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111.
d'Amati G Bagattin A Bauce B Rampazzo A Autore C Basso C King K Romeo MD Gallo P Thiene G Danieli GA Nava A 《Human pathology》2005,36(7):761-767
We report on a family with a history of sudden death and effort-induced polymorphic ventricular arrhythmias. The index case was a 17-year-old boy who died suddenly and at postmortem had evidence of fibrofatty replacement in the right ventricular free wall, consistent with arrhythmogenic right ventricular cardiomyopathy, as well as calcium phosphate deposits within the myocytes. A molecular genetics investigation carried out in the paraffin-embedded myocardium of the subject and in blood samples of family members disclosed a missense mutation in exon 3 (230C-->T; A77V) of the cardiac ryanodine receptor type 2 gene. The carriers showed effort-induced polymorphic ventricular tachycardia in the setting of normal resting electrocardiogram and trivial echocardiographic abnormalities, consistent with catecholaminergic polymorphic ventricular tachycardia. The observation of both arrhythmogenic right ventricular cardiomyopathy type 2 and catecholaminergic polymorphic ventricular tachycardia in the same family suggests that the two entities might correspond to different degrees of phenotypic expression of the same disease. This experience underscores the importance of a precise autopsy diagnosis in the case of sudden cardiac death, including molecular genetics, and the mission of pathologists to guide further clinical investigation of family members. 相似文献
112.
Effective induction of immune tolerance by portal venous infusion with IL-10 gene-modified immature dendritic cells leading to prolongation of allograft survival 总被引:14,自引:0,他引:14
Zhang M Wang Q Liu Y Sun Y Ding G Fu Z Min Z Zhu Y Cao X 《Journal of molecular medicine (Berlin, Germany)》2004,82(4):240-249
Dendritic cells (DC) not only initiate T cell responses, but are also involved in the induction of tolerance. The functional properties of DC are strictly dependent on their state of maturation. It has been shown that immature DC can induce immune tolerance and prolong allograft survival. Interleukin-10 (IL-10) is an important immunosuppressive cytokine which inhibits maturation and function of DC. In order to improve the tolerogenicity of DC, we and others showed that adenovirus vectors can effectively mediate IL-10 genetic modification of DC, and IL-10 genetic modification can inhibit MHC II, B7.2, and CD40 expression, IL-12 secretion and the T cell stimulatory capacity of DC. The primary aim of this study is to examine the in vivo effects of this approach on allograft survival in a murine cardiac allograft transplantation model. To our surprise, we observed that infusion of immature DC genetically modified to express IL-10 (DC-IL-10) via the tail vein could not prolong allograft survival in the recipients, but shortened their survival. More interestingly, portal venous infusion of DC-IL-10 markedly prolonged allograft survival. The diverse effects of DC-IL-10 infusion through different routes may be due to the different immune responses to alloantigens in recipients that received DC-IL-10 via either the portal or the tail vein. Decreased cytotoxicity, polarization of Th2 response, poor T cell stimulating activity of liver DC and enhanced incidence of donor DC in the recipients may contribute to the more efficient prolongation of allograft survival observed after portal venous infusion of DC-IL-10. These results suggest that portal venous infusion may be an effective approach for immature DC to induce immune tolerance or hyporesponsiveness against donor antigens, and prolong allograft survival.Abbreviations
APC
Antigen-presenting cells
-
CTL
Cytotoxic T lymphocytes
-
DC
Dendritic cells
-
DC-IL-10
IL-10 gene-modified immature dendritic cells
-
iDC
Immature dendritic cells
-
IL-10
Interleukin-10
-
MLR
Mixed leukocyte reaction
-
MOI
Multiplicity of infection 相似文献
113.
Jiqing Guo Kyoichi Ono Akinori Noma 《Pflügers Archiv : European journal of physiology》1996,433(1-2):209-211
Under the whole cell clamp, superfusion of the rabbit sinoatrial node cells with a Na+-free solution suppressed the sustained inward current (Ist), and the L-type Ca2+ current (ICa,L) could be recorded on depolarization less negative than –40 mV from the holding potential of –80 mV. On the other hand, replacement
of Ca2+ with Mg2+ in the external solution suppressed inward-going ICa,L and isolated Ist. Under this condition, Ist measured as a nicardipine-sensitive current showed an activation threshold between –60 and –70 mV. The conductance sequence
of Ist for monovalent ions was determined as Na+ > Li+ >> K+ @ Cs+ by replacing the external Na+ with these alkali metal ions. The contribution of Ist to the diastolic depolarization is discussed.
