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Background/PurposeOral giant cell fibromas (GCFs) are found predominantly in Caucasians and rarely in other races. This retrospective study evaluated the clinicopathological features of 24 GCFs in Taiwanese patients.MethodsTwenty-four consecutive cases of oral GCF were investigated from 1987 to 2008. Clinical data and microscopic features were reviewed and analyzed.ResultsThe mean age of patients at the time of diagnosis was 29 years. Oral GCF occurred more commonly in patients between 11 and 40 years of age. There were 12 male and 12 female patients. The lesions were found more frequently on the tongue (8 cases) and gingiva (7 cases). The mean size of the lesion was 5.5 mm (range, 2–10 mm) in greatest dimension. GCF is misdiagnosed frequently as fibroma (19 cases) or papilloma (5 cases). All tumors were treated by total surgical excision and no recurrence was found after treatment. Microscopically, the GCF was a sessile or pedunculated mass covered with a thin layer of parakeratinized or orthokeratinized stratified squamous epithelium. The tumor was composed mainly of loose or dense fibrous connective tissue with well-formed capillaries and no inflammation. The consistent and diagnostic feature was the presence of large stellate giant cells, usually with one or two nuclei. Multinucleated giant cells were seen occasionally. These giant cells were most numerous in the connective tissue just beneath the epithelium.ConclusionOral GCFs show no significant sex predilection and occur in patients in the second to fourth decades of life. Usually, the lesions are < 1 cm in diameter and are found more frequently on the tongue and gingiva. GCF resembles fibroma or papilloma and is difficult to diagnose correctly at the first glance. All GCFs can be treated by conservative surgical excision without subsequent recurrence.

This study used an immunohistochemical method to examine the expression of osteopontin (OPN) in 30 ameloblastomas and of integrin alpha(v) and CD44v6 in 20 of these 30 ameloblastomas. We found that the positive staining rate in ameloblastomas was 87% for OPN, 45% for integrin alpha(v), and 90% for CD44v6. Both ameloblast-like and stellate reticulum-like cells showed a high expression of OPN and CD44v6. There was also a strong integrin alpha(v) immunostaining on the cell membrane of osteoclasts. Binding of OPN to osteoclast cell membrane receptor integrin alpha(v) can activate the osteoclast and increase its osteolytic activity. In addition, binding of OPN to ameloblastoma tumor cell membrane receptor CD44v6 can enhance tumor cell migration, invasion and spread. Therefore, we suggest that the local aggressive behavior and high osteolytic ability of ameloblastomas in the jawbones can be explained by the high expression of OPN and CD44v6 in ameloblastoma cells and the high expression of integrin alpha(v) in osteoclasts.

Background/Purpose: Odontogenic keratocysts (OKCs) are more aggressive and more osteolytic lesions than dentigerous cysts (DCs) and radicular cysts (RCs). Osteopontin (OPN) is related to cancer metastasis and bone destruction. Binding of OPN to its cell membrane receptors integrin α(subscript v) and CD44v6 can enhance tumor cell motility, migration, invasion and spread. This study assessed the possible contribution of OPN, integrin α(subscript v) and CD44v6 to the local aggressive behavior and osteolytic ability of OKCs. Methods: We used an immunohistochemical method to examine the expression of OPN, integrin α(subscript v) and CD44v6 in tissue sections of 20 OKCs, eight DCs and 10 RCs. Results: We found strong cytoplasmic OPN immunostaining in lining epithelial cells of 8 of 20 OKCs but not in any DCs and RCs. Positive OPN staining was also noted in the subepithelial connective tissue of four OKCs with intraepithelial expression of OPN. Diffuse and strong membranous integrin α(subscript v) staining was discovered in osteoclasts in all our tissue sections and in nearly all lining epithelial cells of DCs and RCs, but not in OKCs. In addition, diffuse and strong membranous CD44v6 staining was also observed in nearly all lining epithelial cells of OKCs, DCs and RCs. Conclusion: Binding of OPN to osteoclast cell membrane receptor integrin α(subscript v) can activate the osteoclasts and increase their osteolytic activity. In addition, binding of OPN to OKC lining epithelial cell membrane receptor CD44v6 can enhance the motility, migration, invasion and spread of lining epithelial cells into the surrounding cancellous bone. Therefore, we suggest that the local aggressive behavior and high osteolytic ability of OKCs in the jawbone can be explained at least partially by high expression of OPN and CD44v6 in lining epithelial cells of OKCs and high expression of integrin α(subscript v) in osteoclasts.

BACKGROUND Mucocutaneous type of Behcet's disease (MCBD) is a multisystemic inflammatory disease with oral and genital ulcers with or without skin lesions. METHODS A solid phase, two-site sequential chemiluminescent immunometric assay was used to measure serum levels of interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-alpha in 54 normal control subjects and in 64 MCBD patients before and after treatment with levamisole plus colchicine. RESULTS We found that 67%, 83% or 67% of MCBD patients had a serum IL-6, IL-8 or TNF-alpha level greater than the upper normal limit of 4.7, 8.7 or 7.4 pg/ml, respectively. The mean serum level of IL-6 (9.9 +/- 2.4 pg/ml, P < 0.005), IL-8 (107.5 +/- 21.4 pg/ml, P < 0.001) or TNF-alpha (22.5 +/- 4.1 pg/ml, P < 0.001) in 64 MCBD patients was significantly higher than that (2.1 +/- 0.2, 5.7 +/- 0.2 or 3.8 +/- 0.2 pg/ml for IL-6, IL-8 or TNF-alpha level, respectively) in normal control subjects. In 43 MCBD patients with all the serum IL-6, IL-8 and TNF-alpha levels higher than their upper normal limits, treatment with levamisole plus colchicine for a period of 0.5-11.5 (mean, 3.2 +/- 2.4) months could significantly reduce the mean serum IL-6, IL-8 and TNF-alpha levels from 9.0 +/- 1.7 to 1.6 +/- 0.2 pg/ml (P < 0.001), 134.6 +/-28.2-6.0 +/- 0.4 pg/ml (P < 0.001) and 25.7 +/- 5.6-3.5 +/- 0.4 pg/ml (P < 0.001), respectively. CONCLUSIONS Treatment with levamisole and colchicine can result in a significant reduction of serum IL-6, IL-8 or TNF-alpha level in MCBD patients.

