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1.
Phys Rev Lett ; 126(6): 062501, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33635678

RESUMO

In an emulsion-counter hybrid experiment performed at J-PARC, a Ξ^{-} absorption event was observed which decayed into twin single-Λ hypernuclei. Kinematic calculations enabled a unique identification of the reaction process as Ξ^{-}+^{14}N→_{Λ}^{10}Be+_{Λ}^{5}He. For the binding energy of the Ξ^{-} hyperon in the Ξ^{-}-^{14}N system a value of 1.27±0.21 MeV was deduced. The energy level of Ξ^{-} is likely a nuclear 1p state which indicates a weak ΞN-ΛΛ coupling.

2.
Phys Rev Lett ; 120(21): 211801, 2018 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-29883136

RESUMO

The OPERA experiment was designed to study ν_{µ}→ν_{τ} oscillations in the appearance mode in the CERN to Gran Sasso Neutrino beam (CNGS). In this Letter, we report the final analysis of the full data sample collected between 2008 and 2012, corresponding to 17.97×10^{19} protons on target. Selection criteria looser than in previous analyses have produced ten ν_{τ} candidate events, thus reducing the statistical uncertainty in the measurement of the oscillation parameters and of ν_{τ} properties. A multivariate approach for event identification has been applied to the candidate events and the discovery of ν_{τ} appearance is confirmed with an improved significance level of 6.1σ. |Δm_{32}^{2}| has been measured, in appearance mode, with an accuracy of 20%. The measurement of the ν_{τ} charged-current cross section, for the first time with a negligible contamination from ν[over ¯]_{τ}, and the first direct evidence for the ν_{τ} lepton number are also reported.

3.
Phys Rev Lett ; 120(13): 132505, 2018 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-29694189

RESUMO

We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}→1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}→1/2^{+}), E1(1/2^{-}→1/2^{+}), and E1(1/2^{-}→3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.

4.
Microsurgery ; 38(1): 21-25, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27392815

RESUMO

OBJECTIVE: This study seeks to demonstrate the safety of anastomosing free flaps to the common or proper digital artery, and to the volar or dorsal digital vein in soft tissue reconstruction of the hand; as well, as to discuss the advantages of this technique. METHODS: Retrospective review of all patients who underwent free flap reconstruction of the hand in two institutions over a period of 5 years. RESULTS: A total of 29 free flaps (9 great toe pulp, 7 anterolateral thigh, 6 second toe pulp, 4 radial artery perforator, 2 partial medial rectus, 1 lateral arm) in 28 patients met our inclusion criteria. All recipient vessels were the proper or common digital artery and the volar or dorsal digital vein. There was one case of venous congestion that resolved with leeching. There was no partial or total loss of any of the flaps. CONCLUSION: Anastomosing soft tissue free flaps to the common or proper digital artery, and the volar or dorsal digital vein is a safe and effective approach with numerous advantages that should be considered in the reconstruction of soft tissue defects of the hand. © 2016 Wiley Periodicals, Inc. Microsurgery, 38:21-25, 2018.


Assuntos
Artérias/cirurgia , Dedos/irrigação sanguínea , Retalhos de Tecido Biológico/irrigação sanguínea , Traumatismos da Mão/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Veias/cirurgia , Anastomose Cirúrgica , Dedos/cirurgia , Retalhos de Tecido Biológico/transplante , Humanos , Estudos Retrospectivos , Resultado do Tratamento
5.
Pharmazie ; 73(10): 609-612, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30223927

RESUMO

A cross-sectional survey of 358 patients was conducted among type 2 diabetes patients recruited at medical institutions or via an online research company. Medication adherence was measured using the 8-item Morisky Medication Adherence Scale (MMAS-8). Univariate and multivariate regression analyses of glycosylated hemoglobin (HbA1c) were performed in addition to assessing demographic and disease characteristics and MMAS-8. In conclusion, medication adherence as measured by the MMAS-8 score independently contributes to altering the HbA1c level in the range of 1.12 %. The number of medications prescribed and insulin use are also related to HbA1c.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Adesão à Medicação/estatística & dados numéricos , Idoso , Povo Asiático , Glicemia/metabolismo , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/psicologia , Feminino , Hemoglobinas Glicadas/metabolismo , Carga Glicêmica , Humanos , Japão , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Inquéritos e Questionários
7.
Phys Rev Lett ; 115(22): 222501, 2015 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-26650298

