Biomedical subjects
Publications and source records attributed to J Q Chen.
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Resistance genes (R-genes) act as an immune system in plants by recognizing pathogens and inducing defensive pathways. Many R-gene loci are present in plant genomes, presumably reflecting the need to maintain a large repertoire of resistance alleles. These loci also often segregate for resistance and susceptibility alleles that natural selection has maintained as polymorphisms within a species for millions of years. Given the obvious advantage to an individual of being disease resistant, what prevents these resistance alleles from being driven to fixation by natural selection? A cost of resistance is one potential explanation; most models require a lower fitness of resistant individuals in the absence of pathogens for long-term persistence of susceptibility alleles. Here we test for the presence of a cost of resistance at the RPM1 locus of Arabidopsis thaliana. Results of a field experiment comparing the fitness of isogenic strains that differ in the presence or absence of RPM1 and its natural promoter reveal a large cost of RPM1, providing the first evidence that costs contribute to the maintenance of an ancient R-gene polymorphism.
BACKGROUND: Aims of our study were to explore whether and to what extent exposure to other lung carcinogens, or staging and clinical features of silicosis modify or confound the association between silica and lung cancer. METHODS: We used data from a nested case-control study, conducted in the late 1980s in 29 Chinese mines and potteries (10 tungsten mines, 6 copper and iron mines, 4 tin mines, 8 pottery factories, and 1 clay mine), that included 316 lung cancer cases and 1,356 controls, matched by decade of birth and facility type. The previous analysis of these data presented results by type of mine or factory. RESULTS: In our study, pooling all 29 Chinese work sites, lung cancer risk showed a modest association with silica exposure. Risk did not vary after excluding subjects with silicosis or adjusting the risk estimates by radiological staging of silicosis. Strong correlation among exposures prevented a detailed evaluation of the role of individual exposures. However, lung cancer risk was for the most part absent when concomitant exposure to other workplace lung carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), nickel or radon-daughters, was considered. The cross classification of lung cancer risk by categories of exposure to respirable silica and total respirable dust did not show an independent effect of total respirable dust. Silicosis showed a modest association with lung cancer, which did not vary by severity of radiological staging, or by radiological evidence of disease progression, or by level of silica exposure. However, among silicotic subjects, lung cancer risk was significantly elevated only when exposure to cadmium and PAH had occurred. CONCLUSIONS: Our results suggest that, among silica-exposed Chinese workers, numerous occupational and non-occupational risk factors interact in a complex fashion to modify lung cancer risk. Future epidemiological studies on silica and lung cancer should incorporate detailed information on exposure to other workplace lung carcinogens, total respirable dust, and on surface size and age of silica particles to understand whether and to what extent they affect the carcinogenic potential of silica.
OBJECTIVES: To investigate the risk of silicosis among tin miners and to investigate the relation between silicosis and cumulative exposure to dust (Chinese total dust and respirable crystalline silica dust). METHODS: A cohort study of 3010 miners exposed to silica dust and employed for at least 1 year during 1960-5 in any of four Chinese tin mines was conducted. Historical total dust data from China were used to create a job exposure matrix for facility, job title, and calendar year. The total dust exposure data from China were converted to estimates of exposure to respirable crystalline silica for comparison with findings from other epidemiological studies of silicosis. Each worker's work history was abstracted from the complete employment records in mine files. Diagnoses of silicosis were based on 1986 Chinese pneumoconiosis Roentgen diagnostic criteria, which classified silicosis as stages I-III-similar to an International Labour Organisation (ILO) classification of 1/1 or greater. RESULTS: There were 1015 (33.7%) miners identified with silicosis, who had a mean age of 48.3 years, with a mean of 21.3 years after first exposure (equivalent to 11.0 net years in a dusty job). Among those who had silicosis, 684 miners (67.4%) developed silicosis after exposure ended (a mean of 3.7 years after). The risk of silicosis was strongly related to cumulative exposure to silica dust and was well fitted by the Weibull distribution, with the risk of silicosis less than 0.1% when the Chinese measure of cumulative exposure to total dust (CTD) was under 10 mg/m(3)-years (or 0.36 mg/m(3)-years of respirable crystalline silica), increasing to 68.7% when CTD exposure was 150 mg/m(3)-years (or 5.4 mg/m(3)-years of respirable crystalline silica). Latency period was not correlated to the risk of silicosis or cumulative dose of exposure. This study predicts about a 36% cumulative risk of silicosis for a 45 year lifetime exposure to these tin mine dusts at the CTD exposure standard of 2 mg/m(3), and a 55% risk at 45 years exposure to the current United States Occupational Safety and Health Administration and Mine Safety and Health Administration standards of 0.1 mg/m(3) 100% respirable crystalline silica dust. CONCLUSIONS: A clear exposure-response relation was detected for silicosis in Chinese tin miners. The study results were similar to most, but not all, findings from other large scale exposure-response studies.
