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1.
J Dent Res ; 96(9): 984-991, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28521114

RESUMEN

Transplantation of mesenchymal stem cells (MSCs), which possess self-renewing properties and multipotency, into a periodontal defect is thought to be a useful option for periodontal tissue regeneration. However, developing more reliable and predictable implantation techniques is still needed. Recently, we generated clumps of an MSC/extracellular matrix (ECM) complex (C-MSC), which consisted of cells and self-produced ECM. C-MSCs can regulate their cellular functions in vitro and can be grafted into a defect site, without any artificial scaffold, to induce bone regeneration. Accordingly, this study aimed to evaluate the effect of C-MSC transplantation on periodontal tissue regeneration in beagle dogs. Seven beagle dogs were employed to generate a premolar class III furcation defect model. MSCs isolated from dog ilium were seeded at a density of 7.0 × 104 cells/well into 24-well plates and cultured in growth medium supplemented with 50 µg/mL ascorbic acid for 4 d. To obtain C-MSCs, confluent cells were scratched using a micropipette tip and were then torn off as a cellular sheet. The sheet was rolled up to make round clumps of cells. C-MSCs were maintained in growth medium or osteoinductive medium (OIM) for 5 or 10 d. The biological properties of C-MSCs were evaluated in vitro, and their periodontal tissue regenerative activity was tested by using a dog class III furcation defect model. Immunofluorescence analysis revealed that type I collagen fabricated the form of C-MSCs. OIM markedly elevated calcium deposition in C-MSCs at day 10, suggesting its osteogenic differentiation capacity. Both C-MSCs and C-MSCs cultured with OIM transplantation without an artificial scaffold into the dog furcation defect induced periodontal tissue regeneration successfully compared with no graft, whereas osteogenic-differentiated C-MSCs led to rapid alveolar bone regeneration. These findings suggested that the use of C-MSCs refined by self-produced ECM may represent a novel predictable periodontal tissue regenerative therapy.


Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Matriz Extracelular/metabolismo , Regeneración Tisular Guiada Periodontal/métodos , Trasplante de Células Madre Mesenquimatosas/métodos , Enfermedades Periodontales/terapia , Ingeniería de Tejidos/métodos , Animales , Diferenciación Celular , Células Cultivadas , Modelos Animales de Enfermedad , Perros , Ilion/citología , Células Madre Mesenquimatosas/citología , Microtomografía por Rayos X
2.
Oral Dis ; 21(5): 626-33, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25703825

RESUMEN

OBJECTIVE: A large number of individuals have halitosis. The total amount of volatile sulfur compounds, which are the main cause of halitosis, has been correlated with periodontitis following bacterial infection. In this study, Porphyromonas gingivalis (Pg), a major periodontopathogenic bacterium, was isolated from patients with halitosis by the amplification of 16S rRNA, and the ability of isolated Pg to produce methyl mercaptan (CH3 SH) was determined to clarify the relationship between halitosis and Pg infection. MATERIALS AND METHODS: CH3 SH concentrations were measured in patients using Oral Chroma. The production of CH3 SH by Pg standard and clinical strains was also measured in vitro. Real-time PCR was performed to compare the expression of mgl mRNA (which encoded l-methionine-a-deamino-g-mercaptomethane-lyase) among the Pg strains. The production of CH3 SH and the expression of mgl mRNA were also determined to assess the effects of oriental medicine. RESULTS: The production of CH3 SH and the expression of mgl mRNA strongly correlated with each other in the presence of l-methionine. The expression of mgl mRNA by Pg W83 was strongly inhibited by magnoliaceae. CONCLUSION: The production of CH3 SH was correlated with the expression of mgl. Furthermore, the oriental medicine, magnoliaceae, may represent a potential treatment for halitosis.


Asunto(s)
Halitosis/microbiología , Porphyromonas gingivalis/genética , Porphyromonas gingivalis/metabolismo , ARN Mensajero/biosíntesis , Compuestos de Sulfhidrilo/metabolismo , Adulto , Anciano , Antiinfecciosos/farmacología , Proteínas Bacterianas/efectos de los fármacos , Infecciones por Bacteroidaceae/metabolismo , Infecciones por Bacteroidaceae/microbiología , Medicamentos Herbarios Chinos/farmacología , Femenino , Humanos , Magnoliaceae , Masculino , Metionina/metabolismo , Metionina/farmacología , Persona de Mediana Edad , Periodontitis/metabolismo , Periodontitis/microbiología , Porphyromonas gingivalis/aislamiento & purificación , ARN Mensajero/efectos de los fármacos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Adulto Joven
3.
Clin Exp Immunol ; 160(2): 283-92, 2010 May.
Artículo en Inglés | MEDLINE | ID: mdl-20030669

