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P Liu

Publications and source records attributed to P Liu.

At least 37 records · Page 2Linked to original sources
PubMed2003

Long-term changes in hippocampal n-methyl-D-aspartate receptor subunits following unilateral vestibular damage in rat.

Previous studies have indicated that damage to the peripheral vestibular system results in dysfunction of hippocampal place cells and an impairment of spatial learning and memory. The aim of this study was to determine whether lesions of one vestibular labyrinth (unilateral vestibular deafferentation, UVD) result in changes in the expression of the NR1 and NR2A subunits of the N-methyl-D-aspartate (NMDA) receptor, and the GluR2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor, in subregions of the rat hippocampus (CA1, CA2/3 and the dentate gyrus) at 10 h or 2 weeks following UVD. Compared with sham surgery controls and anaesthetic controls, the expression of the NR1 subunit was significantly reduced in the ipsilateral CA2/3 region at 2 weeks post-UVD. The expression of the NR2A subunit was also significantly reduced in the ipsilateral CA2/3 and, to a smaller extent, in the contralateral CA2/3 region, at 2 weeks post-UVD. The only other change in NR2A expression was an increase in the ipsilateral CA1 at 10 h post-UVD. No other changes in NR1, NR2A or GluR2 expression were observed in any hippocampal subregion, at any time point, or in cortical tissue at any time point. These results suggest that UVD may result in long-term changes in NMDA receptor subunit expression in the rat hippocampus.

Animals↗
PubMed2003

Regional variations and age-related changes in nitric oxide synthase and arginase in the sub-regions of the hippocampus.

L-arginine can be metabolised by nitric oxide synthase (NOS) with the formation of L-citrulline and nitric oxide (NO), or arginase with the production of L-ornithine and urea. In contrast to studies showing a potential involvement of NOS/NO in the aging process, the role of arginase has not been well documented. The present study investigates for the first time the regional variations and age-related changes in both NOS and arginase in sub-regions of the hippocampus. In young adult rats, although the total NOS activity was not significantly different across the hippocampal CA1, CA2/3 and the dentate gyrus (DG) sub-regions, the total arginase activity showed a clear regional variation with the highest level in DG. Western blotting revealed that the highest levels of neuronal NOS (nNOS) and endothelial NOS (eNOS) proteins were located in CA1. Arginase I is expressed at a very low level in the brain (the whole hippocampus) as compared with the liver. By contrast, arginase II protein shows an extremely high expression in the brain with little or no expression in the liver. There was no regional variation in arginase I or arginase II protein expression across the sub-regions of the hippocampus. When a comparison was made between young (4-month-old) and aged (24-month-old) rats, a significant increase in total NOS activity was found in DG and significant decreases in arginase activity were observed in the CA1 and CA2/3 regions in the aged animals. Western blotting further revealed a dramatic decrease in eNOS protein expression in aged CA2/3 with no age-associated changes in nNOS, arginase I and II protein expression in any region examined. Interestingly, evidence of activity or protein expression of the inducible isoform of NOS (iNOS) was not detected in any tissue from either group. The present results, in conjunction with previous findings, support the contribution of NOS/NO to aging but question the involvement of iNOS in the normal aging process. Region-specific changes in arginase suggest that this enzyme may also contribute to aging.

Aging↗
PubMed2003

Glycaemic glucose equivalent: validation as a predictor of the relative glycaemic effect of foods.

BACKGROUND: Glycaemic glucose equivalent (GGE) content of a quantity of a food, based on glycaemic index, food composition and food quantity, is the theoretical weight of glucose that would induce a glycaemic response equivalent to that induced by the given amount of food. OBJECTIVES: To test whether GGE content predicts glycaemic response to foods differing in glycaemic index, carbohydrate content and intake, over a practical range of carbohydrate intakes. DESIGN: : Controlled randomised study. SETTING: Clinical trials unit at the Department of Human Nutrition, University of Otago, Dunedin, New Zealand. SUBJECTS: In all, 12 volunteers with and 12 without type II diabetes were recruited. All but one subject completed the trial. METHOD: Yams, biscuits, white rice and porridge were consumed at 10 and 20 GGE doses, and 2-minute noodles at 24 and 48 GGE, following an overnight fast. Incremental areas under the blood glucose response curves (IAUC) over 3 h were calculated for each individual for all foods, and individual glycaemic responsiveness was determined as IAUC/GGE. RESULTS: Within GGE dose, blood glucose responses to all foods, except rice, were similar. Doubling GGE dose approximately doubled glycaemic response. Relative glycaemic effects were accurately predicted by GGE intake after adjusting for individual glycaemic sensitivity (individual average IAUC/GGE). The accuracy of prediction of relative glycaemic effect from GGE intake was affected little by carbohydrate dose. CONCLUSION: GGE content predicted glycaemic impact of foods over a practical range of carbohydrate intakes, and may therefore be useful for accurate dietary management of glycaemia in diabetes mellitus. The predictive validity of GGE in mixed meals now needs to be tested. SPONSORSHIP: Health Research Council of New Zealand contract 00/453.

Blood Glucose↗
PubMed2003

Portopulmonary hypertension in decompensated cirrhosis with refractory ascites.

BACKGROUND: The prevalence of portopulmonary hypertension (PPHTN) in patients with cirrhosis and refractory ascites is unknown. Its presence may preclude patients from receiving a transjugular intrahepatic portosystemic shunt or liver transplantation as a definitive treatment for their end stage cirrhosis. PURPOSE: To determine the prevalence, possible aetiological factors, and predictive factors for the development of PPHTN in these patients. METHODS: Sixty two patients (53 males, nine females; mean age 54.5 (1.4) years) with biopsy proven cirrhosis and refractory ascites underwent angiographic measurements of pulmonary and splanchnic haemodynamics. Endothelin 1 levels were measured from the pulmonary artery. Forty nine patients underwent radionuclide angiography for measurements of central blood volume, pulmonary vascular, and cardiac chamber volumes. Forty seven patients also underwent two dimensional echocardiography for measurements of cardiac structural and functional parameters. Cardiac output, and systemic and pulmonary vascular resistance were calculated. RESULTS: Ten patients (16.1%) fulfilled the criteria for PPHTN (mean pulmonary artery pressure >/= 25 mm Hg and pulmonary vascular resistance >/= 120 dynxs/cm(5)), with significantly higher mean right atrial (15.4 (1.2) v 7.9 (0.5) mm Hg; p<0.001), and right ventricular pressures (24.7 (1.5) v 14.7 (0.6) mm Hg; p<0.001), and endothelin 1 levels (3.04 (0.40) v 1.98 (0.12) pg/ml; p=0.02). No significant differences in any of the other parameters measured were detected between the two groups. A right atrial pressure of >/= 14 mm Hg had a 83% positive predictive value for the presence of PPHTN. CONCLUSIONS: Portopulmonary hypertension is common in cirrhosis with refractory ascites, possibly due to excess endothelin 1 in the pulmonary circulation. An elevated right atrial pressure >/= 14 mm Hg predicts the presence of PPHTN, which may be helpful in deciding management options in these patients.

Ascites↗
PubMed2002

A new sensitive HPLC assay for methoxyamine and its analogs.

Methoxyamine (MOA) and its analogs are polymerization regulators, building blocks and intermediates for agrichemicals and pharmaceuticals. MOA induces mutagenesis of nucleic acids and has been considered for anti-cancer and anti-virus therapy. It has been studied as a DNA repair modifier in anti-cancer therapy. HPLC procedures available in the literature for MOA are all based on electrochemical detection, which is not commonly available. This paper describes the development and validation of a HPLC assay with UV detection for MOA and its analogs. The analytes are first reacted with o-phthalaldehyde to form an oxime derivative before chromatography with an ODS column. Detection is achieved by UV at 254 nm. The chromatography resolves MOA from its decomposition products and analogs. The assay is reproducible (R.S.D. < 0.8%), linear (r(2) = 0.9997), and accurate (error < 1%). The method is sensitive and has a lower detection limit of 5 pmol (0.4 ng of MOA.HCl), which is comparable to that of electrochemical detection.

Chromatography, High Pressure Liquid↗
PubMed2002

Directing the expression of a green fluorescent protein transgene in differentiated osteoblasts: comparison between rat type I collagen and rat osteocalcin promoters.

The osteocalcin (OC) and a 2.3 kb fragment of the collagen promoter (Col2.3) have been used to restrict transgenic expression of a variety of proteins to bone. Transgenic mice carrying a green fluorescent protein (GFP) gene driven by each promoter were generated. Strong GFP expression was detected in OC-GFP mice in a few osteoblastic cells lining the endosteal bone surface and in scattered osteocytes within the bone matrix in long bones from 1-day-old to 6-month-old transgenic animals. Similar findings were noted in the forming tooth in which only individual odontoblasts expressed GFP without detectable expression from the dental pulp. This limited pattern of OC-GFP-positive cells contrasts with the uniform expression in the Col2.3GFP mice in which large proportion of osteoblasts, odontoblasts, and osteocytes strongly expressed the transgene. To assess transgene expression during in vitro differentiation, marrow stromal cell and neonatal calvarial osteoblast cultures were analyzed. The activity of both transgenes was restricted to mineralized nodules but the number of positive cells was lower in the OC-GFP-derived cultures. The different temporal and spatial pattern of each transgene in vivo and in vitro reveals potential advantages and disadvantages of these two transgene models.

Animals↗
PubMed2001

Use of VSV-G pseudotyped retroviral vectors to target murine osteoprogenitor cells.

Marrow stromal cells (MSC) and neonatal calvarial cells have the potential to differentiate and express markers of mature osteoblasts. Furthermore, MSCs can generate multiple differentiated connective tissue phenotypes. These properties and their ability to be expanded ex vivo make them good models for ex vivo gene therapy. In this study we examined the ability of vesicular stomatitis virus (VSV-G) pseudotyped retroviral vectors to transduce osteoprogenitor cells derived from bone marrow and from neonatal calvaria. Retrovectors encoding either beta-galactosidase or green fluorescent protein (eGFP) were used for transduction of primary murine marrow stromal and primary neonatal calvarial cell cultures. High infection efficiency was demonstrated by fluorescence-activated cell analysis when GFP was used as a marker or by estimating the number of beta-galactosidase-positive cells. Expression of markers of differentiated bone cells, including Col1a1, bone sialoprotein, and osteocalcin mRNA and alkaline phosphatase activity was not impaired by retroviral transduction. Our data suggest that VSV-G pseudotypes retroviral vectors are suitable for introducing genes into osteoprogenitor cells without affecting osteoprogenitor lineage progression.

Alkaline Phosphatase↗
PubMed2001

High-performance liquid chromatographic analysis for a non-chromophore-containing phosphatidyl inositol analog, 1-((1-O-octadecyl-2-O-methyl-sn-glycero)phospho)-1D-3-deoxy-myo-inositol, using indirect UV detection.

Phosphatidylinositide-3-kinase (PI3 kinase) is an important constituent of growth factor regulation. It is also involved in oncogene signaling pathways. An ether-containing phosphatidyl inositol(PI) analog, OMDPI, 1-[(1-O-octadecyl-2-O-methyl-sn-glycero)-phospho]-1D-3-deoxy-myo-inositol, is a potent inhibitor of this pathway and may be clinically useful in the treatment of a variety of neoplasms. OMDPI is currently being investigated as an anti-tumor agent by the National Cancer Institute, NIH. OMDPI, a non-chromophore-containing PI analog, is not directly adaptable to the commonly used UV detection of HPLC. This paper reports the development and validation of an HPLC assay for OMDPI based on indirect UV detection, in which a UV-absorbing ion-pair reagent (the probe), protriptyline, is added to the mobile phase to induce a signal for the compound. The method is sensitive (limit of detection <5 microl of 1 microg/ml or 5 ng), precise (R.S.D.<2.5%), linear (r2=0.9995) and accurate (error<0.7%). It is superior to refractive index detection and evaporative light scattering detection in either sensitivity or linearity and does not require special equipment.

Chromatography, High Pressure Liquid↗
PubMed2001

Similarity of ventricular function in patients alive 5 years after randomization to surgery or angioplasty in the BARI trial.

BACKGROUND: Left ventricular ejection fraction (LVEF) is a recognized determinant of survival in patients with coronary artery disease. In major trials comparing surgical and percutaneous revascularization approaches, the long-term effect of the coronary revascularization strategy on LVEF has not been reported. METHODS AND RESULTS: In the NHLBI-sponsored Bypass and Angioplasty Revascularization Investigation (BARI) randomized trial comparing angioplasty and bypass surgery as initial treatment strategies, 1220 (75%) of the 1617 surviving randomized patients had their EF measured by radionuclide ventriculography 5 years after study entry. For the total study group, the 5-year EF in the CABG group (n=623) was 55.8+/-12.3, compared with 55.7+/-12.7 in PTCA group (n=597, P:=0.82). There was no significant difference in measured EF between the CABG group and the PTCA group within multiple subgroups determined by the presence or absence of diabetes, 3-vessel disease, complete revascularization, or prior myocardial infarction. In a multiple linear regression model developed to predict 5-year EF, treatment assignment to PTCA or CABG was not significant (P:=0.95). If an EF of 0 was imputed for patients who were dead and missing EF data, however, there was a higher EF in the CABG group (P:=0.0018) among diabetic patients only. CONCLUSIONS: In the BARI randomized trial, initial treatment assignment to angioplasty was not associated with any difference in long-term ventricular function compared with initial treatment assignment to surgery. These results apply, however, only to patients who were alive at 5 years.

Angioplasty↗
PubMed2001

Aerobic capacity in adults with various congenital heart diseases.

As an increasing number of patients with congenital heart disease reach adulthood, more information is needed regarding outcomes. The first signs of impaired heart function may appear during exercise testing. The aim of the present study was to establish mean values for maximal oxygen uptake in adults with various congenital heart diseases. Patients from 6 major diagnostic groups were identified, including patients with atrial septal defect (ASD, n = 93), transposition of the great arteries corrected with the Mustard procedure (n = 84), congenitally corrected transposition of the great arteries (CCTGA, n = 41), Tetralogy of Fallot (n = 168), Ebstein's anomaly (n = 37), and Modified Fontan procedure (n = 52). Diminished maximal oxygen uptake was found in all diagnostic groups across age compared with healthy subjects. A significant decrease in maximal oxygen uptake with aging was found in those with ASD (p <0.0001), CCTGA (p = 0.01), and Tetralogy of Fallot (p <0.0001). There was no significant decline, however, in Ebstein's anomaly (p = 0.270), Fontan procedure (p = 0.182), and in the Mustard patients (p = 0.188). All patients achieved significantly lower heart rates than predicted (mean for all groups, p <0.0001). Forced vital capacity values (3.51 L, mean SD +/- 1.02) were lower than predicted values (4.10 L, mean SD +/- 0.90, p <0.0001) for all patients groups except those with ASD. Mean values, however, were within the accepted 20% range of variance. This study showed diminished aerobic capacity in all diagnostic groups when compared with a healthy population. The maximal oxygen uptake values across age groups can be used as reference values in patients with similar diagnoses and as the basis for further research.

Adolescent↗
PubMed2001

CD45 is a JAK phosphatase and negatively regulates cytokine receptor signalling.

The regulation of tyrosine phosphorylation and associated signalling through antigen, growth-factor and cytokine receptors is mediated by the reciprocal activities of protein tyrosine kinases and protein tyrosine phosphatases (PTPases). The transmembrane PTPase CD45 is a key regulator of antigen receptor signalling in T and B cells. Src-family kinases have been identified as primary molecular targets for CD45 (ref. 4). However, CD45 is highly expressed in all haematopoietic lineages at all stages of development, indicating that CD45 could regulate other cell types and might act on additional substrates. Here we show that CD45 suppresses JAK (Janus kinase) kinases and negatively regulates cytokine receptor signalling. Targeted disruption of the cd45 gene leads to enhanced cytokine and interferon-receptor-mediated activation of JAKs and STAT (signal transducer and activators of transcription) proteins. In vitro, CD45 directly dephosphorylates and binds to JAKs. Functionally, CD45 negatively regulates interleukin-3-mediated cellular proliferation, erythropoietin-dependent haematopoieisis and antiviral responses in vitro and in vivo. Our data identify an unexpected and novel function for CD45 as a haematopoietic JAK phosphatase that negatively regulates cytokine receptor signalling.

Animals↗
PubMed2001

High beta-galactosidase and ganglioside GM1 levels in the human parotid gland.

BACKGROUND: Ganglioside G(M1) is a membrane glycolipid typical of nerve cell membranes, where it partakes in neurotransmitter release and is catabolized by the lysosomal beta-galactosidase (GM1ase) (EC 3.2.1.23). After demonstrating a novel degenerative disease of the parotid gland in mice deficient in GM1ase, mimicking the human storage disease GM(1) gangliosidosis, we studied GM1ase and ganglioside G(M1) content in the human parotid glands. STUDY DESIGN: Levels of GM1ase and ganglioside G(M1) were determined in samples of parotid tissues and neighboring muscle (as a negative control) for 3 subjects. Tissues were also processed for histochemical demonstration of GM1ase. RESULTS: The mean specific activity of GM1ase was more than 6-fold higher in the healthy human parotid tissues (1.4 +/- 0.5 nmol of 4-methylumbelliferone per minute per milligram of protein) relative to the neighboring muscle tissue (0.23 +/- 0.07 nmol of 4-methylumbelliferone per minute per milligram of protein). Activity of GM1ase was histochemically localized mainly to striated duct and acinar cells of the parotid gland. Ganglioside G(M1) content in the parotid gland was on average 30-fold higher relative to muscle. CONCLUSIONS: Our results are consistent with previous findings reported in the mouse and the rabbit, and probably reflect a general property of the mammalian parotid glands. The novel mechanism we previously proposed for the mouse parotid saliva secretion, mimicking neurotransmitter release in ganglioside G(M1)-containing nerve cells, is probably applicable also to the human parotid gland. Similarly, the human parotid gland is probably also severely affected in GM(1) gangliosidosis.

Adult↗
PubMed2001

Pharmacokinetic and local tissue disposition of [14C]sodium diclofenac following iontophoresis and systemic administration in rabbits.

The systemic pharmacokinetics and local drug distribution of sodium diclofenac in skin and underlying tissues was studied. Iontophoresis facilitated local and systemic delivery of diclofenac sodium compared with passive diffusion. The maximum plasma concentration of sodium diclofenac was achieved within 1 h of iontophoresis, and the delivery was proportional to applied current density (371 +/- 141 and 132 +/- 62 microg/L at 0.5 and 0.2 mA/cm(2), respectively). The in vivo delivery efficiency for diclofenac in rabbit was 0.15 mg/mA.h. The concentrations of sodium diclofenac in the skin, subcutaneous tissue, and muscle beneath the drug application site (cathode) were significantly greater than plasma concentrations and concentrations of drug in similar tissues at the untreated sites. The results thus suggest that the cutaneous microvasculature is not always a perfect "sink" and that transdermal iontophoresis facilitated the direct penetration of diclofenac sodium to deeper tissues. No skin irritation was observed up to 0.5 mA/cm(2) current density and 7 mg/mL sodium diclofenac concentration.

Animals↗
PubMed2001

A randomized, controlled, single-blind trial of leflunomide in the treatment of rheumatoid arthritis.

The efficacy and safety of leflunomide (LEF) in the treatment of rheumatoid arthritis (RA) were evaluated and the comparison with methotrexate's (MTX's) was performed in a 12-week, single-blind, randomized, parallel trial for treating 81 patients with RA. There were 56 cases in LEF group and 25 cases in MTX group. The dose of LEF was 20 mg per day and MTX 15 mg per week. All patients took oxaproxin simultaneously at the 4th to 6th week after the trail. The results showed that the general effective rate and notable effective rate were 94.64% and 73.21% in LEF group, 72% and 44% in MTX group, respectively, with the differences being statistically significant between the two groups (P < 0.05). LEF and oxaprozin could obviously improve the symptoms, signs and joint functions. The incidence of side reactions was lower in LEF group (17.86%) than in MTX group (40.00%, P < 0.05). LEF had a good therapeutic effect for RA, especially for refractory RA and had slight side reactions, and could be regarded as a superior immunosuppressive agent used in the treatment of RA and other connective tissue diseases.

Adolescent↗
PubMed2001

Stability-indicating HPLC assay and solution stability of a new diaziridinyl benzoquinone.

RH1, 3-methyl-6-hydroxymethyl-2,5-diaziridinyl-1,4-benzoquinone, is a NQO1 (NAD(P)H quinone oxidoreductase) directed anti-tumor agent. It is designed as a water soluble analog of MeDZQ (3,6-dimethyl-2,5-diaziridinyl-1,4-benzoquinone) and is a drug candidate for clinical evaluation. A HPLC assay has been developed for its analysis. The assay is sensitive (ldl<0.2 ng), precise (rsd<1%), linear (r(2)=0.9997), accurate (error<0.6%), and stability-indicating. Using the developed assay, aqueous stability of RH1 has been evaluated. Both aziridine rings in MeDZQ are known to be easily hydrolyzable in aqueous solutions, however, hydrolysis of the second aziridine ring in RH1 appears inhibited.

Aziridines↗