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Biomedical subjects

F Zhou

Publications and source records attributed to F Zhou.

At least 19 recordsLinked to original sources
PubMed2005

Anti-human immunodeficiency virus type 1 microbicide cellulose acetate 1,2-benzenedicarboxylate in a human in vitro model of vaginal inflammation.

The sexual transmission of human immunodeficiency virus type 1 (HIV-1) is facilitated by inflammation and related epithelial barrier perturbation. Microbicides for vaginal applications are currently being developed to reduce the risk of HIV-1 transmission. However, little is known about their interference with epithelial immune function. In recent clinical trials, nonoxynol-9 (N-9), a virucide with a long history of intravaginal use as a contraceptive, failed to protect against HIV-1 possibly due to mucosal inflammatory damage. Cellulose acetate 1,2-benzenedicarboxylate, also named CAP (for "controls AIDS pandemic"), is an anti-HIV-1 microbicide selected from pharmaceutical excipients that are regarded as safe for oral administration but have not been assessed for potential effects on inflammatory factors in the vaginal environment. Here we use a sensitive human cell culture system to evaluate proinflammatory profiles of soluble CAP in reference to N-9 and known epithelial activators such as tumor necrosis factor alpha (TNF-alpha) and bacterial lysates. Within 6 h of exposure, TNF-alpha and N-9 triggered NF-kappaB and AP-1/cFos activation and upregulated interleukins and an array of chemokines by vaginal and polarized cervical epithelial cells. The induced proinflammatory status continued after removal of stimuli and was confirmed by enhanced transepithelial neutrophil migration. While sustaining stability and anti-HIV-1 activity in the epithelial environment, CAP did not increase the production of proinflammatory mediators during or after exposure, nor did it modify the epithelial resistance to leukocyte traffic. CAP attenuated some TNF-alpha-induced responses but did not interfere with epithelial cytokine responsiveness to gonococcal determinants. The described system may be useful for predicting proinflammatory side effects of other microbicide candidates for vaginal application.

Anti-HIV Agents↗
PubMed2004

Dichotomy between nodal and antinodal quasiparticles in underdoped (La2-xSrx)CuO4 superconductors.

High resolution angle-resolved photoemission measurements on an underdoped (La(2-x)Srx)CuO4 system show that, at energies below 70 meV, the quasiparticle peak is well defined around the (pi/2,pi/2) nodal region and disappears rather abruptly when the momentum is changed from the nodal point to the (pi,0) antinodal point along the underlying "Fermi surface." It indicates that there is an extra low energy scattering mechanism acting upon the antinodal quasiparticles. We propose that this mechanism is the scattering of quasiparticles across the nearly parallel segments of the Fermi surface near the antinodes.

Journal Article↗
PubMed2004

Demonstration of high-trapping efficiency and narrow energy spread in a laser-driven accelerator.

Laser-driven electron accelerators (laser linacs) offer the potential for enabling much more economical and compact devices. However, the development of practical and efficient laser linacs requires accelerating a large ensemble of electrons together ("trapping") while keeping their energy spread small. This has never been realized before for any laser acceleration system. We present here the first demonstration of high-trapping efficiency and narrow energy spread via laser acceleration. Trapping efficiencies of up to 80% and energy spreads down to 0.36% (1 sigma) were demonstrated.

Journal Article↗
PubMed2002

Surface-roughness wakefield measurements at brookhaven accelerator test facility.

An experiment has been carried out at the Brookhaven Accelerator Test Facility to investigate the effect of a surface-roughness wakefield in narrow beam tubes with artificially created bumps. The measurements show that the synchronous modes decay significantly due to the randomization of the roughness pattern. It is pointed out that this decay mechanism has not been investigated in the previous experiment at DESY and the investigators' conclusion does not apply for surface-roughness wakefields in real surfaces.

Journal Article↗
PubMed2002

Cellular lipid peroxidation end-products induce apoptosis in human lens epithelial cells.

