Distinct roles of P2X receptors in modulating glutamate release at different primary sensory synapses in rat spinal cord

Using spinal cord slice preparations and patch-clamp recordings in lamina II and lamina V regions, we tested a hypothesis that P2X receptor subtypes differentially modulate glutamate release from primary afferent terminals innervating different sensory regions. We found that activation of P2X receptors by alpha,beta-methylene-ATP increased glutamate release onto >80% of DH neurons in both lamina regions. However, two distinct types of modulation, a transient and a long-lasting enhancement of glutamate release were observed. In lamina II recordings, >70% of the modulation was transient. In contrast, P2X receptor-mediated modulation was always long-lasting in lamina V. Pharmacologically, both transient and long-lasting types of modulation were blocked by 10 microM pyridxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium, a broad-spectrum P2X receptor antagonist. Transient modulation was not observed in the presence of 1 microM trinitrophenyl-ATP (TNP-ATP), a subtype-selective P2X receptor antagonist, suggesting that homomeric P2X3 receptors may be involved in the transient modulation in lamina II. The long-lasting modulation remained in the presence of 1 microM TNP-ATP. Selective removal of P2X3-expressing afferent terminals by the targeting toxin saporin-conjugated isolectin B4 or surgical removal of superficial DH did not affect P2X receptor-mediated long-lasting modulation in lamina V. Taken together, these results suggest that P2X receptor subtypes play distinct roles in sensory processing in functionally different sensory regions.     

Delayed fracture of beta titanium orthodontic wire in fluoride aqueous solutions

Hydrogen embrittlement of a beta titanium orthodontic wire has been examined by means of a delayed-fracture test in acid and neutral fluoride aqueous solutions and hydrogen thermal desorption analysis. The time to fracture increased with decreasing applied stress in 2.0% and 0.2% acidulated phosphate fluoride (APF) solutions. The fracture mode changed from ductile to brittle when the applied stress was lower than 500MPa in 2.0% APF solution. On the other hand, the delayed fracture did not occur within 1000h in neutral NaF solutions, although general corrosion was also observed similar to that in APF solutions. Hydrogen desorption of the delayed-fracture-tested specimens was observed with a peak at approximately 500 degrees C. The amount of absorbed hydrogen was 5000-6500 mass ppm under an applied stress in 2.0% APF solution for 24h. It is concluded that the immersion in fluoride solutions leads to the degradation of the mechanical properties and fracture of beta titanium alloy associated with hydrogen absorption.     

Palpebral edema as a cutaneous manifestation of hyperthyroidism

Three cases of palpebral edema associated with Graves' disease are described. These patients had unilateral edema and minimal erythema of the upper eyelid. Notable was that, histologically, dermal edema and dilation of lymphatic vessels were observed, but deposition of mucopolysaccharides was not. In 2 cases, edema of the eyelid was resistant to treatment with an antithyroid drug. Unilateral edema of the upper eyelid is an important cutaneous manifestation that indicates the presence of hyperthyroidism.     

A case of infantile epileptic apnea with congenital brain anomaly

Two months-old girl with psychomotor retardation had aminophylline-resistant apnea attacks and was investigated by video-EEG recording. She had hypogenesis of cerebral cortex and cerebellum and complete agenesis of corpus callosum. Left hemispheric 2 Hz rhythmic delta wave burst originating from the posterior temporal area lasted about 20 seconds, and was followed by an apnea attack persisting for 30 seconds. During the apnea attack, the basic activity of EEG was suppressed. The diagnosis of epileptic apnea was made, and the attacks were controlled with valproate sodium. Reports of cases of brain anomaly presenting with epileptic apnea are rare and this interesting case provided a clue to the pathomechanism of this condition.     

A tripartite motif protein TRIM11 binds and destabilizes Humanin,a neuroprotective peptide against Alzheimer's disease-relevant insults

Humanin (HN) is a newly identified neuroprotective peptide that specifically suppresses Alzheimer's disease (AD)-related neurotoxicity. HN peptide has been detected in the human AD brain as well as in mouse testis and colon by immunoblot and immunohistochemical analyses. By means of yeast two-hybrid screening, we identified TRIM11 as a novel HN-interacting protein. TRIM11, which is a member of protein family containing a tripartite motif (TRIM), is composed of a RING finger domain, which is a putative E3 ubiquitin ligase, a B-box domain, a coiled-coil domain and a B30.2 domain. Deletion of the B30.2 domain in TRIM11 abolished the interaction with HN, whereas the B30.2 domain alone did not interact with HN. For their interaction, at least the coiled-coil domain was indispensable together with the B30.2 domain. The intracellular level of glutathione S-transferase-fused or EGFP-fused HN peptides or plain HN was drastically reduced by the coexpression of TRIM11. Disruption of the RING finger domain by deleting the first consensus cysteine or proteasome inhibitor treatment significantly diminished the effect of TRIM11 on the intracellular level of HN. These results suggest that TRIM11 plays a role in the regulation of intracellular HN level through ubiquitin-mediated protein degradation pathways.     

