Biomedical subjects

Li Zhang

Publications and source records attributed to Li Zhang.

At least 523 records · Page 29Linked to original sources

PubMed2004

[Effect of epidermal growth factor receptor-selective tyrosine kinase inhibitor gefitinib on nasopharyngeal carcinoma xenografts].

BACKGROUND & OBJECTIVE: Gefitinib,an anilinoquinazoline,is an orally active,selective epidermal growth factor receptor(EGFR) tyrosine kinase inhibitor,which has been approved for the treatment of advanced non-small cell lung cancer. We have found that the proliferation of nasopharyngeal carcinoma (NPC) cell lines CNE1,CNE2,and SUNE1 was inhibited by Gefitinib. The present study was designed to evaluate the effect of Gefitinib alone or in combination with cisplatin (DDP) on NPC CNE2 xenografts. METHODS: Exponentially growing CNE2 cells were prepared into cell suspension (1 x 10(7) cells/ml). Suspension of 200 mul of CNE2 cells was injected s.c. into the right flank area of the mice. After 7 days,when well-established tumors of 100-200 mm(3) were detected,mice were randomized into five groups: control group,Gefitinib (100 mg/kg) group,Gefitinib (200 mg/kg) group,DDP group,and Gefitinib (100 mg/kg) plus DDP group. Gefitinib was administered by oral gavage on days 1-5 of each week for 4 weeks. DDP was administered i.p. once a week for 4 weeks. Tumor volume was determined by direct measurement with caliper and calculated by the formula 1/2x(large diameter)x(small diameter)(2). The mice were sacrificed at two days after the treatment ended; tumor masses were removed and weighed. The tumor inhibition rates were calculated. The student's test was used to evaluated the statistical significance of the results. RESULTS: Growth curves showed that tumor masses of control group grew more rapidly than ones of every treatment group. The average tumor volume was significantly smaller in Gefitinib (200 mg/kg) group than in control group (P=0.02). The average tumor volume had no significant difference between Gefitinib (100 mg/kg) group and control group. The average tumor volume of DDP or Gefitinib (100 mg/kg) plus DDP group was smaller than that of control group(P=0.007 and 0.001,respectively). The average tumor volume had no significant difference between DDP and Gefitinib (100 mg/kg) in combination with DDP group. The tumor inhibition rates of Gefitinib (100 mg/kg) group,Gefitinib (200 mg/kg) group,DDP group,and Gefitinib (100 mg/kg) plus DDP group were 26.3%, 30.6%, 45.7% and 54.8%,respectively. The average tumor weight after treatment had no significant difference between Gefitinib (100 mg/kg) group and control group. The average tumor weights of Gefitinib (200 mg/kg) group,DDP group,Gefitinib (100 mg/kg) plus DDP group were all smaller than that of control group. The average tumor weight had no significant difference between DDP group and Gefitinib (100 mg/kg) plus DDP group. CONCLUSION: Gefitinib could inhibit the growth of NPC CNE2 xenografts. Gefitinib in combination with DDP did not significantly potentiate the effect of DDP on NPC CNE2 xenografts.

Animals↗

PubMed2004

[Gemcitabine plus cisplatin versus gemcitabine plus vinorelbine in treatment of advanced non-small cell lung cancer (NSCLC)].

BACKGROUND & OBJECTIVE: Although platin-based chemotherapy has become a standard treatment for non-small cell lung cancer (NSCLC), its severe toxicities limit clinical application, and a new replacement is required. The study was to evaluate the efficacy, survival rate and toxicity between the combination of gemcitabine and cisplatin (GP arm) and the combination of gemcitabine and vinorelbine (GN arm) in the treatment of advanced NSCLC. METHODS: Eighty-two patients with locally advanced or metastatic NSCLC were enrolled into this study. 42 patients and 40 patients were randomized into GP group and GN group respectively. The patients' characteristics were similar between the two groups. They were treated with gemcitabine (1 000 mg/m(2) d(1), d(8)) plus cisplatin (80 mg/m(2), d(1)) in GP group, or gemcitabine plus vinorelbine (25 mg/m(2) d(1), d(8)) in GN group. The chemotherapy was repeated every 3 weeks as a cycle. Every patient was treated two cycles at least. RESULTS: An objective response rate of 28.6% was observed in GP arm versus 25% in GN arm (P=0.346). The 1-year survival rate was 64% in GP arm and 66% in GN arm. The median survival time was 9.87 months for GN arm and 8.78 months for GP arm. Nausea and vomiting were the major dose-limiting toxicity. The incidence of grade III/IV nausea and vomiting was significantly higher in the GP arm than in the GN arm (P=0.000). The Leukopenia incidence was similar in two groups (P=0.130). CONCLUSION: The efficacy of GN regimen (platinum-free regimen) was similar to that of GP regimen, but the toxicity of GN regimen is lighter than that of GP regimen.

