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Biomedical subjects

C Möller

Publications and source records attributed to C Möller.

At least 19 recordsLinked to original sources
PubMed1999

Endogenous histamine reduces plasma insulin-like growth factor I via H1 receptor-mediated pathway in the rat.

Endotoxin has been recently shown to reduce plasma insulin-like growth factor I. As it was reported that histamine can induce gut-derived endotoxemia, we wanted to determine whether histamine has a similar effect on plasma insulin-like growth factor I. Compound 48/80 (a histamine releaser) was injected subcutaneously into rats, then blood was taken for plasma insulin-like growth factor I assay and the livers were assayed for insulin-like growth factor I mRNA. Like endotoxin, injection of compound 48/80 significantly reduced plasma insulin-like growth factor I. Six hours post-injection, plasma insulin-like growth factor I was reduced by 61% (P < 0.001), and 24 h post-injection, it was still lower (by 35% P < 0.001) than in the control group. Hepatic insulin-like growth factor I mRNA was not reduced by this treatment. The effect of compound 48/80 on plasma insulin-like growth factor I was significantly attenuated by oral administration of the histamine H1 receptor antagonist (chlorpheniramine), but not by the histamine H2 receptor antagonists (cimetidine and ranitidine). Oral administration of polymyxin B (an antiendotoxin antibiotic) did not attenuate the effect of compound 48/80 on plasma insulin-like growth factor I at all. In conclusion, endogenous histamine reduces plasma insulin-like growth factor I via H1 receptor-mediated pathway. Our study suggests a novel role of histamine in the regulation of insulin-like growth factor I metabolism in vivo.

Animals↗
PubMed1999

Efficacy of once-daily versus twice-daily administration of budesonide by Turbuhaler(R) in children with stable asthma.

We evaluated the efficacy of once-daily versus twice-daily treatment with budesonide, delivered by a Turbuhaler(R), in the management of children with stable asthma in a randomized, double-blind, parallel-group study involving 206 children (age 5-15 years). After a 2-week run-in period during which the children were maintained on their usual dose of budesonide (200 microg or 400 microg/day), patients were randomized to receive the same daily dose in either two daily administrations (morning and evening) or as a single dose in the morning over a period of 12 weeks. The primary efficacy variable was morning peak expiratory flow (PEF). The mean morning PEF during the run-in phase was 271 L/min in patients randomized to once-daily treatment and 264 L/min in those randomized to twice-daily treatment. The mean change from baseline to the last 2 weeks of the treatment period in the two groups was -0.3 L/min (95% confidence limits -6.6 to +6.0) and 2.5 L/min (-4.3 to +9.3). The estimated difference between the groups was -2.8 L/min, with 90% confidence limits of -10.4 + 4.5; these were close to the limits regarded as indicative of equivalence (-10 to +10), and hence the difference was not regarded as clinically relevant. Similarly, there were no significant differences between the groups in regard to secondary efficacy measures such as spirometric tests and symptom scores. Both treatments were well tolerated. We conclude that once-daily administration of budesonide by Turbuhaler(R) is as effective as twice-daily treatment in the management of stable asthma in children treated with inhaled steroids at doses of 200-400 microg/day.

Administration, Inhalation↗
PubMed1999

Growth characteristics and influence of antibiotics on rough/smooth phenotypic variants of Helicobacter pylori.

Helicobacter pylori shows a rather high variability of several biochemical markers including lipopolysaccharide structures. This study aimed to determine whether Helicobacter pylori has a potential for phenotypic variability and to describe its effects on bacterial pathogenesis. From colonies of three clinical strains of Helicobacter pylori with rough (R) colony morphology, spontaneous phenotypic variants with smooth (S) colony morphology were isolated that occurred with a frequency of 10(-2) to 10(-3), irrespective of growth conditions. R-variant bacteria produced exclusively low-molecular-mass lipopolysaccharide. They exhibited increased lysis in the presence of plain air. In contrast, the S variants produced low- and high-molecular-mass lipopolysaccharide and did not exhibit increased lysis in the presence of plain air. Cocultivation of bacterial cells with AGS stomach cancer cells revealed that R-variant bacteria but not S-variant bacteria effected an inhibition of high molecular-weight glycoprotein biosynthesis and secretion by the host cells. Skirrow supplement added as selective agent to liquid and/or solid media was tolerated to a similar extent among R- and S-variant bacteria, while all variants proved sensitive to metronidazole, amoxicillin and clarithromycin except for the R and S isolates of strain Hp57, which showed resistance to the latter compound. It was concluded that R- and S-variants of Helicobacter pylori may have distinct roles in pathogenesis; nevertheless, these bacteria may be isolated by traditional methods and eradicated by conventional anti-infective therapy.

Anti-Bacterial Agents↗
PubMed1999

Tapping-mode atomic force microscopy produces faithful high-resolution images of protein surfaces.

Compared to contact-mode atomic force microscopy (CMAFM), tapping-mode atomic force microscopy (TMAFM) has the advantage of allowing imaging surfaces of macromolecules, even when they are only weakly attached to the support. In this study, TMAFM is applied to two different regular protein layers whose structures are known to great detail, the purple membrane from Halobacterium salinarum and the hexagonally packed intermediate (HPI) layer from Deinococcus radiodurans, to assess the faithfulness of high-resolution TMAFM images. Topographs exhibited a lateral resolution between 1.1 and 1. 5 nm and a vertical resolution of approximately 0.1 nm. For all protein surfaces, TMAFM and CMAFM topographs were in excellent agreement. TMAFM was capable of imaging the fragile polypeptide loop connecting the transmembrane alpha-helices E and F of bacteriorhodopsin in its native extended conformation. The standard deviation (SD) of averages calculated from TMAFM topographs exhibited an enhanced minimum (between 0.1 and 0.9 nm) that can be assigned to the higher noise of the raw data. However, the SD difference, indicating the flexibility of protein subunits, exhibited an excellent agreement between the two imaging modes. This demonstrates that the recently invented imaging-mode TMAFM has the ability to faithfully record high-resolution images and has sufficient sensitivity to contour individual peptide loops without detectable deformations.

Bacterial Proteins↗
PubMed1999

Anxiogenic-like action of galanin after intra-amygdala administration in the rat.

The neuropeptide galanin is expressed in brain structures implicated in regulation of emotionality. The amygdala is known to play a central role in mechanisms of fear and anxiety. We therefore examined the effects of galanin (0.2 and 0.6 nmol/side) on experimental anxiety upon microinjection into the amygdala. Two established animal models of anxiety were used: a punished drinking test, and the elevated plus-maze. Punished responding was dose dependently suppressed by intra-amygdala galanin, whereas unpunished responding, drinking motivation, locomotor activity, and shock thresholds were unaffected. No effects on experimental anxiety were seen in the plus-maze following galanin injection. When injected into parietal cortex, no anxiety promoting properties of galanin were detected. These data suggest that activation of galanin receptors in amygdala modulates neurotransmission involved in fear and experimental anxiety.

Amygdala↗
PubMed1999

Mite fauna in the home and sensitivity to house-dust and storage mites.

In search of potential new indoor allergen sources, all mites in dust from homes of 55 asthmatic children living in three climatic regions in Sweden were counted and identified by light microscope. Antibodies of the IgE class against three house-dust mites and three storage mites were measured in corresponding serum samples. Mites were found in all but two homes from the northernmost area, where levels also were lower than in the other regions. The highest mite densities were most often found in bedrooms (50%) and living rooms (40%). Mite density was increased in homes with high humidity and was higher in bungalows than in flats. House-dust mites predominated in the south and storage mites in the east central area, particularly in kitchens and bathrooms. Mite-density and IgE-antibody levels against house-dust mites were significantly associated. The same association applied to storage mites. Other species numbered around 100 mites/g dust in some homes. Microscopy helps to identify potentially important mites. Analysing home dust only for house-dust mites will underestimate mite exposure. Storage mites may be as relevant to sensitivity as house-dust mites. As other species occasionally were found in high numbers, their relevance should also be assessed.

Allergens↗
PubMed1999

Acute and short-term effects of growth hormone on insulin-like growth factors and their binding proteins: serum levels and hepatic messenger ribonucleic acid responses in humans.

We investigated the acute (4-5 h) and short-term (5 days) effects of GH treatment on hepatic messenger RNA (mRNA) levels of the genes for the insulin-like growth factors (IGFs), insulin-like growth factor binding protein-1, -2, and -3 (IGFBPs), and the acid labile subunit (ALS), as well as serum levels of these proteins in humans. At the mRNA level, we observed an increase in IGF-1 transcription (+173%) following GH treatment in the acute group, which remained elevated in the short-term treatment group. IGFBP-2 mRNA decreased after short-term GH treatment, without changes in IGFBP-1 or -3 expression. The ALS transcript level increased after 5 days. In serum, we found increased levels of IGF-I and insulin, and decreased levels of IGF-II, in the short-term treatment group. IGFBP-1 decreased in both treatment groups, whereas IGFBP-2 was reduced after 5 days treatment. ALS increased in the short-term group. We observed increased IGFBP-3 serum levels after 5 days of GH treatment, likely due to increased formation of the ternary complex. Our results show that the metabolic effects by GH on the IGF axis are complex. In addition to a direct stimulation of IGF-I and ALS expression, GH inhibits IGFBP-1 serum levels and IGFBP-2 expression in an indirect manner, possibly facilitating enhanced IGF bioavailability to target tissues.

Adult↗
PubMed1999

Early prophylaxis with recombinant human interleukin-11 prevents spontaneous diabetes in NOD mice.

We evaluated the effects of recombinant human (rh) interleukin (IL)-11 on the development of spontaneous and cyclophosphamide-induced diabetes in female NOD mice. Prolonged treatment with rhIL-11 10 microg i.p. five consecutive times a week between the 4th and 22nd weeks of age significantly suppressed both development and cumulative incidence of type 1 diabetes. Disease protection was transient because most of the animals developed type 1 diabetes within 3 months of treatment withdrawal. In contrast, rhIL-11 failed to prevent type 1 diabetes when administered for the first time to euglycemic 18-week-old NOD mice. Most likely, this discrepancy was not due to age-dependent differences in the immunological responses of NOD mice to rhIL-11 because staphylococcus aureus enterotoxin B-induced tumor necrosis factor (TNF) and IL-12 production were equally suppressed by rhIL-11 in 12- and 25-week-old NOD mice. Relative to controls, NOD mice pretreated with rhIL-11 also showed significantly diminished blood levels of TNF, interferon-gamma, and IL-12 induced by anti-CD3 antibody and/or lipopolysaccharide. The results demonstrate that rhIL-11 has powerful anti-inflammatory effects that are capable of down-regulating early immunodiabetogenic pathways in NOD mice.

Aging↗
PubMed1998

Audiological disturbances caused by long-term exposure to industrial solvents. Relation to the diagnosis of toxic encephalopathy.

Sixty workers, consecutively admitted due to suspicion of solvent-induced chronic toxic encephalopathy (CTE), were investigated with pure-tone audiometry, determination of speech recognition of monosyllabic words and distorted speech and cortical response audiometry (CRA). Eighteen workers not exposed to occupational solvents and noise were also investigated. The scores in the distorted speech test were significantly lower and the CRA latencies were significantly longer in the solvent group than in the control group. There was no difference between the groups in the pure-tone and monosyllabic speech recognition tests. In the solvent group, 19 subjects had one or several pathological audiological test results (values exceeding the mean result of the control group by 2 SD). Independently of the audiological examination all the workers in the solvent group underwent the traditional clinical assessment of CTE, which is based on symptoms, history of exposure, clinical neurological examination and a neuropsychological investigation. They were classified in three groups--CTE, incipient CTE and non-CTE. There was no correlation between these groups and the audiological test results. A previous report on vestibular pathology in the same group of subjects and the present investigation on hearing deficits suggest that long-term exposure to solvents causes disturbances of the central pathways in the otovestibular system. Hitherto, no attention has been paid to these disturbances in the definition of the CTE syndrome.

Adult↗
PubMed1998

Environmental assessment of Dermatophagoides mite-allergen levels in Sweden should include Der m 1.

The major allergen of Dermatophagoides microceras, Der m 1, as well as the allergens of D. pteronyssinus and D. farinae, Der p 1 and Der f 1, were analyzed in the homes of 111 asthmatic children in three climatic regions in Sweden. The numbers and species of mites were determined by microscopy, and circulating IgE antibodies against mites were measured. Der f 1 was the predominant house-dust-mite (HDM) allergen, Der p 1 the least often found, and Der m 1 represented 31% of the allergen load. However, in the Linköping area, Der m 1 was the major HDM allergen (58%). Mite counts and allergen levels correlated well. Current exposure to HDM allergens at home was associated with the serum IgE antibody response to HDM in the children with no threshold level. Of the children with IgE antibodies against HDM, 67% reacted to all three mites. Mite sensitization rates were marginally increased (7%) by the addition of IgE analysis of D. microceras to the routine analysis of IgE antibodies against D. pteronyssinus and D. farinae. Thus, Der m 1 may be an important HDM allergen and should be considered when HDM exposure data are assessed in areas with a climate like that of Sweden.

Adolescent↗
PubMed1997

Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats.

