| 1. |
- Bergsten, Göran, et al.
(författare)
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Do type 1 fimbriae promote inflammation in the human urinary tract?
- 2007
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Ingår i: Cellular Microbiology. - : Hindawi Limited. - 1462-5814 .- 1462-5822. ; 9:7, s. 1766-1781
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Tidskriftsartikel (refereegranskat)abstract
- Type 1 fimbriae have been implicated as virulence factors in animal models of urinary tract infection (UTI), but the function in human disease remains unclear. This study used a human challenge model to examine if type 1 fimbriae trigger inflammation in the urinary tract. The asymptomatic bacteriuria strain Escherichia coli 83972, which fails to express type 1 fimbriae, due to a 4.25 kb fimB-fimD deletion, was reconstituted with a functional fim gene cluster and fimbrial expression was monitored through a gfp reporter. Each patient was inoculated with the fim+ or fim- variants on separate occasions, and the host response to type 1 fimbriae was quantified by intraindividual comparisons of the responses to the fim+ or fim- isogens, using cytokines and neutrophils as end-points. Type 1 fimbriae did not promote inflammation and adherence was poor, as examined on exfoliated cells in urine. This was unexpected, as type 1 fimbriae enhanced the inflammatory response to the same strain in the murine urinary tract and as P fimbrial expression by E. coli 83972 enhances adherence and inflammation in challenged patients. We conclude that type 1 fimbriae do not contribute to the mucosal inflammatory response in the human urinary tract.
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| 2. |
- Bergsten, Göran, et al.
(författare)
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PapG-dependent adherence breaks mucosal inertia and triggers the innate host response
- 2004
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 189:9, s. 1734-1742
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Tidskriftsartikel (refereegranskat)abstract
- Mucosal pathogens differ from normal flora constituents in that they provoke a host response that upsets mucosal integrity. We investigated whether the elaboration of discrete adherence factors is sufficient to break the inertia of the mucosal barrier. PapG-mediated adherence was selected as an example, because P fimbrial expression characterizes uropathogenic Escherichia coli and because adherence starts the attack on the mucosal barrier. Patients were inoculated intravesically with transformed nonvirulent E. coli strains expressing functional P fimbriae (E. coli pap(+)) or mutant fimbriae lacking the adhesin (E. coli DeltapapG). E. coli pap(+) was shown to activate the innate host response, and adherent gfp(+) bacteria were observed on excreted uroepithelial cells. E. coli DeltapapG failed to trigger a response and was nonadhesive. We conclude that PapG-mediated adherence breaks mucosal inertia in the human urinary tract by triggering innate immunity and propose that this activation step differentiates asymptomatic carriage from infection.
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| 3. |
- Bobjer, Johannes, et al.
(författare)
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High Prevalence of Hypogonadism and Associated Impaired Metabolic and Bone Mineral Status in Subfertile Men.
- 2016
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Ingår i: Clinical Endocrinology. - : Wiley. - 1365-2265 .- 0300-0664. ; 85:2, s. 189-195
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Tidskriftsartikel (refereegranskat)abstract
- It is yet unknown to which degree young subfertile men present with signs of hypogonadism and whether low testosterone concentration, like in older men, is associated with risk of osteoporosis and metabolic derangements in those subjects. The objective was, therefore, to investigate the prevalence of hypogonadism and its association with metabolic and bone parameters in young subfertile men.
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| 4. |
- Giwercman, Aleksander, et al.