This study used an immunohistochemical technique to examine the expression of receptor-binding cancer antigen expressed on SiSo cells (RCAS1) in 84 specimens of oral squamous cell carcinoma (OSCC), 106 specimens of oral epithelial dysplasia (OED, 32 mild, 44 moderate, and 30 severe OED cases), and 20 specimens of normal oral mucosa (NOM). We found that the mean RCAS1 labeling indices (LIs) increased significantly from NOM (12+/-5%) through mild OED (31+/-13%), moderate OED (44+/-17%), and severe OED (56+/-18%) to OSCC samples (68+/-20%, p0.001). A significant correlation was found between the higher mean RCAS1 LI and OSCCs with larger tumor size (p=0.001), positive lymph node metastasis (p0.001), or more advanced clinical stages (p0.001). Positive lymph node metastasis (p=0.0073) and RCAS1 LIor = 60% (p=0.048) were identified as independent unfavorable prognosis factors by multivariate analyses with Cox regression model. Kaplan-Meier curve showed that OSCC patients with a RCAS1 LIot = 60% had a significantly poorer cumulative survival than those with a RCAS1 LI60% (log-rank test, p=0.0113). We conclude that the expression of RCAS1 is an early event in oral carcinogenesis. The RCAS1 LI in OSCC samples can predict the progression of OSCCs and the survival of OSCC patients.

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.

Expression of p53 protein was examined in oral squamous cell carcinoma (SCC) from patients who were areca quid (AQ) chewers and/or tobacco smokers, using anti-p53 antibodies with an immunoperoxidase technique. Positive p53 stain was observed in 47 of 81 (58%) cases of oral SCC. p53 overexpression was found to be higher in patients without AQ chewing and smoking habits than in patients with these two habits (80% vs 52%, P=0.076). No significant correlation was found between p53 expression and the patients' age, sex, cancer location, clinical staging, primary tumor TNM status, or histological differentiation of SCC. The Kaplan-Meier analysis showed that the prognosis for patients with p53-negative tumors was significantly better than that for patients with p53-positive tumors (P

This study used an immunohistochemical technique to examine the expression of human telomerase reverse transcriptase (hTERT) protein in 82 specimens of OSCC, 116 specimens of oral epithelial dysplasia (OED), and 21 specimens of normal oral mucosa (NOM). The cytoplasmic and nuclear hTERT staining intensity (SI; 0, no staining; 1, weak; 2, moderate; 3, strong), labeling indices (LIs, defined as the percentage of positive cells in total cells), and labeling scores (LSs, defined as LI x SI) in OSCC, OED, and NOM samples were calculated and compared among groups. The correlation between the cytoplasmic or nuclear hTERT LS in OSCCs and clinicopathological parameters or survival of OSCC patients was analyzed statistically. The mean cytoplasmic hTERT LSs increased significantly from NOM (87+/-17%) through OED (95+/-18%) to OSCC samples (114+/-33%, p=0.000). The mean nuclear hTERT LSs also increased from NOM (80+/-14%) to OED (91+/-20%) and then decreased to OSCC samples (86+/-35%) with no statistically significant difference among the 3 groups. A significant correlation was found between the higher mean cytoplasmic hTERT LSs and OSCCs occurring in male patients (p=0.023), with larger tumor sizes (T3 and T4, p=0.048), with more advanced clinical stages (stages 3 and 4, p=0.033), or from patients with areca quid chewing (p= 0.029), cigarette smoking (p=0.027), or alcohol drinking habit (p=0.025). In addition, OSCC patients with nuclear hTERT LSs greater than 100% were prone to have a higher recurrence rate (p=0.044) and a lower 5-year survival rate (p=0.011). Our results indicate that the increased expression of hTERT protein is an early event in oral carcinogenesis and hTERT may be a biomarker for OSCCs. Measuring the amount of cytoplasmic or nuclear expression of hTERT in OSCC samples may predict the oral cancer progression, recurrence, and prognosis in Taiwan.

