Gene therapy improves dental manifestations in hypophosphatasia model mice.

BACKGROUND AND OBJECTIVE: Hypophosphatasia is a rare inherited skeletal disorder characterized by defective bone mineralization and deficiency of tissue non-specific alkaline phosphatase (TNSALP) activity. The disease is caused by mutations in the liver/bone/kidney alkaline phosphatase gene (ALPL) encoding TNSALP. Early exfoliation of primary teeth owing to disturbed cementum formation, periodontal ligament weakness and alveolar bone resorption are major complications encountered in oral findings, and discovery of early loss of primary teeth in a dental examination often leads to early diagnosis of hypophosphatasia. Although there are no known fundamental treatments or effective dental approaches to prevent early exfoliation of primary teeth in affected patients, several possible treatments have recently been described, including gene therapy. Gene therapy has also been applied to TNSALP knockout mice (Alpl-/- ), which phenocopy the infantile form of hypophosphatasia, and improved their systemic condition. In the present study, we investigated whether gene therapy improved the dental condition of Alpl-/- mice. MATERIAL AND METHODS: Following sublethal irradiation (4 Gy) at the age of 2 d, Alpl-/- mice underwent gene therapy using bone marrow cells transduced with a lentiviral vector expressing a bone-targeted form of TNSALP injected into the jugular vein (n = 3). Wild-type (Alpl+/+ ), heterozygous mice (Alpl+/- ) and Alpl-/- mice were analyzed at 9 d of age (n = 3 of each), while Alpl+/+ mice and treated or untreated Alpl-/- mice were analyzed at 1 mo of age (n = 3 of each), and Alpl+/- mice and Alpl-/- mice with gene therapy were analyzed at 3 mo of age (n = 3 of each). A single mandibular hemi-section obtained at 1 mo of age was analyzed using a small animal computed tomography machine to assess alveolar bone formation. Other mandibular hemi-sections obtained at 9 d, 1 mo and 3 mo of age were subjected to hematoxylin and eosin staining and immunohistochemical analysis of osteopontin, a marker of cementum. RESULTS: Immunohistochemical analysis of osteopontin, a marker of acellular cementum, revealed that Alpl-/- mice displayed impaired formation of cementum and alveolar bone, similar to the human dental phenotype. Cementum formation was clearly present in Alpl-/- mice that underwent gene therapy, but did not recover to the same level as that in wild-type (Alpl+/+ ) mice. Micro-computed tomography examination showed that gene therapy improved alveolar bone mineral density in Alpl-/- mice to a similar level to that in Alpl+/+ mice. CONCLUSIONS: Our results suggest that gene therapy can improve the general condition of Alpl-/- mice, and induce significant alveolar bone formation and moderate improvement of cementum formation, which may contribute to inhibition of early spontaneous tooth exfoliation.

Chronic administration of DSP-7238, a novel, potent, specific and substrate-selective DPP IV inhibitor, improves glycaemic control and beta-cell damage in diabetic mice.

