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Biomedical subjects

W Zhu

Publications and source records attributed to W Zhu.

At least 55 records · Page 3Linked to original sources
PubMed2001

Brain dopamine and obesity.

BACKGROUND: The cerebral mechanisms underlying the behaviours that lead to pathological overeating and obesity are poorly understood. Dopamine, a neurotransmitter that modulates rewarding properties of food, is likely to be involved. To test the hypothesis that obese individuals have abnormalities in brain dopamine activity we measured the availability of dopamine D2 receptors in brain. METHODS: Brain dopamine D2 receptor availability was measured with positron emission tomography (PET) and [C-11]raclopride (a radioligand for the dopamine D2 receptor). Bmax/Kd (ratio of the distribution volumes in striatum to that in cerebellum minus 1) was used as a measure of dopamine D2 receptor availability. Brain glucose metabolism was also assessed with 2-deoxy-2[18F]fluoro-D-glucose (FDG). FINDINGS: Striatal dopamine D2 receptor availability was significantly lower in the ten obese individuals (2.47 [SD 0.36]) than in controls (2.99 [0.41]; p < or = 0.0075). In the obese individuals body mass index (BMI) correlated negatively with the measures of D2 receptors (r=0.84; p < or = 0.002); the individuals with the lowest D2 values had the largest BMI. By contrast, neither whole brain nor striatal metabolism differed between obese individuals and controls, indicating that striatal reductions in D2 receptors were not due to a systematic reduction in radiotracer delivery. INTERPRETATION: The availability of dopamine D2 receptor was decreased in obese individuals in proportion to their BMI. Dopamine modulates motivation and reward circuits and hence dopamine deficiency in obese individuals may perpetuate pathological eating as a means to compensate for decreased activation of these circuits. Strategies aimed at improving dopamine function may be beneficial in the treatment of obese individuals.

Adult↗
PubMed2001

The role of galectin-3 in endocytosis of advanced glycation end products and modified low density lipoproteins.

Galectin-3, a member of beta-galactoside-binding lectin family, is suggested to be an AGE-receptor. To examine this possibility, we prepared CHO cells overexpressing human galectin-3 (galectin-3-CHO cells). Galectin-3-CHO cells showed a specific and saturable binding to (125)I-AGE-BSA with Kd of 3.1 microg/ml. (125)I-AGE-BSA was endocytosed by galectin-3-CHO cells and underwent lysosomal degradation. The endocytosis of (125)I-AGE-BSA was inhibited not only by unlabeled AGE-BSA but also by acetylated LDL and oxidized LDL, ligands for the scavenger receptor family. Furthermore, (125)I-oxidized LDL and (125)I-acetylated LDL were actively endocytosed by galectin-3-CHO cells and the incubation with acetyl-LDL led to intracellular accumulation of cholesteryl esters, indicating the role of galectin-3 in endocytosis of AGE-proteins and modified LDLs. Since galectin-3 was localized and up-regulated in foam cells at human atherosclerotic lesions, the present results suggest that galectin-3 plays an important role in formation of atherosclerotic lesions in vivo, by modulating endocytic uptake of AGE-proteins and modified LDLs.

Animals↗
PubMed2001

The presence of morphine in ganglionic tissues of Modiolus deminissus: a highly sensitive method of quantitation for morphine and its derivatives.

Morphine and morphine-6-glucuronide, a morphine metabolite, have been identified and quantified in Modiolus deminissus pedal ganglia at a level of 2.41 and 0.95 ng/ganglia, respectively. These opiate alkaloids are normally found at low concentrations in invertebrate and vertebrate tissues, including neural. Given this problem, we also describe a new opiate extraction protocol as well as a high-performance liquid chromatography purification procedure that can separate and quantify morphine and its derivatives at sub-nanogram concentrations. Furthermore, both morphine and morphine-6-glucuronide were identified in this mollusk's pedal ganglia by mass spectrometry analysis.

Animals↗
PubMed2001

Bayesian optimal designs for estimating a set of symmetrical quantiles.

We propose multiple-objective Bayesian optimal designs for the logit model. As an example, we consider the design problem for estimating several percentiles with possibly unequal interest in each of the percentiles. Characteristics of these designs are studied and illustrated for the case when the interest lies in estimating the three quartiles. We compare these optimal designs with the sequential designs generated via a generalized Pólya urn model and found the latter to be highly efficient. In addition, comparisons are made between locally optimal designs and Bayesian optimal designs.