Background: Primary mucosal melanomas (MMs) of the head and neck are a rare entity. Melanomas with characteristic melanin-pigmented tumor cells are easy to diagnose, but those without melanin-pigmented tumor cells, amelanotic melanomas, are difficult to identify and need immunohistochemistry (IHC) to confirm the final diagnosis. In this study, we examined the expression of three melanocytic differentiation markers, HMB-45, S-100, and Melan-A in primary oral and nasal MMs. We tried to evaluate whether HMB-45, S-100, and Melan-A were useful for diagnosis of primary oral and nasal MMs and to find out which marker was the best of the three. Methods: This study used IHC to examine the expression of HMB-45, S-100, and Melan-A in 17 formalin-fixed paraffin-embedded specimens of primary oral and nasal MMs. The staining intensities (SIs) and labeling indices (LIs) of HMB-45, S-100, and Melan-A in 17 MMs were calculated and compared between any two markers. Results: Immunostaining results showed that the positive rate was 94% (16 of 17) for HMB-45, 88% (15 of 17) for S-100, and 71% (12 of 17) for Melan-A in 17 MMs. The SI of HMB-45 was significantly higher than that of S-100 (P = 0.0011) or of Melan-A (P = 0.0034). In addition, the mean LI of Melan-A (59 ± 43%) was significantly lower than that of HMB-45 (83 ± 28%, P = 0.0065) or of S-100 (79 ± 33%, P = 0.0237). Conclusions: Our results indicate that both HMB-45 and S-100 show a high positive rate and LI in MMs and therefore may be good markers for immunohistochemical diagnosis of primary oral and nasal MMs. In addition, HMB-45 may be a more sensitive marker than S-100 because HMB-45 shows a significantly higher SI than S-100 in this study.

Background: Previous study has shown a high incidence of autoantibodies including antinuclear (ANA), antismooth muscle (SMA), antigastric parietal cell (GPCA), antithyroid microsomal (TMA), and antireticulin antibodies in a small group of 26 patients with oral submucous fibrosis (OSF). The reasons why some of the OSF patients have high titers of autoantibodies in serum have not been completely explained and no further study on autoantibodies in OSF patients has been done in a large group of patients. Methods: In this study, we determined the serum levels of ANA, SMA, GPCA, and TMA in a large group of 109 male Taiwanese patients with OSF by an indirect immunofluorescence technique (for ANA, SMA, and GPCA), and by a semiquantitative microtiter particle agglutination test (for TMA). The presence of serum autoantibodies in OSF patients was further correlated with patients' oral habits and the severity of OSF measured by maximum mouth opening (MMO) and sites of involvement. Results: We found that the frequencies of presence of serum ANA (23.9%), SMA (23.9%), and GPCA (14.7%) in OSF patients were significantly higher than those (9.2, 7.3, and 5.5%, respectively) in healthy control subjects (P 0.05). The presence of serum GPCA in OSF patients was significantly associated with daily areca quid (AQ) consumption (P

Recombinant viruses were constructed to have an Escherichia coli replicon containing a mutagenesis marker, the supF gene, integrated within the thymidine kinase locus ( tk ) of herpes simplex virus type 1. These viruses expressed either wild-type or mutant DNA polymerase (Pol) and were tested in a mutagenesis assay for the fidelity of their replication of the supF gene. A mutation frequency of approximately 10 −4 was observed for wild-type strain KOS-derived recombinants in their replication of the supF gene. However, recombinants derived from the PAA r 5 Pol mutant, which has been demonstrated to have an antimutator phenotype in replicating the tk gene, had three- to fourfold increases in supF mutation frequency ( P < 0.01), a result similar to that exhibited when the supF gene was induced to replicate as episomal DNA (Y. T. Hwang, B.-Y. Liu, C.-Y. Hong, E. J. Shillitoe, and C. B. C. Hwang, J. Virol. 73:5326-5332, 1999). Thus, the PAA r 5 Pol mutant had an antimutator function in replicating the tk gene and was less accurate in replicating the supF gene than was the wild-type strain. The spectra of mutations and distributions of substituted bases within the supF genes that replicated as genomic DNA were different from those in the genes that replicated as episomal DNA. Therefore, the differences in sequence contents between the two target genes influenced the accuracy of the Pol during viral replication. Furthermore, the replication mode of the target gene also affected the mutational spectrum.

Estrogens modulate the catabolic effects of PTH on bone in vivo and in vitro. PTH-stimulated cAMP accumulation in osteoblasts is thought to be linked to increased osteoclastic activity, but the precise mechanism is still unknown. In cocultures of clonal marrow stromal cells (MS1) and normal mouse spleen cells, both 1,25-dihydroxyvitamin D3 and rat PTH (rPTH)-(1-34) can induce the formation of tartrate-resistant acid phosphatase- and calcitonin receptor-positive multinucleated osteoclast-like cells, which can attach to dentine slices and produce resorption pits. In this system, osteoclastogenesis stimulated by PTH, but not by 1,25-dihydroxyvitamin D3, was suppressed by 17beta-E2 (10(-10)-10(-8) M), whereas 17alpha-E2 (10(-8) M) had no effect. Exposure to 10(-8) M 17beta-E2, but not 17alpha-E2, also significantly decreased the PTH-induced attachment of osteoclast-like cells to dentine slices. 17beta-E2 inhibited osteoclast-like cell formation induced by 8-bromo-cAMP (10(-4) M), 12-O-tetradecanoylphorbol 13-acetate (10(-8) M), or rat PTH-(1-34) (10(-7) M) in combination with either rp-adenosine-3',5'-cyclic monophosphorothioate (10(-4) M) or 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (10(-5) M). 17beta-E2 suppressed the partial stimulation of tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cell formation induced by [Arg(2)]human (h) PTH-(1-34) (10(-7) M) or hPTH-(3-34) (10(-7) M), but not that caused by 10(-7) M hPTH-(53-84). We conclude that estrogens suppress PTH-stimulated osteoclast-like cell formation by blocking both the cAMP-dependent PKA pathway and the PLC-coupled calcium/PKC pathway. In addition to inhibiting formation of osteoclasts and promoting their apoptosis, estrogen may regulate bone resorption by blocking attachment of osteoclasts to bone.

