RESUMEN
A 39-year-old woman had exercise-induced ST segment depression associated with chest pain. Cardiac evaluation revealed moderate aortic stenosis (AS), related to the bicuspid valves, with an aortic mean pressure gradient of 22 mmHg, a calculated aortic valve area of 1.3 cm2 and normal left ventricular (LV) peak systolic and end-diastolic pressures, but no LV hypertrophy, resulting in normal LV wall stress. Although the coronary arteries were angiographically normal, rapid atrial pacing and an intracoronary papaverine injection revealed a significantly decreased coronary flow reserve (CFR), which may have played an important role in the pathogenesis of angina pectoris in this patient. Though the CFR is usually decreased in patients with AS, as well as in microvascular angina, in this particular case, it appeared to have decreased as a consequence of microvascular dysfunction rather than of AS-related mechanisms.
Asunto(s)
Estenosis de la Válvula Aórtica/patología , Angina Microvascular/etiología , Adulto , Estenosis de la Válvula Aórtica/fisiopatología , Vasos Coronarios/patología , Vasos Coronarios/fisiopatología , Electrocardiografía , Ejercicio Físico , Femenino , Humanos , Angina Microvascular/patología , Angina Microvascular/fisiopatología , Papaverina/administración & dosificación , Flujo Sanguíneo Regional , Vasodilatadores/administración & dosificaciónRESUMEN
The predictive power of elevated heart rate for total mortality was evaluated in a Japanese general population. A total of 573 male participants, aged 40 to 64, who underwent a health examination in 1977, were followed until 1994. Heart rate (beats per minute; bpm) was measured using an electrocardiogram. During the 18 years, 82 subjects died; 18 from cerebro-cardiovascular diseases and 36 from cancer. In a multivariate proportional hazards regression model, age, elevated systolic and diastolic blood pressures, antihypertensive medication, heart rate, uric acid, vital capacity (inversely), and serum cholesterol (inversely) were significantly associated with all-cause death. Of these variables, elevated heart rate was the strongest predictor of all-cause death after adjustment for age. Resting heart rate levels were classified into five groups: < 60 (G1), 60-69 (G2), 70-79 (G3), 80-89 (G4), and > or = 90 (G5) bpm. Heart rates of 60-69 (G2) bpm showed the lowest death rate (14.3%) and heart rate > or = 90 (G5) bpm showed the highest death rate (38.2%) after adjustments for age and other confounding factors. The relative risk of G2 versus G5 was 2.68. An increased mortality risk was shown in men whose heart rate was > or = 90 bpm. Moreover, a continuous model suggested a graded increase in risk, so that risk is likely elevated even for heart rates less than 90 bpm, and lowest risk may be around 60 bpm.
Asunto(s)
Frecuencia Cardíaca , Mortalidad , Taquicardia/epidemiología , Adulto , Enfermedades Cardiovasculares/mortalidad , Trastornos Cerebrovasculares/mortalidad , Estudios de Cohortes , Electrocardiografía , Estudios de Seguimiento , Humanos , Japón/epidemiología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Neoplasias/mortalidad , Valor Predictivo de las PruebasRESUMEN
Insulin resistance and/or diabetes are risk factors for coronary artery disease. However, it is still controversial whether they are associated with the development of stroke. A total of 304 Japanese men and women, aged 20-69 years, were selected on the basis of casual high blood glucose concentrations from 2732 participants of a population-based health examination in 1980. They all underwent a 50 g oral glucose tolerance test in 1981. Homa IR (index of insulin resistance) and Homa beta-cells (index of beta-cell function) were calculated from their fasting insulin and glucose using the formulas for the homeostasis model. They were followed-up for 18 years. Incidence of stroke was investigated by computed tomography. During 18 years, 28 subjects had a stroke; 21 had ischemic and nine had hemorrhagic strokes (two had both). Baseline variables, which showed an independent association with the incidence of stroke in the Cox proportional hazard model, were blood pressure, use of anti-hypertensive medications, and Homa beta-cell index (inversely) after adjustments for age and sex. After further adjustment for blood pressure using a step-forward method, Homa beta-cell was significantly related to the incidence of stroke (Hazard ratio: 0.65, 95% confidence interval: 0.44-0.95). In addition to hypertension, diabetes but not insulin resistance, is a risk factor for stroke.
