Biomedical subjects

H Karlsson

Publications and source records attributed to H Karlsson.

At least 37 records · Page 2Linked to original sources

PubMed2001

Persistence of the influenza A/WSN/33 virus RNA at midbrain levels of immunodefective mice.

Strains of influenza A virus are known to infect specific subpopulations of neurons in the mouse brain. Here we report that all segments of the genome of the neurotropic influenza A virus, strain WSN/33, can persist in the brains of immunodefective transporter associated with Antigen Processing 1 (TAP1) mutant mice. Ten to 17 months after injection of virus into the olfactory bulbs, viral RNA encoding the nonstructural NS1 protein was detected in sections from the brain at midbrain levels by RT-PCR in almost all animals. Both negative-strand genomic RNA (vRNA) and positive-strand RNA, including mRNA, were found. RNA encoding nucleoprotein and polymerases, which form the replicative complex of the virus, were detected in fewer brains. RNA encoding envelope proteins were found only in occasional brains. No viral cDNA could be identified. This observation shows that certain regions of the brain in immunodefective mice may harbor the genome of influenza A virus including the NS1 gene, the products of which may play a regulatory role in host-cell metabolism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2000

Sequencing of sulfated oligosaccharides from mucins by liquid chromatography and electrospray ionization tandem mass spectrometry.

As part of a strategy for profiling diverse mixtures of sulfated mucin-derived oligosaccharides, liquid chromatography coupled to electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the negative ion mode has been explored. Two mixtures of sulfated oligosaccharide alditols from porcine stomach and large intestine were analyzed by straight phase chromatography using an amino-bonded column connected to a Q-TOF instrument. Nine sulfated mucin-derived oligosaccharide alditols from porcine stomach underwent extensive fragmentation allowing determination of their sequence. The fragmentation generated primary, secondary, and tertiary fragment ions informative for the elucidation of the saccharide sequence and localization of the sulfate group. From a single chromatographic analysis, the sequences of 28 different sulfated mucin oligosaccharide alditols purified from porcine large intestine were elucidated, revealing information concerning prominent core sequences and terminal blood group-type epitopes. Analysis of these two sulfated oligosaccharide mixtures demonstrated the usefulness of HPLC-ESI-MS/MS: the on-line separation of multiple isomeric suffated oligosaccharides as present in biological samples, informative fragmentation allowing the identification of the sequence of nonderivatized oligosaccharides, and a sensitivity sufficient for the analysis of quantities as obtained from natural sources.

Animals↗

PubMed2000

Habituation of the blink reflex in first-episode schizophrenia, psychotic depression and non-psychotic depression.

OBJECTIVE: Electrophysiological recording of the electrically elicited blink reflex is the most reliable method of investigating habituation of the startle reflex. The purpose of this study was to compare the habituation and the late R3-component of the blink reflex between control subjects (N=19) and first-episode patients with schizophrenia (N=17), psychotic depression (N=23), and severe non-psychotic depression (N=25). METHODS: The blink reflex was evoked by electrical stimulation of the supraorbital nerve, and the deficient habituation of the R2i-component was measured with a computer-assisted integral area measurement. Prefrontal executive function of the patients was assessed with the Wisconsin Card Sorting Test. Current psychiatric symptoms were assessed with the Brief Psychiatric Rating Scale, the Hamilton Depression Scale, the Positive and Negative Syndrome Scale, and the Calgary Depression Scale. RESULTS: Deficient habituation of the blink reflex and occurrence of the late R3 component were associated both with a previous diagnosis of psychotic disorder and with the presence of current psychosis. The sensitivity and specificity of the abnormal habituation of the blink reflex in detecting psychotic disorder were 0.50 and 0.80, respectively. The abnormalities of the blink reflex were not associated with psychotropic medication. In schizophrenic patients, defective habituation of the blink reflex was associated with negative and cognitive symptoms, and in depressive patients with the presence of delusions. CONCLUSIONS: The deficient habituation of the blink reflex and occurrence of the late R3 component seem to be both trait and state markers of a psychotic disorder. The results suggest that schizophrenia and psychotic depression share some common neurobiological mechanisms involved in the modulation of the startle reflex.

