Objective To study the effect of methylmercury on the behavioral teratogenesis in filial r ats.Method Pregnant rats were injected intra-abdominally with 0 ,0.75,1.50,3.00 mg/kg methylmercury every other day,then early physiological fun ctions and behavioral functions of their filial rats were observed. Results The results indicated that when impregnated female ra ts were heavily exposed to methylmercury, early physiological development and be havioral development of their filial rats were retarded.Conclusion The methylmercury likely has the effect on behavioral teratogenesis of rats. J Appl Clin Pediatr,2005,20(2):153-155

Objective To investigate the effects of integrin β1 gene expression inhibited by short hairpin RNA (shRNA) on invasion of pancreatic carcinoma PANC1 cells in vitro,and investigate the mechanism.Methods The eukaryotic expression plasmid of shRNA targeting integrin β1 gene ( integrin β1 shRNA) and control eukaryotic expression plasmid shRNA (c-shRNA) was constructed and was transfected into PANC1 cells.The cells without plasmid transfection were used as control.The expressions of integrinβ1,MMP 2,MMP 9 mRNA and protein were detected by real-time PCR and Western blotting.The invasive ability of PANC1 cells was observed with Transwell cell culture chamber.Results Integrinβ1 mRNA expressions in integrinβ1 shRNA group,c-shRNA group and control group were 0.0029 ± 0.0004,0.0131 ± 0.0009,0.0138 ± 0.0005 ; the expressions of integrinβ1 protein were 0.0159 ± 0.0062,0.3215 ± 0.0126,0.3107 ±0.0094; the inhibitory rate of integrinβ1 mRNA and protein expression in integrinβ1 shRNA group was (78.6 ±7.2 ) ％ and (92.9 ± 3.2) ％ ( P ＜ 0.01 ).But there was no difference between the c-shRNA group and control group (P =0.2999).Number of penetrating cells in integrinβ1 shRNA group decreased from 52 ±5 to 21 ±4( P ＜ 0.01 ) ; the expression of MMP 2 and MMP 9 mRNA decreased from 0.592 ± 0.073,0.847 ± 0.069 to 0.102 ± 0.034,0.273 ± 0.071 ; the expression of M MP2 and MMP 9 protein decreased from 0.225 ± 0.046,0.416 ±0.081 to 0.059 ±0.013,0.106 ±0.022(P ＜0.05).Conclusions Recombinant integrinβ1 shRNA expression plasmid can effectively inhibit the expression of integrinβ1 gene and suppress the invasion of PANC1 cells in vitro by down-regulating MMP 2 and MMP 9 gene expression.

BACKGROUNDThe presence of autoantibodies against multiple epidermal proteins is an important feature in paraneoplastic pemphigus (PNP). Circulating anti-desmoglein 3 autoantibody, the major pathogenic autoantibody in pemphigus vulgaris (PV), has been proved pathogenic in PNP. Because of many clinical differences between PNP and PV, we speculate about the involvement of other autoantibodies in the pathogenesis of PNP. Envoplakin (EPL) and periplakin (PPL) are recognized by most PNP sera. Their linker subdomains are highly homologous and necessary for the association of intermediate filaments.

METHODSWe characterized the autoantibodies against the linker subdomains of EPL and PPL in PNP patients' sera and their associated tumors by enzyme-linked immunosorbent assay (ELISA) and immunofluorence. We also applied the purified autoantibodies against EPL and PPL from PNP sera to cultured human epidermal keratinocytes (HEK), to evaluate the changes of cell-cell adhesion.

RESULTSAutoantibodies against EPL and PPL were detected in most PNP patients by ELISA, and the decrease of these autoantibodies after removal of the tumors was roughly comparable to the improvement of clinical symptoms. Cultured tumor cells from PNP patients secreted these autoantibodies. Specific immunoglobulin receptors for EPL and PPL were found on B lymphocytes in tumors from PNP. Furthermore, purified anti-EPL and anti-PPL autoantibodies from PNP sera were capable of dissociating cultured human epidermal keratinocytes.

