Search PubMed⌕ Search

Biomedical subjects

Min Huang

Publications and source records attributed to Min Huang.

At least 37 records · Page 2Linked to original sources
PubMed2006

Relationship of glutathione S-transferase genotypes with side-effects of pulsed cyclophosphamide therapy in patients with systemic lupus erythematosus.

AIMS: Cyclophosphamide (CTX) is an established treatment of severe systemic lupus erythematosus (SLE). Cytotoxic CTX metabolites are mainly detoxified by multiple glutathione S-transferases (GSTs). However, data are lacking on the relationship between the short-term side-effects of CTX therapy and GST genotypes. In the present study, the effects of common GSTM1, GSTT1, and GSTP1 genetic mutations on the severity of myelosuppression, gastrointestinal (GI) toxicity, and infection incidences induced by pulsed CTX therapy were evaluated in patients SLE. METHODS: DNA was extracted from peripheral leucocytes in patients with confirmed SLE diagnosis (n = 102). GSTM1 and GSTT1 null mutations were analyzed by a polymerase chain reaction (PCR)-multiplex procedure, whereas the GSTP1 codon 105 polymorphism (Ile-->Val) was analyzed by a PCR-restriction fragment length polymorphism (RFLP) assay. RESULTS: Our study demonstrated that SLE patients carrying the genotypes with GSTP1 codon 105 mutation [GSTP1*-105I/V (heterozygote) and GSTP1*-105 V/V (homozygote)] had an increased risk of myelotoxicity when treated with pulsed high-dose CTX therapy (Odds ratio (OR) 5.00, 95% confidence interval (CI) 1.96, 12.76); especially in patients younger than 30 years (OR 7.50, 95% CI 2.14, 26.24), or in patients treated with a total CTX dose greater than 1.0 g (OR 12.88, 95% CI 3.16, 52.57). Similarly, patients with these genotypes (GSTP1*I/V and GSTP1*V/V) also had an increased risk of GI toxicity when treated with an initial pulsed high-dose CTX regimen (OR 3.33, 95% CI 1.03, 10.79). However, GSTM1 and GSTT1 null mutations did not significantly alter the risks of these short-term side-effects of pulsed high-dose CTX therapy in SLE patients. CONCLUSIONS: The GSTP1 codon 105 polymorphism, but not GSTM1 or GSTT1 null mutations, significantly increased the risks of short-term side-effects of pulsed high-dose CTX therapy in SLE patients. Because of the lack of selective substrates for a GST enzyme phenotyping study, timely detection of this mutation on codon 105 may assist in optimizing pulsed high-dose CTX therapy in SLE patients.

Adult↗
PubMed2006

Influences of 3-methylcholanthrene, phenobarbital and dexamethasone on xenobiotic metabolizing-related cytochrome P450 enzymes and steroidogenesis in human fetal adrenal cortical cells.

AIM: To explore the influence and possible mechanism of xenobiotics on adrenal steroidogenesis during fetal development. METHODS: Primary human fetal adrenal cortical cells were prepared, cultured and treated with 3-methylcholanthrene, phenobarbital and dexamethasone. The activities of 7-ethoxyresorufin O-dealkylase, benzphetamine, aminopyrine and erythromycin N-demethylases were measured by enzyme assays. At the same time, quantitative analysis of steroid hormones cortisol, aldosterone, testosterone and progesterone were carried out in cultural medium by radioimmunoassays. RESULTS: The activities of benzphetamine and aminopyrine N-demethylase were increased in the cultural fetal adrenal cells treated with phenobarbital (0.25-1 mmol/L) for 24 h. Dexamethasone (25-100 micromol/L) also increased the activity of erythromycin N-demethylase. The activity of 7-ethoxyresorufin O-dealkylase was undetected in the cells treated without and with 3-methylcholanthrene (0.5-2 micromol/L). Meanwhile, the contents of medium cortisol, aldosterone and progesterone were decreased after treatment with 3-methylcholanthrene. Cortisol, aldosterone and progesterone concentrations were also slightly decreased with phenobarbital. Dexamethasone enhanced the productions of cortisol and progesterone remarkably. The trend of testosterone concentration was uncertain after 3-methylcholanthrene, phenobarbital or dexamethasone treatment. CONCLUSION: 3-Methylcholanthrene, phenobarbital or dexamethasone could interfere with the synthesis of cortisol, aldosterone and progesterone in primary human fetal adrenal cortical cells, which likely act through xenobiotic metabolizing-related cytochrome P450 isoform activation.

