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Nicholas Johnson

Publications and source records attributed to Nicholas Johnson.

15 recordsLinked to original sources
PubMed2006

Lyssavirus infection activates interferon gene expression in the brain.

To investigate the innate immune response within the brain to lyssavirus infection, key transcripts indicative of innate defences were measured in a mouse model system. Following infection with Rabies virus, transcript levels for type 1 interferons (IFN-alpha and -beta), the inflammatory mediator interleukin 6 (IL-6) and the antiviral protein Mx1 increased in the brains of mice. Intracranial inoculation resulted in the early detection of virus replication and rapid expression within the brain of the innate immune response genes. Transcripts for type 1 IFNs declined as the disease progressed. Peripheral, extraneural inoculation delayed the host response until virus entered the brain, but then resulted in a large increase in the level of IFN-beta, IL-6 and Mx1 transcripts. Induction of this response was also observed following infection with the related European bat lyssaviruses, a group of zoonotic viruses capable of causing fatal, rabies-like disease in mammalian species.

Animals↗
PubMed2006

European bat lyssavirus type 2 RNA in Myotis daubentonii.

Organ distribution of European bat lyssavirus type 2 viral RNA in its reservoir host, Myotis daubentonii (Daubenton's bat), was measured with a novel quantitative reverse transcription-polymerase chain reaction assay. High levels of genomic RNA were found in the brain and were also detectable in the tongue, bladder, and stomach.

Animals↗
PubMed2005

Viruses selectively upregulate Toll-like receptors in the central nervous system.

The resting CNS is an immunospecialized environment, devoid of most immune processes, although substantial inflammatory responses can be initiated. The innate immune mechanisms mediating recognition of CNS infections are unknown. This study provides a comprehensive analysis of Toll-like receptor (TLR) gene expression in the resting and virus-infected murine CNS. TLR transcripts were expressed in the resting CNS with strikingly high expression of TLR 3. Extraneural infection with neuroinvasive Semliki Forest virus resulted in CNS infection followed by rapid selective upregulation of TLR gene expression. Upregulation was independent of T-cell responses. Upregulation of TLR gene expression was also observed following rabies virus infection. TLR upregulation was appropriate to the pathogen and proportional to the virus load. Upregulation of TLR 3 and 9 was dependent upon the type-I interferon response and may act to increase the threshold of sensitivity to detect virus infection in cells surrounding virally infected cells.

Alphavirus Infections↗
PubMed2004

Cyclophilin-D promotes the mitochondrial permeability transition but has opposite effects on apoptosis and necrosis.

Cyclophilin-D is a peptidylprolyl cis-trans isomerase of the mitochondrial matrix. It is involved in mitochondrial permeability transition, in which the adenine nucleotide translocase of the inner membrane is transformed from an antiporter to a non-selective pore. The permeability transition has been widely considered as a mechanism in both apoptosis and necrosis. The present study examines the effects of cyclophilin-D on the permeability transition and lethal cell injury, using a neuronal (B50) cell line stably overexpressing cyclophilin-D in mitochondria. Cyclophilin-D overexpression rendered isolated mitochondria far more susceptible to the permeability transition induced by Ca2+ and oxidative stress. Similarly, cyclophilin-D overexpression brought forward the onset of the permeability transition in intact cells subjected to oxidative stress. In addition, in the absence of stress, the mitochondria of cells overexpressing cyclophilin-D maintained a lower inner-membrane potential than those of normal cells. All these effects of cyclophilin-D overexpression were abolished by cyclosporin A. It is concluded that cyclophilin-D promotes the permeability transition in B50 cells. However, cyclophilin-D overexpression had opposite effects on apoptosis and necrosis; whereas NO-induced necrosis was promoted, NO- and staurosporine-induced apoptosis were inhibited. These findings indicate that the permeability transition leads to cell necrosis, but argue against its involvement in apoptosis.

Amino Acid Sequence↗
PubMed2003

Case report: isolation of a European bat lyssavirus type 2a from a fatal human case of rabies encephalitis.

