Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 46
Filtrar
Más filtros











Base de datos
Intervalo de año de publicación
1.
Oncogene ; 36(9): 1276-1286, 2017 03 02.
Artículo en Inglés | MEDLINE | ID: mdl-27546618

RESUMEN

The transcription factor nuclear factor-κB (NF-κB) has important roles for tumorigenesis, but how it regulates cancer stem cells (CSCs) remains largely unclear. We identified insulin-like growth factor 2 (IGF2) is a key target of NF-κB activated by HER2/HER3 signaling to form tumor spheres in breast cancer cells. The IGF2 receptor, IGF1 R, was expressed at high levels in CSC-enriched populations in primary breast cancer cells. Moreover, IGF2-PI3K (IGF2-phosphatidyl inositol 3 kinase) signaling induced expression of a stemness transcription factor, inhibitor of DNA-binding 1 (ID1), and IGF2 itself. ID1 knockdown greatly reduced IGF2 expression, and tumor sphere formation. Finally, treatment with anti-IGF1/2 antibodies blocked tumorigenesis derived from the IGF1Rhigh CSC-enriched population in a patient-derived xenograft model. Thus, NF-κB may trigger IGF2-ID1-IGF2-positive feedback circuits that allow cancer stem-like cells to appear. Then, they may become addicted to the circuits. As the circuits are the Achilles' heels of CSCs, it will be critical to break them for eradication of CSCs.


Asunto(s)
Neoplasias de la Mama/patología , Regulación Neoplásica de la Expresión Génica , Proteína 1 Inhibidora de la Diferenciación/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Recurrencia Local de Neoplasia/patología , Células Madre Neoplásicas/patología , Animales , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Carcinogénesis , Femenino , Humanos , Proteína 1 Inhibidora de la Diferenciación/genética , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/genética , Ratones , Ratones Desnudos , FN-kappa B/genética , FN-kappa B/metabolismo , Clasificación del Tumor , Invasividad Neoplásica , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/metabolismo , Células Madre Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinasa/genética , Fosfatidilinositol 3-Quinasa/metabolismo , Pronóstico , Transducción de Señal , Esferoides Celulares , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
2.
Dig Liver Dis ; 36(2): 125-9, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-15002820

RESUMEN

BACKGROUND: Postoperative small bowel obstruction following abdominal procedures is more common in patients who have undergone laparotomy. However, little is known about the influence of climate on the incidence of postoperative small bowel obstruction. METHODS: To evaluate whether seasonal climatic variations are a risk factor for postoperative small bowel obstruction, hospital-based, retrospective case series was designed from medical records of 230 patients suffering from postoperative small bowel obstruction admitted to the Tokyo University Branch Hospital. Detailed analysis of weather charts from the Japanese Meteorological Agency and review of medical records for selected patients who were diagnosed with postoperative small bowel obstruction. The obstruction was diagnosed by abdominal X-ray imaging, clinical examination, and patient interviews. RESULTS: A total of 233 patients diagnosed with postoperative small bowel obstruction were identified. Analysis of the medical records of these 233 patients revealed that the variables associated with an increased risk of postoperative small bowel obstruction included low ambient temperatures of 5-10 degrees C, an increase in air humidity by 40-50% and air pressure of 1010-1015 hPa. CONCLUSION: The typical winter weather in Tokyo is characterised by low temperatures, low humidity and moderate air pressure. These winter climate conditions could be correlated with an increased incidence of postoperative small bowel obstruction in Tokyo during our period.


Asunto(s)
Laparotomía/efectos adversos , Estaciones del Año , Adherencias Tisulares/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Presión Atmosférica , Niño , Femenino , Humanos , Incidencia , Obstrucción Intestinal/etiología , Obstrucción Intestinal/fisiopatología , Intestino Delgado , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Tokio , Tiempo (Meteorología)
3.
Acta Physiol Scand ; 178(3): 225-30, 2003 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12823180

RESUMEN

AIM: The purpose of this study was to clarify the effect of various exercise intensities on damage to the hepatic parenchymal cells. METHODS: Male Wistar rats were subjected to forced exercise by treadmill running at 60 and 80% of maximum oxygen uptake (VO2max) for 120 min, sacrificed immediately and 6 h after the exercise, and then the perfused liver was stained with trypan blue solution to estimate the local damage to the liver. RESULTS: Although there were no significant increases in damaged hepatic cells immediately after both intensities of exercise, these damaged cells, in particular pericentral hepatocytes, significantly increased at 6 h after the exercise at the 80% VO2max. However, there were no significant increases in the serum glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) activities immediately and 6 h after both intensities of exercise. CONCLUSIONS: These results suggested that hepatocytes suffered damage after high-intensity exercise, although these histochemical findings in the liver were not observed immediately after the exercise. In addition, in the case of physical activity, there might not be an intimate relationship between the release of enzyme as a hepatic functional biomarker and hepatocyte damage.


