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Multiple myeloma (MM) is a hematopoietic malignancy characterized by monoclonal proliferation of plasma cells. MM features bony radiolucencies called punched-out lesions (POLs), which require appropriate diagnosis due to increased risk of surgically-related adverse events. Although dental surgeons can identify dental focal infections (DFIs) in MM patients, the prevalence and characteristics of POLs in the jawbone of MM patients have not been investigated. We examined the prevalence of POLs in the mandible of MM patients, evaluated its relationship with MM International Staging System progression, and examined panoramic radiographs as a diagnostic reference for POLs in a single center in Japan. We identified 98 patients (55 men, 43 women) with a median age of 63 (range, 34 to 91) years. Of these, 18 patients (18.4%) had POLs in the mandible, including two patients in stage I (2/37; 5.4%), six in stage II (6/43; 14.0%), and ten in stage III (10/18; 55.6%). The prevalence of POLs significantly increased with MM stage progression (p < 0.0001). POLs confirmed on computed tomography (CT) were also detected on panoramic radiographs. The Hounsfield unit value at the site of POLs was nearly the same or lower than that of the mental foramen. Although the prevalence of POLs in the mandible is low, dental surgeons need to differentiate POLs as radiological findings when examining DFIs in MM patients. Confirmation of POLs in the mandible is possible by CT and panoramic radiography, and the mental foramen is likely to be a reference for discrimination.

We aimed to assess the rate and risk factors of postoperative complications following tooth extraction in HIV-infected patients by CD4 count. The study participants were 231 HIV-infected patients who underwent tooth extraction at our institution between January 2007 and December 2011. Blood test results, underlying diseases, surgical site, extraction method, and postoperative complication data were obtained from medical records. Potential risk factors of postoperative complications were analyzed using multivariate logistic regression. Patients were divided into two groups: 61 (26%) patients with a CD4 count < 200/μL, and 170 (74%) with a CD4 count ≥ 200/μL. Of the 231 patients, 12 (5.2%) developed postoperative complications (alveolar osteitis, n = 10; surgical site infection, n = 2). The rate of complications did not differ between the CD4 < 200/μL group (1.6%) and the CD4 ≥200/μL group (6.5%) (adjusted odds ratio [aOR]: 9.328, 95% confidence interval [CI]: 0.470, 185.229; P = 0.1431). Surgical extraction with bone excavation, but without CD4 count, was identified as a risk factor for post-extraction complications (aOR: 22.037, 95% CI: 1.519, 319.617; P = 0.0234). A low CD4 count is not a risk factor for post-extraction complications in patients with HIV infection. We conclude that tooth extraction should be performed based on dental/oral conditions, and not delayed until CD4 count improvement.

Perioperative oral management (POM) is used to prevent pneumonia in patients with cancer. However, the factors that expose hospitalized patients to increased risk of developing pneumonia remain unclear. For example, no study to date has compared the incidence of pneumonia in hospitalized patients by cancer primary lesion, or POM implementation, or not. We determined which patients were most likely to benefit from POM and examined the effects of POM on pneumonia prevention and mortality. In a total of 9441 patients with cancer who underwent surgery during hospitalization, there were 8208 patients in the No POM group, and 1233 in the POM group. We examined between-group differences in the incidence of pneumonia and associated outcomes during hospitalization. There was no significant between-group difference in the incidence of pneumonitis, however, patients with lung, or head and neck cancers, demonstrated a lower incidence of postoperative pneumonia. Among patients with lung and pancreatic cancers, mortality was significantly lower in the POM group. POM appears effective at reducing the risk of postoperative pneumonia in patients with certain cancers. Further, mortality was significantly lower in patients with lung and pancreatic cancers who received POM; hence, POM may be an effective adjuvant therapy for patients with cancer.

