| 1. |
- Ahmed, Aisha S., et al.
(författare)
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Activation of NF-kappa B in Synovium versus Cartilage from Patients with Advanced Knee Osteoarthritis : A Potential Contributor to Inflammatory Aspects of Disease Progression
- 2018
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Ingår i: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 201:7, s. 1918-1927
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to assess the activation and association of the NF-kappa B system across synovial membrane (SM) and articular cartilage (AC) in patients with knee osteoarthritis (OA) and ascertain its potential effects on catabolic mediator expression in advanced OA. SM and AC were obtained from 40 OA patients undergoing total knee arthroplasty and from 19 postmortem control subjects. NF-kappa B subunit RelA in nuclear and cytosolic fractions and NF-kappa B1-DNA binding in nuclear extracts was assessed by ELISA, whereas NFKB1, RELA, IL-8, IL-6, and MMP3 gene expression were analyzed by reverse transcriptase-quantitative PCR in tissues. We observed higher SM nuclear RelA protein levels and upregulated NF-kappa B1-DNA binding in OA patients compared with postmortem controls. However, in AC, lower nuclear RelA levels were observed compared with cytosolic extracts in patients. Nuclear RelA levels correlated positively with NF-kappa B1-DNA binding in SM and AC in patients. SM RELA and MMP3 mRNA levels were upregulated, whereas IL-8 and IL-6 as well as AC RELA were downregulated in patients compared with controls. In SM, nuclear RelA levels correlated positively with MMP3 gene expression in patients. A negative correlation was observed between SM nuclear RelA levels and AC NF-kappa B1-DNA binding, and SM nuclear NF-kappa B1-DNA binding correlated negatively with AC MMP3 and NFKB1 mRNA levels in patients. These findings highlight NF-kappa B-triggered cross-talk and feedback mechanisms between SM and AC in OA. Further, our findings strongly support a role for an activated NF-kappa B system in the transcriptional mechanism of inflammatory processes, especially in SM of patients with advanced OA.
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| 2. |
- Ahmed, Aisha S, et al.
(författare)
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NF-κB-Associated Pain-Related Neuropeptide Expression in Patients with Degenerative Disc Disease.
- 2019
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Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 20:3
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Tidskriftsartikel (refereegranskat)abstract
- The role of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) has been highlighted in mechanisms underlying inflammatory and neuropathic pain processes. The present study was designed to investigate whether NF-κB signaling is associated with pain-related neuropeptide expression in patients with chronic back pain related to degenerative disc disease (DDD). Intervertebral disc (IVD) tissues were collected from forty DDD patients undergoing disc replacement or fusion surgery, and from eighteen postmortem (PM) control subjects. RELA, NFKB1, CGRP, TAC1, TRPV1, and MMP-3 gene expression were analyzed by RT-qPCR, while NF-κB subunit RelA and NF-κB1⁻DNA binding in nuclear extracts and calcitonin gene related peptide (CGRP), substance P (SP), and transient receptor potential, subfamily V, member 1 (TRPV1) protein levels in cytosolic extracts of tissues were assessed by enzyme-linked immunosorbent assay (ELISA). An upregulated NF-κB1⁻DNA binding, and higher CGRP and TRPV1 protein levels were observed in DDD patients compared to PM controls. In DDD patients, NF-κB1⁻DNA binding was positively correlated with nuclear RelA levels. Moreover, NF-κB1⁻DNA binding was positively associated with TRPV1 and MMP-3 gene and SP and TRPV1 protein expression in DDD patients. Our results indicate that the expression of SP and TRPV1 in IVD tissues was associated with NF-κB activation. Moreover, NF-κB may be involved in the generation or maintenance of peripheral pain mechanisms by the regulation of pain-related neuropeptide expression in DDD patients.
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| 3. |
- Alkass, Kanar, et al.
(författare)
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Analysis of radiocarbon, stable isotopes and DNA in teeth to facilitate identification of unknown decedents
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:7, s. e69597-
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Tidskriftsartikel (refereegranskat)abstract
- The characterization of unidentified bodies or suspected human remains is a frequent and important task for forensic investigators. However, any identification method requires clues to the person’s identity to allow for comparisons with missing persons. If such clues are lacking, information about the year of birth, sex and geographic origin of the victim, is particularly helpful to aid in the identification casework and limit the search for possible matches. We present here results of stable isotope analysis of 13C and 18O, and bomb-pulse 14C analyses that can help in the casework. The 14C analysis of enamel provided information of the year of birth with an average absolute error of 1.8±1.3 years. We also found that analysis of enamel and root from the same tooth can be used to determine if the 14C values match the rising or falling part of the bomb-curve. Enamel laydown times can be used to estimate the date of birth of individuals, but here we show that this detour is unnecessary when using a large set of crude 14C data of tooth enamel as a reference. The levels of 13C in tooth enamel were higher in North America than in teeth from Europe and Asia, and Mexican teeth showed even higher levels than those from USA. DNA analysis was performed on 28 teeth, and provided individual-specific profiles in most cases and sex determination in all cases. In conclusion, these analyses can dramatically limit the number of possible matches and hence facilitate person identification work.
