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- Craggs, L. J. L., et al.
(författare)
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Clusterin/Apolipoprotein J immunoreactivity is associated with white matter damage in cerebral small vessel diseases
- 2016
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Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 42:2, s. 194-209
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Tidskriftsartikel (refereegranskat)abstract
- AimBrain clusterin is known to be associated with the amyloid- deposits in Alzheimer's disease (AD). We assessed the distribution of clusterin immunoreactivity in cerebrovascular disorders, particularly focusing on white matter changes in small vessel diseases. MethodsPost-mortem brain tissues from the frontal or temporal lobes of a total of 70 subjects with various disorders including cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), cerebral amyloid angiopathy (CAA) and AD were examined using immunohistochemistry and immunofluorescence. We further used immunogold electron microscopy to study clusterin immunoreactivity in extracellular deposits in CADASIL. ResultsImmunostaining with clusterin antibodies revealed strong localization in arterioles and capillaries, besides cortical neurones. We found that clusterin immunostaining was significantly increased in the frontal white matter of CADASIL and pontine autosomal dominant microangiopathy and leukoencephalopathy subjects. In addition, clusterin immunostaining correlated with white matter pathology severity scores. Immunostaining in axons ranged from fine punctate deposits in single axons to larger confluent areas with numerous swollen axon bulbs, similar to that observed with known axon damage markers such as non-phosphorylated neurofilament H and the amyloid precursor protein. Immunofluorescence and immunogold electron microscopy experiments showed that whereas clusterin immunoreactivity was closely associated with vascular amyloid- in CAA, it was lacking within the granular osmiophilic material immunolabelled by NOTCH3 extracelluar domain aggregates found in CADASIL. ConclusionsOur results suggest a wider role for clusterin associated with white matter damage in addition to its ability to chaperone proteins for clearance via the perivascular drainage pathways in several disease states.
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- Fratiglioni, L, et al.
(författare)
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Very Old Women at Highest Risk of Dementia and Alzheimer's Disease : Incidence Data from the Kungsholmen Project, Stockholm
- 1997
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Ingår i: Neurology. - : American Academy of Neurology. - 0028-3878 .- 1526-632X. ; 48:1, s. 132-138
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine the incidence of different types of dementia in the very old, and to explore the relation with age and gender. Design: A dementia-free cohort was followed for an average of three years in Stockholm, Sweden. At the end of the follow-up, the subjects were interviewed by nurses, clinically examined by physicians, and cognitively assessed by psychologists. Deceased cohort members were studied using death certificates, hospital clinical records, and discharge diagnoses. Dementia diagnoses were made according to the DSM-III-R criteria independently by two physicians. Participants: The cohort consisted of 1,473 subjects (75+ years old), of which 987 were clinically examined at follow-up, 314 died before the examination, and 172 refused to participate. Results: During the follow-up, 148 subjects developed dementia. In the age-group 75 to 79, the incidence rates for dementia were 19.6 for women and 12.4 for men per 1,000 person-years, whereas for 90+ year-old subjects the corresponding figures were 86.7 and 15.0 per 1,000 person-years. A similar pattern of distribution by age and gender was seen for Alzheimer's disease. In each age stratum, the incidence rates of dementia and Alzheimer's disease were higher for women than for men. The age-adjusted odds ratio for women was 1.9 for dementia and 3.1 for Alzheimer's disease. Conclusions: (1) The incidence of dementia increases with age, even in the oldest age groups; (2) women have a higher risk of developing dementia than men, especially at very old ages; (3) this pattern is mainly due to the age and gender distribution of Alzheimer's disease, rather than vascular dementia.
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- Heikela, H., et al.
(författare)
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Hydroxysteroid (17 beta) dehydrogenase 12 is essential for metabolic homeostasis in adult mice
- 2020
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Ingår i: American Journal of Physiology-Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 319:3
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Tidskriftsartikel (refereegranskat)abstract
- Hydroxysteroid 17 beta dehydrogenase 12 (HSD17B12) is suggested to be involved in the elongation of very long chain fatty acids. Previously. we have shown a pivotal role for the enzyme during mouse development. In the present study we generated a conditional Hsd17b12 knockout (HSD17B12cKO) mouse model by breeding mice homozygous for a floxed Hsd17b12 allele with mice expressing the tamoxifen-inducible Cre recombinase at the ROSA26 locus. Gene inactivation was induced by administering tamoxifen to adult mice. The gene inactivation led to a 20% loss of body weight within 6 days, associated with drastic reduction in both white (83% males, 75% females) and brown (65% males. 60% females) fat, likely due to markedly reduced food and water intake. Furthermore, the knockout mice showed sickness behavior and signs of liver toxicity. specifically microvesicular hepatic steatosis and increased serum alanine aminotransferase (4.6-fold in males, 7.7-fold in females). The hepatic changes were more pronounced in females than males. Proinflammatory cytokines, such as interleukin-6 (IL-6), IL-17, and granulocyte colony-stimulating factor, were increased in the HSD17B12cKO mice indicating an inflammatory response. Serum lipidomics study showed an increase in the amount of dihydroceramides, despite the dramatic overall loss of lipids. In line with the proposed role for HSD17B12 in fatty acid elongation, we observed accumulation of ceramides, dihydroceramides, hexosylceramides, and lactosylceramides with shorter than 18-carbon fatty acid side chains in the serum. The results indicate that HSD17B12 is essential for proper lipid homeostasis and HSD17B12 deficiency rapidly results in fatal systemic inflammation and lipolysis in adult mice.