Adenocarcinoma↗

PubMed2004

[Phase III randomized clinical trial of intratumoral injection of E1B gene-deleted adenovirus (H101) combined with cisplatin-based chemotherapy in treating squamous cell cancer of head and neck or esophagus].

BACKGROUND & OBJECTIVE: H101 is an E1B-55 kDa gene-deleted replication-selective adenovirus, which showed a significant antitumor activity. This study was to compare effects and toxicities of intratumoral H101 injection combined with cisplatin plus 5-fluorouracil (PF) regimen or adriamycin plus 5-fluorouracil (AF) regimen versus PF or AF regimen alone in treating patients with head and neck or esophagus squamous cell cancer. METHODS: A total of 160 patients were recruited. PF regimen (cisplatin 20 mg/m(2) ivgtt, qd x 5d; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients have no history of PF chemotherapy,or sensitive to PF chemotherapy,while AF regimen (adriamycin 50 mg/m(2) iv,d1; 5-fluorouracil 500 mg/m(2) ivgtt, qd x 5d) was administered to patients didn't response to PF regimen. All patients were randomized to either receive intratumoral H101 injection (5.0 x 10(11)-1.5 x 10(12) VP/day for 5 consecutive days every 3 weeks) or not. Treatment repeated every 3 weeks,all patients have to receive at least 2 cycles of chemotherapy. RESULTS: Among 123 accordant patients,overall response rate of PF plus H101 group (group A1) was 78.8% (41/52),of PF alone group (group B1) was 39.6% (21/53),of AF plus H101 group (group A2) was 50.0% (7/14),of AF alone group (group B2) was 50.0% (2/4). Differences of response rates between group A1 and group B1,between group A1+A2 and group B1+B2 were significant (P=0.000). Main side effects were fever (45.7%), injection site reaction (28.3%),and influenza-like symptoms (9.8%). CONCLUSION: Intratumoral H101 injection showed a distinct efficacy in patients with squamous cell cancer of head and neck or esophagus,and was relatively safe.

Adenoviridae↗

PubMed2004

[Clinical analysis of rituximab combined with chemotherapy in treating aggressive B-cell non-Hodgkin's lymphoma].

BACKGROUND & OBJECTIVE: The efficacy of standard treatment, including cyclophosphamide, adriamycin, vincristine, and prednisone (CHOP regimen), for patients with aggressive B-cell non-Hodgkin's lymphoma (B-NHL) is still unsatisfactory. Rituximab, a chimeric monoclonal antibody against B-cell antigen CD20, has therapeutic activity in B-NHL. This study was to determine efficacy and safety of the combination of rituximab and chemotherapy in treating Chinese patients with aggressive B-NHL, and to analyze influence factors on the response. METHODS: Records of 75 patients with aggressive B-NHL,received infusions of 375 mg/m(2) of rituximab combined with or without chemotherapy in our center,have been retrospectively analyzed. Influence of age, clinical stage, serum level of lactate dehydrogenase (LDH), international prognostic index (IPI) score, and bulk disease on response were evaluated. RESULTS: Response rate of rituximab alone group was 83.3% (5/6)with complete response (CR) rate of 66.7% (4/6). In 43 naive patients, the combination of rituximab and chemotherapy achieved an overall response rate (ORR) of 90.7% with CR rate of 67.4%; while in 26 recurrent or relapsed patients, the combination therapy achieved an ORR of 79.2% with CR rate of 29.2% (7/26), and partial response (PR) rate of 50.0% (13/26), 6 patients had a progressive disease (20.8%). Efficacy of immunochemotherapy was poor on patients with advanced disease(P=0.046), increased serum level of LDH (P=0.024), recurrence or relapse (P=0.009), and bulk disease (P=0.013). All patients can tolerate the treatment. No treatment-related death occurred. CONCLUSION: The addition of rituximab to the chemotherapy regimen increases the response rate and CR rate in Chinese patients with aggressive B-NHL, without a clinically significant increase in toxicity. Patients with advanced disease, higher serum level of LDH, recurrence or relapse, and bulk disease had a poor response.

