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Biomedical subjects

Z Liu

Publications and source records attributed to Z Liu.

At least 217 records · Page 12Linked to original sources

Peptide derived from insulin with regulatory activity of dopamine transporter.

A nonapeptide derived from the C terminus of the insulin B chain, H(2)N-Arg-Gly-Phe-Phe-Tyr-Thr-Pro-Lys-Ala-COOH, was found to strongly inhibit dopamine (DA) uptake by rat dopamine transporter (DAT) stably expressed in CHO cells (designated D8 cells). The kinetic experiments on D8 cells gave a curve typical of competitive inhibition with an IC(50)=6.9 microM. This inhibitory effect was also confirmed by experiments on striatal synaptosomes. The rat administered with the nonapeptide unilaterally into substantia nigra showed dose-dependent velocity and duration of the round movement contralateral to the nonapeptide-injected side. In addition, the nonapeptide dose-dependently reduced the binding of the tritium-labeled cocaine analog (-)-2 beta-carbomethoxy-3 beta-(4-fluorophenyl)tropane (WIN35,428) to DAT of D8 cells, which suggests that the nonapeptide may inhibit the transport activity of DAT in the way as cocaine does. Meanwhile, the peptide DOI (insulin with 8 amino acid residues deleted at the C terminus of the B chain) shows a significantly stimulating effect on DAT uptake activity in D8 cells. So insulin is proposed as a kind of neuropeptide precursor in the brain and insulin-derived peptides may be involved in the process of regulating the DA system, and these peptides may be developed into new medicines for disorders concerning the DA system such as Parkinson's disease and cocaine addiction.

Aminobutyrates↗

The effect of orientation learning on contrast sensitivity.

Regan and Beverley [Regan, D., & Beverley, K. I. (1985). Postadaptation orientation discrimination. Journal of the Optical Society of America A, 2(2), 147-155] previously demonstrated that adapting to an oriented visual stimulus improves sensitivity to subtle orientation differences while impairing contrast sensitivity. Here, we investigated whether practice-based improvements in orientation sensitivity would, like adaptation, impair contrast sensitivity. To the contrary, we found that contrast sensitivity actually improved significantly after observers demonstrated practice-based increases in orientation sensitivity. Therefore, while orientation sensitivity can be enhanced either by orientation-discrimination training or by adapting to visual stimuli, these two procedures have opposite effects on contrast sensitivity. This difference suggests that adaptation and perceptual learning on orientation discrimination cannot be explained sufficiently by a shared underlying cause, such as a reduction in neural activity.

Adaptation, Physiological↗

Re-evaluation of cellulose acetate polymer: angiographic findings and histological studies.

BACKGROUND: Cellulose acetate polymer (CAP) is a new liquid embolic material that has been used experimentally in intravascular treatment of intracranial aneurysms. But this compound is still controversial in some aspects such as safety, efficiency, and histological changes. In this study, we re-evaluated the material with regard to intravascular treatment of aneurysms. METHODS: The carotid arteries of rats and experimental aneurysms in canines were embolized with CAP. The effects of CAP were evaluated according to angiographic and histological results. RESULTS: A strong chemo-corrosive effect was observed. This led to severe damage to vessels and rupture of two thrombosed canine aneurysm models. There were significant technical difficulties including out-flow of CAP and a high rate of occlusion of the parent arteries. CONCLUSIONS: We conclude that currently CAP is not an ideal embolic material for intracranial aneurysms. Further tests and improvements are needed before it can be widely used clinically.

Angiography, Digital Subtraction↗

Changes in NADPH diaphorase expression in the fish visual system during optic nerve regeneration and retinal development.

The various functions of nitric oxide (NO) in the nervous system are not fully understood, including its role in neuronal regeneration. The goldfish can regenerate its optic nerve after transection, making it a useful model for studying central nervous regeneration in response to injury. Therefore, we have studied the pattern of NO expression in the retina and optic tectum after optic nerve transection, using NADPH diaphorase histochemistry. NO synthesis was transiently up-regulated in the ganglion cell bodies, peaking during the period when retinal axons reach the tectum, between 20-45 days after optic nerve transection. Enzyme activity in the tectum was transiently down-regulated and then returned to control levels at 60 days after optic nerve transection, during synaptic refinement. To compare NO expression in the developing and regenerating retina, we have looked at NO expression in the developing zebrafish retina. In the developing zebrafish retina the pattern of staining roughly followed the pattern of development with the inner plexiform layer and horizontal cells having the strongest pattern of staining. These results suggest that NO may be involved in the survival of ganglion cells in the regenerating retina, and that it plays a different role in the developing retina. In the tectum, NO may be involved in synaptic refinement.

