RESUMO
OBJECTIVES: Cognitive social capital (SC), such as attitude, trust, or norms, may help improve resilience among survivors, thus improving their health. However, the association between cognitive SC and the risk of all-cause mortality among survivors after the natural disaster has never been investigated. The purpose of the present study is to investigate the association between cognitive SC and the risk of all-cause mortality among survivors of the Great East Japan Earthquake (GEJE). STUDY DESIGN: Prospective cohort study. METHODS: We conducted a health survey on 1654 residents aged ≥18 years who lived in two areas affected by the GEJE. One year after the GEJE, between June and August 2012, cognitive SC (helping each other, trust, greeting, and solving problems together) was assessed using a self-administrated questionnaire. We divided the subjects into two groups based on response to questionnaire: "high" or "low." We obtained information on death and emigration from the Residential Registration Record and followed up on the participants from June 2012 to November 2020. The Cox proportional hazards regression analysis was used for estimating the multivariate-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of all-cause mortality according to each cognitive SC indicator. RESULTS: During the 8.5 years of follow-up, 213 subjects died (12.9%). For greeting, compared with subjects who were "high," subjects who were "low" were significantly associated with the risk of all-cause mortality (HR: 2.92, 95% CI: 1.19-7.17). No statistically significant association was observed for helping each other, trust, and solving problems together. CONCLUSION: Our findings suggest that perception of greeting may be associated with the risk of all-cause mortality in survivors after natural disasters.
Assuntos
Terremotos , Capital Social , Adolescente , Adulto , Cognição , Humanos , Japão/epidemiologia , Estudos Prospectivos , SobreviventesRESUMO
BACKGROUND: The objective of this randomized phase II trial was to evaluate efficacy and safety of the therapeutic sequence of regorafenib followed by cetuximab, compared with cetuximab followed by regorafenib, as the current standard sequence for metastatic colorectal cancer patients. PATIENTS AND METHODS: Patients with KRAS exon 2 wild-type metastatic colorectal cancer after failure of fluoropyrimidine, oxaliplatin, and irinotecan were randomized to receive sequential treatment with regorafenib followed by cetuximab ± irinotecan (R-C arm), or the reverse sequence [cetuximab ± irinotecan followed by regorafenib (C-R arm)]. The primary end point was overall survival (OS). Key secondary end points included progression-free survival (PFS) with initial treatment (PFS1), PFS with second treatment (PFS2), safety, and quality of life. Exploratory end points included serial biomarker analyses, including oncogenic alterations from circulating tumor DNA or multiple serum or plasma proteins. RESULTS: One-hundred one patients were randomized and eligible for efficacy analysis. Sequential treatment was successful in 86% patients in both arms. Median OS for R-C and C-R was 17.4 and 11.6 months, respectively (P = 0.0293), with a hazard ratio (HR) of 0.61 for OS [95% confidence interval (CI) 0.39-0.96]. The HR for PFS1 (regorafenib in R-C versus cetuximab in C-R) was 0.97 (95% CI 0.61-1.54), and PFS2 (C in R-C versus R in C-R) was 0.29 (95% CI 0.17-0.50). No unexpected safety signals were observed. The quality of life scores during the entire treatment period was not significantly different between the two arms. Circulating biomarker analyses showed emerging oncogenic alterations in RAS, BRAF, EGFR, HER2, and MET, which were more commonly detected after cetuximab than after regorafenib. CONCLUSIONS: The therapeutic sequence of regorafenib followed by cetuximab suggests a longer OS than the current standard sequence.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adenocarcinoma/secundário , Idoso , Cetuximab/administração & dosagem , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Compostos de Fenilureia/administração & dosagem , Prognóstico , Piridinas/administração & dosagem , Taxa de SobrevidaRESUMO
BACKGROUND: Improving patients' oral hygiene is an option for preventing postoperative pneumonia that may be caused by aspiration of oral and pharyngeal secretions. Whether preoperative oral care by a dentist can decrease postoperative complications remains controversial. A retrospective cohort study was undertaken to assess the association between preoperative oral care and postoperative complications among patients who underwent major cancer surgery. METHODS: The nationwide administrative claims database in Japan was analysed. Patients were identified who underwent resection of head and neck, oesophageal, gastric, colorectal, lung or liver cancer between May 2012 and December 2015. The primary outcomes were postoperative pneumonia and all-cause mortality within 30 days of surgery. Patient background was adjusted for with inverse probability of treatment weighting using propensity scoring. RESULTS: Of 509 179 patients studied, 81 632 (16·0 per cent) received preoperative oral care from a dentist. A total of 15 724 patients (3·09 per cent) had postoperative pneumonia and 1734 (0·34 per cent) died within 30 days of surgery. After adjustment for potential confounding factors, preoperative oral care by a dentist was significantly associated with a decrease in postoperative pneumonia (3·28 versus 3·76 per cent; risk difference - 0·48 (95 per cent c.i. -0·64 to-0·32) per cent) and all-cause mortality within 30 days of surgery (0·30 versus 0·42 per cent; risk difference - 0·12 (-0·17 to -0·07) per cent). CONCLUSION: Preoperative oral care by a dentist significantly reduced postoperative complications in patients who underwent cancer surgery.
