Abstract:Objective The -455 G/A(HaeIII)polymorphism of β-fibrinogen gene influences levels of plasma fibrinogen. We further investigated whether it influences the risk of ischemic cerebrovascular disease. Methods We accumulated 134 acute ischemic cerebrovascular disease(ICVD)cases and compared their -455 G/A status with a control group(n = 166). The β-fibrinogen gene -455 G/A polymorphism was analyzed for all subjects by PCR-RFLP with the restrictive enzyme HaeIII. Results Plasma fibrinogen was higher in AA homozygous participants(341 mg/dL)than in partici-pants carrying the G allele: GA(290 mg/dL), GG(298 mg/dL)in the control group. Plasma fibrinogen was also higher in AA homozygous patients(353 mg/dL)than in cases carrying the G allele: GA(287 mg/dL), GG(302 mg/dL)in the ICVD group. However, there was no significant association between β-fibrinogen gene -455 G/A polymorphism and ICVD group. Conclusions Although a small effect cannot be excluded, β-fibrinogen gene -455 G/A polymor-phism is an independent predictor of plasma fibrinogen, but not of ischemic cerebrovascular disease.
Abstract:Objective To investigate the potential effects of angiogenic process by secretory phospholipase A2 (sPLA2)inhibitor-HyPE(linking N-derivatized phosphatidyl-ethanolamine to hyaluronic acid)on human bone marrow endothelial cell line(HBME-1). Methods In order to examine the suppressing effects of HyPE on HBME-1 proliferation, migration, and capillary-like tube formation, HBME-1 were activated by angiogenic factor, specifically by basic fibroblast growth factor(b-FGF), vascular endothelial growth factor(VEGF),and oncostatin M(OSM)(at a final concentration of 25, 20, and 2.5 ng/mL, respectively), then HBME-1 proliferation, migration, and tube forma-tion were studied in the absence or presence of HyPE. HBME-1 tube formation was specially analyzed in fibrin gel. Results HyPE effectively inhibited HBME-1 proliferation and migration as a dose-dependent manner, whatever HBME-1 were grown in the control culture medium or stimulated with b-FGF, VEGF, or OSM. In fibrin, the formations of HBME-1 derived tube-like structures were enhanced by all angiogenic factors, but these were strongly suppressed by HyPE. Conclusions The results support the involvement of sPLA2 in angiogenesis. It is proposed that sPLA2 inhibitor introduces a novel approach in the control of cancer development.
Keywords:angiogenesis;phospholipase A2 inhibitor;endothelial cell line
Abstract:Objective The platelet membrane glycoprotein (GP)Ⅰa/Ⅱa plays a major part as a primary colla-gen receptor in platelet function. Previous studies indicated that variations of GPⅠa/Ⅱa density and function are associated with the 807 C/T polymorphism of GPⅠa gene in American and Spanish Cau-casian populations. This study investigated the correlation between acute coronary syndrome (ACS) and 807 C/T dimorphism of GPⅠa gene in Chinese of Han ethnicity. Methods A case-control study was carried out, including 75 patients with either acute myocar-dial infarction (AMI) or unstable angina pectoris (UAP), and 65 controls with no history of coronary heart disease, thrombogenic and hemorrhagenic diseases. Genotypes of GPⅠa were checked by polymerase chain reaction-sequence specific primers(PCR-SSP)technique. Results The frequencies of both homozygotes and heterozygotes for T807 allele(TT+TC)were significantly higher in patients with AMI than in controls(62.16% vs 33.85%, P < 0.01; odds ratio 3.21). The prevalence of (TT+TC) genotypes was also markedly higher in patients with UAP than in controls(65.79% vs 33.85%, P < 0.005; odds ratio 3.76). There was significant difference in the distribution of(TT+TC)genotypes not only between all patients and controls(64.00% vs 33.85%, P <0.005; odds ratio 3.47)but also between the two subgroups aged < 60 years(70.00% vs 38.24%, P <0.005; odds ratio 3.77). However, there was no significant difference in the distribution of(TT+TC)genotypes between patients with AMI and with UAP. Platelet GPⅠa T807 allele remained significantly associated with AMI and UAP by multiple logistic regression(odds ratio 4.94). Conclusion This study suggests a strong association between presence of GPⅠa T807 allele and ACS. T807 allele can be a marker of genetic susceptibility to ACS.
