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Biomedical subjects

G Andersson

Publications and source records attributed to G Andersson.

At least 91 records · Page 5Linked to original sources
PubMed1998

Retroelements in the human MHC class II region.

Molecular genetic studies of the human major histocompatibility complex (MHC) have led to the identification of more than 200 genes. Besides the large number of genes in the MHC, densely clustered areas of retroelements have been identified. These include short and long interspersed elements (SINEs and LINEs), and human endogenous retroviruses (HERVs). The presence of retroelements in the MHC provides a clear example of how these elements affect the genome plasticity of the host. Comparative analyses of these retroelements have proven highly useful in evolutionary studies of the MHC. Recently, HERV-encoded superantigens have been implicated as candidate autoimmune genes in type I diabetes and multiple sclerosis. In addition, genetic analyses have revealed that autoimmune diseases show strong associations with MHC class II genes. The intriguing correlations between retroviral encoded antigens, MHC class II genes and the development of autoimmune disease merit intense future investigations of retroelements, in particular those endogenous retroviruses located in the MHC class II region proper.

Antigens↗
PubMed1998

Feasibility and effectiveness of providing vestibular rehabilitation for dizzy patients in the community.

Since the majority of people with dizziness in the community are never referred for specialist testing and treatment, the purpose of this study was to investigate whether it was desirable and feasible to provide vestibular rehabilitation for this patient population. Demand for therapy was assessed by a survey of 9198 working age people randomly sampled from six general practices. One in 10 respondents reported current, handicapping dizziness, but fewer than 2% of those with dizziness severe enough to merit treatment proved suitable and willing to attend hospital for testing and rehabilitation. Nevertheless, vestibular rehabilitation was clearly beneficial for the 16 patients who completed the therapy programme, as their scores on measures of symptoms, disability, handicap and postural stability improved significantly post-therapy to near-normal levels. We conclude that there is a need for provision of vestibular rehabilitation in primary care for patients with dizziness in the community.

Adolescent↗
PubMed1998

Beneficial role of human endogenous retroviruses: facts and hypotheses.

Human endogenous retroviruses (HERVs) have recently been suggested as mediators of normal biological processes such as cellular differentiation and regulation of gene expression. Moreover, a direct role for HERVs in pathogenesis and the development of disease is now better appreciated. Elucidation of the mechanisms regulating HERV biology should provide information about fundamental cellular activities and the pathogenesis of multifactorial diseases such as cancer and autoimmune disease. The importance of understanding the roles of HERVs is underscored by the recently obtained insight that activation of endogenous retroviruses poses potential risks following xenotransplantation and in gene therapy using retroviral vectors. Furthermore, HERV-encoded superantigens have recently been implicated as causes of autoimmune disease. This review discusses the established and possible biological roles of HERVs, and proposes hypotheses concerning their involvement as mediators of fundamental cellular responses. We propose that the evolutionary persistence of endogenous retroviruses in the genomes of eukaryotic cells reflects their indispensability in important normal functions in specialized cellular environments. HERVs can also be potentially hazardous through their involvement in the development of disease. In addition, the creation of new retroviruses can occur through recombination, between different HERVs and between HERVs and exogenous retroviruses.

Cell Differentiation↗
PubMed1998

Activated transcription of the human neuropeptide Y gene in differentiating SH-SY5Y neuroblastoma cells is dependent on transcription factors AP-1, AP-2alpha, and NGFI.

Activated transcription of the human neuropeptide Y gene (NPY) was investigated in SH-SY5Y neuroblastoma cells at the onset of sympathetic neuronal differentiation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA) and serum or by nerve growth factor (NGF). As determined by transient expression, two NGF response elements (REs) were required for transcription induced by NGF in SH-SY5Y cells with stable expression of an exogenous NGF receptor TRK-A gene (SH-SY5Y/trk). TPA treatment in the presence of serum induced NPY transcription in both wild-type SH-SY5Y (SH-SY5Y/wt) and SH-SY5Y/trk cells. A TPA RE (TRE), overlapping the proximal NGF RE, was identified by expression of the v-Jun oncoprotein that enhanced NPY transcription. Suppression of TPA-induced NPY transcription was obtained by expression of a dominant negative Jun protein, selective protein kinase C inhibition, or introduction of a mutated TRE, whereas NGF-induced NPY transcription was inhibited to a lesser degree. The transcription factor AP-2alpha was shown to bind cooperatively to the NPY promoter with either AP-1 or NGFI-A to the shared TRE and NGF RE and to the distal NGF RE, respectively. These results show that transcription factors AP-1, AP-2alpha, and NGFI-A are involved in activated NPY transcription during the onset of neuronal differentiation.