Adult↗

PubMed2004

[Efficacy of modified BFM-90 regimen on children and adolescents with T cell lymphoblastic lymphoma: a report of 20 cases].

BACKGROUND & OBJECTIVE: T-cell lymphoblastic lymphoma in childhood and adolescence is an aggressive malignant disease with higher mortality. BFM-90 regimen for lymphoblastic lymphoma is one of the most effective regimens. This study was designed to evaluate efficacy and toxicities of modified BFM-90 regimen on Chinese children and adolescents with lymphoblastic lymphoma. METHODS: A total of 20 naive children and adolescents with T cell lymphoblastic lymphoma were enrolled, 7 in stage III, and 13 in stage IV. Eighteen (90%) patients suffered from mediastinal mass with superior vena obstruction syndrome,10(50%) suffered from marrow invasion. All patients received modified BFM-90 regimen consisting of induction, consolidation and central nervous system prophylaxis, reinduced alleviation, and maintenance therapy. Total treatment duration was 2 years. Kaplan-Meier method was used to evaluate long-term survival rate. RESULTS: After induction remission,18 patients (90%) achieved complete remission (CR), 1 had partial remission (PR), and 1 had progressive disease (PD), overall response rate was 95%. The 2 patients with PR or PD died of tumor progression. Of 2 patients at CR1 received APBSC, 1 relapsed after transplantation, but achieved CR and survived after salvage chemotherapy;1 survived all along. Of other patients achieved CR, 5 relapsed; of these 5 patients, 1 survived after allogeneic stem cell transplantation, 1 survived after autologous stem cell transplantation, 3 died of progressive disease after chemotherapy. The overall 3-year survival rate was 74%. All patients had myelosuppression of grade III-IV during the induction and reinduction phases, but the hemotologic toxicity was manageable. CONCLUSIONS: Modified BFM-90 regimen is feasible for Chinese children and adolescent patients with lymphoblastic lymphoma, and may improve survival rate of these patients. The major side effect is myelosuppression, but it is manageable.

Adolescent↗

PubMed2004

[Discordance of estrogen receptor (ER), progestin receptor (PR), and HER-2 receptor statuses between primary and metastatic focuses of breast cancer].

BACKGROUND & OBJECTIVE: Hormone and Herceptin therapy for metastatic breast cancer is commonly based on expression of estrogen receptor (ER) and progestin receptor (PR), and over-expression of HER-2 in primary breast cancer, but studies comparing receptor statuses in primary and metastatic focuses of the same patient are limited. This study was designed to investigate discordance of ER, PR,and HER-2 statuses between primary and metastatic focuses of breast cancer. METHODS: Immunohistochemistry assay was used to detect expression of ER, PR, and HER-2 receptor in primary and metastatic focuses of 65 cases of breast cancer. RESULTS: Positive rate of ER in primary focuses was 56.9% (37/65), significantly higher than that in metastatic focuses (33.8%, 22/65)(P< 0.01); while positive rates of PR and HER-2 receptor have no significant difference between primary and metastatic focuses. Total discordance rates of ER, PR, and HER-2 were 35.4%, 29.2%, and 16.9%, respectively. CONCLUSION: Difference in expression level of ER between primary and metastatic focuses of breast cancer was significant, while differences of expression of PR, and HER-2 wasn't significant, but we still should think highly of the expression differences of ER,PR,and HER-2 in our clinical practices.