Adult↗
PubMed2001

Separation selectivity patterns in the capillary electrophoretic separation of anionic enantiomers by octakis-6-sulfato-gamma-cyclodextrin.

The capillary electrophoretic separation of anionic enantiomers with multiply-charged, single-isomer, anionic resolving agents was reexamined with the help of the charged resolving agent migration model. Three general model parameters were identified that influence the shape of the separation selectivity and enantiomer mobility difference curves: parameter b, the binding selectivity (K(RCD)/K(SCD)), parameter s, the size selectivity (micro0RCD/micro0SCD), and parameter a, the complexation-induced alteration of the analyte's mobility (micro0SCD/micro0). Function analysis of the model indicates that there are six unique separation selectivity vs. resolving agent concentration patterns: in two of the patterns, separation selectivity asymptotically increases to the limiting value set by parameter b; in two other patterns, separation selectivity passes a local maximum and asymptotically decreases to the limiting value set by parameter b; and in the last two patterns, separation selectivity passes a local maximum, decreases to unity, then, after reversal of the intrinsic migration order, asymptotically increases to the limiting value set by parameter b. Though the patterns with asymptotically increasing selectivities were observed in earlier work, this paper reports the first experimental verification of the existence of the local selectivity maximum during the capillary electrophoretic separation of the enantiomers of several weak acids in high pH background electrolytes with octakis-6-sulfato-gamma-cyclodextrin as the resolving agent.

Cyclodextrins↗
PubMed2001

Captopril, a specific inhibitor of angiotensin converting enzyme, enhances both trypsin and vitellogenin titers in the grey fleshfly Neobellieria bullata.

A strong and constitutive angiotensin converting enzyme- or ACE-like activity was demonstrated in the hemolymph of the adult grey fleshfly Neobellieria bullata. In a competition assay, the N. bullata trypsin modulating oostatic factor (Neb-TMOF) was confirmed to be an in vitro substrate for this circulating Neb-ACE. Oral uptake of captopril, a selective and specific inhibitor of ACE, resulted in a complete phenotypic knockout of circulating ACE activity. When compared with control animals, captopril-fed female flies showed an increase in the liver meal-induced trypsin peak in the midgut and elevated levels of protein meal-induced yolk polypeptides in the hemolymph. The latter effect was not due to a slower vitellogenin uptake by the ovaries, because oocyte growth was not affected by the captopril treatment. The apparent synergism between the demonstrated ACE functionality and the previously reported effects of the oostatic peptide Neb-TMOF are discussed in the context of our recent finding that Neb-TMOF represents a prime candidate for being the first known in vivo substrate for circulating insect ACE. Arch.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2001

A novel inborn error in the ligand-binding domain of the vitamin D receptor causes hereditary vitamin D-resistant rickets.

Mutations in the vitamin D receptor (VDR) cause hereditary vitamin D-resistant rickets (HVDRR), an autosomal recessive disease resulting in target organ resistance to 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. In this report, we describe the clinical case and molecular basis of HVDRR in an Asian boy exhibiting the typical clinical features of the disease including alopecia. Using cultured dermal fibroblasts from the patient, 1,25(OH)(2)D(3) resistance was demonstrated by a shift in the dose response required for 25-hydroxyvitamin D-24-hydroxylase (24-hydroxylase) mRNA induction. Western blot showed that the cells express a normal size VDR but contained reduced levels of receptor compared to normal cells. At 24 degrees C, the affinity of the patient's VDR for [(3)H]1,25(OH)(2)D(3) was 50-fold lower than the VDR in normal fibroblasts. Sequence analysis identified a unique T to G missense mutation in exon 6 that changed phenylalanine to cysteine at amino acid 251 (F251C). The recreated F251C mutant VDR showed reduced transactivation activity using a 24-hydroxylase promoter-luciferase reporter. Maximal transactivation activity exhibited by the WT VDR was not achieved by the mutant VDR even when the cells were treated with up to 10(-6) M 1,25(OH)(2)D(3). However, the transactivation activity was partially rescued by addition of RXRalpha. In the yeast two-hybrid system and GST-pull-down assays, high concentrations of 1,25(OH)(2)D(3) were needed to promote F251C mutant VDR binding to RXRalpha, indicating defective heterodimerization. In conclusion, a novel mutation was identified in the VDR LBD that reduces VDR abundance and its affinity for 1,25(OH)(2)D(3) and interferes with RXRalpha heterodimerization resulting in the syndrome of HVDRR.

