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Biomedical subjects

Y Yu

Publications and source records attributed to Y Yu.

At least 271 records · Page 15Linked to original sources
PubMed1999

Induction of G(1) checkpoint in the gastric mucosa of aged rats.

Although in Fischer 344 rats aging is found to be associated with increased gastric mucosal proliferative activity, little is known about specific changes in the regulatory mechanisms of this process. To determine whether changes in cell cycling events could partly contribute to the age-related rise in gastric mucosal proliferative activity, the present investigation examines changes in cyclin-dependent kinase (Cdk2) activity and the regulation of this process in the gastric mucosa of Fischer 344 rats aged 4 (young), 13 (middle aged), and 24 (old) mo. We observed that aging is associated with a progressive rise in activity and protein levels of Cdk2 in the gastric mucosa. This is also found to be accompanied by a concomitant increase in cyclin E but not cyclin D1 levels. On the other hand, the levels of p21(Waf1/Cip1) (total as well as the fraction associated with Cdk2), a nuclear protein that is known to inhibit different cyclin-Cdk complexes, are found to decline in the gastric mucosa with advancing age. In contrast, with aging, there was a steady rise in p53 levels in the gastric mucosa. We have also observed that the levels of phosphorylated retinoblastoma protein, a form that participates in regulating progression through the S phase, are markedly elevated in the gastric mucosa of aged rats. In conclusion, our data suggest that, in the gastric mucosa, aging enhances transition of G(1) to S phase as well as progression through the S phase of the cell cycle. However, the age-related decline in p21(Waf1/Cip1) in the gastric mucosa appears to be independent of p53 status.

Aging↗
PubMed1999

Preparation of DNA-immobilized immunoadsorbent for treatment of systemic lupus erythematosus.

A new DNA-immobilized immunoadsorbent was prepared to remove the pathogenic anti-DNA antibody from the serum of systemic lupus erythematosus (SLE) patients. A non-woven poly(ethylene terephthalate) (PET) fabric made of 3.5-microm diameter fibers was used as the support of the immunoadsorbent. A cationic monomer, N,N-dimethylaminoethyl methacrylate (DAM), was graft polymerized onto the PET fiber surface by UV irradiation or with a chemical initiator. Polyion complexation between the cationic groups of the graft chains and DNA molecules was employed to immobilize DNA onto the fiber surface. No DNA leaching was observed when the DNA-immobilized fabrics were placed in 0.9 and 2.0 wt% NaCl solution at 37 degrees C overnight. In vitro evaluation of this DNA-immobilized immunoadsorbent demonstrated that this adsorbent could selectively adsorb anti-DNA antibody from the serum of SLE patients.

Adsorption↗
PubMed1999

Alteration in aortic wall stiffness and accumulation of collagen during the prediabetic stage of type II diabetes mellitus in rats.

Aortic damage during the prediabetic stage of diabetes mellitus (DM) was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, as an animal model of type II DM. In 30 OLETF and 30 nonDM rats, an oral glucose tolerance test was performed at 10, 20 and 30 weeks of age. At 15 and 30 weeks, intravascular ultrasound images and aortic pressure were recorded and the stiffness parameter beta was calculated. The aortic walls were excised at 5, 15 and 30 weeks for histopathology and the measurement of hydroxyproline. At 10 weeks, blood glucose (mg/dl) and insulin concentrations (ng/ml) of the OLETF rats (2h; 168+/-30 and 0.82+/-0.15) were significantly high (nonDM: 118+/-15; p = 0.02 and 0.16+/-0.64; p = 0.003). At the prediabetic stage (15 weeks), beta in the OLETF rats (2.5+/-0.9) was larger than in nonDM rats (1.4+/-0.4; p = 0.0006), and the collagen (hydroxyproline) content/dry weight (mg/g) of the aortic wall was significantly higher in OLETF (33.5+/-3.1) than in nonDM rats (28.7+/-3.5; p<.05). Histopathological examination showed that from 15 weeks of age the medial wall thickness increased gradually. In the prediabetic stage, collagen accumulation may contribute to impairment of aortic wall stiffness in the OLETF rats, which would accelerate the aging process in the aortic wall.