Adult↗

PubMed2000

[Five new antiepileptic agents approved during the 1990's--an observation study on the utilization of the new preparations in routine clinical practice].

Since 1990, five new antiepileptic drugs have been approved in Sweden for add-on therapy of partial epilepsy. The optimal use of these drugs has not yet been established. In a county general hospital, 75 of 382 adult patients with epilepsy were treated with newer antiepileptic drugs. Fifty-two continued treatment with a newer drug for one year or longer mainly because of improved seizure control. The newer drugs represented 18 per cent of total sales of antiepileptic drugs in the area served by the hospital but the corresponding cost was 70 per cent. Despite their higher price, use of the newer drugs seems justifiable when significant improvement of seizure control can be achieved.

Adult↗

PubMed2000

Endogenous retroviruses and schizophrenia.

Retroviruses are biologically complex infectious agents which are capable of cellular infection and subsequent integration into the host genome. Retroviruses can exist in an endogenous form in which viral sequences are integrated into the human germline and are vertically transmitted in a Mendelian fashion. The transcriptional activation of these viral sequences in cells within the central nervous system can affect the transcriptional regulation of adjacent genes and result in alterations of neural functioning. This report discusses evidence for a possible role of endogenous retroviruses in the etiopathogenesis of schizophrenia and other human brain diseases. Evidence of endogenous retrovirus activity is manifested by the identification of viral sequences in the brains and cerebrospinal fluids of affected individuals. In addition, affected individuals display evidence of increased activity of virally-encoded reverse transcriptase. The identification of a retroviral component of schizophrenia would be consistent with genetic, environmental, and neurodevelopmental aspects of the disease process. The delineation of a role for retroviruses in disease pathogenesis might lead to new methods for the diagnosis and treatment of schizophrenia.

Animals↗

PubMed2000

Antidepressant-induced lipidosis with special reference to tricyclic compounds.

Cationic amphiphilic drugs, in general, induce phospholipid disturbances. Tricyclic, as well as other antidepressants belong to this group. In experimental animals, antidepressants induce lipid storage disorders in cells of most organs, a so-called generalized phospholipidosis. This disorder is conveniently detected by electron microscopic examination revealing myelin figures. Myelin figures or myeloid bodies are subcellular organelles containing unicentric lamellar layers. The lipidotic induction potency during in vivo is related to the apolarity of the compound. Metabolism of phospholipids takes place within the cell continuously. Several underlying mechanisms may be responsible for the induction of the phospholipid disturbance. For instance, it has been suggested that the compounds bind to phospholipids and such binding may alter the phospholipid's suitability as a substrate for phospholipases. Free TCA or metabolites thereof may also inhibit phospholipases directly, as has been demonstrated for sphingomyelinase in glioma and neuroblastoma cells. Both these mechanisms might result in phospholipidosis. Interaction between drug and phospholipid bilayer has been investigated by nuclear magnetic resonance technique. There seems to be large differences in the sensitivities amongst different organs. Steroid-producing cells of the adrenal cortex, testis and ovaries are in particular susceptible to drug-induced lipidosis. The so-called foam cells are lung macrophages located in the interstitium which become densely packed with myelin figures during TCA exposure. It requires about 3-6 weeks of treatment to develop this converted cell. In cell cultures however, phospholipidosis is demonstrated already after 24 h only. It appears that the cells that undergo TCA-induced lipidosis may recover after withdrawal of the drug. The time required to achieve complete recovery ranges from 3-4 weeks to several months, depending on the organ affected. Little is known about the functional significance of lipidosis. Even if TCA and other antidepressants show other effects, it has not been possible to exclusively relate it to phospholipidosis. However, few attempts have been made to correlate the physiological effects of TCAs in experimental animals to the morphological changes associated with phospholipidosis. There is an increasing evidence however, that cationic amphiphilic drugs may have effects on immune function, signal transduction and receptor-mediated events, effects that to some extent might be related to disturbances in phospholipid metabolism.

Animals↗

PubMed2000

Differences between patients with identified and not identified psychiatric disorders in primary care.

