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OBJECTIVES: This population-based study aimed to evaluate the association between bowel habits from midlife and dementia. STUDY DESIGN: This was a cohort study using certification records for national long-term care insurance in Japan. METHODS: Participants aged 50 to 79 years who reported bowel habits from eight districts within the Japan Public Health Center-based Prospective Study (JPHC Study) were followed from 2006 to 2016 for incident dementia. Hazard ratio (HR) and 95% confidence interval (CI) were estimated for men and women separately using Cox proportional hazards models accounting for various lifestyle factors and medical histories. RESULTS: Among 19,396 men and 22,859 women, 1889 men and 2685 women were diagnosed with dementia. In men, the multivariable-adjusted HRs compared with bowel movement frequency (BMF) of once/day were 1.00 (95% CI: 0.87-1.14) for twice/day or more, 1.38 (1.16-1.65) for 5-6 times/week, 1.46 (1.18-1.80) for 3-4 times/week, and 1.79 (1.34-2.39) for <3 times/week (P for trend <0.001). In women, the corresponding HRs were 1.14 (0.998-1.31), 1.03 (0.91-1.17), 1.16 (1.01-1.33), and 1.29 (1.08-1.55) (P for trend = 0.043). Harder stool was associated with higher risk (P for trend: 0.0030 for men and 0.024 for women), with adjusted HRs compared to normal stool of 1.30 (1.08-1.57) for hard stool and 2.18 (1.23-3.85) for very hard stool in men, and 1.15 (1.002-1.32) and 1.84 (1.29-2.63) in women. CONCLUSIONS: Lower BMF and harder stool were each associated with higher risk of dementia.
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Defecação , Demência , Masculino , Humanos , Feminino , Constipação Intestinal/complicações , Estudos de Coortes , Estudos Prospectivos , Japão/epidemiologia , Fatores de Risco , Demência/epidemiologiaRESUMO
In recent years, millisecond-duration radio signals originating in distant galaxies appear to have been discovered in the so-called fast radio bursts. These signals are dispersed according to a precise physical law and this dispersion is a key observable quantity, which, in tandem with a redshift measurement, can be used for fundamental physical investigations. Every fast radio burst has a dispersion measurement, but none before now have had a redshift measurement, because of the difficulty in pinpointing their celestial coordinates. Here we report the discovery of a fast radio burst and the identification of a fading radio transient lasting ~6 days after the event, which we use to identify the host galaxy; we measure the galaxy's redshift to be z = 0.492 ± 0.008. The dispersion measure and redshift, in combination, provide a direct measurement of the cosmic density of ionized baryons in the intergalactic medium of ΩIGM = 4.9 ± 1.3 per cent, in agreement with the expectation from the Wilkinson Microwave Anisotropy Probe, and including all of the so-called 'missing baryons'. The ~6-day radio transient is largely consistent with the radio afterglow of a short γ-ray burst, and its existence and timescale do not support progenitor models such as giant pulses from pulsars, and supernovae. This contrasts with the interpretation of another recently discovered fast radio burst, suggesting that there are at least two classes of bursts.
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The purpose of this study was to concomitantly determine oxidative DNAdamage and bone resorption following a rapid body mass reduction in association with energy restriction and exercise training, considering 17ß-estradiol level, in female collegiate judokas. Eighteen nationally ranked university female judokas were enrolled as participants in this study. All participants continuously managed to reduce their body mass 8 days just before a competition. To detect cumulative effects of oxidative DNA damage and bone resorption, urinary samples were collected in the morning on three different days (Day 1= the beginning of body mass reduction; Day 4=mid-term of body mass reduction; Day 7=the day before the competition) for the later analysis of 8-hydroxy-2- deoxyguanosine (8-OHdG) as well as cross-linked N-terminal telopeptides of Type I collagen (NTx). Urinary 8-OHdG and NTx levels were determined with high performance liquid chromatography and enzyme-linked immunosorbent assay, respectively. No significant alterations were observed in urinary 8-OHdG or NTx levels over a rapid body mass reduction period. The findings of the present study indicate that female judokas appear to have relatively less oxidative DNA damage determined by quantification of 8-OHdG and bone resorption over a rapid body mass reduction period, potentially due to the enhanced endogenous defense responses (training adaptation). These data can provide athletes and coaches with valuable information in considering an optimal body mass management program to avoid detrimental physiological and biological conditions.
