Biomedical subjects
Publications and source records attributed to E Hansen.
Posterior dislocation of the shoulder is frequently overlooked. Early diagnosis is a prerequisite for successful treatment. Supplementary axillary or apical oblique projections should be included in the routine radiograms to confirm the diagnosis.
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Studies on the regulation of interferon (IFN) responsive genes have mainly been centred on the highly conserved IFN stimulated responsive elements (ISREs) which can mediate type I and II IFN inducibility. To date little is known about other functional cis-acting regulatory motifs in IFN responsive genes. We report here on the identification of a repressor element in the human MxA gene defined to a 19 base pair (bp) region which houses a 9 bp direct repeat. DNA-specific protein binding on this element is not affected by IFN treatment and is distinct from ISRE binding proteins. Remarkably, contrary to expectations, when the repressor element is multimerised and spliced, in either orientation, to a reporter gene it behaves like a functional, constitutive promoter. Positioning the multimerised element in front of the SV40 enhancerless promoter also led to enhanced expression. The same protein(s) seem to bind to both the single repressor element and its multimerised form. This discovery of phenotypic reversal on a repressor element via multimerisation may have important implications in vivo.
The diagnoses, according to type and site and the degree of visual impairment, responsible for severe visual impairment in children below the age of 18, were analyzed in a material compiled from the national registers of visually impaired in Denmark, Finland, Iceland and Norway. Among 2527 children the predominant causes of visual impairment are ascribed to congenital malformations, neuro-ophthalmological diseases and retinal diseases. Optic atrophy is the leading single cause of severe visual impairment when all diagnoses are compared, and this also applies when all categories of visual impairment are included. Retinopathy of prematurity is the second principal cause of severe visual impairment, while cerebral amblyopia rates as the third most significant cause. Congenital cataract is also of considerable importance when all categories of visual impairment are compared. The differences registered between the Nordic countries were found to be within reasonable limits, except for a preponderance of neuro-ophthalmological diseases in the Danish material. This could be explained by a better medical supervision of mentally retarded patients in Denmark. Additional impairments occur in a large percentage of patients, but are unevenly distributed in the disease groups. A high frequency of additional impairments are found in the neuro-ophthalmological group and in the groups with congenital malformations, emphasizing the importance of a multidisciplinary evaluation when dealing with the visually impaired child.
A Nordic study group of ophthalmologists, NORDSYN, has compiled registers in Denmark, Finland, Iceland and Norway of 2527 visually impaired children aged 0-17 years. This paper is concerned with the sex-distribution in the registers and has documented a statistically significant excess of males in two of the registers (Denmark and Finland). The dominance of males seems to be related to two main conditions: 1. Genetic factors. 2. Perinatal factors. The genetic factors are mainly concerned with X-linked inheritance. The fact that perinatal influences involve visual impairment in males more than in females is difficult to account for. It may be conjectured, that the basis for perinatal visual damage is determined by unknown prenatal, possibly genetic, factors.
A Nordic study group of ophthalmologists, NORDSYN, has compiled data from registers in Denmark, Finland, Iceland and Norway of 2527 visually impaired children. Each record contains the following information: sex, year of birth, year of registration, classification of visual impairment, ocular diagnosis, systemic diagnosis, aetiology and evt. additional impairments. The ocular diagnoses were compiled into groups, and coding systems for aetiology and additional impairment were developed. The sex distribution revealed a dominance of males compared to the general population at the same age. Cases with non-genetic aetiology showed--through to a lesser extent--the same relative preponderance of males. The diseases in males caused by x-linked genetic factors do, therefore, not fully explain the sex distribution observed in the study. The national prevalences for registration of childhood blindness (WHO-definition: best corrected visual acuity in the best eye less than 3/60 or visual field less than 10 degrees around fixation for the ages 0-15 years) are per 100,000 child-population aged 0-15 years: Denmark 41, Finland 15, Iceland 19 and Norway 15. The differences are primarily presumed to be due to varying efficiency in registration. The proportion of visually impaired children with an additional mobility, hearing or mental impairment is between one-third and one-half of the national materials, thus indicating the need for interdisciplinary tracing of and care for the visually impaired child. This study documents the need of uniform routines for data classification of visually impaired children. The quality of the data in the present study calls for caution in the interpretation of the prevalence estimates. Incidence studies are being prepared to obtain information on whether the amount and causes of visual impairment in children with or without multiple impairments are changing.
