RESUMO
A developing supercritical collisionless shock propagating in a homogeneously magnetized plasma of ambient gas origin having higher uniformity than the previous experiments is formed by using high-power laser experiment. The ambient plasma is not contaminated by the plasma produced in the early time after the laser shot. While the observed developing shock does not have stationary downstream structure, it possesses some characteristics of a magnetized supercritical shock, which are supported by a one-dimensional full particle-in-cell simulation taking the effect of finite time of laser-target interaction into account.
RESUMO
We present an experimental method to generate quasiperpendicular supercritical magnetized collisionless shocks. In our experiment, ambient nitrogen (N) plasma is at rest and well magnetized, and it has uniform mass density. The plasma is pushed by laser-driven ablation aluminum (Al) plasma. Streaked optical pyrometry and spatially resolved laser collective Thomson scattering clarify structures of plasma density and temperatures, which are compared with one-dimensional particle-in-cell simulations. It is indicated that just after the laser irradiation, the Al plasma is magnetized by a self-generated Biermann battery field, and the plasma slaps the incident N plasma. The compressed external field in the N plasma reflects N ions, leading to counterstreaming magnetized N flows. Namely, we identify the edge of the reflected N ions. Such interacting plasmas form a magnetized collisionless shock.
RESUMO
A cDNA clone encoding a novel putative G protein-coupled receptor was isolated from rat aortic vascular smooth muscle cell cDNA library by the polymerase chain reaction (PCR) using degenerate oligonucleotide primers and subsequent hybridization screening with a cloned PCR product. Sequence analysis of this clone (AGR9) shows that it encodes a 483 amino acid protein with seven streches of hydrophobic amino acids, which are presumed to represent transmembrane domains. In addition, AGR9 protein exhibits several structural features characteristic of the G protein-coupled receptor family, which include the existence of potential N-linked glycosylation sites in the amino-terminal region, phosphorylation sites by serine/threonine kinases in the intracellular regions, and a number of well-conserved residues among most of the G protein-coupled receptors. Northern blot analysis indicates abundant expression of a major 3.9 kb AGR9 mRNA in brain, lung, heart, stomach, intestine, cultured rat aortic smooth muscle cells and cardiac myocytes. Treatment of rat aortic smooth muscle cells with the adenylyl cyclase activator forskolin causes a marked and transient decrease in the steady-state level of AGR9 mRNA. Dibutyryl cyclic AMP and the beta-adrenergic agonist isoproterenol mimick the effect of forskolin. The ligand for AGR9 receptor has yet to be identified, however, these results suggest the existence of a novel G protein-coupled receptor expressed in the cardiovascular, central nervous and digestive systems.
Assuntos
AMP Cíclico/metabolismo , DNA Complementar/isolamento & purificação , Proteínas de Ligação ao GTP/metabolismo , Músculo Liso Vascular/metabolismo , RNA Mensageiro/análise , Receptores de Superfície Celular/genética , Receptores Acoplados a Proteínas G , Animais , Sequência de Bases , Células Cultivadas , Clonagem Molecular , Regulação para Baixo , Regulação da Expressão Gênica , Dados de Sequência Molecular , Ratos , Receptores de Superfície Celular/metabolismo , Sistemas do Segundo Mensageiro , Alinhamento de SequênciaRESUMO
Recently, heme oxygenase-1 (HO-1) has been shown to be present in vascular smooth muscle cells. In the present study, we examined the effect of angiotensin II (Ang II) on HO-1 in rat vascular smooth muscle cells. After treatment with 100 nmol/L Ang II, HO-1 mRNA levels were decreased, with a nadir at 2 hours (39+/-9% of the control level, P<.01). This downregulation was completely blocked by the Ang II type I receptor antagonist losartan. Western blot analysis showed that HO-1 protein is also significantly downregulated, with a nadir at 4 hours (52+/-6% of the control level, P<.01). Heme oxygenase activity was also significantly decreased at 4 hours (control, 0.35+/-0.86 nmol bilirubin/mg per hour; Ang II, 0.10+/-0.06). This downregulation was observed in serum-starved cells to a similar extent as in serum-supplemented cells. Inhibitors of protein kinase C, lipoxygenase, cyclooxygenase, cytochrome P450 monooxygenase, and phospholipase A2 did not block this downregulation. However, this effect was not observed in the absence of calcium and presence of EGTA (2 mmol/L). Furthermore, a 2-hour incubation with calcium ionophore or arginine vasopressin decreased HO-1 mRNA levels, suggesting that an increase of intracellular calcium mediates the downregulation. In conclusion, Ang II decreases HO-1 mRNA in a calcium-dependent manner in vascular smooth muscle cells, which may provide a novel mechanism for the modulation of vascular tone and oxidative stress.