Received: 12 June 1996 / Received after revision: 31 July 1996 / Accepted: 7 August 1996 相似文献
114.
115.
Katrin Banach Moritz Bünemann Jörg Hüser Lutz Pott 《Pflügers Archiv : European journal of physiology》1993,423(3-4):245-250
L-type Ca2+ current (I
Ca) was measured in cultured atrial myocytes from hearts of adult guinea-pigs using whole-cell voltage clamp. Potentiation of I
Ca induced by -adrenergic stimulation (isoprenaline 2· 10–7 M) could be completely antagonized by diluted sera (1100 v/v). Half-maximal inhibition of -receptorstimulated I
Ca occurred at about 11000. Basal I
Ca was not affected by serum. Atropine in a concentration (10–6M) that completely antagonized the anti-adrenergic effect of acetylcholine (ACh, 2·10–6 M) did not interfere with the effect of serum. In cells dialysed with cyclic adenosine monophosphate (cAMP)-containing (10–4 M) pipette solution, potentiated I
Ca was insensitive to both ACh and serum. Preincubation of the myocytes with pertussis toxin almost completely abolished the anti-adrenergic effects of both ACh and serum. The potency of serum was not reduced by dialysis. It is concluded that serum contains a factor which, like ACh, inhibits -receptor-stimulated adenylyl cyclase via Giprotein.A preliminary report of this work has appeared in abstract form [11] 相似文献
116.
The protective effects of Ginkgo biloba Phytosomes (GBP) in isoproterenol (ISO)-induced cardiotoxicity and the antioxidant activity involved in this protection were investigated in rats. Myocardial infarction was produced in rats with 65, 85, 120 and 200mg/kg of ISO administered subcutaneously (sc) twice at an interval of 24h. An ISO dose of 85mg/kg was selected for the present study as this dose offered significant alteration in biochemical parameters and moderate necrosis in heart. Effect of GBP oral treatment for 21 days at two doses (100mg and 200mg/kg body weight) was evaluated against ISO (85mg/kg, sc)-induced cardiac necrosis. Levels of marker enzymes (AST, LDH and CPK) were assessed in serum and heart, antioxidant parameters viz., reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR) and malondialdehde (MDA) were assayed in heart homogenate. Significant myocardial necrosis, depletion of endogenous antioxidants and increase in serum levels of marker enzymes were observed in ISO-treated animals when compared with the normal animals. GBP elicited a significant cardioprotective activity by lowering the levels of serum marker enzymes and lipid peroxidation and elevated the levels of GSH, SOD, CAT, GPx and GR. The present findings have demonstrated that the cardioprotective effects of GBP in ISO-induced oxidative damage may be due to an augmentation of the endogenous antioxidants and inhibition of lipid peroxidation of membrane. 相似文献
117.
Criscione JC Lorenzen-Schmidt I Humphrey JD Hunter WC 《Annals of biomedical engineering》1999,27(2):123-130
Finite extension and torsion tests on cardiac papillary muscles are presently the best way to directly measure the response to shear along myocardial fibers. Quantifying this response is necessary for determining the complete three-dimensional constitutive behavior of myocardium as a transversely isotropic material. Analysis of such tests is complicated, however, since papillary muscles are materially inhomogeneous, consisting of a myocardial core surrounded by an endocardial sheath that is rich in collagen. In this article, we show that the papillary muscle response to extension and torsion additively decouples into the response of the bare myocardial core plus the response of an endocardial sheath filled with fluid (assuming the muscle is a radially inhomogeneous and incompressible continuum with cylindrical symmetry). This result allows the endocardial response to be subtracted from the intact papillary muscle response to obtain the response of the bare myocardial core. An initial estimate suggests that the endocardial sheath affects the axial moment significantly (50% of torque for all twists at low stretch) but affects the axial force only slightly (<10% at moderate twists). © 1999 Biomedical Engineering Society.
PAC99: 8719Hh, 8719Rr, 8719Ff 相似文献
118.