Adult↗

PubMed2004

[The preparation and in vitro release test of sustained release delivery gutta-percha point containing metronidazole].

PURPOSE: To develop sustained release delivery gutta-percha point containing metronidazole (SRDGM) for root canal disinfection, and determine the drug concentration in vitro and the time that the device maintains the effective drug concentration. METHODS: The gutta-percha was selected as the carrier and adsorbed metronidazole etc. The point was coated with mixation of ployethylene glycol and acetate fibre to prepare the groups of SRDGM.The group that released the longest period of the effective drug was selected for the following study. Eight teeth were selected, the SRDGM was used to disinfect the root canal. The adsorption was measured for 24 hours and 10 days. RESULTS: The SRDGM contained metronidazole 2013 microg, it could release 68.24% of the total drug in 24 hours in vitro. The effective metronidazole concentration released lasted more than 10 days. On the 10th day, there was also 33.13 microg/ml metronidazole released which was more than minitory inhibitory concentration of metronidazole. CONCLUSIONS: SRDGM could carry the metronidazole and control the release rate. It could maintain the effective drug concentration for a long time (>10 days) in root canal.

Anti-Infective Agents↗

PubMed2004

[Effectiveness for medicine wastewater treatment biotechnology].

The effectiveness for the XZEH medicine wastewater treatment biotechnology was conducted. The results show that it needs to increase 28% of the aeration tank volume in order to meet the effluent COD concentration at the first grade wastewater discharge standard level in China. If the engineered strain Xhhh and informatics software (Ebis) were used, the specific degradation rate of Xhhh strain may be higher 128% than that of the natural bacterium XZ strain and the aeration tank needed may be 51% decreased. This should be a potential technical patch for improving the biotechnological effectiveness and making the effluent at the first grade discharge standard.

Biodegradation, Environmental↗

PubMed2004

[Association of 7alpha-hydroxylase gene polymorphism with levels of plasma lipids].

To study the distribution of Eco31I restriction polymorphism in nucleotide -204 of 7alpha-hydroxylase gene(CYP7A1)in Sichuan Han population of China and association of the polymorphism with coronary heart disease(CHD),CYP7A1 genotyping was performed by using PCR-RFLP approach in 183 CHD patients and 101 control subjects. 7alpha-hydroxylase gene allele frequencies of C,A were 0.840 and 0.160 in CHD group and 0.822 and 0.178 in control group,respectively. There was no significant difference in frequencies of allele and genotypes in A-204C polymorphism between CHD group and control group (P>0.05). However, in CHD patients there was significant difference in total cholesterol (TC) levels among CC,CA and AA genotypes (P<0.05) ,and the levels of high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) in CHD patients with AA genotype were lower than those in CHD patients with CC and CA genotypes(P<0.05). In control group there was significant difference in TC levels between CC and CA genotypes (P<0.05) . The frequencies of C,A alleles at A-204C polymorphic site were significantly different from those reported in white people(P<0.05). The results indicating that no direct association was found between the A-204C polymorphism and CHD,but there was significant correlation between this polymorphism and the levels of TC ,and there was significant correlation in CHD patient group between this polymorphism and levels of HDL-C and LDL-C.

Adult↗

PubMed2004

[Progress in application of laser scanning confocal microscope to studies on dendritic cells].

The defensive function of immune response in vivo is very important. Antigen presenting cells (APC) is the hinge in starting specific immune response. Dendritic cells (DC) are the most potent APC, which participate in double-regulating the immune response. Laser scanning confocal microscope (LSCM) becomes a powerful tool in the fields of basic medicine and clinical medicine with its high resolving power, high sensitivity, optical section, three-dimensional reconstruction and dynamic analysis. And it makes the study on DC more thoroughly and deeper. In this paper, we review the recent progress in the applications of LSCM to studies on the morphology, immunofluorescence localization and the functional analysis of dendritic cells.