Assuntos
Angiotensina II/fisiologia , Antagonistas de Receptores de Angiotensina , Heme Oxigenase (Desciclizante)/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/enzimologia , Vasoconstritores/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Compostos de Bifenilo/farmacologia , Células Cultivadas , Regulação para Baixo , Imidazóis/farmacologia , Losartan , Masculino , Proteína Quinase C/antagonistas & inibidores , RNA Mensageiro/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Tetrazóis/farmacologiaRESUMO
Caveolae are membrane domains that have been implicated in signal transduction, and caveolins are major structural components of these domains. We found that all reported caveolin isoforms (caveolin-1, -2, and -3) were expressed in vascular smooth muscle cells (VSMCs); however, only caveolin-1 mRNA was regulated by angiotensin II (Ang II). Ang II (100 nmol/L) increased caveolin-1 mRNA, with a peak at 2 hours (193+/-6% of control, P<0.01, n=4). In contrast, Ang II significantly decreased caveolin-1 protein, with a nadir at 4 hours (64+/-5% of control, P<0.01, n=6). [35S]Methionine labeling showed that Ang II increased caveolin biosynthesis (226+/-33% of control labeling at 4 hours), suggesting that the transient decrease in caveolin protein levels is due to increased degradation. When cells were fractionated with sucrose, on agonist stimulation, AT1 receptors appeared in fraction 5 where caveolin was fractionated. This migration was blocked by low temperature and treatment with phenylarsine oxide, interventions that interfere with agonist-induced Ang II type 1 (AT1) receptor sequestration and tonic phase signaling. In addition, caveolin-1 coimmunoprecipitates with AT1 receptor only on agonist stimulation. These data support the concept that the caveola is a specialized signaling domain in VSMCs that can be dynamically accessed by the AT1 receptor. Because of the signaling and coupling proteins that are localized in caveolae and because of evidence that these proteins may interact directly with caveolin, caveola-AT1 receptor interaction likely represents an important focus for dynamic control of receptor signaling in VSMCs.
