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Biomedical subjects

I Lundberg

Publications and source records attributed to I Lundberg.

At least 55 records · Page 3Linked to original sources

Genetic analysis of the contribution of IL10 to systemic lupus erythematosus.

OBJECTIVE: To study the contribution of the IL10 gene to the susceptibility to systemic lupus erythematosus (SLE). METHODS: Analysis by fluorescent-semiautomated genotyping of a dinucleotide repeat located in the promoter region of the IL10 locus (microsatellite G). RESULTS: No significant difference was found in the frequencies of the microsatellite alleles of 330 Mexican patients with SLE compared to 368 controls from the same population. Two-point linkage analyses were carried out using 13 Mexican, 13 Swedish, and 8 Icelandic families with 2 or more cases with SLE. No linkage was revealed between IL10 and SLE, using a variety of parameter settings. CONCLUSION: Our results do not support that the IL10 gene contributes to the susceptibility to SLE in the populations we studied.

Dinucleotide Repeats↗

Central nervous system nitric oxide formation in cerebral systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an inflammatory disease in which up to two thirds of the patients present neurological symptoms. The diagnosis of the disease is based on clinical findings and the presence of autoantibodies, and the pathogenesis is unclear. The purpose of this study was to determine if the pathogenesis was partly mediated via nitric oxide (NO) formation. Cerebrospinal fluid (CSF) samples from 15 patients with cerebral SLE were analyzed for the NO metabolites nitrite and nitrate using capillary electrophoresis. The severity of neurological symptoms was scored by dividing the patients into two groups with either mild or moderate/severe CNS involvement. All patients with cerebral SLE showed increased levels of NO metabolites. In CSF, there was a relationship between signs of NO production and clinical results showing that increased levels of nitrite and nitrate were associated with more severe neurological symptoms. These findings may shed new light on the pathogenesis of cerebral SLE, and analysis of nitrate and nitrate may prove to be of value in monitoring the activity of the disease.

Brain Diseases↗

Ro/SS-A and La/SS-B antibody level variation in patients with Sjögren's syndrome and systemic lupus erythematosus.

To examine both possible correlations between anti-Ro/SS-A and anti-La/SS-B levels and their correlation with clinical disease activity in patients with Sjögren's syndrome (SS) or systemic lupus erythematosus (SLE), an ELISA was developed using purified recombinant Ro 60 kDa, Ro 52 kDa and La antigens. The ELISA was used for testing sequential serum samples from 16 patients with either SS or SLE. The patients were followed for periods between 15 and 128 months, and 3-15 serum samples per patient were analysed and compared with clinically apparent disease activity at the time of sampling in 14 patients. A temporal correlation of antibody levels to Ro and La antigens was found, and antibodies to different epitopes of the Ro 60 kDa protein showed parallel variation in seven of eight patients tested. Co-variation of autoantibody levels and disease activity was found in 11 of 14 patients. In seven of these 11 patients the anti-Ro and anti-La levels were stable and changes in disease activity were minimal during the observation period. In the other four of these 11, changes in disease activity were noted, with an associated change in autoantibody levels. The results suggest that the serological response to Ro and La antigens, as well as to different epitopes of the Ro 60 kDa protein, is antigen driven and regulated by common mechanisms, and indicate a correlation of Ro and La antibodies with pathogenic events.

Adult↗

Increased serum levels of immunoglobulins, C-reactive protein, type 1 and type 2 cytokines in patients with mixed connective tissue disease.

