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1.
Nat Cell Biol ; 2(10): 703-8, 2000 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-11025660

RESUMEN

Only a few RFamide peptides have been identified in mammals, although they have been abundantly found in invertebrates. Here we report the identification of a human gene that encodes at least three RFamide-related peptides, hRFRP-1-3. Cells transfected with a seven-transmembrane-domain receptor, OT7T022, specifically respond to synthetic hRFRP-1 and hRFRP-3 but not to hRFRP-2. RFRP and OT7T022 mRNAs are expressed in particular regions of the rat hypothalamus, and intracerebroventricular administration of hRFRP-1 increases prolactin secretion in rats. Our results indicate that a variety of RFamide-related peptides may exist and function in mammals.


Asunto(s)
Neuropéptidos/aislamiento & purificación , Receptores de Neuropéptido/aislamiento & purificación , Secuencia de Aminoácidos , Animales , Bovinos , Clonación Molecular , Humanos , Ratones , Datos de Secuencia Molecular , Neuropéptidos/química , Neuropéptidos/genética , Ratas , Receptores de Neuropéptido/genética , Homología de Secuencia de Aminoácido , Especificidad de la Especie
2.
Sci Rep ; 10(1): 3380, 2020 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-32098993

RESUMEN

The brightness of aurorae in Earth's polar region often beats with periods ranging from sub-second to a few tens of a second. Past observations showed that the beat of the aurora is composed of a superposition of two independent periodicities that co-exist hierarchically. However, the origin of such multiple time-scale beats in aurora remains poorly understood due to a lack of measurements with sufficiently high temporal resolution. By coordinating experiments using ultrafast auroral imagers deployed in the Arctic with the newly-launched magnetospheric satellite Arase, we succeeded in identifying an excellent agreement between the beats in aurorae and intensity modulations of natural electromagnetic waves in space called "chorus". In particular, sub-second scintillations of aurorae are precisely controlled by fine-scale chirping rhythms in chorus. The observation of this striking correlation demonstrates that resonant interaction between energetic electrons and chorus waves in magnetospheres orchestrates the complex behavior of aurora on Earth and other magnetized planets.

3.
J Cell Biol ; 150(6): 1335-48, 2000 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-10995439

RESUMEN

Cleavage is one of the initial steps of embryogenesis, and is characterized by a series of symmetric and synchronous cell divisions. We showed that p38 MAP kinase (p38) is asymmetrically activated on one side of the blastodisc during the early cleavage period in zebrafish (Danio rerio) embryos. When a dominant negative (DN) form of p38 was uniformly expressed, blastomere cleavage was impaired on one side of the blastodisc, resulting in the formation of blastomeres with a large mass of cytoplasm and an enlarged nucleus on the affected side. The area affected by the DN-p38 expression did not correlate with the initial cleavage plane, but coincided with the side where dharma/bozozok, a dorsal-specific zygotic gene, was expressed (Yamanaka et al. 1998). Furthermore, UV irradiation and removal of the vegetal yolk mass before the first cleavage, both of which inhibit the initiation of the dorsalizing signals, abolished the asymmetric p38 activation. Our findings suggest that asymmetric p38 activation is required for symmetric and synchronous cleavage, and may be regulated by the same machinery that controls the initiation of dorsalizing signals.


Asunto(s)
División Celular/fisiología , Proteínas Quinasas Activadas por Mitógenos/genética , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Animales , Blastómeros/citología , Blastómeros/enzimología , Bromodesoxiuridina/análisis , Polaridad Celular/fisiología , Clonación Molecular , Yema de Huevo/metabolismo , Embrión no Mamífero/citología , Embrión no Mamífero/enzimología , Activación Enzimática/fisiología , Activación Enzimática/efectos de la radiación , Regulación del Desarrollo de la Expresión Génica , Regulación Enzimológica de la Expresión Génica , Genes Reporteros , Hibridación in Situ , Luciferasas/genética , Microtúbulos/metabolismo , ARN Mensajero/análisis , Rayos Ultravioleta , Pez Cebra , Proteínas Quinasas p38 Activadas por Mitógenos
4.
Oral Microbiol Immunol ; 24(6): 502-5, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-19832803