Asunto(s)
Hepatocitos/fisiología , Condicionamiento Físico Animal/fisiología , Alanina Transaminasa/sangre , Animales , Aspartato Aminotransferasas/sangre , Colorantes , Hepatocitos/patología , Masculino , Consumo de Oxígeno/fisiología , Condicionamiento Físico Animal/métodos , Ratas , Ratas Wistar , Azul de Tripano
4.
Cancer Lett ; 164(1): 33-40, 2001 Mar 10.
Artículo en Inglés | MEDLINE | ID: mdl-11166913

RESUMEN

We examined the relation of serum lipids and apolipoprotein E genotype to colorectal adenomas among 205 cases and 220 controls with normal colonoscopy in Japanese men. With adjustment for body mass index, cigarette smoking, alcohol use, and other covaiates, odds ratios of proximal and distal adenomas associated with the presence of an allele varepsilon4 were 0.59 (95% confidence interval 0.23-1.45) and 0.99 (0.50-1.98), respectively. While serum total and LDL cholesterol were unrelated to both proximal and distal adenomas, serum triglycerides were positively related to distal adenomas. The findings suggest that altered lipid metabolism may be differentially associated with tumorigenesis in the proximal and distal colorectum.


Asunto(s)
Adenoma/sangre , Adenoma/genética , Apolipoproteínas E/genética , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/genética , Lípidos/sangre , Consumo de Bebidas Alcohólicas , Alelos , Índice de Masa Corporal , Colesterol/sangre , LDL-Colesterol/sangre , Colonoscopía , Humanos , Japón , Masculino , Oportunidad Relativa , Fumar , Triglicéridos/sangre
5.
Cancer Lett ; 163(2): 201-6, 2001 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-11165755

RESUMEN

Glutathione S-transferases (GSTs) are a superfamily of detoxification enzymes that may play an important role in human carcinogenesis. While the genetic polymorphisms GSTM1 and GSTT1 have drawn particular interest in relation to cancer susceptibility, previous studies of colorectal cancer are inconsistent regarding their role. We examined the relation between GSTM1 and GSTT1 genotypes combined and colorectal adenomas, and the interaction with cigarette smoking among 205 cases of colorectal adenomas and 220 controls with normal total colonoscopy in Japanese men. Neither GSTM1 nor GSTT1 was related to colorectal adenomas, nor were the null genotypes of GSTM1 and GSTT1 combined. The lack of an association with GSTM1 and GSTT1 genotypes combined persisted even when the analysis was done separately for proximal and distal colorectal adenomas. A three- to fivefold significant increase in the odds of colorectal adenomas was observed among men with a high exposure to cigarette smoking across the genotype groups, and a statistically significant increasing trend was noted within each genotype group. The present findings do not support the role for GSTM1 and GSTT1 genotypes in the development of colorectal adenomas.


Asunto(s)
Adenoma/enzimología , Biomarcadores de Tumor/genética , Neoplasias Colorrectales/enzimología , Glutatión Transferasa/genética , Proteínas de Neoplasias/genética , Fumar/efectos adversos , Adenoma/etiología , Neoplasias Colorrectales/etiología , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Análisis de Regresión , Riesgo , Fumar/metabolismo
6.
Hypertens Res ; 23(6): 709-12, 2000 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-11131285

RESUMEN

A 53-year-old male was found to have hypertension caused by the significant secretion of renin from an atrophic left kidney. He had undergone extracorporeal shock-wave lithotripsy (ESWL) for left renal lithiasis 11 years previously. A renal dynamic study with 99mTc-diethylenetriaminepentaacetic acid (DTPA) indicated that the rate of renal excretion and uptake was decreased in the left kidney and normal in the right kidney. Renal angiography demonstrated a normal right renal artery and a small but nonstenotic left renal artery. The ratio of PRA in the left renal vein to that in the right renal vein was 1.7. Blood pressure could be lowered to the range of 140-150/80-90 mmHg with imidapril, an ACE inhibitor. ESWL may cause hypertension via the well-known Page kidney effect. In this case, the kidney, atrophic probably due to ESWL, released a significant amount of renin.