AIMS: The purpose of this study is to assess the in vitro enzyme inhibition profile of DSP-7238, a novel non-cyanopyrrolidine dipeptidyl peptidase (DPP) IV inhibitor and to evaluate the acute and chronic effects of this compound on glucose metabolism in two different mouse models of type 2 diabetes. METHODS: The in vitro enzyme inhibition profile of DSP-7238 was assessed using plasma and recombinant enzymes including DPP IV, DPP II, DPP8, DPP9 and fibroblast activation protein alpha (FAPalpha) with fluorogenic substrates. The inhibition type was evaluated based on the Lineweaver-Burk plot. Substrate selectivity of DSP-7238 and comparator DPP IV inhibitors (vildagliptin, sitagliptin, saxagliptin and linagliptin) was evaluated by mass spectrometry based on the changes in molecular weight of peptide substrates caused by release of N-terminal dipeptides. In the in vivo experiments, high-fat diet-induced obese (DIO) mice were subjected to oral glucose tolerance test (OGTT) following a single oral administration of DSP-7238. To assess the chronic effects of DSP-7238 on glycaemic control and pancreatic beta-cell damage, DSP-7238 was administered for 11 weeks to mice made diabetic by a combination of high-fat diet (HFD) and a low-dose of streptozotocin (STZ). After the dosing period, HbA1c was measured and pancreatic damage was evaluated by biological and histological analyses. RESULTS: DSP-7238 and sitagliptin both competitively inhibited recombinant human DPP IV (rhDPP IV) with K(i) values of 0.60 and 2.1 nM respectively. Neither vildagliptin nor saxagliptin exhibited competitive inhibition of rhDPP IV. DSP-7238 did not inhibit DPP IV-related enzymes including DPP8, DPP9, DPP II and FAPalpha, whereas vildagliptin and saxagliptin showed inhibition of DPP8 and DPP9. Inhibition of glucagon-like peptide-1 (GLP-1) degradation by DSP-7238 was apparently more potent than its inhibition of chemokine (C-X-C motif) ligand 10 (IP-10) or chemokine (C-X-C motif) ligand 12 (SDF-1alpha) degradation. In contrast, vildagliptin and saxagliptin showed similar degree of inhibition of degradation for all the substrates tested. Compared to treatment with the vehicle, single oral administration of DSP-7238 dose-dependently decreased plasma DPP IV activity and improved glucose tolerance in DIO mice. In addition, DSP-7238 significantly decreased HbA1c and ameliorated pancreatic damage following 11 weeks of chronic treatment in HFD/STZ mice. CONCLUSIONS: We have shown in this study that DSP-7238 is a potent DPP IV inhibitor that has high specificity for DPP IV and substrate selectivity against GLP-1. We have also found that chronic treatment with DSP-7238 improves glycaemic control and ameliorates beta-cell damage in a mouse model with impaired insulin sensitivity and secretion. These findings indicate that DSP-7238 may be a new therapeutic agent for the treatment of type 2 diabetes.

Anomalous arterial supply to the gallbladder from the superior mesenteric artery: angiography and computed tomography findings in two cases.

The arterial supply of the gallbladder usually arises from the right hepatic artery. Other origins include the left, proper, and common hepatic arteries. We report cases of the cystic artery arising from the superior mesenteric artery and arising from the dorsal pancreatic artery originating in turn from the superior mesenteric artery, as demonstrated by angiography and computed tomography.

Spheric mass beneath the alar base: MR images of nasolabial cyst and schwannoma.

We report 2 cases of nasolabial cyst and a case of schwannoma beneath the alar base that required a differential diagnosis because of clinical features and MR images that resembled the nasolabial cyst. The morphologic analysis on MR images revealed the characteristic appearance of the nasolabial cyst, and the sagittal MR image may be most helpful for diagnosing this rare disease.

Phase II study of a novel oral formation of 5-fluorouracil in combination with low-dose cisplatin as preoperative chemotherapy of oral squamous cell carcinoma.