Base Sequence↗
PubMed1998

Actual and perceived postural sway during balance specific and non-specific proprioceptive stimulation.

A group of patients with balance complaints (n = 16) was compared with a group of normal subjects (n = 17) by means of posturography, subjective assessments of balance, anxiety and unsteadiness when standing on a force platform with eyes closed. Postural instability was induced by vibratory stimulation of the calf muscles (20, 40, 60, 80 and 100 Hz). As a control condition, the arm (biceps) was stimulated at similar frequencies. In order to control for arousal, blood pressure and heart beat were assessed. Furthermore, questionnaire responses on psychological measures were collected. Results showed clear differences between the groups in terms of imbalance and self-reports. However, the 2 groups displayed similar increases of imbalance during calf stimulation and no increase during arm stimulation. Patients generally rated less increase of unsteadiness when the calf was stimulated than did the controls. No differences in arousal were found between the groups or within conditions. Results are discussed in terms of the proposed desynchrony between symptoms and complaints.

Adult↗
PubMed1998

The beta-gal interferon assay: a new, precise and sensitive method.

Cells of a human glioblastoma line were stably transfected with a glial fibrillary acidic protein (GFAP) promoter sequence/lacZ reporter gene. Following this modification, they produced Escherichia coli beta-galactosidase constitutively in amounts that could be measured through their conversion of an added fluorophore into a product readily estimated by fluorimetry. Human interferons (IFN) selectively and in a dose-dependent manner reduce the formation of beta-galactosidase in this system. We have used it as the basis for a novel assay that is sensitive (4-40 pg/ml), precise, completed in 30 h, and applicable to both type I and type II human IFNs. Statistical analysis showed interassay relative standard deviations ranging from 5% to 11%, and most individual assays revealed potencies with limits of error within 85%-115%. Neither partially trypsin-digested IFN nor the other cytokines and mitogens we tested reacted in this system, except for tumor necrosis factor-alpha (TNF-alpha). The high selectivity was further shown by the loss of response to IFN in the presence of the appropriate specific anti-IFN or anti-IFN-gamma receptor antibodies.

Biological Assay↗
PubMed1998

Correlates of vertigo attacks in Ménière's disease.

BACKGROUND: Ménière's disease is a medical condition that involves hearing loss, tinnitus and attacks of vertigo. The attacks can be severely disabling with nausea, dizziness, and aural sensations. METHOD: Three scales assessing the correlates of vertigo attacks in Ménière's disease were developed and completed by 514 subjects diagnosed with the disease. The three scales measured were somatic sensations (SOM), psychological state (PSYCHOL), and situational characteristics (SIT) associated with an attack. RESULTS: Psychometric properties of the three scales were investigated showing Cronbach's alphas of 0.76, 0.80, and 0.62 for the three scales respectively. The results on the scales were related to disease progression. Principal components factor analyses showed that the SOM scale could be divided into two subscales: dizziness/vertigo/anxiety and sensations in the ear. The PSYCHOL scale showed an energy/awareness factor and a negative emotional state factor. The SIT scale, finally, showed two factors: environmental disturbances and stressful conditions. CONCLUSIONS: Knowledge of somatic, psychological and situational premonitory characteristics of attacks in Ménière's disease could lead to improved therapy and counselling.

Adult↗
PubMed1998

Decreased use of hearing aids following training in hearing tactics.

In this report data on hearing aid use were combined from three randomized controlled studies on behavioural hearing tactics. Daily average hearing aid use at pretreatment and posttreatment were analysed for 63 older hearing-impaired persons who had either received treatment or acted as controls. Analysis showed a significant, albeit weak, decrease in daily hearing aid use for those subjects who had received the treatment. The utility of amount of hearing aid use as an indicator of rehabilitation success is discussed.

Adaptation, Psychological↗
PubMed1998

A critical analysis of directive counselling as a component of tinnitus retraining therapy.

Tinnitus retraining therapy (TRT) has been presented as a new approach to tinnitus management. In this paper a number of theoretical and practical problems with TRT are identified. These problems relate to the distinction between directive counselling and cognitive therapy, the adequacy of the cognitive therapy components, the nature of the outcome data which have been presented to date, the theoretical basis for the treatment, and the conceptual clarity of terms such as perception, attention and coping. The stated goal of removal of the perception of tinnitus may lead to confusion about the likely outcome of TRT for most patients. Methodological limitations in the research which has been published to date preclude any claims about the efficacy of TRT at the present time. It is suggested that randomized, controlled studies which include no-treatment and placebo conditions need to be undertaken. Studies are required in which the efficacy of the counselling and white noise components can be clearly isolated. Suggestions are made about the role of psychologists and non-psychologists in the provision of counselling and cognitive therapy services to tinnitus patients.

