Biomedical subjects

E Törnquist

Publications and source records attributed to E Törnquist.

6 recordsLinked to original sources

PubMed2004

Adding functional entities to plasmids.

Non-viral gene therapy constitutes an alternative to the more common use of viral-mediated gene transfer. Most gene transfer methods using naked DNA are based upon non-sequence-specific interactions between the nucleic acid and cationic lipids (lipoplex) or polymers (polyplex). We have developed a technology in which functional entities hybridize in a sequence-specific manner to the nucleic acid (bioplex). This technology is still in its infancy, but has the potential to become a useful tool, since it allows the construction of highly defined complexes containing a variety of functional entities. In its present form the bioplex technology is based upon the use of peptide/nucleic acids (PNA) as anchors. Single, or multiple, functional entities are directly coupled to the anchors. By designing plasmids, or oligonucleotides, with the corresponding anchor target sequence, complexes with desired composition can easily be generated. The long-term aim is to combine functional entities in order to achieve optimal, synergistic interactions allowing enhanced gene transfer in vivo.

Cell Nucleus↗

PubMed2000

The role of adaptive immunity in atherosclerosis.

Atherosclerosis is an inflammatory disease induced by a lipid metabolic disturbance at sites of hemodynamic strain in the vasculature. Studies in both man and experimental animal models show an involvement of innate and adaptive immune mechanisms in the disease process. Our recent studies in apoE-knockout mice show that the level of hypercholesterolemia affects the functional properties of the immune response. Modulating immune activity by injections of polyclonal immunoglobulins inhibits disease progression, suggesting that immunomodulation may be useful to treat atherosclerosis. Analysis of T cell receptor (TCR) mRNA in atherosclerotic lesions shows expansions of T cells expressing TCR-V beta 6, a receptor type that is also expressed by T cells recognizing oxidized low density lipoprotein (oxLDL). This suggests that oxLDL is an autoantigen that induces strong, local T cell responses in the plaque. Further characterization of this and other candidate antigens, such as heat shock proteins and macromolecular components of Chlamydia pneumoniae, may provide important information on which specific interference with the disease process could be based.

Animals↗

PubMed2000

Oligoclonal T cell expansions in atherosclerotic lesions of apolipoprotein E-deficient mice.

T cells are present in atherosclerotic lesions at all stages of development. They exhibit activation markers and are particularly prominent at sites of plaque rupture. This suggests that T-cell-mediated immune responses are involved in the pathogenesis of atherosclerosis. Antigen-specific T cells reactive with oxidized lipoproteins and heat shock proteins have been isolated from plaques, indicating that local activation and clonal expansion might occur. To analyze different stages of atherosclerosis, we have used a murine model. Targeted deletion of the apolipoprotein E gene results in severe hypercholesterolemia and spontaneous atherosclerosis, with lesions containing large numbers of T cells and macrophages. We have analyzed mRNA for T-cell antigen receptors (TCRs) from aortic fatty streaks, early fibrofatty plaques, and advanced fibrofatty plaques of such mice. Polymerase chain reaction amplification of complementarity-determining region 3 (CDR3 region) of TCRs was followed by spectratyping of fragment lengths. This analysis detected all types of variable (V) segments with a gaussian distribution of CDR3 in lymph nodes. In contrast, a restricted heterogeneity was found in atherosclerotic lesions, with expansion of a limited set of Vbeta and Valpha segments and a monotypic or oligotypic CDR3 spectrum in each lesion. Vbeta6 was expressed in all lesions; Vbeta5.2, Vbeta16, Valpha34s, and Valpha9, in the majority of lesions; and Vbeta6, Vbeta5.2, and Valpha34S, in lesions at all 3 stages of development. The strongly skewed pattern of the CDR3 region in the TCR is indicative of oligoclonal expansions of T cells and suggests the occurrence of antigen-driven T-cell proliferation in atherosclerosis.

Animals↗

PubMed1997

Response of glial cells and activation of complement following motorneuron degeneration induced by toxic ricin.

Motor nerve transection in adult rats induce a series of metabolic and structural changes in the injured neurons as well as in surrounding glial cells; however, without substantial neuronal degeneration. In the present study we found, in contrast with axotomy, a massive neuronal death in the ipsilateral hypoglossal nucleus following injection of toxic ricin (RCA) into the hypoglossal nerve, which is in line with previous observations. Injection of RCA enables examination of the glial reaction in a situation where neuronal degeneration is profound, which has been the approach in the present study. We found an increase in OX42-, GFAP-, and transferrin-immunoreactivity in microglial, astroglial, and oligodendroglial cells respectively, in the ipsilateral hypoglossal nucleus three to seven days following injection of toxic ricin in the hypoglossal nerve. Proliferation was found in astrocytes as well as in microglial cells, as shown by uptake of bromodeoxyuridine. In addition, the complement cascade was activated locally in the ipsilateral hypoglossal nucleus, as demonstrated by immunohistochemical detection of complement components C3d and C9. Complement activation may serve several effects in the glial-neuronal interactions. Stimulation of phagocytosis by reactive microglia is probably the most important one. Furthermore, the degenerative neuronal somata showed increased immunoreactivity for clusterin, which is a known complement inhibitor, but a decrease in clusterin-mRNA. In conclusion, the glial cell response was in several aspects principally different following massive motorneuron degeneration induced by toxic ricin in comparison to previous findings reported after axotomy.

Animals↗

PubMed1997

Intrahospital spread of vancomycin-resistant Enterococcus faecium in Sweden.

During a 17-week period vancomycin-resistant Enterococcus faecium (VRE) was found in clinical specimens from 4 in-patients. All bacterial isolates were phenotypically VanA, showing high-level resistance to vancomycin (MIC 256 micrograms/ml) and teicoplanin (MIC 24-256 micrograms/ml). The corresponding gene (vanA) was detected with PCR in strains from 3 of the patients. Three patients had been hospitalized at the renal unit at Orebro Medical Centre Hospital (OMCH). The fourth patient, diagnosed in another hospital, had received treatment in the oncology unit at OMCH. All patients recovered without treatment specific for VRE. Isolates from 2 patients were indistinguishable by pulsed-field gel electrophoresis of genomic DNA. Genetically, these strains were related to the VRE isolates from the 2 other patients. Screening of hospital staff and other in-patients for gastrointestinal carriage of VRE was negative. Glycopeptide-resistant enterococci have not previously been found in OMCH. No new cases were identified during a 10-month follow-up period. Our cases represent the first nosocomial outbreak of VRE in Sweden.

Aged↗

PubMed1987

Water-melon as a vehicle of transmission of shigellosis.

An epidemic of Shigella sonnei infection is described in which the only common source of infection was the ingestion of water-melon. Bacteriological studies demonstrated that S. sonnei bacteria injected into water-melons could multiply to infective doses. Therefore water-melons should not be excluded as a possible source of S. sonnei infection.

Adult↗