A case of recurrence of synovial chondromatosis of the temporomandibular joint.

This is a case study of a patient with recurrent synovial chondromatosis. It shows some relevant images. It also provides possibilities for why this patient may have had a recurrence and how this was managed.     

Glial S100B Positive Vacuoles In Purkinje Cells: Earliest Morphological Abnormality In SCA1 Transgenic Mice

Spinocerebellar ataxia-1 (SCA1) is caused by the expansion of a polyglutamine repeat within the disease protein, ataxin-1. The overexpression of mutant ataxin-1 in SCA1 transgenic mice results in the formation of cytoplasmic vacuoles in Purkinje neurons (PKN) of the cerebellum. PKN are closely associated with neighboring Bergmann glia. To elucidate the role of Bergmann glia in SCA1 pathogenesis, cerebellar tissue from 7 days to 6 wks old SCA1 transgenic and wildtype mice were used. We observed that Bergmann glial S100B protein is localized to the cytoplasmic vacuoles in SCA1 PKN. These S100B positive cytoplasmic vacuoles began appearing much before the onset of behavioral abnormalities, and were negative for other glial and PKN marker proteins. Electron micrographs revealed that vacuoles have a double membrane. In the vacuoles, S100B colocalized with receptors of advanced glycation end-products (RAGE), and S100B co-immunoprecipated with cerebellar RAGE. In SCA1 PKN cultures, exogenous S100B protein interacted with the PKN membranes and was internalized. These data suggest that glial S100B though extrinsic to PKN is sequestered into cytoplasmic vacuoles in SCA1 mice at early postnatal ages. Further, S100B may be binding to RAGE on Purkinje cell membranes before these membranes are internalized.     

Physiological pharmacokinetic models: some aspects of theory, practice and potential

Models are intellectual constructs that pattern selected relationships among the elements of one system to correspond in some way to elements of a second system. In pharmacokinetics, physiological models provide a clearly articulated, rational, explanatory basis for the integration of empirical data; they do this by partitioning the biological system into relevant components (tissues, organs, etc.) and linking them together through the circulatory system. Unlike conventional mammillary compartment models, there is a clear correspondence between model system elements and physiological entities. By virtue of their high degree of physical and biochemical relevance, these models can help provide deep insight into structure, function and mechanism. Pharmacokinetic (and potentially pharmacodynamic) response-time relationships can thus be understood in terms of interconnections and behavior of constituent subsystems. At their worst, these models provide stale or infertile views of reality and thus frustrate and alienate us with the triviality of their insights. At their best, they allow us to understand the accumulation of thought in pharmacokinetics and pharmacodynamics, and help with the integration of data and improvement of experimental design.     

Glycine site of the excitatory amino acid N-methyl-D-aspartate receptor in neonatal and adult brain.

The N-methyl-D-aspartate (NMDA) receptor complex in brain is a glutamate receptor subtype with several recognition sites including a glycine site that is able to modulate and activate allosterically the receptor. This receptor may be important in the regulation of developmental synaptic plasticity. The release of glutamate and consequent overstimulation of NMDA receptors that follows hypoxia-ischaemia leads to brain damage. Brain tissue obtained at necropsy was studied in a total of 16 term infants aged less than 1 week to 22 weeks and in four adults aged from 66 to 84 years. Glycine sites were determined in brain sections by the binding of the selective ligand [3H]5,7-dichloro-kynurenic acid and measured by autoradiography. In infant brains the amount of binding to the glycine site was higher in temporal cortex and hippocampus than in basal ganglia and was also higher than in comparable areas of adult brain. The amount of glycine site binding in infant cortex increased with postnatal age. The data suggest that infant brain acquires a relatively high density of NMDA receptors in temporal lobe due to postnatal proliferation of glutamatergic synapses. These findings have therapeutic implications as drugs that reduce NMDA receptor function by blocking the glycine modulatory site would be pertinent to preventing brain damage after hypoxia-ischaemia.     

Analysis of the effect of DNA purification on detection of human papillomavirus in oral rinse samples by PCR

Human papillomavirus (HPV) has recently been associated with oral cancers. To prepare for a study of the natural history of oral HPV infection, the effect of the DNA purification method on HPV genomic DNA detection in Scope mouthwash oral rinse samples and the reproducibility of HPV detection in rinse samples collected 7 days apart were investigated. The study was conducted with a population at high risk for oral HPV infection: human immunodeficiency virus-infected men with CD4-cell counts <200. Five DNA purification methods were compared among equal aliquots of oral rinse samples collected from a subset of individuals. The purification methods included (i) proteinase K digestion (PKD) and heat inactivation; (ii) PKD and ethanol precipitation (EP); (iii) PKD, phenol-chloroform extraction, and EP; (iv) use of the Puregene DNA purification kit; and (v) use of the QIAamp DNA Blood Midi kit. HPV was detected by PCR amplification with PGMY09 and PGMY11 L1 primer pools and by use of a Roche linear array. Puregene-purified samples had higher human DNA yields and purities, and Puregene purification detected the greatest number of HPV-positive subjects and total HPV infections in comparison to the numbers detected by all other methods. The total number of HPV infections and HPV prevalence estimates were also higher for Puregene-processed oral rinse samples when a fixed volume (10 mul) rather than a fixed cell number ( approximately 50,000 cells) was used for PCR amplification. A good concordance was observed for oral HPV infection status (agreement, 80%; kappa value, = 0.60) and type-specific infection (agreement, 98%; kappa value, 0.57) in matched oral rinse samples. The method of DNA purification significantly affects the detection of HPV genomic DNA from oral rinse samples and may result in exposure misclassification that could contribute to the inconsistent associations reported in the literature.     

Lack of protection in mice and necrotizing bronchointerstitial pneumonia with bronchiolitis in guinea pigs immunized with vaccines directed against the hsp60 molecule of Mycobacterium tuberculosis

In this study, the hsp60 and hsp70 heat shock protein antigens of Mycobacterium tuberculosis were tested as potential vaccine candidates, using purified recombinant protein antigens or antigens encoded in the form of a DNA plasmid vaccine. Guinea pigs vaccinated with a mixture of the two proteins showed no evidence of resistance to low-dose aerosol challenge infection and quickly developed severe lung damage characterized by necrotizing bronchointerstitial pneumonia and bronchiolitis. As a result, we turned instead to a DNA vaccination approach using a plasmid encoding the hsp60 antigen of M. tuberculosis. Although immunogenic in mice, vaccination with plasmid DNA encoding hsp60 was not protective in that model or in the guinea pig model and again gave rise to similar severe lung damage. This study seriously questions the safety of vaccines against tuberculosis that target highly conserved heat shock proteins.     

A novel dystrophin isoform is required for normal retinal electrophysiology

Dystrophin is present in the outer plexiform layer of the retinaand is required for normal retinal function as measured by electroretinography.We describe the identification of a novel isoform of dystrophln(Dp260) present in the mouse retina. The unIque 5' terminusof the mRNA originates from a newly identified exon and is splicedin frame to exon 30 of the Duchenne muscular dystrophy (DMD)gene. The retinal isoform of dystrophln has 13 novel amino acidsas its N-terminus followed by most of the dystrophin rod domainand the cysteine-rich C-terminal domains. Analysis of mousetissues indicated this isoform of dystrophin Is expressed inretina, brain and cardiac tissue. Comparison of retinal electrophysiologyin mdx and mdx^cv3 mouse suggests that Dp260 is required fornormal retinal function.