Search PubMed⌕ Search

Biomedical subjects

I Lundberg

Publications and source records attributed to I Lundberg.

At least 37 records · Page 2Linked to original sources
PubMed2000

Decreased expression of interleukin-1alpha, interleukin-1beta, and cell adhesion molecules in muscle tissue following corticosteroid treatment in patients with polymyositis and dermatomyositis.

OBJECTIVE: To study the effects of immunosuppressive therapy, in particular, corticosteroids, on morphologic signs of inflammation and expression of cytokines, adhesion molecules, and class I major histocompatibility complex (MHC) antigen in muscle tissue from patients with polymyositis (PM) and dermatomyositis (DM) and to correlate the molecular changes with changes in muscle function. METHODS: Seven patients with PM and 4 patients with DM underwent muscle biopsy before and after 3-6 months of therapy. Ten of the 11 patients were initially treated with prednisolone 30-60 mg/day. The phenotypes of infiltrating inflammatory cells and the expression of interleukin-1alpha (IL-1alpha) and IL-1beta, adhesion molecules, and class I MHC antigen were studied by immunochemistry. Computerized image analysis was used for quantitation of staining. Muscle function was assessed with a muscle function index score. RESULTS: Pronounced improvement of muscle function during the treatment period was noted in 8 of the 11 patients. The changes in muscle function coincided with an almost complete disappearance of inflammatory cells, including CD3+ T cells, in the patients with clinical improvement. These patients also exhibited decreased expression of IL-1alpha, IL-1beta, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), leukocyte function-associated antigen 1alpha, and very late activation antigen 4alpha. Of note, there was persistent expression of IL-1alpha, ICAM-1, and VCAM-1 in capillaries and of class I MHC antigens on muscle fibers in several of the patients who, after corticosteroid treatment, still had muscle weakness despite the disappearance of inflammatory infiltrates. CONCLUSION: Changes in the muscle expression of key molecules in the inflammatory process, such as IL-1alpha and IL-1beta, ICAM-1 and class I MHC antigens, showed a consistent but not complete concordance with changes in and status of muscle function in patients with myositis who received the current standard treatment for the disease. These data indicate that it is possible to further evaluate various therapies for myositis using molecular analysis of muscle biopsy specimens obtained on repeated occasions. In addition, the data demonstrate a dissociation between muscle function and degree of inflammatory infiltration in the affected muscles and suggest that the functional defects are more related to the expression of molecules such as IL-1alpha in muscle capillaries than to the mere presence of inflammatory cells in the affected muscles.

Adrenal Cortex Hormones↗
PubMed2000

A susceptibility locus for human systemic lupus erythematosus (hSLE1) on chromosome 2q.

To identify chromosomal regions containing susceptibility loci for systemic lupus erythematosus (SLE), we performed genome scans in families with multiple SLE patients from Iceland, a geographical and genetic isolate, and from Sweden. A number of chromosomal regions showed maximum lod scores (Z) indicating possible linkage to SLE in both the Icelandic and Swedish families. In the Icelandic families, five regions showed lod scores greater than 2.0, three of which (4p15-13, Z=3.20; 9p22, Z=2.27; 19q13, Z=2.06) are homologous to the murine regions containing the lmb2, sle2 and sle3 loci, respectively. The fourth region is located on 19p13 (D19S247, Z=2.58) and the fifth on 2q37 (D2S125, Z=2.06). Only two regions showed lod scores above 2.0 in the Swedish families: on chromosome 2q11 (D2S436, Z=2. 13) and 2q37 (D2S125, Z=2.18). The combination of both family sets gave a highly significant lod score at D2S125 of Z=4.24 in favor of linkage for 2q37. This region represents a new locus for SLE. Our results underscore the importance of studying well-defined populations for genetic analysis of complex diseases such as SLE.

Animals↗
PubMed2000

Kinetics of anti-fibrillin-1 autoantibodies in MCTD and CREST syndrome.

