Assessing tumor angiogenesis using dynamic contrast-enhanced integrated magnetic resonance-positron emission tomography in patients with non-small-cell lung cancer.

BACKGROUND: Angiogenesis assessment is important for personalized therapeutic intervention in patients with non-small-cell lung cancer (NSCLC). This study investigated whether radiologic parameters obtained by dynamic contrast-enhanced (DCE)-integrated magnetic resonance-positron emission tomography (MR-PET) could be used to quantitatively assess tumor angiogenesis in NSCLC. METHODS: This prospective cohort study included 75 patients with NSCLC who underwent DCE-integrated MR-PET at diagnosis. The following parameters were analyzed: metabolic tumor volume (MTV), maximum standardized uptake value (SUVmax), reverse reflux rate constant (kep), volume transfer constant (Ktrans), blood plasma volume fraction (vp), extracellular extravascular volume fraction (ve), apparent diffusion coefficient (ADC), and initial area under the time-to-signal intensity curve at 60 s post enhancement (iAUC60). Serum biomarkers of tumor angiogenesis, including vascular endothelial growth factor-A (VEGF-A), angiogenin, and angiopoietin-1, were measured by enzyme-linked immunosorbent assays simultaneously. RESULTS: Serum VEGF-A (p = 0.002), angiogenin (p = 0.023), and Ang-1 (p <  0.001) concentrations were significantly elevated in NSCLC patients compared with healthy individuals. MR-PET parameters, including MTV, Ktrans, and kep, showed strong linear correlations (p <  0.001) with serum angiogenesis-related biomarkers. Serum VEGF-A concentrations (p = 0.004), MTV values (p <  0.001), and kep values (p = 0.029) were significantly higher in patients with advanced-stage disease (stage III or IV) than in those with early-stage disease (stage I or II). Patients with initial higher values of angiogenesis-related MR-PET parameters, including MTV > 30 cm3 (p = 0.046), Ktrans > 200 10- 3/min (p = 0.069), and kep > 900 10- 3/min (p = 0.048), may have benefited from angiogenesis inhibitor therapy, which thus led to significantly longer overall survival. CONCLUSIONS: The present findings suggest that DCE-integrated MR-PET provides a reliable, non-invasive, quantitative assessment of tumor angiogenesis; can guide the use of angiogenesis inhibitors toward longer survival; and will play an important role in the personalized treatment of NSCLC.

Parasympathetic effect of deep pressure input on third molar extraction in adolescents.

BACKGROUD/PURPOSE: Deep pressure input is used to normalize physiological arousal due to stress. Third molar extraction is an invasive dental procedure with high stress for the patient, and an alleviation strategy is rarely applied during tooth extraction. In the present study, we investigated the effects of deep pressure input on autonomic responses during the procedures of third molar extraction in healthy adolescents. METHODS: A randomized controlled crossover design was used for adolescents who were allocated to experimental and control groups that received intervention with or without deep pressure input, respectively. Autonomic indicators, namely the heart rate, percentage of low-frequency heart rate variability (LF-HRV), percentage of high-frequency heart rate variability (HF-HRV), and low-frequency/high-frequency heart rate variability ratio (LF/HF-HRV), were assessed at the baseline, during molar extraction, and in the posttreatment phase. RESULTS: The results indicated that third molar extraction caused significant autonomic parameter changes in both groups; however, differential response patterns were observed between two groups. In particular, application of deep pressure input in the experimental group was associated with higher HF-HRV and lower LF/HF-HRV during third molar extraction compared with those in the control group. CONCLUSION: LF/HF-HRV measurement revealed balanced sympathovagal activation in response to deep pressure application. The present study suggests that the application of deep pressure alters the response of HF-HRV and facilitate maintaining sympathovagal balance during third molar extraction.

Significantly higher frequencies of hematinic deficiencies and hyperhomocysteinemia in oral precancer patients.

