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Biomedical subjects

G Andersson

Publications and source records attributed to G Andersson.

At least 163 records · Page 9Linked to original sources

Ultrasound vocalization is not related to corticosterone response in isolated rat pups.

Isolated from their mother, rat pups respond with changes in ultrasound vocalization (USV), a paradigm that can be used as a test for a large range of anxiolytics. Because the relation between corticosterone (CORT) and putative stress responses like USV is not clear, we examined the effects of the benzodiazepine drugs chlordiazepoxide and diazepam vs. the nonbenzodiazepine drugs buspirone and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on USV and plasma CORT concentrations. All drugs caused a dose-related decrease in USV, but only buspirone and 8-OH-DPAT induced a dose-related increase in CORT. We suggest that the seemingly paradoxical effects of buspirone and 8-OH-DPAT, that is, the decrease in USV and the concomitant increase in plasma CORT, are due to the fact that these two drugs act as full agonists at both pre- and postsynaptic 5-HT1A receptors. Our results indicate that, when measured as an increase in the activity of the pituitary adrenocortical axis, the stress response can be interpreted in markedly different ways, depending on whether the increased activity is elicited by an environmental stressor or by pharmacological manipulation.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

Simplifying genetic locus assignment of HLA-DRB genes.

The DR haplotypes of the human major histocompatibility complex have been arranged in five haplotypic groups based on genomic cloning and sequence analyses. To date, the expressed DRB sequences have been assigned to four different loci: DRB1, 3, 4 and 5. DRB1 alleles are present in all haplotypes, whereas DRB3, 4 and 5 are present only in some haplotypes. Here, Göran Andersson and colleagues suggest that DRB3, 4 and 5 sequences may be treated as a single allelic series. They argue that such a model is appropriate, since DRB3, 4 and 5 sequences are inherited in an allelic fashion, have similar genomic localization, exhibit similar levels of gene expression and are, with a few rare exceptions, not present in the same haplotype.

Alleles↗

Oral mucosal changes and nicotine disposition in users of Swedish smokeless tobacco products: a comparative study.

The purpose of this study was to investigate the uptake and metabolism of nicotine by smokeless (oral) tobacco users and to find out if the less pronounced clinical changes in the oral mucosa in users of portion-bag packed oral moist snuff (snus) compared with the changes in the mucosa of loose snus users are correlated to exposure and uptake of tobacco constituents. 54 habitual users of smokeless tobacco were selected for the study: 22 loose snus users, 23 users of portion-bag packed snus and 9 users of chewing tobacco. In accordance with previous findings, less pronounced clinical changes in the oral mucosa were recorded in portion-bag users compared with loose snus users. The clinical findings observed in the oral mucosa of users of chewing tobacco were leukoedema and slight clinical "snus changes". The average intake of nicotine (measured as nicotine equivalents excreted during 24 h) for snus users was 35 mg, and was 50% higher for users of chewing tobacco. The average steady-state saliva cotinine concentration was about 300 ng/ml for both categories of snus users, which is similar to that found in smokers, while the average concentration found in users of chewing tobacco was 50% higher. There was a good correlation between saliva cotinine concentration and the 24 h intake of nicotine. The average excretion profile of nicotine was similar in all three groups of smokeless tobacco users, being on average: nicotine 8%, nicotine-GlcA 3%, cotinine 8%, cotinine-GlcA 9%, 3'-hydroxycotinine 42%, 3'hydroxycotinine-GlcA 19%, nicotine-N'-oxide 9% and cotinine-N-oxide 3%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

The effect of Salinum on the symptoms of dry mouth: a pilot study.

The effect of a new saliva substitute, Salinum, was tested in 37 patients with severe symptoms of reduced salivation. The majority of the patients had suffered from hyposalivation and dry mouth for more than 8 years. The saliva substitute consisted of a water soluble extract of linseed. The physical properties of this extract are similar to those of the glycoproteins of the salivary secretions. The patients used the saliva substitute for a seven days period. Prior to the use of the extract the patients reported that the most severe symptoms of decreased salivation were a feeling of dryness in the mouth and burning sensations in the tongue, pharynx and oesophagus, The majority of the patients reported that the use of Salinum reduced the symptoms of hyposalivation. Great variation in effect occurred from patient to patient. Generally the patients with the most severe symptoms experienced the greatest relief of the symptoms when they used Salinum. Although of short duration the results of this pilot study indicate that an extract of linseeds may compensate for some aspects of the consequences of reduced salivation. Further studies are needed to elucidate the feasibility of the extract as saliva replacement.