Source of fever in chemotherapy patients is often unknown. Fever can also be fatal. No observational studies have determined the incidence of dental focal infection (DFI)-associated fever, despite oral cavity being a potential source of infection. We report the incidence of fever after chemotherapy in patients with hematological malignancies and their association with DFIs in 441 patients visiting our institution during a 6-year period. Dental treatments, including tooth extraction, were performed, and their oral and hematological profiles were monitored after chemotherapy. Fever was evident in 87 (38.5%) of 226 patients (≥ 38˚C) after the first cycle of chemotherapy. Sepsis due to DFIs (n = 4; 4.6%) was evaluated. Chemotherapy was delayed due to DFI in one case. Fever after chemotherapy should be differentiated from oral infections. Our study emphasizes the significance of DFI in patients with fever after chemotherapy and can help in improving the prognosis of patients.

Ventilator-associated pneumonia (VAP) has emerged as a critical issue in the intensive care unit (ICU) because of its high burden on patients and medical staff. Here, we examined the potential for reducing VAP incidence through physical oral care interventions without any medication.This prospective interventional study compared VAP incidence during an 8-month baseline period (usual oral care) and a 9-month intervention period (physical oral care with sponge brush) among patients who received mechanical ventilation for48 h in a tertiary care hospital in Vietnam from 2017 to 2019. Physical oral care was provided by general ICU nurses who had been trained by dentists and infection control nurses. VAP was diagnosed using the Clinical Pulmonary Infection Score.In total, 423 patients were enrolled in the baseline group and 454 patients were enrolled in the intervention group; 303 and 300 patients, respectively, were included in the analysis. Two hundred thirty-eight VAP episodes were identified: 135 (44.6%) during the baseline period and 103 (34.3%) during the intervention period. Univariate analysis revealed significant reduction of VAP occurrence in the intervention period (odds ratio = 0.65; 95% confidence interval = 0.47-0.90; P = 0.010). The incidences of VAP per 1000 ventilator-days were 63.4 (135/2128) during the baseline period and 48.4 (103/2128) during the intervention period (P = 0.038).Physical oral care without any medication (e.g., chlorhexidine) reduced VAP incidence in the ICU. This method could be used to reduce VAP incidence, particularly in countries with limited medical resources.

Oral care is defined in a narrow sense as cleaning of the teeth, oral cavity, and dentures, and in a broad sense as the maintenance of oral functions (feeding, swallowing, chewing, speech, aesthetics, etc.), dental treatment, feeding and swallowing training, and articulation training. In the past, it was recognized as simply cleaning the mouth, but the concept of oral care has gradually expanded, and many studies and surveys have been conducted in cooperation with various other professions. As a result, oral health care is involved not only in the prevention of pneumonia, but also in the onset and suppression for severity of diabetes, cardiovascular diseases, some malignant tumors, cerebrovascular diseases, rheumatoid arthritis, dementia, etc. It is also a powerful supportive therapy in cancer treatment. In the terminal stages of life, oral health care can help people to maintain their dignity by continuing to consume food orally until the end of their lives, and in times of disaster, oral health care has been found to be as important as attention to deep vein thrombosis. It has also been found to be effective in preventing severe diseases such as COVID-19. And, although it has not been discussed much, it has been found to have medical and economic benefits such as reducing the duration of hospitalization and treatment costs. This article reviews the results of research to date.

Chronic non-bacterial osteomyelitis (CNO) is a rare and severe inflammatory bone disorder that can occur in the jaw. It is often associated with systemic conditions including autoimmune deficiency. Medical management of patients and establishment of a correct diagnosis are difficult as the etiology of the disease remains unknown. Therefore, little is known about the disease characteristics at the gene expression level. Here, we explored aspects of CNO based on whole blood RNA sequencing (6 Gb per sample) of 11 patients and 9 healthy controls in Japan and on a recently developed method that is applicable to small datasets, can estimate a directed gene network, and extract a subnetwork of genes underlying patient characteristics. We identified nine subnetworks, comprising 26 differentially regulated edges and 36 genes, with the gene encoding glycophorin C (GYPC) presenting the highest discrimination ability. The expression of the gene was mostly lower in patients with CNO than in the healthy controls, suggesting an abnormal status of red cells in patients with CNO. This study enhances our understanding of CNO at the transcriptome level and further provides a framework for whole blood RNA sequencing and analysis of data obtained for a better diagnosis of the disease.