OBJECTIVE: The aim of this study was to discover the differences between the primary care patients with a psychiatric disorder whose illness was detected and the patients whose disorder was not detected. METHOD: We collected 1000 randomly selected PC patients. We used SCL-25 as a screening method and PSE as a diagnostic tool. RESULTS: Ninety-one (89.2%) of the interviewed patients received a psychiatric diagnosis. The physicians detected a disorder in 36 (36.9%). A larger part of the undetected group belonged to the highest social groups. Also the SCL-25 mean scores differed significantly, indicating that the symptoms of the undetected cases were milder. The detected cases had higher levels of anxiety and depression, but the difference in anxiety symptoms was greater between the groups. Detection was associated with treatment. CONCLUSION: The GPs should also be aware of psychiatric morbidity in patients with a higher social status, a good level of education and milder symptoms.

Adolescent↗

PubMed2000

Polyglycosylceramides recognized by Helicobacter pylori: analysis by matrix-assisted laser desorption/ionization mass spectrometry after degradation with endo-beta-galactosidase and by fast atom bombardment mass spectrometry of permethylated undegraded material.

Human erythrocyte polyglycosylceramides (PGCs) are recognized by the gastric pathogen Helicobacter pylori and are based on a successively extended and highly branched N-acetyllactosamine core linked to ceramide and substituted by fucose and sialic acid. As a step in the identification of the binding epitope we earlier characterized intact PGCs by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, MALDI-TOF MS (Karlsson,H., Johansson,L., Miller-Podraza,H., and Karlsson,K-A. [1999] Glycobiology, 9, 765-778). In the present work, PGCs from human blood group O erythrocytes were digested with endo-ss-galactosidase (Bacterioides fragilis), an enzyme which cleaves the bond 3Galss1-4GlcNAc in linear but not branched poly-N-acetyllactosamine chains. The enzymatic digestion resulted in a mixture of neutral and sialic acid-containing glycolipids together with terminal and internal sequences of mainly neutral oligosaccharides. The products were analyzed by MALDI-TOF MS in both positive and negative ion mode which gave spectra where the ions could be assigned to structures of the neutral and acidic components, respectively. Among glycolipids found were [structure in text] where R could be H, Fuc or NeuAc. Also observed were structures as [structure in text] which indicated linear extension along both branches. Observed at higher masses were fully branched structures obtained by stepwise extension with [structure in text] where R could be H, Fuc or NeuAc. Most probably further branching may occur along both the (1-->3)- and the (1-->6)-linked branches to give a partly dendritic structure. Structures with more than one sialic acid substituted could not be observed in the MALDI spectrum. Complementary information of the terminal sequences was obtained by FAB-MS analysis of permethylated undegraded PGCs. High-temperature gas chromatography/mass spectrometry of reduced and permethylated products from enzyme hydrolysis documented that Fuc was present in a blood group O sequence, Fuc-Hex-HexN-. Fucose may be placed on short (monolactosamine) or longer branches, while sialic acid seems to be restricted to monolactosamine branches. The conclusion is that human erythrocyte PGCs display microheterogeneity within terminal and internal parts of the poly-N-acetyllactosamine chains. The first branch from the ceramide end may be located at the second or third Gal and possibly also on the first Gal. Other branches may occur on every N-acetyllactosamine unit in fully branched domains, or there may be linear extensions between branches resulting in incompletely branched structures. The extended linear sequences may be present in both 3- and 6-linked antennae. Terminal structures are based on one, two or maybe higher number of N-acetyllactosamine units.

Carbohydrate Sequence↗

PubMed1999

Diagnostic efficiency of the Rorschach schizophrenia and depression indices in identifying first-episode schizophrenia and severe depression

We studied the diagnostic efficiency of the Rorschach schizophrenia (SCZI) and depression (DEPI) indices for detecting first-episode schizophrenia and severe depression with and without psychotic features using DSM-IV as a gold standard measure. Twenty-seven patients with first-episode schizophrenia, 13 with bipolar I disorder, 28 with psychotic depression, 29 with non-psychotic depression, and 60 healthy controls were recruited for the study. The SCZI was highly specific with a very low false positive rate. The lowest positive value of 4, however, may yield false positives, especially among manic patients. The DEPI identified severe non-psychotic depression but not psychotic depression, suggesting that these patient groups invoke different perceptual-cognitive processes in formulating and articulating their Rorschach responses. Anyway, both the SCZI and the DEPI based on the psychological organization and functioning that are known to play a clearly formulated role in schizophrenia and depression, respectively, provide a valuable addition for diagnostics characterized by overt symptoms.

