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1.
Ecol Lett ; 22(3): 506-517, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30609108

RESUMEN

Earth system models (ESMs) use photosynthetic capacity, indexed by the maximum Rubisco carboxylation rate (Vcmax ), to simulate carbon assimilation and typically rely on empirical estimates, including an assumed dependence on leaf nitrogen determined from soil fertility. In contrast, new theory, based on biochemical coordination and co-optimization of carboxylation and water costs for photosynthesis, suggests that optimal Vcmax can be predicted from climate alone, irrespective of soil fertility. Here, we develop this theory and find it captures 64% of observed variability in a global, field-measured Vcmax dataset for C3 plants. Soil fertility indices explained substantially less variation (32%). These results indicate that environmentally regulated biophysical constraints and light availability are the first-order drivers of global photosynthetic capacity. Through acclimation and adaptation, plants efficiently utilize resources at the leaf level, thus maximizing potential resource use for growth and reproduction. Our theory offers a robust strategy for dynamically predicting photosynthetic capacity in ESMs.


Asunto(s)
Aclimatación , Dióxido de Carbono , Fotosíntesis , Adaptación Fisiológica , Nitrógeno , Hojas de la Planta , Ribulosa-Bifosfato Carboxilasa
2.
Surg Endosc ; 33(6): 1769-1776, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-30291444

RESUMEN

BACKGROUND: The number of colorectal cancer cases is increasing, and so the number of laparoscopic colectomy procedures being performed is also increasing, leading to an increased workload for surgeons. However, operating for prolonged time periods may cause surgeons to lose their concentration and develop fatigue. We hypothesized that there is a time-of-day variation in outcome for patients with colorectal cancer who undergo laparoscopic colectomy. The present study aimed to compare the operative outcome between laparoscopic colectomy for colorectal cancer performed in the morning versus the afternoon. METHODS: This was a single-center, retrospective study. All 1961 consecutive patients who underwent laparoscopic surgery for colorectal cancer between 2007 and 2017 were included; 1006 of these patients underwent morning surgery, while 955 underwent afternoon surgery. These patients were analyzed using propensity score matching, giving 791 patients in each group. The short- and long-term outcomes in both groups were compared. RESULTS: Before propensity score matching, the morning group had a larger mean tumor size than the afternoon group (30 cm vs 35 cm; P = 0.0035). After matching, the two groups did not significantly differ in any patient characteristics. Compared with the afternoon group, the morning group had a significantly lesser incidence of intra-operative organ injury (0.25% vs 1.13%; P = 0.027), and a significantly greater incidence of post-operative abdominal abscess (2.03% vs 0.75% P = 0.028). The incidences of other complications and morbidities were similar in both groups. The median operative time in the morning group (201 min) was significantly longer than that in the afternoon group (193 min; P = 0.0124). The two groups did not differ in 5-year overall survival rates and 5-year disease-free rates within any disease stage. CONCLUSIONS: Surgical start times are correlated with surgical outcomes. Our data will help to ensure the safest possible surgeries.


Asunto(s)
Neoplasias Colorrectales/cirugía , Tempo Operativo , Anciano , Anciano de 80 o más Años , Colectomía , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Femenino , Humanos , Incidencia , Japón/epidemiología , Laparoscopía , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Estudios Retrospectivos , Análisis de Supervivencia
4.
New Phytol ; 214(3): 1002-1018, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-27389684

RESUMEN

We examined whether variations in photosynthetic capacity are linked to variations in the environment and/or associated leaf traits for tropical moist forests (TMFs) in the Andes/western Amazon regions of Peru. We compared photosynthetic capacity (maximal rate of carboxylation of Rubisco (Vcmax ), and the maximum rate of electron transport (Jmax )), leaf mass, nitrogen (N) and phosphorus (P) per unit leaf area (Ma , Na and Pa , respectively), and chlorophyll from 210 species at 18 field sites along a 3300-m elevation gradient. Western blots were used to quantify the abundance of the CO2 -fixing enzyme Rubisco. Area- and N-based rates of photosynthetic capacity at 25°C were higher in upland than lowland TMFs, underpinned by greater investment of N in photosynthesis in high-elevation trees. Soil [P] and leaf Pa were key explanatory factors for models of area-based Vcmax and Jmax but did not account for variations in photosynthetic N-use efficiency. At any given Na and Pa , the fraction of N allocated to photosynthesis was higher in upland than lowland species. For a small subset of lowland TMF trees examined, a substantial fraction of Rubisco was inactive. These results highlight the importance of soil- and leaf-P in defining the photosynthetic capacity of TMFs, with variations in N allocation and Rubisco activation state further influencing photosynthetic rates and N-use efficiency of these critically important forests.