Using a highly sensitive Radioimmunoassay (RIA), the kinetics of synthesis of anti-fibrillin (Fbn-1) autoantibodies were studied in 17 patients with mixed connective tissue disease (MCTD) and two with CREST syndrome calcinosis, Raynaud's oesophageal dismotility, sclerodectyly and teleangiectasis who were found to be positive for this autoimmune response. IgG autoantibodies specific for recombinant Fbn-1 (rFbn-1) (aa 369-425) were found in all patients excepting one with MCTD, multiple sclerosis, and dermatomyositis. IgM were found in fewer cases. Several kinetics patterns of anti-Fbn-1 autoantibodies were observed: a) long lasting persistence of IgG and IgM autoantibodies up to 14 years; b) fluctuation of antibodies during various periods up to 16 years; c) disappearance of antibody response after several years, and d) patients producing IgG but not IgM autoantibodies. No differences in the synthesis of autoantibodies were observed between MCTD patients with a stable disease, and those developing during the course features of systemic sclerosis (SSc), Sjogren's syndrome, or rheumatoid-like arthritis. In one patient displaying a lupus-like syndrome for 3 years, the appearance of anti-Fbn-1 autoantibodies coincided with the occurrence of MCTD and scleroderma. While the detection of anti-Fbn-1 autoantibodies may be clinically useful in differential diagnosis or eventual prognosis of patients with connective tissue diseases, their role in the pathogenesis of scleroderma syndromes requires further investigation.

Autoantibodies↗
PubMed2000

Association analysis with microsatellite and SNP markers does not support the involvement of BCL-2 in systemic lupus erythematosus in Mexican and Swedish patients and their families.

We have described suggestive linkage between microsatellite markers within the cytogenetic region 18q21-23 and SLE, a region where linkage with other autoimmune diseases has also been detected. The Bcl-2 gene located within this region, is a candidate gene because of its role in apoptosis, a physiological mechanism that could be deregulated in autoimmune disease. Furthermore, several studies have found abnormalities of Bcl-2 expression in SLE patients. We therefore sought to determine if the Bcl-2 gene is involved in SLE by studying members of a large cohort of Mexican SLE patients (n = 378) and 112 Swedish simplex families. Using a microsatellite marker and two single nucleotide polymorphisms located within the gene, we were unable to detect association between Bcl-2 and SLE in either population. We also tested whether combinations of alleles of the Bcl-2 and IL-10.G microsatellites would increase the risk for SLE. Our results do not support such hypothesis. Our findings suggest that linkage between SLE and the 18q21-23 region is due to a gene other than Bcl-2.

Alleles↗
PubMed2000

The safety of a resistive home exercise program in patients with recent onset active polymyositis or dermatomyositis.

The objective was to investigate whether a 12-week resistive home exercise program in addition to conventional medical treatment could be safely performed regarding muscle inflammation, muscle function, and quality of life in patients with active polymyositis (PM) or dermatomyositis (DM). Eleven patients diagnosed with active PM or DM were included. Muscle biopsies and Magnetic Resonance Imaging (MRI) of the thighs were performed. Quality of life, function, and subjective global disease impact (SGDI) were assessed and creatine phosphokinase levels (CPK) were analysed. The patients exercised with the exercise program for 15 minutes and took a 15-minute walk five days a week for 12 weeks. After the exercise period there was no sign of increased muscle inflammation. The group showed significantly improved function and quality of life compared to the start of study. It seems that this exercise program safely can be employed in patients with active PM or DM, and we suggest that physical exercise should be included in the rehabilitation of these patients.

Adult↗
PubMed2000

Increased expression of interleukin 1alpha and MHC class I in muscle tissue of patients with chronic, inactive polymyositis and dermatomyositis.