Animals↗
PubMed1999

Mitral valve replacement with complete mitral leaflet retention: operative techniques.

BACKGROUND AND AIMS OF THE STUDY: This report describes surgical indication and operative technique of complete preservation of the mitral valvular and subvalvular apparatus during mitral valve replacement. METHODS: Twenty patients, 12 with rheumatic lesions and eight with congenital lesions, were operated between 1991 and 1996. The left atrium was opened using a trans-septal approach through the right atrium in 17 patients, and at the intra-atrial groove in three. The valve was sized without excising any mitral valvular or subvalvular tissue. Teflon pledget-reinforced horizontal mattress valve sutures were passed from the left atrium, through the mitral annulus, around the free edge of mitral leaflet, and up through the prosthetic sewing ring. The prosthetic valve was seated and the sutures tied, reefing the native leaflets and compressing them between the sewing ring and native annulus. Thus, chordal tension on the ventricle was evenly maintained. RESULTS: There was no operative or late death. Postoperative results were excellent. Echocardiography showed that none of the patients had any observable anterior leaflet and redundant subvalvular tissue in the left ventricular outflow tract (LVOT); thus, neither LVOT obstruction nor interference with prosthetic valve function occurred. CONCLUSIONS: Based on these findings, it is suggested that when mitral valve replacement is required in patients with mitral insufficiency (MI) or MI with mild stenosis, the mitral valvular and subvalvular tissue should be completely preserved.

Adult↗
PubMed1999

Effects of ZD6169, a K(ATP) channel opener, on the micturition reflex in the rat.

The effects of ZD6169, a new ATP-sensitive potassium channel opener, on reflex urinary bladder activity were evaluated in urethane-anesthetized female Wistar rats. Continuous transvesical slow infusion cystometrograms (0.04 ml/min) were performed in untreated, capsaicin-pretreated (125 mg/kg s.c., 4 days before experiments) and capsaicin vehicle-pretreated rats. Intravesical infusion of ZD6169 in concentrations of 6, 15, 30, and 300 nM for 2 h at each concentration increased the intercontraction interval and pressure threshold for voiding in a concentration-dependent manner in untreated and vehicle-pretreated rats but not in capsaicin-pretreated animals. The effects appeared within 30 min after administration. ZD6169 did not alter baseline bladder pressure, duration of contractions, or the peak pressure during voiding. Glibenclamide (20 mg/kg i.v.) reversed the effects of ZD6169 (30 nM). During transvesical cystometrograms performed at a fast rate (0.21 ml/min), ZD6169 in concentrations between 6 and 300 nM did not alter the intercontraction interval or pressure threshold for voiding. ZD6169 produced smaller and more variable effects during slow transurethral cystometrograms. Capsaicin, a C-fiber afferent neurotoxin, administered s.c. 4 days before the experiment, produced similar changes and also eliminated the effect of ZD6169. These data suggest that ZD6169 raises the threshold for activation of C-fiber mechanoreceptors in the bladder wall and thereby increases the bladder volume for inducing reflex voiding.

Adenosine Triphosphate↗
PubMed1999

Enhanced antitumor immune responses of IL-2 gene-modified tumor vaccine by combination with IL-1 and low dose cyclophosphamide.

To enhance the antitumor immunity induced by IL-2 gene-modified tumor vaccine, we proposed a combined protocol to treat tumor-bearing mice using IL-2 gene-modified tumor vaccine in combination with IL-1 and low-dose Cyclophosphamide(Cy). After treatment with IL-2 gene-modified B16 melanoma cell vaccine alone, the pulmonary metastases of tumor-bearing mice were reduced and their survival time was prolonged. The anti-metastases effect was improved when the vaccine was used in combination with IL-1 or low-dose Cy. The best therapeutic effect was achieved when the IL-2 gene-modified vaccine was combined with IL-1 and low-dose Cy. The cytotoxicity of the splenic CTL, NK, and the levels of IL-2, TNF secreted by splenocytes increased after tumor-bearing mice were treated with the IL-2 gene-modified tumor vaccine. The above antitumor immune functions were augmented more significantly when IL-1, low-dose Cy were used in combination with IL-2 genemodified tumor vaccine. These results demonstrated that the IL-2 gene modified vaccine could exert more potent anti-metastases effects when it is combined with IL-1 or/and low-dose Cy by activating the specific and non-specific antitumor immune responses more effectively.