Adrenal Cortex↗
PubMed2006

[Cytogenetics and application in domesticated silkworm Bombyx mori].

Chromosome identification and karyotype analyses of Bombyx mori (Lepidoptera) have long been hampered by the high number and the absence of suitable markers, such as centromeric position and chromosome bands. Recently, the cytological map has been constructed using comparative genomic hybridization-genomic in situ hybridization and BAC-based fluorescence in situ hybridization. Dense cytogenetic maps are being constructed by integrating cytological map with molecular linkage maps. Molecular and cytogenetics will help us to reveal the structure and function of chromosome of Bombyx mori, the W chromosome is composed largely of dense nested retrotransposons, and telomeres are consist of the TTAGG motifs and two type of telomere-specific non-LTR retrotransposons (TRAS1 and SART1), the TRAS1 and SART1 with abundant transcription activity may be involved in the stabilization of chromosomal ends.

Animals↗
PubMed2006

Topotecan is a substrate for multidrug resistance associated protein 4.

Topotecan (TPT) is a semisynthetic water-soluble derivative of camptothecin (CPT) used as second-line therapy in patients with metastatic ovarian carcinoma, small cell lung cancer, and other malignancies. However, both dose-limiting toxicity and tumor resistance hinder the clinical use of TPT. The mechanisms for resistance to TPT are not fully defined, but increased efflux of the drug by multiple drug transporters including P-glycoprotein (PgP), multidrug resistance associated protein 1 (MRP1) and breast cancer resistance protein (BCRP) from tumor cells has been highly implicated. This study aimed to investigate whether overexpression of human MRP4 rendered resistance to TPT by examining the cytotoxicity profiles using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazonium bromide (MTT) assay and cellular accumulation of TPT in HepG2 cells stably overexpressing MRP4. Two kinds of cell lines, HepG2 with insertion of an empty vector plasmid (V/HepG2), HepG2 cells stably expressing MRP4 (MRP4/HepG2), were exposed to TPT for 4 or 48 hr in the absence or presence of various MRP4 inhibitors including DL-buthionine-(S,R)-sulphoximine (BSO), diclofenac, celecoxib, or MK-571. The intracellular accumulation of TPT and paclitaxel (a PgP substrate) by V/HepG2 and MRP4/HepG2 cells was determined by incubation of TPT with the cells and the amounts of the drug in cells were determined by validated HPLC methods. The study demonstrated that MRP4 conferred a 12.03- and 6.86-fold resistance to TPT in the 4- and 48-hr drug-exposure MTT assay, respectively. BSO, MK-571, celecoxib, or diclofenac sensitised MRP4/HepG2 cells to TPT cytotoxicity and partially reversed MRP4-mediated resistance to TPT. In addition, the accumulation of TPT was significantly reduced in MRP4/HepG2 cells compared to V/HepG2 cells, and one-binding site model was found the best fit for the MRP4-mediated efflux of TPT, with an estimated K(m) of 1.66 microM and V(max) of 0.341 ng/min/106 cells. Preincubation of MRP4/HepG2 cells with BSO (200 microM) for 24 hr, celecoxib (50 microM), or MK-571 (100 microM) for 2 hr significantly increased the accumulation of TPT over 10 min in MRP4/HepG2 cells by 28.0%, 37.3% and 32.5% (P < 0.05), respectively. By contrast, there was no significant difference in intracellular accumulation of paclitaxel in V/HepG2 and MRP4/HepG2 cells over 120 min. MRP4 also rendered resistance to adefovir dipivoxil (bis-POM-PMEA) and methotrexate, two reported MRP4 substrates. MRP4 did not exhibit any significant resistance to other model drugs including vinblastine, vincristine, etoposide, carboplatin, cyclosporine and paclitaxel in both long (48 hr) and short (4 hr) drug-exposure MTT assays. These findings indicate that MRP4 confers resistance to TPT and TPT is the substrate for MRP4. Further studies are needed to explore the role of MRP4 in resistance to, toxicity and pharmacokinetics of TPT in cancer patients.

Antineoplastic Agents↗
PubMed2006

Pharmacokinetic mechanisms for reduced toxicity of irinotecan by coadministered thalidomide.

