Role of kinases in HTLV-I transformation.
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Biomedical subjects
Publications and source records attributed to X Xu.
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Biological activities of human tumor necrosis factor-alpha (hTNF-alpha) and its mutants were compared. In cytotoxicity assay with L929 cells, one mutant, designated as TNF-B, showed 4.5-fold higher activity than TNF examined. And TNF-B also increased cytostatic activity and decreased protein synthesis against U937 cells. In receptor binding assay, TNF-B had almost the same affinity for TNF receports on L929 cells as hTNF-alpha. But another mutant, TNFarg, markedly decreased the all activities of hTNF-alpha and had lower affinity for receports on different types of target cell. These results indicated that the relative activity of TNFs to target cells may correlate with their affinity for receports. We also found that TNF-B retained the cytotoxicity of hTNF-alpha for HEp-2 cells. TNF-B also had two-fold higher affinity than hTNF-alpha for receptors on HEp-2 cells (only carrying hTNF-R55) and lower affinity for receptors on U937 cells (expressing mainly hTNF-R75). These results suggested that TNF-B might still interact with the human TNF-R55 receptor, but it might largely lose its ability to bind to human TNF-R75. Changes of biological activity of TNFs might be due to an altered affinity to the different types of TNF receptor on the target cells.
Biological activities of human tumor necrosis factor-alpha (hTNF-alpha) and its mutants were compared. In cytotoxicity assay with L929 cells, one mutant, designated as TNF-B, showed 4.5-fold higher activity than TNF examined. In receptor binding assay, TNF-B had almost the same affinity for TNF receptors on L929 cells as hTNF-alpha. We also found that TNF-B retained the cytotoxicity of hTNF-alpha for HEp-2 cells. TNF-B also had two-fold higher affinity than hTNF-alpha for receptors on HEp-2 cells (only carrying hTNF-R55) and lower affinity for receptors on U937 cells (expressing mainly hTNF-R75). These results suggested that TNF-B might still interact with the human TNF-R55 receptor, but it might largely lose its ability to bind to human TNF-R75. Changes of biological activity of TNFs might be due to an altered affinity to the different types of TNF receptor on the target cells.
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Based on the qualitative reaction of chemical constituents and TLC, the chemical constituents of Chuanhonghua-I were found similar to those Jianyang honghua. The effective constituents, safflower haematochrome and safflower yellow contents of Chuanhonghua-I, meet the standards of Chinese Pharmacopoeia (Ed. 1990).
Four compounds were isolated from Swertia pubescens. They were identified as isoorientin, gentiopicroside, glucose and oleanolic acid by chemical and physical properties and spectral analysis.
This study describes a correlation between cellular DNA repair capacity and the frequency of mutagen-induced in vitro chromosomal breaks in selected lymphoblastoid cell lines. Two assays, host cell reactivation (HCR) assay for measuring cellular DNA repair capacity and in vitro mutagen sensitivity assay, have recently been shown to be useful biomarkers for such susceptibility. Increased in vitro mutagen sensitivity, measured by the number of induced chromatid breaks, has been postulated to reflect decreased capacity of DNA repair, as measured by the HCR assay. However, these two assays have not been examined in parallel to test this hypothesis. In this study, we performed both assays in 16 established lymphoblastoid cell lines derived from patients with xeroderma pigmentosum (n = 3), ataxia telangiectasia (n = 2), head and neck cancer (n = 3), and melanoma (n = 2), and from normal human subjects (n = 6) using UV light, 4-nitroquinoline-1-oxide (4-NQO; an UV-mimetic agent), and gamma-irradiation as the test agents. The measurements from the HCR assay correlated significantly with the frequency of chromatid breaks induced by either UV irradiation (r = -0.69; P < 0.01) or 4-NQO (r = -0.70; P < 0.01). Although published data suggest that damage induced by UV and 4-NQO may be repaired by different pathways, the two agents induced similar frequencies of chromatid breaks (r = 0.68; P < 0.01) in the tested cell lines. Our results also indicated that the HCR assay is not suitable to test agents that cause DNA strand breaks, such as gamma-irradiation, whereas the mutagen sensitivity assay is. Although reduced cellular DNA repair capacity correlated with increased frequency of mutagen-induced chromatid breaks in these cell lines, these two assays have different sensitivities in measuring the repair of damage induced by different carcinogens; therefore, the use of both assays is recommended for future molecular epidemiological studies of cancer susceptibility.