Assuntos
Assistência Odontológica/estatística & dados numéricos , Neoplasias/cirurgia , Complicações Pós-Operatórias/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Assistência Odontológica/mortalidade , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Neoplasias/mortalidade , Saúde Bucal/estatística & dados numéricos , Pneumonia/etiologia , Pneumonia/mortalidade , Complicações Pós-Operatórias/mortalidade , Cuidados Pré-Operatórios/mortalidade , Cuidados Pré-Operatórios/estatística & dados numéricos , Pontuação de Propensão , Estudos Retrospectivos , Fatores de RiscoRESUMO
PURPOSE: The goal of chemotherapy for metastatic breast cancer (MBC) is to prolong survival and maintain health-related quality of life. This study aimed to evaluate long-term health status of patients with MBC who participated in the phase III randomized SELECT BC trial. METHODS: In the SELECT BC trial, patients were randomly allocated to the S-1 or taxane (paclitaxel or docetaxel) arm. Health status was assessed by EQ-5D at pre-treatment, 3 and 6 months after randomization, and every 6 months thereafter to the extent possible. Least square mean scores were assessed to compare EQ-5D index values between groups. Time to deterioration analysis was also performed by defining the minimally important difference of EQ-5D as 0.05 or 0.1. RESULTS: The number of patients for EQ-5D analysis was 175 and 208 in the taxane and S-1 arms, respectively. Least square mean EQ-5D index values up to 60 months were 0.741 (95 % CI [0.713-0.769]) in the taxane arm and 0.748 [0.722-0.775] in the S-1 arm. The EQ-5D index value during PFS up to 12 months in the S-1 was superior to the corresponding index value in the taxane (0.812 [0.789-0.834] vs. 0.772 [0.751-0.792], P = 0.009). Time to deterioration analysis also revealed that S-1 significantly delayed the deterioration of EQ-5D index value during the period before progression (P = 0.002 and 0.003). CONCLUSIONS: Our findings suggest that the EQ-5D index value was higher in patients treated with S-1 during first-line chemotherapy. Considering non-inferiority of S-1 in terms of OS, obtained quality-adjusted life years may be greater in the S-1 arm.