Asunto(s)
Diabetes Mellitus/fisiopatología , Angiopatías Diabéticas/epidemiología , Hiperglucemia/fisiopatología , Resistencia a la Insulina , Accidente Cerebrovascular/epidemiología , Adulto , Anciano , Pueblo Asiatico , Glucemia/metabolismo , Presión Sanguínea , Complicaciones de la Diabetes , Femenino , Estudios de Seguimiento , Homeostasis , Humanos , Hiperglucemia/complicaciones , Incidencia , Insulina/sangre , Insulina/metabolismo , Secreción de Insulina , Islotes Pancreáticos/metabolismo , Japón/epidemiología , Masculino , Persona de Mediana Edad , Modelos Biológicos , Factores de Riesgo , Accidente Cerebrovascular/diagnóstico por imagen , Factores de Tiempo , UltrasonografíaRESUMEN
To investigate whether the influence of obesity on cardiovascular risk factors and glucose intolerance differs between Japan and the US, we conducted cross-sectional surveys in those with elevated plasma glucose in Tanushimaru, Japan, and a stratified random population sample, in Wadena, MN. Subjects numbered 204 in Tanushimaru and 334 in Wadena. Body mass index (BMI), blood pressure, blood lipids, fasting plasma levels of glucose, glycosylated hemoglobin A(1c,) insulin, and free fatty acids were assessed. Overweight was defined as BMI of 27.5-29.9 kg/m(2) and obesity as BMI> or =30 kg/m(2). Gradual increases in risk factors were seen as BMI increased in both studies. Most risk factors were associated with glucose intolerance, except for BMI in Tanushimaru. In Wadena, glucose intolerance increased sharply among the obese. Adjustment for BMI attenuated the associations of cardiovascular risk factors with glucose intolerance in Wadena, but not in Tanushimaru. Obesity has an exaggerated influence on risk factors, compared with being overweight. The associations of glucose intolerance with cardiovascular risk factors are more affected by adjustment for BMI in Wadena than in Tanushimaru, not because of a different influence of body weight on risk factors between the two cities, but because obesity is rare in Japan.
Asunto(s)
Enfermedades Cardiovasculares/complicaciones , Intolerancia a la Glucosa/complicaciones , Obesidad/complicaciones , Adulto , Anciano , Glucemia/análisis , Presión Sanguínea , Índice de Masa Corporal , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Estudios de Cohortes , Estudios Transversales , Femenino , Intolerancia a la Glucosa/epidemiología , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , Insulina/sangre , Japón/epidemiología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Minnesota/epidemiología , Análisis Multivariante , Obesidad/sangre , Obesidad/epidemiología , Factores de Riesgo , FumarRESUMEN
Although it has been suggested that alcohol intake is related to hypertension, few long-term prospective studies have investigated this relationship. We therefore conducted a prospective study in male residents of a farming community in Japan to determine whether heavy drinking would predispose to the development of hypertension. A total of 325 normotensive (< 140/90 mm Hg) men were enrolled in 1977. Twelve years later, 93 (28.6%) subjects became hypertensive (defined as blood pressure > or = 140/90 mm Hg or use of antihypertensive medication). The probability of the development of hypertension in heavy drinkers predicted from a logistic regression equation was 44.6% (relative risk: 2.05 versus nondrinkers) after adjusting for age and body mass index (BMI). It was 36.2% (relative risk: 1.86 versus nondrinkers) after a further adjustment for systolic blood pressure at baseline. A high odds ratio of 2.39 for the development of hypertension with alcohol intake of < 46 g/day versus > or = 46 g/day at baseline was obtained even after adjustments for age, BMI, and confounding factors. We conclude that habitual heavy drinking of alcohol is a risk factor for the development of hypertension. This is the first report demonstrating a significant relationship between habitual alcohol intake and the development of hypertension in a long-term prospective study in Japan.