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Atletas , Peso Corporal/fisiologia , Reabsorção Óssea , Dano ao DNA/fisiologia , Exercício Físico/fisiologia , 8-Hidroxi-2'-Desoxiguanosina , Composição Corporal/fisiologia , Restrição Calórica , Colágeno Tipo I/urina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/urina , Feminino , Humanos , Artes Marciais , Estresse Oxidativo/fisiologia , Adulto JovemRESUMO
National Regulatory Authorities (NRAs) establish deferral criteria for donors with risk factors for transfusion transmissible infections (TTI). In most jurisdictions, epidemiological data show that men who have sex with men (MSM) have a significantly higher rate of TTI than the general population. Nevertheless, changes from an indefinite donor deferral for MSM have been considered in many countries in response to concerns over a perceived discrimination and questioning of the scientific need. Changes to MSM donor deferral criteria should be based on sound scientific evidence. Safety of transfusion recipients should be the first priority, and stakeholder input should be sought.
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Doadores de Sangue , Homossexualidade Masculina , Políticas de Controle Social , Adulto , Segurança do Sangue , Seleção do Doador , Humanos , Masculino , Fatores de Risco , Reação Transfusional , Viremia/etiologiaRESUMO
DNA markers that allow for identification of resistance genes in rice germplasm have a great advantage in resistance breeding because they can assess the existence of the genes without laborious inoculation tests. Functional markers (FMs), which are designed from functional polymorphisms within the sequence of genes, are unaffected by nonfunctional allelic variation and make it possible to identify an individual gene. We previously showed that the resistance function of the rice blast resistance gene Pit in a resistant cultivar, K59, was mainly acquired by up-regulated promoter activity through the insertion of a long terminal repeat (LTR) retrotransposon upstream of Pit. Here, we developed PCR-based DNA markers derived from the LTR-retrotransposon sequence and used these markers to screen worldwide accessions of rice germplasm. We identified 5 cultivars with the LTR-retrotransposon insertion out of 68 rice accessions. The sequence and expression pattern of Pit in the five cultivars were the same as those in K59 and all showed Pit-mediated blast resistance. The results suggest that the functional Pit identified using the markers was derived from a common progenitor. Additionally, comparison of the Pit coding sequences between K59 and susceptible cultivars revealed that one nucleotide polymorphism, which caused an amino acid substitution, offered another target for a FM. These results indicate that our DNA markers should enhance prediction of Pit function and be applicable to a range of rice varieties/landraces cultivated in various regions worldwide and belonging to the temperate japonica, tropical japonica, and indica groups.
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Marcadores Genéticos , Genoma de Planta , Oryza/genética , Imunidade Vegetal/genética , Sequências Repetidas Terminais/genética , Alelos , Sequência de Aminoácidos , Sequência de Bases , Cruzamento , Genótipo , Geografia , Magnaporthe/patogenicidade , Doenças das Plantas/genética , Mutação Puntual , Polimorfismo Genético , Retroelementos/genéticaRESUMO
OBJECTIVE: To determine the efficacy and tolerability of oral fluoropyrimidine S-1 plus irinotecan in patients with previously untreated advanced colorectal cancer. METHODS: S-1 was administered orally at 80 mg/m(2)/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at a dose of 80 mg/m(2)/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 282 courses of treatment were administered to 40 patients, achieving complete response in 1 and partial responses in 24 with an overall response rate of 62.5% (95% CI: 47.5-77.5%). Median progression-free survival was 7.8 months (95% CI: 6.7-9.6 months). The rates of grade 3 or 4 toxicities were as follows: neutropenia 12.5%, anorexia 12.5%, fatigue 10%, and diarrhea 7.5%. CONCLUSION: Combined treatment with S-1 and irinotecan is an effective, well-tolerated and convenient regimen in patients with advanced colorectal cancer which is easily maintained.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Capecitabina , Neoplasias Colorretais/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Combinação de Medicamentos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Tegafur/administração & dosagem , Tegafur/efeitos adversosRESUMO
BACKGROUND: Metabolic syndrome (MetS) is associated with an increased risk of ischaemic stroke, including silent brain infarction. No study has examined its association with the lacunar subtype. The present cross sectional study examined the relationship between MetS, its components and silent lacunar infarction (SLI) in middle aged subjects. METHODS: We studied 2076 subjects aged 40-59 years with no history of stroke or clinical symptoms, who visited a health care facility for a routine health checkup and underwent brain MRI. MetS was defined according to the National Cholesterol Education Programme Adult Treatment Panel III report. A multiple logistic regression model was used to examine the associations between MetS and SLI while adjusting for age, gender, a past history of ischaemic heart disease and current smoking. RESULTS: MetS was strongly associated with the presence of SLI (adjusted OR 6.52; 95% CI 4.30 to 9.90). Regarding MetS components, elevated blood pressure, impaired fasting glucose, hypertriglyceridaemia and large waist circumference were significantly associated with SLI, independent of an interrelationship between the components, while low high density lipoprotein cholesterol was not significantly associated. CONCLUSIONS: MetS was significantly associated with the prevalence of SLI in middle aged persons. Independent risk factors for SLI not only included elevated blood pressure and impaired fasting glucose, which are well known risk factors, but also hypertriglyceridaemia and large waist circumference.