Asunto(s)
Hipertensión/etiología , Imidazolidinas , Litotricia/efectos adversos , Renina/sangre , Angiografía de Substracción Digital , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Aortografía , Presión Sanguínea/efectos de los fármacos , Humanos , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Hipertensión/fisiopatología , Imidazoles/uso terapéutico , Cálculos Renales/terapia , Masculino , Persona de Mediana Edad , Arteria Renal/diagnóstico por imagen , Venas Renales , Pentetato de Tecnecio Tc 99m
7.
Hypertens Res ; 23(5): 511-9, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11016807

RESUMEN

We have previously shown that both renal dopamine (DA) and kallikrein-kinin systems are activated by exercise in mild hypertensives. We aimed to confirm the effects of exercise on the renal DA system and the stimulatory effects of DA on the renal kallikrein-kinin system in rats. In experiment 1, 12 male Dahl salt-sensitive (DS) rats given a 4% salt diet were divided into two groups. Rats in the exercise group were forced to run at 8 m/min, 60 min/day, 5 days/week for 4 weeks. Daily urinary volume, urinary excretion of sodium, free DA, and kallikrein activity were measured weekly. Renal aromatic-L-amino-acid decarboxylase (AADC) activities were assayed at the end of the experiment. In experiment 2, 15 male Sprague-Dawley (SD) rats were randomly divided into 3 groups, a DA-5 (5 microg of DA/kg/min), a DA-10 (10 microg of DA/kg/min), and a control group. DA or vehicle was administered subcutaneously with an osmotic pump for 2 weeks. Daily urinary volume, urinary excretion of sodium, aldosterone, DA, and kallikrein activity were measured weekly. Plasma renin activity, aldosterone concentration, and renal kallikrein mRNA levels were determined at the end of the experiment. In experiment 1, urinary excretion of free DA and renal AADC activities in the exercise group were significantly higher than those in the non-exercise group at week 4. In experiment 2, renal kallikrein mRNA levels and urinary volume were significantly increased in the DA-10 group compared to the control group, although there were no differences in urinary kallikrein activities. Plasma aldosterone concentration was significantly decreased in the DA-10 group compared to that in the control group despite a lack of differences in plasma renin activities. In conclusion, exercise increased the urinary excretion of free DA, probably through increased renal AADC activity in DS rats. DA amplified renal kallikrein mRNA levels and decreased plasma aldosterone levels, probably through its suppression of aldosterone in the adrenal glands. Activation of the kallikrein-kinin system might be counteracted by post-transcriptional modification of aldosterone. These results suggest that exercise enhances renal dopamine production by activating renal AADC activity, which in turn stimulates the renal kallikrein-kinin system.


Asunto(s)
Cardiotónicos/farmacología , Dopamina/farmacología , Hipertensión/fisiopatología , Sistema Calicreína-Quinina/fisiología , Riñón/enzimología , Esfuerzo Físico/fisiología , Aldosterona/sangre , Animales , Descarboxilasas de Aminoácido-L-Aromático/metabolismo , Presión Sanguínea , Northern Blotting , Peso Corporal , Cardiotónicos/orina , Dopamina/orina , Expresión Génica/fisiología , Frecuencia Cardíaca , Sistema Calicreína-Quinina/efectos de los fármacos , Calicreínas/genética , Calicreínas/orina , Masculino , ARN Mensajero/análisis , Ratas , Ratas Endogámicas Dahl , Ratas Sprague-Dawley , Renina/sangre
8.
Nihon Rinsho ; 58 Suppl 1: 7-12, 2000 Jan.
Artículo en Japonés | MEDLINE | ID: mdl-11026228
9.
Cancer Res ; 60(14): 3749-52, 2000 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-10919645

