RESUMO
AIM: To determine the accuracy of trainees reporting computed tomography (CT) examinations. MATERIAL AND METHODS: Over a 6-month period a single consultant reviewed all the CT examinations reported by registrars in one radiology department. After recording a provisional registrar report each examination was jointly reviewed by the consultant and registrar. The consultant's opinion was regarded as the gold standard. Data collected included: the error rate, whether an error was significant, leading to a change in patient management, and whether the mistake was a false-negative or positive. RESULTS: Three hundred and thirty-one patients were included in the study. There was an overall error rate of 21.5%. A significant error leading to a change in management was made in 10% of reports, and a significant error that did not lead to a change in management was made in 9.3%; 2.1% of reports had insignificant errors; and 69% of errors were false-negatives. CONCLUSION: Registrars make a significant number of errors affecting patient management when reporting CT and ideally all examinations should be reviewed by a consultant.
Assuntos
Competência Clínica/normas , Erros de Diagnóstico , Prontuários Médicos/normas , Corpo Clínico Hospitalar/normas , Radiologia/educação , Tomografia Computadorizada por Raios X , Consultores , Reações Falso-Negativas , Reações Falso-Positivas , Humanos , Auditoria Médica , Corpo Clínico Hospitalar/educação , Estudos Prospectivos , Radiologia/normas , Gestão de RiscosRESUMO
The entire pathway for synthesis of the tyrosine-derived cyanogenic glucoside dhurrin has been transferred from Sorghum bicolor to Arabidopsis thaliana. Here, we document that genetically engineered plants are able to synthesize and store large amounts of new natural products. The presence of dhurrin in the transgenic A. thaliana plants confers resistance to the flea beetle Phyllotreta nemorum, which is a natural pest of other members of the crucifer group, demonstrating the potential utility of cyanogenic glucosides in plant defense.
Assuntos
Arabidopsis/metabolismo , Besouros/fisiologia , Ingestão de Alimentos , Engenharia Genética , Magnoliopsida/enzimologia , Nitrilas/metabolismo , Controle Biológico de Vetores/métodos , Animais , Arabidopsis/genética , Cromatografia Líquida de Alta Pressão , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Cadeia Alimentar , Glucosídeos/análise , Glucosídeos/biossíntese , Magnoliopsida/genética , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Nitrilas/análise , Folhas de Planta/genética , Folhas de Planta/metabolismo , Plantas Geneticamente ModificadasRESUMO
Sequential proteolytic processing of the Amyloid Precursor Protein (APP) by beta- and gamma-secretases generates the 4-kDa amyloid (A beta) peptide, a key component of the amyloid plaques seen in Alzheimer's disease (AD). We and others have recently reported the identification and characterisation of an aspartic proteinase, Asp2 (BACE), as beta-secretase. Here we describe the characterization of a second highly related aspartic proteinase, Asp1 as a second beta-secretase candidate. Asp1 is expressed in brain as detected at the mRNA level and at the protein level. Transient expression of Asp1 in APP-expressing cells results in an increase in the level of beta-secretase-derived soluble APP and the corresponding carboxy-terminal fragment. Paradoxically there is a decrease in the level of soluble A beta secreted from the cells. Asp1 colocalizes with APP in the Golgi/endoplasmic reticulum compartments of cultured cells. Asp1, when expressed as an Fc fusion protein (Asp1-Fc), has the N-terminal sequence ALEP..., indicating that it has lost the prodomain. Asp1-Fc exhibits beta-secretase activity by cleaving both wild-type and Swedish variant (KM/NL) APP peptides at the beta-secretase site.
Assuntos
Precursor de Proteína beta-Amiloide/metabolismo , Ácido Aspártico Endopeptidases/metabolismo , Glicoproteínas/genética , Glicoproteínas/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Secretases da Proteína Precursora do Amiloide , Precursor de Proteína beta-Amiloide/análise , Precursor de Proteína beta-Amiloide/química , Animais , Ácido Aspártico Endopeptidases/química , Sítios de Ligação/fisiologia , Células COS , Clonagem Molecular , Endopeptidases , Feminino , Glicoproteínas/análise , Humanos , Masculino , Proteínas de Membrana/análise , Dados de Sequência Molecular , Coelhos , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Homologia de Sequência de AminoácidosRESUMO
The occurrence of significant mediastinal lymphadenopathy together with pleural effusion or empyema inevitably raises concern about the presence of intrathoracic malignancy or granulomatous disease. Lymph node enlargement may also occur when pneumonia is accompanied by a parapneumonic effusion or empyema. Features that allow "benign" lymph node enlargement to be distinguished from malignant causes have not previously been determined. The present study aims to establish the CT characteristics of enlarged nodes in parapneumonic effusion. The appearances of mediastinal lymph nodes were recorded in 50 consecutive patients with parapneumonic effusion/empyema. 18 (36%) had mediastinal lymphadenopathy (node size greater than 1 cm). The mean number of enlarged nodes was 1.9 (range 1-3) and the mean size was 1.4 cm (2 cm maximum). Seven patients had a single involved site, nine patients two sites and two patients three sites. The right paratracheal area was most commonly involved and the subcarinal area contained the largest nodes. The presence of enlarged nodes did not correlate with biochemical and microbiological stage of pleural infection, length of history, or extent of consolidation. This study shows that mediastinal lymphadenopathy is commonly associated with parapneumonic effusion and that multiple sites may be involved. The degree of enlargement is moderate although lymphadenopathy of greater than 2 cm size should raise the possibility of other pathology.
