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Biomedical subjects

Q Wu

Publications and source records attributed to Q Wu.

At least 289 records · Page 16Linked to original sources

Potentiation of GSK-3-catalyzed Alzheimer-like phosphorylation of human tau by cdk5.

Tau protein from Alzheimer disease (AD) brain is hyperphosphorylated by both proline-dependent protein kinases (PDPKs) and non-PDPKs. It is presently unclear how PDPKs and non-PDPKs interact in tau hyperphosphorylation. Previously we have shown that non-PDPKs can positively modulate the activity of a PDPK (GSK-3) in tau phosphorylation (Singh et al. (1995) FEBS Lett. 358, 267-272). In this study we have investigated whether (A) non-PDPKs can also modulate the activity of the PDPK, cdk5, (B) a PDPK can modulate the activities of another PDPK, as well as non-PDPKs. We found that, like GSK-3, the activity of cdk5 is stimulated if tau were first prephosphorylated by any of several non-PDPKs (A-kinase, C-kinase, CK-1, CaM-kinase II). Prephosphorylation of tau by cdk5 stimulated both the rate and extent of a subsequent phosphorylation catalyzed by GSK-3. Under these conditions thr 231 phosphorylation was especially enhanced (9-fold). No significant stimulation of phosphorylation was observed when the order of these kinases was reversed (i.e. GSK-3 followed by cdk5). By contrast, prephosphorylation of tau by cdk5 served to inhibit subsequent phosphorylation catalyzed by C-kinase and CK-1, but not by A-kinase or CaM-kinase II. Our results suggest that in tau hyperphosphorylation in AD brain, cdk5-catalyzed phosphorylation may serve to upregulate the activity of GSK-3 and down-regulate the activities of C-kinase and CK-1.

Alzheimer Disease↗

Conformational analysis of the thrombin receptor agonist peptides SFLLR and SFLLR-NH2 by NMR: evidence for a cyclic bioactive conformation.

The conformational properties of the pentapeptide Ser-Phe-Leu-Leu-Arg (P5), a human thrombin receptor-derived sequence forming part of a tethered ligand which activates the thrombin receptor, and its more active amide derivative Ser-Phe-Leu-Leu-Arg-NH2 (P5-NH2), have been studied by proton NMR spectroscopy in dimethylsulfoxide. Measurements of nuclear Overhauser effects, performed using two-dimensional rotating frame nuclear Overhauser (ROESY) and one-dimensional nuclear Overhauser enhancement (NOE) spectroscopy, revealed that P5 exists mainly in an extended conformation. However, proton-proton 1D-NOEs between Phe C alpha H and Ser C alpha H Leu3 C alpha H and Leu3 NH, and Leu4 C alpha H and Leu4 NH, as well as between the Ser and Arg sidechains, also implicated a minor conformer for P5 having a curved backbone and a near-cyclic structure. In contrast to P5, measurements of NOEs and ROEs for P5-NH2 revealed a more stabilized cyclic structure which may account for its higher biological potency. Thus strong interresidue sequential NH (i)-NH (i + 1) interactions, as well as C-terminal carboxamide to N-terminal side-chain interactions, i.e., Arg CONH2 to Phe ring and Arg CONH2 to Ser C alpha/C beta beta', observed at lower levels of the ROESY spectrum, supported a curved backbone structure for SFLLR-NH2. Since the higher potency P5-NH2 analogue adopts predominantly a cyclic structure, a cyclic bioactive conformation for thrombin receptor agonist peptides is suggested.

Amino Acid Sequence↗

Cations affect [3H]mazindol and [3H]WIN 35,428 binding to the human dopamine transporter in a similar fashion.

The present study addresses the possibility that there are different cocaine-related and mazindol-related binding domains on the dopamine transporter (DAT) that show differential sensitivity to cations. The effects of Zn2+, Mg2+, Hg2+, Li+, K+, and Na+ were assessed on the binding of [3H]mazindol and [3H]WIN 35,428 to the human (h) DAT expressed in C6 glioma cells under identical conditions for intact cell and membrane assays. The latter were performed at both 0 and 21 degrees C. Zn2+ (30-100 microM) stimulated binding of both radioligands to membranes, with a relatively smaller effect for [3H]mazindol; Mg2+ (0.1-100 microM) had no effect; Hg2+ at approximately 3 microM stimulated binding to membranes, with a relatively smaller effect for [3H]mazindol than [3H]WIN 35,428 at 0 degrees C, and at 30-100 microM inhibited both intact cell and membrane binding; Li+ and K+ substitution (30-100 mM) inhibited binding to membranes more severely than to intact cells; and Na+ substitution was strongly stimulatory. With only a few exceptions, the patterns of ion effects were remarkably similar for both radioligands at both 0 and 21 degrees C, suggesting the involvement of common binding domains on the hDAT impacted similarly by cations. Therefore, if there are different binding domains for WIN 35,428 and mazindol, these are not affected differentially by the cations studied in the present experiments, except for the stimulatory effect of Zn2+ at 0 and 21 degrees C and Hg2+ at 0 degrees C.

