RESUMEN
Tomato (Lycopersicon esculentum) plants were transformed with gene constructs containing a tomato alcohol dehydrogenase (ADH) cDNA (ADH 2) coupled in a sense orientation with either the constitutive cauliflower mosaic virus 35S promoter or the fruit-specific tomato polygalacturonase promoter. Ripening fruit from plants transformed with the constitutively expressed transgene(s) had a range of ADH activities; some plants had no detectable activity, whereas others had significantly higher ADH activity, up to twice that of controls. Transformed plants with fruit-specific expression of the transgene(s) also displayed a range of enhanced ADH activities in the ripening fruit, but no suppression was observed. Modified ADH levels in the ripening fruit influenced the balance between some of the aldehydes and the corresponding alcohols associated with flavor production. Hexanol and Z-3-hexenol levels were increased in fruit with increased ADH activity and reduced in fruit with low ADH activity. Concentrations of the respective aldehydes were generally unaltered. The phenotypes of modified fruit ADH activity and volatile abundance were transmitted to second-generation plants in accordance with the patterns of inheritance of the transgenes. In a preliminary taste trial, fruit with elevated ADH activity and higher levels of alcohols were identified as having a more intense "ripe fruit" flavor.
RESUMEN
Our specific aim was to compare lipoprotein(a) [Lp(a)] measured by two enzyme-linked immunosorbent assays (the Strategic Diagnostics, Inc. Macra Lp(a) and the American Diagnostica, Inc. Imubind Lp(a) Stripwell) in sequentially referred hyperlipidemic patients. The Macra method binds Lp(a) in serum or plasma to monoclonal anti-Lp(a) in microtiter test wells followed by polyclonal anti-Lp(a) and a chromogenic reaction; the Imubind method is similar but uses two polyclonal anti-Lp(a) antibodies. Within run coefficients of variation were 1.5 percent for the Macra (Lp[a] 27.2 +/- 0.4 mg/dl) and 3.4 percent for the Imubind method (Lp[a] = 18.9 +/- 0.6 mg/dl). Between-run coefficients of variation for the Macra method were 4.7 percent (Lp[a] 14.8 +/- 0.7 mg/dl) and 8.3 percent (Lp[a] of 33.5 +/- 2.8 mg/dl). For the Imubind method in nine separate analytical runs, the between run coefficients of variation were 8.4 percent (Lp[a] of 15.4 +/- 1.3 mg/dl), 3.0 percent (18.8 +/- 0.6 mg/dl), and 5.7 percent (25.6 +/- 1.5 mg/dl). The intraclass correlation was 0.92 (p < or = 0.0001) for duplicate aliquots (n = 210) quantitated by both methods, and the lower limit of the 95 percent confidence interval of the intraclass correlation was 0.90. Comparison of the two methods revealed no systematic bias (p = 0.09), since the lower limit of the 95 percent intraclass correlation confidence interval was > or = 0.75, the two methods for measuring Lp(a) are considered interchangeable. Given the importance of Lp(a) as an independent risk factor for coronary heart disease, it is clinically important to have precise and accurate methods for its measurement.
Asunto(s)
Ensayo de Inmunoadsorción Enzimática/métodos , Lipoproteína(a)/análisis , Juego de Reactivos para Diagnóstico , Adolescente , Adulto , Anciano , Anticoagulantes/farmacología , Bancos de Sangre , Calibración , Niño , Ácido Cítrico/farmacología , Ácido Edético/farmacología , Ensayo de Inmunoadsorción Enzimática/economía , Ensayo de Inmunoadsorción Enzimática/estadística & datos numéricos , Femenino , Humanos , Hiperlipidemias/diagnóstico , Lipoproteína(a)/sangre , Masculino , Persona de Mediana Edad , Juego de Reactivos para Diagnóstico/economía , Estadística como Asunto , Factores de TiempoRESUMEN
A cDNA library was constructed from RNA from the pericarp of ripe tomato fruit and four cDNAs encoding ADH2 were isolated and characterized. The cDNAs encode a peptide 379 amino acids in length. They hybridized strongly with a 1.8 kb RNA species well represented in RNA from ripe, but not from mature, unripe fruit, and strongly to a similar RNA species present in hypoxic, but not in aerobic roots. Northern analysis showed that the mRNA for ADH2 in fruit increased in abundance through ripening, particularly during late ripening. In pericarp tissue of fruit, the Adh2 mRNA level increased to a maximum within 8-16 h of exposure to atmospheres with 3% (v/v) oxygen, and returned to the basal level within 16 h of a return to air. The mRNA level was sensitive to the oxygen level in the atmosphere, increasing 20-fold in 12% (v/v) oxygen and 100-fold in 3% oxygen. The homologous tomato Adh2 gene was isolated from a genomic library. The gene has an overall length of 2334 bp from transcription start site to poly(A) addition site and includes eight introns. Southern blot analysis of tomato genomic DNA identified multiple Adh2-related sequences. Two of these, PSA1 and PSA2, were cloned and found to have 94% similarity with each other and 77% similarity with the tomato Adh2 gene over a 1000 bp region. The homologous regions include introns and exons but the equivalent exons contain frame shifts, deletions and stop codons. The two regions are therefore presumptive pseudogenes.
