Effects of derivatives of sulfur dioxide on micronuclei formation in mouse bone marrow cells in vivo.
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Biomedical subjects
Publications and source records attributed to Z Meng.
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The 1-O-hexadecyl-2-O-methyl-sn-glyceryl phosphodiester AZT 4 and hexadecyl-phosphodiester AZT 5 derivatives were synthesized and found to be active against HIV-1, HIV-2, and tumor cell proliferation. Compared to AZT, compound 4 possessed ca. 10-fold lower anti-HIV activity and ca. 10-fold higher anti-tumor cell activity. Compound 5 was 10-fold less potent than compound 4 in both biological tests. In an attempt to correlate biological activity of compounds 4 and 5 with structure, their conformational and thermal effects on membrane bilayers were compared using a combination of NMR spectroscopy, computational analysis, and Differential Scanning Calorimetry. The obtained results showed that compound 4 adopts a compact conformation in which the alkyl chain, the 2-methoxyglyceryl functionality, and the methyl group of thymine are in spatial proximity, while analogue 5 possesses a less compact conformation of the nucleoside base and the alkyl chain. The presence of the 2-methoxyglyceryl group in compound 4 may augment its potency by inducing a turn of the alkyl chain stabilized by hydrophobic interactions. The DSC scans show that conjugate 4 affects less effectively the thermotropic properties of model membrane bilayers than compound 5. This may be attributed to the fact that compound 4 is incorporated in a compact conformation and does not perturb significantly the trans:gauche isomerization of the membrane phospholipids. In contrast, conjugate 5 may enter with a less compact conformation and perturb more the membrane bilayers.
Here we report the design, fabrication, and operation of a polymer-based microchip device interfaced to a nanoelectrospray ionization source and a Fourier transform ion cyclotron resonance mass spectrometer. The poly(methyl methacrylate) micromachined device was fabricated using X-ray lithography to produce a network of channels with high aspect ratios. Fabrication of high aspect ratio channels allows for zero dead volume interfaces between the microchip platform and the nanoelectrospray capillary interface. The performance of this device was evaluated with standard peptide and protein samples. High-quality mass spectral data from peptide and proteins (and mixtures thereof) were obtained without any interfering chemical noise from the polymer or the developers and plasticizers used in the fabrication process. Sample cross-contamination is not a problem using this polymer-based microchip device as demonstrated by the sequential analysis of several proteins. The nanoelectrospray source was operated at flow rates from 20 to 100 nL/min using pressure-driven flow, and uninterrupted operation for several hours is demonstrated without any noticeable signal degradation. The ability to fabricate multiple devices using injection molding or hot-embossing techniques of polymers provides a lower cost alternative to silica-based devices currently utilized with mass spectrometry.
Linkage and linkage disequilibrium tests are powerful tools for mapping complex disease genes. We investigated two approaches to identifying markers associated with disease. One method applied linkage analysis and then linkage disequilibrium tests to markers within linked regions. The other method looked for linkage disequilibrium with disease using all markers. Additionally, we investigated using Simes' test to combine p-values from linkage disequilibrium tests for nearby markers. We applied both approaches to all replicates of the Genetic Analysis Workshop 12 problem 2 isolated population data set. We reported results from the 25th replicate as if it were a real problem and assessed the power of our methods using all replicates. Using all replicates, we found that testing all markers for linkage disequilibrium with disease was more powerful than identifying markers that were in linkage with disease and then testing markers within those regions for linkage disequilibrium with the implementations that we chose. Using Simes' test to combine p-values for linkage disequilibrium tests on correlated markers seemed to be of marginal value.
Effect of five yellow compounds isolated from Quercus dentata on superoxide generation and protein phosphorylation in human neutrophils was investigated. The five yellow compounds examined were Kaempferol 3-O-beta-D-glucopyranoside (B), quercetin 3-O-beta-D-glucopyranoside (DA), Kaempferol 3-O-(6"-trans-p-coumaroyl)-beta-D-glucopyranoside (D1), Kaempferol 3-O-(2"-6"-di-trans-p-coumaroyl)-beta-D-glucopyranoside (D7) and Kaempferol 3-O-(2",4"-di-acetyl-3"-cis-p-coumaroyl-6"-trans-p-coumaroyl)-beta-D-glucopyranoside (A). D7 suppressed significantly the superoxide generation induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP). D1 and DA suppressed significantly the superoxide generation induced by arachidonic acid (AA). However, the superoxide generation induced by phorbol 12-myristate 13-acetate (PMA) was suppressed by all yellow compounds. When the cells were incubated with fMLP and D7, the tyrosyl phosphorylation of 67, 60, 58 and 38 kDa proteins of the cells was markedly decreased in a concentration-dependent manner.