Animals↗

Number and orientations of beams in intensity-modulated radiation treatments.

The fundamental question of how many equispaced coplanar intensity-modulated photon beams are required to obtain an optimum treatment plan is investigated in a dose escalation study for a typical prostate tumor. Furthermore, optimization of beam orientations to improve dose distributions is explored. A dose-based objective function and a fast gradient technique are employed for optimizing the intensity profiles (inverse planning). An exhaustive search and fast simulated annealing techniques (FSA) are used to optimize beam orientations. However, to keep computation times reasonable, the intensity profiles for each beam arrangement are still optimized using inverse planning. A pencil beam convolution algorithm is employed for dose calculation. All calculations are performed in three-dimensional (3D) geometry for 15 MV photons. DVHs, dose displays, TCP, NTCP, and biological score functions are used for evaluation of treatment plans. It is shown that for the prostate case presented here, the minimum required number of equiangular beams depends on the prescription dose level and ranges from three beams for 70 Gy plans to seven to nine beams for 81 Gy plans. For the highest dose level (81 Gy), beam orientations are optimized and compared to equiangular spaced arrangements. It is shown that (1) optimizing beam orientations is most valuable for a small numbers of beams (< or = 5) and the gain diminishes rapidly for higher numbers of beams; (2) if sensitive structures (for example rectum) are partially enclosed by the target volume, beams coming from their direction tend to be preferable, since they allow greater control over dose distributions; (3) while FSA and an exhaustive search lead to the same results, computation times using FSA are reduced by two orders of magnitude to clinically acceptable values. Moreover, characteristics of and demands on biology-based and dose-based objective functions for optimization of intensity-modulated treatments are discussed.

Algorithms↗

Temperature determines the pattern of anaerobic microbial dechlorination of Aroclor 1260 primed by 2,3,4,6-tetrachlorobiphenyl in Woods Pond sediment.

Reductive dechlorination of the Aroclor 1260 residue in Woods Pond (Lenox, Mass.) sediment samples was investigated for a year at incubation temperatures from 4 to 66 degrees C. Sediment slurries were incubated anaerobically with and without 2,3,4,6-tetrachlorobiphenyl (2346-CB; 350 microM) as a primer for dechlorination of the Aroclor 1260 residue. Dechlorination of the Aroclor residue occurred only in live samples primed with 2346-CB and only at 8 to 34 degrees C and 50 to 60 degrees C. The extent and pattern of polychlorinated biphenyl (PCB) dechlorination were temperature dependent. At 8 to 34 degrees C, the dechlorination resulted in 28 to 65% decreases of the hexathrough nonachlorobiphenyls and corresponding increases in the tri- and tetrachlorobiphenyls. At 12 to 30 degrees C, 30 to 40% of the hexa- through nonachlorobiphenyls were dechlorinated in just 3 months. The optimal temperature for overall chlorine removal was 20 to 27 degrees C. We observed four different microbial dechlorination processes with different but partially overlapping temperature ranges, i.e., Process N (flanked meta dechlorination) at 8 to 30 degrees C, Process P (flanked para dechlorination) at 12 to 34 degrees C, Process LP (unflanked para dechlorination) at 18 to 30 degrees C, and Process T (a very restricted meta dechlorination of specific hepta- and octachlorobiphenyls) at 50 to 60 degrees C. These temperature ranges should aid in the development of strategies for the enrichment and isolation of the microorganisms responsible for each dechlorination process. The incubation temperature determined the relative dominance of the four PCB dechlorination processes and the extent and products of dechlorination. Hence, understanding the effects of temperature on PCB dechlorination at contaminated sites should assist in predicting the environmental fate of PCBs or planning bioremediation strategies at those sites.

Anaerobiosis↗

Two anaerobic polychlorinated biphenyl-dehalogenating enrichments that exhibit different para-dechlorination specificities.

