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Therapeutic relationships within psychiatric settings are highlighted as important throughout the literature. However, research from the forensic inpatient perspective is limited. We address this gap by exploring the patient-staff relationships within forensic mental health inpatient services, from the patient's perspective. Thirty adult male forensic inpatients were interviewed about their experiences on the ward and their interactions with staff. Our analysis examines inpatients experiences of respectful and reciprocal relationships, relationships that empower, a disinterest in their patients' and authoritarian relationships. This study concludes by highlighting the need to prioritise the development of reciprocal relationships within forensic services.
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Transtornos Mentais , Serviços de Saúde Mental , Adulto , Medicina Legal , Humanos , Pacientes Internados , Masculino , Transtornos Mentais/terapia , Saúde MentalRESUMO
ABSTRACTSocially assistive robots have successfully been trialed in residential care facilities (RCFs) for older adults. These robots may have potential for younger adults (i.e. under 65 years old) who also live in RCFs. However, it is important to investigate staff acceptability and ease-of-use of these robots. This pilot study used the Technology Acceptance Model to investigate how staff working in a specialized RCF for younger adults accept Betty, a socially assistive robot who was introduced in the facility for 12 weeks. Twenty-four staff completed pre-questionnaires, reporting that they thought Betty would have the ability to engage and entertain the residents they cared for. While there were only eight staff who completed the post-questionnaires, there were significant improvements compared to the pre-questionnaire results in areas such as residents enjoying the contact and activities. Impacting on ease-of use were technical difficulties. Although this study had limitations and could be improved by a better response rate and investigating the residents' acceptability of Betty, this study is one of the first to report that this novel technology may have much potential for engaging adults in RCFs.
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Moradias Assistidas/organização & administração , Atitude do Pessoal de Saúde , Assistência de Longa Duração/métodos , Satisfação do Paciente , Robótica/métodos , Austrália , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Avaliação da Tecnologia BiomédicaRESUMO
BACKGROUND: Inequalities in survival from colorectal cancer (CRC) across socioeconomic groups and by area of residence have been described in various health care settings. Few population-wide datasets which include clinical and treatment information are available in Australia to investigate disparities. This study examines socio-demographic differences in survival for CRC patients in South Australia (SA), using a population-wide database derived via linkage of administrative and surveillance datasets. METHODS: The study population comprised all cases of CRC diagnosed in 2003-2008 among SA residents aged 50-79 yrs in the SA Central Cancer Registry. Measures of socioeconomic status (area level), geographical remoteness, clinical characteristics, comorbid conditions, treatments and outcomes were derived through record linkage of central cancer registry, hospital-based clinical registries, hospital separations, and radiotherapy services data sources. Socio-demographic disparities in CRC survival were examined using competing risk regression analysis. RESULTS: Four thousand six hundred and forty one eligible cases were followed for an average of 4.7 yrs, during which time 1525 died from CRC and 416 died from other causes. Results of competing risk regression indicated higher risk of CRC death with higher grade (HR high v low =2.25, 95% CI 1.32-3.84), later stage (HR C v A = 7.74, 95% CI 5.75-10.4), severe comorbidity (HR severe v none =1.21, 95% CI 1.02-1.44) and receiving radiotherapy (HR = 1.41, 95% CI 1.18-1.68). Patients from the most socioeconomically advantaged areas had significantly better outcomes than those from the least advantaged areas (HR =0.75, 95% 0.62-0.91). Patients residing in remote locations had significantly worse outcomes than metropolitan residents, though this was only evident for stages A-C (HR = 1.35, 95 % CI 1.01-1.80). These disparities were not explained by differences in stage at diagnosis between socioeconomic groups or area of residence. Nor were they explained by differences in patient factors, other tumour characteristics, comorbidity, or treatment modalities. CONCLUSIONS: Socio-economic and regional disparities in survival following CRC are evident in SA, despite having a universal health care system. Of particular concern is the poorer survival for patients from remote areas with potentially curable CRC. Reasons for these disparities require further exploration to identify factors that can be addressed to improve outcomes.