We conducted a case-control study of 207 lung cancer patients and 283 controls to estimate the association of the MspI polymorphism in the cytochrome P450 CYP1A1 gene with lung cancer. The analysis of the CYP1A1 gene polymorphism was performed by RFLP analysis of PCR-amplified DNA. The association of the CYP1A1 polymorphism with lung cancer was assessed by logistic regression using the generalized additive modeling technique to adjust for race, education, smoking status, pack years, time since quitting smoking, asbestos exposures, and family cancer history. The frequencies of the MspI homozygote and heterozygote variant genotypes of CYP1A1 were 1% and 17%, respectively, in both lung cancer patients and controls. A significant association was found between the combined heterozygous and homozygous MspI variant of the CYP1A1 gene and lung cancer; the estimated odds ratio was 2.08 (95% confidence interval, 1.15-3.73). The association remained significant when we excluded the homozygous MspI variant individuals, the non-Caucasians, or the long-time tobacco quitters, and it was not modified by gender or cumulative cigarette consumption. In a specific histological cell type analysis, a positive association was found for each subtype of lung cancer, with no appreciable difference between cell types. In summary, our study demonstrated that the MspI variant CYP1A1 genotype is significantly associated with an increased risk of lung cancer among Caucasians with the odds ratio approximately, equivalent to 2 after controlling for important confounding factors. These results are similar to those obtained from reanalysis of published data on the combined CYP1A1 genotypes in a Japanese population (combined odds ratio, 1.95; 95% confidence interval, 1.17-3.28). Moreover, the elevated risk is noted in heterozygotes, i.e., individuals who carry only one copy of the variant gene.
OBJECTIVE: Our goal was to determine the role of nitric oxide (NO) on the coronary vasodilation induced by prostacyclin (PGI2) in conscious dogs. METHODS: Dogs were chronically instrumented for the measurements of coronary blood flow (CBF), left ventricular pressure (LVP), mean arterial pressure (MAP) and heart rate (HR). RESULTS: Intravenous injections of PGI2 caused dose-dependent increases in CBF, and decreases in MAP and late diastolic coronary resistance (LDCR). For instance, CBF increased by 128 +/- 19% (P < 0.05) from 30 +/- 3.5 ml/min and LDCR decreased by 73 +/- 3% (P < 0.05) from 2.57 +/- 0.20 mmHg/ml/min following injection of PGI2 (1.0 microgram/kg). After infusion of nitro-L-arginine (NLA, 35 mg/kg) intravenously, the coronary vasodilation induced by PGI2 was partially attenuated. PGI2 (1.0 microgram/kg) increased CBF by 55 +/- 15% from 33 +/- 5.3 ml/min and decreased LDCR by 42 +/- 9% (both P < 0.05, compared with before NLA) from 3.29 +/- 0.39 mmHg/ml/min. Infusion of L-arginine (100 mg/kg) reversed the action of NLA. For example, PGI2 (1.0 microgram/kg) increased CBF by 115 +/- 15% from 36 +/- 6 ml/min and decreased LDCR by 68 +/- 3% from 3.02 +/- 0.36 mmHg/ml/min (both P > 0.05, compared with before NLA). Atropine (0.1 mg/kg) partially attenuated the coronary vasodilation induced by PGI2 the magnitude of which was almost identical to that by NLA. NLA or atropine also blunted the coronary vasodilation induced by acetylcholine, while the coronary vasodilation induced by nitroglycerin was not affected by NLA. CONCLUSION: Our results indicate that the coronary vasodilation induced by PGI2 was partially attenuated by NLA or atropine, suggesting that the coronary vasodilation induced by PGI2 is due to two components: a reflex parasympathetic cholinergic vasodilation mediated by NO and a direct action of PGI2.
