Biomedical subjects

H Zhao

Publications and source records attributed to H Zhao.

At least 199 records · Page 11Linked to original sources

PubMed2000

Requirements for effective inhibition of immunostimulatory CpG motifs by neutralizing motifs.

The DNA of bacteria and many viruses contain unmethylated CpG dinucleotides in particular sequence contexts that activate vertebrate immune cells. A subset of these CpG motifs was previously found to oppose the effects of immunostimulatory (CpG-S) motifs and has been termed neutralizing (CpG-N) motifs. Here we show that oligodeoxynucleotides (ODNs) composed of clusters of CpG-N motifs could partially inhibit the induction of interleukin-12 (IK-12) from mouse spleen cells by ODN containing CpG-S motifs. However, non-CpG-containing ODN were also inhibitory, suggesting that neutralization of CpG-S ODNs by CpG-N ODNs in trans was nonspecific. Neutralization of CpG-S motifs by CpG-N motifs in cis was specific, but the degree of inhibition was strongly dependent on the particular CpG-S motif being neutralized, with motifs having an A residue 5' to the CG being much more resistant to inhibition than motifs having a T residue 5' to the CG. The degree of inhibition was dependent on the spacing between the CpG-S and CpG-N motifs, with the ability to neutralize inversely correlating with distance. In addition, whereas ODNs containing extended clusters of CpG-N motifs were nonstimulatory, isolated CpG-N motifs remained stimulatory in most sequence contexts. Finally, CpG-N ODNs were shown to be nonstimulatory when instilled into the lungs of BALB/c mice, but the ability of CpG-N motifs to neutralize CpG-S motifs in cis was not observed. These results show that there are precise and fairly complex interactions between immunostimulatory and inhibitory sequence motifs that govern whether a given DNA is able to activate the vertebrate immune system.

Adjuvants, Immunologic↗

PubMed2000

Household exposure to passive cigarette smoking and serum micronutrient concentrations.

BACKGROUND: The associations observed between passive smoking and adverse health outcomes have generated controversy. In part, this could be because the diets of passive smokers, like those of active smokers, differ from those of persons who are not exposed to cigarette smoke, especially with regard to antioxidants. OBJECTIVE: Our objective was to assess the relation between household exposure to passive smoking and serum concentrations of retinol, tocopherols, and carotenoids. DESIGN: A cross-sectional study was conducted in Washington County, MD, to compare exposure to passive smoking at home, recorded in a private census of county residents in 1975, with micronutrient concentrations assayed in serum collected in 1974. This comparison was possible for 1590 control subjects in nested case-control studies conducted between 1986 and 1998. RESULTS: Among persons who were not current smokers, those who lived with smokers tended to have lower serum total carotenoid, alpha-carotene, ss-carotene, and cryptoxanthin concentrations than did those who lived in households with no smokers. There was little evidence that exposure to passive smoking was associated with reduced serum concentrations of lutein and zeaxanthin, lycopene, retinol, alpha-tocopherol, or gamma-tocopherol. CONCLUSIONS: Among nonsmokers, exposure to passive smoking tended to be associated with lower serum concentrations of the carotenoids most strongly associated with active smoking (total carotenoids, alpha-carotene, ss-carotene, and cryptoxanthin). The associations were weaker for passive smoking than for active smoking. The consistency of the associations observed for active and passive smoking indicates that exposure to passive smoking may result in decreased circulating concentrations of selected micronutrients.

Adult↗

PubMed2000

Optical mapping of BAC clones from the human Y chromosome DAZ locus.

The accurate mapping of clones derived from genomic regions containing complex arrangements of repeated elements presents special problems for DNA sequencers. Recent advances in the automation of optical mapping have enabled us to map a set of 16 BAC clones derived from the DAZ locus of the human Y chromosome long arm, a locus in which the entire DAZ gene as well as subsections within the gene copies have been duplicated. High-resolution optical mapping employing seven enzymes places these clones into two contigs representing four distinct copies of the DAZ gene and highlights a number of differences between individual copies of DAZ.

Chromosome Mapping↗

PubMed2000

Heat conduction in one-dimensional nonintegrable systems

Two classes of one-dimensional nonintegrable systems represented by the Fermi-Pasta-Ulam (FPU) model and the discrete straight phi(4) model are studied to seek a generic mechanism of energy transport on a microscopic level sustaining macroscopic behaviors. The results enable us to understand why the class represented by the straight phi(4) model has a normal thermal conductivity and the class represented by the FPU model does not even though the temperature gradient can be established.

