Julia Yu Fong Chang

Central Ossifying Fibroma: A Clinicopathologic Study of 28 Cases

BACKGROUND/PURPOSE Central ossifying fibroma (COF) is the most common benign fibro-osseous lesion of the jaw. This retrospective study evaluated the clinical and histopathologic features of 28 COFs in Taiwanese patients. METHODS Twenty-eight consecutive cases of COF were collected from 1988 to 2006. The clinical data and microscopic features of these cases were reviewed and analyzed. RESULTS The mean age of patients at the time of diagnosis was 34 years. There were six male and 22 female patients. Twenty-six (93%) cases were found in the mandible and two (7%) in the maxilla. The most common sites for COFs were the molar region (17 cases, 61%), followed by the premolar (8 cases, 28%), and incisor/canine (3 cases, 11%) regions. Bone swelling or expansion (96%, 26/27) was the most frequent clinical presentation. Six (21%) COFs presented as a radiolucent lesion, 17 (61%) as a mixed lesion, and five (18%) as a radio-opaque lesion. No recurrence of the lesion was found after surgical excision in this series. Microscopically, COFs showed trabeculae of woven bone (25 cases) and/or lamellar bone (5 cases) and/or spherules of cementoid (19 cases) in a cellular fibrous connective tissue stroma. The stromal component was highly cellular in 21 cases, moderately cellular in seven cases, prominently vascular in 11, and collagenous in six. CONCLUSION COFs occur more frequently in female patients and in those in the second to fourth decades of life. The most commonly affected site is the mandible, especially the molar region. The majority of COF lesions present as a well-defined, mixed lesion radiographically. Most COFs can be treated by conservative surgical excision without subsequent recurrence.

Significantly higher frequencies of presence of serum autoantibodies in Chinese patients with oral lichen planus

BACKGROUND Previous studies have shown the presence of serum anti-nuclear (ANA), anti-smooth muscle (SMA), anti-mitochondrial (AMA), anti-gastric parietal cell (GPCA), anti-thyroglobulin (TGA) and anti-thyroid microsomal autoantibodies (TMA) in small groups of patients with oral lichen planus (OLP). METHODS In this study, the serum levels of ANA, SMA, AMA, GPCA, TGA and TMA were measured in a group of 320 Chinese OLP patients and 53 healthy control subjects to assess whether Chinese OLP patients had significantly higher frequencies of serum autoantibodies than healthy control subjects and to assess which risk factors had a significant influence on the possession of a specific serum autoantibody in OLP patients. RESULTS We found that autoantibodies were present in 195 (60.9%) of the 320 OLP patients. The frequencies of presence of serum ANA (28.1%), GPCA (26.3%), TGA (21.3%) and TMA (24.4%) in OLP patients were significantly higher than those (5.7%, 1.9%, 1.9% and 1.9%, respectively) in healthy control subjects (all P-values were < 0.005). Forty-one (12.8%) OLP patients also had anti-hepatitis C virus antibody (HCVA) in their sera. The multivariate logistic regression found that major erosive OLP (EOLP) [odds ratio (OR) = 1.786], TGA/TMA-positivity (OR = 2.517), and HCVA-positivity (OR = 2.214) were significant risk factors to influence ANA-positivity in OLP patients. Moreover, only major EOLP (OR = 1.879) and ANA-positivity (OR = 2.581) were significant risk factors to influence TGA/TMA-positivity in OLP patients. CONCLUSIONS There are significantly higher frequencies of presence of ANA, GPCA, TGA and TMA in Chinese OLP patients than in healthy control subjects.