Background: Previous studies have shown that the local and systemic upregulation of fibrogenic cytokines and downregulation of antifibrotic cytokine are central to the pathogenesis of oral submucous fibrosis (OSF). The milk from cows immunized with human intestinal bacteria (immune milk) contains an anti-inflammatory component that may suppress the inflammatory reaction and modulate cytokine production. Therefore, it was decided to test whether immune milk may have some beneficial effects on controlling the symptoms and signs in OSF patients. Methods: In this preliminary study, 26 OSF patients who received immune milk treatment (45 g of immune milk powder twice a day) for 3 months and oral habit intervention were included in the experimental group. Another 20 OSF patients who received only oral habit intervention served as the control group. Results: We found that the interincisor distance was significantly improved (≧3 mm of the baseline measurement) in 18 of the 26 (69.2%) OSF patients in the experimental group at exit. However, in the control group none of the OSF patients had an increase in interincisor distance greater than 2 mm. In addition, disappearance or significant improvement of symptoms at exit was observed in 80% (16/20) of the patients with intolerance to spicy foods (P

To test whether the oral epithelia of oral submucous fibrosis (OSF), epithelial hyperkeratosis (EH) and epithelial dysplasia (ED) may have increased proliferative activity under the long-term exposure to areca quid ingredients and whether there is an increased expression of proliferating cell nuclear antigen (PCNA) in oral premalignant lesions with disease progression, we used an immunohistochemical technique with the mouse monoclonal antibody PC10 to investigate PCNA expression in histologic sections of OSF, EH, ED and normal oral mucosa (NOM). Positive PCNA staining was found mainly in basal and parabasal epithelial cells in all specimens of OSF, EH, ED and NOM. The mean PCNA labeling indices (LI) in NOM, OSF, EH and ED were 8.8+/-2.7%, 22.1+/-12.5%, 25.5+/-5. 2% and 44.9+/-15.4%, respectively. Significant differences in the PCNA LI were noted between NOM and OSF (P0.01), EH (P0.001) or ED (P0.001), as well as between ED and OSF (P0.001) or EH (P0.01). The gradual increase of PCNA expression with the morphologic transformation of normal epithelial cells into dysplastic epithelial cells suggests that there is increased proliferative activity in oral premalignant lesions with disease progression. However, no significant correlation was found between PCNA LI in OSF epithelium and the clinicohistologic parameters of OSF. In addition, the mean PCNA LI of p53-positive OSF cases (23.7+/-12.0%) was very close to that of p53-negative OSF cases (23.9+/-13.1%), suggesting that there was no association between PCNA and p53 expression in OSF.

A mutagenesis system was developed for the in vivo study of the fidelity of DNA replication mediated by wild-type herpes simplex virus type 1 (HSV-1) strain KOS and its polymerase (Pol) mutant derivatives PAA r 5, Y7, and YD12. The pHOS1 shuttle plasmid, which contained the SupF mutagenesis marker gene and the HSV ori s sequence, was used for analysis of the mutation frequency and the mutation spectrum. All three Pol mutants induced significant increases in the mutation frequencies of the target gene, despite the fact that PAA r 5 was previously shown to have an antimutator phenotype by the thymidine kinase mutagenesis assay (J. D. Hall, D. M. Coen, B. L. Fisher, M. Weisslitz, S. Randall, R. E. Almy, P. Gelep, and P. A. Schaffer, Virology 132:26–37, 1984; C. B. C. Hwang and J.-H. Chen, Gene 152:191–193, 1995). Altered spectra of mutated target genes induced by these three mutants were also observed. The relative frequencies of both deletion and complex mutations found in mutants induced by exonuclease-proficient Pols were significantly higher than those induced by exonuclease-deficient Pols. On the other hand, the exonuclease-deficient Pols induced significant increases in the frequency of base substitutions, which comprised predominantly G · C-to-T · A transversions, as well as mutations at additional hot spots. These results suggest that the HSV-1 DNA Pol can incorporate purine-purine or pyrimidine-pyrimidine mispaired bases which may be preferentially proofread by its intrinsic exonuclease activity. Furthermore, the effects of the sequence context of the target gene and the assay method should also be considered carefully in any analysis of replication fidelity.

The purpose of this study was to evaluate the effect of levamisole on the immune system of patients with recurrent aphthous ulcers (RAU) or oral lichen planus (OLP) in an open trial. Lymphocyte subsets, serum immunoglobulins, and circulating immune complexes (CIC) in patients with RAU or OLP and in normal control subjects were determined by an indirect immunofluorescence (ML) technique with monoclonal anti-lymphocyte antibodies, by single radial immunodiffusion, and by precipitation with 3% polyethylene glycol, respectively. In addition, the anti-nuclear antibodies (ANA) and anti-basal cell antibodies (anti-BCA) in sera were detected by an IIF technique. We found a significant improvement in clinical symptoms and normalization of the decreased CD4/CD8 ratio in RAU patients after levamisole treatment. Moreover, the decreased CD4/CD8 ratio, which persisted until the remission stage in the untreated RAU patients, reverted to normal m the active late stage in the levamisole-treated patients. This reversion of aberrant cellular immunity in an earlier stage of the ulcer cycle may explain why RAU patients experience symptom improvement after levamisole treatment. Although RAU patients treated with levamisole for 1 to 3 or 4 months still had higher than normal levels of CIC and serum immunoglobulins, the levels of their IgA and IgM returned to normal values after 4 months of levamisole treatment. The serum ANA detected m 6 patients with RAU and 3 patients with erosive OLP disappeared after 1-22 months of levamisole treatment. The disappearance of serum anti-BCA was also observed in 50%, of the anti-BCA-positive patients with erosive OLP after 3–13 months of levamisole treatment. These findings suggest that levamisole has modulating effects on both cell-mediated and humoral immunity in patients with RAU or OLP.