Journal Article↗

PubMed2000

Zigzag structures and domain walls in electroconvection of nematic liquid crystal

To describe the secondary-bifurcation scenario in ac-driven electroconvection of a planarly aligned nematic liquid crystal layer, we have constructed a generic phase equation coupled to the cinsertion mark director. The equations are applicable in particular in the vicinity of the codimension-2 point, where the zigzag and the abnormal roll instabilities meet. This point is also the origin of a line of homoclinic bifurcations, which separates a region where one has stationary zigzag walls from one with spontaneously accelerated abnormal roll walls. The final velocity of the walls depends linearly on the distance from the bifurcation. We analyze the scenario analytically, test it numerically and propose an experimental check.

Journal Article↗

PubMed2000

A hybrid, inverse approach to the design of magnetic resonance imaging magnets.

This paper describes a hybrid numerical method of an inverse approach to the design of compact magnetic resonance imaging magnets. The problem is formulated as a field synthesis and the desired current density on the surface of a cylinder is first calculated by solving a Fredholm equation of the first kind. Nonlinear optimization methods are then invoked to fit practical magnet coils to the desired current density. The field calculations are performed using a semi-analytical method. The emphasis of this work is on the optimal design of short MRI magnets. Details of the hybrid numerical model are presented, and the model is used to investigate compact, symmetric MRI magnets as well as asymmetric magnets. The results highlight that the method can be used to obtain a compact MRI magnet structure and a very homogeneous magnetic field over the central imaging volume in clinical systems of approximately 1 m in length, significantly shorter than current designs. Viable asymmetric magnet designs, in which the edge of the homogeneous region is very close to one end of the magnet system are also presented. Unshielded designs are the focus of this work. This method is flexible and may be applied to magnets of other geometries.

Algorithms↗

PubMed2000

Increased blood pressure in alpha-calcitonin gene-related peptide/calcitonin gene knockout mice.

Nerves that contain calcitonin gene-related peptide (CGRP) are components of the sensory nervous system. Although these afferent nerves have traditionally been thought to sense stimuli in the periphery and transmit the information centrally, they also have an efferent vasodilator function. Acute administration of a CGRP receptor antagonist increases the blood pressure (BP) in several models of hypertension, which indicates that this potent vasodilator plays a counterregulatory role to attenuate the BP increase in these settings. To determine the role of this peptide in the long-term regulation of cardiovascular function, including hypertension, we obtained mice that have a deletion of the alpha-calcitonin gene-related peptide (alpha-CGRP) gene. Although the beta-calcitonin gene-related peptide (beta-CGRP) gene is intact in these mice, alpha-CGRP is by far the predominant species of CGRP produced in dorsal root ganglia (DRG) sensory neurons. Initially, we examined the effect of deletion of the alpha-CGRP on baseline BP and beta-CGRP and substance P mRNA expression. Systolic BP was significantly higher in the knockout mice (n=7) compared with wild-type in both male (160+/-6.1 vs 125+/-4.8 mm Hg) and female (163+/-4.8 vs 135+/-33 mm Hg) mice. Next, groups (n=7) of knockout and wild-type mice had catheters surgically placed in the right carotid artery for mean arterial pressure recording. With the animals fully awake and unrestrained, the knockout mice displayed an elevated mean arterial pressure compared with wild-type in both male (139+/-4.9 vs 118+/-4.9 mm Hg) and female (121+/-3.4 vs 107+/-3.1 mm Hg) mice. Northern blot analysis of DRG RNA samples confirmed the absence of alpha-CGRP mRNA in the knockout mice. Substance P mRNA content in DRG was unchanged between the 2 groups; however, beta-CGRP mRNA levels were reduced 2-fold in the knockout mice. These results indicate for the first time that alpha-CGRP may be involved in the long-term regulation of resting BP and suggest that these mice are particularly sensitive to challenges to BP homeostasis because of the loss of a compensatory vasodilator mechanism.

Animals↗

PubMed2000

Family-based association studies.

