RESUMO
BACKGROUND: Enhancements in surgical techniques have led to improved outcomes for esophageal cancer. Recent findings have showed that esophageal cancer is frequently associated with multiple primary cancers, and surgical resection is usually complicated in such cases. The aim of this study was to clarify the clinical significance of surgery for patients with esophageal squamous cell cancer associated with multiple primary cancers. METHODS: The clinical outcomes of surgical resection for esophageal cancer were compared among 79 patients with antecedent and/or synchronous cancers (Multiple cancer group) and 194 patients without antecedent and/or synchronous cancers (Single cancer group). RESULTS: The most common site of multiple primary cancers was the pharynx (36 patients; 29.7%), followed by the stomach (24 patients; 19.8%). The reconstruction method was more complicated in the Multiple cancer group as a result of the prolonged surgery time and increased blood loss. However, postoperative morbidity and overall survival (OS) did not differ between the two groups. After esophagectomy, metachronous cancers were observed in 26 patients, with 30 regions in total, and 93.1% were found to be curable. Sex was the only independent risk factors for developing metachronous cancer after esophagectomy. CONCLUSIONS: The presence of antecedent and synchronous cancers complicates the surgical resection of esophageal cancer; however, no differences were found in the OS and postoperative morbidity between the two groups. Therefore, surgical intervention should be selected as a first-line treatment. Because second primary cancers are often observed in esophageal cancer, we recommend a close follow-up using esophagogastroduodenoscopy and contrast-enhanced computed tomography.
Assuntos
Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Recidiva Local de Neoplasia/patologia , Neoplasias Primárias Múltiplas/cirurgia , Idoso , Carcinoma de Células Escamosas/mortalidade , Distribuição de Qui-Quadrado , Estudos de Coortes , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Esofagectomia/métodos , Esofagectomia/mortalidade , Feminino , Humanos , Japão , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/mortalidade , Estadiamento de Neoplasias , Neoplasias Primárias Múltiplas/mortalidade , Neoplasias Primárias Múltiplas/patologia , Segurança do Paciente , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVES: The purpose of this study was to elucidate the existence of the experience of and the frequency and severity of related concerns of distressful ethical situations encountered by nursing professionals in organ transplantation. METHODS: An anonymous self-administered questionnaire was mailed to 569 nurses in 79 facilities that performed organ transplantation with living or brain-dead donors who provided approval for this study. The questionnaire, developed according to the Likert method, was composed of 12 items referring to the basic attributes of nursing professionals based on the results of previous studies and the scientific literature, as well as 27 items referring to the presence or absence and the frequency and severity of concerns regarding ethical situations. The data were analyzed using descriptive statistics. RESULTS: The questionnaire was distributed to 569 nursing professionals working in 79 facilities that had provided consent for study participation. Responses were obtained from 218 participants (recovery rate: 38.3%). Among the 3 highest-ranking items, those in the first and second positions in terms of the presence or absence and the frequency of worries were the same as those in the second and third positions in terms of the severity of concerns. In addition, the 3 lower-ranking items also were the same. Among the ethical situations encountered by nursing professionals, the ones most often experienced that caused the most concern were the following: "I have questioned whether it was better for the recipient, who could not do self-care after the transplant, to undergo transplantation", and "I have felt that a recipient decided to receive a transplant without considering the importance of posttransplant self-management when making a decision about transplant surgery." CONCLUSIONS: The results indicate that most of the ethical issues related to organ transplantation in nursing practice were experienced because recipients, their families, and donors could not foresee the various problems that might occur after transplantation.