OBJECTIVE: To reveal the distribution characteristics of serum lipids, lipoproteins, and apolipoproteins levels in different nationalities. METHODS: Quantitative levels of those traits mentioned above were determined and body height (H), weight (W) and body mass index (BMI = W/H2) were assessed in 773 Kazaks (men 360 and women 413) and 911 Han nationality (men 466 and women 445) from the Xinjiang Autonomous Region of China. RESULTS: Kazaks men and women, respectively, had significantly higher serum levels of HDL-c and ApoA1 (all P < 0.001) and significantly lower serum levels of TG (men P < 0.01, women P < 0.001), Lp(a) (all P < 0.005), ApoB (men P < 0.005, women P < 0.001) and ApoB/A1 (men P < 0.01, women P < 0.001) than their Han nationality controls. The threshold points of ApoA1 (< 1.2 g/L) and ApoB (> 1.2 g/L) are higher in Hans than in Kazaks for ApoA1 (20.7 vs 9.8%) and ApoB (18.6 vs 14.3%); the serum levels of TG, HDL-c, Lp(a), ApoA1 and ApoB/A1 are all closely correlated with nationality (P < 0.001, P = 0.001, and P < 0.05, respectively). CONCLUSION: The results suggest that the nationality differences exist in serum levels of lipids, lipoproteins, and apolipoproteins, and Kazaks have a superior serum lipid pedigree to Hans. This differences may come from genetic differences, which affect the serum levels of lipids, lipoproteins, and apolipoproteins by controlling lipid metabolism patterns. Future study will be needed to dissect to the role of genetic factors on serum lipids.
OBJECTIVE: To decrease the prevalence of blindness and low vision in Laiwu City. METHODS: The therapeutic effects and postoperative complications of each method of cataract surgery were investigated and statistically analyzed. The cases with postoperative complications were treated after surgery. RESULTS: In the investigation, 1,274 eyes of 1,089 cases had undergone cataract surgeries, including couching for cataract, intracapsular cataract extraction (ICCE), extracapsular cataract extraction (ECCE) and ECCE with intraocular lens implantation. The prevalence of blindness and low vision was 4.87% and 23.70%, respectively. There were postoperative complications in 650 eyes (51.02%). They were corneal decompensation, secondary glaucoma, opacity of posterior capsuler, cystoid macular edema and retinal detachment. After treatment for the postoperative complications, the prevalence of blindness and low vision was decreased to 1.96% and 6.01%, respectively. The cases having escaped the blindness and handicap after treatment were lowest in the groups of couching and ICCE. CONCLUSIONS: The survey on the population having undergone cataract surgery in rural district is important. The postoperative complications can be treated in time and the prevalence of blindness and low vision can be decreased.
In this paper, we describe the development and clinical application of the Rejuvenator and report the result of our study on its mechanism for the treatment of functional erectile dysfunction (FED). The Rejuvenator, which can be used both at home and in hospitals to treat patients with FED, was developed on the basis of our clinical practice in the light of the modern theory of traditional Chinese medicine and by integrating multiple techniques of engineering science. It works by means of the paraoral use of the special herbal medicine, electro-magnetic effects, thermal moxibustion and drug-ingression. 2250 patients with FED received the treatment. Using combined electro-neurophysiological techniques, pulsed ultrasound Doppler and microcomputer image-scanning, we further studied the mechanism of the Rejuvenator for the treatment of FED. The total effective rate was 92%. The clinical data and result of study indicate that the Rejuvenator for the patients with functional erectile dysfunction is a safe, effective and scientific new method.
The DNA-DNA homologies among Pseudomonas cocovenenans subsp. farinofermentans and 11 species in genus Burkholderia were determined with microdilution plate hybridization method. The results showed: the homologies among P. cocovenenans subsp. farinofermentans, B. gladioli and B. cocovenenans were all over 75%. It was advised that these three species were synonym, and should be renamed as Burkholderia gladioli.
We have reported that six steroidal saponins isolated from Anemarrhenae rhizoma had various effects on stimulus-induced superoxide generation in human neutrophils. In this paper, two novel steroidal saponins, timosaponins E1 and E2 were isolated from Anemarrhenae rhizoma, and the effects of these steroidal saponins on superoxide generation in human neutrophils were investigated. Timosaponins E1 and E2 significantly inhibited N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation in a concentration-dependent manner, but not that induced by arachidonic acid (AA). On the other hand, both compounds enhanced superoxide generation induced by phorbol 12-myristate 13-acetate (PMA) in a concentration-dependent manner. The superoxide generation induced by PMA with timosaponins E1 and E2 was suppressed by staurosporine, an inhibitor of protein kinase C, but was not suppressed by genistein, an inhibitor of protein tyrosine kinase. Tyrosyl phosphorylation of a 58 kDa protein, which was increased by fMLP, was inhibited by timosaponins E1 and E2. Timosaponins E1 and E2 also inhibited the generation of a 47 kDa protein and platelet aggregation in human blood. The results suggest that protein tyrosine kinase participates in fMLP-mediated superoxide generation by timosaponin E1- and E2-treated human neutrophils.
