No abstract

Gnathodiaphyseal dysplasia (GDD) is a rare skeletal syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of the jawbone. By linkage analysis of a large Japanese family with GDD, we previously mapped the GDD locus to chromosome 11p14.3-15.1. In the critical region determined by recombination mapping, we identified a novel gene (GDD1) that encodes a 913-amino-acid protein containing eight putative transmembrane-spanning domains. Two missense mutations (C356R and C356G) of GDD1 were identified in the two families with GDD (the original Japanese family and a new African American family), and both missense mutations occur at the cysteine residue at amino acid 356, which is evolutionarily conserved among human, mouse, zebrafish, fruit fly, and mosquito. Cellular localization to the endoplasmic reticulum suggests a role for GDD1 in the regulation of intracellular calcium homeostasis.

In mammals, 16 members of the Fgf family have so far been described with diverse roles in embryonic cell growth and differentiation. Here, we report the expression from early streak stage to midgestation of two newly-identified murine genes, Fgf17 and Fgf18, that are most closely related to Fgf8 (63.7% and 56.8% identical, respectively, at the amino acid level). Fgf17 is expressed during gastrulation but at lower levels than Fgf8, while Fgf18 RNA is not expressed until later, in paraxial mesoderm. In the developing tail bud, each Fgf gene shows a different pattern of transcription. Distinct and overlapping expression patterns are also described in the developing brain and limbs.

Chemokines are characterized by the homing activity of leukocytes to targeted inflammation sites. Recent research indicates that chemokines play more divergent roles in various phases of pathogenesis as well as immune reactions. The chemokine receptor, CCR1, and its ligands are thought to be involved in inflammatory bone destruction, but their physiological roles in the bone metabolism in vivo have not yet been elucidated. In the present study, we investigated the roles of CCR1 in bone metabolism using CCR1-deficient mice. Chemokines are initially identified as small cytokines that direct the homing of circulating leukocytes into sites of inflammation (1). Chemokines are now recognized to be major factors in inflammation and immune development as well as tumor growth, angiogenesis, and osteolysis. Chemokine receptors are expressed in a well organized spatiotemporal manner in various types of leukocytes, including lymphocytes, granulocytes, and macrophages. They facilitate the recruitment of these cells into inflammatory sites during the appropriate phase of inflammation.Recent findings indicate that chemokine receptors, including CCR1 7 and its related chemokines, CCL3 and CCL9, are involved in the pathogenesis of a variety of diseases. In particular, CCL3 (also called MIP-1␣), a major pro-inflammatory chemokine produced at inflammatory sites, appears to play a crucial role in pathological osteoclastogenesis (2, 3). In osteolytic bone inflammation (e.g. rheumatoid arthritis-associated bone destruction), CCL3 induces ectopic osteoclastogenesis (4) * This work was supported in part by Grant H19-nano-012 from the Ministry of Health, Labor and Welfare (to K. Y.) and by a research fellowship from the Japan Society for the Promotion of Science for Young Scientists (2007Scientists ( -2009 ( The abbreviations used are: CCR, C-C chemokine receptor; M-CSF, macrophage-colony stimulation factor; BALP, bone-specific alkaline phosphatase; CCL, C-C chemokine ligand; MCP-1, macrophage chemoattractant protein-1; MIP-1, macrophage inflammatory protein-1; CT, computed tomography; PTX, pertussis toxin from Bordetella pertussis; RANK, receptor activator of NF-B; RANKL, receptor activator of NF-B ligand; RANTES, regulated upon activation normal T expression and secreted; TRAP, tartrate-resistant acid phosphatase; NTx, N-telopeptides.

