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Biomedical subjects

Y Cai

Publications and source records attributed to Y Cai.

At least 109 records · Page 6Linked to original sources

Effects of endothelin B receptor antagonists, BQ788 and ET-1(11-21) fragment on the bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs.

OBJECTIVE: To explore the role of endothelin (ET) in the pathogenesis of exercise-induced asthma (EIA), we investigated the effects of ETB receptor antagonists, ET-1(11-21) fragment and N-cis-2, 6-dimethylpiperidinocardonyl-L-gamma-methylleucyl-D-1-methoxycarbonyl tryptophanyl-D-norleucine (BQ788) on bronchoconstriction elicited by isocapnic hyperpnea in guinea pigs. METHODS: Eighteen pathogen-free Hartley guinea pigs were randomly divided into three groups. A: normal saline (NS) inhalation control group (n = 6), B: BQ788 group (n = 6), and C: ET-1(11-21) fragment group (n = 6). Guinea pigs were anesthetized with pentobarbital sodium. After measuring the basal value of lung resistance (RL) and dynamic compliance of the respiratory system (Cdyn), NS (0.96 ml), BQ788 (9 nmol) and ET-1(11-21) fragment (9 nmol) were inhaled. A rodent respirator with a dry 5% CO(2)-95% O2 mixture at room temperature provided mechanical ventilation (VT8 ml/animal, 100 breaths/min) for 5 min. RL and Cdyn of the 3 groups were measured again after isocapnic hyperpnea challenge. RESULTS: In the control group, isocapnic hyperpnea of dry gas elicited a marked increase in RL and decrease in Cdyn. RL and Cdyn of the guinea pigs from BQ788 group and ET-1(11-21) fragment group did not change significantly. CONCLUSION: It was demonstrated that selective ETB receptor antagonists, ET-1(11-21) fragment and BQ788, inhibited the bronchoconstriction induced by isocapnic hyperpnea in guinea pigs. The data showed that ETs are potent constrictors of guinea pig airway smooth muscle via a direct effect on ET receptors. It was suggested that ET receptor antagonists, especially ETB receptor antagonist, might be beneficial in preventing EIA.

Airway Resistance↗

Co-modification of IL-2-TNF alpha fusion gene and B7.1 gene to murine breast tumor cells leads to improved tumor rejection and vaccine effect.

OBJECTIVE: To improve the vaccine potency of gene-modified tumor cells. METHODS: Using recombinant adenoviruses, we expressed the B7.1 gene in murine breast tumor cell line EMF6 and a subline previously transfected with retrovirus vector XdF harboring the IL-2-TNF alpha fusion gene. RESULTS: Immunization/challenge experiments demonstrated that IL-2-TNF alpha/B7.1 co-modified tumor cells possessed a lower tumorigenicity in vivo and an improved tumor-specific vaccine potency compared with single gene transfectant (P < 0.05). Three weeks after immunization with a variety of tumor cells, the mixed lymphocyte and tumor cells reaction assay (MLTB) and 51Cr-release assay were performed to test cellular immunity function. The results indicated that IL-2-TNF alpha and B7.1 together induced a more potent antitumor immune response than either molecule alone, 25% higher than IL-2-TNF alpha and 20% higher than B7.1, respectively. CONCLUSION: The IL-2-TNF alpha fusion gene and B7.1 gene act in concert to improve their antitumor effectiveness.

Animals↗

Detection of hepatitis B virus polymerase variations resistant to lamivudine therapy.

OBJECTIVE: To investigate variations in hepatitis B virus (HBV) polymerase gene in chronic HBV infected patients resistant to lamivudine therapy. METHODS: Specimens were obtained from nine patients with chronic HBV infection, who were resistant to lamivudine therapy. Partial segments of the HBV DNA polymerase gene were amplified by polymerase chain reaction (PCR). Nucleotide sequence was performed using an applied 373 automated sequencer. Titre of HBV DNA was measured by branched-DNA assay (Chiron). RESULTS: Of nine patients with HBV DNA positive after 64 weeks of treatment, five (56%) had variations in the highly conserved YMDD motif in domain C of the HBV polymerase, three of those were substitutions of isoleucine for methionine (M), and two were substitutions of valine(V) for methionine. Additionally, in two patients with variations characterized by substitutions of V for M, one had a simultaneous amino acid change from the first aspartic acid to glycine and this pattern of variation was not reported in other literatures. With respect to virernia, in two subjects with low titre of HBV DNA (< 100 MEq/ml), no variation was found in the YMDD motif, whereas in seven patients with high titre of HBV DBA (> 300 MEq/ml), five (71%) had variations in the YMDD motif. CONCLUSIONS: Lamivudine is a potent anti-viral agent for treatment of chronic HBV infection. Resistance to lamivudine is likely caused by the variations in the YMDD motif of the HBV polymerase gene.