Animals↗
PubMed2001

Nitric oxide inhibits norepinephrine stimulated contraction of human internal thoracic artery and rat aorta.

The effect of nitric oxide (NO) on norepinephrine-induced vascular contraction was evaluated using segments of rat aorta and human internal thoracic artery (ITA) and the NO donor, SNAP. NO levels were measured directly using an amperometric probe. Concentrations of NO greater than 2 nM were required to reduce vascular contraction induced by 100 nM norepinephrine (NE). Exposure of the aortic rings to SNAP prior to, or after NE addition, resulted in a similar attenuation of NE-induced contraction. In contrast, increased relaxation of ITA segments in response to SNAP was observed relative to that of rat aorta and significant development of contractile tone following NE addition was not observed. Evaluation of cytoskeletal actin demonstrated marked loss of F-actin content in smooth muscle cells following NO exposure, suggesting that NO may have direct and indirect effects on contractile tone. These data taken together suggest that vascular responsiveness to contractile agents may be significantly attenuated by prior or subsequent exposure to NO, and mechanisms in addition to vascular relaxation are likely to contribute to this effect.

Animals↗
PubMed2001

The cell specific temporal expression of nitric oxide synthase isoforms during achilles tendon healing.

OBJECTIVE AND DESIGN: We have previously shown that nitric oxide synthase (NOS) activity is upregulated following tendon injury, and that this activity is important to Achilles tendon healing. The aim of this study was to identify the cellular distribution of nitric oxide synthase isoforms during tendon healing. MATERIAL OR SUBJECTS: Surgical division of the right Achilles tendon was performed in eighty-five male Sprague-Dawley rats. Healing Achilles tendons were harvested at 4, 7, 14 and 21 days following the surgery. The un-injured left Achilles tendons were used as controls. Using RNase protection assays, in situ hybridization and immunohistochemistry, mRNA and protein of NOS isoforms were evaluated. RESULTS: Minimal NOS expression was found in un-injured tendon. A cell specific temporal pattern for the mRNA and protein for all three NOS isoforms was found following injury to the Achilles tendon. iNOS was maximal on day 4 in macrophages and fibroblasts. eNOS was maximal on day 4 in endothelial cells and fibroblasts. bNOS expression gradually increased up to day 21 and was found only in fibroblasts. CONCLUSIONS: These results suggest that all three nitric oxide synthase isoforms are expressed by fibroblasts in a coordinated temporal sequence during tendon healing. The sequential pattern of NOS expression in healing fibroblasts suggests that each NOS isoform may play a different role in the healing process and provides opportunities to modify tendon healing in the clinical setting.

Achilles Tendon↗
PubMed2001

Drosophila SAP18, a member of the Sin3/Rpd3 histone deacetylase complex, interacts with Bicoid and inhibits its activity.

Bicoid directs anterior development in Drosophila embryos by activating different genes along the anterior-posterior axis. However, its activity is down-regulated at the anterior tip of the embryo, in a process known as retraction. Retraction is under the control of the terminal polarity system, and results in localized repression of Bicoid target genes. Here, we describe a Drosophila homolog of human SAP18, a member of the Sin3A/Rpd3 histone deacetylase complex. dSAP18 interacts with Bicoid in yeast and in vitro, and is expressed early in development coincident with Bicoid. In tissue culture cells, dSAP18 inhibits the ability of Bicoid to activate reporter genes. These results suggest a model in which dSAP18 interacts with Bicoid to silence expression of Bicoid target genes in the anterior tip of the embryo.

Amino Acid Sequence↗
PubMed2001

Proteolytic breakdown of the Neb-trypsin modulating oostatic factor (Neb-TMOF) in the hemolymph of different insects and its gut epithelial transport.