RESUMEN

INTRODUCTION: Microorganisms are able to survive and induce persistent infection in periapical tissues. The aim of this study was to investigate the composition of the microflora of persistent apical periodontitis lesions. METHODS: Twenty apical lesion samples were obtained from 20 patients with chronic apical periodontitis by root end surgery and processed using aerobic or anaerobic culture techniques. All isolated strains were identified by 16S ribosomal DNA sequence analysis. RESULTS: Seventy-four strains were isolated, belonging to 31 bacterial species obtained from the 20 apical lesions that were isolated. The majority of the strains were facultative anaerobes (51.6%). Propionibacterium acnes, Staphylococcus epidermidis, Pseudomonas aeruginosa and Fusobacterium nucleatum were isolated from 16.2, 9.5, 6.8 and 5.4% of the samples, respectively. Fifteen samples harboured more than one species. The predominant association was P. acnes, S. epidermidis and F. nucleatum. CONCLUSION: The microbiota of persistent apical periodontitis lesions is composed by diverse types of microorganisms with biofilm-forming capacity, including P. acnes, S. epidermidis and F. nucleatum.


Asunto(s)
Periodontitis Periapical/microbiología , Bacterias Anaerobias/genética , Bacterias Anaerobias/aislamiento & purificación , Biopelículas , Periodontitis Crónica/microbiología , ADN Bacteriano/análisis , ADN Ribosómico/análisis , Femenino , Fusobacterium nucleatum/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , Propionibacterium acnes/aislamiento & purificación , Pseudomonas aeruginosa/aislamiento & purificación , Ribotipificación , Staphylococcus epidermidis/aislamiento & purificación
5.
Curr Med Chem ; 15(6): 604-13, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18336275

RESUMEN

In 1980, Espey proposed a famous hypothesis that mammalian ovulation is comparable to an inflammatory reaction and many researches have proved the validity of his hypothesis in the last three decades. For example, interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)- alpha, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF) and other inflammatory cytokines presence was proven in the preovulatory follicle. Since granulocyte is the major leukocyte and it plays a very important role during inflammation, the importance of granulocyte and its related cytokine, granulocyte colony-stimulating factor (G-CSF) in the mechanism of human ovulation is easily predictable. G-CSF is one of the hemopoietic cytokines and it has strong positive effects on granulocytes. G-CSF increases the number of granulocytes and it improves the function of granulocytes. In this review, the participation of leukocytes in the ovulation mechanism is demonstrated first. Second, the participation of G-CSF is shown in comparison with the above mentioned cytokines. Finally, since G-CSF has been used for more than 20 years as a medicine without severe side effects in the field of oncology, the clinical application of G-CSF for the treatment of an ovulation disorder, luteinized unruptured follicle (LUF), will be discussed.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos/fisiología , Inducción de la Ovulación/métodos , Ovulación/fisiología , Citocinas/sangre , Citocinas/fisiología , Femenino , Factor Estimulante de Colonias de Granulocitos/sangre , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Humanos , Leucocitos/efectos de los fármacos , Leucocitos/fisiología , Modelos Biológicos , Ovulación/sangre , Ovulación/efectos de los fármacos
6.
Mol Cell Biol ; 21(14): 4460-9, 2001 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-11416126

RESUMEN

RNA helicase A (RHA) is a member of an ATPase/DNA and RNA helicase family and is a homologue of Drosophila maleless protein (MLE), which regulates X-linked gene expression. RHA is also a component of holo-RNA polymerase II (Pol II) complexes and recruits Pol II to the CREB binding protein (CBP). The ATPase and/or helicase activity of RHA is required for CREB-dependent transcription. To further understand the role of RHA on gene expression, we have identified a 50-amino-acid transactivation domain that interacts with Pol II and termed it the minimal transactivation domain (MTAD). The protein sequence of this region contains six hydrophobic residues and is unique to RHA homologues and well conserved. A mutant with this region deleted from full-length RHA decreased transcriptional activity in CREB-dependent transcription. In addition, mutational analyses revealed that several tryptophan residues in MTAD are important for the interaction with Pol II and transactivation. These mutants had ATP binding and ATPase activities comparable to those of wild-type RHA. A mutant lacking ATP binding activity was still able to interact with Pol II. In CREB-dependent transcription, the transcriptional activity of each of these mutants was less than that of wild-type RHA. The activity of the double mutant lacking both functions was significantly lower than that of each mutant alone, and the double mutant had a dominant negative effect. These results suggest that RHA could independently regulate CREB-dependent transcription either through recruitment of Pol II or by ATP-dependent mechanisms.


Asunto(s)
Adenosina Trifosfatasas/fisiología , Autoantígenos/fisiología , Proteína de Unión a Elemento de Respuesta al AMP Cíclico/metabolismo , ARN Helicasas/fisiología , Transcripción Genética , Adenosina Trifosfatasas/genética , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfato/metabolismo , Secuencia de Aminoácidos , Animales , Autoantígenos/genética , Autoantígenos/metabolismo , Sitios de Unión , Caenorhabditis elegans , Secuencia Conservada , ARN Helicasas DEAD-box , Humanos , Datos de Secuencia Molecular , Proteínas de Neoplasias , ARN Helicasas/genética , ARN Helicasas/metabolismo , ARN Polimerasa II/metabolismo , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/fisiología , Homología de Secuencia de Aminoácido , Activación Transcripcional
7.
J Natl Cancer Inst ; 86(23): 1781-4, 1994 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-7966417

RESUMEN

BACKGROUND: Cisplatin accumulation is decreased in many cisplatin-resistant cells. An active efflux pump for cisplatin exists in cisplatin-resistant human epidermoid carcinoma cells (called KB cells). A previous study has suggested that the adenosine triphosphate (ATP)-dependent glutathione S-conjugate export pump (GS-X pump), which exports the bis-(glutathionato)-platinum (II) (GS-platinum) complex, could contribute to cellular resistance to cisplatin. PURPOSE: In this study, we examined whether the active efflux pump for cisplatin in the cisplatin-resistant KB cells is the GS-X pump and tested its activity by using an endogenous substrate, [3H]leukotriene C4 ([3H]LTC4). METHODS: Membrane vesicles were prepared from KB-3-1 (clone from parental KB cells) cells and from cisplatin-resistant KCP-4 (a mutant clone derived from KB-3-1 cells) cells. Using a filtration technique, we measured the uptake and transport of [3H]LTC4, a substrate for the GS-X pump, into membrane vesicles at 37 degrees C. RESULTS: The uptake of [3H]LTC4 in the membrane vesicles from both the KB-3-1 and KCP-4 cells was ATP-dependent. In contrast, the ATP-dependent transport of [3H]LTC4 was observed only in KCP-4 membrane vesicles but not in KB-3-1 membrane vesicles. The ATP-dependent transport was vanadate sensitive and was inhibited by GS-platinum complex but only marginally by cisplatin and glutathione and not by vincristine or verapamil. The nucleotide triphosphates, guanosine triphosphate, cytidine triphosphate, uridine triphosphate, and deoxythymidine triphosphate could be substituted for ATP but were less efficient. A nonhydrolyzable ATP analogue, adenosine 5'-(beta,gamma-methylene) triphosphate, was not effective. CONCLUSIONS: The transport of LTC4 in membrane vesicles prepared from KCP-4 cells was facilitated by an ATP-dependent pump that appeared very similar to the GS-X pump. IMPLICATIONS: Our study suggests that the GS-X pump is involved in the decreased accumulation of cisplatin in KCP-4 cells.


Asunto(s)
Adenosina Trifosfato/fisiología , Carcinoma de Células Escamosas/metabolismo , Cisplatino , Glutatión/metabolismo , Leucotrieno C4/metabolismo , Transporte Biológico Activo , Carcinoma de Células Escamosas/tratamiento farmacológico , Membrana Celular/metabolismo , Cisplatino/uso terapéutico , Resistencia a Medicamentos , Humanos , Células Tumorales Cultivadas
8.
Cancer Res ; 55(19): 4225-9, 1995 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-7671225

RESUMEN

We have synthesized and characterized a positron-emitting carbon-11-labeled 1,2-diacylglycerol to study phosphoinositide turnover in tumor cells. Rapid incorporation of the 1,2-diacylglycerol was observed in the C6 glioma cell line. The incorporated lipid fraction consisted chiefly of phosphoinositide pool and another phospholipid pool in the proliferative state. When the state was inhibited by (-)-3D-3-deoxy-3-fluoro-myo-inositol, incorporation into the phosphoinositide pool decreased selectively. This suggested that phosphoinositide turnover is the leading regulator of tumor proliferation potential. On the basis of the concept of carbon-11-labeled 1,2-diacylglycerol as a specific probe for visualizing the tumor signal transduction in vivo, we obtained proliferating images of implanted C6 glioma cells in the rat brain by autoradiography and visualized the proliferation signal in human glioma by positron emission tomography.


Asunto(s)
Radioisótopos de Carbono , Diglicéridos/metabolismo , Glioma/metabolismo , Transducción de Señal , Animales , Glioma/diagnóstico por imagen , Humanos , Fosfatidilinositoles/metabolismo , Ratas , Ratas Wistar , Tomografía Computarizada de Emisión , Células Tumorales Cultivadas
9.
Cancer Res ; 47(15): 4146-9, 1987 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-3607756

RESUMEN

An in vitro methylcellulose technique was used in an attempt to culture neuroblastoma cells from 25 bone marrows from eight children with neuroblastoma. Colonies appeared within 5 days in histologically positive bone marrows. Light microscopy, linearity study, and marker study provided evidence for the neuroblastoma origin of the colonies. These colonies could be distinguished from other colonies under the inverted microscope because of its distinct feature. In one case, the characteristic morphology of neuroblastoma was shown in 3 days of culture, while histological evidence is absent. The diagnosis of neuroblastoma was confirmed by subsequent catecholamine determination. All histologically negative specimens formed no colonies, while all positive specimens formed more than three colonies. Potential application of this culturing technique for monitoring of bone marrow involvement and differential diagnosis in children with neuroblastoma is presented.


Asunto(s)
Células Clonales/patología , Técnicas de Cultivo/métodos , Neuroblastoma/patología , Médula Ósea/patología , Niño , Células Clonales/enzimología , Medios de Cultivo , Diagnóstico Diferencial , Células Madre Hematopoyéticas/patología , Humanos , Metilcelulosa , Proteínas de Neoplasias/análisis , Células Madre Neoplásicas/patología , Neuroblastoma/diagnóstico , Neuroblastoma/enzimología , Fosfopiruvato Hidratasa/análisis , Pronóstico
10.
Biochim Biophys Acta ; 1538(2-3): 162-71, 2001 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-11336787

RESUMEN

We analyzed the tissue distribution of apelin mRNA in rats by a quantitative reverse transcription-polymerase chain reaction and that of immunoreactive apelin (ir-apelin) by an enzyme immunoassay (EIA) using a monoclonal antibody. The expression levels of apelin mRNA and ir-apelin seemed to be consistent among tissues: they were highly expressed in the lung and mammary gland. By the combination of gel filtration and EIA, we found that the molecular forms of apelin differ among respective tissues: apelin molecules with sizes close to apelin-36 (long forms) were major components in the lung, testis, and uterus, but both long and short (whose sizes were close to [

Asunto(s)
Proteínas Portadoras/análisis , Receptores Acoplados a Proteínas G , Secuencia de Aminoácidos , Animales , Apelina , Receptores de Apelina , Proteínas Portadoras/síntesis química , Proteínas Portadoras/metabolismo , Cromatografía en Gel , Femenino , Técnicas para Inmunoenzimas , Péptidos y Proteínas de Señalización Intercelular , Pulmón/metabolismo , Masculino , Glándulas Mamarias Animales/metabolismo , Datos de Secuencia Molecular , Peso Molecular , ARN Mensajero/análisis , Ratas , Ratas Wistar , Receptores de Dopamina D2 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Testículo/metabolismo , Útero/metabolismo
11.
Biochim Biophys Acta ; 1452(1): 25-35, 1999 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-10525157

RESUMEN

By using a strategy that we have developed to search for the ligands of orphan seven-transmembrane-domain receptors [S. Hinuma et al., Nature 393 (1998) 272-276], we have recently identified a natural ligand, apelin, for the orphan 7TMR, APJ [K. Tatemoto et al., Biochem. Biophys. Res. Commun. 251 (1998) 471-476]. In this paper, we isolated rat and mouse apelin cDNAs, and analyzed the tissue distribution of apelin mRNA in rats. Although apelin mRNA was widely detected in a variety of tissues, the highest expression of apelin mRNA was detected in the mammary gland of pregnant rats. In the mammary gland, biologically active apelin and its mRNA considerably increased during pregnancy and lactation, and reached a maximal level around parturition. Moreover, a large amount of apelin (14-93 pmol/ml) was found to be secreted in the bovine colostrum, and it was still detectable even in commercial bovine milk. Since apelin partially suppressed cytokine production by mouse spleen cells in response to T cell receptor/CD3 cross-linking, the oral intake of apelin in the colostrum and milk might modulate immune responses in neonates.


Asunto(s)
Proteínas Portadoras/metabolismo , Calostro/metabolismo , Receptores Acoplados a Proteínas G , Adipoquinas , Secuencia de Aminoácidos , Animales , Apelina , Receptores de Apelina , Células CHO , Proteínas Portadoras/síntesis química , Proteínas Portadoras/genética , Bovinos , Colforsina , Cricetinae , AMP Cíclico/metabolismo , ADN Complementario/aislamiento & purificación , Femenino , Péptidos y Proteínas de Señalización Intercelular , Lactancia/metabolismo , Ligandos , Masculino , Glándulas Mamarias Animales/metabolismo , Ratones , Leche/química , Datos de Secuencia Molecular , Embarazo/metabolismo , ARN Mensajero/análisis , Ratas , Ratas Wistar , Receptores de Dopamina D2/química , Receptores de Dopamina D2/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa
12.
Biochim Biophys Acta ; 1540(3): 221-32, 2001 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-11583817

RESUMEN

We have recently identified RFamide-related peptide (RFRP) gene that would encode three peptides (i.e., RFRP-1, -2, and -3) in human and bovine, and demonstrated that synthetic RFRP-1 and -3 act as specific agonists for a G protein-coupled receptor OT7T022. However, molecular characteristics and tissue distribution of endogenous RFRPs have not been determined yet. In this study, we prepared a monoclonal antibody for the C-terminal portion of rat RFRP-1. As this antibody could recognize a consensus sequence among the C-terminal portions of rat, human, and bovine RFRP-1, we purified endogenous RFRP-1 from bovine hypothalamus on the basis of immunoreactivity to the antibody. The purified bovine endogenous RFRP-1 was found to have 35-amino-acid length that corresponds to 37-amino-acid length in human and rat. We subsequently constructed a sandwich enzyme immunoassay using the monoclonal antibody and a polyclonal antibody for the N-terminal portion of rat RFRP-1, and analyzed the tissue distribution of endogenous RFRP-1 in rats. Significant levels of RFRP-1 were detected only in the central nervous system, and the highest concentration of RFRP-1 was detected in the hypothalamus. RFRP-1-positive nerve cells were detected in the rat hypothalamus by immunohistochemical analyses using the monoclonal antibody. In culture, RFRP-1 lowered cAMP production in Chinese hamster ovary cells expressing OT7T022 and it was abolished by pre-treatment with pertussis toxin, suggesting that OT7T022 couples G(i)/G(o) in the signal transduction pathway.


Asunto(s)
Hipotálamo/metabolismo , Neuropéptidos/metabolismo , Receptores Acoplados a Proteínas G , Proteínas de Saccharomyces cerevisiae , Secuencia de Aminoácidos , Animales , Encéfalo/metabolismo , Células CHO , Bovinos , Cromatografía en Gel , Cricetinae , Técnicas para Inmunoenzimas , Inmunohistoquímica , Datos de Secuencia Molecular , Neuropéptidos/análisis , Neuropéptidos/aislamiento & purificación , Ratas , Receptores de Superficie Celular/metabolismo , Alineación de Secuencia
13.
Clin Cancer Res ; 4(8): 1825-32, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9717808

RESUMEN

Determination of tumor boron-10 (10B) levels is required for accurate neutron dosimetry during boron neutron capture therapy. We assessed a new method for quantitative measurement of boronated drug uptake in high-grade gliomas. This method uses positron emission tomography (PET) with fluorine-18-labeled L-fluoroborono-phenylalanine (L-18F-10B-FBPA), which was synthesized as an analogue of L-boronophenylalanine. We studied the accumulation of L-18F-10B-FBPA by PET in patients with high-grade gliomas. Dynamic PET studies of brain tumors revealed that L-18F-10B-FBPA accumulated gradually after bolus injection, and the value of PET activity divided by the integrated plasma activity reached a constant level 42 min after injection, which was defined as the incorporation constant (Ic*). This constant reflected the appropriate L-18F-10B-FBPA accumulation in tumor tissue. Based on the Ic* constant, the methods for estimating tumor 10B concentration were devised. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This method was based solely on PET and can potentially provide data that would assist in the selection of patients for future treatment with boron neutron capture therapy after surgical resection of their brain tumors.


Asunto(s)
Compuestos de Boro/farmacocinética , Terapia por Captura de Neutrón de Boro/métodos , Boro/farmacocinética , Glioma/diagnóstico por imagen , Glioma/metabolismo , Fenilalanina/análogos & derivados , Fármacos Sensibilizantes a Radiaciones/farmacocinética , Tomografía Computarizada de Emisión/métodos , Boro/análisis , Boro/uso terapéutico , Compuestos de Boro/análisis , Compuestos de Boro/uso terapéutico , Radioisótopos de Flúor , Glioma/radioterapia , Humanos , Isótopos , Fenilalanina/análisis , Fenilalanina/farmacocinética , Fenilalanina/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/análisis , Fármacos Sensibilizantes a Radiaciones/uso terapéutico
14.
Clin Cancer Res ; 4(8): 1833-41, 1998 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-9717809

RESUMEN

Based on pharmacokinetic findings of fluorine-18-labeled L-fluoroboronophenylalanine by positron emission tomography (PET), methods for estimating tumor 10B concentration were devised. In clinical practice of boron neutron capture therapy (BNCT) for high-grade gliomas, a large amount of L-boronophenylalanine (L-10B-BPA)-fructose solution is used. Under these conditions, a slow i.v. infusion of L-10B-BPA-fructose solution should be performed for BNCT; therefore, the changes over time in 10B concentration in the target tissue were estimated by convoluting the actual time course of changes in plasma 10B concentration with a PET-based weight function including the proper rate constants [K1 (ml/g/min), k2 (min(-1)), k3 (min(-1)), and k4 (min(-1))]. With this method, the estimated values of 10B concentration in gliomas were very close to the 10B levels in surgical specimens. This demonstrated the similarity in pharmacokinetics between fluorine-18-labeled L-fluoroboronophenylalanine and L-10B-BPA. This method, using the appropriate rate constant, permits the determination of tumor 10B concentration and is widely suitable for clinical BNCT, because the averaged PET data are enough to use in future patients without individual PET study.


Asunto(s)
Compuestos de Boro/farmacocinética , Terapia por Captura de Neutrón de Boro/métodos , Boro/farmacocinética , Glioma/diagnóstico por imagen , Glioma/metabolismo , Fenilalanina/análogos & derivados , Fármacos Sensibilizantes a Radiaciones/farmacocinética , Tomografía Computarizada de Emisión/métodos , Boro/uso terapéutico , Compuestos de Boro/sangre , Compuestos de Boro/uso terapéutico , Radioisótopos de Flúor , Glioma/radioterapia , Humanos , Isótopos , Cómputos Matemáticos , Fenilalanina/sangre , Fenilalanina/farmacocinética , Fenilalanina/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/uso terapéutico
15.
FEBS Lett ; 261(2): 283-6, 1990 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-2311759

RESUMEN

NH2-terminal amino acid sequence of the pS2 protein produced and secreted by human gastric cancer cells, MKN-45, was determined to be identical to that of MCF-7 cells. A clone encoding pS2 protein was isolated from the cDNA library constructed from MKN-45 cells. The nucleotide sequence was identical to that of pS2 cDNA previously isolated from human breast cancer cells, MCF-7, except for one nucleotide in the 3' untranslated region. Thus, in this cell line, the pS2 gene product is translated and secreted as in MCF-7 cells. RNA blot hybridization analysis revealed that pS2 gene was expressed well in two (MKN-45 and KATO-III; derived from poorly differentiated adenocarcinoma) but not in three cell lines (MKN-1, MKN-28 and MKN-74; from well differentiated adenocarcinoma), suggesting that expression of the pS2 gene depends on the state of cell differentiation. These results suggest that pS2 is expressed in human gastric cancer cells in an estrogen-independent manner and is possibly associated with the malignant state of cells.


Asunto(s)
Adenocarcinoma/metabolismo , Expresión Génica , Proteínas de Neoplasias/genética , Proteínas , Neoplasias Gástricas/metabolismo , Secuencia de Aminoácidos , Secuencia de Bases , Neoplasias de la Mama/análisis , ADN/genética , ADN/aislamiento & purificación , Estrógenos/farmacología , Humanos , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , ARN Mensajero/análisis , Factor Trefoil-1 , Células Tumorales Cultivadas , Proteínas Supresoras de Tumor
16.
J Nucl Med ; 34(9): 1543-51, 1993 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-8394884

RESUMEN

Receptor-mediated membrane processing plays an essential role in neural function in the synapses. In such neurotransmission process, the phosphoinositide (PI) response, an effector in the production of second-messengers, can be used to assess in vivo signal transduction. Using in vivo autoradiography and positron emission tomography (PET), we attempted to visualize the PI response to muscarinic cholinergic receptor (mAChR)-stimulation in rats and monkeys, which were administered 1,2-[11C]diacylglycerol (DAG) intravenously. Enhancement of 1,2-[11C]DAG incorporation was observed in the rat ipsilateral hippocampus and cortex in which mAChR-agonist was administered by local injection, but this was in contrast to spreading cortical depression in the ipsilateral cortex using KCl. In monkey PET studies, dynamic brain scanning revealed increase in activity over time for about 15 min after a bolus injection of 1,2-[11C]DAG in an awake state. The activity then remained at a constant level. This finding documented the theoretical "membrane-trapping" mechanism. The systemic mAChR-stimulation accelerated incorporation in the cerebral cortices of the same monkey brain. Radioactivity uptake did not differ significantly between the mAChR-stimulated and nonstimulated early scan images. This suggested that cerebral blood flow does not greatly affect DAG incorporation. In sequential membrane processes of PI turnover, diacylglycerol kinase rapidly metabolizes DAG, included in PI turnover. In conclusion 1,2-[11C]DAG incorporation was limited by receptor-mediated PI turnover, which can represent real synaptic transmission in neural networks.


Asunto(s)
Encéfalo/diagnóstico por imagen , Radioisótopos de Carbono , Diglicéridos , Fosfatidilinositoles/metabolismo , Receptores Muscarínicos/fisiología , Transducción de Señal/fisiología , Tomografía Computarizada de Emisión , Animales , Arecolina/farmacología , Encéfalo/metabolismo , Depresión de Propagación Cortical/fisiología , Macaca , Masculino , Ratas , Ratas Wistar , Receptores Muscarínicos/efectos de los fármacos , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Distribución Tisular
17.
J Nucl Med ; 34(3): 431-9, 1993 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-8441035

RESUMEN

Protein kinase C plays a crucial role in signal transduction for a variety of biologically active substances which activates cellular functions and their proliferation. The actions are closely related to both normal and abnormal functions in the nervous system. Tumor-promoting phorbol esters can substitute for diacylglycerols which are important ligands that bind to protein kinase C. Three typical phorbol esters, phorbol 13-[1-11C]butyrate, phorbol 12,13-[1-11C]dibutyrate and 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate, were synthesized by using [11C]ethylketene with a high specific activity (186GBq/mumol). Their in vivo autoradiograms demonstrated a heterogenous distribution in rat brain. 12-deoxyphorbol 13-isobutyrate-20-[1-11C]butyrate was particularly suited for in vivo use due to its nontumor-promoting activity and its ready permeability to the blood-brain barrier. High optical density was observed in the cortex, amygdala and hippocampus. The in vivo binding properties of this compound to protein kinase C were confirmed by in vivo displacement studies with unlabeled 12-deoxyphorbol 13-isobutyrate-20-butyrate and unlabeled phorbol 12,13-dibutyrate. This suggests that 12-deoxyphorbol 13-isobutyrate-20-[1-11C] butyrate has a specific binding affinity for protein kinase C.


Asunto(s)
Encéfalo/enzimología , Radioisótopos de Carbono , Ésteres del Forbol , Proteína Quinasa C/metabolismo , Tomografía Computarizada de Emisión , Animales , Autorradiografía , Encéfalo/diagnóstico por imagen , Masculino , Ésteres del Forbol/química , Ésteres del Forbol/farmacocinética , Ratas , Ratas Wistar
18.
J Nucl Med ; 33(3): 413-22, 1992 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-1311037

RESUMEN

The uptake mechanism of 1,2-[11C]diacylglycerols (DAG) was studied and its use as a probe for the measurement of phosphatidylinositol (PI) turnover was verified. A method of synthesis for producing rac-1,2-[11C]DAG using [11C]ethylketene was developed to label the 1- or 3-hydroxyl group of 2-monoacylglycerol. After intravenous injection, these tracers were metabolized rapidly in the rat brain cortex to phosphatidic acids, phosphatidylinositols and phosphatidylinositol phosphates. The brain cortex anesthetized by barbiturate, which represents inhibited state of synaptic transmission, did not produce differences in uptake values between sn-1,2-[11C]DAG and rac-1,2-[11C]DAG. However, in the liver, lung, and pancreas under the same conditions, the uptake values of rac-1,2-[11C]DAG were higher than those of sn-1,2-[11C] DAG, in which the labeling position was on the 2-hydroxyl group in the sn type. These findings suggest that the lipase activity in the brain should be disregarded because lipase predominantly hydrolyzes the 1- or 3-position of rac-1,2-[11C] DAG, which should be the main factor producing the differences in uptake values in other organs. Cholinergic stimulation prompted accumulation of 1,2-[11C]DAG in the conscious rat brain. In conclusion, sn-1,2-[11C]DAG, administered even in the racemic mixture, could serve as a tracer that becomes mixed with receptor-linked PI turnover and could accumulate in the brain based on the membrane trapping mechanism.