The clinical use of irinotecan (CPT-11) is hindered by dose-limiting diarrhea and myelosuppression. Recent clinical studies indicate that thalidomide, a known tumor necrosis factor-alpha inhibitor, ameliorated the toxicities induced by CPT-11. However, the mechanisms for this are unknown. This study aimed to investigate whether combination of thalidomide modulated the toxicities of CPT-11 using a rat model and the possible role of the altered pharmacokinetic component in the toxicity modulation using in vitro models. The toxicity model was constructed by treatment of healthy rats with CPT-11 at 60 mg/kg per day by intravenous (i.v.) injection. Body weight, acute and delayed-onset diarrhea, blood cell counts, and macroscopic and microscopic intestinal damages were monitored in rats treated with CPT-11 alone or combined therapy with thalidomide at 100 mg/kg administered by intraperitoneal (i.p.) injection. Single dose and 5-day multiple-dose studies were conducted in rats to examine the effects of concomitant thalidomide on the plasma pharmacokinetics of CPT-11 and its major metabolites SN-38 and SN-38 glucuronide (SN-38G). The effect of CPT-11 on thalidomide's pharmacokinetics was also checked. Rat liver microsomes and a rat hepatoma cell line, H4-II-E cells, were used to study the in vitro metabolic interactions between these two drugs. H4-II-E cells were also used to investigate the effect of thalidomide and its hydrolytic products on the transport of CPT-11 and SN-38. In addition, the effect of thalidomide and its hydrolytic products on rat plasma protein binding of CPT-11 and SN-38 was examined. Administration of CPT-11 by i.v. for 4 consecutive days to rats induced significant body weight loss, decrease in neutrophil and lymphocyte counts, severe acute- and delayed-onset diarrhea, and intestinal damages. These toxicities were alleviated when CPT-11 was combined with thalidomide. In both single-dose and 5-day multiple-dose pharmacokinetic study, coadministered thalidomide significantly increased the area under the plasma concentration-time curve (AUC) of CPT-11, but the AUC and elimination half-life (t(1/2)) of SN-38 were significantly decreased. However, CPT-11 did not significantly alter the pharmacokinetics of thalidomide. Thalidomide at 25 and 250 microM and its hydrolytic products at a total concentration of 10 microM had no significant effect on the plasma protein binding of CPT-11 and SN-38, except for that thalidomide at 250 microM caused a significant increase in the unbound fraction (f(u)) of CPT-11 by 6.7% (P < 0.05). The hydrolytic products of thalidomide (total concentration of 10 microM), but not thalidomide, significantly decreased CPT-11 hydrolysis by 16% in rat liver microsomes (P < 0.01). The formation of both SN-38 and SN-38G from CPT-11, SN-38 glucuronidation, or intracellular accumulation of both CPT-11 and SN-38 in H4-II-E cells followed Michaelis-Menten kinetics with the one-binding site model being the best fit for the kinetic data. Coincubation or 2-hr preincubation of thalidomide at 25 microM and 250 microM and its hydrolytic products at 10 microM did not show any significant effects on CPT-11 hydrolysis and SN-38 glucuronidation. However, preincubation of H4-II-E cells with thalidomide (250 microM), its hydrolytic products (total concentration of 10 microM), or phthaloyl glutamic acid (one major thalidomide hydrolytic product, 10 microM) significantly increased the intracellular accumulation of SN-38, but not CPT-11 (P < 0.01). The dose-limiting toxicities of CPT-11 were alleviated by combination with thalidomide in rats and the pharmacokinetic modulation by thalidomide may partially explain its antagonizing effects on the toxicities of CPT-11. The hydrolytic products of thalidomide, instead of the parental drug, modulated the hepatic hydrolysis of CPT-11 and intracellular accumulation of SN-38, probably contributing to the altered plasma pharmacokinetics of CPT-11 and SN-38. Further studies are needed to explore the role of both pharmacokinetics and pharmacodynamic components in the protective effect of thalidomide against the toxicities of CPT-11.

Angiogenesis Inhibitors↗
PubMed2006

Medicinal chemistry of probimane and MST-16: comparison of anticancer effects between bisdioxopiperazines.

