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1.
Proc Natl Acad Sci U S A ; 116(29): 14714-14723, 2019 07 16.
Article in English | MEDLINE | ID: mdl-31262819

ABSTRACT

Conventional dendritic cells (cDCs) derive from bone marrow (BM) precursors that undergo cascades of developmental programs to terminally differentiate in peripheral tissues. Pre-cDC1s and pre-cDC2s commit in the BM to each differentiate into CD8α+/CD103+ cDC1s and CD11b+ cDC2s, respectively. Although both cDCs rely on the cytokine FLT3L during development, mechanisms that ensure cDC accessibility to FLT3L have yet to be elucidated. Here, we generated mice that lacked a disintegrin and metalloproteinase (ADAM) 10 in DCs (Itgax-cre × Adam10-fl/fl; ADAM10∆DC) and found that ADAM10 deletion markedly impacted splenic cDC2 development. Pre-cDC2s accumulated in the spleen with transcriptomic alterations that reflected their inability to differentiate and exhibited abrupt failure to survive as terminally differentiated cDC2s. Induced ADAM10 ablation also led to the reduction of terminally differentiated cDC2s, and restoration of Notch signaling, a major pathway downstream of ADAM10, only modestly rescued them. ADAM10∆DC BM failed to generate cDC2s in BM chimeric mice with or without cotransferred ADAM10-sufficient BM, indicating that cDC2 development required cell-autonomous ADAM10. We determined cDC2s to be sources of soluble FLT3L, as supported by decreased serum FLT3L concentration and the retention of membrane-bound FLT3L on cDC2 surfaces in ADAM10∆DC mice, and by demonstrating the release of soluble FLT3L by cDC2 in ex vivo culture supernatants. Through in vitro studies utilizing murine embryonic fibroblasts, we determined FLT3L to be a substrate for ADAM10. These data collectively reveal cDC2s as FLT3L sources and highlight a cell-autonomous mechanism that may enhance FLT3L accessibility for cDC2 development and survival.


Subject(s)
ADAM10 Protein/metabolism , Amyloid Precursor Protein Secretases/metabolism , Cell Differentiation/immunology , Dendritic Cells/physiology , Membrane Proteins/metabolism , Spleen/cytology , ADAM10 Protein/genetics , ADAM10 Protein/immunology , Amyloid Precursor Protein Secretases/genetics , Amyloid Precursor Protein Secretases/immunology , Animals , Bone Marrow Transplantation , Cell Membrane/immunology , Cell Membrane/metabolism , Cell-Derived Microparticles/immunology , Cell-Derived Microparticles/metabolism , DNA-Binding Proteins/genetics , Female , Fibroblasts , Hematopoietic Stem Cells/physiology , Immunity, Cellular , Male , Membrane Proteins/genetics , Membrane Proteins/immunology , Mice , Mice, Inbred C57BL , Mice, Knockout , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Spleen/immunology , Transplantation Chimera
2.
Dev Biol ; 464(2): 137-144, 2020 08 15.
Article in English | MEDLINE | ID: mdl-32565279

ABSTRACT

Tissue macrophages, which are ubiquitously present innate immune cells, play versatile roles in development and organogenesis. During development, macrophages prune transient or unnecessary synapses in neuronal development, and prune blood vessels in vascular development, facilitating appropriate tissue remodeling. In the present study, we identified that macrophages contributed to the development of pupillary morphology. Csf1op/op mutant mice, in which ocular macrophages are nearly absent, exhibited abnormal pupillary edges, with abnormal protrusions of excess iris tissue into the pupillary space. Macrophages located near the pupillary edge engulfed pigmented debris, which likely consisted of unnecessary iris protrusions that emerge during smoothening of the pupillary edge. Indeed, pupillary edge macrophages phenotypically possessed some features of M2 macrophages, consistent with robust tissue engulfment and remodeling activities. Interestingly, protruding irises in Csf1op/op mice were only detected in gaps between regressing blood vessels. Taken together, our findings uncovered a new role for ocular macrophages, demonstrating that this cell population is important for iris pruning during development.