RESUMEN

Vitamin K is a family of fat-soluble compounds including phylloquinone (vitamin K1), menaquinone (vitamin K2) and menadione (vitamin K3). Recently, it was reported that vitamin K, especially vitamins K1 and K2, exerts a variety of biological effects, and these compounds are expected to be candidates for therapeutic agents against various diseases. In this study, we investigated the anti-inflammatory effects of vitamin K3 in in vitro cultured cell experiments and in vivo animal experiments. In human embryonic kidney (HEK)293 cells, vitamin K3 inhibited the tumour necrosis factor (TNF)-alpha-evoked translocation of nuclear factor (NF)-kappaB into the nucleus, although vitamins K1 and K2 did not. Vitamin K3 also suppressed the lipopolysaccharide (LPS)-induced nuclear translocation of NF-kappaB and production of TNF-alpha in mouse macrophage RAW264.7 cells. Moreover, the addition of vitamin K3 before and after LPS administration attenuated the severity of lung injury in an animal model of acute lung injury/acute respiratory distress syndrome (ARDS), which occurs in the setting of acute severe illness complicated by systemic inflammation. In the ARDS model, vitamin K3 also suppressed the LPS-induced increase in the serum TNF-alpha level and inhibited the LPS-evoked nuclear translocation of NF-kappaB in lung tissue. Despite marked efforts, little therapeutic progress has been made, and the mortality rate of ARDS remains high. Vitamin K3 may be an effective therapeutic strategy against acute lung injury including ARDS.


Asunto(s)
Lesión Pulmonar Aguda/tratamiento farmacológico , Antiinflamatorios no Esteroideos/uso terapéutico , Lipopolisacáridos/toxicidad , FN-kappa B/antagonistas & inhibidores , Vitamina K 3/uso terapéutico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/metabolismo , Animales , Antiinflamatorios no Esteroideos/farmacología , Líquido del Lavado Bronquioalveolar/citología , Células Cultivadas/efectos de los fármacos , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Riñón , Pulmón/inmunología , Pulmón/metabolismo , Pulmón/patología , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Neutrófilos/efectos de los fármacos , Factor de Necrosis Tumoral alfa/biosíntesis , Factor de Necrosis Tumoral alfa/metabolismo , Vitamina K 1/farmacología , Vitamina K 1/uso terapéutico , Vitamina K 2/farmacología , Vitamina K 2/uso terapéutico , Vitamina K 3/farmacología
4.
J Clin Pharm Ther ; 32(3): 277-85, 2007 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-17489880

RESUMEN

BACKGROUND: Upregulation of oligopeptide transport activity by dietary protein, certain dipeptides and amino acids has been reported in the rat intestine and a human intestinal cell line. OBJECTIVE: In this study, the pharmacokinetics of cefdinir were investigated after L-phenylalanine supplementation and a high-protein diet (HPD) in humans to explore changes in the activities of intestinal and renal oligopeptide transporters. METHODS: A normal-protein diet (NPD, 73.2 +/- 2.6 g/day), NPD + l-phenylalanine (7.5 g/day), or HPD (141.3 +/- 3.7 g/day) was given to six male healthy volunteers for 12 days followed by a single dose of cefdinir after an overnight fast in a randomized three-way crossover study with a 22-day washout. Blood and urine were collected over a 12-h period after administration of cefdinir. Concentrations of cefdinir in plasma and/or urine were measured by high-performance liquid chromatography. RESULTS: Plasma concentrations and urinary excretion of the drug did not change throughout the study. Physiological variables and laboratory values did not reveal any differences between the three periods except for serum and urinary nitrogen levels and serum triglyceride. DISCUSSION: A reason for the unchanged pharmacokinetics of cefdinir may be due to lower doses of L-phenylalanine and protein in humans than in animals when converting animal effective doses to humans. CONCLUSION: In humans, L-phenylalanine supplementation and HPD do not seem to upregulate intestinal and renal oligopeptide transport in the ranges of duration and dose examined.


Asunto(s)
Cefalosporinas/farmacocinética , Proteínas en la Dieta/administración & dosificación , Suplementos Dietéticos , Fenilalanina/administración & dosificación , Adulto , Alanina Transaminasa/sangre , Antibacterianos/sangre , Antibacterianos/farmacocinética , Antibacterianos/orina , Área Bajo la Curva , Nitrógeno de la Urea Sanguínea , Cefdinir , Cefalosporinas/sangre , Cefalosporinas/orina , Estudios Cruzados , Humanos , Absorción Intestinal/efectos de los fármacos , Pruebas de Función Renal , Masculino , Tasa de Depuración Metabólica/efectos de los fármacos , Política Nutricional , Proyectos Piloto , Factores de Tiempo , Triglicéridos/sangre
5.
J Colloid Interface Sci ; 303(1): 195-204, 2006 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-16920135