Assuntos
Neoplasias da Mama/psicologia , Nível de Saúde , Ácido Oxônico/uso terapêutico , Anos de Vida Ajustados por Qualidade de Vida , Taxoides/uso terapêutico , Tegafur/uso terapêutico , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Combinação de Medicamentos , Feminino , Humanos , Pessoa de Meia-Idade , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: A major challenge to understanding osteoarthritis (OA) pathology is identifying the cellular events that precede the onset of cartilage damage. The objective of this study is to determine the effect of joint destabilization on early changes to fibrocartilage in the joint. DESIGN/METHODS: The anterior cruciate ligament was transected in collagen reporter mice (Col1CFP and ColXRFP). Mineralization labels were given every 2 weeks to measure new mineralized cartilage apposition. Novel fluorescent histology of mineralized tissue was used to characterize the changes in fibrocartilage at 2 and 4 weeks post-injury. RESULTS: Changes in fibrocartilaginous structures of the joint occur as early as 2 weeks after injury and are well developed by 4 weeks. The alterations are seen in multiple entheses and in the medial surface of the femoral and tibial condyles. In the responding entheses, mineral apposition towards the ligament midsubstance results in thickening of the mineralize fibrocartilage. These changes are associated with increases in ColX-RFP, Col1-CFP reporter activity and alkaline phosphatase enzyme activity. Mineral apposition also occurs in the fibrocartilage of the non-articular regions of the medial condyles by 2 weeks and develops into osteophytes by 4 weeks post-injury. An unexpected observation is punctate expression of tartrate resistant acid phosphatase activity in unmineralized fibrochondrocytes adjacent to active appositional mineralization. DISCUSSION: These observations suggest that fibrocartilage activates prior to degradation of the articular cartilage. Thus clinical and histological imaging of fibrocartilage may be an earlier indicator of disease initiation and may indicate a more appropriate time to start preventative treatment.
Assuntos
Lesões do Ligamento Cruzado Anterior , Fibrocartilagem/fisiopatologia , Instabilidade Articular/fisiopatologia , Fosfatase Ácida/metabolismo , Animais , Calcificação Fisiológica/fisiologia , Cartilagem Articular/patologia , Condrócitos/metabolismo , Modelos Animais de Doenças , Feminino , Fêmur/patologia , Fibrocartilagem/patologia , Genes Reporter , Proteínas de Fluorescência Verde , Isoenzimas/metabolismo , Instabilidade Articular/metabolismo , Instabilidade Articular/patologia , Camundongos Transgênicos , Fosfatase Ácida Resistente a Tartarato , Tíbia/patologiaRESUMO
OBJECTIVE: To better understand the role of the professional oral health care for elderly in improving geriatric oral health, the effects of short-term professional oral health care (once per week for 1 month) on oral microbiological parameters were assessed. METHODS: Parallel, open-labelled, randomize-controlled trial was undertaken in a nursing home for elderly in Shizuoka, Japan. Thirty-four dentate elderly over 74 years were randomly assigned from ID number to the intervention (17/34) and control (17/34) groups. The outcomes were changes in oral microbiological parameters (number of bacteria in unstimulated saliva; whole bacteria, Streptococcus, Fusobacterium and Prevotella: opportunistic pathogens detection: and index of oral hygiene evaluation [Dental Plaque Index, DPI]) within the intervention period. Each parameter was evaluated at before and after intervention period. Four elderly were lost from mortality (1), bone fracture (1), refused to participate (1) and multi-antibiotics usage (1). Finally, 30 elderly were analysed (14/intervention and 16/control). RESULTS: At baseline, no difference was found between the control and intervention groups. After the intervention period, the percentage of Streptococcus species increased significantly in the intervention group (Intervention, 86% [12/14]; Control, 50% [8/16]: Fisher's, right-tailed, P < 0.05). Moreover, DPI significantly improved in the intervention group (Intervention, 57% [8/14]; Control, 13% [2/16]: Fisher's, two-tailed, P < 0.05). The improvement in DPI extended for 3 months after intervention. None of side effects were reported. CONCLUSION: The short-term professional oral health care can improve oral conditions in the elderly.
