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Biomedical subjects

J G Brun

Publications and source records attributed to J G Brun.

At least 19 recordsLinked to original sources
PubMed2006

Circulating cytokines in Norwegian patients with psoriatic arthritis determined by a multiplex cytokine array system.

OBJECTIVES: Serum cytokines play an important role in the pathogenesis of psoriatic arthritis (PsA) by initiating and perpetuating various cellular and humoral autoimmune processes. The aim of this study was to describe a broad spectrum of T- and B-cell cytokines, growth factors and chemokines in patients with PsA and healthy individuals. METHODS: A novel protein array system, denoted as multiplex cytokine assay was utilized to measure simultaneously the levels of 23 circulating cytokines of patients with PsA and healthy individuals. Additionally, correlational clustering and discriminant function analysis (DFA), two multivariate, supervised analysis methods were employed to identify a subset of biomarkers in order to describe potential functional inter-relationships among these pathological cytokines and identify biomarkers with prognostic and diagnostic utility. RESULTS: Univariate analysis demonstrated that serum levels of a complex set of immune and inflammatory modulating cytokines are significantly up-regulated in patients with PsA relative to unaffected controls including interleukin (IL)-10, IL-13, interferen (IFN)-alpha, epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), fibroblast growth factor [CCL3 macrophage inflammatory protein (MIP)-1alpha], CCL4 (MIP-1beta) and CCL11 (Eotaxin), while granulocyte-colony stimulating factor was significantly reduced in PsA patients. Correlational clustering was able to discriminate among, and hence subclassify, patients with varying levels of disease activity, which may prove useful in guiding therapy in these apparently phenotypically distinct disease subsets. DFA identified EGF, IFN-alpha, VEGF, CCL3 (MIP-1alpha) and IL-12p40 as analytes with the strongest discriminatory power among various PsA patients and controls. CONCLUSIONS: Our findings suggest that these factors modulate PsA pathology and the articular involvement in a synergistic manner. Identifying factors could be used in the development of clinical diagnostic tests, which are valuable to guide evidence-based diagnosis and disease management of PsA.

Adult↗
PubMed2005

Salivary gland and temporomandibular joint involvement in rheumatoid arthritis: relation to disease activity.

OBJECTIVES: To study temporomandibular joint (TMJ) involvement, salivary gland dysfunction and oral mucosal lesions in rheumatoid arthritis (RA), and to investigate the relationship to general disease activity. SUBJECTS AND METHODS: The TMJ dysfunction index (D(i)), mean salivary flow and disease activity score (DAS28), were calculated for 50 RA-patients, and 23 non-RA patients (controls). RESULTS: Median D(i) was 5.5 (range: 0-21) for the RA-patients compared with 2.0 (range: 0-9) for the controls (P < 0.0001). Pain on movement of the TMJ (P = 0.015), muscular pain (P = 0.006), TMJ pain (P = 0.019) and D(i) as a total (P = 0.009), significantly correlated with DAS28. Mean resting whole saliva (RWS) flow was 2.6 (s.d. 2.4) ml per 15 min for the RA-patients and 4.5 (s.d. 3.0) for the controls (P = 0.003). RWS correlated positively with haemoglobin (P = 0.021) and negatively with Westergren erythrocyte sedimentation rate (ESR) (P = 0.029). No major differences in frequency of oral mucosal lesions were seen between RA-patients and controls. CONCLUSIONS: Higher frequency of TMJ and salivary gland dysfunction in RA-patients compared with controls has been demonstrated. RA disease activity is associated with hyposalivation and TMJ dysfunction.

Adult↗
PubMed2004

Reduced joint pain after short-term duodenal administration of seal oil in patients with inflammatory bowel disease: comparison with soy oil.

