Search PubMed⌕ Search

Biomedical subjects

H Liu

Publications and source records attributed to H Liu.

At least 91 records · Page 5Linked to original sources

Aquaporin gene expression and regulation in the ovine fetal lung.

Fetal lung development is dependent upon secretion of liquid into the future airways which must be cleared at birth to establish air-breathing. Aquaporins (AQP) 1, 3, 4 and 5 are membranous water channel proteins that are present in the lung after birth in rodents, with little expression before birth. Our aim was to describe the changes in AQP1, 3, 4 and 5 expression and protein levels in the fetal lung of a long-gestation species (sheep) and in response to physiological factors known to alter fetal lung liquid dynamics. Both mRNA and high protein levels were detected for AQP1, 3, 4 and 5 by day 100 (term is ~150 days in ovine fetuses). A cortisol infusion (120-131 days) significantly (P < 0.05) increased AQP1 (0.9 +/- 0.2 (n = 4) vs.1.8 +/- 0.3 (n = 5)) and AQP5 (8.8 +/- 0.6 vs. 14.1 +/- 1.2) mRNA levels in fetal lung (measured by real-time PCR). Ten days of tracheal obstruction significantly (P < 0.05) decreased AQP5 mRNA levels (6.1 +/- 0.9 (n = 5) vs. 2.7 +/- 0.3 (n = 5)). Immunohistochemistry was used to show that protein levels changed in parallel with the mRNA changes. These findings suggest that AQPs could be involved in lung liquid production and reabsorption during fetal development in long-gestation species.

Aging↗

In vivo deamination of cytosine-containing cyclobutane pyrimidine dimers in E. coli: a feasible part of UV-mutagenesis.

We have estimated in vivo deamination rates for cytosines in cyclobutane pyrimidine dimers (CPD or PyPy) in UV-irradiated E. coli deficient in uracil DNA glycosylase. The protocol consisted of UV-irradiation, holding in buffer to allow for deamination of cytosines in CPDs and photoreversal (PR) to establish uracils where cytosines in CPD deaminated. The deamination rate at TC photoproducts targeting glutamine tRNA suppressor mutations was estimated from the increase in the mutation frequency after PR (MF(PR)) that developed as UV-irradiated cells were held before PR. Evidence suggested that an earlier study with this protocol under-estimated the deamination rate at sites producing the same mutations in an E. coli B/r strain. With a K12 strain, where the targeting apparently is principally by CPD and not (6-4) photoproducts, a larger rate of k = 0.0091 min(-1) at 42 degrees C resulted. The dark assay for MF also increased significantly with time for deamination consistent with a model for efficient mutation by translesion synthesis at uracil-containing CPD. In addition, we used a strain constructed by Cupples and Miller in which beta-galactosidase was inactive because -GGG- was at codon 461 and would revert to Lac(+) only when replaced by -GAG- or -GAA- for glutamate. CC photoproducts at this target site in the opposite DNA strand could reveal effects of first and second deaminations in the same CPD. MF(PR) for Lac(+) mutations increased and then decreased as a function of deamination time (at six temperatures 36-48 degrees C). Fitting an approximate model equation that distinguished two different deamination rates to these data suggested a first deamination producing Lac(+) at a rate about eight-fold less than a second deamination restoring the Lac(-) phenotype. We conclude that deamination, changing a cytosine-containing CPD to a uracil-containing CPD, could be an integral part of UV-induced C-to-T mutations.

Cytosine↗

Age-related differences in Na+-dependent Ca2+ accumulation in rabbit hearts exposed to hypoxia and acidification.

In this study, we test the hypothesis that in newborn hearts (as in adults) hypoxia and acidification stimulate increased Na(+) uptake, in part via pH-regulatory Na(+)/H(+) exchange. Resulting increases in intracellular Na(+) (Na(i)) alter the force driving the Na(+)/Ca(2+) exchanger and lead to increased intracellular Ca(2+). NMR spectroscopy measured Na(i) and cytosolic Ca(2+) concentration ([Ca(2+)](i)) and pH (pH(i)) in isolated, Langendorff-perfused 4- to 7-day-old rabbit hearts. After Na(+)/K(+) ATPase inhibition, hypoxic hearts gained Na(+), whereas normoxic controls did not [19 +/- 3.4 to 139 +/- 14.6 vs. 22 +/- 1.9 to 22 +/- 2.5 (SE) meq/kg dry wt, respectively]. In normoxic hearts acidified using the NH(4)Cl prepulse, pH(i) fell rapidly and recovered, whereas Na(i) rose from 31 +/- 18.2 to 117.7 +/- 20.5 meq/kg dry wt. Both protocols caused increases in [Ca](i); however, [Ca](i) increased less in newborn hearts than in adults (P < 0.05). Increases in Na(i) and [Ca](i) were inhibited by the Na(+)/H(+) exchange inhibitor methylisobutylamiloride (MIA, 40 microM; P < 0.05), as well as by increasing perfusate osmolarity (+30 mosM) immediately before and during hypoxia (P < 0.05). The data support the hypothesis that in newborn hearts, like adults, increases in Na(i) and [Ca](i) during hypoxia and after normoxic acidification are in large part the result of increased uptake via Na(+)/H(+) and Na(+)/Ca(2+) exchange, respectively. However, for similar hypoxia and acidification protocols, this increase in [Ca](i) is less in newborn than adult hearts.

Acids↗

Adenovirus DNA replication.

Replication of the adenovirus genome is catalysed by adenovirus DNA polymerase in which the adenovirus preterminal protein acts as a protein primer. DNA polymerase and preterminal protein form a heterodimer which, in the presence of the cellular transcription factors NFI/CTFI and NFIII/Oct-1, binds to the origin of DNA replication. DNA replication is initiated by DNA polymerase mediated transfer of dCMP onto preterminal protein. Further DNA synthesis is catalysed by DNA polymerase in a strand displacement mechanism which also requires adenovirus DNA binding protein. Here, we discuss the role of individual proteins in this process as revealed by biochemical analysis, mutagenesis and molecular modelling.

Adenoviridae↗

The roles of functional MRI in MR-guided neurosurgery in a combined 1.5 Tesla MR-operating room.

BACKGROUND AND PURPOSE: During MR-guided neurosurgical procedures performed in a combined 1.5 Tesla MR-operating room (MR-OR), we have successfully implemented and validated a functional MRI (fMRI) scheme for efficiently localizing eloquent functional areas and assessing their proximity to a lesion volume immediately prior to the craniotomy. METHODS: The fMRI examination consists of a dynamical blood oxygenation level dependent (BOLD) MR imaging technique and a task paradigm that is designed to activate the brain area of interest. The functional imaging technique was based on gradient-echo (GE) echo-planar imaging (EPI) (TR/TE = 2000-3000/40-50 msec). The motor task paradigm involves a periodic movement task, such as alternating between thumb and the other four fingers as a finger-tapping task, while the language involved a covert repeat of a series of words given as a task stimulus. While patient is performing the task, a dynamical fMRI was performed concurrently covering the volume of interest every 2 or 3 sec. Also, we have used a temporal series averaging (TSA) method for correcting the background drift in the raw fMRI signal, and developed a scheme for presenting fMRI results to neurosurgeons in an intuitive 3-dimensional volume-rendered display format. RESULTS: By using the fMRI scheme, we have successfully performed sixteen fMRI examinations immediately prior to neurosurgery in the combined MR-OR on the same surgical table to localize various eloquent functional areas of interests. TSA was successful in reducing the background drift in the fMRI time course data, and the 3-dimensional volume-rendered display was proven effective in presenting the resulting brain activations to neurosurgeons. More importantly, in three representative cases (one biopsy and two tumor resections) presented, the information provided by fMRI have indeed contributed significantly in making the optimal surgical decisions prior to craniotomy. CONCLUSIONS: Intra-operative fMRI can be an indispensable tool for determining the location of a neighboring eloquent functional area of concern in reference to a targeted lesion. Information provided by fMRI has helped in improving the outcome and clinician confidence of all surgeries performed.

Adolescent↗

Costs and benefits of intraoperative MR-guided brain tumor resection.

We retrospectively compared the costs and benefits of brain tumor resection in the conventional operating room (cOR) with the interventional magnetic resonance (iMR) suite from 1993-1998. Comparisons were made for adults (diagnosis-related group (DRG) 001) and children (DRG 003) for length of stay (LOS), hospital charges and payments, hospital total direct and indirect costs, readmission rates, repeat resection (RR) interval, and net health outcome. Statistical analysis was with ANOVA, Dunnett's, and Bonferroni tests. For DRG 001, iMR LOS (3.7 days (d)) was 54.9% shorter than for cOR (8.2 d) for first resections (FR) (P < 0.001) and RR (6.0 vs. 8.7 d (31.0%), P < 0.05). IMR hospital charges were 12.2% lower ($4063) for FR and 4.1% lower ($922) for RR than for cOR. Total iMR hospital costs were 14.4% lower ($3415) than for cOR for FR and 3.3% lower ($723) than costs for RR. Cost-to-charge ratio (c/c) for FR was 69.6% (iMR) and 71.4% (cOR) and for RR 70.9% (iMR) and 71.1% (cOR). For DRG 003, iMR LOS (4.5 d) was shorter than for cOR (14.1 d, P < 0.001) for FR and for RR (8.0 vs. 13.3 d). IMR hospital charges were 43.8% lower than for cOR for FR (P < 0.05) and RR. The iMR costs were lower for FR (46.4%, P < 0.01) and RR (44.7%) than cOR. IMR c/c was 71.4% and 74.8% for cOR. For RR, the iMR c/c was 72.8% and 73.9% for cOR. No RR have followed iMR surgery. COR RR rate was 20% in adults and 30% in children. The mean time from iMR surgery was 11.3 months in adults and 18.0 in children. For the cOR, the mean time to RR was 9.3 months in adults and 13.3 in children. This data suggests that iMR surgery improves net health outcomes by reduced LOS, reduced RR, and reduced hospital charges and costs.

Adolescent↗

Influence of 1.5-Tesla intraoperative MR imaging on surgical decision making.

To determine the frequency that high-field magnetic resonance (MR) imaging sequences influenced surgical decision making during intraoperative MR-guided surgery. From January 1997 to February 2001, 346 MR-guided procedures were performed using a 1.5-Tesla MR system (NT-ACS, Philips Medical Systems). This system can perform functional MR imaging (fMRI), diffusion weighted imaging (DWI), MR spectroscopy (MRS), MR angiography (MRA), and MR venography (MRV) in addition to T1-weighted, T2-weighted, and turbo FLAIR (fluid-attenuated inversion recovery) imaging. FMRI was used to determine areas of brain activation for language, motor function, and memory. DWI was utilized after tumor resection to exclude cerebral ischemia or infarction. MRS was obtained to identify areas of elevated choline that were suspected to correlate with tumor presence. MRA and MRV localized vascular structures adjacent to tumors prior to resection. The intraoperative procedures performed included 140 brain biopsies of which 82 utilized a trajectory guide and prospective stereotaxy. MRS was used in 42 biopsies (30%), of which 29 had turbo spectroscopic imaging (TSI) and 21 had single voxel spectroscopy (SVS). In all biopsy cases, diagnostic tissue was obtained. There were 103 tumor resections of which 18 (17%) had MRS. Functional MRI was used in 17 cases; 3 biopsies (2%) and 14 planned resections (14%). Speech function was localized in 3 cases, memory function in 3, and motor function in 11. In one case where the motor function of the tongue was intimately involved with a low-grade glioma, resection was not attempted. DWI was used in less than 10% of tumor resections. MRA and MRV were performed in 3 (3%) and 2 (2%) of tumor resections, respectively. The imaging capabilities (i.e., fMRI, DWI, MRA, MRV) associated with high-field intraoperative MR influenced surgical decision making primarily for tumor resections. MRS influenced target selection during brain biopsy.

Biopsy↗

Suppression of hippocampal neurogenesis is associated with developmental stage, number of perinatal seizure episodes, and glucocorticosteroid level.

Seizures increase dentate granule cell proliferation in adult rats but decrease proliferation in young pups. The particular period and number of perinatal seizures required to cause newborn granule cell suppression in development are unknown. Therefore, we examined cell proliferation with bromodeoxyuridine (BrdU) immunohistochemistry during the peak of neurogenesis (e.g., P6 and P9) and at later postnatal ages (e.g., P13, P20, or P30) following single and multiple episodes of perinatal status epilepticus induced by kainate (KA). Because an inverse relationship exists between glucocorticosteroids (CORT) levels and granule cell proliferation, plasma CORT levels and electroencephalographic (EEG) activity were simultaneously monitored to elucidate underlying mechanisms that inhibit cell proliferation. In control animals, the number of BrdU-labeled cells increased then declined with maturation. After 1x KA or 2x KA administered on P6 and P9, the numbers of BrdU-labeled cells were not different from age-matched controls. However, rat pups with 3x KA (on P6, P9, and P13) had marked suppression of BrdU-labeled cells 48-72 h after the last seizure (43 +/- 6.5% of control). Cell proliferation was also significantly inhibited on P20 after 2x KA (to 56 +/- 6.9%) or 3x KA (to 54 +/- 7.9%) and on P30 with 3x KA (to 74.5 +/- 8.2% of age-matched controls). Cell death was not apparent as chromatin stains showed increased basophilia of only inner cells lining the granule cell layers, in the absence of eosinophilia, argyrophilia, or terminal deoxynucleotidyl dUTP nick endlabeling (TUNEL) labeling at times examined. In P13 pups with 3x KA, electron microscopy revealed an increased number of immature granule cells and putative stem cells with irregular shape, condensed cytoplasm, and electron dense nuclei, and they were also BrdU positive. The EEG showed no relationship between neurogenesis and duration of high-synchronous ictal activity. However, endocrine studies showed a correlation with BrdU number and age, sustained increases in circulating CORT levels following 1x KA on P6 (0.7 +/- 0.1 to 2.40 +/- 0.86 microg/dl), and cumulative increases that exceeded 10 microg/dl at 4-8 h after 3x KA on P13 or P20. In conclusion, a history of only one or two perinatal seizure(s) can suppress neurogenesis if a second or third seizure recurs after a critical developmental period associated with a marked surge in CORT. During the first 2 weeks of postnatal life sustained increases in postictal circulating CORT levels but not duration or intensity of ictal activity has long-term consequences on neurogenesis. The occurrence of an increased proportion of immature granule cells and putative stem cells with irregular morphology in the absence of neurodegeneration suggests that progenitors may not differentiate properly and remain in an immature state.

Animals↗

Propagation of Bleustein-Gulyaev waves in a prestressed layered piezoelectric structure.

Based on the theories of nonlinear continuum mechanics, piezoelectricity and elastic waves in solids, theoretical analysis of Bleustein-Gulyaev surface acoustic wave propagation in a prestressed layered piezoelectric structure are described. Numerical calculations are performed for the case that the layer and the substrate are identical LiNbO(3) except that they are polarized in opposite directions. It is found that an almost linear behavior of the relative change in phase velocity versus the initial stress is obtained for both surface electrically free and shorted cases. Potential applications in the design of acoustic wave devices are suggested.

Acoustics↗

The enhancement of TiO2 photocatalytic activity by hydrogen thermal treatment.

In this study, conventional TiO2 powder was heated in hydrogen (H2) gas at a high temperature as pretreatment. The photoactivity of the treated TiO2 samples was evaluated in the photodegradation of sulfosalicylic acid (SSA) in aqueous suspension. The experimental results demonstrated that the photodegradation rates of SSA were significantly enhanced by using the H2-treated TiO2 catalysts and an optimum temperature for the H2 treatment was found to be of 500-600 degrees C. The in situ electron paramagnetic resonance (EPR) signal intensity of oxygen vacancies (OV) and trivalent titanium (Ti3+) associated with the photocatalytic activity was studied. The results proved the presence of OV and Ti3+ in the lattice of the H2-treated TiO2 and indicated that both were contributed to the enhancement of photocatalytic activity. Moreover, the experimental results presented that the EPR signal intensity of OV and Ti3+ in the H2-treated TiO2 samples after 10 months storage was still significant higher than that in the untreated TiO2 catalyst. The experiment also demonstrated that the significant enhancement occurred in the photodegradation of phenol using the H2-treated TiO2.

Benzenesulfonates↗

Suppression of genioglossus muscle tone and activity during reflex hypercapnic stimulation by GABA(A) mechanisms at the hypoglossal motor nucleus in vivo.

The genioglossus muscle is involved in the maintenance of an open airway for effective breathing. Inhibitory neurotransmitters may be responsible for the major suppression of hypoglossal motor output to genioglossus muscle that occurs in certain behaviours such as rapid-eye-movement sleep. There is evidence for GABA(A) receptor-mediated inhibition of hypoglossal motoneurons in vitro. However, comparable studies have not been performed in vivo and the interactions of such mechanisms with integrative reflex respiratory control have also not been determined. Urethane-anaesthetised, tracheotomized and vagotomized rats were studied whilst diaphragm and genioglossus muscle activities, blood pressure and the electroencephalogram were recorded. Microdialysis probes were implanted into the hypoglossal motor nucleus, with sites verified by histology. Genioglossus responses to microdialysis perfusion of muscimol (GABA(A) agonist: 0, 0.1, 1 and 10 microM in artificial cerebrospinal fluid) were recorded at inspired CO(2)s of 0, 5 and 7.5% in six rats. Responses to bicuculline (GABA(A) antagonist, 0, 1, 10, 100 and 1000 microM) were also studied in six rats with and without CO(2) stimulation. Genioglossus activity decreased with muscimol (P<0.0001), with major suppression at 1 and 10 microM during air breathing (decreases=70.2% and 92.8%, P<0.005). Genioglossus activity increased with CO(2) (P=0.003), but genioglossus activation with 5 and 7.5% CO(2) were almost abolished with 10-microM muscimol. Responses were specific to genioglossus muscle as there were no changes in diaphragm, respiratory rate or blood pressure with muscimol (P>0.144). Antagonism of GABA(A) receptors increased genioglossus activity (P<0.001). These results show that GABA(A) receptor stimulation at the hypoglossal motor nucleus suppresses both genioglossus muscle tone and activity in the presence of reflex stimulation produced by hypercapnia. Recruitment of such mechanisms may contribute to the major suppression of genioglossus activity observed with and without CO(2) stimulation in behaviours such as rapid-eye-movement sleep.

Animals↗

PPARgamma ligands and ATRA inhibit the invasion of human breast cancer cells in vitro.

Invasion and metastasis are the main causes of death in breast cancer patients. Increased expression of matrix metalloproteinases (MMPs), especially gelatinases (MMP-2 and -9), has been closely associated with tumor progression. One of the nuclear hormone receptors (NHR), peroxisome proliferator-activated receptor gamma (PPARgamma), is a ligand-activated transcriptional factor that regulates cell proliferation, differentiation and apoptosis in both normal and cancer cells. Recent data indicate that PPARgamma activation by its ligands can also lead to the inhibition of gelatinase B (MMP-9) and the blockage of migration in macrophages and muscle cells, implying the possibility that PPARgamma ligands may possess anti-invasive activities on tumor cells. In this study, we showed that treatment of the highly aggressive human breast cancer cell line MDA-MB-231 with the synthetic PPARgamma ligands pioglitazone (PGZ), rosiglitazone (RGZ), GW7845 or its natural ligand 15-deoxy-delta 12, 14-prostaglandin J2(15d-PGJ2), at concentrations at which no obvious cytotoxicity was observed in vitro, led to a significant inhibition of the invasive capacities of this cell line through a reconstituted basement membrane (Matrigel) in a Transwell chamber model. All-trans-retinoic acid (ATRA), a ligand for retinoic acid receptor (RAR), was also studied and showed a similar inhibitory effect on invasion. Although no change was observed in the expression of MMP-9 after challenge with PPARgamma ligands and/or ATRA on this cell line, the natural tissue inhibitor of gelatinases, namely the tissue inhibitor of MMP 1 (TIMP-1) was upregulated by these treatments and the gelatinolytic activities of gelatinases in the conditioned media were decreased. Since MMP-2 was not detectable in the conditioned media of MDA-MB-231 cells, and the gelatinolytic activities of the conditioned media were reduced only by MMP-9 neutralizing antibodies, it is most likely that the reduction of gelatinolytic activities by PPARgamma ligands and/or ATRA was due to the decrease of MMP-9 activities. Because MMP-9 was absolutely required in the transmigration of this cell line through Matrigel in our in vitro model as demonstrated by neutralizing antibodies against MMP-2 and -9, we concluded that down-regulation of gelatinase activities is, at least in part, responsible for the reduction of the invasive capacities of MDA-MB-231 cell line in vitro. Our results, for the first time, indicate that PPARgamma ligands may have therapeutic value for the treatment of highly invasive breast cancer by targeting its invasive behavior.

Breast Neoplasms↗

Effects of the neutral endopeptidase inhibitor thiorphan on cardiovascular and renal function in cirrhotic rats.

1. Cirrhosis is associated with cardiovascular and renal dysfunction including sodium retention. Many vasoactive peptides such as atrial natriuretic peptide (ANP) and endothelin-1 (ET-1) are degraded by neutral endopeptidase 24.11 (NEP). We investigated the hemodynamic and renal effects of thiorphan, a NEP inhibitor, in a rat cirrhosis model. 2. Cirrhosis was induced by chronic bile duct ligation, and controls had sham operation. Systemic and renal hemodynamics in conscious, restrained animals were determined using radiolabeled microspheres, and glomerular filtration rate (GFR) was measured by (3)H-inulin clearance. Plasma ANP and ET-1, and renal cGMP and Na(+) - K(+) ATPase activity were assayed. These variables were measured at baseline and after intravenous infusion of thiorphan (0.5 mg kg(-1) loading dose followed by 0.1 mg kg(-1) min(-1) x 30 min). 3. Thiorphan significantly decreased cardiac output, and increased systemic vascular resistance in controls, whereas in cirrhotic rats these variables were unchanged. 4. Compared to the controls, cirrhotic rats showed a decreased baseline GFR and urine sodium excretion, and the latter was significantly increased by thiorphan. 5. Thiorphan increased plasma ET-1 levels in controls, but not cirrhotic rats. ANP levels were not significantly increased in either group by thiorphan. 6. Thiorphan significantly increased cGMP concentrations and decreased Na(+) - K(+) ATPase activity of renal medulla but not cortex in cirrhotic rats; no effect was observed in the control rats. 7. We conclude that thiorphan induces natriuresis in cirrhotic rats by a direct renal medullary mechanism via cGMP and Na(+) - K(+) ATPase, without affecting systemic hemodynamics. This may potentially be useful in patients with ascites.

Animals↗

Adenovirus-mediated interleukin-2 gene therapy of nociception.

The effect of adenovirus-mediated interleukin-2 (IL-2) gene on rat basal nociceptive response and chronic neuropathic pain was explored. The paw withdrawal latency induced by radiant heat was used to evaluate the antinociceptive effect of adenovirus type 5 (Ad5) and Ad5-IL-2. The results showed that intrathecal delivery of Ad5-IL-2 exhibited obvious antinociceptive effects on basal nociceptive response and chronic neuropathic pain, which were maintained for 3 and 4 weeks, respectively. This suggested that the antinociceptive effect of Ad5-IL-2 on chronic neuropathic pain was greater than its effect on basal nociceptive response. Human IL-2 mRNA was detected by in situ hybridization in the spinal pia mater and parenchyma of the lumbar, sacral, thoracic and cervical regions, and gray matter had higher level of IL-2 expression than white matter. These data demonstrated that the IL-2 gene was transfected into spinal cord regions relevant to pain modulation. The expressed IL-2 protein profile in spinal cord detected by enzyme-linked immunosorbent assay coincided almost exactly with its antinociceptive effect. This supported the hypothesis that the therapeutic effect of IL-2 gene was related to IL-2 protein expression. The study indicates that intrathecal delivery of adenovirus-mediated IL-2 gene has a relatively long antinociceptive effect.

Adenoviridae↗