Adaptation, Psychological↗
PubMed1998

Psychometric evaluation of the Gothenburg Profile for measurement of experienced hearing disability and handicap: applications with new hearing aid candidates and experienced hearing aid users.

The Gothenburg Profile (GP) for measurement of experienced hearing disability and handicap was developed with content partly taken from the shortened Hearing Measurement Scale (HMS25). The GP consists of 20 items divided into two subscales. The first subscale measures Experienced Disability as to hearing speech (items 1-5) and sound localization (items 6-10). The second subscale targets the Experienced Handicap in social settings (items 11-15) and the personal reactions to the experienced handicap (items 16-20). In this study, data are presented for new hearing aid candidates (NewHA) (n=441) and for experienced hearing aid users (ExpHA) (n=476). Principal components factor analyses were conducted and a three-factor solution was obtained, supporting the two factors of the Experienced Disability subscale, but just confirming one factor in the Experienced Handicap subscale. The internal consistency reliability (coefficient alpha) was good (0.85 to 0.95) for the subscales as was the test-retest reliability. The ExpHA group expressed significantly greater disability (first subscale) as well as experienced handicap (second subscale). However, when controlling for hearing level the differences disappeared. The clinical use of the GP for assessment of rehabilitation needs is recommended.

Adolescent↗
PubMed1998

The inhibitory effect in experimental autoimmune encephalomyelitis by the immunomodulatory drug Linomide (PNU-212616) is not mediated via release of endogenous glucocorticoids.

The immunomodulatory drug Linomide (PNU-212616) is an efficient inhibitor of experimental autoimmune encephalomyelitis (EAE) and a variety of other models of autoimmunity. The mechanism of action of the drug is, however, incompletely resolved. It was recently suggested that Linomide might exert its immunomodulatory activity by stimulation of the hypothalamic-pituitary-adrenal axis. To investigate the relevance of this mechanism of action, we monitored the plasma levels of endogenous corticosterone after treatment with Linomide, and also directly compared the inhibitory activity of the drug on acute EAE induced in sham or adrenalectomized SJL/N mice. Treatment with Linomide resulted in a dose related inhibition of EAE in line with previously reported results. Upon onset of clinical signs of EAE, there was a 7-10 fold elevation of plasma corticosterone from the normal baseline level. Administration of Linomide did however not by itself result in any change in plasma corticosterone levels, neither at the pre-symptomatic phase of the disease nor during acute short term treatment. In adrenal ectomized animals immunized for EAE, paralytic disease developed rapidly and was of a more severe and fatal nature as compared to sham-operated controls. Treatment with Linomide had a profound inhibitory effect on development of paralytic disease in both the ectomized and sham-operated groups. These results strongly suggest that Linomide does not exert its immunomodulatory activity via the release of endogenous glucocorticoids.

Adjuvants, Immunologic↗
PubMed1998

Expression of human endogenous retrovirus ERV3 (HERV-R) mRNA in normal and neoplastic tissues.

We investigated the mRNA expression of the human endogenous retrovirus ERV3 (HERV-R) in several normal and corresponding tumor tissues. The env gene of ERV3 is expressed as mRNA in several tissues. Comparison of ERV3 mRNA expression by Northern analyses, revealed a non-systematic variation. Expression was shown to be particularly high in the adrenal gland and some cases of lung cancer. This tissue-tropism should be seen in relation to the high expression previously found in syncytiotrophoblasts in placenta and sebaceous glands of the skin, suggesting profound influences by steroid hormonal regulation.

Blotting, Northern↗
PubMed1998

Folate and neural tube defects. Recommendations from a Danish working group.

A working group was established to evaluate the need for an increased folate intake in Danish women to decrease the risk of neural tube defects (NTDs). NTD are birth defects which include anencephaly, encephalocele and spina bifida. In Denmark the incidence is about 1.4 per 1,000 pregnancies. Folate is a B-vitamin found in most food groups. In case-control studies and randomised studies, a protective effect of folic acid supplements on NTDs has been found. The studies show that a periconceptional folic acid supplement of 360 micrograms to 4 mg daily decreases the recurrence rate of NTDs. Likewise, in the few studies which calculate folate intake from the diet, a lower risk of NTD with higher intake of folate from the diet has been found. The folate intake can be increased by the diet, by folic acid supplements or by fortification of food with folic acid. It is concluded that the incidence of NTDs in Denmark will decrease if the folate intake in fertile women increases. All women planning pregnancy should receive dietary counselling. Women who do not eat according to the Nordic Nutrition Recommendations, and women with an increased risk due to diseases are recommended a supplement of 400 micrograms folic acid daily from a multivitamin/folic acid tablet. Women who have had a child with NTD and women who themselves have NTDs are recommended a supplement of 5 mg folic acid daily. Dietary changes and supplements should be initiated when pregnancy is planned.

