Biomedical subjects

D He

Publications and source records attributed to D He.

At least 19 recordsLinked to original sources

PubMed2006

Human cytosolic sulfotransferase 2B1: isoform expression, tissue specificity and subcellular localization.

Sulfation is an important Phase II conjugation reaction involved in the synthesis and metabolism of steroids in humans. Two different isoforms (2B1a and 2B1b) are encoded by the sulfotransferase (SULT) 2B1 gene utilizing different start sites of transcription resulting in the incorporation of different first exons. SULT2B1a and SULT2B1b are 350 and 365 amino acids in length, respectively, and the last 342 aa are identical. Message for both SULT2B1 isoforms is present in human tissues although SULT2B1b message is generally more abundant. However, to date only SULT2B1b protein has been detected in human tissues or cell lines. SULT2B1b is localized in the cytosol and/or nuclei of human cells. A unique 3'-extension of SULT2B1b is required for nuclear localization in human BeWo placental choriocarcinoma cells. Nuclear localization is stimulated by forskolin treatment in BeWo cells and serine phosphorylation has been identified in the 3'-extension. SULT2B1b is selective for the sulfation of 3beta-hydroxysteroids such as dehydroepiandrosterone and pregnenolone, and may also have a role in cholesterol sulfation in human skin. The substrate specificity, nuclear localization, and tissue localization of SULT2B1b suggest a role in regulating the responsiveness of cells to adrenal androgens via their direct inactivation or by preventing their conversion to more potent androgens and estrogens.

Amino Acid Sequence↗

PubMed2006

Porcine reproductive and respiratory syndrome virus productively infects monocyte-derived dendritic cells and compromises their antigen-presenting ability.

Dendritic cells (DC) are potent antigen-presenting cells that play an important role in inducing primary antigen-specific immune responses. However, some viruses have evolved to specifically target DC to circumvent the host's immune responses for their persistence in the host. Porcine reproductive and respiratory syndrome virus (PRRSV) causes a persistent infection in susceptible animals. Although it is generally believed that the existence of PRRSV quasispecies is partly responsible for the virus persistence, other mechanisms of immune evasion or immune suppression may also exist. Here, we studied the role of DC in PRRSV persistence and immune suppression. Our results showed that PRRSV underwent a productive replication in pig monocyte-derived DC (Mo-DC) as measured by both immunofluorescence staining of viral nucleocapsid protein and virus titration assays, leading to cell death via both apoptosis and necrosis mechanisms. Additionally, PRRSV infection of Mo-DC resulted in reduced expression of MHC class I, MHC class II, CD14 and CD11b/c. This was in agreement with the impaired mixed lymphocyte reaction of PRRSV-infected Mo-DC compared to that of mock-infected Mo-DC. We also examined the cytokine profiles of PRRSV-infected Mo-DC using a quantitative ELISA method. Results indicated that no apparent change in the levels of IL-10, IL-12 and IFN-gamma was detected. Taken together, our data demonstrate that PRRSV productively infects Mo-DC and impairs the normal antigen presentation ability of Mo-DC by inducing cell death, down-regulating the expression of MHC class I, MHC class II, CD11b/c and CD14 and by inducing minimal Th1 cytokines.

Animals↗

PubMed2006

Significance of heat-stable and heat-labile enterotoxins in porcine colibacillosis in an additive model for pathogenicity studies.