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Neoplasias Colorretais , Demografia , Intervalo Livre de Doença , Classe Social , Idoso , Neoplasias Colorretais/patologia , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Armazenamento e Recuperação da Informação , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Fatores Socioeconômicos , Austrália do SulRESUMO
One study is presented which explores the biasing effects of irrelevant contextual information on a fingerprint matching task. Bias was introduced by providing the outcomes of a DNA test relating to each fictitious case under consideration. This was engineered to suggest either a match, no match, or an inconclusive outcome, and was thus either consistent, misleading or unbiased depending on the ground truth of each fingerprint pair. The results suggested that, when the difficulty of the fingerprint matching task was measurably increased, participants became more vulnerable to the biasing information. Under such conditions, when performance was good, misleading evidence lowered accuracy, and when performance was weaker, consistent evidence improved accuracy. As such, the results confirmed existing demonstrations of cognitive bias from contextual information in the fingerprint task. Moreover, by taking a process-based approach, it became possible to articulate the concerns, and the potential solutions, at each stage of the workflow. The results offer value for the forensic science community in extending the evidence-base regarding cognitive bias, and in articulating routes to improve the credibility of fingerprint decisions.
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Viés , Impressões Digitais de DNA , Tomada de Decisões , Dermatoglifia , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The data accessible here represents the training tool used with novice students prior to an assessment of their performance in a fingerprint matching task (Stevenage and Pitfield, 2016; Stevenage and Bennett, in preparation) [1,2]. The training tool was compiled following semi-structured interviews with practicing fingerprint experts within the UK (Stevenage and Pitfield, 2016) [1], and has been verified as being a useful summary document by a subset of these experts. Also provided are the performance data of trained student participants on a fingerprint matching task. This was undertaken under biased and unbiased contextual conditions, and under control conditions in which no contextual information was provided. These resources are provided here to enable the interested reader to extend analysis in this area through studying the performance of non-naïve participants, and to complete a meta-analysis across relevant studies.
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This study examined male prisoners' experiences of participating in the Chromis programme, which aims to address violent behaviour in offenders with high levels of psychopathic traits. Four men who had completed Chromis and moved to new locations were purposefully sampled. This provided the opportunity for men to discuss their experiences after participating in the full programme and away from any influences of the treatment environment. Interview schedules were designed using interpretative phenomenological analysis (IPA). Interview transcripts were analysed independently by two researchers using IPA who then compared and contrasted findings to develop superordinate themes across the group. Four superordinate themes resulted. These were "It's me and what I want that matters," Reaping the rewards, "It's treatment itself that makes things hard," and Make or break external influences. Across the board, participants benefited at some level from Chromis. Participants' experiences highlighted useful information that can inform practice with individuals with high levels of psychopathy. The clinical implications are discussed.
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Transtorno da Personalidade Antissocial/terapia , Prisioneiros/psicologia , Avaliação de Programas e Projetos de Saúde , Psicoterapia/métodos , Adulto , Transtorno da Personalidade Antissocial/psicologia , Humanos , Entrevista Psicológica , Masculino , Reino UnidoRESUMO
AIM: To describe the disease and psychosocial outcomes of an inflammatory bowel disease (IBD) transition cohort and their perspectives. METHODS: Patients with IBD, aged > 18 years, who had moved from paediatric to adult care within 10 years were identified through IBD databases at three tertiary hospitals. Participants were surveyed regarding demographic and disease specific data and their perspectives on the transition process. Survey response data were compared to contemporaneously recorded information in paediatric service case notes. Data were compared to a similar age cohort who had never received paediatric IBD care and therefore who had not undergone a transition process. RESULTS: There were 81 returned surveys from 46 transition and 35 non-transition patients. No statistically significant differences were found in disease burden, disease outcomes or adult roles and responsibilities between cohorts. Despite a high prevalence of mood disturbance (35%), there was a very low usage (5%) of psychological services in both cohorts. In the transition cohort, knowledge of their transition plan was reported by only 25/46 patients and the majority (54%) felt they were not strongly prepared. A high rate (78%) of discussion about work/study plans was recorded prior to transition, but a near complete absence of discussion regarding sex (8%), and other adult issues was recorded. Both cohorts agreed that their preferred method of future transition practices (of the options offered) was a shared clinic appointment with all key stakeholders. CONCLUSION: Transition did not appear to adversely affect disease or psychosocial outcomes. Current transition care processes could be optimised, with better psychosocial preparation and agreed transition plans.