Animals↗
PubMed1999

The outcome of heregulin-induced activation of ovarian cancer cells depends on the relative levels of HER-2 and HER-3 expression.

Members of the epidermal growth factor receptor family of tyrosine kinases, including epidermal growth factor receptor, c-erbB-2 (HER-2), c-erbB-3 (HER-3), and c-erbB-4 (HER-4), can be coexpressed at different levels in nonhematopoietic tissues. Amplification and overexpression of HER-2 is found in approximately one-third of cancers that arise in the breast and ovary. In our previous studies, heregulin (HRG) and anti-HER-2 antibodies inhibited proliferation, increased invasiveness, and enhanced tyrosine autophosphorylation of SKBr3 breast cancer cells that overexpressed HER-2. In the present report, the effects of HRG and anti-HER-2 antibody have been compared in six ovarian cancer cell lines. HRG inhibited anchorage-independent growth of SKOv3 cells that overexpressed HER-2 (10(5) receptors/cell) but stimulated the growth of OVCA420, OVCA429, OVCA432, OVCA433, and OVCAR-3 cells that expressed lower levels of the receptor (10(4) receptors/cell). Thus, cell lines with a high level of HER-2 relative to HER-3 or HER-4 were growth inhibited, whereas cell lines with lower levels of HER-2 were growth stimulated by HRG. Stimulation or inhibition of clonogenic growth did not correlate with endogenous expression of HRG or with the impact of exogenous HRG on phosphorylation of HER-2, HER-3, or HER-4. Anti-HER-2 antibodies inhibited the growth of SKOv3 cells but failed to affect the growth of the other cell lines. In OVCAR-3 cells that had been transfected with HER-2 cDNA to increase expression to 10(5) receptors/cell, HRG inhibited rather than stimulated growth. Conversely, when HER-2 expression by SKOv3 cells was downregulated by transfection of the viral E1A gene, HRG stimulated rather than inhibited growth. To evaluate the relative importance of HER-3 and HER-4, NIH 3T3 cells were cotransfected with HER-2 and HER-3 or with HER-2 and HER-4. HRG inhibited the growth of cells with a high ratio of HER-2:HER-3, whereas HRG stimulated the growth of cells with low levels of the two receptors. In cells that express only HER-2 and HER-4, HRG stimulated the growth of cells that expressed HER-4 independent of HER-2 levels. Anti-HER-2 antibodies inhibited the growth of transfectants with high levels of HER-2 expression independent of HER-3 or HER-4 expression. In ovarian cancer cells that express all three receptors, the relative levels of HER-2 and HER-3 appear to determine the response to HRG. Taken together, these studies support the concept that the level of HER-2 expression can modulate response to HRG, determining whether the response is stimulatory or inhibitory. In contrast, agonistic antibodies that bind to HER-2 alone inhibit anchorage-independent growth but fail to mimic HRG's ability to stimulate growth of cells with low HER-2: HER-3 ratios.

Antibodies, Monoclonal↗
PubMed1999

[Effects of lovastatin on plasma lipid, plasma glucose and insulin metabolism of patients with type II B hyperlipemia].

This study was directed at the effects of lovastatin on plasma glucose and insulin metabolism of patients with Type II B hyperlipemia. Thirty patients with Type II B hyperlipemia were observed. At the beginning, We detected the patients' TC, TG, HDL-C, VLDL-C with enzyme assay, calculated their LDL-C with formula, determined their plasmaglucose(PG) with oxidase assay and plasma insulin(PI) with immunoradioassay, and then we performed OGTT and insulin release test, these indices were detected again after the administration of 8 weeks' lovastatin therapy (20 mg per day). The results showed that, aftert the therapy, TC and LDL-C decreased significantly(P < 0.05), TG, HDL-C and VLDL-C had no significant change(P > 0.05). Fasting plasma glucose(FPG) and fasting plasma insulin(FPI) increased (the former, P < 0.05). Two hours after administration of glucose, the level of plasma glucose(2hPG) and plasma insulin(2hPI)increased(the latter, P < 0.05). 1/(FPG x FPI) had no significant change, but 1/(2hPG x 2hPI) decreased (P < 0.05). These data indicate that long-period use of lavastatin may cause insulin resistance. So we advise patients with Type II B hyperlipemia treated by statin to limit their glucose intake in case of hyperinsulinemia and insulin resistance.

Aged↗
PubMed1999

Augmentation of antitumor effect of adenovirus-mediated CD suicide gene therapy by cotransfer of interleukin 2 gene in melanoma-bearing mice.

OBJECTIVE: To investigate the antitumor effect of combined adenovirus encoding E. coli cytosine deaminase (AdCD) and adenovirus encoding murine interleukin 2 (AdIL-2) on murine melanoma. METHODS: C57BL/6 mice were inoculated s.c. with B16F10 melanoma cells and 3 days later received injections of AdCD and/or AdIL-2 at the site of tumor inoculation followed by administration of 5-flurocytosine (5FC) 300 mg/kg per day for 10 days. RESULTS: Mice receiving AdCD/5FC/AdIL2 therapy developed tumors more slowly and survived much longer when compared with mice treated with AdCD/5FC, AdIL2, AdlacZ/5FC, or PBS. Immunological analysis illustrated that combined treatment could enhance NK activity and CTL activity. Flow cytometry demonstrated that AdCD/5FC/AdIL2 therapy increased the expression of MHC-1 and CD80 molecules on freshly isolated tumor cells. The CD4+ and CD8+ T cell infiltration in the tumor increased significantly after the combined therapy. CONCLUSIONS: Our data showed that combined transfer of CD suicide gene and IL-2 gene could inhibit the tumor growth more significantly. The increased specific and non-specific antitumor immunity might be responsible for the enhanced therapeutic effect.

Adenoviruses, Human↗
PubMed1999

[The effect of intestinal ischemia/reperfusion on increased sensitivity to endotoxin and its potential mechanism].

OBJECTIVE: To investigate the effect of intestinal ischemia/reperfusion injury (I/R) on increased sensitivity to endotoxin and its potential mechanism(s). METHODS: Sprague-Dawley rats underwent 45 minutes of superior mesenteric artery occlusion followed by reperfusion. Twelve hours after reperfusion, endotoxin (Escherichia coli LPS, 1.5 mg/kg) was injected intravenously and rats were killed 12 hours later for measurement of organ function parameters. Also, in vitro study was performed to determine LPS-induced tumor necrosis factor (TNF)release in whole blood. RESULTS: LPS injection after I/R resulted in marked hemodynamic dysfunction and multiple organ damage(P < 0.01), while no significant or only minor changes in organ function parameters were observed in both I/R and LPS groups. In whole blood, monoclonal antibody to CD14 significantly blocked the release of TNF at low LPS concentration (< or = 10 ng/ml), and this response was dose dependent. Moreover, TNF release in LPS-stimulated whole blood obtained after I/R was inhibited to a significantly greater degree than that in baseline blood samples or sham-operation group(P < 0.05-0.01). CONCLUSION: Splanchnic artery occlusion followed by reperfusion could lead to increased sensitivity to the subsequent LPS challenge, which may be associated with a shift toward CD14-dependent mechanism(s).

Animals↗
PubMed1999

[Direct, rapid detection for rifampin susceptibility to M. tuberculosis].

OBJECTIVE: To evaluate the use of molecular biotechnology for direct, rapid detection of rifampicin-resistance mutations in M. tuberculosis. METHODS: 45 M. tuberculosis clinical isolates and 70 sputum samples were tested by polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP) technique. M. tuberculosis strain H37Rv was used as control and compared with the result of susceptibility test. DNA sequencing was also performed in some of the strains. RESULTS: All tested susceptible isolates displayed identical SSCP patterns. Of 29 RFP resistance strains, 26(90%) had distinct mobility shifts that can be discriminated from susceptible isolates. 9 sputum samples which were succeasfully evaluated by PCR-SSCP showed concordant result acquired from BACTEC 460 method. As the result of DNA sequencing, it was observed that seven RFP-resistance phenotype of M. tuberculosis strains had missense mutation, in which 5 isolates displayed TCG-->TTG or CAG mutations at codon 531.2 had CAC-->TAC mutation at codon 526. On the other hand, one strain which was susceptible to rifampin exhibited identical nucleotide alignment to the sequence of rpoB gene. CONCLUSIONS: PCR-SSCP could be used as a method for simple, rapid, and reliable detection of rifampicin-resistance mutations in clinical samples of M. tuberculosis.

Antibiotics, Antitubercular↗
PubMed1999

[Hepatic resection with removal of tumor thrombi for hepatocellular carcinoma with tumor thrombi in portal vein and curative analysis].

OBJECTIVE: To study the therapeutic effects of surgical treatment for hepatocellular carcinoma (HCC) with tumor thrombi in the main trunk or the first branch of the portal vein (PVTT) and factors affecting prognosis. METHODS: 111 HCC patients with PVTT underwent hepatic resection with removal of tumor thrombi in the first left or the right branch of the portal vein or removal of tumor thrombi by direct opening of the main trunk of the portal vein. Hepatic artery infusion and/or portal vein infusion were performed after hepatic resection with removal of tumor thrombi for HCC with PVTT in 22 of the patients. Among 111 patients, 32 received postoperative transhepatic arterial chemoembolization and/or portal vein chemotherapy. Conservative treatment and surgical exploration or hepatic artery ligation (HAL) and infusion (HAI) and/or portal vein infusion (PVI) were performed in other 14 and 20 HCC patients with PVTT, respectively. RESULTS: The 1-, 2-, 3-, 4- and 5- year survival rates were 61.7%, 36.2%, 32.3%, 24.4% and 22.4% in the resected group, respectively, whereas 14 HCC patients with PVTT treated conservatively died in three months and the 1-, 2- year survival rates were 6.0% and 0 in the 20 patients with surgical exploration or HAL and HAI and/or PVI respectively. CONCLUSIONS: Hepatic resection with removal of tumor thrombi for HCC with PVTT should be encouraged for the prolongation of life span and quality of life.

Adult↗
PubMed1999

[Deep venous incompetence of legs: experimental studies].

OBJECTIVE: To seek best wrapping materials of valvular wrapping operation of deep veins in the lower limbs and to understand the value of diagnostic value of duplex scanning for incompetence of the deep veins and the function of the popliteal valve. METHODS: Strips of the autogenous saphenous vein, autogenous fascia lata and PEFE graft were used respectively as the material for valve constriction. The results were compared of duplex scanning and trans-popliteal venography. RESULTS: In the saphenous vein and fascia lata groups, diffuse fibrosis and marked narrowing of the femoral vein were found, whereas in the vascular graft group the graft was intact without prominent fibrosis and narrowing of the vein. The accurate rates of duplex scanning and trans-popliteal venography were 91.86%. at the same time the thigh and popliteal valve was closed when held breath. CONCLUSIONS: Vascular graft is the best constriction material. Duplex scanning is a important method. Popliteal valve is an important barrier for protecting the function of the deep vein.

Adult↗
PubMed1999

[The level of expression of adhesion molecules CD44v6 and E-cadherin in colorectal cancer and analysis of correlates with metastasis].

OBJECTIVE: To determine the expression of adhesion molecules CD44v6 and E cadherin in colorectal cancer and its relation with metastasis. METHODS: The expression of CD44v6 and E-cadherin in 32 patients with colorectal carcinoma was investigated using immunohistochemical staining, which was performed on surgical specimens. RESULTS: No significant correlation with CD44v6 and histologic type, TNM and Dukes staging was noted, but it was significantly correlated with lymph node and hematogenous metastasis. E-cadherin was strongly expressed in normal epithelium examined. However, E-cadherin expression in colorectal carcinoma was reduced (positive rate 46.9%). Metastatic colorectal carcinoma showed significant reduction (positive rate 20%). CONCLUSION: CD44v6, E-cadherin immunoreactivity are significantly correlated with lymph node and hematogenous metastasis.

Cadherins↗