Journal Article↗

PubMed1999

Cis desensitizes GH induced Stat5 signaling in rat liver cells.

Recently a novel family of proteins, the Cis/Socs family, has been shown to constitute negative regulators of cytokine-induced Jak/Stat signaling. Here we demonstrate that Socs-2 and Cis mRNA expression in rat liver is dependent on the presence of growth hormone (GH), and that GH induce Cis mRNA expression in cultures of primary rat hepatocytes. Furthermore, cotransfection studies in the rat liver cell line, BRL-4, revealed that constitutive expression of Cis, but not Socs-2, inhibited the GH-induced transactivation of a Stat5-responsive reporter gene construct. This indicates a functional role for Cis in the desensitization of GH activated Jak/Stat5 signaling in rat liver cells. In response to the intermittent pattern of GH secretion in male rats, GH activates Stat5b signaling whereas this activation is blunted in female rats having a continuous pattern of GH secretion. We hypothesize that GH induction of Cis could be one mechanism by which sexually dimorphic GH signaling via Stat5b is achieved in the rat liver.

Animals↗

PubMed1999

Mass spectrometric analysis of ceramide composition in mono-, di-, tri-, and tetraglycosylceramides from mouse kidney: an experimental model for uropathogenic Escherichia coli.

Many bacteria have been shown to bind to the carbohydrate part of glycosphingolipids, but also the lipid moieties of receptor-active glycolipids are of importance. To investigate the chemistry of the ceramides of kidney glycolipids to which the uropathogenic Escherichia coli bind, different mass spectrometric techniques were utilized. First, a mixture of glycolipids isolated from man and mice kidney was separated by thin-layer chromatography (TLC) and scanned by direct desorption from the plate by fast atom bombardment mass spectrometry (TLC/FAB-MS). Second, the glycolipids were purified by preparative TLC and analyzed by negative-ion FAB-MS. After methylation, further analyses were made with positive-ion FAB-MS, positive-ion electron ionization (EI)-MS, high-temperature capillary gas chromatography (GC/EI-MS) and positive-ion matrix-assisted laser desorption/ionization (MALDI)-MS. The ceramide compositions of the four glycolipids were determined using all these MS techniques and the reliability of the different methods for this type of analyses is discussed. Comparison of the mouse kidney glycolipids with the corresponding glycolipids from human kidney showed the same degree of hydroxylation of ceramides among mono- and disaccharide glycolipids, but a significantly higher degree of hydroxylation among mouse kidney glycolipids with three and four sugar residues. This result might be of relevance for the binding of P-fimbriated E. coli to the urinary tract tissues.

Animals↗

PubMed1999

Acoustic characteristics of /s/ in adolescents.

The goal of the current study was to construct a reference database against which misarticulations of /s/ can be compared. Acoustic data for 26 typically speaking 9- to 15-year-olds were examined to resolve measurement issues in acoustic analyses, including alternative sampling points within the /s/ frication; the informativeness of linear versus Bark transformations of each of the 4 spectral moments of /s/ (Forrest, Weismer, Milenkovic, & Dougall, 1988); and measurement effects associated with linguistic context, age, and sex. Analysis of the reference data set indicates that acoustic characterization of /s/ is appropriately and optimally (a) obtained from the midpoint of /s/, (b) represented in linear scale, (c) reflected in summary statistics for the 1 st and 3rd spectral moments, (d) referenced to individual linguistic-phonetic contexts, (e) collapsed across the age range studied, and (f) described individually by sex.

Adolescent↗

PubMed1999

Fingerprinting of large oligosaccharides linked to ceramide by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: highly heterogeneous polyglycosylceramides of human erythrocytes with receptor activity for Helicobacter pylori.

Highly microheterogeneous polyglycosylceramides (PGCs) of human erythrocytes with an average composition of about 25 monosaccharides linked to ceramide were analyzed by matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS). The human gastric pathogen Helicobacter pylori was earlier shown to bind this glycosphingolipid mixture by thin-layer chromatogram binding assay. The receptor activity was present along the whole nonresolved chromatographic interval. Mass spectra of intact PGCs were compared with corresponding spectra of oligosaccharides enzymatically released from the ceramides. Two subfractions of PGCs containing less than one and more than one sialic acid residue per molecule were used. MALDI-MS spectra were recorded in both linear and reflectron mode with the accuracies of </=0.08% and </=0.02%, respectively, which allowed determination of the constituent parts of the detected ions in form of ceramide and number of hexoses, N-acetylhexosamines, fucoses and sialic acids. Molecular species were found based on ceramide with mainly sphingosine and fatty acids 24:0 and 24:1 (with less amounts of 22:0), and with a total number of monosaccharides ranging from 11 (neutral, m/z = 2605 for [M+Na](+)) to 41 (one sialic acid, m/z = 8057 for [M-H](-)). The saccharide composition obtained supported a successively extended and branched N -acetyllactosamine core with substitutions of fucoses (0 up to 8) and sialic acid (0 to 1). The reliable molecular analysis of large oligosaccharides linked to ceramide using this approach will be of great help for the further structure analysis in order to define the epitope for the sialic acid-dependent binding by the bacterium.

Animals↗

PubMed1998

Heparin ameliorates pulmonary hypertension induced by platelet-activating factor in pigs.

The purpose of this study was to investigate the effects of heparin on the haemodynamic changes which were induced by platelet-activating factor in the pulmonary and systemic circulation in pigs. Mean arterial pressure and mean pulmonary arterial pressure were measured continuously in five anaesthetised juvenile pigs. Bolus doses of platelet-activating factor (0.2-2 microg) were given intravenously to establish a dose response curve. Heparin (300 units/kg) was given intravenously. Thirty minutes later, the same doses of platelet-activating factor were repeated to establish a second dose response curve. Platelet-activating factor caused a dose dependent pulmonary artery hypertension, associated with an initial systemic hypotension followed by systemic hypertension. Heparin effectively reduced the low dose (0.2 microg) platelet-activating factor-induced pulmonary arterial hypertension (p<0.01) but not the higher doses. It had no effect on the platelet-activating factor-induced systemic hypotension or hypertension. The pulmonary and systemic circulation responded differently to platelet-activating factor after giving heparin. While heparin ameliorated the platelet-activating factor-induced pulmonary hypertension, it did not affect the changes in the systemic circulation.

Animals↗

PubMed1998

Application of microcalorimetry for recording basal metabolic and Na+, K+-ATPase activity in LLC-PK1 cells, a model for the renal tubular epithelial cell.

In the present study we have employed a microcalorimetric procedure to measure the heat generated by a porcine renal tubule cell line (LLC-PK1) and its Na+, K+-ATPase. Microplates with an area of 2.2 cm2 were found to be optimal in terms of producing sufficient heat and a steady-state power curve. We compared the rate of heat production by cells in suspension and on monolayers and found a much lower value in suspension, that is, 1.42+/-0.2 versus 2.54+/-0.19 microW/microg DNA. Ouabain, the specific Na+, K+-ATPase inhibitor, caused a reduction in this heat output. The maximal inhibition in cell suspensions was 40% and remained unchanged with as much as 100 microM ouabain, the highest concentration tested. With cells cultured on microplates, ouabain in the concentration interval 0.1-3 microM caused a 25% inhibition of heat output. With 25-100 microM ouabain, a 50% inhibition was observed and at higher concentrations, no further inhibition occurred. Furthermore, upon removal of ouabain, full recovery of the Na+, K+-ATPase was observed, a process that could easily be monitored by using cell monolayers cultured on microplates.

Animals↗

PubMed1998

Different O-glycosylation of respiratory mucin glycopeptides from a patient with cystic fibrosis.