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Presión Sanguínea , Hipertensión/etiología , Adulto , Consumo de Bebidas Alcohólicas/etnología , Índice de Masa Corporal , Estudios Transversales , Estudios de Seguimiento , Humanos , Hipertensión/etnología , Incidencia , Japón/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Factores de RiesgoRESUMEN
The amount of alcohol intake has been increasing in Japan. We investigated whether this might affect dietary habits in middle-aged men. In 1989, we conducted a health examination of 809 Japanese males aged 40-69. Food and nutrient intakes were estimated from 24-hour dietary recall. Mean values of total energy, protein, fat, and carbohydrate were evaluated according to alcohol intake. Consumption of total calories and proteins, especially animal proteins, increased and carbohydrate intake decreased proportionately with the amount of alcohol intake. Meat, fish, and soybean intake were increased in heavy drinker, along with niacin, sodium, and phosphorus intake. Despite their higher caloric intake, moderate and heavy drinkers were not more obese than non- or light-drinkers. Japanese heavy drinkers took more animal protein and sodium instead of carbohydrate compared to non- and light- drinkers. In our series, heavy drinking was not related to obesity.
Asunto(s)
Consumo de Bebidas Alcohólicas , Dieta , Conducta Alimentaria , Obesidad , Adulto , Anciano , Consumo de Bebidas Alcohólicas/epidemiología , Índice de Masa Corporal , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Encuestas NutricionalesRESUMEN
The development of CD8+ intestinal intraepithelial T lymphocytes (IEL) was analyzed in mice that are deficient in the expression of MHC class I molecules, owing to either a mutated beta 2-microglobulin (beta 2m) gene or a mutated transporter associated with Ag processing 1 (TAP1) gene, and in mice doubly homozygous for beta 2m and TAPI mutations. In all mutant mice, the population size of major CD8 alpha alpha+ and CD8 alpha beta+ alpha beta-IEL subsets was reduced drastically, and this resulted in a conspicuous decrease in the total number of alpha beta-IEL. Concomitantly, a compensatory two- to threefold increase in the number of gamma delta-IEL consisting mostly of CD8 alpha alpha+ subset was noted. In radiation bone marrow chimeras, this wild-type/mutant phenotype was determined by the genotype of radioresistant host cells, but was not determined by the genotype of reconstituting bone marrow-derived cells. In beta 2m X TCR-delta double mutant mice, however, the CD8 alpha alpha+ but not CD8 alpha beta+ alpha beta-IEL subset expanded dramatically. Thus, in the absence of gamma delta-IEL, alpha beta-IEL in beta 2m-deficient mice outnumbered those in wild-type littermates. These results indicate that the generation of CD8 alpha alpha+ lymphocyte population of alpha beta- and gamma delta-IEL is not dependent, but that of CD8 alpha beta+ lymphocyte population of alpha beta-IEL is dependent on beta 2m- and/or TAP1-dependent MHC class I molecules, expressed by the controlling cells present in the anatomical site, where the development of IEL takes place.
Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Antígenos CD8/genética , Linfocitos T CD8-positivos/clasificación , Mucosa Intestinal/citología , Microglobulina beta-2/deficiencia , Microglobulina beta-2/genética , Transportador de Casetes de Unión a ATP, Subfamilia B, Miembro 2 , Animales , Secuencia de Bases , Médula Ósea/inmunología , Antígenos CD8/efectos de la radiación , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de la radiación , Diferenciación Celular/inmunología , Células Epiteliales , Epitelio/inmunología , Epitelio/efectos de la radiación , Femenino , Antígenos de Histocompatibilidad Clase I/genética , Inmunofenotipificación , Mucosa Intestinal/inmunología , Mucosa Intestinal/efectos de la radiación , Activación de Linfocitos/genética , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Mutantes , Datos de Secuencia Molecular , Quimera por Radiación , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Timo/citologíaRESUMEN
Although T cells bearing gamma delta T-cell receptors have long been known to be present in the epithelial lining of many organs, their specificity and function remain elusive. In the present study, we examined the intestinal epithelia of T-cell-receptor mutant mice, which were deficient in either gamma delta T cells or alpha beta T cells, and of normal littermates. The absence of gamma delta T cells was associated with a reduction in epithelial cell turnover and a downregulation of the expression of major histocompatibility complex class II molecules. No such effects were observed in alpha beta T-cell-deficient mice. These findings indicate that intraepithelial gamma delta T cells regulate the generation and differentiation of intestinal epithelial cells.
Asunto(s)
Mucosa Intestinal/inmunología , Intestino Delgado/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/fisiología , Linfocitos T/fisiología , Animales , Secuencia de Bases , Cruzamientos Genéticos , Cartilla de ADN , Epitelio/fisiología , Femenino , Citometría de Flujo , Regulación de la Expresión Génica , Antígenos de Histocompatibilidad Clase II/biosíntesis , Homeostasis , Inmunohistoquímica , Activación de Linfocitos , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos , Ratones Mutantes , Datos de Secuencia Molecular , Reacción en Cadena de la Polimerasa , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Especificidad de la Especie , Linfocitos T/inmunologíaRESUMEN
We have previously reported a new spontaneous recessive mutation that induces a generalized lack of lymph nodes (LNs) and Peyer's patches (PPs) accompanied by immunodeficiency in mice (gene symbol, aly). In this study, we have analyzed gut-associated lymphatic tissues of the mutant aly/aly mice and have compared the intestinal intraepithelial T lymphocytes (IEL) in aly/aly and normal aly/+ littermate mice. Immunohistochemical studies revealed that colonization of IEL and lamina propria T cells takes place in the absence of PPs and IgA-producing B cells in the lamina propria. Absolute numbers of Thy-1- IEL-alpha beta and -gamma delta are not altered in aly/aly mutant mice, whereas absolute numbers of Thy-1+ IEL-alpha beta and -gamma delta in aly/aly mice are about half of those in aly/+ mice. In IEL-alpha beta from aly/aly mice, the major CD8 alpha alpha+ and CD8 alpha beta+ subsets are maintained, whereas CD4+ and CD4+, CD8+ subsets are reduced. Although the population size of major CD8 alpha alpha+ and CD4-, CD8- IEL-gamma delta subsets is slightly reduced, the use of TCR-gamma- and -delta-chain variable gene segments by IEL-gamma delta remains almost the same in aly/aly mice. The constitutive cytolytic activity of IEL-alpha beta and -gamma delta is attenuated sharply in the aly/aly condition. This activity is, however, augmented significantly after in vitro stimulation with anti-CD3 mAb. These results indicate that most of the IEL subpopulations develop independently of passage through PPs and mesenteric LNs and that the aly mutation interrupts cytotoxic IEL development during relatively late differentiation steps that convert cytotoxic precursors to the constitutively cytolytic state.