Assuntos
Angiotensina II/fisiologia , Caveolinas , Proteínas de Membrana/fisiologia , Músculo Liso Vascular/fisiologia , Receptores de Angiotensina/fisiologia , Vasoconstritores/farmacologia , Angiotensina II/farmacologia , Animais , Anti-Hipertensivos/farmacologia , Caveolina 1 , Células Cultivadas , Cães , Interações Medicamentosas , Ionomicina/farmacologia , Ionóforos/farmacologia , Losartan/farmacologia , Proteínas de Membrana/biossíntese , Proteínas de Membrana/efeitos dos fármacos , Músculo Liso Vascular/efeitos dos fármacos , Testes de Precipitina , RNA Mensageiro/isolamento & purificação , Ratos , Receptores de Angiotensina/agonistas , Transdução de Sinais/efeitos dos fármacosRESUMO
Monocyte chemoattractant protein-1 (MCP-1), a potent monocyte chemoattractant synthesized by vascular cells and monocytes, has been proposed to be an important mediator of inflammatory responses in the arterial vasculature. It was recently demonstrated that hypertension is associated with an inflammatory response in the arterial wall. To determine the effect of hypertension on arterial MCP-1 expression, we induced hypertension in Sprague-Dawley rats by infusing angiotensin II (0.75 mg x kg[-1] x d[-1] SC) for 7 days. Using Northern blot analysis, we detected a 3.6-fold increase in MCP-1 mRNA in the aortas of hypertensive rats. When we normalized blood pressure in angiotensin II-treated rats through oral administration of the nonspecific vasodilator hydralazine (15 mg x kg[-1] x d[-1]), aortic MCP-1 mRNA expression was significantly reduced. Similar results were obtained with a norepinephrine model of hypertension. Taken together, these data suggest that mechanical factors may be responsible in part for the upregulation of expression. Consistent with this interpretation, we found that cultured rat aortic vascular smooth muscle cells exposed to mechanical strain (20% peak deformation at 1 Hz) exhibited a marked increase in MCP-1 expression, suggesting the hemodynamic strain imparted onto arterial cells in hypertension is an important stimulus underlying this phenomenon. These results provide important insights into the in vivo regulation of MCP-1 and have potential implications for understanding the influence of hypertension on atherosclerosis.
Assuntos
Angiotensina II/farmacologia , Aorta/metabolismo , Quimiocina CCL2/biossíntese , Hipertensão/metabolismo , Músculo Liso Vascular/metabolismo , Transcrição Gênica/efeitos dos fármacos , Angiotensina II/administração & dosagem , Animais , Aorta/fisiologia , Aorta/fisiopatologia , Pressão Sanguínea/efeitos dos fármacos , Hidralazina/farmacologia , Hipertensão/induzido quimicamente , Hipertensão/fisiopatologia , Infusões Parenterais , Macrófagos/metabolismo , Masculino , Músculo Liso Vascular/fisiologia , Músculo Liso Vascular/fisiopatologia , Norepinefrina/farmacologia , RNA Mensageiro/biossíntese , Ratos , Ratos Sprague-Dawley , Estresse MecânicoRESUMO
We investigated whether application of non-distending hydrostatic pressure facilitates gene transfer into vein grafts. An external jugular vein was placed in a chamber with 100 microl adenovirus solution at a titer of 10(10) pfu/ml and was pressurized to up to 8 atm above ambient pressure for 10 min. Histochemical analysis demonstrated a positive transgene expression in all layers of the vessel wall. Gene transfer with 8 atm pressurization resulted in an approximately 50 times higher transgene expression than that without pressurization. Under 8 atm pressurization, the efficiency of gene transfer reached a plateau at 7.5 min. The application of hydrostatic pressure may improve the effectiveness of intraoperative genetic engineering of vein grafts.
Assuntos
Adenoviridae/genética , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Veias Jugulares/metabolismo , Veias Jugulares/transplante , Transgenes/genética , Animais , Anticorpos Monoclonais/imunologia , Linhagem Celular , Células Cultivadas , Expressão Gênica , Genes Reporter/genética , Heme Oxigenase (Desciclizante)/genética , Heme Oxigenase (Desciclizante)/imunologia , Heme Oxigenase (Desciclizante)/metabolismo , Heme Oxigenase-1 , Pressão Hidrostática , Técnicas In Vitro , Veias Jugulares/citologia , Veias Jugulares/cirurgia , Óperon Lac/genética , Masculino , Músculo Liso Vascular/citologia , Músculo Liso Vascular/metabolismo , Coelhos , Ratos , Soluções , Transplante AutólogoRESUMO
Recent studies have suggested that prolonged hypoxia results in increased production of reactive oxygen species in cardiomyocytes, which leads to apoptosis of these cells. We previously showed that lecithinized recombinant human copper, zinc-superoxide dismutase (rhSOD) showed increased bioavailability through greater membrane affinity and a longer half-life than unmodified SOD. The purpose of this study was to investigate whether lecithinized SOD plays a protective role against hypoxic injury in cardiomyocytes. Cultured rat cardiomyocytes incubated with lecithinized SOD (100 U/ml), unmodified SOD (100 U/ml), or vehicle alone were subjected to hypoxia for up to 72 h. Lecithinized SOD, but not unmodified SOD, was successfully delivered intracellularly, which was verified by Western blot and confocal laser-scanning microscopy. Treatment of cells with lecithinized SOD significantly suppressed hypoxia-induced cell damage. Since lecithinized SOD also suppressed hypoxia-induced DNA fragmentation, the improved cell survival provided by lecithinized SOD is thought to be mediated by its antiapoptotic effect. In summary, lecithinization resulted in a facilitated rhSOD delivery into cultured cardiomyocytes, which reduced mortality of cardiomyocytes exposed to prolonged hypoxia.