Collaborative studies of Chinese workers, using over four decades of dust monitoring data, are being conducted by the National Institute for Occupational Safety and Health (NIOSH) and Tongji Medical University in China. The goal of these projects is to establish exposure-response relationships for the development of diseases such as silicosis or lung cancer in cohorts of pottery and mine workers. It is necessary to convert Chinese dust measurements to respirable silica measurements in order to make results from the Chinese data comparable to other results in the literature. This article describes the development of conversion factors and estimates of historical respirable crystalline silica exposure for Chinese workers. Ambient total dust concentrations (n>17000) and crystalline silica concentrations (n=347) in bulk dust were first gathered from historical industrial hygiene records. Analysis of the silica content in historical bulk samples revealed no trend from 1950 up to the present. During 1988-1989, side-by-side airborne dust samples (n=143 pairs) were collected using nylon cyclones and traditional Chinese samplers in 20 metal mines and nine pottery factories in China. These data were used to establish conversion factors between respirable crystalline silica concentrations and Chinese total dust concentrations. Based on the analysis of the available evidence, conversion factors derived from the 1988-1989 sampling campaign are assumed to apply to other time periods in this paper. The conversion factors were estimated to be 0.0143 for iron/copper, 0.0355 for pottery factories, 0.0429 for tin mines, and 0.0861 for tungsten mines. Conversion factors for individual facilities within each industry were also calculated. Analysis of variance revealed that mean conversion factors are significantly different among facilities within the iron/copper industry and within the pottery industry. The relative merits of using facility-specific conversion factors, industry-wide conversion factors, or a weighted average of the two are discussed. The exposure matrix of the historical Chinese total dust concentrations was multiplied by these conversion factors to obtain an exposure matrix of historical respirable crystalline silica concentrations.
AIM: To evaluate effects of certain H1-antagonists on spatial memory with 8-arm radial maze performance of rats. METHODS: Eight-arm radial maze performance was used to measure spatial memory in rats. RESULTS: Chronic treatments of classical H1-antagonists, diphenhydramine (5 mg/kg) and pyrilamine (20 mg/kg) impaired acquisition memory process regarding both parameters of radial maze performance. In addition, the memory retrieval process was also impaired significantly by a single administration of diphenhydramine (5, 10 mg/kg) and pyrilamine (50 mg/kg). However, the newly developed H1-antagonist, epinastine caused no appreciable effect on both acquisition and retrieval memory even at a high dose of 50 mg/kg. The memory deficit induced by diphenhydramine (10 mg/kg) or pyrilamine (50 mg/kg) was reversed by tacrine (1 mg/kg). CONCLUSION: Histamine H(1)-receptors plays a certain role in spatial cognition, and its action may be due to both histaminergic and cholinergic neurons.
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The objective of this study was to explore whether a medical history for non-malignant respiratory disease contributes to an increased lung cancer risk among workers exposed to silica. We analyzed data from a nested case-control study in 29 dusty workplaces in China. The study population consisted of 316 lung cancer cases and 1356 controls matched to cases by facility type and decade of birth who were alive at the time of diagnosis of the index case and who were identified in a follow-up study of about 68,000 workers. Age at first exposure and cigarette smoking were accounted for in the analysis. Smoking was the main risk factor for both lung cancer and chronic bronchitis. Lung cancer risk showed a modest association with silicosis and with cumulative silica exposure, which did not vary by history of previous pulmonary tuberculosis. Among subjects without a medical history for chronic bronchitis or asthma, lung cancer risk was associated with silicosis (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.1 to 2.2), and it was increased in each quartile of cumulative silica exposure. However, risk was not elevated in the highest quartile (OR, 1.3, 1.6, 1.8, 1.4). Among subjects with a medical history for chronic bronchitis or asthma, lung cancer risk was associated with neither silicosis (subjects with chronic bronchitis: OR, 0.6; subjects with asthma: OR, 0.4) nor with silica exposure. In this study population, we observed a modest association of both silicosis and cumulative exposure to silica with lung cancer among subjects who were not previously diagnosed with chronic bronchitis or asthma, but not among subjects who had a medical history for either disease. Risk of lung cancer associated with silicosis or cumulative exposure to silica did not vary by previous medical history of pulmonary tuberculosis.