Degenerative joint disease of the temporomandibular joints (DJD-TMJ) clinically manifests with symptoms such as orofacial pain, joint sounds and limited jaw movements. Our research group previously reported the functional necessity of a chemokine-chemokine receptor axis of CCL5-CCR5 in osteoclasts. Accumulated studies reported that this axis was involved in the pathogenesis of bone and joint destructive diseases, suggesting CCL5 as a potent biomarker. This study investigated whether or not the serum level of CCL5 can be a biomarker of DJD-TMJ and concomitantly analyzed changes in the serum and urine levels of bone markers to see whether or not changes in the rate of bone metabolism were predisposing. We enrolled 17 female subjects with diagnosed DJD-TMJ and sexually and age-matched 17 controls. The serum CCL5 level in DJD-TMJ subjects was significantly higher than that in the control subjects. Multivariate analyses indicated an association between an augmented CCL5 level and the rate of bone metabolism, especially in relatively young DJD-TMJ subjects without other systemic symptoms. A principal component analysis of serum markers and our pharmacological experiment using a postmenopausal model of ovariectomized rats suggested that an augmented serum CCL5 level specifically reflected DJD-TMJ and that covert changes in the rate of bone metabolism predisposed individuals to DJD-TMJ.

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.

Perioperative oral management is widely recognized in the healthcare system of Japan. Conventionally, the surgeon refers patients with oral problems to a dental or oral surgery clinic in the hospital. However, frequent in-house referrals were found to increase the number of incoming patients resulting in unsustainable situations due to an insufficient workforce. In 2011, the Center for Perioperative Medicine was established at our hospital to function as a management gateway for patients scheduled to undergo surgery under general anesthesia. The “oral triage” system, wherein a dental hygienist conducts an oral screening to select patients who need preoperative oral hygiene and functional management, was established in 2012. A total of 37,557 patients who underwent surgery at our hospital from April 2010 to March 2019 (two years before and seven years after introducing the system) were evaluated in this study. The sustainability and effectiveness of introducing the system were examined in 7715 cancer surgery patients. An oral management intervention rate of 20% and a significant decrease in the incidence of postoperative pneumonia (aOR = 0.50, p = 0.03) indicated that this system could be useful as a sustainable and developmental oral management strategy to manage surgical patients with minimal human resources.

Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by tumorigenesis and physical deformities. Although more than 50 clinical manifestations have been described, only two major criteria or one major and two minor criteria are necessary for diagnosis. The most frequently observed manifestation in the oral and the maxillofacial region is an odontogenic keratocyst. In this study, we describe a 14-year-old boy with a diagnosis of NBCCS who presented with a central odontogenic fibroma (COF) in the mandible. This report highlights the importance of precise diagnosis and the choice of surgical method for COF.

A 42-year-old man diagnosed with acute myeloid leukemia complained of progressive swelling of the right side of his face with pain 11 days after the third cycle of consolidation therapy with high-dose arabinosylcytosine-cytarabine. Head and neck magnetic resonance imaging showed a mass lesion in his right maxillary sinus with parapharyngeal involvement, which included the right masseter muscle, intraorbital involvement, and an abscess in his brain. Chest computed tomography revealed peribronchial small nodules in his right upper lobe and a necrotic tumor in his right lower lobe. Molds identified as Cunninghamella bertholletiae were isolated from the necrotic ulcer. According to these results, chemotherapy for leukemia was discontinued. High-dose liposomal amphotericin (10 mg/kg/day) was initiated. Because renal dysfunction occurred, the dosage was decreased to 6 mg/kg and combined with 150 mg/day micafungin. Debridement of necrotic tissue in the right maxillary sinus and establishment of the fenestration between the sinus and oral cavity were performed. Subsequently, brain and lung lesions were surgically removed. Rhinocerebral mucormycosis was successfully treated without relapse over 3 years by a 112-day course of intravenous anti-fungal therapy and 223-day course of terbinafine and partial surgical removal, respectively, to maintain masticatory and ocular functions. To our knowledge, there has been no other report of a long-term survival case of rhinocerebral mucormycosis due to C. bertholletiae.

