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Biomedical subjects

G Wu

Publications and source records attributed to G Wu.

At least 253 records · Page 14Linked to original sources
PubMed1999

On the shape of the probability weighting function.

Empirical studies have shown that decision makers do not usually treat probabilities linearly. Instead, people tend to overweight small probabilities and underweight large probabilities. One way to model such distortions in decision making under risk is through a probability weighting function. We present a nonparametric estimation procedure for assessing the probability weighting function and value function at the level of the individual subject. The evidence in the domain of gains supports a two-parameter weighting function, where each parameter is given a psychological interpretation: one parameter measures how the decision maker discriminates probabilities, and the other parameter measures how attractive the decision maker views gambling. These findings are consistent with a growing body of empirical and theoretical work attempting to establish a psychological rationale for the probability weighting function.

Humans↗
PubMed1999

Enhanced apoptosis mediates inhibition of EBV-transformed lymphoblastoid cell line proliferation by curcumin.

BACKGROUND: Epstein-Barr virus (EBV)-associated B-cell lymphomas occur more frequently in immunodeficient states such as organ transplantation and HIV infection. We have previously reported that B cell immortalization with EBV was promoted by cyclosporin A (CyA) and that curcumin (Cur), a natural phenol with known antioxidant and antitumor properties, blocked EBV-induced B cell immortalization. In the following experiments we show that Cur inhibits the proliferation of EBV-transformed lymphoblastoid cell lines (LCL) via enhanced apoptosis. METHODS: LCL were generated by infecting freshly isolated human B cells with EBV (B95-8) for 12 h and coculturing with predetermined optimal concentrations of CyA (500 ng/ml) for 4 weeks. LCL were then either frozen for future use or propagated for immediate experiments. These cells were then plated in 96-well plates with 20 microM Cur or 0.1% DMSO (vehicle control). The number of immortalized colonies/well, cell count, and (3)H uptake were used as an index of immortalization. To assess apoptosis rate LCL were cultured with 0.1% DMSO or Cur (20 microM) for 0, 18, and 42 h in culture flasks and then stained with MC540 and H33342, as markers for apoptosis, and analyzed by FACS. RESULTS: A profound inhibition of proliferation was seen in the LCL with 20 microM curcumin compared to 0.1% DMSO control. The colony count reduced from 34.5 +/- 3.4 to 0/well (P = 0.005), cell number reduced from 101,250 +/- 12,093 to 3750 +/- 1500/well (P = 0.002), and (3)H uptake reduced from 40,889 +/- 3669 to 70 +/- 5.2/well (P = 0.001). The apoptosis rate of LCL in the DMSO control at 24.07 and 16.87% increased significantly with 20 microM Cur to 76.4 and 95.1% at 18 and 42 h, respectively (P = 0.02). CONCLUSION: Cur is a potent inhibitor of EBV-transformed LCL. This effect appears to be mediated through enhanced apoptosis. A further investigation of this effect may be useful in prevention and therapy of B-cell lymphoma in immunodeficient patients.

Antineoplastic Agents↗
PubMed1999

Pharmacodynamic modelling of levodopa, 3-O-methyldopa and their effects: an application of the Dixon equation.

The modified Dixon equation was applied to describe the relationship between levodopa, 3-O-methyldopa (3OMD) concentrations and tapping test in 16 patients with Parkinson's disease treated with controlled release levodopa/carbidopa association. The sigmoid equation was also used to describe the relationship between levodopa and tapping test, and the results were compared to those obtained using the Dixon equation. Graphically, the fittings using the Dixon equation can be constructed in a three-dimensional space, whereas the fittings using the sigmoid equation can be constructed in a two-dimensional plane. The results show that the fittings in the three-dimensional space are slightly better than those in the two-dimensional plane. The advantage of the Dixon equation over the sigmoid equation is that the Dixon equation can take 3OMD into consideration for pharmacodynamic modelling.

Aged↗
PubMed1999

Gadolinium-containing copolymeric chelates--a new potential MR contrast agent.