AIM: To analysis the sequence variation of the origin region (D-loop) of mitochondrial DNA (mtDNA) in elite endurance athletes and sedentary subjects in order to find the genetic markers related with performance. METHODS: Using a new established PCR method by virtue of tracing sample analysis, the restricted fragment length polymorphism (RFLP) of D-loop in mtDNA was assessed in 76 elite Chinese endurance athletes (EEA), 33 endurance athletes with average-level(GEA) and 20 sedentary control(sc). RESULTS: There is a significant difference in distribution of the polymorphism in mtDNA D-loop between the EEA and SC(chi 2 = 33.3, P < 0.01). CONCLUSION: The sequence variation of D-loop region of mtDNA in the elite endurance athletes may contribute to the individual difference in aerobic performance and trainability.
Acute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARalpha and one of four fusion partners: PML, PLZF, NPM, and NuMA genes. To study the leukemogenic potential of the fusion genes in vivo, we generated transgenic mice with PLZF-RARalpha and NPM-RARalpha. PLZF-RARalpha transgenic animals developed chronic myeloid leukemia-like phenotypes at an early stage of life (within 3 months in five of six mice), whereas three NPM-RARalpha transgenic mice showed a spectrum of phenotypes from typical APL to chronic myeloid leukemia relatively late in life (from 12 to 15 months). In contrast to bone marrow cells from PLZF-RARalpha transgenic mice, those from NPM-RARalpha transgenic mice could be induced to differentiate by all-trans-retinoic acid (ATRA). We also studied RARE binding properties and interactions between nuclear corepressor SMRT and various fusion proteins in response to ATRA. Dissociation of SMRT from different receptors was observed at ATRA concentrations of 0.01 microM, 0.1 microM, and 1.0 microM for RARalpha-RXRalpha, NPM-RARalpha, and PML-RARalpha, respectively, but not observed for PLZF-RARalpha even in the presence of 10 microM ATRA. We also determined the expression of the tissue factor gene in transgenic mice, which was detected only in bone marrow cells of mice expressing the fusion genes. These data clearly establish the leukemogenic role of PLZF-RARalpha and NPM-RARalpha and the importance of fusion receptor/corepressor interactions in the pathogenesis as well as in determining different clinical phenotypes of APL.
Phospholipase D (PLD) is widely distributed in mammalian cells, where it is regulated by a variety of extracellular signals. Its major substrate is phosphatidylcholine (PC), which is hydrolyzed to phosphatidic acid (PA) and choline. The PLD-catalysed PC hydrolysis is believed to be an important mechanism of signal transduction in cells. More and more lines of evidence indicate that PLD is tightly involved in inflammation. This review introduces the recent advances of PLD in respiratory burst, degranulation and arachidonic acid release.
Studies were carried out to examine the role of phosphodiesterase(PDE) III and PDE IV in the development of tachyphylaxis of isolated guinea pig trachea to beta 2 adrenoceptor agonists. Treating trachea with salbutamol(SB) 1 mumol.L-1 for 1 h produced a 5-fold rightward shift of the SB concentration-response curve for the spasmolytic effect against methacholine-induced bronchocontraction and decreased the maximum SB-induced relaxation by 30%, i.e. induced tolerance of airway response of SB in vitro. The PDE IV inhibitor rolipram (Rol, 1 mumol.L-1, IC50), but not the PDE III inhibitor siguazodan (SK&F 94836, 1 mumol.L-1, IC50), reversed the SB tolerance. However, the protein synthesis inhibitor cycloheximide(10 mumol.L-1) did not abolish the SB tolerance. These results indicate that the SB tolerance may be related to increase in PDE IV activity.
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UNLABELLED: Based on the biodistribution and kinetics of biotinylated 188Re-chimeric BR96 (chiBR96), the enhancement of the tumor-to-normal tissue (T/N) radioactivity ratio using extracorporeal immunoadsorption (ECIA) was evaluated and compared with that of avidin "chase" in colon carcinoma-isografted Brown Norwegian rats. METHODS: Extracorporeal immunoadsorption (ECIA) was performed 6 or 12 hr after intravenous administration of biotinylated 188Re-chiBR96. Radioactivity redistribution was investigated just after ECIA [8 or 14 hr postinjection of the antibody] and 40 or 34 hr after ECIA performance (48 hr postinjection). Avidin was administered intraperitoneally at 6 hr postinjection. Tumor radioactivity uptake and T/N activity ratios of biotinylated 188Re-chiBR96 were compared using ECIA and avidin chase and were also compared with controls. RESULTS: Both ECIA and avidin chase can rapidly increase the radioactivity tumor-to-blood ratio without significantly interfering with the tumor uptake. ECIA at 8 hr postinjection increased the T/N ratios in blood-rich tissues, such as liver and bone marrow, from 6 and 8 to 10 and 18, respectively. Corresponding T/N ratios at 14 hr increased from 9 and 10 to 24 and 36. In contrast, when avidin chase was used, there were no T/N improvements, except in blood. Moreover, avidin chase caused a significant accumulation of radioactivity in the liver. CONCLUSION: The ECIA approach, with direct removal of unbound circulating biotinylated 188Re-chiBR96, thus can rapidly improve and maintain T/N ratios without overloading the liver with radioactivity, in contrast to avidin chase.
