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Biomedical subjects

Z L Xu

Publications and source records attributed to Z L Xu.

At least 19 recordsLinked to original sources

Optimization of transcriptional regulatory elements for constructing plasmid vectors.

In studies regarding both gene therapy and gene function, transgene expression by plasmid vectors benefits from the use of transcriptional regulatory elements which permit high-level gene expression. Therefore, with respect to transgene (luciferase) expression activity both in vitro (using HeLa, HepG2, and ECV304 cells) and in vivo (mouse liver and skeletal muscle), we investigated the effective combination of commonly-used regulatory elements, such as the promoter/enhancer, intron, and polyadenylation signal (P(A)) sequence by constructing a series of plasmids that differed only in the particular sequence element being evaluated. Of the several promoter/enhancers that were tested, hybrid CA promoter/enhancer containing human cytomegalovirus immediate-early 1 gene (CMV) enhancer and chicken beta-actin promoter with the beta-actin intron sequence, and the improved CMV promoter/enhancer containing the largest intron of CMV (intron A) produced the highest levels of expression both in vitro and in vivo. P(A) sequences were found to have significant effects on transgene expression. The effect of a multiple enhancer was also examined. Optimized plasmids of this study were pCASL3 (composed of CMV enhancer, beta-actin promoter, beta-actin intron, Simian virus (SV40) P(A) sequence and SV40 enhancer) and pCMVSL3 (composed of CMV enhancer, CMV promoter, intron A, SV40 P(A) sequence and SV40 enhancer). These comparative analyses could provide a systematic reference for the development of vector construction for gene therapy, vaccine development, and gene transfer experiments.

Animals↗

[Comparative studies on the fatty acids contained in four species of medicinal plants from family Euphorbiaceae and their endophytic fungi].

OBJECTIVE: The relation of four species of medicinal plants from family Euphorbiaceae and their endophytic fungi was studied to find the source of active substances for developing new pharmaceutical resources. METHOD: The main fatty acids contained in Sapium sebiferum, Euphorbia pekinensis, Euphorbia helioscopia, Bischofia polycarpam and their 28 strains of endophytic fungi were compared and analysed by GC. RESULT: The main fatty acids of the plants are: alpha-linolenic acid, palmitic acid, linolenic acid and oleic acid. Linolenic acid, palmitic acid and oleic acid are the main fatty acids of the endophytic fungi. CONCLUSION: The fatty acids could be produced by the endophytic fungi, which could be used as a factor for identification. There are great differences at the contents of alpha-linolenic acid between the plants and their endophytic fungi, which were suggested to be related with the nutrition absorption and the relationship between the endophytes and the host plant.

Euphorbia↗

Effect of ischemic preconditioning on myocardial oxygen consumption during ischemia.

Ischemic preconditioning (IPC) in the heart may reduce myocardial energy demand. The present study was undertaken to examine changes in myocardial oxygen consumption (MVO2) during ischemia by IPC in Langendorff perfused rat hearts. We assessed MVO2 during ischemia from the measurement of mitochondrial cyt. aa3 redox state by a two-wavelength reflectance spectrophotometry where T(1/2), the time from the onset of ischemia to the point for half reduction of cyt. aa3, was assumed to represent MVO2. The heart was preconditioned by three cycles of 5 min ischemia plus 5 min reperfusion and then subjected to 30 min global ischemia followed by reperfusion for 30 min. The T(1/2) was significantly longer in the preconditioned heart (30 +/- 6 s, n = 10) than the control heart (14 +/- 5 s, n = 9, P<0.001), indicating a reduction of MVO2 during ischemic period by IPC. The prolongation of T(1/2) was evident after only one IPC episode. When the heart was perfused with high K+ solution to abolish MVO2 for contractions, we still found the prolongation of T1(1/2) in the preconditioned heart (116 +/- 12 s, n = 6) compared to the control heart (86 +/- 10 s, n = 6, P<0.01), suggesting that decrease in contractile activity may be, in part but not completely, responsible for the reduction of MVO2. In contrast, the prolongation of T(1/2) was completely abolished by administration of a NO synthase inhibitor N omega-nitro-L-arginine in the high K+ arrested heart, demonstrating involvement of NO in the reduction of MVO2, presumably by suppression of mitochondrial respiratory chain. In conclusion, IPC reduces MVO2 during ischemia. The reduction of MVO2 in the preconditioned heart may be accounted for by decreased contractile activity and by depression of respiratory chain by NO.

Animals↗

Direct observation of radial intracellular PO2 gradients in a single cardiomyocyte of the rat.

The purpose of the present study was to directly visualize radial gradients of intracellular PO2 in a single individual cardiomyocyte isolated from the rat ventricle. Microspectrophotometry with the use of cytosolic myoglobin as an oxygen probe was conducted at 410 nm. When the quiescent cell was incubated with 1 microM carbonyl cyanide m-chlorophenylhydrazone to increase oxygen consumption approximately eightfold, gradual decreases in myoglobin oxygen saturation (SMb) were demonstrated toward the core of the cell, whereas these decreases disappeared when the cell was treated with 2 mM NaCN. These results highlighted the importance of diffusional oxygen transport in determining intracellular oxygenation in cardiac cells. From the measured SMb, we assessed the profile of radial changes in intracellular PO2 at the mean SMb comparable to that in vivo ( approximately 0.5). Quite steep PO2 gradients were demonstrated in the vicinity of the sarcolemma that were rapidly attenuated toward the cell core. These radial profiles of intracellular PO2 demonstrate the significance of myoglobin-facilitated diffusion of oxygen. Furthermore, the shallow gradients of PO2 near the center of the cell might arise from partial depression of oxygen consumption near the cell core.

Animals↗

[Extracellular matrix].

Extracellular matrix is composed of four families: collagens, proteoglycans, elastin and extracellular matrix structural glycoproteins. The extracellular matrix should not be viewed as merely providing strength and physical support for tissues and organisms. It is now quite clear that this matrix exerts profound influence on both the behaviour (e.g. adherence, spreading, and migration) and the pattern of gene expression of the cells. Extracellular matrix research is an active field in biology.

Animals↗

[Evaluation of the redox tolerance index on hepatic energy charge of hepatitis B patients].

To evaluate hepatic energy charge, we detected the redox tolerance index (RTI) in 27 patients with chronic hepatitis B (CH) and 34 patients with post-hepatitis B liver cirrhosis (LC). The results demonstrated that RTI was significantly lower in CH and LC than that in the normal controls (P < 0.01). There was no difference between CH and LC. The active LC showed RTI significantly lower than that of the inactive LC (P < 0.05). The results also indicated that there was no correlation between the RTI and routine liver function. Our findings suggest that RTI based on redox theory is of value in predicting hepatic energy charge accurately.

Adult↗

[Arterial ketone body ratio as an indicator of energy charge in patients with hepatic encephalopathy].

Arterial ketone body ratio (AKBR) was continuously measured in 39 cases with hepatic encephalopathy (HE) in order to evaluate the immediate energy charge of the liver and predict the occurrence of HE and its prognosis. The results demonstrated that AKBR in patients before the onset of HE was significantly lower than that in healthy subjects (P < 0.005). AKBR was less than 0.65 when HE occurred. Patients were classified into three groups according to the value of AKBR. Patients in group A had AKBR above 0.7, patients in group B had a transient drop of AKBR to 0.4, and patients in group C had consistently low AKBR value of less than 0.4. The death rates in these three groups were 0, 33.3% (5/15) and 100% (14/14) respectively; the difference was quite significant (P < 0.001). Hepatic functional tests such as alanine transaminase, serum bilirubin, prothrombin time and albumin did not show such difference. Our findings suggest that AKBR can predict hepatic energy charge accurately. Patients whose AKBR value was consistently below 0.4 would have a poor prognosis.

Adult↗

[Detoxifying effect of lisheng-se on cisplatin and its relation to metallothionein induction].

The effects of Lisheng-Se (Seleninized wheat germ) on metallothionein (MT) induction, lethal systemic toxicity, nephrotoxicity, hemotoxicity and anticancer activity of cisplatin (CDDP), were investigated in mice. The systemic toxicity of CDDP was significantly reduced by preadministration of Lisheng-Se (P < 0.05 or P < 0.01). The protective effects were better than its inorganic form (Na2SeO3) and Bi (BSN), (0.05 < P < 0.1). The MT level in the liver, kidney, heart and tumor tissues of mice treated with one of those compounds was determined. The results show that the levels of MT induced by Lisheng-Se were significantly increased in liver and kidney (P < 0.01 and P < 0.05). It was just in conformity with the conclusion that the best protective effect appeared in the groups treated with Lisheng-Se. These results suggest that increased MT synthesis in the liver and kidney may be involved in the protective effects of Lisheng-Se tested on the lethal toxicity, nephrotoxicity and hemotoxicity produced by CDDP. The experiments also show that Lisheng-Se did not affect the anticancer activity of CDDP in vitro and in vivo, while the MT level was not increased in cancer (P < 0.05), so Lisheng-Se might not only improve the therapeutic index of CDDP, but also did not cause drug-resistance of cancer cells.

Animals↗

[The protective effects of two hydration protocols against cisplatin nephrotoxicity].

A comparative study was performed in 37 patients with breast cancer who received high doses of cisplatin (100 mg/m2, I.V. drip) accompanied by two different hydration protocols. The new hydration protocol is based on the study of relationship between the pharmacokinetic parameters of plasma and urinary platinum concentration and the cisplatin-induced nephrotoxicity. In the new hydration protocol the diuretic drugs were given twice- amid and twelve hours after the cisplatin infusion instead of giving once--immediately after the cisplatin infusion, and 1,000ml drinking water was given by p.o. before taking cisplatin. Because of the increase in urinary volume the peak levels of urinary platinum were decreased from 47.34 micrograms/ml to 13.49 micrograms/ml, so that the rate of the nephrotoxicity was reduced from 36.8% (7/19) to 5.6% (1/18). The results suggest that the new hydration protocol is more effective than that previously used to protect against cisplatin nephrotoxicity.

Adult↗

[Effect of combined chemotherapy against human intestinal nematode eggs].

The effect of a combination of albendazole and mebendazole was evaluated by stool examination in 7 patients with Ascaris lumbricoides eggs, 7 patients with Trichuris trichiura eggs and 9 patients with hookworm eggs. Albendazole and mebendazole were given at 300 mg and 375 mg, respectively. Both drugs were divided into 3 parts, one part b. id., and given in 1.5 days. The fecal eggs turned negative in all the patients with Ascaris infection in 3 days, while the fecal eggs were negative in all patients with Trichuris or hookworm infection in 5 days. The development rates of the eggs were remarkably lower post-treatment than pre-treatment. It was found that the ovicidal rates in human ascariasis, trichuriasis and ancylostomiasis were 98.8%, 100% and 100%, respectively on the second day following the initiation of treatment. The results showed that the worm-repelling and ovicidal effect of the combined chemotherapy was more evident.

Adolescent↗

[Autologous pericardial patch angioplasty of Budd-Chiari syndrome].

21 patients with inferior vena cava (IVC) or hepatic vein (HV) stenosis were treated by autologous pericardial patch angioplasty. Postoperative recovery was uneventful and the patients were followed up for 4 to 51 months. Signs of ascites, edema or varices in the lower extremities, and hepatomegaly disappeared in 1 to 3 months after operation in all patients. Ascending varicosities of the truncal vein and esophageal varices disappeared in 5 and 16 of '8 patients in 1 to 3 months respectively. Hepatic dysfunction in 6 patients returned to normal after operation. B-mode ultrasonography showed good patency of the reconstructed IVC or HV in the 18 patients.

Adult↗

[The effect of zinc glycyrrhizate on toxicity and anticancer activity of cisplatin in mice].

The preventive effects of Zn Glycyrrhizate (Gly-Zn) on lethal toxicity, nephrotoxicity, hemotoxicity, testicular toxicity and anticancer activity of cisplatin (CDDP) were investigated in mice. The toxicity of CDDP evaluated by the above criterion was significantly reduced by preadministration of Gly-Zn 400 mg.kg-1.d-1 x 5 (P < 0.05 or P < 0.01). The protective effects were better than bismuth subnitrate (BSN) which has been studied previously (0.05 < P < 0.1). The metallothionein (MT) level in the liver, kidney, heart and cancer of mice treated with one of these compounds were determined. The results showed that the levels of MT induced by Gly-Zn were significantly increased in liver and kidney (P < 0.05). It was just in conformity with the conclusion that the best protective effect appeared in the groups treated with preadministration of Gly-Zn. These results suggest that increased MT synthesis in the liver and kidney may be involved in the protective effect of Gly-Zn on the toxicities produced by CDDP. The experiments also showed that Gly-Zn did not affect the anticancer effect of CDDP in vitro and in vivo, while the MT level was not increased in cancer (P < 0.05), so Gly-Zn might improve the therapeutic index of CDDP.

Animals↗

Production of anti-tumor human monoclonal antibodies using different approaches.