Assuntos
Assistência Odontológica para Idosos , Nível de Saúde , Saúde Bucal , Idoso , Carga Bacteriana , Índice de Placa Dentária , Higienizadores de Dentadura/uso terapêutico , Seguimentos , Fusobacterium/isolamento & purificação , Humanos , Pessoa de Meia-Idade , Boca/microbiologia , Prevotella/isolamento & purificação , Pseudomonas aeruginosa/isolamento & purificação , Saliva/metabolismo , Saliva/microbiologia , Streptococcus/isolamento & purificação , Escovação Dentária/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: To analyze changes in the capsule from idiopathic frozen shoulders and clarify their etiology. MATERIALS AND METHODS: Samples (the rotator interval capsule, middle glenohumeral ligament (MGHL), and inferior glenohumeral ligament (IGHL)) were collected from 12 idiopathic frozen shoulders with severe stiffness and 18 shoulders with rotator cuff tears as a control. The number of cells was counted and the tissue elasticity of the samples was calculated by scanning acoustic microscopy (SAM). The amount of glycosaminoglycan content was assessed by alcian blue staining. Gene and protein expressions related to fibrosis, inflammation, and chondrogenesis were analyzed by quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). Furthermore, the total genes of the two groups were compared by DNA microarray analysis. RESULTS: The number of cells was significantly higher and the capsular tissue was significantly stiffer in idiopathic frozen shoulders compared with shoulders with rotator cuff tears. Staining intensity of alcian blue was significantly stronger in idiopathic frozen shoulders. Gene expressions related to fibrosis, inflammation, and chondrogenesis were significantly higher in idiopathic frozen shoulders compared with shoulders with rotator cuff tears assessed by both qPCR and DNA microarray analysis. CONCLUSION: In addition to fibrosis and inflammation, which used to be considered the main pathology of frozen shoulders, chondrogenesis is likely to have a critical role in pathogenesis of idiopathic frozen shoulders.
Assuntos
Bursite/patologia , Condrogênese/fisiologia , Cápsula Articular/patologia , Articulação do Ombro/patologia , Adulto , Bursite/metabolismo , Bursite/fisiopatologia , Elasticidade , Feminino , Fibrose , Perfilação da Expressão Gênica/métodos , Humanos , Inflamação/metabolismo , Inflamação/patologia , Inflamação/fisiopatologia , Cápsula Articular/metabolismo , Cápsula Articular/fisiopatologia , Masculino , Microscopia Acústica , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Reação em Cadeia da Polimerase em Tempo Real/métodos , Manguito Rotador/patologia , Lesões do Manguito Rotador , Articulação do Ombro/metabolismo , Articulação do Ombro/fisiopatologiaRESUMO
OBJECTIVES: We have previously reported that the level of leucine-rich alpha-2-glycoprotein (LRG) expression is specifically increased in cerebrospinal fluid (CSF) of idiopathic normal pressure hydrocephalus (INPH). The objective of this study is to examine the localization of LRG - the cerebral areas where it is expressed. METHOD: The histological sections of autopsied brain specimens from ten subjects, five adult cases (mean age 43.6 years; range 34-50 years) and five senile cases (mean age 76.0 years; range 67-88 years) were prepared, multistained with antibodies against human LRG, glial fibrillary acidic protein (GFAP), CD31, and aquaporin-4 (AQP4), and reviewed for the expression sites of LRG. RESULTS: Immunostains of GFAP and LRG were compared in standard brain specimens from elderly patients. The results indicated that LRG is distributed throughout the entire brain, with especially high expression in the deep cerebral cortex. In addition, the cells that express LRG showed similar morphology to astrocytes. Double staining of CD31 and LRG revealed a significant expression of LRG in the pericapillary regions. The expression was observed in resident astrocytes, as well as in the capillary vessel to which astrocytic processes grow and adhere. When age-related comparisons were made between senile and adult specimens, LRG expression increased with age. CONCLUSION: LRG expression in resident astrocytes increased with age.
Assuntos
Encéfalo/metabolismo , Regulação da Expressão Gênica , Glicoproteínas/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Aquaporina 4/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Transportador de Glucose Tipo 5/metabolismo , Glicoproteínas/genética , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/metabolismo , Fator de Transcrição 2 de Oligodendrócitos , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , RNA Mensageiro/metabolismoRESUMO
Antigen-specific mucosal immunity is generally induced by the stimulation of inductive mucosal sites. In this study, we found that the replication-deficient vaccinia virus vector, DIs, generates antigen-specific mucosal immunity and systemic responses. Following intradermal injection of recombinant DIs expressing simian immunodeficiency virus gag (rDIsSIVgag), we observed increased levels of SIV p27-specific IgA and IgG antibodies in faecal extracts and plasma samples, and antibody-forming cells in the intestinal mucosa and spleen of C57BL/6 mice. Antibodies against p27 were not detected in nasal washes, saliva, and vaginal washes. The enhanced mucosal and systemic immunity persisted for 1 year of observation. Induction of Gag-specific IFN-gamma spot-forming CD8(+) T cells in the spleen, small intestinal intraepithelial lymphocytes, and submandibular lymph nodes was observed in the intradermally injected mice. Heat-inactivated rDIsSIVgag rarely induced antigen-specific humoral and T-helper immunity. Moreover, rDIsSIVgag was detected in MHC class II IA antigen-positive (IA(+)) cells at the injection site. Consequently, intradermal delivery of rDIs effectively induces antigen-specific humoral and cellular immunity in gut-mucosal tissues of mice. Our data suggest that intradermal injection of an rDIs vaccine may be useful against mucosally transmitted pathogens.