Bisdioxopiperazines, including ICRF-154 and razoxane (ICRF-159, Raz), are a family of anticancer agents developed in the UK, specifically targeting neoplastic metastases. Two other bisdioxopiperazine derivatives, probimane (Pro) and MST-16, were synthesized at the Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. In order to determine the similarities and differences between these agents in medical chemistry, we evaluated the anti-tumor and anti-metastatic effects of Pro and MST-16 in vitro and in vivo against a number of human tumor cell lines and one of murine origin (Lewis lung carcinoma, LLC), and one human tumor xenograft (LAX-83) in nude mice. Our results show that Pro was cytotoxic to human tumor cell lines in vitro (IC50 < 50 microM for 48 h), approximately 3 to 20-fold more than MST-16. Pro and MST-16 manifested more prolonged cytotoxicity than some other first-line anticancer drugs including 5-fluorouacil, vincristine and doxorubicin, and maintain their cytotoxic effects for 4 days in vitro. In animal experiments, Pro and Raz were active against primary tumor growth (35-50 %) and significantly inhibited pulmonary metastasis of LLC (inhibition > 90 %) at dosage below LD(5). Both Raz and Pro were effective in administration schedules of 1, 5 and 9 days. Both Raz (25-32 %) and Pro (55-60 %) caused statistically significant inhibition of the growth of LAX 83 (a human lung adeno-carcinoma xenograft) in nude mice. In this model, Pro was more effective against LAX83 than Raz at equitoxic dosages. These findings suggest that Pro is active against more categories of tumors both in vivo and in vitro, which in some circumstances may make it superior to the currently-used anticancer bisdioxopiperazines, including razoxane and MST-16.

Animals↗
PubMed2006

Epidemiologic pictures of Kawasaki disease in Shanghai from 1998 through 2002.

BACKGROUND: Epidemiologic features of Kawasaki disease in China is still not clear. METHODS: A questionnaire form and diagnostic guidelines for Kawasaki disease were sent to hospitals in Shanghai, which provided with pediatric medical care. All patients with Kawasaki disease diagnosed during January 1998 through December 2002 were recruited in this study. RESULTS: A total of 768 patients with Kawasaki disease were reported. The incidence rates of Kawasaki disease for each year were 16.79 (1998), 25.65 (1999), 28.16 (2000), 28.05 (2001), and 36.76 (2002) per 100,000 children under 5 years of age. The male/female ratio was 1.83:1. The age at onset ranged from 1 month to 18.8 years (median: 1.8 years). The disease occurred more frequently in spring and summer. Fever was the most common clinical symptom, followed by oral changes, extremities desquamate, rash, conjunctive congestion, lymphadenopathy, extremities swelling, and crissum desquamate. Cardiac abnormalities were found in 24.3% of patients. The most common cardiac abnormality was coronary artery lesions including dilatation (68%) and aneurysm (10%). The case-fatality rate at acute stage of the disease was 0.26%. A second onset of the disease occurred in 1.82% of patients. CONCLUSIONS: The incidence rate of Kawasaki disease in Shanghai is lower than that reported in Japan, but higher than those in western countries. The increasing trend in incidence, sex distribution and cardiac abnormalities are similar to those in previous reports. The seasonal distribution is similar to the report from Beijing and different from other reports.

Adolescent↗
PubMed2006

Involvement of ALF in human spermatogenesis and male infertility.

We conducted this study to explore functions of TF II Aalpha/beta-like factor (ALF) during human spermatogenesis, and the relationship of its expression levels with male infertility. The RT-PCR and Western blot analyses illustrated that ALF was highly expressed in adult testis. Immunohistochemistry and immunoflurescence showed that ALF is located in the spermatid nuclei and in the annulus of spermatozoa. Further, to reveal whether ALF is related to male infertility, we performed the same experiments in infertility patients. The changes in the expression levels of ALF in the male infertility samples lead us to believe that ALF may function in spermatogenesis, especially in spermiogenesis. We also detected the ALF DNA methylation level by real-time methylation-specific PCR (MSP) both in testes of adult, fetal and infertile patient. The differential expression level of ALF gene in different types of testes was regulated by DNA methylation. Our research identified ALF as a human spermatogenesis related gene, the abnormal expression of ALF might be the partial cause for human infertility.

Gene Expression Profiling↗
PubMed2006

Performance of balance impaired elders on three balance tests under two visual conditions.

PURPOSE: This study compared differences in balance measures among elderly adults with different degrees of balance impairments under different visual conditions. METHODS: This study was conducted on 89 adults (> 60 years) with balance impairments. Subjects were divided into 3 groups based on the initial Tinetti score: low risk of fall (LRF, n=29), moderate risk of fall (MRF, n=30) and high risk of fall (HRF, n=30). Three balance measures-Tinetti, Timed-up and Go (TUG), and Functional Reach-were tested with 2 different visual conditions: eyes open with normal vision (EONV) and eyes open with blurred vision (EOBV). All data were analyzed using repeated measures analysis of variance. RESULTS: Subjects with EOBV had significantly decreased Tinetti (P < .01 ) and Functional Reach (P < .01 ) scores and increased TUG (P < .01 ) scores regardless of fall group. Subjects in the LRF group performed better in all 3 tests than those in MRF (P < .01 ) and HRF (P < .01 ) groups. Subjects in the MRF group performed better in all 3 tests than those in HRF (P < .01 ). There were significant interactions between vision and risk of falls in Tinetti (P < .01 ) and TUG (P < .01 ) scores. However, there was no significant interaction between vision and risk of falls in Functional Reach (P > .05) scores. CONCLUSION: Blurred vision significantly altered all 3 balance measure scores in all risk groups. However, blurred vision had a greater influence on Tinetti and TUG scores than Functional Reach scores in subjects with higher risk of falls.

