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1.
Sci Rep ; 6: 25806, 2016 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-27194388

RESUMO

Human respiratory syncytial virus (hRSV) is a leading cause of acute lower respiratory tract infection in infants, elderly and immunocompromised individuals. To date, no specific antiviral drug is available to treat or prevent this disease. Here, we report that the Smoothened receptor (Smo) antagonist cyclopamine acts as a potent and selective inhibitor of in vitro and in vivo hRSV replication. Cyclopamine inhibits hRSV through a novel, Smo-independent mechanism. It specifically impairs the function of the hRSV RNA-dependent RNA polymerase complex notably by reducing expression levels of the viral anti-termination factor M2-1. The relevance of these findings is corroborated by the demonstration that a single R151K mutation in M2-1 is sufficient to confer virus resistance to cyclopamine in vitro and that cyclopamine is able to reduce virus titers in a mouse model of hRSV infection. The results of our study open a novel avenue for the development of future therapies against hRSV infection.


Assuntos
Vírus Sincicial Respiratório Humano/fisiologia , Transcrição Genética , Proteínas Virais/metabolismo , Replicação Viral/fisiologia , Alcaloides/farmacologia , Animais , Linhagem Celular , RNA Polimerases Dirigidas por DNA/metabolismo , Modelos Animais de Doenças , Farmacorresistência Viral/efeitos dos fármacos , Feminino , Regulação Viral da Expressão Gênica/efeitos dos fármacos , Humanos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Infecções por Vírus Respiratório Sincicial/tratamento farmacológico , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sincicial Respiratório Humano/efeitos dos fármacos , Receptor Smoothened/metabolismo , Transcrição Genética/efeitos dos fármacos , Veratrum/química , Alcaloides de Veratrum/química , Alcaloides de Veratrum/farmacologia , Alcaloides de Veratrum/uso terapêutico , Replicação Viral/efeitos dos fármacos , Replicação Viral/genética
2.
J Dairy Sci ; 99(1): 152-66, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26506552

RESUMO

Previous standards in the area of effect of heat treatment processes on milk protein denaturation were based primarily on laboratory-scale analysis and determination of denaturation degrees by, for example, electrophoresis. In this study, whey protein denaturation was revisited by pilot-scale heating strategies and liquid chromatography quadrupole time-of-flight mass spectrometer (LC/MC Q-TOF) analysis. Skim milk was heat treated by the use of 3 heating strategies, namely plate heat exchanger (PHE), tubular heat exchanger (THE), and direct steam injection (DSI), under various heating temperatures (T) and holding times. The effect of heating strategy on the degree of denaturation of ß-lactoglobulin and α-lactalbumin was determined using LC/MC Q-TOF of pH 4.5-soluble whey proteins. Furthermore, effect of heating strategy on the rennet-induced coagulation properties was studied by oscillatory rheometry. In addition, rennet-induced coagulation of heat-treated micellar casein concentrate subjected to PHE was studied. For skim milk, the whey protein denaturation increased significantly as T and holding time increased, regardless of heating method. High denaturation degrees were obtained for T >100°C using PHE and THE, whereas DSI resulted in significantly lower denaturation degrees, compared with PHE and THE. Rennet coagulation properties were impaired by increased T and holding time regardless of heating method, although DSI resulted in less impairment compared with PHE and THE. No significant difference was found between THE and PHE for effect on rennet coagulation time, whereas the curd firming rate was significantly larger for THE compared with PHE. Micellar casein concentrate possessed improved rennet coagulation properties compared with skim milk receiving equal heat treatment.


Assuntos
Temperatura Alta , Desnaturação Proteica , Proteínas do Soro do Leite/química , Soro do Leite/química , Cromatografia Líquida , Quimosina/metabolismo , Manipulação de Alimentos , Concentração de Íons de Hidrogênio , Lactoglobulinas/química , Espectrometria de Massas , Micelas , Projetos Piloto
3.
J Fish Dis ; 38(11): 1005-19, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25557127

RESUMO

Infectious pancreatic necrosis virus (IPNV) is a prevalent pathogen in fish worldwide. The virus causes substantial mortality in Atlantic salmon juveniles and smolts when transferred to sea water and persistent infection in surviving fish after disease outbreaks. Here, we have investigated the occurrence of the virus as well as the innate immune marker Mx in the head kidney (HK) of Atlantic salmon throughout an experimental challenge covering both a fresh and a seawater phase. The fish were challenged with a high (HV) and low virulence (LV) IPNV. Both isolates caused mortality due to reactivation of the virus after transfer to sea water. In the freshwater phase, higher levels of virus transcripts were detected in the HK of fish infected with LV IPNV compared to HV, suggesting that the HV isolate is able to limit its own replication to a level where the innate immune system is not alerted. Further, ex vivoHK leucocytes derived from fish infected with the two isolates were stimulated with CpG DNA. Significantly, higher IFN levels were found in the LV compared to the HV group in the freshwater phase. This suggests that the viruses attenuate the antiviral host immune response at different levels which may contribute to the observed differences in disease outcome.