Adolescent↗
PubMed1998

A dual-task study of interference between mental activity and control of balance.

OBJECTIVE: This study aimed to examine interference between mental activity and control of balance. STUDY DESIGN: In a mixed design, dual-task study, the performance of patients and healthy control subjects was compared on computerized dynamic posturography, on a visuospatial mental task, and when performing the mental task while balancing. SETTING: The study was performed at a tertiary referral outpatient neuro-otology clinic. PATIENTS AND SUBJECTS: The patient group comprised 24 patients seen consecutively at the clinic because of vertigo and dizziness. The control group consisted of 24 subjects with no complaint or medical history of dizziness or balance disorder, matched with the patients for age and gender. MAIN OUTCOME MEASURES: Performance on a visuospatial mental task and on the computerized dynamic posturography test (conditions 4 and 5) was measured. RESULTS: Balancing on the posturography test resulted in a deterioration in performance on the mental task for both patients and control subjects. The effect was more marked when subjects had their eyes closed. Results on the balance test showed that normal subjects and patients with normal balance also swayed more when performing the mental task, whereas patients who had failed the posturography test swayed less when performing the mental task. CONCLUSIONS: These results show that mental performance deteriorates when performing a demanding balance task. In addition, in both normal subjects and patients, balance also may be affected by mental activity in complex and varied ways that merit further investigation.

Adult↗
PubMed1997

Characterization of ligand binding of a soluble human insulin-like growth factor I receptor variant suggests a ligand-induced conformational change.

Details of the signal transduction mechanisms of the tyrosine kinase family of growth factor receptors remain elusive. In this work, we describe an extensive study of kinetic and thermodynamic aspects of growth factor binding to a soluble extracellular human insulin-like growth factor-I receptor (sIGF-IR) variant. The extracellular receptor domains were produced fused to an IgG-binding protein domain (Z) in transfected human 293 cells as a correctly processed secreted alpha-beta'-Z dimer. The receptor was purified using IgG affinity chromatography, rendering a pure and homogenous protein in yields from 1 to 5 mg/liter of conditioned cell media. Biosensor technology (BIAcore) was applied to measure the insulin-like growth factor-I (IGF-I), des(1-3)IGF-I, insulin-like growth factor-II, and insulin ligand binding rate constants to the immobilized IGF-IR-Z. The association equilibrium constant, Ka, for the IGF-I interaction is determined to 2.8 x 10(8) M-1 (25 degrees C). Microcalorimetric titrations on IGF-I/IGF-IR-Z were performed at three different temperatures (15, 25, and 37 degrees C) and in two different buffer systems at 25 degrees C. From these measurements, equilibrium constants for the 1:1 (IGF-I:(alpha-beta'-Z)2) receptor complex in solution are deduced to 0.96 x 10(8) M-1 (25 degrees C). The determined heat capacity change for the process is large and negative, -0.51 kcal (K mol)-1. Further, the entropy change (DeltaS) at 25 degrees C is large and negative. Far- and near-UV circular dichroism measurements display significant changes over the entire wavelength range upon binding of IGF-I to IGF-IR-Z. These data are all consistent with a significant change in structure of the system upon IGF-I binding.

Biosensing Techniques↗
PubMed1997

Genetically engineered superantigens as tolerable antitumor agents.

Superantigens (SAg) are a family of bacterial and viral proteins with strong immunostimulatory properties. SAg bound to major histocompatibility complex (MHC) class II molecules activate a high frequency of T cells and represent the most potent known activators of T cells to date. To explore the use of SAg for T cell-based tumor therapy we have created a tumor-reactive SAg by engineering a fusion protein composed of a tumor-reactive mAb (C215Fab) and the bacterial SAg staphylococcal enterotoxin A (SEA). A point mutation D227A was introduced at the major MHC class II binding site in SEA to reduce systemic toxicity. Treatment of tumor bearing mice with the Fab-SEA D227A fusion protein resulted in profound antitumor effects with a markedly reduced toxicity as compared with the wild-type Fab-SEA fusion protein. The reduced toxicity was probably due to a weak distribution of the SEA D227A fusion protein in tissues with a high MHC class II expression and low systemic cytokine levels as exhibited in mice and rabbits. The data presented demonstrate the efficacy of immunoconjugates containing a mutated SAg in directing a T cell attack against tumor cells with minimal systemic immune activation.

Animals↗