RESUMO
BACKGROUND: Total pancreatectomy is required to completely clear tumours that are locally advanced or located in the centre of the pancreas. However, reports describing clinical outcomes after total pancreatectomy are rare. The aim of this retrospective observational study was to assess clinical outcomes following total pancreatectomy using a nationwide registry and to create a risk model for severe postoperative complications. METHODS: Patients who underwent total pancreatectomy from 2013 to 2017, and who were recorded in the Japan Society of Gastroenterological Surgery and Japanese Society of Hepato-Biliary-Pancreatic Surgery database, were included. Severe complications at 30 days were defined as those with a Clavien-Dindo grade III needing reoperation, or grade IV-V. Occurrence of severe complications was modelled using data from patients treated from 2013 to 2016, and the accuracy of the model tested among patients from 2017 using c-statistics and a calibration plot. RESULTS: A total of 2167 patients undergoing total pancreatectomy were included. Postoperative 30-day and in-hospital mortality rates were 1·0 per cent (22 of 2167 patients) and 2·7 per cent (58 of 167) respectively, and severe complications developed in 6·0 per cent (131 of 2167). Factors showing a strong positive association with outcome in this risk model were the ASA performance status grade and combined arterial resection. In the test cohort, the c-statistic of the model was 0·70 (95 per cent c.i. 0·59 to 0·81). CONCLUSION: The risk model may be used to predict severe complications after total pancreatectomy.
ANTECEDENTES: La pancreatectomía total está indicada cuando se requiere la resección completa de tumores localmente avanzados o ubicados en el centro del páncreas. Sin embargo, existen pocos artículos que describan los resultados clínicos después de una pancreatectomía total. El objetivo de este estudio observacional retrospectivo fue evaluar los resultados clínicos después de una pancreatectomía total utilizando un registro nacional y crear un modelo de riesgo de complicaciones postoperatorias graves. MÉTODOS: Se incluyeron aquellos pacientes que se sometieron a una pancreatectomía total entre 2013 y 2017 y que fueron registrados en la base de datos de la Sociedad Japonesa de Cirugía Gastrointestinal y de la Sociedad Japonesa de Cirugía Hepato-Bilio-Pancreática. Las complicaciones graves a los 30 días se definieron como Clavien-Dindo grado III con reintervención o grado IV/V. Se analizó la aparición de complicaciones graves de los pacientes desde 2013 a 2016 y se evaluó la precisión del modelo entre los pacientes operados desde 2017 usando estadísticos c y un gráfico de calibración. RESULTADOS: Se incluyeron 2.167 pacientes sometidos a una pancreatectomía total. La mortalidad postoperatoria a los 30 días y la mortalidad hospitalaria fueron del 1,0% (22/2167) y del 2,7% (58/2167), respectivamente, y las complicaciones graves ocurrieron en el 6,0% (131/2167) de los pacientes. Los factores que mostraron una fuerte asociación positiva con los resultados en este modelo de riesgo fueron el estado funcional según la Sociedad Americana de Anestesiología y la resección arterial combinada. En la cohorte de prueba, el estadístico c del modelo fue de 0,70 (i.c. del 95% 0,59-0,81). CONCLUSIÓN: El modelo de riesgo puede usarse para predecir las complicaciones graves después de una pancreatectomía total.
Assuntos
Regras de Decisão Clínica , Pancreatectomia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Complicações Pós-Operatórias/epidemiologia , Curva ROC , Análise de Regressão , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
PURPOSE: The purpose of this study was to examine the efficacy of an ovarian tissue transportation network for fertility preservation (FP) for cancer patients in Japan. METHODS: PubMed was searched for papers on transportation of human ovarian tissue for FP. We analyzed population, area, number of cancer patients for ovarian tissue cryopreservation (OTC), quality control/assessment and safety, cost of a cryopreservation center for the building for 30 years, and medical fees of cancer patients (operation, cryopreservation, and storage of ovarian tissue). RESULTS: More than twenty babies have been born in Denmark and Germany through a transportation system. Up to 400 new patients a year need OTC. The fees for removal, cryopreservation, and storage for 5 years, and transplantation of ovarian tissue are around 5,000, 4,000, and 5,000, respectively. It costs more than 5 million to establish and maintain one cryopreservation center for 30 years. If we have a few cryopreservation centers in Japan, we can cryopreserve 400 patients' ovarian tissue per year by safer slow freezing and maintain quality control/assessment. We need to lighten the patients' burden for easy to use FP by a government subsidy and medical insurance coverage. CONCLUSIONS: This model has been termed the Danish model ("the woman stays - the tissue moves"). This is truly patient-centered medicine. We can have maximum effects with the minimum burden. A transportation network like those of Denmark and Germany is the best strategy for FP in Japan. It may be the best system for cancer patients, medical staff, and the Ministry of Health, Labor, and Welfare.