In April 2012, perioperative oral management (POM) was approved for inclusion in the national health insurance system of Japan to prevent the occurrence of pneumonia, a major complication in cancer patients. The subsequent decrease in the incidence of postoperative pneumonia indicated the prophylactic effect of POM. The constant increase in health expenditure necessitates a cost-effectiveness analysis. In addition, the effect of reducing healthcare costs owing to health technologies must be evaluated. In the present multi-institutional study, the cost-effectiveness analysis of POM was conducted by comparing the incidence of postoperative pneumonia and the healthcare costs between patients who received surgery for malignant tumors before (n = 11,886) and after (n = 13,668) the introduction of POM. Additionally, the effect of reducing healthcare costs was evaluated. Reductions in the number of patients who developed pneumonia, duration of hospitalization, and number of deaths were observed after the introduction of POM. The incremental cost-effectiveness ratio was 111,927 yen, hence the prevention of postoperative pneumonia needs 111,927 yen per patient in healthcare costs. Consequently, a maximum reduction of 250,368,129 yen in healthcare costs was observed between the incremental costs for pneumonia treatment and the cost of POM. These findings indicate that improvements in cost-effectiveness can be expected in the future through the development of procedure and system for POM.

Bilateral sagittal split ramus osteotomy (BSSRO) is commonly used in orthognathic surgery. Although abnormal sensation in areas that are innervated by the inferior alveolar nerve is a well-known neurological complication of mandibular osteotomy, facial palsy is rare postoperatively. We present a case of peripheral facial palsy that developed the day after BSSRO to correct a mandibular protrusion in a 42-year-old man. Oral prednisolone was begun on the second day postoperatively, and was gradually tapered off over time. One month after operation, he had gradually recovered all movements in his right facial muscle and, after two months, had completely recovered without residual asymmetry. Possible causes of the palsy were compression of the facial nerve as a result of the insertion of a retractor around the posterior border of the ramus, and postoperative oedema. Peripheral facial palsy after BSSRO should be considered a rare, but possible, complication and as such, should be mentioned in consent forms.

This study aimed to retrospectively evaluate the efficacy and safety of laser treatment of oral vascular lesions using the multiple spot irradiation technique with a single-pulsed wave.In laser therapy for vascular lesions, heat accumulation induced by excessive irradiation can cause adverse events postoperatively, including ulcer formation, resultant scarring, and severe pain. To prevent heat accumulation and side effects, we have applied a multiple pulsed spot irradiation technique, the so-called "leopard technique" (LT) to oral vascular lesions. This approach was originally proposed for laser treatment of nevi. It can avoid thermal concentration at the same spot and spare the epithelium, which promotes smooth healing. The goal of the study was to evaluate this procedure and treatment outcomes.The subjects were 46 patients with 47 oral vascular lesions treated with the LT using a Nd:YAG laser (1064 nm), including 24 thick lesions treated using a combination of the LT and intralesional photocoagulation.All treatment outcomes were satisfactory without serious complications such as deep ulcer formation, scarring, bleeding, or severe swelling.Laser therapy with the LT is a promising less-invasive treatment for oral vascular lesions.

SUMMARY Accurate estimation of self-position is indispensable for autonomous mobile robots. Map-matching-based self-positioning is a promising method; however, adequate matching area selection is an issue to be solved. In this paper, we propose an adjustable map matching method that remedies a defect of the conventional template matching technology. The proposed method was evaluated experimentally, and the results confirmed the advantages of the proposed method.