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Colite Ulcerativa/terapia , Doença de Crohn/terapia , Atenção à Saúde , Conhecimentos, Atitudes e Prática em Saúde , Pacientes/psicologia , Percepção , Transição para Assistência do Adulto , Adolescente , Adulto , Fatores Etários , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/psicologia , Comunicação , Doença de Crohn/diagnóstico , Doença de Crohn/psicologia , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Masculino , Participação do Paciente , Preferência do Paciente , Relações Médico-Paciente , Estudos Retrospectivos , Austrália do Sul , Centros de Atenção Terciária , Resultado do Tratamento , Adulto JovemRESUMO
The formerly named "Dangerous and Severe Personality Disorder" (DSPD) units are no longer standalone services within the criminal justice system in England and Wales. These sites now provide personality disorder treatment services in the high-security prison estate as part of the new national Offender Personality Disorder (OPD) Pathway Strategy. The OPD Pathway intends to take responsibility for the assessment, treatment, and management of offenders who are likely to have a personality disorder and who present a high risk of re-offending (men and women) and serious harm to others (men). Further PD treatment and progression services are being commissioned in lower security prisons and in the community as part of the new PD Strategy. While the suitability criteria for the two male high-security PD treatment sites are the same, the individual units have their own assessment and treatment methods. This article aims to communicate the referral, assessment, and treatment methods employed within the prison-based Westgate Personality Disorder Treatment Service, HMP Frankland.
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Internação Compulsória de Doente Mental/legislação & jurisprudência , Determinação da Personalidade , Transtornos da Personalidade/diagnóstico , Transtornos da Personalidade/terapia , Prisioneiros/psicologia , Encaminhamento e Consulta/legislação & jurisprudência , Comportamento Perigoso , Inglaterra , Feminino , Humanos , Masculino , Transtornos da Personalidade/psicologia , Recidiva , Medidas de Segurança/legislação & jurisprudência , Violência/legislação & jurisprudência , Violência/psicologia , País de GalesRESUMO
Adults (n = 25) completed online free text boxes about their self-harming behaviour. Thematic analysis identified three dominant themes: 'managing the private self', 'managing the public self' and 'moving on'. Transcending these themes was the notion of thresholds of change. Self-harm enables people to manage both their private and public selves. When thresholds of change are surpassed, the public self communicates a need for help. Self-harm exists within a precarious balance of well-being and can be a form of self-care. Help seeking is instigated when this balance is disrupted and continued if it offers a better form of self-management than the individual's own self-harming behaviour.
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Healthcare systems throughout the world continue to face emerging challenges associated with chronic disease management. Due to the likely increase in chronic conditions in the future it is now vital that cooperation and support between specialists, generalists and primary health care physicians is conducted. Inflammatory bowel disease (IBD) is one such chronic disease. Despite specialist care being essential, much IBD care could and probably should be delivered in primary care with continued collaboration between all stakeholders. Whilst most primary care physicians only have few patients currently affected by IBD in their caseload, the proportion of patients with IBD-related healthcare issues cared for in the primary care setting appears to be widespread. Data suggests however, that primary care physician's IBD knowledge and comfort in management is suboptimal. Current treatment guidelines for IBD are helpful but they are not designed for the primary care setting. Few non-expert IBD management tools or guidelines exist compared with those used for other chronic diseases such as asthma and scant data have been published regarding the usefulness of such tools including IBD action plans and associated supportive literature. The purpose of this review is to investigate what non-specialist tools, action plans or guidelines for IBD are published in readily searchable medical literature and compare these to those which exist for other chronic conditions.
