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1.
  • Abrahamsson, Gun, 1947, et al. (author)
  • Ovarian cyst formation in women of reproductive age receiving mitotane as part of the treatment of adrenocortical carcinoma: Clinical and experimental observations
  • 2020
  • In: Acta Obstetricia Et Gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 99:10, s. 1297-1302
  • Journal article (peer-reviewed)abstract
    • Introduction Mitotane is an adrenolytic drug that is used as an adjuvant to treat adrenocortical carcinoma. This study aimed to evaluate the clinical course and pathogenetic mechanisms underlying ovarian cyst formation in women of reproductive age diagnosed with adrenocortical carcinoma and being treated with mitotane as an adjuvant to surgery. Material and methods Five women presented with stage III-IV adrenocortical carcinoma and ovarian cyst formation during mitotane treatment. The clinical course of the disease was followed during and after treatment. The effects of mitotane on progesterone production and cell proliferation were studied in cultured human ovarian granulosa cells. Results Computed tomography and vaginal ultrasonography during mitotane treatment repeatedly demonstrated ovarian cysts of varying size without solid intralocular structures. Two women became amenorrheic during the treatment period. After mitotane cessation, the ovarian cysts disappeared and normal menstrual cycles resumed. One woman had an uncomplicated pregnancy two years after mitotane treatment. In one woman, who underwent salpingo-oophorectomy, histological analysis demonstrated benign ovarian cysts. Mitotane impeded the synthesis of progesterone, reduced the stimulatory effect of gonadotropins on progesterone formation, and reduced labeling with [H-3]thymidine in cultured granulosa cells. Conclusions Therapeutic concentrations of mitotane are associated with the formation of benign ovarian cysts and amenorrhea. Mitotane-induced suppression of ovarian steroidogenesis and impediment of the proliferative capacity of steroid-producing cells are suggested potential pathogenetic mechanisms underlying mitotane-induced ovarian dysfunction and cyst development. Mitotane treatment does not compromise future ovarian function.
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2.
  • Akkoyunlu, Mustafa, et al. (author)
  • Biological activity of serum antibodies to a nonacylated form of lipoprotein D of Haemophilus influenzae
  • 1996
  • In: Infection and Immunity. - 1098-5522. ; 64:11, s. 4586-4592
  • Journal article (peer-reviewed)abstract
    • Protein D, a surface-exposed 42-kDa membrane lipoprotein, is well conserved among both type b and nontypeable Haemophilus influenzae strains, and it is considered a vaccine against H. influenzae infections. Here, we report the large-scale purification of a nonacylated form of protein D (PDm) from the periplasmic space of Escherichia coli overexpressing PDm. Screening of human sera for levels of antibodies to PDm demonstrated that the immunoglobulin G (IgG) antibody level is above background levels in infants less than 6 months of age. Following a drop to background values in the age group 6 months to 1 year, IgG antibody levels start to increase, together with IgA antibody levels, after 1 year of age. The first appearance of serum IgM antibodies is in 6-month- to 1-year-old infants whose IgG antibody levels have dropped to the postnatal background level. Affinity-purified antibodies from humans and from PDm-immunized rats detected epitopes of protein D which are normally exposed on the bacterial surface. Affinity-isolated human anti-PDm antibodies eluted in acidic buffer were not bactericidal against H. influenzae. Loss of bactericidal activity may occur in this buffer, as was demonstrated in pooled human sera with high bactericidal activity after incubation in the same buffer. Hyperimmunization of rats with PDm induced high levels of serum IgG and IgA antibodies against PDm and significant bactericidal activity against homologous and heterologous H. influenzae strains.
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3.
  • Alimohammadi, Mohammad, et al. (author)
  • Pulmonary Autoimmunity as a Feature of Autoimmune Polyendocrine Syndrome Type 1 and Identification of KCNRG as a Bronchial Autoantigen
  • 2009
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 106:11, s. 4396-4401
  • Journal article (peer-reviewed)abstract
    • Patients with autoimmune polyendocrine syndrome type 1 (APS-1) suffer from multiple organ-specific autoimmunity with autoantibodies against target tissue-specific autoantigens. Endocrine and nonendocrine organs such as skin, hair follicles, and liver are targeted by the immune system. Despite sporadic observations of pulmonary symptoms among APS-1 patients, an autoimmune mechanism for pulmonary involvement has not been elucidated. We report here on a subset of APS-1 patients with respiratory symptoms. Eight patients with pulmonary involvement were identified. Severe airway obstruction was found in 4 patients, leading to death in 2. Immunoscreening of a cDNA library using serum samples from a patient with APS-1 and obstructive respiratory symptoms identified a putative potassium channel regulator (KCNRG) as a pulmonary autoantigen. Reactivity to recombinant KCNRG was assessed in 110 APS-1 patients by using immunoprecipitation. Autoantibodies to KCNRG were present in 7 of the 8 patients with respiratory symptoms, but in only 1 of 102 APS-1 patients without respiratory symptoms. Expression of KCNRG messenger RNA and protein was found to be predominantly restricted to the epithelial cells of terminal bronchioles. Autoantibodies to KCNRG, a protein mainly expressed in bronchial epithelium, are strongly associated with pulmonary involvement in APS-1. These findings may facilitate the recognition, diagnosis, characterization, and understanding of the pulmonary manifestations of APS-1.
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4.
  • Dahlman, Disa, et al. (author)
  • High Perineal and Overall Frequency of Staphylococcus aureus in People Who Inject Drugs, Compared to Non-Injectors
  • 2017
  • In: Current Microbiology. - : Springer Science and Business Media LLC. - 0343-8651 .- 1432-0991. ; 74:2, s. 159-167
  • Journal article (peer-reviewed)abstract
    • To investigate the prevalence, distribution, and colonization burden of Staphylococcus aureus (S. aureus) and MRSA in different body sites among people who inject drugs (PWID) and compare it to a control group consisting of non-injectors. In this cross-sectional survey, 49 active PWID from the needle exchange program (NEP) in Malmö, Sweden, and 60 non-injecting controls from an emergency psychiatric inpatient ward at Malmö Addiction Centre were tested for S. aureus (including MRSA) by culture, PCR, and MALDI-TOF. Samples were taken from anterior nares, throat, perineum, and skin lesions if present. Sixty-seven percent of the PWID were colonized with S. aureus, compared to 50% of the controls (P = 0.08). Perineal carriage was significantly more frequent among PWID than in the control group [37 vs 17%, OR 2.96 (95% CI 1.13–7.75), P = 0.03], also after adjusting for sex and age in multivariate analysis [OR 4.01 (95% CI 1.34–12.03)]. Only one individual in the whole cohort (NEP participant) tested positive for MRSA. PWID may be more frequently colonized with S. aureus in the perineum than non-injection drug users, and there was a trend indicating more frequent overall S. aureus colonization in PWID, as well as higher perineal colonization burden. No indication of a high MRSA prevalence among PWID in Sweden was noted. However, further MRSA prevalence studies among PWID are needed. Knowledge about S. aureus colonization is important for the prevention of S. aureus infections with high morbidity in PWID.
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5.