Subject(s)
Macrophages/metabolism , Pupil , Animals , Macrophage Colony-Stimulating Factor/genetics , Macrophage Colony-Stimulating Factor/metabolism , Macrophages/cytology , Mice , Mice, Mutant Strains
3.
J Bone Miner Metab ; 39(3): 372-384, 2021 May.
Article in English | MEDLINE | ID: mdl-33200254

ABSTRACT

INTRODUCTION: Osteonecrosis of the jaw (ONJ) occurring after invasive dental treatment often adversely affects patients' activities of daily living. Long-term administration of strong anti-bone resorptive agents such as bisphosphonates prior to invasive dental treatment is considered an ONJ risk factor; however, pathological mechanisms underlying ONJ development remain unclear. MATERIALS AND METHODS: We developed an ONJ mouse model in which a tooth is extracted during treatment with the bisphosphonate zoledronate. RESULTS: We observed induction of apoptosis in osteocytes, resulting in formation of empty lacunae in jaw bones at sites of tooth extraction but not in other bones of the same mice. We also observed elevated levels of inflammatory cytokines such as TNFα, IL-6 and IL-1 in jaw bone at the extraction site relative to other sites in zoledronate-treated mice. We also report that treatment in vitro with either zoledronate or an extract from Porphyromonas gingivalis, an oral bacteria, promotes expression of inflammatory cytokines in osteoclast progenitor cells. We demonstrate that gene-targeting of either TNFα, IL-6 or IL-1 or treatment with etanercept, a TNFα inhibitor, or a neutralizing antibody against IL-6 can antagonize ONJ development caused by combined tooth extraction and zoledronate treatment. CONCLUSIONS: Taken together, the cytokine storm induced by invasive dental treatment under bisphosphonate treatment promotes ONJ development due to elevated levels of inflammatory cytokine-producing cells. Our work identifies novel targets potentially useful to prevent ONJ.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw/pathology , Cytokines/metabolism , Inflammation Mediators/metabolism , Tooth Extraction/adverse effects , Zoledronic Acid/adverse effects , Animals , Apoptosis/drug effects , Bisphosphonate-Associated Osteonecrosis of the Jaw/microbiology , Bone Density Conservation Agents/adverse effects , Cell Transdifferentiation/drug effects , Cytokine Release Syndrome/complications , Disease Models, Animal , Female , Macrophages/drug effects , Macrophages/metabolism , Macrophages/pathology , Mice, Inbred C57BL , Models, Biological , Osteoclasts/drug effects , Osteoclasts/pathology , Osteocytes/drug effects , Osteocytes/pathology , Osteogenesis/drug effects , Porphyromonas gingivalis/physiology , Risk Factors
4.
Bull Tokyo Dent Coll ; 62(4): 253-260, 2021 Dec 04.
Article in English | MEDLINE | ID: mdl-34776477

ABSTRACT

When pain adversely affects a patient's activities its diagnosis needs to be fast and accurate to allow effective treatment to be commenced as soon as possible. Difficulties may be found in achieving this, however, in elderly patients with age-associated cognitive decline, as they may not be capable of properly understanding or recalling their symptoms. The present case concerns a 77-year-old woman who presented with the chief complaint of pain in the right mandible persisting throughout the day, and severe enough to necessitate her lying down in bed all day long. The use of open-ended questions followed by a structured interview focused on pain with closed-ended questions revealed that she experienced paroxysms of pain throughout the day and that she was afraid of its occurrence. Based on these findings, the diagnosis was trigeminal neuralgia. Carbamazepine decreased the pain with no side effects. The patient continued taking carbamazepine for 3 months, during which time she was closely monitored for adverse reactions. No side effects, such as drowsiness or dizziness, were observed, however, and the pain subsided completely with no recurrence, even after cessation of carbamazepine.


Subject(s)
Trigeminal Neuralgia , Aged , Carbamazepine/therapeutic use , Female , Humans , Treatment Outcome , Trigeminal Neuralgia/diagnosis , Trigeminal Neuralgia/drug therapy
5.
Bull Tokyo Dent Coll ; 60(4): 233-239, 2019 Dec 10.
Article in English | MEDLINE | ID: mdl-31761891