Adult↗

Determination of interleukin 6 in human urine and epithelial cell supernatants.

Interleukin 6 (IL-6) is a cytokine with many biological functions. It is produced by different tissues in response to infection and is secreted into the local body fluids. The aim of this study was to find a suitable assay to measure IL-6 in human urine. IL-6 was quantitated by a bioassay and by immunoassays based on neutralizing or nonneutralizing antibodies. The effect of human urine on the quantitation of IL-6 by these assays was analyzed using pooled human urine with added recombinant or natural human IL-6. Urine was found to disturb the growth of the B9 cells. When fractions from gel-filtered human urine were tested, a fraction corresponding to a protein molecular weight range of 10,000-1,000 was found to have a strong inhibitory effect in the B9 assay. In contrast, the low molecular weight fractions containing salts and pigments were not found to disturb the assay. The inhibitory effect of urine was avoided by diluting the samples > 80 times (final dilution in the test plate) or by dialysis. Furthermore, we analyzed IL-6 in urine samples from patients with urinary tract infection and supernatants from epithelial cells stimulated with bacteria in vitro. The B9 assay and the immunoassay based on non-neutralizing anti-IL-6 antibodies were more sensitive than the immunoassays based on neutralizing antibodies. While most of the B9 activity in the urine samples and supernatants could be neutralized by anti-IL-6 antibodies, some samples contained unneutralizable activity. These components remain to be defined. The results demonstrate considerable variation between assays used to quantitate natural IL-6.

B-Lymphocytes↗

Immunological and hematological characterizations of the wasting pig syndrome.

After weaning, pigs may develop a wasting syndrome characterized by slow growth, decreased disease resistance, and increased mortality. This study was conducted to determine whether differences in immune indices exist between wasting and normal pigs of a common age. Treatments were normal controls (N), wasting pigs (WP), and WP treated with the neuroleptic drug amperozide (WPA). Blood samples were taken on the day of treatment (d 0) and 7 and 21 d after treatment. Cortisol concentrations and hematological values were measured, and functional immune assays were conducted on all samples. Body weight was lower (P < .05) for wasting pigs at the start of the study. Wasting pigs and WPA also had fewer (P < .05) white blood cells, lymphocytes, and monocytes than normal pigs. The neutrophil:lymphocyte ratio, an index of stress, was greater for WP and WPA (.79, .92, and .59 +/- .07 for WP, WPA, and N, respectively; P = .008). Functional in vitro immune assays did not differ between groups. Differences in numbers of lymphocytes and monocytes in wasting pigs may result from chronic stress and contribute to the decreased disease resistance and increased mortality seen in these pigs.

Animals↗

Behavioral counselling for subjects with acquired hearing loss. A new approach to hearing tactics.

Effects of behavioral counselling of subjects with an acquired hearing loss were evaluated in an experimental design. The study included a group of 20 hearing-impaired subjects who were assessed and randomly allocated to a treatment or control group. Behavioural counselling, individualized according to the results of functional analysis, was then given to 10 subjects and included the teaching of 'hearing tactics'. The groups were measured three times, pre-counselling and post-counselling and at a 15-month follow-up, after which treatment results were analysed. Significant (time x treatment) interactions were followed by post-hoc testing revealing that the treated group had improved in several areas of functioning while controls had not. These results were in agreement with interview data. The findings indicate that a behavioural counselling approach to hearing tactics is beneficial in the understanding and rehabilitation of hearing loss, especially over time.

Adaptation, Psychological↗

In the search for a novel class of antipsychotic drugs: preclinical pharmacology of FG5803, a 1-piperazinecarboxamide derivative.