Assuntos
Preservação da Fertilidade , Oócitos/transplante , Ovário/transplante , Meios de Transporte , Criopreservação , Feminino , Humanos , Japão , Neoplasias/complicações , Neoplasias/terapia , Oócitos/crescimento & desenvolvimento , Ovário/crescimento & desenvolvimentoRESUMO
BACKGROUND AND STUDY AIMS: Only a few large cohort studies have evaluated the efficacy and safety of endoscopic necrosectomy for infected walled-off pancreatic necrosis (WOPN). Therefore, a multicenter, large cohort study was conducted to evaluate the efficacy and safety of endoscopic necrosectomy and to examine the procedural details and follow-up after successful endoscopic necrosectomy. PATIENTS AND METHODS: A retrospective review was conducted in 16 leading Japanese institutions for patients who underwent endoscopic necrosectomy for infected WOPN between August 2005 and July 2011. The follow-up data were also reviewed to determine the long-term outcomes of the procedures. RESULTS: Of 57 patients, 43 (75 %) experienced successful resolution after a median of 5 sessions of endoscopic necrosectomy and 21 days of treatment. Complications occurred in 19 patients (33 %) during the treatment period. Six patients died (11 %): two due to multiple organ failure and one patient each from air embolism, splenic aneurysm, hemorrhage from a Mallory - Weiss tear, and an unknown cause. Of 43 patients with successful endoscopic necrosectomy, recurrent cavity formation was observed in three patients during a median follow-up period of 27 months. CONCLUSIONS: Endoscopic necrosectomy can be an effective technique for infected WOPN and requires a relatively short treatment period. However, serious complications can arise, including death. Therefore, patients should be carefully selected, and knowledgeable, skilled, and experienced operators should perform the procedure. Further research into safer technologies is required in order to reduce the associated morbidity and mortality.
Assuntos
Endoscopia do Sistema Digestório , Pâncreas/patologia , Pâncreas/cirurgia , Pancreatopatias/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Drenagem , Endoscopia do Sistema Digestório/efeitos adversos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Necrose/microbiologia , Necrose/cirurgia , Recidiva , Estudos Retrospectivos , Stents , Irrigação Terapêutica , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Despite advances in molecular imaging, preoperative diagnosis of astrocytomas and oligodendrogliomas can be challenging. In the present study, we assessed whether 7T SWI can be used to distinguish astrocytomas and oligodendrogliomas and whether malignant grading of gliomas is possible. MATERIALS AND METHODS: 7T SWI was performed on 21 patients with gliomas before surgery with optimization for sharp visualization of the corticomedullary junction. Scoring for cortical thickening and displacement of medullary vessels, characteristic of oligodendroglial tumors, and cortical tapering, characteristic of astrocytic tumors, was performed. Additionally, characteristics of malignancy, including thickening of the medullary veins, the presence of microbleeds, and/or necrosis were scored. RESULTS: Scoring for oligodendroglial (highest possible score, +3) and astrocytic (lowest score possible, -3) characteristics yielded a significant difference between astrocytomas and oligodendrogliomas (mean, -1.93 versus +1.71, P < .01). Scoring for malignancy was significantly different among the World Health Organization grade II (n = 10), grade III (n = 4), and grade IV (n = 7) tumors (mean, 0.20 versus 1.38 versus 2.79). Cortical thickening was observed significantly more frequently in oligodendrogliomas (P < .02), with a sensitivity of 71.4% and specificity of 85.7%; observation of tapering of the cortex was higher in astrocytomas (P < .01) with a sensitivity of 85.7% and specificity of 100%. CONCLUSIONS: Visualization of the corticomedullary junction by 7T SWI was useful in distinguishing astrocytomas and oligodendrogliomas. Observation of tapering of the cortex was most sensitive and specific for diagnosing astrocytomas. Reliably predicting malignant grade was also possible by 7T SWI.