RESUMEN

Among the different cement minerals, calcium silicate hydrates (C-S-H) are the prime candidates for heavy metal binding because of their abundance and appropriate structure. Immobilization processes of heavy metals by cementitious materials, and in particular C-S-H phases, thus play an important role in multibarrier concepts developed worldwide for the safe disposal of hazardous and radioactive wastes. In this study, the uptake of U(VI) by C-S-H has been investigated using X-ray absorption fine structure (XAFS) spectroscopy. C-S-H phases were synthesized using two different procedures: One is based on the mixing of CaO and SiO2 solids ("direct reaction" method); for the other one starting solutions of Ca and Si are used ("solution reaction" method). XAFS investigations were carried out on samples doped with U(VI). U(VI) was either sorbed onto previously precipitated C-S-H phases (sorption samples) or added during C-S-H synthesis (coprecipitation samples). The coordination environment of U(VI) in the sorption samples was found to be independent of the procedure used for C-S-H synthesis. A split equatorial oxygen shell (Oeq1: R=2.23-2.27 A; Oeq2: R=2.36-2.45 A), neighboring silicon atoms at short (R=3.07-3.11 A) and long (R=3.71-3.77 A) distances, and neighboring Ca atoms (R=3.77-3.81 and 4.15-4.29 A) were observed for all the samples. The structural parameters resemble those reported for uranophane. The coordination environment of U(VI) in the coprecipitation samples depends on the method used for C-S-H synthesis, and further, the spectra differ from those determined for the sorption samples. UU backscattering contributions were observed in the samples prepared using the direct reaction method, whereas no split equatorial shell appeared in the samples prepared using the solution reaction method.


Asunto(s)
Compuestos de Calcio/química , Silicatos/química , Uranio/química , Contaminantes Radiactivos del Agua/química , Absorciometría de Fotón , Cationes/química
6.
Eur Respir J ; 25(6): 1077-83, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15929965

RESUMEN

Bronchial epithelial cells play an important role in airway host defence, and interferon (IFN)-gamma controls immune reactions by regulating the expression of various genes in bronchial epithelial cells. Signal transducer and activator of transcription 1 (STAT1) is the key transcriptional factor in IFN-gamma signalling. Retinoic acid-inducible gene-I (RIG-I) is a member of the DExH box family of proteins and designated a putative RNA helicase. RNA helicases play diverse roles in regulation of gene expression and cellular functions, and RIG-I is implicated in antiviral responses. The aim of the present study was to investigate the effect of IFN-gamma on RIG-I expression in a cell line derived from human bronchial epithelial cells, BEAS-2B. Induction of RIG-I in response to IFN-gamma was found in BEAS-2B cells. Induction of RIG-I by IFN-gamma was also demonstrated in another pulmonary epithelial cell line, NCI-H292. Transfection of BEAS-2B cells with RIG-I complementary DNA resulted in the upregulation of STAT1. Induction of IFN-gamma-inducible protein 10 by IFN-gamma was enhanced in the cells overexpressing RIG-I. It is concluded that retinoic acid-inducible gene-I may play an important role in the regulation of immunological reactions in bronchial epithelial cells elicited by interferon-gamma.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Interferón gamma/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , ARN Helicasas/metabolismo , Mucosa Respiratoria/citología , Mucosa Respiratoria/metabolismo , Transactivadores/metabolismo , Células Cultivadas , Quimiocina CXCL10 , Quimiocinas CXC/metabolismo , Proteína 58 DEAD Box , ARN Helicasas DEAD-box , Humanos , Receptores Inmunológicos , Factor de Transcripción STAT1
7.
Arch Virol ; 150(6): 1135-49, 2005 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-15703850

RESUMEN

We have determined the complete nucleotide sequence of three isolates (two severe and one attenuated) of the potyvirus Leek yellow stripe virus (LYSV), the main causal agent of the garlic mosaic disease that is prevalent in Aomori prefecture, northern Japan. They contained 10,296-10,297 nucleotides and encoded a deduced polyprotein of 3,215 amino acids. Sequence variation among the three isolates was 1.5% at both the nucleotide and amino acid levels. Surprisingly, the sequences of all three isolates were quite different from that of recently described garlic isolate of LYSV from China. Sequence similarities among the 5'-UTR and P1 regions were only 56-57% and 52-53%, respectively, raising the possibility that these isolates may actually be distinct virus species. Phylogenetic analyses using 5'-UTR, P1 protein and coat protein revealed that all LYSV isolates described to date can be divided into three groups; i.e., those from leek, those from garlic in northern Japan, and those from garlic in southern Japan, China, and other parts of the world. The garlic isolates from northern Japan were more closely related to LYSV isolates from leek than to garlic isolates from southern Japan and China, suggesting a different origin for the garlic cultivars now cultivated in northern Japan.