Comparative studies of the 1-piperazinecarboxamide derivative 4-[3-(4-fluorobenzoyl)propyl]-N-cyclohexyl-1-piperazinecarboxamide hydrochloride (FG5803) were made with clozapine and haloperidol. Receptor studies revealed that FG5803 potently and selectively bound to the serotonin type 2A receptors (Ki = 13 nM). FG5803 inhibited 5-hydroxytrophan- and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced head twitches, which indicated potent in vivo serotonin type 2A receptor antagonism. FG5803 caused an acute activation of the tuberoinfundibular dopamine neurons and produced only a transient rise in plasma prolactin. In behavioral studies in rats, FG5803 showed strong antagonistic action on presynaptic dopaminergic autoreceptors but only weak postsynaptic dopamine D2 blockade. FG5803 was not cataleptogenic and did not antagonize amphetamine-induced stereotypies. FG5803 was active in the reduction of aggressive behavior and spontaneous exploratory behavior in mice and rats. Therefore, FG5803 is expected to constitute a promising approach in the search for a novel class of antipsychotic drugs that have a broader spectrum of activity and fewer adverse effects than the conventional, antidopaminergic antipsychotics.

Animals↗

Activation of the human NPY gene during neuroblastoma cell differentiation: induced transcriptional activities of AP-1 and AP-2.

During functional neuronal differentiation of human SH-SY5Y neuroblastoma cells, induced by 12-O-tetradecanoylphorbol-13-acetate (TPA), the mRNA expression of c-fos and c-jun displayed a synchronous and biphasic type of induction for both mRNAs, with an early transient (30 to 120 min) and a later (> 8 h) more persistent increase. This was coupled to increased in vitro DNA binding activity of cFos/cJun AP-1 heterodimers in SH-SY5Y nuclear extracts using the electrophoretic mobility shift assay. Functional AP-1 activity was demonstrated in differentiating SH-SY5Y cells by transient transfection assays using a TPA-responsive reporter plasmid. The second expression phase of these protooncogenes was paralleled by a sustained induction of neuronal differentiation markers, as exemplified by growth-associated protein 43 and neuropeptide tyrosine (NPY) mRNAs. DNA-protein interaction between an evolutionarily conserved region (-73 to -45) of the human NPY promoter, containing potential binding sites for AP-1, AP-2, and Sp1, and nuclear extracts prepared from untreated and TPA-treated SH-SY5Y cells revealed one complex (CI) that was unaffected and three complexes (CII to CIV) that were induced by TPA treatment. Competition for DNA binding using AP-1, AP-2, and Sp1 consensus sequences and an anti-cJun antibody, respectively, revealed cooperative interactions between AP-1, AP-2, and Sp1 transcription factors and the NPY promoter. In addition, TPA-mediated induction of AP-2 DNA binding activity to the NPY promoter was not dependent on increased AP-2 mRNA expression. This high degree of complexity presumably involved in NPY gene expression during neuronal differentiation of SH-SY5Y cells suggests productive cooperative interactions between multiple transcription factors.

Base Sequence↗

Th1/Th2 profiles in tuberculosis, based on the proliferation and cytokine response of blood lymphocytes to mycobacterial antigens.

Proliferation and cytokine production profiles by blood mononuclear cells in response to in vitro stimulation with mycobacterial antigens were compared in patients with active tuberculosis and in sensitized healthy controls. Interleukin-4 (IL-4) and interferon-gamma (IFN-gamma) were detected at single-cell level using the ELISPOT assay. Patients showed significantly (P < 0.01) increased numbers of IL-4-secreting cells and decreased thymidine incorporation, but no significant difference in IFN-gamma-producing cells in response to the 38,000 MW or 19,000 MW antigens and their immunodominant peptide epitopes. Pronounced individual variations were found in both patient and control groups, when comparing the responsiveness to the mycobacterial extract, two protein antigens and five synthetic peptides. None of the antigens or peptides tested showed preferential stimulation of either IL-4- or IFN-gamma-secreting T cells, and proliferation was not correlated with either IL-4 or IFN-gamma production. In particular, cytokine responsiveness was of similar frequency in subjects who did or did not show positive proliferation, indicating that the latter test was not fully representative of the active T-cell repertoire. It is concluded that the demonstrated Th2 type of profile in response to two prominent mycobacterial antigens may play a role in the mechanisms of defective host resistance in tuberculosis.

Adolescent↗

CD8 is critically involved in lymphocyte activation by a T. brucei brucei-released molecule.

