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1.
Breed Sci ; 73(2): 168-179, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37404346

RESUMO

The isolation of disease resistance genes introduced from wild or related cultivated species is essential for understanding their mechanisms, spectrum and risk of breakdown. To identify target genes not included in reference genomes, genomic sequences with the target locus must be reconstructed. However, de novo assembly approaches of the entire genome, such as those used for constructing reference genomes, are complicated in higher plants. Moreover, in the autotetraploid potato, the heterozygous regions and repetitive structures located around disease resistance gene clusters fragment the genomes into short contigs, making it challenging to identify resistance genes. In this study, we report that a de novo assembly approach of a target gene-specific homozygous dihaploid developed through haploid induction was suitable for gene isolation in potatoes using the potato virus Y resistance gene Rychc as a model. The assembled contig containing Rychc-linked markers was 3.3 Mb in length and could be joined with gene location information from the fine mapping analysis. Rychc was successfully identified in a repeated island located on the distal end of the long arm of chromosome 9 as a Toll/interleukin-1 receptor-nucleotide-binding site-leucine rich repeat (TIR-NBS-LRR) type resistance gene. This approach will be practical for other gene isolation projects in potatoes.

2.
Int J Rheum Dis ; 22(1): 81-89, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30168272

RESUMO

AIM: To investigate whether remission can be sustained for rheumatoid arthritis (RA) patients after tapering abatacept (ABT). METHOD: All patients were naïve to biological disease-modifying anti-rheumatic drugs (bDMARDs) and in low or moderate Disease Activity Score of 28 joints with C-reactive protein (DAS)28-CRP). ABT was administrated intravenously (IV) or subcutaneously (SC) for 36 weeks to patients with RA, who had not previously received bDMARDs. As the ABT tapering protocol, ABT was administrated SC at 125 mg every 2 weeks for 12 weeks in patients with remission. RA disease activity was assessed by DAS28-CRP and ultrasonography. Remission was assessed by defining it as DAS28-CRP <2.3. RESULTS: Of the 51 patients, 84.3% were women (mean age 68.7 ± 10.2 years, mean disease duration 7.7 ± 10.2 years). Twenty-nine patients achieved remission and a power Doppler (PD) score ≤1 at each joint at 36 weeks, followed by tapering ABT. Of these patients, 25 sustained DAS28-CRP remission, and DAS28-CRP was not significantly elevated (1.62 ± 0.41 to 1.69 ± 0.49) at 48 weeks, but the total PD score was significantly elevated (1.52 ± 1.21 to 2.59 ± 2.81 P = 0.049). Longer disease duration, higher DAS28-CRP at 24 weeks, and higher total PD score at 24 weeks were predictors of an elevated total PD score after tapering ABT therapy. CONCLUSION: These findings suggest that ABT tapering is a promising short-term strategy to sustain remission in patients with RA, and ultrasonography is a useful tool for monitoring disease activity after tapering ABT.


Assuntos
Abatacepte/administração & dosagem , Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Articulações/efeitos dos fármacos , Idoso , Artrite Reumatoide/sangue , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/fisiopatologia , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Esquema de Medicação , Feminino , Humanos , Mediadores da Inflamação/sangue , Japão , Articulações/diagnóstico por imagem , Articulações/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Fatores de Tempo , Resultado do Tratamento , Ultrassonografia Doppler
3.
Appl Opt ; 53(31): 7230-5, 2014 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-25402881

RESUMO

It is known that liquid crystal (LC) cells are useful as compact and easy-to-handle phase shifters that are readily coupled into the optics of standard microscope systems. Here, a uniformly aligned molecular LC phase shifter is introduced into a polarization microscope to attain a birefringence imaging system, using the phase-shift interferometric technique. Since the birefringence can be determined accurately only when the optical axis of the sample is parallel or perpendicular to the slow axis (variable axis) of the LC phase shifter, an improved data analysis method is proposed for determining the birefringence independently of the direction; a simple method of determining the slow axis distribution is also demonstrated. Measurements of the birefringence and slow axis distribution properties of a potato starch particle are demonstrated to confirm the novel determination method.


Assuntos
Interferometria/instrumentação , Cristais Líquidos/química , Microscopia de Contraste de Fase/instrumentação , Refratometria/instrumentação , Solanum tuberosum/química , Amido/química , Amido/ultraestrutura , Birrefringência , Desenho de Equipamento , Análise de Falha de Equipamento , Imagem Molecular/instrumentação
4.
Toxicology ; 317: 50-7, 2014 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-24530881

RESUMO

While it is known that benzene induces myeloid leukemia in humans, the mechanism has yet to be clarified. Previously, we suggested that myeloperoxidase (MPO) was the key enzyme because it promotes generation of powerful oxidant hypochlorous acid (HOCl) which, reacting with DNA, causes leukemogenesis. In this study, using a whole-human-genome oligonucleotide microarray to clarify the relationships between myelotoxicity of benzene and MPO, we analyzed the genome-wide expression profiles of HL-60 human promyelocytic cell lines exposed to 1,2,4-benzenetriol (BT) with or without MPO inhibition. The microarray analysis revealed that short (1 h) and longer (4 h) exposure to BT changed the expression in HL-60 cells of 1,213 or 1,214 genes associated with transcription, RNA metabolic processes, immune response, apoptosis, cell death, and biosynthetic processes (|Z-score|> 2.0), and that these changes were dramatically lessened by MPO-specific inhibition. The presence of functionally important genes and, specifically, genes related to apoptosis, carcinogenesis, regulation of transcription, immune responses, oxidative stress, and cell-cycle regulation were further validated by real-time RT-PCR. Gene expression profiles along with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation analysis suggest that BT-induced DNA halogenation by MPO is a primary reaction in the leukemogenesis associated with benzene.


Assuntos
Carcinógenos/toxicidade , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Hidroquinonas/toxicidade , Ácido Hipocloroso/metabolismo , Leucemia Promielocítica Aguda/metabolismo , Proteínas de Neoplasias/metabolismo , Peroxidase/metabolismo , Apoptose/efeitos dos fármacos , Carcinogênese/efeitos dos fármacos , DNA de Neoplasias/metabolismo , Perfilação da Expressão Gênica , Células HL-60 , Halogenação/efeitos dos fármacos , Humanos , Ácido Hipocloroso/antagonistas & inibidores , Leucemia Promielocítica Aguda/induzido quimicamente , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos , Estresse Oxidativo/efeitos dos fármacos , Peroxidase/antagonistas & inibidores , Peroxidase/genética , Proteômica/métodos , Interferência de RNA , RNA Interferente Pequeno , Transcrição Gênica/efeitos dos fármacos
5.
Breed Sci ; 64(4): 404-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25914596

RESUMO

The yellowing strain of Soybean dwarf virus (SbDV-YS) causes yellowing and yield loss in common bean (Phaseolus vulgaris). The most effective control is achieved through breeding for resistance. An indeterminate climbing cultivar with a white seed coat, 'Oofuku', is resistant to SbDV-YS in inoculation tests. We crossed 'Oofuku' with an elite cultivar, 'Taisho-Kintoki', which is SbDV-YS-susceptible, determinate dwarf with a red-purple seed coat, and performed amplified-fragment-length polymorphism analysis of F3 lines. From nucleotide sequences of the resistant-specific fragments and their flanking regions, we developed five DNA markers, of which DV86, DV386, and DV398 were closely linked to Sdvy-1, a resistance gene. Using the markers, we developed 'Toiku-B79' and 'Toiku-B80', the near-isogenic lines (NILs) incorporating Sdvy-1 in the background of 'Taisho-Kintoki'. The NILs had similar growth habit, maturity date and seed shape to those of 'Taisho-Kintoki'. The quality of boiled beans was also similar, except that the NILs had more seed coat cracking than 'Taisho-Kintoki'. The NILs showed no SbDV-YS infection in inoculation tests. We suggest that Sdvy-1 is a useful source of SbDV-YS resistance in common bean.

6.
Breed Sci ; 63(3): 353-7, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24273432

RESUMO

Brown stem rot (BSR) caused by Cadophora gregata f. sp. adzukicola (syn. Phialophora gregata) is a serious soilborne disease of adzuki bean (Vigna angularis) in Japan. Cultivation of resistant cultivars is the most effective disease control method, therefore the selection of resistant lines is a priority for breeders. BSR-resistant adzuki bean lines have been screened in pathogen-infected fields. However, field selection using the pathogen and artificial inoculation methods is time-consuming and labor-intensive. In the present study, we used 105 F3 lines derived from a cross between a BSR-resistant cultivar 'Syumari' and a susceptible cultivar 'Buchishoryukei-1' for BSR inoculation tests. Amplified fragment-length polymorphism (AFLP) analyses with 1024 primer sets revealed that six fragments were polymorphic between resistance and susceptible bulked groups. Five DNA markers (Pg77, Pg118, Pg138, Pg139 and Pg126) were developed from the nucleotide sequences of polymorphic AFLP markers and their flanking regions. Pg118, which was derived from E-ACT/M-ACT-118, was tightly linked to the resistance gene Pga1 and was converted into a codominant marker for its easier use in marker-assisted selection for adzuki bean BSR resistance. Finally, the applicability of the developed markers for BSR resistance was tested on 32 adzuki bean accessions or cultivars.

7.
Eur J Nutr ; 52(2): 813-24, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22692501

RESUMO

PURPOSE: Dietary protein content is related clinically to the development of diabetic nephropathy. Here, we investigated how dietary protein content (12-24 % energy) within the range used by humans affected renal manifestations including the expressions of genes involved in the renin-angiotensin (RA) system in control and diabetic mice. Moreover, we examined the effects of dietary protein content on HbA1c and urinary glucose. METHODS: Control (CT) and leptin receptor-deficient obese (db) mice, 5 weeks old, were fed the diets below. Under ad libitum conditions, mice were fed 12, 18, and 24 % energy from protein (L-, M-, and H-diets) for 8 weeks. Under pair-feeding conditions, db mice were supplied H-diet (db-Hp) to the equivalent energy to that consumed by db-L mice. Renal manifestations and values related to glucose and insulin were examined biochemically and pathologically. RESULTS: Under ad libitum conditions, db mice consumed food and water dose dependently of the dietary protein content, although they were consumed similarly by CT mice. CT-L mice showed lower urinary albumin and kidney weight, in association with lower mRNA levels of angiotensinogen and renin, than CT-H mice. Under pair-feeding conditions, db-L mice showed a lower ratio of kidney/body weight, HbA1(C), and urinary glucose, and a higher ß-cell distribution rate in the pancreas than db-Hp mice. CONCLUSIONS: Low-protein intake in the range used by humans may relieve renal manifestations through the suppressed expression of genes in the renal RA system of CT mice. On the other hand, in db mice, low-protein intake improved hyperglycemia and the renal manifestations of diabetes.


Assuntos
Diabetes Mellitus Experimental/dietoterapia , Dieta com Restrição de Proteínas , Glicosúria Renal/dietoterapia , Rim/metabolismo , Albuminúria/dietoterapia , Animais , Glicemia/análise , Peso Corporal , Diabetes Mellitus Experimental/sangue , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/dietoterapia , Proteínas Alimentares/administração & dosagem , Proteínas Alimentares/sangue , Jejum , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/metabolismo , Hiperglicemia/sangue , Hiperglicemia/dietoterapia , Insulina/sangue , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/sangue , Obesidade/dietoterapia , Pâncreas/metabolismo , Sistema Renina-Angiotensina
8.
Breed Sci ; 63(4): 417-22, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24399914

RESUMO

Soybean dwarf virus (SbDV), a Luteoviridae family member, causes dwarfing, yellowing and sterility of soybean (Glycine max), leading to one of the most serious problems in soybean production in northern Japan. Previous studies revealed that the Indonesian soybean cultivar 'Wilis' is resistant to SbDV and that the resistance can be introduced into Japanese cultivars. A major QTL for SbDV resistance has been reported between SSR markers Sat_217 and Satt211 on chromosome 5. In this study, we named this QTL Rsdv1 (resistance to SbDV) and developed near-isogenic lines incorporating Rsdv1 (Rsdv1-NILs) using Sat_217 and Satt211 markers. The Rsdv1-NILs were resistant to SbDV in greenhouse inoculation and field tests, indicating that Rsdv1 alone is sufficient for the resistance phenotype. We fine-mapped Rsdv1 within the 44-kb region between Sat_11 and Sct_13. None of the six genes predicted in this region was closely related to known virus resistance genes in plants. Thus, Rsdv1 may confer resistance by a previously unknown mechanism. We suggest that Rsdv1 may be a useful source for the Japanese soybean breeding program to introduce SbDV resistance.

9.
Breed Sci ; 61(5): 602-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23136498

RESUMO

Soybean cyst nematode (SCN) (Heterodera glycines Ichinohe) is one of the most damaging pests of soybean (Glycine max (L.) Merr.). Host plant resistance has been the most effective control method. Because of the spread of multiple SCN races in Hokkaido, the Tokachi Agricultural Experiment Station has bred soybeans for SCN resistance since 1953 by using 2 main resistance resources PI84751 (resistant to races 1 and 3) and Gedenshirazu (resistant to race 3). In this study, we investigated the genetic relationships of SCN resistance originating from major SCN resistance genes in Gedenshirazu and PI84751 by using SSR markers. We confirmed that race 1 resistance in PI84751 was independently controlled by 4 genes, 2 of which were rhg1 and Rhg4. We classified the PI84751- type allele of Rhg1 as rhg1-s and the Gedenshirazu-type allele of Rhg1 as rhg1-g. In the cross of the Gedenshirazu-derived race 3-resistant lines and the PI84751-derived races 1- and 3-resistant lines, the presence of rhg1-s and Rhg4 was responsible for race 1-resistance. These results indicated that it was possible to select race 1 resistant plants by using marker-assisted selection for the rhg1-s and Rhg4 alleles through a PI84751 origin × Gedenshirazu origin cross.

10.
Breed Sci ; 61(5): 618-24, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23136500

RESUMO

Soybean dwarf virus (SbDV) causes serious dwarfing, yellowing and sterility in soybean (Glycine max). The soybean cv. Adams is tolerant to SbDV infection in the field and exhibits antibiosis to foxglove aphid (Aulacorthum solani), which transmits SbDV. This antibiosis (termed "aphid resistance") is required for tolerance to SbDV in the field in segregated progenies of Adams. A major quantitative trait locus, Raso1, is reported for foxglove aphid resistance. Our objectives were to fine map Raso1 and to reveal whether Raso1 alone is sufficient to confer both aphid resistance and SbDV tolerance. We introduced Raso1 into cv. Toyomusume by backcrossing and investigated the degree of aphid antibiosis to foxglove aphid and the degree of tolerance to SbDV in the field. All Raso1-introduced backcross lines showed aphid resistance. Interestingly, only one Raso1-introduced backcross line (TM-1386) showed tolerance to SbDV in the field. The results demonstrated Raso1 alone is sufficient to confer aphid resistance but insufficient for SbDV tolerance. Tolerance to SbDV was indicated to require additional gene(s) to Raso1. Additionally, Raso1 was mapped to a 63-kb interval on chromosome 3 of the Williams 82 sequence assembly (Glyma1). This interval includes a nucleotide-binding site-leucine-rich repeat encoding gene and two other genes in the Williams 82 soybean genome sequence.

11.
Breed Sci ; 62(1): 11-7, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23136509

RESUMO

Fusarium head blight (FHB) is an important disease of wheat (Triticum aestivum L.). The aim of this study was to determine the effects of quantitative trait locus (QTL) regions for resistance to FHB and estimate their effects on reducing FHB damage to wheat in Hokkaido, northern Japan. We examined 233 F(1)-derived doubled-haploid (DH) lines from a cross between 'Kukeiharu 14' and 'Sumai 3' to determine their reaction to FHB during two seasons under field conditions. The DH lines were genotyped at five known FHB-resistance QTL regions (on chromosomes 3BS, 5AS, 6BS, 2DL and 4BS) by using SSR markers. 'Sumai 3' alleles at the QTLs at 3BS and 5AS effectively reduced FHB damage in the environment of Hokkaido, indicating that these QTLs will be useful for breeding spring wheat cultivars suitable for Hokkaido. Some of the QTL regions influenced agronomic traits: 'Sumai 3' alleles at the 4BS and 5AS QTLs significantly increased stem length and spike length, that at the 2DL QTL significantly decreased grain weight, and that at the 6BS QTL significantly delayed heading, indicating pleiotropic or linkage effects between these agronomic traits and FHB resistance.

12.
Artigo em Inglês | MEDLINE | ID: mdl-22461840

RESUMO

Acupuncture, an alternative medicine, has been widely applied for people with sleep disturbances; therefore, the effects should be evaluated objectively. Micro-minipigs (MMPigs), the smallest miniature pigs for animal experiments, were used. Acupuncture was performed at two different points: Dafengmen is located on the head and is an anatomically similar point to human-Baihui (GV20), an effective acupoint for sleep disturbances in humans; pig-Baihui is on the back. The procedure was performed as follows: shallow, within 5 mm depth for several seconds; deep, 10-20 mm depth for 20 min. The sleep conditions were evaluated by actigraph, and the amount of catecholamine in pooled urine after acupuncture treatment. MMPigs with deep acupuncture at Dafengmen showed significantly efficient values on actigraph and catecholamine analysis as compared with untreated MMPigs. The effective acupoint for sleep conditions in the porcine model is at an anatomically similar point to humans, rather than the point determined by traditional Chinese medicine.

13.
Environ Health Prev Med ; 17(4): 275-84, 2012 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22052204

RESUMO

OBJECTIVES: To determine the impact of long-term voluntary exercise, representing habitual exercise for the prevention of lifestyle-related diseases, on glucose, lipid, and amino acid metabolism in mice. METHODS: Twenty-four mice aged 6 weeks were divided into three groups. Two groups (16 mice) were housed individually in either cages equipped with a running wheel (8 mice, exercising, Ex-mice) or without (8 mice, sedentary, Se-mice) for 24 weeks. The remaining group (8 mice) was sacrificed at 6 weeks of age. Biomarkers related to glucose, lipid, and amino acid metabolism were examined. RESULTS: Ex-mice ran voluntarily, predominantly in the dark. The distance per day peaked at 4 weeks and then decreased until 12 weeks to around the level seen at the beginning of the experimental period, and was maintained at 4.9 ± 0.2 km/day from 12 to 24 weeks. Ex-mice showed a similar adrenal weight and vitamin C content to Se-mice but had a significantly lower body weight and higher food intake. Ex-mice also showed a higher skeletal muscle weight, a lower white adipose tissue and liver weight, associated with lower plasma leptin and insulin-like growth factor-1 levels, and a lower hepatic triglyceride content. Analysis of plasma amino acids showed that Ex-mice had significantly higher phenylalanine, tyrosine, and glutamine levels, resulting in a significantly lower Fischer's ratio. CONCLUSIONS: We present an animal model of long-term voluntary exercise under low stress. Findings related to the effects of long-term voluntary exercise on lipid, and amino acid metabolism in our mouse model indicate that such an exercise regimen may affect pathophysiological states related to appetite and behavior.


Assuntos
Aminoácidos/sangue , Glicemia/metabolismo , Metabolismo dos Lipídeos , Esforço Físico , Tecido Adiposo/metabolismo , Animais , Composição Corporal , Ingestão de Alimentos , Feminino , Regulação da Expressão Gênica , Fígado/metabolismo , Camundongos , Modelos Animais , Reação em Cadeia da Polimerase , RNA Mensageiro/metabolismo , Fatores de Tempo
14.
Environ Health Perspect ; 120(1): 62-7, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21859636

RESUMO

BACKGROUND: Although benzene is known to be myelotoxic and to cause myeloid leukemia in humans, the mechanism has not been elucidated. OBJECTIVES: We focused on 1,2,4-benzenetriol (BT), a benzene metabolite that generates reactive oxygen species (ROS) by autoxidation, to investigate the toxicity of benzene leading to leukemogenesis. METHODS: After exposing HL-60 human myeloid cells to BT, we investigated the cellular effects, including apoptosis, ROS generation, DNA damage, and protein damage. We also investigated how the cellular effects of BT were modified by hydrogen peroxide (H2O2) scavenger catalase, hypochlorous acid (HOCl) scavenger methionine, and 4-aminobenzoic acid hydrazide (ABAH), a myeloperoxidase (MPO)-specific inhibitor. RESULTS: BT increased the levels of apoptosis and ROS, including superoxide (O2•-), H2O2, HOCl, and the hydroxyl radical (•OH). Catalase, ABAH, and methionine each inhibited the increased apoptosis caused by BT, and catalase and ABAH inhibited increases in HOCl and •OH. Although BT exposure increased halogenated DNA, this increase was inhibited by catalase, methionine, and ABAH. BT exposure also increased the amount of halogenated tyrosines; however, it did not increase 8-oxo-deoxyguanosine. CONCLUSIONS: We suggest that BT increases H2O2 intracellularly; this H2O2 is metabolized to HOCl by MPO, and this HOCl results in possibly cytotoxic binding of chlorine to DNA. Because myeloid cells copiously express MPO and because halogenated DNA may induce both genetic and epigenetic changes that contribute to carcinogenesis, halogenative stress may account for benzene-induced bone marrow disorders and myeloid leukemia.


Assuntos
Transformação Celular Neoplásica/induzido quimicamente , Hidroquinonas/toxicidade , Estresse Fisiológico/efeitos dos fármacos , Compostos de Anilina/farmacologia , Apoptose/efeitos dos fármacos , Catalase/fisiologia , DNA/metabolismo , Dano ao DNA , Inibidores Enzimáticos/farmacologia , Células HL-60 , Halogenação/efeitos dos fármacos , Humanos , Metionina/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Tirosina/metabolismo
15.
Environ Health Prev Med ; 16(4): 232-8, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21431792

RESUMO

OBJECTIVES: We investigated whether habitual exercise (HE) (treadmill running) suppresses development of renal cell carcinoma (RCC) induced by ferric nitrilotriacetate (Fe-NTA). METHODS: Male Fischer 344 rats were divided into six groups: group I, saline treatment (12 weeks = initiation period) and non-HE; group II, Fe-NTA treatment (12 weeks) and non-HE; group III, saline treatment and short-term (12 weeks) HE; group IV, Fe-NTA treatment and short-term HE; group V, saline treatment and long-term (40 weeks) HE; and group VI, Fe-NTA treatment and long-term HE. Saline treatment groups did not develop RCC, therefore we investigated the effects of HE among Fe-NTA treatment groups. RESULTS: Gross nodules (diagnosed as RCC), RCC represented by microcarcinomas (Mcs), karyomegalic cells (KCs), and degenerative tubules (DTs) were seen in rats treated with Fe-NTA. The number of Mcs, KCs, and DTs were increased in the short-term HE group when compared with those in the non-HE group, but were decreased in the long-term HE group when compared with those in the short-term HE group. CONCLUSIONS: Short-term (initiation period) HE promoted renal carcinogenesis induced by Fe-NTA; however, long-term HE after the initiation period suppressed the promoted carcinogenesis.


Assuntos
Carcinoma de Células Renais/prevenção & controle , Neoplasias Renais/prevenção & controle , Rim/patologia , Condicionamento Físico Animal , Animais , Carcinógenos , Carcinoma de Células Renais/induzido quimicamente , Carcinoma de Células Renais/patologia , Compostos Férricos , Rim/efeitos dos fármacos , Neoplasias Renais/induzido quimicamente , Neoplasias Renais/patologia , Masculino , Ácido Nitrilotriacético/análogos & derivados , Ratos , Ratos Endogâmicos F344
16.
J Occup Health ; 53(2): 84-92, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21325737

RESUMO

OBJECTIVES: Benzene has been consistently associated with hematological disorders, including acute myeloid leukemia and aplastic anemia, but the mechanisms causing these disorders are still unclear. Various metabolites of benzene lead to toxicity through the production of reactive oxygen species (ROS), the inhibition of topoisomerase and DNA damage. However, benzene itself is considered to have no mutagenic or cytotoxic activity. In this study, we investigated the effects of benzene itself on a human myeloid cell line with or without benzene metabolizing enzyme inhibitors. METHODS: A human myeloid cell line, HL-60, was exposed to benzene with or without cytochrome P450 2E1 or myeloperoxidase inhibitor. Cytotoxicity was evaluated in terms of global DNA methylation levels, induction of apoptosis, and ROS production. RESULTS: Benzene did not change global DNA methylation levels. However, benzene itself increased the levels of apoptosis and ROS. This cytotoxicity did not change with the addition of benzene metabolizing enzyme inhibitors. Benzene itself increased the mRNA levels of oxidative stress-related genes and transcription factors of activator protein-1. CONCLUSIONS: Benzene did not influence global DNA methylation in HL-60 cells, but had cytotoxic effects and changed gene expression levels. To elucidate the mechanisms of benzene toxicity, benzene itself as well as benzene metabolites must be investigated.


Assuntos
Apoptose/efeitos dos fármacos , Benzeno/toxicidade , Metilação de DNA/efeitos dos fármacos , Espécies Reativas de Oxigênio , Biotransformação , Regulação da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/genética , Fator de Transcrição AP-1/genética
17.
J Pharmacol Sci ; 115(2): 115-21, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21258170

RESUMO

Atherosclerotic lesions were observed in male and ovariectomized female Microminipig (MMP) fed a high fat and cholesterol diet with sodium cholate (HFCD/SC) for 3 months. HFCD/SC induced hypercholesterolemia accompanied by an increase in serum total cholesterol (T-Cho), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and cholesterol ester (CE). Unlike the mouse or rabbit, a dominant LDL-C fraction in the intact MMP, similar to that in humans, was observed by serum lipoprotein analysis. HFCD/SC increased body weight gain. At the end of the experiment, computed tomography scans of conscious animals showed that HFCD/SC had decreased liver attenuation values (Hounsfield unit) and increased subcutaneous and abdominal fat, suggesting the induction of fatty liver and obesity. HFCD/SC induced atherosclerotic lesions in systemic arteries, including the external and internal iliac arteries, abdominal aorta, coronary artery, and cerebral arterial circle. Atherosclerosis and pathological findings induced by HFCD/SC in MMP were similar to those in humans. The MMP is a potentially suitable tool for investigating human atherosclerosis.


Assuntos
Aterosclerose , Dieta Aterogênica , Modelos Animais de Doenças , Porco Miniatura , Animais , Aterosclerose/sangue , Aterosclerose/patologia , Cruzamento , Colesterol/sangue , Colesterol na Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Feminino , Humanos , Lipídeos/sangue , Masculino , Suínos
18.
Breast Cancer Res Treat ; 126(2): 443-51, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21221770

RESUMO

This study compared the efficacy and safety of a 3-monthly 10.8-mg depot goserelin (Zoladex(TM)) injection with the current 3.6 mg monthly dose in pre-menopausal Japanese women with estrogen receptor-positive (ER+) early breast cancer. This was a multicenter, open-label, randomized study. Primary endpoint was a non-inferiority analysis (10.8/3.6 mg) of the area under the concentration-time curve (AUC) of estradiol (E(2)) over the first 24 weeks. Secondary endpoints included E(2) and follicle-stimulating hormone (FSH) concentrations, menstruation, and safety and tolerability. In total, 170 patients were randomized to receive goserelin 10.8 mg every 3 months (n = 86) or 3.6 mg every month (n = 84). Mean AUCs for E(2) were similar between treatment groups (18.32 and 18.95 pg/ml·week for goserelin 10.8 and 3.6 mg, respectively). AUC ratio was 0.974 (95% confidence interval, 0.80, 1.19), indicating non-inferiority for goserelin 10.8 mg. Serum E(2) and FSH remained suppressed throughout the study and no patient experienced menses after week 16. No clinically important differences in safety and tolerability were observed between the two groups. In terms of E(2) suppression, 3-monthly goserelin 10.8 mg was non-inferior to monthly goserelin 3.6 mg in pre-menopausal women with ER+ breast cancer.


Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Gosserrelina/uso terapêutico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Receptores de Estrogênio/metabolismo , Adulto , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/farmacocinética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Gosserrelina/efeitos adversos , Gosserrelina/farmacocinética , Fogachos/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/cirurgia , Osteoartrite/induzido quimicamente , Pré-Menopausa , Projetos de Pesquisa
19.
FEMS Microbiol Lett ; 317(2): 109-16, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21241358

RESUMO

The emergence of drug-resistant microorganisms is an important medical and social problem. Drug-resistant microorganisms are thought to grow selectively in the presence of antibiotics. Most clinically isolated drug-resistant microorganisms have mutations in the target genes for the drugs. While any of the many mutagens in the environment may cause such genetic mutations, no reports have yet described whether these mutagens can confer drug resistance to clinically important microorganisms. We investigated how environmental mutagens might be implicated in acquired resistance to antibiotics in clinically important microorganisms, which causes human diseases. We selected mutagens found in the environment, in cigarette smoke, or in drugs, and then exposed Pseudomonas aeruginosa to them. After exposure, the incidence of rifampicin- and ciprofloxacin-resistant P. aeruginosa strains markedly increased, and we found mutations in genes for the antibiotic-target molecule. These mutations were similar to those found in drug-resistant microorganisms isolated from clinical samples. Our findings show that environmental mutagens, and an anticancer drug, are capable of inducing drug-resistant P. aeruginosa similar to strains found in clinical settings.


Assuntos
Antibacterianos/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Proteínas de Bactérias/genética , Benzopirenos/toxicidade , Carmustina/toxicidade , Ciprofloxacina/farmacologia , DNA Girase/genética , Farmacorresistência Bacteriana/genética , Metanossulfonato de Etila/toxicidade , Compostos de Metilureia/toxicidade , Nitrosaminas/toxicidade , Reação em Cadeia da Polimerase , Rifampina/farmacologia
20.
Theor Appl Genet ; 122(3): 633-42, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20981401

RESUMO

In yellow soybean, seed coat pigmentation is inhibited by post-transcriptional gene silencing (PTGS) of chalcone synthase (CHS) genes. A CHS cluster named GmIRCHS (Glycine max inverted-repeat CHS pseudogene) is suggested to cause PTGS in yellow-hilum cultivars. Cold-induced seed coat discoloration (CD), a commercially serious deterioration of seed appearance, is caused by an inhibition of this PTGS upon exposure to low temperatures. In the highly CD-tolerant cultivar Toyoharuka, the GmIRCHS structure differs from that of other cultivars. The aim of this study was to determine whether the variation of GmIRCHS structure among cultivars is related to variations in CD tolerance. Using two sets of recombinant inbred lines between Toyoharuka and CD-susceptible cultivars, we compared the GmIRCHS genotype and CD tolerance phenotype during low temperature treatment. The GmIRCHS genotype was related to the phenotype of CD tolerance. A QTL analysis around GmIRCHS showed that GmIRCHS itself or a region located very close to it was responsible for CD tolerance. The variation in GmIRCHS can serve as a useful DNA marker for marker-assisted selection for breeding CD tolerance. In addition, QTL analysis of the whole genome revealed a minor QTL that also affected CD tolerance.


Assuntos
Aciltransferases/genética , Adaptação Fisiológica/genética , Temperatura Baixa , Glycine max/genética , Sequências Repetidas Invertidas/genética , Pigmentação/genética , Sementes/genética , Marcadores Genéticos , Variação Genética , Genótipo , Endogamia , Fenótipo , Pseudogenes/genética , Locos de Características Quantitativas/genética , Análise de Regressão , Glycine max/enzimologia
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