| 11. |
- Sjöbring, Ulf, et al.
(författare)
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Induction of platelet thrombi by bacteria and antibodies
- 2002
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 100:13, s. 4470-4477
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Tidskriftsartikel (refereegranskat)abstract
- We have characterized 2 distinct mechanisms through which infectious agents may promote platelet adhesion and thrombus formation in flowing blood, thus contributing to the progression of disease. In one case, the process initiates when the integrin alpha(IIb)beta(3) mediates platelet arrest onto immobilized bacterial constituents that have bound plasma fibrinogen. If blood contains antibodies against the bacteria, immunoglobulin (Ig) G may cluster on the same surface and activate adherent platelets through the FcgammaRIIA receptor, leading to thrombus growth. As an alternative, bacteria that cannot bind fibrinogen may attach to substrates, such as immobilized plasma proteins or components of the extracellular matrix, which also support platelet adhesion. As a result of this colocalization, IgG bound to bacteria can activate neighboring platelets and induce thrombus growth regard-less of their ability to initiate platelet-surface contact. Our results demonstrate that intrinsic constituents of infectious agents and host proteins play distinct but complementary roles in recruiting platelets into thrombi, possibly contributing to complications of acute and chronic infections.
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| 12. |
- Sun, HM, et al.
(författare)
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Plasminogen is a critical host pathogenicity factor for group A streptococcal infection
- 2004
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 305:5688, s. 1283-1286
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Tidskriftsartikel (refereegranskat)abstract
- Group A streptococci, a common human pathogen, secrete streptokinase, which activates the host's blood clot-dissolving protein, plasminogen. Streptokinase is highly specific for human plasminogen, exhibiting little or no activity against other mammalian species, including mouse. Here, a transgene expressing human plasminogen markedly increased mortality in mice infected with streptococci, and this susceptibility was dependent on bacterial streptokinase expression. Thus, streptokinase is a key pathogenicity factor and the primary determinant of host species specificity for group A streptococcal infection. In addition, local fibrin clot formation may be implicated in host defense against microbial pathogens.
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| 13. |
- Tegern, Matthias, et al.
(författare)
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Inter-rater and test-retest reliability of movement control tests for the neck, shoulder, thoracic, lumbar, and hip regions in military personnel
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:9
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Tidskriftsartikel (refereegranskat)abstract
- Strategies are needed to mitigate the high rates and related risks of musculoskeletal complaints and injuries (MSCI) in the military aviator community. Previous work on Swedish Armed Forces (SwAF) soldiers have shown that proper screening methods have been successful in reducing early discharge from military training. Research has pointed at the importance of optimal spinal movement control in military aviators. The aim of this work was to investigate the inter-rater and test-retest reliability of a battery of clinical tests for evaluating movement control in the neck, shoulders, thoracic, lumbar, and hip regions in a population of SwAF military personnel. Inter-rater and test-retest reliability of 15 movement control tests were assessed by crude and prevalence-adjusted kappa coefficient. The study included 37 (inter-rater) and 45 (test-retest) SwAF personnel and was performed with two physiotherapists simultaneously observing and rating the movements on the first occasion and repeated with one physiotherapist on the second occasion. For inter-rater reliability, the kappa coefficient ranged from .19 to .95. Seven tests showed substantial to almost perfect agreement (kappa > .60). With the adjusted kappa, three more tests reached the level of substantial agreement. The corresponding values for test-retest reliability ranged from .26 to .65. Substantial agreement was attained for two tests, three with adjusted kappa. The following tests can reliably be used when screening for biomechanically less advantageous movement patters in military aviators: Shoulder flexion, and rotation, Neck flexion in sitting and supine, Neck extension and rotation in sitting, Pelvic tilt, Forward lean and Single and Double knee extension tests. Grading criteria for tests in supine and quadruped positions need to be further elaborated.
