| 61. |
- Kristensen, Karl, et al.
(författare)
-
Increased plasma levels of ss(2)-microglobulin, cystatin C and ss-trace protein in term pregnancy are not due to utero-placental production.
- 2008
-
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 68, s. 649-653
-
Tidskriftsartikel (refereegranskat)abstract
- Objective . To study concentration gradients of the low molecular mass proteins, ss(2)-microglobulin, cystatin C and ss-trace protein, between the uterine and ante-cubital veins, the umbilical artery and vein and in the amniotic fluid compartment. Material and methods. The study comprised 27 healthy women with uncomplicated pregnancies undergoing caesarean section at term. Samples were collected simultaneously and paired t-tests were used to compare mean plasma concentrations. Results . There was no significant concentration gradient in the plasma levels of ss(2)-microglobulin, cystatin C or ss-trace protein between the uterine and antecubital veins. There were no correlations between the protein levels in the compartments. Conclusion . The utero-placental unit does not contribute significantly to the maternal levels of ss(2)-microglobulin, cystatin C and ss-trace protein in normal pregnancy, and the proteins are not likely to be transferred across the placental barrier.
|
|
| 62. |
- Kristensen, Karl, et al.
(författare)
-
Serum Amyloid A Protein and C-Reactive Protein in Normal Pregnancy and Preeclampsia.
- 2009
-
Ingår i: Gynecologic and Obstetric Investigation. - : S. Karger AG. - 1423-002X .- 0378-7346. ; 67:4, s. 275-280
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: To study plasma levels of serum amyloid A protein and C-reactive protein in pregnant women with and without preeclampsia and non-pregnant women. Plasma levels of haptoglobin, orosomucoid and ceruloplasmin were also analyzed. Methods: The study included 295 women with uncomplicated pregnancies, 57 women diagnosed with preeclampsia, and 58 healthy non-pregnant women. Plasma concentrations of acute phase proteins were analyzed by particle-enhanced immunoassays. Non-parametric Kruskal-Wallis and Mann-Whitney U tests were used to test differences between the groups. Results: Plasma levels of C-reactive protein and ceruloplasmin were increased in pregnant women with and without preeclampsia compared to non-pregnant women. Plasma levels of serum amyloid A protein and C-reactive protein were not elevated in women with preeclampsia compared to women with normal pregnancy. Conclusion: The description of preeclampsia as a systemic inflammatory state was not reflected in the plasma levels of serum amyloid A protein and C-reactive protein.
|
|
| 63. |
- Kristensen, Karl, et al.
(författare)
-
Temporal changes of the plasma levels of cystatin C, beta-trace protein, beta(2)-microglobulin, urate and creatinine during pregnancy indicate continuous alterations in the renal filtration process
- 2007
-
Ingår i: Scandinavian Journal of Clinical & Laboratory Investigation. - : Informa UK Limited. - 1502-7686 .- 0036-5513. ; 67:6, s. 612-618
-
Tidskriftsartikel (refereegranskat)abstract
- Objective. To determine the plasma levels of the renal functional markers creatinine, urate, cystatin C, beta(2)-microglobulin and beta-trace protein in samples from the first, second, early third and late third trimesters of 398 healthy women with uncomplicated singleton pregnancies. Material and methods. Plasma samples from 58 healthy non-pregnant women served as controls. The creatinine levels were significantly lower at all time-points in pregnancy, whereas the urate levels were lower during the first and second trimesters but increased in the late third trimester. The cystatin C, beta(2)-microglobulin and beta-trace protein levels displayed similar changes with increased levels in the third trimester but unaltered levels during the first and second trimesters. Results. The results indicate an increased filtration of low-molecular weight molecules during pregnancy, particularly during the first and second trimesters, whereas filtration of 10-30 kDa molecules is decreased in the third but unaltered in the first and second trimesters. The levels of albumin and alpha(2)-macroglobulin were measured in the same samples. Conclusions. The albumin levels decreased in the second and third trimesters, whereas the levels of alpha(2)-macroglobulin were unchanged, which is compatible with a virtually unaltered transfer of alpha(2)-macroglobulin between the intra-and extravascular space during pregnancy and a significantly increased extravascular fraction of albumin.
|
|
| 64. |
- Kristensen, Lars Erik, et al.
(författare)
-
Efficacy and tolerability of anti-TNF therapy in psoriatic arthritis patients: Results from the South Swedish Arthritis Treatment Group Register.
- 2008
-
Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 67, s. 364-369
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The use of tumour necrosis factor (TNF) blocking agents in psoriatic arthritis (PsA) is increasing, and the SSATG register has followed patients with PsA for more than 5 years. The aim of the present work therefore was to present efficacy and tolerability data of TNF-blocking agents on PsA in clinical practice, and to study potential predictors for drug survival (the length of time a patient continues to take a particular drug). Materials and methods: Patients (n = 261) with active PsA, starting anti-TNF therapy for the first time in southern Sweden, were included. Basal characteristics, disease activity measures, and termination reason for blockers were prospectively collected during the period April 1999 to September 2006. Cox proportional hazard models were used to investigate predictors for treatment termination. Results: Overall, response rates at 3–12 months for global visual analogue scale (VASglobal50) and pain VAS (VASpain50) were about 50%, whereas response rates for European League Against Rheumatism (EULAR) scoring "overall" and EULAR "good" were around 75% and 55%, respectively. Concomitant methotrexate (MTX) (hazard ratio (HR) 0.64, 95% CI 0.39–0.95, p = 0.03), etanercept (HR 0.49, 95% CI 0.28–0.86, p = 0.01), and high C-reactive protein (CRP) levels (HR 0.77, 95% CI 0.61–0.97, p = 0.03) at treatment initiation were associated with better overall drug survival. The improved drug survival of concomitant MTX appeared to be related to significantly fewer dropouts because of adverse events (HR = 0.24 (0.11–0.52), p<0.01). The blockers were well tolerated with a rate of serious adverse events of 5–6% per year. No unexpected serious adverse events were observed. Conclusion: Concomitant MTX and high CRP levels are associated with treatment continuation of anti-TNF therapy in patients with PsA regardless of joint distribution. The positive effect of MTX was primarily linked to fewer dropouts because of adverse events.
|
|
| 65. |
- Kristensen, Lars Erik, et al.
(författare)
-
Is Swollen to Tender Joint Count Ratio a New and Useful Clinical Marker for Biologic Drug Response in Rheumatoid Arthritis? Results From a Swedish Cohort
- 2014
-
Ingår i: Arthritis Care and Research. - : Wiley. - 2151-4658 .- 2151-464X. ; 66:2, s. 173-179
-
Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo study the impact of swollen to tender joint count ratio (STR) and other baseline characteristics on treatment response to a first course of anti-tumor necrosis factor (anti-TNF) therapy in rheumatoid arthritis (RA) patients. MethodsPatients with RA initiating their first course of anti-TNF treatment were included in a structured clinical followup protocol. Based on pragmatic thresholds and plausibility, patients were categorized as having low (STR <0.5), moderate (0.5 STR 1.0), or high (STR >1.0) joint count ratios. The data were collected and followed during the period of March 1999 through December 2010. ResultsA total of 2,507 patients were included in the study (median age 56 years, 78% women). Of these patients, 344 (14%) had a low STR, 1,180 (47%) had a moderate STR, and 983 (39%) had a high STR. According to these STR thresholds, 23% of patients (95% confidence interval [95% CI] 18-29%) with low, 39% (95% CI 35-43%) with moderate, and 40% (95% CI 36-44%) with high STR achieved the American College of Rheumatology criteria for 50% improvement (ACR50) response at 6 months after initiation. Correlation tests showed that STR was associated with ACR50 response independent of both swollen and tender joint counts. Logistic regression analysis consistently showed that moderate STR, high STR, not using prednisolone, high baseline Disease Activity Score in 28 joints, and low baseline Health Assessment Questionnaire scores were significantly associated with favorable ACR50 response with odds ratios of 1.93 (P < 0.01), 2.82 (P < 0.01), 0.65 (P < 0.01), 1.49 (P < 0.01), and 0.47 (P < 0.01), respectively. ConclusionSTR is a new and feasible predictor of treatment response in RA. RA patients with a moderate to high STR have a 2- to 3-fold increased likelihood of responding according to ACR50 criteria.
|
|
| 66. |
- Kristensen, Lars Erik, et al.
(författare)
-
Predictors of response to anti-TNF therapy according to ACR and EULAR criteria in patients with established RA: results from the South Swedish Arthritis Treatment Group Register.