Assuntos
Imunidade nas Mucosas/imunologia , Vacinas contra a SAIDS/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/imunologia , Vaccinia virus/imunologia , Animais , Anticorpos Antivirais/sangue , DNA/química , DNA/genética , Feminino , Produtos do Gene gag/genética , Produtos do Gene gag/imunologia , Vetores Genéticos/imunologia , Imunidade nas Mucosas/efeitos dos fármacos , Imunização/métodos , Injeções Intradérmicas , Interferon gama/sangue , Camundongos , Camundongos Endogâmicos C57BL , Reação em Cadeia da Polimerase , Vacinas contra a SAIDS/administração & dosagem , Síndrome de Imunodeficiência Adquirida dos Símios/prevenção & controle , Organismos Livres de Patógenos Específicos , Estatísticas não ParamétricasRESUMO
We studied the immunogenicity of completely replication-deficient vaccinia virus Dairen I strain recombinant encoding simian immunodeficiency virus (SIV) gag/pol (rDIs) in both mucosal and systemic compartments. When administered either intranasally or intragastrically, rDIs elicited enhanced levels of both SIV Gag p27-specific IgA antibodies and specific plasma antibodies, and the enhanced immunity persisted for the 1-year of observation by intranasal immunization. Increases were observed in antigen-specific IgA antibody-forming cells (AFC) in intestinal mucosal tissues and in IgG AFC in spleens. Furthermore, induction of type 1 and 2 helper cytokines in CD4+ spleen T cells and of CD8+ IFN-gamma spot-forming cells in mucosal tissues was observed in the intranasally immunized mice. Moreover, not even high-dose rDIs generated an SIV gene signal in the brain tissues of immunized mice. These findings suggest that mucosal immunization with the DIs recombinant hold promise as a safe mucosal vector.
Assuntos
Imunidade nas Mucosas/imunologia , Vacinas contra a SAIDS/imunologia , Vírus da Imunodeficiência Símia/imunologia , Vaccinia virus/imunologia , Administração Intranasal , Animais , Anticorpos Antivirais/sangue , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Citocinas/análise , Citocinas/imunologia , Ensaio de Imunoadsorção Enzimática , Imunidade nas Mucosas/efeitos dos fármacos , Imunoglobulina A/sangue , Mucosa Intestinal/imunologia , Mucosa Intestinal/virologia , Camundongos , Camundongos Endogâmicos C57BL , Vacinas contra a SAIDS/administração & dosagem , Vírus da Imunodeficiência Símia/genética , Organismos Livres de Patógenos Específicos , Estatísticas não Paramétricas , Vacinas Sintéticas/administração & dosagem , Vacinas Sintéticas/imunologia , Vaccinia virus/genéticaRESUMO
Birt-Hogg-Dubé (BHD) syndrome is characterized by the development of pneumothorax, hair folliculomas and renal tumors and the responsible BHD gene is thought to be a tumor suppressor. The function of folliculin (Flcn), encoded by BHD, is totally unknown, although its interaction with Fnip1 has been reported. In this study, we identified a novel protein binding to Flcn, which is highly homologous to Fnip1, and which we named FnipL (recently reported in an independent study as Fnip2). The interaction between FnipL/Fnip2 and Flcn may be mediated mainly by the C-terminal domains of each protein as is the case for the Flcn-Fnip1 interaction. FnipL/Fnip2 and Flcn were located together in the cytoplasm in a reticular pattern, although solely expressed Flcn was found mainly in the nucleus. Cytoplasmic retention of Flcn was canceled with C-terminal truncation of FnipL/Fnip2, suggesting that FnipL/Fnip2 regulates Flcn distribution through their complex formation. By the employment of siRNA, we observed a decrease in S6K1 phosphorylation in the BHD-suppressed cell. We also observed a decrease in S6K1 phosphorylation in FNIP1- and, to a lesser extent, in FNIPL/FNIP2-suppressed cells. These results suggest that Flcn-FnipL/Fnip2 and Flcn-Fnip1 complexes positively regulate S6K1 phosphorylation and that FnipL/Fnip2 provides an important clue to elucidating the function of Flcn and the pathogenesis of BHD.
