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Biomedical subjects

C Möller

Publications and source records attributed to C Möller.

At least 19 recordsLinked to original sources
PubMed1995

Modulation of carbon monoxide production and enhanced spatial learning by tin protoporphyrin.

Endogenous carbon monoxide (CO), produced by haem oxygenase (HO), may play a role in hippocampal long-term potentiation (LTP). Its role in learning and memory in intact animals is less well known. Tin protoporphyrin (Sn-PP; 25 mg kg-1, i.p.) effectively but transiently inhibited HO activity in brain homogenates, and improved acquisition in the Morris water maze. Locomotor activity was unaffected, indicating a behavioural specificity of the learning effect. The analogue zinc protoporphyrin (25 mg kg-1, i.p.), which does not pass the blood-brain barrier, did not affect learning. If the observed memory effect is related to inhibition of HO, the role of CO in spatial learning may be different from that suggested by LTP studies.

Animals↗
PubMed1995

Mite allergens in relation to home conditions and sensitization of asthmatic children from three climatic regions.

We investigated the levels of mite (Der p I and Der f I) allergen in dust from bedrooms, living rooms, kitchens, and bathrooms from 130 homes of asthmatic children in three climatic zones of Sweden. Bedroom dust samples included the child's mattress, carpets, floors, and other plain surfaces. Living-room dust samples were taken from sofas and other furniture, carpets, floors, and other plain surfaces. The allergen levels were related to home characteristics, including absolute indoor humidity (AIH), relative humidity (RH), and air changes per hour (ach). Mite allergen was detected in 62% of the homes. Levels of Der p I varied between < 16 ng and 50 micrograms/g dust, and Der f I between < 16 ng and 73 micrograms/g dust. Because we have designed a composite type of dust collection in our study, the allergen levels found tend to average down the results. Mite allergen levels were higher in homes with dampness problems, in homes with a smoker, and in homes without a basement. Homes with high absolute humidity (> or = 7 g/kg) or relative humidity (> or = 45%) and poor ventilation (< 0.5 ach) contained higher levels of mite allergens than homes with lower humidity and better ventilation. However, the number of ach measurements in homes was not high, and few homes had > 0.5 ach. Sensitization to house-dust mites was more common in southern than in northern and central Sweden. High levels of house-dust mite allergen in a temperate climate where mites are not ubiquitous are thus associated with dampness problems in homes and with tobacco smoking. Our data confirm and extend previous findings that high AIH and RH and poor ventilation increase the risk of mite infestation in homes. It seems to be important and necessary to control indoor humidity and ventilation levels, to avoid high mite allergen exposure in a temperate climate, because 34% of mite-sensitized asthmatic children were exposed to levels of mite allergen < 2 micrograms/g dust in their homes. The study also shows that mite allergen levels below the suggested threshold level (2 micrograms/g dust) are associated with mite sensitivity in children with perennial symptoms of asthma.

Allergens↗
PubMed1995

Clinical and molecular genetics of Usher syndrome.

Usher syndrome is an autosomal-recessive disorder manifested by hearing impairment, retinitis pigmentosa (RP), and variable vestibular deficit. Recent progress in the characterization of the genetics of Usher syndrome has shown that this disorder is phenotypically and genetically complex. This progress impacts the approach of the clinicians in the study of patients who may potentially have Usher syndrome. There are three major phenotypic classes: Usher I, II, and III. Usher I is distinguished from Usher II by having a more severe audiologic involvement and by the presence of vestibular areflexia. Usher III has a progressive hearing loss with variable vestibular involvement. A minimum of three genes have been identified as being responsible for Usher I; two have been identified as being responsible for Usher II. It is not yet clear whether other manifestations such as progressive hearing loss, associated mental retardation, or other physical anomalies are associated with the known Usher genes or whether they represent as yet undiscovered genetic disorders. As progress towards the identification of the Usher genes is made, the clinician will gradually gain new and effective diagnostic procedures for the identification and delineation of the Usher syndromes.

Adult↗
PubMed1995

Gene mapping of Usher syndrome type IIa: localization of the gene to a 2.1-cM segment on chromosome 1q41.