TS-1 is a novel oral 5-fluorouracil containing tegaful (prodrug of 5-FU) and two biochemical modulators. These modulators feature effect-enhancing and adverse reaction-reducing activity. We investigated the histological response and toxicities of combination chemotherapy with TS- 1 and low-dose cisplatin and evaluated its usefulness as preoperative chemotherapy Forty-four newly diagnosed patients with stage Il-IV oral squamous cell carcinoma were enrolled in this study from February 2002 to April 2004. Patients were administered TS-1 80 mg/m2/day (days 1-14) and cisplatin 5 mg/m2/day (days 1-5 and 8-12) followed by radical surgery within 2 weeks. The histopathological effect of chemotherapy, which was a surrogate endpoint of this trial, was evaluated with surgical or biopsy specimens. The rate of histological antitumor effect was as follows: complete response (CR) 36.4%, partial response (PR) 25.0%, minor response (MR) 18.1% and no change (NC) 20.5%. The rate of histological response (CR + PR) was 61.4%. The CR rate of effective cases was 59.3%. The main toxicities occurred in bone marrow and the digestive tract. The incidence of severe toxicity such as grade 3 or 4 was 4.5% in anemia, 9% in leukocytopenia, 11.4% in neutropenia, 4.5% in thrombocytopenia and 2.3% in anorexia, diarrhea and urticaria. Most patients showed no toxicity or mild toxicities. TS- 1 with low-dose cisplatin has highly effective antitumor activity and mild toxicities. In particular, the CR rate was very high. It is suggested that this regimen is suitable for neoadjuvant chemotherapy. We expect that this chemotherapy will contribute to avoidance of surgery for small tumors (stages I and II) and will enable function-preserving surgery for advanced tumors.

Expression of dentin matrix protein 1 (DMP1) during fracture healing.

Dentin matrix protein 1 (DMP1) is one of the acidic phosphorylated extracellular matrix proteins called the SIBLING (small integrin-binding ligand, N-linked glycoproteins) family. Recent studies showed that DMP1 is expressed in the mineralized tissues and suggested that DMP1 is involved in the mineralization. We investigated the precise localization of DMP1 messenger RNA (mRNA) and protein during fracture healing. In situ hybridization demonstrated that DMP1 mRNA was strongly expressed in preosteocytes and osteocytes in the bony callus during intramembranous and endochondral ossification while DMP1 mRNA was not detected in osteoblasts and chondrocytes. During endochondral ossification, however, a low number of DMP1-expressing cells were identified in the cluster of hypertrophic chondrocytes. However, these DMP1-expressing cells were not hypertrophic and were likely to be osteoblast-lineage cells, which were embedded in the matrix of bone or cartilage, because type I collagen-expressing cells and invasion of capillary vessels were observed in the same area. Northern blot, in situ hybridization, and immunohistochemical analyses showed that DMP1 mRNA and protein expressions were increased until day 14 postfracture, when bony callus was formed, and then declined to a lower level during remodeling of the bony callus. Therefore, DMP1 is likely to play an important role in the mineralization of the bony callus.

Ongoing clinical trials of lipid reduction therapy in patients with renal disease.

BACKGROUND: Lipid abnormalities in renal disease are associated with both a progressive decline in renal function and cardiovascular complications. Whether or not lipid anomalies are causal is not yet clear. Experimental studies have demonstrated that potentially atherogenic lipoproteins, such as low density lipoproteins (LDL), are associated with renal pathophysiological changes that result in progressive glomerular and interstitial damage and an ultimate reduction in renal function. These findings indicate that hyperlipidemia accelerates glomerular and interstitial damage in renal disease. Clinical studies also show that renal function declines more rapidly among patients with primary renal disease or diabetic nephropathy who have hyperlipidemia. However, few reports have demonstrated the effect of hypolipidemic agents on the progression of renal function among patients with renal disease, and those renal patients who were treated with lipid-lowering agents have not been clinically studied under large-scale controlled conditions. In addition, although cardiovascular complications are the most important factors associated with mortality in dialysis patients, randomized, large-scale trials studying the relationship between therapeutic intervention by lipid-lowering agents and prevention of cardiovascular complications have not been implemented. METHODS: We reviewed controlled and uncontrolled reported studies that examined the effects of lipid-lowering therapy in patients with renal disease. RESULTS: Most studies showed that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors reduce cholesterol-rich apolipoprotein (apo)B-containing lipoproteins with no effects on renal function or proteinuria among patients with progressive renal disease. Small uncontrolled studies show that simvastatin and probucol moderately reduce proteinuria among patients with membranous nephropathy. One small retrospective study showed that long-term vitamin E therapy reduces aortic calcification in dialysis patients. CONCLUSIONS: Prospective, randomized large-scale trials including ongoing clinical trials of lipid reduction therapy and therapeutic interventions such as the use of the combination therapy with hypolipidemic agents and angiotensin converting enzyme (ACE) inhibitors, vitamins, or LDL apheresis are urgently required. Such trials will clarify the effect of treating dyslipidemia on the progression of renal insufficiency and dialysis-related cardiovascular complications.