BACKGROUND/PURPOSE: Our previous studies found relatively higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia in patients with different types of oral mucosal diseases. This study evaluated whether patients with oral precancerous lesions (oral precancer patients) had significantly higher frequencies of anemia, hematinic deficiencies, and hyperhomocysteinemia than healthy control subjects. METHODS: The complete blood count, serum iron, vitamin B12, folic acid, and homocysteine levels in 131 oral precancer patients including 96 oral leukoplakia, 26 oral erythroleukoplakia, and 9 oral verrucous hyperplasia patients and in 131 age- and sex-matched healthy control subjects were measured and compared. RESULTS: We found significantly lower mean serum iron (for women only), vitamin B12, and folic acid levels and a significantly higher mean serum homocysteine level in oral precancer patients than in healthy control subjects (all P-values < 0.05). Moreover, 131 oral precancer patients had significantly higher frequencies of blood hemoglobin (3.1%), vitamin B12 (43.5%), and folic acid (46.6%) deficiencies and hyperhomocysteinemia (22.1%) than 131 healthy control subjects (all P-values < 0.05). Of 131 oral precancer patients, lower mean serum folic acid levels were found in 87 cigarette smokers than in 44 non-smokers (P = 0.002), in 26 smokers consuming > 20 cigarettes per day than in 61 smokers consuming ≤ 20 cigarettes per day (P = 0.024), and in 52 betel quid chewers than in 79 non-chewers (P = 0.051). CONCLUSION: There are significantly higher frequencies of anemia, serum vitamin B12, and folic acid deficiencies, and hyperhomocysteinemia in oral precancer patients than in healthy control subjects.

Gastric parietal cell and thyroid autoantibodies in oral precancer patients.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) may be present in oral mucosal disease patients. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in 131 oral precancer patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 131 oral precancer patients including 96 oral leukoplakia, 26 oral erythroleukoplakia, and 9 oral verrucous hyperplasia patients and in 131 age- and sex-matched healthy control subjects. RESULTS: We found that 131 oral precancer patients had higher frequencies of serum GPCA (10.7% vs. 2.3%, P = 0.012, statistically significant), TGA (4.6% vs. 2.3%, P = 0.498), and TMA (8.4% vs. 2.3%, P = 0.054, marginal significance) positivities than 131 healthy control subjects. We also found that 1 (0.8%), 6 (4.6%), and 16 (12.2%) oral precancer patients had the presence of three (GPCA + TGA + TMA), two (GPCA + TGA, GPCA + TMA, or TGA + TMA), or one (GPCA only, TGA only, or TMA only) autoantibody in their sera, respectively. Of 10 TGA/TMA-positive oral precancer patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 80%, 10%, and 10% of these 10 TGA/TMA-positive oral precancer patients had normal, lower, and higher serum TSH levels, respectively. We also found a significantly higher GPCA positive rate in 26 smokers consuming >20 cigarettes per day than in 61 smokers consuming ≤20 cigarettes per day (P = 0.008). CONCLUSION: Approximately 17.6% of 131 oral precancer patients have serum GPCA/TGA/TMA positivity. Only approximately 20% of TGA/TMA-positive oral precancer patients have either hypothyroidism or hyperthyroidism.

Arecoline activates latent transforming growth factor ß1 via mitochondrial reactive oxygen species in buccal fibroblasts: Suppression by epigallocatechin-3-gallate.

BACKGROUND/PURPOSE: Oral submucous fibrosis (OSF) is a premalignant condition caused by the chewing of areca nut (AN). Transforming growth factor ß (TGFß) plays a central role in the pathogenesis of OSF. Connective tissue growth factor (CTGF or CCN2) and early growth response-1 (Egr-1) are important mediators in the fibrotic response to TGFß in several fibrotic disorders including OSF. Arecoline, a major AN alkaloid, induced the synthesis of CCN2 and Egr-1 in human buccal mucosal fibroblast (BMFs). The aims of this study were to investigate whether arecoline-induced CCN2 and Egr-1 syntheses are mediated through TGFß1 signaling and to inspect the detailed mechanisms involved. METHODS: Western blot and TGFß1 Emax® ImmunoAssay were used to measure the effect of arecoline on the TGFß signaling pathways. 2',7'-dichlorodihydrofluorescein diacetate and MitoSOX™ Red were used to measure the effect of arecoline on the cellular and mitochondrial reactive oxygen species (ROS). RESULTS: Arecoline induced latent TGFß1 activation, Smad2 phosphorylation, and mitochondrial and total cellular ROS in BMFs. TGFß-neutralizing antibody completely inhibited the arecoline-induced synthesis of CCN2 and Egr-1. Mito-TEMPO, a mitochondria-targeted antioxidant, completely suppressed arecoline-induced latent TGFß1 activation and mitochondrial and total cellular ROS. Epigallocatechin-3-gallate (EGCG) dose-dependently inhibited arecoline-induced TGFß1 activation and mitochondrial ROS in BMFs. CONCLUSION: Our results indicated that arecoline-induced mitochondrial ROS plays pivotal roles in the activation of latent TGFß1 leading to the initiation of TGFß1 signaling and subsequent increase in the synthesis of CCN2 and Egr-1. EGCG can be a useful agent in the chemoprevention and treatment of OSF.

