| 1. |
- Dunham, I, et al.
(författare)
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The DNA sequence of human chromosome 22
- 1999
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 402:6761, s. 489-495
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Liu, H R, et al.
(författare)
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Screening of serum autoantibodies to cardiac beta1-adrenoceptors and M2-muscarinic acetylcholine receptors in 408 healthy subjects of varying ages.
- 1999
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Ingår i: Autoimmunity. - 0891-6934. ; 29:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies to cardiac beta1-adrenoceptors and M2-muscarinic receptors have mainly been found in the sera of patients with idiopathic dilated cardiomyopathy (DCM). In order to elucidate the pathological significance of these autoantibodies in DCM, it is necessary to understand their characteristic distribution in a healthy population of different genders and ages. The peptides corresponding to the sequences of the second extracellular loops of the human beta1-adrenoceptor and M2-muscarinic receptors were therefore used as antigens to screen the sera of 408 healthy subjects of different ages (ranging from 0.5 to 85 years). Of 408 sera, 41 (10.0%) and 46 (11.3%) recognized the beta1-adrenoceptor and M2-muscarinic receptor peptides respectively. Of the positive sera for beta1-adrenoceptors and M2-muscarinic receptors, up to 63.4% and 56.5% had both anti-beta1-adrenoceptor and anti-M2-muscarinic receptor autoantibodies respectively. The antibody titres of the positive sera of healthy subjects were all of a low level, with a geometric mean titre of 1:42+/-1.9 for anti-beta1-adrenoceptor antibodies and 1:51+/-1.7 for anti-M2-muscarinic receptor antibodies. The frequency of occurrence of autoantibodies to both receptors in the sera of healthy subjects increased significantly with age. In conclusion, the autoantibodies to beta1-adrenoceptors and M2-muscarinic receptors in the sera of healthy subjects are characterized by a low frequency of occurrence and low titre, with the frequency of occurrence increasing with age.
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| 3. |
- Wang, W Z, et al.
(författare)
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Effects of anti-peptide antibodies against human M2 muscarinic receptors on cardiac function in rats in vivo.
- 1996
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Ingår i: Blood pressure. Supplement. - 0803-8023. ; 3, s. 25-7
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Tidskriftsartikel (refereegranskat)abstract
- The effects of anti-peptide antibodies (Ab) against the second extracellular loop of human muscarinic receptor-2 on cardiac function in rats in vivo were studied. These effects were compared with those of the muscarinic receptor agonist, carbachol (Carb). It was shown that: (1) both Carb and Ab administered intravenously in the same doses of 0.4 nmol, 1.0 nmol, and 2.0 nmol were able to inhibit the maximal rate of rise of ventricular pressure (+dp/dt max) in a dose-dependent manner. (2) The isoproterenol (Iso)-induced increase in HR and +dp/dt max were also markedly inhibited by Carb and Ab. Administration of 1.0 nmol Carb decreased the Iso-stimulated increase of HR from 13.6 +/- 2.0 to 4.9 +/- 0.7% and decreased the increase of +dp/dt max from 27.9 +/- 3.2 to 4.8 +/- 0.6%, respectively; whereas Ab decreased the HR to 6.5 +/- 1.1% and +dp/dt max to 13.5 +/- 1.2%, respectively. (3) Both the inhibitory effects of Carb and Ab could be significantly blocked by atropine (1.4 nmol). These findings suggest that the Ab display a stimulatory muscarinic activity similar to Carb in inhibiting the cardiac function as evidenced by its negative chronotropic and inotropic effects.
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| 4. |
- Wang, W Z, et al.
(författare)
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Effects of anti-peptide antibodies against human M2 muscarinic receptors on the cAMP generating system in guinea pig ventricles.
- 1996
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Ingår i: Blood pressure. Supplement. - 0803-8023. ; 3, s. 22-4
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Tidskriftsartikel (refereegranskat)abstract
- The effects of anti-peptide antibodies (Ab) against the second extracellular loop of human muscarinic receptor-2 on the cAMP generating system in guinea pig ventricles were studied. These effects were compared with those of the muscarinic receptor agonist carbachol (Carb). It was shown that: (1) both Carb and Ab were able to inhibit the isoproterenol (Iso)-stimulated cAMP production of ventricles in a dose-dependent manner. Carb at 2 microM, 10 microM and 50 microM decreased Iso-stimulated cAMP production by 8.0 +/- 1.1, 15.8 +/- 1.2 and 28.4 +/- 1.7%, respectively; whereas Ab at 50 nM, 100 nM and 400 nM decreased it by 5.8 +/- 0.4, 16.8 +/- 1.4 and 30.6 +/- 2.5%, respectively. (2) Both Carb and Ab could also inhibit the basal cAMP content of ventricles significantly. Carb at 10 microM and Ab at 100 nM decreased it by 46.9 +/- 4.2% and 60.2 +/- 4.6%, respectively. (3) The inhibitory effects of both Ab and Carb on Iso-stimulated cAMP production were significantly prevented by atropine at 1.5 microM. (4) The inhibitory effect of Ab at 100 nM was almost completely abolished by the peptide (700 nM) used as immunogen. These findings suggest that the antibodies exhibit a stimulatory muscarinic activity similar to carbachol in the inhibitory modulation of cAMP production.
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| 5. |
- Zhu, L, et al.
(författare)
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Immunocytochemical studies of M2 muscarinic receptors in guinea pig atria and ventricles using anti-peptide antibodies.
- 1996
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Ingår i: Blood pressure. Supplement. - 0803-8023. ; 3, s. 19-21
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The localization and density of M2 muscarinic receptors in guinea pig atria and ventricles were studied by immunocytochemical techniques, with anti-peptide antibodies against the second extracellular loop of human muscarinic receptor-2. It was shown that the positive immunoreaction of M2 muscarinic receptor was characterized by brown-yellow granules of variable size and shape, which were located mainly on the cell surface and in the cytoplasm far from nuclei. The positive immunoreactive substances appeared in both atrial and ventricular myocytes, with the density being greater in atria than in ventricles. Pre-incubation with atropine, but not carbachol, significantly reduced the intensity of positive immunoreactivity. This indicates that the binding of antibody to receptor site can be partially blocked by M2 muscarinic receptor antagonist.
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| 6. |
- Peukert, S, et al.
(författare)
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The frequency of occurrence of anti-cardiac receptor autoantibodies and their correlation with clinical manifestation in patients with hypertrophic cardiomyopathy.
- 1999
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Ingår i: Autoimmunity. - 0891-6934. ; 29:4, s. 291-7
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to investigate the frequency of occurrence of autoantibodies against G-protein coupled cardiovascular receptors and their relation to the clinical manifestation of hypertrophic cardiomyopathy (HCM). Autoantibodies against beta1-receptors, Muscarin-2-receptors, Angiotensin-II-receptor subtype 1 and alpha1-receptors were determined with ELISA in 52 patients with HCM (37 male, 15 female, mean age 55 +/- 15 years) and 40 healthy, age and sex matched controls. The clinical characterization of the HCM-patients included ECG, 24-h Holter, and echocardiography. The results showed that there is no significant difference in the frequency of a single autoantibody between HCM-patients and controls. However, if the number of patients who have autoantibodies against beta1-receptors and/or Muscarin-2-receptors were counted together, there are significantly more autoantibodies in HCM compared to controls (11 vs. 2, p = 0.035). Analysis of clinical data from this pooled group of patients showed that in patients with autoantibodies, heart rate variability (HRV), ultra low frequency (ULF) and very low frequency (VLF) were decreased (HRV by 20%, ULF by 50%, and VLF by 46%, p < 0.008) whereas the QTc-interval was increased by 8% (p < 0.02 each). The ratio of septal to posterior wall thickness was increased by 23% (p = 0.05), and the preejection period was prolonged by 46% in patients with autoantibodies (p < 0.001). These results suggest that the existence of these autoantibodies could be associated with an advanced stage or a severe manifestation of HCM.
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| 7. |
- Zhao, R, et al.
(författare)
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Effects of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic acetylcholine receptors on transmembrane potentials and currents in guinea pig ventricular myocytes.
- 1996
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Ingår i: Molecular and cellular biochemistry. - 0300-8177. ; 163-164, s. 185-93
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Tidskriftsartikel (refereegranskat)abstract
- The effects of anti-peptide antibodies against the second extracellular loop of human M2 muscarinic receptor on transmembrane potentials and currents in guinea pig single ventricular cells were analyzed using whole-cell patch clamp technique. These effects were compared with those of the muscarinic receptor agonists carbachol and acetylcholine. The antibodies shortened the action potential duration in a dose-dependent manner. By using a ramp or step rectangular pulse protocol, it was found that the antibodies increased the outward K+ current and decreased the inward basal ICa significantly. The reversal potential of both carbachol- and antibody-induced extra currents were close to -80 mV, being in proximity to the calculated Ek of -90 mV. A beta-adrenergic receptor agonist, isoprenaline, prolonged the action potential and increased the overshoot which could be inhibited by both antibody and carbachol. Isoprenaline increased inward ICa and outward Ik simultaneously. Both antibody and carbachol could significantly reduce the isoprenaline-stimulated ICa but not the isoprenaline-stimulated Ik. The antibody- or carbachol-induced outward K+ current and the depressant effects of antibody and carbachol on isoprenaline-stimulated ICa were partially antagonized by atropine. These results suggest that the anti-M2 muscarinic receptor antibodies display a stimulatory activity similar to muscarinic receptor agonist on the receptor-mediated electrophysiological events.
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