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Doenças Inflamatórias Intestinais/terapia , Médicos de Atenção Primária , Atenção Primária à Saúde/métodos , Comportamento Cooperativo , Fidelidade a Diretrizes , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Comunicação Interdisciplinar , Equipe de Assistência ao Paciente , Médicos de Atenção Primária/normas , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Atenção Primária à Saúde/normas , Fatores de Tempo , Resultado do TratamentoRESUMO
RATIONALE, AIMS AND OBJECTIVES: Population level data on colorectal cancer (CRC) management in Australia are lacking. This study assessed broad level patterns of care and concordance with guidelines for CRC management at the population level using linked administrative data from both the private and public health sectors across South Australia. Disparities in CRC treatment were also explored. METHOD: Linking information from the South Australian Cancer Registry, hospital separations, radiotherapy services and hospital-based cancer registry systems provided data on the socio-demographic, clinical and treatment characteristics for 4641 CRC patients, aged 50-79 years, diagnosed from 2003 to 2008. Factors associated with receiving site/stage-specific treatments (surgery, chemotherapy and radiotherapy) and overall concordance with treatment guidelines were identified using Poisson regression analysis. RESULTS: About 83% of colon and 56% of rectal cancer patients received recommended treatment. Provision of neo-adjuvant/adjuvant therapies may be less than optimal. Radiotherapy was less likely among older patients (prevalence ratio 0.7, 95% confidence interval 0.5-0.8). Chemotherapy was less likely among older patients (0.7, 0.6-0.8), those with severe or multiple co-morbidities (0.8, 0.7-0.9), and those from rural areas (0.9, 0.8-1.0). Overall discordance with treatment guidelines was more likely among rectal cancer patients (3.0, 2.7-3.3), older patients (1.6, 1.4-1.8), those with multiple co-morbid conditions (1.3, 1.1-1.4), and those living in rural areas (1.2, 1.0-1.3). CONCLUSIONS: Greater emphasis should be given to ensure CRC patients who may benefit from neo-adjuvant/adjuvant therapies have access to these treatments.
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Neoplasias Colorretais/terapia , Padrões de Prática Médica , Idoso , Coleta de Dados , Feminino , Humanos , Masculino , Registro Médico Coordenado , Pessoa de Meia-Idade , Terapia Neoadjuvante , Distribuição de Poisson , Sistema de Registros , Austrália do SulRESUMO
OBJECTIVE: To describe the outcome of cats treated with gastrointestinal tract decontamination, IV fluid diuresis, or both after ingestion of plant material from lilies of the Lilium and Hemerocallis genera. Design-Retrospective case series. ANIMALS: 25 cats evaluated after ingestion of lily plants. PROCEDURES: Medical records of cats examined at the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania with known lily ingestion between July 2001 and April 2010 were reviewed. Inclusion in the study required evidence of lily plant ingestion within the preceding 48 hours. Type of lily ingested, time of ingestion, gastrointestinal tract decontamination procedures performed, and IV fluid diuresis were recorded. The presence or absence of acute kidney injury was determined by evaluating BUN concentration, creatinine concentration, and urine specific gravity. Outcome was defined as survival to discharge, death, or euthanasia. RESULTS: The time from ingestion until evaluation at the Matthew J. Ryan Veterinary Hospital of the University of Pennsylvania ranged from < 30 minutes to 48 hours. Nineteen cats received gastrointestinal tract decontamination (18 cats at our hospital and 1 cat by the referring veterinarian). Twenty-three cats were admitted to the hospital for IV fluid diuresis, supportive care, and monitoring. Seventeen of these 23 (74%) cats had normal BUN and creatinine concentrations throughout hospitalization. At the time of discharge from the hospital, 2 of the 23 (9%) hospitalized cats had an increased BUN concentration, creatinine concentration, or both. All 25 (100%) cats survived to discharge from the hospital. CONCLUSIONS AND CLINICAL RELEVANCE: In this series of cats treated with gastrointestinal tract decontamination, IV fluid diuresis, or both within 48 hours after lily ingestion, the outcome was good, with a low incidence of acute kidney injury. Future studies are needed to determine the most effective gastrointestinal tract decontamination procedures and optimal duration of IV fluid therapy.
