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Biomedical subjects

Qiang Chen

Publications and source records attributed to Qiang Chen.

At least 73 records · Page 4Linked to original sources

Endomorphins, endogenous opioid peptides, induce apoptosis in human leukemia HL-60 cells.

Opioids play a role in the apoptosis machinery. We studied the induction of apoptosis in endomorphin 1 (EM1) and endomorphin 2 (EM2), 2 newly isolated endogenous mu-opioid receptor agonists. These endomorphins were able to reduce the viability of cultured HL-60 cells. The antiproliferative properties of endomorphins appeared to be attributable to their induction of apoptotic cell death as determined by ultrastructural change, internucleosomal DNA fragmentation, and increased proportion of the subdiploid cell population. To elucidate molecular events in the apoptosis, protein expressions of Bcl-2, Bax, Fas, and FasL were measured by western blotting using specific antibodies in HL-60 cells. The level of Bcl-2 indicated down-regulation, but the Bax, Fas, and FasL expression showed up-regulation as compared with the untreated control cells. These data support the idea that endomorphins induce apoptosis in HL-60 cells through the activation of the Bcl-2-Bax and the Fas-FasL pathway. We suggest that endomorphins may play an important role in the regulation of tumor cell death.

Apoptosis↗

[Effect of liuwei dihuang pill on erythrocyte aldose reductase activity in early diabetic nephropathy patients].

OBJECTIVE: To observe the inhibitory effect of Liuwei Dihuang Pill (LDP) on erythrocyte aldose reductase (EAR) activity in early diabetic nephropathy (DN) patients and to explore the clinical significance of applying LDP in prevention and treatment of DN as an inhibitor of aldose reductase. METHODS: Seventy-two patients diagnosed as early DN with TCM Syndrome of both Qi-yin deficiency were randomly divided into the control group (31 patients) treated by conventional therapy (orally taken Gliquidone or injection of insulin) and the treated group (41 patients) treated by conventional therapy plus LDP for 3 months as one therapeutic course. Changes of symptoms, physical signs, fasting blood glucose (FBG), blood glucose 2 hrs post breakfast (2hPBG), blood total cholesterol (TC), triglyceride (TG), EAR activity, urinary albumin excretion rate (UAER), blood and urinary beta2-microglobulin (beta2-MG) in patients before and after treatment were observed. RESULTS: LDP could improve the symptoms and signs of patients with DN, it could significantly inhibit EAR activity, to make it significantly lower than that in the control group (P < 0.05), and the levels of UAER, beta2-MG in blood and urine in the treated group after treatment were obviously lower than those in the control group (P < 0.05), and LDP showed no apparent effect on blood glucose, lipids and mean arterial pressure (P < 0.05). CONCLUSION: LDP could obviously inhibit the activity of EAR in patients with early DN, improve various indexes of DN, so as to be helpful for its treatment.

Adult↗

[The reverse forearm flap pedicled with the ulnar branch of the ulnar artery].

OBJECTIVE: To introduce a new flap for the repair of soft tissue defects in the hand. METHODS: The distally pedicled ulnar flap is based on the ascending branch of the upper-wrist cutaneous branch of the ulnar artery. The retrograde flow is ensured by the dorsal carpal arch via the descending branch. RESULTS: From 2000 to 2003, the flap was used to treat 8 cases of hand defects, including 3 dorsal defects, 2 palmar defects and 3 the first web defects. All flaps survived and the appearance was satisfactory. CONCLUSIONS: The reverse forearm flap pedicled with the ulnar branch of the ulnar artery provides a long vascular pedicle. The donor site scar is aesthetically acceptable.

Adult↗

Endomorphins, endogenous opioid peptides, provide antioxidant defense in the brain against free radical-induced damage.