Dendritic Cells↗

PubMed2004

[In vitro effect of pulse Nd: YAG laser plus NaF on ultrastructure and fluoride distribution of enamel].

OBJECTIVE: To investigate the effect of pulse Nd: YAG laser combined with NaF on caries resistance of human enamel in vitro. METHODS: 24 caries-free, constant premolares were cut into enamel mass. Surface ultrastructure and fluoride distribution of enamel in laser-NaF treated group, laser treated group, NaF treated group and control group were observed by scanning electron microscope (SEM) and electron probe microanalyzer. RESULTS: (1) SEM observation: In laser-NaF treated group, the smear layer was almost removed, the enamel surface showed partially melted-like and bubble-like appearance, diffuse white-small particles distributed on enamel surface, and melted position, microcrack and microhole appeared whitely blocking-reflection. (2) Electron probe microanalyzer analysis: In enamel samples, the highest average Ci of F- and the hightest depth which F- entered in enamel were recorded in the laser-NaF treated group. The average Ci of F- in laser-NaF treated group was significantly increased compared with that in NaF-treated group or laser-treated group or control group (P < 0.001). CONCLUSION: The pulsed Nd:YAG laser combined with sodium fluoride could make the enamel surface partially melt, change the structure of the crystal, enhance the absorption of fluoride, and clear smear layer. This technology may resist the caries.

Dental Enamel↗

PubMed2004

[Palmitic acid induces apoptosis in human hepatoma cell line, HepG2 cells].

OBJECTIVE: To investigate the effects of palmitic acid (PA) on human hepatocytes and its mechanism. METHODS: We administered a mimic hyperlipidemia condition of 0.2-0.4 mmol/L PA to human hepatoma cell line, HepG2 cells. Cell viability was determined by Trypan blue staining. Cell cycle and early apoptosis were determined by propidium iodide and/or Annexin V staining, and the levels of Bcl-2 and Bax were analyzed by flow cytometry. RESULTS: An inhibition of cell growth was observed at a dose- and time-dependent manner in HepG2 cells after the treatment of PA. An apoptosis with appearance of sub-G1 fraction determined by cell cycle analysis significantly increased after the treatment of PA for 4 days. Bcl-2 level slightly decreased; in contrast, Bax level elevated markedly, which resulted in a significant decrease of Bcl-2/Bax ratio. CONCLUSION: PA may induce cell death on hepatocytes via mitochondria-mediated apoptosis by reducing the level of Bcl-2/Bax.

Apoptosis↗

PubMed2004

[Vocal function of benign vocal fold lesions and outcomes assessment after CO2 phonomicrosurgery].

OBJECTIVE: To investigate the nature of benign vocal fold lesions and its outcomes assessment after CO2 phonomicrosurgery. METHOD: Vocal function of 292 cases of benign vocal fold lesions (vocal nodules, Reinke's edema, vocal fold cyst, vocal fold polyp and chronic laryngitis) and their outcomes assessment after CO2 phonomicrosurgery were evaluated. Vocal function was examined by acoustic analysis, aerodynamic analysis and videostroboscopic examination. RESULT: Young women with professional occupation were predominant in vocal nodules and the higher age showered in Reinke's edema. Vocal function of vocal nodules and vocal fold polyps had improved distinctly only one month after operation. For Reinke's edema, vocal function can recover three months after operation steadily. Although vocal function of vocal cyst also had improved distinctly only one month after operation, there was depression instead of cyst, the outcome of vocal quality would be affected by that. Vocal function of chronic laryngitis did not change so much after operation. However, ventricular dysphonia did not changed any more. CONCLUSION: Benign vocal fold lesion was located in the cover layer of the vocal fold. According to different lesions, the degree of voice disorder were differently. CO2 phonomicrosurgery can control the range of the operation and protect the cover layers delicately. Vocal function can recover three months after operation steadily. The localized lesions recovered only one month after operation. As the supraglottal hyperfunction remained post-operation, it is regarded as incorrect vocalization and effect on the prognosis.

Female↗

PubMed2004

[Differential expression of a homing-related molecule repertoire among umbilical cord blood, mobilized peripheral blood and bone marrow-derived hematopoietic stem/progenitor cells].