Hydrogen peroxide (H(2)O(2)), an oxidant present in high concentrations in the aqueous humor of the elderly eyes, is known to impart toxicity to the lens---apoptosis being one of the toxic events. Since H(2)O(2) causes lipid peroxidation leading to the formation of reactive end-products, it is important to investigate whether the end-products of lipid peroxidation are involved in the oxidation-induced apoptosis in the lens. 4-Hydroxynonenal (HNE), a major cytotoxic end product of lipid peroxidation, has been shown to mediate oxidative stress-induced cell death in many cell types. It has been shown that HNE is cataractogenic in micromolar concentrations in vitro, however, the underlying mechanism is not yet clearly understood. In the present study we have demonstrated that H(2)O(2) and the lipid derived aldehydes, HNE and 4-hydroxyhexenal (HHE), can induce dose- and time-dependent loss of cell viability and a simultaneous increase in apoptosis involving activation of caspases such as caspase-1, -2, -3, and -8 in the cultured human lens epithelial cells. Interestingly, we observed that Z-VAD, a broad range inhibitor of caspases, conferred protection against H(2)O(2)- and HNE-induced apoptosis, suggesting the involvement of caspases in this apoptotic system. Using the cationic dye JC-1, early apoptotic changes were assessed following 5 h of HNE and H(2)O(2) insult. Though HNE exposure resulted in approximately 50% cells to undergo early apoptotic changes, no such changes were observed in H(2)O(2) treated cells during this period. Furthermore, apoptosis, as determined by quantifying the DNA fragmentation, was apparent at a much earlier time period by HNE as opposed to H(2)O(2). Taken together, the results demonstrate the apoptotic potential of the lipid peroxidation end-products and suggest that H(2)O(2)-induced apoptosis may be mediated by these end-products in the lens epithelium.

Aldehydes↗
PubMed2002

Sex chromosomes in the spiny eel (Mastacembelus aculeatus) revealed by mitotic and meiotic analysis.

Lower vertebrates like fish exhibit tremendous diversity in sex determination. There are wide interplays between environment-dependent sex differentiation ranging from natural hermaphroditism to sex reversal and genetic sex determination. Diverse systems of male and female heterogamety coexist in fish and sex chromosomes are rarely distinguishable in morphology. Here we show that the spiny eel ((Mastacembelus aculeatus) of the Perciformes, has evolved highly heteromorphic X and Y chromosomes. The metacentric X and Y chromosomes are the largest among 24 homologous pairs, differ from each other in size and morphology, and become distinct after C-banding because of conspicuous heterochromatin blocks which exhibit alternate distribution around the centromeric region. Chromosome painting using probes from the microdissected X chromosome revealed sequence homology between X and Y. During the pachytene stage of meiosis the X and Y form a bivalent. However, their synapsis is delayed which is particularly evident in one terminus. Therefore, the X and Y have resulted from a pericentric inversion in the Y. We conclude that M. aculeatus represents an example of a highly advanced stage of sex chromosome evolution in fish.

Animals↗
PubMed2001

Eliciting the low-activity aldehyde dehydrogenase Asian phenotype by an antisense mechanism results in an aversion to ethanol.

A mutation in the gene encoding for the liver mitochondrial aldehyde dehydrogenase (ALDH2-2), present in some Asian populations, lowers or abolishes the activity of this enzyme and results in elevations in blood acetaldehyde upon ethanol consumption, a phenotype that greatly protects against alcohol abuse and alcoholism. We have determined whether the administration of antisense phosphorothioate oligonucleotides (ASOs) can mimic the low-activity ALDH2-2 Asian phenotype. Rat hepatoma cells incubated for 24 h with an antisense oligonucleotide (ASO-9) showed reductions in ALDH2 mRNA levels of 85% and ALDH2 (half-life of 22 h) activity of 55% equivalent to a >90% inhibition in ALDH2 synthesis. Glutamate dehydrogenase mRNA and activity remained unchanged. Base mismatches in the oligonucleotide rendered ASO-9 virtually inactive, confirming an antisense effect. Administration of ASO-9 (20 mg/kg/day for 4 d) to rats resulted in a 50% reduction in liver ALDH2 mRNA, a 40% inhibition in ALDH2 activity, and a fourfold (P < 0.001) increase in circulating plasma acetaldehyde levels after ethanol (1 g/kg) administration. Administration of ASO-9 to rats by osmotic pumps led to an aversion (-61%, P < 0.02) to ethanol. These studies provide a proof of principle that specific inhibition of gene expression can be used to mimic the protective effects afforded by the ALDH2-2 phenotype.

Acetaldehyde↗
PubMed2001

New insights into the heparan sulfate proteoglycan-binding activity of apolipoprotein E.