BACKGROUND: Rheumatic joint pain is a common extra-intestinal complication of inflammatory bowel disease (IBD). Because the high ratio of n-6 to n-3 fatty acids (FAs) of the Western diet might promote rheumatic disorders, we sought to compare the effects of short-term duodenal administration of n-3-rich seal oil and n-6-rich soy oil on IBD-related joint pain. METHODS: Nineteen patients with IBD-related joint pain were included in the study; 9 had Crohn disease and 10 had ulcerative colitis. Ten millilitres seal oil (n = 10) or soy oil (n = 9) was self-administered through a nasoduodenal feeding tube 3 times daily for 10 days. RESULTS: Compared with soy oil treatment, seal oil significantly reduced the duration of morning stiffness (P = 0.024), number of tender joints (P = 0.035), intensity of pain (P = 0.025) and the doctor's scoring of rheumatic disease activity (P = 0.025) at the end of the 10-day treatment period. Analysis of the effects as area under the curve (area between the curve and baseline, zero) for the entire period from start of treatment until 6 months' post-treatment suggested a long-lasting beneficial effect of seal oil administration on joint pain, whereas soy oil tended (not significantly) to aggravate the condition. Consistently, the serum ratios of n-6 to n-3 FAs (P < 0.01) and arachidonic acid to eicosapentaenoic acid (P < 0.01) were reduced after treatment with seal oil. CONCLUSION: The results suggest distinctive, differential prolonged effects on IBD-related joint pain of short-term duodenal administration of n-3-rich seal oil (significant improvement) and n-6-rich soy oil (tendency to exacerbation).

Adolescent↗
PubMed2004

Circulating cytokines in primary Sjögren's syndrome determined by a multiplex cytokine array system.

Plasma cytokines play an important role in the pathogenesis of Sjögren's syndrome (SS) by initiating and perpetuating various cellular and humoural autoimmune processes. The aim of the present study was to describe a broad spectrum of T-cell and B-cell cytokines, growth factors, chemokines and molecules that could contribute to cell death in SS. A novel protein array system was utilized to measure simultaneously the levels of 25 plasma cytokines of patients with primary SS and healthy individuals. Furthermore, we correlated these plasma cytokine levels with potential laboratory and clinical parameters related to disease activity in SS. A subset of plasma cytokines [e.g. interleukin-1beta (IL-1beta), IL-6, CXCL8 (IL-8), IL-12 p40, IL-15, tumour necrosis factor-alpha (TNF-alpha), epidermal growth factor, CCL4 (MIP-1beta), CCL2 (MCP-1), CCL11 (Eotaxin), CCL5 (RANTES), TNF-RI and TNF-RII] was found to significantly differ between patients and controls. Also, distinct populations of cytokines were found to differentiate between patients with normal versus elevated ESR or IgG levels and patients with the presence or absence of extra-glandular manifestations (EGMs). Our results support the assumption that the multiplex cytokine array system can be successfully utilized in the diagnosis and disease management of SS. Furthermore, it may provide a powerful tool in the design of individualized anticytokine therapies.

Adult↗
PubMed2002

Sjögren's syndrome in an out-patient clinic: classification of patients according to the preliminary European criteria and the proposed modified European criteria.

OBJECTIVES: To investigate whether out-patients with a clinical diagnosis of Sjögren's syndrome (SS) satisfied current preliminary European criteria for SS, and to determine the proportion of patients who satisfied the proposed modified European criteria for SS and thus had indication of an autoimmune process. METHODS: Out-patients with a clinical diagnosis of SS registered between 1 January 1999 and 1 November 2000 were included in the study. RESULTS: Of 203 patients with a clinical diagnosis of SS, 116 (57.1%) satisfied the current European criteria and 83 (40.9%) satisfied the proposed modified criteria. CONCLUSIONS: Sicca symptoms and signs may have a variety of causes. In our study only 40.9% of the patients with a clinical diagnosis of SS satisfied the proposed modified European criteria and had evidence of SS as an autoimmune condition. Our findings indicate that for patient populations with an established diagnosis of SS according to the preliminary European criteria, approximately one-third will lose the diagnosis according to the modified criteria.

Autoimmunity↗
PubMed1999

Complement activation in patients with systemic lupus erythematosus without nephritis.

OBJECTIVE: To study the association between disease activity and complement activation prospectively in patients with systemic lupus erythematosus (SLE). PATIENTS AND METHODS: Twenty-one SLE patients were examined monthly for 1 yr. Disease activity, autoantibodies, conventional complement tests and the following complement activation products were investigated: C1rs-C1inh complexes, C4bc, Bb, C3a, C3bc, C5a and the terminal SC5b-9 complement complex (TCC). RESULTS: Modest variation in disease activity was noted. None of the patients had nephritis. Flare was observed at 27 visits. Four patients had anti-C1q antibodies in conjunction with modestly low C1q concentrations. The complement parameters were rather constant during the observation period. Slightly to moderately decreased C4 (0.05-0.10 g/l) was found in 10 patients and severely decreased C4 (<0.05 g/l) in seven patients. Decreased C4 was not associated with increased complement activation. Complement activation products were either normal or slightly elevated. TCC was the only activation product correlating significantly with score for disease activity at flare. None of the variables tested predicted flares. CONCLUSION: Complement tests are of limited importance in routine examination of SLE without nephritis, although TCC is suggested to be one of the most sensitive markers for disease activity.