Accidental Falls↗
PubMed2006

[An on-the-spot sampling and survey method for soil nutrient cycling study].

In this paper, an on-the-spot sampling and survey method for studying the soil nutrient cycling in a regional scale was discussed, with considering the principles of representation, reproducibility, randomness and timeliness. Firstly, some representative sampling areas in a definite region should be selected, based on the relevant hypsographic maps and airscapes. During the course of sampling soil and plant, a field survey related to the sampling sites should be carried out to understand the natural affecting factors on the soil nutrient cycling in a regional agro-ecosystem scale. Moreover, the farmers' basic status, crop production, and applied amount of fertilizers and their allotment should be also investigated. A case study of nutrient cycling in subtropical regions of China was carried out to approach the application of the method in the study of soil nutrient cycling in some regions.

Crops, Agricultural↗
PubMed2006

[Single-trial estimation of visual evoked potentials in single channel single-trial estimation].

We constructed a Brain-computer interface-based mental speller which realizes user-computer interaction. The feature signals of user's intention are embedded in spontaneous EEG background. Single-trial feature estimation should be used on this online occasion instead of the grand average usually used in cognitive or clinical experiments. To demonstrate this technique beyond laboratories, fewer EEG recording channels are preferred. A unique paradigm, which is called imitating-natural-reading, was exploited to induce visual evoked potentials. We explored the single-trial estimation of VEP recorded in single channel using support vector machine on three subjects, and obtained satisfactory data, the classification accuracy being 92.1%, 94.1% and 91.5%, respectively. These results put forward a significant step fowards the ultimate realization of our mental speller.

Adult↗
PubMed2006

[Association of psychological factors with post-partum hemorrhage and labor duration].

OBJECTIVE: To investigate the impact of psychological factors on post-partum hemorrhage and labor duration. METHODS: A questionnaire-based investigation was conducted in 180 healthy single-fetus spontaneous delivery primigravida to understand their psychological status and related factors, and the duration of labor and postpartum hemorrhage were recorded. RESULTS: Anxiety and depression were common in pregnant women and positively related to age, profession, education and social support. The scores of SAS and SDS of postpartum hemorrhage-free group were significantly lower than those in postpartum hemorrhage group, and the duration of first and the second stage was significantly longer in women with high SAS and SDS score than in those with lower scores. CONCLUSIONS: The mental health status of pregnant women may vary significantly depending on the social community they belong to. Anxiety and depression may increase the risk of postpartum hemorrhage and prolonged labor, so that psychological counseling can be of importance to improve the care in the department of obstetrics.

Adult↗
PubMed2006

[The profile and clinical significance of azathioprine metabolic enzymes activity in rheumatological patients].

OBJECTIVE: To detect the activity of thiopurine methyltransferase (TPMT) and its relationship with azathioprine (AZA) tolerance. METHODS: 200 patients of rheumatism need AZA were included in the study. RBC TPMT activity was detected with high performance liquid chromatography. Then the patients took AZA doses of 50 mg/d for the first month, 100 mg/d for the second month and 150 mg/d for the third month. RESULTS: TPMT activity of 200 patients ranged from 0.75 - 32.35 U/ml RBC, averaged (12.04 +/- 6.90) U/ml RBC. The activity of TPMT showed a normal skewness distribution and no activity deficiency was founded. 194 patients (97%) completed the 3 month follow-up. 18 showed bone marrow depression including 2 severe hematological crisis and 6 showed hepatic damage during the 3 months. Bone marrow depression was recorded of 7 cases with the TPMT activity of 2.24 - 5.97 U/ml RBC, averaged (3.47 +/- 1.21) U/ml RBC, among the dose of 50 mg/d and 11 cases with the TPMT activity of 4.01 - 11.17 U/ml RBC, averaged (7.08 +/- 2.58) U/ml RBC, among the dose of 100 - 150 mg/d. The other 176 cases did not show bone marrow depression at all, with TPMT activity of 4.47 - 32.35 U/ml RBC, averaged (13.02 +/- 6.07) U/ml RBC. TPMT activities in the 3 groups of patients were significantly different according to statistical analysis (P < 0.01). CONCLUSIONS: Hematological side effects were highly associated with TPMT activity in AZA usage. Patients with low TPMT activity should use low dose of AZA routinely, even though, toxicity may occur. Test of TPMT activity before AZA description was of significance.