OBJECTIVE: To compare the expression profiles of a set of homing-related molecules (HRM) repertoire expressed on hematopoietic stem/progenitor cells (HS/PC) from different sources. METHOD: The expression levels of HRM on HS/PC from umbilical cord blood (UCB), mobilized peripheral blood (mPB) and bone marrow (BM) were assessed using a highly sensitive 4-color flow cytometric analysis. RESULTS: UCB-derived CD34(bright) cells, as well as mPB- and BM-derived CD34(bright) cells strongly expressed CD44, CD11a, CD18, CD62L, CD31 and CD49d. On the other hand, significantly lower expressions of CD49e, CD49f, CXCR-4 and CD54 on UCB-derived CD34(bright) and CD34(bright)CD38(-) cells, compared with those on mPB- and BM-derived CD34(bright) and CD34(bright)CD38(-) cells, were observed. None of UCB-, mPB- and BM-derived CD34(bright) cells expressed other chemokine receptors, including CCR-1, CCR-2, CCR-3, CCR-5, CXCR-1, CXCR-2, CXCR-3 and CXCR-5. Another striking finding was that only mPB-derived CD34(bright) cells expressed significant levels of both the matrix metalloproteinases MMP-2 \[(11.4 +/- 4.9)%\] and MMP-9 \[(27.6 +/- 7.8)%\]. CONCLUSION: HS/PC from UCB have some defects of expression of HRM repertoire, which might partly explain the cause(s) of delayed hematopoietic reconstitution after UCB transplant.

Antigens, CD34↗

PubMed2004

[Growth inhibitory effects of recombinant granzyme B containing different N-terminal translocating peptides].

Translocating protein and translocating peptides have therapeutic potential against tumors by exposing the cytotoxic domains of toxic proteins to the cell cytosol. The aim of this study is to investigate the effect of N-terminally fused PE translocating peptides on granzyme B (GrBa) activity. PE II-GrBa fusion protein genes were constructed by replacing N-terminal signal and acidic dipeptide sequence of human granzyme B gene with two truncated translocating sequences of Pseudomonas exotoxin A (PE II aa 280-364/358) by recombinant PCR, and then cloned into pIND inducible expression vector. The resulting pIND-PE II-GrBa expression vectors were co-transfected with assistant plasmid pVgRXR into HeLa cells through lipofectamine, followed by selection on G418 and zeocin. The resistant cells were collected and induced with ponasterone A. Western blot analysis demonstrated that ponasterone A induction caused the expression of PE II-GrBa fusion proteins, and indirect immunofluorescence detected giant sized multinucleated cells, suggesting cytoskeletal and mitotic abnormalities as reported in our previous studies. Western blot, enzymatic activity assay and cell counting analysis indicated that two types of PE II-GrBa fusion proteins were capable of cleaving both endogenous and exogenous substrates of granzyme B, and inhibiting the growth of cells. The PE II (aa 280-358)-GrBa was shown to have higher serine protease activity and stronger growth inhibitory effect. Such inhibition was presumably associated with G2 arrest as determined by cell cycle analysis. These data prove that PE II-GrBa fusion proteins have cell inhibitory effect similar to GrBa, and that the shorter PE-derived peptide exerts less influence on GrBa activity. This study helps to optimize the construction of recombinant protein comprising translocating peptides and cytotoxic molecules for tumor cell killing.

ADP Ribose Transferases↗

PubMed2004

The role and mechanisms of double negative regulatory T cells in the suppression of immune responses.