Animals↗

Detection of T suppressor cells in patients with organ allografts.

Specific immunosuppression of host's immune response to donor HLA antigens has been a major goal to clinical transplantation. Recent evidence has been accumulating to show that a distinct population of T cells expressing the CD8(+) CD28(-) phenotype display suppressor function and inhibit Th activation and proliferation by modulating the APC function. To assess the presence of Ts in transplant recipient's circulation, we have developed a flow cytometry method that measures the expression of costimulatory molecules on donor APC exposed to recipient Th and Ts. Our results demonstrate that quantitation of the capacity of CD8(+) CD28(-) T cells from patient circulation to suppress the activation of costimulatory molecules (CD80, CD86) on donor APC offers a reliable tool for monitoring specific immunosuppression against the graft in solid organ transplantation.

Antigen-Presenting Cells↗

Synthesis and pharmacology of site specific cocaine abuse treatment agents: a new synthetic methodology for methylphenidate analogs based on the Blaise reaction.

In order to make new analogs of the dopamine (DA) uptake inhibitor methylphenidate, a synthetic methodology based on the Blaise reaction was developed. The reaction between alpha-bromophenylacetic acid esters, zinc and alpha-cyano-omega-mesylates gave stable primary enamines. After reduction of the enamines with cyanoborohydride, the amines could be cyclized to methylphenidate analogs in which the amine ring size and aromatic ring were varied. These compounds were tested for inhibitory potency against [(3)H]WIN 35,428 binding to the cocaine recognition site and [(3)H]DA uptake using rat striatal tissue. When the heterocyclic ring size was varied, the six-membered ring of methylphenidate appeared to be the optimum ring size. When the aryl ring was varied the 4-trifluoromethylphenyl analog was less potent than methylphenidate, the beta-naphthyl congener was considerably more potent, whereas the alpha-naphthyl congener was less potent. Most of the compounds tested had ratios of uptake to binding inhibition (discrimination ratio) that were similar to cocaine and were therefore not lead compounds for the development of cocaine antagonists.

Animals↗

Risk factors and child mortality among the Miao in Yunnan, Southwest China.

Environmental factors and the lifestyle of communities in developing countries as in the industrialized world have a great deal to do with their health status. This study carried out among the Miao people of southeastern Yunnan province in Southwest China has demonstrated important links between child mortality (one indicator of health status) and specific risk factors. These include lifestyle variables such as geographic mobility, the age of weaning and religious belief. In addition, the use of available health care facilities was another explanatory variable. Perhaps surprisingly, a history of tuberculosis seemed also to be empirically related to the presence or absence of child mortality. Although it was impossible to show a significant statistical relationship between traditional practices and child mortality from the study's database, the authors have observed qualitatively that birthing customs play an important role in explaining the perinatal component of child mortality. These various relationships shed some light on potential areas for intervention with a view to reducing the levels of child mortality among minority peoples in China and elsewhere.

China↗

The simultaneous determination of diazepam and its three metabolites in dog plasma by high-performance liquid chromatography with mass spectroscopy detection.

A fast, sensitive and specific LC/MS/MS method for the simultaneous determination of diazepam and its three metabolites, oxazepam, temazepam and desmethyldiazepam, in dog plasma is described. The method consists of an automated 96-well solid phase extraction procedure and electrospray LC/MS/MS analysis. D(5)-Diazepam is used as the internal standard for all the compounds. Intra-day and inter-day assay coefficients of variations are less than 12.7%. The lower limit of quantitation (LLOQ) is 1 nM for each analyte, based on 0.1 ml aliquots of dog plasma. The analytical run time was 5 min. Linearity is observed over the range of 1--500 nM. This method has been used to support the discovery of pharmacokinetic studies.

Animals↗

Comparison of two commercial systems (Vitek and MicroScan-WalkAway) for antimicrobial susceptibility testing of Pseudomonas aeruginosa isolates from cystic fibrosis patients.

Antimicrobial susceptibility testing of cystic fibrosis (CF) isolates of Pseudomonas aeruginosa is difficult because the organisms are often mucoid and slow-growing. This study of 498 CF strains examined the correlation of results derived from two commonly used commercial systems (Vitek, MicroScan-WalkAway) with a reference method for 10 antimicrobials. Correlation to reference results was unacceptably low for all agents and both commercial systems had a high rate of very major (false-susceptible) errors. Although mucoid strains produced a 4.8% greater intermethod error, it was not markedly different than non-mucoid strains for the Vitek System. Overall, these tested commercial systems performed poorly for CF isolates in contrast to earlier reported, high correlations with the reference methods (broth microdilution frozen panels and agar dilution) of the National Committee for Clinical Laboratory Standards, the standardized disk diffusion test, and the Etest (AB BIODISK, Solna, Sweden).