Defective binding of apolipoprotein E (apoE) to heparan sulfate proteoglycans (HSPGs) is associated with increased risk of atherosclerosis due to inefficient clearance of lipoprotein remnants by the liver. The interaction of apoE with HSPGs has also been implicated in the pathogenesis of Alzheimer's disease and may play a role in neuronal repair. To identify which residues in the heparin-binding site of apoE and which structural elements of heparan sulfate interact, we used a variety of approaches, including glycosaminoglycan specificity assays, (13)C nuclear magnetic resonance, and heparin affinity chromatography. The formation of the high affinity complex required Arg-142, Lys-143, Arg-145, Lys-146, and Arg-147 from apoE and N- and 6-O-sulfo groups of the glucosamine units from the heparin fragment. As shown by molecular modeling, using a high affinity binding octasaccharide fragment of heparin, these findings are consistent with a binding mode in which five saccharide residues of fully sulfated heparan sulfate lie in a shallow groove of the alpha-helix that contains the HSPG-binding site (helix 4 of the four-helix bundle of the 22-kDa fragment). This groove is lined with residues Arg-136, Ser-139, His-140, Arg-142, Lys-143, Arg-145, Lys-146, and Arg-147. In the model, all of these residues make direct contact with either the 2-O-sulfo groups of the iduronic acid monosaccharides or the N- and 6-O-sulfo groups of the glucosamine sulfate monosaccharides. This model indicates that apoE has an HSPG-binding site highly complementary to heparan sulfate rich in N- and O-sulfo groups such as that found in the liver and the brain.

Animals↗
PubMed2001

Constitutive expression of ectopic c-Myc delays glucocorticoid-evoked apoptosis of human leukemic CEM-C7 cells.

Sensitivity to glucocorticoid (GC)-evoked apoptosis in lymphoid cell lines correlates closely with GC-mediated suppression of c-Myc expression. To establish a functional role for c-Myc in GC-mediated apoptosis, we have stably expressed MycER(TM), the human c-Myc protein fused to the modified ligand-binding domain of the murine estrogen receptor alpha, in GC-sensitive CEM-C7-14 cells. In CEM-C7-14 cells, MycER(TM) constitutively imparts c-Myc functions. Cells expressing MycER(TM) (C7-MycER(TM)) exhibited a marked reduction in cell death after 72 h in 100 nM dexamethasone (Dex), with 10-20-fold more viable cells when compared to the parental CEM-C7-14 clone. General GC responsiveness was not compromised, as evidenced by Dex-mediated suppression of endogenous c-Myc and cyclin D3, and induction of c-Jun and the glucocorticoid receptor. MycER(TM) also blunted Dex-mediated upregulation of p27(kipI) and suppression of the Myc target p53. In comparison to parental CEM-C7-14 cells, Dex-evoked DNA strand breaks were negligible and caspase activation was delayed, but the extent of G1 cell cycle arrest was similar in C7-MycER(TM) cells. Myc-ER(TM) did not result in permanent, complete resistance to GC however, and the GC-treated cells eventually died, indicative of redundant or interactive mechanisms in the GC-evoked lytic response of lymphoid cells. Our results emphasize the importance of c-Myc suppression in GC-evoked apoptosis of CEM-C7-14 cells.

Antineoplastic Agents, Hormonal↗
PubMed2001

Spin correlation and discrete symmetry in spinor Bose-Einstein condensates.

We study spin correlations in Bose-Einstein condensates of spin 1 bosons with scatterings dominated by a total spin equal 2 channel. We show that the low energy spin dynamics in the system can be mapped into an o(n) nonlinear sigma model. n = 3 at the zero magnetic field limit and n = 2 in the presence of weak magnetic fields. In an ordered phase, the ground state has a discrete Z2 symmetry and is degenerate under the group [U(1)xS(n-1)]/Z(2). We explore consequences of the discrete symmetry and propose some measurements to probe it.

Journal Article↗
PubMed2001

Involvement of caspases in 4-hydroxy-alkenal-induced apoptosis in human leukemic cells.

