| 1. |
- Abu-Humaidan, Anas H., et al.
(författare)
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Persistent intracellular Staphylococcus aureus in keratinocytes lead to activation of the complement system with subsequent reduction in the intracellular bacterial load
- 2018
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Ingår i: Frontiers in Immunology. - : Frontiers Media SA. - 1664-3224. ; 9:MAR
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Tidskriftsartikel (refereegranskat)abstract
- The complement system is an ancient part of the innate immune system important for both tissue homeostasis and host defense. However, bacteria like Staphylococcus aureus (SA) possess elaborative mechanisms for evading both the complement system and other parts of the immune system. One of these evasive mechanisms-important in causing chronic and therapy resistant infections-is the intracellular persistence in non-immune cells. The objective of our study was to investigate whether persistent intracellular SA infection of epidermal keratinocytes resulted in complement activation. Using fluorescence microscopy, we found that persistent SA, surviving intracellularly in keratinocytes, caused activation of the complement system with formation of the terminal complement complex (TCC) at the cell surface. Skin samples from atopic dermatitis patients analyzed by bacterial culture and microscopy, demonstrated that SA colonization was associated with the presence of intracellular bacteria and deposition of the TCC in epidermis in vivo. Complement activation on keratinocytes with persistent intracellular bacteria was found with sera deficient/depleted of the complement components C1q, Mannan-binding lectin, or complement factor B, demonstrating involvement of more than one complement activation pathway. Viable bacterial counts showed that complement activation at the cell surface initiated cellular responses that significantly reduced the intracellular bacterial burden. The use of an inhibitor of the extracellular signal-regulated kinase (ERK) abrogated the complement-induced reduction in intracellular bacterial load. These data bridge the roles of the complement system in tissue homeostasis and innate immunity and illustrate a novel mechanism by which the complement system combats persistent intracellular bacteria in epithelial cells.
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| 2. |
- Abu-Humaidan, Anas, et al.
(författare)
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The epidermal growth factor receptor is a regulator of epidermal complement component expression and complement activation.
- 2014
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Ingår i: Journal of immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 192:7, s. 3355-3364
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Tidskriftsartikel (refereegranskat)abstract
- The complement system is activated in response to tissue injury. During wound healing, complement activation seems beneficial in acute wounds but may be detrimental in chronic wounds. We found that the epidermal expression of many complement components was only increased to a minor extent in skin wounds in vivo and in cultured keratinocytes after exposure to supernatant from stimulated mononuclear cells. In contrast, the epidermal expression of complement components was downregulated in ex vivo injured skin lacking the stimulation from infiltrating inflammatory cells but with intact injury-induced epidermal growth factor receptor (EGFR)-mediated growth factor response. In cultured primary keratinocytes, stimulation with the potent EGFR ligand, TGF-α, yielded a significant downregulation of complement component expression. Indeed, EGFR inhibition significantly enhanced the induction of complement components in keratinocytes and epidermis following stimulation with proinflammatory cytokines. Importantly, EGFR inhibition of cultured keratinocytes either alone or in combination with proinflammatory stimulus promoted activation of the complement system after incubation with serum. In keratinocytes treated solely with the EGFR inhibitor, complement activation was dependent on serum-derived C1q, whereas in keratinocytes stimulated with a combination of proinflammatory cytokines and EGFR inhibition, complement activation was found even with C1q-depleted serum. In contrast to human keratinocytes, EGFR inhibition did not enhance complement component expression or cause complement activation in murine keratinocytes. These data demonstrate an important role for EGFR in regulating the expression of complement components and complement activation in human epidermis and keratinocytes and, to our knowledge, identify for the first time a pathway important for the epidermal regulation of complement activation.
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| 3. |
- Andersen, Claus Yding, et al.
(författare)
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Preovulatory progesterone concentration associates significantly to follicle number and LH concentration but not to pregnancy rate
- 2011
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Ingår i: Reproductive BioMedicine Online. - : Elsevier BV. - 1472-6491 .- 1472-6483. ; 23:2, s. 187-195
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Tidskriftsartikel (refereegranskat)abstract
- Using data from a large prospective randomized controlled trial that evaluated the effect of recombinant LH (rLH) co-administration for ovarian stimulation, the present study assessed whether progesterone concentration on the day of human chorionic gonadotrophin (HCG) administration was associated with pregnancy outcome. Progesterone concentration was measured on stimulation day 1 and on the day of HCG administration in 475 patients who underwent IVF/intracytoplasmic sperm injection treatment following ovarian stimulation with gonadotrophin-releasing hormone (GnRH) agonist and recombinant FSH with or without rLH administration from day 6 of stimulation. There was no significant association between the late-follicular-phase progesterone concentration and the clinical pregnancy rate. However, progesterone concentration was strongly associated with the number of follicles and retrieved oocytes. Late-follicular-phase LH concentration also showed a significant positive association with progesterone concentration (P = 0.018). Administration of rLH during ovarian stimulation did not affect progesterone concentration. The present study does not support an association between progesterone concentration on the day of HCG administration and the probability of clinical pregnancy in women undergoing ovarian stimulation with GnRH agonists and gonadotrophins for assisted reproduction treatment. Instead, late-follicular-phase progesterone concentration appears to be governed by the number of preovulatory follicles and LH concentration. (C) 2011, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
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| 4. |
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| 5. |
- Bungum, Leif, et al.
(författare)
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The circadian variation in anti-müllerian hormone in patients with polycystic ovary syndrome differs significantly from normally ovulating women.