T. brucei brucei released a lymphocyte triggering factor (TLTF), which triggered purified CD8+, but not CD4+, T cells to interferon gamma (IFN-gamma) mRNA expression and secretion and to [3H]thymidine incorporation. TLTF also induced mRNA for transforming growth factor beta, but not for interleukin-4. The action of this TLTF on mononuclear cell (MNC) cultures was blocked by anti-CD8 antibodies and by soluble CD8. MNCs from a mutant mouse strain lacking CD8 expression were not triggered by TLTF. IFN-gamma provides a growth stimulus for T. brucei brucei, and infected CD8- mice had much lower parasitemia and survived longer than CD8+ mice. The host-parasite interaction in experimental African trypanosomiasis thus involves parasite release of TLTF, which by binding to CD8 triggers CD8+ cells to produce the parasite growth-promoting cytokine IFN-gamma.

Animals↗

Human liver microsomal glutathione transferase. Substrate specificity and important protein sites.

Human liver microsomal glutathione transferase displays the following glutathione peroxidase/transferase activities: dilinoleoylphosphatidylcholine hydroperoxide (0.03 and 0.17 mumol/min.mg, unactivated and N-ethylmaleimide-activated enzyme, respectively), linoleic acid hydroperoxide (0.09 and 0.15 mumol/min.mg), cumene hydroperoxide (0.04 and 3 mumol/min.mg), methyl linoleate ozonide (0.02 and 1.2 mumol/min.mg) and 1-chloro-2,4-dinitrobenzene (1.9 and 24 mumol/min.mg). The activation of glutathione peroxidase activities are much higher than previously observed. The activity towards a phospholipid hydroperoxide is noteworthy since protection against lipid peroxidation has been implied. Methyl linoleate ozonide has not previously been characterised as substrate for any microsomal glutathione transferase. Human liver microsomal glutathione transferase displays an isoelectric point of 9.4 and a structure in agreement with that deduced from the cDNA sequence. Gel electrophoretic analysis shows that proteolytic activation of the human enzyme corresponds to cleavage at Lys-41, thus defining the critical activation site.

Amino Acids↗

Number of interleukin-4- and interferon-gamma-secreting human T cells reactive with tetanus toxoid and the mycobacterial antigen PPD or phytohemagglutinin: distinct response profiles depending on the type of antigen used for activation.

The enzyme-linked immunospot (ELISPOT) assay has been proven to be an efficient and sensitive method for the enumeration of single cells secreting antibodies or cytokines. Here we have used this method to determine the number of interleukin-4 (IL-4)- and interferon-gamma (IFN-gamma)-producing cells in vitro secondary responses to tetanus toxoid (TT) and the mycobacterial antigen (purified protein derivative; PPD) or the mitogen phytohemagglutinin (PHA). PHA-induced IL-4 and IFN-gamma secretion was well correlated suggesting polyclonal activation of cells. This was not the case with the specific antigens, where PPD preferentially induced IFN-gamma- and very few IL-4-producing cells, while TT-induced both IL-4 and IFN-gamma. These differences are probably a reflection of the types of immunity the two antigens induce, mycobacteria preferentially inducing a cell-mediated T helper type 1 (Th 1) type of immunity, while immunity to tetanus is an antibody-dependent, Th 2 type of response. In individuals recently boosted with TT, a significant increase in both IL-4- and IFN-gamma-producing cells in response to TT was seen at day 7 after boost, followed by decline. This was in contrast to what was seen in response to PPD where an increase of IFN-gamma-producing cells after the TT boost at day 7 persisted for at least 14 days. These results suggest that after an in vivo boost both antigen-specific and nonspecific T cells are activated and that antigen-specific cells home to other organs and therefore may be difficult to demonstrate in the circulation. Our data show that the ELISPOT assay is a powerful tool for determining the frequency of cells secreting cytokines. The assay has several advantages over other assays since it is sensitive, measures the number of actually secreting cells, and avoids the problems of binding of cytokines to their cell-bound or soluble receptors.

Adult↗

The coupling between transforming growth factor-alpha and the epidermal growth factor receptor during rat liver regeneration.

