Biomedical subjects

M L Liu

Publications and source records attributed to M L Liu.

At least 19 recordsLinked to original sources

PubMed2005

Investigating spiritual care perceptions and practice patterns in Hong Kong nurses: results of a cluster analysis.

AIM: Nurses' spiritual care perceptions and practices are explored by identifying profiles of nurses studying in a part-time baccalaureate course in a local Hong Kong university. Relationships between nurses' spiritual care perceptions and their practices are explored. RESEARCH METHOD: Hundred and ninety three nurses completed a structured questionnaire. OUTCOME MEASURES: Spiritual care perceptions and practices. RESULTS: Two-step cluster analysis yielded three clusters. Clusters A, B, and C consisted of 15.0% (n = 29), 44.6% (n = 86), and 40.4% (n = 78), respectively. Cluster A nurses were characterized by relatively negative spiritual care perceptions and practices. Cluster C nurses reported positive perceptions, but negative practices; they mainly chose 'uncertain' for most items on both scales. Cluster B was a large group of nurses holding both positive spiritual care perceptions and practices. Significant differences towards spiritual care were found among clusters. Nurses' perceptions were significant positively correlated with practices (r = 0.62). High positive correlations were found between the two scales (r = 0.83) for nurses in Cluster A, for nurses in Clusters B and C, low positive correlations (r = 0.37) were found. CONCLUSION: Three clusters of Hong Kong nurses were differentiated. They showed differences in the level of their spiritual care perceptions and practices. Despite their level of spiritual care perceptions, nurses seldom incorporated spiritual care practices into their daily nursing care, and the level of spiritual care awareness of some nurses was low. Findings may be used to improve support of nurses, to ensure sensitive spiritual care in their daily practices, and to enhance nursing curricula.

Adult↗

PubMed2004

Analysis of competitive binding of ligands to human serum albumin using NMR relaxation measurements.

The competitive binding of two ligands, ibuprofen (IBP) and salicylic acid (SAL), to human serum albumin (HSA) was studied by using nuclear magnetic resonance (NMR) relaxation measurements. When the concentration of one ligand was increased in the solution containing IBP, SAL and HSA, the fractions of free IBP and SAL were increased because of the competitive binding. The 1H relaxation rates (R1) of both ligands were subsequently decreased. If a ligand is in fast exchanging between the free and bound forms, the observed 1H relaxation rate is a weighted average of that for the free ligand and the protein-ligand complex. The concentrations of the free and bound ligands can be quantitatively derived from the relaxation rates. The results presented in this work revealed that IBP and SAL shared certain low-affinity binding sites on the HSA molecule, in addition to the same high-affinity binding site of AIII.

Humans↗

PubMed2004

Associations between HDL oxidation and paraoxonase-1 and paraoxonase-1 gene polymorphisms in families affected by familial combined hyperlipidemia.

BACKGROUND AND AIM: It has been shown in vitro that the HDL-bound enzyme paraoxonase-1 (PON1) protects LDL against oxidation, and PON1 and PON1 gene polymorphisms may affect the oxidation of HDL particles. The aim of this study was to investigate the associations between in vitro HDL oxidation parameters, endogenous PON1 and PON1 genotypes in families affected by asymptomatic FCHL. METHODS AND RESULTS: Serum arylesterase (ARE) and PON1 activities, PON1 mass, PON1 genotypes and the kinetics of CuSO4-induced HDL oxidation in vitro were measured in 150 members of FCHL families free of clinical CAD. At univariate analysis, log PON1/apoA-I and the PON1 mass/apoA-I ratio significantly correlated with lag time, maximum diene formation and the propagation rate. The oxidation parameters also correlated with PON1 genotypes. Multivariate analysis showed that the associations between PON1 mass/unit apoA-I and the oxidation parameters were independent of the other variables. The lag time of HDL oxidation was also associated with the PON1 genotype 192QR. CONCLUSIONS: Endogenous PON1 may have protective effects on the different stages of HDL oxidation in the members of families affected by FCHL. This protective effect is independent of other biochemical factors, but may be influenced by the PON1 gene polymorphism. The endogenous PON1 content of HDL seems to be an important determinant of the anti-atherogenicity of this lipoprotein.

Adult↗

PubMed2001

[Effect of hyperinsulinism on NO production in vascular smooth muscle cells].

Nitrate reductasing and immunoblotting test were used to investigate the modulation of protein kinase C (PKC) activity in cultured rat vascular smooth muscle cells (VSMCs) with high concentration of insulin (HI) and the effect of HI on lipopolysaccharides + gamma-interferon (LPS + gamma-IFN)-induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression with or without PKC inhibitor H7. The results were that membrane PKC activity preincubated with HI was significantly higher than that with the control group(P < 0.05), and NO production pretreated by HI was obviously lower than that of the control group(P < 0.01). PKC inhibitor H7 ameliorated the down-regulation of LPS + gamma-IFN induced NO production by high concentration of insulin. Immunoblotting test revealed a decrease induced by the high level insulin in the expression of iNOS in VSMCs. It is suggested that hyperinsulinism may activate PKC to partly inhibit the expression of iNOS and decrease NO production in VSMCs.

Animals↗

PubMed2001

Determination of molecular self-diffusion coefficient using multiple spin-echo NMR spectroscopy with removal of convection and background gradient artifacts.

A new approach is presented for the measurement of the self-diffusion coefficients of molecules in solution. It has been applied to metabolites in biofluids such as seminal and blood plasma at physiological temperature. The method is based on the double-gradient-spin-echo pulse sequence in which CPMG and bipolar gradient pulses have been implemented. The double-gradient spin-echo is shown to be useful in reducing the thermal convection that can cause over-estimation of the diffusion coefficients. The multiple spin-echoes in association with the CPMG approach is also insensitive to background gradient artifacts. In addition, the CPMG sequence enables longer diffusion periods (up to seconds) to be used without phase distortion; therefore, the proposed method is suitable for determining the diffusion coefficients of small metabolites in biofluids, where the resonances of large molecules, such as proteins, are suppressed during the spin-echo period as a result of their fast relaxation.

Amino Acids↗

PubMed2001

Haploid loss of Ki-ras delays mammary tumor progression in C3 (1)/SV40 Tag transgenic mice.

We have previously demonstrated that amplification and overexpression of the Ki-ras gene is associated with mammary tumor progression in C3(1)/SV40Tag transgenic mice (Liu et al., 1998). To further evaluate the functional significance of the Ki-ras proto-oncogene in mammary cancer development, in vivo studies were conducted to examine the effect of Ki-ras gene dosage on tumor progression. The lack of one normal Ki-ras allele C3(1)/SV40Tag transgenic mice resulted in significantly delayed mammary intraepithelial neoplasia (MIN) formation as well as in a decreased number of mammary gland carcinomas. However, despite the retardation of tumor development by reduced Ki-ras gene dosage, overall survival was only modestly affected. This appears to be due to several factors including significant mammary tumor growth associated with Ki-ras gene amplification and over-expression that occurs during the advanced stage of oncogenesis in mice carrying either one or two normal Ki-ras alleles. The retardation of tumor progression due to the haploid loss of Ki-ras did not appear to be related to accelerated apoptosis, or a reduced rate of cell proliferation at the tumor stages examined. These data strongly suggest that the gene dosage of Ki-ras affects tumor promotion at an early stage of mammary tumor progression in this SV40 Tag-induced model of mammary oncogenesis.

Animals↗

PubMed2001

Some factor VIII exon 14 frameshift mutations cause moderately severe haemophilia A.

Factor VIII's exon 14 codes for its B domain that includes nearly one-third of its amino acid sequence that is not necessary for function. Frameshift mutations appear to occur more frequently within exon 14 than in other exons. To assess exon 14 frameshift mutations and their clinical correlates, a series of unrelated, severe or moderately severe haemophilia A patients were screened for heteroduplex formation in amplified exon 14 fragments. In 25 families, a frameshift mutation was identified by sequencing. Occurrence of haemophilia was isolated in 18 of these families. Moderate severity was noted in at least six out of 13 families with an A insertion or deletion at one of two sequences where the frameshift resulted in a sequence of 8-10 As. Inhibitors occurred in five of the other 12 families including one with an A insertion within a sequence of six As. Recurrent insertions into an A(8) (codons 1439-1441) or an A(9) (codons 1191-1194) sequence or of an A deletion from the A(9) sequence are common, recurrent causes of haemophilia A that may have a moderately severe phenotype.

Adolescent↗

PubMed2001

Targeted disruption of the methionine synthase gene in mice.

Alterations in homocysteine, methionine, folate, and/or B12 homeostasis have been associated with neural tube defects, cardiovascular disease, and cancer. Methionine synthase, one of only two mammalian enzymes known to require vitamin B12 as a cofactor, lies at the intersection of these metabolic pathways. This enzyme catalyzes the transfer of a methyl group from 5-methyl-tetrahydrofolate to homocysteine, generating tetrahydrofolate and methionine. Human patients with methionine synthase deficiency exhibit homocysteinemia, homocysteinuria, and hypomethioninemia. They suffer from megaloblastic anemia with or without some degree of neural dysfunction and mental retardation. To better study the pathophysiology of methionine synthase deficiency, we utilized gene-targeting technology to inactivate the methionine synthase gene in mice. On average, heterozygous knockout mice from an outbred background have slightly elevated plasma homocysteine and methionine compared to wild-type mice but seem to be otherwise indistinguishable. Homozygous knockout embryos survive through implantation but die soon thereafter. Nutritional supplementation during pregnancy was unable to rescue embryos that were completely deficient in methionine synthase. Whether any human patients with methionine synthase deficiency have a complete absence of enzyme activity is unclear. These results demonstrate the importance of this enzyme for early development in mice and suggest either that methionine synthase-deficient patients have residual methionine synthase activity or that humans have a compensatory mechanism that is absent in mice.

5-Methyltetrahydrofolate-Homocysteine S-Methyltran↗

PubMed2001

Determination of 14 chemical constituents in the traditional Chinese medicinal preparation Huangqin-Tang by high performance liquid chromatography.

The high performance liquid chromatographic (HPLC) method for the identification and determination of baicalin (BG), wogonoside (WG), oroxylin-A-glucoside (OG), baicalein (B), wogonin (W), orxylin-A (O), paeoniflorin (PF), glycyrrhizic acid (GL), glycyrrhetinic acid (GA), liquiritin (LG), isoliquirition (ILG), liquiritigenin (L), isoliquiritigenin (IL) and ononin (ON) in Huangqin-Tang [Chinese characters: see text] was established. The samples were separated with a Wakosil C18 column (4.6 x 150 mm) by linear gradient elution using A (MeOH-HAC 100:1, v/v)-B (Water-HAC 100:1, v/v) (0 min, 30:70; 15 min, 40:60; 30 min, 60:40; 45 min, 80:20; 60 min, 100:0) as the mobile phase at a flow-rate of 1.0 ml/min. The detection was by diode-array UV/Vis detector (DAD), and the wavelength was set at the range of 200-400 nm. Satisfactory results were obtained within 60 min for the simultaneous determination of the 14 constituents. The repeatability (RSD) of the method was generally less than 2% (n=5, interday and intraday). The recovery of BG was 96.9+/-1.71, WG was 98.9+/-2.99, PF was 99.7+/-0.52, LG was 95.3+/-2.67, GL was 96.7+/-3.44, and GA was 94.8+/-4.16, respectively.

Chromatography, High Pressure Liquid↗

PubMed2001

Characteristic behavioral seizures and abnormal signal asymmetry of magnetic resonance imaging in an electrogenic rat model of chronic epilepsy.

Chronic tetani (60 Hz, 2 s, 0.4~0.6 mA) were administered to the dorsal hippocampus (DHPC) or the medial temporal lobe neocortex (MTNC) of rats, to study the role of the entorhinal cortex (EC)-hippocampal loop in temporal lobe epileptogenesis. This was repeated once a day for 7 or 10 days. Magnification of hyper-intensity was induced by tetanization of the HPC or the MTNC, as detected by contralateral T(2) weighed magnetic resonance imaging (T(2)-WI). The effects were associated with an enlarged volume of the lateral ventricle (LV), which was verified histologically. T(2)-WI hper-intensities, contralateral to the tetanized hemispheres, were observed with high frequency primary wet dog shakes (WEDS) in the DHPC-stimulated rats and with low frequency WEDS in the MTNC-stimulated rats. It seems likely that the same neural mechanisms are shared by chronic tetanization of the right HPC and the righ MTNC, involving the closed EC-HPC loop. Poor correlation between contralateral T(2)-WI hper-intensities and light primary behavioral seizures in the MTNC-stimulated rats might be attributed to a controlled information flow into or out of this loop because of potential EC gating. In addition, asymmetric T(2)-WI hyper-intensities in the LV area reflected a hemispheric dependence, contralateral to the electrogenic focus in our model of rat epilepsy.

Animals↗

PubMed2001

Possible role of dentate gyrus in greneration of rat temporal lobe epilepsy induced by electrical stimulation.

Possible role of the dentate gyrus (DG) and the hippocampus (HPC) in temporal lobe epileptogensis was investigated in an electrogenic model of rat epilepsy. Chronic tetani (60 Hz, 0.4-0.6 mA. 2 s) were administered once daily for 7 days to the right dorsal hippocampus (DHPC) or the right DG. Animal behavior was observed and depth electro-graphic seizures and T(2)-weighted magnetic resonance images (T(2)-WI) were measured. Results indicated that the frequency of primary wet dog shakes (WEDS) in the DG-stimulated rats was much lower than that in the DHPC-stimulated rats (P<0.05). The mean maximal wave-amplitude in DG electrographs was also much lower than that in HPC electrographs (P<0.05). The oscillations proportion of DHPC electrographs increased after DHPC-tetanization (from 2/9 up to 7/9 rats). T(2)-WI hyperintensity in the lateral ventricle area was detected only in the DHPC-tetanized rats, not in the DG-tetanized rats (P<0.05). These results suggest that the DG acts as a filtering site in the entorhinal cortex-HPC neuronal circuitry and its dysfunction causes damage to the HPC and the generation of temporal lobe epilepsy.

Animals↗

PubMed2000

Hemophilic factor VIII C1- and C2-domain missense mutations and their modeling to the 1.5-angstrom human C2-domain crystal structure.

Factor VIII C domains contain key binding sites for von Willebrand factor (vWF) and phospholipid membranes. Hemophilic patients were screened for factor VIII C-domain mutations to provide a well-characterized series. Mutated residues were localized to the high-resolution C2 structure and to a homology model of C1. Of 30 families found with mutations in the C domains, there were 14 missense changes, and 9 of these were novel. Of the missense mutations, 10 were associated with reduced vWF binding and 8 were at residues with surface-exposed side chains. Six of the 10 mutants had nearly equivalent factor VIII clotting activity and antigen level, suggesting that reduced vWF binding could cause hemophilia by reducing factor VIII stability in circulation. When the present series was combined with previously described mutations from an online international database, 11 C1 and C2 mutations in patients with mild or moderately severe hemophilia A were associated with antibody-inhibitor development in at least one affected individual. Of these substitutions, 6 occurred at surface-exposed residues. As further details of the C1 structure and its interface with C2 become available, and as binding studies are performed on the plasma of more patients with hemophilic C-domain mutations, prediction of surface binding sites should improve, allowing confirmation by site-specific mutagenesis of surface-exposed residues.

Amino Acid Sequence↗

PubMed2000

The C3(1)/SV40 T-antigen transgenic mouse model of mammary cancer: ductal epithelial cell targeting with multistage progression to carcinoma.

The 5' flanking region of the C3(1) component of the rat prostate steroid binding protein (PSBP) has been used to successfully target the expression of the SV40 large T-antigen (Tag) to the epithelium of both the mammary and prostate glands resulting in models of mammary and prostate cancers which histologically resemble the human diseases. Atypia of the mammary ductal epithelium develops at about 8 weeks of age, progressing to mammary intraepithelial neoplasia (resembling human ductal carcinoma in situ [DCIS]) at about 12 weeks of age with the development of invasive carcinomas at about 16 weeks of age in 100% of female mice. The carcinomas share features to what has been classified in human breast cancer as infiltrating ductal carcinomas. All FVB/N female mice carrying the transgene develop mammary cancer with about a 15% incidence of lung metastases. Approximately 10% of older male mice develop anaplastic mammary carcinomas. Unlike many other transgenic models in which hormones and pregnancy are used to induce a mammary phenotype, C3(1)/Tag mice develop mammary tumors in the mammary epithelium of virgin animals without hormone supplementation or pregnancy. Although mammary tumor development appears hormone-responsive at early stages, invasive carcinomas are hormone-independent, which corresponds to the loss of estrogen receptor-alpha expression during tumor progression. Molecular and biologic factors related to mammary tumor progression can be studied in this model since lesions evolve over a predictable time course. Genomic alterations have been identified during tumor progression, including an amplification of the distal portion of chromosome 6 containing ki-ras and loss of heterozygosity (LOH) in other chromosomal regions. We have demonstrated that stage specific alterations in the expression of genes which are critical regulators of the cell cycle and apoptosis are functionally important in vivo. C3(1)/Tag mice appear useful for testing particular therapies since growth of the mammary tumors can be reduced using chemopreventive agents, cytokines, and an anti-angiogenesis agent.

Androgen-Binding Protein↗

PubMed2000

[Studies on behavioral and electrographic seizures and structural abnormalities using magnetic resonance image in chronic epilepsy model in rats--hippocampal-entorhinal-tempral neocortex neural pathway].

AIM AND METHODS: Repeated tetanus (60 Hz, 0.4-0.6 mA, 2 s) were delivered into the right and the left dorsal hippocampus (HPC), or into the right and the left medial temporal neocortex (MTNC) respectively to establish chronic temporal lobe epilepsy model in rats. The possible role of the HPC-Entorhinal cortex (EC)-MTNC-Neocortex neural pathway in epileptogenesis was discussed based on observing the abnormalities in behavior and in EEG or depth electrographes and in T2-weighted magnetic resonance images (T2-MRI). RESULTS: 1. Occurrence of primary, secondary WEDS and kindling effects were higher in the right dorsal HPC experimental group than those in other three experimental groups (P < 0.005, P < 0.001). T2-MRI signal hyperintensity was remarkable in lateral ventricles close to the HPC (P < 0.05), but not in the EC or in the MTNC. 2. These T2-MRI intensity increases were related to behavioral abnormalities in some MTNC-stimulated rats. 3. Asymmetric behavioral abnormalities and T2-MRI changes were observed in the left and the right DHPC-stimulated groups. CONCLUSION: HPC may be an "origin" for epileptogenesis and EC may play a "gating" role in it.

Animals↗

PubMed1999

Haploid loss of bax leads to accelerated mammary tumor development in C3(1)/SV40-TAg transgenic mice: reduction in protective apoptotic response at the preneoplastic stage.

The dramatic increase in apoptosis observed during the development of preneoplastic mammary lesions is associated with a significant elevation in Bax expression in C3(1)/SV40 large T antigen (TAg) transgenic mice. The significance of Bax expression during tumor progression in vivo was studied by generating double-transgenic mice carrying the C3(1)/TAg transgene and mutant alleles for bax. C3(1)/TAg transgenic mice carrying mutant bax alleles exhibited accelerated rates of tumor growth, increased tumor numbers, larger tumor mass and decreased survival rates compared with mice carrying wild-type bax. Accelerated tumorigenesis associated with the bax+/- genotype did not require the loss of function of the second bax allele. Thus, haploid insufficiency of bax is enough to accelerate tumor progression, suggesting that the protective effect of Bax is dose-dependent. While levels of apoptosis in the preneoplastic lesions, but not carcinomas, were reduced in bax+/- or bax-/- mice compared with bax+/+ mice, rates of cellular proliferation in mammary lesions were similar among all bax genotypes. These data demonstrate that bax is a critical suppressor of mammary tumor progression at the stage of preneoplastic mammary lesion development through the upregulation of apoptosis, but that this protective effect is lost during the transition from preneoplasia to invasive carcinoma.

Animals↗

PubMed1999

A prospective study of elective stenting in unprotected left main coronary disease.

The standard treatment of left main coronary artery (LMCA) disease has been bypass surgery (CABG). Recent reports suggested that stenting of LMCA disease might be feasible. From January 1995 to April 1998, we carried out a prospective study of elective stenting of unprotected LMCA disease to evaluate its immediate and long-term results. Of 61 consecutive patients with unprotected LMCA disease, 6 were excluded. Acute procedural success was 100% for the remaining 55 patients, without any complications such as stent thrombosis, myocardial infarction, CABG, or death. During a mean follow-up of 16.1+/-9.6 months, 11 patients (20%) had symptomatic recurrence, between 2 to 6 months after their procedure. Seven patients underwent CABG, two had repeat intervention, one continued with medical therapy, and one died before planned angiography. There was no late sudden death. Forty-four patients (80%) remained asymptomatic. We conclude that elective stenting may be a safe alternative to CABG in unprotected LMCA disease.

Aged↗

PubMed1999

Intense physical training decreases circulating antioxidants and endothelium-dependent vasodilatation in vivo.

Physical training increases free radical production and consumes antioxidants. It has previously been shown that acute exercise markedly increases the susceptibility of LDL to oxidation but whether such changes are observed during physical training is unknown. We measured circulating antioxidants, lipids and lipoproteins, and blood flow responses to intrabrachial infusions of endothelium-dependent (acetylcholine, ACh, L-N-monomethyl-arginine, L-NMMA) and -independent (sodium nitroprusside, SNP) vasoactive agents, before and after 3 months of running in 9 fit male subjects. Maximal aerobic power increased from 53 +/- 1 to 58 +/- 2 ml/kg min (P < 0.02). All circulating antioxidants (uric acid, SH-groups, alpha-tocopherol, beta-carotene, retinol) except ascorbate decreased significantly during training. Endothelium-dependent vasodilatation in forearm vessels decreased by 32-35% (P < 0.05), as determined from blood flow responses to both a low (10.8 +/- 2.1 vs. 7.3 +/- 1.5 ml/dl min, 0 vs. 3 months) and a high (14.8 +/- 2.6 vs. 9.6 +/- 1.8) ACh dose. The % endothelium-dependent blood flow (% decrease in basal flow by L-NMMA), decreased through training from 37 +/- 3 to 22 +/- 7% (P < 0.05). Blood flow responses to SNP remained unchanged. The decrease in uric acid was significantly correlated with the change in the % decrease in blood flow by L-NMMA (r = 0.74, P < 0.05). The lag time for the susceptibility of plasma LDL to oxidation in vitro, LDL size and the concentration of LDL cholestetol remained unchanged. We conclude that relatively intense aerobic training decreases circulating antioxidant concentrations and impairs endothelial function in forearm vessels.

Acetylcholine↗

PubMed1999

NMR diffusion and relaxation study of drug-protein interaction.

In this work, NMR diffusion and relaxation measurements are applied to the study of the interaction between the anti-inflammatory drug salicylate and the human serum albumin (HSA) in solutions. The self-diffusion coefficients and the spin-lattice relaxation rates of salicylate are measured as a function of the concentration. The dissociation constant, Kd, for drug/HSA complexes and the number of binding sites, n, are evaluated.

Anti-Inflammatory Agents, Non-Steroidal↗