ABSTRACT

The need for flexible thermoplastic denture base materials has increased due to patient demand for better esthetic outcomes. Designs aimed at improving esthetic outcomes can cause difficulties for prosthodontists, however, from the viewpoint of function and maintenance. Therefore, the purpose of this study was to investigate vertical displacement in unilateral extension base denture models, comparing that obtained by flexible removable dentures with that by conventional metal clasp dentures. Models of unilateral extension base flexible removable dentures for mandibular defects were prepared. Periodontal ligament and jaw mucosa were simulated using a silicone impression material. Four types of flexible removable denture, with or without a metal rest, and two metal clasp dentures made of acrylic resin as a conventional design were used as dental prostheses. The amount of vertical displacement in the defect areas was measured under a load of 50 N at the first and second molars. Among the 6 types of dentures investigated, the amount of vertical displacement was greater with flexible removable dentures than with metal clasp dentures. This vertical displacement tended to decrease significantly, however, with the use of a metal rest with the flexible removable dentures. Esteshot with a metal rest, in particular, showed the smallest amount of displacement in the flexible removable dentures (first molar, 0.265±0.007 mm; second molar, 0.423±0.008 mm). These results indicate the importance of the application of rests in unilateral extension base flexible removable dentures. It may be useful to employ a metal rest in conjunction with a flexible removable denture to reduce load on the underlying mucosa, as is done with conventional partial dentures.


Subject(s)
Denture, Partial, Removable , Denture Bases , Denture Design , Denture, Partial , Esthetics, Dental , Humans
6.
Differentiation ; 92(5): 270-280, 2016 12.
Article in English | MEDLINE | ID: mdl-27178356

ABSTRACT

Mesenchymal stem cells (MSCs) are defined as non-hematopoietic, plastic-adherent, self-renewing cells that are capable of tri-lineage differentiation into bone, cartilage or fat in vitro. Thus, MSCs are promising candidates for cell-based medicine. However, classifications of MSCs have been defined retrospectively; moreover, this conventional criterion may be inaccurate due to contamination with other hematopoietic lineage cells. Human MSCs can be enriched by selection for LNGFR and THY-1, and this population may be analogous to murine PDGFRα+Sca-1+ cells, which are developmentally derived from neural crest cells (NCCs). Murine NCCs were labeled by fluorescence, which provided definitive proof of neural crest lineage, however, technical considerations prevent the use of a similar approach to determine the origin of human LNGFR+THY-1+ MSCs. To further clarify the origin of human MSCs, human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs) were used in this study. Under culture conditions required for the induction of neural crest cells, human ESCs and iPSCs-derived cells highly expressed LNGFR and THY-1. These LNGFR+THY-1+ neural crest-like cells, designated as LT-NCLCs, showed a strong potential to differentiate into both mesenchymal and neural crest lineages. LT-NCLCs proliferated to form colonies and actively migrated in response to serum concentration. Furthermore, we transplanted LT-NCLCs into chick embryos, and traced their potential for survival, migration and differentiation in the host environment. These results suggest that LNGFR+THY-1+ cells identified following NCLC induction from ESCs/iPSCs shared similar potentials with multipotent MSCs.


Subject(s)
Cell Differentiation/genetics , Induced Pluripotent Stem Cells/cytology , Mesenchymal Stem Cells/cytology , Nerve Tissue Proteins/genetics , Receptors, Nerve Growth Factor/genetics , Thy-1 Antigens/genetics , Animals , Cell Culture Techniques , Cell Lineage/genetics , Cell Proliferation/genetics , Chick Embryo , Human Embryonic Stem Cells , Humans , Mesenchymal Stem Cells/metabolism , Mice , Neural Crest/cytology , Neural Crest/growth & development
7.
Odontology ; 105(2): 262-266, 2017 Apr.
Article in English | MEDLINE | ID: mdl-27368962

ABSTRACT

Oral lichen planus is a chronic inflammatory mucocutaneous disease. Topical use of steroids and other immuno-modulating therapies have been tried for this intractable condition. Nowadays, tacrolimus ointment is used more commonly as a choice for treatment. However, a number of discussions have taken place after tacrolimus was reported to be carcinogenic. This report describes a patient who applied tacrolimus ointment to the lower lip after being diagnosed with oral lichen planus in 2008, and whose lesion developed squamous cell carcinoma in 2010. Since the relationship between tacrolimus and cancer development has been reported in only a few cases, including this case report, the clinician must be careful selecting tacrolimus as a second-line treatment for oral lichen planus.