RATIONALE AND OBJECTIVES: To develop and partially characterize a new class of potential blood pool magnetic resonance (MR) contrast agents. METHODS: Various copolymeric chelates of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA) were prepared with differing molecular weights of polyethylene glycol (PEG) or polypropylene glycol (PPG) as linkers between the monomeric chelate units. Gadolinium content of the polymeric chelates was determined by atomic absorption spectra. Relaxivity of the polymeric chelates was measured at 1.5 Tesla and compared with Gadolinium DTPA. MR angiography (MRA) was performed in rabbits comparing Gd-DTPA with Gd copolymers. RESULTS: The gadolinium content of the copolymeric chelates ranged from 2.95 to 22.2% on weight basis. The molecular weight of the PEG linkers in the copolymers ranged from about 150 to about 3400. The r1 (1/T1, mM(-1) s(-1)) for Gd DTPA = 4.1. The r1 values for the different Gd-containing polymers ranged from 3.8 to 5.8, with the lowest r1 for the polymer prepared with the lowest-molecular-weight complex. The higher-molecular-weight complexes resulted in moderately higher relaxivity. MRA with Gd-copolymers, in rabbits, showed markedly greater vascular enhancement relative to an equivalent dose of Gd-DTPA. Vascular enhancement was much more sustained with the copolymeric agent and confined to vascular space; i.e. no appreciable background tissue enhancement--a reflection of distribution into extravascular fluid space--was observed. CONCLUSIONS: Relative to Gd-DTPA monomers, PEG-containing Gd DTPA polymeric complexes provided moderate increases in relaxivity but markedly greater efficacy during in vivo MRA. In vitro relaxivity studies of Gd-copolymers showed only an approximately 50% increase in r1 relaxivity compared with Gd-DTPA. The PEG-containing complex's lack of rigidity may have diminished the effect of spin diffusion on relaxation, thereby accounting for this modest increase. The greater efficacy of Gd-copolymers during in vivo MRA may reflect compartmentalization within the vascular space and possibly enhanced relaxation of the macromolecular copolymers in the blood. Gd-copolymers are promising agents that merit additional study.

Animals↗
PubMed1999

Clustering of Pacinian corpuscle afferent fibres in the human median nerve.

To further study the functional organisation of human peripheral nerves, the intrafascicular arrangement of afferent fibres supplying Pacinian corpuscles (PCs) was explored by percutaneous microneurography using thin-calibre, concentric needle electrodes. In normal adults, 20 PC afferents were identified in 13 recording sites. Low-amplitude (less than 30 microm) vibratory stimuli to the skin were applied with tuning forks oscillating at 128 Hz or 256 Hz and response patterns of individual PC units were studied. In many recording sites, two, sometimes even three, PC afferents with adjacent or overlapping receptive fields in the hand were clustered in the nerve. The observed incidence in the records containing a certain number of PC units was compared with the expected probability calculated according to the hypothesis that all nerve fibres are randomly organised in peripheral nerves. The results suggested that PC afferents are partially segregated in the nerve. In addition, PC afferents were neighbouring on slowly adapting type II (SAII) units and skin sympathetic activity in individual fascicles. SAII units often innervated the same skin area as PC units, but did not respond to vibration. The data provided additional information regarding the functional organisation of the human peripheral nerve and the mechanisms underlying the sense of vibration in man with special regard to population behaviour of neighbouring PC mechanoreceptors.

Adult↗
PubMed1999

Localization and sex steroid regulation of androgen receptor gene expression in rhesus monkey uterus.

