| 1. |
- Andersson, Niklas, 1970, et al.
(författare)
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Investigation of central versus peripheral effects of estradiol in ovariectomized mice
- 2005
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Ingår i: J Endocrinol. - : Bioscientifica. - 0022-0795 .- 1479-6805. ; 187:2, s. 303-9
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Tidskriftsartikel (refereegranskat)abstract
- It is generally believed that estrogens exert their bone sparing effects directly on the cells within the bone compartment. The aim of the present study was to investigate if central mechanisms might be involved in the bone sparing effect of estrogens. The dose-response of central (i.c.v) 17beta-estradiol (E2) administration was compared with that of peripheral (s.c.) administration in ovariectomized (ovx) mice. The dose-response curves for central and peripheral E2 administration did not differ for any of the studied estrogen-responsive tissues, indicating that these effects were mainly peripheral. In addition, ovx mice were treated with E2 and/or the peripheral estrogen receptor antagonist ICI 182,780. ICI 182,780 attenuated most of the estrogenic response regarding uterus weight, retroperitoneal fat weight, cortical BMC and trabecular bone mineral content (P<0.05). These findings support the notion that the primary target tissue that mediates the effect of E2 on bone is peripheral and not central.
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| 2. |
- Billhult, Annika, et al.
(författare)
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The effect of massage on cellular immunity, endocrine and psychological factors in women with breast cancer -- a randomized controlled clinical trial.
- 2008
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Ingår i: Autonomic neuroscience : basic & clinical. - : Elsevier BV. - 1566-0702. ; 140:1-2, s. 88-95
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The purpose of this study was to examine the effect of repeated effleurage massage treatments compared with a visit control group on circulating lymphocytes by studying the number and activity of peripheral blood NK cells, CD4+ and CD8+ T cells in women with breast cancer. Furthermore, the effect of repeated effleurage massage treatments on the levels of cortisol in saliva and oxytocin in plasma as well as degree anxiety, depression and quality of life was studied. DESIGN: A single centre, prospective, randomized, controlled trial. SETTINGS/LOCATION: The study was conducted in a radiation department, in a hospital in south-western Sweden. SUBJECTS: Twenty-two women (mean age=62) with breast cancer undergoing radiation were included in this study. INTERVENTIONS: The patients were randomly assigned to effleurage massage therapy (20 min of effleurage on ten occasions) or to control visits (ten 20-minute visits). OUTCOME MEASURES: Blood samples were collected before the first and last massage/control visit for analysis of peripheral blood NK, T cells and oxytocin. Saliva was analysed for cortisol. In addition, the patients completed the Hospital Anxiety and Depression Scale, Life Satisfaction Questionnaire and Spielbergers State Trait Anxiety Inventory prior to the first and last massage/control visit. RESULTS: Effleurage massage treatment had no significant effect on the number, frequencies or activation state of NK cells or CD4+ or CD8+ T cells. Furthermore, no significant changes between groups were detected on cortisol and oxytocin concentrations, anxiety, depression or quality of life. CONCLUSIONS: Significant effect of effleurage massage on cellular immunity, cortisol, oxytocin, anxiety, depression or quality of life could not be demonstrated in this study. Several possible explanations to the results of this study are discussed.
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| 3. |
- Billhult, Annika, et al.
(författare)
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The effect of massage on immune function and stress in women with breast cancer - A randomized controlled trial.
- 2009
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Ingår i: Autonomic neuroscience. - : Elsevier BV. - 1872-7484 .- 1566-0702. ; 150:1-2, s. 111-115
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To examine the short-term effects of light pressure effleurage on circulating lymphocytes by studying the number and activity of peripheral blood natural killer (NK) cells in patients with breast cancer compared to a control group. Furthermore, the effect of light pressure effleurage on salivary cortisol levels, heart rate and blood pressure was studied. DESIGN: Single centre, prospective, randomized and controlled study. METHODS: Thirty women, aged 50 to 75 years (mean 61 sd=7.2) with breast cancer undergoing radiation therapy in a hospital in southwestern Sweden were enrolled in the study. They were allocated to either receive massage in the form of a full-body light pressure effleurage treatment, or a control visit where they were given an equal amount of attention. Blood samples, saliva, notation of heart rate and blood pressure were collected before and after massage/control visit. Differences in change over time between groups were analyzed by Student's t-test. RESULTS: Light pressure effleurage massage decreased the deterioration of NK cell activity occurring during radiation therapy. Furthermore it lowered heart rate and systolic blood pressure. No effects were demonstrated on cortisol and diastolic pressure. CONCLUSIONS: A single full-body light pressure effleurage massage has a short-term effect on NK cell activity, systolic blood pressure and heart rate in patients with breast cancer. However, the long-term clinical importance of these findings needs to be further investigated.