Assuntos
Ética em Enfermagem , Papel do Profissional de Enfermagem , Enfermeiras e Enfermeiros/psicologia , Transplante de Órgãos/ética , Transplante de Órgãos/enfermagem , Adulto , Família/psicologia , Relações Familiares , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Transplante de Órgãos/efeitos adversos , Pacientes/psicologia , Medição de Risco , Fatores de Risco , Autocuidado/ética , Inquéritos e Questionários , Doadores de Tecidos/psicologia , Transplantados , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: It remains unclear whether glycemic fluctuation can affect plaque rupture in acute myocardial infarction (AMI). Here we investigate the impact of glucose fluctuation on plaque rupture, as observed by optical coherence tomography (OCT), and monocyte subsets in patients with AMI. METHODS AND RESULTS: We studied 37 consecutive patients with AMI. All patients underwent OCT examination, which revealed 24 patients with plaque rupture and 13 patients without plaque rupture at the culprit site. Peripheral blood sampling was performed on admission. Three monocyte subsets (CD14(+)CD16(-), CD14(bright)CD16(+), and CD14(dim)CD16(+)) were assessed by flow cytometry. Glycemic variability, expressed as the mean amplitude of glycemic excursion (MAGE), was determined by a continuous glucose monitoring system 7 days after the onset of AMI. MAGE was significantly higher in the rupture patients than in the non-rupture patients (P=0.036). Levels of CD14(bright)CD16(+) monocytes from the rupture patients were significantly higher than those from the non-rupture patients (P=0.042). Of interest, levels of CD14(bright)CD16(+) monocytes correlated positively and significantly with MAGE (r=0.39, P=0.02). CONCLUSION: Dynamic glucose fluctuation may be associated with coronary plaque rupture, possibly through the preferential increase in CD14(bright)CD16(+) monocyte levels.
Assuntos
Glicemia/metabolismo , Monócitos/citologia , Placa Aterosclerótica/sangue , Idoso , Angiografia Coronária , Eletrocardiografia , Feminino , Citometria de Fluxo , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/patologia , Placa Aterosclerótica/patologia , Estudos Prospectivos , Tomografia de Coerência ÓpticaRESUMO
Postoperative pulmonary complications (PPCs) after esophagectomy have been reported to occur in 15.9-30% of patients and lead to increased postoperative morbidity and mortality, prolonged duration of hospital stay, and additional medical costs. The purpose of this retrospective cohort study was to investigate the possible prevention of PPCs by intensive preoperative respiratory rehabilitation in esophageal cancer patients who underwent esophagectomy. The subjects included 100 patients (87 males and 13 females with mean age 66.5 ± 8.6 years) who underwent esophagectomy. They were divided into two groups: 63 patients (53 males and 10 females with mean age 67.4 ± 9.0 years) in the preoperative rehabilitation (PR) group and 37 patients (34 males and 3 females with mean age 65.0 ± 7.8 years) in the non-PR (NPR) group. The PR group received sufficient preoperative respiratory rehabilitation for >7 days, and the NPR group insufficiently received preoperative respiratory rehabilitation or none at all. The results of the logistic regression analysis and multivariate analysis to correct for all considerable confounding factors revealed the rates of PPCs of 6.4% and 24.3% in the PR group and NPR group, respectively. The PR group demonstrated a significantly less incidence rate of PPCs than the NPR group (odds ratio: 0.14, 95% confidential interval: 0.02~0.64). [Correction added after online publication 25 June 2012: confidence interval has been changed from -1.86~ -0.22] This study showed that the intensive preoperative respiratory rehabilitation reduced PPCs in esophageal cancer patients who underwent esophagectomy.
Assuntos
Esofagectomia/efeitos adversos , Pneumopatias/prevenção & controle , Terapia Respiratória/métodos , Fatores Etários , Idoso , Estudos de Coortes , Intervalos de Confiança , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Esofagectomia/mortalidade , Feminino , Seguimentos , Humanos , Modelos Logísticos , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios/métodos , Valores de Referência , Testes de Função Respiratória , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the association of polymorphisms of the SSA1 gene (OMIM 109092) with primary Sjögren's syndrome (SS) and anti-SS-A/Ro52 antibody production. METHODS: Polymorphisms of SSA1 gene in 111 Japanese SS patients and in 97 healthy controls were analyzed with polymerase chain reaction and automated DNA sequencing. RESULTS: A new single-nucleotide polymorphism (SNP) was identified in intron 1 at position 7216. The allele frequency and genotype of 7216A/G were not significantly different between SS patients and control subjects. However, the allele frequency and genotype of 7216A/G were associated with the presence of anti-SS-A/Ro52 antibody among primary SS patients. The association was not found in patients with SLE, suggesting the limited role for the SNP in anti-SS-A/Ro52 antibody production. The 9571C/T polymorphism, which has been shown to associate with anti-SS-A/Ro52 antibody in Caucasian patients, was not associated with the presence of anti-SS-A/Ro52 antibody in Japanese patients. CONCLUSIONS: 7216A/G polymorphism of SSA1 gene may be one of the genetic factors that determine the presence of anti-SS-A/Ro52 antibody in patients with primary SS.