Gastric parietal cell and thyroid autoantibodies in patients with Behcet's disease.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) were rarely examined in Behcet's disease (BD) patients. This study mainly assessed the frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients. METHODS: The frequencies of serum GPCA, TGA, and TMA positivities in 63 BD patients, 19 major-typed recurrent aphthous stomatitis (RAS)/BD (major RAS/BD) patients, 44 minor-typed RAS/BD (minor RAS/BD) patients, 520 RAS patients, and 126 healthy control subjects were calculated and compared. RESULTS: We found that 14.3%, 20.6%, and 20.6% of 63 BD patients, 21.1%, 21.1%, and 26.3% of 19 major RAS/BD patients, 11.4%, 20.5%, and 18.2% of 44 minor RAS/BD patients, 11.5%, 18.5%, and 18.3% of 520 RAS patients, and 1.6%, 2.4%, and 2.4% of 126 healthy control subjects had serum GPCA, TGA, and TMA positivities, respectively. BD, major RAS/BD, minor RAS/BD, and RAS patients all had significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects (all P-values < 0.05). However, there were no significant differences in different serum autoantibody frequencies between BD, major RAS/BD, or minor RAS/BD patients and RAS patients. Of 16 TGA/TMA-positive BD patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 87.5%, 6.3%, and 6.3% of these TGA/TMA-positive BD patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: Approximately 35% BD patients have serum GPCA/TGA/TMA positivity. However, BD patients do not have significantly higher frequencies of serum GPCA, TGA, and TMA positivities than RAS patients.

Gastric parietal cell and thyroid autoantibodies in recurrent aphthous stomatitis patients with concomitant oral lichen planus.

BACKGROUND/PURPOSE: Gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) have not yet been reported in recurrent aphthous stomatitis (RAS) patients with concomitant oral lichen planus (OLP/RAS patients). This study mainly assessed the frequencies of serum GPCA, TGA, and TMA (GPCA/TGA/TMA) positivities in 44 OLP/RAS patients. METHODS: The frequencies of serum GPCA/TGA/TMA positivities in 44 OLP/RAS patients, OLP/RAS patients of four different subgroups, 520 RAS patients, and 352 healthy control subjects were calculated and compared. RESULTS: We found that 20.5%, 27.3%, and 31.8% of 44 OLP/RAS patients, 75.0%, 100.0%, and 100.0% of 4 OLP/major-typed RAS (OLP/major RAS) patients, 15.0%, 20.0%, and 25.0% of 40 OLP/minor-typed RAS (OLP/minor RAS) patients, 45.5%, 72.7%, and 54.5% of 11 atrophic glossitis-positive OLP/RAS (AG+OLP/RAS) patients, and 12.1%, 12.1%, and 24.2% of 33 AG-negative OLP/RAS (AGÖ¾OLP/RAS) patients had the presence of GPCA, TGA, and TMA in their sera, respectively. OLP/RAS patients and OLP/RAS patients of four different subgroups all had significantly higher frequencies of GPCA/TGA/TMA positivities than healthy control subjects. Moreover, OLP/RAS patients had a significantly higher frequency of TMA positivity than RAS patients, and OLP/major RAS and AG+OLP/RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than RAS patients. Furthermore, OLP/major RAS patients had significantly higher frequencies of GPCA/TGA/TMA positivities than OLP/minor RAS patients. CONCLUSION: For OLP/RAS patients, the concomitant OLP may play a role in causing an increased frequency of TMA positivity, and major RAS and the concomitant AG are contributory factors causing the elevated frequencies of GPCA/TGA/TMA positivities.

Gastric parietal cell and thyroid autoantibodies in Behcet's disease patients with or without atrophic glossitis.

