PRG4 (proteoglycan 4) has been identified as megakaryocyte stimulating factor and articular superficial zone protein. PRG4 has characteristic motifs including somatomedin B and hemopexin domains, a chondroitin sulfate-attachment site and mucin-like repeats. During a screen of genes implicated in ectopic ossification, we found a novel mouse gene highly homologous to human and bovine PRG4 genes. Here, we report isolation, characterization and mapping of the gene, Prg4 together with characterization of its human orthologue. Prg4 cDNA was 3,320 bp long, encoding a 1,054 amino-acid protein. Human and mouse PRG4 genes each consisting of 12 exons spanned 18 and 16 kb, respectively. Characteristic motifs were conserved across species; however, the mucin-like repeat regions were highly diverse in length between species with a tendency that larger animals had longer repeats. Expression of human and mouse PRG4 genes was similar and found not only in cartilage, but also in liver, heart, lung, and bone. Expression of the mouse gene increased with progression of ectopic ossification. Multiple tissue-specific splicing variants lacking some of the motifs were found in both human and mouse. Although a specific role in the articular joint has previously been reported, the presence of multi-functional motifs as well as unique expression and alternative splicing patterns suggest that PRG4 functions in several distinctive biological process including regulation of ossification.
The changes in the expression of brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in the rat neuromuscular system as a result of three different types of sciatic nerve injuries have been evaluated. The changes in mRNA and protein levels for BDNF, NT-3, and NT-4 in the soleus muscle and sciatic nerve were assessed 4-28 days after sciatic nerve transection (neurotmesis), sciatic nerve crush (axonotmesis), and mild acute compression (neurapraxia). BDNF mRNA levels increased dramatically with nerve transection in the soleus muscle and the sciatic nerve 7-14 days after injury, whereas the changes were low in other types of injury. The changes of protein levels for BDNF were also similar. The mRNA and the protein levels of NT-3 in the soleus muscle did not show any significant difference. The mRNA for NT-4 in the soleus muscle decreased from 4 to 14 days after sciatic nerve transection, and the protein level was also minimum 14 days after sciatic nerve transection. Our results indicate that the neurotrophic factors in the neuromuscular system could play a role in differentiating peripheral nerve injury.
This study presents a retrospective review of the management of schwannomas in the limbs and examines the relationship between pre-operative clinical examination, operative findings and postoperative neurological complications. Eighteen tumours with a histological diagnosis of schwannoma in 17 patients who underwent surgery between 1998 and 2004 were the basis of this study. Enucleation of the tumour was possible in 14 cases. None of these patients had neurological complications pre-operatively but eight had mild neurological complications postoperatively. The complications consisted of sensory deficit in five cases, motor weakness in one and both in two. Enucleation of the tumours was impossible in four cases. These schwannomas originated in the brachial plexus in three cases and the ulnar nerve in the proximal arm in one case. Tumours with pre-operative symptoms and masses located at a proximal site in the limb were more likely to be impossible to enucleate completely.
Alkali-metal-graphite intercalation compounds (alkali-metal-GIC's) absorb hydrogen in two ways: physisorption and chemisorption. Hydrogen uptake through the physisorption process occurs at low temperatures below about 200 K in higher stage alkali-metal-GIC's, where hydrogen molecules are stabilized to form a two-dimensional condensed phase in the galleries of the graphite sheets. The concentration of absorbed hydrogen molecules is saturated at a rate of H2/alkali metal atom ∼2. The hydrogen physisorption shows a strong isotope effect and a swelling effect on c-axis lattice expansion. In the case of hydrogen uptake through the chemisorption process, dissociated hydrogen species are stabilized in the intercalate spaces. The activity of the chemisorption increases in the order Cs < Rb < K. The introduction of hydrogen generates a charge transfer from the host alkali metal GIC's to the hydrogen since hydrogen has strong electron affinity. The hydrogenated potassium-GIC's have intercalates consisting of K+-H−-K+ triple atomic layer sandwiches which are inserted between metallic graphite sheets. The inserted two-dimensional hydrogen layer is suggested to consist of H ions with a weakly metallic nature. The superconductivity of the hydrogenated potassium-GIC is also discussed in terms of the change in the electronic and lattice dynamical properties by hydrogen uptake. The hydrogen-absorption in alkali-metal-GIC's is an interesting phenomenon in comparison with that in transition metal hydrides from the point of hydrogen storage. The hydrogen-alkali-metal-ternary GIC's obtained from hydrogen absorption have novel electronic properties and lattice structures which provide attractive problems for GIC research. The studies of hydrogen-alkali-metal ternary GIC's are reviewed in this article.
We investigated clinicopathologically the pyramidal signs, including spasticity, hyperreflexia, and Babinski's sign, and the involvement of the pyramidal tract and primary motor cortex, in seven Japanese autopsy cases of multiple system atrophy (MSA). Pyramidal signs were observed in six (86%) of the seven autopsy cases. Hyperreflexia and Babinski's sign were each evident in five patients, but spasticity was observed in only one patient. Loss of Betz cells and presence of glial cytoplasmic inclusions in the primary motor cortex were noticed in all seven cases. Astrocytosis in the fifth layer of the primary motor cortex was noticed in five cases, but its presence was not related to the duration of the disease. Involvement of the pyramidal tract in the spinal cord, particularly of the small myelinated fibers, was observed in all seven cases, but no involvement of the pyramidal tract in the midbrain was evident in any of the six cases in which this structure was examined. In MSA, pyramidal signs were shown to be present more frequently than believed before, and the clinicopathological correlation between pyramidal signs and involvement of the pyramidal tract was obvious. Constant involvement of Betz cells in MSA has not been reported. Our clinicopathological findings may also make a contribution to the understanding of the clinicopathological hallmarks of MSA.
Reactive oxygen species (ROS) are involved in the pathophysiology of ischemia/reperfusion injury. To protect mouse hepatocytes from ischemia/reperfusion injury, we prepared two different sizes of citric acid-protected platinum nanoparticles (Pt-NPs), which exhibited ROS-scavenging activities and selective delivery to a specific type of liver cell. Small Pt-NPs (30 nm) reduced the superoxide anion, hydrogen peroxide, and hydroxyl radical levels in solution to a greater extent than did large Pt-NPs (106 nm). Large and small Pt-NPs predominantly accumulated in hepatic nonparenchymal cells after intravenous injection into mice. In a mouse model of ischemia/reperfusion injury, in which hepatic injury was induced by occluding the portal vein for 15 min followed by 6 h reperfusion, the increase in plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities was inhibited by a bolus intravenous injection of either large or small Pt-NPs. However, small Pt-NPs inhibited the increase in these markers of hepatic injury to a greater extent than did large Pt-NPs. These results indicate that Pt-NPs can be used to prevent hepatic ischemia/reperfusion injury. To our knowledge, this is the first report demonstrating the pharmacokinetics and efficacy of Pt-NPs to prevent hepatic ischemia/reperfusion injury.
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