Phosphotyrosine of macrophage by low-density lipoproteins from hemodialysis patients.

BACKGROUND: Because of the possible importance of tyrosine phosphorylation in the signal transduction process, we investigated whether an interaction of low-density lipoprotein (LDL) from hemodialysis patients (HD-LDL) and human macrophages induces tyrosine-phosphorylated proteins in the macrophages. METHODS: Human monocyte-derived macrophages were incubated with HD-LDL (100 micrograms/ml) or native LDL (100 micrograms/ml) for 15 minutes at 37 degrees C. Whole cells were lyzed with Tris-HCl buffer containing vanadate and Triton X-100. After centrifugation, lyzed proteins were divided into Triton-soluble and -insoluble fractions. Both fractions (soluble and insoluble) were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and were electroblotted onto a polyvinylidene difluoride (PVDF) membrane. Immunoblotting was performed using an antibody against phosphotyrosine or c-Src. RESULTS: Several proteins in the range 40 to 100 kDa were found to be phosphorylated constitutively in the macrophages and not affected by the addition of HD-LDL. HD-LDL did not induce any tyrosine-phosphorylated proteins either in the soluble or insoluble fractions. Macrophages pretreated with tyrosine kinase inhibitor genestein drastically inhibited tyrosine phosphorylation of these proteins. The nonreceptor tyrosine kinase, c-Src p60, was also strongly tyrosine phosphorylated in the macrophages, and this was not enhanced by the stimulation of HD-LDL. CONCLUSION: These data suggest that tyrosine autophosphorylated proteins may play a role in the early step of signal transduction in the macrophages.

Effect of vitamin E on lipid metabolism and atherosclerosis in ESRD patients.

BACKGROUND: Oxidative stress is enhanced in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). Bioincompatibility represents an important source of reactive oxygen species. HD patients exhibit altered anti-oxidative defences and anti-oxidative vitamins such as vitamin E and C are altered in uremia. Frequently, HD patients also suffer from atherosclerotic cardiac disease. We have previously reported that low density lipoprotein (LDL) of HD patients is rich in malondialdehyde (MDA), an end product of lipid peroxidation. MDA rich LDL is thought to be an atherogenic lipoprotein due to its enhancement of macrophage foam cell formation. METHODS: We conducted a controlled study for two years comparing the effects of a vitamin E coated cellulose membrane dialyzer and an ordinary cellulose membrane dialyzer on lipid metabolism and the progress of atherosclerosis. LDL-MDA and oxidized LDL (ox-LDL) were measured in HD patients using these two types of dialyzers. Plasma vitamin E and lipid concentrations were also evaluated. The aortic calcification index (ACI) was evaluated by CT scan to assess the progress of atherosclerosis before and for every year after treatment. RESULTS: Use of a vitamin E coated cellulose membrane dialyzer for six months, one year and two years resulted in a significant reduction in LDL-MDA and ox-LDL compared to the ordinary cellulose membrane dialyzer. Treatment with a vitamin E-coated dialyzer significantly reduced the percentage increase in ACI after 24 months compared to the control. There were no significant changes in plasma vitamin E and lipid concentrations between the two groups. CONCLUSIONS: These results suggest that the oxidative stress could be one of the stimulating factors of abnormal lipid metabolism and atherosclerosis in ESRD patients.

Effect of simvastatin on the lipid profile of hemodialysis patients.

