| 1. |
- Watanabe, Hiroyuki, et al.
(författare)
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Asymmetry of the Endogenous Opioid System in the Human Anterior Cingulate : a Putative Molecular Basis for Lateralization of Emotions and Pain
- 2015
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Ingår i: Cerebral Cortex. - United kingdom : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 25:1, s. 97-108
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Tidskriftsartikel (refereegranskat)abstract
- Lateralization of processing of positive and negative emotions and pain suggests an asymmetric distribution of the neurotransmitter systems regulating these functions between the left and right brain hemispheres. By virtue of their ability to selectively mediate euphoria, dysphoria and pain, the m-, d- and k-opioid receptors and their endogenous ligands may subserve these lateralized functions. We addressed this hypothesis by comparing the levels of the opioid receptors and peptides in the left and right anterior cingulate cortex (ACC), a key area for emotion and pain processing. Opioid mRNAs and peptides and five “classical” neurotransmitters were analyzed in postmortem tissues from 20 human subjects. Leu-enkephalin-Arg and Met-enkephalin-Arg-Phe, preferential d-/m- and k-/m-opioid agonists demonstrated marked lateralization to the left and right ACC, respectively. Dynorphin B strongly correlated with Leu-enkephalin-Arg in the left but not right ACC suggesting different mechanisms of conversion of this k-opioid agonist to d-/m-opioid ligand in the two hemispheres; in the right ACC dynorphin B may be cleaved by PACE4, a proprotein convertase regulating left-right asymmetry formation. These findings suggest that region-specific lateralization of neuronal networks expressing opioid peptides underlyes in part lateralization of higher functions including positive and negative emotions and pain in the human brain.
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| 2. |
- 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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| 3. |
- 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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| 4. |
- 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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| 5. |
- 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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| 6. |
- 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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| 7. |
- 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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| 8. |
- Brooke, Hannah Louise, et al.
(författare)
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The Swedish cause of death register
- 2017
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Ingår i: European Journal of Epidemiology. - : Springer. - 0393-2990 .- 1573-7284. ; 32:9, s. 765-773
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Tidskriftsartikel (refereegranskat)abstract
- Sweden has a long tradition of recording cause of death data. The Swedish cause of death register is a high quality virtually complete register of all deaths in Sweden since 1952. Although originally created for official statistics, it is a highly important data source for medical research since it can be linked to many other national registers, which contain data on social and health factors in the Swedish population. For the appropriate use of this register, it is fundamental to understand its origins and composition. In this paper we describe the origins and composition of the Swedish cause of death register, set out the key strengths and weaknesses of the register, and present the main causes of death across age groups and over time in Sweden. This paper provides a guide and reference to individuals and organisations interested in data from the Swedish cause of death register.
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| 9. |
- Carlie, Anne, et al.
(författare)
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Archaeology, forensics and the death of a child in Late Neolithic Sweden
- 2014
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Ingår i: Antiquity. - 0003-598X .- 1745-1744. ; 88:342, s. 1148-1163
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Tidskriftsartikel (refereegranskat)abstract
- The discovery of a child's skeleton in a Late Neolithic well in Sweden raises again the issue of watery rituals and human sacrifice in prehistoric societies. Analysis of diatoms from the right humerus and from the surrounding sediment indicated that the child died by drowning and had not simply been disposed of in the well after death. The scenarios of accidental drowning and murder are examined to account for this discovery. The preferred hypothesis, based on a comparative study of similar finds from north-western Europe, interprets this instead as a ritual sacrifice. The use of diatom analysis to establish drowning as the cause of death adds a new weapon into the armoury of forensic archaeology.
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| 10. |
- Druid, Henrik, et al.
(författare)
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A compilation of fatal and control concentrations of drugs in postmortem femoral blood
- 1997
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Ingår i: Journal of Forensic Sciences. - 0022-1198 .- 1556-4029. ; 42:1, s. 79-87
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Tidskriftsartikel (refereegranskat)abstract
- A compilation of postmortem femoral blood concentrations of drugs is presented. The samples are collected from cases in which the cause of death was: A) certified intoxication by one substance alone, B) certified intoxication by more than one substance and/or alcohol, and C) certified other cause of death without incapacitation due to drugs. The concentrations were compared with blood concentrations detected in suspected drugged drivers (D), and with previously published fatal and therapeutic concentrations. The special features of this compilation are: 1) exclusively femoral blood concentrations are quoted, 2) all analyses are based on samples handled according to a standardized, quality-controlled procedure, 3) two control groups are included, and 4) one-substance-only intoxications are separated from other intoxications. The material is based on a selection of 15,800 samples sent to the Department of Forensic Chemistry in Linkoping, Sweden, during 1992 to 1995 from the six forensic pathology units in Sweden, and the list includes 83 drugs. The compilation includes drugs, where previously published data are scarce. Furthermore, the data gathered from cases with other cause of death than intoxication (group C) constitute a new kind of reference information, which probably offers a better estimate of obviously non fatal levels in postmortem blood than any compilation of therapeutic concentrations in living subjects. The possible factors influencing postmortem drug concentrations are discussed.
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