Two anaerobic polychlorinated biphenyl (PCB)-dechlorinating enrichments with distinct substrate specificities were obtained: a 2,3,4,6-tetrachlorobiphenyl (2346-CB) para-dechlorinating enrichment derived from Aroclor 1260-contaminated Woods Pond (Lenox, Mass.) sediment and a 2,4,6-trichlorobiphenyl (246-CB) unflanked para-dechlorinating enrichment derived from PCB-free Sandy Creek Nature Center (Athens, Ga.) sediment. The enrichments have been successfully transferred to autoclaved soil slurries over 20 times by using 300 to 350 microM 2346-CB or 246-CB. Both enrichments required soil for successful transfer of dechlorination activity. The 2346-CB enrichment para dehalogenated, in the absence or presence of 2346-CB, only 4 of 25 tested para halogen-containing congeners: 234-CB, 2345-CB, 2346-CB, and 2,4,6-tribromobiphenyl (246-BrB). In the presence of 246-CB, the 246-CB enrichment para dehalogenated 23 of the 25 tested congeners. However, only three congeners (34-CB, 2346-CB, and 246-BrB) were dehalogenated in the absence of 246-CB, indicating that these specific congeners initiate dehalogenation in this enrichment culture. The addition of the 2346-CB (para)-dechlorinating enrichment did not further stimulate the 2346-CB-primed dechlorination of the Aroclor 1260 residue in Woods Pond sediment samples. Compared to the addition of the primer 246-CB or the 246-CB unflanked para-dechlorinating enrichment alone, the addition of both 246-CB (300 microM) and the 246-CB enrichment stimulated the unflanked para dechlorination of the Aroclor 1260 residue in Woods Pond sediments. These results indicate that the two enrichments contain different PCB-dechlorinating organisms, each with high substrate specificities. Furthermore, bioaugmentation with the enrichment alone did not stimulate the desired dechlorination in PCB-contaminated Woods Pond sediment.

Anaerobiosis↗

Effect of Incubation Temperature on the Route of Microbial Reductive Dechlorination of 2,3,4,6-Tetrachlorobiphenyl in Polychlorinated Biphenyl (PCB)-Contaminated and PCB-Free Freshwater Sediments.

We studied the influence of temperature (4 to 66(deg)C) on the microbial dechlorination of 2,3,4,6-tetrachlorobiphenyl (2,3,4,6-CB) incubated for 1 year in anaerobic sediments from Woods Pond in Lenox, Mass., and Sandy Creek Nature Center Pond (SCNC) in Athens, Ga. Seven discrete dechlorination reactions were observed, four of which occurred in both sediments. These were 2,3,4,6-CB (symbl) 2,4,6-CB, 2,3,4,6-CB (symbl) 2,3,6-CB, 2,4,6-CB (symbl) 2,6-CB, and 2,3,6-CB (symbl) 2,6-CB. Three additional reactions occurred only in Woods Pond sediment. These were 2,4,6-CB (symbl) 2,4-CB, 2,4-CB (symbl) 2-CB, and 2,4-CB (symbl) 4-CB. The dechlorination reactions exhibited at least four different temperature dependencies in SCNC sediment and at least six in Woods Pond sediment. We attribute the discrete dechlorination reactions to different polychlorinated biphenyl (PCB)-dechlorinating microorganisms with distinct specificities. Temperature influenced the timing and the relative predominance of parallel pathways of dechlorination, i.e., meta versus para dechlorination of 2,3,4,6-CB and ortho versus para dechlorination of 2,4,6-CB and 2,4-CB. meta dechlorination of 2,3,4,6-CB to 2,4,6-CB dominated at all tested temperatures except at 18 and 34(deg)C, where para dechlorination to 2,3,6-CB dominated in some replicates. The dechlorination of 2,4,6-CB was restricted to (symbl)15 to 30(deg)C in both sediments. Temperature affected the lag time preceding the dechlorination of 2,4,6-CB in both sediments and affected the preferred route of its dechlorination in Woods Pond sediment. para dechlorination dominated at 20(deg)C, and ortho dechlorination dominated at 15(deg)C, but at 18 and 22 to 30(deg)C the relative dominance of ortho versus para dechlorination of 2,4,6-CB varied. These data indicate that field temperatures play a significant role in controlling the nature and the extent of the PCB dechlorination that occurs at a given site.

Journal Article↗

Inhibition of trans-retinoic acid-resistant human breast cancer cell growth by retinoid X receptor-selective retinoids.