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| 4. |
- Bokarewa, Maria, 1963, et al.
(författare)
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Efficacy of anti-CD20 treatment in patients with rheumatoid arthritis resistant to a combination of methotrexate/anti-TNF therapy.
- 2007
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Ingår i: Scandinavian journal of immunology. - : Wiley. - 0300-9475 .- 1365-3083. ; 66:4, s. 476-83
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Tidskriftsartikel (refereegranskat)abstract
- Rheumatoid arthritis (RA) is characterized by chronic joint inflammation and destruction. B cells play important role in modulating immune responses in RA. In the present study we assessed the impact of the B cell targeting as a third line treatment option. Forty-six patients with established erosive RA non-responding to combination treatment with DMARDs and TNF-alpha inhibitors were treated with anti-CD20 antibodies (rituximab). Rituximab was given intravenously once weekly on four occasions. All patients continued with the previous DMARD. Patients were followed by DAS28, levels of circulating B cells, frequency of immunoglobulin-producing cells, immunoglobulins, and rheumatoid factor levels during the period of 12-58 months. Clinical improvement was achieved in 34 of 46 patients (73%) supported by a significant reduction in DAS28 (from 6.04 to 4.64, P < 0.001). Infusion of rituximab resulted in the elimination of circulating B cells in all but one patient. Within 12 months follow-up, B cells returned to circulation in 86% of patients. Fifty-three percent of the patients were successfully retreated with rituximab or re-started with anti-TNF-alpha treatment. Of the 11 non-responders, five were retreated with anti-CD20 within 2 months, four of them with success, four patients received TNF-alpha inhibitors, the remaining two patients received an additional DMARD. Most of the RA patients resistant to TNF-alpha inhibitors may be effectively treated with anti-CD20 antibodies. The treatment is well tolerated and may be used repeatedly in the same patient and potentially increase sensitivity to previously inefficient treatment modalities.
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| 5. |
- Enarsson, Karin, 1975, et al.
(författare)
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Differential mechanisms for T lymphocyte recruitment in normal and neoplastic human gastric mucosa
- 2006
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Ingår i: Clin Immunol. - : Elsevier BV. ; 118:1, s. 24-34
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Forskningsöversikt (refereegranskat)abstract
- Worldwide, gastric adenocarcinoma (GC) is the second most common cause of death from malignant disease. The reason why immune responses are unable to clear the tumour is not fully understood, although aberrant lymphocyte recruitment to the tumour site might be one factor. Therefore, we investigated the homing phenotype of mucosal T lymphocytes in GC, compared to tumour-free mucosa. We could detect significantly decreased frequencies of mucosal homing alpha4beta7+ T cells in the tumour tissues and increased frequencies of L-selectin+ T cells. This was probably due to the correlated decrease in MAdCAM-1 positive and increase in PNAd positive blood vessels in the tumour mucosa. There were also fewer CXCR3+ T lymphocytes in the tumour tissue. These findings provide evidence that endothelial cells within tumours arising at mucosal sites do not support extravasation of typical mucosa-infiltrating T cells. This may be of major relevance for future immunotherapeutic strategies for treatment of GC.
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| 6. |
- Jonsson, Ing-Marie, 1949, et al.
(författare)
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mgrA regulates staphylococcal virulence important for induction and progression of septic arthritis and sepsis.
