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1.
Public Health ; 181: 114-118, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32006854

RESUMO

OBJECTIVES: With the progress of aging, fall injuries have become a global public health issue. This research was conducted to describe in detail situations of injury occurrence among the elderly by distinguishing between falls from heights and ground-level falls. We assume that different fall mechanisms occur in different situations and result in a wide range of consequences. STUDY DESIGN: This is a registry-based descriptive study. METHODS: The analysis included 55,126 patients with fall injuries, aged 65 years and more, having an Injury Severity Score (ISS) ≧9, and registered in a trauma registry in Japan between 2004 and 2015. We described patients' distribution in terms of age, severity, outcome, season, time, and injured body parts by gender and fall mechanisms. RESULTS: Falls from heights (n = 15,748) were more common among men and those younger than 75 years. Ground-level falls (n = 39,378) were more common among women and those older than 75 years. The ISS was high in men and for those who fell from heights. Falls from heights were common in autumn, whereas ground-level falls were common in winter. Both mechanisms occurred frequently during the daytime. The head and lower extremities were the most commonly injured parts for those who fell from heights and ground-level falls, respectively. Injuries to the head, chest, spine, upper extremities, and pelvis were common among those who fell from heights. Injuries to the lower extremities were common in ground-level fallers. Among those who fell from heights, women had more frequent lower extremity injuries than did men. Among ground-level fallers, men had more frequent head injuries than did women. The highest case-fatality rate was recorded for abdominal injuries among those who fell from heights and head injuries among ground-level fallers. In both mechanisms of injury, the case-fatality rate of limbs was the lowest. CONCLUSIONS: Our study showed different patterns between falls from heights and ground-level falls, whereas previous studies rarely distinguished between these two fall mechanisms.


Assuntos
Acidentes por Quedas/estatística & dados numéricos , Envelhecimento , Sistema de Registros , Ferimentos e Lesões/mortalidade , Traumatismos Abdominais/etiologia , Traumatismos Abdominais/mortalidade , Acidentes por Quedas/mortalidade , Idoso , Idoso de 80 Anos ou mais , Traumatismos Craniocerebrais/mortalidade , Feminino , Fraturas Ósseas/etiologia , Fraturas Ósseas/mortalidade , Geriatria , Humanos , Escala de Gravidade do Ferimento , Japão/epidemiologia , Masculino , Estudos Retrospectivos , Estações do Ano , Ferimentos e Lesões/etiologia
3.
Public Health ; 141: 74-79, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27932019

RESUMO

OBJECTIVES: Road traffic injuries, particularly pedestrian injuries, are a major health issue among children worldwide. The present study quantitatively analyzed the time trends of child pedestrian injuries in Japan from 1975 to 2013 by age. STUDY DESIGN: Time trend analysis of nationally aggregated data. METHODS: We analyzed police data on pedestrian injuries requiring medical treatment among children aged 0-15 years occurring between 1975 and 2013. To quantify the time trends of pedestrian injury morbidity rates and to identify change-points in the trends, joinpoint regression analysis was applied by age group. Children were categorized into the age groups of 0-3, 4-6, 7-9, 10-12, and 13-15 years old. RESULTS: Preschool children aged 0-6 years old showed continuous declining trends throughout the study period; these declining trends accelerated in the 2000s. School-age children aged 7-15 years old showed minimal changes from the early 1970s to the 1990s; of this age group, children aged 7-12 years old showed slight but significant declining trends in the first half and increasing trends in the latter half of this period. Children aged 7-15 years old showed declining trends in the 2000s. Despite the consistent declining trends among all age groups in the 2000s, the younger age groups showed steeper declines during this period. CONCLUSIONS: The declining trends in all age groups in the 2000s may reflect the improved traffic environments in Japan although the environmental approaches are not yet sufficiently adopted yielding modest effects. The continuing contrast between preschool and school-age children may reflect different behaviour changes by age such as more restricted outdoor activities among young children.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Pedestres/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Japão/epidemiologia , Morbidade/tendências , Estudos Retrospectivos
4.
Br J Cancer ; 111(3): 506-14, 2014 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-24874475