Antiviral Agents↗

[The extent of paradoxical thoracoabdominal motion during exercise was improved with oxygen therapy in patients with stable moderate to severe chronic obstructive pulmonary disease].

OBJECTIVE: To assess the synergetic change of thoracoabdominal motion in COPD patients during incremental exercise testing, and to evaluate the effect of oxygen therapy on thoracoabdominal synergetic motion. METHODS: 30 stable moderate to severe COPD patients performed incremental exercise test with ergometer twice while breathing either air or 30% oxygen. Thoracoabdominal motion (assessed by TCD/VT) was monitored with respigraph during the whole test. RESULTS: 18 of 30 patients had TCD/VT > 1.20 during maximal exercise. TCD/VT at maximal exercise (TCD/VTmax) was significantly correlated with FEV1, FVC, MVV and PaCO2(r = -0.66, -0.63, -0.51, and 0.51), but not correlated with DLCO. The thoracoabdominal synergetic motion could be obviously improved with oxygen therapy. CONCLUSIONS: The change of thoracoabdominal synergetic motion during exercise in COPD patients was related with ventilatory function and blood gases. Oxygen therapy could obviously ameliorate paradoxical thoracoabdominal motion.

Abdomen↗

[Pulmonary lymphangioleiomyomatosis].

OBJECTIVE: To improve the diagnosis and treatment of pulmonary lymphangioleiomyomatosis (PLAM). METHODS: Three patients with PLAM confirmed by pathological assessment were presented and relevant literatures were reviewed. RESULTS: PLAM is a rare pulmonary disease of unknown cause. The clinical manifestations were pneumothorax, exertional dyspnea and hemoptysis. Pulmonary function test showed obstructive or compound ventilative defect and hypoxemia. HRCT showed bilateral diffuse cystic airspaces change. Pathological features showed abnormal smooth muscle proliferation occurred along lymphatics. Lymphatics dilated and proliferated. CONCLUSIONS: The prognosis of PLAM is poor. There is no effective method for the treatment of this disease at present.

Adult↗

[Antitumor effect of radiation combined with tumor draining lymphocytes on human ACC-M cell in vitro].

OBJECTIVE: To find whether there is any synergistic effect of radiation combined with interleukin-2(IL-2) activated tumor draining lymph nodes lymphocytes (DNL) from oral-carcinoma patients on high-lung metastatic salivary adenoid cystic carcinoma cell line(ACC-M). METHODS: Colony-forming test was used to investigate antitumor effect and analyzed using linear-quadratic(LQ) equation and single hit multi targets equation. RESULTS: The ratio of effect to targets was 25:1. The cytotoxicity of DNL was 49.06%. Radiation combined with DNL showed higher antitumor activity compared with radiation alone, alpha value, Dq and S2 were 0.7688 and 0.342 0; 1.5901 and 0.5995; 0.4481 and 0.1135 respectively(P < 0.05). CONCLUSIONS: It indicates that in initial region of survival curve, DNL significantly increased sublethal damage on ACC-M.

Carcinoma, Adenoid Cystic↗

[Long-term results of combined therapy for primary osteosarcoma in extremities].

OBJECTIVE: To evaluate the survival rates, functional outcome, and complications between the combined and non-combined treatment of primary osteosarcoma of the extremities. METHOD: From 1977 through 1992, 170 patients with high-graded, nonmetastatic osteosarcoma were treated. Their average age at diagnosis was 21 years old (ranging from 6 to 52). Tumors were observed at distal femurs in 80 patients (47%), proximal tibia in 51 (30%), proximal humors in 10 and other locations in 22. Combined therapy (en bloc resection of tumor with preoperative and postoperative neoadjuvant chemotherapy) was given 104 patients and non-combined therapy (tumor resection only) to 66. Ninety-four patients underwent limb salvage surgery. In 76 patients who received amputations or disarticulations 33 received chemotherapy. RESULTS: The 5-and 10-year-survival rates were 61% and 53% in the combined therapy group and 28% and 26% in the non-combined therapy group. Local recurrence rate was 23% in limb salvage surgery group and 5.2% in amputation group. Functional evaluation of 80 patients showed that the patients who underwent salvage surgery had higher functional scores than those who had an amputation according to MSTS scoring system (1993). The average scores reached 71% in the salvage surgery group and 53% in the amputation group. CONCLUSIONS: In this study, long-term that combined therapy raised the survival rate of the patients with osteosarcoma. The ase of en bloc resection of bone tumor and reconstructive technique, has enable limb salvage procedures possible to produce excellent functional outcomes. The patients who well have responses to preoperative chemotherapy may have a higher survival rate.

