| 11. |
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| 12. |
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| 13. |
- I. Sinning, G.J. Kleywegt, S.W. Cowan, P. Reinemer, H.W. Dirr, R. Huber, G.L. Gilliland, R.N. Armstrong, X. Ji, P.G. Board, B. Olin, B. Mannervik & T.A. Jones
(författare)
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Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the mu and pi class enzymes
- 1993
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Ingår i: Journal of Molecular Biology. ; 232, s. 192-212
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Tidskriftsartikel (refereegranskat)
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| 14. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum.
- 2022
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Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 79:3, s. 228-243
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Tidskriftsartikel (refereegranskat)abstract
- One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.Alzheimer disease biomarkers detected on PET or in CSF.Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.Among the 19097 participants (mean [SD] age, 69.1 [9.8] years; 10148 women [53.1%]) included, 10139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P=.04). Gaussian mixture modeling-based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P=.004), subjective cognitive decline (9%; 95% CI, 3%-15%; P=.005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P=.004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, -2% to 9%; P=.18).This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than PET-based estimates in people without dementia, whereas the results were similar among people with dementia. This finding suggests that preclinical and prodromal AD may be more prevalent than previously estimated, which has important implications for clinical trial recruitment strategies and health care planning policies.
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| 15. |
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| 16. |
- Mannervik, B, et al.
(författare)
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An evolutionary approach to the design of glutathione-linked enzymes
- 1998
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Ingår i: CHEMICO-BIOLOGICAL INTERACTIONS. - : ELSEVIER SCI IRELAND LTD. - 0009-2797. ; 112, s. 15-21
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Studies of protein structure provide information about principles of protein design that have come into play in natural evolution. This information can be exploited in the redesign of enzymes for novel functions. The glutathione-binding domain of glutathi
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| 17. |
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| 18. |
- Olin, Håkan, et al.
(författare)
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Scanning tunneling microscopy of oxidized titanium surfaces in air
- 1992
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Ingår i: Ultramicroscopy. - 0304-3991 .- 1879-2723. ; 42:Part A, s. 567-571
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Tidskriftsartikel (refereegranskat)abstract
- Using an STM in air, we have studied three different electropolished Ti surfaces. One sample was analyzed without further treatment. The second was thermally oxidized in air at 500-degrees-C. The third was exposed to an argon glow discharge and then oxidized in pure oxygen. The samples were characterized by Auger spectroscopy prior to STM measurements. Electropolished and thermally oxidized samples showed a granular structure, with a low corrugation between 2 and 10 nm. At a larger scale, the glow discharge treated sample showed a high corrugation approximately 100 nm.
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| 19. |
- Sinning, I, et al.
(författare)
-
Structure determination and refinement of human alpha class glutathione transferase A1-1, and a comparison with the Mu and Pi class enzymes.
- 1993
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Ingår i: J Mol Biol. - 0022-2836. ; 232:1, s. 192-212
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Tidskriftsartikel (refereegranskat)abstract
- The crystal structure of human alpha class glutathione transferase A1-1 has been determined and refined to a resolution of 2.6 A. There are two copies of the dimeric enzyme in the asymmetric unit. Each monomer is built from two domains. A bound inhibitor, S-benzyl-glutathione, is primarily associated with one of these domains via a network of hydrogen bonds and salt-links. In particular, the sulphur atom of the inhibitor forms a hydrogen bond to the hydroxyl group of Tyr9 and the guanido group of Arg15. The benzyl group of the inhibitor is completely buried in a hydrophobic pocket. The structure shows an overall similarity to the mu and pi class enzymes particularly in the glutathione-binding domain". The main difference concerns the extended C terminus of the alpha class enzyme which forms an extra alpha-helix that blocks one entrance to the active site and makes up part of the substrate binding site.
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| 20. |
- Terzidis, Emmanouil, 1994, et al.
(författare)
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Tumor volume definitions in head and neck squamous cell carcinoma - Comparing PET/MRI and histopathology
- 2023
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Ingår i: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140. ; 180
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: In cancer treatment precise definition of the tumor volume is essential, but despite development in imaging modalities, this remains a challenge. Here, pathological tumor volumes from the surgical specimens were obtained and compared to tumor volumes defined from modern PET/ MRI hybrid imaging. The purpose is to evaluate mismatch between the volumes defined from imaging and pathology was estimated and potential clinical impact.Methods and Materials: Twenty-five patients with head and neck squamous cell carcinoma were scanned on an integrated PET/MRI system prior to surgery. Three gross tumor volumes (GTVs) from the primary tumor site were delineated defined from MRI (GTVMRI), PET (GTVPET) and one by utilizing both anatomical images and clinical information (GTVONCO). Twenty-five primary tumor specimens were extracted en bloc, scanned with PET/MRI and co-registered to the patient images. Each specimen was sectioned in blocks, sliced and stained with haematoxylin and eosin. All slices were digitalized and tumor delineated by a head and neck pathologist. The pathological tumor areas in all slices were interpolated yielding a pathological 3D tumor volume (GTVPATO). GTVPATO was compared with the imaging GTV's and potential mismatch was estimated.Results: Thirteen patients were included. The mean volume of GTVONCO was larger than the GTV's defined from PET or MRI. The mean mismatch of the GTVPATO compared to the GTVPET, GTVMRI and GTVONCO was 31.9 %, 54.5 % and 27.9 % respectively, and the entire GTVPATO was only fully encompassed in GTVONCO in 1 of 13 patients. However, after the addition of a clinical 5 mm margin the GTVPATO was fully encompassed in GTVONCO in 11 out of 13 patients.Conclusions: Despite modern hybrid imaging modalities, a mismatch between imaging and pathological defined tumor volumes was observed in all patients. A 5 mm clinical margin was sufficient to ensure inclusion of the entire pathological volume in 11 out of 13 patients.(c) 2023 The Authors. Published by Elsevier B.V. Radiotherapy and Oncology 180 (2023) 1-8 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
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