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1.
Int J Med Sci ; 15(5): 475-483, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29559836

RESUMO

AIMS: SjÓ§gren Syndrome is a disorder involving oral tissues, with xerostomia, dysgeusia, dysphagia, tooth decay, gingivitis, angular cheilitis and glossitis. Temporomandibular disorders are a generic term referred to clinical conditions involving the jaw muscles and temporomandibular joint. The aim of this study was to investigate the prevalence of oral manifestations and temporomandibular disorders (TMD) in SjÓ§gren Syndrome (SS) patients compared with healthy people. METHODS: The study group included 72 SS patients (2 men, 70 women) diagnosed according to the American-European Consensus Group (AECG) Criteria. A randomly selected group of 72 patients, matched by sex and age, served as control group. The examination for TMD signs and symptoms was based on the standardized Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) through a questionnaire and clinical examination. RESULTS: SS patients complained more frequently (95.8%) of oral symptoms (xerostomia, dysgeusia, dysphagia) than controls (22.2%) (χ2= 80.66 p< 0.001). TMD symptoms (muscle pain on chewing, difficulty in mouth opening, arthralgia, headaches, tinnitus) were complained by 91.7% of SS patients and by 84.7% of controls (χ2= 1,667 p= 0,196). At the clinical examination, 91,7% of SS had at least one oral sign respect to 75 % of controls. The salivary flow measurements showed high statistical significance between the two groups (Unpaired test, p< 0,0001). Myofascial pain (caused by muscular contracture) was significantly higher in the study group than in the control one (p≤ 0,05). Furthermore 18,05% of SS patients showed deflection versus 5,5% of controls (χ2=5,402 p=0,020). CONCLUSIONS: SjÓ§gren's Syndrome seems to play a role in temporomandibular joint disorders.


Assuntos
Arcada Osseodentária/fisiopatologia , Músculo Esquelético/fisiopatologia , Síndrome de Sjogren/fisiopatologia , Transtornos da Articulação Temporomandibular/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/fisiopatologia , Disgeusia/etiologia , Disgeusia/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite/fisiopatologia , Síndrome de Sjogren/complicações , Inquéritos e Questionários , Articulação Temporomandibular/fisiopatologia , Transtornos da Articulação Temporomandibular/etiologia , Xerostomia/etiologia , Xerostomia/fisiopatologia
2.
Mediators Inflamm ; 2018: 2453265, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30405318

RESUMO

Rheumatoid arthritis (RA) patients are at high risk of cardiovascular (CV) events, and the chronic inflammatory state may generate quantitative and qualitative changes in lipoprotein fractions. The anti-IL-6 receptor tocilizumab (TCZ), even if effective in inflammation and joint damage prevention, determined significant alterations to RA patients' lipid levels in randomized controlled trials, but real-world data are lacking. We evaluated the changes in lipid fraction levels and disease activity in a longitudinal cohort of RA patients on long-term treatment with tocilizumab (TCZ) in a community setting. We retrospectively selected 40 naïve-biologic RA patients on treatment with intravenous TCZ compared to 20 RA patients on methotrexate treatment as the control group. Total cholesterol (Tot-Chol), low-density lipoproteins (LDL), high-density lipoprotein (HDL), and triglyceride (TG) levels were measured at the baseline and at 12, 24, and 52 weeks thereafter. At the same points, 28-joint disease activity score (DAS28), clinical disease activity index (CDAI), and EULAR clinical responses were also assessed. During the first 24 weeks, we observed in TCZ-treated patients a progressive statistically significant (p < 0.001) increase in Tot-Chol, LDL, HDL, and TG, which returned close to the baseline at 52 weeks. But no changes in the lipid-related CV risk indices Tot-Chol/HDL and LDL/HDL ratios and the atherogenic index (log10 TG/HDL) were detectable. Notably, we observed a statistically significant negative correlation between changes in lipid fractions and DAS28 or CDAI. The prolonged treatment with TCZ was associated to a transient increase in cholesterol's fractions during the first 6 months of treatment, with inverse correlation to disease activity, but with no impact on surrogate lipid indices of atherogenic risk. These findings may aid clinicians in interpreting the RA patient's lipid profile in daily clinical practice.