This study was designed to evaluate the effect of recombinant human fibroblast growth factor-2 (rhFGF-2) on the amount and period of new bone formation in rabbit mandibular distraction models using beta-tricalcium phosphate (beta-TCP) as a bone graft substitute. Sixteen male Japanese White rabbits were divided into the following four experimental groups: 1, distraction alone; 2, distraction with beta-TCP granules; 3, distraction with rhFGF-2 (25 microg/50 microL) injected into beta-TCP granules; and 4, distraction with rhFGF-2 (100 microg/50 microL) injected into beta-TCP granules. The bones were harvested at 4 weeks after the operation and examined using soft radiography, micro-computed tomography (micro-CT), and peripheral quantitative computed tomography (pQCT). The dissected mandibles were stained using the Villanueva bone staining method, and the amount of new bone formed, bioresorption of beta-TCP, and new blood vessel formation were morphometrically calculated using bone histomorphometry. Radiopaque areas were observed more frequently in the distracted area of groups 3 and 4. Micro-CT analysis revealed partial new bone formation in the central region of the distracted area in groups 3 and 4. pQCT analysis revealed increased bone mineral density in groups 3 and 4. Histomorphometric analysis revealed increased newly formed bone and blood vessel areas in groups 3 and 4. In group 4, the number of osteoclasts around the beta-TCP granules had significantly increased. The present findings suggested that the combined use of rhFGF-2 and beta-TCP reduced the treatment period for distraction osteogenesis and accelerated the formation of a new high-quality bone.

A case of surgical ciliated cyst after Le Fort I osteotomy is described. A 32-year-old man who had undergone Le Fort I osteotomy in 1992 was referred to our hospital because of swelling in the left cheek. Radiographic and computed tomographic examinations showed a unilocular cystic lesion in the left side of the maxilla. The lesion was diagnosed as a maxillary cyst. We treated the lesion surgically. The lesion and thin bony wall between the cystic cavity and maxillary sinus were removed, so that the bony cavity commuted with the inferior nasal meatus. The postoperative course was uneventful, and there was no evidence of recurrence 12 months after surgery. On the basis of the clinical course and histopathological findings of the surgical specimen (i.e., the cyst had a thick fibrous wall lined by stratified ciliated columnar or cuboidal epithelium), the lesion was diagnosed as a surgical ciliated cyst.

Objectives We investigated distracted keratinized epithelium to elucidate any proliferative and degenerated changes and to estimate the stability of the gingival tissues in mandibular distraction osteogenesis in a rabbit model. Study design Twenty-two rabbits were subjected to unilateral vertical osteotomy. After a latency period of 4 days, devices were activated 3, 6, and 10 days at a rate of 1 mm/day. We additionally investigated the recovery of the distracted gingiva in consolidation periods for 3 weeks. The animals were examined by histologic and immunohistologic methods using proliferating cell nuclear antigen (PCNA), single-stranded DNA (ssDNA), and keratin. Results Atrophy of distracted gingiva was observed characterized by loss of rete ridges, acanthosis, vacuolation in the prickle cell layer, and cleavage of the keratin layer. Proliferating cell nuclear antigen–positive cells and ssDNA-positive cells were observed in the basal and prickle layers, respectively. During consolidation periods, slight recovery of rete ridges, thinning of the keratin layer, and immature epithelial layer was observed. Conclusions Proliferative and degenerated changes occurred to compensate for cell death and distracted space. Thickness of gingival tissues was maintained by high mitotic activity and delay in the rate of cell maturation. Immature epithelial layer was related to sensitive and weak resistance against various stimulating factors, such as cleavage of the keratin layer among distracted gingival tissues.