Usher syndrome type II is associated with hearing loss and retinitis pigmentosa but not with any vestibular problems. It is known to be genetically heterogeneous, and one locus (termed USH2A) has been linked to chromosome 1q41. In an effort to refine the localization of USH2A, the genetic map of the region between and adjacent to the marker loci previously recognized as flanking USH2A (D1S70 and PPOL) is updated. Analysis of marker data on 68 Usher II families places the USH2A gene into a 2.1-cM region between the markers D1S237 and D1S229. The gene for transforming growth factor beta 2 (TGFB2) and the gene for the homeodomain box (HLX1) are both eliminated as candidates for USH2A, by virtue of their localization outside these flanking markers. The earlier finding of genetic heterogeneity was confirmed in six new families, and the proportion of unlinked Usher II families is estimated at 12.5%. The placement of the USH2A gene into this region will aid in the physical mapping and isolation of the gene itself.

Chromosome Mapping↗
PubMed1994

c-fos expression in the amygdala: in vivo antisense modulation and role in anxiety.

1. The amygdaloid complex is a key structure in mechanisms of fear and anxiety. Expression of the immediate-early gene c-fos has been reported in the central nucleus of the amygdala following various stressors, but the functional role of this phenomenon has remained unknown. 2. c-fos expression was observed in the central nucleus when rats were subjected to a pharmacologically validated animal model of anxiety, the Vogel conflict test, but not after mere exposure to the test apparatus. Bilateral amygdala injection of a 15-mer phosphorothioate c-fos antisense oligodeoxynucleotide prior to testing blocked conflict-induced c-fos expression and had behavioral effects similar to those of established antianxiety drugs. 3. Separate experiments determined that antisense treatment did not affect conflict behavior by acting on shock thresholds or drinking motivation. 4. These findings provide evidence that neuronal activation and c-fos induction in the amygdala may be of importance for mechanisms of fear and anxiety.

Amygdala↗
PubMed1994

Growth hormone regulation of lipid metabolism in cells transfected with growth hormone receptor cDNA.

The functional properties of the growth hormone (GH) receptor was studied using cellular transfection of GH receptor cDNA. GH treatment (1.5-2 h) of Chinese hamster ovary cells, stably transfected with GH receptor cDNA (CHO4), resulted in increased cellular lipid synthesis (240% of control). This effect was blocked by staurosporine, suggesting a dependence on cellular kinases. However, if GH treatment of CHO4 cells was prolonged (16 h), this instead stimulated lipolysis (128% of control). The GH receptor in CHO4 cells was also shown to be functional in terms of ligand internalization. A GH receptor mutant, in which 183 amino acids had been deleted in the carboxyterminal of the intracellular domain was functionally active, while a receptor without its intracellular domain was shown to be inactive. In conclusion, GH receptors expressed in CHO cells are functional and GH was also shown to have both an acute insulin-like effect, which was kinase dependent, and a long-term anti-insulin-like effect on the lipid metabolism. This suggests that an approach using GH receptor cDNA transfected cells can be of value in understanding the mechanism of GH action.

Alkaloids↗
PubMed1994

Nedocromil sodium 2% eye drops for twice-daily treatment of seasonal allergic conjunctivitis: a Swedish multicentre placebo-controlled study in children allergic to birch pollen.

This was a multicentre, double-blind, randomized group comparative study in which 77 children, aged 6-16 years, received 2% nedocromil sodium eye drops and 72 received placebo, one drop into each eye twice daily. The treatment period was 4 weeks, covering the peak birch pollen season. Prior to the start of the season, patients who had attended the clinic the previous 2 years because of seasonal allergic conjunctivitis (SAC) to birch pollen, entered a one week baseline period during which symptoms were assessed, dairy cards completed, and routine sampling of blood and urine carried out. The double-blind treatment period then commenced at the onset of the birch pollen season. Patients/parents kept daily diary record cards of eye symptom severity and concomitant therapy. Conjunctivitis was mild in both treatment groups but nedocromil sodium was more effective than placebo in controlling symptoms. During the 2-3 weeks of peak pollen counts, this therapeutic effect was statistically significant for itching (P < 0.01), watering (P < 0.05) and total symptom score (P < 0.01), but was not significant for grittiness (P = 0.08) or redness (P = 0.06). Global opinions of efficacy showed no difference between treatments, due to a high placebo effect (however, the diary card data indicated a significant improvement with nedocromil sodium). We therefore conclude that nedocromil sodium 2% eye drops, administered twice daily, is an effective treatment for SAC in children.

