RESUMO
The known I^{π}=8_{1}^{+}, E_{x}=2129-keV isomer in the semimagic nucleus ^{130}Cd_{82} was populated in the projectile fission of a ^{238}U beam at the Radioactive Isotope Beam Factory at RIKEN. The high counting statistics of the accumulated data allowed us to determine the excitation energy, E_{x}=2001.2(7) keV, and half-life, T_{1/2}=57(3) ns, of the I^{π}=6_{1}^{+} state based on γγ coincidence information. Furthermore, the half-life of the 8_{1}^{+} state, T_{1/2}=224(4) ns, was remeasured with high precision. The new experimental information, combined with available data for ^{134}Sn and large-scale shell model calculations, allowed us to extract proton and neutron effective charges for ^{132}Sn, a doubly magic nucleus far-off stability. A comparison to analogous information for ^{100}Sn provides first reliable information regarding the isospin dependence of the isoscalar and isovector effective charges in heavy nuclei.
RESUMO
The level structure of the neutron-rich ^{77}Cu nucleus is investigated through ß-delayed γ-ray spectroscopy at the Radioactive Isotope Beam Factory of the RIKEN Nishina Center. Ions of ^{77}Ni are produced by in-flight fission, separated and identified in the BigRIPS fragment separator, and implanted in the WAS3ABi silicon detector array, surrounded by Ge cluster detectors of the EURICA array. A large number of excited states in ^{77}Cu are identified for the first time by correlating γ rays with the ß decay of ^{77}Ni, and a level scheme is constructed by utilizing their coincidence relationships. The good agreement between large-scale Monte Carlo shell model calculations and experimental results allows for the evaluation of the single-particle structure near ^{78}Ni and suggests a single-particle nature for both the 5/2_{1}^{-} and 3/2_{1}^{-} states in ^{77}Cu, leading to doubly magic ^{78}Ni.
RESUMO
Esophagectomy, one of the most invasive of all gastrointestinal operations, is associated with a high frequency of postoperative complications and in-hospital mortality. The purpose of the present study was to determine whether exposure to the atomic bomb explosion at Hiroshima in 1945 might be a preoperative risk factor for in-hospital mortality after esophagectomy in esophageal cancer patients. We thus reviewed the outcomes of esophagectomy in 31 atomic bomb survivors with esophageal cancer and 96 controls (also with cancer but without atomic bomb exposure). We compared the incidences of postoperative complications and in-hospital mortality. Of the clinicopathological features studied, mean patient age was significantly higher in atomic bomb survivors than in controls. Of the postoperative complications noted, atomic bomb survivors experienced a longer mean period of endotracheal intubation and higher incidences of severe pulmonary complications, severe anastomotic leakage, and surgical site infection. The factors associated with in-hospital mortality were exposure to the atomic bomb explosion, pulmonary comorbidities, and electrocardiographic abnormalities. Multivariate analysis revealed that exposure to the atomic bomb explosion was an independent significant preoperative risk factor for in-hospital mortality. Exposure to the atomic bomb explosion is thus a preoperative risk factor for in-hospital death after esophagectomy to treat esophageal cancer.
Assuntos
Neoplasias Esofágicas/mortalidade , Esofagectomia/mortalidade , Mortalidade Hospitalar , Pneumopatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Cinza Radioativa/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Idoso , Fístula Anastomótica/epidemiologia , Estudos de Casos e Controles , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Armas Nucleares , Fatores de Risco , SobreviventesRESUMO
Interferon γ (IFN-γ), an anticancer agent, is a strong inducer of indoleamine 2,3-dioxygenase 1 (IDO1), which is a tryptophan-metabolizing enzyme involved in the induction of tumor immune tolerance. In this study, we investigated the IDO1 expression in organs after IFN-γ gene transfer to mice. IFN-γ gene transfer greatly increased the mRNA expression of IDO1 in many tissues with the highest in the liver. This upregulation was associated with reduced L-tryptophan levels and increased L-kynurenine levels in serum, indicating that IFN-γ gene transfer increased the IDO activity. Then, Lewis lung carcinoma (LLC) tumor-bearing wild-type and IDO1-knockout (IDO1 KO) mice were used to investigate the effects of IDO1 on the antitumor activity of IFN-γ. IFN-γ gene transfer significantly retarded the tumor growth in both strains without any significant difference in tumor size between the two groups. By contrast, the IDO1 activity was increased only in the wild-type mice by IFN-γ gene transfer, suggesting that cells other than LLC cells, such as tumor stromal cells, are the major contributors of IDO1 expression in LLC tumor. Taken together, these results imply that IFN-γ gene transfer mediated IDO1 upregulation in cells other than LLC cells has hardly any effect on the antitumor activity of IFN-γ.