Over the past decade, attention has turned from positional cloning of Mendelian disease genes to the dissection of complex diseases. Both theoretical and empirical studies have shown that traditional linkage studies may be inferior in power compared to studies that directly utilize allele status. Case-control association studies, as an alternative, are subject to bias due to population stratification. As a compromise between linkage studies and case-control studies, family-based association designs have received great attention recently due to their potentially higher power to identify complex disease genes and their robustness in the presence of population substructure. In this review, we first describe the basic family-based association design involving one affected offspring with its two parents, all genotyped for a biallelic genetic marker. Extensions of the original transmission disequilibrium tests to multiallelic markers, families with multiple siblings, families with incomplete parental genotypes, and general pedigree structures are discussed. Further developments of statistical methods to study quantitative traits, to analyse genes on the X chromosome, to incorporate multiple tightly linked markers, to identify imprinting genes, and to detect gene-environment interactions are also reviewed. Finally, we discuss the implications of the completion of the Human Genome Project and the identification of hundreds of thousands of genetic polymorphisms on employing family-based association designs to search for complex disease genes.

Alleles↗

PubMed2000

Selective estrogen receptor modulators: structure, function, and clinical use.

The sex hormone estrogen is important for many physiologic processes. Prolonged stimulation of breast ductal epithelium by estrogen, however, can contribute to the development and progression of breast cancer, and treatments designed to block estrogen's effects are important options in the clinic. Tamoxifen and other similar drugs are effective in breast cancer prevention and treatment by inhibiting the proliferative effects of estrogen that are mediated through the estrogen receptor (ER). However, these drugs also have many estrogenic effects depending on the tissue and gene, and they are more appropriately called selective estrogen receptor modulators (SERMs). SERMs bind ER, alter receptor conformation, and facilitate binding of coregulatory proteins that activate or repress transcriptional activation of estrogen target genes. Theoretically, SERMs could be synthesized that would exhibit nearly complete agonist activity on the one hand or pure antiestrogenic activity on the other. Depending on their functional activities, SERMs could then be developed for a variety of clinical uses, including prevention and treatment of osteoporosis, treatment and prevention of estrogen-regulated malignancies, and even for hormone replacement therapy. Tamoxifen is effective in patients with ER-positive metastatic breast cancer and in the adjuvant setting. The promising role for tamoxifen in ductal carcinoma-in-situ or for breast cancer prevention is evolving, and its use can be considered in certain patient groups. Other SERMs are in development, with the goal of reducing toxicity and/or improving efficacy, and future agents have the potential of providing a new paradigm for maintaining the health of women.

Animals↗

PubMed2000

TrkC expression predicts good clinical outcome in primitive neuroectodermal brain tumors.

PURPOSE: To identify biologic prognostic factors in childhood primitive neuroectodermal tumors (PNET), including medulloblastoma, that accurately define patient groups with sufficiently good prognosis to permit a reduction in treatment intensity. PATIENTS AND METHODS: We determined expression levels of the neurotrophin receptor TrkC mRNA in formalin-fixed tumor samples from 87 well characterized PNET patients using in situ hybridization. Comparison of TrkC mRNA expression levels with clinical and other laboratory variables was performed using univariate and multivariate Cox regression analysis. RESULTS: High TrkC mRNA expression was found to be associated more with higher 5-year cumulative survival rate than was low TrkC mRNA expression (89% v 46%, respectively). When compared with established clinical prognostic factors and laboratory variables of potential prognostic significance, TrkC mRNA expression, by univariate analysis, was found to be the single most powerful predictor of outcome (hazards ratio, 4.81; P <.00005), exceeding all clinical prognostic factors. In multivariate analysis, the hazards ratio remained significant (P <.00005). CONCLUSION: High TrkC mRNA expression in PNET is a powerful independent predictor of favorable clinical outcome. Assessment of TrkC mRNA levels may aid in treatment planning for patients with PNETs and should be incorporated prospectively into PNET clinical trials.

Adolescent↗

PubMed2000

A retrograde signal is involved in activity-dependent remodeling at a C. elegans neuromuscular junction.

