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 Behçet'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.
Our findings indicate that placental tissue from normal early pregnancies and neoplastic tissue from GTD possess similar levels of telomerase activity. Decreasing regulation of telomerase activity is present in normal pregnancies but not in complete hydatidiform mole. The fact that telomerase activity decreases in cases of fetal demise, and as pregnancy progresses, also suggests that placental senescence may play a role in the development and ageing of the placenta.
In this study we used the polymerase chain reaction (PCR), slot blot and Southern blot hybridization, direct sequencing and in situ hybridization (ISH) to show the possible presence of EBV‐DNA in pre‐ulcerative oral aphthous lesions of patients with recurrent aphthous ulcers (RAU) or Behet's disease (BD). For this purpose, formalin‐fixed biopsy specimens were obtained from 13 pre‐ulcerative oral aphthous lesions of nine RAU and four BD patients. Five specimens of normal oral mucosa (NOM) from five normal control subjects and 10 specimens of oral erosive or ulcerative lesions from 10 patients with erosive lichen planus (ELP) were also included. EBV‐DNA was detected by PCR in 5 of the 13 (38.5%) pre‐ulcerative oral aphthous lesions, two from RAU patients and three from BD patients. However, no EBV‐DNA was demonstrated in five NOM specimens from normal control subjects and in 10 specimens of oral lesions from ELP patients. EBV‐DNA was also demonstrated in patients’peripheral blood lymphocytes and/ or plasma, suggesting that the lymphocytes may be the reservoir of latent EBV infection and there is EBV shedding in the plasma. EBV‐DNA was detected by ISH in only one PCR‐positive case; the reaction product was found to deposit on the nuclei of some of the epithelial cells and lymphocytes. By immunohistochemistry, expression of Epstein‐Barr nuclear antigen and EBV/C3d receptors was also noted in some of the epithelial cells and lymphocytes in this ISH‐positive case. Therefore, we suggest that the epithelial cells of pre‐ulcerative oral aphthous lesions may be infected by EBV through EBV‐infected lymphocytes; also, the cytotoxic T lymphocyte‐induced lysis of the EBV‐infected epithelial cells, but not the virus‐induced cytolysis, may be the main mechanism causing oral ulcer formation. Our data provide preliminary evidence for an association of EBV with pre‐ulcerative oral aphthous lesions in RAU and BD patients.
The phenotype and haplotype frequencies of human leukocyte antigens (HLA)-DR and -DQ in 32 Chinese patients with the mucocutaneous (MC) type of Behçet'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)<0.005] and the haplotype frequencies of HLA-DRw8/DQw1 (Pc<0.005), -DRw8/DQw5(w1) (Pc<0.0005), -DRw12(5)/DQw1 (Pc<0.005), -DRw12(5)/DQw6(w1) (Pc< 0.0005), and -DRw52/DQw1 (Pc<0.005) in patients with the MC type of BD were significantly greater than those in healthy control subjects. This finding suggests that individual Chinese with HLA-DRw8 antigen and HLA-DRw8/DQw1, -DRw8/DQw5(w1), -DRw12(5)/DQw1, -DRw12(5)/DQw6(w1) and -DRw52/DQw1 haplotypes are more likely to have the MC type of BD. Furthermore, the relative risks (RRs) of HLA-DRw8/DQw1 (5.6), -DRw8/ DQw5 (w1) (10.0), and -DRw12(5)/DQw6(w1) (14.4) haplotypes in patients with the MC type of BD were equal to or higher than the RR of HLA-DRw8 phenotype (5.6), suggesting that some of the HLA-DR/DQ haplotypes may play more important roles than the individual HLA-DR and -DQ phenotypes for the development of the MC type of BD. The phenotype frequencies of HLA-DR5 (Pc<0.01), -DRw8 (Pc<0.005) and -DQw1 (Pc<0.05) as well as the haplotype frequencies of HLA-DR5/DQw1 (P<0.005) and -DRw8/DQw1 (Pc<0.00005) in patients with the MC type of BD were significantly higher than those in patients with RAS. Moreover, the RRs of HLA-DR5/DQw1 (29.1) and -DRw8/DQw1 (47.4) haplotypes were greater than the RRs of HLA-DR5 (10.4), -DRw8 (23.4) and -DQw1 (4.0) antigens. These results suggest that some specific HLA-DR/DQ haplotypes may be more important than the individual HLA-DR and -DQ phenotypes in the disease shift from RAS to the MC type of BD.
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