(författare)
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Novel protein markers of androgen activity in humans : proteomic study of plasma from young chemically castrated men
- 2022
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Ingår i: eLife. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: Reliable biomarkers of androgen activity in humans are lacking. The aim of this study was, therefore, to identify new protein markers of biological androgen activity and test their predictive value in relation to low vs normal testosterone values and some androgen deficiency linked pathologies. Methods: Blood samples from 30 healthy GnRH antagonist treated males were collected at three time points: (1) before GnRH antagonist administration; (2) 3 weeks later, just before testosterone undecanoate injection, and (3) after additional 2 weeks. Subsequently, they were analyzed by mass spectrometry to identify potential protein biomarkers of testosterone activity. Levels of proteins most significantly associated with testosterone fluctuations were further tested in a cohort of 75 hypo- and eugonadal males suffering from infertility. Associations between levels of those markers and cardiometabolic parameters, bone mineral density as well as androgen receptor (AR) CAG repeat lengths, were explored. Results: Using receiver operating characteristic analysis, 4-hydroxyphenylpyruvate dioxygenase (4HPPD), insulin-like growth factor-binding protein 6 (IGFBP6), and fructose-bisphosphate aldolase (ALDOB), as well as a Multi Marker Algorithm, based on levels of 4HPPD and IGFBP6, were shown to be best predictors of low (<8 nmol/l) vs normal (>12 nmol/l) testosterone. They were also more strongly associated with metabolic syndrome and diabetes than testosterone levels. Levels of ALDOB and 4HPPD also showed association with AR CAG repeat lengths. Conclusions: We identified potential new protein biomarkers of testosterone action. Further investigations to elucidate their clinical potential are warranted. Funding: The work was supported by ReproUnion2.0 (grant no. 20201846), which is funded by the Interreg V EU program.
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| 5. |
- Gustafsson, Lotta, et al.
(författare)
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Treatment of skin papillomas with topical alpha-lactalbumin-oleic acid
- 2004
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 350:26, s. 2663-2672
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We studied the effect on skin papillomas of topical application of a complex of α-lactalbumin and oleic acid (often referred to as human α-lactalbumin made lethal to tumor cells [HAMLET]) to establish proof of the principle that α-lactalbumin-oleic acid kills transformed cells but not healthy, differentiated cells. METHODS: Forty patients with cutaneous papillomas that were resistant to conventional treatment were enrolled in a randomized, placebo-controlled, double-blind study, in which α-lactalbumin-oleic acid or saline placebo was applied daily for three weeks and the change in the volume of each lesion was recorded. After this first phase of the study, 34 patients participated in the second phase, an open-label trial of a three-week course of α-lactalbumin-oleic acid. Approximately two years after the end of the open-label phase of the study, 38 of the original 40 patients were examined, and long-term follow-up data were obtained. RESULTS: In the first phase of the study, the lesion volume was reduced by 75 percent or more in all 20 patients in the α-lactalbumin-oleic acid group, and in 88 of 92 papillomas; in the placebo group, a similar effect was evident in only 3 of 20 patients (15 of 74 papillomas) (P<0.001). After the patients in the initial placebo group had been treated with α-lactalbumin-oleic acid in the second phase of the study, a median reduction of 82 percent in lesion volume was observed. At follow-up two years after the end of the second phase, all lesions had completely resolved in 83 percent of the patients treated with α-lactalbumin-oleic acid, and the time to resolution was shorter in the group originally assigned to receive a-lactalbumin-oleic acid than among patients originally in the placebo group (2.4 vs. 9.9 months; P<0.01). No adverse reactions were reported, and there was no difference in the outcomes of treatment between immunocompetent and immunosuppressed patients. CONCLUSIONS: Treatment with topical α-lactalbumin-oleic acid has a beneficial and lasting effect on skin papillomas.
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| 6. |
- Hjelmér, Ida, et al.