Although heat-stable (ST) and heat-labile (LT) enterotoxins produced by enterotoxigenic Escherichia coli (ETEC) have been documented as important factors associated with diarrheal diseases, investigations assessing the contributions of individual enterotoxins to the pathogenesis of E. coli infection have been limited. To address the individual roles of enterotoxins in the diarrheal disease caused by K88-positive ETEC in young pigs, enterotoxin-positive and -negative isogenic E. coli strains were constructed by using pBR322 to clone and express LT and STb. Four strains, K88+ astA, K88+ astA/pBR322, K88+ astA STb+, and K88+ astA LT+, were constructed and subsequently included in gnotobiotic piglet challenge studies, and their pathogenesis was assessed. The results indicated that all K88+ isogenic strains were able to colonize the small intestines of piglets exhibiting the K88 receptor. However, only LT- and STb-positive strains caused appreciable diarrhea. Piglets inoculated with the K88+ astA LT+ strain became dehydrated within 18 h, while those inoculated with the K88+ astA STb+ strain did not, although diarrhea developed in several piglets. The changes in the blood packed-cell volume and plasma total protein of gnotobiotic piglets inoculated with the LT-positive strains were significantly greater than those of pigs inoculated with the K88 astA/pBR322 strain (P = 0.012, P = 0.002). Immunochemistry image analysis also suggested that LT enhanced bacterial colonization in a gnotobiotic piglet model. This investigation suggested that LT is a major contributor to the virulence of K88+ ETEC and that isogenic constructs are a useful tool for studying the pathogenesis of ETEC infection.

Animals↗

PubMed2005

Structural analysis of a set of proteins resulting from a bacterial genomics project.

The targets of the Structural GenomiX (SGX) bacterial genomics project were proteins conserved in multiple prokaryotic organisms with no obvious sequence homolog in the Protein Data Bank of known structures. The outcome of this work was 80 structures, covering 60 unique sequences and 49 different genes. Experimental phase determination from proteins incorporating Se-Met was carried out for 45 structures with most of the remainder solved by molecular replacement using members of the experimentally phased set as search models. An automated tool was developed to deposit these structures in the Protein Data Bank, along with the associated X-ray diffraction data (including refined experimental phases) and experimentally confirmed sequences. BLAST comparisons of the SGX structures with structures that had appeared in the Protein Data Bank over the intervening 3.5 years since the SGX target list had been compiled identified homologs for 49 of the 60 unique sequences represented by the SGX structures. This result indicates that, for bacterial structures that are relatively easy to express, purify, and crystallize, the structural coverage of gene space is proceeding rapidly. More distant sequence-structure relationships between the SGX and PDB structures were investigated using PDB-BLAST and Combinatorial Extension (CE). Only one structure, SufD, has a truly unique topology compared to all folds in the PDB.

Databases, Protein↗

PubMed2005

Arg9-peptide facilitates the internalization of an anti-CEA immunotoxin and potentiates its specific cytotoxicity to target cells.

Arginines-containing membrane translocational signals (MTS), such as Tat(47-57) and VP22(267-300), and synthetic arginine-rich peptides have been reported to be efficient carriers for transporting various types of biomolecules into cytoplasmic and nuclear compartments of living cells. Among those arginines-containing MTS, a 9-mer arginine peptide (Arg9) was proved the most economical and efficient. We fused Arg9-peptide to an anti-CEA (Carcinoembryonic antigen) immunotoxin, PE35/CEA(Fv)/KDEL, at the position between the toxin moiety and the binding moiety. Strong binding and internalization of this fusion protein was observed in all detected cell lines, but little cytotoxicity to the cells that lack the CEA molecules on the cell surface was detected. However, the cytotoxicity besides the binding activity of the fusion protein to specific tumor cells expressing large amount of CEA molecules on the cell surface was improved markedly, indicating that the Arg9-peptide is capable of facilitating the receptor-mediated endocytosis of this immunotoxin, which leads to the increase of the specific cytotoxicity of this immunotoxin.

Arginine↗

PubMed2005

Inhibition by lipopolysaccharide of naloxone-induced luteinising hormone secretion is accompanied by increases in corticotropin-releasing factor immunoreactivity in hypothalamic paraventricular neurones in female rats.

