[Protection of workers' health and the development of labour hygiene].
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Humans↗
Biomedical subjects
S Yin
Publications and source records attributed to S Yin.
Increased translocations and aneusomy in chromosomes 8 and 21 among workers exposed to benzene.
Chromosome aberrations in peripheral blood lymphocytes have been used for many years to monitor human populations exposed to potential carcinogens. Recent reports have confirmed the validity of this approach by demonstrating that elevated levels of chromosome aberrations in lymphocytes are associated with subsequent increased cancer risk, especially for increased mortality from hematological malignancies including acute myeloid leukemia (AML). We postulated that this approach could be improved in two ways: (a) by detecting oncogenic disease-specific aberrations; and (b) by using chromosome painting so that many more metaphases could be analyzed. Numerical and structural aberrations in chromosomes 8 and 21 are commonly observed in AML. In the present study, we painted chromosomes 8 and 21 in lymphocyte metaphases from 43 healthy workers exposed to benzene, an established cause of AML, and from 44 matched controls. To examine dose-response relationships the workers were divided into two groups at the median exposure level, a lower-exposed group (< or = 31 ppm; n = 21), and a higher-exposed group (> 31 ppm; n = 22). Benzene exposure was associated with significant increases in hyperdiploidy of chromosomes 8 (1.2, 1.5, and 2.4 per 100 metaphases; P < 0.0001) and 21 (0.9, 1.1, and 1.9 per 100 metaphases; P < 0.0001). Translocations between chromosomes 8 and 21 were increased up to 15-fold in highly exposed workers (0.01, 0.04, and 0.16 per 100 metaphases; P < 0.0001). In one highly exposed individual, these translocations were reciprocal and were detectable by reverse transcriptase-PCR. These data indicate a potential role for t(8;21) in benzene-induced leukemogenesis and are consistent with the hypothesis that detection of specific chromosome aberrations may be a powerful approach to identify populations at increased risk of leukemia.
Acute Disease↗
Keratinocyte growth factor protects mice from chemotherapy and radiation-induced gastrointestinal injury and mortality.
Keratinocyte growth factor (KGF) stimulates the proliferation and differentiation of epithelial cells including those of the gastrointestinal tract. Although chemotherapeutics and radiation exposure kill rapidly proliferating tumor cells, rapidly dividing normal cells of the host's gastrointestinal tract are also frequently damaged, leading to the clinical condition broadly termed "mucositis." In this report, recombinant human KGF used as a pretreatment in several mouse models of chemotherapy and/or radiation-induced gastrointestinal injury significantly improved mouse survival. Using multiple-dose 5-fluorouracil, methotrexate, and radiation in combination and total body radiation alone models, KGF increased survival by 55% or greater. In the models that used chemotherapy with or without radiation, KGF significantly ameliorated weight loss after injury and accelerated weight gain during recovery. The basis of these systemic benefits appears to be due in part to the trophic effects of the growth factor on the intestinal epithelium because KGF pretreatment caused an increase in measures of mucosal thickness (villus height and crypt depth) that persisted during the course of 5-fluorouracil chemotherapy. Treatment with KGF also afforded a 3.5-fold improvement in crypt survival in the small intestine, suggesting that KGF also has a direct effect on the crypt stem cells. These data indicate that KGF may be therapeutically useful to lessen the intestinal side effects of current cancer therapy regimens.
Animals↗
Molecular characterization of tobacco squalene synthase and regulation in response to fungal elicitor.