Adolescent↗

[Telangiectatic osteosarcoma: report of 10 cases].

OBJECTIVE: To raise the level of early diagnosis of telangiectatic osteosarcoma (TOS). METHODS: Ten patients with TOS were treated from July 1991 to December 1998. The patients included men 6 and 4 women, aged from 4 to 44 years (average 23.7 years). The lesions were located at the proximal femur (1 patient), distal femur metaphysis (2), femur shaft (1), proximal tibia metaphysis (2), distal tibia (1) and humerus shaft (3). Preoperative pathologic examination showed two cases of TOS by open biopsy(negative by needle biopsy); the rest were found negative (2 patients), metastasis (1), and sarcoma (5) by needle biopsy. Eight patients received preoperative chemotherapy. Operations including limb-salvage (3) and amputation (7) were performed in all patients. All patients accepted postoperative chemotherapy. RESULTS: 10 Follow-up for a mean of 28 months (range 6 - 72 months) showed no local recurrences: disease-free in 4 patients and pulmonary metastasis in, 6, of whom 5 died and 1 is still alive with lung metastasis. CONCLUSION: TOS is often misdiagnosed and needs early diagnosis and correct treatment under the cooperation of clinicians, radiologists and pathologists.

Adolescent↗

[Observation on curative effect of acute ischemic cerebrovascular disease treated with different dosage of ligustrazine].

OBJECTIVE: To compare clinical curative effect of acute ischemic cerebrovascular diseases (ICVD) treated with different dosage of ligustrazine and to observe the effect of ligustrazine on hemorrheology. METHODS: Sixty-nine patients with ICVD were randomized into three groups, the Group A, B and C treated with 120 mg, 240 mg and 480 mg of ligustrazine respectively, the clinical curative effect, the changes in nerve function deficit score and hemorrheologic parameters before and after treatment were observed. RESULTS: The clinical curative effect and improvement of hemorrheologic parameters in Group C were better than those in Group A and B significantly (P < 0.05, P < 0.01 respectively). Ligustrazine also showed obvious effect in lowering blood level of fibrinogen in Group C. CONCLUSION: Treatment of acute ICVD with large dose of ligustrazine is good in improving clinical effect and hemorrheology, and without side effect basically.

Adult↗

The schizontocidal activity of daphnetin against malaria parasites in vitro and in vivo.

OBJECTIVE: To investigate the in vitro and in vivo schizontocidal activity of daphnetin. METHODS: Schizontocidal activity of daphnetin was tested using an in vitro assay based on the routine in vitro cultivation of P. falciparum FCC1 strain. The in vivo antimalarial effects of daphnetin at various dosages were assessed in mice infected with P. b. erghei ANKA according to "4-day suppress assay". RESULTS: In vitro, daphnetin exhibited potent schizontocidal activity comparable to chloroquine(CQ) at the dose range of 1-10 mumol/L. In vivo, 50 or 100 mg/kg.d-1 x 4 d daphnetin i.g. and 10, 50 or 100 mg/kg.d-1 x 4 d dephnetin i.p. showed antimalarial efficacy comparable to CQ 10 mg/kg.d-1 x 4 d i.g. in mice infected with P. berghei ANKA, evaluated by both the reduction rate of parasitemia on D4 and the average surviving days in 30 days. CONCLUSION: Daphnetin displays certain schizontocidal activity both in vitro and in vivo.

Animals↗

[The influence of external stimulation on content and quality of volatile oil in Lignun Santali albi].