Adult↗
PubMed1999

Seasonal variations in activity of systemic lupus erythematosus in a subarctic region.

Photosensitivity is one of the major clinical features of Systemic Lupus Erythematosus (SLE), and is considered to be implicated in the disease pathogenesis. We studied seasonal variations of SLE disease activity at latitude 70 degrees North where there is no sunlight in the winter time, in contrast to 24 h daily sunlight in the summer (midnight sun). The associations between the level of plasma melatonin in June and December with disease manifestations were also studied. Twenty-one SLE patients were examined each month for 1 y, and disease activity was assessed by laboratory parameters as well as clinical disease activity parameters SLEDAI and doctor's global assessment. Melatonin levels were quantified by a RIA-assay. There was no significant change of clinical measures or laboratory parameters of disease activity from one month to the next during the one year, except photosensitive rashes. January was the only month without SLE-flares or arthritis, in contrast to rest of the year. The levels of plasma melatonin were highest in December for seven patients and highest in June for one patient (P < 0.005). Plasma melatonin levels did not correlate with measures of clinical disease activity. At a latitude of 70 degrees North there were no major seasonal variations in SLE disease activity during the one year. There was an accumulation of photosensitivity in the summer months, but no indications of worsening of the disease in the winter months. In contrast to the rest of the year, there was no flare in January which had only 5.6 h of sunshine. The level of p-melatonin did not correlate with measures of disease activity.

Adult↗
PubMed1996

Immunohistochemical characterization of the cellular infiltrates in Sjögren's syndrome, rheumatoid arthritis and osteoarthritis with special reference to calprotectin-producing cells.

The aim of this study was to analyse the nature of infiltrating cells in minor salivary glands of patients with Sjögren's syndrome (SS). Furthermore, we wanted to characterize the tissue distribution of calprotectin-producing cells in inflamed salivary gland tissue of SS and in synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Cryostat sections of labial salivary gland tissue from patients with SS and synovial tissue from RA and OA patients were stained (ABC-immunoperoxidase technique) using monoclonal antibodies (MoAbs) to T cells (CD3), monocytes/macrophages (CD14, CD68), and calprotectin. Monocytes and macrophages were widely distributed in focal infiltrates of salivary gland tissue from SS patients. Calprotectin markers showed a distinct staining of infiltrating macrophages and around blood vessel walls. In synovial tissue samples, calprotectin was expressed in a high percentage of cells in the synovial lining, the subsynovium, and vessel walls. The percentages of cells stained for calprotectin were significantly higher in RA than in OA and SS tissues. Antibodies to the calprotectin complex stained cells with a similar distribution as antibodies against the separate polypeptide chains of calprotectin. The localization and differentiated expression of calprotectin in these chronic inflammatory conditions indicate a role in the inflammatory process and may be an additional marker of macrophages/granulocytes in SS, RA and OA.

Arthritis, Rheumatoid↗
PubMed1996

Pristane-induced arthritis in rats: a new model for rheumatoid arthritis with a chronic disease course influenced by both major histocompatibility complex and non-major histocompatibility complex genes.

We present a novel animal model for rheumatoid arthritis induced with a well defined synthetic adjuvant oil, pristane. Two weeks after a single intradermal injection of 150 microliters of pristane, the rats developed severe and chronic arthritis. The inflammation was restricted to the joints and involved pannus formation, major histocompatibility complex (MHC) class II expression, and T lymphocyte infiltration. The initial development as well as the chronic stage of pristane-induced arthritis was ameliorated by treatment with antibodies to the alpha beta-T-cell receptor showing that the disease is T cell dependent. Increased levels of interleukin in serum was seen after pristane injection but not during the chronic stage of arthritis. Joint erosions were accompanied by elevated serum levels of cartilage oligomeric matrix protein. Comparison of MHC congenic LEW strains showed that the severity and chronicity of arthritis varied among the different MHC haplotypes. Rats with RT1f haplotype showed a significantly higher susceptibility to pristane-induced arthritis. A strong influence of non-MHC genes was also suggested by the variability of arthritis susceptibility among different strains with the same MHC haplotype; the most susceptible background was the DA and the least susceptible was the E3. Arthritis induced with a well defined nonimmunogenic adjuvant, with a disease course that closely resembles that of rheumatoid arthritis, makes a suitable animal model for future studies of the pathology and genetics of rheumatoid arthritis.