Asunto(s)
Altitud , Bosques , Humedad , Fotosíntesis/fisiología , Hojas de la Planta/fisiología , Clima Tropical , Dióxido de Carbono/metabolismo , Pruebas de Enzimas , Cinética , Modelos Biológicos , Nitrógeno/metabolismo , Perú , Hojas de la Planta/anatomía & histología , Hojas de la Planta/química , Ribulosa-Bifosfato Carboxilasa/metabolismo , Especificidad de la Especie , Temperatura
5.
New Phytol ; 210(3): 1130-44, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26719951

RESUMEN

Simulations of photosynthesis by terrestrial biosphere models typically need a specification of the maximum carboxylation rate (Vcmax ). Estimating this parameter using A-Ci curves (net photosynthesis, A, vs intercellular CO2 concentration, Ci ) is laborious, which limits availability of Vcmax data. However, many multispecies field datasets include net photosynthetic rate at saturating irradiance and at ambient atmospheric CO2 concentration (Asat ) measurements, from which Vcmax can be extracted using a 'one-point method'. We used a global dataset of A-Ci curves (564 species from 46 field sites, covering a range of plant functional types) to test the validity of an alternative approach to estimate Vcmax from Asat via this 'one-point method'. If leaf respiration during the day (Rday ) is known exactly, Vcmax can be estimated with an r(2) value of 0.98 and a root-mean-squared error (RMSE) of 8.19 µmol m(-2) s(-1) . However, Rday typically must be estimated. Estimating Rday as 1.5% of Vcmax, we found that Vcmax could be estimated with an r(2) of 0.95 and an RMSE of 17.1 µmol m(-2) s(-1) . The one-point method provides a robust means to expand current databases of field-measured Vcmax , giving new potential to improve vegetation models and quantify the environmental drivers of Vcmax variation.


Asunto(s)
Dióxido de Carbono/metabolismo , Luz , Fotosíntesis/efectos de la radiación , Plantas/metabolismo , Respiración de la Célula , Bases de Datos como Asunto , Cinética , Estomas de Plantas/fisiología , Temperatura
6.
Eur J Paediatr Dent ; 17(2): 155-63, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-27377116

RESUMEN

AIM: To investigate the developmental process of palate morphology, including the alveolar ridge, in healthy infants for the predental period of 7 months from immediately after birth. METHODS: The subjects were 32 healthy infants. Four or more dental casts were taken of each subject from immediately after birth until 7 months, for a total of 144 dental casts. Twelve characteristics were then measured in order to morphologically study the subjects' palate development. Principal component analysis (PCA) was performed to investigate morphological changes in the palatal vault. RESULTS: The 12 characteristics were classified into either the alveolar ridge characteristics group, which determined the size of the alveolar ridge, or the palate characteristics group, which determined palate morphology, with each group showing different growth patterns. The characteristics of width and length increased with age in the alveolar ridge characteristics group; this correlation was maintained throughout the predental period. Meanwhile, in the palate characteristics group, the characteristics showed major developmental changes in the first 2 to 3 months after birth, but the changes were subsequently fewer from 3 to 7 months. The PCA of the palatal vault showed that the first principal component increased until 3 months but subsequently ceased to change. CONCLUSIONS: In predental infants, growth patterns of palate morphology differed according to their characteristics. There were major developmental changes in the palate during the first 3 months after birth. The study findings suggest that palate growth in the first half of the predental period may affect subsequent palate growth.