Accumulating evidence has demonstrated that regulatory T (Treg) cells play an important role in the maintenance of immunologic self-tolerance and in down-regulating various immune responses. Thus, there has recently been an increasing interest in studying the biology of Treg cells as well as their potential application in treating immune diseases. Many types of Treg cell subsets have been reported in a variety of disease models. Among these subsets, alpha beta TCR(+)CD3(+)CD4(-)CD8(-) double negative (DN) Treg cells are defined by their capability of inhibiting immune responses via directly killing effector T cells in an antigen specific fashion. Furthermore, DN Treg cells have been shown to develop regulatory activity after encountering specific antigens, partially mediated by the acquisition of MHC-peptide complexes from antigen presenting cells (APCs). The presentation of acquired alloantigens on DN T cells allows for the specific interaction between DN Treg cells and alloantigen reactive effector T cells. Once the DN Treg and target cells have come into contact, killing is then mediated by Fas/Fas-ligand interactions, and perhaps through other unidentified pathways. Further characterization of the functions, molecular expression and mechanisms of activation of DN Treg cells will help in the development of novel therapies to induce antigen specific tolerance to self and foreign antigens.

Animals↗

PubMed2003

Direct activation by dopamine of recombinant human 5-HT1A receptors: comparison with human 5-HT2C and 5-HT3 receptors.

The effects of dopamine (DA) on the function of human 5-HT1A receptors expressed in Xenopus oocytes and CHO-K1 cells were investigated. In addition, the effect of DA on the activation of three different types of human 5-HT receptors (5-HT1A, 5-HT2C, and 5-HT3) were studied comparatively in Xenopus oocyte expression system. Application of 5-HT or DA in oocytes coexpressing 5-HT1A receptors and G-protein-activated inwardly rectifying potassium channels (GIRK1) induced inward currents with respective EC50 values of 4.2 nM and 11.2 microM. Maximal responses induced by DA were 85 +/- 4% of maximal 5-HT currents and DA responses were blocked by the specific 5-HT1A antagonist, WAY-100635 (50 nM). In CHO-K1 cells expressing 5-HT1A receptors, 5-HT and DA inhibited the specific binding of selective antagonist [3H]-8-OH-DPAT with IC50 values of 10.2 nM and 1.4 microM, and both 5-HT and DA inhibited the forskolin-induced accumulation of cAMP. In oocytes expressing 5-HT2C receptors, 5-HT and DA induced inward currents with respective EC50 values of 6.2 nM and 67.7 microM. Magnitudes of maximal DA induced currents were 42 +/- 3% of maximal 5-HT responses and blocked by the 5-HT2 antagonist, piperazine (1 microM). In oocytes expressing 5-HT3 receptors, 5-HT and DA induced fast inward currents with respective EC50 values of 2.1 microM and 266.3 microM. Maximal DA induced currents were 37 +/- 3% of maximal 5-HT responses and blocked the specific 5-HT3 antagonist LY-278584 (0.1 microM). Comparison of the potencies and efficacies of 5-HT and DA indicated that the relative potency of DA increased in the order of 5-HT3 > 5-HT1A > 5-HT2C, and relative efficacy increased in the order of 5-HT1A > 5-HT2C > 5-HT3. These results suggest that although DA activates different subtypes of human 5-HT receptors directly, the potency and efficacy of the binding site varies significantly among different receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2003

Recipient T cells mediate reperfusion injury after lung transplantation in the rat.

Leukocytes have been implicated in ischemia-reperfusion (IR) injury of the lung, but the individual role of T cells has not been explored. Recent evidence in mice suggests that T cells may play a role in IR injury. Using a syngeneic (Lewis to Lewis) rat lung transplant model, we observed that recipient CD4(+) T cells infiltrated lung grafts within 1 h of reperfusion and up-regulated the expression of CD25 over the ensuing 12 h. Nude rats (rnu/rnu) and heterozygous rats (rnu/+) were used to determine the role of T cells in IR injury. No significant difference in lung function was observed between nude and heterozygous recipient rats after 2 h of reperfusion. However, after 12 h of reperfusion, recipient nude rats had significantly higher oxygenation and lower peak airway pressure than recipient heterozygous rats. This was associated with significantly lower levels of IFN-gamma in transplanted lung tissue of recipient nude rats. Reconstitution of recipient nude rats with T cells from heterozygous rats restored IR injury after 12 h of reperfusion. The effect of T cells was independent of neutrophil recruitment and activation in the transplanted lung. These results demonstrate that recipient T cells are activated and mediate IR injury during lung transplantation in rats.

Adoptive Transfer↗