Assuntos
Hipóxia Celular , Coração/fisiologia , Miocárdio/patologia , Superóxido Dismutase/metabolismo , Animais , Animais Recém-Nascidos , Células Cultivadas , Dano ao DNA , Portadores de Fármacos , Coração/efeitos dos fármacos , Humanos , Cinética , Microscopia Confocal , Fosfatidilcolinas , Ratos , Ratos Wistar , Proteínas Recombinantes/farmacocinética , Proteínas Recombinantes/farmacologia , Superóxido Dismutase/farmacologiaRESUMO
Leukotriene A(4) (LTA(4)) hydrolase is essential for the conversion of LTA(4) to LTB(4), an inflammatory lipid mediator. We investigated whether LTA(4) hydrolase was regulated in the heart by angiotensin II (ang II) infusion. Continuous ang II infusion via an osmotic minipump for up to 7 days upregulated mRNA and protein levels of LTA(4) hydrolase ( approximately 3.5-fold of control) in the heart in a pressor-dependent manner. Immunohistochemistry demonstrated intense LTA(4) hydrolase staining in the myofibroblast as well as migrated monocytes/macrophages. These data suggest that the cardiac LTA(4) hydrolase-LTB(4) system plays a positive role in the promotion of cardiac inflammation in hypertension.
Assuntos
Angiotensina II/farmacologia , Epóxido Hidrolases/biossíntese , Hipertensão/metabolismo , Miocárdio/enzimologia , Animais , Anti-Hipertensivos/farmacologia , Northern Blotting , Western Blotting , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Hemodinâmica/efeitos dos fármacos , Hidralazina/farmacologia , Hipertensão/induzido quimicamente , Imidazóis/farmacologia , Imuno-Histoquímica , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Pró-Fármacos/farmacologia , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Tetrazóis/farmacologia , Fatores de Tempo , Regulação para Cima , Vasodilatadores/farmacologiaRESUMO
The aim of this study was to determine whether a single local probucol administration could suppress neointimal formation in balloon-injured rat carotid artery. Rats were divided into four groups; (i) rats receiving no probucol (control group); (ii) rats receiving topical application of 50 mg probucol at the time of ballooning (p-top group); (iii) rats fed chow containing 1% probucol (p-fed group; (iv) rats receiving both topical application of 50 mg probucol and chow containing 1% probucol (p-top/fed group). Although serum total cholesterol levels did not significantly differ between the control and the p-top groups at two weeks after balloon injury, the p-top group had a smaller intimal/medial ratio or intimal area than the control group (0.97 +/- 0.11 vs. 0.53 +/- 0.08 or 0.15 +/- 0.02 mm2 vs. 0.08 +/- 0.02 mm2 respectively, P < 0.01). Neointimal formation was suppressed to a similar extent in the p-fed group, in which serum total cholesterol level was approximately 40% lower than that in the control group. Thus, a single local delivery of probucol can suppress neointimal formation in balloon-injured rat carotid artery without altering serum lipid level.