Assuntos
Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/efeitos adversos , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Aterosclerose/induzido quimicamente , Lipídeos/sangue , Adulto , Idoso , Colesterol/sangue , Feminino , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipoproteínas LDL/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
3.
Rev Med Suisse ; 13(563): 1049-1051, 2017 May 17.
Artigo em Francês | MEDLINE | ID: mdl-28636297

RESUMO

With the increased incidence of cancers due to an aging population, and a prolonged survival thanks to advances in cancer treatments, new therapeutic challenges have arisen. The management of symptoms, the tolerance of increasingly effective oncologic treatments and, finally, quality of life are central concerns of patients and their loved ones. Supportive care in oncology has helped meet these challenges, offering a holistic approach, encompassing somatic, psychiatric and social aid. Inaugurated in 2005, the oncologic supportive care unit of the Geneva University Hospitals allows many cancer patients access to a team of multidisciplinary care-givers to help meet their needs.


Avec le vieillissement de la population à l'origine d'une augmentation de l'incidence des cancers et face aux progrès thérapeutiques qui permettent aux patients atteints de vivre plus longtemps, surgissent de nouveaux défis de prise en charge. La gestion des symptômes, la tolérance aux traitements oncologiques de plus en plus nombreux et efficaces, et finalement la qualité de vie sont au centre des préoccupations des patients et de leurs proches. Les soins de support en oncologie permettent de répondre à ces attentes en proposant une prise en charge globale, aussi bien somatique que psychique et sociale. Inaugurée en 2005, l'unité hospitalière des soins de support en oncologie des HUG permet à de nombreux patients, atteints de cancer, d'avoir accès à une équipe multidisciplinaire de soignants afin de répondre à ces objectifs.


Assuntos
Oncologia/métodos , Neoplasias/terapia , Cuidados Paliativos/métodos , Humanos , Oncologia/organização & administração , Equipe de Assistência ao Paciente/organização & administração , Satisfação do Paciente , Qualidade da Assistência à Saúde , Qualidade de Vida
4.
Rev Med Suisse ; 13(566): 1207-1211, 2017 Jun 07.
Artigo em Francês | MEDLINE | ID: mdl-28640567

RESUMO

Nausea is a common symptom among patients affected by chronic diseases or undergoing various treatments. Because nausea can result from many origins, there is a large differential diagnosis to explore. Its pathophysiology relies on numerous neurotransmitters, on which 5 types of antiemetic antagonists are effective (NK-1 receptor antagonists, antiserotoninergic, antidopaminergic, antihistaminic and anticholinergic agents). Glucocorticoids and benzodiazepines are also used to treat some types of nausea. Choosing the appropriate antiemetic can improve quality of life and treatment compliance.


Les nausées sont un symptôme retrouvé fréquemment en consultation chez les patients atteints de maladies chroniques et/ou traités par certains médicaments. L'absence de spécificité des nausées doit faire ouvrir un large diagnostic différentiel à explorer. Le mécanisme physiopathologique fait intervenir de nombreux neurotransmetteurs, que 5 familles d'antiémétiques antagonisent (antisérotoninergiques, antidopaminergiques, antagonistes du récepteur NK-1, antihistaminiques, anticholinergiques). Les glucocorticoïdes et les benzodiazépines sont également utilisés pour traiter certains types de nausées. Le choix du traitement le plus adéquat amène une amélioration de la qualité de vie et une meilleure compliance thérapeutique.


