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1.
Molecules ; 26(20)2021 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-34684790

RESUMEN

In this study, hydrogen boride films are fabricated by ion-exchange treatment on magnesium diboride (MgB2) films under ambient temperature and pressure. We prepared oriented MgB2 films on strontium titanate (SrTiO3) substrates using pulsed laser deposition (PLD). Subsequently, these films were treated with ion exchangers in acetonitrile solution. TOF-SIMS analysis evidenced that hydrogen species were introduced into the MgB2 films by using two types of ion exchangers: proton exchange resin and formic acid. According to the HAXPES analysis, negatively charged boron species were preserved in the films after the ion-exchange treatment. In addition, the FT-IR analysis suggested that B-H bonds were formed in the MgB2 films following the ion-exchange treatment. The ion-exchange treatment using formic acid was more efficient compared to the resin treatment; with respect to the amount of hydrogen species introduced into the MgB2 films. These ion-exchanged films exhibited photoinduced hydrogen release as observed in a powder sample. Based on the present study, we expect to be able to control the morphology and hydrogen content of hydrogen boride thin films by optimising the ion-exchange treatment process, which will be useful for further studies and device applications.

2.
J Chem Phys ; 152(23): 231101, 2020 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-32571043

RESUMEN

Light irradiation onto a semiconductor generates heat; however, its electronic structure under high temperature has not yet been well investigated. In this study, we have carefully examined the temperature dependence on the bandgap of simple metal oxides, which are well-known photocatalysts, i.e., TiO2, CeO2, Nb2O5, SnO2 Ta2O5, WO3, ZnO, and ZrO2, using operando UV-visible spectroscopy under controlled temperature (from room temperature to 500 °C). Consequently, a linear decrease in bandgap was seen as a function of temperature with a different slope for each semiconductor. We found that the slope was dependent on the bonding distance between metal and oxygen. This finding is essential to develop a photocatalyst used under the condition involving photo-thermal effect.

3.
Phys Rev Lett ; 123(11): 113201, 2019 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-31573273

RESUMEN

We experimentally and theoretically determine the magic wavelength of the (5s^{2})^{1}S_{0}-(5s5p)^{3}P_{0} clock transition of ^{111}Cd to be 419.88(14) and 420.1(7) nm. To perform Lamb-Dicke spectroscopy of the clock transition, we use narrow-line laser cooling on the ^{1}S_{0}-^{3}P_{1} transition to cool the atoms to 6 µK and load them into an optical lattice. Cadmium is an attractive candidate for optical lattice clocks because it has a small sensitivity to blackbody radiation and its efficient narrow-line cooling mitigates higher order light shifts. We calculate the blackbody shift, including the dynamic correction, to be fractionally 2.83(8)×10^{-16} at 300 K, an order of magnitude smaller than that of Sr and Yb. We also report calculations of the Cd ^{1}P_{1} lifetime and the ground state C_{6} coefficient.

4.
Phys Rev Lett ; 123(22): 222501, 2019 Nov 29.
Artículo en Inglés | MEDLINE | ID: mdl-31868403

RESUMEN

The low-lying isomeric state of ^{229}Th provides unique opportunities for high-resolution laser spectroscopy of the atomic nucleus. We determine the energy of this isomeric state by taking the absolute energy difference between the excitation energy required to populate the 29.2-keV state from the ground state and the energy emitted in its decay to the isomeric excited state. A transition-edge sensor microcalorimeter was used to measure the absolute energy of the 29.2-keV γ ray. Together with the cross-band transition energy (29.2 keV→ground) and the branching ratio of the 29.2-keV state measured in a recent study, the isomer energy was determined to be 8.30±0.92 eV. Our result is in agreement with the latest measurements based on different experimental techniques, which further confirms that the isomeric state of ^{229}Th is in the laser-accessible vacuum ultraviolet range.