The enzyme squalene synthase (SS) represents the first commitment of carbon from the general isoprenoid pathway toward sterol biosynthesis and is a potential point for regulation of sterol biosynthesis. The isolation and characterization of tobacco (Nicotiana tabacum) squalene synthase (TSS) cDNA and genomic DNA clones, as well as determination of the steady state level of TSS mRNA in response to elicitor treatment, were investigated. cDNA clones for TSS were isolated from poly (A)+ RNA using a reverse transcription/polymerase chain reaction (RT/PCR) method. A 1233-bp cDNA clone was generated that contained an open reading frame of 411 amino acids giving a predicted molecular mass of 46.9 kDa. Comparison of the TSS deduced amino acid sequence with currently described SS from different species showed the highest identify with Nicotiana benthamiana (97%), followed by Glycyrrhiza glabra (81%), Arabidopsis thaliana (74%), rat (40%), and yeast (37%). Expression of a soluble form of the TSS enzyme with enzymatic activity in Escherichia coli was achieved by truncating 24 hydrophobic amino acids at the carboxy terminus. Characterization of genomic TSS (gTSS) revealed a gene of 7.086 kb with a complex organization of small exons and large introns not typical of plant genes. Southern blot hybridization indicated only two copies of the SS gene in the tobacco genome. Treatment of tobacco cell suspension cultures with a fungal elicitor dramatically reduced TSS enzymatic activity, lowering it to zero within 24 h. Analysis of TSS mRNA levels, by RNA blot hybridization and primer extension assays, in elicitor-treated cells indicated that the transcript level remained largely unchanged over this 24-h period. These results suggest that the suppression of TSS enzyme activity in elicitor-treated cells may result from a posttranscriptional modification of TSS.
Amino Acid Sequence↗
Keratinocyte growth factor decreases pulmonary edema, transforming growth factor-beta and platelet-derived growth factor-BB expression, and alveolar type II cell loss in bleomycin-induced lung injury.
Keratinocyte growth factor (KGF), a potent growth factor for type II pneumocytes and Clara cells, has been shown to prevent the end-stage pulmonary fibrosis and mortality in a rat model of bleomycin-induced lung injury. In this study, protective effects of KGF were explored during the earlier course of bleomycin-induced lung injury by studying protein exudation in alveolar edema fluids, pulmonary expression of transforming growth factor-beta (TGF beta) and platelet-derived growth factor-BB (PDGF-BB), and changes in type II pneumocytes and Clara cells after i.t. (intratracheal) bleomycin injection following KGF- or saline-pretreatment in rats. Total protein in bronchoalveolar lavage (BAL) fluids after bleomycin injury from KGF-pretreated rats was significantly lower than the levels in saline-pretreated rats. TGF beta protein in BAL fluids which peaked at day 3 after i.t. bleomycin in saline-pretreated lungs was not significantly increased at any time points in KGF-pretreated rats. PDGF-BB protein in whole lung tissues of KGF-pretreated rats also remained near normal throughout the course after i.t. bleomycin, in contrast to the significant increase in saline-pretreated rats. Numbers of type II pneumocytes and Clara cells in KGF-pretreated lungs after a high dose of bleomycin were close to the normal in intact lungs. At the same dose of bleomycin injury, type II pneumocytes in saline-pretreated lungs were markedly decreased, while the number of Clara cells in these rats was relatively preserved as the pre-injury level. In conclusion, KGF prevents bleomycin-induced end-stage pulmonary injury and mortality probably at least partly by decreasing protein-rich pulmonary edema, protein expression of fibrogenic cytokines TGF beta and PDGF-BB, and type II cell loss during the course of lung injury.
Animals↗
Increased aneusomy and long arm deletion of chromosomes 5 and 7 in the lymphocytes of Chinese workers exposed to benzene.
Two of the most common cytogenetic changes in therapy- and chemical-related leukemia are the loss and long (q) arm deletion of chromosomes 5 and 7. The detection of these aberrations in lymphocytes of individuals exposed to potential leukemogens may serve as useful biomarkers of increased leukemia risk. We have used a novel fluorescence in situ hybridization (FISH) procedure to determine if specific aberrations in chromosomes 1, 5 and 7 occur at an elevated rate in the blood cells of workers exposed to benzene. Forty-three healthy workers exposed to a wide range of benzene concentrations (median 31 p.p.m., 8 h time-weighted average) and 44 unexposed controls from Shanghai were studied. Whole blood was cultured and metaphase spreads were harvested at 72 h. Benzene exposure was associated with increases in the rates of monosomy 5 and 7 but not monosomy 1 (P < 0.001, P < 0.0001 and P = 0.94, respectively) and with increases in trisomy and tetrasomy frequencies of all three chromosomes. Long arm deletion of chromosomes 5 and 7 was increased in a dose-dependent fashion (P = 0.014 and P < 0.0001) up to 3.5-fold in the exposed workers. These results demonstrate that leukemia-specific changes in chromosomes 5 and 7 can be detected by FISH in the peripheral blood of otherwise healthy benzene-exposed workers. We suggest that aberrations in chromosomes 5 and 7 may be useful biomarkers of early biological effect for benzene exposure.