  • Ekeblad, Sara, et al. (author)
  • Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors
  • 2007
  • In: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:10, s. 2986-2991
  • Journal article (peer-reviewed)abstract
    • Purpose: A retrospective analysis of the toxicity and efficacy of temozolomide in advanced neuroendocrine tumors. Experimental Design: Thirty-six patients with advanced stages of neuroendocrine tumor (1 gastric, 7 thymic and 13 bronchial carcinoids, 12 pancreatic endocrine tumors, 1 paraganglioma, 1 neuroendocrine foregut, and 1 neuroendocrine cecal cancer) were treated with temozolomide (200 mg/m2) for 5 days every 4 weeks. Patients had previously received a mean of 2.4 antitumoral medical regimens. Tumor response was evaluated radiologically according to the Response Evaluation Criteria in Solid Tumors every 3 months on an intent-to-treat basis. The circulating tumor marker plasma chromogranin A was also assessed. The expression of 06-methylguanine DNA methyltransferase, an enzyme implicated in chemotherapy resistance, was studied by immunohistochemistry (n = 23) and compared with response to temozolomide. Results: Median overall time to progression was 7 months (95% confidence interval, 3-10). Radiologic response was seen in 14% of patients and stable disease in 53%. Side effects were mainly hematologic; 14% experienced grade 3 or 4 thrombocytopenia (National Cancer Institute toxicity criteria). Ten patients had tumors with 06-methylguanine DNA methyltransferase immunoreactivity in <10% of nuclei, whereas four patients showed radiologic responses. Conclusions: Temozolomide as monotherapy had acceptable toxicity and antitumoral effects in a small series of patients with advanced malignant neuroendocrine tumors and four of these showed radiologic responses.
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6.
  • Fagevik Olsén, Monika, 1964, et al. (author)
  • A comparison of high- versus low-intensity, high-frequency transcutaneous electric nerve stimulation for painful postpartum uterine contractions
  • 2007
  • In: Acta obstetricia et gynecologica Scandinavica. - : Wiley. - 0001-6349 .- 1600-0412. ; 86:3, s. 310-4
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Breast-feeding in the postpartum period is known to induce intense uterine contractions with pain in the lower abdomen. AIMS: The primary aim of this study was to compare the effects of high and low intensity, high frequency Transcutaneous Electric Nerve Stimulation (TENS) on pain and discomfort of postpartum uterine contractions. The secondary aim was to evaluate discomfort experienced from the stimulation itself. METHODS: Twenty-one newly delivered women participated in this single-blind trial, 12 women received high intensity, high-frequency TENS (HI TENS) and 9 women received low intensity, high-frequency TENS (LI TENS). The electrodes were placed abdominally on each side of the uterus. Stimulation was done during one minute. Visual analogue scales were used to evaluate the intensity of the pain before and after stimulation. A verbal scale was used to estimate sensation of discomfort before, during and after stimulation. RESULTS: The median decrease in pain ratings before and after treatment by VAS was larger in the HI TENS group -49 mm (95% CI -66.5--33.2) than in the LI TENS group -21 mm (95% CI -39.0--20.0). The reduction of pain was most pronounced in the HI TENS group (median difference 28 (95% CI was 14.0-53.0). Furthermore, the HI TENS group experienced significantly less discomfort of the uterine contractions after stimulation (p<0.01) but they also experienced more discomfort of the stimulation than women in the LI TENS group (p<0.01). CONCLUSION: The women treated with HI TENS, experienced significantly less postpartum pain and discomfort to those treated with LI TENS even though the discomfort from the stimulation with HI TENS was greater.
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7.
  • Forsgren, Arne, et al. (author)
  • Isolation and characterization of a novel IgD-binding protein from Moraxella catarrhalis
  • 2001
  • In: Journal of Immunology. - 1550-6606. ; 167:4, s. 2112-2120
  • Journal article (peer-reviewed)abstract
    • A novel surface protein of the bacterial species Moraxella catarrhalis that displays a high affinity for IgD (MID) was solubilized in Empigen and isolated by ion exchange chromatography and gel filtration. The apparent molecular mass of monomeric MID was estimated to approximately 200 kDa by SDS-PAGE. The mid gene was cloned and expressed in Escherichia coli. The complete mid nucleotide gene sequence was determined, and the deduced amino acid sequence consists of 2123 residues. The sequence of MID has no similarity to other Ig-binding proteins and differs from all previously described outer membrane proteins of M. catarrhalis. MID was found to exhibit unique Ig-binding properties. Thus, in ELISA, dot blots, and Western blots, MID bound two purified IgD myeloma proteins, four IgD myeloma sera, and finally one IgD standard serum. No binding of MID was detected to IgG, IgM, IgA, or IgE myeloma proteins. MID also bound to the surface-expressed B cell receptor IgD, but not to other membrane molecules on human PBLs. This novel Ig-binding reagent promises to be of theoretical and practical interest in immunological research.
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8.
  • Forsgren, Arne, et al. (author)
  • Protein D of Haemophilus influenzae: a protective nontypeable H. influenzae antigen and a carrier for pneumococcal conjugate vaccines.
  • 2008
  • In: Clinical Infectious Diseases. - : Oxford University Press (OUP). - 1537-6591 .- 1058-4838. ; 46:5, s. 726-731
  • Research review (peer-reviewed)abstract
    • Protein D (PD) is a highly conserved 42 kDa surface lipoprotein found in all Haemophilus influenzae, including nontypeable (NT) H. influenzae. PD is involved in the pathogenesis of respiratory tract infections, in the context of which it has been shown to impair ciliary function in a human nasopharyngeal tissue culture model and to augment the capacity to cause otitis media in rats. A likely mechanism indicating that PD is a virulence factor is its glycerophosphodiesterase activity, which leads to the release of phosphorylcholine from host epithelial cells. PD has been demonstrated to be a promising vaccine candidate against experimental NT H. influenzae infection. Rats vaccinated with PD cleared NT H. influenzae better after middle ear and pulmonary bacterial challenge, and chinchillas vaccinated with PD showed significant protection against NT H. influenzae-dependent acute otitis media. In a clinical trial involving children, PD was used as an antigenically active carrier protein in an 11-valent pneumococcal conjugate investigational vaccine; significant protection was achieved against acute otitis media not only caused by pneumococci but also caused by NT H. influenzae. This may have great clinical implications, because PD is the first NT H. influenzae antigen that has induced protective responses in humans.
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9.
  • Fowler, Lee, et al. (author)
  • Antibacterial investigation of titanium-copper alloys using luminescent Staphylococcus epidermidis in a direct contact test
  • 2019
  • In: Materials science & engineering. C, biomimetic materials, sensors and systems. - : ELSEVIER SCIENCE BV. - 0928-4931 .- 1873-0191. ; 97, s. 707-714
  • Journal article (peer-reviewed)abstract
    • Commercially pure titanium (CP-Ti), used as oral implants, is often populated by various bacterial colonies in the oral cavity. These bacteria can cause Peri-implantitis, leading to loss of bone tissue and failure of implants. With the increased awareness of antibiotic resistance, research has been directed towards alternative solutions and recent findings have indicated titanium-copper (Ti-Cu) alloys as a promising antibacterial material. The aim of this study was to produce homogeneous Ti-Cu alloys, with various concentrations of copper, and to characterise their antibacterial properties through direct contact tests, using luminescent bacteria, in addition to traditional materials characterisation techniques. Samples of CP-Ti and four different Ti-Cu alloys (1, 2.5, 3 and 10 wt%Cu) were produced in an arc-furnace, heated treated and rapidly quenched. X-ray diffraction revealed that Ti2Cu, was present only in the 10 wt%Cu alloy, however, scanning electron microscopy (SEM) indicated precipitates at the grain boundaries of the 3 wt%Cu alloy, which were confirmed to be of a copper rich phase by energy dispersive x-ray spectroscopy (EDS) analysis. EDS line scans confirmed that the alloys were homogenous. After 6 h, a trend between copper content and antibacterial rate could be observed, with the 10 wt%Cu alloy having the highest rate. SEM confirmed fewer bacteria on the 3 wt%Cu and especially the 10 wt%Cu samples. Although the 10 wt%Cu alloy gave the best antibacterial results, it is desired that the Cu concentration is below similar to 3 wt%Cu to maintain similar mechanical and corrosive performance as CP-Ti. Therefore, it is proposed that future work focuses on the 3 wt%Cu alloy.
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11.