RESUMO

The energy spacing between the spin-doublet bound state of _{Λ}^{4}He(1^{+},0^{+}) was determined to be 1406±2±2 keV, by measuring γ rays for the 1^{+}→0^{+} transition with a high efficiency germanium detector array in coincidence with the ^{4}He(K^{-},π^{-})_{Λ}^{4}He reaction at J-PARC. In comparison to the corresponding energy spacing in the mirror hypernucleus _{Λ}^{4}H, the present result clearly indicates the existence of charge symmetry breaking (CSB) in ΛN interaction. By combining the energy spacings with the known ground-state binding energies, it is also found that the CSB effect is large in the 0^{+} ground state but is vanishingly small in the 1^{+} excited state, demonstrating that the ΛN CSB interaction has spin dependence.

8.
Physiol Res ; 70(3): 475-480, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-33982587

RESUMO

Gamma-glutamyltransferase (GGT), a marker of liver disease, has been shown to be associated with increased risk of diabetes and relative insulin secretion deficiency. However, the mechanism of hepatic Ggt regulation has not been explored fully. In this study, we made a concerted effort to understand the mechanism by investigating the effects of acetylation of histones H3 and H4, and bindings of histone acetyltransferases, CREB binding protein (CBP) and p300, at the Ggt promoter on the regulation of the expression of Ggt gene in the livers of streptozotocin (STZ)-induced moderate hypoinsulinemia rat model. The rats treated with STZ showed remarkably higher serum GGT level and hepatic Ggt/GGT expression than the untreated control rats. Furthermore, the acetylation of histones H3 and H4, and the binding of CBP not p300 at the Ggt promoter regions were significantly higher in the livers of STZ rats than those of the control rats. These results suggest that an enhanced hepatic expression of Ggt is associated with increased acetylation of histones H3 and H4 and CBP binding at the Ggt promoter in STZ-induced moderate hypoinsulinemic rats.


Assuntos
Proteína de Ligação a CREB/metabolismo , Diabetes Mellitus Experimental/genética , Proteína p300 Associada a E1A/metabolismo , Histonas/metabolismo , Fígado/enzimologia , gama-Glutamiltransferase/genética , Acetilação , Animais , Diabetes Mellitus Experimental/enzimologia , Histona Acetiltransferases/metabolismo , Masculino , Regiões Promotoras Genéticas , Ratos , Ratos Wistar , gama-Glutamiltransferase/biossíntese
9.
Sci Data ; 8(1): 218, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34385471

RESUMO

The OPERA experiment was designed to discover the vτ appearance in a vµ beam, due to neutrino oscillations. The detector, located in the underground Gran Sasso Laboratory, consisted of a nuclear photographic emulsion/lead target with a mass of about 1.25 kt, complemented by electronic detectors. It was exposed from 2008 to 2012 to the CNGS beam: an almost pure vµ beam with a baseline of 730 km, collecting a total of 1.8·1020 protons on target. The OPERA Collaboration eventually assessed the discovery of vµâ†’vτ oscillations with a statistical significance of 6.1 σ by observing ten vτ CC interaction candidates. These events have been published on the Open Data Portal at CERN. This paper provides a detailed description of the vτ data sample to make it usable by the whole community.

10.
J Chem Phys ; 132(14): 144502, 2010 Apr 14.
Artigo em Inglês | MEDLINE | ID: mdl-20405996

RESUMO

Secondary ion mass spectra have been measured for the first time for a liquid ethanol target bombarded by 2.0 MeV He(+) ions. Positive and negative ion spectra exhibit evidently a series of cluster ions of the forms [(EtOH)(n)H](+) and [(EtOH)(n)-H](-), respectively, in addition to light fragment ions from intact parent molecules. It was found that these cluster ions are produced only from liquid phase ethanol. Both positive and negative secondary ion spectra show similar cluster size distributions with almost the same decay slope. We also present for the first time the cluster ion distribution emitted from the liquid at different liquid temperatures.


Assuntos
Etanol/química , Íons/química , Espectrometria de Massa de Íon Secundário
11.
Gene Ther ; 16(2): 297-302, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18800152

RESUMO

Adenovirus (Ad) serotype 35 (Ad35) vectors have attracted remarkable attention as alternatives to conventional Ad serotype 5 (Ad5) vectors. In a previous study, we showed that intravenously administered Ad35 vectors exhibited a safer profile than Ad5 vectors in cynomolgus monkeys, which ubiquitously express CD46, an Ad35 receptor, in a pattern similar to that in humans. However, the Ad35 vectors poorly transduced the organs. In this study, we examined the transduction properties of Ad35 vectors after local administration into organs of cynomolgus monkeys. The vectors transduced different types of cells depending on the organ. Hepatocytes and microglia were mainly transduced after the vectors were injected into the liver and cerebrum, respectively. Injection of the vectors into the femoral muscle resulted in the transduction of cells that appeared to be fibroblasts and/or macrophages. Conjunctival epithelial cells showed transgene expression following infusion into the vitreous body of the eyeball. Transgene expression was limited to areas around the injection points in most of the organs. In contrast, Ad35 vector-mediated transgene expression was not detected in any of the organs not injected with Ad35 vectors. These results suggest that Ad35 vectors are suitable for gene delivery by direct administration to organs.


Assuntos
Adenoviridae/genética , Vetores Genéticos/genética , Transdução Genética , Adenoviridae/classificação , Administração Tópica , Animais , Regulação da Expressão Gênica/genética , Vetores Genéticos/administração & dosagem , Injeções , Macaca fascicularis , Proteína Cofatora de Membrana/metabolismo , Distribuição Tecidual/genética , Transgenes/genética , beta-Galactosidase/biossíntese , beta-Galactosidase/genética
12.
J Cell Biol ; 115(1): 67-73, 1991 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-1918140

RESUMO

A new microscope technique, termed "W" (double view video) microscopy, enables simultaneous observation of two different images of an object through a single video camera or by eye. The image pair may, for example, be transmission and fluorescence, fluorescence at different wavelengths, or mutually perpendicular components of polarized fluorescence. Any video microscope can be converted into a dual imager by simple insertion of a small optical device. The continuous appearance of the dual image assures the best time resolution in existing and future video microscopes. As an application, orientations of actin protomers in individual, moving actin filaments have been imaged at the video rate. Asymmetric calcium influxes into a cell exposed to an intense electric pulse have also been visualized.


Assuntos
Actinas/metabolismo , Cálcio/metabolismo , Microscopia/instrumentação , Gravação em Vídeo/instrumentação , Citoesqueleto de Actina/ultraestrutura , Animais , Movimento Celular , Eletricidade , Fertilização , Miosinas/fisiologia , Dispositivos Ópticos , Ouriços-do-Mar/embriologia
13.
Eur J Clin Pharmacol ; 65(9): 913-7, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19471911

RESUMO

OBJECTIVE: The chiral pharmacokinetics and pharmacodynamics of ritodrine in patients pregnant with singletons and twins were investigated to determine the optimal use of ritodrine. METHODS: Eight and 20 patients with threatened preterm delivery of singletons and twins, respectively, were infused with ritodrine diastereomers. Serum concentrations of the drug were then measured using a newly developed method of chiral high-performance liquid chromatography. RESULTS: Almost double the dosage of racemic ritodrine was required to prolong pregnancies with twins compared with those of singletons (2.20 +/- 1.06 vs. 1.24 +/- 0.36 microg/min per kilogram; p < 0.0001). The mean ratios of (-)-ritodrine to (+)-ritodrine in singleton and twin pregnancies were 1.17 +/- 0.10 and 1.16 +/- 0.10, respectively. However, the serum concentration and dosage ratio (C/D ratio) of (-)-ritodrine as significantly higher than that of (+)-ritodrine (p < 0.0001), whereas the clearance of (-)-ritodrine was significantly lower than that of (+)-ritodrine (p < 0.0001). A comparison of the gestation period (weeks) and diastereomer clearance did not reveal significant regression in the total analysis of the data obtained from singleton and twin pregnancies. CONCLUSION: These results indicate that the clinical effectiveness of ritodrine diastereomers should be evaluated and that administration guidelines should be established based upon serum concentrations so that ritodrine can be more effectively administered to pregnant patients carrying either singletons or twins.