BACKGROUND: Simvastatin, a 3-hydroxy 3-methylglutaryl co-enzyme A (HMG-CoA) reductase inhibitor, is used widely for treatment of hypercholesterolemia. Simvastatin may be a suitable treatment for dyslipidemia in hemodialysis (HD) patients. However, investigation of the side-effects and safety of long-term administration of simvastatin to HD patients has been limited. In this study, we investigated the effects and safety of simvastatin and its effects on lipoprotein metabolism in hypercholesterolemic patients on HD. METHODS: Simvastatin was administered at a dosage of 5 mg/day for 24 weeks to 38 HD patients with high serum total cholesterol (TC) levels (200 mg/dl) or low high-density lipoprotein cholesterol (HDL-C) levels (35 mg/dl). Every four weeks, serum lipids, apolipoprotein, lipoprotein (a) [Lp(a)] and malondialdehyde (MDA) levels were measured. In addition, lipid levels were determined in each lipoprotein fraction separated by ultracentrifugation. RESULTS: After 24 weeks of simvastatin administration, TC significantly decreased by 25.7%, and low-density lipoprotein cholesterol (LDL-C) was significantly decreased by 33.6%. Triglyceride (TG) and HDL-C showed no significant changes. Apolipoprotein (apo) B significantly decreased by 24.5% and apo E by 30.0%. No significant changes were observed in the other apolipoproteins. MDA was also significantly decreased, whereas Lp(a) was not significantly altered. In the lipoprotein fractions, very LDL cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C), LDL1 cholesterol (LDL1-C), and LDL2 cholesterol (LDL2-C) showed significant decreases. No particular side-effects were observed during the 12 months of simvastatin administration. CONCLUSIONS: These results suggest that simvastatin appears to be safe and effective in HD patients with hypercholesterolemia.

Characteristics of mastication in the anodontic mouse.

Teeth and periodontal mechanoreceptors play important roles in regulating jaw movements during mastication. However, little is known concerning how jaw movements develop without tooth eruption. To answer this question, we studied masticatory behavior in the osteopetrotic mouse, where tooth eruption does not occur and periodontal mechanoreceptors are missing. A masticatory sequence of the osteopetrotic mouse was divided into two stages: incision and chewing. Incision is characterized by small amplitude and rapid (7 Hz) open-close jaw movements, while slow (5 Hz) and large amplitude open-close jaw movements characterize chewing. The frequency and properties of jaw movements were comparable with those in the normal mouse, though the osteopetrotic mouse had a higher cycle number during incision than did the normal mouse. These results indicate that conversion from sucking to mastication occurs in the anodontic mouse, and the central pattern generator producing the masticatory rhythm develops almost normally without tooth eruption.

Gigantic dense bone island of the jaw.

The clinical and radiographic features of gigantic dense bone islands of the jaw were reviewed in 21 subjects to better determine the pathogenesis of this condition. Most of the islands were asymptomatic. They showed a striking predilection for occurrence in the premolar to molar region of the mandible. The greatest dimension of gigantic dense bone islands measured on panoramic radiographs ranged from 2.5 to 7.0 cm, and they were most commonly structureless radiopaque areas. None showed bony expansion buccolingually, nor did they displace adjacent teeth or bony anatomic structures. It is concluded that gigantic dense bone island is not a benign bone neoplasm and is perhaps merely a large counterpart of smaller dense bone islands or idiopathic osteosclerosis.

Radiographic findings for solitary plasmacytoma of the bone in the anterior wall of the maxillary sinus: A case report.

Radiographic findings for a solitary plasmacytoma of the anterior wall of the maxillary sinus are reported. The diagnostic evaluation for this disease is discussed through use of plain images, computed tomography, and magnetic resonance imaging. The treatment selected was radiation therapy combined with chemotherapy. Computed tomography and magnetic resonance imaging revealed bone destruction, though this was not apparent on plain images. T(1)-weighted magnetic resonance images showed similar or high signal intensity relative to muscle; T(2)-weighted images showed hyperintensity.