Subject(s)
Carcinoma, Squamous Cell/chemically induced , Carcinoma, Squamous Cell/diagnosis , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Lichen Planus, Oral/diagnosis , Lichen Planus, Oral/drug therapy , Mouth Neoplasms/chemically induced , Mouth Neoplasms/diagnosis , Tacrolimus/administration & dosage , Tacrolimus/adverse effects , Administration, Topical , Biopsy , Candidiasis, Oral/diagnosis , Candidiasis, Oral/drug therapy , Carcinoma, Squamous Cell/surgery , Diagnosis, Differential , Diagnostic Errors , Humans , Male , Middle Aged , Mouth Neoplasms/surgery , Surgical Flaps
8.
Mol Pain ; 12: 1744806916683182, 2016.
Article in English | MEDLINE | ID: mdl-28256933

ABSTRACT

Background Fentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity. Results This study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine. We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test. Conclusions Fentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment.


Subject(s)
Fentanyl/therapeutic use , Glucuronosyltransferase/genetics , Orthognathic Surgery , Polymorphism, Single Nucleotide/genetics , Adolescent , Adult , Analgesics, Opioid/therapeutic use , Female , Genotype , Humans , Male , Middle Aged , Morphine/therapeutic use , Pain Measurement/methods , Pain Threshold/drug effects , Pain, Postoperative/drug therapy , Young Adult
9.
BMC Oral Health ; 16: 22, 2016 Feb 18.
Article in English | MEDLINE | ID: mdl-26888092

ABSTRACT

BACKGROUND: The purpose of the present study was to examine the in vitro responses of ERM cells under the combination of centrifugal and compression forces, in terms of their expression of HSP70 mRNA. METHODS: The ERM cells were positive for CK19 indicating that they were derived from the odontogenic epithelium. Cultured ERM cells were applied centrifugal force and compressing force at one to three times as mechanical forces. After addition of forces, cells were observed using scanning electron microscope (SEM) and were measured expression of HSP70 mRNA by RT-PCR. RESULTS: SEM observations showed the cells were flattened immediately after the application of mechanical force, but nuclear protrusions recovered the same as the control 3 h later. A significantly higher expression of HSP70 mRNA was observed in ERM cells under mechanical force compared with the control, but it gradually decreased with time. No accumulation of HSP70 mRNA expression occurred with intermittent force. However, the expression of HSP70 mRNA with intermittent force repeated 3 times was significantly higher compared with intermittent force applied only once or twice. CONCLUSIONS: These findings suggest that ERM cells express HSP70 mRNA in response to mechanical force, and that intermittent force maintains the level of HSP70 mRNA expression.


Subject(s)
Epithelial Cells/metabolism , HSP70 Heat-Shock Proteins/metabolism , Microscopy, Electron, Scanning , Animals , Cells, Cultured , Epithelial Cells/ultrastructure , RNA, Messenger/metabolism , Stress, Mechanical , Swine
10.
Microb Pathog ; 79: 41-6, 2015 Feb.
Article in English | MEDLINE | ID: mdl-25602787

ABSTRACT

This study aimed to assess changes in antimicrobial susceptibilities of subgingival bacteria in acute periodontal lesions following systemic administration of a new-generation fluoroquinolone, sitafloxacin and to monitor the occurrence and fate of quinolone low-sensitive strains. Patients with acute phase of chronic periodontitis were subjected to microbiological assessment of their subgingival plaque samples at baseline (A1). Sitafloxacin was then administered systemically (100 mg/day for 5 days). The microbiological examinations were repeated one week after administration (A2). Susceptibilities of clinical isolates from acute sites to various antimicrobials were determined using broth and agar dilution methods. At A2, subgingival bacteria with low sensitivity to levofloxacin were identified in four patients, and they were subjected to a follow-up microbiological examination at on the average 12 months after sitafloxacin administration (A3). The patients received initial and supportive periodontal therapy during the period A2 to A3. From the examined subgingival sites, 8 and 19 clinical isolates were obtained at A2 and A3, respectively. Some Streptococcus strains isolated at A2 were found to be resistant to levofloxacin (MIC 16-64 µg/ml), azithromycin (MIC 2->128 µg/ml) or clarithromycin (MIC 1->32 µg/ml). At A3, isolated streptococci were highly susceptible to levofloxacin (MIC 0.5-2 µg/ml), while those resistant to azithromycin or clarithromycin were still isolated. It is suggested that the presence of the quinolone low-sensitive strains in initially acute lesions after sitafloxacin administration was transient, and they do not persist in the subgingival milieu during the periodontal therapy.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Bacteria/drug effects , Dental Plaque/microbiology , Drug Resistance, Bacterial , Fluoroquinolones/therapeutic use , Periodontitis/drug therapy , Periodontitis/microbiology , Bacteria/isolation & purification , Humans , Longitudinal Studies , Microbial Sensitivity Tests
11.
Microb Pathog ; 71-72: 1-7, 2014.
Article in English | MEDLINE | ID: mdl-24747615

