Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 145
Filtrar
Mais filtros










Intervalo de ano de publicação
1.
Science ; 346(6212): 996-1000, 2014 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-25414313

RESUMO

We introduce the antibody landscape, a method for the quantitative analysis of antibody-mediated immunity to antigenically variable pathogens, achieved by accounting for antigenic variation among pathogen strains. We generated antibody landscapes to study immune profiles covering 43 years of influenza A/H3N2 virus evolution for 69 individuals monitored for infection over 6 years and for 225 individuals pre- and postvaccination. Upon infection and vaccination, titers increased broadly, including previously encountered viruses far beyond the extent of cross-reactivity observed after a primary infection. We explored implications for vaccination and found that the use of an antigenically advanced virus had the dual benefit of inducing antibodies against both advanced and previous antigenic clusters. These results indicate that preemptive vaccine updates may improve influenza vaccine efficacy in previously exposed individuals.


Assuntos
Anticorpos Antivirais/imunologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vacinas contra Influenza/imunologia , Influenza Humana/imunologia , Vacinação , Anticorpos Antivirais/sangue , Variação Antigênica/genética , Variação Antigênica/imunologia , Evolução Molecular , Humanos , Vírus da Influenza A Subtipo H3N2/genética , Influenza Humana/sangue , Influenza Humana/prevenção & controle
2.
J Virol ; 81(8): 4315-22, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17287258

RESUMO

In the early 1970s, a human influenza A/Port Chalmers/1/73 (H3N2)-like virus colonized the European swine population. Analyses of swine influenza A (H3N2) viruses isolated in The Netherlands and Belgium revealed that in the early 1990s, antigenic drift had occurred, away from A/Port Chalmers/1/73, the strain commonly used in influenza vaccines for pigs. Here we show that Italian swine influenza A (H3N2) viruses displayed antigenic and genetic changes similar to those observed in Northern European viruses in the same period. We used antigenic cartography methods for quantitative analyses of the antigenic evolution of European swine H3N2 viruses and observed a clustered virus evolution as seen for human viruses. Although the antigenic drift of swine and human H3N2 viruses has followed distinct evolutionary paths, potential cluster-differentiating amino acid substitutions in the influenza virus surface protein hemagglutinin (HA) were in part the same. The antigenic evolution of swine viruses occurred at a rate approximately six times slower than the rate in human viruses, even though the rates of genetic evolution of the HA at the nucleotide and amino acid level were similar for human and swine H3N2 viruses. Continuous monitoring of antigenic changes is recommended to give a first indication as to whether vaccine strains may need updating. Our data suggest that humoral immunity in the population plays a smaller role in the evolutionary selection processes of swine H3N2 viruses than in human H3N2 viruses.


Assuntos
Antígenos Virais/imunologia , Evolução Molecular , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H3N2/imunologia , Infecções por Orthomyxoviridae/veterinária , Doenças dos Suínos/virologia , Substituição de Aminoácidos , Animais , Sequência de Bases , Evolução Biológica , Europa (Continente) , Deriva Genética , Testes de Inibição da Hemaglutinação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Vírus da Influenza A Subtipo H3N2/classificação , Vírus da Influenza A Subtipo H3N2/isolamento & purificação , Influenza Humana/virologia , Dados de Sequência Molecular , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Filogenia , Análise de Sequência de DNA , Suínos , Doenças dos Suínos/imunologia
6.
Genetica ; 112-113: 297-319, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11838772

RESUMO

Field censuses, breeding experiments, and a quantitative model are used to obtain insight into the extent and consequences of genetic mixing between locally adapted populations of a desert spider. Typically, 9% of the matings of desert riparian spiders (non-aggressive phenotype) in native habitat involve an arid-land partner (aggressive phenotype). Mating was found to be random with respect to behavioral phenotype, but linearly related to both the rate of immigration and survival of immigrants from surrounding arid habitats in the riparian area. Genetic mixing between riparian and arid-land spiders produces offspring that exhibit lower rates of survival in riparian habitat. Two extreme behavioral phenotypes were also observed in the field studies: approximately 5% of the female spiders attacked all males they encountered while another 22% ran from all potential mates. Punnett square analyses of the potential genotypes produced by introgression between arid- and riparian-adapted spiders indicate that these extreme phenotypes appear in F2 generation hybrids and backcrosses. Because there is a costly wastage of gametes in the case of mixed phenotype mating, model results indicate that within three generations of the cessation of gene flow, the riparian population would be free of mixed genotypes and moving towards genetic differentiation.