FRS2α-Mediated FGF Signals Suppress Premature Differentiation of Cardiac Stem Cells Through Regulating Autophagy Activity

Rationale: Although the fibroblast growth factor (FGF) signaling axis plays important roles in heart development, the molecular mechanism by which the FGF regulates cardiogenesis is not fully understood. Objective: To investigate the mechanism by which FGF signaling regulates cardiac progenitor cell differentiation. Methods and Results: Using mice with tissue-specific ablation of FGF receptors and FGF receptor substrate 2&agr; (Frs2&agr;) in heart progenitor cells, we demonstrate that disruption of FGF signaling leads to premature differentiation of cardiac progenitor cells in mice. Using embryoid body cultures of mouse embryonic stem cells, we reveal that FGF signaling promotes mesoderm differentiation in embryonic stem cells but inhibits cardiomyocyte differentiation of the mesoderm cells at later stages. Furthermore, we also report that inhibiting FRS2&agr;-mediated signals increases autophagy and that activating autophagy promotes myocardial differentiation and vice versa. Conclusions: The results indicate that the FGF/FRS2&agr;-mediated signals prevent premature differentiation of heart progenitor cells through suppressing autophagy. The findings provide the first evidence that autophagy plays a role in heart progenitor differentiation.

Significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high homocysteine level with recurrent aphthous stomatitis

BACKGROUND A portion of patients with recurrent aphthous stomatitis (RAS) may have nutritional deficiency. This study evaluated whether there was an intimate association of the deficiencies of hemoglobin, iron, vitamin B12, and folic acid and high blood homocysteine level with RAS. METHODS The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations in 273 RAS patients were measured and compared with the corresponding levels in 273 age- and sex-matched healthy control subjects. RESULTS We found that 57 (20.9%), 55 (20.1%), 13 (4.8%), and 7 (2.6%) RAS patients had deficiencies of hemoglobin (Men < 13 g/dl, Women < 12 g/dl), iron (<60 μg/dl), vitamin B12 (<200 pg/ml), and folic acid (<4 ng/ml), respectively. Moreover, 21 (7.7%) RAS patients had abnormally high blood homocysteine level. RAS patients had a significantly higher frequency of hemoglobin, iron, vitamin B12, or folic acid deficiency and of abnormally elevated blood homocysteine level than healthy control subjects (all P-values = 0.000 except for folic acid P = 0.022). If 273 RAS patients were further divided into 32 patients with major-typed RAS (MjRAS) and 241 patients with minor-typed RAS (MiRAS), we found that male MjRAS patients had a significantly lower mean hemoglobin concentration than MiRAS patients (P = 0.021), but MjRAS patients had a significantly higher mean homocysteine level than MiRAS patients (P = 0.000). CONCLUSION We conclude that there is a significant association of deficiencies of hemoglobin, iron, vitamin B12, and folic acid and abnormally high blood homocysteine level with RAS.

Type 1 Fibroblast Growth Factor Receptor in Cranial Neural Crest Cell-derived Mesenchyme Is Required for Palatogenesis

Background: How Fgfr1 mutations cause cleft palate is unclear. Results: Deleting Fgfr1 in neural crest cells caused defects in both palate shelf epithelium and mesenchyme and led to cleft palate. Conclusion: FGFR1 signaling in cranial neural crest (CNC) cells regulates palate shelf growth and fusion during palatogenesis. Significance: The finding for the first time demonstrates how FGF signaling in CNC cells regulates palatogenesis. Cleft palate is a common congenital birth defect. The fibroblast growth factor (FGF) family has been shown to be important for palatogenesis, which elicits the regulatory functions by activating the FGF receptor tyrosine kinase. Mutations in Fgf or Fgfr are associated with cleft palate. To date, most mechanistic studies on FGF signaling in palate development have focused on FGFR2 in the epithelium. Although Fgfr1 is expressed in the cranial neural crest (CNC)-derived palate mesenchyme and Fgfr1 mutations are associated with palate defects, how FGFR1 in palate mesenchyme regulates palatogenesis is not well understood. Here, we reported that by using Wnt1Cre to delete Fgfr1 in neural crest cells led to cleft palate, cleft lip, and other severe craniofacial defects. Detailed analyses revealed that loss-of-function mutations in Fgfr1 did not abrogate patterning of CNC cells in palate shelves. However, it upset cell signaling in the frontofacial areas, delayed cell proliferation in both epithelial and mesenchymal compartments, prevented palate shelf elevation, and compromised palate shelf fusion. This is the first report revealing how FGF signaling in CNC cells regulates palatogenesis.