Asunto(s)
Ajo/virología , Cebollas/virología , Enfermedades de las Plantas/virología , Potyvirus/clasificación , Potyvirus/patogenicidad , Regiones no Traducidas 5'/genética , Proteínas de la Cápside/genética , China , Clonación Molecular , Japón , Corea (Geográfico) , Filogenia , Potyvirus/genética , Análisis de Secuencia de ADN , Proteínas Virales/genética
8.
Microb Ecol ; 46(4): 442-53, 2003 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12904913

RESUMEN

Microbial population changes were monitored immediately after the Nakhodka oil spill accident in January 1997 at the heavily oil-contaminated Mikuni coast along the Sea of Japan. The total cell number was almost stable for one year at 2-5 x 10(5) cells mL(-1), while the relative occurrence of culturable heterotrophs and degraders of oil components such as C-heavy oil, kerosene, and n-tetradecane varied, showing a maximum (>50% of the total) immediately following the accident. Gene amplification and phylogenetic analysis of a dilution culture using C-heavy oil as the sole carbon and energy source revealed that one of the predominant oil degraders at the oil-contaminated coast in 2 weeks after the accident closely resembled the aromatic hydrocarbon decomposer Cycloclasticus pugetii. Microbial community composition in oil-contaminated seawater was estimated at the molecular level using newly developed oligonucleotide probes, probe wash-off curve estimation, and quantitative fluorescence dot-blot hybridization techniques. At two different oil-polluted sites, harbor and intertidal regions, the C. pugetii group was estimated to make up 23-25% of the total Bacteria population, followed by the aliphatic hydrocarbon decomposer Alcanivorax borkumensis, which formed 4-7% of the Bacteria. In incubation experiments using floated oil slick and indigenous microbes collected at the harbor, oil degradation activities were enhanced by the addition of both organic and inorganic nutrients. Significant decreases were found in aromatic and aliphatic hydrocarbon fractions: 54-60% and 22-24% in 2 weeks to 68-77% and 23-32% in 2 months, respectively.


Asunto(s)
Contaminación Ambiental , Petróleo/microbiología , Filogenia , Piscirickettsiaceae/genética , Selección Genética , Secuencia de Bases , Análisis por Conglomerados , ADN Ribosómico/genética , Desastres , Japón , Microscopía Fluorescente , Técnicas de Sonda Molecular , Datos de Secuencia Molecular , Dinámica Poblacional , Análisis de Secuencia de ADN , Navíos
9.
Osteoporos Int ; 13(8): 650-6, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12181624

RESUMEN

Despite an intriguing understanding of trabecular bone dynamics, little is known about corticosteroid-induced cortical bone loss and fractures. Recently, we verified a steroid-induced decrease in cortical bone volume and density using peripheral quantitative computed tomography (pQCT) in adult asthmatic patients given oral corticosteroids. Subsequently, the pQCT parameters and presence of vertebral fractures were investigated to further clarify the role of cortical bone quality in fractures in 86 postmenopausal (>5 years after menopause) asthmatic patients on high-dose oral steroid (>10 g cumulative oral prednisolone) (steroid group) and 194 age-matched controls (control group). Cortical and trabecular bone was subjected to measurement of various parameters using pQCT (Stratec XCT960). Relative Cortical Volume (RCV) was calculated by dividing the cortical area by the total bone area. Strength Strain Index (SSI) was determined in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. Patients treated with high doses of oral steroid (>10 g cumulative oral prednisolone) were found to have an increased risk of fracture compared with control women receiving no steroid medication (odds ratio, 8.85; 95% CI, 4.21-18.60) after adjustment was made for years since menopause, body mass index and RCV. In both groups, the diagnostic and predictive ability of the pQCT parameters for vertebral fracture was assessed by the areas under their receiver operating characteristic (ROC) curves. All parameters were found to be significant predictors ( p<0.0001) in the control group. In the steroid group, however, the cortical bone mineral density (BMD) ( p = 0.001), RCV ( p<0.0001) and SSI ( p = 0.001) were found to be significant predictors, but not trabecular BMD ( p = 0.176). For comparison between the two groups, thresholds of all parameters for vertebral fracture were also calculated by the point of coincidence of sensitivity with specificity in ROC testing and the 90th percentile value. Although a rise in fracture threshold in the steroid group was suggested, considerable difference in the values obtained by the two methods of calculation precluded any conclusion. High-dose oral steroid administration was associated with an increased risk of fracture. Cortical bone parameters obtained by pQCT could play a role as good predictors of future corticosteroid-induced vertebral fractures.