We report a rare case of Warthin tumor accompanied by bone formation. A 57-year-old woman with pus discharge in the right mandibular gingiva visited our hospital in August 1995. Several fistulas in the right mandibular gingiva and a rough-surfaced tumor 1.5 cm in diameter on the right side of the tongue were found. The clinical diagnosis was osteomyelitis of the mandible and tongue cancer. Sequestrotomy of the mandible and partial glossectomy were performed in October 1995. At that time, a computed tomographic (CT) scan showed 1-cm-diameter lesion in the right parotid gland; however, she hesitated to undergo surgery. In April 2001, a CT scan revealed a bilateral mass 1.2 cm in diameter near the parotid glands, and the mass in the right parotid gland increased to 2 cm in diameter and possessed a small calcified granule inside. 99mTc scintigraphy of the salivary glands showed a hot spot in the both parotid glands, consistent with the tumor. In March 2002, she underwent extirpation of the tumors arising in the both parotid glands. Histopathological examination showed a typical Warthin tumor appearance, with bone formation in the hyalinized structure of the tumor. At present, the patient has no evidence of disease.

Objective To examine neurosensory changes in the chin following bilateral sagittal split ramus osteotomy (BSSRO) using the heat flux technique. Study design Twelve healthy adults (C-group) and 23 patients undergoing BSSRO (P-group) were examined. The warm sense threshold (WHF) and cold sense threshold (CHF) in the chin of these patients were measured by the heat flux technique. In the P-group, touch sensation also was measured with a visual analog scale (VAS) and the Semmes-Weinstein monofilament test (SW test). Results Both WHF and CHF were significantly larger in the P-group than in the C-group ( P = .024). Touch sensation (VAS and SW test) were damaged in some patients of the P-group. However, no correlation was revealed between thermal sensation (WHF and CHF) and touch sensation (VAS and SW test) in the P-group. Conclusions These results suggest that the thermal sensation in the chin was damaged after BSSRO. The heat flux technique appears to be one of the useful methods for the examination of neurosensory disturbance in the chin.

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.

Trichorhinophalangeal syndrome (TRPS) type I is characterized by slowly progressing systemic osseous dysplasia, exhibiting craniofacial and other skeletal deformities. However, there have been few reports describing this syndrome after undergoing orthognathic surgery. In this report, we present a patient with TRPS I who successfully underwent orthognathic surgery. In addition, we examined the skeletal stability of the patient for 2 years after the surgery.

Soft tissue changes in the chin were compared between patients undergoing sagittal split ramus osteotomy (SSRO) for mandibular setback with and without reduction genioplasty. Twenty patients with symmetrical skeletal Class III malocclusion were examined. Twelve underwent SSRO alone (group I), and 8 underwent SSRO combined with reduction genioplasty (group II). Reduction genioplasty was performed by two horizontal osteotomies, removing the bony wedge, and posterosuperior movement of the inferior segment of the chin. Lateral cephalograms were obtained preoperatively and 6 months postoperatively. Pre- to postoperative changes in the positions of hard-tissue points (B-point [B], pogonion [Ng], and menton [Me]) and soft-tissue B-point [sB], soft-tissue pogonion [sPog], and menton [sMe] were measured on the cephalograms. The ratio of the soft tis-sue movement to the hard tissue movement was also calculated. Though superior movement of Me was significantly larger in group II than in group I, there were no significant differences in the superior movement ratios of sMe to Me between the two groups. However, the posterior movement ratio of sPog to Pog was significantly larger in group I than in group H. These results suggest that the reduction genioplasty performed by two horizontal osteotomies, removing the bony wedge, and posterosuperior movement of the inferior segment of the chin had little effect on the posterior movement of the chin. Therefore, in patients with skeletal class III malocclusion, reduction genioplasty should be applied mainly to vertical shortening of the chin.

Here we report that successful bone formation with a vascular flap inside a cylindrical mold was induced from fat tissue with the use of recombinant human bone morphogenetic protein-2 in rats. Fat tissue connected to blood vessels was prepared to fit into the mold and implanted intramuscularly into the hind leg in Wistar rats. RhBMP-2 (20 μg) was applied in a collagen sheet previously placed on the inside surface of the mold. Bone formation was confirmed radiologically and morphologically at 2, 4, and 8 weeks after the surgery. In the control group without rhBMP-2 or the group with ligation of the blood vessels before the implantation, bone formation was not observed. Our success in bone formation having a definite size, shape, and blood supply may lead to a therapeutic approach to effective bone reconstitution. The present study is the first report on bone induction from fat tissue by rhBMP-2 in vivo.