RESUMEN

Cigarette smoking has been related to increased risk of colorectal adenomas, but the underlying mechanisms are unknown. Genetic polymorphisms are known for enzymes involved in the activation of polycyclic aromatic hydrocarbons and other tobacco-related carcinogens. Polycyclic aromatic hydrocarbons are activated by cytochrome P4501A1 (CYP1A1) and detoxified by glutathione S-transferases. We investigated the relation of CYP1A1 MspI and GSTM1 genotypes to the risk of colorectal adenomas with special reference to interaction with cigarette smoking among 205 cases of colorectal adenomas and 220 controls with normal total colonoscopy in a male Japanese population. Cigarette smoking was strongly associated with increased risk of colorectal adenomas. Overall, neither the CYP1A1 MspI genotype nor the GSTM1 genotype was related to colorectal adenomas. A significant trend for increased risk of colorectal adenomas associated with smoking was observed for each of the CYP1A1 MspI genotypes, and the increasing trends did not differ by MspI genotype. The positive association between smoking and colorectal adenomas did not vary much with GSTM1 genotypes. Among former and current smokers, adenoma risk did not differ according to the combination of CYP1A1 MspI and GSTM1 genotypes. CYP1A1 MspI and GSTM1 genotypes do not seem to modify the risk of colorectal adenomas associated with cigarette smoking.


Asunto(s)
Adenoma/etiología , Adenoma/genética , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/genética , Citocromo P-450 CYP1A1/genética , Glutatión Transferasa/genética , Glicoproteínas/genética , Proteínas Gestacionales/genética , Fumar/efectos adversos , Colonoscopía , Genotipo , Humanos , Isoenzimas/genética , Masculino , Oportunidad Relativa , Polimorfismo Genético , Factores de Riesgo
10.
Hypertens Res ; 23(4): 317-22, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10912767

RESUMEN

Angiotensin-converting enzyme (ACE) inhibitors are known to be the most effective antihypertensive drugs for reducing left ventricular mass in hypertensives when compared to other classes of drugs. In the present study, we evaluated the effects of imidapril, an ACE inhibitor, on serum procollagen type III amino-terminal peptide (PIIIP) levels as well as the left ventricular mass index (LVMI). The subjects consisted of 15 patients (12 men and 3 women) in the outpatient clinic of our hospital who were diagnosed as essential hypertensives and who had not been treated with any antihypertensive medication prior to the study. Left ventricular hypertrophy was observed in all of the patients, ie., LVMI >110 g/m2 in men and >106 g/m2 in women. Blood pressure, LVMI, and serum PIIIP levels were measured before and after treatment with imidapril for 6 months. The starting dose of imidapril was 5 mg, and this was increased to 10 mg. Finally, 1 mg of trichlormethiazide was added to obtain adequate control of blood pressure. Blood pressure significantly decreased in 12 patients, and the mean LVMI decreased significantly from 153.1 +/- 9.0 to 135.4 +/- 6.3 (p< 0.01) after treatment. The changes in LVMI and PIIIP levels with treatment had significant correlation (r=0.639, p< 0.05). The present study showed that imidapril reduces the left ventricular mass in hypertensives after 6 months of treatment, and that this may at least in part be due to a decrease in the collagen content of the hypertrophied heart, suggesting that serum PIIIP levels are a useful marker of the regression of left ventricular hypertrophy.


Asunto(s)
Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Hipertensión/sangre , Hipertensión/complicaciones , Hipertrofia Ventricular Izquierda/tratamiento farmacológico , Hipertrofia Ventricular Izquierda/etiología , Imidazoles/uso terapéutico , Imidazolidinas , Fragmentos de Péptidos/sangre , Procolágeno/sangre , Adulto , Anciano , Antihipertensivos/uso terapéutico , Presión Sanguínea/efectos de los fármacos , Quimioterapia Combinada , Ecocardiografía , Femenino , Humanos , Hipertensión/fisiopatología , Hipertrofia Ventricular Izquierda/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Triclormetiazida/uso terapéutico
11.
J Biomed Mater Res ; 51(1): 37-46, 2000 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-10813743

RESUMEN

The hypothesis that bioactive glass particulate increases the rate of bone proliferation over that of synthetic hydroxyapatite and bioactive glass-ceramic was tested in these experiments. Three types of bioactive particles-45S5 Bioglass(R), synthetic hydroxyapatite, and A-W glass-ceramic-were implanted in 6-mm-diameter holes drilled in the femoral condyles of mature rabbits. Bone growth rate was measured using an image processor. 45S5 Bioglass(R) produced bone more rapidly than either A-W glass-ceramic or hydroxyapatite. At the later time periods, 45S5 Bioglass(R) was resorbed more quickly than A-W glass-ceramic. Synthetic hydroxyapatite was not resorbed at all. Backscattered electron imaging suggested that the resorption process occurred by solution-mediated dissolution, which produced chemical changes in the enclosed particulate. It was concluded that the rate of bone growth correlates with the rate of dissolution of silica as the particles resorb.