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Doenças do Gato/induzido quimicamente , Hidratação/veterinária , Hemerocallis/intoxicação , Lilium/intoxicação , Plantas Tóxicas/toxicidade , Animais , Nitrogênio da Ureia Sanguínea , Doenças do Gato/terapia , Gatos , Diurese , Intoxicação por Plantas/veterinária , Estudos RetrospectivosRESUMO
Dysphagia lusoria is a term used to describe dysphagia secondary to vascular compression of the oesophagus. The various embryologic anomalies of the arterial brachial arch system often remain unrecognised and asymptomatic, but in 30%-40% of cases can result in tracheo-oesophageal symptoms, which in the majority of cases manifest as dysphagia. Diagnosis of dysphagia lusoria is via barium swallow and chest Computed tomography scan. Manometric abnormalities are variable, but age-related manometric changes may contribute to clinically relevant dysphagia lusoria in patients who present later in life. Our report describes a case of late-onset dysphagia secondary to a right aortic arch with an aberrant left subclavian artery, which represents a rare variant of dysphagia lusoria. The patient had proven additional oesophageal dysmotility with solid bolus only and a clinical response to dietary modification.
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Aneurisma/diagnóstico , Anormalidades Cardiovasculares/diagnóstico , Transtornos de Deglutição/diagnóstico , Doenças do Esôfago/diagnóstico , Artéria Subclávia/anormalidades , Idoso , Aneurisma/patologia , Anormalidades Cardiovasculares/patologia , Transtornos de Deglutição/patologia , Endoscopia , Esôfago/patologia , Fluoroscopia , Humanos , Masculino , Manometria , Pessoa de Meia-Idade , Fatores de Risco , Artéria Subclávia/patologia , Tomografia Computadorizada por Raios XRESUMO
In some species DNA vaccines elicit potent humoral and cellular immune responses. However, their performance in humans and non-human primates is less impressive. There are suggestions in the literature that an increase in the intercellular distribution of protein expressed from a DNA vaccine may enhance immunogenicity. We incorporated the Herpes Simplex Virus type 1 (HSV) VP22 gene, which encodes a protein that has been described as promoting intercellular spread, into a DNA vector in which it was fused to enhanced green fluorescent protein (EGFP). Following transfection of the plasmid DNA into mammalian cells, distribution of the fusion protein VP22-EGFP was not increased compared to EGFP alone. Furthermore, we found no evidence to suggest that VP22 was capable of mediating intercellular spread. However, when these constructs were used as DNA vaccines to immunise mice, antibody levels specific to EGFP were significantly enhanced when EGFP was fused to VP22. These data suggest that amplification of the immune response may occur via mechanisms other than VP22-mediated intercellular spread of antigen.
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Adjuvantes Imunológicos , Vacinas de DNA/imunologia , Proteínas Estruturais Virais/farmacologia , Animais , Formação de Anticorpos/efeitos dos fármacos , Western Blotting , Células COS , Chlorocebus aethiops , Proteínas de Fluorescência Verde/imunologia , Metanol , Camundongos , Camundongos Endogâmicos BALB C , Plasmídeos/imunologia , Fixação de Tecidos , Transfecção , Proteínas Virais de Fusão/farmacologiaRESUMO
A DNA vaccine was constructed which expressed the binding domain of Clostridium botulinum neurotoxin serotype F fused to a signal peptide. Three intra-muscular doses fully protected Balb/c mice against 10(4) MLD of serotype F toxin. Priming of the immune response by DNA vaccination followed by a single booster with type F binding domain protein resulted in high levels of antibody against the binding domain. This study demonstrates the utility of DNA vaccination for protection against botulinum neurotoxin type F and indicates that a prime-boost regimen could be an efficient method of generating antibody for passive immune therapy in cases of botulism involving serotype F toxin.