Assuntos
Carcinoma Pulmonar de Lewis/terapia , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Interferon gama/sangue , Interferon gama/genética , Fígado/metabolismo , Animais , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/patologia , Regulação Neoplásica da Expressão Gênica , Técnicas de Inativação de Genes , Terapia Genética , Vetores Genéticos/administração & dosagem , Rim , Cinurenina/sangue , Pulmão , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Plasmídeos/genética , Baço , Triptofano/sangue , Células Tumorais CultivadasRESUMO
The half-lives of 20 neutron-rich nuclei with Z=27-30 have been measured at the RIBF, including five new half-lives of (76)Co(21.7(-4.9)(+6.5) ms), (77)Co(13.0(-4.3)(+7.2) ms), (79)Ni(43.0(-7.5)(+8.6) ms), (80)Ni(23.9(-17.2)(+26.0) ms), and (81)Cu(73.2 ± 6.8 ms). In addition, the half-lives of (73-75)Co, (74-78)Ni, (78-80)Cu, and (80-82)Zn were determined with higher precision than previous works. Based on these new results, a systematic study of the ß-decay half-lives has been carried out, which suggests a sizable magicity for both the proton number Z = 28 and the neutron number N=50 in (78)Ni.
RESUMO
A low-lying state in 131In82, the one-proton hole nucleus with respect to double magic 132Sn, was observed by its γ decay to the Iπ=1/2- ß-emitting isomer. We identify the new state at an excitation energy of Ex=1353 keV, which was populated both in the ß decay of 131Cd83 and after ß-delayed neutron emission from 132Cd84, as the previously unknown πp3/2 single-hole state with respect to the 132Sn core. Exploiting this crucial new experimental information, shell-model calculations were performed to study the structure of experimentally inaccessible N=82 isotones below 132Sn. The results evidence a surprising absence of proton subshell closures along the chain of N=82 isotones. The consequences of this finding for the evolution of the N=82 shell gap along the r-process path are discussed.
RESUMO
Delayed γ-ray cascades, originating from the decay of (6âº) isomeric states, in the very neutron-rich, semimagic isotopes (136,138)Sn have been observed following the projectile fission of a ²³8U beam at RIBF, RIKEN. The wave functions of these isomeric states are proposed to be predominantly a fully aligned pair of f(7/2) neutrons. Shell-model calculations, performed using a realistic effective interaction, reproduce well the energies of the excited states of these nuclei and the measured transition rates, with the exception of the B(E2;6âºâ4âº) rate of ¹³6Sn, which deviates from a simple seniority scheme. Empirically reducing the νf(7/2)(2) orbit matrix elements produces a 41⺠state with almost equal seniority 2 and 4 components, correctly reproducing the experimental B(E2;6âºâ4âº) rate of ¹³6Sn. These data provide a key benchmark for shell-model interactions far from stability.
RESUMO
The unbound excited states of the neutron drip-line isotope 24O have been investigated via the 24O(p,p')23O + n reaction in inverse kinematics at a beam energy of 62 MeV/nucleon. The decay energy spectrum of 24O* was reconstructed from the momenta of 23O and the neutron. The spin parity of the first excited state, observed at E(x) = 4.65±0.14 MeV, was determined to be J(π) = 2+ from the angular distribution of the cross section. Higher-lying states were also observed. The quadrupole transition parameter ß2 of the 2(1)+ state was deduced, for the first time, to be 0.15±0.04. The relatively high excitation energy and small ß2 value are indicative of the N = 16 shell closure in 24O.