Asunto(s)
Proceso Alveolar/crecimiento & desarrollo , Hueso Paladar/crecimiento & desarrollo , Dentición , Humanos , Lactante , Estudios Longitudinales
7.
Oecologia ; 178(3): 659-72, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25752617

RESUMEN

Photosynthesis/nutrient relationships of proximally growing forest and savanna trees were determined in an ecotonal region of Cameroon (Africa). Although area-based foliar N concentrations were typically lower for savanna trees, there was no difference in photosynthetic rates between the two vegetation formation types. Opposite to N, area-based P concentrations were-on average-slightly lower for forest trees; a dependency of photosynthetic characteristics on foliar P was only evident for savanna trees. Thus savanna trees use N more efficiently than their forest counterparts, but only in the presence of relatively high foliar P. Along with some other recent studies, these results suggest that both N and P are important modulators of woody tropical plant photosynthetic capacities, influencing photosynthetic metabolism in different ways that are also biome specific. Attempts to find simple unifying equations to describe woody tropical vegetation photosynthesis-nutrient relationships are likely to meet with failure, with ecophysiological distinctions between forest and savanna requiring acknowledgement.


Asunto(s)
Bosques , Pradera , Nitrógeno/metabolismo , Fósforo/metabolismo , Fotosíntesis , Árboles/metabolismo , África , Biodiversidad , Camerún , Ecosistema , Transporte de Electrón , Hojas de la Planta/metabolismo , Hojas de la Planta/fisiología , Ribulosa-Bifosfato Carboxilasa/metabolismo , Especificidad de la Especie , Árboles/fisiología , Clima Tropical
8.
Clin Exp Dermatol ; 37(4): 335-40, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22276575

RESUMEN

BACKGROUND: Hyperacute graft-versus-host disease (GVHD) is defined as GVHD occurring within 14 days after haematopoietic stem-cell transplantation (HSCT). AIM: To evaluate the usefulness of skin biopsy in assessing hyperacute GVHD. METHODS: We examined 19 cases of hyperacute GVHD from a total of 134 consecutive HSCT cases at Shinshu University Hospital between 1999 and 2008. RESULTS: Exanthemas were seen in all patients, which were mainly disseminated maculopapular erythemas, commonly present in acute GVHD as well. Most patients presented with a high fever, and a few had mild hepatic dysfunction and/or diarrhoea. The clinical grade of GVHD was 1-2 in all patients; there were no cases of clinical grades 3-4. The histological findings of skin biopsy were divided into three groups: (i) eight had grade 2 changes, characterized by diffuse vacuolization of basal cells, with dyskeratotic bodies; (ii) five had grade 1 changes, characterized by vacuolization of epidermal basal cells (all these cases were diagnosed as acute GVHD with grade 2 histological changes at subsequent biopsy); (iii) and six had no significant changes (these cases were also diagnosed as acute GVHD with grade 2 (four cases) or grade 1 (one case) histological changes on the second biopsy). Many of the patients developed acute and later chronic GVHD. CONCLUSION: Skin biopsy should be considered when eruption develops after HSCT even before engraftment, especially when other organ involvement is minimal. If the first skin biopsy is inconclusive, follow-up biopsy within a short time is helpful in the diagnosis of hyperacute GVHD.


Asunto(s)
Enfermedad Injerto contra Huésped/patología , Enfermedad Aguda , Adolescente , Adulto , Biopsia , Niño , Preescolar , Femenino , Enfermedad Injerto contra Huésped/clasificación , Humanos , Lactante , Masculino , Persona de Mediana Edad , Adulto Joven
9.
Nat Commun ; 13(1): 5005, 2022 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-36008385

RESUMEN

Tropical forests take up more carbon (C) from the atmosphere per annum by photosynthesis than any other type of vegetation. Phosphorus (P) limitations to C uptake are paramount for tropical and subtropical forests around the globe. Yet the generality of photosynthesis-P relationships underlying these limitations are in question, and hence are not represented well in terrestrial biosphere models. Here we demonstrate the dependence of photosynthesis and underlying processes on both leaf N and P concentrations. The regulation of photosynthetic capacity by P was similar across four continents. Implementing P constraints in the ORCHIDEE-CNP model, gross photosynthesis was reduced by 36% across the tropics and subtropics relative to traditional N constraints and unlimiting leaf P. Our results provide a quantitative relationship for the P dependence for photosynthesis for the front-end of global terrestrial C models that is consistent with canopy leaf measurements.