  • Hulsart Billström, Gry, 1982-, et al. (author)
  • Thromboinflammation as bioactivity assessment of H2O2-alkali modified titanium surfaces
  • 2019
  • In: Journal of materials science. Materials in medicine. - : Springer Science and Business Media LLC. - 0957-4530 .- 1573-4838. ; 30:6
  • Journal article (peer-reviewed)abstract
    • The release of growth factors from platelets, mediated by the coagulation and the complement system, plays an important role in the bone formation around implants. This study aimed at exploring the thromboinflammatory response of H2O2-alkali soaked commercially pure titanium grade 2 discs exposed to whole human blood, as a way to assess the bioactivity of the discs. Commercially pure titanium grade 2 discs were modified by soaking in H2O2, NaOH and Ca(OH)2. The platelet aggregation, coagulation activation and complement activation was assessed by exposing the discs to fresh whole blood from human donors. The platelet aggregation was examined by a cell counter and the coagulation and complement activation were assessed by ELISA-measurements of the concentration of thrombin-antithrombin complex, C3a and terminal complement complex. The modified surface showed a statistically significant increased platelet aggregation, coagulation activation and complement activation compared to unexposed blood. The surface also showed a statistically significant increase of coagulation activation compared to PVC. The results of this study showed that the H2O2-alkali soaked surfaces induced a thromboinflammatory response that indicates that the surfaces are bioactive.
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12.
  • Janson, Håkan, et al. (author)
  • Effects on the ciliated epithelium of protein D-producing and -nonproducing nontypeable Haemophilus influenzae in nasopharyngeal tissue cultures
  • 1999
  • In: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 180:3, s. 737-746
  • Journal article (peer-reviewed)abstract
    • A pair of isogenic, nontypeable Haemophilus influenzae strains, one expressing protein D and the other protein D-negative, was compared in their ability to cause damage in a human nasopharyngeal tissue culture model. Damage was assessed by measuring the ciliary beat frequency (CBF) of tissue specimens at 12 h intervals. Cultures inoculated with H. influenzae manifested a decrease in CBF beginning after 12 h, with a maximum decrease after 36 h. The impairment of ciliary function by the protein D-expressing strain was significantly greater than that caused by the protein D-negative mutant (P<.01). Tissue specimens examined by scanning and transmission electron microscopy after 24 h appeared normal. After 48 h of incubation, the protein D-expressing strain caused a significant loss of cilia. These findings suggest that protein D is involved in the pathogenesis of upper respiratory tract infections due to nontypeable H. influenzae, probably by enhancing functional and morphological damage to cilia.
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13.
  • Janson, Håkan, et al. (author)
  • Limited diversity of the protein D gene (hpd) among encapsulated and nonencapsulated Haemophilus influenzae strains
  • 1993
  • In: Infection and Immunity. - 1098-5522. ; 61:11, s. 4546-4552
  • Journal article (peer-reviewed)abstract
    • Protein D is a surface-exposed lipoprotein of the gram-negative bacterium Haemophilus influenzae with affinity for human immunoglobulin D myeloma protein. The gene encoding protein D (hpd) in a serotype b strain of H. influenzae was cloned. Escherichia coli carrying the hpd gene bound human myeloma immunoglobulin D. Nucleotide sequence analysis identified an 1,092-bp open reading frame that was more than 99% identical to the hpd gene from a nontypeable H. influenzae strain. In the deduced amino acid sequences for protein D, only 2 of 364 amino acid residues differed. The restriction fragment length polymorphism of the hpd region in different strains was analyzed by Southern blot analyses of PstI- or EcoRI-digested genomic DNA from 100 H. influenzae strains. The analysis was performed by using isolated fragments of the cloned hpd gene, originating from the nontypeable H. influenzae 772, as probes. All strains tested had DNA sequences with a high degree of homology to the hpd probes. The analysis also showed that restriction endonuclease sites within the gene were more conserved than sites adjacent to the hpd gene. An interesting difference between type b strains and unencapsulated strains was observed. The majority of type b strains seem to have a 1.4-kbp DNA fragment upstream of the hpd gene that is absent in nontypeable strains. On the basis of the high degree of conservation of the hpd gene among H. influenzae strains, we conclude that protein D is a possible vaccine candidate.
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14.
  • Janson, Harald, et al. (author)
  • Prediction of adolescent and adult delinquency from childhood Rorschach ratings
  • 2003
  • In: Journal of Personality Assessment. - : Lawrence Erlbaum. - 0022-3891 .- 1532-7752. ; 81:1, s. 51-63
  • Journal article (peer-reviewed)abstract
    • Relatively few studies have predicted adolescent or adult delinquency from childhood Rorschach data. Incremental validity of Rorschach measures over other known consistent and more easily obtained predictors has typically not been investigated. We addressed Rorschach data's incremental validity over mother's reports of externalizing behavior and mother-child relations for predicting officially registered adolescent and adult delinquency in a longitudinal study of 122 Swedish men. The Rorschach measures we used were aggregates of blind, prospectively performed, global expert ratings based on a holistic evaluation of protocols. An aggregate of Rorschach-based ratings of ego strength significantly improved the prediction of delinquency in adolescence and adulthood over and above earlier identified best predictors (mother's ratings of mother-child relations and externalizing problem behavior).  
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15.
  • Janson, Håkan, et al. (author)
  • Protein D, an immunoglobulin D-binding protein of Haemophilus influenzae: cloning, nucleotide sequence, and expression in Escherichia coli
  • 1991
  • In: Infection and Immunity. - 1098-5522. ; 59:1, s. 119-125
  • Journal article (peer-reviewed)abstract
    • The gene for protein D, a membrane-associated protein with specific affinity for human immunoglobulin D, was cloned from a nontypeable strain of Haemophilus influenzae. The gene was expressed in Escherichia coli from an endogenous promoter, and the gene product has an apparent molecular weight equal to that of H. influenzae protein D (42,000). The complete nucleotide sequence of the gene for protein D was determined, and the deduced amino acid sequence of 364 residues includes a putative signal sequence of 18 amino acids containing a consensus sequence, Leu-Ala-Gly-Cys, for bacterial lipoproteins. The sequence of protein D shows no similarity to those of other immunoglobulin-binding proteins. Protein D is the first example of immunoglobulin receptors from gram-negative bacteria that has been cloned and sequenced.
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16.
  • Janson, Håkan, et al. (author)
  • Protein D, the glycerophosphodiester phosphodiesterase from Haemophilus influenzae with affinity for human immunoglobulin D, influences virulence in a rat otitis model
  • 1994
  • In: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 62:11, s. 4848-4854
  • Journal article (peer-reviewed)abstract
    • A mutant lacking the ability to express the surface-exposed lipoprotein protein D was constructed by linker insertion and deletion mutagenesis of a cloned DNA insert containing the protein D structural gene from a nontypeable Haemophilus influenzae strain (NTHi). An isogenic NTHi mutant was isolated after transformation of genetically competent bacteria. The transformant was unreactive to a protein D-specific monoclonal antibody in a colony immunoassay. In addition, the mutant lacked the ability to synthesize detectable levels of protein D by protein staining, immunoblot methods, glycerophosphodiester phosphodiesterase activity, and binding studies of radiolabelled immunoglobulin D. The isogenic protein D-deficient mutant was compared with its parental strain for its ability to induce experimental otitis media in rats challenged with bacteria. An approximately 100-times-higher concentration of the mutant compared with that of the wild-type strain was required in order to cause otitis among all rats challenged with that given dose. The protein D mutant exhibited a generation time that was equal to that of the wild-type strain in complex broth medium. No difference in lipopolysaccharide expression was found between the mutant and the parental strain. These results suggest that protein D may influence the pathogenesis of NTHi in the upper respiratory tract.
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17.
