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Biomedical subjects

Hong Guo

Publications and source records attributed to Hong Guo.

At least 19 recordsLinked to original sources
PubMed2007

Effects of biaxial stretch on arteriolar function in vitro.

Mounting evidence suggests that the normal biomechanical state of arteries may include a nearly equibiaxial intramural stress and that arteries tend to undergo rapid and dramatic remodeling when perturbed from this normal state. Technical developments since the early 1980s have enabled in vitro (acute) and ex vivo (chronic culture) study of isolated, perfused microvessels, and it is clear that these vessels share many functional similarities with arteries. To date, however, there has been no systematic study of the effects of in-plane biaxial loading on the biomechanical behavior of arterioles. Here we describe a modification to a prior in vitro arterial test system that allowed us to investigate the role of altered axial stretch on the passive, myogenic, and norepinephrine-stimulated biaxial behavior of isolated rat cremaster arterioles. We show that axial stretches from 85% to 110% of values often used in the laboratory and consistent with those normally experienced in situ induce modest changes in the measured mean circumferential and axial stress-stretch behavior and in measures of distensibility and myogenic index. Nevertheless, altered axial stretch has a dramatic effect on the biaxial state of stress, and nearly equibiaxial stresses occur at axial stretches larger than those typically used in isolated arteriole studies. This finding is consistent with estimates of material and functional behavior in arterioles and suggests that long-term ex vivo studies, wherein vessel growth and remodeling are critical, should be performed at higher axial lengths than have been used during most prior in vitro tests.

Animals↗
PubMed2006

Translational control of glial glutamate transporter EAAT2 expression.

Glutamate is the major excitatory neurotransmitter in the central nervous system. Its activity is carefully modulated in the synaptic cleft by glutamate transporters. The glial glutamate transporter EAAT2 is the main mediator of glutamate clearance. Reduced EAAT2 function could lead to accumulation of extracellular glutamate, resulting in a form of cell death known as excitotoxicity. In amyotrophic lateral sclerosis and Alzheimer disease, EAAT2 protein levels are significantly decreased in affected areas. EAAT2 mRNA levels, however, remain constant, indicating that alterations in EAAT2 expression are due to disturbances at the post-transcriptional level. In the present study, we found that some EAAT2 transcripts contained 5'-untranslated regions (5'-UTRs) greater than 300 nucleotides. The mRNAs that bear long 5'-UTRs are often regulated at the translational level. We tested this possibility initially in a primary astrocyte line that constantly expressed an EAAT2 transcript containing the 565-nt 5'-UTR and found that translation of this transcript was regulated by many extracellular factors, including corticosterone and retinol. Moreover, many disease-associated insults affected the efficiency of translation of this transcript. Importantly, this translational regulation of EAAT2 occurred in vivo (i.e. both in primary cortical neurons-astrocytes mixed cultures and in mice). These results indicate that expression of EAAT2 protein is highly regulated at the translational level and also suggest that translational regulation may play an important role in the differential EAAT2 protein expression under normal and disease conditions.

5' Untranslated Regions↗
PubMed2006

First principles modeling of tunnel magnetoresistance of Fe/MgO/Fe trilayers.

We report ab initio calculations of nonequilibrium quantum transport properties of Fe/MgO/Fe trilayer structures. The zero bias tunnel magnetoresistance is found to be several thousand percent, and it is reduced to about 1000% when the Fe/MgO interface is oxidized. The tunnel magnetoresistance for devices without oxidization reduces monotonically to zero with a voltage scale of about 0.5-1 V, consistent with experimental observations. We present an understanding of the nonequilibrium transport by investigating microscopic details of the scattering states and the Bloch bands of the Fe leads.

Journal Article↗
PubMed2006

Dynamical conductance of model DNA sequences.

Using a tight binding model, we have investigated charge transport in model DNA sequences under external ac bias. The numerical results of emittance for several model DNA sequences are found to be well described by an analytical formula, especially when the dynamic response is inductivelike. This formula can be understood from general considerations of scattering matrix theory. The temperature dependence of emittance is also studied numerically within the tight binding model, and dynamic response of the model DNA sequences can change from inductivelike to capacitivelike as temperature is varied.

Base Sequence↗
PubMed2006

Universal spin-Hall conductance fluctuations in two dimensions.

We report a theoretical investigation on spin-Hall conductance fluctuation of disordered four-terminal devices in the presence of Rashba or/and Dresselhaus spin-orbital interactions in two dimensions. As a function of disorder, the spin-Hall conductance GsH shows ballistic, diffusive, and insulating transport regimes. For given spin-orbit interactions, a universal spin-Hall conductance fluctuation (USCF) is found in the diffusive regime. The value of the USCF depends on the spin-orbit coupling tso but is independent of other system parameters. It is also independent of whether Rashba or Dresselhaus or both spin-orbital interactions are present. When tso is comparable to the hopping energy t, the USCF is a universal number approximately 0.18e/4pi. The distribution of GsH crosses over from a Gaussian distribution in the metallic regime to a non-Gaussian distribution in the insulating regime as the disorder strength is increased.

Journal Article↗
PubMed2006

Catalytic role of proton transfers in the formation of a tetrahedral adduct in a serine carboxyl peptidase.

Quantum mechanical/molecular mechanical molecular dynamics and 2D free energy simulations are performed to study the formation of a tetrahedral adduct by an inhibitor N-acetyl-isoleucyl-prolyl-phenylalaninal (AcIPF) in a serine-carboxyl peptidase (kumamolisin-As) and elucidate the role of proton transfers during the nucleophilic attack by the Ser278 catalytic residue. It is shown that although the serine-carboxyl peptidases have a fold resembling that of subtilisin, the proton transfer processes during the nucleophilic attack by the Ser residue are likely to be more complex for these enzymes compared to the case in classical serine proteases. The computer simulations demonstrate that both general base and acid catalysts are required for the formation and stabilization of the tetrahedral adduct. The 2D free energy maps further demonstrate that the proton transfer from Ser278 to Glu78 (the general base catalyst) is synchronous with the nucleophilic attack, whereas the proton transfer from Asp164 (the general acid catalyst) to the inhibitor is not. The dynamics of the protons at the active site in different stages of the nucleophilic attack as well as the motions of the corresponding functional groups are also studied. It is found that the side chain of Glu78 is generally rather flexible, consistent with its possible multifunctional role during catalysis. The effects of proton shuffling from Asp82 to Glu78 and from Glu32 to Asp82 are examined, and the results indicate that such proton shuffling may not play an important role in the stabilization of the tetrahedral intermediate analogue.

Aspartic Acid↗
PubMed2006

Disruption of EphA2 receptor tyrosine kinase leads to increased susceptibility to carcinogenesis in mouse skin.

EphA2 receptor tyrosine kinase is frequently overexpressed in different human cancers, suggesting that it may promote tumor development and progression. However, evidence also exists that EphA2 may possess antitumorigenic properties, raising a critical question on the role of EphA2 kinase in tumorigenesis in vivo. We report here that deletion of EphA2 in mouse led to markedly enhanced susceptibility to 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate (DMBA/TPA) two-stage skin carcinogenesis. EphA2-null mice developed skin tumors with an increased frequency and shortened latency. Moreover, tumors in homozygous knockout mice grew faster and were twice as likely to show invasive malignant progression. Haploinsufficiency of EphA2 caused an intermediate phenotype in tumor development but had little effects on invasive progression. EphA2 and ephrin-A1 exhibited compartmentalized expression pattern in mouse skin that localized EphA2/ephrin-A1 interactions to the basal layer of epidermis, which was disrupted in tumors. Loss of EphA2 increased tumor cell proliferation, whereas apoptosis was not affected. In vitro, treatment of primary keratinocytes from wild-type mice with ephrin-A1 suppressed cell proliferation and inhibited extracellular signal-regulated kinase 1/2 (ERK1/2) activities. Both effects were abolished in EphA2-null keratinocytes, suggesting that loss of ERK inhibition by EphA2 may be one of the contributing mechanisms for increased tumor susceptibility. Interestingly, despite its tumor suppressive function, EphA2 was overexpressed in skin tumors compared with surrounding normal skin in wild-type mice, similar to the observations in human cancers. EphA2 overexpression may represent a compensatory feedback mechanism during tumorigenesis. Together, these results show that EphA2 is a novel tumor suppressor gene in mammalian skin.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed2006

Brief cognitive-behavioral audiotape interventions for cancer-related pain: Immediate but not long-term effectiveness.

BACKGROUND: Few studies have evaluated cognitive-behavioral interventions as an adjunct treatment for chronic cancer-related pain. A randomized clinical trial was performed evaluating the efficacy of 3 brief cognitive-behavioral techniques: relaxation, distraction, and positive mood interventions. METHODS: Fifty-seven patients with chronic cancer-related pain taking opioid medications were randomly assigned to either the relaxation, distraction, positive mood, or waiting-list control group. The patients in the 3 intervention groups received audiotapes of the cognitive-behavioral technique and were asked to practice regularly at home. The tapes were supplemented with written instructions and follow-up telephone calls. RESULTS: Patients in the relaxation and distraction groups reported significantly reduced pain intensity immediately after listening to the tapes. The pain reduction was not maintained, however. At the 2-week follow-up assessment, no significant differences in pain intensity or interference were found among the treatment groups. The groups also did not differ with regard to secondary outcome measures assessing quality of life, mood, self-efficacy, and other symptoms. The results of qualitative interviews indicated that patients often had difficulty focusing on the audiotapes and preferred their own methods of pain reduction. CONCLUSIONS: Brief relaxation and distraction audiotape interventions produced immediate pain reductions but not longer-term pain relief. Additional research with a more individualized intervention is needed to evaluate cognitive-behavioral interventions for cancer pain control.

Adult↗
PubMed2006

Nonlinear spin current and magnetoresistance of molecular tunnel junctions.

We report on a theoretical study of spin-polarized quantum transport through a Ni-bezenedithiol(BDT)-Ni molecular magnetic tunnel junction (MTJ). Our study is based on carrying out density functional theory within the Keldysh nonequilibrium Green's function formalism, so that microscopic details of the molecular MTJ are taken into account from first principles. A magnetoresistance ratio of approximately 27% is found for the Ni-BDT-Ni MTJ which declines toward zero as bias voltage is increased. The spin currents are nonlinear functions of bias voltage, even changing sign at certain voltages due to specific features of the coupling between molecular states and magnetic leads.

Journal Article↗
PubMed2006

Apomorphine-induced activation of dopamine receptors modulates FGF-2 expression in astrocytic cultures and promotes survival of dopaminergic neurons.

Apomorphine (APO), a potent D1/D2 dopamine receptor agonist, is currently used as an antiparkinsonian drug. We have shown previously that APO stimulates synthesis and release of multiple trophic factors, such as brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF), in both mesencephalic and striatal neurons, thereby effectively preventing dopaminergic neuron loss in vitro. The present study was designed to investigate the effects of APO on fibroblast growth factor-2 (FGF-2) expression and regulation in astrocytes, and furthermore, to identify signaling mechanisms underlying these effects. Here, we show that FGF-2 expression is robustly induced in cultured astrocytes in response to APO. FGF-2 expression was proportional to APO concentration and time-dependent. Conversely, treatment with S-APO, a derivative of R-APO lacking DA receptor agonist activity, did not alter FGF-2 levels. APO treatment resulted in enhanced cytosol FGF-2 immunoreactivity, export of high MW forms of FGF-2 to the cytoplasm from the nucleus and increased extracellular release of FGF-2. Interestingly, both high and low MW forms of FGF-2 were detectable in conditioned medium of APO-treated cultures. This APO-induced effect was correlated with activation of D1 and D2 receptors, as it could be either mimicked by dopamine receptor agonists (SKF38393, quinpirole) or partially blocked by antagonists (SCH23390, SKF83566, haloperidol). Activation of the D1 receptor preferentially increased PKA activity, whereas activation of the D2 receptor only promoted phosphorylation of MAPK. Importantly, APO-modulated FGF-2 expression was independent of Akt/phosphoinositide 3-kinase signaling. These data suggest that APO can enhance biosynthesis and release of FGF-2 through activation of dopamine receptors in striatal astrocytes. Both cAMP/PKA and MEK/MAPK signaling cascades are major steps mediating this process.

Animals↗
PubMed2006

Genetic restoration of aldose reductase to the collecting tubules restores maturation of the urine concentrating mechanism.

To investigate the underlying causes for aldose reductase deficiency-induced diabetes insipidus, we carried out studies with three genotypic groups of mice. These included wild-type mice, knockout mice, and a newly created bitransgenic line that was homozygous for both the aldose reductase null mutation and an aldose reductase knockin transgene driven by the kidney-specific cadherin promoter to direct transgene expression in the collecting tubule epithelial cells. We found that from early renal developmental stages onward, urine osmolality did not exceed 1,000 mosmol/kgH2O in aldose reductase-deficient mice. The functional defects were correlated with significant renal cellular and structural abnormalities that included cell shrinkage, apoptosis, disorganized tubular and vascular structures, and segmental atrophy. In contrast, the transgenic aldose reductase expression in the bitransgenic mice largely but incompletely rescued urine concentrating capacity and significantly improved renal cell survival, cellular morphology, and renal structures. Together, these results suggest that aldose reductase not only plays important roles in osmoregulation and medullary cell survival but may also be essential for the full maturation of the urine concentrating mechanism.

Aldehyde Reductase↗
PubMed2006

Cerebral autoregulation is preserved during orthostatic stress superimposed with systemic hypotension.

We sought to determine whether cerebral autoregulation (CA) is compromised during orthostatic stress superimposed with systemic hypotension. Transient systemic hypotension was produced by deflation of thigh cuffs previously inflated to suprasystolic pressure, combined with or without lower body negative pressure (LBNP). Cardiac output (CO) decreased from a baseline of 5.0+/-0.5 l/min by -8.3+/-1.7, -19.2+/-2.0, and -30.6+/-3.4% during LBNP of -15, -30, and -50 Torr, respectively. Mean arterial pressure (MAP) was maintained during LBNP, despite decreases in systolic and pulse pressures. Middle cerebral arterial blood flow velocity (VMCA) decreased significantly from a baseline of 64+/-3 to 58+/-4 cm/s (-9.7+/-2.4%) at -50 Torr of LBNP. The reduction in VMCA was associated with a decrease in regional cerebral O2 saturation. However, the percent decrease in VMCA was markedly less than that of CO. This suggests that the magnitude of the change in VMCA (an index of cerebral blood flow) is less than would be predicted, given the decrease in CO. Transient systemic hypotension decreased MAP by -21+/-2, -24+/-2, -28+/-3, and -26+/-3% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Likewise, this acute hypotension resulted in decreases in VMCA of -20+/-2, -21+/-2, -24+/-25, and -19+/-2% and regional cerebral O2 saturation of -5+/-1, -6+/-1, -6+/-1, and -7+/-2% at rest and during LBNP of -15, -30, and -50 Torr, respectively. Complete recovery of VMCA to baseline values following transient hypotension (ranging from 5 to 8 s) occurred significantly earlier compared with MAP (from 10 to 12 s). No subjects experienced syncope during acute hypotension. We conclude that CA is preserved during LBNP, superimposed with transient systemic hypotension, despite the decrease in VMCA associated with sustained central hypovolemia in normal healthy individuals. This preserved CA is vital for the prevention of orthostatic syncope.

Adult↗
PubMed2006

Comment on "partially coherent flat-topped beam and its propagation".

We point out that the expression of the cross-spectral density (CSD) of a partially coherent flat-topped beam (PCFB) given by Ge et al. [Appl. Opt. 43, 4732 (2004)] is incorrect. The results show that the M2 factor derived based on Ge's expression leads to M2 < 1 in some cases, which is physically unacceptable. A new expression of the CSD for a PCFB is given.

Comment↗
PubMed2006

Efficacy of low-release-rate fluocinolone acetonide intravitreal implants to treat experimental uveitis.

OBJECTIVE: To determine the efficacy of 0.5-mg and 0.1-mg sustained-release fluocinolone acetonide intravitreal implants to inhibit ocular inflammation in a rabbit model of severe uveitis. METHODS: The in vitro pharmacokinetic profile of both the 0.5-mg and 0.1-mg sustained-release fluocinolone intravitreal implants was determined during a 10-day period. A sustained-release fluocinolone acetonide intravitreal implant with a release rate of either 0.5 microg/d (n = 16) or 0.1 microg/d (n = 16) was implanted into the vitreous cavity of the right eye in albino rabbits after a subcutaneous injection of tuberculin antigen. Control animals (n = 14) received empty devices. Uveitis was induced with an intravitreal tuberculin antigen injection. A masked observer graded anterior chamber flare, anterior chamber cells, vitreous opacity, and inflammation on histologic sections. RESULTS: In vitro, the drug was released from both devices in a linear manner. In vivo, treated eyes were significantly less inflamed than untreated eyes (P< or =.02). Inflammation was suppressed to a greater degree with the 0.5-microg/d implant compared with the 0.1-microg/d implant. CONCLUSION: Sustained-release fluocinolone intravitreal implants suppress ocular inflammation in a rabbit model of severe uveitis. CLINICAL RELEVANCE: The efficacy demonstrated with the 0.1-microg/d implant provides the rationale for future human studies with lower-release-rate implants than are currently used in noninfectious uveitis clinical trials.

Animals↗
PubMed2006

Status of cancer pain in Hanoi, Vietnam: A hospital-wide survey in a tertiary cancer treatment center.

Little is known about the prevalence of cancer pain in many developing countries. We report a hospital-wide survey of pain in a tertiary cancer center in Hanoi, Vietnam. All inpatients and outpatients age 18 years or older were approached for participation in the study. Data were collected using the Brief Pain Inventory. Results showed a 70% response rate. Prevalence of moderate to severe pain was 50% (89/178), with 23% reporting severe ratings of pain at its "worst" and 33% reporting severe impairment in their ability to work due to pain. Only 1% and 40% reported total and partial pain relief from medications, respectively. This study is among the first to provide a representative view of pain in a tertiary cancer treatment center in Hanoi, Vietnam. The findings provide empirical support for the need for better programmatic efforts to improve relief of cancer pain in developing countries, including Vietnam.

Adult↗
PubMed2006

Filipino version of the M. D. Anderson Symptom Inventory: validation and multisymptom measurement in cancer patients.

Assessing cancer-related symptoms requires a brief, reliable, valid, and culturally adapted symptom screening tool. In the Philippines, cancer patients (n=206) and community-dwelling adults (n=170) participated in a cross-sectional validation study of the Filipino version of the M. D. Anderson Symptom Inventory (MDASI-F). Both exploratory factor analysis and hierarchical cluster analysis revealed two underlying symptom severity constructs--general and gastrointestinal symptoms--consistent with the English, Japanese, and Chinese versions of the MDASI. Cronbach alpha coefficients of 0.79 and 0.77, respectively, demonstrated acceptable internal consistency for the two factors. Known-group validity was confirmed by significant differences on MDASI-F items by performance status (P<0.01 or P<0.001). Fatigue, sadness, distress, and pain were significant predictors of symptom interference. Cancer patients reported significantly greater symptom severity on multiple items than did the community sample. The MDASI-F is reliable and valid for evaluating cancer-related symptoms and their impact on Filipino cancer patients.

Adolescent↗
PubMed2006

Multiple gene genealogical analyses reveal both common and distinct population genetic patterns among replicons in the nitrogen-fixing bacterium Sinorhizobium meliloti.

Sinorhizobium meliloti is a Gram-negative alpha-proteobacterium that can form symbiotic relationships with alfalfa and fix atmospheric nitrogen. The complete genome of a laboratory strain, Rm1021, was published in 2001, and the genome of this strain is arranged in three replicons: a chromosome of 3.65 million base pairs (Mb), and two megaplasmids, pSymA (1.35 Mb) and pSymB (1.68 Mb). However, the potential difference in genetic variation among the three replicons in natural strains remains poorly understood. In this study, a total of 16 gene fragments were sequenced, four from pSymA and six each from the chromosome and pSymB, for 49 natural S. meliloti strains. The analyses identified significant differences in divergence among genes, with the mean Hasegawa-Kishino-Yano-1985 (HKY85) distance ranging from 0.00157 to 0.04109 between pairs of strains. Overall, genes on pSymA showed the highest mean HKY85 distance, followed by those on pSymB and the chromosome. Although evidence for recombination was found, the authors' population genetic analyses revealed overall significant linkage disequilibria among genes within both pSymA and the chromosome. However, genes on pSymB were in overall linkage equilibrium, consistent with frequent recombination among genes on this replicon. Furthermore, the genealogical comparisons among the three replicons identified significant incongruence, indicating reassortment among the three replicons in natural populations. The results suggest both shared and distinct patterns of molecular evolution among the three replicons in the genomes of natural strains of S. meliloti.

Genes, Bacterial↗