Asunto(s)
Apatitas , Materiales Biocompatibles , Desarrollo Óseo/efectos de los fármacos , Cerámica , Durapatita , Ácido Silícico , Animales , Huesos/anatomía & histología , Huesos/citología , Fémur/crecimiento & desarrollo , Microesferas , Conejos , Factores de Tiempo
12.
Cancer Lett ; 151(2): 181-6, 2000 Apr 14.
Artículo en Inglés | MEDLINE | ID: mdl-10738112

RESUMEN

A homozygous mutation at bp 677 in the gene for the methylenetetrahydrofolate reductase (MTHFR) was previously shown to be associated with a decreased risk of colorectal cancer. We examined the relation between the MTHFR genetic polymorphism and risk of colorectal adenoma in Japanese men using 205 cases of colorectal adenomas and 220 controls of normal total colonoscopy. The homozygous mutation was not measurably associated with colorectal adenomas. The findings corroborate the lack of an association between the MTHFR genotype and colorectal adenomas, but do not deny the possibility that the genotype may be involved in the late stage of colorectal carcinogenesis.


Asunto(s)
Adenoma/genética , Neoplasias Colorrectales/genética , Predisposición Genética a la Enfermedad/genética , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Polimorfismo Genético/genética , Adenoma/enzimología , Adenoma/etiología , Adenoma/patología , Consumo de Bebidas Alcohólicas , Neoplasias Colorrectales/enzimología , Neoplasias Colorrectales/etiología , Neoplasias Colorrectales/patología , Homocigoto , Humanos , Japón , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Mutación/genética , Estadificación de Neoplasias , Oportunidad Relativa
13.
Genetica ; 108(3): 259-62, 2000.
Artículo en Inglés | MEDLINE | ID: mdl-11294612

RESUMEN

We have isolated a novel human cDNA coding for human salt-tolerant protein (HSTP), that is a homologue of the rat salt-tolerant protein (STP) and may contribute to salt-induced hypertension by modulating renal cation transport. The nucleotide sequence (1988bp) of the HSTP cDNA contains an open reading frame encoding a polypeptide comprising 545 amino acids, two residues fewer than the rat STP cDNA. The predicted amino acid sequence exhibits 92% identity to that of the rat protein. HSTP contains predicted coiled-coil domains and Src Homology 3 domain, and shows a high degree of identity to CIP4 (Cdc42 target protein) and human Trip 10 (thyroid-hormone receptor interacting protein). We have mapped the HSTP gene to human chromosome 19 by fluorescence in situ hybridization.


Asunto(s)
Proteínas Portadoras/genética , ADN Complementario/genética , Proteínas Asociadas a Microtúbulos , Secuencia de Aminoácidos , Animales , Proteínas Portadoras/química , Proteínas Portadoras/fisiología , Mapeo Cromosómico , Cromosomas Humanos Par 19/genética , Clonación Molecular , ADN Complementario/aislamiento & purificación , Humanos , Hipertensión/etiología , Hibridación Fluorescente in Situ , Antígenos de Histocompatibilidad Menor , Datos de Secuencia Molecular , Ratas , Homología de Secuencia de Aminoácido , Cloruro de Sodio Dietético/efectos adversos
14.
Immunopharmacology ; 44(1-2): 15-9, 1999 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-10604519

RESUMEN

We previously purified a kallikrein-like enzyme from the dog heart and demonstrated that it is not only able to form kinins but can also convert angiotensin (Ang) I to Ang II. The aim of the present study was to clarify the structure and tissue localization of this enzyme. Western blot analysis of various canine tissues was performed with antiserum against the purified dog heart enzyme. The purified enzyme was subjected to a determination of its amino acid composition and a sequence analysis. Western blotting indicated that this enzyme was present in the heart, aorta, kidney, pancreas, lung, liver, spleen, small intestine, and skeletal muscle. The amino acid composition of the enzyme was different from that of dog urinary kallikrein. Amino acid sequence analysis indicated that it is likely to be N-terminally blocked. The present study showed that this kallikrein-like enzyme is different from previously reported kallikrein and is distributed not only in the heart, but also in other tissues such as the aorta, kidney, lung, liver, spleen, small intestine, and skeletal muscle. This enzyme may exert local effects by generating kinins and Ang II.