The authors analyzed the quality of Ligmum Santali Albi formed by the external stimulation of hormone and windburn by GC-MS-DS. The results showed that the content of volatile oil is 2.34% in the heart wood formed in 10 years tree age of Santalum album (SA) after 2 years stimulation continuously with a definite concentration of hormone, which is near to the 25 years tree age of SA in the same place. The GC-MS analysis showed that the content of santalol and other chemical components in volatile oil are similar to the 25 years tree age of SA. It is indicated that a definite concentration of hormone stimulated the SA may shorten the formation of the heart wood. The heart wood can be also formed by the broken branches after 2 years windburn, but its content of volatile oil is only 1/2 of the heart wood formed by hormone stimulation.

Age Factors↗

[Expression and deletion analysis of EcoR II endonuclease and methylase gene].

OBJECTIVE: To clone complete EcoR II restriction endonuclease gene (ecoR II R) and methyl-transferase (ecoR II M) gene into one vector and to analyzing the expression of the whole system. METHODS: Unidirective deletion subclones constructed with Exo III, ecoR II R/M genes were preliminarily located in the cloned fragments according to the enzyme activities of each subclone, exact deletion sites were determined by sequencing, and transcriptional start sites were mapped by S1 mapping. RESULTS: The DNA fragment which was cloned into pBluescript SK+ contained the complete ecoR II R gene and ecoR II M gene, there are two transcriptional start sites in ecoR II R gene, 132 bp to 458 bp from 3' and of ecoR II R gene are indispensable to enzyme activities and deletion of 202 bp from 3' end of ecoR II M gene made it lose the capability to resist specific cut of EcoR II R enzyme, deletion of coding region and flanking sequence of one gene did not affect the expression of the other gene, the recombinant only containing ecoR II R gene appeared to be lethal to dcm + host. CONCLUSIONS: ecoR II M gene closely linking to ecoR II R gene was very important for the existence of the R-M system in process of evolution, but the key to control EcoR II R enzyme acted later than EcoR II M enzyme did not exist in transcriptional level.

Cloning, Molecular↗

[Changes of plasma nitric oxide and tumor necrosis factor-alpha in lung elastase injury induced inflammatory response of hamster].

OBJECTIVE: To investigate the role of the NO and TNF-alpha in lung elastase injury induced inflammatory response of hamster. METHODS: Lung elastase injury induced inflammatory hamster model was established. NOS activity in airway epithelial cells and lung monocytes/macrophage, as well as the serum content of NO and TNF-alpha were measured respectively. RESULTS: The results indicated that iNOS activity in epithelium and monocytes/macrophages were significantly enhanced. In the early period of inflammation the NO and TNF-alpha content in serum increased obviously and maintained in a high level (P < 0.001). CONCLUSIONS: This Study suggested that both NO and TNF-alpha are important mediators participating in the lung elastase injury-induced inflammatory response. Our data suggested NO might play a regulatory role in the release of TNF-alpha.

Animals↗

The beta4 integrin subunit rescues A431 cells from apoptosis through a PI3K/Akt kinase signaling pathway.

To study whether alpha6beta4 integrin regulates apoptosis, human A431 cells were plated on bacteria plates in the presence or absence of mAb beta4. In the absence of mAb beta4, A431 cells demonstrated morphological characteristics of apoptosis by 24 h and most cells died by 48 h. In contrast, in the presence of mAb beta4, cells remained viable, and at the end of 48 h, 70-80% of cells survived. Treatment of A431 cells with mAb beta4 resulted in tyrosine phosphorylation of the p85 subunit of PI3 kinase; PI3 kinase activity increased within 15 min and peaked at 60 min. Stimulation of beta4 in A431 cells resulted in a time-dependent phosphorylation of Akt with a concomitant and parallel phosphorylation of Bad. Inactivation of PI3 kinase with inhibitors blocked the anti-apoptotic effect induced by mAb beta4. These are the first results to suggest that ligation of alpha6beta4 integrin protects cells from apoptosis through a PI3K/Akt kinase signaling pathway.

Antigens, CD↗

Identification and characterization of polycystin-2, the PKD2 gene product.