Assuntos
Astrocitoma , Neoplasias Encefálicas , Glioma , Oligodendroglioma , Humanos , Oligodendroglioma/diagnóstico por imagem , Oligodendroglioma/patologia , Neoplasias Encefálicas/patologia , Astrocitoma/patologia , Glioma/patologia , Imageamento por Ressonância MagnéticaRESUMO
In plants there are three microtubule arrays involved in cellular morphogenesis that have no equivalent in animal cells. In animals, microtubules are decorated by another class of proteins - the structural MAPS - which serve to stabilize microtubules and assist in their organization. The best-studied members of this class in plants are the MAP-65 proteins that can be purified together with plant microtubules after several cycles of polymerization and depolymerization. Here we identify three similar MAP-65 complementary DNAs representing a small gene family named NtMAP65-1, which encode a new set of proteins, collectively called NtMAP65-1. We show that NtMAP65-1 protein localizes to areas of overlapping microtubules, indicating that it may function in the behaviour of antiparallel microtubules in the mitotic spindle and the cytokinetic phragmoplast.
Assuntos
Nicotiana/genética , Proteínas de Plantas/genética , Plantas Tóxicas , Sequência de Aminoácidos , Compartimento Celular , DNA Complementar/genética , DNA de Plantas/genética , Imunofluorescência , Proteínas Associadas aos Microtúbulos/isolamento & purificação , Dados de Sequência Molecular , Proteínas de Plantas/isolamento & purificação , Análise de Sequência , Homologia de Sequência de AminoácidosRESUMO
Main features of rheumatoid arthritis (RA), hyperplasia of fibroblast-like synoviocytes (FLS) and joint destruction are caused by inflammatory cytokines produced in chronic autoimmune inflammation. Cell-intrinsic acquisition of tumour-like phenotypes of RA-FLS could also be responsible for the aggressive proliferation and invasion, which are supported by the fact that in some cases RA-FLS has mutations of a tumour suppressor gene TP53. However, the underlying molecular mechanism for TP53 mutations in RA-FLS has not yet been clarified. Recently it has been reported that the non-lymphoid cells in the inflammatory tissues express ectopically the activation-induced cytidine deaminase (AID) gene that induces somatic hypermutations, not only at the immunoglobulin (Ig) gene variable regions in germinal centre B lymphocytes but also at coding regions in TP53. Real-time polymerase chain reaction (PCR) analyses revealed more than half (five of nine) of the RA-FLS lines we established showed the markedly increased expression of AID. AID transcription in RA-FLS was augmented by tumour necrosis factor (TNF)-alpha and even by physiological concentration of beta-oestradiol that could not induce AID transcription in osteoarthritis-FLS. Furthermore, AID-positive RA-FLS presented a higher frequency of somatic mutations in TP53. Cytological and immunohistochemical analyses demonstrated clearly the ectopic expression of AID in the FLS at the RA synovium. These data suggested strongly a novel consequence of RA; the ectopic expression of AID in RA-FLS causes the somatic mutations and dysfunction of TP53, leading to acquisition of tumour-like properties by RA-FLS.
Assuntos
Artrite Reumatoide/patologia , Citidina Desaminase/fisiologia , Genes p53 , Mutação , Membrana Sinovial/enzimologia , Proteína Supressora de Tumor p53/fisiologia , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/enzimologia , Artrite Reumatoide/genética , Linhagem Celular Transformada/enzimologia , Linhagem Celular Transformada/metabolismo , Linhagem Celular Transformada/patologia , Transformação Celular Neoplásica , Sistemas Computacionais , Citidina Desaminase/biossíntese , Indução Enzimática , Estradiol/farmacologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hiperplasia , Masculino , Pessoa de Meia-Idade , Osteoartrite/genética , Osteoartrite/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Transcrição Gênica/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
BACKGROUND AND AIMS: Chromosomal instability (CIN) is recognised as a hallmark of cancer and is caused by a spindle assembly checkpoint disorder or chromosome mis-segregation during mitosis. Although the recent identification of human shugoshin (hSgo1), an important player in proper chromosome segregation, has suggested the involvement of hSgo1 in colorectal tumourigenesis, little is known about how it is involved. The aim of this study was to obtain information about the status of hSgo1 in human colorectal cancer. METHOD AND RESULTS: Among the 46 colorectal cancer cases, hSgo1 mRNA expression was decreased in the tumour tissue in comparison with the corresponding normal tissue (p = 0.032). Human Sgo1-downregulated tumours (tumour to normal mucosa ratio<0.5) had preferential location on the left side large bowel rather than on the right side (p = 0.012), and a higher variation of centromere numbers revealed by fluorescence in situ hybridisation (FISH). To assess the effects of hSgo1 downregulation, hSgo1 knockdown was performed by transfecting the diploid HCT116 cell line with a short hairpin RNA expression vector. hSgo1 knockdown cells proliferated slowly because of both G(2)/M arrest and apoptosis (p<0.001), and markers of CIN in the form of aneuploidy (p<0.001) and micronuclei (p<0.005) were later observed in hSgo1 knockdown cells. Increased centrosome amplification (p<0.05), the presence of binucleated cells and mitotic catastrophes were also noted in hSgo1 knockdown cells. CONCLUSIONS: These findings suggest that hSgo1-downregulated colorectal cancers have a clinicopathological character of CIN, and hSgo1 downregulation leads to CIN in colorectal cancer cells.