Gene-activated matrix (GAM) is a matrix, such as collagen-containing plasmid vector, that encodes a protein to stimulate tissue regeneration. In the original GAM system, gene transfer efficiency was extremely low. We have recently reported that modifying GAM with calcium-phosphate precipitates (CaP) enhances the efficiency of gene transfer. The purpose of this study was to evaluate the effects of our modified GAM on tissue regeneration. We prepared critical size segmental bone defects in rat tibiae and transplanted GAM consisting of bovine atelocollagen and expression plasmid vector (bmp2), which encodes human BMP2, with or without CaP. The tibiae were later examined radiographically, histologically, and mechanically. Implantation of bmp2-CaP-collagen at 12 microg bmp2 bridged the bone defect at 4 weeks, and the strength of the bone was comparable to that of an intact tibia at 6 weeks. Implantation of bmp2-collagen at the same dose of bmp2 bridged the defect to a smaller extent. Neither collagen alone nor vacant vector-CaP-collagen bridged the defect. These results indicate that our modified GAM with CaP has the potential to be effective in tissue regeneration at lower plasmid DNA doses than used in previous studies.

Aim We conducted a multicenter study to explore the risk factors of developing pneumonia and the effectiveness of perioperative oral management (POM) for the prevention of pneumonia in postsurgical patients. Methods and results A survey covering eight regional hospitals was conducted over 4 years, from April 2010 to March 2014. Using the Diagnosis Procedure Combination database, a target group of 25,554 patients with cancer who underwent surgery was selected and assessed from a population of 346,563 patients without pneumonia on admission (sample population). The study compared the incidence of pneumonia and attempted to identify the significant predictive factors for its occurrence in these patients using multiple logistic regression analysis. Comparative assessment for the occurrence of pneumonia before and after POM implementation showed a significant incidence decrease after POM introduction in the target group, with no such change observed in the sample population. Multiple logistic regression analysis showed that the odds ratio for pneumonia occurrence after POM introduction was 0.44, indicating a reduced risk of pneumonia. Conclusion POM in cancer patients was indeed effective in reducing the incidence of pneumonia in hospitals and thereby helped in preventing pneumonia during hospitalization.

Tissue-nonspecific-type alkaline phosphatase is found in the bone, liver, kidney, and other tissues, and its gene consists of 12 exons with the coding sequence beginning in the second exon. Recently, an alternative noncoding first exon was identified in the liver message which differed from that of the previously known osteoblast-derived cDNA sequence. Although these two mRNAs produce an identical protein, they have different promoter regions. The periodontal ligament tissue expresses a high level of alkaline phosphatase activity. To identify its mRNA type, we isolated a full-length cDNA for alkaline phosphatase from a cultured human periodontal ligament cell expression library, using bone-derived tissue-nonspecific alkaline phosphatase cDNA as a hybridization probe. The size of this clone was 2.5 kb, and its 5' and 3' untranslated sequences were identical to those of the human tissue-nonspecific type isolated from osteoblastic cells but not to those of the liver type. In addition, the same fragments as in bone-derived tissue-nonspecific-type cDNA were detected by the treatment of the cDNA clone with restriction enzymes Hinc II and Pst I. The results suggest that expression of the same alkaline phosphatase isozyme in human periodontal ligament cells may be regulated by the same transcriptional mechanism as in bone.

The novel coronavirus pandemic has resulted in an urgent need to study the risk of infection from aerosols generated during dental care and to conduct a review of infection controls. However, existing studies on aerosol particles related to dental treatment have mainly evaluated only the scattering range. Few studies have been conducted on the specifics of the generation of aerosol particles in clinical settings, their mechanisms and patterns of distribution throughout open or enclosed spaces, the duration that they remain suspended in air, and the amount and size of particles present. To minimize the influence of background particles, laser lights, a high-sensitivity camera, and particle counters were used in a large super clean laboratory to investigate the dynamics of aerosols generated during the operation of dental micromotors. The results indicate that aerosols tend to scatter upward immediately after generation and then gradually disperse into the surroundings. Most of the particles are less than 5 µm in size (only a few are larger), and all particles are widely distributed over the long term. Our research clearly elucidates that aerosols produced in dental care are distributed over a wide area and remain suspended for a considerable time in dental clinics before settling.