The production of anti-tumor human monoclonal antibodies (MAbs) by human-human or human-mouse hybridoma technology was studied. UC729-6, a human lymphoblastoid cell line, or NS-1, a mouse myeloma cell line, were fused with lymphocytes isolated from regional lymph modes of 26 patients with breast or gastrointestinal cancer, resulting in 130 immunoglobulin-secreting human-human hybrids and 21 human-mouse hybrids. The supernatants of 88 hybrids were screened against a panel of cancer cells. The supernatants of 37 human-human hybrids and 2 human-mouse hybrids reacted with cancer cell lines. After three times subcloning, only one anti-breast cancer hybrid human MAb, IgG(lambda) human-human hybridoma (MUBL-6), and one anti-gastric cancer human MAb, IgM(lambda) human-mouse hybridoma (HMG-1), were obtained. The antibody-secreting level was 1-4 micrograms/ml/24 h. Production of anti-breast cancer human MAbs by Epstein-Barr virus (EBV) hybridoma was also studied. Human lymphocytes were derived from draining lymph nodes of a breast cancer patient, whose serum antibody strongly reacted with tumor associated antigen (TAA). The enriched B cells were transformed with EBV in vitro. Positive antibody-secreting B cells were selected, expanded, and fused with heteromyeloma SHMD-33. The fusion frequency was 28/10(7) lymphocytes. Among them were 16 hybridomas secreting human immunoglobulin. After subcloning, 60% of the cloned hybridomas kept their antibody-secreting ability. Six observed hybridomas remained stable for more than 1 year in tissue cultures. The antibody-secreting level was 2.9-30 micrograms/ml/24 h. Supernatants from these hybridomas all reacted with breast cancer cell lines but not with gastric cancer cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Chemical studies on essential oils from 6 Artemisia species].

The constituents of the essential oils obtained from the leaves of Artemisia argyi, A. argyi cv.qiai, A. lavandulaefolia, A. mongolica, A. princeps and A. argyi var. gracilis were analysed by GC-MS. 96 compounds including alpha-thujene, 1,8-cineole, camphor and artemisia alcohol, etc. were identified. Their percentages in the oils were given.

Drugs, Chinese Herbal↗

[Study of collagen abnormality in Marfan's syndrome].

Unique picrosirius-polarization method was used to detect the distribution of collagen fibers in aorta and skin of patients with Marfan's syndrome (MS). The adventitia of aortae of MS patients was noticed to be composing of a certain amount of thin type III collagen fibers, and the reticular layer of skin consisted of large amount of thin type III collagen fibers. The results indicated that the distribution of collagen type in Marfan's syndrome becomes abnormal. Hydroxyproline assay analysis showed no significant difference obtained on the total collagen content of aorta and skin between the MS patients and the controls. Anyhow, content of acid soluble collagen in the aortae of MS patients was learnt to be increased significantly (P < 0.01). CNBr-cleavage electrophoresis showed also change of fragment CB8 band in one case.

Aorta↗

Serine utilization as a precursor of phosphatidylserine and alkenyl-(plasmenyl)-, alkyl-, and acylethanolamine phosphoglycerides in cultured glioma cells.

In several tissues and cell lines, serine utilized for phosphatidylserine (PS) synthesis is an eventual precursor of the base moiety of ethanolamine phosphoglycerides (PE). We investigated the biosynthesis and decarboxylation of PS in cultured C6 glioma cells, with particular attention to 1-O-alk-1'-enyl-2-acyl-sn-glycero-3-phosphoethanolamine (plasmenylethanolamine) biosynthesis. Incorporation of [3H]serine into PS reached a maximum within 4-8 h, and label in nonplasmenylethanolamine phosphoglyceride (NP-PE) and plasmenylethanolamine was maximal by 12-24 h and 48 h, respectively. After 8 h, label in PS decreased even though 40-60% of initial label remained in the culture medium. Serial additions of fresh [3H]serine restored PS synthesis to higher levels of labeled PS accumulation followed by a subsequent decrease in 4-8 h. High performance liquid chromatographic analyses confirmed that medium serine was depleted by 8 h, and thereafter metabolites, including acetate and formate, accounted for radioactivity in the medium. The rapid but transient appearance of labeled glycine and ATP inside the cells indicated conversion of serine by hydroxymethyltransferase. 78-85% of label from serine was in headgroup of PS or of PE formed by decarboxylation. A precursor-product relationship was suggested for label from [3H]serine appearing in the headgroup of diacyl, alkylacyl, and alkenylacyl subclasses of PE. By 48 h, a constant specific activity, ratio of approximately 1:1 was reached between plasmenylethanolamine and NP-PE, similar to the molar distribution of these lipids. In contrast, equilibrium was not achieved in cells incubated with [1,2-14C]ethanolamine; plasmenylethanolamine had 2-fold greater specific activity than labeled NP-PE by 72-96 h. These observations indicate that in cultured glioma cells 1) serine serves as a precursor of the head group of PS and of both plasmenyl and non-plasmenyl species of PE; 2) exchange of headgroup between NP-PE and plasmenylethanolamine may involve different donor pools of PE depending on whether the headgroup originates with exogenous serine or ethanolamine; 3) serine is rapidly converted to other metabolites, which limits exogenous serine as a direct phospholipid precursor.

Animals↗