Objectives:To test whether or not alveolar ridge preservation reduces vertical changes in the posterior maxilla compared to spontaneous healing following tooth extraction. Materials and methods:Forty subjects requiring extraction of maxillary posterior teeth with root apices protruding into the maxillary sinus floor were consecutively enrolled. Patients were randomly assigned to either one of two surgical interventions: an alveolar ridge preservation procedure using collagenated bovine bone mineral and a resorbable collagen membrane (test) or no grafting (control). Cone-beam computed tomographies were taken immediately and at 6 months after surgery, prior to dental implant placement.Results: Based on radiographic data, the level of the sinus floor remained stable over time (baseline to 6 months) in the test group (−0.14 mm [−0.31, −0.02]). In the control group, the sinus floor level shifted more coronally (−1.16 mm [−1.73, −0.61]) than the test group (p < 0.05). The test group demonstrated a significantly larger residual bone height than the control group at 6 months (7.30 mm [6.36, 8.20] vs. 4.83 mm [3.94, 5.76], respectively, p < 0.05). Implant placement without any additional sinus augmentation procedure was performed in 42.9% of test group cases, whereas in all of the subjects in the control group an additional augmentation procedure was needed (100% of the cases).Conclusion: Alveolar ridge preservation in the posterior maxilla maintained the vertical bone height more efficiently and resulted in less need for sinus augmentation procedures at 6 months compared to spontaneous healing. K E Y W O R D Salveolar ridge preservation, cone-beam CT, maxillary sinus, pneumatization, sinus augmentation, superimposition, vertical dimension

IkappaB kinase (IKK) and Jun N-terminal kinase (Jnk) signaling modules are important in the synthesis of immune effector molecules during innate immune responses against lipopolysaccharide and peptidoglycan. However, the regulatory mechanisms required for specificity and termination of these immune responses are unclear. We show here that crosstalk occurred between the drosophila Jnk and IKK pathways, which led to downregulation of each other's activity. The inhibitory action of Jnk was mediated by binding of drosophila activator protein 1 (AP1) to promoters activated by the transcription factor NF-kappaB. This binding led to recruitment of the histone deacetylase dHDAC1 to the promoter of the gene encoding the antibacterial protein Attacin-A and to local modification of histone acetylation content. Thus, AP1 acts as a repressor by recruiting the deacetylase complex to terminate activation of a group of NF-kappaB target genes.

PurposeLactobacilli are probiotic bacteria that are effective in the management of allergic diseases or gastroenteritis. It is hypothesized that such probiotics have immunoregulatory properties and promote mucosal tolerance. Our goal was to investigate whether Lactobacillus casei rhamnosus Lcr35 could inhibit airway inflammation in an ovalbumin (OVA)-induced murine model of asthma.MethodsBALB/c mice aged 6 weeks were used in the present study. Lactobacillus casei rhamnosus Lcr35 was administered daily, starting 1 week prior to the first OVA sensitization (group 1) and 2 days before the first 1% OVA airway challenge (group 2). Mice that received only saline at both sensitization and airway challenge time points were used as negative controls (group 3), and those that had OVA-induced asthma were used as positive controls (group 4). Airway responsiveness to methacholine was assessed, and bronchoalveolar lavage (BAL) was performed. At the endpoint of the study, total IgE as well as OVA-specific IgE, IgG1 and IgG2a in serum was measured by enzyme-linked immunosorbent assay. Lung pathology was also evaluated.ResultsAirway hyperresponsiveness, total cell counts and the proportion of eosinophils in BAL fluid were significantly decreased in group 1 compared with group 4 (P<0.05). Total serum IgE levels were also significantly decreased in group 1 compared with group 4. Serum levels of OVA-specific IgE, IgG1 and IgG2a were not significantly influenced by treatment with Lcr35. There was significantly less peribronchial and perivascular infiltration of inflammatory cells in group 1 compared with group 4; however, there were no significant differences in methacholine challenge, BAL, serology or histology between groups 2 and 4.ConclusionsOral treatment with Lcr35 prior to sensitization can attenuate airway inflammation and hyperreactivity in a mouse model of allergic airway inflammation. These results suggest that Lcr35 may have potential for preventing asthma.

In the yeast two-hybrid screening, we have isolated a cDNA clone from a human heart library using Nck Src homology 3 (SH3) domains as bait. The full-length cDNA, which encoded 722 amino acids, was identified as a VIP54-related gene containing an SH3 domain, prolinerich motifs, a serine/threonine-rich region, and a long C-terminal hydrophobic region. We refer to this protein as SPIN90 (SH3 Protein Interacting with Nck, 90 kDa). The amino acid sequence of the SH3 domain has the highest homology with those of Fyn, Yes, and c-Src. SPIN90 was broadly expressed in human tissues; in particular, it was highly expressed in heart, brain, and skeletal muscle, and its expression was developmentally regulated during cardiac myocyte differentiation. SPIN90 is able to bind to the first and third SH3 domains of Nck, in vitro, and is colocalized with Nck at sarcomere Z-discs within cardiac myocytes. Moreover, treatment with antisera raised against SPIN90 disrupted sarcomere structure, suggesting that this protein may play an important role in the maintenance of sarcomere structure and/or in the assembly of myofibrils into sarcomeres.

