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Biomedical subjects

G Wu

Publications and source records attributed to G Wu.

At least 307 records · Page 17Linked to original sources
PubMed1998

Regulation of transforming growth factor-beta type II receptor expression in human breast cancer MCF-7 cells by vitamin D3 and its analogues.

In view of the tumor suppressor role of the transforming growth factor-beta (TGFbeta) type II receptor (RII), the identification and characterization of agents that can induce the expression of this receptor are of potential importance to the development of chemoprevention approaches as well as treatment of cancer. To date, the identification of exogenous agents that control RII expression has been rare. We demonstrated that proliferation of MCF-7 early passage cells (MCF-7 E), which express RII and are sensitive to TGFbeta growth inhibition activity, was significantly inhibited by vitamin D3 and its analogue EB1089. In contrast, proliferation of MCF-7 late passage cells (MCF-7 L), which have lost cell surface RII and are resistant to TGFbeta, was not affected by these two compounds. TGFbeta-neutralizing antibody was able to block the inhibitory effect on MCF-7 E cells by these compounds, indicating that treatment induced autocrine-negative TGFbeta activity. An RNase protection assay showed approximately a 3-fold induction of the RII mRNA, while a receptor cross-linking assay revealed a 3-4-fold induction of the RII protein. In contrast, there was no change in either RII mRNA or protein in the MCF-7 L cells.

Antineoplastic Agents↗
PubMed1998

Examination of trial-independent characteristics of body kinematics in response to similar postural perturbations.

This study investigated the variability of certain kinematic features describing body segmental movement in response to a series of consecutive, translational movements of the supporting base along the anterior-posterior direction of the subject. These kinematic features included the amplitude and timings of the angular displacement, velocity and acceleration of the head, trunk, thigh and shank. A group of 21 subjects was tested, with their ages ranging from 22 to 77 years. The results showed that the amplitudes changed significantly from the first trial to the later trials in most of the variables observed. However, there existed certain features, other than the amplitude, that were invariant over consecutive trials. Specifically, the time at which the initial peak amplitude occurred, the onset time was found to be similar between trials. Copyright 1997 Elsevier Science B.V.

Journal Article↗
PubMed1998

Cloning and characterization of the alpha 1-antichymotrypsin produced by human prostate tissue.

BACKGROUND: alpha 1-antichymotrypsin (ACT) forms stable complexes with prostate-specific antigen (PSA), a serine protease, and this complex is the major form of PSA in the blood circulation. alpha 1-antichymotrypsin occurs in the blood in approximately 10(5) molar excess to PSA, mainly due to hepatic production, but local prostatic production of ACT has been demonstrated by immunohistochemistry and in situ hybridization. The present study was performed to further characterize this prostate-produced ACT. METHODS: The nucleotide structure of the prostatic transcript was determined from ACT coding clones isolated from prostatic cDNA. The occurrence of a prostatic ACT transcript was analyzed by Northern blot. RT-PCR was used to detect ACT transcripts in cultured prostatic cancer cells. RESULTS: Screening of two prostatic cDNA libraries showed the frequency of ACT transcripts to be about 1 clone in 40,000. The cDNA sequence of prostatic ACT is identical to that of the previously published hepatic ACT. Northern blot analysis of mRNA extracted from prostatic tissue showed a single transcript of approximately 1.5 kb. RT-PCR analysis demonstrated an ACT transcript in cultured prostatic cancer cells. CONCLUSIONS: In this study we provide further evidence for a local, prostatic production of ACT. The cDNA sequence data suggest that the peptide backbone of prostatic ACT is identical to the protein derived from the liver, and thus may be functional as a protease inhibitor.

Base Sequence↗
PubMed1998

Carnitine acetyltransferase is not a cytosolic enzyme in rat heart and therefore cannot function in the energy-linked regulation of cardiac fatty acid oxidation.

The subcellular location of cardiac carnitine acetyltransferase (CAT) was investigated by measuring the release of carnitine acetyltransferase and of marker enzymes from isolated rat myocytes permeabilized with digitonin. Additionally, the carnitine acetyltransferase activity exposed to the cytosolic compartment was quantified. The results indicate that soluble acetyl transferase is not present in the cytosol, and that only 5% of the cellular carnitine acetyltransferase activity is positioned to catalyse the formation of cytosolic acetyl coenzyme A. This situation makes it unlikely that the energy-linked regulation of cardiac fatty acid oxidation proceeds by mechanisms which require the conversion of acetylcarnitine to acetyl coenzyme A in the cytosol.

Animals↗
PubMed1998

Effect of vaporized ethanol on [1-14C]pyruvate kinetics in mice using a four-compartment closed model.

The effect of the inhalation of vaporized ethanol on injected [1-14C]pyruvate kinetics was studied in mice. The [1-14C]pyruvate kinetics were modelled by means of a four-compartment closed model, i.e. injected site, blood, periphery and expired 14CO2. The results show that the inhalation of vaporized ethanol can stimulate expiration of 14CO2. The compartmental analysis suggests that the stimulation of expiration of 14CO2 is attributed to the increased trans-membrane and trans-tissue processes.

Animals↗
PubMed1998

Estimation of drug excretion rate from blood into the gut using a three-compartment closed model.

After administration and absorption, some drugs can be excreted via various mechanisms from blood into the gut; the determination of this drug excretion rate may have important clinical and pharmaceutical implications. A three-compartment closed model with first-order absorption was designed using absorption, blood and eliminated compartments to estimate the drug transfer rate from blood into the gut. Theoretically, the excretion rates of drugs whose blood concentrations can be described by the one-compartment open model with first-order absorption can be estimated using the developed model. This theoretical deduction was supported by 100 Monte Carlo simulations performed in the present study. A sensitivity analysis suggests that the estimated drug transfer rate from blood into gut is very sensitive to blood drug concentrations. Meanwhile, an example also shows the limitation of the developed model.

Body Fluid Compartments↗
PubMed1998

Cytogenic studies of Hynobiidae (Urodela). XIV. Analysis of the chromosome of a Chinese salamander, Batrachuperus pinchonii (David).

The chromosome number of a Chinese salamander, Batrachuperus pinchonii, was re-examined Adults and embryonic specimens had a diploid number of 66, with 33 bivalents during meiosis, in contrast to previous reported results. Furthermore, when C-banding analysis was performed with embryos, chromosomes with banding patterns homoeologous to those of Salamandrella keyserlingii and Hynobius species were found. It appears, therefore, that Batrachuperus, Salamandrella and Hynobius might be derived from a common ancestral species in eastern Asia.

Animals↗
PubMed1998

Application of the queueing theory with Monte Carlo simulation to inhalation toxicology.

Various models have been developed in modelling of inhalation toxicology. The deterministic approach, which has been used to date in most of the models, needs to consider numerous factors, e.g. anatomical structure, breathing frequency, humidity, metabolism rate, partition coefficients, pulmonary ventilation, perfusion rates, unidirectional/cyclic air flow, non-steady-state, steady-state, etc. In the present study, a stochastic approach was used in the modelling of inhalation toxicology, because there is a phenomenological analogy between the queueing system and respiratory system dealing with inhaled toxicants. Using the queueing theory, the amounts of toxicants in the respiratory system, the time needed to remove the accumulated amounts of toxicants from the respiratory system, etc. can be estimated. The Monte Carlo simulation of queueing process was performed to analyse cigarette smoking, and shows the potential use of the queueing theory in inhalation toxicology.

Administration, Inhalation↗
PubMed1998

Consistency of unitary shapes in dual lead recordings from myelinated fibres in human peripheral nerves: evidence for extracellular single-unit recordings in microneurography.

Percutaneous microneurography is a powerful technique allowing studies of activity in single nerve fibres of conscious humans. However, the mechanisms by which single-unit recordings are achieved with this technique are not fully understood. To further elucidate these mechanisms, dual-lead recordings, using a modified concentric needle electrode with two separate recording surfaces at the tip, were performed in normal subjects. Sixty-two single units supplied by large myelinated afferents were studied. The majority (90%) of the units were recorded simultaneously on both surfaces but with different action potential amplitudes. Four types of unitary waveforms were encountered. The potentials recorded on the two channels were of the same type, although occasionally some details differed. Parallel waveform changes of the same units occurred simultaneously on the two surfaces. A displacement of a single fibre from one recording surface to the other with or without concomitant waveform-type transitions was observed when the electrode was slightly repositioned intraneurally. The results provided direct evidence to confirm that concentric needle electrodes record single-unit activity extracellularly from myelinated nerve fibres, probably at or close to a node of Ranvier. All the types of action potentials encountered with conventional tungsten electrodes were also identified in dual-channel recordings with concentric electrodes, which casts doubt on the previous explanation that single-unit activity recorded with tungsten electrodes is derived from intracellular sources. Some biological and technical aspects of the findings are discussed, especially concerning the applicability of in vivo measurements of the time course of the action potentials in humans and ways to improve microneurography towards multichannel recordings.

Action Potentials↗
PubMed1998

Mg2+ block and inward rectification of mechanosensitive channels in Xenopus oocytes.

The effects of Mg2+ on single mechanosensitive (MS) channel currents recorded from Xenopus oocytes were studied using cell-attached and inside-out patch configurations. Mg2+ both permeates and blocks MS channels. Under symmetrical ionic conditions, the blocking effects of Mg2+ can be described by a Hill coefficient of 0.9 at +/-100 mV and IC50s of 0.12 mM (-100 mV) and 0.60 mM at (+100 mV). Although block by intracellular Mg2+ may contribute to inward MS channel rectification, significant current rectification is retained even under symmetrical KCl concentrations and in the complete absence of Mg2+. The observed voltage dependencies of the IC50 for Mg2+ block and the Km for K+ current saturation indicate asymmetries in the MS channel pore. In addition, the absence of K+ self block and anomalous mole fraction effects with K+/Tl+ mixtures indicate a single site pore model.

Animals↗
PubMed1998

Effect of human apolipoprotein E isoforms on plasma lipids, lipoproteins and apolipoproteins in apolipoprotein E-deficient mice.

The current study compared the acute effect of human apolipoprotein (apo) E isoforms on plasma lipids, lipoproteins and apolipoproteins 6 h after a bolus intravenous injection of individual isoforms into apo E-deficient mice. We found a large accumulation of remnant particles not only in the d<1.019 g/ml fraction but also in the d = 1.019-1.063 mg/dl fraction in the setting of absence of endogenous mouse apo E. A significant reduction in total cholesterol (49, 47 and 18%) (P<0.005), cholesterol in the d<1.019 g/ml fraction (56, 50 and 18%) and in the d = 1.019-1.063 mg/dl fraction (38, 40 and 17%) was obtained with apo E-3, E-4 and E-2, respectively. Apo E-3 and E-4 showed more pronounced total cholesterol lowering effect than E-2 (P<0.0001). In the d<1.019 g/ml fraction, apo E-3 and E-4 resulted in a marked decrease in apo B-100 (36 and 34%), B-48 (48 and 52%), A-I (48 and 44%) and A-IV (52 and 46%), respectively. The decrease caused by apo E-2 in apo B-100 (19%), B-48 (16%), A-I (18%) and A-IV (33%) was less than that of E-3 or E-4. In the d = 1.019-1.063 g/ml fraction, an apparent decline in apo B-48 (42 and 38%), A-I (39 and 40%) and an increase in apo B-100 (25 and 18%) were observed after apo E-3 and E-4 injection, respectively, while apo E-2 did not cause an appreciable change in these apolipoproteins (-4 to 6%). Compared to normal saline, liver total cholesterol content was increased by 37, 34 and 16% (P<0.05) after apo E-3, E-4 and E-2 injection, respectively. Apo E-3 and E-4 showed the same high affinity binding to mice hepatic LDL receptor, while apo E-2 was severely defective in binding. These findings indicate that apo E polymorphism is an important factor modulating remnant lipoprotein metabolism.

Animals↗
PubMed1998

Characterization of the cell-specific expression of parathyroid hormone-related protein in normal and neoplastic prostate tissue.

OBJECTIVES: Parathyroid hormone-related protein (PTHrP) is a primary factor in the pathogenesis of malignancy-associated hypercalcemia. By alternative splicing, the human PTHrP gene can generate three different species of mRNA that encode three initial translational isoforms of 139, 173, and 141 amino acids. We recently reported that PTHrP was present in normal prostatic neuroendocrine cells and was overexpressed in prostate cancer tissue as demonstrated by immunostaining. This study was undertaken to further clarify the complex expression of PTHrP gene in normal prostate tissue and prostate cancer. METHODS: PTHrP mRNA in samples prepared from normal prostate tissue, prostate cancer, and three prostate cancer cell lines, PC3, LNCaP, and DU145 was assessed using Northern hybridization. Expressed PTHrP isoforms were deduced from differential reverse transcription-polymerase chain reaction (RT-PCR) assays with exon-specific primers. Further localization of different species of PTHrP mRNA was performed using nonradioactive in situ hybridization with exon-specific probes on consecutive sections of normal and neoplastic prostate tissue. RESULTS: Northern hybridization showed that the PTHrP expression level was higher in prostate cancer than in normal prostate tissue. All three PTHrP isoforms could be detected in normal prostate tissues and prostate cancer with differential RT-PCR. Further analysis using in situ hybridization with exon-specific probes revealed that all three PTHrP isoforms were present in prostatic neuroendocrine cells and only PTHrP-1-139 isoform could be clearly detected in prostate cancer tissue. Two androgen-insensitive cell lines, PC3 and DU145, derived from a bone metastasis and a brain metastasis, respectively, expressed all three mRNA species encoding for the three isoforms, but DU145 cells expressed less than PC3 cells. Androgen-sensitive LNCaP cells exhibited a low level of expression of mRNA species encoding for PTHrP-1-139 and PTHrP-1-173, and no expression of PTHrP1-141 isoform. CONCLUSIONS: All three initial translational isoforms of PTHrP are produced by prostatic neuroendocrine cells. The mature products of PTHrP might exert their effects on other prostatic epithelial cells in a paracrine fashion and also participate in the homeostatic regulation of the ejaculate. In prostate cancer, differential expression of these three isoforms is evident and PTHrP-1-139 isoform is more abundant than the other two forms. These findings are valuable for designing future research studies to further elucidate the biological functions of PTHrP in normal prostatic glands and prostate cancer.

Blotting, Northern↗
PubMed1998

Interleukin-1 induces the expression of mu opioid receptors in endothelial cells.

Immunocytokines, such as interleukin-1 (IL-1), have been shown to be involved in the activation and/or induction of a variety of transcription factors which may modulate the expression of genes possessing DNA binding sites on which these transcription factors act. The promoter DNA sequence of the mu opioid receptor gene contains IL-1 response elements such as NF-IL6, and, therefore, the receptor gene may be responsive to IL-1. To investigate the effect of IL-1 on the opioid receptor gene, the in vitro expression of mu opioid receptor mRNA in neural microvascular endothelial cells (NMVEC) was determined before and after IL-1 treatment. PCR analysis revealed that there was virtually no mu opioid receptor expression at basal levels and no increase after either IL-1alpha or IL-1beta treatment. However, simultaneous treatment with both IL-1alpha and IL-1beta increased mu opioid receptor expression. This upregulation of mu opioid receptor expression provides direct evidence of a relationship between opioid and cytokine actions, and suggests that opioid-dependent pathways may be modulated in the disease state.

Cells, Cultured↗
PubMed1998

Compartmentation and kinetics of urea cycle enzymes in porcine enterocytes.

We have recently reported the synthesis of urea from ammonia, glutamine and arginine in enterocytes of postweaning pigs. The present study was conducted to determine the compartmentation and kinetics of urea cycle enzymes in these cells. Carbamoyl phosphate synthase I (CPS I) and ornithine carbamoyltransferase (OCT) were located exclusively in mitochondria, whereas argininosuccinate synthase (ASS) and argininosuccinate lyase (ASL) were found in the cytosol. Arginase isozymes were present in both the cytosol and mitochondria of enterocytes, and differed in their sensitivity to heat inactivation. Except for OCT, Vmax values of urea cycle enzymes were much lower in enterocytes than in the liver of pigs, and vice versa for their Km values. Because of a low rate of ureagenesis in enterocytes compared with the liver, intestinal urea cycle enzymes may function primarily to synthesize citrulline. The co-localization of CPS I and OCT and a high activity of OCT in enterocyte mitochondria favors the intestinal synthesis of citrulline from ammonia, HCO3- and ornithine. Low activities of cytosolic ASS and ASL minimize the conversion of citrulline into arginine and therefore, the recycling of citrulline into ornithine via arginase in postweaning-pig enterocytes. These kinetic properties of intestinal urea cycle enzymes maximize the net synthesis of citrulline from glutamine and explain the release of large amounts of citrulline by the pig small intestine. The two compartmentally separated arginase isozymes in enterocytes may play an important role in regulating the intestinal metabolism of proline, nitric oxide and polyamines.

Animals↗
PubMed1998

Distribution of phosphate-activated glutaminase isozymes in the chicken: absence from liver but presence of high activity in pectoralis muscle.

The distribution of glutaminase expression in a uricotelic species, the chicken, has been examined using cDNA probes to the rat isozymes. The results suggest that chickens do not possess a glutaminase isozyme equivalent to the liver-type isozyme of mammalian liver. Measurements of enzymic activity also showed very low glutaminase activity in chicken liver. Extra-hepatic tissues in the chicken do express a glutaminase isozyme mRNA which is detected by rat kidney-type glutaminase cDNA. The abundance of this mRNA was highest in kidney and breast muscle and relatively abundant in brain, spleen and adipose tissue. Chicken small intestine expressed relatively low levels of the mRNA. The high level of glutaminase mRNA in chicken pectoralis muscle was accompanied by high glutaminase enzymic activity. In contrast, in mixed leg muscle glutaminase mRNA was barely detectable by Northern blot and glutaminase activity was relatively low. Starvation for 48 h resulted in a slight decrease in the activity of glutaminase in pectoralis muscle, but a large decrease in the relative abundance of the mRNA. The results suggest that in the chicken, hepatic glutamine hydrolysis is not quantitatively important, but skeletal muscle may be a major site of glutamine catabolism.

Animals↗
PubMed1998

Using three-, four-, and n-compartment closed models to estimate glomerular filtration rate during and after a constant rate intravenous infusion.

The two-compartment open model is currently used to assess the glomerular filtration rate (GFR) after a single intravenous injection or a constant rate intravenous infusion. This model needs multiple blood samples from a patient, thus numerous limited sampling models have been so far developed to reduce the number of blood samples. In the present study, the three-, four- and n-compartment closed models have been developed to assess GFR after and during a constant rate intravenous infusion, which include the renal and all possible non-renal elimination pathways. Although more non-renal elimination compartments were included in the modelling, the results show it only leads to the increase in the similar analytical solutions for these compartments and the analytical solution for the blood compartment is the same as that in the two-compartment open model. Theoretically, the developed models can be used to assess GFR with a single blood sample at any sampling time with several urine samples.

Body Fluid Compartments↗