Abstract:Objective To investigate the expression of PTEN and Caspase-3 in malignant lymphoma of the stomach and explore their role in progression of primary gastric malignant lymphoma. Methods Formalin-fixed paraffin embedded tissues from 56 cases of primary gastric malignant lymphoma and their adjacent non-tumor mucosa were evaluated for PTEN and Caspase-3 protein ex-pression by streptavidin-biotin-complex (SABC) immunohistochemistry. Their expression was compared with clinical tumor parameters with the relationship between PTEN and Caspase-3 expression concerned as well. Results The positive rate of PTEN expression in primary gastric lymphomas(50.0%, 28/56) was significantly lower than that in adjacent non-tumor gastric mucosa(96.4%, 27/28)(P < 0.05). Meanwhile,43 of 56(76.8%)gastric lymphomas indicated Caspase-3 expression, less than that in adjacent non-tumor mucosa (93.5%, 29/31) (P < 0.05). The expression of PTEN was negatively correlated with invasion and lymph node metastasis of gastric lymphoma(P < 0.05), while the Caspase-3 expression was negatively associated with the latter one(P < 0.05). Additionally, the PTEN expression was posi-tively correlated with Caspase-3 expression in the primary gastric malignant lymphoma(P < 0.05). Conclusions The down-regulated expression of PTEN and Caspase-3 played an important role in progression of primary malignant gastric lymphoma. PTEN, as a molecular marker of pathobiological behaviors of tumor, contributes to tumor progression by increasing cell mobility and angiogenesis, as well as decreasing cell adhesion and apoptosis.
Abstract:Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary(n = 5), ovarian cyst (n =5), ovarian borderline tumor (n = 9), epithelial ovarian cancer(n = 60), and ovarian cancer cell line (n = 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clini-copathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5(7.1%)cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst(P < 0.05). The level of PTEN gene mRNA expression was negatively correlated with clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05=. Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.
Abstract:Objective To explore the strategies which reduce the amount of xenoantigen Galα1, 3 Gal. Methods Human α-galactosidase gene and α1,2-fucosyltransferase gene were transferred into cul-tured porcine vascular endothelial cells PEDSV.15 and human α-galactosidase transgenic mice were produced. The Galα1,3Gal on the cell surface and susceptibility of cells to human antibody-mediated lysis were analyzed. Results Human α-galactosidase gene alone reduced 78% of Galα1,3Gal on PEDSV.15 cell surface while human α-galactosidase combined with α1,2-fucosyltransferase genes removed Galα1,3Gal completely. Decrease of Galα1,3Gal could reduce susceptibility of cells to human antibody-mediated lysis, especially during co-expression of α-galactosidase gene and α1,2-fucosyltransferase gene. RT-PCR indicated positive human α-galactosidase gene expression in all organs of positive human α-galacto-sidase transgenic F1 mice including heart, liver, kidney, lung, and spleen, the amount of Galα1,3Gal antigens on which was reduced largely. 58% of spleen cells from F1 mice were destroyed by comp-lement-mediated lysis compared with 24% of those from normal mice. Conclusions Human α-galactosidase gene and α1,2-fucosyltransferase gene effectively reduce the expression of Galα1,3Gal antigens on endothelial cell surface and confers resistance to human serum-mediated cytolysis. The expression of human α-galactosidase in mice can also eliminate the Galα1,3Gal antigens in most tissues and decrease the susceptibility of spleen cells to human serum-mediated cytolysis.
Abstract:Objective To study the effects of liver specific antigen(LSA)on liver allotransplantation rejection. Methods Orthotopic liver transplantation was performed in this study. GroupⅠ: syngeneic control(Wistar-to-Wistar); GroupⅡ: acute rejection(SD-to-Wistar). GroupIII: thymic inoculation of SD rat LSA day 7 before transplantation. The observation of general condition and survival time, rejection grades and the NF-кB activity of splenocytes were used to analyze severity of acute rejection and immune state of animals in different groups. Results The general condition of groupⅠwas fair post transplantation with no sign of rejection. All recipients of group Ⅱ died within days 9 to 13 post transplantation with median survival time of 10.7 ±1.37 days. As for group III, 5 out of 6 recipients survived for a long period with remarkably better ge-neral condition than that of group Ⅱ. Its rejection grades were significantly lower than groupⅡ(P < 0.05).NF-кB activity was only detected in groupⅠbetween days 5 and 7 after transplantation, whereas highactivity of NF-кB was detected at all points in group Ⅱ and low NF-кB activity was detected in group III which was significantly lower than that of group Ⅱ(P < 0.05). Conclusions LSA is an important transplantation antigen directly involved in the immunorejection of liver transplantation. Intrathymic inoculation of LSA can alleviate the rejection of liver allotransplantation,grafts survive for a period of time thereby, allowing a novel way to liver transplantation immunotolerance.
Keywords:liver specific antigen;liver transplantation;immunotolerance
Abstract:Objective To search novel method for diagnosis and therapy of B-lymphoma, specific small mo-lecular peptide ligands against binding site of tumor cells were screened and its effects on signal transduction and cell apoptosis were tested. Methods Specific peptide ligands were screened by binding with site of human B lymphoma cell(OC1LY8)using peptide-bead libraries. The identified peptides were characterized with responsible cellsby rebinding test. The role of tyrosine phosphorylation of peptide ligand was tested by Western blot; and its apoptosispromoting role was observed by confocal fluorescent microscope. Results Specific peptide ligand was able to bind specifically to site on cell surface and enter into cytoplasm. Tetrameric peptide ligand was able to strongly trigger signal transduction resulting in tyrosine phosphorylation and cellular apoptosis in OC1LY8 cell line. Conclusion Screened peptide ligand can effectively bind with OC1LY8 cell, stimulate cellular tyro-sine phosphorylation and induce cellular apoptosis.
Abstract:Objective To explore the causes, prevention, and management of the complications during intra-cranial aneurysm embolization with controllable coils (mechanical detachable spiral, MDS; and Guglielmi detachable coil, GDC). Methods Retrospective review of 120 cases with 125 intracranial aneurysms embolized with con-trollable coils from March 1995 to July 1999 was conducted. The 20 accidents(in 18 cases) including aneurysm rupture, over-embolization, protrusion of coil end into the parent artery, and thrombosis of the parent artery were analyzed. Results Among the 20 accidents, there were 6 aneurysm ruptures, 6 over-embolizations (in 5 cases), 6 coil protrusions, and 2 thromboses (one was secondary to coil protrusion). The embolization-related mortality was 3.33% (4/120), the permanent neurological deficit was 1.67% (2/120), and the transitory neurological deficit was 3.33%(4/120). The occurrence and outcome of the complications were related to the embolizing technique, the pattern of aneurysm and its parent artery, the imperfection of embolic materials, and the observation and management during embolization. Conclusion Skilled embolizing technique, better understanding of the angio-anatomy of an aneurysm and its parent artery, correct judgement and management during embolization, and improvement of embolic materials are beneficial to the reduction of complications and to the melioration of the outcome of complications.
Abstract:Objective To evaluate the relationship between levels of soluble Fas(sFas)and soluble Fas ligand(sFasL)in serum and peritoneal fluid of endometriosis-associated infertility. Methods The soluble Fas ligand and soluble Fas levels in serum and peritoneal fluid of 20 infertile patients with endometriosis were assessed with enzyme-linked immunosorbent assay, and were compared with 14 infertile patients due to chronic pelvic infectious disease and 16 fertile controls. Results The sFasL levels were significantly higher in infertile patients with endometriosis(175.09 ± 80.55 pg/mL in serum and 284.50 ± 152.38 pg/mL in peritoneal fluid)than those of infertile controls (88.47 ± 43.55 pg/mL in serum and 17.30 ± 9.62 pg/mL in peritoneal fluid)and fertile controls(16.13 ± 11.75 pg/mL in serum and 8.84 ± 2.31 pg/mL in peritoneal fluid). In contrast, as for the sFas levels, infertile patients with endometriosis(828.60 ± 429.65 pg/mL in serum and 349.61 ± 288.89 pg/mL in peritoneal fluid)did not show any significant difference compared with those in infertile patients resulting from pelvic infectious disease(868.75 ± 570.48 pg/mL in serum and 181.76 ± 157.78 pg/mL in peritoneal fluid)and fertile control(822.26 ± 129.12 pg/mL in serum and 318.42 ± 145.16 pg/mL in peritoneal fluid). Conclusions Based upon these results, high level of sFasL in serum and peritoneal fluid and thus apoptosis mediated by it may be implicated in the mechanism involved in endometriosis-related infertility.
Abstract:Objective To evaluate the possibility of vaginal hysterectomy for patients with moderately enlarged uterus of benign lesions. Methods One hundred and seventeen women with benign uterine diseases underwent vaginal hysterectomy. These patients were divided into two groups according to uterine weight. Group Ⅰ contained 60 patients with uterine enlargement to a weight of 200 to 750 g, and group Ⅱ contained 57 patients with uterine weight of less than 200 g. Uterine morcellation was performed in some cases. The peri-operative data in both groups were analyzed. Results In group Ⅰ, 59 cases underwent transvaginal hysterectomy successfully, except 1 case con-verted to abdominal operation and the uterine morcellation was performed in 21 women. In group Ⅱ, all patients successfully underwent transvaginal hysterectomy without any assistance of special technique. The mean uterine weight of group Ⅰ was significantly heavier than that of group Ⅱ(280.18 ± 100.40 g vs 146.48 ± 35.19 g). The mean operating time was significantly longer for group Ⅰ than that for group Ⅱ(83.93 ± 26.26 minutes vs 35.22 ± 20.55 minutes). There were no significant differences in blood loss and complications between groupⅠ and group Ⅱ. There was no injury of urinary bladder or rectum, and no vaginal vault infection. Conclusions Vaginal hysterectomy of moderately enlarged uterus can be safely and effectively performed by experienced operators. In some cases, in order to reduce the uterine volume, uterine mor-cellation should be used to shorten operative time, reduce the bleeding, and lower the postoperative complications.
Abstract:Objective To examine the clinical application of pulsed Doppler tissue imaging(DTI)for regional left ventricular function assessment in normal subjects. Methods We examined 50 healthy subjects(range 12-42 years,mean age 28.3 ± 6.9 years)using pulsed Doppler tissue imaging to characterize the diastolic and systolic velocity profiles of mitral annulus. Recordings were made along the long axis in the apical 4-chamber, 2-chamber, and long apical views of 6 sites(posterior-septum, lateral, anterior, inferior, anterior-septum, posterior)at the mitral annulus. Myocardial velocities were determined with use of variance F statistical analysis. Correlation analysis was employed to test the relationship between age and mitral annular velocities. Results Both early diastolic and systolic velocities at the septum were lower than other sites. There were no differences in mitral annulus late diastolic velocities. Mean early diastolic and systolic velocities was negatively correlated with age. Conclusions Doppler tissue imaging can directly reflect regional left ventricular function.
Keywords:Doppler tissue imaging;left ventricular function
Abstract:Three cases of pituitary metastases were reported. They all had operations and the pathological exami-nation confirming the diagnosis. The clinical features of diabetes insipidus and extraocular nerve palsy were presented. In two cases, the original tumors were bronchioloalveolar carcinoma; in the other one, the original tumor was unknown. All three cases had poor outcome. These cases illustrate the fact that a pituitary metastasis can closely mimic a pituitary benign tumor, such as pituitary adenoma. Especially in the presence of suggestive symptoms such as diabetes insipidus and/or cranical nerve paralysis, the possibility of metastatic disease in the differential diagnosis of a pituitary mass should always be considered.