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The ß-decay half-lives of 38 neutron-rich isotopes from (36)Kr to (43)Tc have been measured; the half-lives of (100)Kr, (103-105)Sr, (106-108)Y, (108-110)Zr, (111,112)Nb, (112-115)Mo, and (116,117)Tc are reported here. The results when compared with previous standard models indicate an overestimation in the predicted half-lives by a factor of 2 or more in the A≈110 region. A revised model based on the second generation gross theory of ß decay better predicts the measured half-lives and suggests a more rapid flow of the rapid neutron-capture process (r-matter flow) through this region than previously predicted.
RESUMO
The low-lying states in ¹°6Zr and ¹°8Zr have been investigated by means of ß-γ and isomer spectroscopy at the radioactive isotope beam factory (RIBF), respectively. A new isomer with a half-life of 620 ± 150 ns has been identified in ¹°8Zr. For the sequence of even-even Zr isotopes, the excitation energies of the first 2⺠states reach a minimum at N = 64 and gradually increase as the neutron number increases up to N = 68, suggesting a deformed subshell closure at N = 64. The deformed ground state of ¹°8Zr indicates that a spherical subshell gap predicted at N = 70 is not large enough to change the ground state of ¹°8Zr to the spherical shape. The possibility of a tetrahedral shape isomer in ¹°8Zr is also discussed.
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BACKGROUND: Gastrin has a role in gastrointestinal (GI) malignancy. This study provides pre-clinical evaluation of a novel, orally-active gastrin/cholecystokinin-2 receptor (CCK-2R) antagonist, Z-360. METHODS: (125)I gastrin-17 (G17) displacement and G17-stimulated calcium assays were used in classical CCK-2R-transfected cell lines. Akt phosphorylation was assessed by Western blotting. Z-360 efficacy in vivo was evaluated in three human xenograft models, and microvessel density and apoptosis in these models were investigated by immunohistochemistry. RESULTS: Z-360 inhibited (125)I G17 binding to cells expressing CCK-2R, and G17-stimulated signalling. Reduced Akt phosphorylation in an oesophageal cell-line treated with Z-360 was reversed by co-treatment with G17. Z-360 increased survival in a gastric ascites model (p=0.011) and decreased tumour growth in a hepatic metastasis model (81%, p=0.02). In an orthotopic pancreatic model, Z-360 combined with gemcitabine decreased final tumour weight compared to single agents (84%, p=0.002) and there was increased apoptosis and decreased microvessel density in ex vivo tumour tissue. CONCLUSIONS: These results show that the orally-active CCK-2R antagonist, Z-360 has high sub-nM affinity for classical CCK-2R, is well tolerated in vivo and exerts an anti-tumour effect.
Assuntos
Benzodiazepinonas/química , Benzodiazepinonas/farmacologia , Neoplasias Gastrointestinais/tratamento farmacológico , Receptor de Colecistocinina B/antagonistas & inibidores , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Estrutura MolecularAssuntos
Infecções Estafilocócicas , Cálculos Urinários , Infecções Urinárias , Urolitíase , Humanos , Staphylococcus saprophyticus , Infecções Urinárias/complicações , Infecções Urinárias/tratamento farmacológico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/tratamento farmacológicoRESUMO
To clarify the physiological role of placental corticotropin-releasing hormone (CRH), we measured plasma CRH, ACTH, and cortisol throughout pregnancy. Cerebrospinal fluid (CSF) CRH levels and ACTH responsiveness to synthetic CRH were also quantified in pregnant and nonpregnant women. Maternal plasma CRH levels, which increased progressively during pregnancy, correlated well with both ACTH and cortisol in early labor, delivery, and postpartum samples, and also with cortisol levels in samples before labor. CSF CRH levels in term pregnant women did not differ from those of nonpregnant women. CRH infusion that attained similar plasma CRH levels to those found in late pregnancy elicited significant ACTH release in vivo and regular CRH test provoked normal ACTH response during early pregnancy but no response during late pregnancy. We concluded that: (a) maternal pituitary-adrenal axis correlates well with plasma CRH levels, which are high enough to provoke ACTH release from maternal pituitary; (b) hypothalamic CRH secretion in term pregnant women is not exaggerated; and (c) maternal pituitary is responsive to synthetic CRH in early but not late pregnancy, suggesting that maternal pituitary-adrenal axis is already activated by high circulating CRH. Placental CRH may be an important stimulator of the maternal pituitary-adrenal axis during pregnancy.
Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Hormônio Liberador da Corticotropina/fisiologia , Hipófise/metabolismo , Placenta/fisiologia , Hormônio Adrenocorticotrópico/sangue , Adulto , Hormônio Liberador da Corticotropina/sangue , Feminino , Humanos , Hidrocortisona/sangue , Trabalho de Parto/sangue , Período Pós-Parto/sangue , GravidezRESUMO
Human antiidiotypic antibodies to anti-DNA antibodies can be separated into at least two categories based on their binding to anti-DNA, antiidiotypic antibodies, and antigens. One type was found mainly in inactive stage of SLE. The antiidiotypic antibodies appear to be directed towards idiotype (Id) determinants in the antigen-binding sites of anti-DNA antibodies. Antibody from patient T.K. acted like a mirror image of anti-single-stranded DNA antibodies, O-81, as determined by a competitive inhibition RIA. Antibodies from patient S.U. also seemed to be Ab 2 beta and Ab 2 gamma to anti-double-stranded(ds) DNA antibodies, NE-1. Most of normal subjects, on the other hand, had antibodies that bound to the human monoclonal anti-ds DNA antibodies, NE-1, NE-13, 7F4, and O-81. The Id-anti-Id interaction was not inhibited by the addition of DNA. Thus, normal subjects had Ab2 alpha activity that recognizes Id determinants in the framework region common among anti-DNA antibodies, whereas antiidiotypic antibodies in most SLE sera appear to show Ab 2 beta and Ab 2 gamma activity. The results provide evidence that the Id network system regulates immunological tolerance to DNA in humans.
Assuntos
Anticorpos Antinucleares/análise , Especificidade de Anticorpos , Autoanticorpos/análise , Sítios de Ligação de Anticorpos , DNA/imunologia , Idiótipos de Imunoglobulinas/imunologia , Anticorpos Monoclonais/análise , Autoanticorpos/isolamento & purificação , Autoanticorpos/fisiologia , Ligação Competitiva , Feminino , Humanos , Lúpus Eritematoso Sistêmico/imunologia , MasculinoRESUMO
Serum osteocalcin was measured in patients with idiopathic hypoparathyroidism or pseudohypoparathyroidism, before or during the treatment with active vitamin D3 (1,25(OH)2D3 or 1 alpha OHD3). Serum osteocalcin and plasma 1,25(OH)2D were decreased in 11 patients with idiopathic hypoparathyroidism before treatment (2.8 +/- 1.27 ng/ml, P less than 0.001 and 14.3 +/- 4.27 pg/ml, P less than 0.001, respectively). In 24 patients with idiopathic hypoparathyroidism during the treatment, serum osteocalcin and plasma 1,25(OH)2D were within the normal range (4.5 +/- 0.74 ng/ml and 25.7 +/- 5.69 pg/ml, respectively). In five patients with pseudohypoparathyroidism before treatment, plasma 1,25(OH)2D was decreased (15.6 +/- 10.6 pg/ml, P less than 0.001) but serum osteocalcin was normal (7.8 +/- 1.66 ng/ml). In nine patients with pseudohypoparathyroidism during the treatment with active vitamin D3, serum osteocalcin and plasma 1,25(OH)2D were normal (6.8 +/- 1.47 ng/ml and 27.2 +/- 6.0 pg/ml, respectively). Serum PTH in pseudohypoparathyroidism was increased before treatment (0.70 +/- 0.34 ng/ml, P less than 0.05) and was normal during the treatment (0.50 +/- 0.13 ng/ml). In idiopathic hypoparathyroidism, the active vitamin D3 increased serum osteocalcin without PTH. In pseudohypoparathyroidism, PTH may increase serum osteocalcin or modulate the effect of active vitamin D3 on serum osteocalcin.
