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Biomedical subjects

John P Rossiter

Publications and source records attributed to John P Rossiter.

7 recordsLinked to original sources
PubMed2006

Expression of Toll-like receptor 3 in the human cerebellar cortex in rabies, herpes simplex encephalitis, and other neurological diseases.

There is recent in vitro evidence that human neurons express the innate immune response receptor, Toll-like receptor-3 (TLR-3), and that expression is enhanced in viral infections. The authors examined the immunohistochemical expression of TLR-3 in the cerebellar cortex of postmortem human brains. Purkinje cells were found to express TLR-3 in all cases of rabies (4 of 4) and herpes simplex encephalitis (2 of 2) as well as in cases of amyotrophic lateral sclerosis (1 of 2), stroke (1 of 2), and Alzheimer's disease (3 of 3). In cases of viral infection, direct viral infection was not necessary for enhanced neuronal TLR-3 expression, suggesting that soluble factors likely play an important role in inducing TLR-3 expression. In addition to neurons, occasional Bergmann glia expressed TLR-3 in some cases. This study has provided evidence that human brain neurons can express TLR-3 in vivo and suggests that neurons may play an important role in initiating an inflammatory reaction in a variety of neurological diseases.

Adolescent↗
PubMed2006

Approach to diagnosis of Parkinson disease.

OBJECTIVE: To review the clinical features of Parkinson disease (PD) and other causes of motor parkinsonism with an emphasis on diagnosis in elderly patients. SOURCES OF INFORMATION MEDLINE: and Google Scholar were searched for original research articles describing clinical diagnosis of parkinsonism. Consensus statements and articles summarizing diagnostic criteria for parkinsonian syndromes were also reviewed. Most evidence was levels II or III. MAIN MESSAGE: Diagnosis of PD is made clinically and can be challenging. In older patients, PD can present with general functional decline and nonspecific symptoms. Clinical criteria for diagnosing PD and the TRAP mnemonic can be helpful. A 2-week trial of levodopa-carbidopa treatment can be considered. Specific signs and a minimal response to levodopa treatment suggest other causes of parkinsonism. Clinical features of other causes of parkinsonism are reviewed in the article. CONCLUSION: Parkinsonism and PD are common in older patients. Family physicians should consider parkinsonism in the differential diagnosis of patients who have falls and exhibit general functional decline.

Aged↗
PubMed2005

Comparative pathogenesis of the SAD-L16 strain of rabies virus and a mutant modifying the dynein light chain binding site of the rabies virus phosphoprotein in young mice.

Recent reports have suggested that rabies virus phosphoprotein (P) interaction with dynein minus-end-directed microtubule motor proteins may be of fundamental importance in the axonal transport of rabies virus. A deletion of 11 amino acids was introduced into recombinant rabies virus SAD-L16 (L16) that modified the dynein light chain (LC8) binding site of the rabies virus P, producing mutant L-DeltaP11. This mutant is a useful tool for determining the role of P-LC8 interaction in viral spread and pathogenesis. Seven-day-old ICR mice were inoculated into a hindlimb thigh muscle with L16 or L-DeltaP11. Histopathological and immunohistochemical analyses of their brains were performed at serial time points in order to determine the pattern of viral spread. L16 spread to the brain and caused a severe encephalitis with apoptotic neuronal changes. L-DeltaP11 infected specific brain areas (brainstem and hippocampus) 1-2 days later than L16 and involved a smaller number of neurons in some brain regions. However, the neuronal apoptotic changes produced by both viruses were similar in most brain regions. Following peripheral inoculation, deletions modifying the LC8 binding site had an effect on delaying viral spread, but did not significantly alter the pattern of rabies virus encephalitis. The precise role of the rabies virus P-dynein interaction in the axonal transport of rabies virus, particularly the importance of this interaction during natural infection, merits further study.

Animals↗
PubMed2005

Recombinant rabies virus vaccine strain SAD-l16 inoculated intracerebrally in young mice produces a severe encephalitis with extensive neuronal apoptosis.

Seven-day-old ICR mice were infected by intracerebral inoculation with recombinant rabies virus vaccine strain SAD-L16. Infected mice developed severe and fatal encephalitis with rabies virus-infected neurons in widespread regions of the brain. There was extensive neuronal death with predominant features of apoptosis, as assessed by light and electron microscopy, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining, and immunohistochemical staining for activated caspase-3. Although SAD-L16 is a neuroattenuated rabies virus, it is fully capable of spreading efficiently and inducing widespread neuronal apoptosis in the immature mouse brain.

Animals↗
PubMed2004

Development of a guinea pig model of chorioamnionitis and fetal brain injury.

OBJECTIVE: The purpose of this study was to develop a guinea pig model of chorioamnionitis to study the mechanisms that lead to fetal brain injury. Study design Pregnant guinea pigs at 70% gestation were inoculated intracervically with 1000 to 2500 colony-forming units of Escherichia coli. Guinea pigs were killed 2 to 3 days after bacterial inoculation. Maternal blood and fetal amniotic fluid samples were analyzed for proinflammatory cytokine tumor necrosis factor-alpha, interleukin-1beta, and interleukin-6 levels with the use of enzyme-linked immunosorbent assay kits. Fetal brains were stained for evidence of cell death with NeuroTacs stain. RESULTS: Of 34 maternal guinea pigs that were given an intracervical inoculation of E coli, 8 guinea pigs showed microbiologic evidence of chorioamnionitis in the amniotic fluid. Tumor necrosis factor-alpha and interleukin-6 were significantly higher (P<.05) in amniotic fluid samples that were obtained from sows that were subjected to intracervical inoculation with bacteria as compared with control animals (n=6 control maternal animals). These results were observed even if no bacteria were found subsequently on culture of the amniotic fluid from inoculated animals, which indicated that indirect exposure to infectious agents was sufficient to cause an elevated inflammatory response in the fetus. Levels of white matter injury were greater in fetuses that were exposed to bacterial infection in utero, as compared with control animals (P<.05). This result was found in the staining of periventricular and cortical white matter for the immunolabeling of activated caspase 3 and NeuroTacs staining for cells that exhibited evidence of apoptotic cell death (positive stain with evidence of karyorrhexis). CONCLUSION: Intracervical inoculation with E coli results in chorioamnionitis in guinea pigs that is associated with fetal brain injury.

Amniotic Fluid↗