Asunto(s)
Alcohol Deshidrogenasa/genética , Genes de Plantas/genética , Isoenzimas/genética , Seudogenes/genética , Solanum lycopersicum/genética , Secuencia de Aminoácidos , Secuencia de Bases , ADN Complementario/genética , Expresión Génica , Genoma de Planta , Solanum lycopersicum/enzimología , Solanum lycopersicum/crecimiento & desarrollo , Datos de Secuencia Molecular , ARN Mensajero/análisis , Homología de Secuencia de Ácido Nucleico , Factores de Tiempo , Distribución TisularRESUMEN
The authors' specific aim was to assess hypocholesterolemia in 203 patients hospitalized because of affective disorders (depression, bipolar disorder, and schizoaffective disorder) compared with 1,595 self-referred subjects in an urban supermarket screening and with 11,864 subjects in the National Health and Nutrition Examination Survey II, a national probability sample. Low plasma cholesterol concentrations (< 160 mg/dL) were much more common in patients with affective disorders (20%) than in urban supermarket screenees (4%, P < or = 0.001) or in the National Health and Nutrition Examination Survey II subjects (10%, P < or = 0.001). When paired with supermarket screenees by age and sex, patients with affective disorders had much lower plasma total cholesterol (P < or = 0.0002), low-density lipoprotein cholesterol (P < or = 0.001), and high-density lipoprotein cholesterol (P < or = 0.0001), and higher triglyceride concentrations (P < or = 0.03). Neither the severity of the affective disorders nor severity-age interactions were associated with plasma cholesterol concentrations (P > 0.1); age and plasma cholesterol were positively associated (P = 0.01). None of the psychoactive drugs had a significant independent association with the patients' low-density lipoprotein cholesterol. Plasma cholesterol in patients hospitalized with affective disorders is shifted markedly downward toward hypocholesterolemic concentrations (< 160 mg/dL). There is no evidence that low plasma cholesterol could cause or worsen affective disorders.
Asunto(s)
Colesterol/sangre , Trastornos del Humor/sangre , Trastorno Bipolar/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Depresión/sangre , Femenino , Encuestas Epidemiológicas , Humanos , Masculino , Trastornos del Humor/epidemiología , Trastornos Psicóticos/sangre , Triglicéridos/sangre , Población UrbanaRESUMEN
Two distinct partial cDNAs, PRF1 and PRF3, similar in sequence to previously described polygalacturonases, were amplified from ripe peach (Prunus persica L. Batsch cv Flavorcrest) fruit cDNA by the polymerase chain reaction. PRF1-related RNA was present in fruit from early ripening at levels not detected by northern analysis. PRF3-related RNA was readily detectable in ripe fruit by northern analysis. PRF3 was used to isolate a cDNA with a complete open reading frame, PRF5, from a lambda ZAP II cDNA library prepared from poly(A)+ RNA of ripe peach fruit. PRF5 coded for a predicted protein of 393 amino acids with a molecular mass of 41,500 D. The derived amino acid sequence of PRF5 included a putative leader sequence of 23 amino acids, followed by a sequence that matched the N terminus of endopolygalacturonase protein purified from ripe peach fruit. By northern analysis, PRF3-related RNA was undetectable in firm, unripe Flavorcrest fruit. It appeared at low levels as a 1.7-kb transcript in fruit that had begun to ripen and soften and was very abundant in ripe fruit that had undergone the "melting" stage of softening. The marked increase in PRF3-related RNA levels took place over a period of less than 2 d at 20 degrees C and coincided with the climacteric peak in ethylene evolution. Levels of 1-aminocyclopropane-1-carboxylate oxidase-related RNA increased during ripening at a much earlier stage than levels of PRF3-related RNA. Lower levels of 1.7-kb RNA transcript were detected by PRF3 in ripe fruit of the melting cultivar Fragar, which are firmer than Flavorcrest fruit. In ripe fruit of the nonmelting cultivar Carolyn, PRF3 detected a 1.45-kb RNA transcript that was present at low levels. Transcripts of a peach polygalacturonase-related genomic sequence were not detected in ripening fruit.
Asunto(s)
Frutas/enzimología , Poligalacturonasa/genética , ARN Mensajero/biosíntesis , Secuencia de Aminoácidos , Secuencia de Bases , Cartilla de ADN , ADN Complementario/química , ADN Complementario/aislamiento & purificación , Etilenos/metabolismo , Frutas/genética , Datos de Secuencia Molecular , Poligalacturonasa/biosíntesis , Reacción en Cadena de la Polimerasa/métodos , ARN Mensajero/análisis , Homología de Secuencia de AminoácidoRESUMEN
To assess the hypothesis that beta blocker use and hypertension are associated with high lipoprotein(a) [Lp(a)] or with reduced basal fibrinolytic activity, the authors studied relationships of hypertension and beta blockers to Lp(a), lipids, lipoproteins, apolipoproteins, and basal fibrinolytic activity in 385 patients consecutively referred for diagnosis and therapy of hyperlipidemia. A second aim was to determine possible gender differences in fibrinolytic activity among patients with hypertension. Ninety-nine patients (58 women [88% post-menopausal] and 41 men) had drug-treated hypertension. In women, hypertension was a positive, independent predictor of the major inhibitors of fibrinolysis, plasminogen activator inhibitor antigen (p = 0.017), and plasminogen activator inhibitor activity (p = 0.004). In men and women, major risk factors for atherosclerosis were significant, independent predictors of reduced basal fibrinolysis. Median Lp(a) in the 99 patients with hypertension (16 mg/dL) did not differ from Lp(a) (18 mg/dL) in normotensive patients (p > 0.1). Of the 385 patients, the 39 beta blocker users had higher plasminogen activator inhibitor activity (p = 0.01), higher triglyceride (p = 0.02) levels, and higher Quetelet Indices (p = 0.01) than non-users (n = 346). After covariance adjusting for age, Quetelet Indices, sex, and triglycerides, plasminogen activator inhibitor activity was not higher in beta blocker users than in non-users (p > 0.1). Median Lp(a) did not differ in beta blocker users (16 mg/dL) and in non-users (17 mg/dL), p greater than 0.1. Hypertensive, predominantly post-menopausal women are likely to have high plasminogen activator inhibitor activity and plasminogen activator inhibitor antigen with concurrent reduced fibrinolytic activity, as well as high fibrinogen levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Fibrinólisis/fisiología , Hiperlipidemias/sangre , Hipertensión/sangre , Lipoproteína(a)/sangre , Antagonistas Adrenérgicos beta/farmacología , Análisis de Varianza , Apolipoproteínas/análisis , Arteriosclerosis/epidemiología , Diuréticos/uso terapéutico , Femenino , Fibrinólisis/efectos de los fármacos , Humanos , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Lípidos/sangre , Lipoproteínas/sangre , Masculino , Factores de Riesgo , Factores SexualesRESUMEN
Our specific aim was to assess within-family relationships of basal fibrinolytic activity and its determinants in hyperlipidemic probands (n = 34) with high lipoprotein (a) [Lp(a)] levels (> 35 mg/dL) and their first-degree relatives (n = 74) and in hyperlipidemic probands (n = 19) with Lp(a) < 35 and their first-degree relatives (n = 23). Probands' plasminogen activator inhibitor activity (PAI-Fx), the major fibrinolysis inhibitor, correlated with first-degree relatives' PAI-Fx in high-Lp(a) kindreds (r = .30, P = .06) and in Lp(a) < 35 kindreds (r = .43, P < or = .05). Probands' tissue plasminogen activator activity (tPA-Fx), the major fibrinolysis activator, was inversely associated with first-degree relatives' PAI-Fx in high-Lp(a) kindreds (r = -.30, P = .06) and in Lp(a) < 35 kindreds (r = -.49, P < or = .025). These correlations [irrespective of probands' Lp(a)] pointed to within-family heritability of the major fibrinolysis inhibitor, PAI-Fx, and the fibrinolysis stimulator, tPA-Fx. There were many other within-family