- 2008
-
Ingår i: Rheumatology (Oxford, England). - : Oxford University Press (OUP). - 1462-0332 .- 1462-0324. ; 47:4, s. 495-499
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify factors predicting response to first TNF blocking treatment course in patients with established RA with a special focus on gender differences. METHODS: Patients with active RA initiating their first treatment course of TNF-blocking therapy were enrolled. The study period was March 1999 through September 2006. The prospective protocol included information on demographics, clinical characteristics of patients and response measures. Fulfilment of ACR 50-70% improvement and European League Against Rheumatism (EULAR) good response or remission [28-joint disease activity score (DAS28) <2.6] at 3 months were chosen as primary outcome measures. Potential predictors of responses were identified using multivariate binary logistic regression models. RESULTS: In total, 1565 patients were included in the study. Gender did not influence treatment response. Consistently, concomitant methotrexate (MTX) was significantly associated with EULAR remission, EULAR good response, ACR50 response and ACR70 response with odds ratios (ORs) 1.97, 2.13, 2.10 and 1.75, respectively. Concurrent treatment with other DMARDs was also significantly associated with EULAR remission, EULAR good response and ACR50 response (OR: 1.96, 2.24 and 1.94, respectively). Likewise, low HAQ at baseline consistently predicted good clinical outcome. Disease activity at baseline was directly associated with favourable response when measured by ACR50 and ACR70 (OR: 1.59 and 1.60, respectively), whereas DAS28 score at baseline was inversely associated with EULAR remission (OR: 0.78). CONCLUSIONS: In this observational study of patients with established RA, gender did not predict response to anti-TNF therapy, whereas treatment with concomitant DMARDs, especially MTX and low disability were associated with good response. Choice of outcome measures may influence the predictive value of baseline features.
|
|
| 67. |
- Kristensen, O, et al.
(författare)
-
Is tRNA binding or tRNA mimicry mandatory for translation factors?
- 2002
-
Ingår i: Current Protein and Peptide Science. - 1875-5550. ; 3:1, s. 133-141
-
Forskningsöversikt (refereegranskat)abstract
- tRNA is the adaptor in the translation process. The ribosome has three sites for tRNA, the: A-, P-, and E-sites. The tRNAs bridge between the ribosomal subunits with the decoding site and the mRNA on the small or 30S subunit and the peptidyl transfer site on the large or 50S subunit. The possibility that, translation release factors could mimic tRNA has been discussed for a long time, since their function is very similar to that of tRNA. They identify stop codons of the mRNA presented in the decoding site and hydrolyse the nascent peptide from the peptidyl tRNA in the peptidyl transfer site. The structures of eubacterial release factors are not yet known, and the first example of tRNA mimicry was discovered when elongation factor G (EF-G) was found to have a closely similar shape to a complex of elongation factor Tu (EF-Tu) with aminoacyl-tRNA. An even closer imitation of the tRNA shape is seen in ribosome recycling factor (RRF). The number of proteins mimicking tRNA is rapidly increasing. This primarily concerns translation factors. It is now evident that in some sense they are either tRNA mimics, GTPases or possibly both.
|
|
| 68. |
- Kristensen, O, et al.
(författare)
-
Structural characterization of the stringent response related exopolyphosphatase/guanosine pentaphosphate phosphohydrolase protein family
- 2004
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 43:28, s. 8894-8900
-
Tidskriftsartikel (refereegranskat)abstract
- Exopolyphosphatase/guanosine pentaphosphate phosphohydrolase (PPX/GPPA) enzymes play central roles in the bacterial stringent response induced by starvation. The high-resolution crystal structure of the putative Aquifex aeolicus PPX/GPPA phosphatase from the actin-like ATPase domain superfamily has been determined, providing the first insights to features of the common catalytic core of the PPX/GPPA family. The protein has a two-domain structure with an active site located in the interdomain cleft. Two crystal forms were investigated (type I and 11) at resolutions of 1.53 and 2.15 Angstrom, respectively. This revealed a structural flexibility that has previously been described as a "butterfly-like" cleft opening around the active site in other actin-like superfamily proteins. A calcium ion is observed at the center of this region in type I crystals, substantiating that PPX/GPPA enzymes use metal ions for catalysis. Structural analysis suggests that nucleotides bind at a similar position to that seen in other members of the superfamily.
|
|
| 69. |
- Kvale, Gerd, et al.