Assuntos
Carcinoma/genética , Proteínas de Ciclo Celular/metabolismo , Instabilidade Cromossômica , Neoplasias Colorretais/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Idoso , Idoso de 80 Anos ou mais , Aneuploidia , Biomarcadores/análise , Western Blotting/métodos , Carcinoma/metabolismo , Carcinoma/patologia , Proteínas de Ciclo Celular/análise , Proteínas de Ciclo Celular/genética , Centrossomo/ultraestrutura , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Antígeno Ki-67/análise , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Transfecção/métodosRESUMO
BACKGROUND: Emerging evidence suggests that stemness in cancer cells is a cause of drug resistance or metastasis and is an important therapeutic target. PR [positive regulatory domain I-binding factor 1 (PRDI-BF1) and retinoblastoma protein-interacting zinc finger gene (RIZ1)] domain containing 14 (PRDM14), that regulates pluripotency in primordial germ cell, has reported the overexpression and function of stemness in various malignancies, suggesting it as the possible therapeutic target. However, to our knowledge, there have been no reports on the expression and function of PRDM14 in colorectal cancer (CRC). Therefore, we investigated the expression and the role of PRDM14 in CRC. METHODS: We performed immunohistochemistry evaluations and assessed PRDM14 expression on 414 primary CRC specimens. Colon cancer cell lines were subjected to functional and stemness assays in vitro and in vivo. RESULTS: We found that PRDM14 positive staining exhibited heterogeneity in the CRC primary tumor, especially at the tumor invasion front. The aberrant expression of PRDM14 at the invasion front was associated with lymph node metastasis and disease stage in patients with CRC. Furthermore, the multivariate analysis revealed high PRDM14 expression as an independent prognostic factor in the patients with Stage III CRC. Overexpression of PRDM14 enhanced the invasive, drug-resistant and stem-like properties in colon cancer cells in vitro and tumorigenicity in vivo. CONCLUSION: Our findings suggest that PRDM14 is involved in progression and chemoresistance of CRC, and is a potential prognostic biomarker and therapeutic target in the CRC patients.
Assuntos
Adenocarcinoma/genética , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a RNA/genética , Fatores de Transcrição/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Idoso , Animais , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas de Ligação a DNA/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Fluoruracila/farmacologia , Humanos , Imuno-Histoquímica , Irinotecano/farmacologia , Linfonodos/patologia , Metástase Linfática , Masculino , Camundongos Nus , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Transplante de Neoplasias , Oxaliplatina/farmacologia , Prognóstico , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de Transcrição/metabolismo , Carga TumoralRESUMO
With bioactivity-guided phenotype screenings, a potent anti-inflammatory compound f152A1 has been isolated, characterized and identified as the known natural product LL-Z1640-2. Metabolic instability precluded its use for the study on animal disease models. Via total synthesis, a potent, metabolically stabilized analog ER-803064 has been created; addition of the (S)-Me group at C4 onto f152A1 has resulted in a dramatic improvement on its metabolic stability, while preserving the anti-inflammatory activities.