Gnathodiaphyseal dysplasia (GDD) is a syndrome characterized by bone fragility, sclerosis of tubular bones, and cemento-osseous lesions of jawbones. Although some cases of this syndrome exist in families with autosomal dominant inheritance, the underlying gene has never been identified. We analyzed a large four-generation family with GDD by linkage analysis using genomic DNA from nine affected and six nonaffected family members. A genome-wide search using a set of highly polymorphic microsatellite markers showed evidence for linkage to chromosome 11p14.3-15.1. Two-point linkage analysis of microsatellite markers spanning this locus resulted in a maximum logarithm of odds (LOD) score of 2.70 with a recombination fraction (theta) of 0 at D11S1755, D11S1759, and D11S915, and a maximum LOD score of 3.01 at D11S4114 was obtained in multipoint linkage analysis. Haplotype analysis detected no recombination between GDD and six closely linked markers (D11S928, D11S1755, D11S4114, D11S1759, D11S915, and D11S929) and established the candidate interval of 8.7 cM on chromosome 11p for GDD. Although GDD has been considered to be a variation of osteogenesis imperfecta (MIM 166260), our results indicate that this syndrome is a new and distinct disease entity from other systemic bone diseases. Furthermore, these genetic markers are useful for presymptomatic diagnosis of GDD in some families and for identification of the GDD gene.

Screening of a human dental pulp cells cDNA library with mouse Msx-1 and Msx-2 cDNA probes led to the isolation of human MSX-2. Sequence and Northern Blotting analysis revealed that two different type of transcripts due to the length of 3' untranslated region were expressed in the human dental pulp cells.

We had demonstrated that single nucleotide polymorphism (787TC) in the tissue-nonspecific ALP (TNSALP) gene was associated with the bone mineral density (BMD). BMD was the lowest among TNSALP 787T homozygotes (TT-type) and highest among TNSALP 787TC homozygotes (CC-type) in postmenopausal women. In the present study, we investigated the effects of the TNSALP genotype on associations among serum bonespecific alkaline phosphatase (BAP), serum calcium, and phosphorus in healthy young Japanese subjects.Young healthy adult subjects (n=193) were genotyped for the polymorphism, and we measured the levels of serum BAP, serum calcium, and phosphorus. Dietary nutrient intakes were calculated based on 3-day food records before the day of blood examinations.Grouped by the TNSALP genotype, a significant negative correlation between serum BAP and phosphorus was observed in 787TC homozygotes (CC-type), but not in heterozygotes (TCtype), nor in 787T homozygotes (TT-type).In the present study, we revealed that the single nucleotide polymorphism 787TC in the TNSALP gene had effects on the correlation between serum BAP and phosphorus in young adult subjects. These results suggest that variation in TNSALP may be an important determinant of phosphate metabolism. Our data may be useful for planning strategies to prevent osteoporosis.

Zinc oxide (ZnO) films were deposited on a soft polyimide sheet substrate by radio frequency sputtering with a ZnO powder target, and the films' crystal orientations and residual stress were investigated using x-ray diffraction as a function of substrate temperature. C-axis oriented ZnO films were achieved using this ZnO powder target method. The ZnO films exhibited high compressive residual stresses between −0.7 and −1.4 GPa. Finally, the authors examined the strength of the obtained film by applying tensile bending loads. No cracks were observed on the surfaces of the ZnO films after a bending test using cylinders with diameters >25 mm. After a bending test using a cylinder with a diameter of 19 mm, large cracks were formed on the films. Therefore, the authors concluded that the tensile bending strength of the obtained films was greater than ∼420 MPa.