Cemento-osseous dysplasia of the jaws in 54 Japanese patients: a radiographic study.

OBJECTIVE: The aim of this study was to describe the radiographic patterns of cemento-osseous dysplasia. STUDY DESIGN: Fifty-four patients affected with benign fibro-osseous jaw lesions that showed periapical radiopacities and/or radiolucencies in a focal or a multiplex form were studied. The clinical, radiographic, and histopathologic features of the patients with cemento-osseous dysplasia were retrospectively studied. Radiographic features of the cemento-osseous dysplasia lesions were classified according to the appearance of calcified bodies. Radiographic visibility of periodontal ligament spaces of related teeth was assessed. RESULTS: Forty-nine (91 %) of the 54 patients were women. The mean age of the total group was 50.8 years, and that of the male group was 64.6 years. The cemento-osseous dysplasia lesions could be classified into 6 types radiographically. Eighteen patients had at least 2 or more types of cemento-osseous dysplasia lesions. Of 147 related teeth, 142 had periodontal ligament spaces clearly visible. Six of 9 patients who had a total of 25 teeth with active hypercementosis showed concomitant occurrence of other types of cemento-osseous dysplasia lesions. Biopsy specimens showed various amounts of bonelike and cementumlike tissues. CONCLUSIONS: It is likely that cemento-osseous dysplasia consists of 3 variations of a single entity, all with the same unknown cause. In one variation, the entity originates from the periodontium; in another, it is of medullary bone origin; and in the third it results from the simultaneous involvement of both tissues.

A unique case of desmoplastic ameloblastoma of the mandible: report of a case and brief review of the English language literature.

A unique case of desmoplastic ameloblastoma is reported from the clinical, radiographic, and histologic viewpoints. The patient was a 56-year-old man who complained of a painless swelling on the buccal aspect of the left mandible. Periapical and panoramic radiographs revealed a rounded, slightly radiolucent area with blurred osteosclerotic margins. Occlusal radiograph and computed tomography images disclosed buccal bone expansion outlined by thinned cortices. Computed tomography images exhibited an enhanced area in the anterior portion of the lesion. Interestingly, the coronal computed tomography images revealed a close relationship between the periodontal membrane of the left mandibular second premolar and the enhanced area. Biopsy specimens from the anterior portion of the lesion displayed typical histologic features of the desmoplastic variant of ameloblastoma. However, those from the posterior portion disclosed a large cystic formation. Oxytalan fibers were identified in the stromal tissue of the tumor, which suggested that the tumor arose from the epithelial rests of Malassez in the periodontal membrane of the related tooth. We also reviewed previously reported 41 cases. In 36 of 38 cases in which the location was specified, the tumor was found in the anterior to premolar region of the maxilla or mandible. A radiographic description was given in only 29 previous cases, 28 of which involved multilocular lesions. No cyst as large as the one in the present case was found among the previously reported desmoplastic ameloblastomas. Although the present case deviates from the usual desmoplastic variant of ameloblastoma in terms of locus, radiologic appearance, and cyst formation, it still meets the histologic criteria for this variant in both the stromal and epithelial components.

Mucus escape reaction that involves the mandible: a case report and diagnostic imaging considerations.

We present a case of mucus escape reaction in which we encountered difficulty in interpreting the images acquired by plain radiography, computed tomography, and magnetic resonance imaging. The 48-year-old male Japanese patient was referred for evaluation of a gradual swelling subjacent to the inferior border of the left mandible. At the early imaging examinations, magnetic resonance imaging provided information crucial to resolving the issue of whether the lesion consisted of a central malignant disease process or a malignant disease in the submandibular space or both of these two separate disease entities. Magnetic resonance imaging demonstrated no evidence of tumorous lesion, but rather showed a fluid-containing cavity that was also confirmed by the subsequent intrasurgical inspection. On further consideration of these imaging findings, we concluded that the entity was mucus escape reaction with simultaneous occurrence of an intraconnective tissue hemorrhage adjacent to the left submandibular gland, concomitant extensive bony defect of the left mandible and lingual cortical defect, and chronic sialoadenitis of the left submandibular gland.