ABSTRACT

The aim of this study was to assess the effect(s) of systemic administration of sitafloxacin on subgingival microbial profiles of acute periodontal lesions. Antimicrobial susceptibility of clinical isolates was also investigated. Patients with acute phases of chronic periodontitis were subjected to clinical examination and microbiological assessment of their subgingival plaque samples by culture technique. Sitafloxacin was then administered (100 mg/day for 5 days) systemically. The clinical and microbiological examinations were repeated 6-8 days after administration. Susceptibilities of clinical isolates to various antimicrobials were determined using the broth and agar dilution methods. From the sampled sites in 30 participants, a total of 355 clinical isolates (34 different bacterial species) were isolated and identified. Parvimonas micra, Prevotella intermedia and Streptococcus mitis were the most prevalent cultivable bacteria in acute sites. Systemic administration of sitafloxacin yielded a significant improvement in clinical and microbiological parameters. Among the antimicrobials tested, sitafloxacin was the most potent against the clinical isolates with an MIC90 of 0.12 µg/ml at baseline. After administration, most clinical isolates were still highly susceptible to sitafloxacin although some increase in MICs was observed. The results suggest that systemic administration of sitafloxacin is effective against subgingival bacteria isolated from acute periodontal lesions.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Bacteria/drug effects , Biota , Fluoroquinolones/administration & dosage , Gingiva/microbiology , Periodontitis/drug therapy , Administration, Intravenous , Adult , Aged , Female , Humans , Male , Microbial Sensitivity Tests , Middle Aged , Periodontitis/microbiology , Periodontitis/pathology
12.
Cureus ; 16(3): e56176, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38618407

ABSTRACT

Epstein-Barr virus-positive mucocutaneous ulcer (EBV-MCU) is characterized by ulcers confined to the skin and mucus membranes. EBV-MCU is an EBV-positive lymphoproliferative disorder that occurs during the use of immunosuppressive drugs such as methotrexate. We herein report a case of EBV-MCU in the maxillary gingiva. A 73-year-old woman was referred to our department in March 2021. During the initial examination, bone exposure and ulceration were observed in the extraction socket of the maxillary bilateral central incisors. The patient was taking methotrexate for rheumatoid arthritis and was unable to stop due to disease progression. In March 2021, curettage of the extraction socket of the maxillary anterior teeth and extraction of the maxillary right lateral incisor, which was difficult to preserve due to severe tooth mobility, was performed under local anesthesia. The extraction site epithelialized and healed well. Three months later, inflammation flared, and ulceration was observed. Extraction of the unsalvageable maxillary teeth and an excisional biopsy of the palatal gingiva were performed. The histopathological diagnosis was EBV-MCU. The postoperative course was uneventful, and no evidence of recurrence was found two years postoperatively; follow-up will be continued. There are many reports of EBV-MCU remission with the cessation of methotrexate treatment. In our patient, withdrawal was difficult because of the progression of rheumatoid arthritis, but remission was achieved by improving the oral cavity environment through an excisional biopsy and tooth extraction.

13.
J Craniomaxillofac Surg ; 52(6): 715-721, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38582669

ABSTRACT

This prospective cohort study aimed to investigate the impact of medication-related osteonecrosis of the jaw (MRONJ) on health-related quality of life (HRQOL) and oral health-related QOL (OHRQOL) and the association between the downstaging of MRONJ and OHRQOL. The HRQOL and OHRQOL of 44 patients with MRONJ were assessed using the SF-36v2 and the General Oral Health Assessment Index (GOHAI), respectively. Treatment was performed in accordance with the AAOMS position paper (2014). The SF-36v2 and GOHAI scores at the beginning of the survey were used to evaluate the impact of MRONJ on QOL. Potential confounders affecting the association between downstaging and QOL improvement were selected using directed acyclic graphs. Multiple regression analysis was performed to evaluate causal inferences. HRQOL scale scores declined below the national average. The three-component summary score (3CS), comprising the physical component summary (PCS), mental component summary (MCS), and role/social component summary (RCS), revealed that performance status and primary disease significantly affected the PCS and RCS (P = 0.005 and P < 0.001, respectively) and PCS and MCS (P = 0.024 and P = 0.003, respectively). The MRONJ stage did not influence the 3CS; however, OHRQOL declined in a stage-dependent manner (P = 0.005). Downstaging of MRONJ was independently associated with the improvement rate of the total GOHAI scores after adjusting for variables (P = 0.045). The HRQOL of patients with MRONJ declined; however, this may depend on the underlying disease status rather than the MRONJ stage. Improvement of the disease status can potentially predict an improvement in OHRQOL, regardless of the treatment modality.