Assuntos
Empiema Pleural/diagnóstico por imagem , Doenças Linfáticas/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Pneumonia Bacteriana/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Empiema Pleural/etiologia , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Doenças Linfáticas/etiologia , Masculino , Mediastino/diagnóstico por imagem , Pessoa de Meia-Idade , Derrame Pleural/etiologia , Pneumonia Bacteriana/complicações , Tomografia Computadorizada por Raios XAssuntos
Tubos Torácicos , Toracostomia/instrumentação , Tubos Torácicos/efeitos adversos , Empiema Pleural/terapia , Desenho de Equipamento , Falha de Equipamento , Humanos , Derrame Pleural/terapia , Derrame Pleural Maligno/terapia , Pleurodese/instrumentação , Pneumotórax/terapia , Radiografia Intervencionista , Reologia , Toracostomia/efeitos adversos , Resultado do TratamentoRESUMO
The protein composition of the grape (Vitis vinifera cv Muscat of Alexandria) berry was examined from flowering to ripeness by gel electrophoresis. A protein with an apparent molecular mass of 24 kD, which was one of the most abundant proteins in extracts of mature berries, was purified and identified by amino acid sequence to be a thaumatin-like protein. Combined cDNA sequence analysis and electrospray mass spectrometry revealed that this protein, VVTL1 (for V. vinifera thaumatin-like protein 1), is synthesized with a transient signal peptide as seen for apoplastic preproteins. Apart from the removal of the targeting signal and the formation of eight disulfide bonds, VVTL1 undergoes no other posttranslational modification. Southern, northern, and western analyses revealed that VVTL1 is found in the berry only and is encoded by a single gene that is expressed in conjunction with the onset of sugar accumulation and softening. The exact role of VVTL1 is unknown, but the timing of its accumulation correlates with the inability of the fungal pathogen powdery mildew (Uncinula necator) to initiate new infections of the berry. Western analysis revealed that the presence of thaumatin-like proteins in ripening fruit might be a widespread phenomenon.
Assuntos
Frutas/fisiologia , Proteínas de Plantas/biossíntese , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Dados de Sequência Molecular , Peso Molecular , Proteínas de Plantas/química , Proteínas de Plantas/isolamento & purificação , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/química , Proteínas Recombinantes/isolamento & purificação , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , EdulcorantesRESUMO
Dichelobacter nodosus is the principal causative agent of ovine footrot. Nucleotide (nt) sequences from the D. nodosus genome have been isolated and a series of overlapping lambda clones defining vap (virulence-associated protein) regions 1, 2 and 3 have been reported [Katz et al., J. Bacteriol. 176 (1994) 2663-2669]. In the present study, the limits of the virulence-associated (va) DNA around vap regions 1 and 3 were determined by dot-blot hybridization experiments using plasmid subclones to probe genomic DNA from the D. nodosus virulent strain A198 and the benign strain C305. This va region was found to be approx. 11.9 kb in length, and to be interrupted by a short DNA segment which is also found in the benign D. nodosus strain. Sequence analysis of the entire region revealed an ORF, intA, which is very similar to the integrases of bacteriophages phi R73, P4 and Sf6. Bacteriophages phi R73 and P4 integrate into the 3' ends of tRNA genes, with the integrase genes adjacent to the tRNA genes. A similar arrangement was found in the D. nodosus va region. A 19-bp nt sequence was found to be repeated at the ends of the va region, and may represent the bacteriphage attachment site. These findings suggest that D. nodosus may have acquired these DNA sequences by the integration of a bacteriophage, or an integrative plasmid that contains a bacteriophage-related integrase gene. The high similarity of the D. nodosus integrase to integrases from coliphages suggests that these va sequences may be transferred between distantly related bacteria.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Bacteriófagos/genética , DNA Nucleotidiltransferases/genética , Genes Bacterianos , Bactérias Anaeróbias Gram-Negativas/genética , Sequência de Aminoácidos , Sequência de Bases , Elementos de DNA Transponíveis , DNA Bacteriano/genética , Pododermatite Necrótica dos Ovinos/microbiologia , Genoma Bacteriano , Bactérias Anaeróbias Gram-Negativas/enzimologia , Bactérias Anaeróbias Gram-Negativas/patogenicidade , Integrases , Dados de Sequência Molecular , Família Multigênica , Hibridização de Ácido Nucleico , Plasmídeos , RNA de Transferência de Serina/genética , Sequências Repetitivas de Ácido Nucleico , Origem de Replicação , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Homologia de Sequência do Ácido Nucleico , Virulência/genética , Integração ViralRESUMO