Assuntos
Evolução Biológica , Comportamento Sexual Animal , Aranhas/genética , Alelos , Animais , Feminino , Genética Populacional , Genótipo , Células Germinativas , Masculino , Modelos Genéticos , Comportamento Predatório , Reprodução , Especificidade da Espécie , Aranhas/fisiologia
7.
Mol Ecol ; 9(9): 1415-9, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10972780

RESUMO

We estimated the rate of extra-pair fertilizations (EPFs) in waved albatrosses (Phoebastria irrorata) on Isla Española, Galápagos, Ecuador, using multilocus minisatellite DNA fingerprinting. Waved albatrosses are socially monogamous, long-lived seabirds whose main population is on Española. Aggressive extra-pair copulation (EPC) attempts have been observed in the breeding colony during the days preceding egg-laying. Our genetic analyses of 16 families (single chicks and their attending parents) revealed evidence of EPFs in four families. In all cases males were the excluded parent. These data suggest that waved albatrosses have an unusually high rate of EPF relative to taxa with similar life histories. Future behavioural observations will determine the extent to which forced vs. unforced EPCs contribute to this high EPF rate.


Assuntos
Aves/genética , Animais , Sequência de Bases , Aves/fisiologia , Primers do DNA/genética , Equador , Feminino , Fertilização/genética , Masculino , Paternidade , Comportamento Sexual Animal
10.
J Cogn Neurosci ; 12(6): 965-76, 2000 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-11177417

RESUMO

Neural regions associated with retrieval success were identified using event-related fMRI procedures and randomly ordered trials on a recognition memory test. Differences between hits and correct rejections (CRs) occurred multiple regions, including bilateral anterior and right dorsolateral prefrontal cortex, bilateral inferior parietal cortex, and right superior parietal cortex (all hits > CRs), and right occipital cortex (CRs > hits). The hit > CR pattern is not compromised by time-on-task explanations because response latencies for correctly rejected words exceeded those for hits. Converging evidence for the claim that the hit > CR pattern identified neural correlates of retrieval success was obtained by unconfounding item history and retrieval success. That is, we implemented a third condition in which nonstudied words were presented, yet retrieval success was hypothesized to facilitate CRs of these lures. Specifically, in when confronted with a familiar, yet nonstudied word, (e.g., nosedive after studying nosebleed and skydive), subjects might adopt a strategy whereby they recall the studied word(s) that gave rise to the familiarity (nosebleed, skydive) and thereby reject the lure. This method of instantiating retrieval success under conditions in which the target word had not been studied offers converging evidence for the claim that anterior-prefrontal cortex (among other regions) demonstrates enhanced activation during retrieval success.


Assuntos
Memória/fisiologia , Córtex Pré-Frontal/fisiologia , Adolescente , Adulto , Análise de Variância , Cognição/fisiologia , Sensibilidades de Contraste , Feminino , Humanos , Imagem por Ressonância Magnética , Masculino , Aprendizagem Verbal/fisiologia
11.
Am J Trop Med Hyg ; 61(1): 163-70, 1999 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-10432074

RESUMO

We report on the ongoing epidemic of typhoid fever in Tajikistan that started in 1996. It has involved more than 24,000 cases to date, and is characterized by multiple point sources, overflow of sewage, contaminated municipal water, and person-to-person spread. Of the Salmonella typhi isolates available for testing in western laboratories, more than 90% are multidrug-resistant (MDR). Most recently, 28 (82%) of 34 isolates are resistant to ciprofloxacin, representing the first reported epidemic of quinolone-resistant typhoid fever. In the past, mass immunization during typhoid fever epidemics has been discouraged. A review of this policy is recommended in light of the alarming emergence of quinolone-resistant strains of S. typhi, the availability of improved vaccines, and the ongoing epidemic in Tajikistan. Mass immunization may be a useful measure for the control of prolonged MDR typhoid fever epidemics, as an adjunct to correction of municipal infrastructure and public health intervention.


Assuntos
Programas de Imunização , Salmonella typhi/patogenicidade , Febre Tifoide/prevenção & controle , Vacinas Tíficas-Paratíficas/uso terapêutico , Anti-Infecciosos/uso terapêutico , Ciprofloxacino/uso terapêutico , Resistência a Múltiplos Medicamentos , Humanos , Saúde Pública , Saneamento , Tadjiquistão/epidemiologia , Febre Tifoide/epidemiologia , Febre Tifoide/imunologia , Microbiologia da Água , Organização Mundial da Saúde
13.
Med Oncol ; 14(2): 91-8, 1997 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9330268