The promoter region of the midecamycin 4"-hydroxyl propionyltransferase gene (mpt) gene was reconstructed by PCR, and ligated with a fragment from the midecamycin producing strain (Streptomyces mycarofaciens var. 68) which contained fairly strong promoter activity (PLF). Recombinant plasmids pCHFPE2 (promoter region of mpt was reconstructed by combining the PLF in the upstream of its own promoter) and pCHFPE3 (the promoter of mpt was replaced by PLF) were obtained. The extent of expression of mpt was measured according to the amount of propionylspiramycin bioconverted from exogenous spiramycin by transformants of S. lividans TK24 containing pCHFPE2 and pCHFPE3. The results showed that the PLF could increase the expression of mpt in S. lividans TK24 up to 89.02% and 58.53%, respectively, and also enhance the expression in the industrial spiramycin producing strain S. spiramyceticus to a great extent.
OBJECTIVE: To evaluate the rapid prenatal diagnosis method for beta-thalassemia by reverse dot blot (RDB) analysis. METHODS: Using RDB analysis which can detect 18 types of beta-thalassemia mutation, 60 fetuses (with 1 twin) suspected of beta-thalassemia from 59 couples in Southern China were investigated. RESULTS: 15 fetus had normal genotype, 34 were carriers of heterozygous with one of parental affected gene; 10 had both parental affected genes-heterozygous or homozygous; and 1 was not able to identified. Three rare types of beta-thalassemia mutations (CD43, CD14-15, CD27-28) were detected. CONCLUSIONS: The RDB assay is able to complete the screening of beta-thalassemia mutation by DNA hybridization in only one single working day. It is simple, accurate and convenient to operate without radio-isotopes. It can be used as a routine technique in clinical laboratory for the detection of carriers and prenatal diagnosis of beta-thalassemia.
OBJECTIVE: To investigate the role of natural killer (NK) cell activity in the development of endometriosis. METHODS: The NK cell activity in peripheral blood (PB) and in peritoneal fluid (PF) of 72 patients with endometriosis was studied by means of MTT-assay and compared with that of infertile women and fertile controls. RESULTS: The NK cell activity in PB and in PF of patients with endometriosis was lower than that in those of infertile and fertile controls, and decreased as the stage of endometriosis increased. Follow-up of 8 patients with stage II/N endometriosis demonstrated that the NK cell activity in PB had a moderate increase shortly after excision of endometriotic lesions, but decreased again to the preoperative level 6-9 months later. CONCLUSIONS: Patients with endometriosis have a primary defect in their NK cell function, and the defect may be related to the pathogenesis of the disease.
The purpose of this study is to investigate the effects of repeated rotating stimuli on electronystagmogram (ENG) and electrogastrogram (EGG) in guinea pigs. ENG and EGG were separately recorded prior to the stimuli and on the next day and 30 days after repeated stimuli in 14 guinea pigs with normal pinna reflexes. The results showed that the numbers of the bilateral vestibular nystagmus (L and R separately represented the numbers of left and right nystagmus) of postrotation (L = 682, R = 657) were obviously less than that of prerotation (L = 857, R = 842) (P < 0.01, pairing t-test), and EGG amplitude of postrotation (4506 microV) during the whole course of rotating stimuli was lower than that of prerotation (5279 microV) (P < 0.01, pairing t-test). The numbers of bilateral nystagmus (L = 845, R = 826) were obviously raised again 30 days after stopping rotating stimuli (P < 0.01, compared with next day after stopping repeated stimuli; P > 0.05 compared with before rotating stimuli). It was concluded that repeated rotating stimuli can decrease the vestibulo-ocular and vestibulo autonomic reflexes in guinea pigs, but the effects were not timeless.