BACKGROUND/PURPOSE: Behcet's disease (BD) patients should have recurrent aphthous stomatitis (RAS) but they may or may not have atrophic glossitis (AG). This study mainly assessed the frequencies of serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) positivities in 30 AG-positive RAS/BD (AG+RAS/BD) and 33 AG-negative RAS/BD (AGÖ¾RAS/BD) patients. METHODS: The frequencies of serum GPCA, TGA, and TMA positivities in 30 AG+RAS/BD patients, 33 AGÖ¾RAS/BD patients, and 126 healthy control subjects were calculated and compared. RESULTS: We found that 20.0%, 30.0%, and 26.7% of 30 AG+RAS/BD patients, 9.1%, 12.1%, and 15.2% of 33 AGÖ¾RAS/BD patients, and 1.6%, 2.4%, and 2.4% of 126 healthy control subject had the presence of GPCA, TGA, and TMA in their sera, respectively. The 30 AG+RAS/BD patients had significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects (all P-values < 0.001). The 33 AGÖ¾RAS/BD patients had a higher frequency of serum TGA positivity (P = 0.051, marginal significance) and a significantly higher frequency of serum TMA positivity (P = 0.011) than healthy control subjects. Although the 30 AG+RAS/BD patients had higher frequencies of serum GPCA, TGA, and TMA positivities than the 33 AGÖ¾RAS/BD patients, the differences were not significant. CONCLUSION: AG+RAS/BD patients do have significantly higher frequencies of serum GPCA, TGA, and TMA positivities than healthy control subjects. This finding indicates that the concomitant presence of AG may result in significantly elevated frequencies of serum GPCA, TGA, and TMA positivities in BD patients.

Hemoglobin, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia in Behcet's disease patients with atrophic glossitis.

BACKGROUND/PURPOSE: Behcet's disease (BD) patients should have recurrent aphthous stomatitis (RAS) but they may or may not have atrophic glossitis (AG). This study mainly assessed whether 30 AG-positive RAS/BD (AG+RAS/BD) patients had significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than 33 AG-negative RAS/BD (AGÖ¾RAS/BD) patients or 126 age- and sex-matched healthy control subjects. METHODS: The blood hemoglobin, iron, vitamin B12, folic acid, and homocysteine concentrations were measured and compared among 30 AG+RAS/BD patients, 33 AGÖ¾RAS/BD patients, and 126 healthy control subjects. RESULTS: We found that 43.3%, 33.3%, 13.3%, 6.7%, and 20.0% of 30 AG+RAS/BD patients and 18.2%, 36.4%, 0%, 6.1%, and 9.1% of 33 AGÖ¾RAS/BD patients had hemoglobin, iron, vitamin B12, and folic acid deficiencies and hyperhomocysteinemia, respectively. Moreover, 30 AG+RAS/BD patients had significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than healthy control subjects (all P-values < 0.05), and had a higher frequency of hemoglobin deficiency (P = 0.058, marginal significance) and a significantly higher frequency of vitamin B12 deficiency (P = 0.046) than 33 AGÖ¾RAS/BD patients. In addition, the 33 AGÖ¾RAS/BD patients had significantly higher frequencies of hemoglobin and iron deficiencies than healthy control subjects (both P-values < 0.001). CONCLUSION: We conclude that AG+RAS/BD patients do have significantly higher frequencies of hemoglobin, iron, vitamin B12, and folic acid deficiencies and of hyperhomocysteinemia than healthy control subjects and have significantly higher frequencies of hemoglobin and vitamin B12 deficiencies than AGÖ¾RAS/BD patients.

Antigastric parietal cell and antithyroid autoantibodies in patients with desquamative gingivitis.

BACKGROUND: Desquamative gingivitis (DG) is principally associated with erosive oral lichen planus (EOLP), mucous membrane pemphigoid (MMP), and pemphigus vulgaris (PV). METHODS: Serum autoantibodies including antigastric parietal cell antibody (GPCA), antithyroglobulin antibody (TGA), and antithyroid microsomal antibody (TMA) were measured in 500 patients with DG, 287 EOLP without DG (EOLP/DG- ) patients, and 100 healthy control subjects. RESULTS: The 500 patients with DG were diagnosed as having EOLP in 455 (91%), PV in 40 (8%), and MMP in five (1%) patients. We found that 37.0%, 43.6%, and 42.6% of 500 patients with DG, 39.6%, 46.4%, and 45.1% of 455 EOLP with DG (EOLP/DG) patients, and 18.5%, 27.5%, and 30.3% of 287 EOLP/DG- patients had the presence of GPCA, TGA, and TMA in their sera, respectively. DG, EOLP/DG, and EOLP/DG- patients all had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control subjects (all P-values < 0.001). Moreover, 455 EOLP/DG patients had a significantly higher frequency of GPCA, TGA, or TMA positivity than 287 EOLP/DG- patients (all P-values < 0.001). Of 210 TGA/TMA-positive patients with DG whose serum thyroid-stimulating hormone (TSH) levels were measured, 84.3%, 6.7%, and 9.0% patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: We conclude that 73.4% DG, 77.1% EOLP/DG, and 47.4% EOLP/DG- patients may have GPCA/TGA/TMA positivity in their sera. Because part of GPCA-positive patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and part of TGA/TMA-positive patients may have thyroid dysfunction, these patients should be referred to medical department for further management.