It is controversial whether mixed connective tissue disease (MCTD) should be regarded as a distinct disease entity. In the present study, we investigated immunological parameters in patients with MCTD by studying serum levels of immunoglobulins, C-reactive protein (CRP) and cytokines and compared the results to the corresponding values in systemic lupus erythematosus (SLE), in rheumatoid arthritis (RA) patients and in healthy controls. Using the ELISA technique, serum levels of the cytokines interferon-gamma (IFN-gamma), interleukin-10 (IL-10) and tumour necrosis factor-alpha (TNF-alpha) were investigated. Cytokine levels in SLE and MCTD were correlated to disease activity as assessed by systemic lupus activity measure (SLAM). They were also correlated to serum levels of CRP, IgG, IgA and IgM in the three patient groups. The MCTD patients had the highest levels of immunoglobulins, followed by the SLE patients. In contrast, the highest CRP levels were observed in RA patients, followed by the MCTD patients. The MCTD patients had the highest serum levels of IL-10, but also had elevated IFN-gamma and TNF-alpha levels similar to the RA patients. There was no correlation between the investigated cytokine levels and disease activity, as assessed by SLAM. We conclude that MCTD patients have high immunoglobulin levels as well as high CRP levels and that this situation is compatible with the observed increase in both type 1 and type 2 cytokine levels. The findings imply that MCTD shares some distinct immunological properties with both RA and SLE and that MCTD may also be considered as a separate disease entity according to these properties.

Adult↗

Explanations of social class differences in alcoholism among young men.

The aim of this study was to analyse the role of differences in alcohol consumption and other risk factors for alcoholism established in late adolescence, for later differences in the distribution of alcoholism between social classes among young men. Data on risk factors in childhood and adolescence, e.g. risk use of alcohol, was collected among 49,323 men, born 1949-1951, at conscription for compulsory military training 1969/1970. Data on socio-economic group was obtained from the 1975 census and data on alcoholism diagnoses from the national in-patient care register 1976-1983. Several risk factors for alcoholism, such as risk use of alcohol, psychiatric diagnosis at conscription, parental divorce, low emotional control and contact with police and child care authorities, seemed to be more common among those who were recruited to blue-collar occupations compared to those who were recruited to non-manual occupations. In multivariate analyses, taking the background variables into consideration, the increased relative risks among manual workers for alcoholism diagnoses, found in univariate analyses, diminished considerably. Several risk factors had a stronger effect on the outcome among unskilled workers compared with non-manual employees at medium or higher degree. It is concluded that risk factors for poor health established in late adolescence could explain much of the increased relative risk of alcoholism among young unskilled and skilled male workers in this study.

Adult↗

Mortality of short-term workers in two international cohorts.

The purpose of this study was to compare the pattern of mortality of blue-collar workers employed less and more than 1 year in the man-made vitreous fiber (MMVF) and the reinforced plastic industries, the latter group being exposed to styrene. We conducted an analysis among 21,784 workers with less than 1 year of employment (short-term workers) and 19,117 workers with 1 or more years of employment (long-term workers) employed in eight European countries. We conducted analyses based on external as well as internal comparisons. In both cohorts, the standardized mortality ratio for all causes among short-term workers was approximately 40% higher, compared with that for longer-term workers. In internal comparisons, the difference was reduced to 9% in the MMVF cohort and 11% in the styrene cohort. Workers with less than 1 month of employment displayed an increased mortality in both cohorts and in most countries. The increased mortality among short-term workers was not concentrated shortly after they quit employment. In both cohorts, short-term workers had a higher mortality from external causes, while little difference was seen in mortality from ischemic heart disease and malignant neoplasms. Although extra-occupational factors may contribute to increase the mortality of short-term workers and, in particular, of those employed for less than 1 month, the difference observed in analyses adjusted for characteristics of employment suggested a relatively small difference in mortality from most causes.

Adult↗

Why is learning to read a hard task for some children?

In this brief review of some of my research on reading disability, I argue that a child's development into literacy has two major ontogenetic roots, one involving early informal literacy socialization and one related to phonological awareness. Although failure in reading acquisition might be a question of cultural deprivation, the dynamic interaction between genetic dispositions and environment must be acknowledged, especially in a society providing rich sources of print exposure. The crucial transition in literacy development involves a step from implicit to explicit control of the phonemic units of language. When the cipher of the alphabetic system is understood the child is equipped with a powerful instrument for self teaching. A primary source of reading disability is then related to problems of segmenting the speech stream into phonemic units. The poor functioning of the phonological module seems to be a circumscribed deficit not related to general cognitive ability. The causal and reciprocal relationship between phonological awareness and learning to read has been demonstrated in my research over 20 years. Some of these studies are briefly reviewed in this article. The preventive and remedial implications of the findings are rather obvious.