- 2013
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- To improve the biologic understanding of the Polycystic Ovarian Syndrome (PCOS) condition by examining the circadian variation and relationship between Anti Müllerian Hormone (AMH), gonadotropins and ovarian steroids in PCOS patients compared to normally ovulating and menstruating women. By comparing the pattern of co-variation between AMH and Luteinizing Hormone, two compounds closely linked to hyperandrogenism and anovulation in PCOS, the involvement of the Hypothalamic-Pituitary-Ovarian axis in PCOS pathology could be elucidated.
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| 6. |
- Bungum, Mona, et al.
(författare)
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A prospective study, using sibling oocytes, examining the effect of 30 seconds versus 90 minutes gamete co-incubation in IVF.
- 2006
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 21:2, s. 518-523
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Traditionally oocytes have been exposed to sperm overnight, for 16-20 h. This long period of co-incubation, however, has been shown to create problems with high levels of reactive oxygen species (ROS), which may affect embryo viability and cause hardening of the zona pellucida. Recently, a positive effect of reducing the co-incubation time to 90-120 min was reported. The objective of this study was to evaluate whether a further reduction of the co-incubation period could benefit the outcome of IVF. METHODS: In this prospective study, 777 sibling oocytes from 81 women undergoing IVF were divided via alternate allocation to co-incubation for either 30 s (ultrashort co-incubation) (group A) or for 90 min (standard co-incubation) (group B). Endpoints were normal fertilization (two-pronuclear, 2PN), polyspermy (> 2PN), embryo quality (EQ), clinical pregnancy (CP) and implantation (IR). RESULTS: The normal fertilization rates of the two groups were comparable: group A 58.6% versus group B 58.0%. Significantly lower rates of polyspermy were seen in group A compared to group B (2.8 versus 7.2%, P = 0.008). No statistically significant differences in EQ, CP or IR were seen. CONCLUSION: This is the first study demonstrating the achievement of good fertilization rates in IVF with ultrashort co-incubation. Significantly lower rates of polyspermy were seen in the group with ultrashort compared to the standard co-incubation group. Further studies are, however, needed in order to evaluate whether ultrashort co-incubation has any effect on the outcome of IVF.
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| 7. |
- Bungum, Mona, et al.
(författare)
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Polymorphisms in the protein C inhibitor gene in in vitro fertilization failure.
- 2010
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Ingår i: Fertility and Sterility. - : Elsevier BV. - 1556-5653 .- 0015-0282. ; 93:1, s. 277-279
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine whether total fertilization failure in human IVF can be partially explained by alterations in the gene that codes for protein C inhibitor. Forty-six men had IVF total fertilization failure and 51 controls with normal fertilization were screened for mutations in the protein C inhibitor gene by direct sequencing. The main finding was that in men involved in total fertilization failure, a heterozygous adenosine/guanine (A/G) base combination in position 1389 (rs2069990) (exon 6) in the protein C inhibitor gene was significantly more common compared with controls (10.9% vs. 0).
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| 8. |
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| 9. |
- Bungum, Mona, et al.
(författare)
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Sperm chromatin structure assay parameters measured after density gradient centrifugation are not predictive for the outcome of ART
- 2008
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Ingår i: Human Reproduction. - : Oxford University Press (OUP). - 0268-1161 .- 1460-2350. ; 23:1, s. 41374-41374
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The sperm chromatin structure assay (SCSA) parameter DNA fragmentation index (DFI) has been shown to predict in vivo and in vitro fertility. So far most SCSA studies have been based on SCSA analysis performed on neat semen. The aim of this study is to assess whether SCSA analysis of sperm prepared by density gradient centrifugation (DGC) could add more information in regard to the prediction of treatment outcome. METHODS The study included 510 assisted reproductive technique (ART) cycles. SCSA was performed in neat semen and post DGC. SCSA results were expressed in terms of DFI and high DNA stainability (HDS) cell fractions. The outcome parameter was clinical pregnancy (CP). RESULTS Scatter-plot diagrams demonstrated that for DGC samples, no DFI cut-off values could be set for in vivo or in vitro fertility. In intrauterine insemination, IVF and ICSI groups the mean difference (95% CI) in DFI post DGC between those who achieved CP and those who did not was 0.2% (-1.7 to 2.0%), 0.4% (-1.9 to 2.8%) and 1.3% (-3.1 to 5.9%), respectively, none of these being statistically significant. The corresponding differences for HDS were 0.1% (-1.3 to 1.5%), 0.1% (-0.7 to 0.9%) and 0.6% (-1.6 to 2.7%), respectively (all P-values >0.6). CONCLUSIONS SCSA performed in semen prepared by DGC cannot predict the outcome of ART.
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| 10. |
- Humaidan, Peter, et al.
(författare)
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Pain relief during oocyte retrieval--exploring the role of different frequencies of electro-acupuncture.
- 2006
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Ingår i: Reproductive biomedicine online. - 1472-6483. ; 13:1, s. 120-5
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Tidskriftsartikel (refereegranskat)abstract
- Electro-acupuncture has previously proven its analgesic effect in oocyte retrieval for IVF. The aim of the present prospective randomized study was to explore the optimal frequency for analgesia when electro-acupuncture was applied a few minutes prior to oocyte retrieval. A total of 152 patients were prospectively randomized to receive either a combination of high (80 Hz) and low frequency (2 Hz), 3 s each, a so-called mixed frequency, or a fixed frequency of 20 Hz during oocyte retrieval. In addition to electro-acupuncture, both groups had a paracervical block and manual acupuncture. No differences in pain before, during or after oocyte retrieval between the two groups were seen. In the fixed frequency group, however, a higher level of anxiety (P < 0.05) before oocyte retrieval was seen, and a higher level of nausea after aspiration of one ovary (P < 0.01) was seen in the mixed frequency group. No differences were seen regarding clinical outcome parameters. Contrary to previous reports on acute and chronic pain, the analgesic effect of the mixed frequency and the fixed frequency was similar when used for short duration electro-acupuncture.
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