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Biomedical subjects

L Karlsson

Publications and source records attributed to L Karlsson.

At least 37 records · Page 2Linked to original sources
PubMed2001

A key role for ICAM-1 in generating effector cells mediating inflammatory responses.

We investigated how the accessory molecule interactions encountered during T cell priming influence T cell-mediated destruction of insulin-producing beta cells and lead to type 1 diabetes. T cell receptor (TCR)-transgenic CD4+ T cells were primed under controlled conditions in vitro before being adoptively transferred into transgenic recipients expressing membrane ovalbumin under the control of the rat insulin promoter (RIP-mOVA). During priming, antigen-presenting cell expression of B7-1 without intracellular adhesion molecule 1 (ICAM-1) led to the generation of effector cells that migrated to the pancreata of RIP-mOVA recipients but did not cause diabetes. In contrast, when T cells were primed with APCs expressing both B7-1 and ICAM-1, pronounced destruction of beta cells and a rapid onset of diabetes were observed. Pathogenicity was associated with T cell production of the macrophage-attracting chemokines CCL3 and CCL4. Thus, interactions of lymphocyte function-associated antigen 1 with ICAM-1 during priming induce both qualitative and quantitative alterations in T effector function and induce potentially autodestructive responses.

Animals↗
PubMed2001

Evaluation of methods aimed at complete removal of template from molecularly imprinted polymers.

Polymers imprinted with clenbuterol were used to study the influence of various post-polymerization treatments [e.g., thermal annealing, microwave assisted extraction (MAE), Soxhlet extraction and supercritical fluid template desorption] on the bleeding of residual template. The aim of the study was to reduce the bleeding to levels that would allow the use of the materials as affinity phases for extraction of clenbuterol from bovine urine at concentrations below 1 ng ml-1. After treatment, the clenbuterol imprinted polymers were packed into solid-phase extraction columns and the bleeding was estimated by quantifying the amount of template released in 10 ml of methanol-acetic acid (9 + 1 v/v). This was followed by an assessment of selectivity and recovery in comparison with non-treated material. The lowest bleeding level was found after MAE using 100% trifluoroacetic acid for 3 x 20 min at 100 degrees C. The collected eluate contained in this case 3 ng ml-1 of clenbuterol. The same material was subsequently used for the extraction of clenbuterol from spiked bovine urine. The resulting selectivity and recovery were lower compared with those obtained using the untreated material. A milder but still efficient method to reduce the bleeding level was found to be MAE with formic acid. In this case a bleeding level of 14 ng ml-1 was found after only a 1 h extraction time. In a second model system, using a polymer imprinted with L-phenylalanine anilide, the bleeding was reduced to a similar level by extensive on-line washing in good swelling solvents containing acid or base additives and after thermal annealing of the polymers in the dry state.

Journal Article↗
PubMed2001

Evaluation of phagocytic activity in human monocyte-derived dendritic cells.

Dendritic cells play a central role in initiation of primary T lymphocyte responses to foreign antigens. Their potency in antigen presentation vis-à-vis reported low or lack of ability to phagocytize particulate matter has limited our understanding of the role that they play in inducing immunity to particulate antigens. One hypothesis is that dendritic cells may possess a high phagocytic capacity when immature and located in peripheral tissues, which they lose on maturation. Our goal was to characterize the phagocytic capacity in human immature dendritic cells. The phagocytic capacity of human monocyte-derived immature dendritic cells was studied by morphological and morphometric means, and compared to that of professional phagocytes, human alveolar macrophages, their progenitors, the peripheral blood monocytes, and mature dendritic cells. Phagocytic index (proportion of phagocytic cells) was decreased by 42.8% (immature dendritic cells) and 74.2% (mature dendritic cells) with respect to monocytes. Similarly, the phagocytic index was decreased by 46.5% (immature dendritic cells) and 75.9% (mature dendritic cells) with respect to macrophages. Volume density of phagocytized particles was decreased by 76.1% (immature dendritic cells) and 96.7% (mature dendritic cells) with respect to the monocytes. However, volume density was decreased by 34.3% (immature dendritic cells) and 91% (mature dendritic cells) with respect to alveolar macrophages. These results show that human monocyte-derived immature dendritic cells possess a phagocytic capacity that is lower than that of peripheral blood monocytes and alveolar macrophages but higher than that of mature dendritic cells.