Asunto(s)
Calicreínas/química , Aminoácidos/análisis , Animales , Aorta Torácica/enzimología , Western Blotting , Perros , Activación Enzimática , Glicosilación , Calicreínas/aislamiento & purificación , Calicreínas/metabolismo , Calicreínas/orina , Riñón/enzimología , Peso Molecular , Miocardio/enzimología , Especificidad de Órganos , Mapeo Peptídico , Análisis de Secuencia de Proteína
15.
Clin Diagn Lab Immunol ; 6(6): 844-50, 1999 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-10548574

RESUMEN

Assessment of circulating endotoxin during the perioperative period, which is only demonstrated by the Limulus amebocyte lysate (LAL) test, may be modulated by several endotoxin-binding proteins. Endotoxin-neutralizing capacity (ENC) and the plasma levels of soluble CD14 (sCD14), lipopolysaccharide-binding protein, and bactericidal/permeability-increasing protein (BPI) were determined in 40 patients 6 h prior to skin incision for major abdominal surgery. The bioactivity of plasma endotoxin was tested by the polymyxin B-inhibited stimulatory activity of the plasma samples on healthy monocytes as measured by the release of tumor necrosis factor alpha. Plasma endotoxin levels in almost all patients increased from 0.05 +/- 0.01 to 0.23 +/- 0.03 experimental units (EU) per ml (P < 0.001); more specifically, 17 of 40 samples showed endotoxin levels of greater than 0.2 EU per ml and corresponding reductions in ENC. Soluble CD14 plasma levels were decreased from 5. 6 +/- 0.3 to 4.6 +/- 0.3 microg per ml (P < 0.05). ENC was strongly correlated with the sCD14 plasma concentration throughout the period of observation. The addition of sCD14-neutralizing monoclonal anti-sCD14 antibodies reduced ENC both pre- and postoperatively. No correlation could be established between ENC and the plasma levels of BPI, high-density lipoproteins, or low-density lipoproteins determined by measuring the concentrations of apoprotein A and apoprotein B. Biologically active endotoxin was found in only 6 of 17 samples with endotoxin levels greater than 0.2 EU per ml in the LAL test. These samples could be characterized by their perioperative loss of at least 35% of their sCD14. No change in sCD14 was detected in the remaining 11 samples. The perioperative loss of ENC is partly caused by the loss of sCD14 resulting from its consumption by endotoxin reaching the bloodstream. This study demonstrated the role of sCD14 on the bioactivity of circulating endotoxin in a human model of endotoxemia after major abdominal surgery.


Asunto(s)
Abdomen/cirugía , Proteínas de Fase Aguda , Proteínas Sanguíneas/metabolismo , Proteínas Portadoras/sangre , Receptores de Lipopolisacáridos/sangre , Receptores de Lipopolisacáridos/inmunología , Glicoproteínas de Membrana , Proteínas de la Membrana , Adulto , Anciano , Antibacterianos , Péptidos Catiónicos Antimicrobianos , Apolipoproteínas A/sangre , Apolipoproteínas B/sangre , Procedimientos Quirúrgicos Electivos , Femenino , Humanos , Cinética , Prueba de Limulus , Lipopolisacáridos/análisis , Lipopolisacáridos/sangre , Lipopolisacáridos/inmunología , Masculino , Persona de Mediana Edad , Monocitos/química , Monocitos/inmunología , Polimixina B , Periodo Posoperatorio , Albúmina Sérica , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/inmunología
16.
Kidney Int ; 56(2): 421-7, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10432380

RESUMEN

BACKGROUND: Lipoprotein glomerulopathy (LPG) is characterized by intraglomerular lipoprotein thrombosis and high plasma concentrations of apolipoprotein (apo) E. An apo E variant, apo E2 (Arg145Pro) Sendai, was recently identified in three patients with LPG. We detected a novel point mutation in the apo E gene in a patient with LPG, and we characterized the mutant apo E. METHODS: The propositus was a 32-year-old male patient on maintenance hemodialysis because of LPG. The mutation was detected by sequencing of genomic DNA from the patient and was confirmed by restriction fragment length polymorphism (RFLP) with Aor51HI. Recombinant apo E2 (Arg25Cys) Kyoto and normal apo E3 were expressed from COS-1 cells. Low-density lipoprotein (LDL) receptor-binding activities of the variants were determined in an in vitro competition assay. RESULTS: The propositus had the apo E phenotype E2/E4, as determined by isoelectric focusing, and the genotype epsilon3/epsilon4, as determined by RFLP with HhaI. Sequence analysis of amplified DNA showed a C to T transition, changing the codon for residue 25 from arginine to cysteine. The proband was a heterozygous carrier for apo E2 (Arg25Cys) Kyoto. A family study showed that the mother was a heterozygous carrier of apo E2 Kyoto and had dysbetalipoproteinemia, but no LPG. The pathophysiological effect of this mutation was investigated in vitro by binding studies of recombinant apo E2 Kyoto to LDL receptors on human fibroblasts. The ability of recombinant apo E2 Kyoto to displace LDL was reduced to 10% compared with recombinant apo E3. CONCLUSIONS: Apo E2 (Arg25Cys) Kyoto is a novel mutation of apo E that is etiologically related to LPG. However, our case indicates that the development of LPG may involve other genetic or environmental factors. Furthermore, our data suggest that arginine-25 of apo E plays an important functional role by influencing the receptor-binding ability of apo E.