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.

A cDNA for the rat bone morphogenetic protein (BMP) type IA receptor (BMPR-IA) was isolated from a dental pulp cell cDNA library. The rat BMPR-IA cDNA encodes a protein of 532 amino acids with a single transmembrane domain and a putative serine/threonine kinase domain. The overall amino acid sequence identity between the rat and human BMPR-IA was 97 %. Reverse transcriptase-polymerase chain reaction analysis revealed that BMPR-IA mRNA was highly expressed in the BMP-induced bone forming tissues throughout the stages tested.

BMPは強力な骨誘導活性を持つ, TGF-βスーパーファミリーに属するタンパク質である。著者はPCRによって得たマウスBMP-2をプローブとして用い, ヒト胎盤cDNAライブラリーからhBMP-4のほぼ全長と思われるcDNAをクローニングした。このcDNAは従来報告されていたものと一部その塩基配列を異にしていた。このcDNAをバキュロウイルスの一種であるAcNPVが有する強力なポリヘドリンプロモーターの下流に接続し, 真核細胞である昆虫細胞内で組み換え型hBMP-4を発現させることを試みた。大量に発現したhBMP-4はそのほとんどが細胞内に蓄積しており, 培養上清中への分泌はほとんどなく, 発現量は72時間後にピークに達した。ウェスタンブロッティングの結果では天然型のものと比べて異なる分子量の位置に泳動された。これらの結果から, hBMP-4の昆虫細胞内での翻訳後修飾については, 哺乳類の系と異なっている可能性が示唆された。

骨形成タンパク質 (BMP) は骨誘導を起こさせる強力なサイトカインであり, 骨誘導能を持つ骨補填材料への利用が期待されている。その臨床応用へ向けての遺伝子工学的アプローチの第一歩として, 今回, 著者らはヒト骨肉腫由来細胞株MG63より作製したcDNA-mRNA混合物から, polymerase chain reaction (PCR) 法により, 2種のプライマーを用いてヒトBMP -2およびヒトBMP-4のcDNAの増幅, 単離を試みた。その結果ヒトBMP-2の成熟活性領域をコードすると思われる塩基配列をもつ4つのクローンの増幅に成功した。このうちの1つのcDNAについて, PCR法により3'末端に終止コドンを付加し, またプロ鎖をコードする領域に存在した塩基欠失部分の削除を行った。このようにしてつくられたcDNAには, なおいくつかの塩基の置換もあったが, 成熟活性領域の塩基をアミノ酸に翻訳すると天然のものと全く同じであり, hBMP-2の成熟活性部位の全領域をコードするcDNAを得ることができた。

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. Ccr1(-/-) mice have fewer and thinner trabecular bones and low mineral bone density in cancellous bones. The lack of CCR1 affects the differentiation and function of osteoblasts. Runx2, Atf4, Osteopontin, and Osteonectin were significantly up-regulated in Ccr1(-/-) mice despite sustained expression of Osterix and reduced expression of Osteocalcin, suggesting a lower potential for differentiation into mature osteoblasts. In addition, mineralized nodule formation was markedly disrupted in cultured osteoblastic cells isolated from Ccr1(-/-) mice. Osteoclastogenesis induced from cultured Ccr1(-/-) bone marrow cells yielded fewer and smaller osteoclasts due to the abrogated cell-fusion. Ccr1(-/-) osteoclasts exerted no osteolytic activity concomitant with reduced expressions of Rank and its downstream targets, implying that the defective osteoclastogenesis is involved in the bone phenotype in Ccr1(-/-) mice. The co-culture of wild-type osteoclast precursors with Ccr1(-/-) osteoblasts failed to facilitate osteoclastogenesis. This finding is most likely due to a reduction in Rankl expression. These observations suggest that the axis of CCR1 and its ligands are likely to be involved in cross-talk between osteoclasts and osteoblasts by modulating the RANK-RANKL-mediated interaction.