Biomedical subjects

Ji Zhang

Publications and source records attributed to Ji Zhang.

84 records · Page 5Linked to original sources

PubMed2002

Development of a catalytic enantioselective conjugate addition of 1,3-dicarbonyl compounds to nitroalkenes for the synthesis of endothelin-A antagonist ABT-546. Scope, mechanism, and further application to the synthesis of the antidepressant rolipram.

The enantioselective synthesis of endothelin-A antagonist ABT-546 has been accomplished via the discovery and development of a highly selective catalytic asymmetric conjugate addition of ketoesters to nitroolefins. Employing just 4 mol % bis(oxazoline)-Mg(OTf)(2) complex with an amine cocatalyst, we obtained the product nitroketone with 88% selectivity at the aryl-bearing stereocenter and in good yield on scales ranging to 13 mol. The effects of ligand structure, metal salt, and solvent on the reaction are described. Particularly important to the reaction is the water content. While water is necessary during the generation of the catalyst, the water must be then removed to maximize stereoselectivity and reactivity. The reaction has been extended to other dicarbonyl substrates, and a variety of substitution patterns are tolerated on the nitroolefin partner. The reaction has also been employed in the synthesis of the antidepressant rolipram. Investigations relating to the mechanism of the reaction are also described.

Alkenes↗

PubMed2002

[Detection of Mycoplasma hyorhinis in gastric cancer using bio-chip technology].

OBJECTIVE: To determine the prevalence of Mycoplasma hyorhinis in archived paraffin-embedded gastric cancer tissue and to find whether Mycoplasma hyorhinis infection can influence gene expression level in gastric cancer cells. METHODS: A high-dense tissue microarray containing 105 gastric cancer samples, 101 benign margin samples and 62 non-cancerous gastric disease samples resected during operation was constructed. PD4, a specific anti-Mycoplasma-hyorhinis Mab, was used to detect the infection rate in all the samples in the tissue microarrays immunohistochemically. Then, cDNA microarray was used to pinpoint differentially the expressed genes between gastric cancer cell line MGC803 samples with and without Mycoplasma hyorhinis infection. RESULTS: The infection rate of M. hyorhinis was 54.1% 53/98 in gastric cancer samples, 51.7% 45/87 in benign margin samples, and 15.8 % 9/57 in non-cancerous disease samples respectively. The difference of infection rates between gastric cancer and non-cancerous gastric disease was statistically significant (P = 0.001). Highly differentiated adenocarcinomas had more opportunity (84.6%) to be infected with M. hyorhinis than poorly differentiated ones (45.9%)(P < 0.05). Intestinal type of gastric cancers (according to Lauren's classification) got the infection more often than diffused type. About 409 gene expression alterations were detected in 48 000 sites from two gastric cancer cell lines and the expression levels of some genes correlating with cell apoptosis and cell adhesion were down regulated after Mycoplasma hyorhinis infection. CONCLUSION: The infection rate of M. hyorhinis is significantly higher in gastric cancer than in other gastric diseases, thus indicating the association between Mycoplasma infection and gastric cancer. Mycoplasma hyorhinis infection influences the gene expression level in gastric cancer cell line MGC803, which indicates that the infection could have something to do with the process of gastric cancer. The question whether M.hyorhinis has oncogenic potential remains to be elucidated.

Adult↗

PubMed2002

A note on ANOVA assumptions and robust analysis for a cross-over study.

Analysis of variance (ANOVA) methods are usually applied to analyse continuous data from cross-over studies. The analysis, however, may not have appropriate type I error when certain assumptions are violated. In this paper, we first clarify a conventionally minimum set of assumptions that validate the F-tests of ANOVA models for cross-over studies. We then provide a practical verification/remedy procedure based upon the theoretical developments. By applying the verification/remedy procedure, more robust analysis results can be expected from the ANOVA models.

Analysis of Variance↗

PubMed2002

Improvement of aspirin-intolerant asthma by montelukast, a leukotriene antagonist: a randomized, double-blind, placebo-controlled trial.