A bioactive macrophage factor, the polypeptide daintain/allograft inflammatory factor 1 (AIF1), has been isolated from porcine intestine. It was discovered when searching for intestinal peptides with effects on insulin release, and its purification was monitored by the influence of the peptide fractions on pancreatic glucose-induced insulin secretion. Daintain/AIF1 is a 146-aa residue polypeptide with a mass of 16,603 Da and an acetylated N terminus. An internal 44-residue segment with the sequence pattern -KR-KK-GKR- has a motif typical of peptide hormone precursors, i.e., dibasic sites for potential activation cleavages and at the sequentially last such site, the structure GKR. The latter is a signal for C-terminal amide formation in the processing of peptide hormones. Daintain/AIF1 is immunohistochemically localized to microglial cells in the central nervous system and to dendritic cells and macrophages in several organs. A particularly dense accumulation of daintain/AIF1-immunoreactive macrophages was observed in the insulitis affecting the pancreatic islets of prediabetic BB rats. When injected intravenously in mice, daintain/AIF1 at 75 pmol/kg inhibited glucose (1 g/kg)-stimulated insulin secretion, with a concomitant impairment of the glucose elimination, whereas at higher doses (7.5 and 75 nmol/kg), daintain/AIF1 potentiated glucose-stimulated insulin secretion and enhanced the glucose elimination. Its dual influence on insulin secretion in vivo at different peptide concentrations, and the abundance of macrophages expressing daintain/AIF1 in the pancreatic islets of prediabetic rats, suggest that daintain/AIF1 may have a role in connection with the pathogenesis of insulin-dependent diabetes mellitus.

Amino Acid Sequence↗
PubMed1997

Decreased experimental anxiety and voluntary ethanol consumption in rats following central but not basolateral amygdala lesions.

A long-debated 'tension reduction' hypothesis postulates anti-anxiety effects to be important for ethanol reward, and states that elevated anxiety levels might predispose for ethanol consumption and addiction. Human data are contradictory, possibly due to heterogeneity of patient samples. In rats, baseline levels of experimental anxiety have been reported to correlate with voluntary ethanol consumption. Here, we addressed the possibility that mechanisms underlying experimental anxiety might be causally related to regulation of voluntary ethanol intake. Rats were bilaterally lesioned in central amygdala using microinjections of ibotenic acid. This resulted in a robust release of punished drinking in a modified Vogel conflict test, an effect typically seen with anxiety reducing drugs. This effect was specific, as unpunished drinking was unaffected by the lesion. On the elevated plus-maze, central amygdala lesions did not affect behaviour under baseline conditions, but attenuated the anxiogenic effect of restraint stress. Measures of locomotor activity were not affected. Voluntary ethanol consumption was examined in a two-bottle, free choice paradigm. Ethanol intake was markedly decreased in the lesion group. Total fluid intake was not affected. Basolateral amygdala lesions, which did not affect conflict behaviour, also left ethanol intake unaffected. These results are consistent with previous reports of an important role for central amygdala in anxiety related behaviours, and suggest that cell bodies located in central amygdala might be important in this context. Further, our results support a relation between experimental anxiety and voluntary ethanol consumption.

Alcohol Drinking↗
PubMed1997

The lymphopenia (lyp) gene controls the intrathymic cytokine ratio in congenic BioBreeding rats.

The lymphopenia gene (lyp) on rat chromosome 4 is closely linked to autoimmune diabetes in the BioBreeding (BB) rat. Lyp controls the number of peripheral lymphocytes by reducing T cells of the RT6+ phenotype by almost 90%. Following nine cycle of marker-assisted cross-intercross breeding we have developed congenic lyp/lyp, lyp/+ and +/+ (wildtype) rats on the background of DR rats. Prediabetic and insulitis free lyp/lyp, lyp/+ and +/+ rats were used to determine the effect of lyp on cytokine expression in the thymus. In situ hybridization of thymus cryosections showed that the interferon gamma (IFN gamma) mRNA expression was highest in lyp/lyp rats and the hybridization signal was restricted to the medullary compartment. The frequency of IFN gamma and interleukin (IL)-10 mRNA expressing cells in isolated thymocytes determined by quantitative image analysis, demonstrated an increased IFN gamma: IL-10 ratio in thymocytes from lyp/lyp homozygotes compared to lyp/+ and +/+ rats. This confirmed a lyp gene dose-dependent segregation of the IFN gamma high phenotype. Recombinant human glutamic acid decarboxylase (GAD65) increased the number of IFN gamma and IL-10 mRNA expressing thymocytes after in vitro culture. We conclude that the quantitative ratio of cytokine producing thymocytes is associated with the lyp genotype. These potentially autoreactive thymocytes may explain the establishment of beta-cell directed autoimmunity in the BB rat despite peripheral lymphopenia.

Animals↗
PubMed1997

B cells of aging rats: impaired stimulus-secretion coupling but normal susceptibility to adverse effects of a diabetic state.

A diabetic state impairs B-cell function and survival. We tested whether the negative effects are exacerbated by the aging process. Islets were isolated from old (63.3 +/- 2.3 weeks) and young (11.3 +/- 0.5 weeks) inbred Wistar rats. Age did not affect DNA and insulin content, yet both glucose-induced (27.8 mmol/L) and arginine-induced induced (10 mmol/L) insulin responses in old islets were significantly reduced. Islets were transplanted under the kidney capsule of recipients that were either nondiabetic or severely diabetic after streptozotocin (STZ) treatment (blood glucose > 20 mmol/L). Following 8 weeks' transplantation to nondiabetic recipients, perfused kidneys with grafts of old islets exhibited the same insulin responses to glucose as grafts of young islets. However, responses to arginine were reduced in grafts of old islets (28 +/- 4 microU/min) relative to grafts of young islets. (70 +/- 18 microU/min, P < .05). Insulin mRNA content was similar in grafts of old islets and grafts of young islets. Following 8 weeks' transplantation to diabetic recipients, 27.8 mmol/L glucose failed to induce insulin secretion in grafts of old islets and grafts of young islets alike, whereas arginine-induced insulin secretion was unaffected in grafts of old islets but reduced in grafts of young islets. Insulin mRNA content was reduced to a similar extent by the diabetic state (to 28% in grafts of old islets and to 27% in grafts of young islets grafts in nondiabetic recipients). We conclude that aging, although leading to impaired stimulus-secretion coupling, does not increase susceptibility to the negative effects of a diabetic state on B-cell function as presently tested.

Aging↗
PubMed1997

Responses in skin microcirculation to vestibular stimulation before and during motion sickness.

BACKGROUND: Observation of physiological changes during motion sickness is required to quantify the degree of sickness. The review of the literature does not show unifying results. An objective symptom of motion sickness is facial pallor. It reflects changes in skin microcirculation which have not been measured so far. METHODS: Eleven healthy volunteers susceptible to motion sickness were subjected to eccentric vertical axis rotation. The dynamics and the correspondence of the changes in skin blood flow in two segments, forehead and finger, were measured by laser Doppler flowmeter. RESULTS AND CONCLUSIONS: The difference in the microcirculatory skin blood flow across the phases of motion sickness is significant for the forehead but not for the fingertip: the established dynamics of the forehead blood flow during motion sickness will be of benefit in quantifying the degree of sickness; there is no correlation between the blood flow changes in both measured areas; the rhythmic blood flow fluctuation increases during motion sickness; there is a difference between the blood flow responses to vestibular stimulation before the appearance of motion sickness and in the course of the sickness. Laser Doppler flowmetry is a reliable method in quantifying the degree of motion sickness.

Adult↗
PubMed1997

Effect of cardiopulmonary bypass on the plasma concentrations of fentanyl and alcuronium.

This study was conducted to examine the effect of cardiopulmonary bypass surgery on the total and unbound plasma concentrations of fentanyl and the total plasma concentrations of alcuronium. Total fentanyl concentrations were measured by gas chromatography, the plasma protein binding of fentanyl by ultrafiltration, and alcuronium concentrations by high-performance liquid chromatography. Sixteen patients were studied. On initiation of cardiopulmonary bypass (CPB), there were mean decreases of 58.8 +/- 7.1% and 47 +/- 3.2% for total concentrations of fentanyl in plasma and haemoglobin in blood, respectively. The magnitude of these reductions in individual patients was significantly related (Spearman p = 0.65, P < 0.05). The unbound fraction of fentanyl rose from 0.23 to 0.34 after the start of CPB. The total fentanyl concentration remained relatively stable during bypass until near the end of CPB when the mean total concentration increased, coinciding with rewarming. The size of the increase was related to the body mass index (BMI) of the patient (Spearman p = 0.85, P < 0.01). The estimated elimination half-life of fentanyl using the grouped data was 4.7 h. The total alcuronium concentration in plasma fell by 29% on initiation of CPB and there was no increase on rewarming. The estimated elimination half-life of alcuronium using the grouped data was 234 min. Despite marked declines in the plasma concentrations of both drugs on initiation of CPB, suitable levels of anaesthesia were maintained throughout the procedure.

Adjuvants, Anesthesia↗