Adult↗
Hemoglobin and albumin adducts of benzene oxide among workers exposed to high levels of benzene.
Benzene oxide (BO) reacts with cysteinyl residues in hemoglobin (Hb) and albumin (Alb) to form protein adducts (BO-Hb and BO-Alb), which are presumed to be specific biomarkers of exposure to benzene. We analyzed BO-Hb in 43 exposed workers and 42 unexposed controls, and BO-Alb in a subsample consisting of 19 workers and 19 controls from Shanghai, China, as part of a larger cross-sectional study of benzene biomarkers. The adducts were analyzed by gas chromatography-mass spectrometry following reaction of the protein with trifluoroacetic anhydride and methanesulfonic acid. When subjects were divided into controls (n = 42) and workers exposed to < or =31 (n = 21) and >31 p.p.m. (n = 22) benzene, median BO-Hb levels were 32.0, 46.7 and 129 pmol/g globin, respectively (correlation with exposure: Spearman r = 0.67, P < 0.0001). To our knowledge, these results represent the first observation in humans that BO-Hb levels are significantly correlated with benzene exposure. Median BO-Alb levels in these 3 groups were 103 (n = 19), 351 (n = 7) and 2010 (n = 12) pmol/g Alb, respectively, also reflecting a significant correlation with exposure (Spearman r = 0.90, P < 0.0001). The blood dose of BO predicted from both Hb and Alb adducts was very similar. These results clearly affirm the use of both Hb and Alb adducts of BO as biomarkers of exposure to high levels of benzene. As part of our investigation of the background levels of BO-Hb and BO-Alb found in unexposed persons, we analyzed recombinant human Hb and Alb for BO adducts. Significant levels of both BO-Hb (19.7 pmol/g) and BO-Alb (41.9 pmol/g) were detected, suggesting that portions of the observed background adducts reflect an artifact of the assay, while other portions are indicative of either unknown exposures or endogenous production of adducts.
Benzene↗
Intravenous keratinocyte growth factor protects against experimental pulmonary injury.
Keratinocyte growth factor (KGF) administered by intratracheal instillation is well documented to stimulate the proliferation of alveolar and bronchial cells. In the present study, intravenous KGF was also shown to stimulate the proliferation of alveolar and bronchial cells in mice and rats, although to a lesser degree than intratracheal KGF. Despite the decreased potency of intravenous KGF on pulmonary cell 5-bromo-2'-deoxyuridine incorporation compared with intratracheal KGF, intravenous KGF was very effective in preventing experimental bleomycin-induced pulmonary dysfunction, weight loss, and mortality in either mice or rats and experimental hyperoxia-induced mortality in mice. The effectiveness of intravenous administration of KGF in preventing lung injury suggests that the mechanisms of the protective effect of KGF may involve more than pulmonary cell proliferation and also suggests the potential use of systemic KGF for clinical trials in settings of pulmonary injury.
Animals↗
[Study on expression of nm23-H1 protein/NDPK-A in laryngeal carcinoma].
To investigate the expression of nm23-H1 gene in laryngeal squamous cell carcinoma, immunohistochemistry was carried out with a monoclonal antibody against nm23-H1. Of 48 cancer tissues tested, 35(72.9%) showed a positive immuno-reaction for nm23-H1. The percentage of nm23-H1 positivity was significantly lower (P < 0.01) in the tumors with cervical lymph node metastasis than in those without metastasis. Moreover, the percentage of nm23-H1 positivity was significantly lower (P < 0.05) in tumors of stages III-IV than in those of stages I-II. No significant correlation was found between nm23-H1 expression and tumor sites or histopathological grades. Analyzed with following up date, we found that the overall survival was better (P < 0.01) in patients with nm23-H1 expression than in those without expression. These results suggest that nm23-H1 gene may play a role in the suppression of lymph node metastasis and tumor progression in laryngeal carcinoma, and the expression of nm23-H1 gene is a useful predictor of prognosis.
Adult↗
[Influence of pravastatin therapy on expression of P-selectin].