Leukotriene antagonists block the proinflammatory actions of leukotrienes (LT) and have been introduced as new treatments for asthma. Conventional therapy with glucocorticosteroids does not inhibit the biosynthesis of leukotrienes. We therefore tested whether addition of the leukotriene receptor antagonist montelukast was of therapeutic benefit in a group of aspirin-intolerant patients with asthma of whom 90% already were treated with moderate to high doses of glucocorticosteroids. Under double-blind conditions, 80 aspirin-intolerant patients with asthma were randomized to receive 4 wk oral treatment of either 10 mg of montelukast or placebo once daily at bedtime. Pulmonary function was measured as forced expiratory volume in 1 s (FEV(1)) once a week in the clinic and daily as morning and evening peak expiratory flow rate (PEFR). Asthma symptoms and use of rescue bronchodilator were also recorded daily. Asthma specific quality of life (QoL) was assessed before and after the treatments. The group receiving montelukast showed a remarkable improvement of their asthma, whereas the group given placebo showed no change. Thus, from equal baseline values, the mean difference between the groups over the 4-wk treatment period was 10.2% for FEV(1) and 28.0 L for morning PEFR (p for both < 0.001). The improved pulmonary function in the group receiving montelukast occurred at the same time as 27% less bronchodilator was used (p < 0.05), and it was associated with fewer asthma symptoms than in the group given placebo, including 1.3 nights more of sleep per week and 54% fewer asthma exacerbations (p < 0.05). There was also an improvement in asthma-specific QoL (p < 0.05). The therapeutic response to montelukast was consistent across patients with different baseline characteristics and did not correlate with baseline urinary LTE(4). Addition of a leukotriene receptor antagonist such as montelukast improves asthma in aspirin-intolerant patients over and above what can be achieved by glucocorticosteroids.

Acetates↗

PubMed2002

Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcoma, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes.

In this investigation, we selected PAX3/FKHR and PAX7/FKHR fusion transcript-positive and -negative alveolar rhabdomyosarcomas (ARMSs) and embryonal rhabdomyosarcomas (ERMSs) with and without anaplastic features, to ascertain genomic imbalance differences and/or similarities within these histopathologic and genetic rhabdomyosarcoma (RMS) variants. Comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) studies were performed on 45 rhabdomyosarcoma specimens consisting of 23 ARMSs and 22 ERMSs (12 ERMS cases were included from an earlier study). The anaplastic variant of RMS has not previously been subjected to CGH analysis. Overall, the most prominent imbalances were gain of chromosomes or chromosomal regions 2/2q (40%), 7/7q (31%), 8/8p (53%), 11/11q (31%), 12q13-15 (49%), 13q14 (22%), and 20/20p (31%), and loss of 1p36 (27%), 3p14-21 (22%), 9q21-22 (33%), 10q22-qter (18%), 16q (27%), 17p (22%), and 22 (22%). These gains and losses were distributed equally between ARMS and ERMS histologic subtypes (excluding 7/7q and 11/11q gain that were observed chiefly in ERMS), demonstrating that these entities are similar with respect to recurrent genomic imbalances. Moreover, genomic imbalances were also evenly distributed among the ARMS fusion transcript subtypes, providing evidence for a genetic kinship despite the absence of a fusion transcript in some cases. Genomic amplification was detected in 26% and 23% of the ARMS and ERMS cases, respectively (with nearly all of the latter subset exhibiting anaplastic features). One amplicon, involving 15q25-26, corresponds to the locus of the insulin-like growth factor type I receptor (IGF1R) gene. Amplification of IGF1R was confirmed molecularly in the cases exhibiting a 15q25-26 amplicon. In summary, these results indicate that genomic gains and losses involve alike chromosomes with similar frequencies within the histopathologic and genetic subtypes of rhabdomyosarcoma, that genomic amplification is frequent not only in the alveolar histologic subtype of rhabdomyosarcoma but also in ERMS with anaplasia, and that amplification of IGF1R possibly plays a role in the development or progression of a subset of rhabdomyosarcomas.

Adolescent↗

PubMed2002

Effect of montelukast, a once-daily leukotriene receptor antagonist, on peak expiratory flow variability.