Background: Oral verrucous hyperplasia (OVH) is a premalignant lesion that may transform into an oral cancer. Methods: Sixty consecutive OVH cases were collected from 2003 to 2004. Clinicopathological features and the 5-year malignant transformation rate of these 60 OVH lesions were evaluated and analyzed. Results: We found that 84% of OVH lesions occurred in patients between 40 and 69 years of age. The most common site for OVH lesions was the buccal mucosa (48%), followed by the tongue (20%), palate (18%), gingiva (7%), and labial mucosa (7%). Approximately 91% of OVH patients were areca quid chewers and 89% were smokers. When 60 OVH lesions were classified into 30 plaque-typed and 30 mass-typed OVH lesions, the mass-typed OVH lesions had a higher malignant transformation rate of 17% (5/30) than the plaque-typed OVH lesions (3%, 1/30) during a mean follow-up period of 59 ± 7 months. The mean time for malignant transformation was 22 ± 11 months. Of the 6 OVH lesions with malignant transformation, 2 underwent total surgical excision and 4 did not receive any form of therapy. Conclusions: We conclude that OVH lesions occur more commonly on the buccal mucosa and are highly associated with the areca quid chewing and cigarette smoking habits. The overall 5-year malignant transformation rate of 60 OVH lesions was 10%. The mass-typed OVH lesions had a higher malignant transformation rate than the plaque-typed OVH lesions and thus should receive an immediate treatment, such as total surgical excision or photodynamic therapy, after the histopathologic diagnosis.

Mucocutaneous type of Behcet's disease (MCBD) is a multisystemic inflammatory disease with oral and genital ulcers with or without skin lesions.A solid phase, two-site sequential chemiluminescent immunometric assay was used to measure serum levels of interleukin (IL)-6, IL-8 and tumour necrosis factor (TNF)-alpha in 54 normal control subjects and in 64 MCBD patients before and after treatment with levamisole plus colchicine.We found that 67%, 83% or 67% of MCBD patients had a serum IL-6, IL-8 or TNF-alpha level greater than the upper normal limit of 4.7, 8.7 or 7.4 pg/ml, respectively. The mean serum level of IL-6 (9.9 +/- 2.4 pg/ml, P0.005), IL-8 (107.5 +/- 21.4 pg/ml, P0.001) or TNF-alpha (22.5 +/- 4.1 pg/ml, P0.001) in 64 MCBD patients was significantly higher than that (2.1 +/- 0.2, 5.7 +/- 0.2 or 3.8 +/- 0.2 pg/ml for IL-6, IL-8 or TNF-alpha level, respectively) in normal control subjects. In 43 MCBD patients with all the serum IL-6, IL-8 and TNF-alpha levels higher than their upper normal limits, treatment with levamisole plus colchicine for a period of 0.5-11.5 (mean, 3.2 +/- 2.4) months could significantly reduce the mean serum IL-6, IL-8 and TNF-alpha levels from 9.0 +/- 1.7 to 1.6 +/- 0.2 pg/ml (P0.001), 134.6 +/-28.2-6.0 +/- 0.4 pg/ml (P0.001) and 25.7 +/- 5.6-3.5 +/- 0.4 pg/ml (P0.001), respectively.Treatment with levamisole and colchicine can result in a significant reduction of serum IL-6, IL-8 or TNF-alpha level in MCBD patients.

Background/purpose Oral verruciform xanthoma (VX) is an uncommon oral mucosal lesion. This retrospective study evaluated the clinical and histopathologic features of 15 oral VXs occurring in Taiwanese patients. Methods Fifteen consecutive cases of oral VX were collected from January 1988 to December 2005. Clinical data and microscopic features of these cases were reviewed and analyzed. Results The mean age of patients was 45 years (range, 18-79 years). There were eight male and seven female patients. Seven (46.6%) cases occurred on the gingiva, four (26.7%) on the tongue, and four (26.7%) on the buccal or vestibular mucosa. The greatest mean dimension of the lesions was 0.8 cm (range, 0.3-2.0 cm). Three patients had concomitant other oral mucosal lesions such as oral submucous fibrosis, squamous cell carcinoma, and erosive oral lichen planus. Microscopically, all specimens showed varying degrees of surface parakeratosis and the accumulation of numerous foam cells in the connective tissue papillae among uniformly elongated epithelial ridges. Individuals or aggregates of foam cells were also found underneath the epithelial ridges in nine (60%) cases. When the oral VX lesions were further classified into three types according to the microscopic surface architecture, seven (47%) lesions were of the verrucous type, three (20%) the papillary type, and five (33%) the flat type. All patients received surgical excision of the lesions and no recurrence was noted during follow-up of up to 18 years. Conclusion Oral VXs occur more frequently in the fifth decade of life. The more commonly affected site is the gingiva. The treatment of choice for oral VXs is surgical excision. The prognosis is excellent and recurrence was not seen in this study. [ J Formos Med Assoc 2007;106(2):141-147]

