine. CONCLUSION: The WHO re-treatment regimen would theoretically be effective for the treatment of all non-MDR-TB patients in this study. A proposed 12-month re-treatment regimen for MDR-TB patients would include a fluoroquinolone in combination with streptomycin, pyrazinamide, isoniazid, ethambutol and clofazimine. There is an urgent need for more research to define safe and inexpensive treatment regimens for MDR-TB patients in low-income countries.
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5.
  • Abbasinejad Enger, Shirin, et al. (författare)
  • Gadolinium neutron capture brachytherapy (GdNCB), a new treatment method for intravascular brachytherapy
  • 2006
  • Ingår i: Medical physics (Lancaster). - 0094-2405. ; 33:1, s. 46-51
  • Tidskriftsartikel (refereegranskat)abstract
    • Restenosis is a major problem after balloon angioplasty and stent implantation. The aim of this study is to introduce gadolinium neutron capture brachytherapy (GdNCB) as a suitable modality for treatment of stenosis. The utility of GdNCB in intravascular brachytherapy (IVBT) of stent stenosis is investigated by using the GEANT4 and MCNP4B Monte Carlo radiation transport codes. To study capture rate, Kerma, absorbed dose and absorbed dose rate around a Gd-containing stent activated with neutrons, a 30 mm long, 5 mm diameter gadolinium foil is chosen. The input data is a neutron spectrum used for clinical neutron capture therapy in Studsvik, Sweden. Thermal neutron capture in gadolinium yields a spectrum of high-energy gamma photons, which due to the build-up effect gives an almost flat dose delivery pattern to the first 4 mm around the stent. The absorbed dose rate is 1.33 Gy/min, 0.25 mm from the stent surface while the dose to normal tissue is in order of 0.22 Gy/min, i.e., a factor of 6 lower. To spare normal tissue further fractionation of the dose is also possible. The capture rate is relatively high at both ends of the foil. The dose distribution from gamma and charge particle radiation at the edges and inside the stent contributes to a nonuniform dose distribution. This will lead to higher doses to the surrounding tissue and may prevent stent edge and in-stent restenosis. The position of the stent can be verified and corrected by the treatment plan prior to activation. Activation of the stent by an external neutron field can be performed days after catherization when the target cells start to proliferate and can be expected to be more radiation sensitive. Another advantage of the nonradioactive gadolinium stent is the possibility to avoid radiation hazard to personnel.
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6.
  • Abbasinejad Enger, Shirin, et al. (författare)
  • Monte Carlo calculations of thermal neutron capture in gadolinium: A comparison of GEANT4 and MCNP with measurements
  • 2006
  • Ingår i: Medical Physics. - American Association of Physicists in Medicine. - 0094-2405. ; 33:2, s. 337-341
  • Tidskriftsartikel (refereegranskat)abstract
    • GEANT4 is a Monte Carlo code originally implemented for high-energy physics applications and is well known for particle transport at high energies. The capacity of GEANT4 to simulate neutron transport in the thermal energy region is not equally well known. The aim of this article is to compare MCNP, a code commonly used in low energy neutron transport calculations and GEANT4 with experimental results and select the suitable code for gadolinium neutron capture applications. To account for the thermal neutron scattering from chemically bound atoms [S(alpha, beta)] in biological materials a comparison of thermal neutron fluence in tissue-like poly (methylmethacrylate) phantom is made with MCNP4B, GEANT4 6.0 patch 1, and measurements from the neutron capture therapy (NCT) facility at the Studsvik, Sweden. The fluence measurements agreed with MCNP calculated results considering S(alpha, beta). The location of the thermal neutron peak calculated with MCNP without S(alpha, beta) and GEANT4 is shifted by about 0.5 cm towards a shallower depth and is 25%-30% lower in amplitude. Dose distribution from the gadolinium neutron capture reaction is then simulated by MCNP and compared with measured data. The simulations made by MCNP agree well with experimental results. As long as thermal neutron scattering from chemically bound atoms are not included in GEANT4 it is not suitable for NCT applications. (c) 2006 American Association of Physicists in Medicine.
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7.