Subject(s)
Bisphosphonate-Associated Osteonecrosis of the Jaw , Quality of Life , Humans , Male , Female , Prospective Studies , Aged , Middle Aged , Surveys and Questionnaires , Aged, 80 and over
14.
Biomolecules ; 13(8)2023 07 28.
Article in English | MEDLINE | ID: mdl-37627242

ABSTRACT

Teeth are unique and multifaceted tissues that are necessary for routine functions, such as crushing food and constructing articulated sounds, as well as for esthetic symbols [...].


Subject(s)
Signal Transduction , Tooth
15.
J Med Case Rep ; 17(1): 19, 2023 Jan 20.
Article in English | MEDLINE | ID: mdl-36658639

ABSTRACT

BACKGROUND: Orthodontic treatment involves movement of teeth by compression and resorption of the alveolar bone using orthodontic forces. These movements are closely linked to the interactions between the teeth and the periodontal tissues that support them. Owing to an increase in adults seeking orthodontic treatment, orthodontists increasingly encounter patients with periodontal diseases, in whom orthodontic treatment is contraindicated. In rare cases, periodontitis may develop after treatment initiation. However, no approach for treating periodontitis after the initiation of orthodontic treatment has been established. Here, we present an approach for managing localized severe periodontitis manifesting after initiating orthodontic treatment. CASE PRESENTATION: A 32-year-old Japanese woman was referred to the Department of Dentistry and Oral Surgery by an orthodontist who observed symptoms of acute periodontitis in the maxillary molars that required periodontal examination and treatment. A detailed periodontal examination, including oral bacteriological examination, revealed localized severe periodontitis (stage III, grade B) in the maxillary left first and second molars and in the mandibular right second molar. After consultation with the orthodontist, the orthodontic treatment was suspended based on the results of the bacteriological examination to allow for periodontal treatment. Full-mouth disinfection was performed with adjunctive oral sitafloxacin. Periodontal and bacteriological examinations after treatment revealed regression of the localized periodontitis with bone regeneration. Thereafter, orthodontic treatment was resumed, and good progress was achieved. CONCLUSIONS: Orthodontists should recognize the risk of acute severe periodontitis in young adults. Asymptomatic patients with localized severe periodontitis may clear a screening test before orthodontic treatment but develop acute symptoms with bone resorption during orthodontic treatment. Therefore, patients requiring orthodontic treatment should be examined by their family dentist or a periodontist to rule out periodontal issues that may impede orthodontic treatment. The patients should also be informed of age-related risks. Further, periodontists, family dentists, and orthodontists who treat adults should be informed about periodontitis and the need for interdisciplinary collaboration. In patients who develop periodontitis after orthodontic treatment initiation, temporary interruption of orthodontic treatment and aggressive periodontal intervention may facilitate recovery.


Subject(s)
Periodontitis , Female , Young Adult , Humans , Adult , Periodontitis/therapy
16.
Front Biosci (Landmark Ed) ; 28(10): 265, 2023 10 25.
Article in English | MEDLINE | ID: mdl-37919086

ABSTRACT

The oral cavity serves as the initial segment of the digestive system and is responsible for both nutritional supplementation and the mechanical breakdown of food. It comprises distinct hard and soft tissues; the oral mucosa is subject to mechanical stress and interaction with microbiota. In oral cancer, tumors exhibit abnormal cellular networks and aberrant cell-cell interactions arising from complex interplays between environmental and genetic factors. This presents a challenge for clinicians and researchers, impeding the understanding of mechanisms driving oral cancer development and treatment strategies. Lesions with dysplastic features are categorized under oral potentially malignant disorders, including oral leukoplakia, erythroplakia, oral submucous fibrosis, and proliferative verrucous leukoplakia, carrying a high malignancy risk. In this review, we discuss oral cancer cell characteristics and the stiffness of the surrounding matrix. We also discuss the significance of stiffness equilibrium in oral potentially malignant disorders, particularly oral submucous fibrosis, possibly triggered by mechanical stress such as betel quid chewing.