Assuntos
Infecções por Birnaviridae/veterinária , Doenças dos Peixes/microbiologia , Interações Hospedeiro-Patógeno/imunologia , Vírus da Necrose Pancreática Infecciosa/patogenicidade , Salmo salar/microbiologia , Animais , Infecções por Birnaviridae/microbiologia , Infecções por Birnaviridae/mortalidade , Doenças dos Peixes/mortalidade , Dados de Sequência Molecular , Proteínas de Resistência a Myxovirus/metabolismo
4.
J Comp Pathol ; 147(2-3): 343-53, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22534025

RESUMO

A porcine model was used to examine the potential of human and porcine Staphylococcus aureus isolates to induce haematogenously spread osteomyelitis. Pigs were inoculated in the right femoral artery with one of the following S. aureus strains: S54F9 (from a porcine lung abscess; n = 3 animals), NCTC-8325-4 (a laboratory strain of human origin; n = 3 animals) and UAMS-1 (a human osteomyelitis isolate; n = 3 animals). Two pigs were sham inoculated with saline. At 11 or 15 days post infection the animals were scanned by computed tomography before being killed and subjected to necropsy examination. Osteomyelitis lesions were present in the right hind limb of all pigs inoculated with strain S54F9 and in one pig inoculated with strain NCTC-8325-4. Microscopically, there was extensive loss of bone tissue with surrounding granulation tissue. Sequestrated bone trabeculae were intermingled with colonies of S. aureus as demonstrated immunohistochemically. By peptide nucleic acid fluorescence in situ hybridization bacterial aggregates were demonstrated to be embedded in an opaque matrix, indicating that the bacteria had formed a biofilm. Development of experimental osteomyelitis was therefore dependent on the strain of bacteria inoculated and on the formation of a biofilm.


Assuntos
Biofilmes/crescimento & desenvolvimento , Modelos Animais de Doenças , Osteomielite/patologia , Infecções Estafilocócicas/patologia , Doenças dos Suínos/patologia , Animais , Osso e Ossos/microbiologia , Osso e Ossos/patologia , DNA Bacteriano/análise , Feminino , Membro Posterior , Hibridização in Situ Fluorescente , Osteomielite/microbiologia , Organismos Livres de Patógenos Específicos , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/genética , Staphylococcus aureus/isolamento & purificação , Suínos , Doenças dos Suínos/microbiologia
5.
J Comp Pathol ; 146(2-3): 253-7, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21737093

RESUMO

Matrix metalloproteinases (MMPs) play a variety of roles during organogenesis, in the immune response and during acute and chronic diseases as well as in tissue remodelling. During the last decade, the pig has become used increasingly as a model for human diseases; however, studies on the expression of porcine MMPs are limited. In the present study species-specific antibodies were produced to investigate the expression of MMP-9 and MMP-12 immunohistochemically in lungs from pigs infected with Actinobacillus pleuropneumoniae, Pasteurella multocida and Staphylococcus aureus. The immunolabelling of lung tissues (one infected and one control pig representing each infection) was evaluated for cellular distribution and intensity, which was scored semiquantitatively. When compared with healthy, non-infected controls, the expression of both MMP-9 and MMP-12 was higher in infected lungs. The highest expressions were seen in the alveolar epithelium (MMP-9) and alveolar macrophages (MMP-12). These results are in accordance with studies of human lungs.