Oxidative stress has been considered to be a major cause of cellular injuries in a variety of chronic health problems, such as carcinogenesis and neurodegenerative disorders. The brain appears to be more susceptible to oxidative damage than other organs. Therefore, the existence of antioxidants may be essential in brain protective systems. The antioxidative and free radical scavenging effects of endomorphin 1 (EM1) and endomorphin 2 (EM2), endogenous opioid peptides in the brain, have been investigated in vitro. The oxidative damage was initiated by a water-soluble initiator 2,2'-azobis(2-amidinopropane hydrocholoride) (AAPH) and hydrogen peroxide (H2O2). The linoleic acid peroxidation, DNA and protein damage were monitored by formation of hydroperoxides, by plasmid pBR 322 DNA nicking assay and single-cell alkaline electrophoresis, and by SDS-polyacrylamide gel electrophoresis. Endomorphins can inhibit lipid peroxidation, DNA strand breakage, and protein fragmentation induced by free radical. Endomorphins also reacted with galvinoxyl radicals in homogeneous solution, and the pseudo-first-order rate constants were determined spectrophotometrically by following the disappearance of galvinoxyl radicals. In all assay systems, EM1 was more potent than EM2 and GSH, a major intracellular water-soluble antioxidant. We propose that endomorphins are one of the protective systems against free radical-induced damage in the brain.

Amidines↗

Protein preparation, crystallization and preliminary X-ray crystallographic studies of a thermostable hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis.

Native and His-tagged mutant (L160I) hypoxanthine-guanine phosphoribosyltransferase (HGPRT) from Thermoanaerobacter tengcongensis were cloned, expressed in Escherichia coli and purified. Both proteins were crystallized with polyethylene glycol as the main precipitant at 293 K using the hanging-drop vapour-diffusion method. The crystal of native HGPRT belongs to space group C222(1), with unit-cell parameters a = 65.77, b = 137.73, c = 95.27 A, and diffracted to 2.2 A resolution on an in-house X-ray generator. The crystal of the His-tagged mutant (L160I) HGPRT belongs to the space group I222, with unit-cell parameters a = 52.21, b = 88.36, c = 93.03 A, and diffracted to 1.7 A resolution in-house.

Bacillaceae↗

Cloning, purification, and characterization of thermostable hypoxanthine-guanine phosphoribosyltransferase from Thermoanaerobacter tengcongensis.

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT, EC 2.4.2.8) from a newly characterized thermophile Thermoanaerobacter tengcongensis was expressed in Escherichia coli and purified. Analytical gel filtration suggested that the enzyme exist as a homotetramer in solution. The optimal pH for the forward reaction was found to be 8.0 and the optimal temperature 70 degrees C. The steady-state kinetic characteristics suggest that hypoxanthine is the most effective substrate. This enzyme showed a half-life of 75min at 50 degrees C and no apparent loss of activity after 3 months at 4 degrees C.

Amino Acid Sequence↗

[Oxaliplatin in combination with LV5FU2 for advanced/metastatic gastric cancer-a multicenter study].

OBJECTIVE: To evaluate the effects and safety of OXA-LV5FU2 regimen for patients with advanced/metastatic gastric cancer. METHODS: OXA 100 mg/m(2) i.v. 2hr d1, LV200 mg/m(2) i.v. 2hr followed by 5-Fu 400 mg/m(2) i.v. bolus and 5-Fu 600 mg/m(2) i.v. 22hr d1, 2 were given, and repeated every 2 weeks. Efficacy was evaluated at 4 cycles (8 weeks). RESULTS: Forty three patients have been entered into the study. Patients with primary tumor resected or non-resected were 17 and 26. The evaluable lesions were 26 primary lesions, 22 lymph node metastases, 12 liver metastases, 1 pancreas metastasis and 2 soft tissue metastases. Forty patients were evaluable for clinical response. Four patients achieved CR (10.0%), 13 PR (32.5%), ORR 42.5% (95% CI 27.2 - 57.8), 17 SD (42.5%) and 6 PD (15.0%). Overall response rate (ORR) for chemotherapy naive (1(st) line) and pretreated (2(nd) line) patients were 50.0% (14/28) and 25.0% (3/12), respectively. Median time to progress (mTTP) was 5 months and median overall survival (mOS) was 8 months. Forty-three patients were evaluable for toxicity, with Grade 3, 4 WHO toxicity of neutropenia in 7 patients (16.3%), thrombocytopenia in 3 patients (7.0%), nausea/vomiting in 1 patient (2.3%). There were no Grade 3, 4 peripheral neuropathy toxicity or any deaths during treatment. CONCLUSION: OXA-LV5FU2 is a high response regimen for advanced gastric cancer with mild toxicity, which can be practiced safely.