Subject(s)
Carcinoma, Squamous Cell , Mouth Neoplasms , Oral Submucous Fibrosis , Precancerous Conditions , Humans , Oral Submucous Fibrosis/complications , Oral Submucous Fibrosis/pathology , Precancerous Conditions/complications , Precancerous Conditions/pathology , Leukoplakia, Oral/complications , Leukoplakia, Oral/pathology , Mouth Neoplasms/etiology , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/pathology
17.
Biochem Biophys Res Commun ; 421(4): 785-9, 2012 May 18.
Article in English | MEDLINE | ID: mdl-22554514

ABSTRACT

Bone defects caused by traumatic bone loss or tumor dissection are now treated with auto- or allo-bone graft, and also occasionally by artificial bone transplantation, particularly in the case of large bone defects. However, artificial bones often exhibit poor affinity to host bones followed by bony union failure. Thus therapies combining artificial bones with growth factors have been sought. Here we report that platelet derived growth factor bb (PDGFBB) promotes a significant increase in migration of PDGF receptor α (PDGFRα)-positive mesenchymal stem cells/pre-osteoblastic cells into artificial bone in vivo. Growth factors such as transforming growth factor beta (TGFß) and hepatocyte growth factor (HGF) reportedly inhibit osteoblast differentiation; however, PDGFBB did not exhibit such inhibitory effects and in fact stimulated osteoblast differentiation in vitro, suggesting that combining artificial bones with PDGFBB treatment could promote host cell migration into artificial bones without inhibiting osteoblastogenesis.


Subject(s)
Bone and Bones/cytology , Cell Movement/drug effects , Mesenchymal Stem Cells/drug effects , Proto-Oncogene Proteins c-sis/pharmacology , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Animals , Becaplermin , Cell Movement/physiology , Cell Proliferation/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Humans , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/physiology , Mice , Osteoblasts/cytology , Osteoblasts/enzymology
18.
Am J Pathol ; 179(2): 795-806, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21718682

ABSTRACT

Pemphigus vulgaris is an autoimmune disease caused by IgG antibodies against desmoglein 3 (Dsg3). Previously, we isolated a pathogenic mAb against Dsg3, AK23 IgG, which induces a pemphigus vulgaris-like phenotype characterized by blister formation. In the present study, we generated a transgenic mouse expressing AK23 IgM to examine B-cell tolerance and the pathogenic role of IgM. Autoreactive transgenic B cells were found in the spleen and lymph nodes, whereas anti-Dsg3 AK23 IgM was detected in the cardiovascular circulation. The transgenic mice did not develop an obvious pemphigus vulgaris phenotype, however, even though an excess of AK23 IgM was passively transferred to neonatal mice. Similarly, when hybridoma cells producing AK23 IgM were inoculated into adult mice, no blistering was observed. Immunoelectron microscopy revealed IgM binding at the edges of desmosomes or interdesmosomal cell membranes, but not in the desmosome core, where AK23 IgG binding has been frequently detected. Furthermore, in an in vitro dissociation assay using cultured keratinocytes, AK23 IgG and AK23 IgM F(ab')(2) fragments, but not AK23 IgM, induced fragmentation of epidermal sheets. Together, these observations indicate that antibodies must gain access to Dsg3 integrated within desmosomes to induce the loss of keratinocyte cell-cell adhesion. These findings provide an important framework for improved understanding of B-cell tolerance and the pathophysiology of blister formation in pemphigus.


Subject(s)
Desmoglein 3/chemistry , Immunoglobulin G/chemistry , Immunoglobulin M/chemistry , Pemphigus/immunology , Amino Acid Sequence , Animals , B-Lymphocytes/cytology , Blister/immunology , Cell Adhesion , Flow Cytometry/methods , Hybridomas/metabolism , Immunoglobulin M/metabolism , Keratinocytes/cytology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Microscopy, Fluorescence/methods , Microscopy, Immunoelectron/methods , Models, Genetic , Molecular Sequence Data
19.
J Orofac Pain ; 26(4): 288-95, 2012.
Article in English | MEDLINE | ID: mdl-23110268

