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Biomedical subjects

L Wei

Publications and source records attributed to L Wei.

At least 217 records · Page 12Linked to original sources

7,12-dimethylbenz[a]anthracene induces oxidative DNA modification in vivo.

Initiation and promotion are major stages in the multistage carcinogenesis process. Formation of initiating carcinogen-DNA base adducts leads to heritable genetic changes, but the tumor-promoting events induced by complete carcinogens have not, as yet, been elucidated. Oxidant production and oxidative DNA damage induced by phorbol esters (i.e., 12-O-tetradecanoyl-phorbol-13-acetate) are associated with tumor promotion, while antioxidants and inhibitors of oxidative DNA damage suppress promotion and carcinogenesis. Our goal was to establish whether a carcinogen that requires oxidative metabolism for its activity can also induce oxidant production and DNA base oxidation. We found that topical treatment of SENCAR mice with 7,12-dimethylbenz[a]anthracene, which induces tumors in 40-50% of the mice, also causes hydrogen peroxide production and formation of oxidized bases (i.e., 8-hydroxyl-2'-deoxyguanosine and 5-hydroxymethyl-2'-deoxyuridine) in epidermal DNA. The levels of oxidized bases were of comparable magnitude to those mediated by the potent tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate. The oxidized bases persisted over several weeks in epidermal DNA. These oxidative events appear to be temporally associated with inflammatory responses that include edema and polymorphonuclear leukocyte infiltration, which remained elevated over longer periods of time and at higher levels than those induced by phorbol ester. Because these processes are usually associated with tumor promotion, our results support the conjecture that oxidative events may be involved in what is operationally referred to as the tumor promotion process by 7,12-dimethylbenz[a]anthracene.

8-Hydroxy-2'-Deoxyguanosine↗

Nicotine raises the influx of permeable solutes across the rat blood-brain barrier with little or no capillary recruitment.

Nicotine (1.75 mg/kg s.c.) was administered to rats to raise local CBF (lCBF) in various parts of the brain, test the capillary recruitment hypothesis, and determine the effects of this increase in lCBF on local solute uptake by brain. lCBF as well as the local influx rate constants (K1) and permeability-surface area (PS) products of [14C]antipyrine and [14C]-3-O-methyl-D-glucose (3OMG) were estimated by quantitative autoradiography in 44 brain areas. For this testing, the finding of significantly increased PS products supports the capillary recruitment hypothesis. In 17 of 44 areas, nicotine treatment increased lCBF by 30-150%, K1 of antipyrine by 7-40%, K1 of 3OMG by 5-27%, PS product of antipyrine by 0.20% (mean 7%), and PS product of 3OMG by 0-23% (mean 8%). Nicotine had no effect on blood flow or influx in the remaining 27 areas. The increases in lCBF and K1 of antipyrine were significant, whereas those in K1 of 3OMG and in PS for both antipyrine and 3OMG were not statistically significant. The lack of significant changes in PS products implies that in brain areas where nicotine increased blood flow: (a) essentially no additional capillaries were recruited and (b) blood flow within brain capillary beds rises by elevating linear velocity. The K1 results indicate that the flow increase generated by nicotine will greatly raise the influx and washout rates of highly permeable materials, modestly elevate those of moderately permeable substances, and negligibly change those of solutes with extraction fractions of < 0.2, thereby preserving the barrier function of the blood-brain barrier.

3-O-Methylglucose↗

Ministrokes in rat barrel cortex.