A 55-year-old bat conservationist was admitted to Ninewells Hospital, Dundee, Scotland, on November 11, 2002, with an acute haematemesis. He gave a 5-day history of pain and paraesthesia in the left arm, followed by increasing weakness of his limbs with evidence of an evolving encephalitis with cerebellar involvement. The patient had never been vaccinated against rabies and did not receive postexposure treatment. Using a hemi-nested reverse transcriptase-polymerase chain reaction (RT-PCR), saliva samples taken intravitam from different dates proved positive for rabies. A 400-bp region of the nucleoprotein gene was sequenced for confirmation and identified a strain of European bat lyssavirus (EBLV) type 2a. The diagnosis was confirmed using the fluorescent antibody test (FAT) and by RT-PCR on three brain samples (cerebellum, medulla, and hippocampus) taken at autopsy. In addition, a mouse inoculation test (MIT) was performed. Between 13 and 17 days postinfection, clinical signs of a rabies-like illness had developed in all five inoculated mice. Brain smears from each infected animal were positive by the FAT and viable virus was isolated. This fatal incident is only the second confirmed case of an EBLV type-2 infection in a human after exposure to bats.

Animals↗
PubMed2003

Rabies emergence among foxes in Turkey.

Sixteen rabies isolates recently collected from mainland Turkey and two isolates held within a British archive were used to form a representative cohort from a range of vectors, and were analyzed to identify potential causes for an increase of rabies within the fox (Vulpes vulpes) population in Turkey. Each isolate was characterized by sequence analysis of the nucleoprotein gene and compared phylogenetically to the cohort, to isolates from neighboring countries and to isolates from continental Europe and Russia. From this analysis the isolates could be divided into three groups associated with geographic location. This included a western group, an eastern group, and one isolate that did not group with any other Turkish isolate. This observation was also found using the heteroduplex mobility assay as an alternative method for typing rabies virus isolates. Further comparison with isolates from neighboring countries suggests that this isolate was related to viruses present in Georgia and could represent a recent import to Turkey from that country. Within the two larger groups, sequence data were obtained from both infected dogs and foxes suggesting that there has been transmission of virus between these two species. The direction of transmission could not be identified by the phylogenetic analysis, although absence of rabies within the fox population in previous years suggests that this could represent a recent spillover from the domestic dog to the fox.

Animals↗
PubMed2003

Predicting residual disease after excision of cervical dysplasia.

Dysplastic epithelium at the resection margin after a cervical cone is known to predict persisting disease. We followed 702 women for 30 months after cervical excision to see which resection margin was predictive. The risk of persisting cytological abnormalities was doubled when CIN extended to the endocervical resection margin and was doubled when there was evidence of HPV. In contrast, disease at the ectocervical resection margin and the grade of CIN were not associated with a higher risk of residual disease.

Adolescent↗
PubMed2002

Investigation of a human case of rabies in the United Kingdom.

In May of 2001 a Nigerian woman visiting the United Kingdom presented with fever, headache and difficulty swallowing. Within 24 h she showed a marked deterioration and died shortly afterwards. Autopsy samples from a range of tissues were analysed to confirm a clinical diagnosis of rabies. Phylogenetic analysis of the viral nucleoprotein gene confirmed that this was an infection with a genotype 1 virus (classical rabies) belonging to the Africa 2 group, which is endemic in Northern Africa. Comparison of both the nucleoprotein and glycoprotein coding sequences of this isolate with an imported case of human rabies from 1996, also from Nigeria, showed that the two viruses were 99% homologous.

Amino Acid Sequence↗
PubMedDate not supplied

Mitochondrial intermembrane junctional complexes and their involvement in cell death.

Mitochondria establish contact sites between the inner and outer membranes. The contact sites are held together by junctional complexes of the adenine nucleotide translocase (ANT; inner membrane) and the voltage-dependent anion channel (VDAC; outer membrane). The junctional complexes act as multifunctional recruitment centres, binding a range of proteins according to the function to be executed. Some of these, involving kinases and enzymes of lipid transfer, are readily understood as ongoing functions in energy and lipid metabolism. But the roles of other proteins recruited to the junctional complexes are less well defined. Here, we focus on the complexes formed with Bax and with cyclophilin-D, and their possible roles in apoptotic and necrotic cell death. We have isolated both types of complexes using glutathione-S-transferase fusion proteins of Bax and of cyclophilin-D. The VDAC/ANT/cyclophilin-D complex reconstitutes Ca(2+)- and cyclosporin A-sensitive permeability transition pore activity when incorporated into proteoliposomes. The complex forms readily in the absence of factors required for pore opening in isolated mitochondria, suggesting that these factors act on the preexisting complex, rather than drive its assembly, and that the complex is a physiological entity in healthy cells.

Adenosine Triphosphate↗