OBJECTIVE: To further survey the protective efficacy of the standard attenuated live hepatitis A vaccines (H(2) strain). METHODS: Randomized and controlled trials were performed in Fucheng county, Hebei province. A total of 12 036 children were assigned into vaccine group (5 551) and control group (6 485) by cluster sampling. The morbidity of hepatitis A was observed and the blood was collected once hepatitis A showed epidemic to detect anti-HAV IgG and IgM. RESULTS: During the period of the first 7 months after vaccination, hepatitis A was sporadic, the morbidity of hepatitis A was 0.55/100 000, and only 1 case occurred in the control group and no case in the vaccine group. From January to August 1998, hepatitis A showed epidemic in a township of this county. The morbidities were 0.37% and 6.69% for vaccine group and control group, respectively. The protective efficacy of the vaccine was 94.47%. The ratios of clinical cases to subclinical infections were 1 to 11 and 1 to 1 for vaccine and control groups, respectively (P < 0.05). CONCLUSION: The H(2) strain vaccine has a very good protective efficacy, and obviously decreases the attack rate, new infection rate and clinical cases by HAV infection.
OBJECTIVE: To study the immunology effects of live attenuated hepatitis A vaccine in different doses and schedules groups, and compare with inactivated hepatitis A vaccine (Havrix, Smithkline). METHODS: 318 susceptible children were enrolled in Guangxi and Hebei province. These subjects were divided into six groups. Each group was vaccinated with either inactivated vaccine or different doses and schedules of live attenuated vaccine. Serum specimens were collected and tested for anti-HAV antibody at different time after the vaccination. RESULTS: GMT of each group arrived at the peak 1 months after re-vaccination, then declined, and GMT of 6 months after booster dose was still significantly higher than that after primary immunization. Sero-conversion rates in all groups reached 100% after a booster dose, and kept at 6 months after booster dose. CONCLUSIONS: A booster dose of live attenuated vaccine can induce secondary immune response well. The immunology effects after booster dose are comparable with inactivated vaccine and it should be useful to the immune persistence.
OBJECTIVE: To investigate the protective efficacy of H(2) strain live attenuated hepatitis A vaccine (H(2)-strain vaccine) locally produced in an outbreak of hepatitis A (HA). METHODS: A nonrandomized controlled design was used in a trial for HA vaccination. Five thousand five hundred and fifty-one children at preschool classes and at grades 1 - 3 of primary schools were selected in 14 villages. Epidemiological and serological methods were used to evaluate its protective efficacy of the vaccines and serum immunoglobulin M against hepatitis A virus (IgM anti-HAV) was detected with ELISA for 271 subjects in vaccinated group and 341 in the control one. RESULTS: An outbreak of HA occurred one year after the vaccination with 26 cases in the vaccinated group, including one vaccine-related case with an attack rate of 0.28% (1/356), and 25 cases in the control group with an attack rate of 5.92% (25/422). The protective efficacy of vaccines was 95.27% (95% confidence interval of 85.83% to 104.72%). Positivity of IgM anti-HAV, i.e., newly-infected cases, was 4.43% (12/271) in the vaccinated group and 13.38% (42/314) in the control group, respectively. Clinically apparent cases accounted for 8.33% (1/12) and 50.00% (21/42) in newly-infected cases in vaccinated and control groups, respectively. CONCLUSION: Vaccination with H(2) strain vaccines locally produced was effective in reducing occurrence of HA during its outbreak, but not so effective in preventing its infection. A booster dose of HA vaccine should be vaccinated for children in adequate time.
