Assessment of class-specific antibodies against denatured DNA in patients with systemic lupus erythematosus

In this retrospective study 103 serum samples from 16 females with systemic lupus erythematosus (SLE), obtained during a mean follow-up time of 2 years, were investigated for the presence of anti-denatured [single-stranded (ss)] DNA antibodies of the IgG, IgM, and IgA classes. The anti-ssDNA antibodies were determined by an enzyme-linked immunosorbent assay (ELISA), and the results were expressed in three ways: as units derived from a single serum dilution and as two parameters,E andA, calculated from the dose-response curve,E being an estimate of the effective amount of antibodies andA a function of the reaction constant between the antigen and the antibody. The simultaneous occurrence of anti-ssDNA antibodies of all three immunoglobulin classes was seen most often in the patients with the shortest duration of the disease. Clinically active disease was found to correlate with high reaction constants of the IgA anti-ssDNA antibodies. There was also an association between the IgA anti-ssDNA antibody levels and the presence of nephritis. Great fluctuations in the amounts of effective antibodies of the IgG class were seen in seven patients, in six of whom changes in the disease activity also were seen. Changes in the disease activity were unaccompanied by fluctuations in the IgG anti-ssDNA levels in four patients; two of these patients were positive for antibodies against extractable nuclear antigens. We conclude that it is of value to express the results of the anti-ssDNA ELISA as a function of the dose-response curve when monitoring patients with SLE and that immunoglobulin class-specific determinations of anti-ssDNA antibodies may provide information about the disease activity in many patients with SLE.     

Haplotypic association of DDAH1 with susceptibility to pre-eclampsia

Association between pre-eclampsia (PEE1) and the dimethylarginine dimethylaminohydrolase (DDAH) 1 and 2 genes, which play a role in the regulation of nitric oxide synthesis and release, was studied. In a case-control study design single nucleotide polymorphisms (SNPs) were determined at eight sites in the DDAH1 gene and at one site (Pro231Pro) in the DDAH2 gene from 132 women with pre-eclampsia and 112 healthy controls. Three SNPs in the DDAH1 gene were associated with pre-eclampsia, showing complete linkage disequilibrium with each other, but none of the associations in the allele or genotype data reached statistical significance in either of the genes after the correction for multiple testing. Haplotype frequencies were estimated using a population based on a maximum likelihood method (EM algorithm). Four common DDAH1 haplotypes were present and a significant association of haplotypes H2 and H3 with pre-eclampsia (P=0.03) was found. The risk of pre-eclampsia was greatest in individuals (odds ratio: 3.93; 95% confidence interval: 1.54-9.99) who had two copies of the high-risk haplotypes (H2 or H3). The observed haplotypic association provides the first evidence of the importance of DDAH1 polymorphisms in pre-eclampsia susceptibility.     

Characterization of GPRA, a novel G protein-coupled receptor related to asthma

We recently identified a novel positional asthma susceptibility gene, GPRA, which belongs to the G protein-coupled receptor family. In the present studies, we show that isoform specific activation of GPRA-A with its agonist, Neuropeptide S (NPS) resulted in significant inhibition of cell growth. GPRA has several variants due to extensive alternative splicing. We observed that only the full-length variants, GPRA-A and GPRA-B, with 7 transmembrane topology are transported into the plasma membrane, while the truncated proteins retain intracellular compartments. To clarify disease mechanism, we studied co-expression of the variants without finding any indication that truncated variants would inhibit the receptor transport into the plasma membrane. By using in situ hybridization and immunohistochemistry, we detected ubiquitous expression of GPRA-B, and frequent expression of GPRA-A in the epithelia of several organs including bronchi and gastrointestinal tract. Furthermore, we observed aberrant mRNA and protein expression levels of GPRA in the asthmatic bronchi. Finally, we demonstrate that GPRA and NPS are co-expressed in bronchial epithelium. In summary, this study provides evidence that GPRA might have functional relevance in modulating asthma by increased expression levels in the relevant tissues under diseased state and by potential inhibitory effect of GPRA-A activation on cell growth.     

beta2-adrenergic receptor gene polymorphisms in myasthenia gravis (MG)

The beta2-adrenergic receptor (beta2-AR) belongs to the group of G-protein coupled receptors and is present mainly on skeletal and cardiac muscle cells and lymphocytes. The gene encoding beta2-AR (ADRB2) displays a moderate degree of heterogeneity in the human population. The distribution of polymorphisms at amino acid positions 16, 27 and 164 is changed in asthma, hypertension and obesity. We have earlier reported a decreased density of the beta2-AR on peripheral blood mononuclear cells and the presence of beta2-AR antibodies in patients with MG. Since certain polymorphisms affect the function of the beta2-AR, it was of interest to analyse these in MG. Using allele-specific polymerase chain reaction amplification, we revealed an over-representation of homozygosity for Arg16 and a lower prevalence of homozygosity for Gly16 in MG patients compared with healthy individuals. The increased frequency of homozygosity for Arg16 was due to a contribution from patients with generalized MG but not from patients with only ocular disease. Homozygosity for Glu27 was negatively associated with both the presence of beta2-AR antibodies and severity of disease. Moreover, acetylcholine receptor (AChR) antibodies were more often present in patients being homozygous for Gln27. Our results imply that homozygosity for Arg16 confers susceptibility to generalized MG, and that certain polymorphisms at amino acid position 27 are associated with subgroups of patients.     

