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Biomedical subjects

H Karlsson

Publications and source records attributed to H Karlsson.

At least 19 recordsLinked to original sources

Neuroanatomical substrata of amusement and sadness: a PET activation study using film stimuli.

The aim of the present study was to explore the neuroanatomical substrata of film-induced amusement and sadness, aiming at maximal reliability by using strict statistics. Film-induced changes in regional cerebral blood flow (rCBF) were measured using positron emission tomography and [15O]water. It appeared that many brain regions were involved similarly and symmetrically in both emotions. Activation of the occipitotemporal and anterior temporal cortex and cerebellum during both emotions agreed well with the earlier findings. Contrary to some earlier studies, the posterior cingulate gyrus and some frontal areas were deactivated in both emotions. The strict explorative analysis did not reveal activations in the limbic or subcorticai structures seen in some earlier studies. However, an additional analysis restricted to the subcortical and limbic system structures revealed bilateral activation of the amygdala in both target emotions. The outcomes of imaginal studies of emotions seem to be largely dependent on the conservativeness of the statistical analysis and very likely also on the method of emotion induction.

Adult↗

Severe somatization in women is associated with altered cerebral glucose metabolism.

BACKGROUND: Somatization is a clinical phenomenon characterized by multiple, medically unexplained somatic symptoms. The pathophysiology remains unknown. We aimed to test the hypothesis of a central nervous system dysfunction in the pathophysiology of this disorder. METHOD: We studied 10 female patients diagnosed as having somatization disorder or undifferentiated somatoform disorder with no current Axis I disorders according to DSM-IV. They were compared with 17 healthy female volunteers using brain [18F]-fluorodeoxyglucose-PET with MRI reference. RESULTS: The patients had lower cerebral metabolism rates of glucose (P<0.05) in both caudate nuclei, left putamen and right precentral gyrus compared with healthy volunteers. CONCLUSIONS: This is the first study to demonstrate changes in brain metabolism in somatizing women. The regional cerebral hypometabolism is probably associated with the pathophysiology of somatization.

Adult↗

Tricyclic antidepressants prevent the differentiation of monocytes into macrophage-like cells in vitro.

The investigation was designed to determine whether the two tricyclic antidepressant agents (TCAs) clomipramine and imipramine and the selective reuptake inhibitor citalopram affect differentiation of human monocytes to macrophage-like cells (MAC-LCs). We established primary adherent cultures of peripheral blood monocytes and monitored their morphology, capacity for phagocytosis and antigen expression during transformation to MAC-LCs. As expected, maturation of monocytes to MACs is accompanied by changes in morphology, elevated expression of the antigens CD16 and CD51 and an increase in the percentage of phagocytic cells. Treatment of cells with the TCAs clomipramine (40 micromol/L) or imipramine (100 micromol/L) and with citalopram (100 micromol/L), for 11 days resulted in the following observations: (1) monocytes treated with TCAs never developed the morphology characteristic of the MAC-LCs; (2) TCAs reduced the percentage of phagocytic cells; (3) TCAs had little influence on the expression of CD14, CD16, CD51, and HLA-DR. However, when added after monocyte differentiation into MAC-LCs, citalopram and clomipramine no longer reduced the percentage of phagocytic cells and these effects were not simply due to irreversible cytotoxicity. Thus clomipramine, imipramine, and citalopram inhibit differentiation of human monocytes into MAC-LCs in vitro, but in a reversible manner.

Antidepressive Agents, Tricyclic↗

Cognitive functioning in severe somatization--a pilot study.

OBJECTIVE: Somatizing patients often report cognitive complaints but neuropsychological research on somatization is scarce. We investigated somatizing patients for functioning in different cognitive domains. METHOD: Ten female patients with somatization disorder or undifferentiated somatoform disorder and 10 non-somatizing controls participated in neuropsychological examinations. RESULTS: The patients performed at a lower level than the controls in tests involving semantic memory, verbal episodic memory and visuo-spatial tasks, and were slower in attentional tasks. CONCLUSION: Somatization patients may suffer from substantial problems in cognitive performance.

Adult↗

Structural magnetic resonance imaging in patients with first-episode schizophrenia, psychotic and severe non-psychotic depression and healthy controls. Results of the schizophrenia and affective psychoses (SAP) project.

BACKGROUND: Structural brain abnormalities are prevalent in patients with schizophrenia and affective disorders. AIMS: To study how regional brain volumes and their ratios differ between patients with schizophrenia, psychotic depression, severe non-psychotic depression and healthy controls. METHOD: Magnetic resonance imaging scans of the brain on first-episode patients and on healthy controls. RESULTS: Patients with schizophrenia had a smaller left frontal grey matter volume than the other three groups. Patients with psychotic depression had larger ventricular and posterior sulcal cerebrospinal fluid (CSF) volumes than controls. Patients with depression had larger white matter volumes than the other patients. CONCLUSIONS: Left frontal lobe, especially its grey matter volume, seems to be specifically reduced in first-episode schizophrenia. Enlarged cerebral ventricles and sulcal CSF volumes are prevalent in psychotic depression. Preserved or expanded white matter is typical of non-psychotic depression.

Adult↗

Retroviral RNA identified in the cerebrospinal fluids and brains of individuals with schizophrenia.