Aminoglycosides↗

Expression and significance of cell cycle-related proteins Cyclin Dl, CDK4, p27, E2F-l and Ets-1 in chondrosarcoma of the jaws.

To elucidate the expression and significance of cell cycle-associated proteins in chondrosarcoma of the jaws, Cyclin Dl, CDK4, p27, E2F-l and Ets-l expressions were examined in chondrosarcoma and osteochondroma of the jaws by immunohistochemical ABC method. The results demonstrated that Cyclin Dl, CDK4, p27, E2F-1 and Ets-1 were positive 75% (15 of 20), 60% (12 of 20), 25% (5 of 20), 65% (13 of 20) and 60% (12 of 20) in chondrosarcoma of the jaws, respectively. There was no remarkable difference in the expression of these proteins among histological grades of the chondrosarcoma (P>0.05). In osteochondroma of the jaws, CDK4 and E2F with an equal positivity of 12.5% (1 of 8), whereas p27 was positive 75% (6 of 8). None of the osteochondroma cases was immunohistochemically positive for Cycin Dl and Ets-1. In addition, the positive rate of Cyclin Dl, CDK4, E2F-l and Ets-1 proteins was significantly higher, whereas p27 was lower in chondrosarcoma than in osteochondroma of the jaws (P<0.05). These data show that the expression of cell cycle regulatory proteins is altered in chondrosarcoma of the jaws: cyclin Dl, CDK4, E2F-1 and Ets-1 are over-expressed and p27 is low-expressed.

Adolescent↗

Th1- and Th2-cell commitment during infectious disease: asymmetry in divergent pathways.

The development of T helper 1 (Th1) versus Th2 cells is a major branch point in the immune response. It is an important determinant of whether the response to an infectious pathogen will lead to protection of the host or dissemination of the disease. Recent studies have suggested that this process is governed by distinct sets of signals provided by dendritic cells upon interactions with specific infectious agents. A model is proposed that links together the pathogen, the innate response and Th-cell polarization.

Animals↗

Multivariate calibration for the determination of total azadirachtin-related limonoids and simple terpenoids in neem extracts using vanillin assay.

Two-component and multivariate calibration techniques were developed for the simultaneous quantification of total azadirachtin-related limonoids (AZRL) and simple terpenoids (ST) in neem extracts using vanillin assay. A mathematical modeling method was also developed to aid in the analysis of the spectra and to simplify the calculations. The mathematical models were used in a two-component calibration (using azadirachtin and limonene as standards) for samples containing mainly limonoids and terpenoids (such as neem seed kernel extracts). However, for the extracts from other parts of neem, such as neem leaf, a multivariate calibration was necessary to eliminate the possible interference from phenolics and other components in order to obtain the accurate content of AZRL and ST. It was demonstrated that the accuracy of the vanillin assay in predicting the content of azadirachtin in a model mixture containing limonene (25% w/w) can be improved from 50% overestimation to 95% accuracy using the two-component calibration, while predicting the content of limonene with 98% accuracy. Both calibration techniques were applied to estimate the content of AZRL and ST in different parts of the neem plant. The results of this study indicated that the relative content of limonoids was much higher than that of the terpenoids in all parts of the neem plant studied.

Benzaldehydes↗

Influence of operating parameters on the use of the microwave-assisted process (MAP) for the extraction of azadirachtin-related limonoids from neem (Azadirachta indica) under atmospheric pressure conditions.

The use of the microwave-assisted process (MAP) for the extraction of azadirachtin-related limonoids (AZRL) from various parts of the neem tree was investigated under different operating conditions. The influence of microwave power, solvent, and irradiation time on the recovery of AZRL was studied. The efficiency of the microwave-assisted extraction (MAE) of the seed kernel, the seed shell, the leaf, and the leaf stem was compared to that of conventional extraction methods. The content of AZRL in the extracts was estimated with a vanillin-based colorimetric assay and a multivariate calibration technique. The results showed that the MAE technique can enhance the extraction of AZRL from different parts of neem possessing microstructures. Investigation of the influence of the solvent also indicted that the solvent used not only influences the efficiency but also affects the selectivity of the MAE.

Atmospheric Pressure↗

Synthesis and quantitative structure-activity relationships of fluorine-containing 4,4-dihydroxylmethyl-2-aryliminooxazo(thiazo)lidines as trehalase inhibitors.