Cells, Cultured↗
PubMed2001

The potential of telemedicine: barriers, incentives and possibilities in the implementation phase.

Between 1998 and 1999, the Swedish Institute for Health Services Development (Spri) evaluated three applications in which specialist competence was being accessed via telemedicine. The results indicated that these kinds of application can be cost-effective in an organization well adapted to new technology and that telemedicine can improve continuity of care for patients. However, the new technology was seldom supported by the old organization and better education and technical support are needed. In a study called 'Incentives and Implementation', the Federation of Swedish County Councils interviewed people in Swedish health-care with a lot of experience of telemedicine. The interviewees agreed that telemedicine was likely to affect the whole structure of health-care. Peripheral competence was expected to increase and referral patterns to change, as well as the functions of the personnel and the hospitals. New working conditions and methods of work were expected to be made possible by telemedicine and health-care was expected to become more process oriented, partly because patients are likely to be more demanding and better informed. To be able to utilize this potential, health-care managers will have to show more interest in and commitment to telemedicine. Old organizational patterns must be called into question and be developed along with information technology and telemedicine. It is also important to give priority to training in telemedicine for physicians and nurses.

Attitude of Health Personnel↗
PubMed2000

Application of molecularly imprinted polymers in supercritical fluid chromatography.

Molecularly imprinted polymers (MIPs), for the templates free base racemic propranolol and the L-enantiomer of phenylalanine anilide (L-PA), were investigated as stationary phases in supercritical fluid chromatography (SFC). Large retention differences were observed on the propranolol MIP for both the template molecule and the structural analogue metoprolol compared to that observed on the corresponding blank polymer. Mobile phase composition and solute concentration were found to affect this retention behaviour. The phenylalanine anilide MIP (L-PA MIP) was found to be enantioselective in SFC with stronger retention observed for the template enantiomer. Throughout the study, characteristic imprinting peak shapes for the stronger retained template molecule were observed for both MIPs examined. After a number of days under supercritical fluid conditions, the performance of the photochemically initiated L-PA MIP was found to significantly deteriorate whereas the thermally initiated propranolol MIP revealed only small changes in its separation performance after a long term of operation. The separation behaviour of these two MIPs in SFC was compared with results obtained on the same columns in high-performance liquid chromatography (HPLC) both before and after their application in SFC.

Chromatography↗
PubMed2000

Evaluation of a vancomycin chiral stationary phase in capillary electrochromatography using polar organic and reversed-phase modes.

A vancomycin chiral stationary phase (CSP) was fully evaluated in capillary electrochromatography (CEC) in reversed-phase and polar organic modes for a number of racemic pharmaceutical compounds. High efficiency and resolution values were obtained for a number of compound classes including thalidomide in both the polar organic mode (190000 plates meter(-1) and Rs = 13.8) and reversed-phase mode (125000 plates meter(-1) and Rs = 13.0). Experimental parameters, including organic modifier, organic solvent ratio, ionic strength, pH, temperature, and voltage, were examined in both the aqueous and nonaqueous modes to deduce their effect on the resultant EOF, retention times, resolution, and efficiency of chiral separations. All results were consistent with and found to be a combination of what is known from existing literature on CEC theory and experience obtained with macrocyclic antibiotic CSPs in LC. Column stability was excellent, and each column packed was found to offer repeatable separations even when switching from the aqueous to the nonaqueous mode.

Anti-Bacterial Agents↗
PubMed2000

Leydig cell loss and spermatogenic arrest in platelet-derived growth factor (PDGF)-A-deficient mice.

Platelet-derived growth factor (PDGF)- A-deficient male mice were found to develop progressive reduction of testicular size, Leydig cells loss, and spermatogenic arrest. In normal mice, the PDGF-A and PDGF-Ralpha expression pattern showed positive cells in the seminiferous epithelium and in interstitial mesenchymal cells, respectively. The testicular defects seen in PDGF-A-/- mice, combined with the normal developmental expression of PDGF-A and PDGF-Ralpha, indicate that through an epithelial-mesenchymal signaling, the PDGF-A gene is essential for the development of the Leydig cell lineage. These findings suggest that PDGF-A may play a role in the cascade of genes involved in male gonad differentiation. The Leydig cell loss and the spermatogenic impairment in the mutant mice are reminiscent of cases of testicular failure in man.