Significant association of high-grade inflammation and thick lining epithelium with the increased number of Langerhans cells in dentigerous cysts.

BACKGROUND/PURPOSE: Langerhans cells (LCs) are antigen-presenting cells. This study assessed the LC counts in 80 dentigerous cysts (DCs). METHODS: The CD1a-positive LC numbers in the lining epithelia and subepithelial connective tissues were counted at 80 DC sites without inflammation, 33 DC sites with mild/moderate inflammation, and 9 DC sites with severe inflammation from 80 DC specimens. RESULTS: The mean LC counts in the lining epithelia and subepithelial connective tissues increased significantly from no inflammation (0.5 ± 0.5 and 0.2 ± 0.3 cell/high-power field or HPF, respectively) through mild/moderate inflammation (6.8 ± 1.8 and 2.4 ± 2.0 cells/HPF, respectively) to severe inflammation DC sites (18.9 ± 7.0 and 6.7 ± 5.8 cells/HPF, respectively; all P-values < 0.001). DC sites with inflammation had thicker lining epithelia than those without inflammation. Moreover, the mean LC counts in the lining epithelia and subepithelial connective tissues of DCs were significantly higher in the thicker lining epithelium (>50 µm) group (7.4 ± 6.5 and 2.6 ± 3.4 cells/HPF, respectively) than in the thinner lining epithelium (≦ 50 µm) group (0.5 ± 0.5 and 0.2 ± 0.3 cells/HPF, respectively; both P-values < 0.001). CONCLUSION: A significant association of high-grade inflammation and thick lining epithelium with the increased LC number in DCs is found. The finding of few LCs in the lining epithelia of DCs without inflammation indicates the reduced immunosurveillance ability against DC lining epithelial cells in DC patients. It needs further studies to confirm the role of reduced immunosurveillance in the enlargement of the DC.

Significant association of inflammation grade with the number of Langerhans cells in odontogenic keratocysts.

BACKGROUND/PURPOSE: Langerhans cells (LCs) are antigen-presenting cells. This study assessed the LC counts in odontogenic keratocysts (OKCs). METHODS: The LC numbers in the lining epithelia and subepithelial connective tissues were counted at 60 OKC sites without inflammation, 39 OKC sites with mild/moderate inflammation, and 13 OKC sites with severe inflammation from 60 OKC specimens immunostained with anti-S100 antibodies. RESULTS: The mean LC counts in the lining epithelia and subepithelial connective tissues increased significantly from no inflammation (0.5 ± 0.4 and 0.7 ± 0.6 cell/high-power field or HPF, respectively) through mild/moderate inflammation (5.9 ± 2.7 and 5.0 ± 3.5 cells/HPF, respectively) to severe inflammation OKC sites (14.7 ± 5.3 and 13.3 ± 6.8 cells/HPF, respectively; all P-values < 0.001). OKC sites with inflammation had thicker lining epithelia than those without inflammation. Moreover, the mean LC counts in the lining epithelia and subepithelial connective tissues of OKCs were significantly higher in the thicker lining epithelium (>100 µm) group (7.7 ± 5.6 and 6.5 ± 5.8 cells/HPF, respectively) than in the thinner lining epithelium (≦ 100 µm) group (1.0 ± 2.0 and 1.4 ± 2.6 cells/HPF, respectively; both P-values < 0.001). CONCLUSION: A significant association of inflammation grade with the number of LCs in OKCs is found. The paucity of finding LCs in the lining epithelia of OKCs without inflammation indicates the loss of immunosurveillance ability against the OKC lining epithelial cells; this can explain why OKCs have aggressive clinical behavior, a great growth potential, and a high recurrence rate.

Epigallocatechin-3-gallate inhibits transforming-growth-factor-ß1-induced collagen synthesis by suppressing early growth response-1 in human buccal mucosal fibroblasts.