Assuntos
Antieméticos/uso terapêutico , Náusea/tratamento farmacológico , Padrões de Prática Médica , Antieméticos/farmacologia , Benzodiazepinas/uso terapêutico , Diagnóstico Diferencial , Clínicos Gerais , Glucocorticoides/uso terapêutico , Humanos , Adesão à Medicação , Náusea/etiologia , Náusea/fisiopatologia , Qualidade de Vida
5.
Community Ment Health J ; 52(3): 361-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26081981

RESUMO

This study explored views of 566 Italian psychology students about schizophrenia. The most frequently cited causes were psychological traumas (68 %) and heredity (54 %). Thirty-three percent of students firmly believed that people with the condition could recover. Reporting heredity among the causes, and identifying schizophrenia were both associated with prognostic pessimism, greater confidence in pharmacological treatments and lower confidence in psychological treatments. Schizophrenia labeling was also associated with higher perception of unpredictability and dangerousness. Compared to first year students, fourth/fifth year students more frequently reported heredity among the causes, and were more pessimistic about schizophrenia recovery. Stigma topics should be included in future psychologists' education.


Assuntos
Atitude Frente a Saúde , Psicologia/educação , Esquizofrenia , Psicologia do Esquizofrênico , Estigma Social , Estereotipagem , Estudantes/psicologia , Adulto , Estudos Transversais , Feminino , Humanos , Itália , Masculino , Esquizofrenia/diagnóstico , Esquizofrenia/etiologia , Esquizofrenia/terapia , Adulto Jovem
6.
Drug Dev Res ; 75 Suppl 1: S77-80, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25381986

RESUMO

Patients with active rheumatoid arthritis (RA) frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Inflammatory cytokines, and particularly tumor necrosis factor-alpha (TNF-α), are implicated in the pathogenesis of both atherosclerosis and RA, and also involved in the development of the impaired lipid profile detected in active RA. Although anti-TNF-α agents have been proven effective in controlling joint damage and systemic inflammation, controversy remains about the effect of these drugs on the lipid profile; therefore, the aim of our study was to investigate the effect of anti-TNF-α treatment, in combination with disease-modifying anti-rheumatic drugs (DMARDs) and corticosteroid therapy, on the lipid profile of patients with active RA. Our data suggest that the combination anti-TNF-α/DMARDs/steroids do not significantly interfere with the lipid profile of RA patients. However, analysis of clinical response data showed that patients achieving low disease activity or remission seem to have a protective lipid profile, suggesting that better control of inflammation and disease activity can affect lipid metabolism. The available evidence indicates that high inflammation interferes with lipid metabolism, whereas good control of the chronic inflammatory state may positively influence the lipid profile and cardiovascular risk. Low cholesterol levels at baseline could predict a favorable outcome with anti-TNF-α treatment, but these data need to be confirmed by large prospective studies with long-term follow-up.


Assuntos
Corticosteroides/farmacologia , Antirreumáticos/farmacologia , Artrite Reumatoide/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab , Corticosteroides/uso terapêutico , Adulto , Idoso , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados/farmacologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Aspirina/farmacologia , Aspirina/uso terapêutico , Certolizumab Pegol , Colesterol/sangue , Ciclosporina/farmacologia , Ciclosporina/uso terapêutico , Quimioterapia Combinada , Etanercepte , Feminino , Humanos , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Fragmentos Fab das Imunoglobulinas/farmacologia , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Imunoglobulina G/farmacologia , Imunoglobulina G/uso terapêutico , Infliximab , Masculino , Metotrexato/farmacologia , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Polietilenoglicóis/farmacologia , Polietilenoglicóis/uso terapêutico , Receptores do Fator de Necrose Tumoral/uso terapêutico , Índice de Gravidade de Doença , Sulfassalazina/farmacologia , Sulfassalazina/uso terapêutico , Resultado do Tratamento , Triglicerídeos/sangue
7.
Child Abuse Negl ; 153: 106801, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38677176

RESUMO

BACKGROUND: In the wake of historical sexual abuse across the Catholic Church globally, the Church continues to develop policies and processes to prevent and respond to child sexual abuse, including supporting the skills, knowledge, and confidence of members of the Church. OBJECTIVE: We investigated the safeguarding capabilities of a range of people with different roles within Catholic Church ministries in various countries. PARTICIPANTS AND SETTING: Our 184 participants included lay people, religious men and women, school staff, safeguarding officers and tertiary students associated with the Catholic Church. Data were collected across seven different countries. METHODS: We measured the awareness, confidence, attitudes, and knowledge of participants and examined differences between participants in different roles within the Church and different countries through General Linear Models. RESULTS: We found varying levels of awareness, confidence, attitudes, and knowledge regarding sexual abuse prevention and safeguarding. We pinpointed the significant differences in three of these domains (confidence, attitudes, and knowledge) both between people with different roles in the church worldwide, but also between the countries from which participants came from. CONCLUSIONS: We found that people in various countries and roles within the Church are at different stages of their safeguarding journey. Some are still understanding their roles (attitudes), some are still learning about how it is operationalised (awareness), and others are acquiring skills that will prepare them for enacting safeguarding policies and practices (confidence).