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Toxinas Botulínicas/imunologia , Toxinas Botulínicas/toxicidade , Vacinas de DNA/imunologia , Animais , Anticorpos Antibacterianos/biossíntese , Células COS , Chlorocebus aethiops , Ensaio de Imunoadsorção Enzimática , Feminino , Imunofluorescência , Imunoglobulina G/biossíntese , Imunoglobulina G/imunologia , Imunoglobulinas/biossíntese , Imunoglobulinas/imunologia , Injeções Intramusculares , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Confocal , Plasmídeos/genética , Análise de Sobrevida , Vacinação , Vacinas de DNA/biossínteseRESUMO
Venezuelan equine encephalitis virus (VEEV) replicates in lymphoid tissues following peripheral inoculation and a high titre viraemia develops. Encephalitis develops after the virus enters the central nervous system from the blood, with the earliest neuronal involvement being via the olfactory nerve. Following aerosol challenge with virulent VEEV, the virus is thought to replicate in the nasal mucosa and there could be direct entry into the olfactory nerve via infected neuroepithelial cells. Protection from VEEV infection is believed to be primarily mediated by virus specific antibody. The correlation between protection and neutralising serum antibody titres is, however, inconsistent when the virulent virus is administered by the airborne route. This study demonstrates a link between antibody in serum and the nasal mucosa and protection by means of passive immunisation studies. Intra-nasal administration of antibody increased protection against airborne virus in Balb/c mice. Vaccination of mu MT strain mice that do not have functional B cells and cannot produce antibody revealed normal proliferation of spleen cells in vitro and robust cytokine production. Aerosol challenge of mu MT mice demonstrated that complete protection was only achieved when passive immunisation with antibody was supplemented with active immunisation with the TC-83 vaccine strain of the virus. This implies that cell-mediated immune functions are required for protection against airborne challenge with virulent VEEV.
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Anticorpos Antivirais/sangue , Vírus da Encefalite Equina Venezuelana/patogenicidade , Encefalomielite Equina Venezuelana/imunologia , Encefalomielite Equina Venezuelana/prevenção & controle , Mucosa Nasal/imunologia , Administração Intranasal , Animais , Anticorpos Antivirais/imunologia , Especificidade de Anticorpos , Linhagem Celular , Vírus da Encefalite Equina Venezuelana/imunologia , Encefalomielite Equina Venezuelana/virologia , Imunidade Celular , Imunidade nas Mucosas , Imunização Passiva , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Baço/citologia , Vacinas Atenuadas/administração & dosagem , Vacinas Atenuadas/imunologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologiaRESUMO
Simian herpes B virus (SHBV) is the herpes simplex virus (HSV) homologue for the species MACACA: Unlike in its natural host, and unlike other animal herpesviruses, SHBV causes high mortality in accidentally infected humans. SHBV-infected cells, like those infected with HSV-1 and equine herpesvirus types 1 and 4, express complement C3 receptor activity. To study immunoregulatory functions involved in susceptibility/resistance against interspecies transmission, the SHBV glycoprotein C (gC(SHBV)) gene (encoding 467 aa) was isolated. Sequence analysis revealed amino acid identity with gC proteins from HSV-2 (46.9 %), HSV-1 (44.5 %) and pseudorabies virus (21.2 %). Highly conserved cysteine residues were also noted. Similar to gC(HSV-2), gC(SHBV) is less glycosylated than gC(HSV-1), resulting in a molecular mass of 65 kDa if expressed in replication-deficient vaccinia virus Ankara. Stable transfectants expressing full-length gC(SHBV) on the cell surface induced C3 receptor activity and were substantially protected from complement-mediated lysis; no protection was observed with control constructs. This suggests that expression of the gC homologues on infected cell surfaces might also contribute to the survival of infected cells in addition to decreased virion inactivation. Interestingly, soluble gC(SHBV) isolated from protein-free culture supernatants did not interfere with the binding of the alternative complement pathway activator properdin to C3b, which is similar to our findings with gC(HSV-2) and could be attributed to major differences in the amino-terminal portion of the protein with extended deletions in both gC(SHBV) and gC(HSV-2). Binding of recombinant gC(SHBV) to polysulphates was observed. This, together with the heparin-sensitivity of the gC(SHBV)-C3 interaction on the infected cell surface, suggests a role in adherence to heparan sulphate, similar to the gC proteins of other herpesviruses.