The degradation of the unblocked hexapeptide, trypsin modulating oostatic factor of the flesh fly Neobellieria (Sarcophaga) bullata (Neb-TMOF) was studied in vitro in the hemolymph of the lepidopteran Spodoptera frugiperda, the orthopteran Schistocerca gregaria and the dictyopteran Leucophaea maderae. The half-life in the different species varied from approximately 3min in L. maderae to approximately 25min in S. gregaria. Purification of the degradation products and ESI-Qq-oa-Tof mass spectrometry revealed the fragments Asn-Pro-Thr-Asn, Leu-His and Asn-Pro, which were the same in the hemolymph of all species. Except in Leucophaea, Neb-TMOF was cleaved in dipeptides starting from the C-terminus and the reaction could be, at least partially, inhibited by captopril. These observations suggest that a dipeptidase, which has very similar enzymatic properties as mammalian angiotensin converting enzyme (ACE) and which circulates in the hemolymph, apparently is involved in the breakdown of Neb-TMOF and might be a common but not a universal enzyme in insect hemolymph.The introduction of Neb-TMOF into the gut of S. gregaria with the help of a capillary tube (intubation) demonstrated that the intact peptide is able to cross the gut epithelium and to appear in the hemolymph compartment. Since [3H]-inulin, which is too large to cross cell membranes, was found to penetrate the gut walls at a measurable rate, the paracellular pathway might be also permeable to smaller peptides. There was indeed a clear correlation between the molecular weight of inulin, Neb-TMOF, and inositol and the rate of penetration of these compounds through the gut epithelium to the hemolymph. These are promising findings in view of a potential use of such peptides for insect control purposes.

Journal Article↗
PubMed2001

Application of ferrous hydrogen peroxide for treatment of DSD-acid manufacturing process wastewater.

A pretreatment method for the biological treatment of wastewater from 4,4'-diaminostilbene-2,2'-disulfonic acid (DSD-acid) manufacturing processes, a refractory dye intermediate wastewater, based on combined ferrous hydrogen peroxide oxidation and coagulation-flocculation, was developed. When the wastewater was treated with ferrous hydrogen peroxide oxidation ([Fe2+] = 2.7 mmol/L, [H2O2] = 0.21 mol/L) after a flocculation using an organic flocculant TS-1 at a dosage of 3 g/L, the overall COD and color removals were 64 and 62%, respectively. BOD5/COD value of the effluent was 0.3. Ferrous hydrogen peroxide oxidation treatment can reduce the solubility of organic molecules with sulfonic group and increase the efficiency of coagulation treatment. The COD and color removals were both more than 90% when FeCl3 was used as the coagulation (dosages of two-step coagulation were 0.031 and 0.012 mol/L respectively) after a ferrous hydrogen peroxide oxidation pretreatment at a H2O2 dosage of 0.06 mol/L.

4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfo↗
PubMed2001

Biological conversion of hydrogen sulphide to elemental sulphur in a fixed-film continuous flow photo-reactor.

The green sulphur bacterium Chlorobium thiosulfutophilum was used to remove hydrogen sulphide from synthetic industrial wastewater and convert it to elemental sulphur in a fixed-film continuous-flow photosynthetic bioreactor. Twenty 150 mm x 3 mm ID Tygon tubes formed the active part of the reactor resulting in a total volume of 21.2 mL. Seven steady states were achieved under different experimental conditions using this tubular photo-reactor. Sulphide loading rates ranged from 111 to 328 mg/hL under influent flowrates of 9.0-42.4 mL/h and hydraulic retention times of 0.50-2.35 h. The irradiance at the reactor surface averaged 25.4 W/m2. The sulphide removal rates were found to be 82-100% and elemental sulphur recovery rates were found to be 75-95%. The maximum sustainable sulphide loading rate was found to be 286 mg/h L, which is 2.5 times higher than the previous reported highest value. Sulphide loading rate was found to be the function of radiant flux per unit reactor volume and the bacteriochlorophyll concentration as expressed by the van Niel curve.

Bioreactors↗
PubMed2001

Comparative studies on the concentration of rare earth elements and heavy metals in the atmospheric particulate matter in Beijing, China, and in Delft, The Netherlands.

Atmospheric particulate matter (APM) was collected at three sampling sites in Beijing, China, from February to June 1998. The concentrations of rare earth elements (REE) and cobalt (Co), zinc (Zn), copper (Cu), cadmium (Cd) and lead (Pb) in the APM were determined by inductively coupled plasma mass spectrometry (ICP-MS). The results obtained in Beijing, China, were compared to that obtained in Delft, the Netherlands, in 1997. The influence of coal combustion was considered. The results demonstrated that the content of APM, the concentrations of REE and Co, Zn, Cd, Pb in the APM in Beijing, China, were higher than that in Delft, the Netherlands. From the ratios of La to Ce, and La to Sm, which may be used as tracers for the origin of the REE, it is concluded that the origins of REE in China differ from those in the Netherlands.