We have recently reported that lipopolysaccharide (LPS), a bacterial endotoxin, inhibits steroid-induced as well as naloxone-induced luteinising hormone (LH) secretion in ovariectomised oestrogen-primed rats. In the present study, we examined whether corticotropin-releasing factor (CRF) may be involved in the LPS-induced inhibition of LH secretion. Unanaesthetised rats were treated with an intravenous (i.v.) injection of LPS (10 microg) or saline, followed by an i.v. injection of naloxone (20 mg/kg). After sequential blood samples were collected for determination of serum LH concentrations, the brains were fixed and CRF-immunoreactivity was examined histochemically. In control rats receiving saline injections, only a small number of CRF-immunoreactive (ir) cells were found in the parvocellular portion of the hypothalamic paraventricular nucleus (PVN), and naloxone significantly increased serum LH concentrations within 10 min. By contrast, in LPS-treated rats, the number of CRF-ir cells was significantly greater than that in control rats, and the effect of naloxone was completely abolished. In a separate experiment, an intracerebroventricular injection of 5 microg CRF inhibited naloxone-induced LH release, mimicking the effect of LPS. These results suggest that LPS stimulates production of CRF in PVN neurones, which in turn inhibits LH secretion without opioidergic mediation.

Animals↗

PubMed2005

Lipopolysaccharide increases gamma-aminobutyric acid synthesis in medial preoptic neurones in association with inhibition of steroid-induced luteinising hormone surge in female rats.

Lipopolysaccharide (LPS), an endotoxin produced by gram-negative bacteria, inhibits gonadotrophin secretion and ovulation in female mammals. The present study was undertaken to examine whether gamma-aminobutyric acid (GABA)-synthesising neurones in the medial preoptic area (mPOA) may be involved in the inhibition by LPS of progesterone-induced luteinising hormone (LH) surge in ovariectomised oestrogen-primed rats. An intravenous injection of LPS (10 microg) at noon significantly increased the content of glutamic acid decarboxylase 67 (GAD67), a GABA-synthesising enzyme, in brain tissues including the mPOA. LPS treatment also significantly increased the number of detectable GAD67-immunoreactive (ir) as well as GABA-ir cells in the mPOA, compared to control rats. The same LPS challenge completely eliminated the steroid-induced LH surge, which was normally induced in control rats in the afternoon. A local injection of muscimol (100 ng), a GABA(A) receptor agonist, into the mPOA also significantly attenuated the LH surge, mimicking the effect of LPS. These results suggest that LPS stimulates GABA synthesis in preoptic neurones, which in turn inhibit the LH surge in female rats. The results also support the hypothesis that diminution of the GABAergic suppressive activity in the mPOA permits the LH surge to be induced.

Animals↗

PubMed2003

Lipopolysaccharide inhibits luteinizing hormone release through interaction with opioid and excitatory amino acid inputs to gonadotropin-releasing hormone neurones in female rats: possible evidence for a common mechanism involved in infection and immobilization stress.

Acute immobilization stress suppresses naloxone- and N-methyl-d-aspartate (NMDA)-induced, but not gonadotropin-releasing hormone (GnRH)-induced, luteinizing hormone (LH) release in ovariectomized oestrogen-primed rats. To explore whether a common mechanism may underlie inhibition of gonadotropin secretion by various stressors, we examined in the present study the effect of lipopolysaccharide (LPS) on LH release induced by progesterone, GnRH, naloxone and NMDA. The effect of LPS on Fos expression in GnRH neurones was also examined in association with its effect on steroid-induced LH release. Injection of progesterone (1 mg/rat) at noon induced an LH surge in the afternoon in ovariectomized rats pretreated with oestradiol benzoate. In these rats, the majority of hypothalamic GnRH neurones expressed Fos in the evening. Intravenous (i.v.) administration of LPS (10 micro g/rat) inhibited steroid-induced LH release and also reduced the Fos expression in GnRH neurones. In separate experiments, an i.v. injection of GnRH (50 ng/kg), naloxone (10 mg/kg) or NMDA (20 mg/kg) significantly elevated serum LH concentrations within 10 min. Pretreatment with LPS, which did not affect basal LH release or GnRH-induced LH release, inhibited naloxone-induced and NMDA-induced LH release. These results show that LPS has a suprapituitary site(s) of action to suppress the activity of GnRH neurones in female rats, and suggest that LPS affects the opioid, as well as the excitatory amino acidergic regulation of GnRH neurones. The similarity of effects of LPS and immobilization stress further suggests that a common mechanism is involved in inhibition of GnRH neurones by different stressors.