Assuntos
Anti-Inflamatórios/química , Lactonas/química , Animais , Anti-Inflamatórios/farmacocinética , Desenho de Fármacos , Humanos , Interleucina-6/metabolismo , Lactonas/síntese química , Lactonas/farmacocinética , Camundongos , Microssomos Hepáticos/metabolismoRESUMO
Benzo[a]pyrene diol epoxide (B[a]PDE), the ultimate carcinogenic metabolite of benzo[a] pyrene, has been implicated in the mutagenesis of the p53 gene involved in smoking-associated lung cancer. To further understand the role of B[a]PDE in lung tumour progression, we investigated its effect on the numerical integrity of centrosomes and chromosome stability in lung cancer cells lacking p53. Exposure of p53-deficient H1299 lung cancer cells to B[a]PDE resulted in S-phase arrest, leading to abnormal centrosome amplification. Analysis of H1299 cells stably expressing fluorescence-tagged centrin (a known centriolar marker) revealed that the centrosome amplification was primarily attributable to excessive centrosome duplication rather than to centriole splitting. Forced expression of POLK DNA polymerase, which has the ability to bypass B[a]PDE-guanine lesions in an error-free manner, suppressed the B[a]PDE-induced centrosome amplification. Fluorescence in situ hybridization analyses with probes specific for chromosomes 2, 3, and 16 revealed that B[a]PDE exposure also led to chromosome instability, which was likely to have resulted from centrosome amplification. We extended these findings to primary lung carcinomas containing non-functional p53, and found a strong association between centrosome amplification and a high level of B[a]PDE-DNA accumulation. Therefore B[a]PDE contributes to neoplasia by inducing centrosome amplification and consequent chromosome destabilization as well as its mutagenic activity.
Assuntos
7,8-Di-Hidro-7,8-Di-Hidroxibenzo(a)pireno 9,10-óxido/toxicidade , Centrossomo/ultraestrutura , Instabilidade Cromossômica , Neoplasias Pulmonares/ultraestrutura , Mutagênicos/toxicidade , Proteína Supressora de Tumor p53/deficiência , Idoso , Ciclo Celular/efeitos dos fármacos , Transformação Celular Neoplásica , Distribuição de Qui-Quadrado , Adutos de DNA/análise , DNA Polimerase Dirigida por DNA/metabolismo , Feminino , Citometria de Fluxo , Técnica Indireta de Fluorescência para Anticorpo , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de OligonucleotídeosRESUMO
X-chromosome inactivation pattern (XCIP) analysis can be used to assess the clonality of cell populations of various origin by distinguishing the methylated X chromosome from the unmethylated X chromosome. In this study, the utility of XCIP analysis was improved by incorporating the examination of AC dinucleotide repeats in SLIT and NTRK-like family member 4 (SLITRK4) gene into the previously reported CAG repeat examination of androgen receptor (AR) gene in dogs. The rate of heterozygosity when both genes were analysed (125/150, 83.3%) was higher than AR gene examination alone (86/150, 57.3%). Blood samples from heterozygous dogs in either AC-1 or AC-2 of SLITRK4 gene were examined for the corrected inactivation allele ratio (CIAR), resulting in the determination of a reference range of CIAR <3.8 in non-neoplastic cell/tissue samples. Using this analytical method, 49% (21/43) of neoplastic tissue samples from dogs showed a CIAR >3.8, indicating the presence of a clonal population. Through the present study, the availability of canine XCIP analysis was improved by incorporating the examination of the SLITRK4 gene, providing a highly useful laboratory examination system for the detection of the clonality of various cell/tissue samples in dogs.
Assuntos
Proteínas de Membrana/metabolismo , Receptores Androgênicos/metabolismo , Inativação do Cromossomo X , Cromossomo X/fisiologia , Alelos , Animais , Linhagem da Célula , Doenças do Cão/genética , Doenças do Cão/metabolismo , Cães , Feminino , Regulação da Expressão Gênica , Heterozigoto , Masculino , Proteínas de Membrana/genética , Neoplasias/genética , Neoplasias/metabolismo , Receptores Androgênicos/genéticaRESUMO
Genomic amplification of oncogenes and inactivation of suppressor genes are critical in the pathogenesis of human cancer. To identify chromosomal alterations associated with hepatocarcinogenesis, we performed allelic gene dosage analysis on 36 hepatocellular carcinomas (HCCs). Data from high-density single-nucleotide polymorphism arrays were analysed using the Genome Imbalance Map (GIM) algorithm, which simultaneously detects DNA copy number alterations and loss of heterozygosity (LOH) events. Genome Imbalance Map analysis identified allelic imbalance regions, including uniparental disomy, and predicted the coexistence of a heterozygous population of cancer cells. We observed that gains of 1q, 5p, 5q, 6p, 7q, 8q, 17q and 20q, and LOH of 1p, 4q, 6q, 8p, 10q, 13q, 16p, 16q and 17p were significantly associated with HCC. On 6q24-25, which contains imprinting gene clusters, we observed reduced levels of PLAGL1 expression owing to loss of the unmethylated allele. Finally, we integrated the copy number data with gene expression intensity, and found that genome dosage is correlated with alteration in gene expression. These observations indicated that high-resolution GIM analysis can accurately determine the localizations of genomic regions with allelic imbalance, and when integrated with epigenetic information, a mechanistic basis for inactivation of a tumor suppressor gene in HCC was elucidated.