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Transcriptional activators interact with diverse proteins and recruit transcriptional machinery to the activated promoter. Recruitment of the Mediator complex by transcriptional activators is usually the key step in transcriptional activation. However, it is unclear how Mediator recognizes different types of activator proteins. To systematically identify the subunits responsible for the signal-and activator-specific functions of Mediator in Drosophila melanogaster, each Mediator subunit was depleted by RNA interference, and its effect on transcriptional activation of endogenous as well as synthetic promoters was examined. The depletion of some Mediator gene products caused general transcriptional defects, whereas depletion of others caused defects specifically related to activation. In particular, MED16 and MED23 were required for lipopolysaccharide-and heat-shock-specific gene expression, respectively, and their activator-specific functions appeared to result from interaction with specific activators. The corequirement of MED16 for other forms of differentiation-inducing factor-induced transcription was confirmed by microarray analysis of differentiation-inducing factor (DIF)-and MED16-depleted cells individually. These results suggest that distinct Mediator subunits interact with specific activators to coordinate and transfer activator-specific signals to the transcriptional machinery. Environmental signals induce specific cellular responses. Cell surface receptors and their individual intracellular signaling pathways provide most of the specificity needed to evoke the appropriate cellular responses by activating particular transcription factors (1, 2). For example, heat-shock treatment induces the expression of molecular chaperons (3-5). In response to heat shock, trimerized heat-shock factor (HSF) proteins bind to heat-shock promoters and recruit the Mediator complex to drive the arrested RNA polymerase II into productive elongation. On the other hand, lipopolysaccharide (LPS) treatment of SL2 cells induces a cellular innate immune response mainly manifested by the expression of antimicrobial peptides (AMPs) (6, 7). Nuclear transport and binding of Drosophila NF-B homologues Relish, differentiationinducing factor, and dorsal to the AMP promoters in response to LPS induces transcriptional activation of the AMP genes (8, 9). Despite the difference in the environmental triggers and their signaling pathways, both types of activator require the Mediator complex to activate their target genes.Diverse transcriptional activation processes have been shown to require the Mediator complex. We have reported previously that the MED17 subunit of the Mediator complex is required for transcriptional activation of Drosomycin when Toll is activated (10). MED23 and MED1 have been shown to mediate transcriptional activation of E1A (11, 12) and ligand-bound nuclear receptors (13,14), respectively, in the mouse. In addition, a recent study revealed that MED15 is a critical mediator of transforming growth factor type ␤͞activin͞Nod...

Many types of cancer cells are resistant to Fas-mediated apoptosis by several mechanisms, including the mutations of the genes involved in Fas-mediated apoptosis. In this study, to explore the possibility that the mutations of the genes involved in the proximal pathway of Fas-mediated apoptosis (Fas, FADD, caspase 8 and caspase 10) are involved in cancer metastasis, we have analysed somatic mutation and deletion of these genes in 80 non-small cell lung cancers (NSCLCs) with (n=43) and without (n=37) metastasis to the regional lymph nodes. We found 12 mutations (four Fas, four FADD, and four caspase 10 mutations) in 11 of 80 NSCLCs (13.8%). Interestingly, of these mutations, most mutations (10 out of 12) were detected in the NSCLCs with metastasis, and the frequency in the metastasis lesions (23%) was higher than that in the primary lesions of the NSCLCs without metastasis (5.4%). Furthermore, transfection study revealed that the tumor-derived mutants have decreased apoptosis inductions compared to the wild types. These data suggest that the inactivating mutations of the genes in the proximal pathway of Fas-mediated apoptosis may lead to a decreased cancer cell death and play a role in the metastasis of NSCLC.

ObjectivesThis study histologically analyzed biopsy samples obtained from sites of damaged extraction socket grafting using deproteinized bovine bone mineral (DBBM) or deproteinized porcine bone mineral (DPBM) with coverage by a collagen membrane.Material and methodsOne hundred patients participated in this randomized controlled clinical trial of extraction socket grafts performed in cases of periodontally compromised teeth. All participants were blinded to their group allocations, and each material was grafted with coverage by collagen membranes after extraction of the tooth and removal of granulation tissue. At implant placement at 4 months, a biopsy was harvested at the implant site using a trephine was analyzed histologically.ResultsEighty‐five biopsy samples were acquired, of which 81 were finally included in the histologic analysis (42 in DBBM and 39 in DPBM group). Both DBBM and DPBM groups showed comparable proportions of residual biomaterial (12.37 ± 5.67% and 12.21 ± 5.75%, respectively), newly formed bone (15.07 ± 10.52% and 18.47 ± 11.47%, respectively), and nonmineralized tissue (72.56 ± 10.07% and 71.55 ± 15.47%, respectively). There were no significant differences in these histologic parameters between the two groups with different biomaterials.ConclusionComparable histologic bone formation was found in both socket grafted groups with DBBM or DPBM covered by collagen membranes in periodontally damaged extraction sockets. However, a wide variation in new bone formation was found after 4 months of postsurgical healing and a tendency of higher new bone formation was shown at damaged sockets that had an intact unilateral residual wall regardless of buccal or lingual side.