  • Janson, Håkan, et al. (author)
  • Protein D, the immunoglobulin D-binding protein of Haemophilus influenzae, is a lipoprotein
  • 1992
  • In: Infection and Immunity. - 1098-5522. ; 60:4, s. 1336-1342
  • Journal article (peer-reviewed)abstract
    • Protein D is an immunoglobulin D-binding membrane protein exposed on the surface of the gram-negative bacterium Haemophilus influenzae. Results reported here indicate that protein D is a lipoprotein. The protein is apparently synthesized as a precursor with an 18-residue-long signal sequence modified by the covalent attachment of both ester-linked and amide-linked palmitate to the cysteine residue, which becomes the amino terminus after cleavage of the signal sequence. Globomycin inhibited maturation of protein D in H. influenzae, implying that protein D is exported through the lipoprotein export pathway. A mutant expressing a protein D lacking the cysteine residue was constructed by oligonucleotide site-directed mutagenesis. The mutated protein D molecule was not acylated and partitioned in the aqueous phase after Triton X-114 extraction of intact bacteria, unlike native and recombinant protein D, which partitioned in the detergent phase. The nonacylated protein D molecule was localized to the periplasmic space of Escherichia coli. The hydrophilic protein D molecule will be used in investigations concerning its ability to function as a vaccine component.
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20.
  • Janson, Oscar, et al. (author)
  • Debridement of Bacterial Biofilms with TiO2/H2O2 Solutions and Visible Light Irradiation
  • 2018
  • In: International Journal of Biomaterials. - : Hindawi Publishing Corporation. - 1687-8787 .- 1687-8795. ; 2018
  • Journal article (peer-reviewed)abstract
    • Objectives. The aim of the study was to explore the debridement efficacy of different solutions of H2O2 and rutile particles against Staphylococcus epidermidis and Pseudomonas aeruginosa biofilms attached to titanium surfaces when exposed to visible light. Materials and Methods. Titanium discs cultivated with biofilms of Staphylococcus epidermidis or Pseudomonas aeruginosa were subjected for 1 min to suspensions consisting of rutile particles mixed with high (950 mM) or low (2 mM) concentrations of H2O2 under visible light irradiation (405 nm; 2.1 mW/cm2). Discs were rinsed and the degree of debridement was determined through scanning electron microscopy and viability assessment of the remaining bacteria using luminescence measurements and/or a metabolic activity assay. Results. Cleaning mixtures containing the higher concentration of H2O2 showed a significantly improved debridement compared to the negative control in all experiments. The addition of rutile particles was shown to have a statistically significant effect in one test with S. epidermidis. Limited evidence of the catalytic effect of visible light irradiation was seen, but effects were relatively small and statistically insignificant. Conclusions. H2O2 at a concentration of 950 mM proved to be the strongest contribution to the debridement and bactericidal effect of the cleaning techniques tested in this study.
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24.
  • Janson, Oscar, et al. (author)
  • Evaluation of an alkali-treated and hydroxyapatite-coated orthopedic implant loaded with tobramycin
  • 2019
  • In: Journal of biomaterials applications. - : SAGE Publications. - 0885-3282 .- 1530-8022. ; 34:5, s. 699-720
  • Journal article (peer-reviewed)abstract
    • An approximately 1-µm thick hydroxyapatite coating was biomimetically deposited on an alkali-treated, commercially available orthopedic screw surface (type II anodized titanium). Tobramycin loaded into the coating via a simple soaking method was shown to provide a sustained release above the minimal inhibitory concentration 0.2 µg/µl for up to two days. Agar diffusion tests showed that the tobramycin-loaded coating was able to produce a zone of inhibition against Staphylococcus aureus for up to five days. Biocompatibility testing using outgrowth endothelial cells and primary osteoblasts suggested that good cell compatibility of the coating can be expected in vivo. A rabbit distal femur condyle model was used for in vivo evaluation of the antibacterial efficacy of the tobramycin-loaded coating, and this pilot study showed that the release of tobramycin was sufficient to locally eliminate very large amounts of bacteria in vivo (inoculation dose 104–105 CFU S. aureus/test site).
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25.
  • Janson, Oscar, et al. (author)
  • Modification of titanium surfaces to enhance bacteriostatic properties
  • 2016
  • Conference paper (peer-reviewed)abstract
    • Introduction: Infections caused by bacterial biofilm on dental implants affect a considerable amount of patients. Anodic oxidation and physical vapor deposition are current methods in modifying the surface of implants in order to make them more resistant to bacterial biofilm formation[1]. An easier and economically attractive method is soaking the surface in hydrogen peroxide (H2O2), sodium hydroxide (NaOH) and calcium dihyroxide (Ca(OH)2). This method is hypothesized to not only provide antibacterial activity, but also preserve the bioactive properties and biocompatibility of the surface. The aim of this study was to determine which surface treatment provides the best antibacterial effect, as well as examine if the addition of calcium ions results in additional bioactivity.Method: Discs of grade 2 Ti were punched into circular coins with diameter 9 mm and 1 mm thickness. The coins were sequentially sonicated for 15 min in acetone, ethanol and dH2O, before being immersed in H2O2 for 1 h at 90 °C. Subsequently the coins were soaked in NaOH for 15 min. The coins were divided in six test groups where three groups were further soaked in Ca(OH)2 for 15 min and then either heated at 200 °C for 1 h (Ti200_Ca), autoclaved at 125°C for 1 h (TiAuto_Ca), or simply kept at room temperature for 1 h (Ti25_Ca). The remaining three groups received the same final heat treatment, but without the soaking in Ca(OH)2 (Ti200 TiAuto and Ti25, respectively). The coins were then immersed in Dulbecco’s PBS enriched with Ca2+- and Mg2+-ions in an incubator at 37 °C for 7 days. The coin surfaces were examined for hydroxyapatite (HA) in a LEO 1550 scanning electron microscope.The coins were checked for H2O2 release by studying the degradation of the organic dye rhodamine B.Two cell lines; MC3T3 murine preosteoblasts and human dermal fibroblasts (hDF) were seeded onto the coins. Cell viability was measured after 3 days using the Alamar Blue assay.Results: The test groups soaked in Ca(OH)2 showed a higher degree of HA formation compared to the test groups not soaked in Ca(OH)2, see Fig. 1. Treatment in room temperature showed better HA formation than 200 °C and autoclaving. The rhodamine B degradation test showed that the test groups Ti200_Ca, TiAuto_Ca, Ti25 and Ti200 showed approximately 30 % degradation after 7 days (Fig. 2). The hDF cells had no observed changes in cell viability as compared to the control after 3 days. The MC3T3s, however, had greater proliferation on the modified coins, compared to the unmodified Ti (Fig. 3).  Discussion and conclusions: Calcium ion addition increased the bioactivity, providing more available sites for phosphate to bind to calcium. Preliminary tests with rhodamine B suggest an antibacterial activity of the modified surfaces. Future studies will be conducted to further investigate this potential effect with bacteria. VinnovaReferences:[1] LIU, X., CHU, P., & DING, C. (2004). Surface modification of titanium, titanium alloys, and related materials for biomedical applications. Materials Science and Engineering: R: Reports, 47(3-4), 49–121. doi:10.1016/j.mser.2004.11.001
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26.