Polymorphisms at - 174 and in the 3' flanking region of interleukin-6 (IL-6) gene in patients with myasthenia gravis

We examined the bi-allelic polymorphism at - 174 in the promoter region and the polymorphism in the 3' flanking AT rich region of the interleukin-6 (IL-6) gene in Swedish patients with myasthenia gravis (MG) and ethnically matched healthy individuals. There was no association between the polymorphisms and the disease. There was no relation of the polymorphisms to the clinical variables, the thymic histopathologies, the level of serum acetylcholine receptor antibodies or the concentrations of IgG and its subclasses. Our data yield no evidence for the IL-6 gene contributing to the disease susceptibility.     

Trusting and misleading. Parents’ and children’s communication and negotiation about alcohol as described by teenagers

Background: Typically, research on parents’ and children’s interactions around alcohol issues focuses on how parenting styles and parents’ examples affect teenager’s drinking habits. In this paper, we approach the theme from the youngsters’ perspective. We ask how teenagers describe the interaction on alcohol-related issues with their parents and how they would like their parents to act during these interactions.

Data and methods: The article applies the concept of trust, which is seen as a feature connecting all kinds of communities, and especially families. We pay attention to whether alcohol issues challenge trustful relations and give rise to contradictions and complications in the interactions between parents and children.

Results: The analysis shows the ways how trust is maintained and challenged in teenagers? accounts of communication regarding alcohol with their parents. It also shows that although trust is tested in several ways, it is essential for teenagers. Even though teenagers tell how they can mislead their parents by using strategies that challenge trust, they nevertheless highlight the importance of trusting ties with parents. Teenagers do not exclude their parents from alcohol-related discussion but expect rules, communication and authority from them. Our data suggest that teenagers also want to protect their parents from disappointments caused by their own actions.

Conclusions: A trusting parent–child relationship, based on dialog rather than opposition, seems to play a significant role in guiding teenagers’ alcohol-related attitudes and practices.     

The holistic approach to rehabilitation: A commentary

Abstract

Maria Pachalska's approach to aphasia rehabilitation is from a holistic perspective. Traditionally, aphasia therapists have tried to promote communicative ability using several methods. Pachalska has combined the most important approaches and created a model which she calls the Complex Aphasia Rehabilitation Model (CARM). She offers this model as an example of a holistic approach to aphasia rehabilitation. It stresses the importance of taking into account both psychological and social factors in aphasia rehabilitation.     

Low biological aggressiveness of screen-detected lung cancers may indicate over-diagnosis

All cases of lung cancer diagnosed in the Tampere University Hospital catchment area in 1983–1987 were identified, analyzed for DNA flow cytometry and followed up to 1992. The patients were classified into 3 groups: screen-detected, symptom-detected, and detected by chance. The biological aggressiveness as indicated by DNA flow cytometry was not related to the survival of the symptom-detected patients. Also the screen-detected patients with an aggressive tumour (aneuploid or high S-phase fraction, SPF) had the same survival as the symptom-detected patients. The survival of screen-detected patients with a diploid or low SPF tumour was significantly better than that in the other groups. It is concluded that some of the previously known discrepancy of no effect on mortality and effect on survival of lung-cancer screening may be due to over-diagnosis, i.e., detection of morphologically malignant but biologically indolent lesions by screening. © 1996 Wiley-Liss, Inc.     

Clinical characteristics and factors affecting growth in long-term survivors of cancer

We evaluated clinical characteristics and growth in 51 (24 males) long-term survivors of childhood cancer (median follow up 12.7 years). Patients were shorter, had a higher proportion of body fat and higher systolic blood pressure than their controls. The change in relative height during treatment was −0.83 standard deviation score (S.D.S.) in patients with cranial irradiation and −0.32 S.D.S. in patients without cranial irradiation; the figures after treatment were −0.56 and 0.20 S.D.S., respectively. Half (r² = 0.50) of the variation in growth retardation during therapy could be explained by the cumulative doses of 6-mercaptopurine (6-MP) and vincristine and relative height at diagnosis. Cranial irradiation, increased relative height at diagnosis and young age at diagnosis were significant predictors of growth failure over the total observation period, explaining 43% of the variation. We conclude that long-term survivors of childhood cancer have impaired linear growth, increased body fat mass and elevated systolic blood pressure. Young children who are tall for their age at diagnosis and treated with cranial irradiation have the highest risk of impaired growth after the diagnosis. High doses of 6-MP seem to contribute significantly to growth retardation during therapy. © 1996 Wiley-Liss, Inc.