Awareness↗

Mortality and cancer incidence among Swedish paint industry workers with long-term exposure to organic solvents.

OBJECTIVES: The aim of this update on a cohort of male paint industry workers was to determine whether an excess of mortality and incidence of lymphatic and hematopoietic tumors, particularly multiple myeloma, still exists, and, if so, to determine if it is due to exposures occurring before the mid-1950s, when benzene disappeared as a solvent in the Swedish paint industry. METHODS: The cohort of 411 men who had worked in the Swedish paint industry and had been exposed to organic solvents for at least 5 years during 1955-1975 was followed from 1961 to 1994 for causes of death in the mortality register and from 1961 to 1992 for cases of cancer in the Swedish cancer register. RESULTS: The number of paint industry workers who had died, plus the number of deaths in the major disease groups and the number of cancers reported to the cancer registry, was close to the expected. The incidence of prostatic cancer increased somewhat [standardized incidence ratio (SIR) 1.5, 95% confidence interval (95% CI) 1.0-2.2]. Among the workers first employed in 1956 or earlier, there was an increase in both the incidence and mortality from all lymphatic and hematopoietic tumors [SIR 2.3, 95% CI 1.0-2.2; standardized mortality ratio (SMR) 2.0, 95% CI 0.7-4.4]. The excess was particularly marked for multiple myeloma (SIR 3.8, 95% CI 0.8-11; SMR 4.4, 95% CI 0.9-13). CONCLUSIONS: Employment in the Swedish paint industry before 1957 may have entailed some excess risk of lymphatic and hematopoietic tumors, particularly multiple myeloma. A significant excess of prostatic cancer was not linked to any particular employment period and deserves further investigation.

Adult↗

Work control, work demands, and work social support in relation to alcoholism among young men.

OBJECTIVES: The aim of the study was to estimate the impact of psychosocial work-environment factors, such as low work control, on alcoholism among young men. METHODS: Data on circumstances during childhood and adolescence, such as on risk use of alcohol, were collected for 49,323 young men, born 1949 to 1951 at time of enlistment for compulsory military training in 1969/1970. On the basis of census data on occupation in 1975, all individuals were classified into groups with regard to psychosocial work-environment factors in accordance with a job-exposure matrix. Follow-up for alcoholism diagnoses from inpatient care registers (1976 to 1983) was undertaken for each of the groups. A number of potential confounding factors were taken into account RESULTS: Low work control and also low job demands and low workplace social support were found to be related to later alcoholism. On separate analysis, the pattern among blue-collar workers was found to be similar to that of the entire population. When the analyses were extended to include indicators of risk use of alcohol and other relevant background factors, the relative risks decreased, but were still significantly high in the cases of low work control and low work social support. A combination of low demands and low control, what might be called a "passive" work environment, was related to an increased relative risk of psychiatric alcoholism diagnosis after controlling for relevant background factors. CONCLUSIONS: Low work control, in particular in combination with low work demands, and low work social support are related to later alcoholism even after controlling for previously known risk factors (including risk use of alcohol). The results suggest that young men may respond to an undemanding occupational environment by increasing their alcohol consumption.

Adolescent↗

Risk of cancer and exposure to gasoline vapors.