BACKGROUND: Peak expiratory flow (PEF) is an important measure of airway functin in asthma. PEF variability (PEFvar) assessment is described in asthma treatment guidelines as another means of evaluating patient status and response to therapy. OBJECTIVE: The goal of this study was to determine the clinical effect of oral montelukast, a leukotriene receptor antagonist, on PEFvar in asthmatic patients and to assess the relationship of PEFvar with other clinical measures. METHODS: This was a retrospective analysis of data from a multicenter, randomized, double-blind, placebo-controlled, parallel-group study, details of which have been published previously. Eligible patients had chronic stable asthma, had a forced expiratory volume in 1 second (FEV1) that was 50% to 85% of the predicted value, used inhaled beta-agonists, had at least 15% improvement in absolute FEV1 after inhaled beta-agonist administration, and showed a minimal predefined level of daytime asthma symptoms. Treatment consisted of a 2-week, single-blind, placebo run-in period followed by a 12-week, double-blind treatment period (montelukast 10 mg or matching placebo once daily at bedtime). RESULTS: Six hundred eighty-one patients (age range, 15-79 years) were randomized to treatment at 50 centers. Baseline PEFvar was 11.44% +/- 6.55% and 10.62% +/- 6.48% in the montelukast and placebo groups, respectively. PEFvar decreased 20.1% and 7.5% from baseline in the montelukast and placebo groups, respectively. The between-group difference was significant (P < 0.001). PEFvar had low correlation with other clinical measures. CONCLUSIONS: Over 12 weeks of treatment, montelukast significantly reduced PEFvar compared with placebo, indicating improved asthma control. The relative reduction in PEFvar was similar in patients with different degrees of variability at baseline. PEFvar did not correlate highly with other outcome variables and may measure different aspects of the disease.

Acetates↗

PubMed2002

Proenkephalin A gene products activate a new family of sensory neuron--specific GPCRs.

Several peptide fragments are produced by proteolytic cleavage of the opioid peptide precursor proenkephalin A, and among these are a number of enkephalin fragments, in particular bovine adrenal medulla peptide 22 (BAM22). These peptide products have been implicated in diverse biological functions, including analgesia. We have cloned a newly identified family of 'orphan' G protein--coupled receptors (GPCRs) and demonstrate that BAM22 and a number of its fragments bind to and activate these receptors with nanomolar affinities. This family of GPCRs is uniquely localized in the human and rat small sensory neuron, and we called this family the sensory neuron--specific G protein--coupled receptors (SNSRs). Receptors of the SNSR family are distinct from the traditional opioid receptors in their insensitivity to the classical opioid antagonist naloxone and poor activation by opioid ligands. The unique localization of SNSRs and their activation by proenkephalin A peptide fragments indicate a possible function for SNSRs in sensory neuron regulation and in the modulation of nociception.

Amino Acid Sequence↗

PubMed2002

In altering the release of glucocorticoids, ketorolac exacerbates the effects of systemic immune stimuli on expression of proinflammatory genes in the brain.

Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used for their antiinflammatory, antipyretic, and analgesic properties. The molecular basis for the therapeutic action of NSAIDs is believed to be in their ability to inhibit cyclooxygenase (COX) activity and thereby blocking the production of prostaglandins. Emerging evidence now suggests that NSAIDs can exert their pharmacological effects through other mechanisms. This study investigated the influence of a nonselective COX-inhibitor ketorolac on IL-1beta- and TNFalpha-induced expression of proinflammatory genes in the brain. Systemic injection of both cytokines caused a rapid and transient transcriptional activation of COX-2 gene within the cerebral microvasculature, which was significantly enhanced by ketorolac. Expression of genes encoding the index of nuclear factor kappaB activity and the chemokine monocyte chemoattractant protein-1 was also increased by the NSAID. We speculated here that such effect was indirectly mediated via an altered secretion of plasma glucocorticoids because ketorolac is a potent inhibitor of the hypothalamic-pituitary-adrenal axis during systemic inflammation. As expected, pretreatment with the glucocorticoid receptor antagonist RU-486 exacerbated the influence of systemic immune stimuli on proinflammatory signaling. In contrast, exogenous corticosterone abolished the effects of ketorolac on IL-1beta-induced COX-2 and monocyte chemoattractant protein-1 gene expression in the cerebral endothelium. This drug plays therefore a paradoxical role in its ability to inhibit the circulating levels of glucocorticoids that are essential inhibitory feedback on the proinflammatory signal transduction pathways and gene transcription. In altering the production of key prostaglandins that are involved in the control of hypothalamic-pituitary-adrenal axis, ketorolac may have proinflammatory properties in the central nervous system during systemic immune stimuli.