RESUMO

This study evaluates the use of granulocyte-macrophage colony stimulating factor (GM-CSF) in patients with prolonged haematopoietic dysfunction (> 21 days) after using chemotherapy to treat cancer. One hundred and seven patients were identified who had a leucocyte count below 1000 cells/mm3 more than 21 days after start of chemotherapy (81 patients) or after bone marrow transplantation (BMT)(26 patients). There were 66 males and 40 females ranging in age from 4.5 to 82 years. The duration of aplasia was 48 +/- 43 days in the chemotherapy alone group, and 79 +/- 57 days in the post BMT group. Over 80% of the patients had haematologic malignancies and 70% had an infection prior to the start of the cytokine. Patients received 5 micrograms GM-CSF/kg1 body weight daily i.v. or s.c. for 14 +/- 11 days in the chemotherapy group and 20 +/- 26 days in the BMT group. Sixty percent of chemotherapy patients and 58% of BMT patients had a haematological response to treatment (leucocyte count > 2000 cells/mm3. Median times to haematologic recovery were 7 days in the chemotherapy group and 10 days in the BMT group. There was a significant reduction in the number of infections (73% to 28% in the chemotherapy group). Clinical responses in the two groups were 55% and 50%, respectively. No severe, drug-related adverse events were reported and no evidence of stimulation of malignant clones was observed. It is concluded that GM-CSF is effective and well tolerated in patients with prolonged bone marrow dysfunction after chemotherapy or BMT. Although results from an open-label trial must be viewed with caution, this observation confirms the value and safety of GM-CSF therapy in patients with this severe, and often fatal, condition.


Assuntos
Antineoplásicos/efeitos adversos , Transplante de Medula Óssea/efeitos adversos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Doenças Hematológicas/tratamento farmacológico , Doenças Hematológicas/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Terapia Combinada , Feminino , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Hematopoese/efeitos dos fármacos , Humanos , Contagem de Leucócitos/efeitos dos fármacos , Leucopenia/tratamento farmacológico , Leucopenia/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/sangue , Neoplasias/tratamento farmacológico , Neoplasias/terapia
14.
Br J Dermatol ; 136(5): 737-42, 1997 May.
Artigo em Inglês | MEDLINE | ID: mdl-9205509

RESUMO

Terbinafine (Lamisil) has been registered throughout the world for the treatment of finger and toenail onychomycosis. The recommended duration of treatment of toenail onychomycosis based on phase III studies is 12 weeks. This study was designed to determine: (i) if patients in whom the proximal part of the toenails was not affected respond as well after 6 weeks treatment as after 12 weeks treatment; (ii) to identify factors which may allow selection of patients for shorter treatment duration; and (iii) confirm that 6 weeks therapy is sufficient in fingernail mycosis. One hundred and forty-eight patients received 250 mg terbinafine daily for either 6 or 12 weeks in a double-blinded manner, and were allowed until 48 weeks after start of therapy. Cure of the nail infection was defined as negative mycological tests (mycological cure) and progressive growth of normal nail (clinical cure). Mycological cure was recorded in 43 of 72 (59.7%) in the 6-week group and 55 of 76 (72.4%) in the 12-week group. In those who completed the study per protocol in the 6-week group, 34 of 61 (55.7%) were cured mycologically corresponding to 46 of 56 (82.1%) in the 12-week group. The overall clinical and mycological cure rates for the two groups were 28 of 61 (45.9%) and 33 of 56 (58.9%), respectively. In the small number of patients with associated fingernail infection, all were improved and six of eight (75.0%) were cured after a duration of treatment of 6 weeks. A priori risk factors for failure of cure could not be identified in either group. However, shorter duration of disease prior to treatment and no involvement of the big toenail was associated with a trend toward better responses in both groups. It can be concluded from this study that, in toenail mycosis without visible matrix involvement, 6 weeks treatment of terbinafine is generally not sufficient, whereas fingernail infections respond well to this short therapy.


Assuntos
Antifúngicos/administração & dosagem , Naftalenos/administração & dosagem , Onicomicose/tratamento farmacológico , Adulto , Idoso , Antifúngicos/uso terapêutico , Método Duplo-Cego , Esquema de Medicação , Dermatoses do Pé/tratamento farmacológico , Dermatoses da Mão/tratamento farmacológico , Humanos , Pessoa de Meia-Idade , Naftalenos/uso terapêutico , Seleção de Pacientes , Terbinafina , Resultado do Tratamento
16.
Nurse Educ ; 22(1): 6-8, 1997.
Artigo em Inglês | MEDLINE | ID: mdl-9069934

RESUMO

The use of telecommunication technology in nursing education is increasing dramatically. Interactive television courses are effective and efficient in overcoming barriers of distance and access. Faculty members using the technology find many opportunities for innovation and creativity as courses are implemented. The authors describe a nursing graduate course offered collaboratively between two schools of nursing.