PKD2, the second gene for the autosomal dominant polycystic kidney disease (ADPKD), encodes a protein, polycystin-2, with predicted structural similarity to cation channel subunits. However, the function of polycystin-2 remains unknown. We used polyclonal antisera specific for the intracellular NH(2) and COOH termini to identify polycystin-2 as an approximately 110-kDa integral membrane glycoprotein. Polycystin-2 from both native tissues and cells in culture is sensitive to Endo H suggesting the continued presence of high-mannose oligosaccharides typical of pre-middle Golgi proteins. Immunofluorescent cell staining of polycystin-2 shows a pattern consistent with localization in the endoplasmic reticulum. This finding is confirmed by co-localization with protein-disulfide isomerase as determined by double indirect immunofluorescence and co-distribution with calnexin in subcellular fractionation studies. Polycystin-2 translation products truncated at or after Gly(821) retain their exclusive endoplasmic reticulum localization while products truncated at or before Glu(787) additionally traffic to the plasma membrane. Truncation mutants that traffic to the plasma membrane acquire Endo H resistance and can be biotinylated on the cell surface in intact cells. The 34-amino acid region Glu(787)-Ser(820), containing two putative phosphorylation sites, is responsible for the exclusive endoplasmic reticulum localization of polycystin-2 and is the site of specific interaction with an as yet unidentified protein binding partner for polycystin-2. The localization of full-length polycystin-2 to intracellular membranes raises the possibility that the PKD2 gene product is a subunit of intracellular channel complexes.

Amino Acid Sequence↗

Role of O6-alkylguanine-DNA alkyltransferase in protecting against cyclophosphamide-induced toxicity and mutagenicity.

Cyclophosphamide is used to treat a wide range of human malignancies. However, it is also a known carcinogen associated with induction of therapy-related leukemia and bladder cancer. The DNA repair protein, O6-alkylguanine-DNA alkyltransferase (AGT), protects cells from the toxic and mutagenic effects of O6-alkylating agents. We report here the contribution of AGT in protecting against the toxic and mutagenic effects of cyclophosphamide. CHO cells transduced with wild-type human AGT (CHO(AGT)) and pcDNA3 (CHOpcDNA3) were treated with activated cyclophosphamide derivatives, 4-hydroperoxycyclophosphamide (4-HC), 4-hydroperoxydidechlorocyclophosphamide (4-HDC), a progenitor of acrolein, and phosphoramide mustard (PM). The results show that CHO(AGT) is 7- or 20-fold less sensitive to the toxic effects of 30 microM 4-HC or 300 microM 4-HDC, respectively, than CHOpcDNA3 cells as measured by cell survival using a colony-forming assay. CHO(AGT) cells treated with 20 microM 4-HC or 200 microM 4-HDC produced 4- or 7-fold lower mutation frequency as measured at the HPRT locus than CHOpcDNA3 cells treated with the same dose of drugs. At 30 microM acrolein, the cell survival for CHO(AGT) was 30% compared with 18.7% for CHOpcDNA3. The mutation frequency of acrolein at the same dose was 57 mutants/10(6) cells in CHOpcDNA3 compared with no mutants in CHO(AGT). In contrast, CHO(AGT) and CHOpcDNA3 cells treated with PM had similar survival curves and exhibited no difference in mutation frequency. The present study demonstrates that AGT plays an important role in protecting against the toxic and mutagenic effect of cyclophosphamide and suggests that acrolein, not PM, is responsible for generating the toxic and mutagenic lesion(s) protected by the AGT protein.

Alkyl and Aryl Transferases↗

Body distribution in mice of intravenously injected camptothecin solid lipid nanoparticles and targeting effect on brain.

The objective of the present study was to investigate the specific drug targeting of anticarcinogenic drugs, such as camptothecin (CA), after intravenous (i.v.) injection by incorporation into solid lipid nanoparticles (SLN). A CA loaded SLN suspension consisted of 0.1% (w/w) camptothecin, 2.0% (w/w) stearic acid, 1.5% (w/w) soybean lecithin and 0.5% (w/w) polyoxyethylene-polyoxypropylene copolymer (Poloxamer 188) was prepared by high pressure homogenization. In vitro drug release was investigated in pH 7.4 phosphate-buffered saline at 37 degrees C. The concentrations of camptothecin in various organs were determined using reversed-phase high-performance liquid chromatography with a fluorescence detector after i.v. administration of CA-SLN and a camptothecin control solution (CA-Sol). The results showed that the CA-SLN had an average diameter 196.8 nm with a Zeta potential of -69.3 mV and in vitro drug release was achieved for up to a week. In tested organs, the AUC/dose and the mean residence times (MRT) of CA-SLN were much higher than those of CA-Sol, especially in brain, heart and reticuloendothelial cells containing organs. The brain AUC ratio of CA-SLN to CA-Sol was the highest among the tested organs. These results indicate that SLN are a promising sustained release and drug targeting system for lipophilic antitumour drugs, and may also allow a reduction in dosage and a decrease in systemic toxicity.

Animals↗