OBJECTIVE: To study the mechanism of pravastatin enhancing atherosclerosis regression. METHODS: Patients with hypercholesterolemia were treated with pravastatin 10-20 mg/d for 4 and 8 weeks. The changes of blood cholesterol and platelet functions were examined. RESULTS: After 4 weeks and 8 weeks treatment, the expression of platelet membrane P-selectin was decreased from 748 +/- 154 molecular number(MN)/platelet to 478 +/- 110 MN/platelet and 378 +/- 119 MN/platelet, respectively, plasma P-selectin was decreased from 24.3 +/- 9.9 micrograms/L to 16.8 +/- 4.5 and 16.1 +/- 4.0 micrograms/L, respectively, correlative with the lowering of blood cholesterol. Platelet P-selectin was positively correlated with plasma P-selectin(r = 0.8722). CONCLUSION: The early benefit of pravastatin in enhancing atherosclerosis regression was partly due to the improvement of platelet function.
Female↗
[Trans-ethmoidal optic nerve decompression in traumatic optic neuropathy].
UNLABELLED: To evaluate the outcome of trans-ethmoidal optic nerve decompression (TOND). METHOD: Between November 1984 and May 1996, 35 patients with traumatic optic neuropathy (TON) underwent TOND. While 6 patients were treated with high dose corticosteroids (HDC). RESULTS: 13(37.14%) cases of 35 patients who underwent TOND showed improvement in vision. 1 (16.67%) of 6 patients who were treated with HDC showed improvement in vision. Of the 12 patients with some initial vision, 8 patients underwent TOND and 7(87.5%) patients showed improvement in vision. Another 4 patients treated with HDC, 1(25.0%) patient showed improvement in vision. Of the 29 patients who presented with no light perception, 27 patients underwent TOND and 6(22.22%) patients showed improvement in vision. 2 patients treated with HDC failed to get vision improvement. CONCLUSION: TOND can improve vision in patients with TON. It is rational to perform surgical decompression early. Using of HDC before and after surgery may improve the outcome of TON. No light perception and absence of waveform on visual evoked response is not contradict, some patients may show improvement in vision.
Adolescent↗
Benzene poisoning, a risk factor for hematological malignancy, is associated with the NQO1 609C-->T mutation and rapid fractional excretion of chlorzoxazone.
Benzene is a ubiquitous occupational hematotoxin and leukemogen, but people vary in their response to this toxic agent. To evaluate the impact of interindividual variation in enzymes that activate (i.e., CYP2E1) and detoxify (i.e., NQO1) benzene and its metabolites, we carried out a case-control study in Shanghai, China, of occupational benzene poisoning (BP; i.e., hematotoxicity), which we show is itself strongly associated with subsequent development of acute nonlymphocytic leukemia and the related myelodysplastic syndromes (relative risk, 70.6; 95% confidence interval, 11.4-439.3). CYP2E1 and NQO1 genotypes were determined by PCR-RFLP, and CYP2E1 enzymatic activity was estimated by the fractional excretion of chlorzoxazone (fe(6-OH)) for 50 cases of BP and 50 controls. Subjects with both a rapid fe(6-OH). and two copies of the NQO1 609C-->T mutation had a 7.6-fold (95% confidence interval, 1.8-31.2) increased risk of BP compared to subjects with a slow fe(6-OH) who carried one or two wild-type NQO1 alleles. In contrast, the CYP2E1 PstI/RsaI polymorphism did not influence BP risk. This is the first report that provides evidence of human susceptibility to benzene-related disease. Further evaluation of susceptibility for hematotoxicity and hematological malignancy among workers with a history of occupational exposure to benzene is warranted.
Benzene↗
Regulation of sesquiterpene cyclase gene expression. Characterization of an elicitor- and pathogen-inducible promoter.