correlations. High-Lp(a) probands' tPA-Fx, the stimulator of fibrinolysis, correlated with first-degree relatives' tPA-Fx (r = .32, P < or = .05). High-Lp(a) probands' plasminogen was inversely correlated with first-degree relatives' alpha 2-antiplasmin, a major fibrinolytic inhibitor (r = -.41, P < or = .01), and with their Lp(a) [r = -.24, P < or = .05]. High-Lp(a) probands' tPA-Fx correlated inversely with first-degree relatives' apolipoprotein (apo) B (r = -.28) and triglyceride ([TG] r = -.41), and positively with their high-density lipoprotein cholesterol ([HDLC] r = .40) and apo A-1 (r = .33; all P < or = .025). High-Lp(a) probands' PAI-Fx correlated positively with first-degree relatives' apo B (r = .34) and TG (r = .47), and inversely with HDLC (r = -.34) and apo A-1 (r = -.30; all P < or = .01). By stepwise regression, the Quetelet index (a measure of relative ponderosity) was independently inversely associated with tPA-Fx (P < or = .05) and positively associated with tPA-Ag and PAI-Fx (P < or = .05). TG was a positive independent determinant of PAI-Fx (P < or = .05), alpha 2-antiplasmin (P < or = .05), and plasminogen (P < or = .05). Lp(a) was a positive, independent determinant of fibrinogen (P < or = .05).(ABSTRACT TRUNCATED AT 400 WORDS)
Asunto(s)
Fibrinólisis/genética , Hiperlipidemias/genética , Adulto , Enfermedades Cardiovasculares/complicaciones , Ayuno/metabolismo , Femenino , Fibrinógeno/análisis , Humanos , Hiperlipidemias/complicaciones , Hiperlipidemias/metabolismo , Lípidos/sangre , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Plasminógeno/análisis , Inactivadores Plasminogénicos/análisis , Estudios Prospectivos , Análisis de Regresión , Activador de Tejido Plasminógeno/análisis , alfa 2-Antiplasmina/análisisRESUMEN
To assess relationships of endogenous testosterone with fibrinolysis and coronary heart disease risk factors in 55 newly referred hyperlipidemic men, we studied the relationships of testosterone to basal fibrinolytic activity, lipids, lipoproteins, and apolipoproteins. Testosterone correlated positively with the major stimulator of fibrinolysis, tissue plasminogen activator activity (r = 0.30; p = 0.02) and correlated inversely with two independent coronary heart disease risk factors, plasminogen activator inhibitor activity, the major fibrinolysis inhibitor (r = -0.33; p = 0.01), and fibrinogen (r = -0.39; p = 0.004). Testosterone correlated inversely with plasma triglycerides (r = -0.33; p = 0.01). Stepwise multiple regression was done with fibrinolytic activities as the dependent variables, and age, Quetelet Index (relative ponderosity), apolipoprotein A-I, apolipoprotein B, triglyceride, testosterone, time of blood sampling, and lipoprotein (a) as explanatory variables. Testosterone was an inverse, independent predictor of fibrinogen (p = 0.002); 53% of the variance of fibrinogen could be accounted for by age and triglyceride level (positive; p = 0.001, p = 0.01), and by apolipoprotein A-I and testosterone (negative; p = 0.02, p = 0.002). Testosterone was an independent inverse predictor of tissue plasminogen activator antigen (p = 0.0008), with tissue plasminogen activator antigen correlating inversely with tissue plasminogen activator activity. Quetelet index and apolipoprotein B were independent negative predictors of tissue plasminogen activator activity (p = 0.02, p = 0.03); Quetelet index and triglycerides were independent positive predictors of plasminogen activator inhibitor activity (p = .0001, p = .0001) and alpha 2-antiplasmin (p = 0.0003, p = 0.009).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Enfermedad Coronaria/epidemiología , Fibrinólisis , Hipercolesterolemia/sangre , Testosterona/sangre , Apolipoproteína A-I/análisis , Apolipoproteínas B/análisis , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Fibrinógeno/análisis , Humanos , Lipoproteína(a)/sangre , Masculino , Persona de Mediana Edad , Plasminógeno/análisis , Inactivadores Plasminogénicos/sangre , Factores de Riesgo , Activador de Tejido Plasminógeno/sangre , Triglicéridos/sangre , alfa 2-Antiplasmina/análisisRESUMEN