Animals↗
PubMed2000

Utilization of fat retainers in supercritical fluid extraction for the selective extraction of polychlorinated biphenyls from a model fat sample.

Two common fat retainers used in supercritical fluid extraction--basic alumina and the silica based adsorbent Florisil--were investigated using lard fat as model material. With a fat retainer in the extraction cell it was possible to obtain fat-free time windows. Activation by heating did not influence the length of the time windows, while deactivation of the retainers with 10% water (w/w) drastically decreased the fat retaining capabilities. The influence of modifier addition was also investigated. Finally, a method was developed, where basic alumina was utilized to selectively extract polychlorinated biphenyls (PCBs) from a model fat sample, containing PCBs, triglycerides and phospholipids. The PCBs could be quantitatively extracted in a totally fat-free time window.

Chromatography↗
PubMed2000

KIR expression on self-reactive CD8+ T cells is controlled by T-cell receptor engagement.

Natural killer cell tolerance is maintained by the interaction of killer inhibitory receptors (KIRs) with self-major histocompatibility complex class I gene products. A subset of T cells also expresses inhibitory receptors, but the functional significance of these receptors on T cells is unclear. Here we show that, in the absence of T-cell receptor (TCR) engagement, KIRs expressed on CD8+ T cells are slowly downregulated by KIR ligands expressed on antigen-presenting cells. The resulting expression levels of KIR are no longer able to inhibit T-cell function. In contrast, TCR engagement sustains KIR expression, and re-induces functional levels of KIR expression after ligand-induced downregulation of KIR. Our data indicate that KIR expression on CD8+ T cells in vivo may be maintained through continuous encounters with antigen. As KIR-mediated inhibition of T-cell activation can be bypassed at high antigen concentrations, dynamic KIR expression may mediate T-cell tolerance to self-antigens by sparing self-reactive T cells, thus enabling them to mediate potentially useful immune functions to quantitatively or qualitatively different antigens.

Anti-Bacterial Agents↗
PubMed2000

A subpopulation of CD8+ T cells specific for melanocyte differentiation antigens expresses killer inhibitory receptors (KIR) in healthy donors: evidence for a role of KIR in the control of peripheral tolerance.

In cancer patients, NK cell inhibitory receptors (IR) are expressed on a fraction of melanoma-specific lymphocytes with a unique reactivity for tumor antigens derived from normal, nonmutated genes (differentiation antigens). It is presently not known whether expression of these receptors is induced during an immune response against melanoma cells or whether these receptors can be found on T cells harboring a self specificity for such differentiation antigens in healthy donors. By analyzing short-term cultures of CD8+ T cells primed in vitro with melanocyte differentiation antigens, we found expression of NK cell receptors on a small but consistent fraction of CD8+ T cells derived from healthy donors. Both long and short forms of NK cell receptors were expressed. Interestingly, only long forms were functional and inhibited effector functions (cytotoxicity and IFN-gamma production) of these CD8+ T cells. Short forms were devoid of any detectable activating function. The presence of T cells specific for differentiation antigens and expressing NK cell receptors, with an exclusive inhibitory function, in healthy donors strengthens the notion that IR may serve to control T cell tolerance to some peripheral antigens.

Amino Acid Sequence↗
PubMed2000

Automatic carpal tunnel syndrome tester.

OBJECTIVE: A device for automatic testing of sensory latency across the carpal tunnel is described. A fixed bar contains a stimulating electrode distally and a bipolar recording set up with the two poles at 7 and 14 cm distance proximally. The device is thus based on the so called 14/7 method, using orthodromic testing. METHODS: Automatic testing of electrode resistance and muscle relaxation precedes the self triggered start of stimulation. The latencies are analyzed according to a special algorithm. The proximal/distal latency index is increased in carpal tunnel syndrome (CTS). RESULTS: Healthy controls (32 hands in 32 subjects) and patients referred with suspicion of CTS (258 hands) were studied with the new device, by conventional technique and sometimes by inching (centimetering) across the carpal tunnel. A positive CTS result with the tester was in accordance with the routine test in 94% of the patients. Conversely, routine studies showed CTS in 118 hands. Among those, the tester agreed in 44, showed no signals in 70 and indicated normal findings in 4 hands. In cases with a combination of polyneuropathy and CTS, the CTS was detected in 5 out of 6 cases. A complete test takes about 1 min per hand. CONCLUSIONS: The results are very promising.