Amyloid deposition associated with generalized morphea-like scleroderma

A 62-year-old man with amyloid deposition associated with generalized morphea-like scleroderma is described. He had been occupationally exposed to organic solvents. Physical examination showed sclerosis of fingers, forearms, and trunk. Erythema was noted on the border of patchy sclerotic plaques on his chest and back. In addition, firm miliary, keratotic papules were found on the lateral forearms. Amyloid deposition was demonstrated by Congo-red stain at papillary layers of overlying sclerotic dermis in the biopsied specimen taken from the left forearm. As far as we know, amyloid deposition associated with generalized morphea-like scleroderma has not been reported until now.     

The prognosis in spindle-cell sarcoma depends on the expression of cyclin-dependent kinase inhibitor p27(Kip1) and cyclin E

The aim of the present study was to examine the prognostic significance of p27^Kip1 and cyclin E expression in patients with spindle-cell soft tissue sarcomas. In 46 cases of spindle-cell sarcoma including 17 pre-operative biopsy materials, the expression of p27^Kip1 and cyclin e was immunohistochemically examined. The expression of p27^Kip1 decreased in the nuclei of metastatic primary tumor cells (stage IV), whereas the expression of cyclin E increased in those lesions. On univariate analysis, when the expression of p27^Kip1 and cyclin E was analyzed together, patients with spindle-cell sarcoma exhibiting low expression of p27^Kip1 and high expression of cyclin E showed lower distant-metastasis-free survival (DMFS) and overall survival (OS) than those with other combinations of the two parameters (both P <0.0001). Multivariate analysis revealed that patients with low p27^Kip1 and high cyclin E expression also showed a decrease in DMFS ( P =0.0007, relative risk=21.3) and OS (P=0.005, relative risk=20.8). These results suggest that the combination analysis of p27^Kip1 and cyclin E expression even in biopsy specimens allows the prediction of the clinical behavior of spindle-cell sarcoma. (Cancer Sci 2003; 94: 412–417)     

New regulatory mechanisms for human extravillous trophoblast invasion

Human extravillous trophoblasts (EVT) invade maternal deciduas and reconstructed maternal spiral arteries during early placentation. However, the precise regulatory mechanisms to induce EVT invasion toward arteries and/or to protect EVT from further invasion have not been well understood. Recently, it was found that EVT that had already ceased their invasion, specifically expressed cluster of differentiation (CD9) and dipeptidyl peptidase IV (DPPIV) on their cell surface. In addition, EVT migrating to maternal spiral arteries expressed CC chemokine receptor type-1 (CCR-1), which is a chemokine receptor for regulated on activation normal T cell expressed and secreted (RANTES) and so on. CD9 is associated with integrin molecules on the cell surface and is considered to modulate integrin function. In contrast, DPPIV is a cell surface peptidase that can metabolize RANTES at extracellular sites before its accessing to the chemokine receptors. In vitro functional assay showed that CD9, DPPIV and RANTES are involved in the regulation for EVT invasion. From these findings, it can be proposed that CD9 and DPPIV, including chemokines, are new regulatory factors for human extravillous trophoblasts. (Reprod Med Biol 2005; 4 : 189–195)     

Preservation of rat palatal scar tissue myofibroblasts in organ culture

In order to modulate palatal scar tissue, especially its myofibroblastic component, there is a pressing need for an in vitro model of this tissue. In the present, study we established an organ culture model of the rat palatal scar tissue. After excision of palatal mucoperiosteum, explants from the developing immature scar tissue and from the normal palatal mucosa were used to observe myofibroblasts in vivo and their maintenance in organ culture. Explants were cultured at the gas-liquid interface in serum-free Waymouth's MB 752/1 medium and in a humid atmosphere containing 55% O2/5% CO2 in air at 37 degrees C for 3 days. Viability of the cultured explants was evaluated with morphological and histological criteria and BrdU incorporation. After organ culture, the scar tissue showed good preservation of the in vivo histology. The myofibroblasts and smooth muscle cells of the cultured scar tissues showed continuous expression of alpha-smooth muscle actin (alpha-SMA), mimicking the in vivo situation. In the normal tissues, only smooth muscle cells of the blood vessels expressed alpha-SMA. These results demonstrate that the established model provides a useful in vitro experimental tool for investigating the palatal scar tissue in general and its myofibroblasts in particular.