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  • 1.
    Aberg, Carola Höglund
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi. Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Sjödin, Bengt
    Lakio, Laura
    Pussinen, Pirkko J
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi. Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Claesson, Rolf
    Umeå universitet, Medicinsk fakultet, Odontologi. Umeå universitet, Medicinsk fakultet, Odontologi, Oral mikrobiologi.
    Presence of Aggregatibacter actinomycetemcomitans in young individuals: a 16-year clinical and microbiological follow-up study.2009Ingår i: Journal of clinical periodontology, ISSN 1600-051X, Vol. 36, nr 10, 815-22 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To look for clinical signs of periodontal disease in young adults who exhibited radiographic bone loss and detectable numbers of Aggregatibacter actinomycetemcomitans in their primary dentition. MATERIAL AND METHODS: Periodontal status and radiographic bone loss were examined in each of the subjects 16 years after the baseline observations. Techniques for anaerobic and selective culture, and checkerboard, were used to detect periodontitis-associated bacterial species. The isolated A. actinomycetemcomitans strains were characterized by polymerase chain reaction. RESULTS: Signs of localized attachment loss were found in three out of the 13 examined subjects. A. actinomycetemcomitans was recovered from six of these subjects and two of these samples were from sites with deepened probing depths and attachment loss. Among the isolated A. actinomycetemcomitans strains, serotypes a-c and e, but not d or f, were found. None of the isolated strains belonged to the highly leucotoxic JP2 clone, and one strain lacked genes for the cytolethal distending toxin. CONCLUSIONS: This study indicates that the presence of A. actinomycetemcomitans and early bone loss in the primary dentition does not necessarily predispose the individual to periodontal attachment loss in the permanent dentition.

  • 2. Al-Otaibi, M
    et al.
    Al-Harthy, M
    Gustafsson, A
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Claesson, Rolf
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral mikrobiologi.
    Angmar-Månsson, B
    Subgingival plaque microbiota in Saudi Arabians after use of miswak chewing stick and toothbrush2004Ingår i: Journal of Clinical Periodontology, ISSN 0303-6979, E-ISSN 1600-051X, Vol. 31, nr 12, 1048-53 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: The chewing stick, the miswak, is used in many developing countries as the traditional means for oral hygiene. It is prepared from the roots, twigs and stem of Salvadora persica or other alternative local plants. OBJECTIVES: To compare the effects of the chewing stick miswak (from S. persica) and toothbrush on subgingival plaque microflora among Saudi Arabian individuals. Further, to investigate whether components extracted from S. persica may interfere with the subgingival plaque micro-organisms. MATERIAL AND METHODS: Fifteen healthy Saudi Arabian male volunteers aged 21-36 years were included in a single-blind, randomized cross-over study. The participants were taught how to use each device properly. Plaque sampling for DNA test was performed at the baseline, 1 week after professional tooth cleaning, and after 3 weeks of either miswak or toothbrush use. Identification and quantification of microbial species were performed by the checkerboard method, using whole genomic, digoxigenin-labelled DNA probes. Inhibition zones around miswak were examined on agar plates with Actinobacillus actinomycetemcomitans and the leukotoxicity of this bacterium was analyzed in a bioassay with macrophages+/-extracts of miswak. RESULTS: Miswak and toothbrushing had a similar influence on the levels of the subgingival microbiota. However, A. actinomycetemcomitans was significantly more reduced by miswak (p<0.05) than by toothbrushing. These results were supported by our in vitro results which, indicated that extracts from S. persica might interfere with the growth and leukotoxicity of A. actinomycetemcomitans. CONCLUSIONS: In contrast to toothbrush use, miswak use significantly reduced the amount of A. actinomycetemcomitans in the subgingival plaque.

  • 3. Belibasakis, George
    et al.
    Brage, Monica
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi. Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Lagergård, Teresa
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi.
    Cytolethal distending toxin upregulates RANKL expression in Jurkat T-cells: Cdt upregulates RANKL2008Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 116, nr 6, 499-506 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cytolethal distending toxin, a bacterial exotoxin produced by a number of Gram-negative species, causes growth arrest and morphological alterations in host cells. Among these species are Haemophilus ducreyi, the etiological agent of chancroid, and the periodontal pathogen Aggregatibacter actinomycetemcomitans, highly implicated in localized aggressive periodontitis. CDT induces receptor activator of NF-kappaB ligand (RANKL) expression in periodontal fibroblasts, the key bone-resorbing cytokine. T-cells are actively involved in localized inflammation-induced bone destruction, including periodontitis. The aim of this study was to investigate the effects of purified CDT on the expression of RANKL and its decoy receptor osteoprotegerin (OPG), in the Jurkat T-cell line. Quantitative real-time PCR indicated that 100 pg/ml of purified H. ducreyi CDT upregulated RANKL mRNA expression by 2.2-fold, after 24 h of exposure. This increase was corroborated by a 2.0-fold increase in RANKL protein release, as determined by ELISA. OPG was not detected in this experimental system. In conclusion, CDT enhances RANKL expression in T-cells, denoting that these cells are a potential target for the toxin and strengthening the potential link between this virulence factor and mechanisms associated with localized bone resorption.

  • 4.
    Belibasakis, Georgios
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral mikrobiologi.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Wang, Ying
    Claesson, Rolf
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral mikrobiologi.
    Chen, Casey
    Asikainen, Sirkka
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral mikrobiologi.
    Kalfas, Sotos
    Inhibited proliferation of human periodontal ligament cells and gingival fibroblasts by Actinobacillus actinomycetemcomitans: involvement of the cytolethal distending toxin2002Ingår i: European Journal of Oral Sciences, ISSN 0909-8836, E-ISSN 1600-0722, Vol. 110, nr 5, 366-373 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Actinobacillus actinomycetemcomitans can inhibit fibroblast proliferation. The objective of this study was to characterize the early proliferative responses of human periodontal ligament cells (PDLC) and gingival fibroblasts (GF) to A. actinomycetemcomitans components and to investigate the possible involvement of the cytolethal distending toxin (cdt) produced by this bacterium. The PDLC and GF were challenged with surface components of A. actinomycetemcomitans. Both DNA and protein synthesis as well as cell lysis or apoptosis were assayed for a 6-h period after addition of the bacterial extract. Unlike the controls, inhibition of DNA synthesis had already occurred in the challenged cells at the end of the initial 3- to 6-h period. No lysis or apoptosis was detected, and the total protein synthesis remained unaffected. The persistence of the effect on cell growth was confirmed after a 72-h period of challenge, during which the cells remained viable but exhibited an elongated and distended cell body. No significant differences were observed between PDLC and GF. When a cdt-knockout strain of A. actinomycetemcomitans was used almost no inhibitory effect on cell proliferation was observed. It was concluded that A. actinomycetemcomitans causes a non-lethal inhibition of proliferation in PDLC and GF as a result of an early arrest of DNA synthesis. Cytolethal distending toxin is responsible for most of this effect. This bacterial property may compromise tissue homeostasis in the periodontium.

  • 5.
    Belibasakis, Georgios N
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi. Umeå universitet, Medicinsk fakultet, Odontologi, Oral mikrobiologi.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Wang, Y
    Chen, C
    Kalfas, S
    Lerner, Ulf
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    The cytolethal distending toxin induces receptor activator of NF-κB ligand expression in human gingival fibroblasts and periodontal ligament cells2005Ingår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 73, nr 1, 342-351 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Actinobacillus actinomycetemcomitans is associated with localized aggressive periodontitis, a disease characterized by rapid loss of the alveolar bone surrounding the teeth. Receptor activator of NF-kappaB Ligand (RANKL) and osteoprotegerin (OPG) are two molecules that regulate osteoclast formation and bone resorption. RANKL induces osteoclast differentiation and activation, whereas OPG blocks this process by acting as a decoy receptor for RANKL. The purpose of this study was to investigate the effect of A. actinomycetemcomitans on the expression of RANKL and OPG in human gingival fibroblasts and periodontal ligament cells. RANKL mRNA expression was induced in both cell types challenged by A. actinomycetemcomitans extract, whereas OPG mRNA expression remained unaffected. Cell surface RANKL protein was also induced by A. actinomycetemcomitans, whereas there was no change in OPG protein secretion. A cytolethal distending toxin (Cdt) gene-knockout strain of A. actinomycetemcomitans did not induce RANKL expression, in contrast to its wild-type strain. Purified Cdt from Haemophilus ducreyi alone, or in combination with extract from the A. actinomycetemcomitans cdt mutant strain, induced RANKL expression. Pretreatment of A. actinomycetemcomitans wild-type extract with Cdt antiserum abolished RANKL expression. In conclusion, A. actinomycetemcomitans induces RANKL expression in periodontal connective tissue cells. Cdt is crucial for this induction and may therefore be involved in the pathological bone resorption during the process of localized aggressive periodontitis.

  • 6.
    Belibasakis, Georgios N
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral mikrobiologi. Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Wang, Y
    Chen, C
    Lagergård, T
    Kalfas, S
    Lerner, Ulf
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Cytokine responses of human gingival fibroblasts to Actinobacillus actinomycetemcomitans cytolethal distending toxin2005Ingår i: Cytokine, ISSN 1043-4666, E-ISSN 1096-0023, Vol. 30, nr 2, 56-63 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Actinobacillus actinomycetemcomitans is implicated in the pathogenesis of localized aggressive periodontitis, and has the capacity to express a cytolethal distending toxin (Cdt). Gingival fibroblasts (GF) are resident cells of the periodontium, which can express several osteolytic cytokines. The aims of this study were a) to investigate the role of Cdt in A. actinomycetemcomitans-induced expression of osteolytic cytokines and their cognate receptors in GF and b) to determine if the previously demonstrated induction of receptor activator of NFkappaB ligand (RANKL) by A. actinomycetemcomitans is mediated by these pro-inflammatory cytokines or by prostaglandin E(2) (PGE(2)). A. actinomycetemcomitans clearly induced interleukin (IL)-6, IL-1beta, and to a minimal extent, tumor necrosis factor (TNF)-alpha mRNA expression. At the protein level, IL-6 but not IL-1beta or TNF-alpha expression was stimulated. The mRNA expression of the different receptor subtypes recognizing IL-6, IL-1beta and TNF-alpha was not affected. A cdt-knockout strain of A. actinomycetemcomitans had similar effects on cytokine and cytokine receptor mRNA expression, compared to its parental wild-type strain. Purified Cdt stimulated IL-6, but not IL-1beta or TNF-alpha protein biosynthesis. Antibodies neutralizing IL-6, IL-1 or TNF-alpha, and the PGE(2) synthesis inhibitor indomethacin, did not affect A. actinomycetemcomitans-induced RANKL expression. In conclusion, a) A. actinomycetemcomitans induces IL-6 production in GF by a mechanism largely independent of its Cdt and b) A. actinomycetemcomitans-induced RANKL expression in GF occurs independently of IL-1, IL-6, TNF-alpha, or PGE(2).

  • 7.
    Belibasakis, Georgios N
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi. Umeå universitet, Medicinsk fakultet, Odontologi, Oral mikrobiologi.
    Mattsson, Anna
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Wang, Ying
    Chen, Casey
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Cell cycle arrest of human gingival fibroblasts and periodontal ligament cells by Actinobacillus actinomycetemcomitans: involvement of the cytolethal distending toxin2004Ingår i: Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS), ISSN 0903-4641, E-ISSN 1600-0463, Vol. 112, nr 10, 674-685 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The cytolethal distending toxin (Cdt) is produced by several Gram-negative bacterial species and causes growth arrest and morphological alterations in mammalian cells. Actinobacillus actinomycetemcomitans, which is involved in the pathogenesis of localized aggressive periodontitis, also produces a Cdt that affects periodontal connective tissue cells. The aim of this study was to investigate in which phase of the cell cycle these cells are arrested and enlarged when challenged with A. actinomycetemcomitans, and to evaluate the involvement of its Cdt. Human gingival fibroblasts and periodontal ligament cells were challenged with A. actinomycetemcomitans extract, or with purified Cdt, and cell cycle analysis was performed by propidium iodide staining and flow cytometry. Cells exposed to an A. actinomycetemcomitans wild-type strain, or to purified Cdt, were arrested in both G1 and G2/M phases, and appeared enlarged compared to the corresponding controls. The cellular enlargement occurred in both G1 and G2/M arrested cells. In contrast, cells exposed to an A. actinomycetemcomitans cdt-knockout mutant strain showed cell cycle phase distribution and size similar to the controls. In conclusion, A. actinomycetemcomitans causes a combined G1 and G2/M growth arrest and enlargement in periodontal connective tissue cells, which is attributed to its Cdt.

  • 8. Belibasakis, GN
    et al.
    Bostanci, N
    Hashim, A
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Aduse-Opoku, J
    Curtis, MA
    Hughes, FJ
    Regulation of RANKL and OPG gene expression in human gingival fibroblasts and periodontal ligament cells by Porphyromonas gingivalis: a putative role of the Arg-gingipains2007Ingår i: Microbial Pathogenesis, ISSN 0882-4010, E-ISSN 1096-1208, Vol. 43, nr 1, 46-53 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Porphyromonas gingivalis is highly implicated in the pathogenesis of periodontitis, which is characterized by the destruction of periodontal connective tissues and the supporting alveolar bone. Receptor Activator of NF-kappaB Ligand (RANKL) stimulates bone resorption, whereas osteoprotegerin (OPG) blocks its action, and this bi-molecular system is implicated in periodontitis. The aim of this work was (a) to investigate the regulation of RANKL and OPG gene expression in human periodontal ligament (PDL) cells and gingival fibroblasts (GF), in response to P. gingivalis culture supernatants, by quantitative real-time PCR and (b) to attempt to identify putative virulence factors involved in this process. The results indicated that P. gingivalis induced RANKL and reduced OPG mRNA expression by the studied cells, resulting in an increased RANKL/OPG expression ratio. Heat-inactivation of P. gingivalis resulted in significant reduction of RANKL mRNA expression. A Lys-gingipain mutant strain did not affect, whereas an Arg-gingipain mutant strain further enhanced RANKL mRNA expression, compared to their parental wild-type strain. In conclusion, P. gingivalis up-regulates the RANKL/OPG expression ratio in GF and PDL cells, denoting an enhanced osteoclastogenic potential by the cells. The component mainly responsible for RANKL induction appears to be proteinaceous, and it may be regulated by the Arg-gingipains.

  • 9.
    Bylund, Annika
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Geriatrik.
    Saarinen, Niina
    Zhang, Jie-Xian
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Bergh, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Widmark, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Lundin, Eva
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Adlercreutz, Herman
    Hallmans, Göran
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Stattin, Pär
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Urologi och andrologi.
    Mäkelä, Sari
    Anticancer effects of a plant lignan 7-hydroxymatairesinol on a prostate cancer model in vivo.2005Ingår i: Experimental biology and medicine (Maywood, N.J.: Print), ISSN 1535-3702, E-ISSN 1535-3699, Vol. 230, nr 3, 217-223 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Clinical intervention studies and experimental studies with lignan-rich diets suggest that lignans may have inhibitory effects on prostate cancer, but no clinical or experimental studies with purified lignans have been published. The purpose of this study was to investigate the effect of a plant lignan 7-hydroxymatairesinol (HMR) on LNCaP human prostate cancer xenografts in athymic mice. Athymic nude male mice were injected subcutaneously with LNCaP cells. Starting 3 days after tumor cell injections, a control diet or a control diet supplemented with 0.15% or 0.30% of HMR was administered to mice and the tumor take rate and growth was observed for 9 weeks. HMR diet inhibited the growth of LNCaP tumors. Mice treated with HMR had smaller tumor volume, lower tumor take rate, increased proportion of nongrowing tumors, and higher tumor cell apoptotic index compared with controls. Furthermore, the cell proliferation index was reduced in mice receiving the 0.30% HMR diet compared with mice receiving the control diet. Our results suggest that dietary HMR started at the early phase of the tumor development inhibits the growth of the LNCaP human prostate cancer xenografts in athymic male mice.

  • 10. Carlsson, G
    et al.
    Wahlin, Ylva-Britt
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral diagnostisk radiologi.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Olsson, A
    Eriksson, T
    Claesson, Rolf
    Umeå universitet, Medicinsk fakultet, Odontologi.
    Hänström, Lennart
    Umeå universitet, Medicinsk fakultet, Odontologi.
    Henter, JI
    Periodontal disease in patients from the original Kostmann family with severe congenital neutropenia2006Ingår i: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 77, nr 4, 744-751 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Patients with Kostmann syndrome (severe congenital neutropenia [SCN]) typically normalize their absolute neutrophil count (ANC) upon granulocyte colony-stimulating factor (G-CSF) therapy. However, although they no longer experience life-threatening bacterial infections, they frequently still have recurrent gingivitis and even severe periodontitis, often starting in early childhood. METHODS: We studied the periodontal disease in the four surviving patients belonging to the family originally described by Kostmann. Their odontological records, x-rays, color photos, bacterial cultures, serum antibodies to oral bacteria, and histopathological examinations were reviewed. The data were also correlated to previous investigations on their antibacterial peptides and molecular biology. RESULTS: Three patients had periodontal disease, despite normal ANC and professional dental care, and had neutrophils deficient in antibacterial peptides. One of these patients also had a heterozygous mutation in the neutrophil elastase gene, had severe periodontal disease and overgrowth of the periodontal pathogen Actinobacillus actinomycetemcomitans in the dental flora, and 15 permanent teeth had been extracted by the age of 27. One bone marrow-transplanted patient had no periodontal disease. CONCLUSIONS: Normalized ANC levels are not sufficient to maintain normal oral health in SCN patients, and because neutrophils are important for first-line defense and innate immunity, the deficiency of the antibacterial peptide LL-37 probably explains their chronic periodontal disease. Professional dental care is still important for SCN patients, despite treatment with G-CSF and normal ANC levels. Whether antibacterial peptides play a role in the pathogenesis of periodontitis in other patients remains to be elucidated.

  • 11.
    Hallmans, Göran
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Näringsforskning.
    Agren, A
    Johansson, G
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Stegmayr, Birgitta
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Jansson, JH
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindahl, B
    Rolandsson, Olov
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Allmänmedicin.
    Söderberg, Stefan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Nilsson, M
    Johansson, Ingegerd
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Kariologi.
    Weinehall, Lars
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Cardiovascular disease and diabetes in the Northern Sweden Health and Disease Study Cohort: evaluation of risk factors and their interactions.2003Ingår i: Scandinavian Journal of Public Health. Supplement Links, ISSN 1403-4956, Vol. 61, 18-24 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The purpose of this paper is, first, to describe the organization, sampling procedures, availability of samples/database, ethical considerations, and quality control program of the Northern Sweden Health and Disease Study Cohort. Secondly, some examples are given of studies on cardiovascular disease and diabetes with a focus on the biomarker programme. The cohort has been positioned as a national and international resource for scientific research.

  • 12.
    Hallmans, Göran
    et al.
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Näringsforskning.
    Zhang, Jie-Xian
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Näringsforskning.
    Lundin, Eva
    Umeå universitet, Medicinsk fakultet, Medicinsk biovetenskap, Patologi.
    Stattin, P
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Johansson, I
    Hultén, K
    Winkvist, A
    Aman, P
    Lenner, P
    Adlercreutz, H
    Rye, lignans and human health2003Ingår i: Proceedings of the Nutrition Society, ISSN 0029-6651, E-ISSN 1475-2719, Vol. 62, nr 1, 193-9 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Rye bran contains a high content not only of dietary fibre, but also of plant lignans and other bioactive compounds in the so-called dietary fibre complex. Blood concentrations of lignans such as enterolactone have been used as biomarkers of intake of lignan-rich plant food. At present,evidence from studies in human subjects does not warrant the conclusion that rye, whole grains orphyto-oestrogens protect against cancer. Some studies, however, have pointed in that direction,especially in relation to cancers of the upper digestive tract. A number of prospective epidemiological studies have clearly shown a protective effect of wholegrain cereals against myocardial infarctions. A corresponding protective effect against diabetes and ischaemic stroke(brain infarct) has also been demonstrated. It seems reasonable to assume that these protective effects are associated with one or more factors in the dietary fibre complex.

  • 13. Jenab, M
    et al.
    Riboli, E
    Ferrari, P
    Friesen, M
    Sabate, J
    Norat, T
    Slimani, N
    Tjonneland, A
    Olsen, A
    Overvad, K
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Boeing, H
    Schulz, M
    Linseisen, J
    Nagel, G
    Trichopoulou, A
    Naska, A
    Oikonomou, E
    Berrino, F
    Panico, S
    Palli, D
    Sacerdote, C
    Tumino, R
    Peeters, PH
    Numans, ME
    Bueno-de Mesquita, HB
    Buchner, FL
    Lund, E
    Pera, G
    Chirlaque, MD
    Sanchez, MJ
    Arriola, L
    Barricarte, A
    Quiros, JR
    Johansson, Ingegerd
    Umeå universitet, Medicinsk fakultet, Odontologi, Kariologi.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Berglund, G
    Bingham, S
    Khaw, KT
    Allen, N
    Key, T
    Carneiro, F
    Save, V
    Del Giudice, G
    Plebani, M
    Kaaks, R
    Gonzalez, CA
    Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition2006Ingår i: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 95, nr 3, 406-415 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Despite declining incidence rates, gastric cancer (GC) is a major cause of death worldwide. Its aetiology may involve dietary antioxidant micronutrients such as carotenoids and tocopherols. The objective of this study was to determine the association of plasma levels of seven common carotenoids, their total plasma concentration, retinol and - and -tocopherol, with the risk of gastric adenocarcinoma in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), a large cohort involving 10 countries. A secondary objective was to determine the association of total sum of carotenoids, retinol and -tocopherol on GCs by anatomical subsite (cardia/noncardia) and histological subtype (diffuse/intestinal). Analytes were measured by high-performance liquid chromatography in prediagnostic plasma from 244 GC cases and 645 controls matched by age, gender, study centre and date of blood donation. Conditional logistic regression models adjusted by body mass index, total energy intake, smoking and Helicobacter pylori infection status were used to estimate relative cancer risks. After an average 3.2 years of follow-up, a negative association with GC risk was observed in the highest vs the lowest quartiles of plasma -cryptoxanthin (odds ratio (OR)=0.53, 95% confidence intervals (CI)=0.30-0.94, Ptrend=0.006), zeaxanthin (OR=0.39, 95% CI=0.22-0.69, Ptrend=0.005), retinol (OR=0.55, 95% CI=0.33-0.93, Ptrend=0.005) and lipid-unadjusted -tocopherol (OR=0.59, 95% CI=0.37-0.94, Ptrend=0.022). For all analytes, no heterogeneity of risk estimates or significant associations were observed by anatomical subsite. In the diffuse histological subtype, an inverse association was observed with the highest vs lowest quartile of lipid-unadjusted -tocopherol (OR=0.26, 95% CI=0.11-0.65, Ptrend=0.003). These results show that higher plasma concentrations of some carotenoids, retinol and -tocopherol are associated with reduced risk of GC.

  • 14.
    Johansson, Anders
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Buhlin, K
    Koski, R
    Gustafsson, A
    The immunoreactivity of systemic antibodies to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in adult periodontitis2005Ingår i: European Journal of Oral Sciences, ISSN 0909-8836, E-ISSN 1600-0722, Vol. 113, nr 3, 197-202 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis secrete several potent virulence factors and are known to be two of the major periodontal pathogens. In the present case-control study, the systemic immunoreactivity to A. actinomycetemcomitans exotoxins, cytolethal distending toxin (Cdt) and leukotoxin was analyzed in adult subjects with periodontitis and in periodontally healthy controls. Furthermore, systemic immunoreactivity to P. gingivalis was analyzed in these subjects. Reactivity to the A. actinomycetemcomitans toxins was determined in bioassays that quantified neutralizing antibodies, and P. gingivalis antibodies were detected by enzyme-linked immunosorbent assay (ELISA). The results showed a significantly enhanced immunoreactivity to P. gingivalis in the subjects with periodontitis, while the reactivity to A. actinomycetemcomitans leukotoxin showed no significant difference between patients and controls. However, combined immunoreactivity to leukotoxin and Cdt was more prevalent in the subjects with periodontitis than in the controls. In addition, immunoreactivity to leukotoxin correlated to periodontitis in men but not in women. In conclusion, data from the present study indicate that immunoreactivity to P. gingivalis is frequent in adult periodontitis, while the role of A. actinomycetemcomitans seems to be more complex and depends on gender of the infected subject as well as the virulence of the bacteria. (c) Eur J Oral Sci, 2005

  • 15.
    Johansson, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Behnam Motlagh, Parviz
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Adenylate cyclase toxin from Bordetella pertussis enhances cisplatin-induced apoptosis to lung cancer cells in vitro.2006Ingår i: Oncology Research, ISSN 0965-0407, E-ISSN 1555-3906, Vol. 15, nr 9, 423-430 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The present study examined the possibility to enhance lung cancer cell cytotoxicity and apoptosis of the anticancer drug cisplatin by exposure with adenylate cyclase (AC) toxin from Bordetella pertussis. A malignant mesothelioma cell line (P31) and a small-cell lung cancer cell line (U1690) were exposed to increasing concentrations of cisplatin and AC toxin, alone or in combination. Cytotoxicity was determined by a fluorescein-based assay and apoptosis by flow cytometry quantification of annexin V binding. Caspase-3, -8, and -9 activities were measured by enzyme activity assays. The cytotoxicity of AC toxin was time and dose dependent with an LD50 value at 72 h of 3 and 7 mg/L for P31 cells and U1690 cells, respectively. Cisplatin showed a similar time- and dose-dependent cytotoxicity, which was increased in the presence of a low toxic concentration (1 mg/L) of AC toxin. Furthermore, cisplatin caused a dose-dependent increase of annexin V binding cells of both cell lines after 24-h incubation, which was also enhanced in combination with AC toxin. AC toxin (1 mg/L) increased cisplatin-induced caspase-3, -8, and -9 activities in U1690 cells. Only minor increases of caspase-8 and -9 were noted for P31 cells. The present results, together with the knowledge that bacterial toxins decrease side effects of traditional cancer treatment, suggest a possibility to use them to enhance the therapeutic effect of cancer chemotherapy with reduced clinical adverse effects.

  • 16.
    Johansson, David
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Grankvist, Kjell
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Klinisk kemi.
    Andersson, Ulrika
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Henriksson, Roger
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Bergström, Per
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Brännström, Thomas
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Patologi.
    Behnam Motlagh, Parviz
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Verotoxin-1 Induction of Apoptosis in Gb3-Expressing Human Glioma Cell Lines2006Ingår i: Cancer Biology & Therapy, ISSN 1538-4047, E-ISSN 1555-8576, Vol. 5, nr 9, 1211-1217 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of this study was to examine the cytotoxicity and mechanism of apoptosis induction of verotoxin-1 (VT-1) in human glioma cell lines. VT-1 is a member of the shiga-toxin family expressed by some serotypes of Escherichia coli and Shigella dysenteriae. Shiga-toxins have been shown to induce apoptosis by binding to its membrane receptor Gb3. The human glioma cell lines SF-767, U-343 MG, and U-251 MG were studied together with BT4C, a rat glioma cell line. Cells were first screened for Gb3 expression by flow cytometry. Fluorescein diacetate was used to determine cell viability after VT-1 and irradiation exposure and apoptosis was studied by TUNEL staining, a mitochondrial membrane potential assay, and caspase activity assays. SF-767 and U-343 MG cells were found to express Gb3 and were also sensitive to VT-1-induced cytotoxicity, whereas nonGb3-expressing U-251 MG and BT4C glioma cells were not. VT-1 depolarized the mitochondrial membrane and activated caspase-9 and -3 of SF-767 and U-343 MG cells. VT-1 exposure for 72 h resulted in approx. 60 and 90% TUNEL-stained cells, respectively. D, L-Threo-1-phenyl-2-palmitoylamino-3-morpholino-1-propanol (PPMP) an inhibitor of glucosylceramide synthesis was used to block Gb3 synthesis. Two mumol/L PPMP for 72 h abolished SF-767 and U-343 MG expression of Gb3 and made the cells completely resistant to VT-1 induced apoptosis. Key components of MAP kinase signalling pathways that control BAX and mitochondrial function were investigated. VT-1 induced JNK phosphorylation in both cell lines, suggesting that survival signal pathways were overruled by VT-1-induced JNK activation leading to mitochondrial depolarization, caspase-9 activation and apoptosis. Immunohistochemistry of cryostat section from glioma biopsies demonstrated expression of Gb3 was in the vascular endothelial cells as well as tumor cells, but not in astrocytes. The high specificity and apoptosis inducing properties of verotoxin-1 indicates that the toxin may be a potential anti-neoplastic agent for Gb3-expressing gliomas.

  • 17.
    Kelk, Peyman
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi. Umeå universitet, Medicinsk fakultet, Klinisk mikrobiologi, Klinisk bakteriologi.
    Inflammatory cell death of human macrophages induced by Aggregatibacter actinomycetemcomitans leukotoxin2009Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Aggregatibacter (Actinobacillus) actinomycetemcomitans is a bacterium mainly associated with aggressive forms of periodontitis. Among its virulence factors, a leukotoxin is suggested to play an important role in the pathogenicity. Periodontal infections with strains producing high levels of the leukotoxin are strongly associated with severe disease. Leukotoxin selectively kills human leukocytes and can disrupt the local defense mechanisms. Previous studies examining the role of the leukotoxin in host-parasite interactions have mainly focused on polymorphonuclear leukocytes (PMNs). In the inflamed periodontium, macrophages play a significant role in the regulation of the inflammatory reactions and the tissue breakdown and remodeling.

    Thus, the aim of this dissertation was to investigate death mechanisms of human macrophages exposed to leukotoxin.

    Human lymphocytes, PMNs, and monocytes/macrophages isolated from venous blood were exposed to purified leukotoxin or live A. actinomycetemcomitans strains producing variable levels or no leukotoxin. Different target cells were characterized by their expression of cell surface molecules. Cell death and viability were studied by examining cell membrane integrity and morphological alterations. Further, processes and cellular markers involved in apoptosis and necrosis were investigated. The expression and activation of pro-inflammatory cytokines of the leukotoxin-challenged leukocytes were examined at the mRNA and protein level. The biological activity of the secreted cytokines was investigated by testing the culture supernatants in a bone resorption assay. Additionally, different intracellular signaling pathways involved in the pro-inflammatory response from the macrophages were examined.

    Monocytes/macrophages were the most sensitive leukocytes for A. actinomycetemcomitans leukotoxin-induced lysis. This process in monocytes/ macrophages involved caspase-1 activation, and in addition, leukotoxin triggered abundant activation and secretion of IL-1β from these cells. The secreted IL-1β was mainly the 17 kDa bioactive protein and stimulated bone resorption. This activity could be blocked by an IL-1 receptor antagonist. When live bacteria were used, the A. actinomycetemcomitans-induced IL-1β secretion from human macrophages was mainly caused by the leukotoxin. Closer examination of the macrophages exposed to leukotoxin revealed that the induced cell death proceeded through a process that differed from classical apoptosis and necrosis. Interestingly, this process resembled a newly discovered death mechanism termed pyroptosis. The extensive leukotoxin induced IL-1β secretion did not correlate to increased levels of mRNA for IL-1β. It was mainly mediated by caspase-1 activation, since blocking it by a specific inhibitor also abolished the secretion of IL-1β. A similar pattern, but at much lower level, was seen for IL-18.

    In conclusion, these results show that A. actinomycetemcomitans leukotoxin induces a death process in human macrophages leading to a specific and excessive pro-inflammatory response. Our results indicate that this novel virulence mechanism of leukotoxin may play an important role in the pathogenic potential of A. actinomycetemcomitans.

  • 18.
    Kelk, Peyman
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Abd, Hadi
    Centre for Microbiological Preparedness, Swedish Institute for Infectious Disease Control, Solna, Sweden.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Sandström, Gunnar
    Centre for Microbiological Preparedness, Swedish Institute for Infectious Disease Control, Solna, Sweden ; Department of Laboratory Medicine, Division of Clinical Microbiology, Karolinska Institute, Stockholm, Sweden.
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Inflammatory cell death of human macrophages in response to Aggregatibacter actinomycetemcomitans leukotoxinManuskript (Övrigt vetenskapligt)
    Abstract [en]

    Aggregatibacter (Actinobacillus) actinomycetemcomitans is a facultative anaerobic gram-negative bacterium associated with severe forms of periodontitis. A leukotoxin, which belongs to the Repeats in Toxin (RTX) family, is believed to be one of its virulence factors and to play an important role in the bacterium's pathogenicity. This toxin selectively kills human leukocytes by inducing apoptosis and lysis. Here we report that leukotoxin-induced cell death of macrophages proceeded through a process that differs from the classical characteristics of apoptosis and necrosis. Interestingly, this process resembled pyroptosis, and resulted in an extensive leukotoxin-induced interleukin-1β (IL-1β) secretion. This activation was mainly mediated by caspase-1 activation, while the levels of mRNA for IL-1β were not affected by the leukotoxin. A similar pattern was seen for IL-18, but the level of that cytokine was about 30 times lower. Both of these cytokines are synthesized as biologically inactive precursors and need active caspase-1 for their activation and secretion. In conclusion, A. actinomycetemcomitans leukotoxin induces a pyroptosis-like cell death in human macrophages and that leads to a specific and excessive pro-inflammatory response. This novel virulence mechanism of the leukotoxin may play an important role in the pathogenic potential of this bacterium.

  • 19.
    Kelk, Peyman
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Chen, Casey
    Sjöstedt, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi, Klinisk bakteriologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi. Parod.
    IL-1beta secretion induced by Aggregatibacter (Actinobacillus) actinomycetemcomitans is mainly caused by the leukotoxin2008Ingår i: International Journal of Medical Microbiology, ISSN 1438-4221, E-ISSN 1618-0607, Vol. 298, nr 5/6, 529-541 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aggregatibacter (Actinobacillus) actinomycetemcomitans forms a leukotoxin that selectively lyses primate neutrophils, monocytes and triggers apoptosis in promyeloic cells and degranulation of human neutrophils. Recently, we showed that the leukotoxin causes activation of caspase-1 and abundant secretion of bio-active IL-1beta from human macrophages. In this study, we show that high levels of IL-beta correlated with a high proportion of A. actinomycetemcomitans in clinical samples from a patient with aggressive periodontitis. To determine the relative contribution of leukotoxin to the overall bacteria-induced IL-1beta secretion, macrophages were isolated from peripheral blood and exposed to different concentrations of live A. actinomycetemcomitans strains with either no, low or high production of leukotoxin. Cell lysis and levels of IL-1beta, IL-6, TNF-alpha and caspase-1 were measured by ELISA and flow cytometry. Leukotoxin was the predominant cause of IL-1beta secretion from macrophages, even in the A. actinomycetemcomitans strain with low leukotoxin production. Macrophages exposed to non-leukotoxic bacteria accumulated cytosolic pro-IL-1beta, which was secreted by a secondary exposure to leukotoxic bacteria. In conclusion, the present study shows for the first time that A. actinomycetemcomitans-induced IL-1beta secretion from human macrophages in vitro is mainly caused by leukotoxin.

  • 20.
    Kelk, Peyman
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Hänström, L
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Lerner, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral cellbiologi.
    Kalfas, S
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Abundant secretion of bioactive interleukin-1beta by human macrophages induced by Actinobacillus actinomycetemcomitans leukotoxin2005Ingår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 73, nr 1, 453-458 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Actinobacillus actinomycetemcomitans produces a leukotoxin that selectively kills human leukocytes. Recently, we reported that macrophages are highly sensitive to leukotoxin and that their lysis involves activation of caspase 1. In this study, we show that leukotoxin also induces the production and release of proinflammatory cytokines from human macrophages. The macrophages were challenged with leukotoxin or lipopolysaccharide (LPS) from A. actinomycetemcomitans or LPS from Escherichia coli, and the production and secretion of interleukin-1beta (IL-1beta), IL-6, and tumor necrosis factor alpha (TNF-alpha) were determined at the mRNA and protein levels by reverse transcription-PCR and enzyme-linked immunosorbent assay, respectively. Leukotoxin (1 to 30 ng/ml) induced abundant production and secretion of IL-1beta, while the effects on IL-6 and TNF-alpha production were limited. Leukotoxin (1 ng/ml) caused a 10-times-higher release of IL-1beta than did LPS (100 ng/ml). The secreted IL-1beta was mainly the bioactive 17-kDa protein. At higher concentrations (>30 ng/ml), leukotoxin caused secretion of mainly inactive cytokine, the 31-kDa pro-IL-1beta. The presence of specific antibodies to IL-1beta or of a caspase 1 inhibitor blocked the secretion and production of the cytokine. Supernatants of leukotoxin-challenged macrophages stimulated bone resorption when tested in a mouse calvarial model. The activity could be blocked by an IL-1 receptor antagonist or specific antibodies to IL-1beta. We concluded that A. actinomycetemcomitans leukotoxin can trigger abundant production and secretion of bioactive IL-1beta by human macrophages, which is mediated by activation of caspase 1.

  • 21.
    Kelk, Peyman
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Johansson, Anders
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Claesson, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Hänström, L
    Kalfas, S
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Oral mikrobiologi.
    Caspase 1 involvement in human monocyte lysis induced by Actinobacillus actinomycetemcomitans leukotoxin2003Ingår i: Infection and Immunity, ISSN 0019-9567, E-ISSN 1098-5522, Vol. 71, nr 8, 4448-4455 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Actinobacillus actinomycetemcomitans, an oral bacterium implicated in the etiology of periodontal diseases, produces a leukotoxin that selectively lyses primate neutrophils and monocytes, the major populations of defense cells in the periodontium. Though lysis requires expression of the receptor lymphocyte function-associated molecule 1 (LFA-1) on the cell surface, not all LFA-1-expressing leukocyte populations are equally susceptible to the toxin. In this study, the susceptibility of human leukocytes to leukotoxin-induced lysis is compared to their expression of LFA-1 and the activity of caspase 1. Cytolysis was determined by the activity of lactate dehydrogenase released from peripheral human leukocytes after 1-h exposure to leukotoxin. Monocytes were lysed at leukotoxin concentrations of > or = 5 ng/ml, while the corresponding values for neutrophils and lymphocytes were approximately 10 times greater. Similar LFA-1 expression was found in all susceptible cell populations irrespective of their degree of sensitivity to the toxin. Exposure of monocytes to leukotoxin increased their caspase 1 activity about fivefold within 10 to 20 min. Presence of the caspase 1 inhibitor Ac-YVAD-CMK significantly blocked the leukotoxin-induced lysis of monocytes only. At sublytic concentrations, leukotoxin induced no apoptotic activity in monocytes, as revealed by the lack of caspase 3 activation and DNA fragmentation. Monocytes are the most lysis-sensitive leukocytes for A. actinomycetemcomitans leukotoxin. Their lysis by this toxin depends on caspase 1 activation and proceeds through a process that differs from classical apoptosis.

  • 22.
    Lindh, Tomas
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Parodontologi.
    Should we extract teeth to avoid tooth-implant combinations?2008Ingår i: Journal of Oral Rehabilitation, ISSN 0305-182X, E-ISSN 1365-2842, Vol. 35, nr Suppl 1, 44-54 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The controversy over combining teeth and implants for support of fixed partial dentures still remains after almost three decades of debate. The aim of this review was to evaluate what support that could be found in the literature for extracting teeth in favour of implants, and to elucidate whether tooth-implant prostheses were inferior to solely implant supported constructions in terms of survival and complications. The methods for gathering relevant information entailed electronic searches on PubMed using relevant key words, as well as complementary manual searches in the retrieved publications. The results showed that there was no support for extracting teeth in favour of placing implants. On the contrary, the healthy tooth had a survival that was life-long, which is yet to be shown for the dental implant. Also the use of teeth as abutments in combination with dental implants for support of fixed dental prostheses could be endorsed in certain situations with solid albeit limited scientific support. in a wider sense, such prostheses could be used as a reliable therapy in all regions of the jaws. However the status of the abutment teeth in terms of periodontal support, pulpal status and risk for carious lesions and biomechanical complications should always be considered in relation to the long-term prognosis of the prosthesis. The conclusion was that teeth should not be extracted in favour of placing dental implants without a specific indication, and that tooth-implant supported prostheses should be considered as a viable prosthetic option.

  • 23. Miranda, LA
    et al.
    Fischer, RG
    Sztajnbok, FR
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Figueredo, CMS
    Gustafsson, A
    Increased interleukin-18 in patients with juvenile idiopathic arthritis and early attachment loss2005Ingår i: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 76, nr 1, 75-82 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Patients with juvenile idiopathic arthritis (JIA) have been shown to have incipient attachment loss (AL) more frequently than systemically healthy individuals. This study investigated neutrophil activity and proinflammatory cytokines in these patients and aged-matched controls. METHODS: Elastase activity, measured with a low molecular weight substrate (S-2484), and interleukin-1beta (IL-1beta), measured with the enzyme-linked immunosorbent assay (ELISA), were analyzed in the gingival fluid of 38 patients with JIA and 29 controls. IL-1beta and interleukin-18 (IL-18) were measured with ELISA in the serum of the same groups. Subgingival plaque was analyzed by DNA probes to detect 12 bacteria. RESULTS: Significantly elevated serum levels of IL-1beta and IL-18 were found in the JIA group. No differences were found in the gingival fluid levels of elastase and IL-1beta between groups, or in the frequency of subjects positive to most of the bacteria analyzed, except F. nucleatum, C. rectus, P. micros, and S. intermedius, which were significantly more frequent in the control group. When the JIA group was subdivided according to the presence/absence of AL, IL-18 was significantly increased in the JIA subgroup with AL compared to those without it. There were no differences in the subgingival microbiota between the subgroups. CONCLUSION: The findings of increased serum IL-18 and IL-1beta in patients with JIA accompanied by a similar subgingival microbiota suggest that the increased frequency of incipient attachment loss observed in these patients might be due to their altered systemic inflammatory response, making them more susceptible to periodontal disease.

  • 24.
    Palmqvist, Py
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Lundberg, Pernilla
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Lundgren, Inger
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Hänström, Lennart
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Lerner, Ulf
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    IL-1beta and TNF-alpha regulate IL-6-type cytokines in gingival fibroblasts.2008Ingår i: Journal of Dental Research, ISSN 0022-0345, E-ISSN 1544-0591, Vol. 87, nr 6, 558-563 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Interleukin-6 (IL-6)-type cytokines are pleiotropic molecules capable of stimulating bone resorption and expressed by numerous cell types. In the present study, we tested the hypothesis that gingival fibroblasts may exert local osteotropic effects through production of IL-6 and related cytokines. IL-6-type cytokine expression and regulation by IL-1beta and tumor necrosis factor-alpha (TNF-alpha) were studied in fibroblasts from the non-inflamed gingiva of healthy individuals. Constitutive mRNA expression of IL-6, IL-11, and leukemia inhibitory factor (LIF), but not of oncostatin M (OSM), was demonstrated, as was concentration-dependent stimulation of IL-6 and LIF mRNA and of protein by IL-1beta and TNF-alpha. IL-11 mRNA and protein were concentration-dependently stimulated by IL-1beta. The signaling pathway involved in IL-6 and LIF mRNA stimulation involved MAP kinases, but not NF-kappaB. The findings support the view that resident cells may influence the pathogenesis of periodontal disease through osteotropic IL-6-type cytokine production mediated by activation of MAP kinases. Abbreviations: IL-1alpha (interleukin-1alpha); IL-1beta (interleukin-1beta); IL-6 (interleukin-6); IL-11 (interleukin-11); LIF (leukemia inhibitory factor); OSM (oncostatin M); alpha(1)-coll. I (alpha(1)-collagen I); ALP (alkaline phosphatase); BMP-2 (bone morphogenetic protein-2); OC (osteocalcin); BSP (bone sialoprotein); TNFR I (tumor necrosis factor receptor I); TNFR II (tumor necrosis factor receptor II); IL-1R1 (interleukin-1 receptor 1); GAPDH (glyceraldehyde-3-phosphate dehydrogenase); RPL13A (ribosomal protein L13A); mRNA (messenger ribonucleic acid); cDNA (complementary deoxyribonucleic acid); PCR (polymerase chain-reaction); BCA (bicinchoninic acid); ELISA (enzyme-linked immunosorbent assay); alpha-MEM (alpha modification of Minimum Essential Medium); and FCS (fetal calf serum).

  • 25.
    Palmqvist, Py
    et al.
    Umeå universitet, Medicinsk fakultet, Odontologi, Kariologi.
    Lundberg, Pernilla
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Persson, Emma
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Johansson, Anders
    Umeå universitet, Medicinsk fakultet, Odontologi, Parodontologi.
    Lundgren, Inger
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Lie, Anita
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Conaway, HH
    Lerner, Ulf
    Umeå universitet, Medicinsk fakultet, Odontologi, Oral cellbiologi.
    Inhibition of hormone and cytokine-stimulated osteoclastogenesis and bone resorption by interleukin-4 and interleukin-13 is associated with increased osteoprotegerin and decreased RANKL and RANK in a STAT6-dependent pathway2006Ingår i: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 281, nr 5, 2414-2429 s.Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Interleukin (IL)-4 and IL-13 are cytokines that inhibit bone resorption. Data showing an inhibitory effect of IL-4 and IL-13 on RANK mRNA in mouse calvariae were first reported at the 22nd American Society for Bone and Mineral Research Meeting (Lerner, U.H., and Conaway, H. H. 2000) J. Bone Min. Res. 15, Suppl. 1, Abstr. SU 230). In the present study, release of 45Ca from cultured mouse calvarial bones stimulated by different cytokines, peptides, and steroid hormones was inhibited by IL-4 and IL-13. IL-4 and IL-13 decreased receptor activator of nuclear factor-kappaB ligand (RANKL) and RANK mRNA and increased osteoprotegerin (OPG) mRNA in calvariae. Additionally, the cytokines decreased RANKL protein and increased OPG protein in calvarial bones. In osteoblasts isolated from calvariae, both an increase in RANKL mRNA and a decrease in OPG mRNA and protein elicited by vitamin D3 were reversed by IL-4 and IL-13. IL-4 and IL-13 decreased the number of tartrate-resistant acid phosphatase positive multinucleated cells and the mRNA expression of calcitonin receptor, tartrate-resistant acid phosphatase, and cathepsin K in mouse spleen cells and bone marrow macrophages (BMM) treated with macrophage colony-stimulating factor and RANKL. Inhibition of mRNA for RANK and the transcription factor NFAT2 was also noted in spleen cell and BMM cultures treated with IL-4 and IL-13. In addition, RANK mRNA and RANK protein were decreased by IL-4 and IL-13 in RAW 264.7 cells. Osteoblasts, spleen cells, and BMM expressed mRNA for the four proteins making up the IL-4 and IL-13 receptors. No effects by IL-4 on bone resorption and osteoclast formation or on RANKL and RANK mRNA expression were seen in Stat6-/- mice. The data indicate that IL-4 and IL-13, via a STAT6-dependent pathway, inhibit osteoclast differentiation and bone resorption by activating receptors on osteoblasts and osteoclasts that affect the RANKL/RANK/OPG system.

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