OBJECTIVE: To characterize the cellular sites and hormonal regulation of uterine androgen receptor gene expression in the monkey. METHODS: Ovariectomized rhesus monkeys (five in each group) were treated with placebo (the control group), estradiol (E2), E2 plus progesterone, or E2 plus testosterone by sustained-release pellets administered subcutaneously. After 3 days of treatment, uteri were removed and uterine sections were analyzed by in situ hybridization for androgen receptor messenger RNA (mRNA). RESULTS: Androgen receptor mRNA was detected in endometrial stromal cells and myometrial smooth muscle cells, with lesser expression in endometrial epithelial cells. Both E2 and E2 plus progesterone treatment doubled androgen receptor mRNA levels in stromal cells (P < .01), whereas E2 plus testosterone treatment increased stromal androgen receptor mRNA levels by about five-fold (P < .001) compared with placebo treatment. In the endometrial epithelium, E2 alone did not increase androgen receptor mRNA levels significantly. However, the E2 plus progesterone and E2 plus testosterone treatments increased epithelial androgen receptor mRNA levels by 4.3 and 5 times, respectively (P = .008 and P < .002, respectively). Androgen receptor mRNA was distributed homogeneously in smooth muscle cells across the myometrium. Estradiol treatment alone did not increase myometrial androgen receptor mRNA levels significantly, but the E2 plus progesterone and E2 plus testosterone treatments increased myometrial androgen receptor mRNA levels by 1.8 and 2 times, respectively (P = .001 and P < .001, respectively). CONCLUSION: Androgen receptor gene expression was detected in all uterine cell compartments where it was subject to significant sex steroid regulation. The fact that androgen receptor mRNA levels were consistently up-regulated by a combined E2 plus testosterone treatment while E2 treatment alone had little or no effect shows that a collaborative action of E2 and testosterone enhances androgen receptor expression in the monkey uterus.

Animals↗
PubMed1999

Sequence analysis of genes encoding ribosomal proteins of amitochondriate protists: L1 of Trichomonas vaginalis and L29 of Giardia lamblia.

Two genes encoding the ribosomal proteins were cloned and sequenced from amitochondriate protists, L1 (L10a in mammalian nomenclature) from Trichomonas vaginalis and L29 (L35 in mammalian nomenclature) from Giardia lamblia. The deduced amino acid sequences were analyzed by sequence alignments and phylogenetic reconstructions. Both the T. vaginalis L1 and the G. lamblia L29 displayed eukaryotic sequence features, when compared with all the homologs from the three primary kingdoms.

Amino Acid Sequence↗
PubMed1999

The effect of macrophage depletion on delayed xenograft rejection: studies in the guinea pig-to-C6-deficient rat heart transplantation model.

The purpose of this study was to investigate the effect of macrophage depletion, using liposome-encapsulated dichloromethylene diphosphonate (Lip-Cl2MDP), on delayed xenograft rejection (DXR) in the guinea pig-to-C6-deficient rat heart transplantation model. In this model, hyperacute rejection does not occur, but, in untreated recipients, xenografts are still destroyed by DXR within 1-2 days. Graft survival was 68 +/- 8.4 h in splenectomized control rats, 77 +/- 16.3 h with Lip-Cl2MDP alone, 99 +/- 10.4 h with deoxysperguarlin (DSG; P < 0.01 vs. controls), and 127 +/- 19.4 h with Lip-Cl2MDP plus DSG (P < 0.01 vs. DSG alone). Treatment with DSG alone or in combination with Lip-Cl2MDP resulted in significant reductions in serum IgM levels at rejection. Immunohistological studies showed that Lip-Cl2MDP alone or in combination with DSG reduced infiltration of grafts by both EDI + and ED2 + macrophages. These experiments support the concept that macrophages play an important role in DXR and suggest that strategies targeting macrophages may be useful in controlling DXR.

Animals↗
PubMed1999

The effects of tetramethylpyrazine on the incidence of arrhythmias and the release of PGI2 and TXA2 in the ischemic rat heart.

Pretreatment with tetramethylpyrazine (TMP, 12 mg/kg/day), a drug originally derived from the rhizomes of Ligusticum wallichii, significantly reduced the incidence of ischemia-induced ventricular tachycardia (VT) and fibrillation (VF) from 100% and 50% of control hearts to 41% (p < 0.05) and 0% (p < 0.05), respectively, in the ischemic rat heart. TMP also diminished the incidence of reperfusion-induced VT and VF from 100% and 100% of control hearts to 33% (p < 0.05) and 41% (p < 0.05), respectively. Pretreatment with TMP produced a slight, but significant increase of 6-keto-PGF1 alpha and a decrease of TXB2 production during aerobic perfusion. Ischemia and reperfusion markedly increased the release of 6-keto-PGF1 alpha and TXB2. Pretreatment with TMP significantly enhanced the release of 6-keto-PGF1 alpha and diminished TXB2 outflow following left coronary artery occlusion and reperfusion.