Assuntos
Anticolesterolemiantes/farmacologia , Artéria Carótida Primitiva/patologia , Probucol/farmacologia , Túnica Íntima/patologia , Administração Tópica , Animais , Anticolesterolemiantes/administração & dosagem , Lesões das Artérias Carótidas , Cateterismo , Colesterol/sangue , Hiperplasia , Masculino , Probucol/administração & dosagem , Ratos , Ratos WistarRESUMO
To elucidate if locally administered cilostazol, an inhibitor of cyclic AMP phosphodiesterase III, suppresses neointimal formation in balloon-injured carotid artery of the rat, 20 mg of cilostazol was topically applied using pluronic gel at the time of balloon injury. Rats were sacrificed 14 days after balloon injury to measure the extent of neointimal formation. Plasma and tissue concentrations of cilostazol were also measured at 1, 3, 7 and 14 days after topical application. The 5-bromo-2'-deoxyuridine (BrdU, a thymidine analogue) was given intraperitoneally to detect proliferation of smooth muscle cells in the injured media at 3 days after balloon injury. At 1 day after injury, plasma and tissue concentrations were 0.147+/-0.043 microg/ml and 1380 microg/g tissue. Although the plasma concentration of cilostazol was undetectable ( < 0.02 microg/ml), a significant amount of cilostazol (46 microg/g tissue) was still detected in the tissue at the site of application even after 2 weeks. The intimal area of the injured carotid after 2 weeks was significantly smaller in the cilostazol-treated group than in the gel-treated control group (0.06+/-0.01 vs 0.15+/-0.02 mm2, P<0.001). BrdU-positive smooth muscle cells in the injured media after 3 days were also significantly fewer in the cilostazol-treated group than in the gel-treated control group (4.3+/-0.5 vs 9.1+/-0.9% of total cells, P < 0.001). These results suggest that local administration of cilostazol using pluronic gel maintains a high concentration of the drug at the application site, has an anti-proliferative effect on smooth muscle cells, and may have potential for clinical therapeutic use for the prevention of restenosis following arterial intervention.
Assuntos
Angioplastia com Balão , Artérias Carótidas/patologia , Inibidores de Fosfodiesterase/administração & dosagem , Tetrazóis/administração & dosagem , Túnica Íntima/patologia , 3',5'-AMP Cíclico Fosfodiesterases/antagonistas & inibidores , Administração Tópica , Animais , Arteriopatias Oclusivas/patologia , Arteriopatias Oclusivas/terapia , Artérias Carótidas/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Cilostazol , Masculino , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/patologia , Inibidores de Fosfodiesterase/farmacocinética , Inibidores de Fosfodiesterase/farmacologia , Ratos , Ratos Wistar , Recidiva , Tetrazóis/farmacocinética , Tetrazóis/farmacologia , Túnica Íntima/efeitos dos fármacosRESUMO
Muscarinic acetylcholine receptor (mAChR) subtype (m1-m4)-specific cDNAs were transfected into NL308 neuroblastoma-fibroblast hybrid cells and clones expressing each of the individual mAChR subtypes m1, m2, m3 and m4 obtained. Acetylcholine increased phosphoinositide (PI) turnover in m1- and m3-transformed cells, but did not produce detectable changes in m2- and m4-transformed cells. In cells expressing m1 and m3 subtypes, ACh produced an initial outward K+ current, followed by a cationic current. In cells expressing m2 and m4 receptors, only the initial K+ current was detected. The outward currents were associated with a rise in intracellular Ca2+ as measured with Fura-2 or Indo-1, and were inhibited by chelating intracellular Ca2+ with external BAPTA-AM, or by external charybdotoxin or Ba2+: hence they were attributed to the activation of a Ca(2+)-dependent K+ current. However, the outward current produced in m2- and m4-transformed cells was blocked by pretreatment with 5 ng ml-1 Pertussis toxin (PTX), whereas that in m1- and m3-transformed cells was not. These results suggest that m2- and m4-receptors in transformed NL308 cells coupled to PTX-sensitive G-protein which is capable of mobilizing intracellular Ca2+ and activate IK(Ca), whereas m1 and m3 receptors activate a similar process through a different, PTX-insensitive G-protein.