Assuntos
Infecções por Actinobacillus/enzimologia , Pneumopatias/enzimologia , Metaloproteinase 12 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Infecções por Pasteurella/enzimologia , Infecções Estafilocócicas/enzimologia , Infecções por Actinobacillus/microbiologia , Actinobacillus pleuropneumoniae , Animais , Pulmão/enzimologia , Pulmão/microbiologia , Pneumopatias/microbiologia , Infecções por Pasteurella/microbiologia , Pasteurella multocida , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Suínos
6.
J Virol Methods ; 162(1-2): 30-9, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19638286

RESUMO

The stability of 6 reference genes, 18S, beta-actin, RPS20, eEF1alpha, G6PDH and GAPDH, was examined in tissues from Atlantic salmon (Salmo salar) and Chinook salmon embryo cells (CHSE-214). The main objective of this study was to determine the most suitable reference genes for use for the normalisation of data in quantitative real-time RT-qPCR assays conducted on infected tissues. The tissue samples selected for analysis were taken from head kidney and pylorus and collected at different time points during a challenge experiment with infectious pancreatic necrosis virus (IPNV). The stability of some of the reference genes was also studied in infected CHSE-214 cells. The ranking of the genes examined was carried out using the geNorm program. This program determines the most stable genes from a set of genes tested in a given cDNA sample. The stability of the reference genes varied in different tissues and in the cell line at different stages of infection with IPNV. This study demonstrated that tissue-specific combinations of reference genes must be used to normalise real time data for use for the quantitation of IPNV.


Assuntos
Infecções por Birnaviridae/veterinária , Doenças dos Peixes/virologia , Perfilação da Expressão Gênica , Vírus da Necrose Pancreática Infecciosa/patogenicidade , Reação em Cadeia da Polimerase Via Transcriptase Reversa/normas , Salmo salar/virologia , Salmão/virologia , Actinas/genética , Actinas/metabolismo , Animais , Infecções por Birnaviridae/virologia , Linhagem Celular , Perfilação da Expressão Gênica/normas , Gliceraldeído-3-Fosfato Desidrogenases/genética , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Vírus da Necrose Pancreática Infecciosa/genética , Vírus da Necrose Pancreática Infecciosa/isolamento & purificação , Rim/metabolismo , Rim/virologia , Piloro/metabolismo , Piloro/virologia , RNA Ribossômico 18S/genética , RNA Ribossômico 18S/metabolismo , RNA Viral/genética , RNA Viral/isolamento & purificação , Padrões de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo
7.
Diabetes Obes Metab ; 11(4): 315-22, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19267709

RESUMO

BACKGROUND: Patients with type 2 diabetes (T2DM) have an increased mortality rate primarily because of macrovascular disease. Where T2DM patients cannot be managed sufficiently through diet, exercise and peroral antidiabetic drugs, that is when haemoglobin A1c (HbA1c) is above 7.0%, it is yet unknown whether a combination of metformin and insulin analogues is superior to insulin analogues alone. Nor is it known which insulin analogue regimen is the optimal. OBJECTIVE: The primary objective of this trial is to evaluate the effect of an 18-month treatment with metformin vs. placebo in combination with one of three insulin analogue regimens, the primary outcome measure being carotid intima-media thickness (CIMT) in T2DM patients. DESIGN: A randomized, stratified, multicentre trial having a 2 x 3 factorial design. The metformin part is double masked and placebo controlled. The insulin treatment is open. The intervention period is 18 months. PATIENT POPULATION: Nine hundred and fifty patients with T2DM and HbA1c > or = 7.5% on treatment with oral hypoglycaemic agents or on insulin treatment and deemed able, by the investigator, to manage once-daily insulin therapy with a long-acting insulin analogue. RANDOMIZATION: Central randomization stratified for age (above 65 years), previous insulin treatment and treatment centre. INTERVENTIONS: Metformin 1 g x two times daily vs. placebo (approximately 475 patients vs. 475 patients) in combination with insulin detemir before bedtime (approximately 315 patients) or biphasic insulin aspart 30 before dinner with the possibility to increase to two or three injections daily (approximately 315 patients) or insulin aspart before the main meals (three times daily) and insulin detemir before bedtime (approximately 315 patients). Intervention follows a treat-to-target principle in all six arms aiming for an HbA1c < or = 7.0%. OUTCOME MEASURES: Primary outcome measure is the change in CIMT from baseline to 18 months. Secondary outcome measures comprises the composite outcome of death, acute myocardial infarction, stroke or amputation assessed by an adjudication committee blinded to intervention, other cardiovascular clinical outcomes, average postprandial glucose increment from 0 to 18 months, hypoglycaemia and any inadvertent medical episodes. In addition, change in plaque formation in the carotids, HbA1c, cardiovascular biomarkers, body composition, progression of microvascular complications and quality of life will be assessed as tertiary outcome measures. TIME SCHEDULE: Patient enrolment started May 2008. Follow-up is expected to finish in March 2011. CONCLUSION: CIMT is designed to provide evidence as to whether metformin is advantageous even during insulin treatment and to provide evidence regarding which insulin analogue regimen is most advantageous with regard to cardiovascular disease.


Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/análogos & derivados , Metformina/uso terapêutico , Adulto , Idoso , Insulinas Bifásicas , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Quimioterapia Combinada , Métodos Epidemiológicos , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insulina/uso terapêutico , Insulina Aspart , Insulina Detemir , Insulina Isófana , Insulina de Ação Prolongada , Masculino , Metformina/administração & dosagem , Pessoa de Meia-Idade , Projetos de Pesquisa , Resultado do Tratamento , Túnica Íntima/patologia , Túnica Média/patologia , Adulto Jovem
8.
J Laryngol Otol ; 123(5): 492-6, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-18845035

RESUMO

OBJECTIVE: To describe problems and complications associated with cochlear implantation, and their management, in a Danish patient population comprising both paediatric and adult patients. DESIGN: Retrospective chart review. SETTING: Tertiary referral centre. SUBJECTS: Three hundred and thirteen consecutive cochlear implantations were studied. The median age of the study population was 10 years. Sixty per cent of patients were children and 40 per cent were adult; 52 per cent were female and 48 per cent were male. INTERVENTION: Two hundred and ninety-four patients received a Cochlear Nucleus implant. The remaining 19 received an Advanced Bionics implant. MAIN OUTCOME MEASURE: Presence of problems and complications after cochlear implantation. RESULTS: Post-operative complications were found in 15.7 per cent of patients. The majority of these complications (11.2 per cent) were minor; 4.5 per cent were major. The major complications included one patient with meningitis, one patient with multiple antibiotic resistant Staphylococcus aureus infection of a radical cavity, and one diabetic patient who developed a severe skin infection and whose implant became exposed. CONCLUSION: Cochlear implantation is a safe procedure within the studied setting. However, it is essential that careful attention be paid to surgical planning and technique, and it is important that healthcare staff and patients be aware of the possible problems and complications.


Assuntos
Implante Coclear/efeitos adversos , Surdez/cirurgia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
9.
Br J Cancer ; 94(12): 1864-73, 2006 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-16773077

RESUMO

The GAGE cancer testis antigen gene family encodes products that can be recognized by autologous T cells, and GAGE proteins have been suggested as potential targets for cancer immunotherapy. Analysis of GAGE expression in tumours has primarily been performed at the level of gene transcription, whereas little is known about GAGE expression at the protein level. To evaluate the potential of GAGE proteins as targets for cancer-specific immunotherapy, we studied the expression of these proteins in normal and malignant cells/tissues using a novel panel of monoclonal antibodies. Immunohistochemical analysis of more than 250 cancer specimens demonstrated that GAGE proteins were frequently expressed in numerous cancer types and correlated with the expression of the cancer testis antigens MAGE-A1 and NY-ESO-1. Significant intercellular and subcellular differences in GAGE protein levels were observed, and most GAGE-positive tumours also contained cancer cells lacking GAGE expression. Studies of genetically homogenous cell lines with similar intercellular heterogeneous GAGE expression showed that GAGE expression was not associated with a specific genotype, but defined a phenotypically distinct population of cells. Surprisingly, in normal tissues we found that GAGE proteins were not restricted to testis, but were also present in a subset of oocytes of resting primordial follicles and in maturing oocytes. This is the first time that a cancer testis antigen has been reported in postfoetal oocytes. The lack of GAGE expression in a subset of cancer cells within GAGE-positive tumours has decisive implications for the development of GAGE-targeted cancer therapy.


Assuntos
Antígenos de Neoplasias/biossíntese , Biomarcadores Tumorais/análise , Proteínas de Neoplasias/biossíntese , Neoplasias/metabolismo , Animais , Anticorpos Monoclonais , Western Blotting , Feminino , Genótipo , Humanos , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/genética , Oócitos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testículo/metabolismo
10.
Int J Sports Med ; 24(3): 183-9, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12740736

RESUMO

Muscle metabolism and force production were studied in sprint trained runners, endurance trained runners and in untrained subjects, using 31P-MRS. 31P-spectra were obtained at a time resolution of 5 s during four maximal isometric contractions of 30-sec duration, interspersed by 60-sec recovery intervals. Resting CrP/ATP ratio averaged 3.3 +/- 0.3, with no difference among the three groups. The sprint trained subjects showed about 20 % larger contraction forces in contraction bouts 1 and 2 (p < 0.05). The groups differed with respect to CrP breakdown (p < 0.05), with sprinters demonstrating about 75 % breakdown in each contraction compared to about 60 % and 40 % for untrained and endurance trained subjects, respectively (p < 0.05). The endurance trained runners showed almost twice as fast CrP recovery (t 1/2 = 12.5 +/- 1.5) compared to sprint trained (t 1/2 = 22.5 +/- 2.53) and untrained subjects (t 1/2 = 26.4 +/- 2.8). From the initial rate of CrP resynthesis the rate of maximal aerobic ATP synthesis was estimated to 0.74 +/- 0.07, 0.73 +/- 0.10 and 0.33 +/- 0.07 mmol ATP x kg -1 wet muscle x sec -1 for sprint trained, endurance trained and untrained subjects, respectively. Only the sprint trained and the untrained subjects displayed a significant drop in pH and only during the first of the four contractions, about 0.2 and 0.1 pH units, respectively, indicating that only under those contractions was the glycolytic proton production larger than the proton consumption by the CK reaction. Also, in the first contraction the energy cost of contraction was higher for the sprinters compared to the two other groups. The simple 31P-MRS protocol used in the present study demonstrates marked differences in force production, aerobic as well as anaerobic muscle metabolism, clearly allowing differentiation between endurance trained, sprint trained and untrained subjects.


Assuntos
Exercício Físico/fisiologia , Espectroscopia de Ressonância Magnética/métodos , Educação Física e Treinamento/métodos , Resistência Física/fisiologia , Corrida/fisiologia , Adulto , Metabolismo Energético/fisiologia , Humanos , Perna (Membro)/fisiologia , Masculino , Contração Muscular/fisiologia , Músculo Esquelético/fisiologia , Fosfocreatina/metabolismo , Isótopos de Fósforo , Valores de Referência
11.
Plant Physiol ; 126(3): 930-8, 2001 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-11457942

RESUMO

The Agrobacterium-mediated transient expression assay in intact tissues has emerged as a rapid and useful method to analyze genes and gene products in plants. In many cases, high levels of active protein can be produced without the need to produce transgenic plants. In this study, a series of tools were developed to enable strong or weak induction of RNA silencing and to suppress RNA silencing in the absence of stable transgenes. Transient delivery of a gene directing production of a double-stranded green fluorescent protein (GFP) transcript rapidly induced RNA silencing of a codelivered GFP reporter gene, effectively preventing accumulation of GFP protein and mRNA. RNA silencing triggered by the strong dsGFP inducer was partially inhibited by the tobacco etch virus silencing suppressor, P1/HC-Pro. In the absence of the strong double-stranded GFP inducer, the functional GFP gene served as a weak RNA silencing inducer in the transient assay, severely limiting accumulation of the GFP mRNA over time. The weak silencing induced by the GFP gene was suppressed by P1/HC-Pro. These results indicate RNA silencing can be triggered by a variety of inducers and analyzed entirely using transient gene delivery systems. They also indicate that RNA silencing may be a significant limitation to expression of genes in the Agrobacterium-mediated transient assay but that this limitation can be overcome by using RNA silencing suppressors.


Assuntos
Regulação da Expressão Gênica de Plantas , Inativação Gênica , Solanaceae/genética , Clonagem Molecular , Cisteína Endopeptidases/genética , Proteínas de Fluorescência Verde , Proteínas Luminescentes/genética , Folhas de Planta/metabolismo , Plantas Tóxicas , Potyvirus/genética , RNA de Plantas/genética , Rhizobium/genética , Solanaceae/metabolismo , Tabaco , Proteínas não Estruturais Virais/genética , Proteínas Virais/genética
12.
Mol Cell Biol ; 21(11): 3789-806, 2001 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-11340171

RESUMO

CCAAT/enhancer binding protein alpha (C/EBPalpha) is an integral factor in the granulocytic developmental pathway, as myeloblasts from C/EBPalpha-null mice exhibit an early block in differentiation. Since mice deficient for known C/EBPalpha target genes do not exhibit the same block in granulocyte maturation, we sought to identify additional C/EBPalpha target genes essential for myeloid cell development. To identify such genes, we used both representational difference analysis and oligonucleotide array analysis with RNA derived from a C/EBPalpha-inducible myeloid cell line. From each of these independent screens, we identified c-Myc as a C/EBPalpha negatively regulated gene. We mapped an E2F binding site in the c-Myc promoter as the cis-acting element critical for C/EBPalpha negative regulation. The identification of c-Myc as a C/EBPalpha target gene is intriguing, as it has been previously shown that down-regulation of c-Myc can induce myeloid differentiation. Here we show that stable expression of c-Myc from an exogenous promoter not responsive to C/EBPalpha-mediated down-regulation forces myeloblasts to remain in an undifferentiated state. Therefore, C/EBPalpha negative regulation of c-Myc is critical for allowing early myeloid precursors to enter a differentiation pathway. This is the first report to demonstrate that C/EBPalpha directly affects the level of c-Myc expression and, thus, the decision of myeloid blasts to enter into the granulocytic differentiation pathway.


Assuntos
Proteínas de Transporte , Proteínas de Ciclo Celular , Proteínas de Ligação a DNA , Granulócitos/citologia , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-myc/genética , Animais , Sítios de Ligação , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Células COS , Diferenciação Celular , Linhagem Celular , Fatores de Transcrição E2F , Regulação da Expressão Gênica , Humanos , Neutrófilos/citologia , Proteína 1 de Ligação ao Retinoblastoma , Fator de Transcrição DP1 , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas , Células U937
13.
Eur J Appl Physiol ; 84(3): 201-5, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11320636

RESUMO

Basal metabolic rate is scaled to body mass to the power of 0.73, and we evaluated whether a similar scaling applies when the O2 transport capacity of the body is challenged during maximal exercise (i.e. at maximal O2 uptake, VO2max). The allometric relationship between VO2max and body mass (y = a.xb, where y is VO2max and x is body mass) was developed for 967 athletes representing 25 different sports, with up to 157 participants in each sport. With an increasing number of observations, the exponent approached 0.73, while for ventilation the exponent was only 0.55. By using the 0.73 exponent for VO2max, the highest value [mean (SD)] for the males was obtained for the runners and cyclists [234 (16) ml.kg-0.73.min-1], and for the females the highest value was found for the runners [189 (14) ml.kg-0.73.min-1]. For the females, aerobic power was about 80% of the value achieved by the males. Scaling may help both in understanding variation in aerobic power and in defining the physiological limitations of work capacity.


Assuntos
Índice de Massa Corporal , Exercício Físico/fisiologia , Consumo de Oxigênio/fisiologia , Adolescente , Adulto , Metabolismo Basal/fisiologia , Ciclismo/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Corrida/fisiologia , Tamanho da Amostra , Fatores Sexuais , Avaliação da Capacidade de Trabalho
14.
Ugeskr Laeger ; 163(10): 1432-6, 2001 Mar 05.
Artigo em Dinamarquês | MEDLINE | ID: mdl-11257752

RESUMO

INTRODUCTION: The management of patients with cervical lymph node metastases from unknown primary tumours is a major challenge in oncology. This study presents data collected from all five oncology centres in Denmark. MATERIALS AND METHODS: Of the 352 consecutive patients with squamous cell or undifferentiated tumours seen from 1975 to 1995, a total of 277 (79%) were treated with radical intent. Most patients received radiotherapy to both sides of the neck as well as elective irradiation of the mucosal sites in nasopharynx, oropharynx, hypopharynx and larynx (81%). Irradiation of the ipsilateral neck only was done in 26 patients (10%). Radical surgery was the only treatment in 23 N1-N2 patients (9%). RESULTS: The five-year estimates of neck control, disease-specific survival and overall survival for radically treated patients were 51%, 48% and 36%, respectively. The emergence of the occult primary was observed in 66 patients (19%). About half of the emerging primaries were within the head and neck region with oropharynx, hypopharynx and oral cavity being the most common sites. Emerging primaries outside the head and neck region were primarily located in the lung (19 patients) and oesophagus (five patients). The most important factor for neck control was nodal stage (5-year estimates 69% [N1], 58% [N2] and 30% [N3]). Other important parameters for neck control and disease-specific survival included haemoglobin, gender and overall treatment time. Patients treated with ipsilateral radiotherapy had a relative risk of recurrence in the head and neck region of 1.9 compared to patients treated at both neck and mucosa. At five years, the estimated control rates were 27% (ipsilateral) and 51% (bilateral; p = 0.05). The 5-year disease-specific survival estimates were 28% and 45%, respectively (p = 0.10). DISCUSSION: Extensive irradiation to both sides of the neck and the mucosa in the entire pharyngeal axis and larynx resulted in significantly fewer loco-regional failures compared to patients treated with ipsilateral techniques, but only a trend towards better survival. Determination of the optimal strategy in terms of loco-regional control, survival and morbidity requires a prospective randomized trial.