(författare)
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Quality of life among female childhood cancer survivors with and without premature ovarian insufficiency
- 2023
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Ingår i: Journal of Cancer Survivorship. - : Springer Science and Business Media LLC. - 1932-2259 .- 1932-2267. ; 17:1, s. 101-109
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Due to an increase in survival, a growing population of childhood cancer survivors (CCS) is present. However, female CCS are at risk of developing premature ovarian insufficiency (POI) after cancer treatment. POI involves a decreased chance of conceiving and the increased infertility state has a large impact on affected individuals’ health and mental life. The objective of this study was to investigate health state and well-being among female CCS with and without POI and healthy controls (HC). Methods: Female CCS treated in southern Sweden between 1964 and 2008 were included. Each patient was matched with a HC. The final study population included 167 female CCS and 164 HC that were examined between October 2010 and January 2015 at the Reproductive Medicine Centre at Skåne University Hospital in Malmö, Sweden. All participants, except for two HCs, answered an EQ-5D-3L questionnaire for measuring health state including a visual analogue scale (VAS) for estimating well-being. Results: There were 22 CCS with POI, none of the HC had POI. The mean health state differed among groups (unadjusted: P = 0.002; adjusted: P = 0.007). A difference in mean experienced well-being among groups was noted (unadjusted: P = 0.003; adjusted: P = 0.012). Lowest well-being was found in the CCS group with POI (P = 0.024). Conclusions: Female CCS have a significantly decreased health state and well-being. Female CCS with POI additionally have the lowest self-estimated well-being. Implications for Cancer Survivors: Female CCS with POI should be identified early in order to give them adequate information and support.
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| 7. |
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| 8. |
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| 9. |
- Lundstedt, Ann-Charlotte, et al.
(författare)
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Inherited susceptibility to acute pyelonephritis: a family study of urinary tract infection.
- 2007
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 195:8, s. 1227-1234
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Tidskriftsartikel (refereegranskat)abstract
- Background. Urinary tract infections (UTIs) are important causes of morbidity and death. The present study investigated whether genetic factors influence susceptibility to acute pyelonephritis (APN). CXCR1 expression was investigated as a factor predisposing to APN, because low CXCR1 expression has been associated with disease susceptibility in mice and disease-prone children. Methods. The families of APN-prone children (n=130) and of age-matched control subjects without UTI (n=101) were studied. Three- generation pedigrees of UTI-associated morbidity were established by means of structured interviews of the families. CXCR1 expression was quantified by flow cytometric analysis of peripheral blood neutrophils obtained from family members and control subjects. Results. APN was significantly more common in the family members of the APN-prone children (20 [15%] of 130 family members) than in the relatives of the control subjects (3 [3%] of 101 family members) (P <.002). Acute cystitis, in contrast, occurred with equal frequency in both groups (19%; P=1.0). Some families included many affected individuals, consistent with a dominant pattern of inheritance, whereas other families showed a recessive pattern of disease susceptibility. CXCR1 expression was significantly lower in the APN-prone children and in their relatives than in pediatric and adult control subjects (P < .0001). Conclusions. Our results suggest that susceptibility to APN is inherited and that low CXCR1 expression might predispose to disease.
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| 10. |
- Ragnarsdottir, Bryndis, et al.
(författare)
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Reduced Toll-like receptor 4 expression in children with asymptomatic bacteriuria
- 2007
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 196:3, s. 475-484
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Tidskriftsartikel (refereegranskat)abstract
- Toll-like receptor (TLR) 4 is essential for the defense against infection with gram-negative pathogens, but reduced TLR4 expression has not been linked to altered disease susceptibility in humans. In mice, Tlr4 controls the mucosal response to Escherichia coli urinary tract infections. Inactivation of mouse Tlr4 causes an asymptomatic carrier state resembling asymptomatic bacteriuria (ABU). The present study compared neutrophil TLR4 expression levels between children with ABU (n = 17) and age-matched control subjects (n = 24), and significantly lower levels were detected in the patients with ABU. We also found elevated levels of the TLR4 adaptor protein TRIF and reduced levels of the TLR4-inhibitor SIGIRR in the patients with ABU, but MyD88 and TRAM levels were not significantly altered. Altered TLR4 and adaptor protein expression might impair TLR4 signaling and explain the weak mucosal response to urinary tract infection in patients who develop ABU rather than symptomatic disease.
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