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- Matsui, S, et al.
(författare)
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Active immunization of combined beta1-adrenoceptor and M2-muscarinic receptor peptides induces cardiac hypertrophy in rabbits.
- 1999
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Ingår i: Journal of cardiac failure. - 1071-9164. ; 5:3, s. 246-54
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The high prevalence of patients with dilated cardiomyopathy (DCM) with anti-beta1-adrenoceptor and/or anti-M2-muscarinic receptor autoantibodies in their sera has been observed. However, the pathophysiological role of these autoantibodies in the development of cardiomyopathy is unknown. We previously reported an experimental model of early-stage DCM-like cardiomyopathy induced by immunizing rabbits for 1 year with synthetic peptides corresponding to the sequence of the second extracellular loop of either beta1-adrenoceptor or M2-muscarinic receptor. Because approximately half the sera of patients with DCM that recognize one of the two receptor sequences also recognize the second sequence, a model was created in rabbits simultaneously immunized with the synthetic peptides corresponding to the second extracellular loop of the beta1-adrenoceptor and M2-muscarinic receptor. METHODS AND RESULTS: All rabbits (n = 8) immunized with both peptides had a high titer of both anti-beta1-adrenoceptor and anti-M2-muscarinic receptor autoantibodies in their sera, whereas none of the sera from control rabbits injected with saline (n = 9) was positive. No significant cross-reaction with peptides other than those used for immunization was found. The weight of the hearts of immunized rabbits increased significantly. The hearts of immunized rabbits showed marked concentric left ventricular hypertrophy with mild inflammatory cell infiltration. In these rabbits, mild or moderate interstitial fibrosis was also observed. In electron micrographs, immunized rabbits showed focal myofibrillar lysis, loss of myofilament, and a marked increase in the number of mitochondria and deposition of dense granules in both sarcoplasm and myofibrils. Conversely, one of the control rabbits showed scant mononuclear cell infiltration. However, in this control rabbit, no significant alteration was found by electron microscopy. CONCLUSION: Our results showed the coexistence of both anti-beta1-adrenoceptor and anti-M2-muscarinic receptor autoantibodies in the sera has pathophysiological importance, shown by their ability to induce cardiac hypertrophy in rabbits.
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| 2. |
- Matsui, S, et al.
(författare)
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Peptides derived from cardiovascular G-protein-coupled receptors induce morphological cardiomyopathic changes in immunized rabbits.
- 1997
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Ingår i: Journal of molecular and cellular cardiology. - : Elsevier BV. - 0022-2828. ; 29:2, s. 641-55
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Tidskriftsartikel (refereegranskat)abstract
- An experimental model of early-stage cardiomyopathy was created by immunizing rabbits for 1 year with synthetic peptides corresponding to the sequence of the second extracellular loop of either beta-adrenoceptors or M2-muscarinic receptors. Thirty male rabbits were used and divided into three groups: a control group (n = 10), a group immunized with the peptide corresponding to the beta-adrenoceptor (beta 1 group) (n = 10) and a group immunized with the peptide corresponding to the M2-muscarinic receptor (M2 group) (n = 10). If the sera from both groups of immunized rabbits high-titres of anti-peptide antibodies were found throughout the study period but not in the sera from control rabbits or in the preimmune sera of immunized rabbits. No significant cross-reaction with peptides other than those used for immunization was found. The myocardial receptor density of both immunized groups displayed a strong trend toward receptor up-regulation. This was significant in the beta 1 group but not in the M2 group. Both groups of immunized rabbits displayed significantly enlarged ventricles and thinner walls, as compared with the control group. However, in contrast to the beta 1 group, which showed enlarged cavities in both left and right ventricles, the M2 group was mainly affected in the right ventricles. Moreover, morphological examinations of the hearts of rabbits from both immunized groups demonstrated focal myofibrillar lysis, loss of myofilament, mitochondrial swelling and condensation, sarcoplasmic vacuolation, deposition of dense granules in the sarcoplasm and the myofibrils. One of the sex control rabbit hearts which were examined showed mild degenerative changes in the myocardium and scant mononuclear cell infiltration. However, when all the control rabbit hearts were examined by electron microscopy, no significant alterations were found. These results suggest that immunization by peptides, corresponding to the target sequences for anti-receptor autoantibodies in idiopathic dilated cardiomyopathy, induces morphological changes in the heart similar to those found in the human disease.
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| 3. |
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| 4. |
- Huh, C, et al.
