[Expression of fragile histidine triad (FHIT) protein and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust].

OBJECTIVE: To study the expression and significance of fragile histidine triad (FHIT) and Ki-67 in transformed epithelial cells induced by Yunnan tin mine dust. METHODS: Every second generation of immortalized human bronchial epithelial cells (BEAS-2B) and human embryo lung fibroblasts (WI-38) were exposed to 100 µg/ml Yunnan tin mine dust for 72 h, until the ninth generation. The cells were subsequently co-cultured from the 11th generation. Experimental setup: B group, B (W) group, B (W 100) group, B100 group, B100 (W) group, B100 (W100) group. The expressions of FHIT and Ki-67 in epithelial cells were determined by the method of immunocytochemistry at the 16th, 26th and 36th generation. The percentage of Ki-67 positive cells was calculated as proliferation index. RESULTS: The expression of FHIT was observed in BEAS-2B cells. The expression levels of FHIT among B group, B (W) group and B (W 100) group had not instinctive difference. At the 16th generation, the expression of FHIT in the B100 group was decreased compared with that in the B group and the expression of FHIT between B100 (W) group and B100 (W100) group was lower than that in the B100 group. At the 26th generation, the expression of FHIT was decreased compared with that at the 16th generation in the B100, B100 (W) and B100 (W100) groups. However, At the 36th generation, positive expression were observed again in the B100, B100 (W) and B100 (W100) groups and the expression levels were in incremental order. At the 16th, 26th and 36th generation, the proliferation indexes of B group, B (W) group and B (W 100) group were all < 3%. The proliferation indexes of B100, B100 (W) and B100 (W100) were increased step by step with the generation elongation. CONCLUSIONS: FHIT could be a target at which Yunnan tin mine dust induces transformation of BEAS-2B cells. The proliferation activation of BEAS-2B cells can be improved by Yunnan tin mine dust.

Tuberculosis in southern Chinese renal-transplant recipients.

OBJECTIVES: To analyze the characteristics of tuberculosis (TB) in Southern Chinese renal transplant recipients, and summarize the corresponding experiences in diagnosis and management. METHOD: Retrospectively study 41 documented post-transplant TB cases out of the 2333 patients who received kidney transplantation in the First Affiliated Hospital of Sun Yat-sen University between Jan. 1991 and Apr. 2007. RESULTS: TB in the post-renal-transplant population in Southern China displayed the following characteristics: (i) high incidence within a short time after transplantation, the median interval between renal transplantation and diagnosis of TB was 8 months (range: 1-156 months) and 56.1% were diagnosed within the first year post-transplant; (ii) high prevalence (51.2%) of extra-pulmonary tuberculosis; (iii) high co-infection rate (19.5%), pathogens included candida albicans, pseudomonas aeruginosa, staphylococcus aureus, Acinetobacter haemolyticus and cytomegalovirus; (iv) fever (82.9%), cough (56.1%) and sputum (39.0%) are the most common clinical manifestations; (v) purified protein derivative of tuberculin (PPD) skin test had little diagnostic value in this group with a negative result in all 41 cases; (vi) acute rejection (29.3%) and liver function damage (17.1%) were the main adverse effects of anti-tuberculosis chemotherapy; (vii) mortality of patients with post-transplant tuberculosis reached up to 22.0%. CONCLUSIONS: Chinese renal transplant recipients face a high risk of TB because of their immuno-compromised state and epidemiological prevalence of the disease. Therefore, attention should be given to this differential diagnosis in clinical practice. Balancing the benefits and disadvantages of anti-tuberculosis chemotherapy is of importance for this specific population.

An extra molecule in addition to human tapasin is required for surface expression of beta2m linked HLA-B4402 on murine cell.