We have characterized how perturbations of normal synaptic activity influence the morphology of cholinergic SAB motor neurons that innervate head muscle in C. elegans. Mutations disrupting components of the presynaptic release apparatus, acetylcholine (ACh) synthesis or ACh loading into synaptic vesicles each induced sprouting of SAB axonal processes. These sprouts usually arose in the middle of the normal innervation zone and terminated with a single presynaptic varicosity. Sprouting SAB neurons with a similar morphology were also observed upon reducing activity in muscle, either by using mutants lacking a functional nicotinic ACh receptor subunit or through muscle-specific expression of a gain-of-function potassium channel. Analysis of temperature-sensitive mutants in the choline acetyltransferase gene revealed that the sprouting response to inactivity was developmentally regulated; reduction of synaptic activity in early larval stages, but not in late larval stages, induced both sprouting and addition of varicosities. Our results indicate that activity levels regulate the structure of certain synaptic connections between nerve and muscle in C. elegans. One component of this regulatory machinery is a retrograde signal from the postsynaptic cell that mediates the formation of synaptic connections.

Acetylcholine↗

PubMed2000

The cell biology of osteoclast function.

Osteoclasts are multinucleated cells responsible for bone resorption. They have developed an efficient machinery for dissolving crystalline hydroxyapatite and degrading organic bone matrix rich in collagen fibers. When initiating bone resorption, osteoclasts become polarized, and three distinct membrane domains appear: a ruffled border, a sealing zone and a functional secretory domain. Simultaneously, the cytoskeleton undergoes extensive re-organisation. During this process, the actin cytoskeleton forms an attachment ring at the sealing zone, the membrane domain that anchors the resorbing cell to bone matrix. The ruffled border appears inside the sealing zone, and has several characteristics of late endosomal membrane. Extensive vesicle transport to the ruffled border delivers hydrochloric acid and proteases to an area between the ruffled border and the bone surface called the resorption lacuna. In this extracellular compartment, crystalline hydroxyapatite is dissolved by acid, and a mixture of proteases degrades the organic matrix. The degradation products of collagen and other matrix components are endocytosed, transported through the cell and exocytosed through a functional secretory domain. This transcytotic route allows osteoclasts to remove large amounts of matrix-degradation products without losing their tight attachment to underlying bone. It also facilitates further processing of the degradation products intracellularly during the passage through the cell.

Animals↗

PubMed2000

[Exclusive mapping on polydactyly with markers on chromosome 7 and 2 in a Chinese kindred].

OBJECTIVE: This study was aimed at mapping polydactyly related genes in a Chinese kindred. METHODS: Linkage analysis was performed using 7 markers on chromosome 7 and 1 marker on chromosome 2. RESULTS: Pairwise linkage analysis showed no linkage between the markers and polydactyly related gene in the kindred. CONCLUSION: The polydactyly related gene in this kindred may be located on a new locus.

Chromosome Mapping↗

PubMed2000

High-level expression of angiogenic factors is associated with advanced tumor stage in human neuroblastomas.

Angiogenesis is essential for tumor growth and metastasis and depends on the production of angiogenic factors by tumor cells. Neuroblastoma (NB) is a common pediatric tumor of neural crest origin, which is biologically and clinically heterogeneous. Increased tumor vascular index correlates with poor outcome of NB. To determine which angiogenic factors contribute to NB angiogenesis and thereby support tumor progression, we examined the expression of eight angiogenic factors [vascular endothelial growth factor (VEGF), VEGF-B, VEGF-C, basic fibroblast growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor alpha, and platelet-derived growth factor (PDGF)] by semiquantitative RT-PCR in 37 NB primary tumors and in 22 NB cell lines. We also analyzed the relationship between angiogenic factor expression and clinicopathological factors as well as patient survival. All eight angiogenic factors examined were expressed at various levels in NB cell lines and tumors, suggesting their involvement in NB angiogenesis. The expression levels of most angiogenic factors were correlated with each other, suggesting their synergy in regulating the angiogenic process. Significantly higher expression levels of VEGF, VEGF-B, VEGF-C, basic fibroblast growth factor, Ang-2, transforming growth factor alpha, and PDGF-A (P < 0.0001-0.026) were found in advanced-stage tumors (stages 3 and 4) compared with low-stage tumors (stages 1, 2, and 4S). Expression of PDGF-A was significantly associated with patient survival (P = 0.04). The redundancy in angiogenic factor expression suggests that inhibition of VEGF bioactivity alone might not be a sufficient approach for antiangiogenic therapy of human NB.

Angiogenesis Inducing Agents↗

PubMed2000

[A preliminary analysis on a group of low molecular weight RNases in wheat and related species].