BACKGROUND/PURPOSE: Transforming growth factor (TGF)-ß is a key regulator in the pathogenesis of oral submucous fibrosis (OSF). Early growth response (Egr)-1 is essential for fibrotic responses to TGF-ß. Because TGF-ß signaling is cell-type- and context-dependent, we investigated the signaling involved in TGF-ß-induced Egr-1 in primary human buccal mucosal fibroblasts (BMFs). METHODS: TGF-ß-induced Egr-1 and its signaling were assessed by western blotting in BMFs. Egr-1 small interfering RNA was used to define the role of Egr-1 on TGF-ß-induced mRNAs of the α1- and α2-chains of type I collagen (COL1A1 and COL1A2) and acid-soluble collagen production (via Sircol collagen assay). The effects of epigallocatechin-3-gallate (EGCG) on TGF-ß-induced Egr-1 protein and acid-soluble collagen were also evaluated. RESULTS: TGF-ß1 stimulated Egr-1 production in BMFs. Pretreatment with PD98059, SP600125, SB431542, and SIS3, but not SB203580, significantly reduced TGF-ß1-induced Egr-1 protein expression. Genetic targeting of Egr-1 completely inhibited TGF-ß1-induced type I collagen mRNAs and collagen protein expression. EGCG fully inhibited TGF-ß1-induced Egr-1 and TGF-ß1-stimulated production of acid-soluble collagens. CONCLUSION: We conclude that activin receptor-like kinase (ALK)5, Smad3, extracellular signal-regulated kinase, and c-Jun N-terminal kinase are involved in the TGF-ß1-induced Egr-1 protein production in BMFs. Egr-1 mediates TGF-ß1-induced COL1A1 and COL1A2 mRNA expression and acid-soluble collagen production in BMFs. EGCG can block TGF-ß1-induced collagen production by attenuating Egr-1 expression in BMFs. Egr-1 is a key mediator in TGF-ß1-induced pathogenesis of OSF. EGCG may be useful in the prevention or treatment of OSF.

Anemia and hematinic deficiencies in anti-gastric parietal cell antibody-positive and -negative recurrent aphthous stomatitis patients with anti-thyroid antibody positivity.

BACKGROUND/PURPOSE: Serum anti-gastric parietal cell (GPCA), anti-thyroglobulin (TGA), and anti-thyroid microsomal antibodies (TMA) can be found in some recurrent aphthous stomatitis (RAS) patients. This study mainly assessed whether serum GPCA, TGA, TMA and RAS itself played significant roles in causing anemia and hematinic deficiencies in TGA/TMA-positive RAS patients with GPCA positivity (GPCA+/TGA/TMA/RAS patients) or negativity (GPCA-/TGA/TMA/RAS patients). METHODS: The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of the four groups of 15 GPCA+/TGA/TMA/RAS patients, 69 GPCA-/TGA/TMA/RAS patients, 240 all autoantibodies-negative RAS patients (Abs-/RAS patients), and 342 healthy control subjects. RESULTS: GPCA+/TGA/TMA/RAS patients had significantly lower mean Hb (for men only) and vitamin B12 levels as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy control subjects. GPCA+/TGA/TMA/RAS patients had lower serum vitamin B12 level and higher MCV as well as a significantly greater frequency of vitamin B12 deficiency than GPCA-/TGA/TMA/RAS patients. Furthermore, both GPCA-/TGA/TMA/RAS and Abs-/RAS patients did have significantly lower mean Hb, MCV, and iron levels as well as significantly greater frequencies of Hb, iron and vitamin B12 deficiencies than healthy control subjects. There were no significant differences in blood data between GPCA-/TGA/TMA/RAS and Abs-/RAS patients CONCLUSION: Both serum GPCA positivity and RAS itself are the contributing factors causing anemia and hematinic deficiencies in GPCA+/TGA/TMA/RAS patients. RAS itself but not TGA/TMA positivity plays a significant role in causing anemia and hematinic deficiencies in GPCA-/TGA/TMA/RAS patients.

Antigastric parietal cell and antithyroid autoantibodies in patients with recurrent aphthous stomatitis.