5.
Phys Rev Lett ; 114(10): 105304, 2015 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-25815943

RESUMEN

The transverse acoustic impedance of superfluid ^{3}He was measured in the A1 and A2 phases up to 13 T to investigate the surface states in nonunitary superfluids. The temperature dependence of the impedance was much larger in the A1 phase than in the A2 phase. This nonsymmetric behavior indicates that momentum exchange with walls for spin-down surface states is quite different from that for spin-up surface states. The spin-dependent response might be a reflection of an essential feature of the nonunitary states where gap amplitudes depend on spin states. Weak-coupling theories ignore any spin-dependent processes and do not account for the nonsymmetric behavior.

6.
Inorg Chem ; 53(12): 5878-80, 2014 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-24853637

RESUMEN

Learning from serendipitous assembly, we have prepared a new family of designed 3d-4f Mn6Ln complexes. The dynamics of relaxation of the magnetization via alternating-current magnetic susceptibility for the new Mn6Ln complexes 1 (Ln = La), 2 (Ln = Tb), and 4 (Ln = Dy) have been studied down to 0.2 K.

7.
Sarcoidosis Vasc Diffuse Lung Dis ; 30(1): 43-51, 2013 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24003534

RESUMEN

BACKGROUND: The serum Krebs von der Lungen-6 (KL-6) level is a useful marker correlated with the severity of various interstitial lung diseases. There have been few reports about the clinical characteristics of organizing pneumonia (OP) associated with the serum KL-6 levels. OBJECTIVE: This study was performed to determine whether the serum KL-6 levels can help determine the optimal treatment for OP. DESIGNS: Patients diagnosed with OP by clinical, radiological and histopathological findings were retrospectively reviewed. The OP patients were classified into two groups based on their serum KL-6 levels: normal KL-6 and high KL-6 groups. The two groups were compared with regard to their clinical and radiological data and therapeutic response one month after the start of treatment. RESULTS: The clinical records of twenty-two patients diagnosed with OP were reviewed. The serum KL-6 level was elevated in 11 of the 22 patients. There were no obvious differences in the clinical data between the two groups, although patients in the normal KL-6 group tended to have a fever. There were no significant differences in the chest X-ray (CXR) score or computed tomography (CT) score between the two groups. The CXR scores were correlated with the serum KL-6 levels. At 1 month after the diagnosis, 11 patients who needed treatment with prednisolone were included in the high KL-6 group. CONCLUSIONS: Patients with normal KL-6 levels showed lower CXR and CT scores. The serum KL-6 level on admission is a useful marker to judge the need for corticosteroid treatment in OP patients.


Asunto(s)
Biomarcadores/sangre , Neumonía en Organización Criptogénica/sangre , Mucina-1/sangre , Corticoesteroides/uso terapéutico , Broncoscopía , Neumonía en Organización Criptogénica/diagnóstico , Neumonía en Organización Criptogénica/diagnóstico por imagen , Neumonía en Organización Criptogénica/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía Computarizada por Rayos X
8.
J Intellect Disabil Res ; 57(1): 67-79, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-22233468

RESUMEN

BACKGROUND: The ventral and dorsal streams are considered to be the brain substrates of vision for perception and action, respectively. Using the Developmental Test of Visual Perception (DTVP), the current study examined whether visual perceptual strengths and weaknesses in adults with intellectual disabilities (ID) were attributable to the dichotomy of the visual streams. METHOD: In study 1, DTVP performance was compared among mild, moderate and severe adult ID groups; study 2 contrasted adult ID groups with and without Down syndrome (DS). To prevent possible contamination by the Flynn effect, participants were matched by birth year with the norm of the DTVP original edition. RESULTS: Independent of the extent of ID among the three groups in study 1 and the aetiological group difference in study 2, relative strength was found for two DTVP tasks: eye-hand coordination and distinguishing target figures from interference background. Relative weakness was obtained in identifying a figural category. Participants with DS demonstrated exceptional weakness in discerning a target from either mirror-imaged or rotated alternatives, in addition to figural-category detection. CONCLUSIONS: Visual perceptual strengths and weaknesses in persons with ID were difficult to explain on the basis of two visual streams. An interpretation originating in a different research context (e.g. frontal-lobe dysfunction) appears to be required for explaining visual perceptual weaknesses in persons with ID. For persons with DS, strong frontal-lobe dysfunction with atypical lateralisation might be the pathological determinant of visual perceptual weaknesses.


Asunto(s)
Síndrome de Down/fisiopatología , Lóbulo Frontal/fisiología , Discapacidad Intelectual/fisiopatología , Trastornos de la Visión/diagnóstico , Percepción Visual/fisiología , Adulto , Estudios de Casos y Controles , Síndrome de Down/complicaciones , Femenino , Desarrollo Humano/fisiología , Humanos , Discapacidad Intelectual/complicaciones , Masculino , Análisis por Apareamiento , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Trastornos de la Visión/complicaciones , Vías Visuales/fisiología , Adulto Joven
9.
Mol Pharm ; 9(6): 1681-92, 2012 Jun 04.
Artículo en Inglés | MEDLINE | ID: mdl-22519912

RESUMEN

The aim of the present study is to synthesize new mannosylated dextran derivative that can be labeled with Tc-99m for potential use in sentinel lymph node detection (SLND). The compound was designed to have a dextran with molecular weight of 10 kDa as a backbone, mannose for binding to mannose receptors of the lymph node and S-derivatized cysteine as a suitable chelator for labeling with [(99m)Tc(H(2)O)(3)(CO)(3)](+) precursor. Reaction of allyl bromide with dextran (MW 11800) yielded the intermediate allyl-dextran (1) with about 40% coupling. Addition of cysteine to allyl-dextran resulted in the S-derivatized cysteine, compound DC15 (2). The final product DCM20 (3) was obtained in good yield after in situ hydrolysis and activation of cyanomethyl tetraacetyl-1-thio-d-mannopyranoside and coupling to DC15. All derivatives were purified by ultrafiltration and characterized by NMR. DC15 and DCM20 were quantitatively labeled with (99m)Tc (>95% radiochemical purity) using the fac-[(99m)Tc(OH(2))(3)(CO)(3)](+) precursor and ligand concentration of 1.5 × 10(-6) M at neutral pH. Both (99m)Tc-labeled compounds (99m)Tc(CO)(3)-DC15 (6) and (99m)Tc(CO)(3)-DCM20 (7) remained stable after 6 h incubation at 37 °C in the presence of excess histidine or cysteine, as well as even after 20-fold dilution and incubation for 24 h at room temperature. The characterization of the compounds 6 and 7 was performed by comparing their HPLC radiochromatograms with those of their rhenium surrogates Re(CO)(3)-DC15 (4) and Re(CO)(3)-DCM20 (5) respectively that were prepared using the precursor [NEt(4)](2)fac-[ReBr(3)(CO)(3)] and characterized by IR and NMR spectroscopy. When injected subcutaneously from the foot pad of mice, (99m)Tc-labeled mannosylated dextran (7) showed accumulation in the popliteal lymph node (SLN in this model) higher than that of non-mannosylated analogue (6) and the (99m)Tc-phytate serving as standard. Compound 7 also exhibited lower radioactivity levels at the injection site compared to (99m)Tc-phytate. The SPECT/CT studies in mice confirmed that 7 accumulated in the popliteal lymph node allowing its clear visualization. The present findings demonstrate that compound 7 ((99m)Tc(CO)(3)-DCM20) is promising and merits further evaluation as a radiopharmaceutical for sentinel lymph node detection.


Asunto(s)
Quelantes/química , Quelantes/síntesis química , Dextranos/química , Dextranos/síntesis química , Ganglios Linfáticos/metabolismo , Manosa/química , Compuestos de Organotecnecio/química , Animales , Humanos , Masculino , Ratones , Imagen Multimodal , Tomografía de Emisión de Positrones , Biopsia del Ganglio Linfático Centinela/métodos , Tomografía Computarizada por Rayos X
10.
Nature ; 444(7121): 909-12, 2006 Dec 14.
Artículo en Inglés | MEDLINE | ID: mdl-17167481

RESUMEN

The magnetic properties of (3)He in its various phases originate from the interactions among the nuclear spins. The spin-polarized 'ferromagnetic' superfluid (3)He A(1) phase (which forms below 3 mK between two transition temperatures, T(c1) and T(c2), in an external magnetic field) serves as a material in which theories of fundamental magnetic processes and macroscopic quantum spin phenomena may be tested. Conventionally, the superfluid component of the A(1) phase is understood to contain only the majority spin condensate, having energetically favoured paired spins directed along the external field and no minority spin condensate having paired spins in the opposite direction. Because of difficulties in satisfying both the ultralow temperature and high magnetic field required to produce a substantial phase space, there exist few studies of spin dynamics phenomena that could be used to test the conventional view of the A(1) phase. Here we develop a mechanical spin density detector that operates in the required regime, enabling us to perform measurements of spin relaxation in the A(1) phase as a function of temperature, pressure and magnetic field. Our mechanical spin detector is based in principle on the magnetic fountain effect; spin-polarized superfluid motion can be induced both magnetically and mechanically, and we demonstrate the feasibility of increasing spin polarization by a mechanical spin filtering process. In the high temperature range of the A(1) phase near T(c1), the measured spin relaxation time is long, as expected. Unexpectedly, the spin relaxation rate increases rapidly as the temperature is decreased towards T(c2). Our measurements, together with Leggett-Takagi theory, demonstrate that a minute presence of minority spin pairs is responsible for this unexpected spin relaxation behaviour. Thus, the long-held conventional view that the A(1) phase contains only the majority spin condensate is inadequate.

11.
Lupus ; 20(12): 1231-9, 2011 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-21980035

RESUMEN

Changes in gene expression in CD3+ T cells associated with disease progression in systemic lupus erythematosus (SLE) patients were determined. The genes related to SLE disease-related activities were identified and their gene regulatory networks were investigated. Analyses of gene expression were performed by both DNA microarray and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). The expression of certain genes including interferon (IFN) regulatory factor (IRF)-related genes, such as IFN-regulated, -related, and -signature genes was increased in the active phase of SLE. Pathway network analyses suggested that these IRF-related genes are regulated through the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. JAK/STAT pathway-mediated regulation of IRF-related genes may have an important role in the disease activity of SLE. Inhibitors of JAK/STAT cascade may be useful as therapeutic agents.


Asunto(s)
Factores Reguladores del Interferón/genética , Quinasas Janus/genética , Quinasas Janus/metabolismo , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/metabolismo , Factores de Transcripción STAT/genética , Factores de Transcripción STAT/metabolismo , Adulto , Anciano , Secuencia de Bases , Cartilla de ADN/genética , Femenino , Regulación de la Expresión Génica , Humanos , Lupus Eritematoso Sistémico/inmunología , Persona de Mediana Edad , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal/genética , Linfocitos T/inmunología , Adulto Joven
12.
Nat Med ; 7(3): 317-23, 2001 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-11231630

RESUMEN

Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum-associated chaperone induced by hypoxia/ischemia. Although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant to hypoxemic stress, whereas astrocytes with inhibited ORP150 expression were more vulnerable. Mice with targeted neuronal overexpression of ORP150 had smaller strokes compared with controls. Neurons with increased ORP150 demonstrated suppressed caspase-3-like activity and enhanced brain-derived neurotrophic factor (BDNF) under hypoxia signaling. These data indicate that ORP150 is an integral participant in ischemic cytoprotective pathways.


Asunto(s)
Muerte Celular/fisiología , Hipoxia de la Célula , Neuronas/patología , Proteínas/fisiología , Animales , Encéfalo/citología , Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Proteínas HSP70 de Choque Térmico , Humanos , Ratones , Neuronas/metabolismo , Proteínas/antagonistas & inhibidores
14.
Int J Clin Pharmacol Ther ; 48(11): 708-17, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20979929

RESUMEN

OBJECTIVE: To investigate potential differences in zibotentan pharmacokinetics between Japanese and Caucasian patients with hormone-resistant prostate cancer (HRPC) following single and multiple dosing. METHODS: In the Japanese study, 18 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 26 days' once-daily dosing. In the Caucasian study, 21 patients received a single dose of zibotentan 5, 10 or 15 mg followed by 72 h washout before 12 days' once-daily dosing. RESULTS: Pharmacokinetic parameters were similar between populations. Absorption of zibotentan was rapid with maximum plasma concentrations typically achieved within 3 h of dosing. Mean clearance, 17.9 and 18.7 ml/min in Japanese and Caucasian patients, respectively (range 7.0 - 36.3 ml/min in Japanese patients and 7.8 - 29.5 ml/min in Caucasian patients) and volume of distribution, 14.0 and 15.6 l for Japanese and Caucasian patients, respectively (range 7.9 - 29.1 l in Japanese patients and 9.6 - 23.8 l in Caucasian patients) were relatively low, and t1/2 was approximately 12 h (range 5.7 - 18.8 h in Japanese patients and 5.0 - 22.9 h in Caucasian patients) following single dosing. Little accumulation was observed following daily dosing and multiple-dose pharmacokinetics were predictable. Exposure levels achieved in some Japanese patients receiving zibotentan 15 mg were higher than those observed in Caucasian patients, however, this may be due to differences in body weight, as exposure levels were similar when data were normalized for body weight. Zibotentan was well tolerated in both populations. CONCLUSIONS: There are no clinically relevant differences in the disposition and pharmacokinetics of zibotentan between Japanese and Caucasian patients with HRPC.


Asunto(s)
Antineoplásicos/farmacocinética , Neoplasias de la Próstata/tratamiento farmacológico , Pirrolidinas/farmacocinética , Anciano , Anciano de 80 o más Años , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Pueblo Asiatico , Peso Corporal , Relación Dosis-Respuesta a Droga , Antagonistas de los Receptores de la Endotelina A , Semivida , Humanos , Japón , Masculino , Persona de Mediana Edad , Neoplasias de la Próstata/patología , Pirrolidinas/administración & dosificación , Pirrolidinas/efectos adversos , Distribución Tisular , Población Blanca
15.
Kyobu Geka ; 63(12): 1049-52, 2010 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-21066846

RESUMEN

A 53-year-old man with Marfan's syndrome was admitted for repair of annulo-aortic ectasia (58 mm). He had also severe pectus excavatum. The skin was incised along the sternal midline. The pectoral muscles were detached laterally. After the perichondrium and costal cartilages were resected bilaterally. the left-sided intercostal muscles and perichondrial sheaths were divided 3 cm lateral to the sternum. To place the retractor in parasternal position, excellent exposure of the heart and aortic root was enabled. The aortic root was replaced with a Carboseal graft. Chest wall reconstructions was completed by modified Ravitch procedure with Gore-tex sheet The patient was discharged after an uneventful recovery on postoperative day 14.


Asunto(s)
Aorta/cirugía , Tórax en Embudo/cirugía , Síndrome de Marfan/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Músculos Pectorales/cirugía
16.
J Cell Biol ; 147(6): 1195-204, 1999 Dec 13.
Artículo en Inglés | MEDLINE | ID: mdl-10601334

RESUMEN

Application of differential display to cultured rat astrocytes subjected to hypoxia allowed cloning of a novel cDNA, termed stress-associated endoplasmic reticulum protein 1 (SERP1). Expression of SERP1 was enhanced in vitro by hypoxia and/or reoxygenation or other forms of stress, causing accumulation of unfolded proteins in endoplasmic reticulum (ER) stress, and in vivo by middle cerebral artery occlusion in rats. The SERP1 cDNA encodes a 66-amino acid polypeptide which was found to be identical to ribosome-associated membrane protein 4 (RAMP4) and bearing 29% identity to yeast suppressor of SecY 6 protein (YSY6p), suggesting participation in pathways controlling membrane protein biogenesis at ER. In cultured 293 cells subjected to ER stress, overexpression of SERP1/RAMP4 suppressed aggregation and/or degradation of newly synthesized integral membrane proteins, and subsequently, facilitated their glycosylation when the stress was removed. SERP1/RAMP4 interacted with Sec61alpha and Sec61beta, which are subunits of translocon, and a molecular chaperon calnexin. Furthermore, Sec61alpha and Sec61beta, but not SERP1/RAMP4, were found to associate with newly synthesized integral membrane proteins under stress. These results suggest that stabilization of membrane proteins in response to stress involves the concerted action of a rescue unit in the ER membrane comprised of SERP1/RAMP4, other components of translocon, and molecular chaperons in ER.


Asunto(s)
Hipoxia de la Célula/fisiología , Proteínas de la Membrana/metabolismo , Secuencia de Aminoácidos , Animales , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Astrocitos/patología , Isquemia Encefálica/patología , Isquemia Encefálica/fisiopatología , Proteínas de Unión al Calcio/metabolismo , Calnexina , Línea Celular , Clonación Molecular , Retículo Endoplásmico/metabolismo , Glicoproteínas/biosíntesis , Glicoproteínas/genética , Glicoproteínas/metabolismo , Glicosilación , Homeostasis/fisiología , Humanos , Masculino , Proteínas de la Membrana/biosíntesis , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Chaperonas Moleculares/metabolismo , Datos de Secuencia Molecular , Unión Proteica , Desnaturalización Proteica , Renaturación de Proteína , ARN Mensajero/análisis , ARN Mensajero/genética , Ratas , Ratas Sprague-Dawley , Canales de Translocación SEC , Homología de Secuencia de Aminoácido
17.
J Cell Biol ; 155(1): 157-66, 2001 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-11581292

RESUMEN

Targeted disruption of core binding factor alpha1 (Cbfa1) showed that Cbfa1 is an essential transcription factor in osteoblast differentiation and bone formation. Furthermore, both in vitro and in vivo studies showed that Cbfa1 plays important roles in matrix production and mineralization. However, it remains to be clarified how Cbfa1 controls osteoblast differentiation, bone formation, and bone remodelling. To understand fully the physiological functions of Cbfa1, we generated transgenic mice that overexpressed Cbfa1 in osteoblasts using type I collagen promoter. Unexpectedly, Cbfa1 transgenic mice showed osteopenia with multiple fractures. Cortical bone, which was thin, porous, and enriched with osteopontin, was invaded by osteoclasts, despite the absence of acceleration of osteoclastogenesis. Although the number of neonatal osteoblasts was increased, their function was impaired in matrix production and mineralization. Furthermore, terminally differentiated osteoblasts, which strongly express osteocalcin, and osteocytes were diminished greatly, whereas less mature osteoblasts expressing osteopontin accumulated in adult bone. These data indicate that immature organization of cortical bone, which was caused by the maturational blockage of osteoblasts, led to osteopenia and fragility in transgenic mice, demonstrating that Cbfa1 inhibits osteoblast differentiation at a late stage.


Asunto(s)
Enfermedades Óseas Metabólicas/fisiopatología , Huesos/fisiología , Proteínas de Neoplasias , Osteoblastos/fisiología , Factores de Transcripción/metabolismo , Animales , Enfermedades Óseas Metabólicas/genética , Huesos/citología , Huesos/diagnóstico por imagen , Colágeno/genética , Colágeno/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Factores de Unión al Sitio Principal , Femenino , Fracturas Óseas/genética , Fracturas Óseas/fisiopatología , Ratones , Ratones Transgénicos , Osteogénesis , Regiones Promotoras Genéticas/genética , Radiografía , Factores de Transcripción/genética
18.
J Cell Biol ; 127(6 Pt 1): 1755-66, 1994 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-7798324

RESUMEN

The implantation of bone morphogenetic protein (BMP) into muscular tissues induces ectopic bone formation at the site of implantation. To investigate the mechanism underlying this process, we examined whether recombinant bone morphogenetic protein-2 (BMP-2) converts the differentiation pathway of the clonal myoblastic cell line, C2C12, into that of osteoblast lineage. Incubating the cells with 300 ng/ml of BMP-2 for 6 d almost completely inhibited the formation of the multinucleated myotubes expressing troponin T and myosin heavy chain, and induced the appearance of numerous alkaline phosphatase (ALP)-positive cells. BMP-2 dose dependently induced ALP activity, parathyroid hormone (PTH)-dependent 3',5'-cAMP production, and osteocalcin production at concentrations above 100 ng/ml. The concentration of BMP-2 required to induce these osteoblastic phenotypes was the same as that required to almost completely inhibit myotube formation. Incubating primary muscle cells with 300 ng/ml of BMP-2 for 6 d also inhibited myotube formation, whereas induced ALP activity and osteocalcin production. Incubation with 300 ng/ml of BMP-2 suppressed the expression of mRNA for muscle creatine kinase within 6 h, whereas it induced mRNA expression for ALP, PTH/PTH-related protein (PTHrP) receptors, and osteocalcin within 24-48 h. BMP-2 completely inhibited the expression of myogenin mRNA by day 3. By day 3, BMP-2 also inhibited the expression of MyoD mRNA, but it was transiently stimulated 12 h after exposure to BMP-2. Expression of Id-1 mRNA was greatly stimulated by BMP-2. When C2C12 cells pretreated with BMP-2 for 6 d were transferred to a colony assay system in the absence of BMP-2, more than 84% of the colonies generated became troponin T-positive and ALP activity disappeared. TGF-beta 1 also inhibited myotube formation in C2C12 cells, and suppressed the expression of myogenin and MyoD mRNAs without inducing that of Id-1 mRNA. However, no osteoblastic phenotype was induced by TGF-beta 1 in C2C12 cells. TGF-beta 1 potentiated the inhibitory effect of BMP-2 on myotube formation, whereas TGF-beta 1 reduced ALP activity and osteocalcin production induced by BMP-2 in C2C12 cells. These results indicate that BMP-2 specifically converts the differentiation pathway of C2C12 myoblasts into that of osteoblast lineage cells, but that the conversion is not heritable.


Asunto(s)
Desarrollo Óseo/fisiología , Músculos/efectos de los fármacos , Osteoblastos/fisiología , Proteínas/farmacología , Proteínas Represoras , Células Madre/efectos de los fármacos , Factores de Transcripción , Fosfatasa Alcalina/biosíntesis , Animales , Proteínas Morfogenéticas Óseas , Diferenciación Celular/efectos de los fármacos , Creatina Quinasa/biosíntesis , AMP Cíclico/biosíntesis , Proteínas de Unión al ADN/biosíntesis , Proteínas de Unión al ADN/genética , Relación Dosis-Respuesta a Droga , Secuencias Hélice-Asa-Hélice , Proteína 1 Inhibidora de la Diferenciación , Ratones , Músculos/citología , Músculos/embriología , Proteína MioD/biosíntesis , Proteína MioD/genética , Miogenina/biosíntesis , Miogenina/genética , Osteocalcina/biosíntesis , Hormona Paratiroidea/biosíntesis , Fenotipo , ARN Mensajero/análisis , Factores de Tiempo , Factor de Crecimiento Transformador beta/farmacología
19.
J Cell Biol ; 113(3): 681-7, 1991 May.
Artículo en Inglés | MEDLINE | ID: mdl-1849907

RESUMEN

The in vitro effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on osteogenic and myogenic differentiation was examined in two clonal cell lines of rat osteoblast-like cells at different differentiation stages, ROB-C26 (C26) and ROB-C20 (C20). The C26 is a potential osteoblast precursor cell line that is also capable of differentiating into muscle cells and adipocytes; the C20 is a more differentiated osteoblastic cell line. Proliferation was stimulated by rhBMP-2 in C26 cells, but inhibited in C20 cells. rhBMP-2 greatly increased alkaline phosphate (ALP) activity in C26 cells, but not in C20 cells. The steady-state level of ALP mRNA was also increased by rhBMP-2 in C26 cells, but not in C20 cells. Production of 3',5'-cAMP in response to parathyroid hormone (PTH) was dose-dependently enhanced by adding rhBMP-2 in both C26 and C20 cells, though the stimulatory effect was much greater in the former. There was neither basal expression of osteocalcin mRNA nor its protein synthesis in C26 cells, but they were strikingly induced by rhBMP-2 in the presence of 1 alpha,25-dihydroxyvitamin D3. rhBMP-2 induced no appreciable changes in procollagen mRNA levels of type I and type III in the two cell lines. Differentiation of C26 cells into myotubes was greatly inhibited by adding rhBMP-2. The inhibitory effect of rhBMP-2 on myogenic differentiation was also observed in clonal rat skeletal myoblasts (L6). Like BMP-2, TGF-beta 1 inhibited myogenic differentiation. However, unlike BMP-2, TGF-beta 1 decreased ALP activity in both C26 and C20 cells. TGF-beta 1 induced neither PTH responsiveness nor osteocalcin production in C26 cells, but it increased PTH responsiveness in C20 cells. These results clearly indicate that rhBMP-2 is involved, at least in vitro, not only in inducing differentiation of osteoblast precursor cells into more mature osteoblast-like cells, but also in inhibiting myogenic differentiation.


Asunto(s)
Sustancias de Crecimiento/farmacología , Músculos/citología , Osteoblastos/citología , Proteínas/farmacología , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Proteínas Morfogenéticas Óseas , Calcitriol/farmacología , Diferenciación Celular/efectos de los fármacos , AMP Cíclico/metabolismo , Humanos , Músculos/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteocalcina/biosíntesis , Osteocalcina/genética , Hormona Paratiroidea/farmacología , ARN Mensajero/análisis , Proteínas Recombinantes/farmacología , Factor de Crecimiento Transformador beta/farmacología
20.
Clin Neuropathol ; 28(2): 105-12, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19353842

RESUMEN

Intestinal ganglioneuromatosis (GN) is an uncommon disease of the enteric nervous system (ENS) and its pathogenesis remains unclear. Here we describe a unique case of diffuse GN of the intestinal wall associated with colon adenocarcinoma occurring in a 38-year-old female. Because it is well-known that glial cell line-derived neurotrophic factor (GDNF) and its receptor components, GDNF family receptor-alpha 1 (GFR-alpha 1) and RET receptor tyrosine kinase, play a crucial role in the development of ENS, their expression was analyzed by immunohistochemistry. Interestingly, GDNF as well as a related neurotrophic factor, neurturin (NTN), were expressed at high levels in adenocarcinoma cells whereas expression of GFR alpha 1 and RET was undetectable in them. In contrast, GFR-alpha 1 showed positive staining in both proliferating ganglion cells and glial cells, and RET immunoreactivity was found mainly in ganglion cell bodies. These findings suggested that GDNF and NTN expression in adenocarcinoma cells may play an important role in the pathogenesis of GN.


Asunto(s)
Adenocarcinoma/metabolismo , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Sistema Nervioso Entérico/patología , Ganglioneuroma/patología , Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Neurturina/metabolismo , Adenocarcinoma/patología , Adulto , Proliferación Celular , Colon/metabolismo , Colon/patología , Sistema Nervioso Entérico/metabolismo , Femenino , Ganglioneuroma/metabolismo , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/metabolismo , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Inmunohistoquímica , Neuroglía/fisiología , Proteínas Proto-Oncogénicas c-ret/metabolismo , Proteínas S100/metabolismo
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