All-trans-retinoic acid (trans-RA) and other retinoids exert anticancer effects through two types of retinoid receptors, the RA receptors (RARs) and retinoid X receptors (RXRs). Previous studies demonstrated that the growth-inhibitory effects of trans-RA and related retinoids are impaired in certain estrogen-independent breast cancer cell lines due to their lower levels of RAR alpha and RARbeta. In this study, we evaluated several synthetic retinoids for their ability to induce growth inhibition and apoptosis in both trans-RA-sensitive and trans-RA-resistant breast cancer cell lines. Our results demonstrate that RXR-selective retinoids, particularly in combination with RAR-selective retinoids, could significantly induce RARbeta and inhibit the growth and induce the apoptosis of trans-RA-resistant, RAR alpha-deficient MDA-MB-231 cells but had low activity against trans-RA-sensitive ZR-75-1 cells that express high levels of RAR alpha. Using gel retardation and transient transfection assays, we found that the effects of RXR-selective retinoids on MDA-MB-231 cells were most likely mediated by RXR-nur77 heterodimers that bound to the RA response element in the RARbeta promoter and activated the RARbeta promoter in response to RXR-selective retinoids. In contrast, growth inhibition by RAR-selective retinoids in trans-RA-sensitive, RAR alpha-expressing cells most probably occurred through RXR-RAR alpha heterodimers that also bound to and activated the RARbeta promoter. In MDA-MB-231 clones stably expressing RAR alpha, both RARbeta induction and growth inhibition by RXR-selective retinoids were suppressed, while the effects of RAR-selective retinoids were enhanced. Together, our results demonstrate that activation of RXR can inhibit the growth of trans-RA-resistant MDA-MB-231 breast cancer cells and suggest that low cellular RAR alpha may regulate the signaling switch from RAR-mediated to RXR-mediated growth inhibition in breast cancer cells.

Antineoplastic Agents↗

Influence of bafilomycin A1 on pHi responses in cultured rabbit nonpigmented ciliary epithelium.

Aqueous humor secretion is in part linked to HCO3- transport by nonpigmented ciliary epithelium (NPE) cells. During this process, the cells must maintain stable cytoplasmic pH (pHi). Because a recent report suggests that NPE cells have a plasma membrane-localized vacuolar H(+)-ATPase, the present study was conducted to examine whether vacuolar H(+)-ATPase contributes to pHi regulation in a rabbit NPE cell line. Western blot confirmed vacuolar H(+)-ATPase expression as judged by H(+)-ATPase 31-kDa immunoreactive polypeptide in both cultured NPE and native ciliary epithelium. pHi was measured using 2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Exposing cultured NPE to K(+)-rich solution caused a pHi increase we interpret as depolarization-induced alkalinization. Alkalinization was also caused by ouabain or BaCl2. Bafilomycin A1 (0.1 microM; an inhibitor of vacuolar H(+)-ATPase) inhibited the pHi increase caused by high K+. The pHi increase was also inhibited by angiotensin II and the metabolic uncoupler carbonyl cyanide m-chlorophenylhydazone but not by ZnCl2, 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS), 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS), omeprazole, low-Cl- medium, HCO3(-)-free medium, or Na(+)-free medium. Bafilomycin A1 slowed the pHi increase after an NH4Cl (10 mM) prepulse. However, no detectable pHi change was observed in cells exposed to bafilomycin A1 under control conditions. These studies suggest that vacuolar H(+)-ATPase is activated by cytoplasmic acidification and by reduction of the proton electrochemical gradient across the plasma membrane. We speculate that the mechanism might contribute to maintenance of acid-base balance in NPE.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗

[Survey on nutritional knowledge, attitude and practice among the residents in Beijing, Guangzhou and Shanghai].

A survey on nutritional knowledge, attitude and practice (K-A-P) was carried out among 965 residents aged between 20 and 50 and randomly selected in Beijing, Guangzhou and Shanghai. The results showed that subjects' knowledge level was not high, and their knowledge scores were significantly correlated with their education levels (r = 0.3011, P < 0.010). Subjects aged above 35 had a higher knowledge level than that of younger ones. Subjects from three cities held a positive and favorable attitude towards the acquisition of nutritional knowledge, reasonable dietary pattern and healthy diet habits. Results of food frequency survey indicated that the consumption of rice/flour, meat/poultry, vegetables, fruits, milk and milk products was relatively high. In addition, 89.5%, 78.8% and 47.8% of subjects selected newspaper, TV and broadcast as their main sources of nutritional information respectively. This survey provided basis on content and method for future nutrition education.

Adult↗

[Pseudohypopyon after vitrectomy for vitreous hemorrhage].