Five fluorine-containing 4,4-dihydroxylmethyl-2-aryliminooxazolidines and five 4,4-dihydroxylmethyl-2-aryliminothiazolidines were synthesized and evaluated for their inhibitory activity against trehalase in vitro. All these compounds were very readily synthesized compared with the natural trehalase inhibitors. They had moderate inhibitory activity toward trehalase, and showed larvicidal activity and inhibition action to insect flight. The steric parameters and semiempirical quantum parameters of these compounds were acquired by using the molecular modeling method and the PM3-SCF-MO method, respectively. A quantitative structure-activity relationship between half-inhibitory concentrations toward trehalase and the above parameters was established.

Animals↗

Identification of beta subunit of the rhesus monkey chorionic gonadotropin (rmCG).

Chorionic gonadotropin (CG) is a placental derived hormone that plays a crucial role in successful implantation and establishment of early pregnancy in the primates. The rhesus monkey was chosen as a model to understand the feasibility of developing human DNA immuno-contraceptive. The coding region of rhesus monkey CG beta-subunit (rmCGbeta) was isolated by the TDRT-PCR method. The nucleotide sequence including the leader peptide was 499 nucleotide long and encoded 166 amino acids. In comparing with the previous known primates CG beta-subunits, the rmCGbeta was the highest degree of homology with baboon CG beta-subunit at the deduced amino acid sequence (94%), 79.5% homology with human CG beta-subunit and 70.4% homology with marmoset monkey CG beta-subunit. The eukaryotic expression vector pCMV4-rmCGbeta inserted full-coding cDNA sequence of rmCGbeta was constructed, and the expression of rmCG beta-subunit in HeLa cells transient expressing system in vitro and BALB/c mice in vivo was determined. The results demonstrated that the recombinant PCMV4-rmCGbeta eukaryotic expression vector could express rmCG beta-subunit in vitro and in vivo.

Amino Acid Sequence↗

The SAND domain structure defines a novel DNA-binding fold in transcriptional regulation.

The SAND domain is a conserved sequence motif found in a number of nuclear proteins, including the Sp100 family and NUDR. These are thought to play important roles in chromatin-dependent transcriptional regulation and are linked to many diseases. We have determined the three-dimensional (3D) structure of the SAND domain from Sp100b. The structure represents a novel alpha/beta fold, in which a conserved KDWK sequence motif is found within an alpha-helical, positively charged surface patch. For NUDR, the SAND domain is shown to be sufficient to mediate DNA binding. Using mutational analyses and chemical shift perturbation experiments, the DNA binding surface is mapped to the alpha-helical region encompassing the KDWK motif. The DNA binding activity of wild type and mutant proteins in vitro correlates with transcriptional regulation activity of full length NUDR in vivo. The evolutionarily conserved SAND domain defines a new DNA binding fold that is involved in chromatin-associated transcriptional regulation.

Amino Acid Motifs↗

The essential role of MEKK3 in TNF-induced NF-kappaB activation.

Activation of IkappaB kinase (IKK) is the key step in stimulation of the transcription factor NF-kappaB, which regulates many genes in the inflammatory response pathway. The molecular mechanism that underlies IKK activation in response to tumor necrosis factor (TNF) is still unknown. Using mitogen-activated protein kinase kinase kinase 3 (MEKK3)-deficient fibroblast cells, we found that MEKK3 plays a critical role in TNF-induced NF-kappaB activation. We have shown that MEKK3 is required for IKK activation and functions downstream of receptor-interacting protein (RIP) and TNF receptor- associated factor 2. We have also shown that MEKK3 interacts with RIP and directly phosphorylates IKK. The kinase activity of MEKK3 is pivotal to its function and, therefore, MEKK3 links RIP and IKK in TNF-induced NF-kappaB activation.

Animals↗

Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet responsiveness locus Sac.

The ability to taste the sweetness of carbohydrate-rich foodstuffs has a critical role in the nutritional status of humans. Although several components of bitter transduction pathways have been identified, the receptors and other sweet transduction elements remain unknown. The Sac locus in mouse, mapped to the distal end of chromosome 4 (refs. 7-9), is the major determinant of differences between sweet-sensitive and -insensitive strains of mice in their responsiveness to saccharin, sucrose and other sweeteners. To identify the human Sac locus, we searched for candidate genes within a region of approximately one million base pairs of the sequenced human genome syntenous to the region of Sac in mouse. From this search, we identified a likely candidate: T1R3, a previously unknown G protein-coupled receptor (GPCR) and the only GPCR in this region. Mouse Tas1r3 (encoding T1r3) maps to within 20,000 bp of the marker closest to Sac (ref. 9) and, like human TAS1R3, is expressed selectively in taste receptor cells. By comparing the sequence of Tas1r3 from several independently derived strains of mice, we identified a specific polymorphism that assorts between taster and non-taster strains. According to models of its structure, T1r3 from non-tasters is predicted to have an extra amino-terminal glycosylation site that, if used, would interfere with dimerization.

Alleles↗