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- Honkanen, M., et al.
(författare)
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Accelerated deactivation studies of the natural-gas oxidation catalyst-Verifying the role of sulfur and elevated temperature in catalyst aging
- 2016
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Ingår i: Applied Catalysis B: Environmental. - : Elsevier BV. - 0926-3373 .- 1873-3883. ; 182, s. 439-448
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Tidskriftsartikel (refereegranskat)abstract
- Accelerated deactivation, caused by thermal aging (TA) and/or sulfur + water poisoning (SW), of the PtPd/gamma-Al2O3 natural-gas oxidation catalyst was studied. Thermal aging and poisoning treatments were performed separately and with varied combinations and comprehensive characterization of the catalyst was carried out after each step. The fresh catalyst has small, oxidized PtPd particles (<5 nm) uniformly distributed in the gamma-alumina washcoat. After the SW-treatment, a small amount of bulk aluminum sulfate was observed near the slightly grown noble metal particles. During the thermal aging, gamma-alumina changed to delta-/theta- and alpha-alumina. In addition, total decomposition of oxidized Pt and partly decomposition of oxidized Pd occurred resulting in the formation of the grown noble metal particles with a bimetallic PtPd core and a polycrystalline PdO shell. Also few, small (similar to 5 nm) bimetallic PtPd particles were still detected. In the TA + SW-treated catalyst with grown noble metal particles, a small amount of bulk aluminum sulfate was detected and it was randomly distributed over the noble metal particles and washcoat. The activity in the terms of methane conversion over the TA-, SW-, and SW + TA-treated catalysts was similar but it was decreased compared to the fresh catalyst. The activity of the TA+SW-treated catalyst was drastically decreased compared to the fresh catalyst due to significant morphological changes and aluminum sulfate formation.
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- Morse, D E, et al.
(författare)
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Dental caries in persons over the age of 80 living in Kungsholmen, Sweden : findings from the KEOHS Project
- 2002
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Ingår i: Community Dental Health. - 0265-539X. ; 19:4, s. 262-267
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The Kungsholmen Elders Oral Health Study (KEOHS) evaluated the oral health status of generally healthy, communitydwelling persons over the age of 80 living in Kungsholmen, an area in central Stockholm. This paper reports findings regarding the prevalence and severity of dental caries among the dentate participants. Basic research design: Caries examinations were conducted on eligible persons participating in the Kungsholmen Project, an ongoing, longitudinal study of older adults. Setting: Caries examinations were carried out between 1994 and 1996 at two local clinics by three standardised examiners using defined visual, tactile criteria. Participants: Among 296 potentially eligible participants, 159 were examined, and a total of 129 had at least one tooth. Main outcome measures: The caries examination identified decayed and filled surfaces and missing teeth. Results: Of the dentate subjects examined, 80% had teeth in both arches; 98% had at least one coronal filling; 81% had one or more restored root surfaces. Depending upon age and gender, between 36% and 56% of those examined had untreated coronal caries, and between 54% and 75% had untreated root caries. Conclusions: These findings document the substantial and ongoing impact of dental caries in a sample of generally healthy, community-dwelling older adults and underscore the importance of continued caries prevention and treatment in the aged.
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- Morse, Douglas E., et al.
(författare)
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Prosthetic crowns and other clinical risk indicators of caries among old-old Swedish adults : Findings from the KEOHS Project. Kungsholmen Elders Oral Health Study
- 2002
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Ingår i: Gerodontology. - : John Wiley & Sons. - 0734-0664 .- 1741-2358. ; 19:2, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The Kungsholmen Elders Oral Health Study (KEOHS) evaluated the oral health status of generally healthy, community-dwelling persons over the age of 80 living in Kungsholmen, Sweden. This paper explored possible clinical risk indicators of coronal and root caries among the KEOHS subjects.Design: In this cross-sectional study, dentate KEOHS subjects received a caries assessment using defined visual, tactile criteria.Setting: Examinations were carried out in two local clinics by standardized examiners.Subjects: One hundred twenty-nine dentate persons were examined.Main Outcome Measures: The examination identified decayed and filled surfaces, prosthetic crowns, and missing teeth.Results: More root than coronal surfaces had untreated decay, and secondary root caries contributed the greatest number of decayed surfaces. Ninety percent of the examined dentate subjects had at least one prosthetic crown. Root surfaces exposed to crown margins were more likely to have caries than root surfaces not so exposed, particularly among women. The presence of untreated coronal caries (yes/no) was positively associated with having untreated root caries and an intermediate number (14–20) of teeth, but inversely associated with having 4+ prosthetic crowns. Active root caries (yes/no) was positively associated with having untreated coronal caries, 14–20 teeth, and 4+ prosthetic crowns. Nearly 20% of ident2ified root lesions were present at or below the gingival margin, and most (88%) were secondary caries associated with crown margins (65%) or other restorations (23%).Conclusions: Our findings suggest that some dental characteristics, including the presence of prosthetic crowns, are risk indicators for the presence of untreated coronal and root caries.
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