Assuntos
Cálcio/metabolismo , Cálcio/farmacologia , Canais de Potássio/fisiologia , Receptores Muscarínicos/fisiologia , Acetilcolina/farmacologia , Animais , Bário/farmacologia , Quelantes/farmacologia , DNA/genética , Fibroblastos , Proteínas de Ligação ao GTP/metabolismo , Células Híbridas/efeitos dos fármacos , Células Híbridas/fisiologia , Cinética , Potenciais da Membrana/efeitos dos fármacos , Camundongos , Neuroblastoma , Toxina Pertussis , Canais de Potássio/efeitos dos fármacos , Regiões Promotoras Genéticas , Quinuclidinil Benzilato/metabolismo , Receptores Muscarínicos/efeitos dos fármacos , Receptores Muscarínicos/genética , Vírus 40 dos Símios/genética , Transfecção , Fatores de Virulência de Bordetella/farmacologiaRESUMO
Employing subtype-specific antisera, we measured the relative immunoreactivity of five muscarinic acetylcholine receptor (mAChR) subtype proteins (m1-m5) in the human iris. The most intensive FITC immunofluorescence was detected by the anti-m3 antibody, followed by anti-m1 and -m5 antisera, in the iris sphincter muscle cells. Only very weak fluorescence was obtained by anti-m2 and -m4 antibodies. In dilator muscle cells, weak but not consistent immunoreactivity was found by anti-m1 and -m5 antibodies. The results suggest that the m3 muscarinic receptor is the predominant subtype in sphincter muscle cells of the human iris.
Assuntos
Iris/metabolismo , Receptores Muscarínicos/metabolismo , Adulto , Neoplasias Oculares/cirurgia , Fluoresceína-5-Isotiocianato , Humanos , Imuno-Histoquímica , Técnicas In Vitro , Melanoma/cirurgia , Microscopia de Fluorescência , Pessoa de Meia-Idade , Reflexo Pupilar/fisiologiaRESUMO
We have reported that lecithin-conjugated recombinant human Cu, Zn-superoxide dismutase (lecithinized SOD) has greater pharmacological potency than unmodified SOD through an increase in cell membrane affinity and half-life in plasma. Recently, ischemia or hypoxia alone has been suggested to result in increased superoxide anions, which lead to apoptosis in cardiomyocytes. We tested the effect of lecithinized SOD in reducing the infarct size following prolonged myocardial ischemia without reperfusion. Rats were subjected to a 24-h left coronary occlusion. Lecithinized SOD, unmodified SOD, free lecithin derivative or PBS was administered intravenously 30 min before coronary occlusion. SOD concentration of the heart, measured by ELISA, was higher in the lecithinized SOD-treated group than in the other groups 24 h after administration. The infarct area ratio of the heart, assessed by TTC staining, in the lecithinized SOD-treated group was significantly smaller than those of the other groups. Both TUNEL-positive cardiomyocytes and DNA laddering were attenuated in the ischemic area of the heart treated with lecithinized SOD. Single bolus administration of lecithinized SOD had a cardioprotective effect against ischemia without reperfusion in the rat model of acute myocardial infarction, possibly due to its sustained high tissue concentration.