Animals↗
PubMed1995

Breast feeding, other reproductive factors and rheumatoid arthritis. A prospective study.

The evidence regarding reproductive events as risk factors for rheumatoid arthritis (RA) is not conclusive. In the present study a population-based cohort consisting of 63,090 women were followed from 1961 to 1989. Detailed data on reproductive factors were collected through personal interviews in the period 1956-9. The endpoint used was mention of RA on the death certificate. Mortality rate ratios were estimated by Poisson regression, controlling for various demographic variables. During 1,485,400 person-yr of observation, a total of 355 cases with RA mentioned on the death certificate were identified. Total time of lactation was associated with a decreased mortality of RA, with an approximate dose-response relationship. The results did not support a role of parity, age at first and last birth, or age at menarche and menopause in the development of RA. This protective effect of lactation on the development of RA has not previously been described, and since a definite biological explanation is lacking, the association should be confirmed in other populations.

Adult↗
PubMed1995

Calprotectin levels in oral fluids: the importance of collection site.

Calprotectin is a major protein of granulocytes and monocytes with antimicrobial properties, and is released during activation or cell death. In the present study the levels of calprotectin in various oral fluids were analyzed in 12 healthy adults using different collection devices. Parotid saliva, stimulated whole saliva and "mucosal transudate" were collected and analyzed by enzyme-linked immunosorbent assay (ELISA). The results showed mean concentrations of 3.2, 22.0 and 40.9 mg/l in the respective oral fluids, illustrating great variation of calprotectin levels between different oral fluids. The results are in accordance with the composition of these saliva samples; the lowest calprotectin level was obtained in parotid saliva, which contains the purest secretion. These findings illustrate the importance of careful sampling procedures. The levels of salivary calprotectin are markedly influenced by the site of collection.

Adult↗
PubMed1995

Effects of calprotectin in avridine-induced arthritis.

Plasma levels of calprotectin correlate with disease activity and clinical assessments of arthritis in various rheumatic diseases, and high levels have been demonstrated in the synovial fluid of patients with rheumatoid arthritis. However, the role of calprotectin in rheumatic inflammation is unclear. The purpose of the present study was to investigate potential intra-articular effects of calprotectin. Calprotectin was injected into joints of healthy male Lewis rats and into joints of rats in the latency period before onset of avridine-induced arthritis. In addition, a group of animals had IgG antibodies to rat calprotectin injected into joints before onset of avridine-induced arthritis. Injection of 0.2 or 10 micrograms calprotectin into the ankles of healthy male Lewis rats resulted in histologically minor and reversible inflammatory changes, but without any circulating antibodies to calprotectin. Furthermore, animals with 40 micrograms calprotectin injected into ankles before the expected onset of avridine-induced arthritis had lower scores for cellular infiltration than were seen in control joints. This difference did not quite reach statistical significance in the two-sided test used. However, the induced arthritis increased in joints injected with IgG antibodies to calprotectin. These findings may indicate that increased local concentrations of calprotectin are partially protective against avridine-induced arthritis. In contrast, reduced local concentrations appear to exacerbate the severity of arthritis. Calprotectin may thus be involved in the regulation of inflammatory processes in joints.

Adjuvants, Immunologic↗
PubMed1994

Effects of human calprotectin (L1) on in vitro immunoglobulin synthesis.

Calprotectin (L1) is a major cytoplasmic protein of neutrophilic granulocytes and monocytes/macrophages which is released from leucocytes during activation or cell death. Apart from in vitro antimicrobial and antiproliferative activity little is known about the biological function of the protein. Since previous investigations have shown that calprotectin plasma levels are elevated in various inflammatory rheumatic diseases, we wanted to investigate if calprotectin has an effect on immune cell functions. Peripheral blood mononuclear cells, either unstimulated or polyclonally stimulated with mitogen, were incubated with calprotectin and effects were assessed by enumeration of immunoglobulin secreting cells (ELISPOT). The results indicate that incubation with high concentrations of calprotectin (> 64 micrograms/ml) inhibit the production of the three classes of immunoglobulins investigated (IgG, IgM and IgA), both for mitogen stimulated and unstimulated lymphocytes. Except for the highest concentration of calprotectin (500 micrograms/ml), it seems plausible that the observed inhibitory effect of calprotectin on Ig production is not a result of a direct toxic effect of calprotection on B lymphocytes. Altogether, these effects of high calprotectin levels might be of importance in the immunoregulation of inflammatory conditions.