Assuntos
Agonistas Adrenérgicos beta/farmacocinética , Gravidez Múltipla , Nascimento Prematuro/prevenção & controle , Ritodrina/farmacocinética , Tocolíticos/farmacocinética , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/sangue , Adulto , Análise de Variância , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Gravidez , Análise de Regressão , Ritodrina/administração & dosagem , Ritodrina/sangue , Estereoisomerismo , Tocolíticos/administração & dosagem , Tocolíticos/sangue
14.
Int Endod J ; 42(12): 1104-11, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19912382

RESUMO

AIM: To examine the effects of sonicated bacterial extracts (SBEs) from three related to periapical disease bacteria (Porphyromonas gingivalis, P. endodontalis and F. nucleatum) on the activation of matrix metalloproteinase (MMP-2) and the inactivation of tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2). METHODOLOGY: Each SBE was added to cultures of human periodontal ligament (PL) cells or HT1080 cells and their supernatants were analysed by zymography for MMP-2. Each SBE was added to PL cell cultures, and the amount of TIMP-1 was determined by ELISA. P. gingivalis SBE was incubated with HT1080 cell culture supernatants, and the amounts of TIMP-1 and TIMP-2 were determined by ELISA. Statistical analysis was performed with the paired Student's t-test. RESULTS: In extracts of PL cells that had been incubated in the presence of P. gingivalis SBE, one representing pro-MMP-2 (72 kDa) and a band corresponding to the active MMP-2 (66 kDa) were observed; but in the other extracts it was not detected. When HT1080 cells were treated with P. gingivalis SBE, the pro-MMPs was processed into 86- and 66-kDa fragments, but in the other extracts, the processing did not occur when the other SBEs were used. When PL cells were incubated with the same SBEs, the amount of TIMP-1 was markedly decreased (P < 0.01), but in the other extracts, it was not. The amounts of both TIMP-1 and TIMP-2 were decreased in a dose-dependent manner when HT1080 cell culture supernatant was incubated with P. gingivalis SBE. CONCLUSIONS: These findings suggest that P. gingivalis SBE may cause connective tissue to be destroyed, contributing to the process of periapical disease, by activating pro-MMP-2 as well as by inactivating TIMP-1 and TIMP-2.


Assuntos
Metaloproteinase 2 da Matriz/metabolismo , Periodontite Periapical/microbiologia , Porphyromonas gingivalis/química , Inibidor Tecidual de Metaloproteinase-1/antagonistas & inibidores , Inibidor Tecidual de Metaloproteinase-2/antagonistas & inibidores , Linhagem Celular Tumoral , Células Cultivadas , Meios de Cultivo Condicionados/farmacologia , Ativação Enzimática , Precursores Enzimáticos/metabolismo , Matriz Extracelular/metabolismo , Fusobacterium nucleatum/química , Gelatinases/metabolismo , Humanos , Periodontite Periapical/enzimologia , Ligamento Periodontal/citologia , Porphyromonas endodontalis/química , Sonicação
15.
Meat Sci ; 82(2): 151-4, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20416773

RESUMO

Myosin, one of the major myofibrillar proteins, is insoluble at low and physiological ionic strength and soluble at high ionic strength. In this study, the behavior and morphology of myosin solubilized in a low ionic strength solution containing l-histidine (l-His) was investigated. More than 80% of myosin was solubilized in a low ionic strength solution with dialysis against a solution containing 1mM KCl and 5mM l-His. Transmission electron microscopy with rotary shadowing demonstrated that the rod of myosin in a low ionic strength solution containing l-His is longer than that of myosin in a high ionic strength solution. The elongation of the myosin rod in a low ionic strength solution containing l-His would inhibit the formation of a filament, resulting in the solubilization of myosin.

