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Biomedical subjects

Wen Liu

Publications and source records attributed to Wen Liu.

At least 91 records · Page 5Linked to original sources
PubMed2003

Anticipatory postural adjustments and the latency of compensatory stepping reactions in humans.

A compensatory stepping response is a commonly used strategy in recovering balance control after a postural perturbation. Unlike gait initiation, the compensatory stepping often occurs without an anticipatory postural adjustment (APA), in which body weight is shifted to the swing leg first and then back to the stance leg prior to foot lifting. In postural perturbation studies using a moving platforms stepping responses without an APA were found to have shorter latency to foot lifting than trials with an APA. We studied stepping responses of healthy young adults under postural perturbation of a pulling force impulse on the subject's waist. In contrast to previous studies, the latency of foot lifting was found in the current study to be shorter in the trials with an APA than trials without an APA. Furthermore, greater amplitude of an APA was associated with a shorter latency of foot lifting. Response with an APA of large amplitude may indicate high level of determinant for foot lifting. A pause as to whether or not to initiate/complete a stepping response is suggested to be partially the cause of delayed foot lifting in trials without an APA or with small amplitude of the APA.

Adaptation, Physiological↗
PubMed2003

Predicting the dynamic postural control response from quiet-stance behavior in elderly adults.

Human postural sway, as measured by fluctuations of the center of pressure (COP) under the feet of a quietly standing individual, can be characterized as a stochastic process. The fluctuation-dissipation theorem (FDT) provides a linear relationship between the fluctuations of a quasi-static, stochastic system to the same system's relaxation to equilibrium following a perturbation. We applied a similar linear relationship, based on the FDT, to the human postural control system to explore whether anterior-posterior (AP) fluctuations of the COP during quiet stance can be used to predict the AP response of the postural control system to a weak posteriorly directed mechanical perturbation (tug or pull at the waist). We tested 10 healthy elderly (mean age of 69yr) and 10 healthy young (mean age of 25yr) adult subjects. We found that this linear relationship was applicable to the postural control system of all 10 young and eight of the 10 elderly adult subjects. These results suggest that it is possible to predict an individual's dynamic response to a mild perturbation using quiet-stance data, regardless of age. The existence of this FDT-based linear relationship with respect to the human postural control system suggests that, for a given individual, the postural control system may use the same control mechanisms during quiet stance and mild-perturbation conditions, regardless of age.

Adult↗
PubMed2003

Protective effects of pseudoginsenoside-F11 on methamphetamine-induced neurotoxicity in mice.

In the present study, pseudoginsenoside-F(11) (PF(11)), a saponin that existed in American ginseng, was studied on its protective effect on methamphetamine (MA)-induced behavioral and neurochemical toxicities in mice. MA was intraperitoneally administered at the dose of 10 mg/kg four times at 2-h intervals, and PF(11) was orally administered at the doses of 4 and 8 mg/kg two times at 4-h intervals, 60 min prior to MA administration. The results showed that PF(11) did not significantly influence, but greatly ameliorated, the anxiety-like behavior induced by MA in the light-dark box task. In the forced swimming task, PF(11) significantly shortened the prolonged immobility time induced by MA. In the appetitively motivated T-maze task, PF(11) greatly shortened MA-induced prolonged latency and decreased the error counts. Similar results were also observed in the Morris water maze task. PF(11) significantly shortened the escape latency prolonged by MA. There were significant decreases in the contents of dopamine (DA), 3,4-dihydroxyphenacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoacetic acid (5-HIAA) in the brain of MA-treated mice. PF(11) could partially, but significantly, antagonize MA-induced decreases of DA. The above results demonstrate that PF(11) is effective in protection of MA-induced neurotoxicity and also suggest that natural products, such as ginseng, might be potential candidates for the prevention and treatment of the neurological disorders induced by MA abuse.

Animals↗
PubMed2003

Influence of anthropometric and mechanical variations on functional instability in the ACL-deficient knee.