Assuntos
Neoplasias de Cabeça e Pescoço/terapia , Metástase Linfática , Neoplasias Primárias Desconhecidas , Adolescente , Adulto , Idoso , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/terapia , Terapia Combinada , Dinamarca/epidemiologia , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/secundário , Humanos , Metástase Linfática/diagnóstico , Metástase Linfática/radioterapia , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/diagnóstico , Prognóstico , Dosagem Radioterapêutica
16.
Acta Oncol ; 40(7): 796-800, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11859977

RESUMO

Two treatment options are widely used for the cure of T1 glottic squamous cell carcinoma: radiotherapy and surgical removal. There is ongoing controversy about whether laser excision should be offered to patients with T1 glottic carcinoma. The purpose of this study is to present a review of studies dealing with treatment outcome after laser excision of T1 glottic carcinoma. Eighteen original papers on outcomes were identified. Recurrence rates ranged from 4% to 35%. The disease-specific survival rate at 5 years was found to be from 89% to 100% and crude survival from 74% to 100%. Of the six studies dealing with voice quality, radiation therapy was found to be more effective in preservation of the voice in three, while in the other three studies, no significant difference could be detected. With respect to costs of treatment, in three out of four studies laser surgery was found to be the more economical treatment option. Laser surgery seems to provide comparably low recurrence rates and high disease-specific survival as compared with radiotherapy. In T1 cancer, laser resection leaves the patient with a poorer voice quality than is the case with radiation therapy, but laser treatment seems to be the cheaper option.


Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Laríngeas/cirurgia , Terapia a Laser , Recidiva Local de Neoplasia , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Humanos , Neoplasias Laríngeas/patologia , Radioterapia Adjuvante , Terapia de Salvação , Resultado do Tratamento
17.
Acta Oncol ; 40(7): 801-9, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11859978

RESUMO

The purpose of this study was to evaluate the outcome of primary treatment and treatment of recurrences in patients with nasopharyngeal carcinoma. The material included 149 consecutive patients seen at the Aarhus University Hospital from 1963 to 1991 (49 females and 100 males). The stage distribution was: Stage I-9%, II-3%, III-28%, and IV-60%. Primary treatment was delivered with curative intent in 145 patients (97%). Persistent or recurrent disease after primary radical treatment was observed in 82 of the patients; 54% at the T-level, 40% at the N-level, and 33% at the M-level. A curative salvage attempt was carried out in 14 patients only, all with nodal recurrence: surgery in 8 patients (4 controlled) and radiotherapy in 6 patients (2 controlled). The 5-year local tumour control, locoregional tumour control, disease-specific survival rate and the overall survival rate for the patients treated with curative intent were 66%, 53%, 50% and 43%, respectively. Most of the patients (88%) had poorly differentiated tumours and these patients had the best prognosis. A major complication in three patients was radiation-induced myelopathy due to high-dose radiation delivered to the brain stem. Significant positive prognostic factors for treatment outcome in univariate analyses were early T-classification, small clinical stage, poor differentiation and low age. The Cox multivariate analysis showed that early T-categories, low N-categories and poor differentiation were independent, positive prognostic factors. Nasopharyngeal carcinoma is curable with primary radiotherapy; patients with poorly differentiated tumours have the best prognosis. Only a few patients were salvaged after recurrence. The factor most essential for success is primary control of the disease at the T- and N-levels.


Assuntos
Carcinoma de Células Escamosas/radioterapia , Carcinoma de Células Escamosas/cirurgia , Neoplasias Nasofaríngeas/radioterapia , Neoplasias Nasofaríngeas/cirurgia , Recidiva Local de Neoplasia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologia , Prognóstico , Terapia de Salvação , Resultado do Tratamento
18.
Dis Aquat Organ ; 47(2): 109-17, 2001 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-11775792

RESUMO

Infectious pancreatic necrosis (IPN) virus (IPNV) infection in Atlantic salmon Salmo salar L. post-smolts and its influence on the outcome of secondary infections with infectious salmon anaemia (ISA) virus (ISAV) or Vibrio salmonicida were studied. The infections with ISAV or V salmonicida were performed both in a period of acute IPN and in the following IPNV carrier stage, 3 and 6 to 8 wk after experimental IPNV challenge, respectively. An IPNV carrier condition at low virus titre did not influence the mortality rates after secondary infections. Neither the ISAV infection nor the V. salmonicida infection in experimentally induced IPNV carriers resulted in mortalities different from those observed after challenge of IPNV-free fish. At higher IPNV titres in Atlantic salmon with acute IPN, the outcome of secondary infections was quite different from that observed in IPNV-free fish and in IPNV carriers. In 2 different experiments significantly more fish died when fish with acute IPN were infected with V salmonicida than when fish were infected with V salmonicida alone. Mortality also started earlier in the double-infected group than in the group challenged with V. salmonicida alone, 3 to 4 and 8 d after V salmonicida infection, respectively. Similar results were observed independent of whether mortalities due to IPN alone were registered in the experiments. When Atlantic salmon with acute IPN were infected with ISAV, significantly fewer fish died than when fish were infected with ISAV alone. The ongoing IPNV infection seemed to provide some protection against development of ISA.