Assuntos
Proteínas de Ligação ao Cálcio/sangue , Colecalciferol/uso terapêutico , Hipoparatireoidismo/sangue , Hormônio Paratireóideo/uso terapêutico , Pseudo-Hipoparatireoidismo/sangue , Adulto , Calcitriol/sangue , Cálcio/sangue , Feminino , Humanos , Hipoparatireoidismo/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Osteocalcina , Hormônio Paratireóideo/sangue , Fósforo/sangue , Pseudo-Hipoparatireoidismo/tratamento farmacológicoRESUMO
The mechanisms of Na+ transport across cell membranes were investigated in the in vitro microperfused hamster ascending thin limb (ATL) of Henle's loop using a fluorescent Na+ indicator sodium-binding benzofuran isophthalate. The intracellular Na+ concentration ([Na+]i) of the ATL cells was 17.1 +/- 1.7 mM (n = 22) when the ATL was microperfused in vitro with Hepes-buffered solution containing 204 mM Na+. Elimination of metabolites such as glucose and alanine from the basolateral solution increased [Na+]i. Applying either 5 mM cyanide or 5 mM iodoacetic acid to the bath also increased [Na+]i. The elimination of K+ and the addition of 10(-4) M ouabain in the bath increased [Na+]i by 25.0 +/- 5.0 mM (n = 5) in 3 min and by 10.7 +/- 2.4 mM (n = 4), respectively. The elimination of luminal and basolateral Na+ resulted in a decrease in [Na+]i, indicating Na+ permeability of both the luminal and basolateral cell membranes. The luminal Na+ permeability was not affected by furosemide. The presence of luminal Na+ permeability and the basolateral Na+/K+ ATPase suggests the presence of net active reabsorption of Na+, which is not a physiologically important amount, in our estimation.
Assuntos
Alça do Néfron/metabolismo , ATPase Trocadora de Sódio-Potássio/metabolismo , Sódio/metabolismo , Alanina/farmacologia , Anfotericina B/farmacologia , Animais , Transporte Biológico Ativo/efeitos dos fármacos , Cricetinae , Cianetos/farmacologia , Glucose/farmacologia , Técnicas In Vitro , Iodoacetatos/farmacologia , Ácido Iodoacético , Túbulos Renais/efeitos dos fármacos , Túbulos Renais/metabolismo , Cinética , Masculino , Mesocricetus , Modelos Biológicos , PerfusãoRESUMO
A new strategy was shown for the manipulation of autoantibody production in humans. Antiidiotypic antibody to human anti-DNA autoantibody was conjugated with neocarzinostatin (NCS), a cytotoxic agent, by using N-succimidyl 3-(2-pyridyldithio) propionate as a coupling agent. Human B cell clones, which produce anti-DNA autoantibodies, were killed by in vitro treatment with antiidiotype (Id)-NCS conjugates, while clones expressing an Id with irrelevant specificity were unaffected. These results indicate that treatment with anti-Id-NCS conjugates can act as a potent and specific means of generating immunosuppression of autoantibody production. This approach will have a significant advantage in aborting clones that are not effectively suppressed for the autoantibodies by anti-Id antibodies alone, and will result in a potential therapeutic treatment for systemic lupus erythematosus.
Assuntos
Antibióticos Antineoplásicos/metabolismo , Anticorpos Anti-Idiotípicos/imunologia , Autoanticorpos/isolamento & purificação , DNA/imunologia , Idiótipos de Imunoglobulinas/imunologia , Zinostatina/metabolismo , Anticorpos Monoclonais , Linfócitos B/metabolismo , Células Cultivadas , Citometria de Fluxo , Fluorescência , HumanosRESUMO
-81 and NE-1 idiotypes (Id) of human nephritogenic anti-DNA antibodies are interspecies Id expressed also in NZB/W F1 mice. We tried to manipulate the synthesis of spontaneously occurring anti-DNA antibody using monoclonal anti-Id antibodies (D1E2 and 1F5) conjugated with a cytotoxic agent, neocarzinostatin (NCS). In vivo administration of anti-Id antibodies conjugated with NCS brought about an improvement in the survival rate of female NZB/W F1 mice. It also caused a retardation of development of lupus nephritis and decreased the numbers of anti-DNA-producing cells. The suppression of anti-DNA antibody synthesis was specific and Id-mediated. The results indicate that the use of a limited number of anti-Id antibodies in combination with a cytotoxic agent may be applicable therapeutically to autoimmune diseases.