Animals↗
PubMed1999

Double-blind placebo-controlled study of concurrent administration of albendazole and praziquantel in schoolchildren with schistosomiasis and geohelminths.

A double-blind placebo-controlled study of the concurrent administration of albendazole and praziquantel was conducted in>1500 children with high prevalences of geohelminths and schistosomiasis. The study sites were in China and the Philippines, including 2 strains of Schistosoma japonicum, and 2 different regions of Kenya, 1 each with endemic Schistosoma mansoni or Schistosoma haematobium. Neither medication affected the cure rate of the other. There was no difference between the side effect rate from albendazole or the double placebo. Praziquantel-treated children had more nausea, abdominal pain, and headache but these side effects were statistically more common in children with schistosomiasis, suggesting a strong influence of dying parasites. The subjects were followed for 6 months for changes in infection status, growth parameters, hemoglobin, and schistosomiasis morbidity. In all 4 sites, a significant 6-month increase in serum hemoglobin was observed in children who received praziquantel, strongly supporting population-based mass treatment.

Adolescent↗
PubMed1999

Myocardial retinoid X receptor, thyroid hormone receptor, and myosin heavy chain gene expression in the rat during adult aging.

Although previous studies have shown that cardiac myosin heavy chain (MHC) composition undergoes a switch from the alpha- to beta-isoform in the heart during adult aging, the underlying mechanisms responsible for this switch are unknown. Cardiac MHC gene expression is regulated, in part, by thyroid hormone responsive elements present in the regulatory control regions of the alpha- and beta-MHC genes. Age-associated changes in the expression of thyroid hormone receptors (THRs) and/or retinoid X receptors (RXRs), the heterodimeric partner for THRs, could explain the age-associated changes in MHC expression. Accordingly, we measured mRNA levels for the cardiac muscle MHCs and the rat THR and RXR genes in the left ventricles of Wistar rats at 2, 6, and 24 months of age. Although there were no significant changes in RXR alpha or RXR beta mRNA levels with age, both alpha 1 and alpha 2 THR mRNA levels decreased significantly between 2 and 6 months of age. During this same time period, the mRNA levels for alpha-MHC declined by more than half, whereas beta-MHC mRNA levels remained low and unchanged. On the other hand, between 6 and 24 months, when mRNA levels for beta-MHC increased and alpha-MHC continued to decrease, there was a significant decline in THR beta 1 and RXR gamma mRNA levels accompanied by a reduction in the THR beta 1 and RXR gamma protein levels. These data show a pattern of change that suggests that the decline in alpha-MHC gene expression may be biphasic and due to a decline in alpha 1 (and possibly alpha 2) THR levels between 2 and 6 months of age and a decline in THR beta 1 and RXR gamma levels at later stages. In contrast, the increase in beta-MHC gene expression was associated only with the changes in THR beta 1 and RXR gamma mRNA and protein levels.

Aging↗
PubMed1999

Glucocorticoids mediate the enhanced expression of intestinal type II arginase and argininosuccinate lyase in postweaning pigs.

Arginine metabolism is enhanced in the small intestine of weanling pigs, but the molecular mechanism(s) involved is not known. The objectives of this study were to determine the following: 1) whether glucocorticoids play a role in induction of intestinal arginine metabolic enzymes during weaning; 2) whether the induction of enzyme activities was due to increases in corresponding mRNA levels; and 3) the identity of the arginase isoform(s) expressed in the small intestine. Jejunum was obtained from 29-d-old weaned pigs that were or were not treated with 17-beta-hydroxy-11beta-(4-dimethylaminophenyl)17alpha-(prop- 1-ynyl)es tra-4,9-dien-3-one (RU486, an antagonist of glucocorticoid receptors), or from age-matched suckling pigs. Activities and mRNA levels for type I and type II arginases, argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) were determined. Activities of arginase, ASL and ASS increased by 635, 56 and 106%, respectively, in weanling pigs, compared with suckling pigs. RU486 treatment attenuated the increase in arginase activity by 74% and completely prevented the ASL induction in weanling pigs, but had no effect on ASS activity. Pig intestine expresses both type I and type II arginases. On the basis of immunoblot analyses, there was no significant difference in levels of intestinal type I arginase among these three groups of pigs, indicating that changes in arginase activity were due only to type II arginase. The mRNA levels for type II arginase and ASL increased by 135 and 198%, respectively, in weanling pigs compared with suckling pigs, and this induction was completely prevented by RU486. In contrast, ASS mRNA levels did not differ between suckling and weanling pigs. These results suggest that intestinal type II arginase, ASS and ASL are regulated differentially at transcriptional and post-translational levels and that glucocorticoids play a major role in the induction of type II arginase and ASL mRNAs in the small intestine of weanling pigs.

Analysis of Variance↗
PubMed1999

Amino acid composition of the fetal pig.

Amino acid composition and accretion were determined in fetal pigs obtained from gilts by hysterectomy at d 40-114 of gestation. The whole homogenate of the fetal pig was used for analysis of dry matter, nitrogen and amino acids. Uterine uptake of amino acids was estimated at d 110-114 of gestation on the basis of uterine arteriovenous concentrations. Nitrogen and amino acid accretion in fetal pigs increased more rapidly with gestation than non-nitrogen dry matter. Amino acid nitrogen represented 83-88% of total nitrogen, and arginine was the most abundant nitrogen carrier in fetal pigs at all gestational ages. Amino acid composition changed with gestation, with glycine and hydroxyproline increasing (P < 0.05) markedly and other amino acids (except ornithine and tryptophan) decreasing (P < 0.05) to a lesser extent. Amino acid concentrations in fetal pigs increased (P < 0.05) progressively from d 60 to 114 of gestation. Uterine uptake of arginine and proline plus hydroxyproline met requirements for fetal growth during late gestation only marginally, and uterine uptake of aspartate/asparagine and glutamate was only 9-29% of fetal accretion. In contrast, uterine uptake of citrulline and ornithine was 55- and 15-fold greater (P < 0.05) than fetal accretion, respectively. On the basis of hydroxyproline content, collagen was estimated to represent approximately 7, 15, 25, 28 and 29% of total body protein at d 40, 60, 90, 110 and 114 of gestation, respectively. Amino acid composition of the fetal pig is similar to that for the human fetus, indicating that the pig is an excellent model for studying amino acid nutrition and metabolism in the human preterm neonate and infant.

Amino Acids↗
PubMed1999

Dietary protein or arginine deficiency impairs constitutive and inducible nitric oxide synthesis by young rats.

Effects of dietary protein or arginine deficiency on constitutive and lipopolysaccharide (LPS)-induced nitric oxide (NO) synthesis were determined in young rats by quantifying urinary nitrate excretion. In Experiment 1, 30-d-old rats (n = 16) were divided randomly into two groups (n = 8/group) and pair-fed on the basis of body weight semipurified isocaloric diets containing 20 or 5% casein. In Experiment 2, 30-d-old rats (n = 24) were divided randomly into three groups (n = 8) and pair-fed on the basis of body weight purified isonitrogenous and isocaloric diets (composed of amino acids) containing 0.0, 0.3 or 1.0% L-arginine. In both experiments, daily collection of urine was initiated 10 d after the start of pair-feeding. On d 17 after the pair-feeding was initiated, LPS (1 mg/kg body wt) was injected intraperitoneally into rats, and urine was collected daily for an additional 7 d. In Experiments 3 and 4, activities of constitutive and inducible NO synthases were measured in macrophages and various tissues from protein- or arginine-deficient rats (n = 6). Body weight was lower in rats fed the 5% casein diet or the 0.0 and 0.3% arginine diets than in those fed 20% casein or 1% arginine, respectively. Dietary protein or arginine deficiency decreased serum concentrations of arginine and urinary nitrate excretion before and after LPS treatment, indicating impaired constitutive and inducible NO synthesis. Protein malnutrition reduced constitutive and inducible NO synthase activities in brain, heart, jejunum, lung, skeletal muscle and spleen, and inducible NO synthase activity in macrophages. Because NO is a mediator of the immune response and is the endothelium-dependent relaxing factor, impaired NO synthesis may help explain immunodeficiency and cardiovascular dysfunction in protein- or arginine-deficient subjects.