(författare)
-
Effect of D-Cycloserine on the Effect of Concentrated Exposure and Response Prevention in Difficult-to-Treat Obsessive-Compulsive Disorder : A Randomized Clinical Trial
- 2020
-
Ingår i: JAMA Network Open. - : American Medical Association (AMA). - 2574-3805. ; 3:8
-
Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: Evidence is lacking for viable treatment options for patients with difficult-to-treat obsessive-compulsive disorder (OCD). It has been suggested that D-cycloserine (DCS) could potentiate the effect of exposure and response prevention (ERP) treatment, but the hypothesis has not been tested among patients with difficult-to-treat OCD.OBJECTIVE: To evaluate whether DCS potentiates the effect of concentrated ERP among patients with difficult-to-treat OCD.DESIGN, SETTING, AND PARTICIPANTS: The study was a randomized placebo-controlled triple-masked study with a 12-month follow-up. Participants were adult outpatients with difficult-to-treat OCD. A total of 220 potential participants were referred, of whom 36 did not meet inclusion criteria and 21 declined to participate. Patients had either relapsed after (n = 100) or not responded to (n = 63) previous ERP treatment. A total of 9 specialized OCD teams within the public health care system in Norway participated, giving national coverage. An expert team of therapists from the coordinating site delivered treatment. Inclusion of patients started in January 2016 and ended in August 2017. Data analysis was conducted February to September 2019.INTERVENTIONS: All patients received individual, concentrated ERP treatment delivered during 4 consecutive days in a group setting (the Bergen 4-day treatment format) combined with 100 mg DCS, 250 mg DCS, or placebo.MAIN OUTCOMES AND MEASURES: Change in symptoms of OCD and change in diagnostic status. Secondary outcomes measures included self-reported symptoms of OCD, anxiety, depression, and quality of life.RESULTS: The total sample of 163 patients had a mean (SD) age of 34.5 (10.9) years, and most were women (117 [71.8%]). They had experienced OCD for a mean (SD) of 16.2 (10.2) years. A total of 65 patients (39.9%) were randomized to receive 100 mg DCS, 67 (41.1%) to 250 mg of DCS, and 31 (19.0%) to placebo. Overall, 91 (56.5%) achieved remission at posttreatment, while 70 (47.9%) did so at the 12-month follow-up. There was no significant difference in remission rates among groups. There was a significant reduction in symptoms at 12 months, and within-group effect sizes ranged from 3.01 (95% CI, 2.38-3.63) for the group receiving 250 mg DCS to 3.49 (95% CI, 2.78-4.18) for the group receiving 100 mg DCS (all P < .001). However, there was no significant effect of treatment group compared with placebo in obsessive-compulsive symptoms (250 mg group at posttreatment: d = 0.33; 95% CI, -0.10 to 0.76; 100 mg group at posttreatment: d = 0.36; 95% CI, -0.08 to 0.79), symptoms of depression and anxiety (eg, Patient Health Questionnaire-9 score among 250 mg group at 12-month follow-up: d = 0.30; 95% CI, -0.17 to 0.76; Generalized Anxiety Disorder-7 score among 100 mg group at 12-month follow-up: d = 0.27; 95% CI, -0.19 to 0.73), and well-being (250 mg group: d = 0.10; 95% CI, -0.42 to 0.63; 100 mg group: d = 0.34; 95% CI, -0.19 to 0.86). No serious adverse effects were reported.CONCLUSIONS AND RELEVANCE: In this study, DCS did not potentiate ERP treatment effect, but concentrated ERP treatment was associated with improvement. This randomized clinical trial evaluates whether D-cycloserine potentiates the effect of concentrated exposure and response prevention among patients with difficult-to-treat obsessive-compulsive disorder.
|
|
| 70. |
- Ladenson, Paul W, et al.
(författare)
-
Use of the Thyroid Hormone Analogue Eprotirome in Statin-Treated Dyslipidemia
- 2010
-
Ingår i: NEW ENGLAND JOURNAL OF MEDICINE. - 0028-4793 .- 1533-4406. ; 362:10, s. 906-916
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Dyslipidemia increases the risk of atherosclerotic cardiovascular disease and is incompletely reversed by statin therapy alone in many patients. Thyroid hormone lowers levels of serum low-density lipoprotein (LDL) cholesterol and has other potentially favorable actions on lipoprotein metabolism. Consequently, thyromimetic drugs hold promise as lipid-lowering agents if adverse effects can be avoided. METHODS We performed a randomized, placebo-controlled, double-blind, multicenter trial to assess the safety and efficacy of the thyromimetic compound eprotirome (KB2115) in lowering the level of serum LDL cholesterol in patients with hypercholesterolemia who were already receiving simvastatin or atorvastatin. In addition to statin treatment, patients received either eprotirome (at a dose of 25, 50, or 100 mu g per day) or placebo. Secondary outcomes were changes in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Patients were monitored for potential adverse thyromimetic effects on the heart, bone, and pituitary. RESULTS The addition of placebo or eprotirome at a dose of 25, 50, or 100 mu g daily to statin treatment for 12 weeks reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively, (mean reduction from baseline, 7%, 22%, 28%, and 32%). Similar reductions were seen in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Eprotirome therapy was not associated with adverse effects on the heart or bone. No change in levels of serum thyrotropin or triiodothyronine was detected, although the thyroxine level decreased in patients receiving eprotirome. CONCLUSIONS In this 12-week trial, the thyroid hormone analogue eprotirome was associated with decreases in levels of atherogenic lipoproteins in patients receiving treatment with statins.
|
|