Individual variations in joint anatomy, tissue mechanical properties, and muscle strength of the knee are believed to affect the clinical outcome of ACL-deficient patients, but the effects have not been studied systematically. The impact of individual anthropometric and mechanical variation on functional stability of the ACL-deficient knee was investigated in this study using a two-dimensional mathematical knee model. The model included the tibiofemoral and the patellofemoral articulations, four ligaments, the medial capsule, and four muscle units surrounding the knee. Simulations were conducted to determine tibial anterior translation as well as tibiofemoral and patellofemoral joint loading at a single selected position during early stance phase of gait. Incremental hamstring muscle forces were applied to the modeled ACL-deficient knee in order to examine the level of the hamstring muscle forces required to prevent abnormal tibial anterior translation relative to the femur. Simulations were repeated using incremental variations in the selected anthropometric and mechanical properties of the ACL-deficient knee. It was found that bony geometry of the knee joint, especially the slope of tibial plateau, strongly affected both the tibial translations in the ACL-deficient knee and the effectiveness of the hamstring muscles to compensate for the ACL deficiency. For instance, simulations indicated that, due to ACL deficiency, the tibial anterior displacement increased by 9.1 mm for a tibial slope angle of 4 degrees compared to 15.2 mm for a tibial slope angle of 12 degrees. Future outcome studies for ACL-deficient knee may be required to include individual anthropometric and mechanical parameters of the knee as covariants.

Adaptation, Physiological↗
PubMed2003

Enediyne natural products: biosynthesis and prospect towards engineering novel antitumor agents.

This review gives a brief account on the current status of enediyne biosynthesis and the prospective of applying combinatorial biosynthesis methods to the enediyne system for novel analog production. Methods for cloning enediyne biosynthetic gene clusters are first reviewed. A unified paradigm for enediyne biosynthesis, characterized with (a) the enediyne PKS, (b) the enediyne PKS accessory enzymes, and (c) tailoring enzymes, is then presented. Strategies and tools for novel enediyne analog production by combinatorial biosynthesis are finally discussed. The results set the stage to decipher the molecular mechanism for enediyne biosynthesis and lay the foundation to engineer novel enediynes by combinatorial biosynthesis for future endeavors.

Antineoplastic Agents↗
PubMed2003

[Expression of telomerase in human ovarian luteinized granulosa cells and its relationship to ovarian function].

OBJECTIVE: To detect the expression of telomerase catalytic subunit (TERT), telomerase in human ovarian luteinized granulosa cells and to investigate the relationship between telomerase expression and the ovarian fecundity. METHODS: Ovarian luteinized granulosa cells were recovered from 22 women with regular menses who underwent in vitro fertilization/intracytoplasmic sperm injection programme. We carried out in situ hybridization histochemistry on luteinized granulosa cells to detect TERT mRNA expression, and telomeric repeat amplification protocol to detect telomerase activity. RESULTS: TERT mRNA were present in luteinized granulosa cells. The expression of TERT mRNA and telomerase activity in ovarian luteinized granulosa cells decreased with increase of age, basal serum follicle stimulating hormone levels. CONCLUSIONS: These results suggest that telomerase may play an active role in ovarian function.A reduced telomerase activity of granulosa cells may be one of the important mechanisms involved in decreased ovarian function in women.

Adult↗
PubMed2003

Detection of distribution of copper inside and outside of lysosomes in cultured hepatolenticular degeneration fibroblasts by electron probe X-ray microanalysis.

OBJECTIVE: To observe the distribution of copper in the subcellular structure for the understanding of primary pathogenesis of hepatolenticular degeneration (HLD). METHODS: Skin fibroblasts taken from HLD patients were cultured as an in vitro model of HLD, and the control cells taken from healthy volunteers were cultured in the same way. The distribution of copper inside and outside of lysosomes in fibroblasts was detected by quantitative electron probe X-ray microanalysis. The relationship between the subcellular location of copper and the genotype of the patients, and relationship between the distribution of copper and the course of the disease were analyzed. RESULTS: The content of Cu2+inside lysosomes of HLD cells (14.6+/-2.1 mmol/kg) and of heterozygote cells (11.6+/-0.6 mmol/kg) was higher than that of normal cells (4.5+/-1.2 mmol/kg) (P<0.01). The content of Cu2+outside lysosomes of HLD cells (17.5+/-4.2 mmol/kg) and of heterozygote cells (12.0+/-0.9 mmol/kg) was higher than that of normal cells (4.7+/-1.2 mmol/kg) (P<0.01). The distribution of copper in the subcellular structure was correlated with disease courses of HLD patients. With the progression of the disease, more copper was deposited in lysosomes (r=0.85, P<0.01). The content of copper in the diffused cytoplasmic compartment in HLD cells was correlated with that of sulfur (r=0.86, P<0.05), but not in heterozygote and normal cells. CONCLUSIONS: In the early stage of HLD, copper is accumulated outside lysosome, which is paralleled with increase of metallothionein-like proteins (copper and sulfur-binding proteins). With the development of the disease, more copper is deposited inside lysosome than outside lysosome. We conclude that the up-regulation expression of copper and sulfur-binding proteins and copper accumulation in lysosomes may play an important role in lowering the ATP7B gene mutation-induced toxic effects of free copper on the cell.

Adolescent↗
PubMed2003

[Molecular chaperone GRP75 reprove cells from injury caused by glucose deprivation].

Glucose-regulated proteins 75(grp75) is a member of hsp70 family. The expression of grp75 is upregulated during glucose starvation (such as ischemia). To evaluate grp75 function, CHL cells were cultured with glucose-free media for 20 h (A) and glucose-free media for 12 h + glucose-containing media for 8 h (ischemia reperfusion) (B). A constructed rat grp75 cDNA expression vector (pcDNA/grp75) was transfected into CHL cells and a cell strain that stably overexpressed grp75 was obtained. The transfected cells and untransfected cells(control group) were cultured with A or B. By MTT, LDH leakage measurement and flow cytometry analysis, growth rate of untransfected cells in B is significantly lower than that in glucose-containing media for 20 h (C) (p < 0.05) and A (p < 0.05). Growth rate of transfected cells is apparently higher than that of control group in B (p < 0.01). LDH liberation percentage of untransfected cells in B is obviously higher than that in C(p < 0.01) and it is not different from A(p > 0.05). LDH liberation percentage of transfected cells is apparently lower than that of control group in B(p < 0.01). Apoptosis of transfected cells is obviously lower by flow cytometry analysis. These results provide evidence for the cytoprotective function of grp75 during glucose starving and ischemia reperfusion.

Animals↗
PubMed2003

[The use of muscle autograft denatured by microwave for repair of gaps in removal of facial neuromas].

OBJECTIVE: To study the clinical value of muscle autograft denatured by microwave for repair of gaps in removal of facial neuromas. METHODS: Two cases of patients with facial nerve Schwann cell neuromas were reported. The operations for removal of facial neuromas were completed, and the gaps of the nerves were repaired with muscle autograft denatured by microwave of 250 W for 120 sec. RESULTS: The patients were followed up for two years, and the recovery of facial function on the affected sides were satisfactory. CONCLUSION: Muscle autograft denatured by microwave technique is convenient, highly efficient for repairing facial nerve gap after removal of facial neuroma.

Adult↗
PubMed2002

Biosynthesis of the enediyne antitumor antibiotic C-1027.

C-1027 is a potent antitumor agent with a previously undescribed molecular architecture and mode of action. Cloning and characterization of the 85-kilobase C-1027 biosynthesis gene cluster from Streptomyces globisporus revealed (i) an iterative type I polyketide synthase that is distinct from any bacterial polyketide synthases known to date, (ii) a general polyketide pathway for the biosynthesis of both the 9- and 10-membered enediyne antibiotics, and (iii) a convergent biosynthetic strategy for the C-1027 chromophore from four building blocks. Manipulation of genes governing C-1027 biosynthesis allowed us to produce an enediyne compound in a predicted manner.

Aminoglycosides↗
PubMed2002

Endogenous released ascorbic acid suppresses ethanol-induced hydroxyl radical production in rat striatum.

Previous studies have shown that acute systemic administration of ethanol induced ascorbic acid release in the striatum. However, the pharmacological implications of ethanol-induced striatal ascorbic acid release are unclear. In the present study, ethanol-induced extracellular changes of ascorbic acid and hydroxyl radical levels were detected in rat striatum by using brain microdialysis coupled to high-performance liquid chromatography with electrochemical detection. It was found that both in male and female rats, ethanol (3.0 g/kg, i.p.) increased striatal ascorbic acid release in the first 60 min after ethanol administration. Meanwhile, the extracellular hydroxyl radical levels, detected as 2,3- and 2,5-DHBA, were significantly decreased. However, when the ascorbic acid levels returned to the baseline, hydroxyl radical levels rebounded. Administration of DL-fenfluramine (20 mg/kg, i.p.) had no effect on the basal levels of ascorbic acid and hydroxyl radical, but significantly blocked ethanol-induced ascorbic acid release and increased hydroxyl radical levels significantly. Exogenous administration of ascorbic acid (20 mg/kg, s.c.) increased the extracellular levels of ascorbic acid in the striatum, and inhibited the increase of 2,3- and 2,5-DHBA in DL-fenfluramine plus ethanol group. These results provide first evidence that release of endogenous ascorbic acid in the striatum plays an important role in preventing oxidative stress by trapping hydroxyl radical in the central nervous system.

Alcohol-Induced Disorders, Nervous System↗
PubMed2002

Efficient synthesis of the A-ring phosphine oxide building block useful for 1 alpha,25-dihydroxy vitamin D(3) and analogues.

The 1 alpha-hydroxy A-ring phosphine oxide 1, a useful building block for vitamin D analogues, was synthesized from (S)-carvone in nine synthetic operations and a single chromatographic purification in 25% overall yield. The synthesis features two novel efficient synthetic transformations: the Criegee rearrangement of alpha-methoxy hydroperoxyacetate 10 in methanol to obtain directly the desired secondary 3 beta-alcohol 11 and the highly chemo- and stereoselective isomerization of dieneoxide ester (E)-7 to the 1 alpha-allylic alcohol with an exocyclic double bond (E)-8. Further insight into the selectivity control of the latter rearrangement was obtained from the reactions of (Z)-epimeric substrates. The new synthetic approach leading to the 1 alpha-hydroxy epimers complements our previously reported synthesis of the corresponding 1 beta-epimers, thus producing all stereoisomers of these versatile building blocks efficiently from carvone.

Catalysis↗
PubMed2002

Noise-enhanced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy.

OBJECTIVE: To test the hypothesis that vibrotactile detection thresholds in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly reduced with the introduction of mechanical noise. DESIGN: A randomized controlled study. SETTING: A university research laboratory. PARTICIPANTS: Twelve healthy elderly subjects (age range, 67-85y), 5 patients with stroke (age range, 24-64y), and 8 patients with diabetic neuropathy (age range, 53-77y). INTERVENTIONS: Each subject's detection thresholds (ie, minimum level of stimulus to be detected) for a vibrotactile stimulus without and with mechanical noise (ie, random vibration with a small intensity) were determined by using a 4-, 2-, and 1-stepping algorithm. The stimuli were applied to the fingertip and/or to the first metatarsal of the foot. MAIN OUTCOME MEASURE: Detection threshold for a vibrotactile stimulus. RESULTS: The detection threshold at the fingertip for the vibration stimulus with mechanical noise was significantly lower than that without mechanical noise for all 12 elderly subjects, for 4 of the 5 patients with stroke, and all 8 patients with diabetic neuropathy. For the 8 patients with diabetes, mechanical noise also significantly reduced the vibrotactile detection threshold at the foot. CONCLUSIONS: Reduced vibrotactile sensitivity in older adults, patients with stroke, and patients with diabetic neuropathy can be significantly improved with input mechanical noise. Noise-based techniques and devices may prove useful in overcoming age- and disease-related losses in sensorimotor function.

Adult↗
PubMed2002

Green tea inhibits vascular endothelial growth factor (VEGF) induction in human breast cancer cells.

Investigators have shown that green tea and its main catechin epigallocatechin-3 gallate (EGCG) may decrease the risk of cancer. Our previous study showed that green tea extract (GTE) as well as its individual catechin components inhibited MDA-MB231 breast cancer cell and human umbilical vein endothelial cell (HUVEC) proliferation. Further, GTE suppressed breast cancer xenograft size and decreased the tumor vessel density in vivo. In the current study, we investigated the effect of GTE on the major angiogenic factor vascular endothelial growth factor (VEGF) in an in vitro experiment. GTE or EGCG (40 mg/L) significantly decreased the levels of the VEGF peptide secreted into conditioned media. This occurred in both HUVEC and human breast cancer cells and the effect was dose dependent. Furthermore, GTE and EGCG decreased the RNA levels of VEGF in MDA-MB231 cells. This inhibition occurred at the transcriptional regulation level and was accompanied by a significant decrease in VEGF promoter activity. We also showed that GTE decreased c-fos and c-jun RNA transcripts, suggesting that activator protein (AP)-1-responsive regions present in the human VEGF promoter may be involved in the inhibitory effect of GTE. Furthermore, GTE suppressed the expression of protein kinase C, another VEGF transcription modulator, in breast cancer cells. Inhibition of VEGF transcription appeared to be one of the molecular mechanism(s) involved in the antiangiogenic effects of green tea, which may contribute to its potential use for breast cancer treatment and/or prevention.

Beverages↗
PubMed2002

A modeling study of partial ACL injury: simulated KT-2000 arthrometer tests.

A partial ACL injury may involve different levels of fiber disruption, orfibers may sustain microscopic changes in their structure without gross disruption, resulting in a change in ligament function. The effect of partial ACL tears on the mechanical and functional stability of the knee has not been well documented, in part because of diagnostic difficulties. A computer model of the knee in the sagittal plane was used in this study to simulate tests using the KT-2000 Knee Arthrometer, which quantifies Lachman's test for ACL injury. A variety of partial ACL anterior and posterior bundle injuries were simulated. Anterior and posterior bundle injuries were subdivided into four different simulated injury levels: mild (one-half tear of the bundle), moderate (complete tear of the bundle), severe (complete tear of the bundle and tear of one-half of the other bundle), and more severe (severe injury plus an additional elongation of the other bundle represented by 5% increases of its initial strain). Force-displacement results obtained from simulated KT-2000 knee arthrometer tests depended on the level of injury. Mild and moderate injuries produced only small change in the anterior tibial translation--at different force levels. Severe injury produced increased anterior tibial translation depending on which bundle was completely ruptured. The compliance index defined as the ratio of the displacement and the force within 68 N and 90 N anterior drawer forces, the stiffness, and the rate of change of stiffness of the anterior force-displacement were found to be better at predicting partial ACL ruptures than simple differences in anterior tibial translation. It was possible in the model results to discriminate knees with various levels of partial ACL injuries using the first and second derivatives of the force-displacement curve.

Anterior Cruciate Ligament↗
PubMed2002

Analysis of NaCl transport in thin ascending limb of Henle's loop in CLC-K1 null mice.

To characterize the nature of NaCl transport in the thin ascending limb (tAL), we examined the transport properties of Na(+) and Cl(-) using in vitro microperfusion of the tAL in CLC-K1 null mice. In the presence of a transmural NaCl concentration gradient (100 mM higher in the lumen), the transepithelial diffusion voltage (V(d)) was 15.5 +/- 1.0 and -7.6 +/- 1.4 mV in CLC-K1(+/+) and CLC-K1(-/-) mice, respectively. Neither Cl(-) transport inhibitor 5-nitro-2-(3-phenylpropylamino)-benzoate (NPPB) nor acidification of the bathing fluid changed the V(d) values in CLC-K1(-/-) mice. The addition of 300 microg/ml protamine, a selective blocker of paracellular conductance, to the bath increased the V(d) values by 5.6 +/- 0.7 and 12.6 +/- 1.5 mV (P < 0.001) in CLC-K1(+/+) and CLC-K1(-/-) mice, respectively. Although efflux coefficients of (36)Cl were significantly decreased in CLC-K1(-/-) mice (188.3 +/- 25.6 in 4 tubules vs. 17.2 +/- 7.0 x 10(-5) cm/s in 6 tubules), those of (22)Na were not different between CLC-K1(+/+) and CLC-K1(-/-) mice. These results clearly indicate that the major component of Cl(-) transport sensitive to NPPB or pH is mediated by CLC-K1 in the tAL.

Angiogenesis Inhibitors↗
PubMed2002

Posttranscriptional compensation for heterozygous disruption of the kidney-specific NaK2Cl cotransporter gene.

Mice homozygous for a loss of function mutation of the kidney-specific NaK2Cl cotransporter, BSC1/NKCC2, do not survive. Here the effects of loss of one copy of the gene are studied. NKCC2 mRNA of NKCC2 +/- kidney was 55 +/- 6% of +/+, yet no differences were found between NKCC2 +/+ and +/- mice in BP, blood gas, electrolytes, creatinine, plasma renin concentration, urine volume and osmolality, ability to concentrate and dilute urine, and response to furosemide. When mice were challenged with 180 mM NH(4)Cl, plasma ammonia and urinary ammonia excretion were increased twofold and fivefold, respectively, but there was still no difference between the two genotypes. NKCC2 +/- mice had a near-normal level of NKCC2 protein and no clear change in the distribution of NKCC2 in the thick ascending limb (TAL) cells. In vitro microperfusion of isolated TAL showed no significant difference between the two genotypes in the basal and vasopressin-stimulated capacity to reabsorb NaCl. There was no difference in the mRNA expressions of thiazide-sensitive NaCl cotransporter, epithelial Na channel (ENaC), aquaporin-2, ROMK, and NaKATPase. Halving the mRNA expression of NKCC2 does not affect BP or fluid balance because of compensatory factors that restore the protein level to near normal. One possible factor is a regulated increase in the movement of cytoplasmic protein to the luminal membrane leading to a restoration of functional transporter to an essentially wild type level.

Adaptation, Physiological↗