Oral manifestations and blood profile in patients with thalassemia trait.

BACKGROUND/PURPOSE Patients with thalassemia trait (TT) may have anemia. This study evaluated whether TT patients had specific oral manifestations and a particular blood profile compared with normal individuals. METHODS The oral manifestations and mean red blood cell count, corpuscular cell volume, red blood cell distribution width, Mentzer index, and Green and King index as well as blood concentrations of hemoglobin, iron, total iron binding capacity, vitamin B12, folic acid, and homocysteine in 65 TT patients and in 130 age- and sex-matched healthy controls were measured and compared. RESULTS TT patients had significantly higher frequencies of all oral manifestations than healthy controls (p < 0.001 for all), in which burning sensation of oral mucosa (90.8%), lingual varicosity (90.8%), dry mouth (72.3%), atrophic glossitis (32.3%), and numbness of the oral mucosa (30.8%) were the five leading oral manifestations for TT patients. Moreover, TT patients had significantly lower mean hemoglobin level, corpuscular cell volume, Mentzer index, and Green and King index (p < 0.001 for all) as well as significantly higher mean red blood cell count and red blood cell distribution width (p < 0.001 for both) than healthy controls. However, no significant difference in the mean blood iron, total iron binding capacity, vitamin B12, folic acid, or homocysteine levels was discovered between 65 TT patients and 130 healthy controls. CONCLUSION TT patients have specific oral manifestations and a particular blood profile compared to normal individuals.

Odontoma: A clinicopathologic study of 81 cases

BACKGROUND AND PURPOSE Odontoma is the most common odontogenic tumor. It includes 2 types, the compound and complex odontomas. There has not been a series study of the clinical and histologic features of odontomas from Taiwan. This study evaluated the clinicopathologic features of odontoma in Taiwanese. METHODS Cases of odontoma treated from 1998 to 2002 identified from medical records were included. The microscopic features, radiographic features, and clinical history of the patients were reviewed and analyzed. RESULTS A total of 81 odontomas in 81 patients (36 males and 45 females) were included. There were 62 compound and 19 complex odontomas. The mean age of the patients was 18 years with the majority of odontomas occurring in the first (32%) and second decade (38%) of life. Odontomas had a marked predilection for the maxilla (70%) and for the anterior region of the jaw (83%), particularly for the anterior maxilla (62%). Sixty four (79%) of the 81 odontomas were associated with 80 impacted teeth, including 71 permanent teeth, 2 deciduous teeth, and 7 supernumerary teeth. Of the 71 impacted permanent teeth, the maxillary central incisor (27%) was most commonly affected, followed by the maxillary canine (26%) and mandibular canine (24%). Histologic examination revealed enamel matrix in 90%, dentin in 100%, cementum in 88%, pulp tissue in 96%, fibrous capsule in 93%, ghost cells in 83%, reduced enamel epithelium in 86%, and nests of odontogenic epithelium in 58% of odontomas. Dentigerous cyst was associated with 9% of odontomas. CONCLUSIONS In this series, odontomas occurred most often in the first and second decade of life. Although complex odontomas are usually found in the posterior jaw, in this Taiwanese series they were most commonly found in the anterior maxilla. Odontoma is frequently associated with an impacted tooth and occasionally with a dentigerous cyst. No recurrence of odontomas was found after surgical excision with follow-up of 1 to 15 years.