Adolescent↗
PubMed1994

Growth hormone (GH) regulation of a rat serine protease inhibitor fusion gene in cells transfected with GH receptor cDNA.

The mechanism by which GH transmits a signal to the nucleus via its membrane-bound receptor is unknown. To study this process, Buffalo rat liver (BRL), rat hepatoma (FAO), human hepatoma (HepG2) and Chinese hamster ovary (CHO) cell lines were transfected with GH receptor cDNA, and stable clones expressing GH receptor mRNA and protein were selected. From previous in vivo studies it is known that GH regulates the expression of the rat hepatic serine protease inhibitor (SPI) 2.1 gene at the transcriptional level. However, in all the cell lines tested, SPI gene expression was less than 0.2% of that measured in rat liver, and GH did not affect the expression of the endogenous SPI gene in GH receptor-expressing cells. A 45 bp GH-responsive element (GHRE) has previously been defined in the SPI 2.1 gene. A construct containing six repeats of this GHRE was assembled with the thymidine kinase promoter and a chloramphenicol acetyl transferase (CAT) reporter gene. Transient transfection of this reporter gene resulted in GH stimulation of CAT activity in all GH receptor-transfected cell lines. A 33-fold induction was measured in the GH receptor-expressing BRL cells. Induction of CAT activity was observed after 8 h of GH treatment in the BRL-GHR638 cell line. Stable BRL cell lines expressing GH receptors with carboxy-terminal truncations (GHR380 and GHR454) did not show increased CAT activity on GH stimulation. This suggests that more than half of the intracellular domain of the GH receptor is required to activate transcription of the SPI 2.1 gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Anxiolytic-like action of centrally administered galanin.

The neuropeptide galanin is present in limbic brain areas important for emotionality. We examined whether central galanin may be involved in mechanisms of anxiety. Rats were tested in a pharmacologically validated animal model of anxiety, the Vogel punished drinking test. A 100% increase of punished responding was seen after 3 nmol galanin i.c.v. After 15 nmol, signs of sedation were seen, and no increase of punished responding could be observed. Drinking motivation, shock thresholds and exploratory locomotor activity were not affected by 3 nmol galanin. These results support a specific anxiolytic-like action of galanin, similar to that of the functionally related peptide, neuropeptide Y.

Animals↗
PubMed1993

Genetic heterogeneity of Usher syndrome type II.

Usher syndrome is an autosomal recessive disorder characterised by retinitis pigmentosa and congenital sensorineural hearing loss. A gene for Usher syndrome type II (USH2) has been localised to chromosome 1q32-q41. DNA from a family with four of seven sibs affected with clinical characteristics of Usher syndrome type II was genotyped using markers spanning the 1q32-1q41 region. These included D1S70 and D1S81, which are believed to flank USH2. Genotypic results and subsequent linkage analysis indicated non-linkage of this family to these markers. The A test analysis for heterogeneity with this family and 32 other Usher type II families was statistically significant at p < 0.05. Further clinical evaluation of this family was done in light of the linkage results to determine if any phenotypic characteristics would allow for clinical identification of the unlinked type. No clear phenotypic differences were observed; however, this unlinked family may represent a previously unreported subtype of Usher type II characterised by a milder form of retinitis pigmentosa and mild vestibular abnormalities. Heterogeneity of Usher syndrome type II complicates efforts to isolate and clone Usher syndrome genes using linkage analysis and limits the use of DNA markers in early detection of Usher type II.

Adolescent↗
PubMed1993

A novel in vitro model for studying signal transduction and gene regulation via the growth hormone receptor.