Assuntos
Adenosina Trifosfatases/genética , Adenosina Trifosfatases/imunologia , Predisposição Genética para Doença , Proteínas de Choque Térmico HSP70/genética , Proteínas de Choque Térmico HSP70/imunologia , Polimorfismo de Nucleotídeo Único , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/imunologia , Síndrome de Sjogren/genética , Síndrome de Sjogren/imunologia , Anticorpos Antinucleares/genética , Autoanticorpos/sangue , Humanos , Japão , Ribonucleoproteínas/genética , Ribonucleoproteínas/imunologiaRESUMO
The maximum likelihood estimation (MLE) is one of the most popular ways to estimate haplotype frequencies of a population with genotype data whose linkage phases are unknown. The MLE is commonly implemented in the use of the Expectation-Maximization (EM) algorithm. It is known that the EM algorithm carries the risk that an estimator may converge erroneously to one of the local maxima or saddle points of the likelihood surface, resulting in serious errors in the MLE of haplotype frequencies. In this note, by theoretical treatments we present the necessary and sufficient conditions that the local maxima or saddle points on the likelihood surface appear. As a rule of thumb, that the difference between the coupling and repulsive haplotype frequencies in phase known individuals is 3/2 times larger than the frequency of phase ambiguous individuals is the sufficient condition that the likelihood surface is unimodal. Moreover, we present the analytic solution to the biallelic two-locus problem, and construct a general algorithm to obtain the global maximum.
Assuntos
Frequência do Gene/genética , Haplótipos/genética , Funções Verossimilhança , Algoritmos , Simulação por Computador , Ligação Genética , Genética Populacional , Genótipo , Humanos , Modelos Genéticos , Modelos EstatísticosRESUMO
The background linkage disequilibrium (LD) in genetic isolates is of great interest in human genetics. Although many empirical studies have evaluated the background LD in European isolates, such as the Finnish and Sardinians, few data from other regions, such as Asia, have been reported. To evaluate the extent of background LD in East Asian genetic isolates, we analyzed the X chromosome in the Japanese population and in four Mongolian populations (Khalkh, Khoton, Uriankhai, and Zakhchin), the demographic histories of which are quite different from one another. Fisher's exact test revealed that the Japanese and Khalkh, which are the expanded populations, had the same or a relatively higher level of LD than did the Finnish, European American, and Sardinian populations. In contrast, the Khoton, Uriankhai, and Zakhchin populations, which have kept their population size constant, had a higher background LD. These results were consistent with previous genetic anthropological studies in European isolates and indicate that the Japanese and Khalkh populations could be utilized in the fine mapping of both complex and monogenic diseases, whereas the Khoton, Uriankhai, and Zakhchin populations could play an important role in the initial mapping of complex disease genes.
Assuntos
Genoma Humano , Desequilíbrio de Ligação , Repetições de Microssatélites , Cromossomo X , DNA Mitocondrial , Humanos , Japão , MongóliaRESUMO
The DNA Data Bank of Japan (DDBJ, http://www.ddbj.nig.ac.jp) has made an effort to collect as much data as possible mainly from Japanese researchers. The increase rates of the data we collected, annotated and released to the public in the past year are 43% for the number of entries and 52% for the number of bases. The increase rates are accelerated even after the human genome was sequenced, because sequencing technology has been remarkably advanced and simplified, and research in life science has been shifted from the gene scale to the genome scale. In addition, we have developed the Genome Information Broker (GIB, http://gib.genes.nig.ac.jp) that now includes more than 50 complete microbial genome and Arabidopsis genome data. We have also developed a database of the human genome, the Human Genomics Studio (HGS, http://studio.nig.ac.jp). HGS provides one with a set of sequences being as continuous as possible in any one of the 24 chromosomes. Both GIB and HGS have been updated incorporating newly available data and retrieval tools.
Assuntos
Bases de Dados de Ácidos Nucleicos , Genoma , Análise de Sequência de DNA , Animais , Arabidopsis/genética , Sequência de Bases , Disciplinas das Ciências Biológicas , Coleta de Dados , Genoma Bacteriano , Genoma Humano , Genoma de Planta , Humanos , JapãoRESUMO
We analyzed the effect of 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of triplex-forming oligonucleotide (TFO) on pyrimidine motif triplex formation at neutral pH, a condition where pyrimidine motif triplexes are unstable. The binding constant of the pyrimidine motif triplex formation at pH 6.8 with 2',4'-BNA modified TFO was about 20 times larger than that observed with unmodified TFO. The observed increase in the binding constant at neutral pH by the 2',4'-BNA modification resulted from the considerable decrease in the dissociation rate constant.