Until the introduction of self-service around 1970, service station workers in the Nordic countries were exposed to gasoline vapors. Based on measurements reported in the literature, the 8-hour time-weighted average benzene exposure was estimated to be in the range of 0.5-1 mg/m3. We studied the cancer incidence in a cohort of 19,000 service station workers from Denmark, Norway, Sweden, and Finland. They were identified from the 1970 censuses and followed through 20 years, where 1,300 incident cancers were observed. National incidence rates were used for comparison. The incidence was not increased for leukemia (observed = 28, standardized incidence ratio (SIR) = 0.9, 95% confidence interval (CI) 0.6-1.3) not for acute myeloid leukemia (observed = 13, SIR = 1.3, 95% CI 0.7-2.1). The incidence was slightly elevated for kidney cancer observed = 57, SIR = 1.3, 95% CI 1.0-1.7) and for pharyngeal, laryngeal, and lung cancer. A 3.5-fold risk of nasal cancer was found (observed = 12, SIR = 3.5, 95% CI 1.8-6.1). This cohort exposed to gasoline vapors with benzene levels estimated to be 0.5-1 mg/m3 showed no excess risk of leukemia or acute myeloid leukemia, a 30% elevated risk of kidney cancer, and a previously unnoticed risk of nasal cancer.

Air Pollutants, Occupational↗

Health-related selection to seafaring occupations and its effects on morbidity and mortality.

This study investigates the relative extents to which health-related selection and the occupation itself might explain increased mortality and morbidity among seafarers. The study group comprised a cohort of young men conscripted for compulsory military training in Sweden during 1969-1970. At conscription, information on ill health and also a number of health-related factors, such as alcohol consumption, was collected. Information on occupation over the period 1970-1990 was extracted from census data. Subjects were 206 men who had been seamen in either 1970 or 1975, or both. These men were compared with 16,292 other men who were unskilled workers during these years. Information on mortality, psychiatric diagnoses and early retirement was collected from relevant registers. Health-related selection was found among persons entering the occupation of seaman. Seamen were also found to have increased relative risks of mortality, early retirement, and psychiatric diagnosis (both related to and not related to alcohol or drug abuse), even after taking into account several background variables concerned with circumstances during childhood and adolescence. Health-related selection was only partly able to explain the increased relative risks faced by seamen found in this study. The occupation itself remains a strong risk indicator, even after controlling for a large number of selection factors.

Cohort Studies↗

Cytokine production in muscle tissue of patients with idiopathic inflammatory myopathies.

OBJECTIVE: To study cytokine expression in muscle tissues of patients with inflammatory myopathies and to compare the profiles of patients with polymyositis (PM), inclusion body myositis (IBM), and dermatomyositis (DM). METHODS: We performed indirect immunohistochemistry studies of muscle tissue sections with a panel of 16 different cytokine-specific monoclonal antibodies, directed against interleukin-1alpha, (IL-1alpha), IL-1beta, IL-1 receptor antagonist (IL-1Ra), IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, IL-13, interferon-gamma (IFN gamma), tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), transforming growth factor beta1 (TGF beta1), TGF beta2, and TGF beta3 in 5 untreated patients each with PM, DM, and IBM and in 4 normal controls. Fresh frozen muscle tissue sections were fixed in formaldehyde before the procedure. The use of saponin as a detergent to permeabilize the cell membranes enabled identification of intracellular cytokine production. RESULTS: The most prominent finding was the expression of IL-1alpha observed in all patients but in none of the normal controls. In all patients with PM, DM, and IBM, IL-1alpha was expressed in endothelial cells of capillaries, arterioles, and venules in areas surrounded by inflammatory cells, and also in areas with no or scarce inflammatory cells in both endomysium and perimysium. Furthermore, IL-1alpha was also expressed in mononuclear inflammatory cells in all 15 cases. IL-1beta was observed in inflammatory cells in 10 of the 15 patients but, in contrast to IL-1alpha, it was not expressed in blood vessel walls. TGF beta1, TGF beta2, and TGF beta3 were strongly positive in all 15 patients, but only scattered cells were positive in the normal controls. The remaining cytokines were observed only in relatively few cells and only in occasional patients (although the patients were selected for the presence of large infiltrates), and in none of the controls. The patterns were similar in PM, DM, and IBM. CONCLUSION: Cytokine expression in muscle tissue of patients with inflammatory myopathy is dominated by IL-1alpha, IL-1beta, and TGF beta1-3. The predominant IL-1alpha expression in the blood vessels indicates an importance of the endothelial cells in the inflammatory process in PM, IBM, and DM. A sustained, local release of T cell-derived cytokines may not be a requirement for tissue injury in the inflammatory myopathies. There does not appear to be a qualitative difference in cytokine expression patterns in PM, IBM, and DM.