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Clonagem Molecular , Complemento C3b/imunologia , Herpesvirus Cercopitecino 1/patogenicidade , Receptores de Complemento 3b/metabolismo , Proteínas do Envelope Viral/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Via Alternativa do Complemento/imunologia , Citotoxicidade Imunológica , Humanos , Dados de Sequência Molecular , Receptores de Complemento 3b/química , Receptores de Complemento 3b/genética , Análise de Sequência de DNA , Transfecção , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genéticaRESUMO
An approach to enhancing the stability of eukaryotic expression plasmids for delivery using attenuated Salmonella has been evaluated. The expression apparatus and beta-galactosidase gene from the expression plasmid, pCMVbeta, was cloned into the low copy number plasmid pLG339. The resulting construct, pLGbetaGAL, was shown to have a lower copy number than pCMVbeta in Salmonella enterica var Typhimurium aroA strain SL7207. Furthermore, beta-galactosidase-specific antibody was induced in mice following intramuscular inoculation with pLGbetaGAL as naked DNA. Following oral administration of mice with SL7207/pCMVbeta, recombinants could not be detected in tissues 3 days after inoculation. In comparison, SL7207/pLGbetaGAL recombinant bacteria could be detected in the Peyer's patches and spleens indicating that the Salmonella strain was stable. However, both SL7207/pCMVbeta and SL7207/pLGbetaGAL failed to induce beta-galactosidase-specific IgG in vivo. The mechanism by which attenuated Salmonella are able to release heterologous DNA for antigen processing and presentation is not yet understood. These results suggest that the mechanism needs to be further elucidated in order to rationally improve the system.
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Células Eucarióticas , Plasmídeos , Salmonella typhimurium/genética , Vacinas de DNA , beta-Galactosidase/metabolismo , Animais , Feminino , Dosagem de Genes , Vetores Genéticos , Humanos , Imunização , Imunoglobulina G/sangue , Camundongos , Camundongos Endogâmicos BALB C , Salmonella typhimurium/metabolismo , Salmonella typhimurium/patogenicidade , Vacinas Atenuadas , beta-Galactosidase/genética , beta-Galactosidase/imunologiaRESUMO
It is desirable to prevent dissemination of B virus (BV) in macaque colonies because transmission of BV to humans causes deadly encephalomyelitis. Vaccination of monkeys is one method that could confine spread of BV within macaque colonies. Availability of a BV DNA vaccine for use in macaques would eliminate the risk of working with infectious BV. Toward this end, we constructed a plasmid expressing the BV glycoprotein D (gD). Immunogenicity of this construct as a DNA vaccine was assessed in adult Japanese macaques by four intracutaneous injections at a dose of 500 microg per head. Results of enzyme-linked immunosorbent assay (ELISA) using a recombinant herpes simplex virus type 1 (HSV1) gD, a homologue of BV gD, showed that significant levels of antibody was induced in all vaccinated animals following each booster injection. Western blot of sera from vaccinated macaques confirmed the specific recognition of authentic BV gD. Immune sera were also demonstrated to contain neutralizing activity against infectious BV. Weak lymphoproliferative responses were also observed in vaccinated macaques using recombinant HSV1 gD as a stimulating antigen and flow cytometry analysis of one individual revealed the presence of HSV1 gD-responsive effector T cells. Thus, the BV gD DNA vaccine was demonstrated to induce both humoral and cellular immune responses in macaques which recognized BV gD.
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Anticorpos Antivirais/biossíntese , Herpesvirus Cercopitecino 1/imunologia , Imunidade Celular , Vacinas de DNA/imunologia , Proteínas do Envelope Viral/imunologia , Vacinas Virais/imunologia , Animais , Anticorpos Antivirais/imunologia , Sequência de Bases , Western Blotting , Primers do DNA , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Macaca , Testes de Neutralização , Reação em Cadeia da Polimerase , Proteínas do Envelope Viral/genéticaRESUMO
Human adenovirus 4 (HAdV-4), the only serotype of the species HAdV-E to be isolated from man, was first identified by its association with outbreaks of acute respiratory disease in military recruits. To combat such outbreaks, a live, oral HAdV-4 vaccine that is delivered via an enteric-coated capsule was developed. This vaccine has been used for nearly 40 years and has been shown to be safe and efficacious. In this study, the complete DNA sequence (35 994 bp) of the vaccine strain is described and its genetic content is analysed. Phylogenetic comparisons confirmed that the closest sequenced relative of HAdV-4 is another serotype of HAdV-E that infects chimpanzees (SAdV-25) and that the great majority of genes in HAdV-E are related most closely to HAdV-B genes. By using the sequence data, a system was constructed to facilitate production of replication-competent HAdV-4 recombinants.