Asunto(s)
Radioisótopos de Carbono , Corteza Cerebral/metabolismo , Diglicéridos , Fosfatidilinositoles/metabolismo , Transmisión Sináptica , Animales , Dióxido de Carbono/metabolismo , Membrana Celular/metabolismo , Cerebelo/metabolismo , Diglicéridos/síntesis química , Diglicéridos/química , Masculino , Fosfatidilinositoles/farmacocinética , Ratas , Ratas Endogámicas , Distribución Tisular , Tomografía Computarizada de Emisión
19.
J Nucl Med ; 39(2): 325-33, 1998 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-9476945

RESUMEN

UNLABELLED: We synthesized fluorine-18-labeled fluoroboronophenylalanine (18F-10B-FBPA), an analog of boronophenylalanine (10B-BPA), and characterized its pharmacokinetics in patients with glioma. We conducted PET studies on three types of gliomas to clarify the relationship between tumor grade and each rate constant [K1 (ml/g/min), k2 (min[-1]) and k3 (min[-1])], and here, we discuss the metabolism of the 10B-BPA analog (18F-10B-FBPA). METHODS: Thirty-three cases of primary gliomas were studied by dynamic PET using DL-18F-10B-FBPA or L-18F-10B-FBPA. Dynamic PET images of 18F-10B-FBPA incorporation into tumors were obtained, and the arterial blood samplings were performed in all cases. RESULTS: When the dynamic PET data were represented as Gjedde-Patlak plots, there was a positive slope, suggesting the involvement of the putative metabolic pool of this tracer. A three-compartment model using rate constants (K1, k2 and k3) was used for the kinetic analysis. The accumulation of 18F-10B-FBPA was found to correlate with the degree of malignancy, and the L form of 18F-10B-FBPA was taken up better than was the DL form. The results of dynamic PET analysis suggested that K1 (measuring amino acid transport process) is a major factor determining the accumulation of 18F-10B-FBPA. A comparison of the rate constants revealed that k3 (metabolic process) did not correlate with the degree of malignancy. The absence of evident differences in k3 between DL and L forms suggests that k3 represents phenomena that are not dependent on the native form of L. CONCLUSION: These PET data will be of practical use for diagnosis of malignancy and direct prediction of the effectiveness of boron neutron capture therapy using 10B-BPA.


Asunto(s)
Compuestos de Boro , Neoplasias Encefálicas/diagnóstico por imagen , Glioma/diagnóstico por imagen , Fenilalanina/análogos & derivados , Radiofármacos , Tomografía Computarizada de Emisión , Astrocitoma/diagnóstico por imagen , Compuestos de Boro/farmacocinética , Neoplasias Encefálicas/fisiopatología , Circulación Cerebrovascular , Radioisótopos de Flúor , Glioblastoma/diagnóstico por imagen , Glioma/fisiopatología , Humanos , Fenilalanina/farmacocinética , Radiofármacos/farmacocinética
20.
J Nucl Med ; 40(10): 1590-4, 1999 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-10520696

RESUMEN

UNLABELLED: It is important to evaluate cerebral function from neural signal transduction in ischemic brain in judging morbid state and prognosis. We synthesized 1-[1-(11)C]-butyryl-2-palmitoyl-rac-glycerol (DAG) for the purpose of imaging the second messenger on PET and applied it to clinical cases of cerebral infarction. METHODS: Five patients, who had ischemic stroke, were examined with PET. [15O]-CO2 and [15O]-O2 inhalation methods were applied to cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2). For the measurement of phosphoinositide turnover after intravenous injection of DAG, dynamic PET data were collected continuously for 46 min. Arterial blood samples were taken to evaluate changes in the serum concentration of DAG. To quantify the metabolic activity of inositol phospholipid, the incorporation constant k*(DAG) was calculated on the basis of the kinetics of DAG. RESULTS: The plasma concentration of DAG increased rapidly and peaked 30 s after injection of DAG solution. In the normal cortex, DAG concentration increased gradually and reached a plateau between 15 and 20 min after injection. In the ischemic core (infarction), DAG concentration increased slowly, and its peak concentration was lower than that in normal tissue. In comparison with blood flow and metabolic parameters, k*(DAG) showed the best correlation with CMRO2, suggesting a reflection of neuronal activity. Locally, CBF and CMRO2 gradually decreased from the normal area toward the ischemic center (infarction), whereas k*(DAG) and OEF significantly decreased only in the ischemic center. CONCLUSION: The k*(DAG) of ischemic brain, including that caused by infarction, significantly correlated with CMRO2, suggesting that metabolic activity of inositol phospholipid reflects neural viability. Maintained metabolic activity of inositol phospholipid in the region around the ischemic core indicated preservation of the signal transduction system through the metabotropic receptor.


Asunto(s)
Isquemia Encefálica/metabolismo , Glicéridos , Fosfatidilinositoles/metabolismo , Radiofármacos , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/fisiopatología , Radioisótopos de Carbono , Circulación Cerebrovascular , Femenino , Glicéridos/farmacocinética , Humanos , Masculino , Persona de Mediana Edad , Oxígeno/metabolismo , Radioisótopos de Oxígeno , Transducción de Señal , Tomografía Computarizada de Emisión/métodos
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