Bone morphogenic proteins (BMPs) are important bone-induction factors, and the development of a suitable carrier for BMPs is a critical step to achieve osteoinductive function. The aims of the present study were to evaluate, at the cellular and molecular levels, the feasibility of recombinant human BMP-2 (rhBMP-2)-collagen composite scaffold and its efficiency for carrying BMP-2 in ectopic bone formation in rats.Scaffolds with (test) or without rhBMP-2 (control) were made and implanted into the calf muscle of 16 5-week-old rats. The tissue responses to the scaffolds were examined by histology. Masson's trichrome and von Kossa stainings were performed to examine collagen matrix deposition and calcification at 3, 7, 10, and 14 days. Expressions of bone phenotypic markers, alkaline phosphatase, osteocalcin, osteopontin, and bone sialoprotein were detected by reverse transcription-polymerase chain reaction and immunohistochemistry.No detectable adverse responses were noted around the implanted scaffolds, and the area of the resorbed scaffold had been replaced by young connective tissue by 3 to 7 days in both groups. In the rhBMP-2 composite scaffold, collagen matrix deposition was found in the implanted site on day 7 and initial signs of endochondral differentiation also appeared. Mineralization and the expressions of key bone proteins were demonstrated in chondroblasts and osteoblasts at 7 to 14 days. Molecular cascades of bone induction were not shown in control specimens.The rhBMP-2-atelocollagen scaffold showed excellent biocompatibility and possessed a bone-inducing capacity in rat within 2 weeks, and, thus, may provide a potential application in tissue engineering of bone tissue.

Incisional biopsy is accepted by most clinicians as a dependable way of assessing the nature of oral leukoplakia (OL). The aim of the present study was to investigate its reliability and analyze risk factors associated with underdiagnosis from incisional biopsy.A cross-sectional retrospective study was conducted in 242 patients with a clinical diagnosis of OL. The discrepancy between provisional diagnosis (from incisional biopsy) and definitive diagnosis (from resection specimen) was analyzed and correlated with clinical variables. Patients who had incisional biopsy taken from a single location and those who received multiple-site biopsies were analyzed separately.In the 200 cases receiving single-site biopsy, the agreement rate between provisional and definitive diagnoses was only 56%, and underdiagnosis from incisional biopsy was noted in 29.5% of patients. Underdiagnosis rate in the 42 patients receiving multiple-site biopsies was significantly lower (11.9%; P.05). The rate of unexpected carcinoma in resection specimen was also significantly lower in the multiple-biopsy patients than in the single-biopsy patients (2.4% vs. 12.0%; P.05). For the single-biopsy group, multivariate analysis revealed that clinical appearance significantly influenced the risk of underdiagnosis and unexpected carcinoma (both P.05). Compared with homogeneous lesions, nonhomogeneous OL were more prone to be underdiagnosed (adjusted odds ratio [AOR] 2.36, 95% confidence interval [CI] 1.16-4.82) and have carcinoma undetected by incisional specimen (AOR 15.94, 95% CI 2.09-121.72).Incisional biopsy was found to have limitations in the assessment of OL, especially for nonhomogeneous lesions. Clinicians should be conscious of the possible underdiagnosis from incisional biopsy, and multiple biopsies should be taken whenever they think that it is necessary.

The issue of existence of malignancy within oral leukoplakia has seldom been addressed in Taiwan. The aims of this study were to investigate the prevalence of carcinoma and dysplasia within oral leukoplakia at the time of clinical diagnosis and to identify the associated risk factors in Taiwan.The prevalence rate of malignancy and dysplasia in 1046 oral leukoplakias at a university hospital was calculated. Univariate and multivariate analyses by the Mantel-Haenszel method and multiple logistic regression model were performed to examine risk factors associated with the presence of carcinoma and dysplasia within the lesions.The prevalence rate of carcinoma was 12.9%. The relative risks for the presence of malignancy in leukoplakias on the tongue/floor of mouth and with nonhomogeneous appearance were 2.72- and 28.13-fold by multivariate logistic regression analysis, when compared with those on buccal mucosa and lesions having homogeneous surface (both P.05). In contrast, patients who both smoked and chewed betel quid had a significantly lower risk for carcinoma than the abstainers (P.05). A synergistic effect between the 2 major risk factors of clinical appearance and lesion site was evident. Nonhomogeneous leukoplakia on tongue/floor of mouth had a 43.10-fold higher risk compared to homogeneous lesions located on buccal mucosa or other sites (P.05). However, homogeneous leukoplakia in buccal mucosa or other sites of the oral cavity still had the possibility of having carcinoma within the lesion. The prevalence of dysplasia was 45.6% among the noncancerous leukoplakias with risk factors similar to those for carcinoma.Our results demonstrate that some leukoplakias contain a malignant component. Lesions with certain features are more prone to carcinoma, but no clinical attributes can bring certitude. Therefore, all oral leukoplakias should be submitted to microscopic analysis before any definite treatment or long-term follow-up.

Background Hepatocyte growth factor (HGF) is a pleotropic growth factor that regulates cell proliferation, migration, survival, tumor angiogenesis, and tumor cell invasion and metastasis. Its diverse biological effects are mediated through its interaction with its receptor, c-met protein. Methods In this study, we examined the expression of HGF and c-met protein in 93 specimens of oral squamous cell carcinoma (OSCC), 10 specimens of oral epithelial dysplasia (OED), 14 specimens of oral epithelial hyperkeratosis (OEH), and 16 specimens of normal oral mucosa (NOM) by immunohistochemistry. The HGF and c-met labeling indices (LIs) in OSCC, OED, OEH, and NOM groups were calculated and compared between groups. The correlation between the expression of HGF or c-met in OSCCs and clinicopathological parameters, or survival of OSCC patients was analyzed statistically to investigate the possible influence of HGF or c-met on the progression and prognosis of OSCCs in Taiwan. Results Positive HGF or c-met staining was mainly cytoplasmic. The mean HGF LI increased significantly from NOM (3.1 +/- 5.1%) through OEH (32.5 +/- 19.8%) and OED (52.0 +/- 19.3%) to OSCC (71.9 +/- 28.6%; P = 0.000). The mean c-met LI also increased significantly from NOM (25.8 +/- 30.8%) and OEH (34.4 +/- 19.3%) through OED (53.0 +/- 20.0%) to OSCC (73.0 +/- 29.4%; P = 0.000). Statistical analysis showed that the c-met LI in either the tumor center or invasion front was significantly associated with T status, N status, and clinical staging of OSCC. However, only the HGF LI in the tumor invasion front was significantly correlated with N status and clinical staging of OSCC. Conclusion Our results suggest that the expression of HGF and c-met protein is an early event in oral carcinogenesis in Taiwan. The HGF LI in the tumor invasion front and the c-met LI in either the tumor center or invasion front can predict the progression of OSCCs in Taiwan.