Assuntos
DNA/química , Metano/análogos & derivados , Oligonucleotídeos/química , Nucleotídeos de Pirimidina/química , Hidrocarbonetos , Cinética , Metano/química , TermodinâmicaRESUMO
Although Fas-mediated cell death may play a role in atherogenesis, causal data in support of this hypothesis are lacking. The present study investigated the possibility that endothelial cells are involved in vascular smooth muscle cell (VSMC) apoptosis via the Fas-FasL pathway, and hence in atherogenesis. FACS analysis detected FasL on the surface of human umbilical vein endothelial cells (HUVECs) and immunofluorescence staining of the HUVECs demonstrated high levels of FasL in the intracellular compartment. FasL was down-regulated 4 h after tumor necrosis factor (TNFalpha) treatment, coinciding with maximal surface expression of the adhesion molecules vascular cell adhesion molecule-1 and E-selectin. However, the down-regulation of FasL expression was transient, as surface expression returned within 24 h of TNFalpha treatment. When cocultured with VSMCs, the FasL-expressing EC could kill the VSMCs in a manner that could be blocked by recombinant Fas-Fc, deployed as a soluble receptor for Fas. Moreover, when human coronary arteries were studied with immunohistochemistry using G247-4 monoclonal antibody for the detection of FasL, few FasL positive EC were observed in diffuse intimal thickening. In contrast, endothelium overlying the plaque showed prominent and uniform expression of FasL. These findings suggest that the Fas/FasL pathway can be used by EC to induce VSMC apoptosis in the atherosclerotic lesion.
Assuntos
Apoptose/efeitos dos fármacos , Endotélio Vascular/química , Glicoproteínas de Membrana/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Adulto , Idoso , Técnicas de Cocultura , Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/patologia , Regulação para Baixo/efeitos dos fármacos , Endotélio Vascular/patologia , Proteína Ligante Fas , Feminino , Humanos , Imuno-Histoquímica , Masculino , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/fisiologia , Pessoa de Meia-Idade , Músculo Liso Vascular/citologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
For development of ideal antisense and antigene molecules, various chemical modifications of oligonucleotides have been studied. However, despite their importance, there is only limited information available on the triplex-forming ability of the conformationally restricted or locked oligonucleotides. We report herein that 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of triplex-forming oligonucleotide (TFO) significantly enhances the binding affinity towards target dsDNA. On Tm measurements, the triplex with the 2',4'-BNA oligonucleotides were found to be stabilized with deltaTm/modification of +4.3 to +5 degrees C at pH 6.6 compared to the triplexes with the unmodified oligonucleotide. By means of gel-retardation assay, the binding constant of the 2',4'-BNA oligonucleotide at pH 7.0 was at least 300-fold higher than that of the natural oligonucleotide. In addition, the 2',4'-BNA oligonucleotide clearly showed the inhibition of the NF-kappaB transcription factor (p50)-target dsDNA binding by forming a stable triplex at pH 7.0.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/síntese química , Oligonucleotídeos/síntese química , Compostos Bicíclicos Heterocíclicos com Pontes/química , Dicroísmo Circular , DNA/química , DNA/efeitos dos fármacos , DNA/metabolismo , Pegada de DNA , Desoxirribonuclease I/química , Indicadores e Reagentes , NF-kappa B/antagonistas & inibidores , Conformação de Ácido Nucleico , Oligonucleotídeos/químicaRESUMO
We examined the effects of two noradrenergic tricyclic antidepressants and two selective serotonin re-uptake inhibitors in the tail suspension test, with a suspension period of 30 min instead of the usual 10 min. Within the first 10 min, desipramine, nortriptyline and fluvoxamine significantly reduced the duration of immobility. Whereas desipramine and nortriptyline were also efficacious in the rest of the test period, fluvoxamine was not. Fluoxetine showed no significant effect throughout the study period. These results suggest that a prolonged tail suspension test results in functional changes in the noradrenergic and serotonergic systems and alters the sensitivity to antidepressants.