Assuntos
Catolicismo , Abuso Sexual na Infância , Humanos , Masculino , Feminino , Adulto , Abuso Sexual na Infância/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Criança , Adulto Jovem , Pessoa de Meia-Idade
8.
Antimicrob Agents Chemother ; 56(3): 1599-601, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22183174

RESUMO

In cystic fibrosis patients, chronic lung infection with Pseudomonas aeruginosa and the associated decline in lung function are the major cause of mortality. In this report, we show that pyocin S2 displays potent activity against P. aeruginosa biofilms, thus representing a potentially improved therapeutic option. Using an invertebrate model of P. aeruginosa infection, we also show that pyocin S2 is highly active in vivo.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Mariposas/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Piocinas/farmacologia , Escarro/microbiologia , Animais , Aztreonam/farmacologia , Biofilmes/crescimento & desenvolvimento , Criança , Fibrose Cística/microbiologia , Humanos , Larva/efeitos dos fármacos , Larva/microbiologia , Larva/fisiologia , Pulmão/microbiologia , Microscopia Eletrônica de Varredura , Mariposas/microbiologia , Mariposas/fisiologia , Pseudomonas aeruginosa/isolamento & purificação , Pseudomonas aeruginosa/fisiologia , Tobramicina/farmacologia
9.
Rev Med Suisse ; 7(317): 2252-6, 2011 Nov 16.
Artigo em Francês | MEDLINE | ID: mdl-22400355

RESUMO

Progresses in cancer treatment transformed cancer into a chronic disease associated with growing nutritional problems. Poor nutritional status of cancer patients worsens morbidity, mortality, overall cost of care and decreases patients' quality of life, oncologic treatments tolerance and efficacy. These adverse effects lead to treatment modifications or interruptions, reducing the chances to control or cure cancer. Implementation of an interdisciplinary and longitudinal integration of nutritional care and nutritional information into cancer treatment (The OncoNut Program) could prevent or treat poor nutritional status and its adversely side effects.


Assuntos
Prestação Integrada de Cuidados de Saúde , Neoplasias/terapia , Terapia Nutricional/métodos , Melhoria de Qualidade , Protocolos Antineoplásicos/normas , Caquexia/etiologia , Caquexia/terapia , Prestação Integrada de Cuidados de Saúde/métodos , Prestação Integrada de Cuidados de Saúde/organização & administração , Educação Médica Continuada , Necessidades e Demandas de Serviços de Saúde/organização & administração , Humanos , Modelos Biológicos , Neoplasias/complicações , Neoplasias/dietoterapia , Terapia Nutricional/normas , Terapia Nutricional/estatística & dados numéricos , Estado Nutricional/fisiologia , Educação de Pacientes como Assunto
10.
Can J Cardiol ; 34(1): 92.e1-92.e3, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29275889

RESUMO

The ever-increasing use of immune checkpoint inhibitors in cancer is leading to a high incidence of autoimmune side effects. This report discusses an autoimmune fulminant myocarditis in an elderly patient with metastatic pulmonary adenocarcinoma in whom the most advanced invasive heart failure therapies were used successfully. She was treated with nivolumab. This case illustrates a severe cardiovascular complication of immunotherapy and highlights to cardiologists the importance of aggressive treatments in patients with metastatic cancers whose prognosis has improved dramatically.