Schizophrenia is a serious brain disease of uncertain etiology. A role for retroviruses in the etiopathogenesis of some cases of schizophrenia has been postulated on the basis of clinical and epidemiological observations. We found sequences homologous to retroviral pol genes in the cell-free cerebrospinal fluids (CSFs) of 10 of 35 (29%) individuals with recent-onset schizophrenia or schizoaffective disorder. Retroviral sequences also were identified in the CSFs of 1 of 20 individuals with chronic schizophrenia. However, retroviral sequences were not identified in any of the CSFs obtained from 22 individuals with noninflammatory neurological diseases or from 30 individuals without evidence of neurological or psychiatric diseases (chi(2) = 19.25, P < 0.001). The nucleotide sequences identified in the CSFs of the individuals with schizophrenia or schizoaffective disorder were related to those of the human endogenous retroviral (HERV)-W family of endogenous retroviruses and to other retroviruses in the murine leukemia virus genus. Transcription of RNA homologous to members of the HERV-W family of retroviruses also was found to be up-regulated differentially in the frontal cortex regions of brains obtained postmortem from individuals with schizophrenia, as compared with corresponding tissue from individuals without psychiatric diseases. The transcriptional activation of certain retroviral elements within the central nervous system may be associated with the development of schizophrenia in at least some individuals. The further characterization of retroviral elements within the central nervous system of individuals with schizophrenia might lead to improved methods for the diagnosis and management of this disorder.

Adult↗

An historical record of toxaphene and its congeners in a remote lake in western Europe.

Historical trends in the concentrations of toxaphene, its component homologue groups, and individual chlorobornane congeners were determined in a dated sediment core from a mountain lake, Lochnagar, in Scotland, U.K., representing the first such profiles outside of North America. The profile of total toxaphene showed a bimodal distribution with maxima in the mid-1970s and early 1990s unlike the unimodal PCB profile (maximum 1973) in the same core. The earlier toxaphene peak shows agreement with the U.S. source curve and therefore may correspond to modeled global patterns while the later peak may be dueto long-rangetransportfrom eastern and southern Europe or from still lower latitudes. Sediment toxaphene concentrations (14 ng/g dry wt (dw) at surface; 40 ng/g dw at maximum) and accumulation rates (surface 0.42 ng cm(-2) yr(-1); maximum 1.6 ng cm(-2) yr(-1)) were considerably higher than levels in untreated sites in the Great Lakes region and the Canadian Arctic and are equivalent to those reported for the Great Lakes themselves where there have been additional riverine inputs. Two toxaphene congeners, B6-923 and B7-1001, accounted for most of the hexa- and heptachlorobornanes, respectively. B6-923 and B7-1001 abundance ratios (relative to the sum of 12 chlorobornane congeners) had doubling times of 17 +/- 3 and 12 +/- 3 yr, respectively. Given the remoteness of the site from areas of toxaphene production and usage, the high sediment levels raise concerns over toxaphene levels in areas of Europe closer to sources, especially where sites are fished for human consumption. Further European data are needed for comparison.

Animals↗

The Nordic Study on schizophrenic patients living in the community. Subjective needs and perceived help.

In a community sample of 418 persons diagnosed with schizophrenia, subjective needs and perceived help was measured by the Camberwell Assessment of Need (CAN). The mean number of reported needs was 6.2 and the mean number of unmet needs 2.6. The prevalence of needs varied substantially between the need areas from 3.6% ('telephone') to 84.0% ('psychotic symptoms'). The rate of satisfaction estimated as the percentage of persons satisfied with the help provided within an area varied between 20.0% ('telephone') and 80.6% ('food'). The need areas concerning social and interpersonal functioning demonstrated the highest proportion of unmet to total needs. In a majority of need areas the patients received more help from services than from relatives, but in the areas of social relations the informal network provided substantial help. In general the patients reported a need for help from services clearly exceeding the actual amount of help received. In a linear regression model symptom load (BPRS) and impaired functioning (GAF) were significant predictors of the need status, explaining 30% of the variance in total needs and 20% of the variance in unmet needs. It is concluded that the mental health system fails to detect and alleviate needs in several areas of major importance to schizophrenic patients. Enhanced collaboration between the care system and the informal network to systematically map the need profile of the patients seems necessary to minimise the gap between perceived needs and received help.

Activities of Daily Living↗

Comparison of clinical and best-estimate research DSM-IV diagnoses in a Finnish sample of first-admission psychosis and severe affective disorder.

The purpose of this study was to investigate diagnostic agreement between clinicians and a research group in a sample of first-admission psychosis and severe affective disorder patients. Clinical DSM-IV discharge diagnoses and best-estimate DSM-IV research diagnoses were compared in 116 first-episode patients in the city of Turku, Finland. The best-estimate research diagnoses were made at consensus meetings by integrating longitudinal data; patients' medical records; and findings of a clinical interview, the structured SCAN-interview, and symptom severity ratings. Overall diagnostic agreement was moderate, with a kappa value 0.51 (95% confidence interval (CI), 0.39- 0.63). Of the diagnostic groups, schizophrenic disorders had the lowest kappa value of 0.44 (95% CI, 0.26-0.63). Clinicians had a tendency to miss depressive symptoms in psychotic patients; to overdiagnose psychotic symptoms in depressive patients; and to fail to discover earlier hypomanic or depressive episodes in depressive patients. In conclusion, hospital diagnoses were not reliable in first-episode patients. Inappropriate diagnoses may compromise both treatment and epidemiologic findings based on discharge diagnoses.

Adolescent↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗

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↗