Assuntos
Inibidores da Captação Adrenérgica/farmacologia , Antidepressivos de Segunda Geração/farmacologia , Antidepressivos Tricíclicos/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Desipramina/farmacologia , Fluoxetina/farmacologia , Fluvoxamina/farmacologia , Masculino , Modelos Animais , Nortriptilina/farmacologia , Ratos , Ratos Endogâmicos , Transmissão Sináptica/efeitos dos fármacos , CaudaRESUMO
Some cationic triglycerides 1Aa-1Cb which have a symmetrical structure were effectively synthesized and formulated into cationic liposomes with the co-lipid dioleoylphosphatidylethanolamine (DOPE) and/or dilauroylphosphatidylcholine (DLPC). The plasmid encoding a luciferase was delivered into CHO cells by using these cationic liposomes. Our symmetrical cationic triglycerides showed high transfection activity when DOPE was used as a co-lipid. Among the symmetrical cationic triglycerides synthesized here, 1Ab and 1Ac, which have an oleoyl group at the 1- and 3-position in the glycerol backbone and also have a relatively long linker connecting the 2-hydroxy group in glycerol with the quaternary ammonium head group, were found to be the most suitable for gene delivery into cells. The transfection activity of the symmetrical cationic triglyceride 1Ab was comparable with that of its asymmetrical congener 6 and several times higher than that of Lipofectin.
Assuntos
Técnicas de Transferência de Genes/normas , Lipossomos/síntese química , Triglicerídeos/síntese química , Animais , Cátions , Humanos , Lipossomos/normas , Lipossomos/uso terapêutico , Luciferases/genética , Espectroscopia de Ressonância Magnética , Fosfatidiletanolaminas , Fosfolipídeos/metabolismo , Triglicerídeos/metabolismo , Triglicerídeos/normasRESUMO
Extreme instability of pyrimidine motif triplex DNA at physiological pH severely limits its use in an artificial control of gene expression in vivo. Stabilization of the pyrimidine motif triplex at physiological pH is, therefore, crucial in improving its therapeutic potential. To this end, we have investigated the thermodynamic and kinetic effects of our previously reported chemical modification, 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of triplex-forming oligonucleotide (TFO), on pyrimidine motif triplex formation at physiological pH. The thermodynamic analyses indicated that the 2',4'-BNA modification of TFO increased the binding constant of the pyrimidine motif triplex formation at neutral pH by approximately 20 times. The number and position of the 2',4'-BNA modification introduced into the TFO did not significantly affect the magnitude of the increase in the binding constant. The consideration of the observed thermodynamic parameters suggested that the increased rigidity itself of the 2',4'-BNA-modified TFO in the free state relative to the unmodified TFO may enable the significant increase in the binding constant at neutral pH. Kinetic data demonstrated that the observed increase in the binding constant at neutral pH by the 2',4'-BNA modification of TFO resulted from the considerable decrease in the dissociation rate constant. Our results certainly support the idea that the 2',4'-BNA modification of TFO could be a key chemical modification and may eventually lead to progress in therapeutic applications of the antigene strategy in vivo.
Assuntos
DNA/química , Pirimidinas/química , Eletroforese , Concentração de Íons de Hidrogênio , Cinética , Conformação de Ácido Nucleico , Espectrofotometria Ultravioleta , TermodinâmicaRESUMO
Fluvoxamine, a selective serotonin reuptake inhibitor, is frequently used along with benzodiazepine anxiolytics in clinics. In this study, the effects of fluvoxamine on the anxiolytic effects as well as adverse effects of benzodiazepines were examined in the light/dark box, rota-rod and passive avoidance tests using mice. Diazepam, ethyl loflazepate and its active metabolite, CM7116, were used as benzodiazepine anxiolytics. The anxiolytic effects of diazepam, ethyl loflazepate and CM7116 were potentiated by intraperitoneal treatment with fluvoxamine at 10 mg/kg, whereas only those of ethyl loflazepate were potentiated by fluvoxamine at 45 mg/kg. The motor incoordination and amnesia induced by ethyl loflazepate and CM7116 were not affected by fluvoxamine, although these adverse effects of diazepam were potentiated by fluvoxamine at 45 mg/kg. Fluvoxamine itself showed no effects in any of the tests. These results suggest that low-dose fluvoxamine potentiates the anxiolytic effects of benzodiazepines, while high-dose fluvoxamine augments the adverse effects depending on the benzodiazepine used. Consequently, when fluvoxamine is administered along with benzodiazepines, the doses of both fluvoxamine and benzodiazepines should be carefully chosen to achieve anxiolytic effects without any adverse results.