BACKGROUND AND PURPOSE: Many stroke models in rats are based on occlusion of the middle cerebral artery, which supplies a significant portion of multifunctional cortical and deep structures in the cerebral hemisphere. The purpose of this study was to develop a model for direct observation in real time of blood flow in and around focal ischemic regions of the cortex of known function. METHODS: Cranial windows were placed over the parietal cortex of adult Wistar and Sprague-Dawley rats anesthetized with ketamine and xylazine. Whisker barrel cortex responding to stimulation of the contralateral whiskers was identified by an intrinsic optical signal. Transits of vital dyes were recorded by videomicroscopy before and after ligation of three to six branches and major collaterals of the middle cerebral artery through the dura. Infarcts were demonstrated with triphenyl-tetrazolium chloride staining; their relation to barrel cortex was determined by Nissl and cytochrome oxidase histology. RESULTS: Reduced blood flow in small ischemic regions was outlined by patient blue violet in the surrounding nonischemic area; arteriovenous latencies increased more than four times in ischemic cortex. Infarcts,typically 3 mm or less, were seen at 24 hours in 8 of 16 Wistar and 9 of 9 Sprague-Dawley rats. The ministrokes were confirmed by histology to be in the somatosensory cortex. CONCLUSIONS: This model of local ischemia, produced deliberately in the functionally defined barrel cortex in rats, leads to ministrokes. Changes can be followed by videomicroscopy as they develop, and processes of recovery can potentially be monitored. Infarcts are confirmed by histology for their location and extent in the somatic representation.

Animals↗

Lung cancer mortality update and prevalence of smoking among copper miners and smelters.

OBJECTIVES: The aim of this investigation was to study the cancer mortality of Chinese copper miners and smelters further, with particular reference to that from lung cancer, and smoking prevalence. METHODS: From an earlier follow-up (1970-1985) of the mortality of the two cohorts, all new death cases registered since 1985 were recorded, and the mortality analysis was extended through 1992. A questionnaire survey of smoking habits was carried out in three samples, randomly chosen from the copper miners (N = 1125), smelters (N = 603), and local residents (N = 1517) of Tongling city. RESULTS: Lung cancer was significantly increased among the copper miners [standardized mortality ratio (SMR) 152, 95% confidence interval (95% CI) 123-187], but not among the copper smelters (SMR 102, 95% CI 53-178). Smoking was more prevalent among copper miners than among local male residents (71.7 versus 64.3%, P < 0.001), whereas among the smelters it was significantly less prevalent (57.4 versus 64.3%, P < 0.005). Similar patterns were found for the average number of cigarettes smoked daily among the miners (21.6 +/- 7.2), smelters (15 +/- 7.1), and local male residents (19.2 +/- 7.3). CONCLUSIONS: In addition to occupational exposures, cigarette smoking may partly play a role in influencing mortality from lung cancer among Chinese copper miners and smelters.

Adult↗

[Chemical constituents of Astragalus chinensis L].

Three compounds have been isolated from the seeds of Astragalus chinensis. Their structures were identified on the basis of spectral data (UV, 13CNMR, 1HNMR, IR and MS) as octacosane, daucosterol and kaempferol.

Alkanes↗

Characterizing oriented protein structural sites using biochemical properties.

A protein site is a region of a three-dimensional protein structure with a distinguishing functional or structural role. Certain sites recur in different protein structures (for example catalytic sites, calcium binding sites, and some types of turns), but maintain critical shared features. To facilitate the analysis of such protein sites, we have developed a computer system for analyzing the spatial distributions of biochemical properties around a site. The system takes a set of similar sites and a set of control nonsites, and finds differences between them. Specifically, it compares distributions of the properties surrounding the sites with those surrounding the nonsites, and reports statistically significant differences. In this paper, we use our method to analyze the features in the active site of the serine protease enzymes. We compare the use of radial distributions (shells) with 3-D grids (blocks) in the analysis of the active site. We demonstrate three different strategies for focusing attention on significant findings, based on properties of interest, spatial volumes of interest, and on the level of statistical significance. Finally, we show that the program automatically identifies conserved sequential, secondary structural and biophysical features of the serine protease active site, using noncatalytic histidine residues as a control environment.

Algorithms↗

[Mutagenicity and anti-mutagenicity assay of airborne suspended particles in Shijiazhuang city].