Assuntos
Carcinoma Hepatocelular/genética , Proteínas de Ciclo Celular/genética , Genômica , Cariotipagem , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Fatores de Transcrição/genética , Proteínas Supressoras de Tumor/genética , Algoritmos , Epigênese Genética , Humanos , Hibridização in Situ Fluorescente , Perda de Heterozigosidade , Família Multigênica , Análise de Sequência com Séries de OligonucleotídeosRESUMO
An immunochromatographic test was developed for rapid diagnosis of bovine viral diarrhea virus (BVDV) infections using monoclonal antibodies against the nonstructural protein, NS3, of the virus. The kit detected specifically the NS3 of various BVDV strains. Using the kit, leukocyte extracts of cattle infected persistently with BVDV were found positive while those of healthy cattle were negative. The sensitivity and specificity of this kit in compared with virus isolation were 100% and 97.2%, respectively. Furthermore, the test also gave positive results for calves infected acutely with BVDV in experimental infection. The BVDV antigen was detected in 1 ml of blood using a relatively simple procedure. This test kit should be useful for rapid diagnosis of BVD.
Assuntos
Antígenos Virais/análise , Doença das Mucosas por Vírus da Diarreia Viral Bovina/diagnóstico , Cromatografia de Afinidade/métodos , Vírus da Diarreia Viral Bovina/imunologia , Vírus da Diarreia Viral Bovina/isolamento & purificação , Peptídeo Hidrolases/análise , RNA Helicases/análise , Proteínas não Estruturais Virais/análise , Animais , Sangue/virologia , Bovinos , Leucócitos/virologia , Kit de Reagentes para Diagnóstico , Sensibilidade e Especificidade , Cultura de VírusRESUMO
We experienced three cases of nocardiosis by Nocardia farcinica in the same ward within a six-month period. The result of gene analysis by randomly amplified polymorphic DNA gave the same pattern. Thus, these three cases were considered to be caused by the same strain of N. farcinica, implying the presence of nosocomial infection.
Assuntos
Infecção Hospitalar/transmissão , Surtos de Doenças , Nocardiose/transmissão , Nocardia/isolamento & purificação , Adulto , Idoso , Anti-Infecciosos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Feminino , Humanos , Japão , Masculino , Nocardia/genética , Nocardia/patogenicidade , Nocardiose/tratamento farmacológico , Técnica de Amplificação ao Acaso de DNA Polimórfico , Combinação Trimetoprima e Sulfametoxazol/uso terapêuticoRESUMO
Complementary DNA for a novel member of the cadherin family, designated K-cadherin, was isolated from a rat renal cell carcinoma complementary DNA library by screening it with a short complementary DNA probe which was initially obtained from the RNA of day 16 fetal Wistar rat stomach mucosa by the polymerase chain reaction. The deduced primary structure of K-cadherin is 789 amino acid residues, which contain five internal repeats in its extracellular domain, a single putative transmembrane domain, and a cytoplasmic tail characteristic of those of classic type cadherins. K-cadherin exhibits low homology with mature proteins of mouse N- (38%), E- (35%), and P-cadherin (32%), and high homology with a partially identified human cadherin-6 protein (95%) at the amino acid level. Northern blot analysis revealed a high level of expression of K-cadherin mRNA in fetal rat kidney and brain, and rat kidney carcinoma with two major transcripts, 4.1 and 8.0 kilobases in size, whereas there was very weak or no expression in any organ of adult rats. The level of K-cadherin expression was also elevated in some human kidney cancer tissues. In the developing kidney, in situ hybridization showed localization of K-cadherin mRNA in the nephroblastic epithelial cells of comma bodies coinciding with those in the process of polarization during glomeruloneogenesis. These results demonstrate that K-cadherin must have important functions in both the process of kidney development and tumorigenesis of some types of kidney cancer.