Assuntos
Antineoplásicos/efeitos adversos , Miocardite/etiologia , Nivolumabe/efeitos adversos , Adenocarcinoma de Pulmão/tratamento farmacológico , Idoso , Antineoplásicos/administração & dosagem , Edema/etiologia , Feminino , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/imunologia , Humanos , Miocardite/imunologia , Peptídeo Natriurético Encefálico/sangue , Nivolumabe/administração & dosagem , Fragmentos de Peptídeos/sangue , Choque Cardiogênico/etiologia , Choque Cardiogênico/imunologia , Troponina/sangue
11.
Am J Orthopsychiatry ; 86(3): 253-64, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26963178

RESUMO

Despite scientific evidence that the majority of people with schizophrenia (PWS) have personal histories of traumatic life events and adversities, their needs for psychological support often remain unmet. Poor availability of nonpharmacological therapies in schizophrenia may be partly because of professionals' attitudes toward people diagnosed with this disorder. As future health professionals, psychology students represent a target population for efforts to increase the probability that PWS will be offered effective psychological therapies. This quasi-randomized controlled study investigated the effect of an educational intervention, addressing common prejudices via scientific evidence and prerecorded audio-testimony from PWS, on the attitudes of psychology students toward PWS. Students in their fifth year of a master's degree in Psychology at the Second University of Naples, Italy were randomly assigned to an experimental group-which attended two 3-hr sessions a week apart-or to a control group. Compared with their baseline assessment, at 1-month reassessment the 76 educated students endorsed more psychosocial causes and more of them recommended psychologists in the treatment of schizophrenia. They were also more optimistic about recovery, less convinced that PWS are recognizable and unpredictable, and more convinced that treatments, pharmacological and psychological, are useful. No significant changes were found, from baseline to 1-month reassessment, in the 112 controls. At 1-month reassessment, educated students were more optimistic about recovery and less convinced that PWS are unpredictable than controls. These findings suggest that psychology students' attitudes toward PWS can be improved by training initiatives including education and indirect contact with users. (PsycINFO Database Record


Assuntos
Atitude do Pessoal de Saúde , Psicologia/educação , Esquizofrenia , Psicologia do Esquizofrênico , Estudantes/psicologia , Adulto , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Necessidades e Demandas de Serviços de Saúde , Humanos , Itália , Masculino , Preconceito/psicologia , Inquéritos e Questionários
12.
CNS Oncol ; 4(6): 387-92, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26497655

RESUMO

Hemangioblastoma is a rare benign neoplasm, accounting for less than 2% of all primitive brain tumors. It may arise sporadically in a solitary form, or associated with Von Hippel-Lindau (VHL) disease with multiple tumors. Surgery is the mainstay treatment, but management is challenging in case of recurrent and/or multiple tumors. VHL protein is defective in both forms of hemangioblastoma, leading to the accumulation of hypoxia-inducible factor, stimulating angiogenesis via VEGF and PDGF mainly. Here, we report a 37-year-old woman's case with recurrent and rapidly progressive VHL-associated hemangioblastomas, causing severe disability. She was treated 24 months with pazopanib, a multityrosine kinase inhibitor (TKI) targeting VEGF and PDGF-ß pathways. Despite moderate radiological changes, progressive improvement in her clinical condition persisting over 3 years was observed. Inhibiting angiogenesis is a therapeutic option that may improve the quality of life and the autonomy of VHL patients disabled with multiple hemangioblastomas.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Hemangioblastoma/tratamento farmacológico , Pirimidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Doença de von Hippel-Lindau/tratamento farmacológico , Adulto , Neoplasias Encefálicas/complicações , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/fisiopatologia , Vértebras Cervicais , Feminino , Seguimentos , Hemangioblastoma/complicações , Hemangioblastoma/patologia , Hemangioblastoma/fisiopatologia , Humanos , Indazóis , Imageamento por Ressonância Magnética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/fisiopatologia , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/patologia , Doença de von Hippel-Lindau/fisiopatologia
13.
Liver Int ; 25(2): 389-402, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15780065