OBJECTIVE: To investigate if there is a molecular correlate in muscle tissue to the persisting decreased muscle function in patients with chronic, inactive polymyositis (PM) and dermatomyositis (DM). METHODS: Muscle function was assessed using a muscle function index of myositis. To assess disease activity both histopathological investigation of muscle biopsies and magnetic resonance imaging (MRI) scans of the thigh muscles were performed. Inactive chronic disease was defined as persisting muscle weakness and absence of inflammatory infiltrates in muscle biopsy and absence of signs of inflammation on MRI. Expression of interleukin 1alpha (IL-1alpha), IL-1beta,, adhesion molecules, and MHC class I molecules in muscle tissue was investigated with immunohistochemistry. RESULTS: Muscle weakness was confirmed by a reduction of muscle function score. No signs of inflammation typical for myositis were observed. The most striking finding in our study was the strong expression of IL-1alpha and MHC class I molecules in muscle tissue from patients with inactive chronic PM and DM. Increased IL-1alpha expression was evident in capillaries and increased MHC class I expression was detected in muscle fiber membranes. CONCLUSION: IL-1alpha and MHC class I molecules may have an importance in the pathogenesis of the chronic muscle weakness and fatigue in patients with PM and DM.

Adult↗
PubMed1999

Key residues revealed in a major conformational epitope of the U1-70K protein.

Epitopes depending on three-dimensional folding of proteins have during recent years been acknowledged to be main targets for many autoantibodies. However, a detailed resolution of conformation-dependent epitopes has to date not been achieved in spite of its importance for understanding the complex interaction between an autoantigen and the immune system. In analysis of immunodominant epitopes of the U1-70K protein, the major autoantigen recognized by human ribonucleoprotein (RNP)-positive sera, we have used diversely mutated recombinant Drosophila melanogaster 70K proteins as antigens in assays for human anti-RNP antibodies. Thus, the contribution of individual amino acids to antigenicity could be assayed with the overall structure of the major antigenic domain preserved, and analysis of how antigenicity can be reconstituted rather than obliterated was enabled. Our results reveal that amino acid residue 125 is situated at a crucial position for recognition by human anti-RNP autoantibodies and that flanking residues at positions 119-126 also appear to be of utmost importance for recognition. These results are discussed in relation to structural models of RNA-binding domains, and tertiary structure modeling indicates that the residues 119-126 are situated at easily accessible positions in the end of an alpha-helix in the RNA binding region. This study identifies a major conformation-dependent epitope of the U1-70K protein and demonstrates the significance of individual amino acids in conformational epitopes. Using this model, we believe it will be possible to analyze other immunodominant regions in which protein conformation has a strong impact.

Amino Acid Sequence↗
PubMed1999

Increased number of interleukin-10-producing cells in systemic lupus erythematosus patients and their first-degree relatives and spouses in Icelandic multicase families.

OBJECTIVE: To evaluate the production of interleukin-10 (IL-10) as well as levels of IgG and antinuclear antibodies (ANA) in systemic lupus erythematosus (SLE) patients and their first-degree relatives and spouses in Icelandic SLE multicase families. METHODS: IL-10 production was studied by enzyme-linked immunospot assay of freshly isolated peripheral blood mononuclear cells. Total IgG and ANA were also investigated. Subjects consisted of 23 SLE patients and 47 of their first-degree relatives in 9 Icelandic multicase families. Subjects were ethnically matched by a group of healthy controls. A separate study investigated 12 SLE patients (also from SLE multicase families) and their spouses and a matched group of healthy controls. A predefined protocol was used to obtain both clinical and laboratory data, including information about SLE and other autoimmune disorders. RESULTS: The SLE patients had a significantly higher number of IL-10-producing cells compared with both first-degree relatives and healthy controls (P = 0.0005 and P < 0.0001, respectively). First-degree relatives also had a significantly higher number of IL-10-producing cells compared with healthy controls (P = 0.01). This was also true for the spouses of SLE patients, who had a higher number of IL-10-producing cells compared with matched healthy controls (P = 0.02). CONCLUSION: SLE patients and their first-degree relatives, as well as a limited number of healthy spouses of SLE patients, had increased numbers of spontaneous IL-10-producing cells. These data support the hypothesis that IL-10 production may be genetically determined, and may predispose one toward development of SLE. This has previously been suggested by studies of SLE patients and their relatives in another ethnic population, using another method for measuring IL-10 production. Although these data are based on a small number of observations, they suggest that not only genetic but also environmental factors may be of importance in determining IL-10 production, since the spouses of SLE patients also had an increased number of IL-10-producing cells.

Autoantibodies↗
PubMed1999

A comparison of genome-scans performed in multicase families with systemic lupus erythematosus from different population groups.

Systemic lupus erythematosus is a disease of unknown etiology. Multiple genetic factors are believed to be involved in its pathogenesis. In addition, and due to genetic heterogeneity, these factors and/or their combinations may be different in different ethnic groups, while some might be shared between populations. We have performed genome scans in multicase families from three different population groups, two from Northern Europe, with a high degree of homogeneity, and the third from a recently admixed population of Mexican Mestizos. Although our family material is relatively small, the results presented here show that using family sets from well defined populations are sufficient to detect susceptibility loci for SLE. Our results also reveal the chromosomal regions most likely to contain susceptibility genes for SLE.

Ethnicity↗
PubMed1999

Psychosocial characteristics in young men as predictors of early disability pension with a psychiatric diagnosis.

BACKGROUND: There is little knowledge about disability pensions (DPs) in psychiatric diagnoses. The aim of this study was to analyse risk factors among men for receiving an early disability pension with a psychiatric diagnosis. METHODS: The study is based on data from a nationwide survey of 49 285 young Swedish men who were conscripted into military service in 1969/1970. Potential psychosocial and behavioural risk factors were linked to records from the Swedish Social Insurance Board up until 1993. RESULTS: The majority (63.4%) of the men granted a DP during follow-up had a psychiatric diagnosis as the main and/or secondary diagnosis. Among those conscripts analysed (41 702), 599 had been granted a disability pension with a psychiatric diagnosis. Of these, 35.4% had a diagnosis of psychosis, 23.2% an alcohol- or drug-related diagnosis, and 41.4% 'other' psychiatric diagnosis. Receiving a psychiatric diagnosis at conscription, showing low emotional control, unemployment after graduation, and ranking low on an "IQ" test were strong predictors of all categories of DP with psychiatric diagnoses. In multivariate analysis controlling for the effect of all other risk indicators included in the model, DP with non-alcohol- and non-drug-related psychiatric diagnoses was related to low social support at adolescence but not to signs of extrovert deviant behaviour (risky use of alcohol or contact with police and child authorities). In contrast, DP with an alcohol- or drug-related diagnosis had strong associations with signs of extrovert deviant behaviour. The risk pattern of DP without psychiatric diagnoses was similar to that of DP with a psychosis but also, though to a lesser extent, to that of DP with 'other' psychiatric diagnosis. These similarities could be interpreted as showing that the diagnoses on the records of disability pensions have a low sensitivity and/or specificity or, alternatively, that the risk factors found are risk factors for life careers steering toward a disability pension rather than toward the specific health outcomes per se. CONCLUSIONS: The results illustrate the importance of psychosocial factors established in late adolescence in the complex pathway of a decision of an early DP.

Adult↗
PubMed1999

Organophosphate neuropathy due to methamidophos: biochemical and neurophysiological markers.

Neuropathy target esterase (NTE), the putative target enzyme for organophosphate induced delayed polyneuropathy (OPIDP), can be measured in lymphocytes but has rarely been assessed in acute human poisoning. Serum autoantibodies to nervous system proteins develop in hens poisoned with neuropathic insecticides and also have not been studied after human poisoning. Serial lymphocyte NTE (LNTE) was measured in a 16-year-old boy after acute poisoning with methamidophos for evaluation as a predictor of subsequent neuropathy. The profiles of serum autoantibodies to neurofilament triplet proteins, myelin basic protein, and glial fibrillary acidic protein were measured in order to characterize changes occurring as a result of OPIDP. Clinical neuropathy characterized by steppage gate and profound lower extremity weakness, decreased grip and pinch strength, and decreased ulnar and absent tibial compound muscle action potentials developed 2 weeks following poisoning. Sensory examination and nerve conduction studies were normal. On day 3 following poisoning LNTE was depressed (77% compared with subsequent baseline enzyme activity). Marked increases in serum immunoglobulin G (IgG) autoantibodies to glial fibrillary acidic protein and to neurofilament 200 were observed after the development of OPIDP. We conclude that inhibition of lymphocyte NTE is predictive of subsequent OPIDP. Serum autoantibody titers to nervous system proteins may be useful markers of neuropathy.