Adrenal Glands↗

PubMed2002

Typing Y chromosome STR haplotypes using redesigned primers.

A panel of Y-specific STR loci, including DYS19, DYS389, DYS390, DYS391, DYS392, and DYS393 was analyzed using horizontal nondenaturing polyacrylamide gel electrophoresis with a discontinuous buffer system (horizontal disk-PAGE). In order to obtain correct results for the larger DYS389 and DYS392 alleles, it was necessary to design new primers that bind closer to the repeat region and lead to a significant reduction of the amplified fragment size. Using the modified primer sets the horizontal disk-PAGE results were consistent with a nondenaturing approach using fluorescent primers and a 377 automated sequencer. The modified procedure also amplifies the second repeat stretch at the duplicated DYS389 locus as a single fragment, which results in an immediate allele identification. The results indicate that horizontal disk-PAGE with silverstaining is a simple approach to type the recommended Y-specific STR markers.

DNA Primers↗

PubMed2002

[Genetic map of 10 STR loci on chromosome 9].

To understand the genetic polymorphism of 10 STR loci on chromosome 9 and reveal the difference on the linkage maps of different populations, the author used a set of nine tetranucleotide- and one tritranucleotide-repeat STR markers on chromosome 9 chosen from Genome Data Bank. EDTA-blood was collected from unrelated family in Baiyin City, Gansu province. DNA was extracted by Chelex-100 method and amplified by the polymerase chain reaction (PCR). The PCR products were analyzed using PAGE electrophoresis. We calculated the allele frequencies and heterozygosity and PIC of every ten STR loci. Using the data of Chinese Han pedigree, we constructed a genetic map of chromosome 9 making up with 10 STR loci. Then we compared our map with the map in GDB. Our results indicate that there are some differences on the genetic map between Chinese and GDB. That means, it is essential to do some population genetic evaluations before using the data of GDB into Chinese population.

China↗

PubMed2002

[Application of an ozone disinfection apparatus for small drinking water supply systems in rural areas].

To design an ozone disinfection apparatus which is inexpensive and to practical for small drinking water supply system in rural areas. And test its effectiveness. Designed apparatus must be rapid, low cost, high automatic and easy for operation. The key technologies are to create ozone of high concentration and to mix it with water very well, and add it into main water pipe automatically. The results showed: In laboratory, at the condition of ozone of 0.2 mg/l for 3 minutes, all germs and bacteria coli were killed. In the field study, the water samples from three villages met the standard for drinking water very well. THE CONCLUSIONS: The apparatus reached the design requirement. An innovative part of the study is that we have improved a device for mixture of ozone with water. The laboratory and field study have proved the apparatus is low cost, high effectiveness, and easy to operate u. It is very useful for small drinking water supply system in rural areas.

Disinfection↗

PubMed2002

[Studies on the chemical constituents of the stems of Alyxia sinensis (I)].

OBJECTIVE: To demonstrate the chemical constituents of Alyxia sinensis. METHOD: Phytochmical experiment was carried out, using column chromatograph technologies. RESULT: Five compounds have been isolated from the petroleum ether soluble part of the stems of A. sinensis. Their structures have been elucidated respectively as heptatriacontane(1), octatriacontane(2), 20-noatriacontannone(3), 20-nonatriacontanone(4), 20-tetraacontanoe(5), physcion(6), emodin(7), chrysophanol(8), coumarin(9), stigmasterol acetate(10), beta-sitosterol acetate(11), lupeol(12), betulin(13), stigmasterol(14), beta-sitosterol(15), ursolic acid(16), oleanolic acid(17). CONCLUSION: All these compounds are firstly been isolated from A. sinensis. And compound 5-9, 10, 11 are also been separated from Alyxiae genus for the first time.

Anthraquinones↗