Asunto(s)
Antiasmáticos/efectos adversos , Asma/tratamiento farmacológico , Huesos/efectos de los fármacos , Osteoporosis/inducido químicamente , Prednisolona/efectos adversos , Fracturas de la Columna Vertebral/etiología , Administración Oral , Anciano , Beclometasona/efectos adversos , Densidad Ósea/efectos de los fármacos , Huesos/fisiología , Estudios Epidemiológicos , Femenino , Humanos , Osteoporosis/complicaciones , Radio (Anatomía)/efectos de los fármacos , Radio (Anatomía)/fisiología , Factores de Riesgo , Tomografía Computarizada por Rayos X/métodos
10.
Biosci Biotechnol Biochem ; 65(4): 947-9, 2001 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-11388478

RESUMEN

Five bufadienolides (1-5) isolated from the leaves of Kalanchoe pinnata and K. daigremontiana x tubiflora (Crassulaceae) were examined for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation in Raji cells induced by the tumor promoter, 12-O-tetradecanoylphorbol-13-acetate. All bufadienolides showed inhibitory activity, and bryophyllin A (1) exhibited the most marked inhibition (IC50 = 0.4 microM) among the tested compounds. Bryophyllin C (2), a reduction analogue of 1, and bersaldegenin-3-acetate (3) lacking the orthoacetate moiety were less active. These results strongly suggest that bufadienolides are potential cancer chemopreventive agents.


Asunto(s)
Anticarcinógenos/farmacología , Antineoplásicos Fitogénicos/farmacología , Bufanólidos/farmacología , Plantas Medicinales/química , Animales , Antígenos Virales/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Herpesvirus Humano 4/genética , Hojas de la Planta/química , Células Tumorales Cultivadas
11.
Osteoporos Int ; 12(4): 266-70, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11420775

RESUMEN

Despite a deepening understanding of the influence of glucocorticoids (GC) on trabecular bone, little is known about GC-induced cortical bone loss. To elucidate the mechanism of GC-induced loss of cortical bone strength with particular reference to cortical bone loss, changes in cortical density, relative cortical volume, and the Strength Strain Index (SSI) based on biomechanical analyses of the geographic distribution of cortical bone material were measured. These parameters were compared, using peripheral quantitative computed tomography (pQCT), among the following age-matched groups: 68 postmenopausal asthmatic patients receiving high-dose oral GC in addition to inhaled GC (oral GC group), 68 postmenopausal asthmatic patients receiving only inhaled GC (inhaled GC group) and 69 postmenopausal controls without asthma or GC therapy (control group). Cortical bone mineral density (BMD) was measured, relative cortical volume was obtained by dividing the cortical area by the total bone area using pQCT (Stratec XCT960), and the Strength Strain Index (SSI) was calculated in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. The number of vertebral fractures per patient correlated highly with cortical BMD, relative cortical volume and SSI values at the radius. The number of vertebral fractures per patient and the number of patients with fracture were similar between the control and inhaled GC group, both being significantly lower than those in the oral GC group. Total BMD, trabecular BMD, cortical BMD, relative cortical volume and SSI were similar between the first two, being significantly higher than in the last group. The slopes of cortical volume-density relationship, however, were identical among the three groups, indicating the persistence of cortical bone remodeling and a similar degree of calcification regardless of GC administration.


Asunto(s)
Antiasmáticos/efectos adversos , Asma/tratamiento farmacológico , Glucocorticoides/efectos adversos , Osteoporosis Posmenopáusica/inducido químicamente , Administración por Inhalación , Administración Oral , Anciano , Fenómenos Biomecánicos , Densidad Ósea/efectos de los fármacos , Femenino , Humanos , Persona de Mediana Edad , Osteoporosis Posmenopáusica/diagnóstico por imagen , Osteoporosis Posmenopáusica/fisiopatología , Radio (Anatomía)/patología , Radio (Anatomía)/fisiopatología , Fracturas de la Columna Vertebral/inducido químicamente , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/fisiopatología , Tomografía Computarizada por Rayos X
12.
Proc Natl Acad Sci U S A ; 98(11): 6500-5, 2001 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-11344269

RESUMEN

Tumor-induced osteomalacia (TIO) is one of the paraneoplastic diseases characterized by hypophosphatemia caused by renal phosphate wasting. Because removal of responsible tumors normalizes phosphate metabolism, an unidentified humoral phosphaturic factor is believed to be responsible for this syndrome. To identify the causative factor of TIO, we obtained cDNA clones that were abundantly expressed only in a tumor causing TIO and constructed tumor-specific cDNA contigs. Based on the sequence of one major contig, we cloned 2,270-bp cDNA, which turned out to encode fibroblast growth factor 23 (FGF23). Administration of recombinant FGF23 decreased serum phosphate in mice within 12 h. When Chinese hamster ovary cells stably expressing FGF23 were s.c. implanted into nude mice, hypophosphatemia with increased renal phosphate clearance was observed. In addition, a high level of serum alkaline phosphatase, low 1,25-dihydroxyvitamin D, deformity of bone, and impairment of body weight gain became evident. Histological examination showed marked increase of osteoid and widening of growth plate. Thus, continuous production of FGF23 reproduced clinical, biochemical, and histological features of TIO in vivo. Analyses for recombinant FGF23 products produced by Chinese hamster ovary cells indicated proteolytic cleavage of FGF23 at the RXXR motif. Recent genetic study indicates that missense mutations in this RXXR motif of FGF23 are responsible for autosomal dominant hypophosphatemic rickets, another hypophosphatemic disease with similar features to TIO. We conclude that overproduction of FGF23 causes TIO, whereas mutations in the FGF23 gene result in autosomal dominant hypophosphatemic rickets possibly by preventing proteolytic cleavage and enhancing biological activity of FGF23.


Asunto(s)
Factores de Crecimiento de Fibroblastos/fisiología , Hemangiopericitoma/complicaciones , Osteomalacia/etiología , Alanina/metabolismo , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Transporte Biológico , Células CHO , Clonación Molecular , Cricetinae , ADN Complementario , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/administración & dosificación , Factores de Crecimiento de Fibroblastos/efectos adversos , Factores de Crecimiento de Fibroblastos/genética , Expresión Génica , Glucosa/metabolismo , Humanos , Hipofosfatemia/etiología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Datos de Secuencia Molecular , Osteomalacia/metabolismo , Osteomalacia/patología , Fosfatos/metabolismo , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/fisiología
13.
Biochem Biophys Res Commun ; 280(1): 348-52, 2001 Jan 12.
Artículo en Inglés | MEDLINE | ID: mdl-11162521

RESUMEN

Inorganic phosphate (Pi) supplement is generally used to accelerate mineralization of cultured bone cells but the mechanism of action is totally unknown. How the action is related with the transactivation of Runx2/Cbfa1,a master gene product of bone formation,was examined. Clonal bone cells (osteoblastic MC3T3-E1, chondrocytic ATDC5 and osteocytic MLO-Y4) on preculture in ascorbate-containing medium constantly expressed and accumulated Cbfa1 in the nuclei, and subsequent increase of Pi concentration to 3 or 10 mM was found to invariably induce nuclear export (not import) of Cbfa1 which was completed in a few hours. In addition, Pi was found to lower the expression of osteocalcin. Leptomycin B completely inhibited Pi-induced nuclear export, suggesting that CRM1/exportin 1 is involved in Pi-induced nuclear export. The result suggests that bone cells are equipped with a novel Pi sensing mechanism which is functionally linked to a nuclear export system of Cbfa1.


Asunto(s)
Núcleo Celular/metabolismo , Carioferinas , Proteínas de Neoplasias , Osteoblastos/fisiología , Osteocitos/fisiología , Osteogénesis/fisiología , Fosfatos/metabolismo , Receptores Citoplasmáticos y Nucleares , Transducción de Señal/fisiología , Factores de Transcripción/metabolismo , Células 3T3 , Animales , Proteínas Portadoras/metabolismo , Núcleo Celular/efectos de los fármacos , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Ácidos Grasos Insaturados/farmacología , Cinética , Ratones , Proteínas Nucleares/metabolismo , Osteoblastos/citología , Osteocitos/citología , Transporte de Proteínas/efectos de los fármacos , Proteína Exportina 1
14.
Arerugi ; 50(12): 1136-42, 2001 Dec.
Artículo en Japonés | MEDLINE | ID: mdl-11830997

RESUMEN

Special apparatus capable of instantly measuring airborne Cryptomeria japonica pollen grains were recently appeared on the market. We examined one of them called real-time pollen monitor KH-3000 (Yamato Manufacturing Co. Ltd.). To confirm the accuracy of the monitor, comparison was made with conventional Burkard Seven-Day Recording Volumetric Spore Trap operating simultaneously at the same place. Most peaks from KH-3000 were coincided with Cry j 1 from Burkard sampler, and the greater part of the counts from KH-3000 had a strong resemblance to the counts from Cry j 1. Therefore, it is confirmed that KH-3000 counts the numbers of airborne C. japonica pollen grains. KH-3000 sometimes counts particles which do not belong to pollen grains, however. It is also confirmed that some pollens other than C. japonica, such as walnut (Juglans spp.) pollen, a part of grass pollen were counted.