Adult↗
PubMed2000

PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor.

Platelet-derived growth factors (PDGFs) are important in many types of mesenchymal cell. Here we identify a new PDGF, PDGF-C, which binds to and activates the PDGF alpha-receptor. PDGF-C is activated by proteolysis and induces proliferation of fibroblasts when overexpressed in transgenic mice. In situ hybridization analysis in the murine embryonic kidney shows preferential expression of PDGF-C messenger RNA in the metanephric mesenchyme during epithelial conversion. Analysis of kidneys lacking the PDGF alpha-receptor shows selective loss of mesenchymal cells adjacent to sites of expression of PDGF-C mRNA; this is not found in kidneys from animals lacking PDGF-A or both PDGF-A and PDGF-B, indicating that PDGF-C may have a unique function.

Animals↗
PubMed2000

Detection of viable Chlamydia pneumoniae in abdominal aortic aneurysms.

OBJECTIVES: to investigate the presence of Chlamydia pneumoniae in the wall of abdominal aortic aneurysms (AAAs) and in the aortas of patients without a history of cardiovascular disease. DESIGN: case-control study. MATERIALS: twenty-six consecutive patients operated for AAA were compared to 17 controls. METHODS: aorta was obtained at surgery or autopsy (controls) and prepared for immunohistochemical (IHC) analysis and culture for C. pneumoniae. Throat swabs from 14/26 patients were analysed by PCR for C. pneumoniae. Blood was obtained from 24/26 patients and from 178 70-year-old males. RESULTS: C. pneumoniae was detected in the aortic aneurysms of 20/26 patients by IHC. C. pneumoniae was cultured from 10 of the 20 IHC-positive patients. Only 1/17 controls was positive for C. pneumoniae by IHC (p=0.0001). PCR was positive for C. pneumoniae in 5/14 patients. Serological analysis by microimmunofluoresence (MIF) showed significantly more high titres of the specific antibodies to C. pneumoniae in patients than in age-matched male controls. CONCLUSIONS: we conclude that C. pneumoniae is often present in AAAs in a viable form and that C. pneumoniae is linked to the pathogenesis of AAA.

Aged↗
PubMed2000

Provision of rhIGF-I/IGFBP-3 complex attenuated development of cancer cachexia in an experimental tumor model.

UNLABELLED: Tumor growth is associated with development of cachexia which includes progressive wasting and anorexia. Our previous studies have indicated that insulin like growth factor-I (rhIGF-I) in complex with its binding protein 3 (IGFBP 3), but not free IGF-I, was a potent stimulator of muscle protein synthesis in rats with chronic undernutrition. The aim of the present study was to evaluate the effect of rhIGF-I/IGFBP-3 on the development of cancer cachexia, and to assess safety data on net tumor growth and progression during treatment. METHODS: A methylcholantrene induced sarcoma was implanted s.c. in C 57 bl mice. The animals were provided with rhIGF-I/rhIGFBP-3 (5 microg/g bw) i.v. twice daily (n= 18). Controls were provided with saline (n= 20). Body weight and food intake were registered daily. Net tumor growth was measured over 10 days. Protein synthesis in liver and muscle, as well as plasma concentrations of glucose, insulin, IGF-I and amino acids were measured at the end of the study. RESULTS: tumor size did not differ between control mice and rhIGF-I/rhIGFBP-3 treated mice (1.5 +/- 0.1 g wet tumor weight vs 1.6 +/- 0.2 g respectively). Saline treated tumor bearing controls lost 9.1 +/- 1.3 % body weight over 10 days due to rapid tumor growth while rhIGF-I/rhIGFBP-3 provision attenuated weight loss to 5.6 +/- 1.3% of body weight in study mice (P< 0.05). Food intake was improved and blood glucose concentration was reduced from 7.1 +/- 0.5 to 5.8 +/- 0.2 (P< 0.05) in response to treatment. CONCLUSION: Our results demonstrate that rhIGF-I/rhIGFBP-3 complex did not affect net tumor growth. Moreover rhIGF-I/rhIGFBP-3 complex improved tumor-host nutritional state by improving food intake, attenuating weight loss and improving glucose metabolism.