Asunto(s)
Bosques , Fósforo , Carbono , Fotosíntesis , Hojas de la Planta/fisiología , Árboles/fisiología
10.
AJNR Am J Neuroradiol ; 41(11): 2107-2113, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-33004340

RESUMEN

BACKGROUND AND PURPOSE: Knowledge about predictors of the outcome of flow-diverter treatment is limited. The aim of this study was to predict the angiographic occlusion status after flow-diverter treatment with computational fluid dynamics using porous media modeling for decision-making in the treatment of large wide-neck aneurysms. MATERIALS AND METHODS: A total of 27 patients treated with flow-diverter stents were retrospectively analyzed through computational fluid dynamics using pretreatment patient-specific 3D rotational angiography. These patients were classified into no-filling and contrast-filling groups based on the O'Kelly-Marotta scale. The patient characteristics, morphologic variables, and hemodynamic parameters were evaluated for understanding the outcomes of the flow-diverter treatment. RESULTS: The patient characteristics and morphologic variables were similar between the 2 groups. Flow velocity, wall shear stress, shear rate, modified aneurysmal inflow rate coefficient, and residual flow volume were significantly lower in the no-filling group. A novel parameter, called the normalized residual flow volume, was developed and defined as the residual flow volume normalized by the dome volume. The receiver operating characteristic curve analyses demonstrated that the normalized residual flow volume with an average flow velocity of ≥8.0 cm/s in the aneurysmal dome was the most effective in predicting the flow-diverter treatment outcomes. CONCLUSIONS: It was established in this study that the hemodynamic parameters could predict the angiographic occlusion status after flow-diverter treatment.


Asunto(s)
Embolización Terapéutica/métodos , Procedimientos Endovasculares/métodos , Hemodinámica/fisiología , Aneurisma Intracraneal/terapia , Modelos Neurológicos , Adulto , Anciano , Anciano de 80 o más Años , Angiografía de Substracción Digital/métodos , Angiografía Cerebral/métodos , Femenino , Humanos , Hidrodinámica , Procesamiento de Imagen Asistido por Computador/métodos , Imagenología Tridimensional/métodos , Aneurisma Intracraneal/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Stents , Resultado del Tratamiento
11.
Ecology ; 100(4): e02641, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30712256

RESUMEN

High rates of land conversion and land use change have vastly increased the proportion of secondary forest in the lowland tropics relative to mature forest. As secondary forests recover following abandonment, nitrogen (N) and phosphorus (P) must be present in sufficient quantities to sustain high rates of net primary production and to replenish the nutrients lost during land use prior to secondary forest establishment. Biogeochemical theory and results from individual studies suggest that N can recuperate during secondary forest recovery, especially relative to P. Here, we synthesized 23 metrics of N and P in soil and plants from 45 secondary forest chronosequences located in the wet tropics to empirically explore (1) whether there is a consistent change in nutrients and nutrient cycling processes during secondary succession in the biome; (2) which metrics of N and P in soil and plants recuperate most consistently; (3) if the recuperation of nutrients during succession approaches similar nutrient concentrations and fluxes as those in mature forest in ~100 yr following the initiation of succession; and (4) whether site characteristics, including disturbance history, climate, and soil order are significantly related to nutrient recuperation. During secondary forest succession, nine metrics of N and/or P cycling changed consistently and substantially. In most sites, N concentrations and fluxes in both plants and soil increased during secondary succession, and total P concentrations increased in surface soil. Changes in nutrient concentrations and nutrient cycling processes during secondary succession were similar whether mature forest was included or excluded from the analysis, indicating that nutrient recuperation in secondary forest leads to biogeochemical conditions that are similar to those of mature forest. Further, of the N and P metrics that recuperated, only soil total P and foliar δ15 N were strongly influenced by site characteristics like climate, soils, or disturbance history. Predictable nutrient recuperation across a diverse and productive ecosystem may support future forest growth and could provide a means to quantify successful restoration of ecosystem function in secondary tropical forest beyond biomass or species composition.