Careful clinical-aetiological assessment of visually impaired children is one of the prerequisites for prevention of future, 'unavoidable' cases of visual impairment of children in the industrialized part of the world. In a collaborative study (NORDSYN) between four Nordic national registers of visual impairment, we analysed and classified some of the factors considered to be essential components for the development of low vision or blindness in children. We discuss the conceptual basis for aetiological classification of eye disorders and visual impairment. An aetiological classification system, based on the type and debut of an essential causal factor is introduced. We present data on 2527 visually impaired children from the Nordic countries. In accordance with several other reports from the last twenty years it is demonstrated that prenatal factors, including genetic aetiologies, were involved in a large proportion (66%) of the cases. In children without additional impairments the corresponding fraction was 74%. Genetic factors accounted for a little over half of the prenatal cases, and in a substantial number of children (40%) with visual impairments of prenatal origin, the causes were obscure. In 1/5 of the material some peri-neonatal causal or modifying factor was identified. In 7% only, the presumed aetiological factor was introduced in the infantile-juvenile period of life. Further prevention of visual impairment among children of the industrialized countries would benefit most from a more comprehensive understanding of prenatal, nongenetic causal factors, further knowledge about regulating mechanisms responsible for gene expression, and additional improvements in perinatal care.
OBJECTIVE: To compare the efficacy and safety of azithromycin and doxycycline in the treatment of males with uncomplicated urethritis caused by chlamydia trachomatis. DESIGN: A multicentre, double-blind, randomised treatment study. SUBJECTS: 130 male outpatients with clinical signs and symptoms of urethritis. SETTING: STD clinics at four Norwegian University Hospitals. METHODS: Patients were randomly allocated to 1000 mg azithromycin as single dose or doxycycline 100 mg twice daily for 7 days. Clinical, bacteriological and safety assessments were made at entry and after 1 and 2 weeks. Safety data were also repeated after 4 weeks. RESULTS: Demographic data were similar in both groups. At the week 1 assessment bacteriological eradication was achieved in 44 of 44 evaluable azithromycintreated patients and in 42 of 42 in the doxycycline group. At the week 2 assessment the corresponding figures were 35 of 35 and 34 of 34 respectively. CONCLUSION: Azithromycin 1000 mg single dose was as effective as doxycycline 100 mg twice daily for 7 days in male patients with chlamydial urethritis.
Fish are cold blooded animals and their muscle function is expected to be greatly affected by environmental temperature. Species that live in the Antarctic ocean have evolved a different contractile system to fish that live in the tropical waters. In the case of Antarctic fish they have a higher specific myofibrillar ATPase activity but 'the trade off' seems to be a lower thermal stability. They are thus capable of a greater muscle power output at low temperatures but the lower thermal stability means they are restricted to living at temperatures below +4 degrees C. Some species, however, experience a wide range of seasonal variations in temperature. We found that these species adapt by changing their myofibrillar apparatus so that they have a higher specific ATPase which physiological studies indicate is due to a different type of myosin crossbridge for low temperature swimming. This is reversible and they develop a contractile system with a greater thermal stability and a commensurate loss of ATPase activity when their environment warms up again. There were several possibilities by which this may be achieved including expression of different isoform genes or the post- translational processing of existing proteins. To elucidate the mechanism we made a carp genomic library and screened this for myosin heavy chain gene using mammalian cDNA sequences under moderate stringency conditions. The clones were restriction mapped which resulted in 28 non overlapping sequences. This indicated that the carp had a reasonably large family of myosin heavy chain genes that is about twice the size of that in mammals. Rather fortuitously the first sequence to be identified was from the gene that is predominantly expressed in white muscle at warm temperatures. This was done by extracting the RNA from red and white muscle of fish acclimated to different 25 degrees C, 18 degrees C or 8 degrees C and carrying out Northern analysis using the gene fragment as the probe. The time course for the expression of this gene when carp maintained at a low temperature were acclimated to a warm temperature was slightly in advance of the change in myofibrillar ATPase which suggested that this strategy for adaptation is regulated at the transcriptional level. Hence these species of fish can adapt to seasonal changes in temperature by expressing different myosin heavy chain isoform genes and rebuilding their myofibrils for either warm or cold temperature swimming. At the present time we are characterising the 5' regulatory (promoter) sequence of this gene to see how a temperature switch may operate.(ABSTRACT TRUNCATED AT 400 WORDS)
We report here for the first time direct injection of genes into fish muscle in vivo. Plasmids used contain either SV40 early promoter, rabbit beta-cardiac myosin heavy chain promoter, human MxA promoter or an artificial promoter, fused to a chloramphenicol acetyltransferase (CAT) or beta-galactosidase reporter gene. CAT assays revealed that most gene constructs were highly expressed. Histochemical analysis showed that beta-galactosidase was strongly expressed at the site of injection within muscle fibres. This method provides an excellent system for testing expression of gene constructs, including those of mammalian origin, in fish muscle in vivo and has the potential for fish vaccination.