  • Abd, H, et al. (författare)
  • Ante mortem diagnosis of amoebic encephalitis in a haematopoietic stem cell transplanted patient
  • 2009
  • Ingår i: Scandinavian Journal of Infectious Diseases. - Informa Healthcare. - 1651-1980. ; 41:8, s. 619-622
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • Acanthamoeba species are widely distributed free-living amoebae showing an increased role as human pathogens causing encephalitis, keratitis, pneumonitis and dermatitis. A haematopoietic stem cell transplanted (HSCT) patient developed purulent meningitis while awaiting regrafting. The meningitis was thought to be an endogenous infection arising from the mucous membranes primarily involving the cervicofacial regions, probably due to haematogenous spread facilitated by surgery. We diagnosed a fatal case of granulomatous amoebic encephalitis caused by Acanthamoeba castellanii by direct microscopy of a cerebrospinal fluid sample (CSF), Acanthamoeba cultivation, Giemsa staining, polymerase chain reaction and sequencing.
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8.
  • Abdelnour, C, et al. (författare)
  • Alzheimer's disease cerebrospinal fluid biomarkers predict cognitive decline in lewy body dementia
  • 2016
  • Ingår i: Movement Disorders. - John Wiley & Sons. - 0885-3185. ; 31:8, s. 1203-1208
  • Tidskriftsartikel (refereegranskat)abstract
    • Introduction: Alzheimer's disease pathologies are common in dementia with Lewy bodies, but their clinical relevance is not clear. CSF biomarkers amyloid beta 1-42, total tau, and tau phosphorylated at threonine 181 reflect Alzheimer's disease neuropathology antemortem. In PD, low CSF amyloid beta 1-42 predict long-term cognitive decline, but little is known about these biomarkers as predictors for cognitive decline in Lewy body dementia. The aim of this study was to assess whether Alzheimer's disease CSF biomarkers predict cognitive decline in Lewy body dementia. Methods: From a large European dementia with Lewy bodies multicenter study, we analyzed baseline Alzheimer's disease CSF biomarkers and serial MMSE (baseline and 1- and 2-year follow-up) in 100 patients with Lewy body dementia. Linear mixed-effects analyses, adjusted for sex, age, baseline MMSE, and education, were performed to model the association between CSF biomarkers and rate of cognitive decline measured with MMSE. An Alzheimer's disease CSF profile was defined as pathological amyloid beta 1-42 plus pathological total tau or phosphorylated tau. Results: The Alzheimer's disease CSF profile, and pathological levels of amyloid beta 1-42, were associated with a more rapid decline in MMSE (2.2 [P < 0.05] and 2.9 points difference [P < 0.01], respectively). Higher total tau values showed a trend toward association without statistical significance (2.0 points difference; P = 0.064), whereas phosphorylated tau was not associated with decline. Conclusions: Reduced levels of CSF amyloid beta 1-42 were associated with more rapid cognitive decline in Lewy body dementia patients. Future prospective studies should include larger samples, centralized CSF analyses, longer follow-up, and biomarker-pathology correlation. © 2016 International Parkinson and Movement Disorder Society.
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9.
  • Abdurahman, Samir, et al. (författare)
  • Isolation and characterization of a small antiretroviral molecule affecting HIV-1 capsid morphology
  • 2009
  • Ingår i: Retrovirology. - BioMed Central. - 1742-4690. ; 6:34
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Formation of an HIV-1 particle with a conical core structure is a prerequisite for the subsequent infectivity of the virus particle. We have previously described that glycineamide (G-NH2) when added to the culture medium of infected cells induces non-infectious HIV-1 particles with aberrant core structures. Results Here we demonstrate that it is not G-NH2 itself but a metabolite thereof that affects HIV-1 infectivity and capsid assembly. The conversion of G-NH2 to its antiviral metabolite is catalyzed by an enzyme present in bovine and porcine but surprisingly not in human serum. Structure determination by NMR suggested that the active G-NH2 metabolite was α-hydroxyglycineamide (α-HGA). Chemically synthesized α-HGA inhibited HIV-1 replication to the same degree as G-NH2, unlike a number of other synthesized analogues of G-NH2 which had no effect on HIV-1 replication. Comparisons by capillary electrophoresis and HPLC of the metabolite with the chemically synthesized α-HGA further confirmed that the antiviral GNH2-metabolite indeed was α-HGA. Conclusions α-HGA has an unusually simple structure and a novel mechanism of antiviral action. Thus, α-HGA could be a lead for new antiviral substances belonging to a new class of anti-HIV drugs, i.e. capsid assembly inhibitors.