Samples of airborne suspended particles collected from five air monitoring sites in Shijiazhuang City in 1993 were analyzed with rapid synchronous mutagenicity and anti-mutagenicity tests. It revealed airborne suspended particles collected had direct and indirect mutagenicity, but no anti-mutagenicity, and there was seasonal difference in their mutagenicity, which showed a decreasing trend with an order of winter, spring, summer and autumn. Mutagenicity related positively to air concentrations of total suspended particles and sulfur dioxide, inversely to those of ozone, and did not related to those of nitrogen oxide and carbon monoxide.

Air Pollutants↗

[Alkaloid constituents in the seeds of Sophora viciifolia Hance].

Six alkaloids were isolated from the mature seeds of Sophora viciifolia for the first time. On the basis of physicochemical and spectroscopic analysis, their structures have been identified as oxymatrine, oxysophocarpine, matrine, sophocarpine, sophoramine and sophoridine.

Alkaloids↗

[Fecundify after treatment of tubal pregnancy].

UNLABELLED: This study is a follow-up analysis of 103 patients who desired to preserve their fertile ability after treatment of tubal pregnancy. Among the 103 cases, 58 were treated by unilateral salpingectomy, 15 by salpingostomy and 30 by drug conservative therapy. RESULTS: 67 cases had intrauterine pregnancy and 9 cases repeated ectopic pregnancy. The intrauterine pregnancy rate of the surgical group (71.2%) was higher than that of the nonsurgical group (50.0%). And the pregnancy rate of salpingostomy group (86.7%) was higher than that of salpingectomy group (67.2%). No repeated ectopic pregnancy occurred in the salpingostomy group. After three months of treatment, 45 cases were randomly sampled for tubal patency test. Bilateral tubal patency rate in salpingostomy group was 93.3% and in drug treatment group was 20.0%. These results indicated that tubal patency is an essential factor for normal pregnancy. Prevention of post-operative adhesion and treatment of pelvic inflammatory disease are important for increasing intrauterine pregnancy rate and decreasing repeated ectopic pregnancy rate.

Fallopian Tube Patency Tests↗

[Time selection of cesarean section in preeclampsia].

OBJECTIVE: To study the relationship between the time of cesarean section and the outcome of mothers and newborns. METHODS: One hundred and three pregnant women suffered from preeclampsia (< 37 weeks 34, > or = 37 weeks 69) and 109 newborns (twins 6) were enrolled for study. The rates of neonatal asphyxia, perinatal mortality and morbidity such as pneumonia, respiratory distress syndrome (RDS) and meconium staining amniotic fluid were observed. RESULTS: The cesarean section rate was 83.06% in preeclampsia cases and it was 94.44% in cases with gestational age less than 37 weeks. There was no maternal death. Neonatal asphyxia rate was 6.67%, and the perinatal mortality rate was 6.67%. After 37 weeks the perinatal mortality rate was 1.41% (P > 0.05) and neonatal asphyxia rate 28.17% (P < 0.01). The rate of pneumonia and meconium staining amniotic fluid were obviously increased. CONCLUSIONS: These observations suggest that fetal lung maturation tended to ahead of gestational age in pregnancy induced hypertension. After 37 weeks complications of both mother and baby increased. In severe preeclampsia cases, pregnancy should be terminated at 34-36 gestational weeks, and cesarean section is the first choice.

Adult↗

[Detection of serum isoferritin level in 195 patients with cancer].

ELISA (double-determinant) was used to detect the serum isoferritin (SIF) levels in 42 patients with nasopharynx cancer (NPC), 38 with lung cancer (LC), 26 with esophageal cancer (EC) and 89 with other cancers, a total of 195 cases (151 males and 44 females). The results revealed that the positive rate of SIF in patients with cancer was 73.8% (144/195), among which, the positive rates in patients of stage I-II, stage III-IV, in patients not operated upon and in those after operation were 64.8%, 81.3%, 81.4% and 63.4%, respectively. Statistics was significantly different in SIF level between the stage I-II and III-IV groups, and between the un-operation and after operation groups (P < 0.001) by rank sum testing. The positive rates of NPC, LC and EC were 73.8%, 86.8% and 73.1%, respectively. The results have demonstrated that isoferritin is a malignant neoplasm associated antigen, and SIF level is related closely with the development of the tumor and operative treatment.