Assuntos
Carcinoma de Células Renais/metabolismo , Proteínas de Transporte/metabolismo , Neoplasias Renais/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Animais , Northern Blotting , Western Blotting , Células COS , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proteínas de Transporte/antagonistas & inibidores , Proteínas de Transporte/genética , Células Cultivadas , Chlorocebus aethiops , Citoplasma/metabolismo , Células HeLa , Humanos , Imunoprecipitação , Rim/metabolismo , Rim/patologia , Neoplasias Renais/genética , Neoplasias Renais/patologia , Fosforilação , Reação em Cadeia da Polimerase , Ligação Proteica , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas/antagonistas & inibidores , Proteínas Proto-Oncogênicas/genética , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/farmacologia , Proteínas Quinases S6 Ribossômicas/metabolismo , Síndrome , Transfecção , Proteínas Supressoras de Tumor/antagonistas & inibidores , Proteínas Supressoras de Tumor/genéticaRESUMO
We report a case of endometriosis in the right inguinal region, attached to the right round ligament in a 28-year-old woman. At the age of 20, laparoscopic left ovarian cystectomy and pelvic adhesiolysis for endometriosis was carried out. She noticed a right tender groin mass 7 months previously, and the tumour size fluctuated with the menstrual cycle. A poorly circumscribed elastic hard mass, measuring 3 cm in diameter, was palpated in her right inguinal region. Magnetic resonance imaging showed a 2.5 cm x 2.5 cm mass in the right inguinal canal and a 5.4 cm x 6.8 cm mass was seen in the left ovary. The mass enlarged during menstruation. The groin mass was removed, in addition to carrying out laparoscopic ovarian cystectomy. At operation, the groin mass was found to be in continuity with the round ligament of extraperitoneal portion. Histological diagnosis of endometriosis was made in both ovarian and inguinal tumours. After surgery, the pain disappeared completely. Worth mentioning is that MRI clearly showed the change of tumour size depending on the menstrual cycle, which aided in arriving at the correct diagnosis of endometriosis in an unusual location.
Assuntos
Endometriose/diagnóstico , Canal Inguinal , Ligamento Redondo do Útero , Adulto , Diagnóstico Diferencial , Endometriose/cirurgia , Feminino , Humanos , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: To investigate the status of education and employment of long-term survivors who became physically handicapped after treatment for high-grade osteosarcoma. METHODS: Of the osteosarcoma patients treated at our hospital, 41 patients aged less than 18 years at the initial presentation who were free of disease for 10 years or longer after the end of treatment were studied. The status of their education and employment was investigated via a questionnaire. RESULTS: Twenty-seven patients responded to the questionnaire (response rate, 65.9%). Of these patients, 73.1% (19/26) could return to the school they had attended before the disease, and 52% (13/25) graduated from college or university. The percentage of those who went to college or university was higher in the limb-sparing group. Seventy-two percent of the patients were engaged in clerical work, and the mean annual income was 4.01 million JPY (corresponding to about 24,000 EUR). No difference was noted in the status of employment between the amputation and limb-sparing groups. CONCLUSIONS: The percentage of patients who went to college or university was similar to the percentage in all Japanese. However, the status of the diseased limb appeared to affect school attendance. The mean annual income of the patients was comparable to that of the national average, and they experienced no major problems in their employment. Physical disabilities posed few problems in their daily living.