CONCLUSIONAutoantibodies against EPL and PPL may also be pathogenic in PNP.

Adolescent ; Adult ; Autoantibodies ; immunology ; pharmacology ; Cell Adhesion ; drug effects ; Cells, Cultured ; Desmoglein 3 ; immunology ; Enzyme-Linked Immunosorbent Assay ; Epidermis ; cytology ; Female ; Humans ; Keratinocytes ; cytology ; drug effects ; Male ; Membrane Proteins ; immunology ; Middle Aged ; Paraneoplastic Syndromes ; immunology ; metabolism ; Pemphigus ; immunology ; metabolism ; Plakins ; immunology ; Protein Precursors ; immunology ; Young Adult

OBJECTIVETo investigate the effect of the vector carrying short hairpin RNA targeting epidermal growth factor receptor (shRNA-EGFR) on the radiosensitivity of human nasopharyngeal carcinoma xenografts in nude mice.

METHODSshRNA-EGFR was transfected into human nasopharyngeal carcinoma cell line CNE1 via Lipofectamine 2000. The transfected cells were collected for quantitative RT-PCR detection of the expression level of EGFR mRNA. Western blotting was used to examine the expression of EGFR protein. CNE1 cells were inoculated into nude mice and the tumor volume was measured every 2 days. shRNA-EGFR was intratumorally injected in the mice, and 16 days after radiotherapy, the mice were sacrificed and tumors examined for radiosensitivity.

RESULTSshRNA-EGFR was effectively delivered via Lipofectamine 2000 into CNE cells to result in a significant downregulation of EGFR mRNA and protein expressions (P<0.05). A significant difference was noted in the tumor volume and weight in the tumor-bearing nude mice between shRNA-EGFR plus radiotherapy group and the control, exclusive radiotherapy and shRNA-EGFR groups (P<0.05).

CONCLUSIONshRNA-EGFR combined with radiotherapy can effectively inhibit the growth of nasopharyngeal carcinoma in nude mice. shRNA-EGFR can enhance sensitivity of nasopharyngeal carcinoma to radiotherapy.

Animals ; Gene Expression Regulation, Neoplastic ; Mice ; Mice, Nude ; Nasopharyngeal Neoplasms ; genetics ; radiotherapy ; RNA, Catalytic ; genetics ; RNA, Small Interfering ; genetics ; Radiation Tolerance ; genetics ; Receptor, Epidermal Growth Factor ; genetics ; Transfection ; Xenograft Model Antitumor Assays

Objective To study the clinical characteristics of bulbar myasthenia gravis (MG). Methods Retrospective review was performed on 166 patients with bulbar type of myasthenia gravis, diagnosed at Tongji Hospital in the period of May 1983 through October 2005.Results Bulbar MG was a relatively rare type of MG,accounting for 5.7% (166/2888) of MG classifications.Females were more often affected than males (the ratio of male:female was 1:1.35).The peak of onset age was at 20—40 years.The incidence of myasthenia crisis in the group was 26.5% (44/166).Myasthenic crisis occurred in 10.8% (18/166) of the bulbar MG patients within 6 months after onset,resulting in a mortality rate of 6.0% (10/166) in the group.Out of the group,30 cases experienced puhnonary infections (18.1%). Thirty cases were initially misdiagnosed as other diseases such as nasopharyngeal disorders (33/166, 19.9%).The routine therapy was not very satisfactory.Median dose cyclophosphamide therapy appeared to be effective for ameliorating refractory MG.Thymectomy was performed in 25 patients,with optimistic efficacy rate up to 80.0% (20/25) in a 3-year follow-up.Conclusions The clinical analysis in the current study suggested that the bulbar MG had its own characteristics in such aspects as progression of the disease, complications,treatment and prognosis.The information of the clinical manifestations presented in this study may be useful in diagnosing and treating bulbar MG.

