Biomedical subjects

P Liu

Publications and source records attributed to P Liu.

At least 55 records · Page 3Linked to original sources

PubMed2001

Human bone marrow stromal cells are efficiently transduced by vesicular stomatitis virus-pseudotyped retrovectors without affecting subsequent osteoblastic differentiation.

This study tested the transduction efficiency of human bone marrow stromal cells (hBMSCs) with vesicular stomatitis virus (VSV)-pseudotyped retrovectors and their subsequent osteogenic differentiation in vitro. Two different retrovectors encoding beta-galactosidase (beta-gal) or enhanced green fluorescent protein (eGFP) as marker genes were examined for transduction of hBMSCs. hBMSCs were obtained from bone marrow filtrates of normal donors (aged 5-35 years), cultured in alpha-minimal essential medium (alpha-MEM) containing 10% fetal calf serum and infected with retrovectors soon after the adherent cells started to form individual colonies. Transduced hBMSCs were observed to express eGFP protein 4-7 days after infection in primary cultures, and the majority of hBMSCs were eGFP-positive. hBMSCs were also stained for beta-gal in the secondary cultures and virtually all hBMSCs expressed beta-gal activity. Transduced hBMSCs were examined for their osteogenic potential. These cells were found to express markers of osteogenic differentiation, including alkaline phosphatase, type I collagen, bone sialoprotein, decorin, and osteocalcin, as strongly as uninfected control cells. Mineralization was also induced by dexamethasone in transduced cells as well as control cells. These results demonstrate that hBMSCs are highly susceptible to infection with VSV-pseudotyped retrovectors with the majority of cultured cells expressing the viral transgenes without antibiotic selection. Transduced cells retain their osteogenic potential in vitro. hBMSCs are a promising cellular vehicle for systemic human gene therapy and VSV-pseudotyped retrovectors should be effective for their in vitro transduction prior to cellular engraftment.

Adolescent↗

PubMed2001

Cardiopulmonary exercise performance in adult survivors of the Mustard procedure.

Most patients with the Mustard procedure are now adults. To date, however, there have been few reports on resting and exercise hemodynamics in a large population of adults with this circulation. The aim of this study is to describe such parameters in one of the largest and oldest populations of adults with the Mustard procedure. The database of the University of Toronto Congenital Cardiac Centre for Adults was examined to identify 84 adults with the Mustard procedure who have undergone cardiopulmonary exercise tests. Magnetic resonance imaging and echocardiography studies were obtained in order to assess right ventricular size, function and baseline hemodynamics. Patients achieved lower maximum uptake of oxygen, maximal heart rate, forced vital capacity, forced expiratory volume in 1 second, and oxygen saturations at maximal exercise compared to a healthy population. Magnetic resonance imaging showed significantly different right ventricular ejection fractions between patients and controls. There were no effects of operative variables or preoperative hemodynamics on current exercise capacity. Patients after the Mustard procedure have subnormal exercise capacities. Factors such as chronotropic incompetence, peripheral deconditioning, and impaired lung function may be responsible for these results.

Adolescent↗

PubMed2001

Effects of salviainolic acid A (SA-A) on liver injury: SA-A action on hepatic peroxidation.

BACKGROUND/AIMS: This study aimed to investigate the actions of salviainolic acid A (SA-A), an antiperoxidative component of Salvia miltiorrhiza (Sm), on rat liver injury and fibrosis. METHODS: Acute and chronic rat liver injury models were established using carbon tetrachloride (CCl4). After 48 h (acute) or during 6 weeks of CCl4 injection, rats were further divided and treated with biphenyl dimethyl-dicarboxylate (BDD) or colchicine, as a control antifibrotic treatment, with Sm, a herbal compound, or SA-A, a water-soluble extract of Sm. Liver function was investigated by assessing alanine transaminase (ALT) and aspartate transaminase (AST) activities, histological analysis, hydroxyproline (Hyp) and malondiadehyde (MDA) content. In vitro, isolated cultured hepatocytes were injured with CCl4 gas for 24 h, followed by treatment with either vitamin E or various concentrations of SA-A. The extent of hepatocyte injury was monitored by analyzing various lipid peroxidative parameters such as superoxide dismutase (SOD), glutathione (GSH), catalase (CAT), lactase dehydrogenase (LDH), and glutathione peroxidase (GSH-PX) levels in hepatocyte supernatants. RESULTS: SA-A significantly decreased abnormal serum ALT activity both in acutely and chronically injured rat livers, decreased abnormal serum AST activity, Hyp and MDA content and attenuated hepatic collagen deposition. After CCl4 incubation and injury, the activities of AST, ALT CAT, GSH-PX and LDH and MDA content in hepatocyte supernatants increased significantly, but GSH levels decreased significantly. SA-A markedly improved these pathological changes in a dose-dependent manner. 10(-4) mol/l SA-A had stronger inhibitory action than vitamin E. CONCLUSIONS: Our studies suggest that SA-A has antiperoxidative effects on injured hepatocytes in liver injury and fibrosis induced by CCl4.

Alanine Transaminase↗

PubMed2001

Excitotoxic lesions of the pre- and parasubiculum disrupt object recognition and spatial memory processes.

Rats with bilateral ibotenic acid lesions centered on the pre- and parasubiculum and control rats were tested in a series of spatial memory and object recognition memory tasks. Lesioned rats were severely impaired relative to controls in both the reference and working memory versions of the water maze task and displayed a delay-dependent deficit in a delayed nonmatch to place procedure conducted in the T-maze. Lesioned rats also displayed reduced exploration in a novel environment, and performance was altered in an object recognition procedure as compared with the control group. These findings indicate that the pre- and parasubiculum plays an important role in the processing of both object recognition and spatial memory.

Animals↗

PubMed2001

The effect of excitotoxic lesions centered on the hippocampus or perirhinal cortex in object recognition and spatial memory tasks.

Rats with bilateral ibotenic acid lesions centered on the hippocampus (HPC) or perirhinal cortex (PRC) and sham-operated controls were tested in a series of object recognition and spatial memory tasks. Both HPC and PRC rats displayed reduced habituation in a novel environment and were impaired in an object-location task. HPC rats were severely impaired in both the reference and working-memory versions of the water maze and radial arm maze tasks. In contrast, although PRC rats displayed mild deficits in the reference memory version of the water maze and radial arm maze tasks, they were markedly impaired in the working-memory version of both the tasks. These findings demonstrate that under certain conditions both the HPC and PRC play a role in the processing of spatial memory. Further investigation of these conditions will provide important new insights into the role of these structures in memory processes.

Animals↗

PubMed2001

DSPP mutation in dentinogenesis imperfecta Shields type II.

We identified a nonsense mutation (Gln45stop) in exon 3 of the dentin sialophosphoprotein (DSPP) gene in a Chinese family with dentinogenesis imperfecta Shields type II (DGI-II), in which the affected members showed discoloration and severe attrition of their teeth, with obliterated pulp chambers.

Asian People↗

PubMed2001

An integrated electrochemical capillary liquid chromatography-dual microelectrode system for bromine based reaction detection.

Amperometric reaction detection of model peptides containing either a thiol or disulfide was successfully achieved with a novel coupled capillary liquid chromatography-dual microelectrode system. Detection is facilitated via dual platinum wire electrodes fabricated directly on a liquid chromatography capillary column. The detection strategy is based on the electrogeneration of bromine at the upstream working electrode followed by reduction of the bromine to bromide at the downstream working electrode. When bromine reacts with analyte eluting from the capillary column, the amount of bromine that reaches the downstream electrode decreases. As a result, the current at the downstream electrode will decrease in proportion to the amount of analyte eluting from the capillary column. Glutathione, glutathione disulfide, alpha-TGF and oxytocin were used to characterize the system and to determine system parameters. The feasibility of the determination of disulfide containing peptides is demonstrated with glutathione disulfide, alpha-TGF and oxytocin.

Bromine↗

PubMed2001

Role of placental tissues in the intrauterine transmission of hepatitis B virus.

OBJECTIVE: The purpose of this study was to determine the mechanism of intrauterine transmission of hepatitis B virus. STUDY DESIGN: Placental tissues from 158 pregnant women who tested positive for hepatitis B surface antigen were examined for hepatitis B virus markers, Fc gamma receptors, and hepatitis B surface antigen-anti-hepatitis B surface antigen in different layers of cells. RESULTS: It was shown that the hepatitis B virus infection rate among different layers of placental cells gradually decreased from the maternal side to the fetal side. Furthermore, the closer the infected cell layer was to the fetal side, the higher the risk of intrauterine hepatitis B virus infection. Fc gamma receptors were found on cells of both hepatitis B surface antigen positive and negative placentas; Fc gamma receptors III were found on trophoblastic cells and villous mesenchymal cells, and Fc gamma receptors II were found on only villous mesenchymal cells. Hepatitis B surface antigen-antibodies to hepatitis B surface antigen was detected in the cytoplasm and on the membrane of trophoblastic cells and villous mesenchymal cells in 2 hepatitis B surface antigen-positive placentas. CONCLUSION: The results support the hypothesis that intrauterine hepatitis B virus transmission could be caused through "cellular transfer" in the placenta. One of the means of cellular transfer could be through Fc gamma receptor III-mediated entry of hepatitis B surface antigen-antibodies to hepatitis B surface antigen into cells.

Adolescent↗

PubMed2001

Prefrontal cortex lesions augment the location-related firing properties of area TE/perirhinal cortex neurons in a working memory task.

It has previously been proposed that prefrontal cortex may have some role in keeping temporal cortex-based representations "on-line" during a working memory task. To test this hypothesis, the effects of electrolytic prefrontal cortex lesions on the firing of area TE and perirhinal cortex (PRC) neurons were examined while rats performed a delayed non-match to position task in the T-maze. The behavioural performance of control (n = 4) and lesioned (n = 4) animals were similar during this task, and many neurons displayed a statistically significant location-related variation in firing rate during the sample (44/56 neurons) and test (39/56 neurons) phases. Units from prefrontal-lesioned animals (82%) were more likely to display a significant variation in firing across the maze compared to controls (50%; P < 0.01), and to have more discrete location-related properties (50% of neurons) compared to the control (5%) group (P < 0.0005). This finding suggests that prefrontal cortex normally modulates the transmission and/or processing of spatial information in area TE/PRC during a working memory task. Modulation could be mediated through direct connections between the structures or via prefrontal control of subcortical structures. This finding has implications for our understanding of prefrontal-temporal involvement in memory and cognitive disorders.

Action Potentials↗

PubMed2001

Inhibition of nitric oxide synthesis by L-name exacerbates acute lung injury induced by hepatic ischemia-reperfusion.

Hepatic Kupffer cells and pulmonary alveolar macrophages together constitute a macrophage-axis involved in the regulation of regional and systemic inflammatory responses. Systemic inflammatory response syndrome induced by overproduced pro-inflammatory mediators is the major cause of adult respiratory distress syndrome. In the present study, we examined the anti-inflammatory role of nitric oxide (NO) in a rat model of acute lung injury induced by hepatic ischemia-reperfusion (HI/R). The left and median lobes of the liver were subjected to 30 min of ischemia by clamping the relevant branches of hepatic artery and portal vein, followed by a 4-h reperfusion achieved by removal of the vascular clamp. Four groups of animals were studied: sham control + saline; sham control + N(omega)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg, i.v., 10 min before reperfusion); HI/R + saline; HI/R + L-NAME. Results show that (1) administration of L-NAME to rats subjected to HI/R decreased plasma NO levels; however, the attenuation of NO increased plasma alanine aminotransferase (ALT) activity and superoxide generation in the ischemic lobes of liver, compared to HI/R alone. (2) Inhibition of NO synthesis with L-NAME in rats subjected to HI/R also enhanced systemic inflammatory response as assessed by the increase in the number of circulating leukocytes and levels of plasma tumor necrosis factor-alpha (TNFalpha) and interleukin 1-beta (IL-1beta). (3) The overwhelming systemic inflammatory response induced by administration of L-NAME in rats subjected to HI/R also augmented pulmonary vascular permeability and superoxide generation in the lung tissue. (4) Pulmonary alveolar macrophages isolated from rats subjected to HI/R + L-NAME produced higher levels of TNFalpha and IL-1beta in the supernatant of culture medium than that of rats subjected to HI/R alone. (5) There were no differences between the groups of sham + saline and sham + L-NAME in terms of plasma NO levels and ALT activity, circulating leukocytes, superoxide generation in the liver and lung, lavage protein levels, and TNFalpha and IL-1beta levels in plasma and bronchoalveolar lavage fluid. Our results suggest that inhibition of NO synthesis by L-NAME in rats subjected to HI/R not only augments ischemic liver injury, but also enhances the systemic inflammatory response and exacerbates remote lung injury. The increase in TNFalpha and IL-1beta production by alveolar macrophages may, in part, account for L-NAME-induced enhancement of acute lung injury.

Alanine Transaminase↗

PubMed2001

Reduction of target gene expression by a modified U1 snRNA.

Although the primary function of U1 snRNA is to define the 5' donor site of an intron, it can also block the accumulation of a specific RNA transcript when it binds to a donor sequence within its terminal exon. This work was initiated to investigate if this property of U1 snRNA could be exploited as an effective method for inactivating any target gene. The initial 10-bp segment of U1 snRNA, which is complementary to the 5' donor sequence, was modified to recognize various target mRNAs (chloramphenicol acetyltransferase [CAT], beta-galactosidase, or green fluorescent protein [GFP]). Transient cotransfection of reporter genes and appropriate U1 antitarget vectors resulted in >90% reduction of transgene expression. Numerous sites within the CAT transcript were suitable for targeting. The inhibitory effect of the U1 antitarget vector is directly related to the hybrid formed between the U1 vector and target transcripts and is dependent on an intact 70,000-molecular-weight binding domain within the U1 gene. The effect is long lasting when the target (CAT or GFP) and U1 antitarget construct are inserted into fibroblasts by stable transfection. Clonal cell lines derived from stable transfection with a pOB4GFP target construct and subsequently stably transfected with the U1 anti-GFP construct were selected. The degree to which GFP fluorescence was inhibited by U1 anti-GFP in the various clonal cell lines was assessed by fluorescence-activated cell sorter analysis. RNA analysis demonstrated reduction of the GFP mRNA in the nuclear and cytoplasmic compartment and proper 3' cleavage of the GFP residual transcript. An RNase protection strategy demonstrated that the transfected U1 antitarget RNA level varied between 1 to 8% of the endogenous U1 snRNA level. U1 antitarget vectors were demonstrated to have potential as effective inhibitors of gene expression in intact cells.

3T3 Cells↗

PubMed2001

The cardiac response to exercise in cirrhosis.

BACKGROUND: Impaired exercise capacity and oxygen consumption are common in cirrhosis. AIM: To explore the relationship between possible myocardial dysfunction and exercise tolerance in cirrhosis. METHODS: Cardiac responses to exercise, using radionuclide angiography and graded upright cycle ergometry with oxygen consumption, were assessed before and after exercise in 39 cirrhotics patients and compared with 12 age and sex matched healthy volunteers. Baseline cardiac chamber dimensions and wall thickness, ejection fraction, and diastolic function were measured using two dimensional echocardiography is all subjects. RESULTS: Baseline diastolic dysfunction with prolonged isovolumic relaxation times (p=0.02), left atrial enlargement, and left ventricular wall thickening were present in all cirrhotics (p=0.02), despite increased mean ejection fraction. With graded exercise, cirrhotics achieved 71 (4)% (p=0.03) (pre-ascitics) and 46 (3)% (p<0.001) (ascitics) of predicted work loads, respectively, without significant increases in ejection fraction. The smaller absolute and percentage increases in cardiac output (p=0.003) in the cirrhotics were associated with significantly reduced oxygen consumption (p=0.003) and anaerobic threshold (p<0.001), and correlated significantly with work and metabolic parameters. CONCLUSIONS: Impaired exercise capacity in cirrhosis is associated with myocardial thickening and ventricular stiffness leading to decreased diastolic function, inotropic and chronotropic incompetence under conditions of stress, with metabolic consequences. This picture is compatible with the condition now known as cirrhotic cardiomyopathy.

Analysis of Variance↗

PubMed2001

Sodium homeostasis with chronic sodium loading in preascitic cirrhosis.

BACKGROUND: Preascitic cirrhotic patients receiving 200 mmol of sodium daily for seven days remain in positive sodium balance. Thereafter, sodium handling is unknown. AIM: To assess renal sodium handling in preascitic cirrhosis on a high sodium diet for five weeks. METHODS: Sixteen biopsy proven preascitic cirrhotics were assessed at weekly intervals for five weeks on a diet of 200 mmol sodium/day using a daily weight diary and weekly 24 hour urinary sodium estimations. Fasting supine neurohormone levels were measured at baseline and weekly for five weeks while haemodynamics were measured at baseline and at five weeks. RESULTS: The daily diet of 200 mmol of sodium resulted in weight gain and a positive sodium balance for three weeks, associated with significant suppression of plasma renin activity and aldosterone levels, and a significant rise in plasma atrial natriuretic peptide levels (p<0.05). Patients' weights plateaued during week 4, associated with complete sodium balance and significant suppression of plasma noradrenaline levels (p<0.05). This was followed by a negative sodium balance and weight loss, and finally complete sodium balance, again despite a mean net gain of 2.3 (0.3) kg, associated with a return of plasma renin activity and aldosterone levels to within normal ranges. The lack of increase in central blood volume in addition to the persistent increase in plasma atrial natriuretic peptide levels indicated that residual volume expansion, consequent to persistent weight gain, was distributed on the venous side of the circulation. No free fluid was seen on repeat abdominal ultrasound after five weeks. CONCLUSION: Preascitic cirrhotics have a natriuretic "escape" after three weeks on high sodium dietary intake, associated with elevated plasma atrial natriuretic peptide levels and suppression of the renin-angiotensin-aldosterone system. With continued suppressed sympathetic activity, preascitics re-establish complete sodium balance but with a net weight gain and presumed increased intravascular volume, but without ascites. This further elucidates the compensated sodium retaining abnormality that characterises preascitic cirrhosis.

Aldosterone↗

PubMed2001

Lung function and aerobic capacity in adult patients following modified Fontan procedure.

OBJECTIVE: To examine cardiopulmonary performance in 52 adult patients with a Fontan circulation. DESIGN: Retrospective cohort study. Values of maximum oxygen uptake (VO(2)max), maximum heart rate (HRmax), forced vital capacity (FVC), and forced expiratory volume in one second (FEV(1)) were compared with predictive values for different age groups. Patients were further subdivided into those with a pulmonary artery connection (RA-PA) or right atrium to right ventricle conduit (RA-RV). RESULTS: At late follow up (median 10 years, range 1 to 26 years), patients with Fontan circulation had greatly diminished VO(2)max, HRmax, FVC, and FEV(1) compared with predicted values. Early age at surgery had a positive impact on aerobic capacity. The FEV(1):FVC ratio indicated restrictive lung function. No differences were found with respect to any variable between patients with RA-PA connections and those with RA-RV connections. CONCLUSIONS: Patients with a Fontan circulation have greatly diminished values of aerobic capacity and a restrictive pattern of lung function. Patients with an early surgical procedure obtained higher values of VO(2)max. The theoretical benefits of including the right ventricle in a Fontan circulation were not apparent.

Adult↗

PubMed2001

Pharmacokinetics, safety, and tolerability of BAY 12-9566 and nonsteroidal anti-inflammatory agents (naproxen, ibuprofen) during coadministration in patients with osteoarthritis.

The pharmacokinetic interactions between BAY 12-9566 and two nonsteroidal anti-inflammatory drugs (NSAIDs), naproxen and ibuprofen, were investigated in osteoarthritis (OA) patients. The study comprised six groups: two NSAID groups with three levels of treatment (BAY 12-9566 400 mg, BAY 12-9566 100 mg, and placebo). Plasma pharmacokinetic parameters (AUC(0-tau), Cmax, and tmax) were determined for each treatment group following 5 days of NSAID administration, 14 days of BAY 12-9566 administration, and 14 days of concurrent NSAID and BAY 12-9566 administration. For most conditions, the total plasma drug concentrations of both NSAID and BAY 12-9566 were diminished by coadministration; total plasma BAY 12-9566 was not affected by ibuprofen treatment. Importantly, the free drug concentrations were largely unaffected by coadministration. Most side effects were mild or moderate in intensity, and all events, with the exception of headache, were reported in both NSAID groups and in both placebo and BAY 12-9566 groups.

Adult↗

PubMed2001

Cell-specific targeting of caveolin-1 to caveolae, secretory vesicles, cytoplasm or mitochondria.

In commonly used tissue culture cells, caveolin-1 is embedded in caveolae membranes. It appears to reach this location after being cotranslationally inserted into ER membranes, processed in the Golgi and shipped to the cell surface. We now report that caveolae are not the preferred location for caveolin-1 in all cell types. Skeletal muscle cells and keratinocytes target caveolin-1 to the cytosol while in exocrine and endocrine cells it accumulates in the secretory pathway. We also found that airway epithelial cells accumulate caveolin-1 in modified mitochondria. The cytosolic and the secreted forms appear to be incorporated into a soluble, lipid complex. We conclude that caveolin-1 can be targeted to a variety of intracellular destinations, which suggests a novel mechanism for the intracellular traffic of this protein.

Adult↗

PubMed2001

Elements in erythrocytes of population with different thyroid hormone status.

The contents of elements K, Ca, Fe, Cu, Zn, Se, and Rb in erythrocytes of 78 cases with different thyroid hormone status have been measured by proton-induced X-ray emission and neutron activation analysis. According to the status of thyroid hormones T3, T4, TSH, FT3, and FT4 detected by radioimmunoassay, the experiment subjects were divided into four groups (i.e., hyperthyroid, hypothyroid, critical [one of thyroid hormones was abnormal], and normal). Elements contents and hormones levels of four groups were analyzed by one-way analysis of variance and correlation using an SPSS/PC statistical package. The results showed that the Se contents of four groups were not significantly different (p<0.05). Zn content of hypothyroid group was significantly higher than those of hyperthyroid and critical groups. The Zn content of the normal group was higher than that of the hypothyroid group and lower than that of the hyperthyroid and critical groups. In the hyperthyroid group, there were significant correlations between elements contents and thyroid hormones levels (except TSH), but not between elements contents and levels of thyroid hormones. However, in the hypothyroid group, relatively strong correlations have been found between elements contents and thyroid hormones levels, especially between Zn and the T3/T4 ratio, and between Zn and TSH.

Animals↗

PubMed2001

The influence of age and gender on the pharmacokinetics of moxifloxacin.

OBJECTIVE: Moxifloxacin is a new 8-methoxyfluoroquinolone with a broad antibacterial spectrum. The purpose of the present study was to determine the effects of age and gender on pharmacokinetics, surrogate pharmacodynamics, safety and tolerability of a single dose of moxifloxacin. DESIGN: This was a randomised, double-blind, placebo-controlled, parallel-group single dose trial in young and elderly healthy volunteers. PATIENTS AND PARTICIPANTS: The study included 36 volunteers in 3 age and gender groups: young males (mean age 32 years), elderly males (mean age 74 years), and elderly females (mean age 74 years). METHODS: Participants received either a single 200mg oral dose of moxifloxacin (8/group) or placebo (4/group). Blood samples for moxifloxacin pharmacokinetics were obtained before and up to 48 hours after administration. Urine samples were collected for pharmacokinetics, and volunteers were monitored for clinical adverse events and laboratory abnormalities. RESULTS: Maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were higher in elderly females than in elderly males; however, when normalised for bodyweight, these pharmacokinetic parameters were not significantly different between the groups. Moreover, the plasma pharmacokinetics in elderly males were not meaningfully different from those in young males. Elimination half-life averaged 12 to 13 hours for the 3 groups. Surrogate pharmacodynamic measures were derived using AUC/MIC (minimal inhibitory concentration) and Cmax/MIC ratios. These assessments indicated that, given the linear pharmacokinetics of moxifloxacin previously demonstrated, a dose of 400mg would produce mean Cmax/MIC values in the different subgroups ranging from 10.4 to 15.4 for an MIC of 0.25, and 20.8 to 30.8 for an MIC of 0.125. The corresponding ranges of projected AUC/MIC ratios would be 112 to 158 for an MIC of 0.25, and 224 to 314 for an MIC of 0.125. The accepted target values of AUC/MIC and Cmax/MIC for quinolones are 125 and 10, respectively. There were no serious adverse events or differences in adverse event profiles between the groups. CONCLUSIONS: Moxifloxacin does not exhibit age- or gender-dependent pharmacokinetics. Oral doses of 200 to 400mg yield effective antibacterial concentrations on the first day of administration.

Administration, Oral↗