Diagnostic imaging for a case of maxillary myxoma with a review of the magnetic resonance images of myxoid lesions.

The findings of conventional radiography, computed tomography, and magnetic resonance imaging are reported for an odontogenic myxoma arising in the left anterior maxilla of a 50-year-old man. The magnetic resonance imaging characteristics of an intraosseous myxoma are described for the first time. The initial conventional radiographic examination disclosed a unilocular radiolucency with poorly delineated margins as typically seen in malignant tumors. Subsequently, acquired computed tomography scans displayed bony expansion and thinning of cortices on the labial aspect of the lesion. Magnetic resonance imaging revealed a well-defined, well-enhanced mass lesion with homogeneous signal intensity on every pulse sequence. The lesion showed intermediate signal intensity on the T1- and T2-weighted images. Magnetic resonance imaging of the present maxillary myxoma revealed a higher signal intensity on T1-weighted and a lower signal intensity on T2-weighted images than for previously reported myxomas of the soft tissues. This discrepancy might be related to the viscosity of the mucoid substance or the protein density of the tumor.

Gross periostitis ossificans in mandibular osteomyelitis. Review of the English literature and radiographic variation.

OBJECTIVE: The purpose of this study was to describe a radiographic variety of gross periostitis ossificans in mandibular osteomyelitis and to determine what types of gross periostitis ossificans are related to a specific form of mandibular osteomyelitis without demonstrable causes. STUDY DESIGN: We reviewed 20 cases of gross periostitis ossificans in patients with mandibular osteomyelitis that had been reported with illustrations in the English literature, and we reviewed our own 14 cases of gross periostitis ossificans, previously reported. The radiographic features of the 34 cases of gross periostitis ossificans were classified according to the status of original contour and the appearance of gross periostitis ossificans. Histopathologic features were studied in 12 cases. RESULTS: The 34 cases of gross periostitis ossificans could be classified radiographically into 4 types. Type A, showing an "onion-skin" appearance, was caused by a carious tooth or followed extraction of a tooth. Type B and type C showed a consolidation form; in the 36.8% (7/19) of these cases in which no infectious source could be identified, it was suspected that the condition was caused by a developing unerupted tooth or a dental follicle. Type D was seen in the most chronic stage. Biopsy specimens of 12 cases commonly showed proliferation of newly formed bone, loose interstitial fibrous tissue, and a low-grade inflammatory cell infiltration. CONCLUSION: Gross periostitis ossificans of type B or type C may be a specific form of mandibular osteomyelitis without demonstrable cause.

Histopathologic and radiographic findings of the simple bone cyst.

OBJECTIVE: The purpose of this study is to examine the correlation between histopathologic and radiographic findings and to discuss the cause of the simple bone cyst. STUDY DESIGN: Histopathologically, we classified 53 simple bone cysts into two types. Type A has a connective tissue membrane and type B has a partially thickened wall with dysplastic bone formation. Radiographically, we evaluated the following: margin, radiolucency, or radiopacity, relationship with tooth apices, bucco-lingual bone expansion, and displacement of the mandibular canal. RESULTS: Bone expansion and radiopacity were closely related to histopathologic findings although there was no correlation between the histopathologic findings and radiographic margin, relationship with tooth apices, and displacement of mandibular canal. Local recurrence was more likely to be observed in patients diagnosed as having type B than type A lesions. CONCLUSIONS: Type A and type B bone cysts may have different causes. Cysts determined radiographically to be radiopaque, those diagnosed as type B histopathologically, and cysts that have been treated surgically should all be followed by radiographic examinations.