RESUMO

BACKGROUND: Liver cell lines closely resembling primary hepatocyte are essential for research on hepatitis viruses and hepatocyte function. Currently used cell lines are derived from hepatic tumours and have altered gene expression. AIMS: The generation and characterisation of novel human hepatocyte lines (HHLs) derived from healthy human liver, retaining the primary hepatocyte phenotype. RESULTS: Primary hepatocytes were immortalised with Moloney's mouse leukaemia virus expressing E6 and E7 proteins of human papillomavirus, and cultures propagated long-term. All HHLs contained markers of hepatocyte and biliary phenotype (cytokeratins 7, 8, 18 and 19), Cytochrome P450 and albumin. The HHLs did not express high levels of p53 or alpha-fetoprotein. When grown in a collagen sandwich culture, or at the air-liquid interface, HHLs were maintained as monolayer whereas Huh-7 and HepG2 formed thick layers. All HHLs showed increased capacity to bind recombinant hepatitis C virus-like particles in comparison with Huh-7 and HepG2. We also demonstrate that HHLs contained active gap junctions, and that the cells respond to stimulation with IFN-alpha by upregulation of major histocompatibility complex (MHC)-I and -II. CONCLUSIONS: These HHLs retain primary hepatocyte phenotype and should be useful for investigating mechanisms of entry and replication of hepatotropic viruses, and should also be valuable in the study of hepatocyte biology and pathology.


Assuntos
Comunicação Celular/imunologia , Hepatócitos/citologia , Hepatócitos/imunologia , Interferon gama/farmacologia , Sítios de Ligação , Comunicação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Feminino , Citometria de Fluxo , Técnica Indireta de Fluorescência para Anticorpo , Junções Comunicantes , Hepatócitos/efeitos dos fármacos , Humanos , Masculino , Valores de Referência , Estudos de Amostragem , Sensibilidade e Especificidade
14.
J Gen Virol ; 83(Pt 7): 1601-1612, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12075078

RESUMO

The human cytomegalovirus (HCMV) tegument phosphoprotein pp71 activates viral immediate early (IE) transcription and thus has a role in initiating lytic infection. Protein pp71 stimulates expression from a range of promoters in a sequence-independent manner, and in this respect behaves similarly to the herpes simplex virus type 1 (HSV-1) IE protein ICP0. The intracellular localization of pp71 was investigated after its expression from transfected plasmids or from HSV-1 mutants constructed to produce pp71 transiently. The protein colocalized with the cell promyelocytic leukaemia (PML) protein at nuclear domain 10 (ND10) structures but, unlike ICP0, pp71 did not induce disruption of ND10. The activity of pp71 in mouse sensory neurons in vivo was investigated after co-inoculation of animals with pairs of HSV-1 mutants, one expressing pp71 and the second containing the E. coli lacZ gene controlled by various promoters. In this system, pp71 stimulated beta-galactosidase expression from a range of viral IE promoters when mice were analysed at 4 days postinoculation. At later times, expression of pp71 resulted in a reduction in numbers of neurons containing beta-galactosidase, indicating cytotoxicity or promoter shutoff. The HSV-1 latency-active promoter was not responsive to pp71, demonstrating specificity in the activity of the protein. Pp71 was as active in mice lacking both copies of the PML gene (PML-/-) as in control animals, and in PML-/- fibroblasts pp71 stimulated gene expression as effectively as in other cell types. Therefore, neither the PML protein nor the normal ND10 structure is necessary for pp71 to stimulate gene expression.


Assuntos
Citomegalovirus/metabolismo , Regulação Viral da Expressão Gênica , Proteínas Nucleares , Proteínas Virais/metabolismo , Animais , Núcleo Celular/metabolismo , Chlorocebus aethiops , Citomegalovirus/química , Feminino , Genes Precoces , Vetores Genéticos , Herpesvirus Humano 1/genética , Humanos , Óperon Lac , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteínas de Neoplasias/deficiência , Proteínas de Neoplasias/genética , Neurônios/metabolismo , Plasmídeos , Proteína da Leucemia Promielocítica , Fatores de Transcrição/deficiência , Fatores de Transcrição/genética , Transcrição Gênica , Proteínas Supressoras de Tumor , Células Vero/metabolismo , Proteínas Virais/análise , beta-Galactosidase/metabolismo
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