BACKGROUND/PURPOSE: Anti-gastric parietal cell antibody (GPCA), anti-thyroglobulin antibody (TGA), and anti-thyroid microsomal antibody (TMA) have not yet been reported in patients with recurrent aphthous stomatitis (RAS). This study mainly assessed the frequencies of the presence of serum GPCA, TGA, and TMA in different types of RAS patients. METHODS: Serum GPCA, TGA, and TMA levels were measured in 355 RAS patients of different subtypes and in 355 age- and sex-matched healthy control individuals. RESULTS: We found that 13.0%, 19.4%, and 19.7% of 355 RAS patients, 16.7%, 23.3%, and 21.7% of 60 major-typed RAS patients, 12.2%, 18.6%, and 19.3% of 295 minor-typed RAS patients, 18.1%, 20.0%, and 21.9% of 160 atrophic glossitis-positive RAS (AG+/RAS) patients, and 8.7%, 19.0%, and 17.9% of 195 AG-negative RAS (AG-/RAS) patients had the presence of GPCA, TGA, and TMA in their sera, respectively. RAS, major-typed RAS, minor-typed RAS, AG+/RAS, and AG-/RAS patients all had a significantly higher frequency of GPCA, TGA, or TMA positivity than healthy control individuals (all p < 0.001). Of 65 TGA/TMA-positive RAS patients whose serum thyroid-stimulating hormone (TSH) levels were measured, 76.9%, 12.3%, and 10.8% of these TGA/TMA-positive RAS patients had normal, lower, and higher serum TSH levels, respectively. CONCLUSION: We conclude that approximately one-third RAS patients may have GPCA/TGA/TMA positivity in their sera. Because some GPCA-positive patients may develop pernicious anemia, autoimmune atrophic gastritis, and gastric carcinoma, and some TGA/TMA-positive patients may have thyroid dysfunction such as hyperthyroidism and hypothyroidism, these patients should be referred to doctors for further management.

Langerhans cell counts in oral epithelial dysplasia and their correlation to clinicopathological parameters.

BACKGROUND/PURPOSE: Langerhans cells (LCs) are antigen presenting cells. This study assessed the LC counts in oral epithelial dysplasia (OED) and their correlation to clinicopathological parameters. METHODS: This study examined the LC counts in the epithelia and subepithelial connective tissues of 58 patients with OED (21 mild, 18 moderate, and 19 severe OED lesions) and 10 specimens of normal oral mucosa (NOM) by anti-S-100 protein immunostaining. RESULTS: We found that the mean LC counts in the epithelia or subepithelial connective tissues increased significantly from NOM samples through mild and moderate OED to severe OED samples. In addition, a significant correlation was found between higher mean LC counts in the dysplastic epithelia of OED samples and OED lesions with thicker epithelial layers (p<0.001) or wider inflammatory zones (p<0.001), and between higher mean LC counts in the subepithelial connective tissues of OED samples and OED lesions with wider inflammatory zones (p<0.001). Moreover, the nine OED lesions with malignant transformation had a significantly lower mean LC count than the 49 OED lesions without malignant transformation. CONCLUSION: The significant and gradual elevation in LC count from NOM through mild and moderate OED to severe OED lesions suggests an upregulation of immunosurveillance ability in OED patients during the early oral carcinogenesis process. A low LC count in OED lesions may suggest the partial loss of immunosurveillance ability against dysplastic cells; this in turn favors the malignant transformation of an OED lesion into oral cancer.

Anemia and hematinic deficiencies in oral mucosal disease patients with microcytosis.

BACKGROUND/PURPOSE: Patients with microcytosis (defined as mean corpuscular volume < 80 fL) are not uncommonly found in oral mucosal disease clinics. This study assessed the anemia statuses and hematinic deficiencies in 240 oral mucosal disease patients with microcytosis. METHODS: The mean red blood cell (RBC) count, mean corpuscular volume, and RBC distribution width, as well as blood concentrations of hemoglobin (Hb), iron, vitamin B12, folic acid, and homocysteine in 240 microcytosis patients and in 240 age- and sex-matched healthy control individuals were measured and compared. RESULTS: Microcytosis patients had significantly lower mean Hb, iron, and folic acid levels as well as significantly higher mean RBC count and RBC distribution width than healthy control individuals. Microcytosis patients also had significantly greater frequencies of Hb, iron, vitamin B12, and folic acid deficiencies as well as of RBC number > 5 × 1012/L, and abnormally high homocysteine levels than healthy control individuals. Moreover, 162 (67.5%) of the 240 microcytosis patients had anemia. Of 162 anemic microcytosis patients, 87 (53.7%) had iron deficiency anemia, 61 (37.7%) had thalassemia trait (TT)-induced anemia, and 14 (8.6%) had other microcytic anemia. CONCLUSION: We conclude that approximately 45%, 4%, and 5% of microcytosis patients have iron, vitamin B12, and folic acid deficiencies, respectively, and approximately 10% of microcytosis patients have abnormally high homocysteine levels. Moreover, 67.5% of 240 microcytosis patients and 50.8% of 120 TT patients had anemia. Iron deficiency anemia is the most common type of anemia in microcytosis patients, followed by TT-induced anemia and other microcytic anemia.