Assuntos
Caderinas/genética , Carcinoma de Células Renais/química , Carcinoma de Células Renais/genética , DNA Complementar/química , DNA Complementar/genética , Neoplasias Renais/química , Neoplasias Renais/genética , Rim/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Caderinas/química , DNA Complementar/isolamento & purificação , Feto , Mucosa Gástrica/química , Hibridização In Situ , Dados de Sequência Molecular , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Ratos , Ratos Endogâmicos ACI , Ratos WistarRESUMO
A 7-year-old neutered male domestic short-haired cat that had undergone contrast radiography of the bowel with barium sulphate after acute episodes of vomiting 2 months previously, was presented with chronic vomiting, anorexia and weight loss. Abdominal radiography and ultrasonography revealed residual contrast enhancement and an obstruction of the small intestine. A contracted and stenosed ileum and distal jejunum were identified by exploratory laparotomy and surgically resected; subsequently, the clinical signs resolved. Histopathological examination of the ileum revealed mucosal ulceration with severe submucosal granulation tissue formation associated with scattered foreign crystalline material. Energy-dispersive X-ray spectroscopy revealed that the crystals contained barium sulphate. This is the first report in animals of the rare complication of barium sulphate incorporation into the gastrointestinal mucosa after contrast radiography.
Assuntos
Obstrução Intestinal/veterinária , Intestino Delgado/patologia , Radiografia/veterinária , Animais , Sulfato de Bário , Gatos , Obstrução Intestinal/etiologia , Masculino , Radiografia/efeitos adversosRESUMO
BACKGROUND: Clinical evidences of inhaled salmeterol/fluticasone propionate combination (SFC) therapy are insufficient in early childhood asthma. OBJECTIVES: To examine the effects of SFC50, a combination product of salmeterol xinafoate (50 µg/day) and fluticasone propionate (100 µg/day), in infants and preschool children with asthma. METHODS: The study was conducted at 31 sites in Japan. 35 patients (6 months to 5 years old) with asthma insufficiently controlled by inhaled corticosteroids (100 µg/day) were initiated to treat with SFC50 twice a day for 12 weeks with pressurized metered dose inhalers. The efficacy of SFC50 was assessed using nighttime sleep disorder score as the primary endpoint and the other efficacy measurements. The safety measurement included the incidences of adverse event (AE). RESULTS: Mean patient age was 3.1 years, and 94.2% had mild-to-moderate persistent asthma (atopic type: 65.7%). Nighttime sleep disorder scores, assessed by a nighttime sleep diary, significantly decreased after treatment with SFC50 throughout the study period (p<0.01). SFC50 also significantly improved other efficacy outcomes including asthma symptom score, frequency of short-acting beta-agonist treatment, frequency of unscheduled visits to clinic, frequency of exacerbation due to virus infection, asthma control score and patient QOL score (p<0.01). AEs of cold, upper respiratory inflammation and asthmatic attack occurred in each of the 3 patients (8.6%); however, these were not regarded as treatment-related AEs. CONCLUSIONS: SFC50 improved nighttime sleep disorder score and other efficacy outcome measures with no safety concerns. The results suggest that SFC50 treatment is useful to control the mild-to-moderate asthma in infant and preschool-aged children.
Assuntos
Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Combinação Fluticasona-Salmeterol/uso terapêutico , Administração por Inalação , Corticosteroides/administração & dosagem , Antiasmáticos/administração & dosagem , Antiasmáticos/efeitos adversos , Antiasmáticos/uso terapêutico , Pré-Escolar , Relação Dose-Resposta a Droga , Feminino , Combinação Fluticasona-Salmeterol/administração & dosagem , Combinação Fluticasona-Salmeterol/efeitos adversos , Humanos , Lactente , Masculino , Resultado do TratamentoRESUMO
The v-sis oncogene encodes a protein structurally and functionally related to human platelet-derived growth factor (PDGF). In the present studies, we show that the primary translational product of the human sis proto-oncogene is a 26-kd protein, p26c-sis. This product is processed to yield a disulfide-linked homodimer, p56c-sis, which is further processed to a 35,000-dalton dimer, p35c-sis. Like the v-sis gene product, the PDGF-2 precursor undergoes N-linked glycosylation, implying its processing through the endoplasmic reticulum. The PDGF-2 product was shown to possess functional properties of PDGF. Whereas lysates of control COS-1 cells lacked mitogenic activity, lysates of COS-1 cells transfected with a c-sis/PDGF-2 expression vector specifically stimulated DNA synthesis of quiescent fibroblasts. Moreover, this activity was completely inhibitable by PDGF antibody. Identical forms of the sis/PDGF-2 product were identified in human tumor cells that expressed c-sis/PDGF-2 transcripts. These proteins were shown to be specifically associated with the membrane component of the tumor cells and were not detectably secreted into the culture medium. These findings support the concept that expression of the sis/PDGF-2 product in human cells responsive to its proliferative actions can be an important step in the processes leading to malignancy.
Assuntos
Fator de Crescimento Derivado de Plaquetas , Proteínas Proto-Oncogênicas/metabolismo , Proto-Oncogenes , Células Tumorais Cultivadas/metabolismo , Divisão Celular , DNA/genética , Regulação da Expressão Gênica , Engenharia Genética , Vetores Genéticos , Técnicas Imunológicas , Substâncias Macromoleculares , Fator de Crescimento Derivado de Plaquetas/genética , Proto-Oncogene Mas , RNA Mensageiro/genética , RNA Neoplásico/genéticaRESUMO
The Eph class is the largest family of receptor tyrosine kinases and has been shown to play various roles in neural development including axon pathfinding and neural crest migration. EphB2 associates with transmembrane ligands Ephrin-B1 and -B2, which leads to tyrosine phosphorylation of both the ligands and receptor and is presumed to regulate cell-to-cell interactions by bidirectional signaling. We have investigated the biological effects of the EphB2-induced signal in the early stage of Xenopus laevis development. Xenopus EphB2 transcripts were detected maternally and were expressed at equal levels between the ventral and dorsal halves of the gastrulae, with expression increasing after the late gastrula stage. EphB2 mRNA expression in dorsal marginal zone explants from gastrulae increases during later development while that in ventral explants does not. We show here that microinjection of RNA encoding EphB2 into a ventral blastomere of embryos induced a partial secondary dorsal axis which consisted of neural tissues, notochord and somites. Analysis with molecular markers verified that the microinjected EphB2 dorsalized the mesoderm of ventral marginal zone explants. These dorsalizing effects of EphB2 in both the whole embryo and ventral explants were inhibited by the coinjection of RNA encoding the soluble form of Ephrin-B1. Furthermore, co-injection of EphB2 and Ephrin-B1 RNAs synergistically enhanced the dorsalization effect. These data show that the interaction between EphB2 and its ligands including Ephrin-B1 causes signaling events which lead to dorsal development, and strongly suggests the existence of proteins which mediate the dorsalization induced by EphB2 in early stage embryos of Xenopus laevis.
Assuntos
Padronização Corporal/fisiologia , Proteínas de Membrana/metabolismo , Receptores Proteína Tirosina Quinases/fisiologia , Sequência de Aminoácidos , Animais , Técnicas de Cultura , Efrina-B1 , Humanos , Ligantes , Mesoderma/metabolismo , Camundongos , Dados de Sequência Molecular , Receptores Proteína Tirosina Quinases/genética , Receptores Proteína Tirosina Quinases/metabolismo , Receptor EphB2 , Homologia de Sequência de Aminoácidos , Transdução de Sinais , Xenopus laevisRESUMO
Numerical chromosomal abnormalities are a well known characteristic of human cancer, but no "chromosome-wide investigation" encompassing almost all of the chromosomes has ever been reported. Furthermore, although the multistep process of carcinogenesis is widely accepted in human cancer, the stepwise numerical aberration of chromosomes has never been addressed. Touch preparations of 24 (male 20, female 4) surgically resected gastric cancer tissue samples in various stages in terms of depth of invasion were analyzed by fluorescence in situ hybridization using centromere-specific probes including 17 chromosomes, 1-4, 6-8, 10-12, 15-18, 20, X, and Y. Microwave irradiation was performed to increase the sensitivity and specificity of the signal. The depth of the tumor invasion in the gastric wall and histological subtypes were recorded by viewing the histology of the adjacent portion. Numerical chromosomal abnormalities of chromosomes 1 and 2 were found most frequently and from the early stage of gastric cancer. The abnormalities observed were limited to chromosomes 1, 2, 4, and 20 in tumors invading to the middle layer of the submucosa of the gastric wall, but these became more extensive, involving almost all of the chromosomes investigated when the tumor had invaded beyond the proper muscle of the gastric wall. Centromeric numbers of chromosomes 3 and 18 were exceptionally stable even after the tumor progressed to advanced stage. These profiles of the sequential process of numerical chromosomal abnormality were similar in both mucocellular and tubular-type gastric cancer, but the prevalence was significantly lower in the mucocellular type (39.0% versus 68.0%). On the basis of fluorescence in situ hybridization analysis of 17 different chromosome centromeres in gastric cancer in various stages, we conclude that the earliest events in gastric carcinogenesis in terms of chromosomal abnormality occur in chromosomes 1 and 2 and that chromosomal numerical aberrations expand in a stepwise manner with cancer progression.