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| 14. |
- Tegern, Matthias, 1982-
(författare)
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Musculoskeletal disorders in Swedish military aircrew : screening and clinical examination of the cervico-thoracic region
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Musculoskeletal disorders (MSD) are a common and growing occupational problem in military aircrew. Intervention studies attempting to reduce such issues have only showed limited preventive effects. Furthermore, in-depth knowledge of the clinical presentation of aircrew members with painful episodes is lacking. This thesis was conducted to add evidence to the ongoing work of the Swedish Armed Forces (SAF) for the prevention of MSD. The overall aim of this thesis was to estimate the occurrence of MSD in general and specifically cervico-thoracic pain and its associated factors among SAF aircrew and to evaluate clinically relevant tests, prior to the adaptation of a musculoskeletal screening protocol (MSP) for use in the SAF medical health care system. All participants included in the four studies of this thesis were employed in the SAF. Two cross-sectional studies (Study I; n=351, Study III; n=73) aimed to establish the occurrence of MSD in aircrew compared with army deployed soldiers (Study I) and between fighter pilots, helicopter pilots and rear crew (Study I), as well as identify associated factors of cervical, thoracic and shoulder region pain (Study I) and cervico-thoracic pain (Study III). Study II had a test-retest design and aimed to examine inter-rater (n=37) and test-retest (n=45) reliability of movement control tests. In study III, test performance was compared between fighter pilots, helicopter pilots and rear crew. Study IV had a cross-sectional (n=18) and a prospective observational cohort (n=47) design and aimed to explore physical symptoms and functional limitations in aircrew with cervico-thoracic pain, establish 12-month cumulative incidence and to identify risk factors for cervico-thoracic pain.The main findings of this thesis were that when compared to deployed soldiers, military aircrew reported higher prevalence of MSD in the cervical, thoracic, shoulder, and lumbar regions (80% reported at least one painful area during the previous year). Working as aircrew, and a lower rating of one’s physical health, were significantly associated with pain in the cervical, thoracic and shoulder regions (Study I). Two physical therapists could reliably rate movement patterns for the majority of movement control tests in the affected areas. Lower reliability was however seen for test-retest conditions (Study II). Movement control and measures of cervical range of motion (ROM), but not cervical strength and endurance, were associated with cervico-thoracic pain among military aircrew. Specifically, less control of both neck and lumbar flexion movements, and lesser cervical flexion ROM were associated with cervico-thoracic pain. Differences were found between fighter pilots, helicopter pilots and rear crew for lumbar flexion movement control and cervical lateral flexion ROM (Study III). Physical symptoms and functional impairments of aircrew with high (pain) intensity, flight-elicited and work-affecting cervico-thoracic pain showed an individual presentation. Previous pain episodes, lesser cervical flexion ROM, and lesser cervical flexor muscle endurance were identified as risk factors for future cervico-thoracic pain, which had a 12-month cumulative incidence of 23% (Study IV).Findings from this thesis strongly indicate that MSD in SAF aircrew is an occupational problem that need to be solved. The cervico-thoracic region was especially common in SAF aircrew. Movement control can reliably be assessed, but with less stability for repeated measures. While pain history and physical performance can to some degree be used to identify aircrew at risk for further cervico-thoracic pain, the clinical presentation of their physical symptoms showed individual presentation. The effects of implementing the MSP in the SAF as a primary and secondary preventive intervention, as well as rehabilitative strategies, need be systematically evaluated.
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| 15. |
- Wistedt, AC, et al.
(författare)
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Identification of a plasminogen-binding motif in PAM, a bacterial surface protein.
- 1995
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Ingår i: Molecular Microbiology. - 1365-2958. ; 18:3, s. 569-578
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Tidskriftsartikel (refereegranskat)abstract
- Surface-associated plasmin(ogen) may contribute to the invasive properties of various cells. Analysis of plasmin(ogen)-binding surface proteins is therefore of interest. The N-terminal variable regions of M-like (ML) proteins from five different group A streptococcal serotypes (33, 41, 52, 53 and 56) exhibiting the plasminogen-binding phenotype were cloned and expressed in Escherichia coli. The recombinant proteins all bound plasminogen with high affinity. The binding involved the kringle domains of plasminogen and was blocked by a lysine analogue, 6-aminohexanoic acid, indicating that lysine residues in the M-like proteins participate in the interaction. Sequence analysis revealed that the proteins contain common 13-16-amino-acid tandem repeats, each with a single central lysine residue. Experiments with fusion proteins and a 30-amino-acid synthetic peptide demonstrated that these repeats harbour the major plasminogen-binding site in the ML53 protein, as well as a binding site for the tissue-type plasminogen activator. Replacement of the lysine in the first repeat with alanine reduced the plasminogen-binding capacity of the ML53 protein by 80%. The results precisely localize the binding domain in a plasminogen surface receptor, thereby providing a unique ligand for the analysis of interactions between kringles and proteins with internal kringle-binding determinants.
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| 16. |
- Wistedt, AC, et al.
(författare)
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Kringle 2 mediates high affinity binding of plasminogen to an internal sequence in streptococcal surface protein PAM.
- 1998
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Ingår i: Journal of Biological Chemistry. - 1083-351X. ; 273:38, s. 24420-24424
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Tidskriftsartikel (refereegranskat)abstract
- Many cells express receptors for plasminogen (Pg), although the responsible molecules in most cases are poorly defined. In contrast, the group A streptococcal surface protein PAM contains a domain with two 13-amino acid residue long repeated sequences (a1 and a2) responsible for Pg binding. Here we identify the region in Pg that interacts with PAM. A radiolabeled proteolytic plasminogen fragment containing the first three kringles (K1-K3) interacted with streptococci expressing PAM or a chimeric surface protein harboring the a1a2 sequence. In contrast, plasminogen fragments containing kringle 4 or kringle 5 and the activable serine proteinase domain failed to bind to PAM-expressing group A streptococci. A synthetic and a recombinant polypeptide containing the a1a2 sequence both bound to immobilized recombinant K2 (rK2) but not to rK1 or rK3. The interaction between the a repeat region and rK2 was reversible, and rK2 completely blocked the binding of Pg to the a1a2 region. The binding of the a repeat containing polypeptide to K2 occurred with an equilibrium association constant of 4.5 x 10(7) M-1, as determined by surface plasmon resonance, a value close to that (1.6 x 10(7) M-1) calculated for the a1a2-Pg interaction. Inhibition experiments suggested involvement of the lysine-binding site of K2 in the interaction. These data demonstrate that K2 contains the major Pg-binding site for PAM, providing the first well defined example of an interaction between an internal Pg-binding region in a protein and a single kringle domain.
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