Adolescent↗
PubMed1999

The roles of social class of origin, achieved social class and intergenerational social mobility in explaining social-class inequalities in alcoholism among young men.

The aim of this study was to investigate the role of intergenerational health-related mobility in explaining social-class inequalities in alcoholism among young men. Data on social class of origin and on risk factors in childhood and adolescence, e.g. risk use of alcohol, were collected for 49,323 men, born 1949-51, at enlistment for compulsory military training in 1969/70. Information on achieved socioeconomic class was obtained from Sweden's 1975 census. Data on alcoholism diagnoses were collected from the national in-patient care register 1976-83. Risk indicators for alcoholism established in adolescence were found to be more common among downwardly mobile individuals, and also among stable manual workers, than among those who ended up as non-manual employees. Downwardly mobile individuals, and also stable manual workers, were also found to have an increased risk of alcoholism diagnosis. The increased relative risk could, to a considerable extent, be attributed to factors from childhood/adolescence. In this longitudinal study, it is shown that intergenerational social mobility associated with health-related factors, albeit not with illness itself, made a major contribution to explaining differences in alcoholism between social classes. Factors established in adolescence were important with regard to differences in alcoholism between social classes among young adults. But such adverse conditions did not seem to be well reflected by social class of origin.

Adult↗
PubMed1999

Antibodies to adult human endothelial cells cross-react with oxidized low-density lipoprotein and beta 2-glycoprotein I (beta 2-GPI) in systemic lupus erythematosus.

Cardiovascular manifestations are common in systemic lupus erythematosus (SLE). Oxidized low-density lipoprotein (oxLDL) is implicated in cardiovascular disease, especially atherosclerosis, and cross-reacts with antibodies to cardiolipin (aCL). beta 2-GPI is a plasma protein participating in the coagulating cascade, and is also cofactor for aCL, and some aCL have been shown to be directed against beta 2-GPI and/or complexes between beta 2-GPI and phospholipids. Lysophosphatidylcholine (LPC) is a phospholipid present both in oxLDL and in damaged endothelium, and we recently showed that LPC is involved in the antigenicity of oxLDL. Antibodies to endothelial cells (aEC) correlate with diseases activity in SLE and vasculitis, and we recently showed that aEC are enhanced in cardiovascular disease such as borderline hypertension and early atherosclerosis. aEC were determined using EC from adult V. Saphena Magna. Antibody levels were determined by ELISA. aEC of IgG type were enhanced in 184 patients with SLE compared with 85 healthy controls. There was a close correlation between aoxLDL, aCL, aLPC, a beta 2-GPI and aEC. Binding of sera to EC was competitively inhibited by beta 2-GPI, LPC and oxLDL. Taken together, the data indicate that EC share antigenic epitopes with beta 2-GPI and with oxLDL, especially LPC. Phospholipids in EC membranes may thus be antigenic epitopes. beta 2-GPI may bind to these phospholipids, and become an autoantigen. LPC is formed by oxidation of phospholipids and/or proinflammatory factors leading to activation of phospholipase A2, and the findings indicate the potential role of both lipid oxidation and phospholipase A2 in SLE.

Adult↗
PubMed1999

Exercise and variations in neuropeptide concentrations in rheumatoid arthritis.