Biomarkers, Tumor↗

Structural determinants of substrate selection by the human insulin-receptor protein-tyrosine kinase.

Using NMR spectroscopy to visualise tyrosine phosphorylation kinetics in real time, we have investigated the sequence-dependent determinants of the selectivity of the human insulin receptor protein-tyrosine kinase for different tyrosine residues. The peptides used encompass the multiple-tyrosine-containing autophosphorylation site sequences from the insulin receptor kinase core domain (Tyr1158, Tyr1162 and Tyr1163) and from its specific C-terminal tail domain (Tyr1328 and Tyr1334). Comparison of the phosphorylation kinetics with those found for the tyrosine residues on a peptide comprising the regulatory tyrosine phosphorylation site of cdc2 points to the role of the primary sequence context of the phosphate acceptor. The particularly deleterious influence of a basic residue immediately C-terminal to the tyrosine is discussed in relation to the autophosphorylation properties of the regulatory loop regions of the insulin and epidermal growth factor receptor kinases. The data further suggest that receptor tyrosine kinase active sites and their substrate targets act in concert to ensure that specific downstream effects are activated.

Amino Acid Sequence↗

Structure-function analysis of angiotensin I-converting enzyme using monoclonal antibodies. Selective inhibition of the amino-terminal active site.

Angiotensin I-converting enzyme (ACE; kininase II) contains two very similar domains (the NH2- and COOH-terminal domains (N and C domains, respectively)), each bearing an active site. These active sites hydrolyze the same peptides, but do not have the same catalytic properties and substrate specificities. In an attempt to develop domain-specific immunological probes, two series of monoclonal antibodies (mAbs), 19 clones in all, were produced and tested against human ACE. These mAbs recognized at least nine different epitopes within three antigenic regions of the ACE molecule. Testing on wild-type recombinant ACE and several mutants with only one intact domain showed that these epitopes were all located in the N domain. None of the mAbs recognized the C domain. This particular specificity and analysis of results obtained with several polyclonal antibodies to human ACE suggest that ACE immunogenicity is determined mainly by the N domain. Two mAbs (3A5 and i2H5) recognizing epitopes from different antigenic regions of ACE inhibited the enzymatic activity of the N (but not of the C) domain. mAb 3A5 had the same inhibitory potency toward hippuryl-His-Leu, benzyloxycarbonyl-Phe-His-Leu, and angiotensin I hydrolysis, with 50% inhibition achieved at a mAb/ACE molar ratio of 6. mAb i2H5 was roughly three times more effective than mAb 3A5 inhibiting the hydrolysis of benzyloxycarbonyl-Phe-His-Leu and the natural substrates angiotensin I and bradykinin (50% inhibition at a molar ratio of 1-2), but was less effective in inhibiting hippuryl-His-Leu cleavage (50% inhibition at a molar ratio of 22-25), indicating that this substrate interacts with a specific subsite. mAb i2H5 almost completely inhibited the hydrolysis of the luteinizing hormone-releasing hormone by the isolated N domain. Both the primary carboxyl- and amino-terminal cleavages of this peptide were suppressed. This antibody suppressed the primary amino-terminal cleavage of the luteinizing hormone-releasing hormone by wild-type ACE by > 90%, indicating that this particular ACE function is mediated mainly by the N domain active site. These data provide evidence for structural differences between the two homologous domains of ACE despite their high degree of sequence homology and show that monoclonal antibodies are able to distinguish between the two active sites in ACE.

Angiotensin I↗