ABSTRACT

AIMS: To compare patients with combined tension-type headache and myofascial temporomandibular disorder (TMD) with control subjects on two measures of central processing-ie, temporal summation and aftersensations to heat stimulation in the trigeminal nerve and spinal nerve territories. METHODS: A novel heat stimulation protocol was used in which 13 females with tension-type headache/TMD and 20 female controls were exposed to 11 painful heat stimuli at a rate of 0.33 Hz. Two temperature ranges (low, 44°C to 46°C; high, 45°C to 47°C) were tested on the cheek and arm in separate trials. Perceived pain was rated on a 100-mm visual analog scale after the second, sixth, and eleventh stimulus presentation and every 15 seconds after the final stimulus presentation (aftersensations) for up to 3 minutes. The duration of aftersensations was compared using the student unpaired t test with Welch correction. RESULTS: Temporal summation was not observed in any of the groups, but aftersensations were consistently reported. The aftersensations lasted longer in tension-type headache/TMD patients (right cheek, 100.4 ± 62.0 seconds; right arm, 115.4 ± 64.0 seconds) than in controls (right cheek, 19.5 ± 2.5 seconds; right arm, 20.3 ± 2.7 seconds) (P < .05). A cutoff value (right cheek, 44.6 seconds; right arm, 41.5 seconds) provided a sensitivity and specificity of 0.77 and 0.95, respectively, with the high stimulus protocol. CONCLUSION: The results from this pilot study suggest that aftersensations to painful heat stimulation can appear without temporal summation. Furthermore, the developed test protocol has a good predictive value and may have the potential to discriminate between tension-type headache/TMD patients and control subjects.


Subject(s)
Central Nervous System Sensitization/physiology , Nociceptive Pain/physiopathology , Postsynaptic Potential Summation/physiology , Temporomandibular Joint Dysfunction Syndrome/complications , Tension-Type Headache/complications , Adolescent , Adult , Case-Control Studies , Excitatory Postsynaptic Potentials/physiology , Female , Hot Temperature , Humans , Physical Stimulation , Pilot Projects , Sensitivity and Specificity , Spinal Nerves/physiology , Temporomandibular Joint Dysfunction Syndrome/diagnosis , Temporomandibular Joint Dysfunction Syndrome/physiopathology , Tension-Type Headache/diagnosis , Tension-Type Headache/physiopathology , Time Factors , Trigeminal Nerve/physiology , Young Adult
20.
J Med Case Rep ; 16(1): 463, 2022 Dec 16.
Article in English | MEDLINE | ID: mdl-36522676

ABSTRACT

BACKGROUND: Felty syndrome is defined by three conditions: neutropenia, rheumatoid arthritis, and splenomegaly. Neutropenia associated with pancytopenia may further affect the dental condition of a patient. Periodontal treatment and surgery in patients with Felty syndrome necessitates cooperation with a hematologist. Here we present a case of a patient with Felty syndrome who was initially referred to the oral surgery hospital attached to the School of Dentistry for extensive periodontitis. She was effectively treated in collaboration with the hematology department. CASE PRESENTATION: A 55-year-old Asian woman visited our department with concerns of worsening tooth mobility, discomfort, and spontaneous gingival bleeding. Initial periodontal examination revealed generalized severe periodontitis (Stage IV Grade C) resulting from leukopenia/neutropenia and poor oral hygiene. A thorough treatment strategy involving comprehensive dental procedures, such as multiple extractions and extensive prosthetic treatment, was implemented. Following the diagnosis of Felty syndrome, the patient was started on treatment with oral prednisolone 40 mg/day, which effectively controlled the disease. Furthermore, there was no recurrence of severe periodontitis after the periodontal treatment. CONCLUSIONS: Dentists and physicians should be aware that immunocompromised individuals with pancytopenia and poor oral hygiene are at risk of developing extensive periodontitis. If their susceptibility to infection and pancytopenia-related bleeding can be managed, such patients can still receive comprehensive dental treatment, including teeth extractions and periodontal therapy. Cooperation among the dentist, hematologist, and patient is necessary to improve treatment outcomes and the patient's quality of life.


Subject(s)
Alveolar Bone Loss , Felty Syndrome , Neutropenia , Pancytopenia , Periodontitis , Female , Humans , Middle Aged , Felty Syndrome/complications , Felty Syndrome/diagnosis , Quality of Life , Pancytopenia/complications , Alveolar Bone Loss/therapy , Alveolar Bone Loss/complications , Periodontitis/complications , Periodontitis/diagnosis , Periodontitis/therapy , Neutropenia/complications
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