Assuntos
Amnésia/induzido quimicamente , Ansiolíticos/efeitos adversos , Ansiolíticos/farmacologia , Ataxia/induzido quimicamente , Benzodiazepinas , Fluvoxamina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Animais , Ansiolíticos/uso terapêutico , Diazepam/efeitos adversos , Diazepam/farmacologia , Diazepam/uso terapêutico , Relação Dose-Resposta a Droga , Interações Medicamentosas , Quimioterapia Combinada , Fluvoxamina/uso terapêutico , Masculino , Camundongos , Camundongos EndogâmicosRESUMO
Novel oligonucleotide analogues, containing a 3'-amino-2',4'-BNA unit, were successfully synthesized, and they showed superior duplex and triplex forming ability as well as BNA itself, along with remarkable enzymatic stability.
Assuntos
Amidas/química , Hidrocarbonetos Aromáticos com Pontes/química , DNA/química , Oligonucleotídeos/síntese química , Ácidos Fosfóricos/química , RNA/metabolismo , Hidrocarbonetos Aromáticos com Pontes/síntese química , Hidrocarbonetos Aromáticos com Pontes/metabolismo , DNA/metabolismo , Estrutura Molecular , Conformação de Ácido Nucleico , Ácidos Nucleicos Heteroduplexes , Oligonucleotídeos/química , Oligonucleotídeos/metabolismo , Diester Fosfórico Hidrolases/farmacologia , RNA/química , Venenos de Serpentes/enzimologiaRESUMO
The clinical features of 8 patients with pulmonary tuberculosis under treatment in the Koebaru Central Hospital, a community hospital without restricted tuberculosis wards, between 1992 and 2000 were evaluated. The major findings in the present study were: i) recently, the number of elderly patients with reactivated pulmonary tuberculosis has increased, ii) none of the patients showed respiratory symptoms, and 3 patients had negative Mantoux skin tests, iii) only one patient showed cavities on chest radiography, and iv) none of the expectorated sputum samples was smear-positive for Mycobacterium tuberculosis. Smears of intrabronchial sputum sampled using a fiberoptic bronchoscope from pulmonary lesions in patients without any symptoms were useful for establishing the diagnoses. Considering all aspects, it is important to perform aggressive evaluations, even for elderly patients, utilizing a fiberoptic bronchoscope for early diagnosis of pulmonary tuberculosis and to prevent nosocomial infections.
Assuntos
Tuberculose Pulmonar/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Broncoscopia , Feminino , Hospitais Comunitários , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose Pulmonar/fisiopatologiaRESUMO
We have previously reported that 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) had unprecedented binding affinity towards its complementary RNA. We reported herein that the antisense 2',4'-BNA oligonucleotides showed potent inhibitory effect on gene expression of Intercellular Adhesion Molecule-1 (ICAM-1) in living cells. The contribution of RNase H to this antisense effect and adequate stability of 2',4'-BNA oligonucleotides to enzymatic degradation were also demonstrated.
Assuntos
Molécula 1 de Adesão Intercelular/genética , Metano/análogos & derivados , Metano/química , Oligonucleotídeos Antissenso/química , Oligonucleotídeos Antissenso/farmacologia , Sequência de Bases , Células Cultivadas , DNA/química , Expressão Gênica/efeitos dos fármacos , Humanos , Hidrocarbonetos , Molécula 1 de Adesão Intercelular/biossíntese , Hibridização de Ácido Nucleico , Oligonucleotídeos Antissenso/metabolismo , RNA Complementar/químicaRESUMO
It is absolutely necessary for practical application of antigene strategy to create nucleoside analogues recognizing pyrimidine.purine interruption in dsDNA. To develop a nucleoside analogue to interact with T.A interruption, we designed and synthesized a novel 2',4'-BNA monomer (HBB), 2-(2'-O,4'-C-methyleneribofuranosyl)phenol, and it was introduced into a triplex-forming oligonucleotide (TFO). On melting temperature (Tm) measurements, HBB was found to interact with T.A interruption with moderate binding affinity, and unprecedented dU.A base pair recognition ability of HBB was also observed.