Adolescent↗
PubMed2006

[Nitrogen stress measurement of canola based on multi-spectral charged coupled device imaging sensor].

Site-specific variable nitrogen application is one of the major precision crop production management operations. Obtaining sufficient crop nitrogen stress information is essential for achieving effective site-specific nitrogen applications. The present paper describes the development of a multi-spectral nitrogen deficiency sensor, which uses three channels (green, red, near-infrared) of crop images to determine the nitrogen level of canola. This sensor assesses the nitrogen stress by means of estimated SPAD value of the canola based on canola canopy reflectance sensed using three channels (green, red, near-infrared) of the multi-spectral camera. The core of this investigation is the calibration methods between the multi-spectral references and the nitrogen levels in crops measured using a SPAD 502 chlorophyll meter. Based on the results obtained from this study, it can be concluded that a multi-spectral CCD camera can provide sufficient information to perform reasonable SPAD values estimation during field operations.

Agriculture↗
PubMed2006

[Effects of land use type on soil organic carbon, total nitrogen, and microbial biomass carbon and nitrogen contents in Karst region of South China].

A total of 721 surface (0-20 cm) soil samples were collected from the paddy field, upland, and woodland in the Karst region of Dacai, Huanjiang County, Guangxi Province, and the contents of their organic carbon (Oc ), total nitrogen (TN), microbial biomass carbon (Bc) , and microbial biomass nitrogen (BN) were determined. The results showed that the Oc and BN contents and soil pH value showed the trend of paddy field = woodland > upland, while TN and Bc contents had the trend of woodland > paddy field > upland. There was a significant positive correlation between Bc and Oc, and between B5 and TN. Soil microbial biomass C and N had rapid responses to the changes of land use type, which could be used as the sensitive biological indicators in evaluating soil quality and fertility in Karst region.

Agriculture↗
PubMed2005

A novel strategy to identify the regulatory DNA-organized cooperations among transcription factors.

To identify the functional contributions of cooperations among transcription factors on regulatory DNA is critical for understanding transcription activation. But so far there is a great lack of effective identifying methods. Here we describe a novel strategy, based on comprehensively perturbed experiments and a computational model, to identify the cooperations among NF-kappaB (p65), CREB, and AP-1 in transcription activation of human cytomegalovirus major IE1 promoter/enhancer (MIEP). In this strategy, functional profiles of protein-MIEP association and RNA synthesis are achieved through comprehensively perturbing the association of p65, CREB or AP-1 with MIEP and then subjected to the computational model. Consequently, the 'real' cooperations contributing to MIEP activation are found to comprise five but not seven types of potential cooperations. Thus, our research provides a facile systematic approach to identifying the DNA-organized cooperations among transcription factors and understanding transcription activation.

Cyclic AMP Response Element-Binding Protein↗
PubMed2005

Metal mediated inhibition of methionine aminopeptidase by quinolinyl sulfonamides.

Quinolinyl sulfonamides, such as N-(quinolin-8-yl)methanesulfonamide (10) and N-(5-chloroquinolin-8-yl)methanesulfonamide (11), were identified as potent methionine aminopeptidase (MetAP) inhibitors by high throughput screening of a diverse chemical library of small organic compounds. They showed different inhibitory potencies on Co(II)-, Ni(II)-, Fe(II)-, Mn(II)-, and Zn(II)-forms of Escherichia coli MetAP, and their inhibition is dependent on metal concentration. X-ray structures of E. coli MetAP complexed with 10 revealed that the inhibitor forms a metal complex with the residue H79 at the enzyme active site; the complex is further stabilized by an extended H-bond and metal interaction network. Analysis of the inhibition of MetAP by these inhibitors indicates that this is a typical mechanism of inhibition for many non-peptidic MetAP inhibitors and emphasizes the importance of defining in vitro conditions for identifying and evaluating MetAP inhibitors that will be capable of giving information relevant to the in vivo situation.

Aminopeptidases↗