Animals↗
PubMed2000

Nonclassical MHC class II molecules.

Major histocompatibility complex (MHC) class II molecules are cell surface proteins that present peptides to CD4(+) T cells. In addition to these wellcharacterized molecules, two other class II-like proteins are produced from the class II region of the MHC, HLA-DM (DM) and HLA-DO (DO) (called H2-M, or H2-DM and H2-O in the mouse). The function of DM is well established; it promotes peptide loading of class II molecules in the endosomal/lysosomal system by catalyzing the release of CLIP peptides (derived from the class II-associated invariant chain) in exchange for more stably binding peptides. While DM is present in all class II- expressing antigen presenting cells, DO is expressed mainly in B cells. In this cell type the majority of DM molecules are not present as free heterodimers but are instead associated with DO in tight heterotetrameric complexes. The association with DM is essential for the intracellular transport of DO, and the two molecules remain associated in the endosomal system. DO can clearly modify the peptide exchange activity of DM both in vitro and in vivo, but the physiological relevance of this interaction is still only partly understood.

Animals↗
PubMed2000

Abnormal gastrointestinal development in PDGF-A and PDGFR-(alpha) deficient mice implicates a novel mesenchymal structure with putative instructive properties in villus morphogenesis.

Development of the gastrointestinal (GI) tract depends on reciprocal epithelial-mesenchymal cell signaling. Here, we demonstrate a role for platelet-derived growth factor-A (PDGF-A) and its receptor, PDGFR-(alpha), in this process. Mice lacking PDGF-A or PDGFR-(alpha) were found to develop an abnormal GI mucosal lining, including fewer and misshapen villi and loss of pericryptal mesenchyme. Onset of villus morphogenesis correlated with the formation of clusters of PDGFR-(alpha) positive cells, 'villus clusters', which remained located at the tip of the mesenchymal core of the growing villus. Lack of PDGF-A or PDGFR-(alpha) resulted in progressive depletion of PDGFR-(alpha) positive mesenchymal cells, the formation of fewer villus clusters, and premature expression of smooth muscle actin (SMA) in the villus mesenchyme. We found that the villus clusters were postmitotic, expressed BMP-2 and BMP-4, and that their formation correlated with downregulated DNA synthesis in adjacent intestinal epithelium. We propose a model in which villus morphogenesis is initiated as a result of aggregation of PDGFR-(&agr;) positive cells into cell clusters that subsequently function as mesenchymal centers of signaling to the epithelium. The role of PDGF-A seems to be to secure renewal of PDGFR-(alpha) positive cells when they are consumed in the initial rounds of cluster formation.

Animals↗
PubMed1999

Intercellular adhesion molecule-1 inhibits interleukin 4 production by naive T cells.

The type of cytokines produced during T cell responses determines susceptibility or resistance to many pathogens and influences the development of autoimmunity and allergy. To define the role of individual accessory molecules in cytokine production during primary immune responses, Drosophila cell lines expressing murine major histocompatibility complex class II molecules with defined combinations of accessory molecules were used to present peptide antigen to naive T cell receptor transgenic T cells. Significantly, expression of B7.1 or B7.2 without additional accessory molecules led to very high production of interleukin (IL)-4, which contrasted with minimal IL-4 production elicited by conventional antigen presenting cells (APC). However, coexpression of ICAM-1 and B7 on Drosophila APC induced little IL-4, suggesting an inhibitory role for intercellular adhesion molecule-1 (ICAM-1). In support of this idea, stimulation of T cell receptor transgenic T cells with peptide presented by splenic APC devoid of ICAM-1 (from ICAM-1-deficient mice) led to high IL-4 production. Thus, the level of IL-4 production by naive CD4(+) T cells during typical primary responses appears to be controlled, at least in part, by T-APC interactions involving ICAM-1.

Animals↗