- 2008
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Ingår i: Microbes and infection / Institut Pasteur. - : Elsevier BV. - 1286-4579. ; 10:12-13, s. 1229-35
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Tidskriftsartikel (refereegranskat)abstract
- Septic arthritis and sepsis are common and feared complications of staphylococcal infections, and the increasing antibiotic resistance among staphylococci urge the extended research for virulence factors involved in these diseases. Staphylcoccus aureus produces a number of virulence factors controlled by several global regulatory genes including agr and sarA. MgrA is a recently identified global regulator, belonging to the SarA subfamily, which upregulates expression of several virulence factors including capsule and sortase. In addition, MgrA has been shown to regulate antibiotic resistance and decrease bacterial autolysis. In this study we have assessed the role of mgrA gene expression on induction and progression of septic arthritis and sepsis. Mice inoculated with the mgrA mutant displayed significantly less severe arthritis and showed a significantly better weight development, than wild-type inoculated mice. Importantly, all 10 mice inoculated with the mgrA mutant survived as compared to 70% mortality in the wild-type inoculated mice (p=0.003). In addition, the mgrA mutant showed significantly less bacterial persistence in kidneys as compared to the wild-type strain. We conclude that mgrA regulates virulence factors important for establishment and progression of septic arthritis and sepsis.
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| 7. |
- Lindberg, Marie, 1975, et al.
(författare)
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Liver-derived IGF-I is permissive for ovariectomy-induced trabecular bone loss
- 2006
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Ingår i: Bone. - : Elsevier BV. - 8756-3282. ; 38:1, s. 85-92
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Estrogen deficiency results in trabecular bone loss, associated with T-cell proliferation in the bone marrow. Insulin-like growth factor I (IGF-I) is involved in the regulation of both bone metabolism and lymphopoiesis. A major part of serum IGF-I is derived from the liver. The aim of the present study was to investigate the role of liver-derived IGF-I for ovariectomy (ovx)-induced trabecular bone loss. MATERIALS AND METHODS: Mice with adult liver-specific IGF-I inactivation (LI-IGF-I-/-) and wild type mice (WT) were either ovx or sham operated. After 5 weeks, the skeletal phenotype was analyzed by pQCT and microCT. The bone marrow cellularity was analyzed using FACS technique, and mRNA levels were quantified using real-time PCR. RESULTS: Ovx resulted in a pronounced reduction in trabecular bone mineral density (-52%, P < 0.001), number (-45%, P < 0.01) and thickness (-13%, P < 0.01) in WT mice while these bone parameters were unaffected by ovx in LI-IGF-I-/- mice. Furthermore, ovx increased the number of T-cells in the bone marrow of the femur in WT but not in LI-IGF-I-/- mice. Interleukin 7 (IL-7) has been reported to stimulate the formation and function of osteoclasts by inducing the expression of receptor activator of NF-kappaB ligand (RANKL) on T-cells. IL-7 mRNA levels and the RANKL/osteoprotegerin ratio in bone were increased by ovx in WT but not in LI-IGF-I-/- mice. CONCLUSIONS: Liver-derived IGF-I is permissive for ovx-induced trabecular bone loss. Our studies indicate that IGF-I might exert this permissive action by modulation of the number of T-cells and the expression of IL-7, which in turn is of importance for the RANKL/OPG ratio and consequently osteoclastogenesis in the bone marrow.
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| 8. |
- Lindholm, Catharina, 1967, et al.
(författare)
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Longterm clinical and immunological effects of anti-CD20 treatment in patients with refractory systemic lupus erythematosus.
- 2008
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Ingår i: The Journal of rheumatology. - 0315-162X. ; 35:5, s. 826-33
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To retrospectively evaluate longterm clinical and immunological effects of anti-CD20 treatment in patients with systemic lupus erythematosus (SLE) with active nephritis or autoantibody-mediated cytopenias refractory to conventional immunosuppressive treatment. METHODS: Anti-CD20 treatment (rituximab) was added to the ongoing immunosuppressive treatment in 31 SLE patients with active nephritis (n = 17), thrombocytopenia (n = 10), and hemolytic anemia (n = 4) refractory to conventional therapy. Disease activity was evaluated by the SLE Disease Activity Index. The median followup time after anti-CD20 treatment was 22 months (range 1-61 mo). RESULTS: Complete B cell depletion was obtained in all patients. In 11 of the 17 lupus nephritis patients complete or partial responses were achieved after 6-12 months. Eight of these patients increased their glomerular filtration rate (GFR) by > 25%. The responders were characterized by having shorter nephritis duration, a baseline GFR > 30 ml/min, and detectable circulating CD19+ B lymphocytes before B cell depletion. Anti-CD20 treatment was highly effective in patients with autoimmune thrombocytopenia, inducing a significant increase of platelet counts after 1 month (p < 0.01). Five of 10 patients achieved complete normalization of their platelet counts within 6 months. The anti-CD20 treatment was followed by a significant reduction of autoantibodies against dsDNA and platelets, in nephritic and in thrombocytopenic patients, respectively. CONCLUSION: Addition of anti-CD20 treatment to conventional immunosuppressive therapy may be a beneficial strategy in refractory lupus nephritis and autoimmune cytopenias, possibly by reducing the levels of pathogenic autoantibodies.