The promoter for a tobacco (Nicotiana tabacum) sesquiterpene cyclase gene, a key regulatory step in sesquiterpene phytoalexin biosynthesis, has been analyzed. The EAS4 promoter was fused to the beta-glucuronidase (GUS) reporter gene, and the temporal and spatial expression patterns of GUS activity were examined in stably transformed plants and in transient expression assays using electroporated protoplasts of tobacco. No GUS activity was observed in any tissues under normal growth conditions. A low level of GUS activity was detected in wounded leaf, root, and stem tissues, whereas a much higher level was observed when these tissues were challenged with elicitors or microbial pathogens. The GUS expression pattern directed by the EAS4 promoter was identical to the induction patterns observed for the endogenous sesquiterpene cyclase genes. Neither exogenous salicylic acid nor methyl jasmonate induced GUS expression; and H2O2 induced GUS expression to only a limited extent. Although the EAS4 promoter contains cis-sequences resembling previously identified transcriptional control motifs, other cis-sequences important for quantitative and qualitative gene expression were identified by deletion and gain-of-function analyses. The EAS4 promoter differs from previously described pathogen-/elicitor-inducible promoters because it only supports inducible gene expression and directs unique spatial expression patterns.
Acetates↗
[Toxicity and mutagenicity of mixed extracts from 7 kinds of natural plants].
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Animals↗
[A study on the mechanism of taurine postponing the aging process of human fetal brain neural cells].
The relationship between taurine and aging of brain neural cells was studied by using primary human fetal brain neural cells cultured in serum-free medium. The results indicated that the activity of superoxide dismutase (SOD) was significantly higher in taurine added group than the control group cultured for 6, 9 and 15 days (P < 0.05). With different taurine levels, the SOD activities of 50 mg/L and 200 mg/L taurine groups were significantly higher than the control group cultured for 6 days (P < 0.05). After 3-day culture, the activity of glutathione peroxidase (GSH-Px) in the taurine added group was significantly higher than the control group (P < 0.05). The membrane lipid fluidity of neural cells decreased with time in control group, but was stable in the group treated with taurine. The fluidity was more stable in the groups treated with 50, 200 and 400 mg/L groups cultured for 6 days, compared with the control group (P < 0.05 or 0.01). The present study showed that taurine is necessary for maintaining membrane lipid fluidity of neural cells in proper levels, and plays an important role in postponing the aging process of brain neural cells.
Brain↗
[A study on the relationship between bone mineral content and the tissue calcium level in rats].
The relationship of bone mineral density (BMD) and bone mineral content (BMC) of femur bone with the tissue and blood calcium contents was studied with 98 Wistar rats (15-week old). The results indicated that the body length, body weight, bone width, BMC, BMC/weight, BMD/weight and BMD/length in male were markedly different from those in female animals. The BMD of alive rats was significantly correlated with the total calcium intake, length, weight and calcium retention rate (P < 0.05). BMC was significantly related to sex, length, weight, liver calcium content and total calcium intake. Multiple regression analysis indicated that the animal body length, weight, total calcium intake and calcium content in heart were positively correlated with the BMD of alive animals. The animal body length and plasma calcium content were positively correlated with BMD of separated bones after the animals were sacrificed. The present results indicated that the BMC and BMD of alive rats could reflect the calcium status and bone mineral accumulation in the body because of the significant correlation with the growth rate, calcium retention rate, muscle and plasma calcium contents, but not with the separated bone BMD or BMC.
Animals↗
[Alkaloids in the seeds of Zyziphs jujuba Mill].
Two alkaloids were isolated from the seeds of Zyziphs jujuba and identified on the basis of spectral data to be lysicamine and juzirine. These two alkaloids were obtained from the genus for the first time.
Alkaloids↗
[Effects of selenium supplement on acute lower respiratory tract infection caused by respiratory syncytial virus].
An intervention study was conducted in 75 young children under one year hospitalized with pneumonia or bronchiolitis caused by respiratory syncytial virus (RSV) to evaluate therapeutic effectiveness of selenium (Se) supplement on acute respiratory lower tract infection caused by RSV with randomly controlled and double-masked method. Trial subjects were divided into two groups, one with 37 children in routine treatment and the other with 38 children in routine treatment plus Se supplement. The control group derived from 35 normal children during their physical check-up in the out-patient department. Sodium selenite was supplemented orally with 1 mg on the second day of hospitalization. Results showed that days needed for their relief of symptoms and signs were fewer in Se supplement group than that in controls and recovery in indicators of cell immune was better in the former than that in the latter. Levels of Se and glutathione peroxidase in plasma and white cells could be increased by Se supplement. It suggests that Se supplement can promote recovery from RSV infection.
Bronchiolitis, Viral↗