Animals↗

PubMed2002

Two-dimensional percolation and cluster structure of the random packing of binary disks.

In this paper we study the short-range correlated percolation and the cluster structure of two-dimensional (2D) random packing of binary disks with size ratio lambda in the range of 1-5. A Monte Carlo simulation model is used to generate the configuration of random packing first. Then a from-neighbor-to-neighbor propagation method is used to identify the number and sizes of the clusters. Results show that for lambda=1 the percolation threshold p(c) lies between the square and triangular site percolation thresholds. As lambda increases the percolation threshold p(c) (the area fraction of small disks) decreases. To characterize the cluster structure at the percolation threshold, we scale the cluster size s(c) with the cluster radius R as s(c) proportional, variant R(D). The fractal dimension D obtained lies between 1.86 and 1.88 and is independent of the size ratio lambda. This value is in good agreement with the 2D theoretical fractal dimension which is equal to 91/48.

Journal Article↗

PubMed2001

Use of a quartz crystal impedance technique to monitor the degradation of chondroitin sulfate by hyaluronidase.

A new quartz crystal impedance hyaluronidase sensing technique, which is based on the changes in viscosity and density during the enzymatic hydrolysis of chondroitin sulfate (CS) by hyaluronidase (HAse), is established in this paper. The variations of equivalent circuit parameters of the piezoelectric quartz crystal (PQC) during the enzymatic degradation are discussed. The initial hydrolysis rate of CS by HAse is obtained from the changes in viscosity and density with incubation time. Kinetic parameters (the Michaelis constant K(m) and the maximum hydrolysis rate V(max)) of the degradation process are estimated by using a linear method of Lineweaver-Burk plot. K(m) is 2.73 +/- 0.20 mg.ml(-1) and V(max) is -(5.43 +/- 0.38) x 10(-4) kg.m(-2).s(-1/2).min(-1.)

Journal Article↗

PubMed2001

Nuclear accumulation of exogenous DNA fragments in viable cells mediated by FGF-2 and DNA release upon cellular injury.

We and others have previously shown that basic fibroblast growth factor (FGF-2 or bFGF) can be used as a targeting molecule to help carry plasmid DNA into cells when the growth factor molecule is physically coupled to the DNA molecule being delivered. Herein we report our observations on the FGF-mediated uptake of exogenous labeled DNA into cultured cells in a manner that is representative of that which may occur under physiological conditions at sites of wounded tissue. Cellular debris at such sites contains nucleic acid fragments released from dead cells, as well as growth factors such as FGF-2 that function early in the wound repair process. Using a cell culture model designed to mimic the local environment of a wound with respect to the presence of soluble FGF-2 and DNA fragments, we have shown that FGF-2 is able to direct the cellular uptake and nuclear localization of fragments of exogenous DNA via the FGF receptor into intact and healthy cells. Furthermore, we can monitor and quantitate this type of FGF-mediated DNA delivery by using indirect immunofluorescence of bromodeoxyuridine-labeled exogenous DNA. Our results suggest that this type of FGF-mediated DNA fragment uptake could allow for the transduction of viable nearest neighbor cells at sites of injury in vivo. Such a phenomenon may lead to mutational aberrations in the recipient cells and enhance the probability of wound carcinogenesis.

Active Transport, Cell Nucleus↗

PubMed2001

Chaoslike behavior in nonchaotic systems at finite computation precision.