(författare)
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Decreased metastatic spread in mice homozygous for a null allele of the cystatin C protease inhibitor gene
- 1999
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Ingår i: Molecular Pathology. - 1366-8714. ; 52:6, s. 332-340
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Increased or altered activities of cysteine proteases have been implicated in serious human disorders such as cancer, rheumatoid arthritis, sepsis, and osteoporosis. To improve the current knowledge of the regulatory role of a major mammalian cysteine protease inhibitor, cystatin C, in such disease processes, a cystatin C deficient mouse was generated and characterized. METHODS: The mouse cystatin C gene was inactivated by insertion of a bacterial neo gene through homologous recombination in 129/Sv embryonic stem cells. Embryonic stem cell clones were injected into C57BL/6J blastocysts followed by injection of the blastocysts into pseudopregnant female mice. F1 offspring with agouti coat colour after mating of chimaeric males with C57BL/6J females were examined by DNA analysis, and mice carrying the targeted mutation were intercrossed to obtain homozygous cystatin C deficient (CysC-/-) mice. To study the role of cysteine proteases and their inhibitors in metastasis, the spread of B16-F10 melanoma cells in CysC-/- and wild-type mice was compared. Analysis of the formation of remote metastases was carried out by intravenous injection of beta-galactosidase transfected B16-F10 cells and subsequent determination of cancer cell colonies in the lungs. RESULTS: Cystatin C deficient mice were fertile and showed no gross pathological abnormality up to 6 months of age. Compared with wild-type mice, seven times fewer large metastatic colonies were counted by means of a dissecting microscope in CysC-/- mice two weeks after tail vein injection of B16-F10 cells. At all of eight time points from 15 minutes to two weeks after intravenous injection of tumour cells, the CysC-/- mice had significantly fewer lung metastases. The observed differences were smaller when beta-galactosidase transfected cells were used to allow counting of small colonies. Subcutaneous and intracerebral tumour growth was not different in the CysC-/- mice. CONCLUSIONS: Cystatin C concentrations in vivo might influence metastasis in some tissues. The decreased metastatic spread of B16-F10 cells in CysC-/- mice is the result of both reduced seeding and reduced growth of tumour cells in their lungs.
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| 5. |
- Ménoret, A, et al.
(författare)
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The expression of carbohydrate blood group antigens correlates with heat resistance.
- 1995
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Ingår i: Journal of cell science. - 0021-9533. ; 108 ( Pt 4), s. 1691-701
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Tidskriftsartikel (refereegranskat)abstract
- Recent data indicate that cells may resist heat shock via more than one route: heat shock protein synthesis and other still ill-defined mechanisms. We investigated this phenomenon using four types of cells derived from a single rat colon carcinoma: clones REGb and PROb; PRO A+, a glycosylation variant of PROb selected for its high expression of blood group A antigen; and Ph8, a thermoresistant variant of PROb selected by repeated sublethal heat treatments. Basal heat resistance was clearly associated with the level of cell surface expression of blood group H and A antigens. Biosynthesis of these carbohydrate structures requires two glycosyltransferases, H and A enzymes, whose activities are also correlated with basal heat resistance. In addition, heat sensitive REGb cells were rendered more resistant by transfection with the gene encoding for H enzyme, allowing expression of H antigen. Thus, these terminal glycosylations could play a role as cellular protectors against heat treatment. Blood group carbohydrate antigens were mainly located on O-linked carbohydrate chains of a major glycoprotein of 200 kDa and to a lesser extent on N-linked chains. Only trace amounts were present as glycolipids.
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| 6. |
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| 7. |
- Xing, K. Z., et al.
(författare)
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The electronic and geometric structures of neutral and potassium-doped poly[3-(4-octylphenyl)thiophene] studied by photoelectron spectroscopy
- 1996
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Ingår i: Synthetic metals. - : Elsevier. - 0379-6779 .- 1879-3290. ; 76:1-3, s. 263-267
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Tidskriftsartikel (refereegranskat)abstract
- The electronic and geometric structures of poly [3-(4-octylphenyl)thiophene] have been studied by X-ray and ultraviolet photoelectron spectroscopy (XPS and UPS, respectively). Thermochromic effects, and new charge induced states generated by potassium doping, have been observed by direct UPS measurements. The experimental results are in very good agreement with the results of theoretical quantum chemical calculations performed with the Austin Model 1 semi-empirical model and the valence-effective Hamiltonian pseudo-potential model.
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| 8. |
- Xing, K. Z., et al.
(författare)
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The electronic structure of neutral and alkali metal-doped poly[3-(4-octylphenyl)thiophene] studied by photoelectron spectroscopy
- 1996
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Ingår i: Synthetic metals. - : Elsevier. - 0379-6779 .- 1879-3290. ; 80:1, s. 59-66
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Tidskriftsartikel (refereegranskat)abstract
- The electronic structure of poly [3-(4-octylphenyl)thiophene] (POPT) has been studied by ultraviolet photoelectron spectroscopy (UPS) and X-ray photoelectron spectroscopy (XPS), as well as by quantum chemical calculations. Both temperature-dependent effects on the electronic structure of the neutral system, as well as the generation of new electronic states induced by doping with alkaline metals, have been observed. The experimental results are in good agreement with the results of the quantum chemical calculations.
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