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The virus- and interferon-inducible human MxA (IFI-78k) gene is a homologue of the murine influenza resistance gene Mx1. Three overlapping human cosmid clones covering most of the gene including its promoter region were isolated. Sequencing the 5' MxA cDNA derived by RT-PCR (reverse transcriptase-polymerase chain reaction) confirmed the most 5' putative transcriptional start site. The MxA promoter does not contain a TATA or CCAAT box but has three Interferon Stimulated Response Element (ISRE) motifs. Strong induction with type I interferons was demonstrated with a fragment containing only two ISREs in human L132 cells. This induced expression was not adversely affected by 2-aminopurine. However, the promoter showed constitutive expression in transiently or stably transfected murine LM cells.
The effect of training competition (TC) on central nervous activation was investigated in order to examine whether motor imagination could serve as a model for complex motor skills concerning information processing and motor control. EEG was recorded before and immediately after the TC. The mean alpha frequency (MAF) was computed from the EEG power density spectra. A significant increase of MAF was found after the TC. Similar changes were found during motor imagination. Thus, motor imagination seems to be a good model to examine activation processes.
The reproductive effect of N,N-dimethylformamide (DMF) administered epicutaneously to rats was examined. The rats were dosed on gestation days 6-15 or on gestation days 1-20 at dose levels of up to 2 ml DMF kg-1 body weight. Body weight, weight gain and pregnancy rate were reduced in those rats receiving 2 ml DMF kg-1 body weight per day on days 6-15. A reduction in the number of live fetuses and in fetal weight, as well as an increase in postimplantation loss, were also observed at this dose level. Similar but more pronounced effects were observed in rats dosed on days 1-20 with 2 ml DMF kg-1 body weight. The lowest effect level was 1 ml DMF kg-1 body weight. No other dose-related effects were found in this study.
Central nervous processes of sensorimotor and behaviour control are prerequisites of skills and motor performance. Eight students (Ss) in sports were tested during motor imagination. They were requested to imagine their own movements when swimming over a distance of 100 m (sitting in a resting position, without any real or imitated movements). Electroencephalograms (EEG), heart rate (HR), skin conductance (SC), and respiration rate (RR) were recorded before, during and after one series of 3 periods of mental training (MT). HR, RR and SC increased during MT. The highest level of SC can be found at the beginning of the first period of imagination. Mean alpha-frequency of the EEG over the left occipital and precentral area in all Ss was higher during MT. The degree of these changes varied during the 3 imagination periods.
Subjects made speeded responses to peripheral luminance increments or decrements preceded by informative central precues. In 4 experiments one of these stimuli was much more likely to occur than the other. In a simple detection task, the likely and unlikely stimuli showed equivalent cuing effects. In a discrimination task (bright/dim), the likely stimuli showed cuing but the unlikely one did not (spotlight failure), and there was a tendency to make the likely response when the unlikely stimulus occurred at the cued location. In Experiment 5, the 2 stimuli were equally likely, and a choice was required. Large cuing effects were observed for both stimuli with no evidence of a speed-accuracy trade-off. A logogen-activation framework is described within which criterion and sensitivity adjustments are needed to accommodate the full pattern of results. Endogenous orienting appears to enhance processing of all stimuli at attended (relative to unattended) locations, an effect that may be masked by specific stimulus or response expectancies.
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Pentoxifylline has been shown to decrease endotoxin-induced tumor necrosis factor alpha production and reverse the inflammatory actions of interleukin-1 (IL-1) and tumor necrosis factor on leukocyte function. Because of the potential role of this cytokine-leukocyte interaction in the pathogenesis of bacterial meningitis, we investigated the ability of pentoxifylline to modulate meningeal inflammation in the rabbit meningitis model. Pentoxifylline treatment (initially an intravenous injection of 20 mg/kg followed by 6 mg/kg per h) started 20 min before intracisternal injection of 20 ng of Haemophilus influenzae type b lipooligosaccharide (endotoxin) reduced significantly concentrations in cerebrospinal fluid of leukocytes (P less than 0.0001), protein (P less than 0.001), and lactate (P less than 0.001) during the 9-h infusion compared with values in intravenous-saline-treated rabbits. When pentoxifylline was given 1 h after H. influenzae type b endotoxin, the mean peak lactate and leukocyte concentrations in cerebrospinal fluid were significantly lower than those in control animals. Pentoxifylline also significantly decreased lactate and protein concentrations (P less than 0.05) and tended to diminish leukocyte counts (P = 0.08) compared with results in control animals after antibiotic-induced release of endotoxin in animals with H. influenzae meningitis. In this regard, dexamethasone was superior to pentoxifylline and no synergism was observed when the drugs were combined. Additionally, pentoxifylline attenuated meningeal inflammatory changes induced by intracisternal inoculation of 10 ng of rabbit recombinant IL-1 beta compared with results in either dexamethasone- or saline-treated animals. We conclude that pentoxifylline is effective in this animal model in modulating the meningeal inflammatory response following intracisternal inoculation of H. influenzae type b endotoxin or organisms or rabbit recombinant IL-1beta.