OBJECTIVE: To search for the application of the retrovirus vector (RV)/herpes simplex virus type I thymidine kinase gene (HSV-tk)/ganciclovior (GCV) gene therapeutic system in the treatment of ovarian cancer. METHODS: Two kinds of vector-producing cells (VPC) which can produce retrovirus vectors constructed to contain neoR gene and two kinds of HSV-tk genes (marked as "HSV-tka" and "HSV-tkc) were employed to transfer those genes into ovarian cancer AO, 3AO cell lines. And the response of those anti-G418 clones to GCV therapy was observed. RESULTS: In the transduction to AO cells, the vector titer of the VPC/HSV-tkc culture was 9.3 x 100,000 cfu/ml, and there were 263 anti-G418 clones in the 25 cm2 cell culture flask in which 1:1,000 diluted VPC/HSV-tkc culture was added, and 235 clones in a similar flask in which 1:10 diluted VPC/HSV-tka culture was added. Further more, all of the HSV-tkc positive clones exposed to 10 micrograms/ml GCV could be eliminated, and 96% of those clones died in 5 days after GCV was used. CONCLUSIONS: The application of the RV/HSV-tk/GCV system is very promising in the gene therapy of ovarian cancer.
Extracorporeal circulation and myocardial protection in 53 children with ventricular septal defect associated with severe pulmonary hypertension were reported. The average aortic cross-clamping time was 45.5 minutes. The hearts were defibrillated spontaneously in 35 patients. We emphasized that full understanding of the pathophysiological characteristics of ventricular septal defect associated with severe pulmonary hypertension in children is fairly important to the use of various extracorporeal circulation techniques during surgical intervention.
In order to investigate the pathologic features of cardiac and pulmonary allografts, endomyocardial biopsies (EMB) and transbronchial lung biopsies (TBLB) were studied in 3 patients after lung and heart transplantation. 2 autopsy examinations after a cardiac and a combined heart and lung transplantation were included in this study. The results demonstrated that the presence and the severity of allograft rejection were closely related to the degree of interstitial and perivascular lymphocyte infiltration. Parenchymal injuries may sometimes be a concomitant sign. One patients died suddenly 7 months after cardiac transplantation because of acute severe allograft rejection in combination with allograft coronary disease. Another patient who received combined heart and lung transplant died early after the operation due to coronary thromboembolism. The patient who received a single lung transplant has already survived 16 months. TBLB at 11 and 13 months after the operation showed the recurrence of pulmonary sarcoidosis in the donor lung. Our study confirmed that EMB and TBLB provided useful information for acute allograft rejection after heart and lung transplantation.
Endoscopic mechanical lithotripsy (EML) was attempted in 41 patients with common bile duct stones unable to be removed by endoscopic sphincterotomy. These patients had altogether 89 stones with stone size ranged from 5 to 30 mm (mean transverse diameter 16.6 +/- 6.0 mm and mean longitudinal diameter 20.0 +/- 7.1 mm). 31 patients had 34 stones greater than or equal to 20 mm in transverse diameter. The overall stone removal rate was 97.6%. The rate of complete removal of the stone fragments with EML at one time was 78.6% (11/14) for large, 58.8% (10/17) for middle and 0 (0/5) for small incision of the sphincter. In patients with diameter of the distal common bile duct greater than or equal to 14 mm and less than 9 mm the rate was 83.3% and 30.8% respectively and the difference was of significance (P < 0.05). The rate of complete removal for using basket and balloon catheter was 6/10 and 4/9 separately and that for combined used of these two methods 83.3% (10/12). The rate of spontaneous passage of the stone (within one week) was 1/5. It is concluded that complete removal of the stone fragments was related mainly to the length of the incision, diameter of distal common bile duct and methods of removing stone fragments after the crush with lithotripsy basket; when the stone is large and there is the no space around the stone for lithotripsy basket manipulation, a large amount of diluted contrast material is injected into the bile duct so as to increase the space and facilitate the ensonaring of the stone with lithotripsy basket. Hard stones can not be crushed easily, so they constitute one of the reasons of failure.
In recent years, the taxol isolated from the stem bark of some plants of Taxus has been widely as an antitumor agent. But the development of taxol is limited by the scarcity of wild Taxus resources. This paper seeks to discuss the ways to conserve and promote the regeneration of these resources.