Air Pollutants↗
PubMed2001

Temporal expression of nitric oxide synthase isoforms in healing Achilles tendon.

We investigated the temporal expressions of the three nitric oxide synthase (NOS) isoforms by semi-quantitative polymerase chain reaction (PCR) assays and by immunoblot analysis, following Achilles tendon transection in rats. Four days after injury, there were increases in the steady-state levels of mRNA for all three NOS isoforms, with peaks for the inducible isoform (iNOS) (23-fold increase) at day 4, the endothelial isoform (eNOS) (24-fold increase) at day 7 and the neuronal isoform (bNOS) (seven-fold increase) at day 21. The temporal expression of NOS isoforms at a protein level was consistent with the results at the mRNA level. We have previously shown a five-fold increase in the NOS activity, as detected by 3H-arginine to 3H-citrulline conversion, at day 7 postinjury. These findings indicate that all three NOS isoforms are expressed during tendon healing with differential expression patterns during the various phases of tendon healing. These findings may prove clinically relevant with respect to strategies for regulating tendon healing.

Achilles Tendon↗
PubMed2001

In vitro degradation of the Neb-Trypsin modulating oostatic factor (Neb-TMOF) in gut luminal content and hemolymph of the grey fleshfly, Neobellieria bullata.

The unblocked hexapeptidic Trypsin Modulating Oostatic Factor of the fleshfly, an inhibitor of both trypsin and ecdysone biosynthesis, resists very well proteolytic breakdown by enzymes present in the lumen of the gut of previtellogenic fleshflies. However, when incubated in hemolymph of adult flies, females and males, its half-life time is a mere 0.5 min. In hemolymph of last instar larvae, this value increases to about 1.5 min. Whereas PMSF, a potent inhibitor of serine proteases has no effect, captopril and lisinopril, both known to be specific inhibitors of mammalian angiotensin I converting enzyme (ACE), effectively inhibit TMOF breakdown in fly hemolymph. Digestion of Neb-TMOF by recombinant Drosophila AnCE on itself results in identical degradation products as with total hemolymph. In both cases ESI-Qq-oa-Tof mass spectrometry demonstrated the appearance of peptide fragments with the sequences NPTN, LH and NP. These observations not only confirm the reported presence of circulating ACE-like activity in flies but also strongly suggest that in flies this hemolymph ACE-like activity might be involved in the regulation of the oostatic activity as exerted by Neb-TMOF.

Animals↗
PubMed2001

Growth hormone signalling and apoptosis in neonatal rat cardiomyocytes.

Growth hormone (GH) has been reported to be useful to treat heart failure. To elucidate whether GH has direct beneficial effects on the heart, we examined effects of GH on oxidative stress-induced apoptosis in cardiac myocytes. TUNEL staining and DNA ladder analysis revealed that hydrogen peroxide (H2O2)-induced apoptosis of cardiomyocytes was significantly suppressed by the pretreatment with GH. GH strongly activated extracellular signal-regulated kinases (ERKs) in cardiac myocytes and the cardioprotective effect of GH was abolished by inhibition of ERKs. Overexpression of dominant negative mutant Ras suppressed GH-stimulated ERK activation. Overexpression of Csk that inactivates Src family tyrosine kinases also inhibited ERK activation evoked by GH. A broad-spectrum inhibitor of protein tyrosine kinases (PTKs), genistein, strongly suppressed GH-induced ERK activation and the cardioprotective effect of GH against apoptotic cell death. GH induced tyrosine phosphorylation of EGF receptor and JAK2 in cardiac myocytes, and an EGF receptor inhibitor tyrphostin AG1478 and a JAK2 inhibitor tyrphostin B42 completely inhibited GH-induced ERK activation. Tyrphostin B42 also suppressed the phosphorylation of EGF receptor stimulated by GH. These findings suggest that GH has a direct protective effect on cardiac myocytes against apoptosis and that the effect of GH is attributed at least in part to the activation of ERKs through Ras and PTKs including JAK2, Src, and EGF receptor tyrosine kinase.

Animals↗