In 14 men and nine women referred because of severe primary hypertriglyceridemia, our specific aim in a 54-week single-blind treatment (Rx) period was to determine whether triglyceride (TG) lowering with a Type V diet and Lopid would lead to improvement in symptoms of depression, improvement in an index of life stressors, change in locus of control index, and improved cognition, as serially tested by Beck (BDI), Hassles (HAS) and HAS intensity indices, Locus of Control index, and the Folstein Mini-Mental status exam. On Rx, median TG fell 47%, total cholesterol (TC) fell 15%, and HDLC rose 19% (all p < or = 0.001). BDI fell at all nine Rx visits (p < or = 0.001), a major reduction in a test of depressive symptoms. The HAS score also fell at all nine visits (p < or = 0.05 - < or = 0.001). Comparing pre-Rx baseline BDI vs BDI at 30 and 54 weeks on Rx, there was a major shift towards absence or amelioration of depressive symptoms (chi 2= 5.9, p = 0.016). On Rx, the greater the percent reduction in TG, the greater the percent fall in BDI (r = 0.47, p < or = 0.05); the greater the percent reduction in TC, the greater the percent fall in HAS (r = 0.41, p < or = 0.05). Improvement in the BDI and HAS accompanied treatment of severe hypertriglyceridemia, possibly by virtue of improved cerebral perfusion and oxygenation. There may be a reversible causal relationship between high TG and symptoms of depression.
Asunto(s)
Trastorno Depresivo/terapia , Hipertrigliceridemia/terapia , Acontecimientos que Cambian la Vida , Adulto , Anciano , Colesterol/sangre , Protocolos Clínicos , Trastorno Depresivo/sangre , Trastorno Depresivo/etiología , Dietoterapia , Femenino , Humanos , Hipertrigliceridemia/sangre , Hipertrigliceridemia/psicología , Control Interno-Externo , Lípidos/sangre , Masculino , Persona de Mediana Edad , Psicometría , Método Simple Ciego , Resultado del Tratamiento , Triglicéridos/sangreRESUMEN
In a 29 year old white male with osteonecrosis of both hips and a shoulder, and in his family, we measured basal and stimulated (10 min cuff venous occlusion at 100 mgHg) fibrinolytic activity to determine whether low fibrinolytic activity might be heritable and etiologically associated with osteonecrosis. The proband's basal tPA-Fx was low, 0.08 IU/ml (normal 0.11-1.94), tPA-Ag was normal (11.6 ng/ml), plasminogen activator inhibitor activity (PAI-Fx) was very high, 119 U/ml (normal 3.5-27), as was his plasminogen activator inhibitor antigen (PAI-Ag), 202 ng/ml (normal 3.2-37.1). The proband's basal PAI-Fx (119) and PAI-Ag (202) were respectively 6 and 13 standard deviations greater than the mean PAI-Fx (17 +/- 15 U/ml) and the mean PAI-Ag (25 +/- 13 ng/ml) in 172 concomitantly studied hyperlipidemic men. Alpha-2 antiplasmin, fibrinogen, plasminogen and Lp(a) were normal. Despite lowering TG to 301 mg/dl, basal tPA-Fx remained low, 0.05; PAI-Fx and PAI-Ag remained very high (109 and 191). Following venous occlusion, stimulated tPA-Fx remained very low, 0.1 (normal 2.3-11.3), but tPA-Ag rose normally to 17 (normal 8.4-31.4); stimulated PAI-Fx and PAI-Ag were very high, 134 and 223, (normal PAI-Fx 3.6-24, PAI-Ag 12-96). Stimulated D-dimer was < the 10th percentile, 0.084 micrograms/ml. With such high PAI-Fx available to bind tPA, occlusion-stimulated tPA-Fx could not rise, and fibrinolysis could not be initiated. Neither diseases nor drugs could explain the high PAI-Fx and PAI-Ag, low tPA-Fx; or osteonecrosis.