The aim of the present study was to investigate the influence of an exercise program on neuropeptide concentrations, disease activity, impairments and disabilities in rheumatoid arthritis (RA). Eleven females (median age 60 years, median disease duration 6.5 years, ARA functional classes I or II) exercised 30 min daily for 4 weeks. The urine concentrations of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and neuropeptide Y-like immunoreactivity (NPY-LI) were analyzed 1 week prior to exercise start, at exercise start, after 2 and 4 weeks of exercise, and after a 4-week follow-up period. Measurements of disease activity, aerobic capacity, grip force, limb muscle function, and activities of daily living (ADL) were also undertaken. The results indicate a decrease (md 5.64 pM to md 3.48 pM, P</=0.05) of CGRP-LI concentrations after 4 weeks' exercise. NPY-LI concentrations remained unchanged, as did disease activity and aerobic capacity. Muscle function and ADL capacity improved significantly (P</=0.05) after the exercise period. Only the improved grip force remained after the follow-up period. In conclusion the results indicate that decreased CGRP-LI concentration, probably reflecting a decreased sympathetic tone, follows physical exercise and suggest that regular physical activity might be important among individuals with RA to maintain a decreased sympathetic tone and less symptoms from their disease.

Adult↗
PubMed1999

Safety of a home exercise programme in patients with polymyositis and dermatomyositis: a pilot study.

OBJECTIVES: To investigate whether a home exercise programme could safely be performed by patients with stable, inactive polymyositis (PM) and dermatomyositis (DM), regarding disease activity, muscle function, health status and pain. METHODS: Ten patients with reduced muscle function completed the study. A home exercise programme including exercises for strength in the upper and lower limbs, neck and trunk, for mobility in the upper limbs and moderate stretching was developed. The patients exercised for 15 min and took a 15 min walk 5 days a week during a 12 week period. Assessments included clinical evaluation of disease activity, serum creatinine phosphokinase (CPK) levels, magnetic resonance imaging (MRI) of the quadriceps, repeated muscle biopsy of the vastus lateralis, a muscle function index (FI), a walking test and a health status instrument (the SF 36) performed at the start of the study and after 12 weeks. RESULTS: After 12 weeks of exercise, there were no signs of increased disease activity as assessed clinically, by CPK values, MRI or muscle biopsy findings. On an individual basis, all patients improved regarding muscle function according to the FI, in six cases the improvement reached statistical significance (P < 0.05). A significant improvement regarding muscle function in the upper and lower limbs, walking distance and general health status was achieved. CONCLUSIONS: Our results indicate that this home exercise programme can be safely employed in patients with stable, inactive PM and DM, with beneficial effects on muscle function.

Adult↗
PubMed1999

Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE.

Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein (oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL) and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2 or by oxidation. We here demonstrate the presence of enhanced antibody levels to LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The antibody reactivity to LPC was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic acid showed equivalent antibody levels as LPC containing unsaturated fatty acids. aPC were significantly lower as compared to aLPC, indicating that hydrolysis of PC at the sn-2 position increases the antigenic potential of the molecule. Beta-glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the antigenicity of these compounds is therefore not directly related to beta2GP1. There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a common antigenic site, which could be formed by removal of a fatty acid at the sn-2 position, possibly due to the activity to phospholipase A2 and/or oxidation. This study indicates the potential role of LDL-oxidation and phospholipase A2 in SLE.

Adult↗
PubMed1999

Collaboration between developing and developed countries and between developing countries in occupational health research and surveillance.

Collaborative occupational health and safety studies between counterparts in developing and developed countries and between developing countries have demonstrated their potential for improving occupational health and safety. Such collaboration in occupational health and safety is encouraged in the development of infrastructure in research empowerment and capacity building. This action includes the setting of priorities, the identification and documentation of problems, sponsorship, data bases and surveillance systems, technical support, methodology, publishing, research and training programs, controlled intervention, information exchange, and networking. Examples of priorities in occupational health and safety in the developing world include the informal sector (informally hired and independent workers), temporary work, pesticides, accidents, dusts, carcinogens, solvents, ergonomics, women and child labor, human immunodeficiency virus/acquired immunodeficiencey syndrome (HIV/AIDS), and transfer of hazardous materials and technologies. The sustainability of occupational health and safety structures and functions in the developing countries is a primary concern. Socioethical principles emphasize local, national, mutual and global gains. Examples of collaboration are given. Pervasive problems and strategies toward their solution are highlighted.

Developed Countries↗