16.
Physiol Res ; 68(6): 1021-1026, 2019 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-31647302

RESUMO

High levels of fructose induce hypertriglyceridemia, characterized by excessive levels of triglyceride-rich lipoproteins such as very low-density lipoprotein (VLDL); however, the underlying mechanisms are poorly understood. The aim of this short communication was to examine hepatic changes in the expression of genes related to cholesterol metabolism in rats with hypertriglyceridemia induced by high-fructose or high-glucose diets. Rats were fed a 65 % (w/w) glucose diet or a 65 % (w/w) fructose diet for 12 days. Serum levels of triglycerides, total cholesterol, and VLDL+LDL-cholesterol, hepatic levels of triglycerides and cholesterol, and ACAT2 expression at the gene and protein levels were significantly higher in the fructose diet group compared to the glucose diet group. The hepatic levels of Abcg5/8 were lower in the fructose group than in the glucose group. Serum high-density lipoprotein (HDL)-cholesterol and hepatic expression levels of Hmgcr, Ldlr, Acat1, Mttp, Apob, and Cyp7a1 did not differ significantly between groups. These findings suggest that high-fructose diet-induced hypertriglyceridemia is associated with increased hepatic ACAT2 expression.


Assuntos
Frutose/efeitos adversos , Hipertrigliceridemia/induzido quimicamente , Hipertrigliceridemia/metabolismo , Fígado/metabolismo , Esterol O-Aciltransferase/biossíntese , Animais , Frutose/administração & dosagem , Expressão Gênica , Hipertrigliceridemia/genética , Fígado/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Esterol O-Aciltransferase/genética , Esterol O-Aciltransferase 2
17.
Rev Sci Instrum ; 79(5): 053302, 2008 May.
Artigo em Inglês | MEDLINE | ID: mdl-18513062

RESUMO

Reported in this article is the generation of unique polarized x-rays in the sub-MeV region by means of the Thomson backscattering of the Nd:YAG laser photon with a wavelength of 1064 nm on the 150 MeV electron from the microtron accelerator. The maximum energy of the x-ray photons is estimated to be about 400 keV. The total energy of the backscattered x-ray pulse is measured with an imaging plate and a LYSO scintillator. The angular divergence of the x-rays is also measured by using the imaging plate. We confirm that the x-ray beam is polarized according to the laser polarization direction with the Compton scattering method. In addition, we demonstrate the imaging of the object shielded by lead with the generated x-rays.

18.
J Clin Invest ; 64(5): 1213-20, 1979 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-91623

RESUMO

The two-color method originally described by Van Rood et al. (Van Rood, J. J., A. Van Leeuwen, and J. S. Ploen. 1976. Simultaneous detection of two cell populations by two-color fluorescence and application to the recognition of B-cell determinants. Nature (Lond.). 262: 795-797) for the typing of homologous leukocytic antibodies, D-region was used for the detection of antilymphocyte antibody (ALA) in systemic lupus erythematosus. In this method, surface immunoglobulin-bearing cells were identified with fluorescein isothiocyanate-labeled anti-immunoglobulin and nuclei of killed cells were stained with ethidium bromide. Therefore, cell type (T or B) of the target cells can be identified without fractionating them. ALA was detected in 87% of lupus sera and had a preferential reactivity with T cells. Its major immunoglobulin class was shown to be immunoglobulin (Ig)M. The subspecificity of ALA was further analyzed using fractionated T-cell subsets as target cells. When T lymphocytes were separated into Fc receptor-bearing (Tgamma) and lacking (Tgamma[-]) cells, 64% of ALA showed preferential reactivity with Tgamma cells and 14% with Tgamma(-) cells. The remainder had no selective reactivity against Tgamma or Tgamma(-) cells. Tgamma cells were shown to have suppressor activity, whereas Tgamma(-) cells were indicated to contain helper cells. The above finding was in agreement with the observation that treatment of T cells with ALA that preferentially react with Tgamma cells considerably enhanced immunoglobulin synthesis in vitro, whereas treatment of T cells with ALA reactive with Tgamma(-) cells clearly suppressed the formation of immunoglobulins. Treatment of ALA with no selective reactivity showed variable effects on in vitro immunoglobulin synthesis. These results indicate that ALA in lupus have heterogeneous specificities against human T-cell subsets.