Asunto(s)
Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente/instrumentación , Monitoreo del Ambiente/normas , Polen
15.
Biosci Biotechnol Biochem ; 64(6): 1310-2, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10923811

RESUMEN

Two insecticidal bufadienolides (1 and 2) were isolated from a methanol extract of the leaves of Kalanchoe pinnata by bioassay-guided fractionation. Compound 1 was identified as known bryophyllin A (bryotoxin C). The structure of new bufadienolide 2, named bryophyllin C, was determined by spectroscopic methods and the chemical transformation of 1. Compounds 1 and 2 showed strong insecticidal activity against third instar larvae of the silkworm (Bombyx mori), their LD50 values being evaluated as 3 and 5 microg/g of diet, respectively.


Asunto(s)
Bufanólidos/química , Bufanólidos/aislamiento & purificación , Colenos/química , Colenos/aislamiento & purificación , Insecticidas/química , Insecticidas/aislamiento & purificación , Plantas Medicinales/química , Animales , Bombyx , Bufanólidos/farmacología , Colenos/farmacología , Insecticidas/farmacología , Dosificación Letal Mediana , Espectroscopía de Resonancia Magnética , Estructura Molecular
16.
J Med Chem ; 43(15): 2946-61, 2000 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-10956203

RESUMEN

A series of 2-substituted 2-aminopropane-1,3-diols was synthesized and evaluated for their lymphocyte-decreasing effect and immunosuppressive effect on rat skin allograft. A phenyl ring was introduced into the alkyl chain of the lead compound 3, which is an immunosuppressive agent structurally simplified from myriocin (1, ISP-I) via compound 2. The potency of the various compounds was dependent upon the position of the phenyl ring within the alkyl side chain. The most suitable length between the quaternary carbon atom and the phenyl ring was two carbon atoms. 2-Substituted 2-aminoethanols were successively synthesized and evaluated for their T-cell-decreasing effect and immunosuppressive effect using a popliteal lymph node gain assay in rats. The absolute configuration at the quaternary carbon affected the activity, and the (pro-S)-hydroxymethyl group of compound 6 was essential for potent immunosuppressive activity. Favorable substituents for the (pro-R)-hydroxymethyl group of 6 were hydroxyalkyl (hydroxyethyl and hydroxypropyl) or lower alkyl (methyl and ethyl) groups. 2-Amino-2-[2-(4-octylphenyl)ethyl]propane-1,3-diol hydrochloride (6, FTY720) was found to possess considerable activity and is expected to be useful as an immunosuppressive drug for organ transplantation.


Asunto(s)
Inmunosupresores/síntesis química , Glicoles de Propileno/síntesis química , Animales , Evaluación Preclínica de Medicamentos , Clorhidrato de Fingolimod , Rechazo de Injerto/prevención & control , Inmunosupresores/química , Inmunosupresores/farmacología , Concentración 50 Inhibidora , Ganglios Linfáticos/efectos de los fármacos , Tamaño de los Órganos , Glicoles de Propileno/química , Glicoles de Propileno/farmacología , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas Lew , Trasplante de Piel , Esfingosina/análogos & derivados , Estereoisomerismo , Relación Estructura-Actividad , Linfocitos T/citología , Linfocitos T/efectos de los fármacos
17.
J Med Chem ; 43(16): 3052-66, 2000 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-10956213

RESUMEN

A series of imidazopyridine thiazolidine-2,4-diones were designed and synthesized from their corresponding pyridines. These compounds represent conformationally restricted analogues of the novel hypoglycemic compound rosiglitazone (5). The series was evaluated for its effect on insulin-induced 3T3-L1 adipocyte differentiation in vitro and its hypoglycemic activity in the genetically diabetic KK mouse in vivo. The structure-activity relationships are discussed. On the basis of the in vivo potency, 5-[4-(5-methoxy-3-methyl-3H-imidazo[4, 5-b]pyridin-2-ylmethoxy)benzyl]thiazolidine-2,4-dione (19a) was selected as the candidate for further studies in a clinical setting.


Asunto(s)
Hipoglucemiantes/síntesis química , Imidazoles/síntesis química , Tiazoles/síntesis química , Tiazolidinedionas , Células 3T3 , Adipocitos/citología , Adipocitos/efectos de los fármacos , Animales , Disponibilidad Biológica , Diferenciación Celular , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/genética , Diseño de Fármacos , Evaluación Preclínica de Medicamentos , Corazón/efectos de los fármacos , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Hipoglucemiantes/toxicidad , Imidazoles/química , Imidazoles/farmacología , Imidazoles/toxicidad , Masculino , Ratones , Tamaño de los Órganos , Ratas , Rosiglitazona , Relación Estructura-Actividad , Tiazoles/química , Tiazoles/farmacología , Tiazoles/toxicidad
18.
J Ethnopharmacol ; 70(3): 219-26, 2000 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-10837986

RESUMEN

Flowers of Spartium junceum L. (Fabaceae) are used for the treatment of gastric ulcers in Turkish folk medicine. Through bioassay-guided fractionation using chemical and chromatographical means and water immersion and restraint-induced stress ulcer model in rats, a saponin fraction was determined as the potent anti-ulcerogenic ingredient. The active fraction was also highly effective in preventing ethanol- and pyloric ligation-induced gastric lesions as well as inhibiting gastric secretion volume, gastric pH and titratable acidity, but did not affect the hexosamine content of the gastric mucosa. A novel oleanen-type triterpenic saponin, named as spartitrioside, was isolated as the active principle by using chromatographical separation techniques.