4-Hydroxynonenal (HNE), a reactive and cytotoxic end-product of lipid peroxidation, has been suggested to be a key mediator of oxidative stress-induced cell death and in various cell types has been shown to induce apoptosis. We have demonstrated that HNE, at micromolar concentrations, induces dose- and time-dependent apoptosis in a leukemic cell line (CEM-C7). Interestingly, much higher concentrations of HNE (> 15-fold) were required to induce apoptosis in leukocytes obtained from normal individuals. We also demonstrate that HNE causes a decrease in clonogenicity of CEM-C7 cells. Furthermore, our data characterize the caspase cascade involved in HNE-induced apoptosis in CEM-C7 cells. Using specific fluorogenic substrates and irreversible peptide inhibitors, we demonstrate that caspase 2, caspase 3, and caspase 8 are involved in HNE-induced apoptosis, and that caspase 2 is the first initiator caspase that activates the executioner caspase 3, either directly or via activation of caspase 8. Our studies also suggest the involvement of another executioner caspase, which appears to be similar to caspase 8 but not caspases 2 and 3, in its specificity. The demonstration of decreased clonogenicity by HNE in the leukemic cells, and their higher susceptibility to HNE-induced apoptosis as compared to the normal cells, suggests that such compounds may have potential for leukemia chemotherapy.

Aldehydes↗
PubMed2001

Economic analysis of a child vaccination project among Asian Americans in Philadelphia, Pa.

OBJECTIVE: To ascertain the cost-effectiveness and the benefit-cost ratios of a community-based hepatitis B vaccination catch-up project for Asian American children conducted in Philadelphia, Pa, from October 1, 1994, to February 11, 1996. DESIGN: Program evaluation. SETTING: South and southwest districts of Philadelphia. PARTICIPANTS: A total of 4384 Asian American children. INTERVENTIONS: Staff in the community-based organizations (1) educated parents about the hepatitis B vaccination, (2) enrolled physicians in the Vaccines for Children program, and (3) visited homes of children due for a vaccine dose. Staff in the Philadelphia Department of Public Health developed a computerized database; sent reminder letters for children due for a vaccine dose; and offered vaccinations in public clinics, health fairs, and homes. MAIN OUTCOME MEASURES: The numbers of children having received 1, 2, or 3 doses of vaccine before and after the interventions; costs incurred by the Philadelphia Department of Public Health and the community-based organizations for design, education, and outreach activities; the cost of the vaccination; cost-effectiveness ratios for intermediate outcomes (ie, per child, per dose, per immunoequivalent patient, and per completed series); discounted cost per discounted year of life saved; and the benefit-cost ratio of the project. RESULTS: For the completed series of 3 doses, coverage increased by 12 percentage points at a total cost of $268 660 for design, education, outreach, and vaccination. Costs per child, per dose, and per completed series were $64, $119, and $537, respectively. The discounted cost per discounted year of life saved was $11 525, and 106 years of life were saved through this intervention. The benefit-cost ratio was 4.44:1. CONCLUSION: Although the increase in coverage was modest, the intervention proved cost-effective and cost-beneficial.

Adolescent↗
PubMed2001

Increased sensitivity of mitochondrial respiration to inhibition by nitric oxide in cardiac hypertrophy.

Cardiac hypertrophy is a significant risk factor for the development of congestive heart failure (CHF). Mitochondrial defects are reported in CHF, but no consistent mitochondrial alterations have yet been identified in hypertrophy. In this study selective metabolic inhibitors were used to determine thresholds for respiratory inhibition and to reveal novel mitochondrial defects in hypertrophy. Cardiac hypertrophy was produced in rats by aortic banding. Mitochondria were isolated from left ventricular tissue and the effects of inhibiting respiratory complexes I and IV on mitochondrial oxygen consumption were measured. At 8 weeks post-surgery, 65+/-2% complex IV inhibition was required to inhibit respiration half maximally in control mitochondria. In contrast, only 52+/-6% complex IV inhibition was required to inhibit respiration half maximally in mitochondria from hypertrophied hearts (P=0.046). This effect persisted at 22 weeks post-surgery and was accompanied by a significant upregulation of inducible nitric oxide synthase (iNOS, 3.0+/-0.7-fold, P=0.006). We conclude that respiration is more sensitive to complex IV inhibition in hypertrophy. Nitric oxide is a well documented inhibitor of complex IV, and thus the combination of increased NO(.)from iNOS and an increased sensitivity to inhibition of one of its targets could result in a bioenergetic defect in hypertrophy that may be a harbinger of CHF.