Asunto(s)
Ecosistema , Árboles , Bosques , Nitrógeno , Fósforo , Suelo , Clima Tropical
12.
Leukemia ; 19(7): 1169-74, 2005 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-15902300

RESUMEN

Natural killer (NK) cell-type lymphoproliferative diseases of granular lymphocytes can be subdivided into aggressive NK cell leukemia (ANKL) and chronic NK cell lymphocytosis (CNKL). One reason for the poor outcome in ANKL is leukemic infiltration into multiple organs. The mechanisms of cell trafficking associated with the chemokine system have been investigated in NK cells. To clarify the mechanism of systemic migration of leukemic NK cells, we enrolled nine ANKL and six CNKL cases, and analyzed the expression profiles and functions of chemokine receptors by flowcytometry and chemotaxis assay. CXCR1 was detected on NK cells in all groups, and CCR5 was positive in all ANKL cells. Proliferating NK cells were simultaneously positive for CXCR1 and CCR5 in all ANKL patients examined, and NK cells with this phenotype did not expand in CNKL patients or healthy donors. ANKL cells showed enhanced chemotaxis toward the ligands of these receptors. These results indicated that the chemokine system might play an important role in the pathophysiology of ANKL and that chemokine receptor profiling might be a novel tool for discriminating ANKL cells from benign NK cells.


Asunto(s)
Células Asesinas Naturales/patología , Leucemia Linfoide/genética , Linfocitosis/genética , Receptores de Quimiocina/genética , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/fisiología , Movimiento Celular/efectos de los fármacos , Movimiento Celular/fisiología , Quimiocinas/farmacología , Niño , Femenino , Perfilación de la Expresión Génica , Humanos , Células Asesinas Naturales/química , Células Asesinas Naturales/inmunología , Leucemia Linfoide/diagnóstico , Leucemia Linfoide/fisiopatología , Linfocitosis/diagnóstico , Masculino , Persona de Mediana Edad , Fenotipo , Receptores CCR5/genética , Receptores CCR5/fisiología , Receptores de Quimiocina/análisis , Receptores de Quimiocina/fisiología , Receptores de Interleucina-8A/genética , Receptores de Interleucina-8A/fisiología
13.
Transplant Proc ; 48(4): 1083-6, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27320563

RESUMEN

BACKGROUND: In this study, we demonstrated our new device for open donor liver surgery with left-sided heptectomy by use of the real-time moving windows (RTMW) method with 8-cm transverse skin incision for living donors from the viewpoints of cosmetic, economic, and safety procedures. METHODS: After the upper abdominal 8-cm transverse skin incision was made, the subcutaneous area was exfoliated and the reverse T-shaped-abdominal incision was made, as in open surgery. After that, the 2 Kent hooks for the upper region and the 2 surgical arms for the lower region were placed. The operative fields of hepatic vein, hepatic hilus, and common hepatic artery were explored, respectively, by use of the RTMW method with the use of the 4 surgical hooks. Hepatic parenchymal dissection was carried out with the use of CUSA and laparosonic coagulating shears. Manipulations of 3 hepatic vessels and the hepatic duct were done by the usual procedure of open surgery. RESULTS: This operative procedure could be performed without laparoscopic techniques. The operative time was 7 hours, without blood transfusion. The operative course was uneventful, and the patient was discharged on postoperative day 11. CONCLUSIONS: Our RTMW method for donor left-sided hepatectomy is considered to be a useful operative procedure from the viewpoints of donor safety, cosmetic advantage, and cost performance.


Asunto(s)
Disección/instrumentación , Hepatectomía/métodos , Trasplante de Hígado , Donadores Vivos , Recolección de Tejidos y Órganos/métodos , Anciano de 80 o más Años , Neoplasias de los Conductos Biliares/cirugía , Colangiocarcinoma/cirugía , Femenino , Humanos , Tempo Operativo , Sitio Donante de Trasplante
14.
Biochim Biophys Acta ; 963(1): 35-41, 1988 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-3179328

RESUMEN

Effects of MK-733 on the absorption and excretion of cholesterol in rabbits were examined using [3H]cholesterol. The animals were divided into six groups; three groups were fed a normal diet, and the other groups a cholesterol diet. MK-733 was administered orally as a single dose of 10 mg/kg on day 8, or multiple doses of 10 mg/kg once a day for 14 days. On the 8th day, [3H]cholesterol was given orally to each animal. In the groups fed a normal diet, single and consecutive administration of MK-733 did not affect the absorption and excretion of [3H]cholesterol. In the cholesterol-fed groups, however, single administration of MK-733 decreased the serum 3H radioactivity slightly, but did not affect the fecal excretion of [3H]cholesterol. However, the consecutive treatment with MK-733 clearly reduced the serum 3H radioactivity. The cumulative excretion of the fecal radioactivity of [3H]cholesterol in the MK-733 group (multiple) was higher than that in the control group. From these results, it is concluded that MK-733 inhibits the absorption of cholesterol from the gastrointestinal wall in cholesterol-fed rabbits.