  • Janson, Oscar, et al. (author)
  • Organic degradation potential of a TiO2/H2O2/UV-Vis system for dental applications
  • 2017
  • In: Journal of Dentistry. - : Elsevier BV. - 0300-5712 .- 1879-176X. ; 67, s. 53-57
  • Journal article (peer-reviewed)abstract
    • ObjectivesThe combination of TiO2 and H2O2 under light activation constitutes a promising method for disinfection of dental prosthetics and implants, due to production of reactive oxygen species (ROS). The aim of this work was to investigate the organic degradation ability of TiO2 particles in combination with H2O2 and under light activation utilizing the organic dye rhodamine B (RhB).MethodsFive different types of TiO2 particles, consisting of anatase, rutile, or a mixture of these crystalline phases, were combined with H2O2 and RhB, and subsequently exposed to UV (365 nm) or visible (405 nm) light at an irradiance of 2.1 mW/cm2.ResultsIt was found that rutile in combination with low concentrations of H2O2 (1.0–3.5 mM) resulted in a degradation of RhB of 96% and 77% after 10 min exposure to 365 nm and 405 nm light, respectively, which was the highest degradation of all test groups. Control measurements performed without light irradiation or irradiation at 470 nm, or without TiO2 particles resulted in little or no degradation of RhB.ConclusionsLow H2O2 concentrations (1.0 mM–3.5 mM) and visible light (405 nm) used in combination with rutile TiO2 particles showed the highest RhB degradation capacity.Clinical significanceA combination of TiO2 particles and H2O2 exposed to low energy UV or high energy visible light has an organic degradation capability that could be utilized in applications to kill or inactivate bacteria on medical devices such as dental implants for treatment against, e.g., peri-implantitis.
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27.
  • Janson, Oscar, et al. (author)
  • Titanium surface modification leading to increased antibacterial ability, bioactivity and biocompatibility
  • 2016
  • Conference paper (peer-reviewed)abstract
    • IntroductionBacterial biofilms can adhere to implants, and may ultimately lead to implant failure. One way to prevent bacterial biofilm formation is to modify the surface to make it antibacterial or bacteriostatic. A straightforward and economically attractive modification method is to soak the surface in hydrogen peroxide, sodium hydroxide and calcium dihyroxide. Hydrogen peroxide has been found to make the surface anti-inflammatory[1] and perhaps antibacterial. Sodium hydroxide has been seen to render the surface bioactive[2], while calcium hydroxide might further increase the bioactivity. In this study we investigated the antibacterial properties, bioactivity and biocompatibility of this surface modification method. MethodsCoupons of cpTi (grade 2) were immersed in H2O2 for 1 h at 80 °C and then soaked in NaOH. Some test groups were also soaked in Ca(OH)2. After soaking, coupons were heat treated at 200 °C, autoclaved at 125 °C for 1 h or simply kept at room temperature. To investigate bioactivity the coupons were immersed in SBF for 7 days. Biocompatibility was assessed by seeding two cell lines on the modified titanium surfaces. To investigate the antibacterial effect, bacterial biofilms were grown on the surfaces for 16 h and assessed for viability with luminescence readings. ResultsCa(OH)2 modified coupons showed an increased bioactivity compared to coupons only soaked in NaOH. Hydroxyapatite formation was strongest for test groups placed in room temperature or 200 °C. Cell proliferation was increased with human dermal fibroblast. Autoclaved surfaces showed a decreased luminescence signal compared to the control, indicating inhibition of bacterial biofilm. ConclusionsCoupons soaked in Ca(OH)2 after soaking in NaOH showed increased bioactivity compared to coupons only soaked in NaOH. Further they exhibit excellent biocompatibility and some degree of antibacterial behavior.  [1]       P. Tengvall, I. Lundström, L. Sjöqvist, H. Elwing, L.M. Bjursten, Biomaterials 10 (1989) 166.[2]       X. LIU, P. CHU, C. DING, Materials Science and Engineering: R: Reports 47 (2004) 49.
  •  
28.
  • Janson, Oscar, et al. (author)
  • Titanium surface modification to enhance antibacterial and bioactive properties while retaining biocompatibility
  • 2019
  • In: Materials science & engineering. C, biomimetic materials, sensors and systems. - : Elsevier BV. - 0928-4931 .- 1873-0191. ; 96, s. 272-279
  • Journal article (peer-reviewed)abstract
    • Bacterial infections associated with metal implants are severe problems affecting a considerable amount of people with dental or orthopedic implants. This study aims to examine the antibacterial effect of a Titanium-peroxy gel layer on the modified surface of commercially pure titanium grade 2. Variations in a multi-step surface modification procedure were tested to determine the best combination that provided an antibacterial effect while enhancing bioactivity without compromising biocompatibility. Soaking the surfaces in 30 wt% hydrogen peroxide held at 80 °C provided antibacterial activity while subsequent surface treatments in concentrated sodium and calcium hydroxide solutions were preformed to enhance bioactivity. Staphylococcus epidermidis was used to determine the antibacterial effect through both direct contact and biofilm inhibition tests while human dermal fibroblast cells and MC3T3 pre osteoblast cells were utilized to test biocompatibility. The greatest antibacterial effect was observed with only hydrogen peroxide treatment, but the resulting surface was neither bioactive nor biocompatible. It was found that subsequent surface treatments with sodium hydroxide followed by calcium hydroxide provided a bioactive surface that was also biocompatible. Additionally, a final treatment with autoclaving showed positive effects with regards to enhanced bioactivity. This multi-step surface modification procedure offers a promising, non-antibiotic, solution for combatting infections associated with biomedical implants.
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29.
  • Janson, Per-Olof, 1940, et al. (author)
  • Acromegaly and Cushing's syndrome due to ectopic production of GHRH and ACTH by a thymic carcinoid tumour: in vitro responses to GHRH and GHRP-6.
  • 1998
  • In: Clinical endocrinology. - 0300-0664. ; 48:2, s. 243-50
  • Journal article (peer-reviewed)abstract
    • A 50-year-old male presented with diabetes mellitus and Cushing's syndrome associated with a large mediastinal mass. The levels of serum cortisol were high (1500-1800 nmol/l) without diurnal variation. Plasma ACTH levels (200-250 ng/l) and urinary excretion of cortisol were also increased. The levels of these hormones did not change in response to stimulation with corticotrophin releasing hormone (CRH) or suppression with high doses of dexamethasone. The patient had an elevated baseline GH level (7.3 mU/l), and the levels of immunoreactive GH-releasing hormone (GHRH) in eight plasma samples were markedly increased (600-1500 ng/l). Circulating levels of IGF-1, chromogranin A and neuropeptide Y (NPY) were also increased. Computer-assisted tomography and octreotide scintigraphy revealed a large mediastinal tumour and metastases in the left supraclavicular fossa. During treatment with octreotide, the baseline GH level was decreased (to 4.4 mU/l), while the GH pulse height was unchanged. Surgical removal of most of the tumour tissue resulted in a further decrease in the baseline serum GH level to a value (1.6 mU/l) about 20% of that before treatment, while the pulse height and mean GH were affected to a lesser extent. Postoperatively, circulating levels of cortisol and IGF-1 decreased, and the patient exhibited clinical improvement. Histological examination showed a neuroendocrine tumour with characteristics consistent with a foregut carcinoid of thymic origin. Immunoreactive GHRH, ACTH and NPY, but not immunoreactive GH, were detected in 80-90% of the tumour cells and the three peptides appeared to be co-localized. In primary culture, cells from this tumour displayed calcium influx in response to GHRH or GH releasing peptide-6 (GHRP-6), while there were not such responses by cells from another carcinoid not producing GHRH, ACTH or NPY. These results demonstrate a rare case of ectopic production of GHRH, ACTH and NPY, and indicate that the tumour cells were responsive to GHRH and GHRP-6 as well as octreotide.
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30.
  • Janson, Sven, et al. (author)
  • Population genetic structure of crucian carp (Carassius carassius) in man-made ponds and wild populations in Sweden
  • 2015
  • In: Aquaculture International. - : Springer Science and Business Media LLC. - 0967-6120 .- 1573-143X. ; 23:1, s. 359-368
  • Journal article (other academic/artistic)abstract
    • Although once popular prior to the last century, the aquaculture of crucian carp Carassius carassius (L. 1758) in Sweden gradually fell from favour. This is the first genetic comparison of crucian carp from historic man-made ponds in the Scandinavian Peninsula. The aim was to identify old populations without admixture and to compare the relationship of pond populations from different provinces in Sweden. In total, nine microsatellite loci from 234 individuals from 20 locations in varied parts of Sweden were analysed. The genetic distances of crucian carp populations indicated that the populations in the southernmost province of Sweden, Scania, shared a common history. A pond population in the province Småland also showed a common inheritance with this group. In the province Uppland, further north in Sweden, the population genetic distances suggested a much more complex history of crucian carp distributions in the ponds. The data showed that there are some ponds with potentially old populations without admixture, but also that several ponds might have been stocked with fish from many sources.