Transcriptional and post-transcriptional regulation of hepatic expression of the epidermal growth factor receptor (EGF-R) and its autocrine ligand, transforming growth factor-alpha (TGF-alpha), were analyzed during liver regeneration. The EGF-R mRNA levels were about twofold induced at 3 h after hepatectomy, caused by transcriptional activation. This was immediately followed by a decrease, reaching a low at half the initial level after 18 h, due to a decreased transcriptional rate. TGF-alpha mRNA expression was detected in normal liver using solution hybridization analysis. Concurrent with the decrease in EGF receptors, an increase of the TGF-alpha mRNA level occurred, starting at 6 h after hepatectomy and peaking at twice the initial TGF-alpha mRNA level after 12-24 h. For TGF-alpha, however, no increase in the rate of gene transcription could be detected. TGF-alpha and EGF competed for binding to the same hepatic receptor in normal as well as in regenerating liver. TGF-alpha bound to a similar number of binding sites as EGF in both control and 18-h posthepatectomy livers, but with 4-5 times lower affinity than EGF. At 18 h posthepatectomy, the number of binding sites was reduced to about 55% for both ligands. When the subcellular distribution of endocytosed 125I-labeled TGF-alpha was compared with that of 125I-labeled EGF, no differences were observed, and furthermore, no changes were observed in the subcellular distribution of 125I-labeled TGF-alpha during liver regeneration. The distinct and coordinate regulation of the two interactors, EGF-R and TGF-alpha, suggests that the EGF-receptor system may be functionally involved in the different phases of the prereplicative growth stimulatory process during liver regeneration.

Animals↗

Epidermal growth factor potentiates interleukin 1 and tumor necrosis factor-induced prostaglandin biosynthesis in human gingival fibroblasts.

The effects of and interactions between epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF-alpha) on arachidonic acid release and prostaglandin biosynthesis in human gingival fibroblasts were studied. IL-1 alpha, IL-1 beta and TNF-alpha, but not EGF nor TGF-alpha, stimulated prostaglandin E2 (PGE2) formation in the gingival fibroblasts. The effect of IL-1 alpha, IL-1 beta and TNF-alpha on PGE2 formation was significantly potentiated by EGF in a dose-dependent manner. Similarly, TGF-alpha synergistically potentiated IL-1 beta stimulated PGE2 formation. IL-1 beta but not EGF stimulated the release of 3H-arachidonic acid (3H-AA) from prelabelled gingival fibroblasts. In contrast to the effect on PGE2 formation, no synergistic interaction between EGF and IL-1 was seen on arachidonic acid (AA) release. Addition of unlabelled exogenous AA, in the presence of EGF, resulted in a significant increase in PGE2 formation compared to that seen in fibroblasts not exposed to EGF. The results demonstrate that EGF and IL-1 as well as EGF and TNF-alpha act in concert to enhance prostanoid formation in gingival fibroblasts. Data indicates that EGF potentiates the IL-1 and TNF-alpha induced PGE2 formation at the level of prostaglandin endoperoxide synthase (cyclooxygenase). The synergistic effects of inflammatory cytokines and growth factors may be of physiological importance for regulation of regenerative tissue growth during inflammation and repair.

6-Ketoprostaglandin F1 alpha↗

The Swedish modification of the tracheostomy tube to permit speech.

Over the last 20 years the Respiratory Unit at Danderyd Hospital, Sweden has treated and rehabilitated more than 90 patients on domiciliary ventilation, the majority of whom require night-time ventilation. Sixteen patients (11 men and 5 women) with high spinal cord lesions have been treated. Of these 16 patients, 9 are using diaphragmatic pacing. Every patient has a customised tube. If the patient can use diaphragmatic pacing the tube, as a rule, is single fenestrated. In patients using the ventilator full time, the tube is made to fit snugly in the trachea. When such a tube fits 'as a bullet in its tube' there is no need for a cuff. The patient has adequate ventilation and the small leak around the tube also permits good speech function. Sometimes a PEEP-valve is used to get a better voice.

Female↗

T and B cell responses to cytomegalovirus antigens in healthy blood donors and bone marrow transplant recipients.

We measured the production of interferon-gamma (IFN-gamma) from single T cells and the T cell proliferative response to different cytomegalovirus (CMV) antigens in healthy blood donors and bone marrow transplant recipients. The antigens consisted of a CMV nuclear antigen (CMV na) containing the pp65-kDa matrix protein and the immediate early antigens but lacking CMV glycoproteins, and an antigen comprising native CMV glycoproteins (CMV gp). We also measured the IgG antibodies to CMV na and CMV gp. The T cells reacted to CMV na in CMV seropositive blood donors both with the production of IFN-gamma and with proliferation, while bone marrow transplant recipients had a deficient T cell response. After stimulation with CMV gp, no T cell response could be observed in CMV seropositive subjects. IgG antibodies to CMV na coexisted in plasma with similar levels of antibodies to CMV gp.

Adolescent↗