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.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.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.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.

Calcifying odontogenic cyst (COC) is a rare type of odontogenic cyst. This retrospective study analyzed the clinical, radiographic, and histopathologic features of COC in Taiwanese.Ten cases of COC in 2 male and 8 female patients with a mean age of 29 years (range, 11 to 48 years) treated from January 1985 to December 2002 were included. Microscopic slides, clinical histories, and radiographic features of these 10 COC cases were reviewed and analyzed.COCs occurred in the maxilla in 3 cases and in the mandible in 7 cases. COCs were associated with impacted teeth in 6 cases and with odontomas in 3 cases. All COCs appeared as either unilocular (9 cases) or multilocular (1 case) radiolucencies. In 7 cases, spotty radiopaque materials were scattered throughout the radiolucency. Histologically, all of the lesions were at least partially lined by epithelium with cuboidal to columnar basal cells and stellate reticulum-like suprabasal cells. Variable numbers of ghost cells, some of which were calcified, were observed in the lining epithelium or in the fibrous connective tissue wall of all 10 cases. Juxta-epithelial dentinoid was also found in all cases. However, proliferation of ameloblastoma-like tumor nests was observed in only 1 case. Based on the above histologic findings, 6 COC lesions were classified as simple unicystic type, 3 as unicystic odontoma-producing type, and 1 as unicystic ameloblastomatous proliferating type.COC occurs frequently in the second and third decades and is commonly associated with an impacted tooth or an odontoma. It usually appears as a mixed radiolucent and radiopaque lesion radiographically. Simple unicystic type is the most common type of COC. No recurrences were found after conservative surgical removal in this series.

Objective The aim of the present study was to investigate whether interleukin (IL)-1beta in diseased tissues adjacent to periodontal pockets can reflect the degree of inflammation and destruction of these tissues pathologically. Background IL-1beta-dependent mechanisms have been strongly implicated in contributing to inflammation and destruction of bone and attachment loss, which are characteristic features of periodontal disease. This biochemical mediator released during pro-inflammatory processes has not been objectively integrated with clinical and histopathologic features of periodontal disease. Methods Periodontitis-affected inflamed tissue and clinically nonaffected healthy gingivae were harvested from 14 periodontal patients, respectively. The severity of tissue inflammation was illustrated by clinical parameters and cellular histologic changes and quantified by histometric assessments. IL-1beta in these extracted specimens was measured with an enzyme-linked immunosorbent assay (ELISA) technique. Pathogenic roles that IL-1beta plays in gingival inflammation and pathologic tissue changes in tissue sections were analyzed statistically. Results The overall total tissue IL-1beta, tissue concentration of IL-1beta, and percentage of inflammatory cell infiltration (PICI) determined from diseased gingivae were obviously higher than those of controls from both healthy sites of periodontitis and non-periodontitis subjects. With increasing gingival index (GI), plaque index (PlI), and probing depth (PD), there was a marked elevation in total tissue IL-1beta. Total tissue IL-1beta was significantly correlated with GI, PlI, the PICI, and tissue alterations. Polymorphonuclear leukocytes (PMNs) and monocyte-macrophage cells seemed to predominate in heavily infiltrated areas of diseased gingiva. These cell types were confirmed by immunocytochemical localization with either monoclonal mouse antihuman neutrophil elastase antibody or monoclonal mouse antihuman macrophage (CD68) antibody, respectively. Total tissue IL-1beta and the PICI were also elevated in diseased gingivae near deeper PD, while neither total IL-1beta nor tissue concentration was statistically correlated with PD. Thus, correlation analysis indicates that IL-1beta level in inflamed periodontal tissues correlates highly with clinical parameters (GI and PlI) and PICI (the degree of inflammation). Conclusions These observations suggest that IL-1beta plays a significant role in the pathogenic mechanisms of periodontal tissue destruction, and that measurement of tissue IL-1beta would be a valuable aid and useful for diagnostic markers of periodontal diseases.

During skeletal development and bone remodeling, bone marrow stromal cells give rise to osteoblasts and provide a critical microenvironment to support osteoclast formation. Estrogen is important for the maintenance of bone balance in adult animals by either increasing bone mass or inhibiting osteoclastic bone resorption. This study sought to determine the role that estrogen plays in coordinating osteogenic differentiation of bone marrow stromal cells and the ability of these cells to support osteoclast formation.A conditionally immortalized mouse bone marrow stromal cell line, MS1, was used to examine the effects of estrogen on stromal cell differentiation and on stromal cell-supported osteoclast formation.On treatment of MS1 cells with 17 beta-estradiol (E2) (10(-12)-10(-8) M), alkaline phosphatase activity and bone nodule formation were increased in a dose-dependent manner, while the proliferation of MS1 cells was dose-dependently inhibited. 17 beta-E2 (10(-12)-10(-8) M) also caused a concentration-dependent inhibition of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell (MNC) formation in parathyroid hormone (PTH)-stimulated MS1 and spleen cell cocultures. Furthermore, estrogen pretreatment of MS1 cells also decreased the number of TRAP-positive MNCs in cocultures. Culturing in PTH-treated conditioned media did not rescue the loss of activity supporting osteoclast-like cell formation in MS1 cells.These results indicate that 17 beta-E2-stimulated osteoblastic differentiation of mouse marrow stromal cells results in bone matrix mineralization and a decrease in activity of supporting PTH-induced osteoclast-like cell formation.