Asunto(s)
Colesterol/farmacocinética , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Lovastatina/análogos & derivados , Administración Oral , Animales , Colesterol en la Dieta/administración & dosificación , Heces/análisis , Lovastatina/administración & dosificación , Lovastatina/farmacología , Masculino , Conejos , Simvastatina , Sitoesteroles/farmacología
15.
Biochim Biophys Acta ; 1004(1): 117-23, 1989 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-2742865

RESUMEN

MK-733 (simvastatin), a potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, was found to inhibit the absorption of cholesterol from the gastrointestinal tract in cholesterol-fed rabbits (Ishida et al. (1988) Biochim. Biophys. Acta 963, 35-41). To clarify the mechanism of action, the effects of MK-733 on acyl coenzyme A:cholesterol acyltransferase (ACAT) and cholesterol esterase activities, which are thought to participate in the absorption of cholesterol, were examined. Dietary administration (0.03% in a 1% cholesterol diet for 7 days, approx. 10 mg/kg) of MK-733 to cholesterol-fed rabbits was found to inhibit the increase in serum total cholesterol levels, and caused a 70% reduction in ACAT activity in microsomes of intestinal mucosa relative to those observed in concurrent control rabbits. MK-733 did not affect cholesterol esterase activity in the cytosol of the intestinal mucosa. The inhibitory effect of MK-733 on cholesterol absorption in cholesterol-fed rabbits is though to be related to a reduction in microsomal ACAT activity in the intestinal mucosa.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Mucosa Intestinal/enzimología , Lovastatina/análogos & derivados , Esterol O-Aciltransferasa/antagonistas & inhibidores , Animales , Colesterol/metabolismo , Colesterol en la Dieta/farmacología , Resina de Colestiramina/farmacología , Citosol/metabolismo , Absorción Intestinal/efectos de los fármacos , Lípidos/sangre , Lovastatina/farmacocinética , Lovastatina/farmacología , Masculino , Microsomas/metabolismo , Conejos , Simvastatina , Esterol Esterasa/metabolismo
16.
Biochim Biophys Acta ; 1168(1): 45-51, 1993 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-8504141

RESUMEN

NB-598, a specific inhibitor of squalene epoxidase, suppressed the secretion of cholesterol and triacylglycerol from HepG2 cells into the medium. L-654,969, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, inhibited the secretion of cholesterol as potently as NB-598, but did not suppress the secretion of triacylglycerol. Both compounds decreased the intracellular cholesterol content almost equally, and neither of the compounds reduced the intracellular triacylglycerol content. The suppression of lipid secretion by NB-598 was associated with a significant reduction in apolipoprotein (apo) B secretion into the medium. Therefore, the suppression of lipid secretion by NB-598 may be caused by a reduction in the number of triacylglycerol-rich lipoprotein particles. In contrast, the suppression of cholesterol secretion by L-654,969 may be due to a modulation of lipoprotein lipid composition, since this agent did not reduce the secretion of apo B or triacylglycerol. The secretion of apo A-I was unaffected by either NB-598 or L-654,969. Pulse chase studies using [35S]methionine showed that the suppression of apo B secretion by NB-598 depended on an enhancement of intracellular degradation of apo B. These results indicate that the secretion of apo B from HepG2 cells is not regulated by the lipid synthesis alone, and suggest that the mechanism of the hypolipidemic effect of NB-598 involves the suppression of triacylglycerol-rich lipoprotein secretion from the liver as well as an inhibition of cholesterol synthesis in the liver.