RESUMO

BACKGROUND: Cancer stem cells (CSCs) are responsible for treatment failure. However, their identification and roles in resistance are not well established in head and neck squamous cell carcinoma (HNSCC). METHODS: Three HNSCC cell lines (FaDu, Detroit562 and BICR6) were treated with cisplatin or radiation. Cell surface antigens were analysed by LyoPlate, a novel cell surface antigen array. The expression levels of antigens highly expressed after treatments were further compared between cisplatin-resistant Detroit562 cells and its parental line. Association of the candidate antigen with CSCs properties, namely sphere formation and in vivo tumourigenicity, was also examined. RESULTS: CD10, CD15s, CD146 and CD282 were upregulated across the treated cell lines, while the increased expression of CD10 was prominent in the cisplatin-resistant cell line. Isolation mediated by FACS revealed that the CD10-positive subpopulation was more refractory to cisplatin, fluorouracil and radiation than the CD10-negative subpopulation. It also showed an increased ability to form spheres in vitro and tumours in vivo. Moreover, the CD10-positive subpopulation expressed the CSC marker OCT3/4 at a higher level than that in the CD10-negative subpopulation. CONCLUSIONS: CD10 is associated with therapeutic resistance and CSC-like properties of HNSCC. CD10 may serve as a target molecule in the treatment of refractory HNSCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias de Cabeça e Pescoço/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neprilisina/metabolismo , Animais , Antineoplásicos/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Pontos de Checagem da Fase G1 do Ciclo Celular , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/efeitos da radiação , Fator 3 de Transcrição de Octâmero/genética , Fator 3 de Transcrição de Octâmero/metabolismo , Tolerância a Radiação , Carcinoma de Células Escamosas de Cabeça e Pescoço , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
5.
Phys Chem Chem Phys ; 13(3): 1189-200, 2011 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-21076765

RESUMO

A transmission electron microscope was used to characterize a powder form of hexagonally-ordered mesoporous silica material. The structural symmetry built into this amorphous material allowed one to obtain three characteristic images, i.e. a hexagonal honey-comb structure and wide/narrow parallel lines. These images were found to originate primarily from phase contrast, which changed sensitively with defocusing. To further understand the contrast behaviour of these images, an analytical form of the defocus contrast theory was developed and applied to the simulation of the characteristic wide/narrow parallel line images. The simulation was found to be in good qualitative agreement with experiments, where changes in focus conditions and specimen thickness were predicted to alter the contrast in the resulting parallel-line type images.

6.
Science ; 253(5018): 427-9, 1991 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-17746398

RESUMO

Bulk YBa(2)Cu(3)O(7-delta) superconductors, under certain processing conditions such as melt texturing, exhibit a very high dislocation density of 10(9) to 10(10) per square centimeter. In addition, the density of low-angle grain boundaries in such samples can be significantly increased (to less than 700-nanometer spacing) through a dispersion of submicrometer-sized Y(2)BaCuO(5) inclusions. These defect densities are comparable to those in high critical current thin films as revealed through scanning tunneling microscopy, and yet the critical current densities in the bulk materials (at 77 kelvin and a field of 1 tesla for example) remain at a 10(4) amperes per square centimeter level, about two orders of magnitude lower than in thin films. The results imply that these defect density levels are not significant enough to explain the difference in flux pinning strength between the thin film and bulk materials. The observation of spiral-like growth of the superconductor phase in bulk Y-Ba-Cu-O is also reported.

7.
Inj Prev ; 15(2): 80-6, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19346419

RESUMO

OBJECTIVE: To explore the effects of working conditions of private-bus drivers on bus crashes in Kandy district, Sri Lanka. METHODS: A case-control study was carried out from August to September 2006. All private-bus drivers registered in Kandy district and involved in crashes reported to the police between November 2005 and April 2006 (n = 63) were selected as cases. Two control groups were included: private-bus drivers working on the same routes as the case drivers (n = 90) and private-bus drivers selected randomly from other routes of the district (n = 111). Data were collected using an anonymous self-administered questionnaire. Associations between working conditions and crashes were analysed using logistic regression. RESULTS: A strong association was observed between drivers' disagreements about working hours and bus crashes (matched controls, adjusted odds ratio (AOR) 5.98, 95% CI 1.02 to 34.90; unmatched controls, AOR 18.74, 95% CI 2.00 to 175.84). A significant association was also observed between low salaries (

Assuntos
Acidentes de Trabalho/estatística & dados numéricos , Acidentes de Trânsito/estatística & dados numéricos , Condução de Veículo/estatística & dados numéricos , Tolerância ao Trabalho Programado , Adulto , Idoso , Algoritmos , Estudos de Casos e Controles , Humanos , Pessoa de Meia-Idade , Setor Privado , Fatores de Risco , Salários e Benefícios , Sri Lanka/epidemiologia , Adulto Jovem
8.
Inj Prev ; 14(2): 106-12, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18388231

RESUMO

BACKGROUND: To address the increasing number of injuries in developing countries, the World Health Organization (WHO) encourages the establishment of hospital-based surveillance systems and systematic data collection. Although a computerized system is preferable in terms of efficiency, many developing countries have difficulty accessing the appropriate resources. OBJECTIVES: To assess the possibility of comparing and sharing data among countries, and then to discuss the possibility of establishing an international data management system through the internet. METHODS: A point-by-point comparison of data directories from injury surveillance systems in Thailand, Cambodia, Sri Lanka, and Japan was conducted using guidelines published by WHO as the standard. RESULTS: Thailand, Cambodia, and Sri Lanka used data items that are comparable to each other and to WHO guidelines, with few, readily amenable, differences. The Japanese system used quite different data items. CONCLUSIONS: Data comparability suggests the feasibility of a global data management system that can store data from various countries. Such a system, if made accessible over the internet, would benefit resource-constrained countries by providing them with a ready-made framework to implement a surveillance system at low cost.


Assuntos
Países em Desenvolvimento , Cooperação Internacional , Ferimentos e Lesões/epidemiologia , Ásia/epidemiologia , Bases de Dados Factuais/normas , Métodos Epidemiológicos , Humanos , Internet , Ferimentos e Lesões/diagnóstico , Ferimentos e Lesões/etiologia
9.
Anticancer Res ; 27(4C): 2673-7, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17695431

RESUMO

UNLABELLED: The aim of this study was to determine the recommended dose of irinotecan in combination with the fixed dose of oral UFT as first-line therapy in patients with advanced or recurrent colorectal cancer, and to evaluate the response rate and overall survival as a phase II study. PATIENTS AND METHODS: Thirteen patients were recruited into a phase I trial. Four doses of irinotecan ranging from 60 to 150 mg/m2/day were administered intravenously on day 1 and day 16 in combination with UFT given orally from day 2 to day 15. In a phase II study, 53 patients received at least one cycle of this therapy. RESULTS: The recommended dose of this combination was determined as irinotecan 120 mg/m2/day and UFT 400 mg/m2/day. Dose-limiting toxicities were neutropenia and prolonged leucopenia. On an intent-to-treat analysis, the response rate in the phase II study was 24.5% (95% confidence interval 13.8% to 38.2%). The median overall survival time was 20.3 months (95% confidence interval, 15.0-22.8 months). Out of 20 patients with stable disease, 17 who received more than 4 cycles of the regimen lived longer than the other 3 patients who received fewer than 3 cycles (p = 0.0353). Hematological adverse events were mainly grade 3/4 neutropenia observed in 6 out of 53 patients. Grade 3 non-hematological toxicities, such as diarrhea, anorexia, nausea/vomiting and alopecia were observed in 6 patients. CONCLUSION: Irinotecan combined with oral UFT was effective and well-tolerated. This regimen may be considered as a first-line therapy for advanced or metastatic colorectal cancer and may result in fairly long survival, even for patients with stable disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/patologia , Esquema de Medicação , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Tegafur/administração & dosagem , Tegafur/efeitos adversos , Uracila/administração & dosagem , Uracila/efeitos adversos
10.
Accid Anal Prev ; 39(2): 356-63, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17034750

RESUMO

To assess the information on safety belt use for pregnant women and infants in maternity and baby magazines, we reviewed 2003 issues of the three top-selling monthly baby and maternity magazines. Articles on safety belt use during pregnancy and child safety seat (CSS) use for infants, and advertisements of the CSS, automobiles, or CSS-related products were examined for their informational content. Of the 9418 pages in the maternity magazines, 46 pages were on infants, 16 pages on pregnant women and 162 pages displayed advertisements. Of the 9750 pages in the baby magazines, 34 pages of articles addressed CSS use; no articles addressed the issue of pregnant women; 83 pages were advertisements. Although the magazines showed accurate information in general; its amount was not sufficient, and little specific information on appropriate use and selection of a CSS was seen. Some information was misleading and even incorrect: specifically related to when to start using a forward-facing seat, what products are attachable to the CSS, and the reuse of a CSS. Greater amounts and accuracy of safety information in these magazines would help pregnant women and parents acquire important safety knowledge that healthcare providers are falling short of providing in Japan.


Assuntos
Equipamentos para Lactente , Disseminação de Informação , Publicações Periódicas como Assunto , Cintos de Segurança , Adulto , Feminino , Humanos , Lactente , Segurança
11.
Neotrop Entomol ; 46(3): 302-309, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28063143

RESUMO

A new satyrine species in the subtribe Euptychiina, Euptychia atlantica Nakahara & Freitas sp. nov., is described from the Atlantic coastal forest of Brazil. Based on the existing museum specimens, E. atlantica sp. nov. is known from the coastal montane forests of Rio de Janeiro to south Bahia, a unique biogeographical region which is undergoing rapid degradation. Illustrations of adults and their genitalia, as well as a distribution map, are provided herein, in addition to a discussion of the relationships and conservation status of the new species.


Assuntos
Borboletas , Espécies em Perigo de Extinção , Animais , Brasil , Florestas
12.
J Phys Condens Matter ; 29(23): 234002, 2017 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-28430107

RESUMO

We report single crystal preparation, resistivity, and nuclear quadrupole resonance (NQR) measurements for new pressure-induced superconductor CrAs. In the first part, we present the difference between crystals made by different thermal sequences and methods, and show the sample dependence of superconductivity in CrAs. In the latter part, we show NQR data focusing the microscopic electronic state at the phase boundary between the helimagnetic and the paramagnetic phases. They suggest strongly that a quantum critical point is absent on the pressure-temperature phase diagram of CrAs, because of the strong first-order character of the magnetic transition; however, the spin fluctuations are observed in the paramagnetic phase. The close relationship between the spin fluctuations and superconductivity can be seen even in the vicinity of the first-order magnetic transition in CrAs.

13.
Cancer Res ; 56(18): 4142-5, 1996 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-8797582

RESUMO

Variants of dihydrofolate reductase (DHFR), which confer resistance to antifolates, are used as dominant selectable markers in vitro and in vivo and may be useful in the context of gene therapy. To identify improved mutant human DHFRs with increased catalytic efficiency and decreased binding to methotrexate, we constructed by site-directed mutagenesis four variants with substitutions at both Leu22 and Phe31 (i.e., Phe22-Ser31, Tyr22-Ser31, Phe22-Gly31, and Tyr22-Gly31). Antifolate resistance has been observed previously when individual changes are made at these active-site residues. Substrate and antifolate binding properties of these "double" mutants revealed that each have greatly diminished affinity for antifolates (> 10,000-fold) yet only slightly reduced substrate affinity. Comparison of in vitro measured properties with those of single-residue variants indicates that double mutants are indeed significantly superior. This was verified for one of the double mutants that provided high-level methotrexate resistance following retrovirus-mediated gene transfer in NIH3T3 cells.


Assuntos
Antagonistas do Ácido Fólico/farmacologia , Tetra-Hidrofolato Desidrogenase/química , Tetra-Hidrofolato Desidrogenase/metabolismo , Células 3T3 , Animais , Sítios de Ligação , Antagonistas do Ácido Fólico/metabolismo , Variação Genética , Humanos , Cinética , Camundongos , Mutagênese Sítio-Dirigida , Fenilalanina , Mutação Puntual , Reação em Cadeia da Polimerase , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Especificidade por Substrato , Tetra-Hidrofolato Desidrogenase/biossíntese , Tirosina
14.
Neotrop Entomol ; 45(6): 675-691, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27283179

RESUMO

A new genus is described for Neonympha griphe C. Felder & R. Felder, 1867, to contribute toward a revision of the polyphyletic genus Euptychoides Forster, 1964. Based on DNA sequence data, Graphita Nakahara, Marín & Barbosa, gen. nov. is strongly supported as a member of a clade of predominantly southeastern Brazilian taxa, in which it is weakly supported as sister to a well-supported clade containing Pharneuptychia Forster, 1964, Moneuptychia Forster, 1964 and the E. castrensis (Schaus, 1902) species complex. The data show that Graphita griphe comb. nov. is not related to other Euptychoides and not very closely related to any other sampled euptychiines, and thus support the description of this new genus. In addition, we provide morphological illustrations and a distribution map for this taxon based on museum specimens.


Assuntos
Borboletas/classificação , Animais , Brasil , Feminino , Filogenia
15.
J Neuropathol Exp Neurol ; 58(5): 442-50, 1999 May.
Artigo em Inglês | MEDLINE | ID: mdl-10331432

RESUMO

The aims of this study were to clarify the mechanism of cell death by apoptosis in the spinal cord after traumatic injury, and to examine the role of the mitogen-activated protein kinase (MAPK) pathways in the transmission of apoptosis signals. The rat spinal cord, experimentally injured by extradural static weight-compression, was studied by hematoxylin and eosin staining, Nissl-staining, terminal deoxynucleotidyl transferase (TdT) mediated dUTP nick-end labeling (TUNEL) staining, and immunostaining using polyclonal antibodies against Apoptosis Signal-regulating Kinase 1 (ASK1), c-Jun N-terminal kinase (JNK), and p38 MAPK. TUNEL-positive cells were present at all stages studied until 7 days after injury, and percentage positivity for these cells was maximal at 3 days after injury. Electron microscopic analysis revealed the occurrence of apoptosis in both neuronal cells and glial cells. TUNEL-positive glial cells were stained by oligodendrocyte-specific maker. Expression of ASK1 was maximal at 24 h after injury in the gray matter and at 3 days after injury in the white matter. Following the expression of ASK1, activated forms of JNK and p38 were observed in apoptotic cells detected by the TUNEL method. Colocalization of ASK1 and activated JNK or activated p38 was observed in the same cell. These findings suggest the involvement of the stress-activated MAPK pathways including ASK1 in the transmission of apoptosis signals after spinal cord injury.


Assuntos
Apoptose/fisiologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno , Quinases de Proteína Quinase Ativadas por Mitógeno , Proteínas Quinases Ativadas por Mitógeno , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Traumatismos da Medula Espinal/metabolismo , Animais , Anticorpos , Proteínas Quinases Dependentes de Cálcio-Calmodulina/análise , Proteínas Quinases Dependentes de Cálcio-Calmodulina/imunologia , Marcação In Situ das Extremidades Cortadas , MAP Quinase Quinase 4 , MAP Quinase Quinase Quinases , Masculino , Microscopia Eletrônica , Neurônios/citologia , Neurônios/enzimologia , Neurônios/ultraestrutura , Proteínas Quinases/análise , Proteínas Quinases/imunologia , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/imunologia , Ratos , Ratos Wistar , Transdução de Sinais/fisiologia , Proteínas Quinases p38 Ativadas por Mitógeno
16.
Am J Clin Nutr ; 54(2): 414-9, 1991 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-1650127

RESUMO

The proposed mechanisms for the action of dietary fiber (DF) on the glycemic response suggest a nonlinear relationship between glycemic index (GI) and DF content. This relationship was analyzed by using the newly reported total DF (TDF) values, assuming a nonlinear regression curve. The empirical equation obtained was Y = 19.9X-0.322. Similar regression curves were also obtained for soluble DF (SDF) and insoluble DF (IDF). The two regression curves indicated that the correlation coefficient between observed GI and GI calculated from the IDF regression curve (-0.781) was virtually identical to that for SDF (-0.780), but a given content (eg, 5% vs available carbohydrate) of SDF gave a lower GI (39) than did IDF (48). This stronger dependency of GI on SDF suggests a major function of SDF in the TDF hypoglycemic effect. From the regression curve of GI vs TDF, we propose a supplemental GI to predict the glycemic response to foods with no published GI.


Assuntos
Glicemia/metabolismo , Fibras na Dieta/farmacologia , Fibras na Dieta/análise , Análise de Alimentos , Humanos , Análise de Regressão , Solubilidade
17.
Cancer Gene Ther ; 5(3): 144-9, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9622097

RESUMO

We have previously shown that successful gene transfer of a mutated dihydrofolate reductase (DHFR) cDNA confers resistance to methotrexate (MTX) upon infected cells. We constructed a retrovirus vector, DC/SV6S31GPT, which carries both the Escherichia coli xanthine-guanine phosphoribosyltransferase gene and the mutated Serine 31 DHFR gene. Mouse fibroblast NIH3T3 cells infected with DC/SV6S31 GPT are more resistant to MTX than cells infected with DC/SV6S31, which carries the Serine 31 DHFR and the neomycin resistance gene cDNA. The mechanism of this augmented resistance is the increased salvaging of purines due to expression of xanthine-guanine phosphoribosyltransferase, as the augmentation does not occur when dialyzed serum, containing little xanthine or guanine, is used for cytotoxicity assays. These results indicate that coexpression of a metabolically related gene can potentiate the resistance carried by a drug resistance gene. This vector may be useful in clinical gene therapy to protect bone marrow from the toxic effects of MTX.


Assuntos
Antimetabólitos Antineoplásicos/farmacologia , Técnicas de Transferência de Genes , Metotrexato/farmacologia , Pentosiltransferases/genética , Purinas/metabolismo , Tetra-Hidrofolato Desidrogenase/genética , Células 3T3 , Animais , Sequência de Bases , Northern Blotting , Células da Medula Óssea , Primers do DNA , Resistencia a Medicamentos Antineoplásicos , Vetores Genéticos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Retroviridae/genética , Tioguanina/farmacologia
18.
Cancer Gene Ther ; 7(6): 910-9, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10880023

RESUMO

We previously reported the protection of hematopoietic cells from methotrexate (MTX) toxicity using an N2-based double copy vector containing serine 31 (S31)-mutated dihydrofolate reductase (DHFR) (DC/SV6S31). To examine whether the use of SFG-based dicistronic vectors will lead to improvement in gene transfer over the DC/SV6 vector, we compared the protection provided by MTX to NIH3T3 cells and hematopoietic progenitor cells infected with these retroviral constructs containing the S31 variant DHFR cDNA. In NIH3T3 cells, the 50% effective dose values of MTX conferred by the SFG vector were 8-fold higher than those obtained with the DC/SV6 vector. DHFR mRNA levels were 22-fold and 38-fold higher than that seen for the DC/SV6 vector according to Northern blot and real-time polymerase chain reaction analysis, respectively. However, DHFR protein expression and DHFR enzyme activity were only 1.5-fold and 2-fold higher in the SFG vector, respectively, indicating that the mRNA from the SFG vector is translated less efficiently than the mRNA generated from the DC/SV6 vector. Furthermore, the degree of MTX protection conferred by each vector in both mouse and human hematopoietic cells was the same. These results indicate that the in vitro transduction efficiency and transgene expression of human DHFR in hematopoietic progenitor cells is equally conferred by both vectors.


Assuntos
Células 3T3/efeitos dos fármacos , Medula Óssea/metabolismo , DNA Complementar/genética , Resistência a Medicamentos/genética , Células-Tronco Hematopoéticas/metabolismo , Metotrexato/farmacologia , Vírus da Leucemia Murina de Moloney/genética , Tetra-Hidrofolato Desidrogenase/genética , Animais , Northern Blotting , Southern Blotting , Western Blotting , Medula Óssea/efeitos dos fármacos , Primers do DNA/química , Regulação Enzimológica da Expressão Gênica , Vetores Genéticos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/análise , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Leucemia/patologia , Masculino , Camundongos , Regiões Promotoras Genéticas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tetra-Hidrofolato Desidrogenase/metabolismo , Transdução Genética , Células Tumorais Cultivadas
19.
Eur J Endocrinol ; 140(3): 231-4, 1999 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-10216518

RESUMO

OBJECTIVE: The present study was undertaken to examine the association of a glucose-stimulated insulin response with the fasting insulin-like growth factor-binding protein (IGFBP)-1 concentration in prepubertal obese children. SUBJECTS AND METHODS: The fasting levels of serum insulin and IGFBP-1 were measured in 17 obese and 16 control children. Furthermore, we performed an oral glucose tolerance test in obese children and examined the association of the area under the curve (AUC) for insulin with the fasting IGFBP-1 level. RESULTS: The mean serum level of IGFBP-1 was significantly lower in obese children (41.0 +/- 4.8 micrograms/l. P < 0.005) than in controls (91.2 +/- 9.9 micrograms/l). Although there was an inverse relationship between the fasting levels of serum insulin and IGFBP-1 in all subjects (r = -0.42, P < 0.05), no significant correlation between these two parameters was observed in the obese group alone. In obese children, the fasting IGFBP-1 level correlated inversely with AUC-insulin (r = -0.70, P < 0.005), whereas there was no significant relationship between the fasting insulin level and AUC-insulin. CONCLUSION: The present study suggests that the serum level of IGFBP-1 may be an early predictor of insulin resistance in prepubertal obesity.


Assuntos
Glucose/metabolismo , Hiperinsulinismo/fisiopatologia , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/fisiologia , Obesidade/fisiopatologia , Área Sob a Curva , Glicemia/análise , Índice de Massa Corporal , Criança , Feminino , Previsões , Teste de Tolerância a Glucose , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/etiologia , Insulina/sangue , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Masculino , Obesidade/complicações , Radioimunoensaio
20.
Eur J Endocrinol ; 141(6): 585-9, 1999 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-10601960

RESUMO

OBJECTIVE: We measured the total and nonphosphorylated insulin-like growth factor-binding protein (IGFBP)-1 concentrations in obese children to determine the effect of obesity on the status of IGFBP-1 phosphorylation. We also measured the serum levels of insulin, total and free IGF-I, and IGFBP-3 to investigate their relationships to the IGFBP-1 phosphorylation status in obese subjects. SUBJECTS AND METHODS: Nineteen prepubertal obese and 15 age-matched control children were included in the study. The serum levels of total and nonphosphorylated IGFBP-1 were determined by noncompetitive RIAs. RESULTS: The serum levels of total and nonphosphorylated IGFBP-1 were significantly lower in the obese group (48.7+/-5.6 microgram/l, P<0.001 and 11.1+/-1.9 microgram/l, P<0.01 respectively) than in the controls (86.7+/-9.0 microgram/l and 28.8+/-6.2 microgram/l respectively). However, the ratio of nonphosphorylated IGFBP-1 to total IGFBP-1 did not differ significantly between the obese and control groups. The circulating free IGF-I level was significantly higher in the obese children than in the controls (P<0.05), while the serum levels of insulin, total IGF-I and IGFBP-3 were not significantly different between the two groups. A stepwise regression analysis of the combined group revealed that only the total IGFBP-1 level was an independent predictor of the free IGF-I concentration (P<0.001). CONCLUSION: The present study shows that both total and nonphosphorylated IGFBP-1 concentrations are decreased in obese children and the increased free IGF-I level in obese children is related to the reduced total IGFBP-1 level, but unrelated to the change in the IGFBP-1 phosphorylation status.


Assuntos
Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Obesidade/sangue , Criança , Feminino , Humanos , Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Masculino , Fosforilação , Puberdade , Análise de Regressão
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