Assuntos
Neoplasias Ósseas/mortalidade , Pessoas com Deficiência/reabilitação , Emprego , Osteossarcoma/mortalidade , Adolescente , Adulto , Neoplasias Ósseas/terapia , Criança , Pessoas com Deficiência/educação , Feminino , Humanos , Japão , Inclusão Escolar , Masculino , Osteossarcoma/terapia , SobreviventesRESUMO
The non-Mendelian inheritance of organellar DNA is common in most plants and animals. In the isogamous green alga Chlamydomonas species, progeny inherit chloroplast genes from the maternal parent, as paternal chloroplast genes are selectively eliminated in young zygotes. Mitochondrial genes are inherited from the paternal parent. Analogically, maternal mitochondrial DNA (mtDNA) is thought to be selectively eliminated. Nevertheless, it is unclear when this selective elimination occurs. Here, we examined the behaviors of maternal and paternal mtDNAs by various methods during the period between the beginning of zygote formation and zoospore formation. First, we observed the behavior of the organelle nucleoids of living cells by specifically staining DNA with the fluorochrome SYBR Green I and staining mitochondria with 3,3'-dihexyloxacarbocyanine iodide. We also examined the fate of mtDNA of male and female parental origin by real-time PCR, nested PCR with single zygotes, and fluorescence in situ hybridization analysis. The mtDNA of maternal origin was completely eliminated before the first cell nuclear division, probably just before mtDNA synthesis, during meiosis. Therefore, the progeny inherit the remaining paternal mtDNA. We suggest that the complete elimination of maternal mtDNA during meiosis is the primary cause of paternal mitochondrial inheritance.
Assuntos
Chlamydomonas/genética , DNA Mitocondrial/genética , Herança Extracromossômica/genética , Meiose/genética , Animais , Benzotiazóis , Southern Blotting , Carbocianinas/metabolismo , Chlamydomonas/fisiologia , Diaminas , Hibridização in Situ Fluorescente/métodos , Microscopia de Fluorescência/métodos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Modelos Biológicos , Compostos Orgânicos/metabolismo , Reação em Cadeia da Polimerase , QuinolinasRESUMO
Caveolin-3 is a muscle-specific membrane protein that serves as a scaffold of various molecules. As previously reported, caveolin-3 deficiency causes muscle degeneration in mice. In the present study, gene expression profiles, analyzed in the skeletal muscles of caveolin-3 deficient mice using the DNA microarray technique, showed that the gene of osteopontin, a versatile regulator of inflammation and tissue repair, was significantly down-regulated. This is in contrast to mdx mice showing a markedly up-regulated osteopontin gene in their skeletal muscles. Recently, osteopontin has been reported to be important in the pathogenesis of muscular dystrophy. We examined whether up-regulated osteopontin gene expression in mdx muscles is altered by the deficiency of caveolin-3. To this end, we developed caveolin-3 and dystrophin double-deficient mice and used them for the analysis. Levels of osteopontin mRNA and protein in the double-deficient mice clearly decreased compared with those in mdx mice.
Assuntos
Caveolina 3/deficiência , Músculo Esquelético/metabolismo , Osteopontina/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos mdx , Músculo Esquelético/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Osteopontina/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
1. TAS-103, a novel condensed quinoline derivative, has been developed as an anticancer drug targeting topoisomerases I and II. 2. The purpose of the present study was to characterize the metabolism and urinary excretion of TAS-103 after the intravenous infusion of a single dose to patients in Phase I clinical trials. 3. Five metabolites were detected using high-performance liquid chromatography (HPLC) photodiode array and a precursor scan by liquid chromatography mass spectrometry mass spectrometry (LC/MS/MS). 4. Structures of the five metabolites were determined using the results of enzymatic hydrolysis and the analysis of production mass spectra obtained by LC/MS/MS, and by comparing HPLC retention times and UV, mass and production mass spectra of authentic standards. 5. The metabolites were identified as demethyl-TAS-103 glucuronide (DM-TAS-103-G), TAS-103 glucuronide (TAS-103-G), TAS-103 glucuronide N-oxide (NO-TAS-103-G), demethyl-TAS-103 (DM-TAS-103) and TAS-103 N-oxide (NO-TAS-103). 6. The mean total amount of TAS-103 and TAS-103-G in urine was only 6.03% of the dose, suggesting that urine is not the main elimination route. TAS-103 was extensively metabolized, and a small percentage of the parent drug (0.41%) was found in urine.