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31.
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32.
  • Jörgensen, Jimmy, et al. (author)
  • Staphylococcus aureus carriage and prevalence of skin and soft tissue infections among people who inject drugs : a longitudinal study
  • 2024
  • In: Scientific Reports. - 2045-2322. ; 14:1
  • Journal article (peer-reviewed)abstract
    • People who inject drugs are frequently colonized with Staphylococcus aureus and have an increased risk for skin and soft tissue infections. This longitudinal study aims to describe S. aureus carriage in this group and the risk for infections during a 1-year follow-up. We included 61 participants from the Malmö Needle Exchange Program. Mapping of S. aureus carriage was conducted by screening cultures every third month and S. aureus growth was semi-quantified. Data regarding infections and living conditions were collected from structured interviews. Statistics included univariate analysis with the Fischer’s exact test, univariate logistic regression and multivariate logistic regression. S. aureus carriage was detected in 46–63% of participants, and 75% reported one or more infections during the study period. Self-reported infections were associated with carriage in perineum (OR 5.08 [95% CI 1.45–17.73]), in skin lesions (OR 1.48 [95% CI 1.21–1.81]), and unstable housing situation (OR 12.83 [95% CI 1.56–105.81]). Thus, people who inject drugs are frequent carriers of S. aureus and report a surprisingly high prevalence of skin and soft tissue infections. Homeless people and those with skin carriage seem to be at highest risk. Effective clinical interventions are needed, aiming at preventing infections in this vulnerable group.
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33.
  • Jörgensen, Jimmy, et al. (author)
  • The majority of MRSA colonized children not given eradication treatment are still colonized one year later. Systemic antibiotics improve the eradication rate
  • 2018
  • In: Infectious Diseases. - : Informa UK Limited. - 2374-4235 .- 2374-4243. ; 50:9, s. 687-696
  • Journal article (peer-reviewed)abstract
    • Background: Colonization with methicillin-resistant Staphylococcus aureus (MRSA) can cause endogenously derived infections and be a source of transmission to other people. Neither colonization time of asymptomatic MRSA colonization nor the effect of treatment aiming at MRSA eradication in children has been thoroughly investigated. Methods: Two hundred ninety-three children <18 years in the mandatory follow-up program for MRSA-carriers in Malmö, Sweden were evaluated. Samples from the throat, nares, perineum and skin lesions from each child were screened for MRSA with a PCR-based broth enrichment method. PVL presence and spa-type were evaluated in a majority of cases. The sampling was repeated approximately every 6 month after initial detection. When three consecutive sets of negative samples during at least a 6-month period were obtained, the MRSA was considered permanently eradicated. MRSA eradication treatment given, on clinical grounds during follow-up, was noted. Results: One year after detection 62% of the untreated children were still MRSA positive and after 2 years 28%. MRSA throat colonization and having MRSA positive household contacts significantly prolonged the observed colonization time. Topical MRSA eradication treatment was successful in 36% of cases and in 65% if systemic antibiotics were added. Presence of PVL correlated with shorter observed colonization time in the older age group and with increased eradication success among throat carriers. Conclusion: MRSA throat colonization and having MRSA positive household contacts prolongs the time of MRSA colonization in children. Systemic antibiotics enhance the effect of MRSA eradication treatment.
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34.
  •  
35.
  • Lazou Ahrén, Irini, et al. (author)
  • Protein D expression promotes the adherence and internalization of non-typeable Haemophilus influenzae into human monocytic cells
  • 2001
  • In: Microbial Pathogenesis. - : Elsevier BV. - 1096-1208 .- 0882-4010. ; 31:3, s. 151-158
  • Journal article (peer-reviewed)abstract
    • Protein D, having a glycerol-3-phosphodiester phosphodiesterase activity, is found at the surface of all Haemophilus influenzae strains and is a possible virulence factor. In the present study, the involvement of protein D in the entry of NTHi into human monocytic cells is reported. Primary monocytes and the monocytic cell lines U-937 and THP-1 were infected with NTHi strain 772 and the mutant 772 Delta hpd 1 (lacking the gene for protein D). NTHi 772 adhered to and entered monocytic cells up to four-fold more efficiently compared to 772 Delta hpd 1. When an Escherichia coli transformant expressing protein D was incubated with monocytic cells, the number of intracellular bacteria increased 1.6-fold compared to protein D-deficient controls. Any correlation between internalization and phosphorylcholine expression was not detected. In conclusion, our data suggest that surface-expressed protein D promotes the adherence of NTHi to human monocytes leading to a higher number of internalized bacteria.
  •  
36.
  • Melhus, Åsa, et al. (author)
  • Amoxicillin treatment of experimental acute otitis media caused by Haemophilus influenzae with non-beta-lactamase-mediated resistance to beta-lactams : aspects of virulence and treatment
  • 1997
  • In: Antimicrobial Agents and Chemotherapy. - 0066-4804 .- 1098-6596. ; 41:9, s. 1979-1984
  • Journal article (peer-reviewed)abstract
    • Through alterations primarily in the penicillin-binding proteins, a non-beta-lactamase-mediated resistance to beta-lactams has evolved in Haemophilus influenzae. The virulence of these chromosomally changed strains has been questioned. To ascertain whether these alterations involve a reduction in virulence of H. influenzae and whether they could be advantageous for the bacterium during amoxicillin treatment of acute otitis media, a total of 70 Sprague-Dawley rats were challenged with a susceptible recipient strain or a genetically similar resistant transformant strain. Antibiotic therapy was started on day 3 after inoculation, and the animals were monitored by daily otomicroscopy and analysis of bacterial samples from middle ear effusions obtained on day 8, the last day of observation. The animals were also sacrificed on days 4 and 8 and after 2 months for morphological examination. Compared with the susceptible recipient strain, recovery from infections caused by the resistant transformant strain was delayed, and the late structural changes were more severe in the animals challenged with the latter strain. The results of the study indicate that chromosomal alterations mediating a relatively low level of resistance to beta-lactams may be advantageous for H. influenzae during antibiotic treatment of a local infection in the rat, and the alterations may occur without any significant loss of virulence.
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37.
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38.
  • Nilsson, Anna, et al. (author)
  • LTX-109 is a Novel Agent for Nasal Decolonisation of Methicillin Resistant and Sensitive Staphylococcus aureus.
  • 2015
  • In: Antimicrobial Agents and Chemotherapy. - 1098-6596. ; 59:1, s. 145-151
  • Journal article (peer-reviewed)abstract
    • Nasal decolonisation has a proven effect on the prevention of severe Staphylococcus aureus infections and in the control of methicillin resistant S. aureus (MRSA). However, rising rates of resistance to antibiotics highlights the need for new substances for nasal decolonisation. LTX-109 is a broad spectrum, fast-acting bactericidal antimicrobial drug for topical treatment, which causes membrane disruption and cell lysis. This mechanism of action is not associated with cross-resistance and has a low propensity for development of resistance. In the present study persistent nasal MRSA and methicillin sensitive S. aureus carriers were treated for three days with vehicle, 1%, 2% or 5% LTX-109, respectively. A significant effect on nasal decolonisation was observed already after 2 days of LTX-109 treatment in subjects treated with 2% or 5% LTX-109 compared to vehicle (P≤0.0012, Dunnett's test). No safety issues were noted during the 9-week follow-up period. Minimal reversible epithelial lesions were observed in the nasal cavity. The systemic exposure was very low with a Cmax 1-2 h post dosing (3.72-11.7 ng/mL). One week after treatment initiation LTX-109 was not detectable in any subject. Summary: Intranasal treatment of S. aureus with LTX-109 is safe and reduces the bacterial load already after a single day of treatment. Hence, LTX-109 has the potential as a new and effective antimicrobial agent with low propensity of resistance development that can prevent infections by MSSA/MRSA during hospitalization. ClinicalTrials.gov: NCT01158235.