OBJECTIVE: To evaluate the effects of Pinyangmycin, Dexamethasonum and Sodium morrhuate injected homochronouly on treatment of cavernous hemangioma in maxillofacial regions. METHODS: The medical records of 115 patients with cavernous hemangioma in maxillofacial regions between September, 1996 and September, 1998 were reviewed. Fifty of the patients were men, and 65 were women, with a ratio of 1:1.3. The age of the patients was from 4 months old to 45 years old. 73 of the hemangioma bodies were sited in maxillofacial regions, 42 were sited in oral cavity. The sizes of the lesions varied from 1 cm x 1 cm to 5 cm x 8 cm. Treatment procedure: 1. Preparation: 8 mg Pinyangmycin was dissolved in 5 mg/ml Dexamethasonum and in 4 ml of 1% procain which were ready for use; 2. Injection: 1-5 ml (Pinyangmycin 1.6-8.0 mg) of mixed solution was first injected to the hemangioma, then followed by an injection of 0.5-2.0 ml Sodium morrhuate according to local appearance, size of the tumor and patient's age. Generally, the amount of each injection should not be over 8 mg Pinyangmycin. If the tumor did not subside after an injection, another injection might be repeated every 5-7 days, and this process might be repeated 3-5 times. The total dose of Pinyangmycin should not be over 40 mg. RESULTS: 115 patients were followed up for 6-24 months. 81 of 115 (70.43%) cases were recovered, and 30 (26.09%) cases were basically recovered. 4 (3.48%) cases got improvement. The recovery rate were 96.52%, and the total efficiency was 100%. CONCLUSION: This method may be a safe, simple and effective therapy to cavernous hemangioma in maxillofacial regions.
Effect of six steroidal saponins isolated from Anemarrhenae rhizoma on superoxide generation in human neutrophils was investigated. The steroidal saponins examined were anemarrhenasaponin-I (An-I), anemarrhenasaponin-Ia (An-Ia), timosaponin B-I (TB-I), timosaponin B-II (TB-II), timosaponin B-III (TB-III) and timosaponin A-III (TA-III). An-I, An-Ia, and TB-III suppressed the superoxide generations induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP) and arachidonic acid (AA) in a concentration-dependent manner, but enhanced that induced by phorbol 12-myristate 13-acetate (PMA). While TB-II also suppressed and enhanced the superoxide generations induced by fMLP and PMA, respectively, the compound significantly enhanced the AA-induced superoxide generation. TB-I enhanced the fMLP-induced superoxide generation in a low concentration range (peak at 40 microM), gave no effect on the PMA-induced superoxide generation and weakly enhanced the AA-induced superoxide generation. TA-III enhanced the fMLP-induced superoxide generation more than twice as much as that by TB-I in the same concentration range. However, TA-III enhanced the PMA-induced superoxide generation and most significantly suppressed the AA-induced superoxide generation.
The marine natural product hapalosin and 22 analogs, which incorporated systematic substituent deletions or variations, were prepared. These compounds were evaluated in a cell-based assay for both MDR-reversing activity and general cytotoxicity. Some substituent modifications resulted in lower cytotoxicities, but most structural changes were either detrimental to or did not seriously alter the MDR-reversing activity.
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Anandamide amidohydrolase (AAH) catalyzes the hydrolysis of arachidonylethanolamide (anandamide), an endogenous cannabinoid receptor ligand. To delineate the structural requirements of AAH substrates, rat brain microsomal AAH hydrolysis of a series of anandamide congeners was studied using two reverse-phase high-performance liquid chromatography (RP-HPLC) assays developed in our laboratory. Arachidonamide (1) was found to be the best substrate with an apparent Km of 2.34 mM and a Vmax of 2.89 nmol/min/mg of protein. Although anandamide (2) has a similar Km value, its Vmax is approximately one-half that of arachidonamide. N, N-Bis(2-hydroxyethyl)arachidonamide (3) was not hydrolyzed, suggesting specificity for unsubstituted or mono-N-substituted arachidonamides. Analogues with a methyl group at the 1'-position of the ethanolamido headgroup were also found to have greater resistance to enzymatic turnover and therefore increased metabolic stability. The enzyme exhibited high stereoselectivity as the rate of hydrolysis of (R)-alpha-methanandamide (2.4%) (anandamide = 100%) was about 10-fold lower than that of its (S)-enantiomer (23%). In contrast, (R)-beta-methanandamide was 6-times more susceptible (121%) than the (S)-beta-enantiomer (21%). Interestingly, an inverse correlation was shown between AAH stereoselectivity and the brain cannabinoid receptor affinity as the enantiomers with high receptor affinity displayed low susceptibility to hydrolysis by AAH. Metabolic stability is also imparted to analogues with a short hydrocarbon headgroup as well as to those possessing 2-monomethyl or 2,2-dimethyl substituents. 2-Arachidonylglycerol and racemic 1-arachidonylglycerol were shown to be excellent AAH substrates. To identify AAH inhibitors, hydrolysis of anandamide was also studied in the presence of a select group of cannabimimetics. Of these, (-)-Delta8-THC and SR141716A, a biarylpyrazole CB1 antagonist, were found to inhibit enzymatic activity. These newly defined enzyme recognition parameters should provide a foundation for the rational development of stable, therapeutically useful anandamide analogues with high receptor affinity.