Asunto(s)
Anticolesterolemiantes/farmacología , Apolipoproteínas B/metabolismo , Bencilaminas/farmacología , Colesterol/metabolismo , Oxigenasas/antagonistas & inhibidores , Simvastatina/análogos & derivados , Tiofenos/farmacología , Triglicéridos/metabolismo , Apolipoproteína A-I/biosíntesis , Apolipoproteína A-I/metabolismo , Apolipoproteínas B/biosíntesis , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas , Hígado/efectos de los fármacos , Hígado/metabolismo , Lovastatina/análogos & derivados , Lovastatina/farmacología , Escualeno/metabolismo , Escualeno-Monooxigenasa , Células Tumorales Cultivadas
17.
Biochim Biophys Acta ; 1042(3): 365-73, 1990 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-2106347

RESUMEN

The preventive effects of simvastatin (MK-733) and pravastatin (CS-514), 3-hydroxy-3-methylglutarylcoenzyme A (HMG-CoA) reductase inhibitors, on hypercholesterolemia induced by 0.25% cholesterol feeding were compared in rabbits. MK-733 (6, 2 and 0.7 mg/kg) was found to prevent the increase in serum total cholesterol levels dose-dependently. High dose CS-514 (18 mg/kg) also limited the increase in the cholesterol levels, but medium (6 mg/kg) and low doses (2 mg/kg) of CS-514 were ineffective in preventing it. MK-733 inhibited the increase in VLDL and LDL cholesterol levels dose-dependently. MK-733 suppressed the increase in serum phospholipid levels. MK-733 inhibited the accumulation of cholesterol in the liver. The high dose of CS-514 also limited it. High dose MK-733 (6 mg/kg) reduced the cholesterol concentration in gallbladder bile. Neither MK-733 nor CS-514 affected bile acid excretion in the gallbladder bile. High dose MK-733 decreased the lithogenic index. MK-733 increased the number of LDL receptors, and high dose CS-514 also increased it. The suppressive effect of CS-514 on serum cholesterol levels at 18 mg/kg was found to be less than that of MK-733 at 0.7 mg/kg.


Asunto(s)
Colesterol en la Dieta/administración & dosificación , Ácidos Heptanoicos/farmacología , Hipercolesterolemia/metabolismo , Lovastatina/análogos & derivados , Naftalenos/farmacología , Animales , Bilis/metabolismo , Colesterol/sangre , Hipercolesterolemia/inducido químicamente , Lipoproteínas/sangre , Lipoproteínas LDL/metabolismo , Lovastatina/farmacología , Masculino , Microsomas Hepáticos/efectos de los fármacos , Microsomas Hepáticos/metabolismo , Pravastatina , Conejos , Receptores de LDL/análisis , Receptores de LDL/efectos de los fármacos , Simvastatina , Estadística como Asunto , Esterol O-Aciltransferasa/análisis , Esterol O-Aciltransferasa/antagonistas & inhibidores
18.
Leukemia ; 18(3): 556-65, 2004 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-14737071

RESUMEN

Natural killer (NK) cell-type lymphoproliferative disease of granular lymphocytes (LDGL) is characterized by the outgrowth of CD3(-)CD16/56(+) NK cells, and can be further subdivided into two distinct categories: aggressive NK cell leukemia (ANKL) and chronic NK lymphocytosis (CNKL). To gain insights into the pathophysiology of NK cell-type LDGL, we here purified CD3(-)CD56(+) fractions from healthy individuals (n=9) and those with CNKL (n=9) or ANKL (n=1), and compared the expression profiles of >12 000 genes. A total of 15 'LDGL-associated genes' were identified, and a correspondence analysis on such genes could clearly indicate that LDGL samples share a 'molecular signature' distinct from that of normal NK cells. With a newly invented class prediction algorithm, 'weighted distance method', all 19 samples received a clinically matched diagnosis, and, furthermore, a detailed cross-validation trial for the prediction of normal or CNKL status could achieve a high accuracy (77.8%). By applying another statistical approach, we could extract other sets of genes, expression of which was specific to either normal or LDGL NK cells. Together with sophisticated statistical methods, gene expression profiling of a background-matched NK cell fraction thus provides us a wealth of information for the LDGL condition.