Asunto(s)
Síndromes de Inmunodeficiencia/patología , Mucosa Intestinal/inmunología , Tejido Linfoide/citología , Ratones Mutantes/inmunología , Ganglios Linfáticos Agregados/citología , Subgrupos de Linfocitos T/inmunología , Animales , Complejo CD3/fisiología , Citotoxicidad Inmunológica , Reordenamiento Génico de la Cadena delta de los Receptores de Antígenos de los Linfocitos T , Reordenamiento Génico de la Cadena gamma de los Receptores de Antígenos de los Linfocitos T , Inmunidad Celular , Síndromes de Inmunodeficiencia/inmunología , Mucosa Intestinal/citología , Ratones , Receptores de Antígenos de Linfocitos T/fisiologíaRESUMEN
A deletion of about 4 kb has been determined in the mutated mitochondrial DNA (mtDNA) in cardiomyocytes with chronic doxorubicin (DOX)-induced cardiotoxicity in mouse. The incidence of the mtDNA deletion increased with the dosage and with the duration of the DOX administration. Coenzyme Q10 administration prevented the mtDNA deletion and decreased the thiobarbituric acid reactive substance content in the heart mitochondria, suggesting some free radical involvement in this mtDNA deletion. This mtDNA deletion may be involved in cardiomyopathy, which is known to be dosage-dependently induced by DOX administration.
Asunto(s)
ADN Mitocondrial/genética , Doxorrubicina/toxicidad , Corazón/efectos de los fármacos , Mitocondrias Cardíacas/metabolismo , Miocardio/metabolismo , Eliminación de Secuencia , Animales , Secuencia de Bases , ADN Mitocondrial/aislamiento & purificación , Masculino , Ratones , Ratones Endogámicos BALB C , Mitocondrias Cardíacas/efectos de los fármacos , Datos de Secuencia Molecular , Miocardio/patología , Oligodesoxirribonucleótidos , Reacción en Cadena de la Polimerasa/métodos , Sustancias Reactivas al Ácido Tiobarbitúrico/análisisRESUMEN
Mast cells play a role in inflammation and immunological reactions. Cardiac mast cells with their granules are demonstrated easily by toluidine blue staining. We evaluated cardiac mast cells in endomyocardial biopsy specimens in patients with acute myocarditis (n = 17), idiopathic dilated cardiomyopathy (n = 17), idiopathic hypertrophic cardiomyopathy (n = 17) and control subjects (n = 12). Cardiac mast cells increase to an extreme degree in patients with acute myocarditis (2.4 counts/mm2) and increase relatively in patients with idiopathic dilated cardiomyopathy (1.4 counts/mm2). Patients with idiopathic hypertrophic cardiomyopathy (0.4 counts/mm2) were similar to control subjects (0.5 counts/mm2). Cardiac mast cells increased in accord with the severity of cellular infiltration and of interstitial fibrosis except for some cases with very severe fibrosis. In the acute myocarditis group, cardiac mast cells were well demonstrated in the early stage of the illness. But degranulations of mast cells did not give us any significant information in this study. Evaluation of cardiac mast cells will provide us with a new aspect in studying primary myocardial diseases.
Asunto(s)
Cardiomiopatías/patología , Mastocitos/fisiología , Miocardio/citología , Adolescente , Adulto , Anciano , Cardiomiopatías/inmunología , Recuento de Células , Femenino , Fibrosis , Humanos , Masculino , Persona de Mediana EdadRESUMEN
To select an appropriate method to analyze quantitatively myocardial fibrosis in myocardial biopsies, two methods, the computer analysis and the point-counting method observed at magnifications of x200 and x400, were compared. Our targeted points of examination were the accuracy and reproducibility of these methods. Twenty patients (10 with dilated cardiomyopathy and 10 with hypertrophic cardiomyopathy) were randomly selected, and the percent area of myocardial fibrosis in myocardial biopsies obtained from the right ventricular septum was measured by both the computer analysis and the point-counting method. Two observers measured the same area twice on the different days, independently. In the area of analysis, the endocardium was excluded to avoid the observer's bias. By comparing the data obtained from two observers, it was shown that the point-counting method tended to give a larger mean value and standard deviation than the computer analysis method, but that the latter indicated better reproducibility than the former. Our result showed that the degree of myocardial fibrosis varied according to methods of analysis and observer's experiences. It is recommended that the comparison of myocardial fibrosis should be made only when the methods of analysis of fibrosis are identical.