Asunto(s)
Antiulcerosos/farmacología , Plantas Medicinales/química , Úlcera Gástrica/prevención & control , Animales , Depresores del Sistema Nervioso Central , Etanol , Ácido Gástrico/química , Mucosa Gástrica/efectos de los fármacos , Mucosa Gástrica/metabolismo , Inmersión , Ligadura , Masculino , Extractos Vegetales/química , Píloro , Ratas , Ratas Wistar , Restricción Física , Saponinas/aislamiento & purificación , Saponinas/farmacología , Úlcera Gástrica/inducido químicamente , Úlcera Gástrica/etiología , Estrés Psicológico/complicaciones , Turquía
19.
Hypertens Res ; 23(3): 195-200, 2000 May.
Artículo en Inglés | MEDLINE | ID: mdl-10821126

RESUMEN

Several dietary factors have been shown to lower blood pressure in elderly patients in clinical trials, but it is not known how eating habits affect blood pressure control in outpatients treated with antihypertensive drugs. We obtained data on dietary information regarding food groups rich in potassium, magnesium, and calcium by submitting a questionnaire to 190 elderly outpatients. Blood pressure levels and the intensity and cost of antihypertensive treatment were obtained from clinical records. The mean age and blood pressure were 72.3 +/- 9.3 years and 138.7 +/- 15.2/74.6 +/- 8.8 mmHg, respectively. Patients were divided into three groups on the basis of the intensity of medication: the LS group (n=52), treated with a low dose of a single drug; the HS group (n=95), treated with a high dose of a single drug; and the M group (n=43), treated with multiple drugs. Average age, body mass index, blood pressure levels, and extent of target organ damage were similar among the three groups. Intake frequency (rarely, once or twice per week, 3 to 6 times per week, or every day) of the food groups was compared among the three groups. The LS group ate fruit (p < 0.05) and seaweed (p < 0.01) with significant frequency compared with the other groups, whereas milk and dairy products were taken with similar frequency by all groups. The monthly cost of antihypertensive medications averaged 17,218 +/- 620 yen in the LS group, 17,746 +/- 375 yen in the HS group, and 20,066 +/- 1,364 yen in the M group. These data suggest that habitual intake of foods rich in potassium and magnesium are associated with reduced intensity and cost of medication and with preservation of blood pressure control in elderly hypertensive outpatients.


Asunto(s)
Antihipertensivos/administración & dosificación , Conducta Alimentaria , Hipertensión/dietoterapia , Hipertensión/tratamiento farmacológico , Anciano , Presión Sanguínea , Calcio/administración & dosificación , Dieta , Femenino , Conductas Relacionadas con la Salud , Humanos , Hipertensión/psicología , Estilo de Vida , Magnesio/administración & dosificación , Masculino , Persona de Mediana Edad , Pacientes Ambulatorios/psicología , Potasio/administración & dosificación , Cloruro de Sodio Dietético/administración & dosificación , Encuestas y Cuestionarios
20.
J Psychosom Res ; 48(2): 161-9, 2000 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-10719133

RESUMEN

OBJECTIVE: The objective of the study was to compare blood pressure (BP) biofeedback treatment (BF) effects between white-coat hypertension and essential hypertension. METHODS: Fifteen white-coat hypertensive out-patients and 23 essential hypertensive out-patients were randomly assigned to groups A or B. Subjects in group A underwent BF once a week for a total of four sessions. Those in group B visited the clinic only to measure BP and later underwent the same BF. RESULTS: In group A, BPs of white-coat hypertensives and essential hypertensives were significantly reduced by 22/11 and 14/8 mmHg, respectively. In group B, they were unchanged during the same period but later suppressed by BF. Under BF, pulse and respiratory rates were significantly higher, and elevation of diastolic BP due to mental stress testing was better suppressed in white-coat hypertensives than in essential hypertensives. CONCLUSION: This treatment was effective in both types of hypertension, and pressor response to stress seems to be important in the differentiated BF effect.


Asunto(s)
Biorretroalimentación Psicológica , Hipertensión/fisiopatología , Hipertensión/terapia , Estrés Psicológico/fisiopatología , Electroencefalografía , Femenino , Respuesta Galvánica de la Piel , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad
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