Adult↗

[Multi-center prospective randomized trial on paclitaxel liposome and traditional taxol in the treatment of breast cancer and non-small-cell lung cancer].

OBJECTIVE: To analyze the effects and side effects of paclitaxel liposome formula on breast cancer and non-small cell lung cancer, compared with traditional taxol. METHODS: 129 patients from multicenters were prospectively randomized into a test group, given paclitaxel liposome at 135 mg/m(2) each session, and a control group, given traditional taxol at 135 mg/m(2) each session. Both groups received these regimens combined with ADM or DDP for two cycles (3 weeks per cycle). RESULTS: Of 129 cases, 128 were eligible for the analysis of side effects and 126 for the overall response rate. The complete remission rate, partial remission rate and overall response rate were 1.6%, 33.3%, 34.9% in the test group and 6.3%, 22.2%, 28.6% in the control group. There was no significant difference between the two groups. Though there was no significant difference in hematological toxicity between the two groups, the toxicity from the mixed solvent of polyethoxylated castor oil and ethanol was significantly lower in the test group than that in the control group. CONCLUSION: Paclitaxel liposome combined with ADM or DDP in the treatment of advanced breast cancer and non-small-cell lung cancer, being similarly effective as taxol, can significantly lower the incidence of serious hypersensitive reactions.

Adult↗

Therapeutic embolization of cavernous sinus dural arteriovenous fistulas via transvenous approach.

OBJECTIVE: To describe the transvenous catheterization technique for the treatment of cavernous sinus dural arteriovenous fistulas (CSdAVFs), including its indications, complications and efficacy. METHODS: Eight patients with symptomatic CSdAVFs were treated by endovascular embolization with platinum coils, via the inferior petrosal sinus (IPS) in 6 patients, and via the Sylvian vein after surgical exposure in other 2 patients. RESULTS: Complete angiographic resolution of the fistula was obtained in six patients immediately after the procedures, and a complete resolution of symptoms and signs was achieved in all patients. The residual fistulas in two patients disappeared completely in the follow-up angiography. CONCLUSION: Transvenous embolization is a useful and safe approach in the management of CSdAVFs.

Aged↗

[Human leucocyte antigen-DPA1 polymorphism distribution in Chengdu Chinese families with intrahepatic cholestasis of pregnancy].

OBJECTIVE: To investigate the relationship between human leucocyte antigen (HLA)-DPA1 region gene polymorphism and intrahepatic cholestasis of pregnancy (ICP). METHODS: The HLA-DPA1 alleles of 25 ICP families and 25 normal control group families were analysed by polymerase chain reaction-sequence specific primers(PCR-SSP) method. RESULTS: The analysis of the frequencies and feto-maternal or couples sharing of the DPA1 alleles showed that no statistically significant difference was observed between the two study groups. CONCLUSION: It is unlikely that an HLA-DPA1 allele is primarily associated with susceptibility or resistance to ICP.

Alleles↗

[Cloning, expression and characterization of the hypoxanthine-guanine phosphoribosyltransferase mutants from T. tengcongensis].

Based on a predicted three-dimensional structure of hypoxanthine-guanine phosphoribosyltransferase (HGPRT) from Thermoanaerobacter tengcongensis, three mutants of HGPRT were designed to modify the purine specificity of HGPRT. Site-directed mutagenesis was used to generate the three mutants, K(133)A, K(133)S, K(133)T. Wild type HGPRT and its mutants were expressed E. coli in BL21 (DE3) pLysS, and the expression products of them reached about 30% of the total protein. The molecular weight of the recombinant proteins was 22 kD. The specific activities of the enzymes were determined. Catalytic activities of mutants K(133)A, K(133)S, K(133)T retained only 4%, 1.1%, 2.7% activities, respectively, of the wild type for hypoxanthine, 1.7% 0.6% 1% activities, respectively, of wild type for guanine. However, the three mutants showed 24-fold, 7-fold, 18-fold activities, respectively, of the wild type for xanthine, and 650-fold, 210-fold, 380-fold activities, respectively, of the wild type for adenine. Comparison of kinetic data for purified recombinant mutant with wild-type HGPRT showed significant difference in the catalytic efficiency (kcat/Km) for purine, xanthine and adenine, the mutants exhibiting more than 40 to 50-fold higher kcat/Km, as a result of nearly 4 to 5-fold decrease in Km, compared with wild-type. These results demonstrate that a single amino acid substitution in HGPRT at the active site can significantly modify the specificity for binding purine.