Asunto(s)
Apolipoproteínas E/genética , Enfermedades Renales/genética , Enfermedades Renales/patología , Glomérulos Renales/patología , Mutación Puntual , Adulto , Anciano , Apolipoproteína E2 , Apolipoproteínas E/sangre , Arginina , Cisteína , Análisis Mutacional de ADN , Cartilla de ADN , Dimiristoilfosfatidilcolina/metabolismo , Dimiristoilfosfatidilcolina/farmacología , Etnicidad/genética , Exones , Salud de la Familia , Femenino , Fibroblastos/metabolismo , Genotipo , Humanos , Indicadores y Reactivos/metabolismo , Indicadores y Reactivos/farmacología , Radioisótopos de Yodo , Japón , Masculino , Persona de Mediana Edad , Fenotipo , Polimorfismo de Longitud del Fragmento de Restricción , Unión Proteica/efectos de los fármacos , Receptores de LDL/metabolismo , Piel/citología
17.
J Biomed Mater Res ; 44(1): 31-43, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10397902

RESUMEN

Various bioceramic materials were implanted into 6-mm-diameter holes made in the femoral condyles of mature Japanese white rabbits using different-sized granules to find an optimal material and granule diameter for use as a bone graft. Bioceramics include a bioinert ceramic (Alumina), surface-bioactive ceramics [hydroxyapatite (HAp) and Bioglass(R)], and resorbable bioactive ceramics [alphatricalcium phosphate (alpha-TCP), beta-TCP, tetracalcium phosphate (TeCP), Te. DCPD, Te. DCPA, and low-crystalline HAp]. Granule sizes were 100-300, 10, and 1-3 microm. Bone growth behavior varied with the kind of bioceramic and the size used. For surface-bioactive ceramics, 45S5 Bioglass(R) led to more rapid bone proliferation than synthetic HAp. In resorbable bioactive ceramics, the order of resorption was: low-crystalline HAp and OCP > TeCP, Te DCPD, Te DCPA > alpha-TCP, beta-TCP. In terms of biocompatibility, alpha-TCP was better than beta-TCP.


Asunto(s)
Sustitutos de Huesos , Huesos/citología , Cerámica , Osteogénesis/fisiología , Óxido de Aluminio , Animales , Huesos/ultraestructura , Durapatita , Microscopía Electrónica de Rastreo , Conejos , Propiedades de Superficie
18.
Anticancer Res ; 19(5A): 3651-7, 1999.
Artículo en Inglés | MEDLINE | ID: mdl-10625933

RESUMEN

Although scientific evidence is relatively limited, rice bran oil (RBO) is tenaciously believed to be a healthy vegetable oil in Asian countries. It exerts hypocholesterolemic activity in relation to more commonly used vegetable oils and is characterized by a relatively high content of non-fatty acid components, some of which are known to have beneficial health effects. Components specific for RBO such as gamma-oryzanol and tocotrienols could participate in its hypocholesterolemic effects. In addition, blending RBO with safflower oil, but not with sunflower oil, may magnify the hypocholesterolemic efficacy. This observation is of particular interest with regard to dietary intervention with RBO. The possible mechanism underlying this effect may at least in part be related to the specific triglyceride structure of safflower oil, differing from that of sunflower oil.