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Infarto Encefálico/epidemiologia , Síndrome Metabólica/epidemiologia , Adulto , Fatores Etários , Infarto Encefálico/diagnóstico , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética , Masculino , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/epidemiologia , Exame Neurológico , Razão de Chances , Fatores de Risco , Fatores Sexuais , Fumar/efeitos adversos , Fumar/epidemiologiaRESUMO
PURPOSE: To report a case in which optical coherence tomography (OCT) showed needle-shaped deposits on the retinal surface oriented toward the vitreous cavity and immunohistochemical findings suggested light chain-related amyloidosis. METHODS: A 59-year-old man with no systemic complications had bilateral neovascular glaucoma and vitreous opacities in the right eye. Vitrectomy was conducted on the right eye and the excised vitreous was examined histopathologically. RESULTS: Glass wool-like opacities were observed during vitrectomy. Postoperative fundus examination of the right eye showed retinal hemorrhage and white deposits around blood vessels and on retinal surface. Fluorescein angiography revealed hyperfluorescence of the optic disc, non-perfusion areas, and vascular focal staining. OCT depicted needle-shaped deposits perpendicular to the retinal surface oriented toward the vitreous. Histologic examination of deposits revealed positive reaction for Congo red stain, and immunohistochemical examination demonstrated positive reactivities for anti-lambda and anti-kappa light chains (precursors of amyloid protein), suggesting a diagnosis of light chain-related amyloidosis. CONCLUSIONS: In this case, OCT showed needle-shaped deposits perpendicular to the retinal surface. Special staining with Congo red revealed the deposit to be amyloid deposition. Immunohistochemical staining suggested light chain-related amyloidosis. Vascular obstructive lesions and neovascular glaucoma secondary to retinal vascular damage in amyloidosis warrant particular attention.
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Amiloidose/diagnóstico , Doenças Retinianas/diagnóstico , Proteína Amiloide A Sérica/metabolismo , Amiloidose/metabolismo , Oftalmopatias/diagnóstico , Oftalmopatias/cirurgia , Angiofluoresceinografia , Glaucoma Neovascular/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Retinianas/metabolismo , Tomografia de Coerência Óptica , Vitrectomia , Corpo Vítreo/patologiaRESUMO
Incompatibility reactions between rice and the blast fungus Magnaporthe grisea produce various degrees of lesions, from large brown flecks to small, nearly invisible lesions. We previously identified four avirulence genes (AvrPia, AvrPii, AvrPit, and Avr-Hattan3) in M. grisea isolates by genetic analysis of progeny from crosses between isolates with differing pathogenicity. Using progeny known to contain a specific avirulence gene, we demonstrated that the type of resistance lesion produced in rice by an avirulent isolate and the degree of leaf blast suppression by preinoculation with that isolate were determined by the combination of avirulence and resistance genes in the isolate and the cultivar. The degree of leaf blast suppression by preinoculation with an avirulent isolate increased with larger resistance lesions. When two genes were involved in an isolate's avirulence, lesions appeared that resembled those expected for the gene that produced the smaller lesion. The degree of leaf blast suppression by the isolate with two avirulence genes was comparable with that induced by the isolate with the avirulence gene that produced the smaller effect. The ability of specific resistance gene combinations that effectively suppress blast disease is discussed for each avirulence gene.
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The aim of this study was to evaluate the suitability of size specific dose estimates (SSDE) to estimate patient dose in Fast kVp switching dual energy CT. An anthropomorphic phantom (RAN-110) was repeatedly scanned (chest, abdomen and the pelvis) using a 64 detector row MDCT (Discovery CT750 HD, GE Healthcare, Milwaukee, WI, USA) with various CT parameters, including Fast kVp switching. Dosimetry was performed using thermo-luminescent dosimeters, positioned both superficially and within the phantom. SSDE was calculated for all slices of the anthropomorphic phantom using both the localiser and axial images. In Fast kVp switching, SSDE underestimated the measured absorbed dose for the chest/abdomen region ~35% at the maximum, but were in closer agreement for the pelvic region about within 10%. In single energy techniques, SSDE could not be applied in the estimation of organ doses, but in Fast kVp switching dual energy techniques, SSDE could be applied for anatomical regions with larger thicknesses.
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Abdome/efeitos da radiação , Pelve/efeitos da radiação , Imagens de Fantasmas , Monitoramento de Radiação , Imagem Radiográfica a Partir de Emissão de Duplo Fóton/métodos , Tomografia Computadorizada por Raios X/métodos , Humanos , Doses de Radiação , Radiografia TorácicaRESUMO
PURPOSE: To determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan plus S-1 in advanced colorectal cancer. PATIENTS AND METHODS: S-1 was administered orally at 80 mg/m2/day for 21 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 60 mg/m2/day, stepping up to 80, 100, 120 or 140 mg/m2/day. Courses were repeated every 5 weeks, unless disease progression or severe toxicities were observed. RESULTS: A total of 20 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 100 mg/m2, because 2 of 3 patients developed dose-limiting toxicities, such as anorexia, fatigue and diarrhea. Therefore, the recommended dose of CPT-11 was set at 80 mg/m2. Tumor responses were seen in 8 of 14 patients with measurable lesions. CONCLUSION: A combination of S-1 with CPT-11 is safe and can be recommended for further phase II studies in patients with advanced colorectal cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Combinação de Medicamentos , Feminino , Humanos , Irinotecano , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Ácido Oxônico/administração & dosagem , Tegafur/administração & dosagemRESUMO
ABSTRACT A selectable marker gene conferring resistance to bialaphos (BI) was introduced into rice blast isolate Y90-71BI and another conferring resistance to blasticidin S (BS) into isolate 3514-R-2BS of Magnaporthe oryzae to demonstrate exchange of DNA. Colonies obtained from co-cultures of these two isolates were resistant to both BI and BS and had both resistance genes as shown by Southern blot analysis of their genomic DNA. Conidia from these BI-BS-resistant isolates had only one nucleus per cell after staining with 4',6-diamidino-2-phenylindole (DAPI). Using flow cytometry, however, these BI-BS-resistant isolates were found to be haploid. Segregation of BI-BS-resistant isolates for pathogenicity (avirulence to virulence) on rice line K59-1 was consistent with a 1:1 ratio, as was segregation for mating type. These BI-BS-resistant isolates were thus apparently derived from parasexual exchange of DNA and the segregation of pathogenicity and of mating type of the parasexual recombinants might correspond to that of the progeny of the offspring of the sexual cross.
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The ICCHIBAN-2 experiment, the first dedicated to the ground-based intercomparison of passive space dosemeters, was carried out between 23 May and 28 May 2002 at the National Institute of Radiological Sciences in Chiba, Japan. The primary objective of the ICCHIBAN-2 experiment was to intercompare the response of passive dosemeters used in space crew dosimetry to monoenergetic heavy ions of charge and energy spanning a significant portion of the galactic cosmic ray (GCR) spectrum. During the ICCHIBAN-2 experiment, dosemeters from 12 different laboratories in 9 countries were irradiated under identical conditions to heavy ion beams of 150 MeV n(-1) (4)He, 400 MeV n(-1) (12)C, 490 MeV n(-1) (28)Si and 500 MeV n(-1) (56)Fe at the NIRS Heavy Ion Medical Accelerator.
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Radiação Cósmica , Íons Pesados , Exposição Ocupacional/análise , Proteção Radiológica/instrumentação , Voo Espacial/instrumentação , Dosimetria Termoluminescente/instrumentação , Relação Dose-Resposta à Radiação , Desenho de Equipamento , Análise de Falha de Equipamento , Internacionalidade , Doses de Radiação , Reprodutibilidade dos Testes , Pesquisa , Sensibilidade e Especificidade , Voo Espacial/métodos , Propriedades de Superfície , Dosimetria Termoluminescente/métodosRESUMO
Atomic force microscopy (AFM) has been applied to the analysis of CR-39 nuclear track detectors for high dose neutron dosimetry. As a feasible study to extract the neutron dose, we have employed a (239)Pu-Be neutron source with the traditional track density measurement of recoil proton etch pits from a high density polyethylene (CH(2)) radiator. After very short etching ( approximately 1 microm), etch pit densities were measured as a function of neutron fluence (neutron dose) up to 1.4 x 10(10) cm(-2) (6.6 Sv). Neutron sensitivity was also measured to be 6.6 x 10(-4). Maximum measurable neutron dose was estimated to be approximately 200 Sv by measuring the fraction of the total image area occupied by the etch pits.
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Microscopia de Força Atômica/métodos , Polietilenoglicóis/química , Polietilenoglicóis/efeitos da radiação , Proteção Radiológica/instrumentação , Dosimetria Termoluminescente/instrumentação , Relação Dose-Resposta à Radiação , Desenho de Equipamento , Análise de Falha de Equipamento , Teste de Materiais , Doses de Radiação , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Propriedades de Superfície , Dosimetria Termoluminescente/métodosRESUMO
alpha-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including breast, urinary bladder, and colon. This study was designed to determine whether DFMO treatment can inhibit tumor growth on chemical-induced colon cancer in rats. Effectiveness of DFMO in combination with mitomycin C (MMC) was also evaluated. Forty-two Sprague-Dawley rats received dimethylhydrazine (20 mg/kg) s.c. once weekly for 20 wk to induce colon cancer. Then a double-contrast barium enema was performed, and colon tumors were detected. The animals were divided into four groups that were subjected to the following treatment: none; DFMO alone; MMC alone; and a combination of DFMO plus MMC. After 5 wk of treatment, the barium enema was repeated. For the evaluation of treatment efficacy, tumor doubling time was adopted. The mean tumor doubling time in the control group was 20.7 +/- 9.1 days (SD). "Response" was judged as effective when tumor doubling time in treatment groups was more than 38.9 days, calculated from the mean + 2 SDs in the control group. Response rates in the DFMO, MMC, and DFMO plus MMC groups were 40.0%, 10.0%, and 82.3%, respectively. DFMO was a more effective inhibitor of tumor growth than MMC, and DFMO in combination with MMC resulted in a synergic diminution of tumor growth. The double-contrast barium enema is useful to observe sequential tumor growth and may be appropriate for the evaluation of new treatment on experimental colon cancer in rats.
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Neoplasias do Colo/patologia , Eflornitina/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Dimetilidrazinas , Masculino , Mitomicina/uso terapêutico , Putrescina/metabolismo , Ratos , Ratos Endogâmicos , Espermidina/metabolismo , Espermina/metabolismoRESUMO
OBJECTIVES: This study sought to examine plasma levels of soluble Fas/APO-1 receptor (sFas), an inhibitor of apoptosis, and soluble Fas ligand (sFas-L), an inducer of apoptosis, and their relation to each other and to other clinical variables, such as New York Heart Association functional class, tumor necrosis factor (TNF) and interleukin-6 (IL-6) in congestive heart failure (CHF). BACKGROUND: It has been recently reported that apoptotic cell death occurs in myocytes of dogs with CHF. Hypoxia is frequently seen in advanced CHF and can stimulate Fas/APO-1 receptors (Fas) to induce apoptosis in cultured myocytes. Fas and Fas ligand (Fas-L) are cell-surface proteins and representative apoptosis-signaling molecules. Fas on the cell membrane induces apoptosis when it binds Fas-L or sFas-L. However, plasma sFas, a molecule lacking the transmembrane domain of Fas, blocks apoptosis by inhibiting binding between Fas and Fas-L or sFas-L on the cell membrane. At present, it is unknown whether plasma sFas-L and plasma sFas increase in the presence of cardiac disease. METHODS: The study included 70 patients (mean [+/-SEM] age 65 +/- 2 years, range 21 to 93) with chronic CHF (coronary artery disease in 28, dilated cardiomyopathy in 27, valvular heart disease in 15) and 62 age- and gender-matched normal control subjects. Plasma levels of sFas, sFas-L, TNF-alpha and IL-6 were measured by enzyme-linked immunosorbent assays using monoclonal anti-human antibodies. RESULTS: There was no significant difference in sFas-L levels between normal subjects and patients in functional classes I to IV; however, sFas increased with severity of functional classification, independent of the underlying disease. sFas levels were significantly higher even in patients in functional class II than in normal subjects and those in functional class I, and were highest in patients in functional class IV (normal subjects; 2.2 +/- 0.1 ng/ml; functional class I: 2.2 +/- 0.2 ng/ml; functional class II: 3.1 +/- 0.2 ng/ml; functional class III: 3.9 +/- 0.3 ng/ml; functional class IV: 5.1 +/- 0.6 ng/ml). Plasma sFas levels were significantly higher in patients with elevated pulmonary artery wedge pressure and a decresed cardiac index than in those with values in the normal range. In patients in functional class IV, there was no significant difference in plasma sFas levels between the survivors and non-survivors during 6-month follow-up. However, plasma levels of sFas tended to decrease in nine patients with clinical improvement (baseline sFas: 5.2 +/- 0.8 ng/ml; 6-month sFas: 4.3 +/- 0.5 ng/ml, p = 0.07) but were similar in patients with no change in functional class. TNF-alpha and IL-6 were increased significantly only in patients in functional class IV, as previously reported, but were not related to sFas. CONCLUSIONS: We found elevated levels of plasma sFas and no increase in plasma sFas-L in human CHF. The increase in sFas may play an important role in the pathophysiologic mechanisms of CHF.
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Apoptose , Insuficiência Cardíaca/sangue , Glicoproteínas de Membrana/sangue , Idoso , Cateterismo Cardíaco , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Proteína Ligante Fas , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Fator de Necrose Tumoral alfa/análiseRESUMO
Activation-induced cytidine deaminase (AID) is required for somatic hypermutation (SHM) and class switch recombination (CSR) of the immunoglobulin (Ig) gene. AID has been reported to be specifically expressed in the germinal center (GC). Follicular lymphoma (FL) cells are known to be exposed to GC reaction, as characterized by a high degree of SHM with some heterogeneity in terms of intraclonal microheterogeneity and antigen selection. The heterogeneity of SHM pattern in FL intrigued us to investigate the AID expression. AID expression was investigated in 19 FL materials consisting of 15 cases of FL fresh cells and four cell lines. In all, 10 fresh cells and three cell lines expressed AID, but the others did not. SHM was investigated in 12 fresh cells and four cell lines. The ongoing mutation was significantly different between AID-positive and AID-negative FL fresh cells (unpaired Student's t-test, P=0.047). Ongoing mutation was not seen in any of the cell lines. AID expression was associated with the ongoing mutation in FL fresh cells (two-tailed Pearson's coefficient correlation, r=0.899, P=0.01). The switch off of AID expression may start in the B-lineage differentiation stage counterpart of FL after optimizing SHM, indicated by the cessation of the ongoing mutation in AID-negative FL fresh cells.
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Citidina Desaminase/genética , Linfoma Folicular/genética , Linfoma Folicular/patologia , Idoso , Idoso de 80 Anos ou mais , Linfócitos B/patologia , Diferenciação Celular , Linhagem Celular Tumoral , Feminino , Humanos , Região Variável de Imunoglobulina/genética , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , Hipermutação Somática de Imunoglobulina , Células Tumorais CultivadasRESUMO
ABSTRACT A rice isolate of Magnaporthe grisea collected from China was avirulent on rice cvs. Hattan 3 and 13 other Japanese rice cultivars. The rice cv. Hattan 3 is susceptible to almost all Japanese blast fungus isolates from rice. The genetic basis of avirulence in the Chinese isolate on Japanese rice cultivars was studied using a cross between the Chinese isolate and a laboratory isolate. The segregation of avirulence or virulence was studied in 185 progeny from the cross, and monogenic control was demonstrated for avirulence to the 14 rice cultivars. The resistance gene that corresponds to the avirulence gene (Avr-Hattan 3) is thought to be located at the Pik locus. Resistance and susceptibility in response to the Chinese isolate in F(3) lines of a cross of resistant and susceptible rice cultivars were very similar to the Pik tester isolate, Ken54-20. Random amplified polymorphic DNA markers and restriction fragment length polymorphism markers from genetic maps of the fungus were used to construct a partial genetic map of Avr-Hattan 3. We obtained several flanking markers and one co-segregated marker of Avr-Hattan 3 in the 144 mapping population.
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A human monoclonal antibody, 11-50, was generated and was shown to recognize an onco-developmental carbohydrate antigen, LcOse4Cer. The isotype of this antibody was IgM, lambda, similar to the previously known human anti-LcOse4 antibodies, such as IgMWOO and HMST-1. We raised a murine anti-idiotypic antibody G3 (IgG1, kappa) against 11-50, and tested its reactivity towards the affinity purified human polyclonal anti-LcOse4 antibodies prepared from pooled human sera using a Gal beta 1-->3GlcNAc beta-immobilized column. The results indicated that at least a part of the human polyclonal anti-LcOse4 antibodies shared the G3 idiotype with 11-50. We further analyzed the sequence of variable regions of the two anti-LcOse4 antibodies, 11-50 and HMST-1. Sequence analysis of the heavy chain variable regions indicated that the VH regions of these two antibodies were highly homologous to each other (93.5% at the nucleic acid level), and these antibodies utilized the germline genes VH1.9III and hv3005f3 as the VH segments, which are closely related germline genes of the VHIII family. It was noted that these germline VH genes are frequently utilized in fetal B cells. The JH region of both antibodies was encoded by the JH4 gene. For the light chain, the V lambda segments of the two antibodies were 96.3% homologous to each other at the nucleic acid level. The V lambda segments of both antibodies showed the highest homology to the rearranged V lambda gene called V lambda II.DS among reported V lambda genes, while the exact germline V lambda genes encoding the two antibodies were not yet registered in available sequence databanks. The amino acid sequences of the J lambda segments of both antibodies were identical. These results indicate that the two human antibodies recognizing the onco-developmental carbohydrate antigen Lc4 are encoded by the same or very homologous germline genes.
Assuntos
Anticorpos Monoclonais/genética , Antígenos de Neoplasias/imunologia , Cadeias Pesadas de Imunoglobulinas/genética , Região Variável de Imunoglobulina/genética , Sequência de Aminoácidos , Anticorpos Anti-Idiotípicos/genética , Especificidade de Anticorpos , Antígenos de Neoplasias/genética , Sequência de Bases , Sequência de Carboidratos , Genes de Imunoglobulinas , Humanos , Dados de Sequência MolecularRESUMO
Coral reefs are in decline worldwide due to a combination of local and global causes. Over 40% of the recent coral loss on Australia's Great Barrier Reef (GBR) has been attributed to outbreaks of the coral-eating Crown-of-Thorns Seastar (CoTS). Testing of the hypotheses explaining these outbreaks is hampered by an inability to investigate the spatio-temporal distribution of larvae because they resemble other planktotrophic echinoderm larvae. We developed a genetic marker and tested it on 48 plankton samples collected during the 2014 spawning season in the northern GBR, and verified the method by PCR amplification of single larva. Surprisingly, most samples collected contained CoTS larvae. Larvae were detected 100 km south of current outbreaks of adult seastars, highlighting the potential for rapid expansion of the outbreak. A minimum estimate suggested that larvae numbers in the outbreak area (>10(10)) are about 4 orders of magnitude higher than adults (~10(6)) in the same area, implying that attempts to halt outbreaks by removing adults may be futile.