Amino Acid Sequence↗

[Preliminary study of lyophilized 10-hydroxycamptothecin in advanced or recurrent malignancies].

BACKGROUND & OBJECTIVE: 10-Hydroxycamptothecin (HCPT) is the inhibitor of topoisomerase I with anti-cancer effectiveness on several solid tumors. TUOXI (lyophilized HCPT) has higher purity and stability in comparison with solution for injection HCPT. The purpose of this study was to investigate the efficacy, toxicity, and proper dosage of TUOXI as single agent in treatment of advanced and recurrent solid tumors. METHODS: Sixty patients with the median age of 53 (range from 17 to 73 years) were enrolled into this multicenter phase II clinical trial. Among them, 18 patients were chemonaive and 42 were recurrent from chemotherapy; 22 patients with NSCLC, 12 nasopharyngeal carcinoma, 9 primary liver cancer, 9 colorectal carcinoma, 2 pancreatic carcinoma, and 6 miscellaneous malignancies. HCPT was given at the dosage of 6-8 mg/m(2) x d for 5-10 consecutive days based on the toxicity. RESULTS: Fifty-one patients were valuable for effectiveness. The objective response rate for the whole group was 15.7%. The partial remission (PR) rates were 16% for 6 mg/m(2) group and 15.4% for 8 mg/m(2) group, respectively. The PR rates were 13.7% (3/22) for NSCLC, 33.3% (3/9) for colorectal carcinoma, and 16.6% (2/12) for advanced nasopharyngeal carcinoma, respectively. The PR rate for 60 intent-to-treat patients was 13.3% (8/60). Myelosuppression was the dose-limiting toxicity and other adverse reactions included nausea/vomiting, diarrhea, and skin rash. The incidence of grade III+IV adverse events were 32%, 8%, 8%, 6%, and 4% for leucopenia, skin rash, thrombocytopenia, nausea/vomiting, and diarrhea, respectively. No renal, pulmonary, and cardiac toxicity were found. CONCLUSION: TUOXI (HCPT lyophilized powder) had relatively broad- spectrum anti-cancer efficacy and was effective on advanced or recurrent NCSLC, colorectal carcinoma, and NPC. And the recommended dosage is 6-8 mg/m(2) as 4 hours infusion for 5-10 consecutive days every 3 weeks. Further clinical investigation on large number of solid tumors cases are warranted.

Adolescent↗

Parallel cloning, expression, purification and crystallization of human proteins for structural genomics.

54 human genes were selected as test targets for parallel cloning, expression, purification and crystallization. Proteins from these genes were selected to have a molecular weight of between 14 and 50 kDa, not to have a high percentage of hydrophobic residues (i.e. more likely to be soluble) and to have no known crystal structures and were not known to be subunits of heterocomplexes. Four proteins containing transmembrane regions were selected for comparative tests. To date, 44 expression clones have been constructed with the Gateway cloning system (Invitrogen, The Netherlands). Of these, 35 clones were expressed as recombinant proteins in Escherichia coli strain BL21 (DE3)-pLysS, of which 12 were soluble and four have been purified to homogeneity. Crystallization conditions were screened for the purified proteins in 96-well plates under oil. After further refinement with the same device or by the hanging-drop method, crystals were grown, with needle, plate and prism shapes. A 2.12 A data set was collected for protein NCC27. The results provide insights into the high-throughput target selection, cloning, expression and crystallization of human genomic proteins.

Base Sequence↗

Repair of tetralogy of Fallot in infancy with a transventricular or a transatrial approach.