Do all the patients with vitamin B12 deficiency have pernicious anemia

BACKGROUND Vitamin B12 deficiency may result in pernicious anemia (PA). This study evaluated whether all the patients with vitamin B12 deficiency had PA. METHODS The blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine concentrations and mean corpuscular volume (MCV) in 90 vitamin B12-deficient patients were measured and compared with the corresponding data in 180 age- and sex-matched healthy control subjects. PA was defined by World Health Organization (WHO) as having an Hb concentration <13 g/dl for men and <12 g/dl for women, an MCV ≧ 100 fl, a serum vitamin B12 level <200 pg/ml, and serum gastric parietal cell antibody (GPCA) positivity. RESULTS We found that 35 (38.9%) and 20 (22.2%) patients with vitamin B12 deficiency had deficiencies of Hb (men <13 g/dl, women <12 g/dl) and iron (<60 μg/dl), respectively. Moreover, 65 (72.2%) and 37 (41.1%) patients with vitamin B12 deficiency had abnormally high blood homocysteine level (>12.7 μM) and high MCV (≧100 fl), respectively. In addition, 43 (47.8%) vitamin B12-deficient patients with had GPCA positivity. Patients with vitamin B12 deficiency had a significantly higher frequency of Hb or iron deficiency, of abnormally elevated blood homocysteine level or high MCV, and of GPCA positivity than healthy control subjects (all P-values < 0.001). However, only 17 (18.9%) of 90 vitamin B12-deficient patients were diagnosed as having PA by the WHO definition. CONCLUSION Only 18.9% of patients with vitamin B12 deficiency are discovered to have PA by the WHO definition.

Hematinic deficiencies and pernicious anemia in oral mucosal disease patients with macrocytosis

BACKGROUND/PURPOSE Macrocytosis is defined as having the mean corpuscular volume (MCV) ≥ 100 fL. This study assessed hematinic deficiencies and pernicious anemia (PA) in oral mucosal disease patients with macrocytosis. METHODS The blood hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine concentrations and MCV in 60 oral mucosal disease patients with macrocytosis were measured and compared with the corresponding data in 120 age- and sex-matched healthy control participants. PA was defined by the World Health Organization (WHO) as having an Hb concentration < 13 g/dL for men and < 12 g/dL for women, an MCV ≥ 100 fL, a serum vitamin B12 level < 200 pg/mL, and serum gastric parietal cell antibody (GPCA) positivity. RESULTS We found that 30 (50.0%), 7 (11.7%), 24 (40.0%), and three (5.0%) oral mucosal disease patients with macrocytosis had deficiencies of Hb (men < 13 g/dL, women < 12 g/dL), iron (< 60 μg/dL), vitamin B12 (< 200 pg/mL), and folic acid (< 4 mg/mL), respectively. Moreover, 38 (63.3%) and 16 (26.7%) macrocytosis patients had abnormally high blood homocysteine level (> 12.3 μM) and serum GPCA positivity, respectively. Macrocytosis patients had a significantly higher frequency of Hb, iron, or vitamin B12 deficiency, of abnormally elevated blood homocysteine level, and of GPCA positivity than healthy control participants (p < 0.001). However, only 16.7% of 60 macrocytosis patients were diagnosed as having PA by the WHO definition. CONCLUSION Only 16.7% of oral mucosal disease patients with macrocytosis are discovered to have PA by the WHO definition.

The FGF-BMP Signaling Axis Regulates Outflow Tract Valve Primordium Formation by Promoting Cushion Neural Crest Cell Differentiation

Rationale: Heart valves develop from precursor structures called cardiac cushions, an endothelial-lined cardiac jelly that resides in the inner side of the heart tube. The cushions are then invaded by cells from different sources, undergo a series of complicated and poorly understood remodeling processes, and give rise to valves. Disruption of the fibroblast growth factor (FGF) signaling axis impairs morphogenesis of the outflow tract (OFT). Yet, whether FGF signaling regulates OFT valve formation is unknown. Objective: To study how OFT valve formation is regulated and how aberrant cell signaling causes valve defects. Methods and Results: By using mouse genetic manipulation, cell lineage tracing, ex vivo heart culture, and molecular biology approaches, we demonstrated that FGF signaling in the OFT myocardium upregulated Bmp4 expression, which then enhanced smooth muscle differentiation of neural crest cells (NCCs) in the cushion. FGF signaling also promoted OFT myocardial cell invasion to the cushion. Disrupting FGF signaling interrupted cushion remodeling with reduced NCCs differentiation into smooth muscle and less cardiomyocyte invasion and resulted in malformed OFT valves. Conclusions: The results demonstrate a novel mechanism by which the FGF-BMP signaling axis regulates formation of OFT valve primordia by controlling smooth muscle differentiation of cushion NCCs.