Assuntos
Infecções por Birnaviridae/veterinária , Doenças dos Peixes/mortalidade , Vírus da Necrose Pancreática Infecciosa/fisiologia , Infecções por Orthomyxoviridae/veterinária , Salmo salar , Vibrioses/veterinária , Animais , Infecções por Birnaviridae/complicações , Portador Sadio/veterinária , Suscetibilidade a Doenças/veterinária , Doenças dos Peixes/microbiologia , Doenças dos Peixes/virologia , Orthomyxoviridae , Infecções por Orthomyxoviridae/complicações , Infecções por Orthomyxoviridae/mortalidade , Vibrioses/complicações , Vibrioses/mortalidade
19.
J Exp Psychol Hum Percept Perform ; 26(6): 1691-720, 2000 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-11129368

RESUMO

Three experiments using the Reicher task show that performance on low-frequency words is disrupted if the incorrect alternative forms a higher frequency word. This neighborhood frequency effect occurs for both energy and pattern masks and for different sets of items. When the upcoming word is primed and its accessibility is enhanced, the neighborhood frequency effect is eliminated. Experiments 4a and 4b tested the neighborhood frequency effect using a same-different task and a signal-detection analysis. Neighborhood frequency affected the decision criterion but not the sensitivity of the perceptual system. Experiment 5 showed that many words with a frequency in the range from 1 to 5 per million are not recognized out of context. These results are consistent with the hypothesis that frequency effects in the Reicher task are caused by a bias in the decision system and can be simulated with the stochastic activation-verification model.


Assuntos
Idioma , Detecção de Sinal Psicológico , Adulto , Tomada de Decisões , Feminino , Humanos , Masculino , Análise e Desempenho de Tarefas
20.
Nucleic Acids Res ; 28(23): 4665-73, 2000 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-11095676

RESUMO

Gene activation in eukaryotes is inherently combinatorial depending on cooperation between different transcription factors. An example where this cooperation seems to be directly exploited for regulation is the Bas1p/Bas2p couple in yeast. Bas1p is a Myb-related transcription factor that acts together with the homeodomain-related Bas2p (Pho2p) to regulate purine and histidine biosynthesis genes in response to extracellular purine limitation. We show that fusion of the two factors abolished adenine repression, suggesting that what is regulated by adenine is the Bas1p-Bas2p interaction. Analysis of Bas1p deletions revealed a critical domain (Bas1p interaction and regulatory domain, BIRD) acting in two-hybrid assays as an adenine-dependent Bas1p-Bas2p interaction domain. BIRD had a dual function, as an internal repressor of a centrally located Bas1p transactivation domain on the ADE1 promoter and as a Bas2p-dependent activator on the HIS4 promoter. This promoter-dependent behavior reflected a differential binding to the two promoters in vivo. On ADE1 Bas1p bound the promoter efficiently by itself, but required adenine limitation and Bas2p interaction through BIRD for derepression. On HIS4 efficient promoter binding and derepression required both factors and adenine limitation. We propose a promoter-dependent model for adenine regulation in yeast based on controlled Bas1p-Bas2p interactions through BIRD and exploited differentially by the two promoters.


Assuntos
Proteínas de Homeodomínio , Proteínas de Saccharomyces cerevisiae , Transdução de Sinais/fisiologia , Fatores de Transcrição/metabolismo , Adenina/farmacologia , Oxirredutases do Álcool , Aminoidrolases , Sítios de Ligação/genética , DNA Recombinante , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Óperon Lac/genética , Proteínas Oncogênicas v-myb/genética , Proteínas Oncogênicas v-myb/metabolismo , Peptídeo Sintases/genética , Peptídeo Sintases/metabolismo , Plasmídeos/genética , Regiões Promotoras Genéticas , Ligação Proteica , Pirofosfatases , Proteínas Recombinantes de Fusão/efeitos dos fármacos , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Deleção de Sequência , Transativadores/genética , Transativadores/metabolismo , Fatores de Transcrição/genética , Ativação Transcricional , Técnicas do Sistema de Duplo-Híbrido
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