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39.
  • Persson, Kenneth, et al. (author)
  • Decline of the new Swedish variant of Chlamydia trachomatis after introduction of appropriate testing.
  • 2012
  • In: Sexually Transmitted Infections. - : BMJ. - 1368-4973 .- 1472-3263. ; 88:6, s. 81-451
  • Journal article (peer-reviewed)abstract
    • Objective: The longitudinal epidemiological development of the new variant of Chlamydia trachomatis was studied after appropriate testing procedures had been introduced when the strain was detected in 2006. Methods: The number of cases of the new variant of C trachomatis was followed from 2007 through 2011 from the laboratory records. Testing for C trachomatis is centralised to one laboratory with around 80-85 000 persons being tested annually in a population of 1.1 million. Results: During the 5-year period, 410 973 patients were tested of which 25 723 cases were positive. The proportion of the new variant of all positive cases declined from 30% in 2007 to 6% in 2011. While the number of the new variant of C trachomatis declined, the ordinary wild-type strains remained largely unchanged. Conclusions: A selective decline of the new variant of C trachomatis has occurred after appropriate laboratory testing was introduced. A new balance point between 5% and 10% for the new variant seems to be gradually approached.
  •  
40.
  • Persson, Stefan, 1963- (author)
  • Adolescents' role in democratic "parenting"
  • 2009
  • Doctoral thesis (other academic/artistic)abstract
    • In research on family democracy there has been a tradition to focus on parents as leaders setting up the family climate. This dissertation challenged this perspective. Keeping with present day’s emphasis on bidirectionality between parents and children democratic family functioning was seen as jointly created by parents and youths. Results showed that youths behaviors and characteristics have to be taken into account if the democratic working of the family is to be fully understood. When controlling for parents’ behaviors, adolescents’ behaviors added significantly to the prediction of a democratic family climate (Study I). Within families, youths democracy compromising behaviors were found to not only have consequences for the individual child. Instead, it was found that changes in younger siblings’ perceptions of family democracy changed as a consequence of an older sibling’s earlier democracy compromising behavior (Study II). Finally, parental openness to communication, youth openness to communication, and parental bad treatment all were found to be separate components of family democracy. Also, these components of family democracy were found to be prospectively linked to adolescents’ perceptions of the democratic climate in their own families. Further, these three components could be used to identify stable family configurations which differed with respect to adolescents’ perceptions of having influence in family matters and their internal-and external adjustment as well as other aspects of the parent-child relationship (Study III). Moreover, changes over-time within families in parental openness to communication, youth openness to communication, and parental bad treatment were associated with changes in youths’ perceptions of having influence in family matters and other features of parent-child relations (Study III). On the whole, these findings lend strong support to seeing children as active agents in the democratic workings of the family and they support a family systems approach to the issue of democratic family functioning. Clearly, young people are human agents with the capacity to interpret and react to their own reality. They are certainly both the harvest and the seeds of democratic family functioning.
  •  
41.
  • Ronander, Elena, et al. (author)
  • Identification of a novel Haemophilus influenzae protein important for adhesion to epithelial cells.
  • 2008
  • In: Microbes and Infection. - : Elsevier BV. - 1769-714X .- 1286-4579. ; 10:1, s. 87-96
  • Journal article (peer-reviewed)abstract
    • Non-typable Haemophilus influenzae (NTHi) is an important human-specific respiratory pathogen colonizing the mucosa of the upper respiratory tract. The bacterium is a common cause of acute otitis media in children and exacerbations in patients with chronic obstructive pulmonary disease (COPD). An immunoglobulin (Ig) D-lambda myeloma protein was found to detect a 16kDa surface protein that we designated protein E (PE). The pe gene was cloned using an NTHi genomic DNA library, and a truncated PE-derived protein lacking the endogenous signal peptide (PE22-160) was synthesized and produced in large amounts in Escherichia coli. Interestingly, PE was expressed at the bacterial surface of NTHi as revealed by flow cytometry using the IgD-lambda myeloma protein or PE-specific polyclonal antibodies. A PE-deficient NTHi mutant was produced and lost 50% of its adhesive capacity as compared to the wild-type counterpart when analysed for adhesion to type II lung alveolar epithelial cells. In parallel, E. coli expressing full-length PE1-160 adhered significantly more efficiently to epithelial cells as compared to wild-type E. coli. Recombinant IgD that recognized the chemical dansyl-chloride did not interact with PE indicating that the IgD-lambda myeloma protein most likely was an antibody directed against the H. influenzae surface epitope. In conclusion, we have discovered a novel NTHi outer membrane protein with adhesive properties using an IgD-myeloma protein.
  •  
42.
  • Song, Xin-Ming, et al. (author)
  • Differences in genetic and transcriptional organization of the glpTQ operons between Haemophilus influenzae type b and nontypeable strains
  • 2003
  • In: Journal of Bacteriology. - 0021-9193. ; 185:24, s. 7285-7290
  • Journal article (peer-reviewed)abstract
    • The glpTQ operon of Haemophilus influenzae type b (Hib) and nontypeable H. influenzae (NTHi) strains is highly conserved, except for a 1.4-kb glpTQ intergenic region that was found in most Hib strains. The presence of this intergenic region results in divergent glpTQ transcriptional profiles for Hib and NTHi where Hib strains appear to have evolved an alternative promoter for glpQ expression. Based on the intergenic region's low G+C content, we speculate that this DNA fragment was acquired by lateral transfer.
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43.
  • Song, Xin-Ming, et al. (author)
  • Fragmentation heterogeneity of 23S ribosomal RNA in Haemophilus species
  • 1999
  • In: Gene. - 1879-0038. ; 230:2, s. 287-293
  • Journal article (peer-reviewed)abstract
    • The fragmentation of 23S rRNA of 23 Haemophilus influenzae strains and eight strains belonging to other Haemophilus species was investigated. Instead of intact molecules, the 23S rRNA molecules were found to be cleaved into two to five smaller conserved fragments in most strains examined, especially in H. influenzae type b (5/6) and nontypeable strains (5/5). One or two conserved potential cleavage sites were identified by PCR analysis of the strains showing a fragmented 23S rRNA pattern. The relevant nucleotide sequences were determined and compared to H. influenzae Rd, which contains intact 23S rRNA molecules. An identical 112bp long intervening sequence (IVS) at position 542 and a conserved 121-123bp IVS sequence at position 1171 were found in two H. influenzae type b strains and one nontypeable strain. Among the strains with fragmented 23S rRNA, nearly half showed a heterogeneous cleavage pattern due to the dispersion of IVSs among different 23S rRNA operons. The localization of the conserved H. influenzae IVSs coincided well with the extensively studied IVSs among other bacteria, but differed in nucleotide sequence from any other reported IVSs. Therefore, the IVSs of Haemophilus 23S rRNA may originate from a common source that is independent of other bacteria.
  •  
44.