The dynamical behavior of a two-dimensional map is investigated numerically. A chaoslike behavior, i.e., a nonsmooth distribution of the attractor and seemly sensitive dependence of the motion on initial condition is found as the system state is nonchaotic (both Lyapunov exponents are nonpositive). The key point for this strange behavior is that the mode corresponding to the second negative Lyapunov exponent contains positive local Lyapunov exponent segments. It is argued that this kind of behavior may be typical and easily observed in practical numerical computations and experiments where small noise is inevitable.

Journal Article↗

PubMed2001

Generalized splay state in coupled chaotic oscillators induced by weak mutual resonant interactions.

Dynamic behavior of coupled chaotic oscillators is investigated. A transition from high-dimensional hyperchaos to a generalized periodic splay state is found for extremely weak coupling. Chaotic nature of a single oscillator and mutual resonant interactions are regarded to be responsible for this self-organized ordering. The functional phase distribution of the generalized splay state, which is essentially different from the equal-phase-separation distribution of the conventional splay states, can be well predicted by analyzing a single periodically forced oscillator.

Journal Article↗

PubMed2001

Effect of acupuncture on smoking cessation or reduction: an 8-month and 5-year follow-up study.

BACKGROUND: This study was undertaken to examine whether acupuncture treatment may have a long-term effect on smoking cessation or reduction. METHODS: Altogether 46 healthy men and women who reported smoking 20 +/- 6 cigarettes per day (mean +/- SD) volunteered in the study. They were randomly assigned to a test group (TG) or to a control group (CG) in which presumed anti-smoking acupoints were stimulated (TG) or acupuncture was applied to acupoints considered to have no effect on smoking cessation (CG). Before each treatment, after the last one, and 8 months and 5 years after the last one, each subject answered questionnaires about his or her smoking habits and attitudes. Blood samples for measuring variables related to smoking, i.e., serum cotinine and serum thiocyanate, were taken. RESULTS: During the treatment period the reported cigarette consumption fell on average by 14 (TG) and 7 (CG) cigarettes per day (P < 0.001). For both groups the reported cigarette consumption rose on average by 5-7 cigarettes during the following 8 months, and there was no systematic change thereafter. Consequently, TG showed a maintained reduction in smoking; no lasting effect was seen for CG. The TG reported that cigarettes tasted worse than before the treatments, and also the desire to smoke fell. For TG the serum concentration of cotinine fell, and the values correlated with the reported smoking. CONCLUSIONS: This study confirms that adequate acupuncture treatment may help motivated smokers to reduce their smoking, or even quit smoking completely, and the effect may last for at least 5 years. Acupuncture may affect the subjects' smoking by reducing their taste of tobacco and their desire to smoke. Different acupoints have different effects on smoking cessation.

Acupuncture↗

PubMed2001

Increase in the number of detectable preoptic glutamic acid decarboxylase 67-immunoreactive cells in immature male rats.

Gonadotropin-releasing hormone (GnRH) neurons are mainly located in the anterior preoptic area (aPOA) and gamma-aminobutyric acid (GABA) is known as a potent regulator of the GnRH neurons. To examine the development of the GABAergic system in the aPOA, immunocytochemistry of glutamic acid decarboxylase 67 (GAD(67)) was performed in immature (postnatal d16, d25 and d30) and mature (postnatal 10 weeks) male rats. All immunocytochemical procedures were simultaneously performed. In the lateral part of the aPOA, the detectable number of GAD(67)-immunoreactive cells was small in the d16 group, but significantly increased in the d25, d30 and mature groups, up to 2.7, 4.8 and 5.7 times the number in the d16 group, respectively. In the diagonal band of Broca (DBB), the number was also small in the d16 group, and significantly increased in the d25, d30 and mature groups upto 1.8, 2.2 and 2.8 times the number in the d16 group, respectively. However, in the cingulate cortex, no significant developmental change was observed. These results suggest that the development of the GABAergic system in the lateral aPOA and the DBB occurs before sexual maturation of male rats.

Aging↗

PubMed2001

Evaluation of a single stage nitroglycerin tilt table test for diagnosis of neurally mediated syncope.

The purpose of this study was to compare clinical outcomes between a single stage head-up tilt table test (HUT) with infusion of 3.44 microg/kg per hour of nitroglycerin and a conventional multistage test with infusion of nitroglycerin from 1.72 microg/kg per hour to 5.16 microg/kg per hour in five successive stages. Thirty-seven patients with recurrent syncope underwent both tests in a prospective, randomized, crossoverfashion. During single stage HUT, a positive response occurred in 24 (64.9%) patients with unexplained syncope, an exaggerated response occurred in 3 (8.1%), a negative response in 7 (18.9%), and drug intolerance in 3 (8.1%). During the multistage HUT, these percentages were 62.2%, 16.2%, 13.5%, and 8.1%, respectively. Twenty healthy control subjects were involved in both tests, One of the control subjects had a positive response to single stage HUT, and two (10%) patients to multistage HUT. The duration of the test in single stage HUT was shorter than that in multistage HUT (8.6 +/- 10.3 vs 38.6 +/- 32.1 minutes, P < 0.01). The results showed that the single stage HUT was a fairly sensitive, specific, and a time-efficient test for provoking neurally mediated syncope.

Adolescent↗

PubMed2001

Assessment of vehicular pollution in China.

As the motor vehicle population in China continues to increase at an annual rate of approximately 15%, air pollution related to vehicular emissions has become the focus of attention, especially in large cities. There is an urgent need to identify the severity of this pollution in China. Based on an investigation into vehicle service characteristics, this study used a series of driving cycle tests of in-use Chinese motor vehicles for their emission factors in laboratories, which indicated that CO and HC emission factors are 5-10 times higher, and NOx 2-5 times higher, than levels in developed countries. The MOBILE5 model was adapted to the Chinese situation and used to calculate the emission of pollutants from motor vehicles. Results show that vehicle emission is concentrated in major cities, such as Beijing, Guangzhou, Shanghai, and Tianjin. Motor vehicle emissions contribute a significant proportion of pollutants in those cities, with contribution rates of CO and NOx greater than 80% and 40%, respectively, in Beijing and Guangzhou. Urban air quality is far worse than the national ambient air quality standard. In conclusion, although China has a relatively small number of motor vehicles, most of them are concentrated within metropolitan areas, and their emissions are closely related to urban air pollution problems in large cities.

Air Pollutants↗

PubMed2001

Toxic emissions from mobile sources: a total fuel-cycle analysis for conventional and alternative fuel vehicles.

Mobile sources are among the largest contributors of four hazardous air pollutants--benzene, 1,3-butadiene, acetaldehyde, and formaldehyde--in urban areas. At the same time, federal and state governments are promoting the use of alternative fuel vehicles as a means to curb local air pollution. As yet, the impact of this movement toward alternative fuels with respect to toxic emissions has not been well studied. The purpose of this paper is to compare toxic emissions from vehicles operating on a variety of fuels, including reformulated gasoline (RFG), natural gas, ethanol, methanol, liquid petroleum gas (LPG), and electricity. This study uses a version of Argonne National Laboratory's Greenhouse Gas, Regulated Emissions, and Energy Use in Transportation (GREET) model, appropriately modified to estimate toxic emissions. The GREET model conducts a total fuel-cycle analysis that calculates emissions from both downstream (e.g., operation of the vehicle) and upstream (e.g., fuel production and distribution) stages of the fuel cycle. We find that almost all of the fuels studied reduce 1,3-butadiene emissions compared with conventional gasoline (CG). However, the use of ethanol in E85 (fuel made with 85% ethanol) or RFG leads to increased acetaldehyde emissions, and the use of methanol, ethanol, and compressed natural gas (CNG) may result in increased formaldehyde emissions. When the modeling results for the four air toxics are considered together with their cancer risk factors, all the fuels and vehicle technologies show air toxic emission reduction benefits.

Air Pollutants↗