Buffalo rat liver cells were stably transfected with an expression vector containing rat GH (rGH) receptor cDNA. Transfected cells expressed rGH receptor mRNA and specifically bound GH with high affinity. When transfected cells were stimulated with GH, levels of lipoprotein lipase (LPL) mRNA were increased in a time- and dose-dependent fashion, while glyceraldehyde-3-phosphate-dehydrogenase mRNA levels were unaffected. No GH binding or LPL mRNA could be detected in untransfected cells. Treatment of transfected cells with actinomycin D inhibited the GH-stimulated increase in LPL mRNA, indicating that GH acts at a transcriptional level. When protein synthesis was inhibited using cycloheximide, basal levels of LPL mRNA were increased, and there was no GH stimulation. This suggests that LPL gene expression is constantly repressed by a labile protein. Chloramphenicol acetyltransferase constructs containing the human LPL promoter could be regulated by GH. In conclusion, stimulation of the rGH receptor in stably transfected Buffalo rat liver cells results in specific induction of LPL gene expression. This provides a novel model to study the mechanism of GH action, particularly in relation to gene regulation.

Animals↗
PubMed1992

Growth hormone (GH) induction of tyrosine phosphorylation and activation of mitogen-activated protein kinases in cells transfected with rat GH receptor cDNA.

The mechanism of growth hormone (GH) action was studied in Chinese hamster ovary (CHO) cells transfected with GH receptor cDNA. Cytosolic extracts from GH- or phorbol ester (12-O-tetradecanoyl 4 beta-phorbol 13-acetate)-treated cells, transfected with full-length GH receptor cDNA, had an enhanced ability to phosphorylate myelin basic protein. Myelin basic protein, a substrate for mitogen-activated protein (MAP) kinase, was maximally phosphorylated using extracts from cells treated with 50 nM bovine GH for 10 min. In addition, GH treatment resulted in an increased cell proliferation by 30-60%. GH and 12-O-tetradecanoyl 4 beta-phorbol 13-acetate cause tyrosine phosphorylation of two proteins with M(r) of 40,000 and 42,000 that are also recognized by MAP kinase antibodies. These proteins were identified as MAP kinases by analyzing phosphotyrosine immunoprecipitates on Western blots using MAP kinase antibodies. In addition, GH induces mitogenicity, as well as MAP kinase activation, in CHO cells expressing a receptor in which 184 amino acids had been deleted in the carboxyl-terminal part of the intracellular domain. No GH effects were seen in untransfected cells, in CHO cells expressing a truncated GH receptor containing only 5 of 349 amino acids in the intracellular domain, or in cells expressing the soluble GH-binding protein. In conclusion, our data show that GH treatment of CHO cells, reconstituted with GH receptors, initiates a phosphorylation cascade which includes MAP kinase.

Animals↗
PubMed1992

Otoneurologic disturbances caused by solvent pollution.

Subjects exposed to industrial solvents may experience vertigo and nausea. Solvents are usually volatile hydrocarbon compounds, which are important parts of everyday life in a modern society. They may also cause neurastenia, personality changes, and reduced intellectual capacity. The syndrome that may develop was formerly named psycho-organic syndrome (POS), but in modern terminology it is called chronic toxic encephalopathy (CTE). The syndrome develops slowly, and during the first years no pathological findings will be found using various test batteries. Somewhat later, when the syndrome still might be reversible, psychometric, auditory, and otoneurologic testing may well unveil disturbances within the posterior fossa structures. Animal experiments suggest one site of effect for solvents to be within the cerebellum and brainstem regions with close relationship to the gamma-amino-butyric acid (GABA) transmission. In the otoneurologic test battery, visual suppression and smooth pursuit are of extreme value, as are some auditory tests such as discrimination of interrupted speech and cortical response audiometry using frequency glides as stimuli. Dynamic posturography and magnetic resonance imaging (MRI) have recently proved valuable in the diagnosis. Research is needed concerning the most efficient test battery for early detection of solvent-induced lesions. During further research it is important to unveil other toxic agents, like heavy metals and alcohol, and their damage to the central nervous system and to make comparisons between these substances and the lesions caused by hydrocarbon solvents.

Animals↗
PubMed1992

Pharmacokinetics of astemizole in children.

Astemizole is often administered to children in the treatment of rhinoconjunctivitis and urticaria with good efficacy and few side effects. Both astemizole and its major metabolite desmethylastemizole (DMA) are clinically effective without annoying side effects such as sedation. The pharmacokinetics in adults is well known. In three different studies we have investigated the pharmacokinetical properties of the drug in children. Study I (absorption): Thirty-eight children 8-16 years old (mean 12.6 years) and weighing 25-80 kg (mean 45 kg), with rhinoconjunctivitis due to birch pollinosis, were pretreated with either astemizole 5 mg daily or placebo for two weeks. Then, all children were treated with astemizole in doses increasing every week, i.e. 5, 10, 20 and 40 mg per day. There was a good correlation between the given dose per kg body weight and the plasma concentration of astemizole plus hydroxylated metabolites, indicating that astemizole is completely absorbed. Study II (time to reach steady state): A group of 21 children 7-18 years old (mean 13.9 years), plus 2 younger children, 2 and 5 years old, with allergy against birch- or grass pollen were treated with astemizole 10 mg daily for 12 weeks. Astemizole had reached steady-state plasma levels when the first sample was taken after 1 week, DMA reached steady state within 4 weeks. Study III (elimination half-life [t1/2 beta]): In 10 of the children from study II, t1/2 beta for astemizole plus DMA could be calculated (two samples) and was 10.8 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Evidence for the importance of a positive charge and an alpha-helical structure of the C-terminus for biological activity of human IL-6.

Thirteen point mutations of human interleukin-6 at the C-terminus were constructed at the cDNA-level. Two degenerate oligonucleotide primers were used for PCR synthesis of two groups of point mutations at positions 182 and 184. The mutated cDNAs were in vitro transcribed and translated and subsequently assayed for biological activity in the B9 cell proliferation test. Our results confirm our former findings obtained with deletion mutants on the importance of the C-terminus of IL-6 for biological activity. In addition, we now present evidence for the importance of an alpha-helix at the C-terminus of IL-6 and the presence of the positive charge at position 182 for biological activity.

Amino Acid Sequence↗
PubMed1991

Saliva composition and caries development in asthmatic patients treated with beta 2-adrenoceptor agonists: a 4-year follow-up study.

In an earlier study, we found that chronic treatment with beta 2-adrenoceptor agonists in asthmatic subjects gave an impaired saliva secretion and a higher caries prevalence than in healthy controls. Twenty-one of the asthmatics and their matched controls were examined 4 yr later in a follow-up study. Samples of whole saliva stimulated by chewing and parotid saliva stimulated by citric acid were collected and dental caries was scored. In the asthmatic group the secretory rates of stimulated whole and parotid saliva decreased by 20% and 35%, respectively, compared to the control group. The number of lactobacilli increased. The asthmatic subjects had a decreased output per minute of total protein, amylase, hexosamine, salivary peroxidase, lysozyme, secretory IgA, a bacteria-aggregating glycoprotein, potassium, and calcium in stimulated parotid saliva. Initial and manifest caries lesions as well as the number of DFS were significantly increased in the asthma group. We conclude that asthmatic patients treated with beta 2-adrenoceptor agonists have an increased caries susceptibility due to an impaired saliva secretion caused by the use of beta-adrenergic agonists.

Adolescent↗
PubMed1991

Correlation between dynamic posturography, clinical investigation, and neurography in patients with polyneuropathy.

Dynamic posturography (PG) is a new objective method to study functional performance in diseases affecting balance. It measures muscle response latencies and sway angles to standardized alterations of a moveable platform and moveable surroundings. Twenty-eight patients with polyneuropathy (PN) were studied by clinical investigation, vibrametry, neurography, and dynamic PG. The results of dynamic PG and vibrametry were compared with those of 29 healthy controls. In the patients with PN, clinical scores correlated to the latencies of the muscle response when the platform was suddenly moved forward, and to equilibrium performance (sway angles) in dynamic PG test conditions with eyes closed and the platform either stable or 'sway-referenced'. That is, the platform moves in response to the patient's anterior-posterior sway, creating a disturbed proprioceptive input to the brain. Clinical scores also correlated to the equilibrium performance when both platform and surroundings were sway-referenced. In conclusion dynamic PG, in addition to clinical investigations and neurophysiology, is a valuable and objective method for estimating the equilibrium performance in patients with PN.

Aged↗