Objective To evaluate the clinical efficacy of detachable balloons,detachable coils and intracranial covered stents in management of intracranial giant aneurysms.Methods From April 1998 to March 2006,20 patients with a giant or very large aneurysm were treated by parent artery occlusion(PAO), coils embolization and covered stent,in which 9 aneurysms were treated by PAO,8 by coils embolization and 3 by covered stent at initial management.Two recurrent aneurysms treated by coils embolization were performed by covered stent.Follow-up 9-83 months,mean 41.1?25.3 months.Immediate postprocedural angiographic outcomes were categorized as complete occlusion(100%),subtotal occlusion(95%-99%),and incomplete occlusion(＜95%)of the aneurysms;and follow-up angiographic outcomes were categorized as stable, thrombosis,and recanalization.Clinical outcomes were graded according to a modified Glasgow Outcome Scale (GOS).Results Endovascular treatment was technically feasible in all aneurysms without procedural-related complications.Immediate postprocedural angiograms showed complete occlusion was achieved in 11 aneurysms, subtotal occlusion in 7 and incomplete occlusion in 2.One patient with incomplete occlusion died on the seventh day with a rebleeding.The final angiographic findings in nineteen survival patients confirmed a complete occlusion in 15 aneurysms,subtotal occlusion in 3 and incomplete occlusion in 1,in which 10 parent arteries were successfully preserved.No rebleeding occurred during the follow-up period.The clinical evaluation performed at final follow-up in 19 patients revealed that the symptoms disappeared in 11 patients and improved in 8 in the modified GOS.Conclusions Treatment of giant intracranial aneurysms with coiling was associated with a low complete occlusion rate and a high recanalization rate.Treatment with endovascular parent artery occlusion remains practical,but this technique may result in damage to the parent artery and cause cerebral ischemic events.The use of an intracranial covered stent proved to be a relatively simple and safe procedure and maintained the pateney of the parent artery.

BACKGROUND: High blood pressure is prevalent in obesity and diabetes, especially noninsulin dependent diabetes mellitus, and both conditions are insulin resistant state. METHOD: To test whether resistance to insulin-stimulated glucose uptake and hyperinsulinemia are involved in the pochogenesis of hypertension, author measured glucose, insulin and C-Peptide reponse after oral glucose loading in 52 cases of essential hypertension and 62 cases of normal controls who had been admitted to the ward of internal medicine, Pusan National University Hospita. RESULTS: Basal plasma glucose, insulin and C-Peptide levels in control subjects were 92.1+/-36.8mg/dl, 8.7+/-5.5microu/ml and 2.2+/-1.8ng/ml and in hypertensive subjects were 95.7+/-32.6mg/dl, 12.2+/-5.3microu/ml and 2.9+/-1.6ng/ml. The basal insulin level was markedly higher than tat of control subjets (p<0.05). The basal glucose and C-Peptide levels in hypertensive patioents were higher than controls but statistically not significant. Plasma glucose levels in time course after glucose load in hypertensive patients showed significantly higher levels in 60,90minutes than controls. Plasma insulin levels in hypertensives in 90 minutes were significantly higher. The C-Peptide levels in hypertensives showed significantly higher in each times 30,60,90,120 minutes than controls. In hypertensive patients, body weight, blood pressure levels and duration of hypertension were not significantly correlated with responses of glucose, insalin and c-peptioce. Hypertensive patients aboce the age of 50 showed significantly higher glucose levels in 60,90,120 minutes than under age of 50. CONCLUSION: These results indicate some tendency of disturbed glucose turnover or insulin-resistant state in essential hypertension. This metabolic disturbance in essential hypertension should be considered in the management of hypertensive patients.
Blood Glucose* ; Blood Pressure ; Body Weight ; Busan ; C-Peptide* ; Diabetes Mellitus ; Glucose ; Humans ; Hyperinsulinism ; Hypertension* ; Insulin Resistance ; Insulin* ; Internal Medicine ; Obesity ; Plasma*