The phenotype and haplotype frequencies of human leukocyte antigens (HLA)-DR and -DQ in 32 Chinese patients with the mucocutaneous (MC) type of Behcet's disease (BD) were calculated and compared with those in 310 healthy control Chinese and with those in 80 Chinese patients with recurrent aphthous stomatitis (RAS). We found that the phenotype frequency of HLA-DRw8 [corrected P (Pc)

Type-1 PTH/PTH-related peptide receptors (PTH1Rs), which activate both adenylyl cyclase and phospholipase C (PLC), control endochondral bone development by regulating chondrocyte differentiation. To directly analyze PTH1R function in such cells, we isolated conditionally transformed clonal chondrocytic cell lines from tibial growth plates of neonatal mice heterozygous for PTH1R gene ablation. Among 104 cell lines isolated, messenger RNAs for PTH1R, collagen II, and collagen X were detected in 28%, 90%, and 29%, respectively. These cell lines were morphologically diverse. Some appeared large, rounded, and enveloped by abundant extracellular matrix; whereas others were smaller, flattened, and elongated. Two PTH1R-expressing clones showed similar PTH1R binding and cAMP responsiveness to PTH and PTH-related peptide but disparate morphologic features, characteristic of hypertrophic (hC1--5) or nonhypertrophic (nhC2--27) chondrocytes, respectively. hC1--5 cells expressed messenger RNAs for collagen II and X, alkaline phosphatase (ALP), and matrix GLA protein, whereas nhC2--27 cells expressed collagen II and Indian hedgehog but not collagen X or ALP. In hC1--5 cells, PTH and cAMP analog, but not phorbol ester, inhibited both ALP and mineralization. PTH1R-null hC1--5 subclones were isolated by in vitro selection and then reconstituted by stable transfection with wild-type PTH1Rs or mutant (DSEL) PTH1Rs defective in PLC activation. ALP and mineralization were inhibited similarly via both forms of the receptor. These results indicate that PLC activation is not required for PTH1R regulation of mineralization or ALP in hypertrophic chondrocytes and are consistent with a major role for cAMP in regulating differentiation of hypertrophic chondrocytes.

Five cases of oral malignant fibrous histiocytoma (MFH) in patients who had previously received radiotherapy in the head or neck region were included in this study. There were 3 men and 2 women. Four patients had been irradiated for nasopharyngeal carcinoma (NPC) and the other for a squamous cell carcinoma (SCC) involving the tongue and mouth floor. The MFH developed 2.5-11 years after the initial radiotherapy. Two cases of MFH occurred in the maxilla, two in the mandible, and the remaining one in the tongue, floor of mouth and mandible. Clinically, the oral post-radiation MFH presented as tender, reddish, elastic, lobulated masses with surface ulceration. Radiographic examination of the involved jaws revealed a poorly defined radiolucent lesion without any periosteal or endosteal reaction. The prognosis of these tumors was very poor. Although aggressive multimodality treatment had been applied, 3 of 5 patients eventually died of the disease, with a mean survival time of 17 months after establishing the diagnosis of MFH. In order to ensure the early diagnosis and treatment of this radiation-induced second malignancy, close oral follow-up is mandatory for patients who have received radiotherapy for head and neck malignancies.

In a preliminary study on anti-human cytomegalovirus (HCMV) antibody (Ab) by ELISA, the serum anti-HCMV/IgG Ab concentrations in 22 patients with recurrent aphthous ulcers (RAU) in the remission stage were found to be significantly higher than in 22 control subjects (121 +/- 42 vs 100 +/- 27, P < 0.05) and in 39 patients with RAU in the active stage (121 +/- 42 vs 88 +/- 45, P < 0.01). Therefore, the potential of HCMV as an etiologic agent in RAU was proposed and studies using the polymerase chain reaction (PCR) and in situ hybridization (ISH) have been performed to investigate the possible presence of HCMV DNA in pre-ulcerative oral aphthous lesions in patients with RAU or Behcet's disease (BD) of the mucocutaneous type. For this purpose, formalin-fixed biopsy specimens were obtained from 13 pre-ulcerative oral aphthous lesions, 2 samples of normal oral mucosa and 1 ileal mucosal lesion from 9 RAU patients and 4 BD patients. Five specimens of normal oral mucosa from 5 normal control subjects and 12 specimens of oral erosive or ulcerative lesions from 12 patients with erosive lichen planus (ELP) were also included. By PCR, HCMV DNA was detected in 5 of the 13 (38.5%) pre-ulcerative oral aphthous lesions, 3 from RAU patients and 2 from BD patients. The ileal mucosa specimen was also HCMV DNA-positive, whereas HCMV DNA was not demonstrated in any of the 7 specimens of normal oral mucosa from RAU patients and normal control subjects; 12 specimens of oral lesions from ELP patients were similarly negative. ISH did not detect HCMV DNA in any of the biopsy specimens from RAU patients and control subjects. Our findings suggest that HCMV may be an etiologic agent in some cases of RAU and BD.