Asunto(s)
Anticolesterolemiantes/farmacología , Grasas Insaturadas en la Dieta/farmacología , Aceites de Plantas/farmacología , Animales , Ácidos Grasos Omega-3/farmacología , Humanos , Aceite de Salvado de Arroz
19.
J Hypertens ; 16(8): 1131-5, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9794716

RESUMEN

BACKGROUND: Liddle's syndrome is an autosomal inheritable disorder that causes hypertension due to excess function of sodium channel. OBJECTIVE: To analyze the DNA sequence of the amiloride-sensitive epithelial sodium channel (ENaC) in three patients who had low-renin hypertension with hypokalemia. The patients included a 24-year-old woman and her 20-year-old brother whose mother was hypertensive. The third patient was a 15-year-old girl with no family history of hypertension. METHODS: The DNA sequence of the ENaC was analyzed as follows. Venous blood samples were collected from the patients and total genomic DNA was prepared by standard methods. Specific primers were used for direct polymerase chain reaction; one set of primers for amplifying the C terminus (codon 523-638) of the , subunit of ENaC, and two sets of primers for amplifying the C terminus (codons 525-587 and 568-650) of the y subunit of ENaC. Polymerase chain reaction products were purified and subjected to direct DNA sequence analysis. RESULTS: Direct sequence analysis demonstrated the presence of a single-base substitution in one segment of the 0 subunit of ENaC, a C-T transition that changed the encoded Pro (CCC) at codon 616 to Ser (TCC) in the siblings (cases 1 and 2). In case 3, we found a missense mutation of Pro (CCC) to Leu (CTC) at codon 616. Case 3 is considered to be sporadic, since DNA sequencing of the PY motif of her parents gave normal results. CONCLUSIONS: The DNA sequences of the ENaC in three patients with Liddle's syndrome were analyzed. In one family case, we found a new missense mutation of Pro (CCC) to Ser (TCC) at codon 616 in the 0 subunit of ENaC. A genetic analysis of the amiloride-sensitive epithelial sodium channel is recommended in assessing patients with low-renin, salt-sensitive hypertension whose blood pressure is not responsive to spironolactone treatment.


Asunto(s)
Hipertensión/genética , Hipertensión/metabolismo , Canales de Sodio/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , ADN/genética , Cartilla de ADN/genética , Canales Epiteliales de Sodio , Epitelio/metabolismo , Femenino , Humanos , Hipopotasemia/genética , Hipopotasemia/metabolismo , Masculino , Persona de Mediana Edad , Mutación Missense , Linaje , Mutación Puntual , Conformación Proteica , Renina/sangre , Canales de Sodio/química , Canales de Sodio/metabolismo , Síndrome
20.
J Am Soc Nephrol ; 9(9): 1574-80, 1998 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-9727364

RESUMEN

Higher dietary salt intake in humans is associated with higher BP, but the BP response to NaCl, so-called salt sensitivity, is heterogeneous among individuals. It has been postulated that modifications in cellular cation metabolism may be related to salt sensitivity in mammalian hypertension. The authors have isolated a novel rat complementary DNA, called salt-tolerant protein (STP), that can functionally complement Saccharomyces cervisiae HAL1, which improves salt tolerance by modulating the cation transport system. On high-salt (8% NaCl) diets, both Dahl salt-sensitive and salt-resistant rats displayed an elevated BP and increased STP mRNA expression. Immunohistochemistry using an anti-rat STP antibody demonstrated the presence of STP immunoreactivity in the proximal tubules. In cells that transiently expressed STP, the intracellular [Na+]/[K+] ratio was higher than that in control cells. STP contains predicted coiled-coil and Src homology 3 domains, and shows a partially high degree of nucleotide identity to human thyroid-hormone receptor interacting protein. These results suggest that STP may play an important role in salt sensitivity through cellular sodium metabolism by mediating signal transduction and a hormone-dependent transcription mechanism.


Asunto(s)
Proteínas Fúngicas/metabolismo , Corteza Renal/metabolismo , Médula Renal/metabolismo , ARN Mensajero/análisis , Cloruro de Sodio Dietético/metabolismo , Secuencia de Aminoácidos , Análisis de Varianza , Animales , Northern Blotting , Proteínas Portadoras/genética , Proteínas Portadoras/metabolismo , Técnicas de Cultivo , ADN Complementario/análisis , Modelos Animales de Enfermedad , Proteínas Fúngicas/análisis , Proteínas Fúngicas/genética , Expresión Génica , Inmunohistoquímica , Corteza Renal/patología , Médula Renal/patología , Masculino , Proteínas Asociadas a Microtúbulos , Antígenos de Histocompatibilidad Menor , Ratas , Ratas Endogámicas Dahl , Ratas Wistar , Cloruro de Sodio Dietético/administración & dosificación
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA