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Biomedical subjects

Z Zhao

Publications and source records attributed to Z Zhao.

At least 19 recordsLinked to original sources
PubMed2006

Nanoscale anisotropic plastic deformation in single crystal aragonite.

The nanoscale anisotropic elastic-plastic behavior of single-crystal aragonite is studied using nanoindentation and tapping mode atomic force microscopy imaging. Force-depth curves coaxial to the axis exhibited load plateaus indicative of dislocation nucleation events. Plasticity on distinct slip systems was evident in residual topographic impressions where four pileup lobes were present after indentation with a conospherical probe and distinct, protruding slip bands were present after indentation with a Berkovich pyramidal probe. A finite element crystal plasticity model revealed the governing roles of the {110}<001>slip system family, as well as the (100)[010], (100)[001], (010)[100], (010)[001], (001)[100] and (001)[010] systems.

Anisotropy↗
PubMed2006

Neuroprotection and neurogenesis: modulation of cornus ammonis 1 neuronal survival after transient forebrain ischemia by prior fimbria-fornix deafferentation.

Severe transient forebrain ischemia causes selective neuronal death in the hippocampal cornus ammonis 1 region. We tested the hypothesis that fimbria-fornix deafferentation can provide long-term protection to cornus ammonis 1 neurons and modulate neurogenesis following ischemia. Fimbria-fornix lesion or sham-fimbria-fornix lesion was performed on Wistar rats 13 days prior to 10 min forebrain ischemia or sham ischemia. Temperature was regulated and rats survived for 7, 14 or 28 days. Immunofluorescent bromodeoxyuridine and neuron specific nuclear protein staining and immunochemistry terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling staining were performed. At 7 days after ischemia, 73%+/-14% of cornus ammonis 1 neurons were damaged, while deafferentation reduced the injury to 36%+/-17% of cornus ammonis 1 neurons. This protection persisted for at least 28 days. Ischemia significantly increased the number of bromodeoxyuridine-positive cells (85-90 cells/section in stroke group vs. 6 to 11 cells/section in normal or sham stroke group), with very few terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling-stained cells adjacent to the hippocampal cornus ammonis 1. Fimbria-fornix lesioning followed by ischemia increased the percentage of new neurons 13-fold over ischemia alone and 6.5-fold over sham lesion plus ischemia. The results indicate that fimbria-fornix deafferentation provides long-term neuroprotection in cornus ammonis 1 following forebrain ischemia and promotes neurogenesis after ischemic insults.

Analysis of Variance↗
PubMed2006

Anatomically discrete functional effects of adenoviral clostridial light chain gene-based synaptic inhibition in the midbrain.

The gene for the Light Chain fragment of Tetanus Toxin (LC) induces synaptic inhibition by preventing the release of synaptic vesicles. The present experiment applied this approach within the rat midbrain in order to demonstrate that LC gene expression can achieve functionally and anatomically discrete effects within a sensitive brain structure. The deep layers of the superior colliculus/deep mesencephalic nucleus (dSC/DpMe) that are located in the rostral midbrain has been implicated in fear-induced increase of the acoustic startle reflex (fear potentiated startle) but exists in close proximity to neural structures important for a variety of critical functions. The dSC/DpMe of adult rats was injected bilaterally with adenoviral vectors for LC, green fluorescent protein, or vehicle. Synaptobrevin was depleted in brain regions of adenoviral LC expression. LC gene expression in the dSC/DpMe inhibited the increase in startle amplitude seen with the control viral infection, and blocked context-dependent potentiation of startle induced by fear conditioning. Although LC gene expression reduced the absolute amount of cue-specific fear potentiated startle, it did not decrease percent potentiated startle to a cue, nor did it reduce fear-induced contextual freezing, nonspecific locomotor activity, or general health, indicating that its effects were functionally and anatomically specific. Thus, vector-driven LC expression inhibits the function of deep brain nuclei without altering the function of surrounding structures supporting its application to therapeutic neuromodulation.

Adenoviridae↗
PubMed2006

Molecular epidemiology of dengue in the Pacific: introduction of two distinct strains of dengue virus type-1 [corrected] into Hawaii.

In 2000, a major dengue epidemic, caused by the type-1 virus (DENV-1), began in the Pacific and Asia, with cases still being reported in 2006. The phylogenetic analysis of full-length sequences of the envelope-protein gene of DENV-1 isolates recovered during outbreaks in Hawaii and Tahiti in 2001-2002 indicated that most Hawaiian isolates were Tahitian in origin. All the Hawaiian and Tahitian isolates were identified as the Pacific subtype (i.e. subtype IV) of DENV-1. A Hawaiian isolate, collected from a resident who had travelled to Samoa, differed significantly at the nucleotide level, however, from all the other Hawaiian strains, clustering, in the phylogenetic analysis, with a virus previously isolated from another visitor to Samoa. These results not only indicate that two distinct strains of DENV-1 were introduced into Hawaii in 2001 but also illustrate the ease with which dengue can be carried across distances of many thousands of miles.

Dengue↗
PubMed2006

Mortality in a large tuberculosis treatment trial: modifiable and non-modifiable risk factors.

SETTING: North America. OBJECTIVES: Tuberculosis (TB) patients in North America often have characteristics that may increase overall mortality. Identifying modifiable risk factors would allow for improvements in outcome. DESIGN: We evaluated mortality in a large TB treatment trial conducted in the United States and Canada. Persons with culture-positive pulmonary TB were enrolled after 2 months of treatment, treated for 4 more months under direct observation, and followed for 2 years (total observation: 28 months). Cause of death was determined by death certificate, autopsy, and/or clinical observation. RESULTS: Of 1075 participants, 71 (6.6%) died: 15/71 (21.1%) HIV-infected persons, and 56/1004 (5.6%) non-HIV-infected persons (P < 0.001). Only one death was attributed to TB. Cox multivariate regression analysis identified four independent risk factors for death after controlling for age: malignancy (hazard ratio [HR] 5.28, P < 0.0001), HIV (HR 3.89, P < 0.0001), daily alcohol (HR 2.94, P < 0.0001), and being unemployed (HR 1.99, P = 0.01). The risk of death increased with the number of independent risk factors present (P < 0.0001). Extent of disease and treatment failure/relapse were not associated with an increased risk of death. CONCLUSIONS: Death due to TB was rare. Interventions to treat malignancy, HIV, and alcohol use in TB patients are needed to reduce mortality in this patient population.

Adult↗
PubMed2005

Metabolic activation of pioglitazone identified from rat and human liver microsomes and freshly isolated hepatocytes.

Pioglitazone is in the class of compounds known as the thiazolidinediones and is used to treat type 2 diabetes mellitus. The first in its class compound, troglitazone, was withdrawn from the U.S. market in 2000 due to a high incidence of hepatotoxicity and drug-induced liver failure. Reactive ring-opened products of troglitazone have been identified and evidence suggests that these reactive intermediates might be a potential cause of hepatotoxicity. The present work shows that pioglitazone has a reactive ring-opened product which was trapped by glutathione and positively identified by high performance liquid chromatography with tandem mass spectrometry accurate mass measurements. The novel thiazolidinedione ring-opened products of pioglitazone were identified in rat and human liver microsomes and in freshly isolated rat but not human hepatocytes.

Animals↗
PubMed2005

Interferon beta-1b is effective in Japanese RRMS patients: a randomized, multicenter study.

OBJECTIVE: To assess the efficacy of interferon beta-1b (IFNB-1b) in Japanese patients with relapsing-remitting multiple sclerosis (RRMS). BACKGROUND: The effects of IFNB in RRMS have been assessed in study populations comprised predominantly of white patients. MS in Japanese patients is different from that in white patients in that there are two different presentations--classic MS (C-MS) and optic-spinal MS (OS-MS)--and chronic progressive forms are infrequent. METHODS: A total of 205 Japanese patients with RRMS were randomized to receive 50 microg or 250 microg (1.6 or 8.0 MIU) IFNB-1b administered SC every other day for up to 2 years. The primary endpoint was annual relapse rate. Secondary endpoints included further relapse-related and MRI outcome measures, as well as changes in Expanded Disability Status Scale and Neurologic Rating Scale. Efficacy was assessed in 188 patients, and safety was assessed in 192 patients. Supplemental ad hoc subgroup analyses were also performed for patients with OS-MS and those with C-MS. RESULTS: Annual relapse rates were 0.763 in the 250 microg group and 1.069 in the 50 microg group, a relative reduction of 28.6% (p = 0.047). Results for all secondary endpoints favored 250 microg IFNB-1b. Subgroup analyses suggested that the magnitude and direction of treatment effect in patients with OS-MS and C-MS was similar, albeit not significant due to small sample size. CONCLUSIONS: Interferon beta-1b (IFNB-1b) 250 microg significantly reduced relapse rates and change in MRI lesion area in Japanese patients with relapsing-remitting multiple sclerosis, and seemed to be comparably effective in optic-spinal multiple sclerosis (MS) and classic MS. The response to treatment with IFNB-1b in Japanese patients with MS suggests that a common pathogenesis and underlying genetic characteristics are shared with white patients.

Adolescent↗
PubMed2005

Opportunity of detecting pre-hypertension: worldwide data on blood pressure overswinging.

Overswinging or CHAT (brief for Circadian Hyper-Amplitude-Tension), that is an excessive circadian variation in blood pressure (BP), has been associated with a large increase in cardiovascular disease risk, present even in the absence of an elevated BP itself. This usually asymptomatic condition is usually overlooked by current practice based on spot-checks, because to be diagnosed, measurements need to be taken around-the-clock, preferably for 7 days at the outset. Once diagnosed, however, a usual circadian BP pattern can be restored by means of certain non-pharmacologic or pharmacologic interventions timed appropriately. Thereby, it is possible to reduce the risk of cardiovascular morbidity and mortality, cerebral ischemic events and nephropathy in particular. For the preparation of guidelines regarding the diagnosis of BP disorders and for the institution of primary as well as secondary preventive measures, it is important to know what the incidence of CHAT is on a global basis. We found 191 cases of CHAT among 1602 mostly 7-day/24-h BP profiles, obtained from several centers in different countries participating in an ongoing project on the BIOsphere and the COSmos (BIOCOS). CHAT incidence is about the same between men and women, but it is diagnosed more often among patients with borderline hypertension or with glucose intolerance. It is also more common among MESOR-hypertensive than among MESOR-normotensive individuals. Priority should be given to the development of an unobtrusive and affordable device to automatically monitor BP and to analyze the data as-one-goes, so that cardiovascular disease risk can be prevented.

Adult↗
PubMed2005

Establishment and properties of fetal dermis-derived mesenchymal stem cell lines: plasticity in vitro and hematopoietic protection in vivo.

Human mesenchymal stem cells (hMSCs) are excellent candidates for ex vivo gene transfer and cell therapy in various systems. However, hMSCs are mortal somatic cells, and thus invariably enter an irreversible growth arrest after a finite number of cell divisions in culture. It has been proposed that this is due to telomere shortening. In this study, pGRN145 plasmid containing human telomerase reverse transcriptase (hTRT) was introduced into fetal dermis-derived hMSCs. Single-cell clones positive for telomerase activity and hTRT mRNA were selected and expanded. Single-cell-derived hTRT(+) cells could be expanded rapidly in vitro and passaged up to 70 doublings without showing senescence. FACScan flow cytometer showed that hTRT(+) cells were positive for CD29, CD44, CD105, and CD166, while CD31, CD45, CD34, vWF, and HLA-DR were negative. Under suitable conditions, hTRT(+) cells have the ability of multiple lineage differentiation, including bone, fat, and nerve. Furthermore, transplantation of hTRT(+) cells could protect NOD/SCID mice from lethal irradiation. Thus, these cells may be an ideal cell source for promoting hematopoietic recovery after radiotherapy.

Animals↗
PubMed2005

RNAi libraries and kinetoplast DNA.

African trypanosomes have a remarkable mitochondrial DNA termed kDNA (kinetoplast DNA) that contains several thousands of topologically interlocked DNA rings. Because of its highly unusual structure, kDNA has a complex replication mechanism. Our approach to understanding this mechanism is to identify the proteins involved and to characterize their function. So far approx. 30 candidate proteins have been discovered and we predict that there are over 100. To identify genes for more kDNA replication proteins, we are using an RNA interference library, which is the first forward genetic approach used for these parasites.

Animals↗
PubMed2005

Transcriptomic analyses support the similarity of gene expression between brain and testis in human as well as mouse.

We previously revealed similarity in gene expression patterns between human brain and testis, based on digital differential display analyses of 760 human Unigenes. In the present work, we reanalyzed the gene expression data in many tissues of human and mouse for a large number of genes almost covering the respective whole genomes. The results indicated that both in human and in mouse, the gene expression profiles exhibited by brain, cerebellum and testis are most similar to each other compared with other tissues.

Animals↗
PubMed2004

All-optical hydrogen-sensing materials based on tailored palladium alloy thin films.

Optical reflectance measurements were performed to determine the hydrogen response characteristics of 20-nm-thick Pd-Au (Ag) films. The response characteristics displayed a strong dependence on alpha, mixed alpha/beta, and beta Pd-hydride phases formed in the films. The response time peaks in the alpha --> beta phase transition region (1625 s at 0.4% H(2) for Pd(0.94)Ag(0.06) and 405 s at 1% H(2) for Pd(0.94)Au(0.06)), consistent with critical slowing down phenomena. The alpha --> beta phase transition region was shifted and inhibited by changing the alloy element to Au and increasing its corresponding content to 40 atom %, respectively. Initial hydrogen uptake rate measurements determined that, due to the adsorption of ambient background gases, the rate-limiting step for alpha or beta phase PdH formation is dissociative chemisorption of hydrogen for each palladium alloy film. By tuning the alloy content and composition of the palladium films, the surface properties of the film become more receptive toward the rapid detection of hydrogen and a novel hydrogen-sensing material using Pd alloyed with 40 atom % Au is presented.

Journal Article↗
PubMed2004

Association between apolipoprotein CI HpaI polymorphism and sporadic Alzheimer's disease in Chinese.

OBJECTIVE: To investigate into the relationship of apolipoprotein CI (ApoCI) polymorphism with sporadic Alzheimer's disease (AD) in Chinese. SUBJECTS AND METHODS: A total of 257 AD patients and 242 age-matched elderly individuals were genotyped for the ApoCI HpaI and apolipoprotein E (ApoE) HhaI polymorphisms. RESULTS: The ApoCI A allele was associated with AD of moderate to severe dementia when patients were divided into two subgroups according to Clinical Dementia Rating scale, and the AA genotype was strongly associated with moderate to severe AD in ApoE epsilon4 allele carriers [odds ratio (OR) = 8.19, 95% confidential interval: 1.28-52.30, after adjusting for age and gender by logistic regression analysis], although in total no significant differences of allele or genotype frequency between patients and controls were found. CONCLUSION: The present study partially confirmed the previous findings, suggesting that the ApoCI A allele might contribute to the susceptibility to moderate to severe sporadic AD in Chinese.

Aged↗
PubMed2004

Nitrate removal from saline water using autotrophic denitrification by the bacterium Thiobacillus denitrificans MP-1.

Autotrophic denitrification of synthetic wastewater by Thiobacillus denitrificans MP-1 isolated from mangrove sediment was investigated in both up-flow packed-bed reactors and fermentor. More than 97.5% and 90% of the nitrate in inflow was removed after 8.8 and 161 hours at 250 and 195 mg l(-1) for the packed-bed reactor and fermentor system, respectively. The nitrate was quickly denitrified at very low flow rates (0.11 m h(-1)) for the packed-bed reactors, but as the flow rate was greater than 0.13 m h(-1), the nitrate removal rate increased as the flow rate increased. In the static fermentor system, the denitrification can be described by a secondary reaction, but at a flow rate between 1.31 to 1.49 m h(-1), the reactor performance can be described using the zero-order reaction in the packed-bed reactor. As the speed increases, the zero-order reaction translates into half-order reaction as the penetration efficiency of nitrate decreases. The mass ratios between the nitrate removed and the sulfate produced were determined to be 6.81 and 9.32 in the reactor column and fermentor, respectively. The results of this study suggest that efficient removal of high concentrations of nitrate in water or wastewater can be achieved effectively using autotrophic bacteria immobilized on surfaces of sulphur granules in packed-bed reactor.

Bioreactors↗
PubMed2003

Effect of soy protein isolate and conjugated linoleic acid on the growth of Dunning R-3327-AT-1 rat prostate tumors.

BACKGROUND: Epidemiologic and animal model studies suggest that consumption of soy isoflavones may be associated with reduced risk of prostate cancer (PC). In addition, animal model studies suggest that conjugated linoleic acid (CLA), a natural positional isomer of linoleic acid, inhibits tumor growth in various models, including models of PC. METHODS: Based on the above-mentioned data, the objective of the present study was to test the hypothesis that supplementation of the diet with combinations of isoflavone-rich soy protein isolate and CLA would act to inhibit the growth of androgen-independent R-3327-AT-1 rat prostate tumor cells inoculated ectopically into male Copenhagen rats. RESULTS: The results of this study indicate that neither an isoflavone-rich soy protein isolate (SPI), nor CLA inhibit the in vivo growth and development of prostate tumor cells when administered in the diet either singly or in combination. Moreover, at the highest concentrations SPI and CLA (i.e., 20% SPI, 1% CLA), there was a statistically significant increase in tumors volume over controls. Administration of SPI at 10% in the diet also enhanced tumor growth, whereas at 5%, SPI exerted no measurable effect. CLA administration alone had no observable effects on AT-1 tumor growth. CONCLUSION: These results, in an established rat model, suggest caution in using isoflavone-rich SPI in human studies involving advanced hormone-refractory prostate cancer until further investigation of these effects are completed.

Animals↗
PubMed2003

A role of P301L tau mutant in anti-apoptotic gene expression, cell cycle and apoptosis.

In exploring the causative role of the most common Pro(301)-to-Leu (TauP301L) tau missense mutation associated with neurodegenerative tauopathies, we examined TauP301L-mediated apoptotic cell death and the expression of a cluster of genes involved in the inhibition of apoptosis (IAPs) in human neuroblastoma SH-SY5Y cells. Our research found that the expression of TauP301L, but not wild-type tau, down regulated the expression of IAPs, including survivin, which plays a role in the mitotic spindle checkpoint. The inhibition of IAPs coincided with the activation of the pro-apoptotic caspase 3, but preceded apoptotic cell death by TUNEL. Furthermore, TauP301L altered the expression of the cell cycle regulatory proteins and induced the cell cycle arrest at G(2)/M phase. Our studies demonstrate that TauP301L downregulates the expression of genes that protect against apoptosis and regulate cell cycle progression. These results suggest a novel mechanism of apoptotic cell death in TauP301L-expressing cells that involves survivin-mediated activation of cell cycle checkpoint.

Apoptosis↗
PubMed2003

Genetic analysis of two distinct reproductive strategies in sexual and asexual field populations of an endoparasitic wasp, Venturia canescens.

Asexual (thelytokous) females of the parasitoid Venturia canescens, which develop inside another insect, exhibit evolutionarily stable mixtures of life-history strategies, allowing two genetically distinct wasp lines to coexist sympatrically on the same host resources. Since the two asexual lines differ in a virus-like particle protein-coding gene (VLP1), the question is whether the VLP1 gene is genetically associated with the phenotype. The recent isolation of facultative sexual (arrhenotokous) and asexual V. canescens strains from the same location in Southern France has enabled an investigation of the genetic basis for the observed phenotypic differences, by comparing the two asexual lines with the corresponding homozygous VLP1 genotypes in arrhenotokous strains. This analysis showed similar patterns of morphological and functional differences exist in the ovaries of the two asexual VLP1 lines and in the two homozygous VLP1 genotypes from the field, suggesting that the VLP1 gene alteration either causes the ovarian phenotype or is genetically closely linked to the putative gene. However, the VLP1-gene may not be the only gene contributing to the phenotypic effects observed in the asexual lines. Although the two VLP1-alleles segregate with the relative differences in the ovary distribution of eggs, the absolute egg numbers differ in the corresponding asexual and sexual genotypes. This suggests that an additional unlinked gene may be involved in the transfer of eggs from the ovarioles into the oviduct.

Animals↗