Assuntos
Antibióticos Antineoplásicos/uso terapêutico , Anticorpos Anti-Idiotípicos/uso terapêutico , Anticorpos Antinucleares/imunologia , Doenças Autoimunes/terapia , Imunotoxinas/uso terapêutico , Zinostatina/uso terapêutico , Animais , DNA de Cadeia Simples/imunologia , Imunoterapia , Nefropatias/patologia , Nefropatias/terapia , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Camundongos , Camundongos Endogâmicos NZB , Proteinúria/terapia , Baço/imunologiaRESUMO
BACKGROUND: Over the past few decades, advanced imaging modalities with excellent diagnostic capabilities have emerged. The aim of the present position statement was to systematically review existing literature to define Canadian recommendations for their clinical use. METHODS: A systematic literature review to 2005 was conducted for positron emission tomography (PET), multidetector computed tomographic angiography and magnetic resonance imaging (MRI) in ischemic heart disease. Papers that met the criteria were reviewed for accuracy, prognosis data and study quality. Recommendations were presented to primary and secondary panels of experts, and consensus was achieved. RESULTS: Indications for PET include detection of coronary artery disease (CAD) with perfusion imaging, and defining viability using fluorodeoxyglucose to determine left ventricular function recovery and/or prognosis after revascularization (class I). Detection of CAD in patients, vessel segments and grafts using computed tomographic angiography was considered class IIa at the time of the literature review. Dobutamine MRI is class I for CAD detection and, along with late gadolinium enhancement MRI, class I for viability detection to predict left ventricular function recovery. Imaging must be performed at institutions and interpreted by physicians with adequate experience and training. CONCLUSIONS: Cardiac imaging using advanced modalities (PET, multidetector computed tomographic angiography and MRI) is useful for CAD detection, viability definition and, in some cases, prognosis. These modalities complement the more widespread single photon emission computed tomography and echocardiography. Given the rapid evolution of technology, initial guidelines for clinical use will require regular updates. Evaluation of their integration in clinical practice should be ongoing; optimal use will require proper training. A joint effort among specialties is recommended to achieve these goals.
Assuntos
Angiografia Coronária , Imageamento por Ressonância Magnética , Isquemia Miocárdica/diagnóstico , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , HumanosRESUMO
Frequent loss of Fhit expression has been reported in human gastrointestinal tract carcinomas; opinions remain divergent regarding Fhit expression in colorectal carcinoma (CRC) cases. Recent studies have suggested that Fhit inactivation can be a consequence of defects in mismatch repair proteins, particularly Msh2. Immunohistochemical analysis of Msh2 and Fhit protein expression in 62 CRC cases was performed. The same CRCs were examined for allelic loss at three loci within or near FHIT and for FHIT mRNA expression by reverse transcription-PCR amplification. Half of the 62 CRC cases were positive for Fhit protein. Fhit protein loss correlated significantly with the progression of carcinoma (P < 0.01) as well as lymph node metastasis (P < 0.05). Loss of Msh2 protein correlated significantly with loss of Fhit protein (P < 0.05) and FHIT locus alteration (P < 0.05). Loss of Fhit protein expression was observed in 50% of sporadic CRCs and was significantly more frequent in more advanced cancers. Interestingly, alteration of the fragile FHIT locus and loss of Fhit protein expression were significantly more frequent in sporadic CRCs lacking Msh2 protein, suggesting that this mismatch repair protein may be important in maintaining the integrity of the common fragile locus within the FHIT gene.