Amino Acids↗
PubMed1999

Isolation, chromosomal localization, and differential expression of mitochondrial manganese superoxide dismutase and chloroplastic copper/zinc superoxide dismutase genes in wheat.

Superoxide dismutase (SOD) gene expression was investigated to elucidate its role in drought and freezing tolerance in spring and winter wheat (Triticum aestivum). cDNAs encoding chloroplastic Cu/ZnSODs and mitochondrial MnSODs were isolated from wheat. MnSOD and Cu/ZnSOD genes were mapped to the long arms of the homologous group-2 and -7 chromosomes, respectively. Northern blots indicated that MnSOD genes were drought inducible and decreased after rehydration. In contrast, Cu/ZnSOD mRNA was not drought inducible but increased after rehydration. In both spring and winter wheat seedlings exposed to 2 degrees C, MnSOD transcripts attained maximum levels between 7 and 49 d. Transcripts of Cu/ZnSOD mRNA were detected sooner in winter than in spring wheat; however, they disappeared after 21 d of acclimation. Transcripts of both classes of SOD genes increased during natural acclimation in both spring and winter types. Exposure of fully hardened plants to three nonlethal freeze-thaw cycles resulted in Cu/Zn mRNA accumulation; however, MnSOD mRNA levels declined in spring wheat but remained unchanged in winter wheat. The results of the dehydration and freeze-thaw-cycle experiments suggest that winter wheat has evolved a more effective stress-repair mechanism than spring wheat.

Chloroplasts↗
PubMed1999

The CLAVATA1 receptor-like kinase requires CLAVATA3 for its assembly into a signaling complex that includes KAPP and a Rho-related protein.

The CLAVATA1 (CLV1) and CLAVATA3 (CLV3) genes are required to maintain the balance between cell proliferation and organ formation at the Arabidopsis shoot and flower meristems. CLV1 encodes a receptor-like protein kinase. We have found that CLV1 is present in two protein complexes in vivo. One is approximately 185 kD, and the other is approximately 450 kD. In each complex, CLV1 is part of a disulfide-linked multimer of approximately 185 kD. The 450-kD complex contains the protein phosphatase KAPP, which is a negative regulator of CLV1 signaling, and a Rho GTPase-related protein. In clv1 and clv3 mutants, CLV1 is found primarily in the 185-kD complex. We propose that CLV1 is present as an inactive disulfide-linked heterodimer and that CLV3 functions to promote the assembly of the active 450-kD complex, which then relays signal transduction through a Rho GTPase.

Arabidopsis Proteins↗
PubMed1999

Lactate inhibits citrulline and arginine synthesis from proline in pig enterocytes.

Hypocitrullinemia and hypoargininemia but hyperprolinemia are associated with elevated plasma concentration of lactate in infants. Because the small intestine may be a major organ for initiating proline catabolism via proline oxidase in the body and is the major source of circulating citrulline and arginine in neonates, we hypothesized that lactate is an inhibitor of intestinal synthesis of citrulline and arginine from proline. To test this hypothesis, jejunum was obtained from 14-day-old suckling pigs for preparation of enterocyte mitochondria and metabolic studies. Mitochondria were used for measuring proline oxidase activity in the presence of 0-10 mM L-lactate. For metabolic studies, enterocytes were incubated at 37 degrees C for 30 min in Krebs bicarbonate buffer (pH 7.4) containing 5 mM D-glucose, 2 mM L-glutamine, 2 mM L-[U-14C]proline, and 0, 1, 5, or 10 mM L-lactate. Kinetics analysis revealed noncompetitive inhibition of intestinal proline oxidase by lactate (decreased maximal velocity and unaltered Michaelis constant). Lactate had no effect on either activities of other enzymes for arginine synthesis from proline or proline uptake by enterocytes but decreased the synthesis of ornithine, citrulline, and arginine from proline in a concentration-dependent manner. These results demonstrate that lactate decreased intestinal synthesis of citrulline and arginine from proline via an inhibition of proline oxidase and provide a biochemical basis for explaining hyperprolinemia, hypocitrullinemia, and hypoargininemia in infants with hyperlactacidemia.

Animal Nutritional Physiological Phenomena↗