Adult↗

European Union System for the Evaluation of Substances (EUSES). Principles and structure.

In the European Union, Directive 92/32/EC and EC Council Regulation (EC) 793/93 require the risk assessment of new and existing substances, respectively. Principles for this risk assessment have been laid down, supported by a detailed package of Technical Guidance Documents. Against this background the European Union System for the Evaluation of Substances (EUSES) has been developed. This software can be used to carry out tiered risk assessments of increasing complexity on the basis of increasing data requirements. The exposure assessment, effects assessment and risk characterisation are carried out for environmental populations as well as for human beings, including workers, consumers and man exposed through the environment. EUSES is the result of a co-ordinated effort of EU Member States, the European Commission and the European Chemical Industry.

Animals↗

Alcoholism in social classes and occupations in Sweden.

BACKGROUND: A number of studies have shown variations in the occurrence of alcoholism between different socioeconomic groups and occupations, but it has not been clear to what extent this is related to the average alcohol consumption in the same socioeconomic groups or occupations. METHODS: The relationship between socioeconomic group and occupation and hospital discharge 1981-1983 due to 'diagnoses related to alcoholism' (AD) (alcohol psychosis, alcoholism, and alcohol intoxication) and liver cirrhosis was studied in a cohort of 375,035 men and 140,139 women in 13 counties in Sweden who had reported the same occupation in the censuses of 1960 and 1970. Data on alcohol consumption in different socioeconomic groups and occupations were collected from a conscription investigation and from the Swedish twin registry with data from 1969/70 and 1973 respectively. RESULTS: Intermediate or higher non-manual employees had lower risk of AD as well as of liver cirrhosis compared to manual workers for both sexes. Among males several, mostly blue-collar, occupations had increased relative risks of AD. A high level of association was found between the relative risks of AD and liver cirrhosis in socioeconomic groups, and the relative risk of AD in occupations, and the average alcohol consumption in the same socioeconomic groups/occupations among males. Such an association was not evident among women. CONCLUSION: The study shows, contrary to previous Swedish evidence, that there is a strong relationship between the incidence of alcoholism in socioeconomic groups and occupations and the average alcohol consumption in these groups among men.

Alcohol Drinking↗

Occurrence of anti-C1q antibodies in IgA nephropathy.

BACKGROUND: The pathogenic mechanisms and the antigens involved in the establishment and progress of IgA nephropathy are unknown. As antibodies against C1q have been reported to correlate with SLE nephritis, we analysed the occurrence of these antibodies in IgA nephropathy in order to investigate the possibility of pathogenetic similarities in these renal disorders. METHODS: The occurrence of IgA- and IgG anti-C1q antibodies (anti-C1q) were determined by ELISA in patients with IgA nephropathy (n = 36) and SLE nephritis (n = 37), diseases both known to be associated with circulating immune complexes. Levels of these antibodies were also determined in two other glomerular diseases, i.e. idiopathic membranous glomerulonephritis (n = 7) and minimal change disease (n = 2), in which circulating immune complexes are usually not present, and in 40 healthy controls. RESULTS: IgA anti-C1q was observed in increased titres in 11/36 of the patients with IgA nephropathy, in 2/37 of the patients with SLE nephritis (both with proliferative disease) and in 1/9 of the patients with membranous and minimal change disease (P < 0.001). Increased titres of IgG anti-C1q were observed in 1/36 of the patients with IgA nephropathy, in 17/37 of the patients with SLE nephritis and in 0/9 of the patients with membranous and minimal change disease (P < 0.001). There were no correlations between the levels of anti-C1q antibodies and clinical parameters such as degree of proteinuria, haematuria, or renal function. Nor was there any correlation to the concentration of C3a and the terminal complement complex (TCC) in patients with IgA nephropathy. CONCLUSIONS: The occurrence of anti-C1q antibodies in both IgA nephropathy and SLE nephritis, albeit of different predominating isotypes, indicates the possibility of a similar pathogenic mechanism involved in these renal disorders. The occurrence of IgA anti-C1q antibodies in patients with IgA nephropathy has to our knowledge not previously been reported.