By employing RNase activity gel analysis, we detected a novel group of RNases in wheat and related species. The molecular weight of the RNases varied from 8-14 kDa, which was lower than that of most plant RNases characterized previously. The small RNases expressed abundantly in seedlings and differed in their optimal pH and ionic requirement in digesting RNA substrate. Several members of the small RNases were detected in dormant and germinating wheat seeds. During germination, the activity of two RNases did not change significantly whereas that of the other two RNases showed a gradual pattern of decrease and increase, respectively.

Molecular Weight↗

PubMed2000

[Recent advance in studies of new intraaortic axial flow pump: "dynamic aortic valve"].

We have previously proposed and demonstrated the feasibility of a new concept of intraaortic axial flow blood pump, termed "Dynamic Aortic Valve(DAV)". Implanted in the position of aortic valve, DAV can serve as either an assistant pump or a mechanical valve subjected to the power input. It has several merits over the traditional axial blood pumps: (1) better anatomic compatibility and biologic compatibility; (2) little foreign material is to be introduced into the corporeality; (3) better resistance to infection; (4) puncturing power line could be eliminated; (5) promoting the failing heart to recovery; (6) simpler structure and better durability. In our recent studies, the structure of DAV is further simplified and performance improved greatly. The structure of DAV is merely an impeller fixed to a magnetic rotor while held by a central shaft hanging from a rigid supporting cage. The rotor-impeller can be driven by an alternative magnetic field derived from a remote magnet, implying that the magnetic source can even be arranged extracorporeally. The DAV can be driven by a rotational magnet placed at a distance of 60 mm. At the state of maximal output of hydraulic power, the flow rate (FR) generated by DAV reaches 5 L/min against an afterload of 70 mmHg(1 mmHg = 0.133 KPa). The maximal pressure differential (PD) maintained by DAV is 131 mmHg. The results further revealed the feasibility of the concept of DAV.

Aortic Valve↗

PubMed2000

Tetramethylpyrazine inhibits phytohemagglutinin-induced upregulation of ICAM-1 and LFA-1 mediated leukocyte adhesion.

The aim of this work was to study the effects of tetramethylpyrazine (TMP) on the interaction between lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesive molecule-1 (ICAM-1) by micropipette technique. A pair of cells, i.e., a human lymphocyte or a S KW-3 cell (human T cell leukemia), LFA-1 was expressed on which cellular surfaces, and a RBC coupled with ICAM-1, were the carriers for LFA-1 and ICAM-1. The adhesion probabilities of this pair of cells were mediated by specific interactions between ICAM-1 and LFA-1. Phytohemagglutinin (PHA) stimulation resulted in the significant increase in the adhesion probability compared to the resting lymphocyte. TMP treatment can inhibit such increase and even make the adhesion probability lower than the resting state. While the LFA-1 expression has not changed significantly with PHA stimulation or with TMP treatment, which indicated that TMP inhibiting effects was realized by a possible conformation change.

Adult↗

PubMed2000

[The molecular epidemiology of transfusion transmitted virus infection in Shanxi Province].

OBJECTIVE: To study the molecular epidemiology of transfusion transmitted virus (TTV) infection and its distribution in different populations in Shanxi Province and the gene types of the isolates. METHODS: TTV DNA in serum samples was detected by polymerase chain reaction. Partial gene of the strains from different populations were cloned and sequenced, and their gene types were analyzed. RESULTS: Of 24 cases with chronic hepatitis B, 31 cases with non A-G hepatitis, 53 cases of professional blood donors, 112 cases of healthy lying -in women, the positive rates of TTV DNA were 41.66%, 29.03%, 58.49% and 8.93%, respectively. TTV DNA in serum samples of 18 cases of 2 - 3 years old healthy children were negative and also were negative in umbilical cord blood of 10 cases of TTV DNA positive healthy lying-in woman. Sequence analysis of 4 isolated strains of Shanxi Province showed that the nucleotide identity among them were more than 90% and they all belonged to the same gene type (la) CONCLUSIONS: This study proved that TTV infection existed in Shanxi Province, TTV might be an important pathogen for non-A to G hepatitis. TTV often coinfected with hepatitis B virus and there were high rates of TTV infection in professional blood donors and in patients with chronic liver disease. The gene type of TTV in Shanxi province was la.

Adult↗