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Trastornos de la Coagulación Sanguínea/genética , Necrosis de la Cabeza Femoral/genética , Fibrinólisis/genética , Osteonecrosis/etiología , Inhibidor 1 de Activador Plasminogénico/análisis , Articulación del Hombro , Adulto , Apolipoproteínas/análisis , Trastornos de la Coagulación Sanguínea/complicaciones , Necrosis de la Cabeza Femoral/sangre , Necrosis de la Cabeza Femoral/fisiopatología , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Genes Dominantes , Humanos , Hiperlipoproteinemia Tipo IV/complicaciones , Hiperlipoproteinemia Tipo IV/genética , Lípidos/sangre , Masculino , Osteonecrosis/sangre , Osteonecrosis/fisiopatología , Linaje , Inhibidor 1 de Activador Plasminogénico/genéticaRESUMEN
In 191 newly referred hyperlipidemic patients, our specific aim was to assess relationships between levels of lipoprotein(a) [Lp(a)], lipids, apolipoproteins, regulators of basal and stimulated fibrinolytic activity, and D-dimer, a measure of in vivo fibrinolysis. Lp(a) levels correlated with none of the measures of basal fibrinolytic regulators or D-dimer. In 25 patients, levels of stimulated regulators of fibrinolytic activity and D-dimer were measured after 10-minute cuff venous occlusion. Lp(a) levels again correlated with none of the stimulated regulators of fibrinolytic activity or D-dimer. However, both basal and stimulated levels of fibrinolytic regulators and D-dimer were closely related to other major risk factors for coronary heart disease (CHD) including triglyceride, apolipoprotein (apo) A1, apo B, Quetelet index (QI), and sex. By stepwise regression in 191 patients, the following standardized partial regression coefficients were significant (P < or = .05), and model R2 and P values were as follows: basal tissue plasminogen activator (tPA) with apo B-.18, with time .17, with QI -.28, R2 = 17%, P < or = .0001; basal plasminogen activator inhibitor (PAI) with apo B..25, with time -.15, with QI .17, R2 = 14%, P < or = .0001; basal alpha 2-antiplasmin with apo A1.14, with apo B.24, with QI.17, with sex .30, R2 = 25%, P < .0001; basal plasminogen with A1.15, with apo B.21, with QI.17, with sex.17, R2 = 15%, P < or = .0001; basal fibrinogen with Lp(a).17, with QI.21, with sex.26, R2 = 14%, P < or = .0001; D-dimer with sex.15, R2 = 21%, P < or = .048. Given the absence of any relationship between Lp(a) levels and inhibition or stimulation of fibrinolysis regulators or D-dimer either in the basal or stimulated state, we postulate that Lp(a)'s major atherogenic effects are mediated by mechanisms other than reduction of fibrinolysis stimulation or in vivo fibrinolysis.
Asunto(s)
Apolipoproteínas/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinólisis , Lípidos/sangre , Lipoproteína(a)/sangre , Arteriosclerosis/sangre , Ejercicio Físico , Femenino , Humanos , Masculino , Inactivadores Plasminogénicos/sangre , Estudios Prospectivos , Tromboflebitis/sangre , Activador de Tejido Plasminógeno/sangreRESUMEN
The aim of this study was to prospectively assess the safety and efficacy of lovastatin in the treatment of cholesteryl ester storage disease in siblings who were ages 11.6 and 5 y at the beginning of treatment. Mean total and LDL cholesterol in the male proband, 7.40 and 5.68 mmol/L, respectively, on diet alone, fell 30% to 5.2 (p < or = 0.001) and 31% to 3.9 mmol/L (p < or = 0.001) on lovastatin 40 mg/d over 3.3 y, with simultaneous resolution of hepatosplenomegaly. In his sister, on lovastatin 20 mg/d for 1.5 y, total and LDL cholesterol fell, but not significantly; her hepatosplenomegaly was also reduced on treatment. Lovastatin was well tolerated without overt side effects or complications and without adverse changes in liver function tests or creatine phosphokinase. Normal and expected accretion of height and weight occurred during the treatment period for both children. Lovastatin appears to be a safe and effective treatment for pediatric cholesteryl ester storage disease.