Adolescent↗

Association between ongoing anti-C1q antibody production in peripheral blood and proliferative nephritis in patients with active systemic lupus erythematosus.

The aim of this study was to compare ongoing production of anti-C1q antibodies (anti-C1q) in peripheral blood with serum anti-C1q levels in patients with systemic lupus erythematosus (SLE), especially in patients with nephritis. Using the ELISPOT technique for the detection of IgG and IgA anti-C1q production, 21 patients with active SLE were investigated. ELISAs for IgG and IgA anti-C1q were compared with the ELISPOT results. Six of the patients were found to have proliferative nephritis (WHO grade III/IV) confirmed by renal biopsy. High numbers of IgG anti-C1q spot-forming cells (SFC), defined as > 20/10(5) plated peripheral blood mononuclear cells (PBMC), were exclusively observed in patients with proliferative nephritis (P < 0.0001). Serum levels of IgG anti-C1q were significantly increased in patients with proliferative nephritis (P = 0.039). High ongoing IgG anti-C1q production was observed in all patients with proliferative nephritis, which may be a contributory factor in the pathogenesis of this disorder. The detection of IgG anti-C1q production may be valuable in the clinical investigation of patients with suspected SLE nephritis.

Adolescent↗

Predisposing factors in sulphasalazine-induced systemic lupus erythematosus.

The aim of this study was to define predisposing factors in patients with sulphasalazine-induced systemic lupus erythematosus (SLE). Eleven patients with onset of SLE or SLE-like syndromes during sulphasalazine treatment are reported. Before the onset of SLE, five of the patients suffered from rheumatoid arthritis (RA), one from psoriatic arthropathy (PsoA), two from juvenile chronic arthritis (JCA) and three from ulcerative colitis (UC). At the time of diagnosis of drug-induced SLE, analysis of antinuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), anti-histone antibodies (anti-histones), acetylator status of the enzyme N-acetyltransferase 2 (NAT2) and HLA classification were performed. All patients were anti-DNA positive at disease onset and were determined to be slow acetylators. HLA A1 occurred in 4/10 patients, B8 in 5/10. HLA DR 3 was represented in one patient and DR 3(17) in five patients. The DQA1* 0501 allele was observed in 7/10 patients and DQB1 0201* in 6/10. Persistent SLE and development of nephritis were noted in patients with long duration of treatment and high cumulative dose of sulphasalazine (> 1000 g). In sulphasalazine-induced SLE, slow acetylator genotype and HLA haplotypes associated with idiopathic SLE seem to predict disease induction. Further, as the risk of developing persistent SLE and nephritis increases with long-standing sulphasalazine medication, it is of importance to monitor the patients with regard to signs of SLE during the entire treatment period.

Adolescent↗

Dual-route and connectionist models: a step towards a combined model.

Current models of word recognition are mainly constructed within the frameworks of either dual-route or connectionist theories. The most important test of a word recognition model is how it succeeds in accounting for various reading behaviors. In the present paper dual-route and connectionist word recognition models are briefly described and evaluated. As a further development of these models, a combined framework is proposed. An amalgamation of the two main types of models might give a more satisfactory account of various phenomena within word recognition.

Child↗