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The construction of a gene encoding Lys-human proinsulin, its direct expression in E. coli, and the simple purification procedure are described here. The temperature inducible promotor was employed for induction in a very short time. The expression level could reach 20-30%. After simple downstream processing and only one step of Sephadex G50 purification, 150 mg recombinant Lys-human proinsulin with a purity of up to 90% could be obtained easily from 1 L of high density fermentation medium. The obtained product is in the form of Met-Lys-human proinsulin because of the failure of the bacterial host to remove the initiator methionine residue. The Lys-human proinsulin could be changed into human insulin by trypsin and carboxypeptidase B treatment in later steps. After separation with DEAE-Sephadex A25, human insulin with expected amino acid composition and full native biological activity could be obtained with a yield of 50 mg/L of fermentation medium.
Hepatic expression of various members of the cytochrome P-450 (CYP) superfamily is suppressed during inflammatory responses. We have shown that the specific expression of P-450 2C11 in male rat liver is suppressed transcriptionally by endotoxin treatment. To investigate the molecular mechanisms underlying this phenomenon, we studied the effects of the inflammatory cytokines interleukin (IL)-1, IL-6, tumor necrosis factor-alpha (TNF), interferon (IFN)-alpha, and IFN-gamma on the expression of P-450 2C11 and the mRNAs of two typical acute-phase protein genes, alpha 1-acid glycoprotein (AGP) and fibrinogen, in primary hepatocyte cultures. IL-1, IL-6, TNF, and IFN-alpha all suppressed P-450 2C11 mRNA, whereas IFN-gamma had no effect. IL-1 and TNF were more effective than IL-6 in the suppression of P-450 2C11 mRNA. Whereas IL-1 and IL-6 effects on P-450 2C11 were accompanied by induction of AGP and fibrinogen mRNAs, IFN-alpha and TNF treatments had no effects on AGP. The suppression of P-450 2C11 and the induction of AGP by IL-1 showed similar time courses. The combination of IL-1 and IL-6 showed additivity in suppression of P-450 2C11, at maximally effective concentrations of cytokines. The effects of IL-1 on P-450 2C11 and AGP expression were blocked by IL-1 receptor antagonist protein. We also studied the effects of IL-1 and IL-6 on the transient expression of chloramphenicol acetyl-transferase reporter gene constructs containing 200 or 1287 base pairs of the 5' flanking region of the CYP2C11 gene, transfected into primary hepatocytes. The chloramphenicol acetyltransferase activities in cells transfected with the 200-base pair construct were reduced to about 33% and 58% of control levels by treatment with IL-1 or IL-6, respectively, suggesting that sequences important for cytokine down-regulation lie within the proximal promoter region of the CYP2C11 gene.
To evaluate the effect and indication of different lymph node dissection (D1+, D2, D3), we performed radical operations for 371 cases of gastric cancer. The results showed that D1+ or D1 lymph node dissection was enough for gastric cancer of Ia stage, D2 was suitable for Ib stage. For localized or massive type gastric cancer of II + III stage, D3, D2 dissection was better than D1+ dissection. For the gastric cancer of the same type in IV stage, the 5-year survival rate after D3 + D2 dissection was 42.9%, but for the gastric cancer of infiltrative type or diffused growth pattern in II + III stage, the effect was not significantly increased even after the D3, D2 dissection. For the gastric cancer of this type in IV stage, the effect was not improved after the extended lymph node dissection. Extended dissection needn't be performed if there was no lymph node metastasis. D3, D2 dissection was better if there was little lymph node metastasis or the metastasis was limited to 1st group. For those metastasized to 2nd group or the quantity was more, D3 was better than D2, D1+. The effect of D3, D2 dissection was not significantly improved in the extensive metastasis case (more than 10 or to the 3rd group).