Adult↗
PubMed1994

Sjögren's syndrome in inflammatory rheumatic diseases: analysis of the leukocyte protein calprotectin in plasma and saliva.

In a hospital population of 154 patients with a wide range of inflammatory rheumatic diseases, patients with sicca symptoms were subjected to objective ocular and oral tests to establish cases with Sjögren's syndrome (SS). The plasma level of the leukocyte protein calprotectin has been shown to be a good indicator of disease activity and inflammation in various rheumatic diseases. In the present study, calprotectin levels in plasma and whole saliva were analysed and evaluated as potential markers of SS and salivary gland disease activity. Plasma calprotectin levels did not differ significantly between patients with SS and patients with no sicca symptoms. However, salivary calprotectin levels correlated significantly with the plasma calprotectin levels and with several ocular variables, weakly with salivary flow and serum rheumatoid factor, but not with focal sialadenitis. In conclusion, this study shows that salivary calprotectin levels seem to be associated with several variables of SS glandular pathology, indicating the need for further and more comprehensive studies on calprotectin in various oral fluids and in lacrimal fluid in relation to SS glandular disease activity.

Blood↗
PubMed1994

Measurement of plasma calprotectin as an indicator of arthritis and disease activity in patients with inflammatory rheumatic diseases.

OBJECTIVE: To investigate if the plasma level of the granulocyte protein calprotectin is a useful indicator of severity of arthritis in patients with inflammatory rheumatic diseases, and to analyze which factors contribute to the raised plasma calprotectin levels. METHODS: Plasma calprotectin levels were measured by ELISA: In a cross sectional study of 154 patients with various inflammatory rheumatic diseases, calprotectin levels were correlated with laboratory and clinical variables. RESULTS: The plasma levels of calprotectin and C-reactive protein (CRP) correlated significantly with the clinical evaluation of swollen joints (r = 0.51, p < or = 0.01 and r = 0.29, p < or = 0.01, respectively). Calprotectin levels, but not CRP levels or erythrocyte sedimentation rate, were significantly lower in patients with no swollen joints than in patients with one or more swollen joints (2613.6 micrograms/l vs 6287.0 micrograms/l, p < 0.001). A significant correlation between calprotectin and number of neutrophils was demonstrated (r = 0.43, p < or = 0.01), indicating that circulating neutrophils contribute to plasma calprotectin levels. CONCLUSION: The plasma calprotectin level may be a useful indicator of arthritis in inflammatory rheumatic diseases.

Adolescent↗
PubMed1993

Calprotectin in patients with systemic lupus erythematosus: relation to clinical and laboratory parameters of disease activity.

Calprotectin (L1) is a granulocyte and monocyte cytosolic protein released during activation of these cells. The plasma level of L1 has been shown to be a good marker of disease activity in rheumatoid arthritis. In this cross-sectional study of 100 patients with systemic lupus erythematosus (SLE), the serum level of L1 was found to be higher in patients than in matched controls (3661 micrograms/l versus 1051 micrograms/l; P < 0.001). The serum level of L1 was the only laboratory parameter with significant association to the disease activity index SLEDAI (r = 0.28; P < 0.01). Furthermore, the serum level of L1 was significantly higher in SLE patients with anti-DNA antibodies compared to patients without anti-DNA antibodies (4501 micrograms/l versus 3279 micrograms/l; P = 0.01). SLE patients with arthritis had higher serum levels of L1 than patients without arthritis (7652 micrograms/l versus 2811 micrograms/l; P < 0.01), indicating that the serum level of L1 also reflects arthritis activity in SLE.

Adult↗
PubMed1992

Morning stiffness and nightime pain in ankylosing spondylitis. A comparison between enteric-coated and plain naproxen tablets.

Thirty-nine patients with ankylosing spondylitis participated in a randomized, double-blind, double-dummy, multi-cross-over study with enteric-coated (ECT) and plain (PT) naproxen tablets. The duration of the study was 24 days with 6 treatment periods of 4 days. The majority of the patients were taking 750 mg naproxen daily. The mean plasma concentration of naproxen in the morning was 36% higher with ECT (p < 0.001). No significant differences regarding duration of morning stiffness and night time pain were found in this patient category. The mean duration of morning stiffness was 116 minutes (ECT) and 125 minutes (PT). We were not able to show correlation between plasma concentration of naproxen and duration of morning stiffness.

Adolescent↗