Murine MHC class I can be readily expressed on the surface of human cell lines, but human class I molecules are expressed on mouse cells at a reduced level. Both human beta-2-microglobulin (beta(2)m) and tapasin (Tpn) have been demonstrated to be required for proper human MHC class I surface expression. Here we report that besides beta(2)m and tapasin, an extra unidentified component is also critical for the expression of certain human class I alleles. By covalently linking HLA-B4402 heavy chain to beta(2)m (beta(2)m-B44) a pre-assembled class I molecule has been created, which can be efficiently expressed and travel to the surface in human cells. In spite of being able to express inside cells, the linked beta(2)m-B44 molecule does not express on the surface of a murine fibroblast. Further investigation shows that lack of appearance on the surface is not due to quick degradation of unloaded class I, since provision of HLA-B4402 binding peptide could not rescue impaired surface expression. Co-expression with human tapasin does not rescue the defect excluding tapasin as the critical component for expression and indicating that a novel component of human origin is required for efficient surface expression of beta(2)m-B44 in murine cells. Surprisingly, not only did the beta(2)m-B44 construct fail to express on murine cells but also the surface expression of native murine MHC class I Kb was greatly reduced in transfected cells. It is likely that the expressed linked chain competitively associates with a component of class I processing in murine cells, reducing the exit rate of assembled mouse class I molecules. The results together suggest an unknown mechanism, which leads to the trapping of class I molecules in the ER.

[The histological research between the mode of invasion and cervical lymph node metastasis in squamous cell carcinoma of the oral cavity].

OBJECTIVE: The relationship between the mode of tumor invasion in the tumor-host borderline and the frequency of cervical lymph node metastasis was investigated in squamous cell carcinoma of the oral cavity. METHODS: 200 cases with histologically proven squamous cell carcinoma of the oral cavity were studied by histological method with HE stained. The mode of invasion in the tumor-host relationship was classified into five grades by Yamamoto's criteria. RESULTS: With regard to the relationship between the mode of invasion and metastasis, the more invasive the tumor tissue was, the more frequent the metastasis formed (P < 0.001). The frequency of metastasis in grades 1 and 2 was low (0 and 5.9%, respectively), The frequency of metastasis in grades 3 was moderate (14.3%), and that in grades 4c and 4d was highly rapid (63.0% and 82.9%, respectively). Single node metastases were frequent in grade 3 and grade 4c (66.7% and 58.8%, respectively), while plural node metastases were frequent in grade 4d (70.6%, P < 0.05). Moreover, the distribution of metastasized lymph nodes was focused on level 1 (41.2%) or level 1 and 2 (79.4%) in grade 4c and was dispersed from level 1 to 4 in grade 4d (P < 0.05). In the present study, the degree of differentiation did not correlate well with the frequency of metastasis. CONCLUSION: These results indicate that the more invasive the tumor cells were to the host, the more frequent the metastasis formed. The different mode of invasion would accompany with different frequency of metastasis, different number and distribution of metastasized lymph nodes.

[Prader-Willi syndrome and genomic imprinting].

OBJECTIVE: Prader-Willi syndrome (PWS) is an example of a human genetic disorder that involves imprinting genes on the proximal long arm of chromosome 15 and SNRPN gene as a candidate gene for this syndrome. The purpose of this study was to show the molecular genetic defects and genomic imprinting basis in Chinese PWS patients and to evaluate the clinical applications of a differential diagnostic test for PWS. METHODS: Fluorescence in situ hybridization (FISH) and methylation-specific PCR (MSPCR) techniques were applied for 4 clinically suspected PWS patients. Using three probes, including SNRPN probe for identification of the critical locus in PWS region, D15Z1 and PML control probes for identification of the 15p arm and 15q arm, the authors detected the deletions 15q in PWS. MSPCR was based on sodium bisulfite treatment of DNA and PCR primers specific for the maternal and paternal allele. RESULTS: When hybridized with mixed probes, it was found in 2 patients that the central specific signal was absent, but both the flanking control signals were retained, indicating SNRPN gene deletion of chromosome 15q11-13. Bisulfite-modified DNA from all PWS children amplified with methylated allele-specific primer pair showed only maternal 131bp PCR product, indicating the maternal uniparental disomy (UPD15). CONCLUSION: Genomic imprinting plays an important role in the molecular pathogenesis of PWS that caused by paternal microdeletions of 15q11-q13 or maternal UPD of chromosome 15. The basic defect seemed to be an absence of function of PWS genes that are normally expressed only from the paternal chromosome 15. MSPCR is a rapid and simple PCR-based assay compared with other cyto-molecular tests and its results were consistent with the clinical diagnosis of PWS, so it seems to be a reliable diagnostic method for PWS patients who show abnormal methylation at SNRPN. The genetic differential tests for PWS are important in determining familial recurrence risk.