Assuntos
Infarto do Miocárdio/patologia , Miocárdio/patologia , Superóxido Dismutase/metabolismo , Animais , DNA/química , Feminino , Coração/efeitos dos fármacos , Hemodinâmica , Marcação In Situ das Extremidades Cortadas , Fosfatidilcolinas , Ratos , Ratos Sprague-DawleyRESUMO
The authors present a rare case of myocardial infarction in a fifty-eight-year-old man without significant coronary artery stenosis apparent on the emergency coronary angiogram. However, a second angiogram two days later revealed a total occlusion of the left anterior descending artery. Intracoronary thrombolytic therapy was performed with a successful outcome. The patient was subsequently readmitted with an acute myocardial infarction, and the coronary angiogram again failed to demonstrate significant stenosis. Thereafter, the patient's left ventricular function deteriorated progressively, with the occurrence of another myocardial infarction and frequent bouts of symptoms related to congestive heart failure. He died of ischemic cardiomyopathy about seven years later. Findings including an autopsy report showed that myocardial ischemia was involved in the pathogenesis of what initially appeared to be primary dilated cardiomyopathy, based on emergency angiograms.
Assuntos
Doença das Coronárias , Isquemia Miocárdica/diagnóstico , Angiografia Coronária , Eletrocardiografia , Evolução Fatal , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/patologia , Isquemia Miocárdica/patologia , Miocárdio/patologia , Fatores de TempoRESUMO
The authors describe a case with an internal mammary artery (IMA) graft that demonstrated prolonged, but reversible, luminal narrowing persisting > twenty-four hours following percutaneous transluminal angioplasty. Luminal narrowing disappeared spontaneously, however, at the time of follow-up angiography one week after the angioplasty. Since haziness at the dilation site had been shown on preprocedural angiogram, suggestive of intraluminal thrombus, this phenomenon may be attributed to either prolonged vasospasm or distal embolization of the IMA graft.
Assuntos
Angioplastia Coronária com Balão , Doença das Coronárias/etiologia , Anastomose de Artéria Torácica Interna-Coronária , Complicações Pós-Operatórias , Constrição Patológica , Angiografia Coronária , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
A nationwide, multicenter study of typical retinitis pigmentosa (RP) was carried out in collaboration with 18 hospitals throughout Japan to obtain current information for genetic counseling. We analyzed the genetic heterogeneity of RP based on the parental consanguinity of 434 probands registered during a 6-month period in 1990. A gradual decline in the frequency of consanguineous marriage was recognized among the normal parents of RP patients. The relative frequencies of inheritance patterns were estimated as: autosomal recessive, 25.2%; autosomal dominant, 16.9%; X-linked, 1.6%; and simplex, 56.3%. A comparison of these results with previous reports in Japan revealed a decline in the relative frequency of autosomal recessive cases and an increase in simplex cases. This suggests a decrease in the incidence of autosomal recessive retinitis pigmentosa in Japan, as well as the necessity for exhaustive investigations aimed at identifying inheritance patterns for RP patients seeking genetic counseling.
Assuntos
Herança Extracromossômica/genética , Heterogeneidade Genética , Retinose Pigmentar/genética , Adolescente , Adulto , Distribuição por Idade , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , Características da Família , Feminino , Aconselhamento Genético , Impressão Genômica , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Retinose Pigmentar/epidemiologia , Estudos RetrospectivosRESUMO
Retinitis pigmentosa (RP) is a group of genetically heterogeneous diseases with autosomal recessive (AR), autosomal dominant, and X-linked modes of inheritance. Autosomal recessive retinitis pigmentosa (ARRP) is the most common form in Japan. A genetic analysis was done to determine the prevalence of ARRP indirectly, to provide an estimation of changing trends in the overall prevalence of RP. Data on the frequency of consanguinity and marriage year of normal parents of 59 ARRP patients were obtained from a nationwide multicenter survey of typical retinitis pigmentosa conducted in 1990. The gene frequency of ARRP was 0.01145 (Dahlberg's formula). In 1990, the number of young symptomatic ARRP patients decreased, while the number of patients aged 40 years and older increased. The total number of symptomatic ARRP patients in 1990 was nearly 21% higher than in 1970. Despite a dramatic decline in consanguinity in recent decades in Japan, the number of ARRP patients has increased. This increase is attributed to greater longevity and overall population growth. Our results suggest that the total number of RP patients has not decreased, and may even have increased.