OBJECTIVE: To describe an uninfective hypopyon phenomenon after vitrectomy (pseudohypopyon). METHODS: 1,250 cases (consecutive cases) who had undergone vitrectomy were collected. Among them, 418 cases were vitreous hemorrhage due to various disorders. Pseudohypopyon was found in 7 cases. All of them were the patients with vitreous hemorrhage. RESULTS: Pseudohypopyon occurred in 3-5 days after vitrectomy, like precipitation of muddy sand; systemic and local treatment of antibiotic and steroid were not effective, intraocular centesis for smear and culture could not find any germs; and the patients were painless and no irritation in the eyes. The relatively effective method for this kind of hypopyon was paracentesis of anterior chamber and its natural absorption. After a follow-up period of 3 months, 3 cases obtained the vision above 0.05. CONCLUSIONS: Pseudo-hypopyon might happen after vitrectomy for vitreous hemorrhage, and it should be differentiated from infective ophthalmitis.

Diagnosis, Differential↗

[The relationship of the permeability coefficients of testosterone with solubility parameters of vehicles].

The effects of vehicles on the penetration through rat skin of testosterone were investigated. The solubilities of testosterone in various vehicles and the fluxes through rat abdomen skin had been determined. The solubility parameters of testosterone (delta i) and vehicles (delta v(n)) were calculated by Hildebrand's method. There was a good inverse parabola correlation between the log permeability coefficients (logp) and (delta v(n)). When delta v(n) approched delta i the permeability coefficients of testosterone approched the minimum as its limit.

Animals↗

[Image analysis of cell nuclear morphology and DNA content in osteosarcoma of the jaws].

The measurement of nuclear morphology and quantitative analysis of nuclear DNA content were made by Interactive Image Analysis System in 47 osteosarcomas of the jaws. The results showed that with a decreased degree of differentiation, the cell nuclei of osteoblastic and chondroblastic osteosarcomas came to be large and irregular, those of fibroblastic osteosarcomas, however, to be small and round. It was revealed that high-grade osteosarcomas had increased amounts of DNA and that the mean of DNA content, proportion of hyperploid cells and tumor ploidy were found to be of important prognostic value.

Cell Nucleus↗

[Extra-anatomical bypass for subclavian artery occlusion].

20 patients with subclavian artery occlusion were treated by extra-anatomical bypass from 1989 to 1996. There were 9 men and 11 women, aged from 20 to 63 years with a duration of 1 month to 18 years. The main causes of illness were Takayasu's arteritis and atherosclerosis. Symptoms of upper extremity ischemia were present in 17 patients and vertebrobasilar insufficiency in 11. Carotid-subclavian/axillary bypass and axilloaxillary bypass were performed on 17 and 3 patients respectively. There were no operative deaths. Relief of symptomes was achieved in all the patients except one who had reocclusion of bypass graft due to rather poor outflow vessel. We stressed the surgiacal technique of extra-anatomical bypass in the treatment of subclavian artery occlusion. With few postoperative complications and high patency rate, we consider extra-anatomical bypass a safe, simple, well-tolerated and durable procedure for the treatment of subclavian artery occlusive disease in high-risk patients.

Adult↗

[Clear cell odontogenic carcinoma].

Histopathologic and immunohistochemical features of 3 cases of clear cell odontogenic carcinoma were studied. The tumors were composed of sheets or islands of clear cells separated by mature collageneous tissue. Basaloid cells were also seen in the tumors. Tumor cells showed positive reactions for epithelial membrane antigen and cytokeratin. More PCNA positive cells were seen in basaloid cells than in clear cells. Metastasis to regional lymph nodes was found in all 3 cases.

Adenocarcinoma, Clear Cell↗

[Antibacterial activity of histidine-rich polypeptides in human parotid saliva].

Two ultrasensitive antibacterial assays were applied to determine the antibacterial activity of histidine-rich polypeptides (HRPs) in human parotid saliva. The results not only confirmed the potent antibacterial activity of HRPs against Streptococcus mutans MT6R, but also showed for the first time that HRPs were effectively antibacterial to Staphylococcus aureus ATCC 25923, Escherichia coli ML-35p and Pseudomonas aeruginosa ATCC 27853. Among HRPs, HRP3, HRP5 and HRP6 were the major antibacterial components which were active against S. mutans, S. aureus, E. coli and P. aeruginosa, whereas HRP1 was only effective against E. coli. S. sanguis was resistant to the action of HRPs. These results suggest that HRPs are actually a family of endogenous antibiotic peptides with broad antimicrobial spectrum including fungi, Gram-positive and Gram-negative bacteria and may play an important role in the prevention of various infection diseases in the oral cavity as well as in the resistance to caries.

Escherichia coli↗