Hiroko Matsuda 《Pflügers Archiv : European journal of physiology》1986,407(5):465-475
An inward current characterized by a slow inactivation, was induced when the extracellular Ca2– concentration was reduced by EGTA. It was suppressed by replacing external Na– with Tris+ or by D-600, increased by epinephrine, and was not affected by TTX. These findings suggest that this current is carried by Na+ ions through the Ca channels. The Na current decreased in amplitude as the concentration of external divalent cations was elevated. Blocking the Na current by divalent cations could be approximated by a bimolecular interaction between divalent cation and channel, with a dissociation constant of 1.2 M for Ca2+ and 60 M for Mg2+. Single channel currents were recorded in the cell-attached configuration. With a pipette solution of pCa=7.5 or pCa>8, the single channel I-V relationship was linear and the slope conductance was 70–75 pS. For 40 mV depolarizations from the resting potential, unitary currents were smaller at pCa=6 than at pCa=7.5. However, single channel events, which were observed after the repolarizing step to the resting potential, were much the same amplitude. The open time histogram was fitted with a single exponential having a time constant of 1.9 ms at around –40 mV (pCa>8, with 5 M Bay K 8644 in the bath solution), which was decreased with increasing the Ca2+ concentration in the pipette solution. Noise power spectra of patch currents at pCa=6 revealed a high-frequency component at around 1500 Hz. These results suggest that Ca binding to the sites with a high affinity for Ca2+ blocks the Na conductance in Ca channels. Reduction of the unitary current at higher concentrations of Ca2+ might be attributed to a rapid block by Ca2+. 相似文献
119.
Victor A. Convertino Karen L. Mathes Mary L. Lasley Clare M. Tomaselli Mary A. B. Frey G. Wyckliffe Hoffler 《European journal of applied physiology》1993,67(6):492-498
Hemodynamic, cardiac, and hormonal responses to lower-body negative pressure (LBNP) were examined in 24 healthy men to test the hypothesis that responsiveness of reflex control of blood pressure during orthostatic challenge is associated with interactions between strength and aerobic power. Subjects underwent treadmill tests to determine peak oxygen uptake (
O2max) and isokinetic dynamometer tests to determine knee extensor strength. Based on predetermined criteria, subjects were classified into one of four fitness profiles of six subjects each, matched for age, height, and body mass: (a) low strength/average aerobic fitness, (b) low strength/high aerobic fitness, (c) high strength/average aerobic fitness, and (d) high strength/high aerobic fitness. Following 90 min of 0.11 rad (6°) head-down tilt (HDT), each subject underwent graded LBNP to –6.7 kPa or presyncope, with maximal duration 15 min, while hemodynamic, cardiac, and hormonal responses were measured. All groups exhibited typical hemodynamic, hormonal, and fluid shift responses during LBNP, with no intergroup differences between high and low strength characteristics. Subjects with high aerobic power exhibited greater (P < 0.05) stroke volume and lower (P < 0.05) heart rate, vascular peripheral resistance, and mean arterial pressure during rest, HDT, and LBNP. Seven subjects, distributed among the four fitness profiles, became presyncopal. These subjects showed greatest reduction in mean arterial pressure during LBNP, had greater elevations in vasopressin, and lesser increases in heart rate and peripheral resistance. Neither
O2max nor leg strength were associated with fall in arterial pressure or with syncopal episodes. We conclude that interactions between aerobic and strength fitness characteristics do not influence responses to LBNP challenge. 相似文献
120.
Minora Ogata Hidekazu Shigematsu Akio Sakai Yasunori Yanagidaira Gou Ueda Toshio Kobayashi 《Pathology international》1988,38(5):549-558
We carried out an experiment to analyze morphological differences in hearts of rats well adapted and poorly adapted to chronic hypoxia. Male and female Wistar rats, 1 week, 4 weeks and 9 weeks old, were employed on the assumption that adaptive ability was dependent on age and sex. These rats were raised at an altitude of 2,400 m and were kept for 7 to 9 weeks. Control groups were maintained at an altitude of 600 m during the same period of time. Each group consisted of 4 to 6 rats. At the end of the experiment, body weight, heart weight, ratio of heart weight to body weight and hematocrit were measured, and ventricular wall thickness, myocardial fiber diameter, capillary supply and mitochondria were morphometrically studied. Of the 6 experimental groups, the 4-week-old male rats (M2) had the highest body weight, as compared with the other experimental groups. In addition, relative to these other experimental groups, the following features were found for M2. Heart weight was intermediate, heart weight/body weight ratio was low and hematocrit was also low. Ventricular wall thickness was intermediate in the right ventricle (RV) and interventricular septum (IVS) but was thin in the left ventricle (LV). Myocardial fiber diameter was intermediate in the RV, large in the IVS and small in the LV. Capillary supply was intermediate in the RV and dense in the IVS and LV. Mitochondria were small but cristal density and percentage area, estimated from electron micrographs, were found to be high. These data showed that in well developed rats under chronic hypoxia, there is good development of capillary supply with corresponding restriction of cardiac hypertrophy, while hematocrit count and mitochondria are also affected. 相似文献