Assuntos
Aminoquinolinas/metabolismo , Aminoquinolinas/urina , Antineoplásicos/metabolismo , Antineoplásicos/urina , Indenos/metabolismo , Indenos/urina , Aminoquinolinas/administração & dosagem , Aminoquinolinas/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/urina , Glucuronídeos/química , Glucuronídeos/metabolismo , Glucuronídeos/urina , Humanos , Indenos/administração & dosagem , Indenos/química , Infusões Intravenosas , Espectrometria de Massas , Estrutura Molecular , Espectrofotometria Ultravioleta , Inibidores da Topoisomerase I , Inibidores da Topoisomerase IIRESUMO
An unusual case of endometriosis involving the right round ligament in a 40-year-old woman is presented. After giving birth to two children, she first noticed a tender mass in the right groin at the age of 36. It didn't change in size but pain appeared at the age of 38, disturbing her daily life. A poorly circumscribed elastic hard mass, measuring 3 cm in diameter, was palpable in her right inguinal region. Magnetic resonance imaging demonstrated a 2x3 cm mass in the right inguinal canal. At operation, a mass was found to be in continuity with the round ligament at the inguinal canal. Histological diagnosis was endometriosis. After operation, she was completely relieved of pain. It is important to include endometriosis in the differential diagnosis for painful inguinal masses in women of childbearing age.
Assuntos
Endometriose/patologia , Endometriose/cirurgia , Canal Inguinal/patologia , Ligamento Redondo do Útero/patologia , Adulto , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Cuidados Pré-OperatóriosRESUMO
In the process of screening of proteins binding to ribostamycin in bovine liver using the affinity column chromatography, we found that ribostamycin inhibited the chaperone activity of protein disulfide isomerase (PDI), but it did not inhibit the isomerase activity. PDI was identified by SDS-PAGE, Western blotting, and N-terminal amino acid sequence analysis. A 100:1 molar ratio of ribostamycin to PDI was almost sufficient to completely inhibit the chaperone activity of PDI. The binding affinity of ribostamycin to purified bovine PDI was determined by the Biacore system, which gave a K(D) value of 3.19 x 10(-4) M. This suggests that ribostamycin binds to region distinct from the CGHC motif of PDI. This is the first report to describe the inhibitor of the chaperone activity of PDI.
Assuntos
Antibacterianos/farmacologia , Chaperonas Moleculares/antagonistas & inibidores , Isomerases de Dissulfetos de Proteínas/antagonistas & inibidores , Ribostamicina/farmacologia , Animais , Antibacterianos/metabolismo , Sítios de Ligação , Bovinos , Enzimas Imobilizadas , Técnicas In Vitro , Cinética , Fígado/enzimologia , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Ligação Proteica , Isomerases de Dissulfetos de Proteínas/química , Isomerases de Dissulfetos de Proteínas/metabolismo , Ribostamicina/metabolismoRESUMO
Bilateral and simultaneous selective venous sampling from the cavernous sinus, inferior petrosal sinus, jugular vein and peripheral vein was performed in 13 patients with hyperprolactinemia in whom dynamic magnetic resonance imaging failed to reveal pituitary adenoma. The prolactin level in peripheral veins of the patients on admission ranged from 35 to 141 ng ml(-1), with a mean value of 69 ng ml(-1). All patients showed disturbance of menstruation or galactorrhea. The indication for surgery in the present study was extremely rare; the patients each wanted to become pregnant and had an intolerance of dopamine agonists. Trans-sphenoidal surgery was performed based on the results of selective venous sampling. The postoperative levels of prolactin were normalized in nine of the patients and normal pituitary function was preserved after surgery. The present study revealed a correspondence of laterality of the peak prolactin level with the main tumor location in patients with latent prolactinoma. However, the tumor/nontumor ratio did not necessarily coincide with the pattern of tumor location, and tumor location was accurately predicted in only 70% of the cases. Selective venous sampling directly from central veins is useful for diagnosis of microprolactinoma.