OBJECTIVE: The optimal time and approach of repair of tetralogy of Fallot (TOF) remain controversial. The purpose of this study was to evaluate the outcome following repair of TOF in infants with particular regard to the surgical approach used. PATIENTS: One hundred and sixty infants (mean age 195+/-89 days, range 11-364 days) undergoing repair of a simple TOF were studied. Between 1974 and 2000, a transventricular approach (RV) was used in 91 and between 1988 and 2000, a transatrial (RA) approach in 69 infants. Ten of these infants (6.2%) had a previous palliative shunt (four in the RV versus six in the RA group). A transannular patch (TAP) was inserted in 96 (60%) infants (76 versus 20). Follow-up was complete (mean 14.5+/-5.2 versus 6+/-1 years). RESULTS: There were three operative deaths (1.9%), (two in RV versus one in RA group). A re-operation for right ventricular outflow tract obstruction (RVOTO) was performed in 19 patients (3 versus 16). Ten-year freedom from re-operation for RVOTO (+/-standard error of the mean) was 88+/-4% (98+/-2 versus 72+/-6%, P<0.0001). Within the RA group, 5-year freedom from re-operation for RVOTO for those who had a TAP was 79+/-9% and it was 75+/-4% for those having a simple repair. Six patients in the RV group required pulmonary valve replacement (PVR). Ten-year freedom from PVR was 98+/-1% (97+/-2 versus 100%, P=0.3). There were two late deaths, one in each group. Ten-year survival was 97+/-1%. One patient in the RV group developed late recurrent ventricular tachycardia requiring the implantation of a defibrillator. At most recent echocardiography, all but the patient who had the defibrillator had good right and left ventricular function. CONCLUSIONS: Transventricular and transatrial repair of TOF in infancy, are associated with an acceptable operative risk, low incidence of late arrhythmia, good bi-ventricular function and excellent survival. In our experience, however, transatrial repair has a disturbing incidence of early and mid-term residual or recurrent RVOTO, even when a TAP has been used.

Cardiac Surgical Procedures↗

Construction of a novel transposon mutagenesis system useful in the isolation of Streptococcus parasanguis mutants defective in Fap1 glycosylation.

Streptococcus parasanguis, a primary colonizer of the tooth surface, has long, peritrichous fimbriae. A fimbria-associated protein, Fap1, is identified as an adhesin of S. parasanguis FW213. The mature Fap1 protein is glycosylated, and the glycosylation is required for fimbria biogenesis and bacterial adhesion. Little is known about the mechanism of Fap1 glycosylation due to the lack of identifiable mutants. A novel transposon mutagenesis system was established and used to generate a mutant library. Screening of the library with a monoclonal antibody specific for a glycan epitope of Fap1 yielded six mutants with decreased expression levels of surface-associated glycosylated Fap1 protein. Southern blot analyses revealed that three of the mutants had the transposon inserted in the fap1 locus, whereas the other three mutants had insertions in other genes. Among the latter three mutants, two expressed Fap1 polypeptides on which no glycosylation was detected by glycan-specific antibodies; the other mutant expressed a partially glycosylated Fap1 polypeptide. These data suggest that three mutants were isolated with defects in genes implicated in Fap1 glycosylation.

DNA Transposable Elements↗

Hyperuricemia induces a primary renal arteriolopathy in rats by a blood pressure-independent mechanism.

Hyperuricemia is associated with hypertension and vascular disease, but whether this represents a causal relationship or an epiphenomenon remains unknown. We recently reported a model of mild hyperuricemia in rats that results in increased blood pressure and mild renal fibrosis. In this study, we examined the effect of hyperuricemia on the renal vasculature. Rats fed 2% oxonic acid and a low-salt diet for 7 wk developed mild hyperuricemia (1.8 vs. 1.4 mg/dl, P < 0.05), hypertension [147 vs. 127 mmHg systolic blood pressure (SBP), P < 0.05], and afferent arteriolar thickening, with a 35% increase in medial area (P < 0.05). Allopurinol or benziodarone prevented the hyperuricemia, hypertension, and arteriolopathy. Hydrochlorothiazide treatment did not prevent the hyperuricemia or arteriolopathy despite controlling blood pressure. In contrast, the arteriolopathy and hypertension were prevented by both enalapril and losartan. Uric acid also directly stimulated vascular smooth muscle cell proliferation in vitro, and this was partially inhibited by losartan. Thus hyperuricemia induces a renal arteriolopathy in rats that is blood pressure independent and involves the renin-angiotensin system.

Administration, Oral↗