The O-linked oligosaccharides from three fractions of highly glycosylated mucin glycopeptides obtained from sputum of a patient with cystic fibrosis were characterized and compared regarding size, composition, sequence and when possible linkage positions. Neutral and sialic acid-containing glycans were permethylated and analyzed by high-temperature GC-MS and MALDI-MS, showing more than 60 different oligosaccharides with a size of up to 15 monosaccharide units. Some of the observed oligosaccharides are novel for respiratory secretions, one being a trifucosylated heptasaccharide with the proposed structure: Fuc-Gal-4(Fuc-3)GlcNAc-(Fuc-)Gal-3GalNAcol. The glycosylation of two of the glycopeptide fractions was similar with regard to the neutral and sialylated oligosaccharides despite their different origins from the sol or gel phase. Analysis of the sulfated oligosaccharides by FAB-MS/MS indicated that the gel fraction contained C-6 linked sulfate groups while the two sol fractions also contained C-3 linked sulfate. The results suggest the presence of different glycosylated mucin domains, probably originating from different mucin glycoforms and/or apoproteins in the airway of cystic fibrosis patients.

Adolescent↗

PubMed1998

Induction of apoptosis in proliferating lymphocytes by tricyclic antidepressants.

We have previously found that tricyclic antidepressants (TCAs) induce apoptosis in quiescent human lymphocytes. The aim of the present study was to evaluate if TCAs induce apoptosis in proliferating human lymphocytes and in established blastoid lymphocytes also. The development of conA-induced lymphoblast populations was followed by measuring the CD25 membrane expression. Three TCA compounds were run with the following concentrations: imipramine (10, 20, 30, 40, 60 microM), clomipramine (1, 10, 20, 30, 40 microM) and citalopram (40, 60, 80, 100, 180 microM). They all induced a dose-dependent apoptosis both in continuously transformed, as well as in established lymphoblasts. Preincubation of the TCA up to 48 h did not significantly increase induction of apoptosis. The three drugs tested were found to be potent inducers of apoptosis in proliferating lymphocytes. Furthermore, we found that the apoptotic populations in proliferating and in established blastoid lymphocytes were of fairly the same magnitude than in the corresponding population in TCA-incubated resting lymphocytes. In conclusion, we demonstrate that TCAs induce apoptosis in proliferating lymphocytes, as they do in quiescent lymphocytes. Furthermore, the extent of apoptosis was even more pronounced in TCA-incubated lymphoblasts compared to TCA-treated resting lymphocytes.

Journal Article↗

PubMed1998

Rapid and sensitive GC/MS characterization of glycolipid released Galalpha1,3Gal-terminated oligosaccharides from small organ specimens of a single pig.

Pig to human xenotransplantation is considered a possible solution to the prevailing chronic lack of human donor organs for allotransplantation. The Galalpha1,3Gal determinant is the major porcine xenogeneic epitope causing hyperacute rejection following human antibody binding and complement activation. In order to characterize the tissue distribution of Galalpha1,3Gal-containing and blood group-type glycosphingolipids in pig, acid and nonacid glycosphingolipids were isolated from the kidney, small intestine, spleen, salivary gland, liver, and heart of a single pig obtained from a semi-inbred strain homozygous at the SLA locus. Glycolipids were analyzed by thin-layer immunostaining using monoclonal antibodies, and following ceramide glycanase cleavage as permethylated oligosaccharides by gas chromatography, gas chromatography-mass spectrometry, and matrix-assisted laser desorption/ionization mass spectrometry. The kidney contained large amounts of Galalpha1,3Gal-containing penta- and hexasaccharides having carbohydrate sequences consistent with the Galalpha1,3nLc4and Galalpha1,3Lexstructures, respectively. The former structure was tentatively identified in all organs by GC/MS. The presence of extended Galalpha1,3Gal-terminated structures in the kidney and heart was suggested by antibody binding, and GC/MS indicated the presence of a Galalpha1,3nLc6structure in the heart. The kidney, spleen, and heart contained blood group H pentaglycosylceramides based on type 1 (H-5-1) and type 2 (H-5-2) chains, and H hexaglycosylceramides based on the type 4 chain (H-6-4). In the intestine H-5-1 and H-6-4 were expressed, in the salivary gland H-5-1 and H-5-2, whereas only the H-5-1 structure was identified in the liver. Blood group A structures were identified in the salivary gland and the heart by antibody binding and GC/MS, indicating an organ-specific expression of blood group AH antigens in the pig.

Animals↗