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| 4. |
- Alkass, Kanar
(författare)
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External and intrinsic signatures in human teeth to assist forensic identification work
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In forensic medicine, dead victim identification constitutes an important task for forensic professionals including forensic pathologists, anthropologists, and odontologists. If no clues are at hand regarding the identity of the deceased, whether it is a victim of a mass disaster or a suspect homicide case, it is vital to know when a person died, and to know the sex and age of the decedent in order to limit the search for possible matching persons. In paper I, teeth from Swedish individuals were examined using both 14C analysis and aspartic acid racemization. The 14C analysis takes advantage of the so-called bombpulse, a tremendous increase of 14C in the atmosphere due to thousands of test detonations of nuclear weapons 1955-1963, which allows for an accurate birth dating of modern biological material. The aspartic acid racemization method gives an estimate of the age at death. The methods showed a significant correlation, and by combining them, we showed how both the year of birth and year of death of an unknown skeleton could be determined. In this study, we also found that14C levels in tooth enamel from Swedish teeth predicted the true date of birth with an average absolute error of 1.3 ± 0.9 years and that analysis of whole crown offered fairly good precision too. In paper II, the possibility of geographical differences in precision due to uneven distribution of bomb-pulse radiocarbon during the test bomb period was addressed. Interestingly, the 14C determinations predicted the true date of birth with a similar precision even when analyzing teeth from different continents. Conversely, the levels of the stable isotope 13C showed significant difference depending on geographical origin. In paper III, teeth were collected from North America to find out if differences in stable isotope concentrations can be detected in the teeth from subjects raised in such a limited geographical region. Teeth collected from subjects raised in Mexico showed extremely high 13C values, most likely due to a high consumption of corn and sugar cane. 13C levels in tooth roots were also higher in Mexican subjects compared with persons raised in United States and Canada, but the difference was not as conspicuous. Incorporation of 18O, another stable isotope, is mainly dependent on the drinking water. Analysis of 18O in tooth roots from subjects raised in Northwestern America showed the lowest levels, whereas this marker was not reliable for discriminating between Mexican and southern United States subjects. The 14C determinations of date of birth on North American teeth showed only slightly higher imprecision (average absolute error 1.8 ± 1.3 years) than Scandinavian teeth. In paper III, these and previous tooth 14C. Finally, a reference guide to birthdating persons using tooth 14C values is provided in paper III. In summary, these studies describe methods to determine date of birth, date of death, and origin of unknown dead victims, information that is expected to facilitate the identification work.
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| 5. |
- Bendel, Olof, et al.
(författare)
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Reproducible loss of CA1 neurons following carotid artery occlusion combined with halothane-induced hypotension
- 2005
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Ingår i: Brain Research. - : Elsevier. - 0006-8993 .- 1872-6240. ; 1033:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- The 2-vessel occlusion approach to produce global ischemia in rats requires concomitant reduction of systemic blood pressure. We have utilized the hypotensive effect of halothane administrated by artificial respiration to prevent respiratory arrest and to ensure stable physiological conditions. Systemic blood pressure was reduced to 40-45 mmHg by instant adjustments of the halothane concentration. Bilateral occlusion of the carotid arteries caused a profound and reproducible ischemia, as analyzed by laser-Doppler flowmetry. In the rats exposed to 11, 12, or 13 min of ischemia, 5% died and 5% developed seizures. The extent of neuronal death in CA1 was highly correlated to the duration of ischemia. Following 11 min of ischemia, CA1 neuronal cell death, as analyzed by Fluoro-Jade, was absent 1 day after injury, variable at day 4, and consistent at day 7. The numbers of cresyl violet- and NeuN-positive neurons at day 7 were 8% and 20% of control, respectively. OX42 immunoreactivity was low and variable at day 4, but pronounced at day 7. In conclusion, this rat global ischemia model is relatively simple to perform, has a low mortality, and produces a profound and highly reproducible delayed cell death of hippocampal CA1 neurons.
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| 6. |
- Bergmann, Olaf, et al.
(författare)
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Dynamics of Cell Generation and Turnover in the Human Heart.