Asunto(s)
Complejo CD3/metabolismo , Antígeno CD56/metabolismo , Perfilación de la Expresión Génica , Células Asesinas Naturales/inmunología , Linfocitos/inmunología , Trastornos Linfoproliferativos/genética , Adolescente , Adulto , Anciano , Células Clonales , Femenino , Expresión Génica , Humanos , Inmunofenotipificación , Trastornos Linfoproliferativos/inmunología , Trastornos Linfoproliferativos/patología , Masculino , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/análisis
19.
Mol Immunol ; 32(9): 613-22, 1995 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-7543974

RESUMEN

A patient (OG) with Glanzmann thrombasthenia became refractory to platelet transfusion following the production of IgG antibodies (Ab1) specific for the integrin subunit beta 3. We generated recombinant VH and VL cDNA libraries using IgG-specific mRNA isolated from OG peripheral blood B-lymphocytes that had been selected for binding to antigen (alpha IIb beta 3 adsorbed to plastic dishes). These antigen-specific B-lymphocytes contain rearranged VH DNA segments that belong exclusively to the VH4 gene family. Recombinant Fab were expressed on the surface of filamentous phage coinfected with VH and VL segments cloned into the phagemid pHEN1 or the phage fd-tet-DOG1. To facilitate selection of the desired recombinant Ab1 Fab, we developed a rabbit polyclonal antibody specific for affinity-purified OG anti-beta 3 Fab (Ab2). Ab2 reacts specifically with Ab1, and this interaction is inhibited by purified alpha IIb beta 3. Following three rounds of phage selection on Ab2 adsorbed to plastic dishes and random reassociation of heavy and light chains, we isolated Ab1 Fab and tested their binding to alpha IIb beta 3. Five Id-positive Fab were selected for further characterization. These Fab use one of two VH genes (H21 or H23) complexed with one of three V lambda genes. Subsequent sequence data demonstrated that all three lambda genes are the same clone L22 which uses a germline V lambda gene segment. Fab using H23 bind to alpha IIb beta 3, while those using H21 do not. Based on sequence homology, both H21 and H23 use VH gene segments belonging to the VH4 gene family. Thus, the idiotype OG is restricted to the VH4 gene family and is the first sequenced prototype of human antibodies that bind close to or at a functional epitope(s) of alpha IIb beta 3.


Asunto(s)
Antígenos CD/inmunología , Inmunoglobulina G/inmunología , Idiotipos de Inmunoglobulinas/inmunología , Integrinas/inmunología , Glicoproteínas de Membrana Plaquetaria/inmunología , Receptores de Superficie Celular/inmunología , Secuencia de Aminoácidos , Secuencia de Bases , Moléculas de Adhesión Celular/inmunología , Clonación Molecular , Cartilla de ADN , Genes de Inmunoglobulinas , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/genética , Integrina beta3 , Datos de Secuencia Molecular , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Trombastenia/inmunología
20.
Thromb Haemost ; 85(1): 108-13, 2001 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-11204560

RESUMEN

Fibrinogen Matsumoto V (M-V) is a dysfibrinogen identified in a 52-year-old woman with systemic lupus erythematous. The triplet AGG encoding the amino acid residue Aalpha19 was replaced by GGG, resulting in the substitution of Arg-->Gly. Residue Aalpha19 has been shown to be one of the most important amino acids in the so-called 'A' site or alpha-chain knob. The thrombin-catalyzed release of fibrinopeptide A from M-V fibrinogen was only slightly delayed yet release of fibrinopeptide B was significantly delayed. Both thrombin-catalyzed fibrin polymerization and fibrin monomer polymerization were markedly impaired compared to normal fibrinogen. In addition, reptilase-catalyzed fibrin polymerization of M-V was much more impaired than thrombin-catalyzed fibrin polymerization. These results indicate 'B' and/or 'b' site of M-V fibrinogen play a more important role in thrombin-catalyzed fibrin polymerization than that of normal control fibrinogen.


Asunto(s)
Fibrinógenos Anormales/genética , Batroxobina/metabolismo , Pruebas de Coagulación Sanguínea , Análisis Mutacional de ADN , Femenino , Fibrina/metabolismo , Fibrinógenos Anormales/efectos de los fármacos , Fibrinopéptido A/metabolismo , Fibrinopéptido B/metabolismo , Variación Genética , Humanos , Cinética , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/genética , Persona de Mediana Edad , Mutación Puntual , Trombina/metabolismo
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