  • Song, Xin-Ming, et al. (author)
  • Glycerol-3-phosphate transport in Haemophilus influenzae: cloning, sequencing, and transcription analysis of the glpT gene
  • 1998
  • In: Gene. - 1879-0038. ; 215:2, s. 381-388
  • Journal article (peer-reviewed)abstract
    • The presence of a functional glpT gene in Haemophilus influenzae could be questioned, since there is only what appears to be a truncated glpT (HI0686, 143 nt in the 5'-end) available in the H. influenzae Rd genome database (Fleischmann et al. , 1995). For cloning of the glpT gene from H. influenzae type b strain Eagan, an isogenic glpT, rec-1 double mutant and a selective medium for detection of the glpT mutant strains were constructed. The recombinant plasmid carrying glpT was able to complement the isogenic glpT mutant to wild-type levels of G3P uptake and permitted growth on a selective medium with G3P as a major carbon source. The nucleotide sequences of the glpT gene were determined both directly from PCR products and from the cloned DNA insert of strain Eagan. An identical 1440 bp open reading frame with 480 deduced amino acids, highly homologous to other bacterial G3P permeases, was identified. A Northern blot analysis showed that the glpT genes in both Eagan and Rd strains were transcribed on a RNA of approximately 1.4 kb in size. Thus, it is likely that HI0686 sequence originates from a mutated glpT clone in Escherichia coli.
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45.
  • Song, Xin-Ming, et al. (author)
  • The gene encoding protein D (hpd) is highly conserved among Haemophilus influenzae type b and nontypeable strains
  • 1995
  • In: Infection and Immunity. - 1098-5522. ; 63:2, s. 696-699
  • Journal article (peer-reviewed)abstract
    • The molecular conservation of a surface-exposed lipoprotein, protein D, of Haemophilus influenzae was studied by cloning and sequencing of the gene encoding protein D from three encapsulated type b strains and three nontypeable strains of H. influenzae. These nucleotide sequences were analyzed with previously reported sequences from one type b strain and one nontypeable strain. The nucleotide sequences and the deduced amino acid sequences for protein D were highly conserved. The deduced amino acid sequence (364 amino acids) of protein D from six strains differed only in two amino acids near the C-terminal end. The remaining two strains, one type b and one nontypeable, differed from the consensus sequence in 7 amino acids each. Protein D is 64 and 36% identical and 77 and 56% similar to the glycerophosphodiester phosphodiesterases (GlpQ) of Escherichia coli and Bacillus subtilis.
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46.
  • Sorbe, Bengt, et al. (author)
  • Tropisetron (Navoban) in the prevention of chemotherapy-induced nausea and vomiting : the Nordic experience
  • 1994
  • In: Supportive Care in Cancer. - 0941-4355 .- 1433-7339. ; 2:6, s. 393-399
  • Journal article (peer-reviewed)abstract
    • An open, noncomparative, Nordic multicenter study was carried out during 1991-1992 to evaluate the 5-HT3 receptor antagonist tropisetron (Navoban) as an antiemetic agent for various types of cancer chemotherapy. A total of 630 patients were recruited from 15 centers in Sweden, Denmark, and Finland. Gynecological cancers (60%), breast cancer (15%), and lung cancer (10%) were the main diagnoses. Prior experience of chemotherapy was documented in 338 patients (54%). In 260 patients (41%), cisplatin was part of the cytostatic regimen. Carboplatin (23%), doxorubicin (27%), and epidoxorubicin (24%) were also frequently included. In all, 23 cytostatic agents were used in various combinations. The mean number of courses studied was 4.6 (range 1-19). Altogether, 394 of 619 evaluable patients (64%) were completely protected from acute nausea and vomiting during the first course of chemotherapy. Delayed nausea and vomiting were completely prevented in 45%-73% (days 2-6) in the complete series. Treatment efficacy remained stable (60%-79%) during ten consecutive courses of chemotherapy. With noncisplatin regimens, complete protection from acute nausea and vomiting was achieved in 72% compared with 52% for cisplatin regimens (P < 0.0001). Patients without prior experience of chemotherapy had higher control rates of acute nausea and vomiting (72%) compared to patients treated before (57%) during the first course, but not later on. There were no differences in delayed nausea and vomiting.
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47.
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48.
  • Sulku, Johanna, et al. (author)
  • Changes in critical inhaler technique errors in inhaled COPD treatment : A one-year follow-up study in Sweden
  • 2022
  • In: Respiratory Medicine. - : Elsevier. - 0954-6111 .- 1532-3064. ; 197
  • Journal article (peer-reviewed)abstract
    • Background: Critical inhaler technique errors have been associated with lower treatment efficacy in chronic obstructive pulmonary disease (COPD). We aimed to assess and follow-up critical inhaler technique errors, and to investigate their association with COPD symptoms and exacerbations.Methods: COPD-diagnosed primary and secondary care outpatients (n = 310) demonstrated inhaler technique with inhaler devices they were currently using. Critical errors in opening, positioning and loading the inhaler device, and exhalation through dry-powder inhalers were assessed and corrected, and the assessment was repeated one year later. COPD Assessment Test, the modified Medical Research Council dyspnoea scale and history of exacerbations were collected at both visits.Results: The proportion of patients making >1 critical inhaler technique error was lower at follow-up in the total population (46% vs 37%, p = 0.01) and among patients with unchanged device models (46% vs 35%, p = 0.02), but not among patients with a new inhaler device model (46% vs 41%, p = 0.56). Not positioning the device correctly was the most common critical error at both visits (30% and 22%). Seventy-four percent of the patients had unchanged COPD treatment from baseline to follow-up. Treatment escalation, de-escalation, and switch was observed in 14%, 11%, and 1% of the patients, respectively. No association was found between critical errors and COPD symptoms or exacerbations.Conclusions: Assessment and correction of inhaler technique was associated with a decrease in critical inhaler technique errors. This effect was most pronounced in patients using the same device models throughout the follow-up period.
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49.
  • Sulku, Johanna, et al. (author)
  • Critical inhaler technique errors in Swedish patients with COPD : a cross-sectional study analysing video-recorded demonstrations
  • 2021
  • In: npj Primary Care Respiratory Medicine. - : Springer Nature. - 2055-1010. ; 31:1
  • Journal article (peer-reviewed)abstract
    • A correct use of inhaler devices is essential in chronic obstructive pulmonary disease (COPD) treatment. Critical errors were studied by analysing 659 video-recorded demonstrations of inhaler technique from 364 COPD patients using six different inhaler device models. The majority of the included patients used two (55%) or more (20%) device models. Overall, 66% of the patients made ≥1 critical error with at least one device model. The corresponding numbers for patients using 1, 2 and ≥3 device models were 43%, 70% and 86%, respectively. The only factor associated with making ≥1 critical error was simultaneous use of two (adjusted odds ratios (aOR) 3.17, 95% confidence interval (95% CI) 1.81, 5.64) or three or more (aOR 8.97, 95% CI 3.93, 22.1) device models. In conclusion, the proportion of patients making critical errors in inhaler technique was substantial, particularly in those using several different device models. To obtain optimal COPD treatment, it is important to assess a patient's inhaler technique and to minimise the number of inhaler device models.
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50.
  • Sundström, Johan, Professor, 1971-, et al. (author)
  • Rationale for a Swedish cohort consortium
  • 2019
  • In: Upsala Journal of Medical Sciences. - : Taylor & Francis Group. - 0300-9734 .- 2000-1967. ; 124:1, s. 21-28
  • Journal article (peer-reviewed)abstract
    • We herein outline the rationale for a Swedish cohort consortium, aiming to facilitate greater use of Swedish cohorts for world-class research. Coordination of all Swedish prospective population-based cohorts in a common infrastructure would enable more precise research findings and facilitate research on rare exposures and outcomes, leading to better utilization of study participants' data, better return of funders' investments, and higher benefit to patients and populations. We motivate the proposed infrastructure partly by lessons learned from a pilot study encompassing data from 21 cohorts. We envisage a standing Swedish cohort consortium that would drive development of epidemiological research methods and strengthen the Swedish as well as international epidemiological competence, community, and competitiveness.
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