Animals↗
PubMed2001

Hibernation, a model of neuroprotection.

Hibernation, a natural model of tolerance to cerebral ischemia, represents a state of pronounced fluctuation in cerebral blood flow where no brain damage occurs. Numerous neuroprotective aspects may contribute in concert to such tolerance. The purpose of this study was to determine whether hibernating brain tissue is tolerant to penetrating brain injury modeled by insertion of microdialysis probes. Guide cannulae were surgically implanted in striatum of Arctic ground squirrels before any of the animals began to hibernate. Microdialysis probes were then inserted in some animals after they entered hibernation and in others while they remained euthermic. The brain tissue from hibernating and euthermic animals was examined 3 days after implantation of microdialysis probes. Tissue response, indicated by examination of hematoxylin and eosin-stained tissue sections and immunocytochemical identification of activated microglia, astrocytes, and hemeoxygenase-1 immunoreactivity, was dramatically attenuated around probe tracks in hibernating animals compared to euthermic controls. No difference in tissue response around guide cannulae was observed between groups. Further study of the mechanisms underlying neuroprotective aspects of hibernation may lead to novel therapeutic strategies for stroke and traumatic brain injury.

Animals↗
PubMed2001

The phase-shift mutation in the glucocorticoid receptor gene: potential etiologic significance of neuroendocrine mechanisms in lupus nephritis.

BACKGROUND: Glucocorticoid (GC), a mediator of the hypothalamo-pituitary-adrenal axis, has been found to play an important role in maintaining the stability of immune endo-environment of the body. The pathogenesis of lupus nephritis, an autoimmune disease, is thought to be related to the intrinsic hyposensitivity to GC secreted by adrenal gland, and impairs the regulation of the immuno-neuro-endocrine axis. METHODS: To test this hypothesis, we examined the response of 39 clinic patients with lupus nephritis to GC and analyzed the molecular structure and function of the GC receptor (GR) on peripheral blood mononuclear cells. RESULTS: There was no difference in the level of ACTH, GC and ligand affinity of GR between the patients and the controls. The GR number on mononuclear cells of lupus patients was lower than that of the controls. There was no difference in GR number between the patients with heterogeneous response, i.e. sensitive, dependent and resistance, to GC. The analysis of exon 9 of the GC receptor with PCR-amplified single strand conformation polymorphism (PCR-SSCP) method showed the polymorphism in exon 9 of GC receptor in 8 of the 39 lupus nephritis patients. DNA sequence analysis revealed an adenine insertion at the 2439 base pair of the GC receptor gene. This phase-shift mutation caused an additional 20 amino acids being translated into protein of GC receptor. CONCLUSION: The decreased number of GC receptor and the molecular variation of GR on mononuclear cells could explain the phenomenon of GC resistance, potentially to endogenous GC, which suggested an etiological significance of neuro-endocrine-immune mechanism in lupus nephritis. This may be useful in the design of lupus nephritis therapy.

Adolescent↗
PubMed2001

The MLA6 coiled-coil, NBS-LRR protein confers AvrMla6-dependent resistance specificity to Blumeria graminis f. sp. hordei in barley and wheat.

The barley Mla locus confers multiple resistance specificities to the obligate fungal biotroph, Blumeria (= Erysiphe) graminis f. sp. hordei. Interspersed within the 240 kb Mla complex are three families of resistance gene homologs (RGHs). Probes from the Mla-RGH1 family were used to identify three classes of cDNAs. The first class is predicted to encode a full-length CC-NBS-LRR protein and the other two classes contain alternatively spliced, truncated variants. Utilizing a cosmid that contains a gene corresponding to the full-length candidate cDNA, two single-cell expression assays were used to demonstrate complementation of AvrMla6-dependent, resistance specificity to B. graminis in barley and wheat. The first of these assays was also used to substantiate previous genetic data that the Mla6 allele requires the signaling pathway component, Rar1, for function. Computational analysis of MLA6 and the Rar1-independent, MLA1 protein reveals 91.2% identity and shows that the LRR domain is subject to diversifying selection. Our findings demonstrate that highly related CC-NBS-LRR proteins encoded by alleles of the Mla locus can dictate similar powdery mildew resistance phenotypes yet still require distinct downstream signaling components.

Amino Acid Sequence↗