Asunto(s)
Enfermedad de Acumulación de Colesterol Éster/tratamiento farmacológico , Lovastatina/uso terapéutico , Niño , Preescolar , Colesterol/sangre , Enfermedad de Acumulación de Colesterol Éster/sangre , Enfermedad de Acumulación de Colesterol Éster/genética , LDL-Colesterol/sangre , Creatina Quinasa/sangre , Tolerancia a Medicamentos , Femenino , Hepatomegalia/tratamiento farmacológico , Hepatomegalia/patología , Humanos , Pruebas de Función Hepática , Lovastatina/efectos adversos , Masculino , Seguridad , Esplenomegalia/tratamiento farmacológico , Esplenomegalia/patologíaRESUMEN
The specific aim of this retrospective, observational study was to assess safety and efficacy of long-term (21 months/patient), open-label, gemfibrozil-lovastatin treatment in 80 patients with primary mixed hyperlipidemia (68% of whom had atherosclerotic vascular disease). Because ideal lipid targets were not reached (low-density lipoprotein (LDL) cholesterol less than 130 mg/dl, high-density lipoprotein (HDL) cholesterol greater than 35 mg/dl, or total cholesterol/HDL cholesterol less than 4.5 mg/dl) with diet plus a single drug, gemfibrozil (1.2 g/day)-lovastatin (primarily 20 or 40 mg) treatment was given. Follow-up visits were scheduled with 2-drug therapy every 6 to 8 weeks, an average of 10.3 visits per patient, with 741 batteries of 6 liver function tests and 714 creatine phosphokinase levels measured. Only 1 of the 4,446 liver function tests (0.02%), a gamma glutamyl transferase, was greater than or equal to 3 times the upper normal limit. Of the 714 creatine phosphokinase levels, 9% were high; only 1 (0.1%) was greater than or equal to 3 times the upper normal limit. With 2-drug therapy, mean total cholesterol decreased 22% from 255 to 200 mg/dl, triglyceride levels decreased 35% from 236 to 154 mg/dl, LDL cholesterol decreased 26% from 176 to 131 mg/dl, and the total cholesterol/HDL cholesterol ratio decreased 24% from 7.1 to 5.4, all p less than or equal to 0.0001. Myositis, attributable to the drug combination and symptomatic enough to discontinue it, occurred in 3% of patients, and in 1% with concurrent high creatine phosphokinase (769 U/liter); no patients had rhabdomyolysis or myoglobinuria.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Gemfibrozilo/uso terapéutico , Hiperlipoproteinemias/tratamiento farmacológico , Lovastatina/uso terapéutico , Adulto , Anciano , Análisis de Varianza , Colesterol/sangre , Terapia Combinada , Creatina Quinasa/sangre , Quimioterapia Combinada , Femenino , Gemfibrozilo/efectos adversos , Humanos , Hiperlipoproteinemias/sangre , Hiperlipoproteinemias/dietoterapia , Pruebas de Función Hepática , Lovastatina/efectos adversos , Masculino , Persona de Mediana Edad , Miositis/inducido químicamente , Estudios Retrospectivos , Triglicéridos/sangreRESUMEN
A commercial competitive enzyme immunoassay kit, Escherichia coli ST EIA, was compared with the conventional infant mouse assay for sensitivity and specificity in detecting E. coli heat-stable enterotoxin. Thirty-one of 46 strains of E. coli tested were positive by both assays, while 15 strains were negative. The sensitivity of the ST EIA kit was up to 64-fold lower than the infant mouse assay.
Asunto(s)
Toxinas Bacterianas/análisis , Bioensayo , Enterotoxinas/análisis , Escherichia coli , Técnicas para Inmunoenzimas , Animales , Animales Recién Nacidos , Unión Competitiva , Proteínas de Escherichia coli , Ratones , Valor Predictivo de las Pruebas , Juego de Reactivos para DiagnósticoRESUMEN
Two commercial agglutination kits, a reserved passive agglutination test (VET-RPLA) and a staphylococcal coagglutination test (Phadebact ETEC-LT Test), were compared with two cell culture assays (Y-1 and Vero) and GM1 ganglioside enzyme-linked immunosorbent assay (GM1-ELISA) for sensitivity in detecting Escherichia coli heat-labile enterotoxin (LT). Of 48 toxigenic strains, 23 were positive by all assays. One strain was negative only by the Phadebact test. Four strains, all LT-II producers, were positive by cell culture only. For LT-I detection, the Phadebact test was the least sensitive but was simple and rapid; VET-RPLA was simple, sensitive, and a good substitute for cell culture or GM1-ELISA.