Antibody-drug conjugate (ADC) is a new class of therapeutics composed of a monoclonal antibody and small cytotoxin moieties conjugated through a chemical linker. ADC molecules bind to the target antigens expressed on the tumor cell surfaces guided by the monoclonal antibody component. The binding ADC molecules can be internalized and subsequently the toxin moieties can be released within the tumor cells via chemical and/or enzymatic reactions to kill the target cells. The conjugation combines the merits of both components, i.e., the high target specificity of the monoclonal antibody and the highly potent cell killing activity of the cytotoxin moieties. However, such complexities make the pharmacokinetic and metabolic studies of ADCs highly challenging. The major challenges should include characterization of absorption, distribution, metabolism and excretion, investigation of underlying mechanisms, assessment of pharmacokinetic- pharmacodynamic relationship, and analytical method development of ADC drugs. This review will discuss common pharmacokinetic issues and considerations, as well as tools and strategies that can be utilized to characterize the pharmacokinetic and metabolic properties of ADCs.
Antibodies, Monoclonal ; pharmacokinetics ; Cytotoxins ; pharmacokinetics ; Humans ; Immunoconjugates ; pharmacokinetics ; Neoplasms ; drug therapy

This study was to investigate the anti-lymphocytic malignancy immunologic effects induced by two types of the idiotypic nucleic acid vaccines which were constructed from the genomic DNA and RNA of the human B lymphoma cell line respectively. Namalwa cell line and BALB/c mice were used as the models. The gene fragments of the IgH variable region (IgHV), which were obtained from the genomic DNA and RNA of Namalwa cell respectively, were cloned into the eukaryocytic expression vector pcDNA 3.0 to be used as the idiotypic nucleic acid vaccines. After transfecting COS cells with one of vaccines constructed from the genomic DNA by using LipofectAMINE, the result of transcription was identified by using RT-PCR. The experimental mice were immunized by intramuscular injection with two types of vaccines. The specific anti-idiotypic antibody was detected by indirect immunofluorescence assay. The results showed that the nucleic acid vaccine constructed from the genomic DNA can be transcribed in COS cells, the transcription product turned shorter, and the intron region of 86 bp was spliced accurately. When immunizing the mice, two vaccines both induced the anti-idiotypic antibody against Namalwa cell, the anti-idiotypic antibody could be detected since detected since after immunization, and got to the peak of titer on the sixth week. It was concluded that the nucleic acid vaccines against lymphoma can be constructed from both the genomic DNA and RNA.
Animals ; Antibodies, Anti-Idiotypic ; blood ; immunology ; Base Sequence ; COS Cells ; DNA, Neoplasm ; genetics ; immunology ; Humans ; Immunoglobulin Heavy Chains ; genetics ; immunology ; Immunoglobulin Variable Region ; genetics ; immunology ; Injections, Intramuscular ; Lymphoma, B-Cell ; genetics ; Mice ; Mice, Inbred BALB C ; Molecular Sequence Data ; Plasmids ; administration & dosage ; genetics ; immunology ; Time Factors ; Tumor Cells, Cultured ; Vaccines, DNA ; genetics ; immunology

OBJECTIVETo investigate the change of zygomatic and temporal soft tissue after coronal incision.

METHODSA retrospective analysis was performed in 33 patients who received firm fixation for unilateral zygomatic comminuted fracture through semi-coronal incision. All the patients were followed up for more than one year. Craniofacial anthropometric measurement through 3D-CT reconstruction and facial profile was performed. The difference between the operated side and healthy side was analyzed.

RESULTSAt the temporal concave point, the soft tissue thickness at healthy side was (1.60 +/- 0. 97) mm more than that at operated side, showing a significant difference between them (P < 0.01). While the soft tissue thickness was not statistically different between two sides at zygion, malar prominence, zygomaxillare, and temporal convex point (P > 0.05).

CONCLUSIONSThe soft tissue atrophy may happen at temporal fat pad after semi-coronal incision, but not at zygomatic area. Intraoperative precise dissection and less stretch of soft tissue may be helpful to avoid the postoperative facial asymmetry.

Adipose Tissue ; anatomy & histology ; Adult ; Female ; Follow-Up Studies ; Fractures, Comminuted ; surgery ; Humans ; Male ; Middle Aged ; Postoperative Period ; Retrospective Studies ; Scalp ; surgery ; Young Adult ; Zygomatic Fractures ; surgery