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| 9. |
- Lundgren, Anna, 1974, et al.
(författare)
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Mucosal FOXP3-expressing CD4+ CD25high regulatory T cells in Helicobacter pylori-infected patients
- 2005
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Ingår i: Infect Immun. ; 73:1, s. 523-31
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Tidskriftsartikel (refereegranskat)abstract
- Helicobacter pylori chronically colonizes the stomach and duodenum and causes peptic ulcers or gastric adenocarcinoma in 10 to 20% of infected individuals. We hypothesize that the inability of patients to clear H. pylori infections is a consequence of active suppression of the immune response. Here we show that H. pylori-infected individuals have increased frequencies of CD4(+) CD25(high) T cells in both the stomach and duodenal mucosa compared to uninfected controls. These cells have the phenotype of regulatory T cells, as they express FOXP3, a key gene for the development and function of regulatory T cells, as well as high levels of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) protein. In contrast, mucosal CD4(+) CD25(low) and CD4(+) CD25(-) cells express little FOXP3 mRNA and low levels of the CTLA-4 protein. Mucosal CD4(+) CD25(high) T cells are present in individuals with asymptomatic H. pylori infections as well as in duodenal ulcer patients. The frequencies of CD4(+) CD25(high) cells are also increased in the stomachs of H. pylori-infected patients with gastric adenocarcinoma, particularly in cancer-affected tissues. These findings suggest that regulatory T cells may suppress mucosal immune responses and thereby contribute to the persistence of H. pylori infections.
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| 10. |
- Shaw, Lindsey N, et al.
(författare)
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Identification and characterization of sigma, a novel component of the Staphylococcus aureus stress and virulence responses.
- 2008
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 3:12
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Tidskriftsartikel (refereegranskat)abstract
- S. aureus is a highly successful pathogen that is speculated to be the most common cause of human disease. The progression of disease in S. aureus is subject to multi-factorial regulation, in response to the environments encountered during growth. This adaptive nature is thought to be central to pathogenesis, and is the result of multiple regulatory mechanisms employed in gene regulation. In this work we describe the existence of a novel S. aureus regulator, an as yet uncharacterized ECF-sigma factor (sigma(S)), that appears to be an important component of the stress and pathogenic responses of this organism. Using biochemical approaches we have shown that sigma(S) is able to associates with core-RNAP, and initiate transcription from its own coding region. Using a mutant strain we determined that sigma(S) is important for S. aureus survival during starvation, extended exposure to elevated growth temperatures, and Triton X-100 induced lysis. Coculture studies reveal that a sigma(S) mutant is significantly outcompeted by its parental strain, which is only exacerbated during prolonged growth (7 days), or in the presence of stressor compounds. Interestingly, transcriptional analysis determined that under standard conditions, S. aureus SH1000 does not initiate expression of sigS. Assays performed hourly for 72 h revealed expression in typically background ranges. Analysis of a potential anti-sigma factor, encoded downstream of sigS, revealed it to have no obvious role in the upregulation of sigS expression. Using a murine model of septic arthritis, sigS-mutant infected animals lost significantly less weight, developed septic arthritis at significantly lower levels, and had increased survival rates. Studies of mounted immune responses reveal that sigS-mutant infected animals had significantly lower levels of IL-6, indicating only a weak immunological response. Finally, strains of S. aureus lacking sigS were far less able to undergo systemic dissemination, as determined by bacterial loads in the kidneys of infected animals. These results establish that sigma(S) is an important component in S. aureus fitness, and in its adaptation to stress. Additionally it appears to have a significant role in its pathogenic nature, and likely represents a key component in the S. aureus regulatory network.
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