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.

Anemia and hematinic deficiencies in gastric parietal cell antibody-positive and antibody-negative erosive oral lichen planus patients with thyroid antibody positivity.

BACKGROUND/PURPOSE: Serum gastric parietal cell antibody (GPCA), thyroglobulin antibody (TGA), and thyroid microsomal antibody (TMA) are found in some erosive oral lichen planus (EOLP) patients. This study assessed whether serum GPCA, TGA and TMA and EOLP itself played significant roles in causing anemia and hematinic deficiencies in TGA/TMA-positive EOLP patients with GPCA positivity (GPCA+/TGA/TMA/EOLP patients) or negativity (GPCA-/TGA/TMA/EOLP patients). METHODS: The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of the four groups of 29 GPCA+/TGA/TMA/EOLP patients, 80 GPCA-/TGA/TMA/EOLP patients, 198 all antibodies-negative EOLP patients (Abs-/EOLP patients), and 218 healthy control individuals. RESULTS: GPCA+/TGA/TMA/EOLP patients had significantly lower mean Hb and vitamin B12 levels as well as significantly greater frequencies of Hb, iron, and vitamin B12 deficiencies than healthy controls. GPCA+/TGA/TMA/EOLP patients had significantly lower serum vitamin B12 level and higher MCV as well as a significantly greater frequency of vitamin B12 deficiency than GPCA-/TGA/TMA/EOLP patients. Furthermore, both GPCA-/TGA/TMA/EOLP and Abs-/EOLP patients did have significantly lower mean Hb, MCV, and iron (for women only) levels, as well as significantly greater frequencies of Hb and iron deficiencies than healthy controls. However, there were no significant differences in measured blood data between GPCA-/TGA/TMA/EOLP and Abs-/EOLP patients. CONCLUSION: We conclude that serum GPCA is the major factor causing vitamin B12 deficiency, macrocytosis and pernicious anemia in GPCA+/TGA/TMA/EOLP patients. ELOP itself but not TGA/TMA positivity plays a significant role in causing anemia and hematinic deficiencies in GPCA-/TGA/TMA/EOLP patients.

Hematinic deficiencies and anemia statuses in recurrent aphthous stomatitis patients with or without atrophic glossitis.

BACKGROUND/PURPOSE: Some of recurrent aphthous stomatitis (RAS) patients had concomitant atrophic glossitis (AG). This study assessed whether RAS patients with AG (AG+/RAS patients) or without AG (AG-/RAS patients) had anemia and hematinic deficiencies and to evaluate whether RAS combined with AG or RAS itself was a significant factor causing anemia and hematinic deficiencies in AG+/RAS or AG-/RAS patients, respectively. METHODS: The mean corpuscular volume (MCV) and mean blood hemoglobin (Hb), iron, vitamin B12, and folic acid levels were measured and compared between any two of three groups of 160 AG+/RAS patients, 195 AG-/RAS patients, and 355 healthy control subjects. RESULTS: Both AG+/RAS and AG-/RAS patients had significantly lower mean Hb, iron, and vitamin B12 levels as well as significantly greater frequencies of Hb, iron, vitamin B12, and folic acid deficiencies than healthy control subjects. Moreover, AG+/RAS patients had significantly lower mean Hb and serum iron level (for women only) and significantly greater frequencies of Hb and iron deficiencies than AG-/RAS patients. Of 69 anemia AG+/RAS patients, 30 (43.5%) had normocytic anemia and 23 (33.3%) had iron deficiency anemia. Of 38 anemia AG-/RAS patients, 26 (68.4%) had normocytic anemia and 5 (13.2%) had iron deficiency anemia. CONCLUSION: We conclude that some of AG+/RAS or AG-/RAS patients do have anemia and hematinic deficiencies and AG+/RAS patients do have severer anemia statuses and iron deficiency than AG-/RAS patients. RAS combined with AG or RAS itself does play a significant role in causing anemia and hematinic deficiencies in AG+/RAS or AG-/RAS patients, respectively.