10.
  • Abe, O, et al. (författare)
  • Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials
  • 2005
  • Ingår i: The Lancet. - Elsevier Limited. - 1474-547X. ; 365:9472, s. 1687-1717
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Quinquennial overviews (1985-2000) of the randomised trials in early breast cancer have assessed the 5-year and 10-year effects of various systemic adjuvant therapies on breast cancer recurrence and survival. Here, we report the 10-year and 15-year effects. Methods Collaborative meta-analyses were undertaken of 194 unconfounded randomised trials of adjuvant chemotherapy or hormonal therapy that began by 1995. Many trials involved CMF (cyclophosphamide, methotrexate, fluorouracil), anthracycline-based combinations such as FAC (fluorouracil, doxombicin, cyclophosphamide) or FEC (fluorouracil, epirubicin, cyclophosphamide), tamoxifen, or ovarian suppression: none involved taxanes, trastuzumab, raloxifene, or modem aromatase inhibitors. Findings Allocation to about 6 months of anthracycline-based polychemotherapy (eg, with FAC or FEC) reduces the annual breast cancer death rate by about 38% (SE 5) for women younger than 50 years of age when diagnosed and by about 20% (SE 4) for those of age 50-69 years when diagnosed, largely irrespective of the use of tamoxifen and of oestrogen receptor (ER) status, nodal status, or other tumour characteristics. Such regimens are significantly (2p=0 . 0001 for recurrence, 2p<0 . 00001 for breast cancer mortality) more effective than CMF chemotherapy. Few women of age 70 years or older entered these chemotherapy trials. For ER-positive disease only, allocation to about 5 years of adjuvant tamoxifen reduces the annual breast cancer death rate by 31% (SE 3), largely irrespective of the use of chemotherapy and of age (<50, 50-69, &GE; 70 years), progesterone receptor status, or other tumour characteristics. 5 years is significantly (2p<0 . 00001 for recurrence, 2p=0 . 01 for breast cancer mortality) more effective than just 1-2 years of tamoxifen. For ER-positive tumours, the annual breast cancer mortality rates are similar during years 0-4 and 5-14, as are the proportional reductions in them by 5 years of tamoxifen, so the cumulative reduction in mortality is more than twice as big at 15 years as at 5 years after diagnosis. These results combine six meta-analyses: anthracycline-based versus no chemotherapy (8000 women); CMF-based versus no chemotherapy (14 000); anthracycline-based versus CMF-based chemotherapy (14 000); about 5 years of tamoxifen versus none (15 000); about 1-2 years of tamoxifen versus none (33 000); and about 5 years versus 1-2 years of tamoxifen (18 000). Finally, allocation to ovarian ablation or suppression (8000 women) also significantly reduces breast cancer mortality, but appears to do so only in the absence of other systemic treatments. For middle-aged women with ER-positive disease (the commonest type of breast cancer), the breast cancer mortality rate throughout the next 15 years would be approximately halved by 6 months of anthracycline-based chemotherapy (with a combination such as FAC or FEC) followed by 5 years of adjuvant tamoxifen. For, if mortality reductions of 38% (age <50 years) and 20% (age 50-69 years) from such chemotherapy were followed by a further reduction of 31% from tamoxifen in the risks that remain, the final mortality reductions would be 57% and 45%, respectively (and, the trial results could well have been somewhat stronger if there had been full compliance with the allocated treatments). Overall survival would be comparably improved, since these treatments have relatively small effects on mortality from the aggregate of all other causes. Interpretation Some of the widely practicable adjuvant drug treatments that were being tested in the 1980s, which substantially reduced 5-year recurrence rates (but had somewhat less effect on 5-year mortality rates), also substantially reduce 15-year mortality rates. Further improvements in long-term survival could well be available from newer drugs, or better use of older drugs.
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