Asunto(s)
Pruebas de Aglutinación/métodos , Toxinas Bacterianas/análisis , Enterotoxinas/análisis , Proteínas de Escherichia coli , Escherichia coli/química , Estudios de Evaluación como Asunto , Juego de Reactivos para DiagnósticoAsunto(s)
Hiperlipoproteinemias/diagnóstico , Hipotiroidismo/diagnóstico , Adulto , Anciano , LDL-Colesterol/sangre , Diagnóstico Diferencial , Estudios de Evaluación como Asunto , Femenino , Humanos , Hiperlipoproteinemias/sangre , Hiperlipoproteinemias/complicaciones , Hipotiroidismo/sangre , Hipotiroidismo/complicaciones , Lípidos/sangre , Lipoproteínas/sangre , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Glándula Tiroides/fisiología , Tirotropina/sangre , Tiroxina/sangre , Tiroxina/uso terapéuticoRESUMEN
Five strains of nonpathogenic Listeria monocytogenes were characterized for (i) hemolysin production, (ii) cytolysis of Chinese hamster ovary (CHO) cells, and (iii) ability to attach and enter intestine 407 cells. Four of the five strains produced variable hemolysis and were weakly cytolytic for Chinese hamster ovary cells, whereas the other isolate was consistently hemolytic and strongly cytolytic for CHO cells. None of the strains was able to penetrate intestine 407 cells. In addition, two of the five strains were found to be nonmotile.
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Listeria monocytogenes/metabolismo , Animales , Adhesión Bacteriana , Células CHO , Cricetinae , Proteínas Hemolisinas/biosíntesis , Intestinos/citología , Intestinos/microbiología , Listeria monocytogenes/patogenicidadRESUMEN
Sandwich enzyme-linked immunosorbent assays (ELISAs) were developed to detect Escherichia coli cytotoxins. Wells were coated with monoclonal antibodies from hybridomas 13C4 and (or) 11E10, and biotin conjugates of these antibodies were used for detecting verotoxin 1 and Shiga-like toxin II, respectively. Sensitivities were about 100 and 200 cytotoxic doses, respectively. Verotoxin 2 was detected by ELISA with monoclonal antibody 11E10, but at a sensitivity of only about 4000 cytotoxic doses. ELISA results of polymyxin-treated cell extracts from cultures of 67 E. coli strains were in agreement with Vero cell assay as regards the presence and type of toxin.
Asunto(s)
Toxinas Bacterianas/análisis , Citotoxinas/análisis , Ensayo de Inmunoadsorción Enzimática/métodos , Escherichia coli/química , Animales , Anticuerpos Antibacterianos/inmunología , Anticuerpos Monoclonales/inmunología , Hibridomas , Células VeroRESUMEN
To assess relationships of serum phytosterols (plant sterols [P]) to serum cholesterol (C), P were measured by gas-liquid chromatography (GLC) in 595 hypercholesterolemics (top C quintile in screening of 3,472 self-referred subjects). A second specific aim was to determine whether high serum P would track over time and whether they would predict familial aggregation of high C, high low-density lipoprotein cholesterol (LDLC), high apolipoprotein (apo) B, and increased premature coronary heart disease (CHD) in hyperphytosterolemic probands and their first-degree relatives. Mean +/- (SD) C was 260 +/- 56 mg/dL, campesterol (CAMP) was 2.10 +/- 1.6 micrograms/mL, stigmasterol (STIG) 1.71 +/- 1.67, sitosterol (SIT) 2.98 +/- 1.61, and total P 6.79 +/- 3.66 micrograms/mL. Serum C correlated with CAMP (r = .15, P less than or equal to .001), STIG (r = .10, P less than or equal to .02), SIT (r = .34, P less than or equal to .0001), and total P (r = .29, P less than or equal to .0001). High serum CAMP and STIG were associated with a personal or family history of CHD in subjects less than or equal to age 55 years (premature CHD). In 21 hyperphytosterolemic probands who initially had at least one P at or above the 95th percentile and a second P at or above the 75th percentile, P were remeasured 2 years later. Initial and 2-year follow-up CAMP, STIG, and SIT did not differ (P greater than .7). Initial and follow-up CAMP were correlated (r = .47, P = .03).(ABSTRACT TRUNCATED AT 250 WORDS)