Assuntos
Autoanticorpos/isolamento & purificação , Imunoglobulina G/isolamento & purificação , Imunoglobulina M/isolamento & purificação , Lúpus Eritematoso Sistêmico/imunologia , Linfócitos T/imunologia , Especificidade de Anticorpos , Autoanticorpos/biossíntese , Testes Imunológicos de Citotoxicidade/métodos , Etídio , Fluoresceínas , Humanos , Imunoglobulina G/biossíntese , Imunoglobulina M/biossíntese , Técnicas In Vitro , Receptores de Antígenos de Linfócitos B/isolamento & purificação , Coloração e Rotulagem/métodos
19.
J Clin Invest ; 108(5): 749-56, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11544281

RESUMO

We studied the distribution of 5-hydroxytryptamine- (5-HT-) containing cells in the guinea pig pancreas and examined the effects of 5-HT on fluid secretion by interlobular pancreatic ducts. The 5-HT-immunoreactive cells with morphological characteristics of enterochromaffin (EC) cells were scattered throughout the duct system and were enriched in islets of Langerhans. The fluid secretory rate in the isolated interlobular ducts was measured by videomicroscopy. Basolateral applications of 5-HT strongly but reversibly reduced HCO(3)-dependent, as well as secretin- and acetylcholine- (ACh-) stimulated, fluid secretion, whereas 5-HT applied into the lumen had no such effects. Secretin-stimulated fluid secretion could be inhibited by a 5-HT(3) receptor agonist, but not by agonists of the 5-HT(1), 5-HT(2), or 5-HT(4) receptors. Under the stimulation with secretin, 5-HT decreased the intracellular pH (pH(i)) and reduced the rate of pH(i) recovery after acid loading with NH(4)(+), suggesting that 5-HT inhibits the intracellular accumulation of HCO3(-). The elevation of intraductal pressure in vivo reduced secretin-stimulated fluid secretion, an effect that could be attenuated by a 5-HT(3) receptor antagonist. Thus, 5-HT, acting through basolateral 5-HT(3) receptors, strongly inhibits spontaneous, secretin-, and ACh-stimulated fluid secretion by guinea pig pancreatic ducts. 5-HT released from pancreatic ductal EC cells on elevation of the intraductal pressure may regulate fluid secretion of neighboring duct cells in a paracrine fashion.


Assuntos
Ductos Pancreáticos/metabolismo , Suco Pancreático/metabolismo , Serotonina/farmacologia , Acetilcolina/farmacologia , Animais , Bicarbonatos/metabolismo , Cálcio/metabolismo , Técnicas de Cultura , Feminino , Cobaias , Concentração de Íons de Hidrogênio , Imuno-Histoquímica , Modelos Biológicos , Pâncreas/química , Ductos Pancreáticos/efeitos dos fármacos , Pressão , Receptores de Serotonina/fisiologia , Receptores 5-HT3 de Serotonina , Secretina/farmacologia , Serotonina/análise , Serotonina/imunologia , Agonistas do Receptor de Serotonina/farmacologia
20.
Cancer Gene Ther ; 14(11): 894-903, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-17693990

RESUMO

Most advanced solid tumors metastasize to different organs. However, no gene therapy effective for multiple tumors has yet been developed. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting multiple tumors. First, we confirmed that mouse MSCs preferentially migrate to multiple tumors of the lung in the Colon-26 (C-26) lung metastasis model. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF), by an adenoviral vector with an RGD motif. MSCs expressing NK4 (NK4-MSCs) strongly inhibited development of lung metastases in the C-26 lung metastasis model after systemic administration via a tail vein. Treatment with NK4-MSCs significantly prolonged survival of the C-26-tumor-bearing mice by inhibiting tumor-associated angiogenesis and lymphangiogenesis and inducing apoptosis of the tumor cells. MSC-based gene therapy did not induce the severe adverse effects induced by conventional adenoviral vectors. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting multiple lung metastatic tumors.


Assuntos
Terapia Genética/métodos , Fator de Crescimento de Hepatócito/genética , Neoplasias Pulmonares/terapia , Transplante de Células-Tronco Mesenquimais , Adenoviridae/genética , Animais , Apoptose , Células da Medula Óssea/fisiologia , Movimento Celular , Humanos , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/secundário , Linfangiogênese , Células-Tronco Mesenquimais/fisiologia , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/terapia
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