- 2015
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 161:7, s. 1566-1575
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Tidskriftsartikel (refereegranskat)abstract
- The contribution of cell generation to physiological heart growth and maintenance in humans has been difficult to establish and has remained controversial. We report that the full complement of cardiomyocytes is established perinataly and remains stable over the human lifespan, whereas the numbers of both endothelial and mesenchymal cells increase substantially from birth to early adulthood. Analysis of the integration of nuclear bomb test-derived (14)C revealed a high turnover rate of endothelial cells throughout life (>15% per year) and more limited renewal of mesenchymal cells (<4% per year in adulthood). Cardiomyocyte exchange is highest in early childhood and decreases gradually throughout life to <1% per year in adulthood, with similar turnover rates in the major subdivisions of the myocardium. We provide an integrated model of cell generation and turnover in the human heart. VIDEO ABSTRACT.
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| 7. |
- Bergmann, Olaf, et al.
(författare)
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Evidence for Cardiomyocyte Renewal in Humans
- 2009
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 324:5923, s. 98-102
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Tidskriftsartikel (refereegranskat)abstract
- It has been difficult to establish whether we are limited to the heart muscle cells we are born with or if cardiomyocytes are generated also later in life. We have taken advantage of the integration of carbon-14, generated by nuclear bomb tests during the Cold War, into DNA to establish the age of cardiomyocytes in humans. We report that cardiomyocytes renew, with a gradual decrease from 1% turning over annually at the age of 25 to 0.45% at the age of 75. Fewer than 50% of cardiomyocytes are exchanged during a normal life span. The capacity to generate cardiomyocytes in the adult human heart suggests that it may be rational to work toward the development of therapeutic strategies aimed at stimulating this process in cardiac pathologies.
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| 8. |
- Bergmann, Olaf, et al.
(författare)
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Turnover of Human Cardiomyocytes
- 2008
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Ingår i: Circulation Research. - 0009-7330. ; 103:12, s. 1494-1495
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Konferensbidrag (refereegranskat)
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| 9. |
- Clara, Alfsdotter, et al.
(författare)
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Development and implementation of forensic anthropology in Swedish forensic practice
- 2022
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Ingår i: Scandinavian Journal of Forensic Science. - : Sciendo. - 2353-0707. ; 28:Supplement 1, s. 10-19
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents the ongoing development of forensic anthropology in Sweden. We discuss the background of the discipline, its application, as well as its current and potential development in Swedish forensic practice. Collaboration with osteoarchaeologists in skeletal forensic cases has a long tradition in Sweden. Analyses of skeletal remains are performed ad-hoc, in contrast to analyses of fleshed human remains. While several law enforcement employees are educated in forensic anthropology and /or osteoarchaeology , they are not employed in these fields, and regional variations are evident. Internationally, forensic anthropology has become an autonomous forensic discipline over the past decades, requiring skills beyond mere skeletal analysis. To keep on a par with international standards, it may be time to revisit the concept of forensic anthropology in Sweden. Despite the limited presence of supporting organisational structures and systems, forensic anthropological and hard-tissue-reliant physico-chemical analyses have proven valuable in Swedish forensic practice, especially in cases of personal identification, trauma analysis and search efforts. We argue that Sweden could benefit from making qualified forensic anthropology expertise available in all law enforcement regions, starting to implement and promote forensic anthropology in routine forensic casework and formalising the role of forensic anthropology practitioners.
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| 10. |
- Druid, Henrik, et al.
(författare)
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Evaluation of the role of abstinence in heroin overdose deaths using segmental hair analysis
- 2007
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Ingår i: Forensic Science International. - : Elsevier BV. - 0379-0738 .- 1872-6283. ; 168:2-3, s. 223-226
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Tidskriftsartikel (refereegranskat)abstract
- In the body heroin is rapidly metabolized to 6-acetylmorphine and morphine. Victims of lethal heroin overdose often present with fairly low blood concentrations of morphine. Reduced tolerance due to abstinence has been proposed to account for this finding. The aim of the present study was to examine the role of abstinence in drug-related deaths by comparing recent and past exposure to opioids using segmental hair analysis with the postmortem blood morphine concentrations in deceased heroin users. The study included 60 deceased drug addicts in the Stockholm area, Sweden. In 32 cases, death was not related to heroin intake. In 18 of the 28 heroin fatalities, opioids were absent in the most recent hair segment, suggesting a reduced tolerance to opioids. However, the blood morphine levels were similar to those found in the 10 subjects that showed continuous opioid use. Hair and blood analysis disclosed an extensive use of additional drugs that directly or indirectly may influence the opioid system. The results suggest that abstinence is not a critical factor for heroin overdose death. Obviously tolerant subjects die after intake of similar doses. Other factors, particularly polydrug use, seem to be more causally important for these deaths.
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