The discriminative stimulus properties of the selective CCKB-receptor antagonist, L-365,260 were evaluated in rats trained to discriminate diazepam (2 mg/kg) or morphine (5 mg/kg) from vehicle, using a two-lever food reinforced technique. In the diazepam drug discrimination, the benzodiazepine-receptor agonist FG8205 (0.063-2 mg/kg) produced dose-related drug associated responding, whereas L-365,260 (0.125-4 mg/kg) treated animals showed vehicle appropriate behaviour. In rats trained to discriminate morphine from saline, L-365,260 (0.063-4 mg/kg) produced saline lever responding. When a dose of 1 mg/kg L-365,260 was administered in combination with morphine, the dose response curve for drug lever responding was not significantly affected. This was in contrast to the effect produced by the opiate antagonist naloxone (0.3 mg/kg) which shifted the dose-response curve to the right. Another group of rats underwent training to discriminate a dose of 6 mg/kg L-365,260 from vehicle. None of the animals learned the discrimination within 50 daily training sessions. In addition, unlike morphine (3 mg/kg), or changing the training dose of cocaine, intravenous administration of L-365,260 (0.3-10 mg/kg) did not modify lever pressing or the number of injections received by rats trained to self administer cocaine (0.25 mg/injection). L-365,260 (0.1-3 mg/kg) produced a dose-related inhibition of pentagastrin-stimulated gastric acid secretion in vivo. When administered dissolved in a mixture of ethanol/propylene glycol/saline, the ID50 was 0.83 mg/kg, and when suspended in an ethanol/carboxymethylcellulose vehicle, it was 0.7 mg/kg. It was concluded: 1) that L-365,260 does not produce discriminative stimuli similar to either diazepam or morphine; 2) that the potentiation of morphine-induced behaviour by L-365,260 does not extend to the discriminative stimulus properties of morphine; 3) that L-365,260 itself does not produce readily discriminable interoceptive stimuli in rats; and 4) that L-365,260 does not substitute for the reinforcing drug cocaine.
Assuntos
Benzodiazepinonas/farmacologia , Discriminação Psicológica/efeitos dos fármacos , Compostos de Fenilureia , Receptores da Colecistocinina/antagonistas & inibidores , Animais , Comportamento Animal/efeitos dos fármacos , Cocaína/administração & dosagem , Diazepam/administração & dosagem , Sinergismo Farmacológico , Ácido Gástrico/metabolismo , Masculino , Morfina/administração & dosagem , Naloxona/farmacologia , Pentagastrina/farmacologia , Ratos , Ratos Sprague-Dawley , Autoadministração , Cloreto de SódioRESUMO
The substituted benzamide derivatives, dazopride and metoclopramide, enhanced field stimulation-induced contractions of guinea-pig stomach strips and gastric emptying in the guinea-pig after peripheral, intracerebroventricular and intrahypothalamic injection. In the isolated vagal nerve preparation from the rabbit, both compounds were shown to be 5-hydroxytryptamine M-receptor antagonists. Dazopride and metoclopramide were equipotent in antagonising cisplatin-induced emesis in the ferret, whereas metoclopramide was approximately 200 times more potent than dazopride in antagonising the emesis caused by the dopamine agonist 2-di-n-propylamino-5,6-dihydroxytetralin in the marmoset. In behavioural tests which indicate dopamine receptor antagonism in the rat, metoclopramide induced catalepsy, antagonised amphetamine-induced stereotypy and the hyperactivity induced by the intrastriatal injection of dopamine, caused body asymmetry on unilateral injection into the striatum and also antagonised apomorphine-induced climbing and circling behaviour in the mouse. In contrast, dazopride had little or no action in these tests and failed to displace [3H]spiperone in radioligand binding assays. The use of dazopride provides evidence to dissociate a dopamine receptor blockade from an ability to facilitate gastric emptying and to antagonise cisplatin-emesis, and indicates that antagonism of 5-hydroxytryptamine M-receptors is the essential basis of action for dazopride and plays an important role in the actions of metoclopramide.