Assuntos
Educação de Pós-Graduação em Enfermagem/organização & administração , Relações Interinstitucionais , Escolas de Enfermagem/organização & administração , Telecomunicações/organização & administração , Humanos , Avaliação de Programas e Projetos de Saúde
17.
Vaccine ; 14(13): 1199-204, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-8961505

RESUMO

Recombinant human granulocyte-macrophage colony stimulating factor (rhGM-CSF) has been shown to augment antigen presentation by macrophages and dendritic cells in vitro, and to increase antibody responses to injected antigens in experimental animals. To evaluate the usefulness of rhGM-CSF as a vaccine adjuvant, 108 healthy volunteers were randomly assigned to receive an injection of rhGM-CSF (n = 81) or placebo (control group; n = 27), followed by an injection with recombinant hepatitis B vaccine into the same site. During the study period of 28 days, protective antibody titers to hepatitis surface antigen (anti-HBs10 mIU ml-1) were observed in 11 of 81 subjects receiving rhGM-CSF, but in none of the controls (P = 0.035). Injections were well tolerated. A single i.m. or s.c. injection of 20-40 micrograms of rhGM-CSF significantly enhances antibody responses when given at the same site as recombinant hepatitis B vaccination.


Assuntos
Adjuvantes Imunológicos/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/imunologia , Vacinas Sintéticas/imunologia , Adolescente , Adulto , Fator Estimulador de Colônias de Granulócitos e Macrófagos/efeitos adversos , Humanos , Masculino , Proteínas Recombinantes
18.
Med Oncol ; 13(3): 141-7, 1996 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-9106172

RESUMO

The haematopoietic growth factor, GM-CSF, has well-documented stimulatory effects on monocyte and macrophage functions. These effects include enhanced proliferation on their progenitor cells, increased endocytosis and metabolism of mature cells, increased function as antigen-presenting cells, and increased inhibition or killing of intracellular fungi, bacteria, protozoa and viruses. The major effect of GM-CSF on monocytes and macrophages is to enhance phagocytic and metabolic functions, including increased synthesis of molecules toxic to microbes, and to release other proinflammatory cytokines. This results in inhibition and/or killing of Candida albicans, Aspergillus, Cryptococcus, Pneumocystis, Leishmania, Mycobacteria, as well as other intracellular pathogens. GM-CSF also enhances the intracellular effectiveness of antiviral and antibacterial drugs. Viral replication may be increased in activated cells, therefore, when GM-CSF is used, a combination with appropriate antiviral drugs is recommended. Several reports in patients of successful management of microbial diseases which depend on macrophage function are now reviewed. These reports support the clinical value of GM-CSF in the management of patients with cancer and chemotherapy related monocyte/macrophage dysfunction and presumed or documented microbial disease.


Assuntos
Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Macrófagos/fisiologia , Proteínas Recombinantes/farmacologia , Animais , Antibacterianos/farmacologia , Infecções Bacterianas/tratamento farmacológico , Doenças Transmissíveis/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/microbiologia , Macrófagos/parasitologia , Monócitos/efeitos dos fármacos , Monócitos/fisiologia , Micoses/tratamento farmacológico , Viroses/tratamento farmacológico
19.
Memory ; 4(2): 159-73, 1996 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8697035

RESUMO

Using a picture naming task, we compared the magnitude of repetition priming after one prior study episode (single test priming) versus multiple prior study presentations (multiple test priming). Pictures were repeated either one, two, or three times, and the interval between tests was either several minutes (blocked test) or one week (spaced test). Priming increased with additional prior presentations (beyond one) in the multiple test format. In addition, single test priming decreased within one hour after initial exposure, with little change from one hour to two weeks. Priming was unaffected by a simultaneous recognition task, suggesting that picture naming is an implicit task relatively immune from explicit memory contamination.


Assuntos
Memória , Prática Psicológica , Percepção Visual , Humanos , Rememoração Mental , Comportamento Verbal
20.
Clin Infect Dis ; 21(6): 1439-49, 1995 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-8749629

RESUMO

Vaccine adjuvants are expected to play an important role in enhancing the immunogenicity of existing and new-generation vaccines against infectious diseases. In particular, adjuvants should direct the immune response in the most appropriate manner--furthering, for example, an expanded B-cell response, a cytotoxic T-cell response, or a T-helper 1 or 2 subset response. While some noncytokine adjuvants have exerted potent effects, their modes of action are most likely mediated by cytokines. Several cytokines have already been shown to be efficient adjuvants in animal models and/or in clinical trials. The mechanisms of cytokine function must be better understood and the techniques for the use of cytokines improved if the full potential of these substances as vaccine adjuvants is to be realized. When used to best advantage, such adjuvants enhance the immunity induced by viral, bacterial, and parasitic vaccines and thereby promote efficient protection or even cure.


Assuntos
Adjuvantes Imunológicos/farmacologia , Controle de Doenças Transmissíveis , Citocinas/farmacologia , Vacinas/administração & dosagem , Animais , Ensaios Clínicos como Assunto , Humanos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA