Biomedical subjects

Jonathan O Rayner

Publications and source records attributed to Jonathan O Rayner.

3 recordsLinked to original sources

PubMed2006

Uncommon respiratory pathogens.

PURPOSE OF REVIEW: In many cases, the specific pathogen responsible for a respiratory infection is not identified and can lead to improper medical treatment, increased duration of illness, and possibly contributes to the development of antibiotic resistance. Molecular-based diagnostic methodologies have significantly improved our ability to identify common respiratory pathogens; these techniques are not useful, however, when a novel pathogen is responsible for the infection and clinicians must rely on differential diagnosis for the treatment of patients. RECENT FINDINGS: New pathogens previously not associated with human infections have been identified in the past few years. In addition, new strains of bacteria and viruses have emerged as the causative agents of pneumonia and acute respiratory distress. Protozoans and saprophytic fungi, which are not normally associated with respiratory infection, have also emerged as respiratory pathogens particularly in individuals with AIDS or in those who are otherwise immunocompromised. SUMMARY: This review discusses the recent literature on newly described respiratory pathogens as well as opportunistic pathogens that can infect the respiratory system of immunocompromised individuals. The studies referenced here reveal the need for expanded laboratory tests and highly trained microbiologists in clinical laboratories worldwide.

Animals↗

PubMed2003

Venezuelan equine encephalitis replicon immunization overcomes intrinsic tolerance and elicits effective anti-tumor immunity to the 'self' tumor-associated antigen, neu in a rat mammary tumor model.

Many tumor-associated antigens (TAAs) represent 'self' antigens and as such, are subject to the constraints of immunologic tolerance. There are significant barriers to eliciting anti-tumor immune responses of sufficient magnitude. We have taken advantage of a Venezuelan equine encephalitis-derived alphavirus replicon vector system with documented in vivo tropism for immune system dendritic cells. We have overcome the intrinsic tolerance to the 'self' TAA rat neu and elicited an effective anti-tumor immune response using this alphavirus replicon vector system and a designed target antigen in a rigorous rat mammary tumor model. We have demonstrated the capacity to generate 50% protection in tumor challenge experiments (p = 0.004) and we have confirmed the establishment of immunologic memory by both second tumor challenge and Winn Assay (p = 0.009). Minor antibody responses were identified and supported the establishment of T helper type 1 (Th1) anti-tumor immune responses by isotype. Animals surviving in excess of 300 days with established effective anti-tumor immunity showed no signs of autoimmune phenomena. Together these experiments support the establishment of T lymphocyte dependent, Th1-biased anti-tumor immune responses to a non-mutated 'self' TAA in an aggressive tumor model. Importantly, this tumor model is subject to the constraints of immunologic tolerance present in animals with normal developmental, temporal, and anatomical expression of a non-mutated TAA. These data support the continued development and potential clinical application of this alphaviral replicon vector system and the use of appropriately designed target antigen sequences for anti-tumor immunotherapy.

Amino Acid Sequence↗

PubMedDate not supplied

Alphavirus vectors and vaccination.

Alphaviruses are positive-stranded RNA viruses that have a broad host range and therefore are capable of replicating in many vertebrate and invertebrate cells. The single-stranded alphavirus genome is divided into two ORFs. The first ORF encodes the nonstructural proteins that are translated upon entry of the virus into the cytoplasm and are responsible for transcription and replication of viral RNA. The second ORF is under the control of a subgenomic promoter and normally encodes the structural proteins, which are responsible for encapsidation of viral RNA and final assembly into enveloped particles. Expression vectors have been engineered from at least three alphaviruses in which the structural protein gene region has been replaced by heterologous genes and have been shown to express high levels of the heterologous protein in cultured cells. These RNA vectors, known as replicons, are capable of replicating on their own but are not packaged into virus-like particles unless the structural proteins are provided in trans. Thus, replicons are single cycle vectors incapable of spreading from infected to noninfected cells. Because of these features, alphavirus replicon vectors are being developed as a platform vaccine technology for numerous viral, bacterial, protozoan and tumour antigens where they have been shown to be efficient inducers of both humoral and T cell responses. In addition, as the alphavirus structural proteins are not expressed in vaccine recipients, antivector immune responses are generally minimal, allowing for multiple effective immunisations of the same individual.

Alphavirus↗