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Biomedical subjects

Z Liu

Publications and source records attributed to Z Liu.

At least 1,423 records · Page 79Linked to original sources
PubMedDate not supplied

Linear viscoelastic properties of bovine brain tissue in shear.

We report the results from a series of rheological tests of fresh bovine brain tissue. Using a standard Bohlin VOR shear rheometer, shear relaxation and oscillating strain sweep experiments were performed on disks of brain tissue 30 mm in diameter, with a thickness of 1.5-2 mm. The strain sweep experiment showed that the viscoelastic strain limit is of the order of 0.1% strain. Shear relaxation data do not indicate the presence of a long-term elastic modulus, indicating fluid-like behavior. A relaxation spectrum was calculated by inverting the experimental data and used to predict oscillatory response, which agreed well with measured data.

Animals↗
PubMedDate not supplied

Systematic studies on synthesis, structural elucidation, and biological evaluation of A-ring diastereomers of 2-methyl-1alpha,25-dihydroxyvitamin D(3) and 20-epi-2-methyl-1alpha,25-dihydroxyvitamin D(3).

All possible A-ring diastereomers of 2-methyl-1alpha,25-dihydroxyvitamin D(3) (2) and 20-epi-2-methyl-1alpha,25-dihydroxyvitamin D(3) (3) were synthesized by palladium-catalyzed coupling reaction of A-ring 'enyne' synthons with CD-ring portions. The A-ring synthons were rationally synthesized via a novel and practical route, starting with methyl (R)-(+)- and (S)-(-)-3-hydroxy-2-methyl-propionate, in good yields. X-ray crystallographic analysis of 2alpha-methyl-1alpha,25-dihydroxyvitamin D(3) (2b) and conformational analysis of the A-ring of 2alpha-methyl-(2b) and 2beta-methyl-1alpha,25-dihydroxyvitamin D(3) (2f) were carried out, and the results are described. All A-ring diastereomers (2 and 3), thus synthesized, were biologically evaluated both in vitro and in vivo. The biologic potency was highly dependent on the stereochemistry of the A-ring substituents. In particular, 2b showed 4-fold higher vitamin D receptor [VDR] binding activity than the natural hormone, and its 20-epimer (3b) exhibited exceptionally high activity, 12-fold more potent in VDR binding, 7-fold in calcium mobilization, and 590-fold in induction of human promyelocytic leukemia (HL-60) cell differentiation as compared with the natural hormone. Further, the 20-epi-2beta-Me-1beta, 3alpha(OH)(2) isomer (3g) had significant biologic potencies compared to the natural hormone despite having 1beta-OH configuration. The transcriptional activities on human osteocalcin gene promoter, including VDRE in transfected mammalian cells, were also evaluated. Finally, there was a clear contrast between the effects of the 2-methyl group on the HL-60 cell differentiation- and apoptosis-inducing activities of 2 and 3.

Animals↗
PubMedDate not supplied

Effects of lead exposure on long-term potentiation induced by 2-deoxy-D-glucose in area CA1 of rat hippocampus in vitro.

Chronic developmental lead exposure is known to be associated with cognitive dysfunction in children. Previous studies have demonstrated that chronic lead exposure could impair the induction and maintenance of long-term potentiation induced by high-frequency stimulation (HFS-LTP). In area CA1 of rat hippocampus, long-term potentiation could also be induced following temporary replacement of 10 mM 2-deoxy-D-glucose (2-DG) for 10 mM glucose in the normal perfusate (artificial cerebrospinal fluid). The present study was carried out to investigate whether chronic lead exposure affected long-term potentiation induced by 2-DG (2-DG-LTP). Neonatal Wistar rats were exposed to lead from parturition to weaning via milk of dams whose drinking water contained 0.2% lead acetate. Field excitatory postsynaptic potentials (EPSPs) in area CA1 of hippocampus were recorded on postnatal days 25-30. 2-DG application was followed by an increase in EPSP slopes in a time-course-dependent manner in both control and lead-exposed rats, while the amplitude of 2-DG-LTP in the lead-exposed rats (225.9+/-19.0%, n=12) was significantly greater than that in controls (155.2+/-9.8%, n=12). In contrast to the effects of lead exposure on 2-DG-LTP, the amplitude of HFS-LTP in the lead-exposed rats (121.5+/-13.7%, n=12) was significantly less than that in controls (183.9+/-18.6%, n=12). These results indicate that chronic lead exposure had opposite effects on the two types of LTP induced by HFS and 2-DG. This would suggest that the effects of lead on HFS-LTP and 2-DG-LTP are the result of different sites of lead toxicity.

Animals↗
PubMedDate not supplied

Effects of disruption of the mitochondrial electrochemical gradient on steroidogenesis and the Steroidogenic Acute Regulatory (StAR) protein.

The steroidogenic acute regulatory (StAR) protein, which mediates cholesterol delivery to the inner mitochondrial membrane and the P450scc enzyme, has been shown to require a mitochondrial electrochemical gradient for its activity in vitro. To characterize the role of this gradient in cholesterol transfer, investigations were conducted in whole cells, utilizing the protonophore carbonyl cyanide m-chlorophenylhydrazone (m-CCCP) and the potassium ionophore valinomycin. These reagents, respectively, dissipate the mitochondrial electrochemical gradient and inner mitochondrial membrane potential. Both MA-10 Leydig tumor cell steroidogenesis and mitochondrial import of StAR were inhibited by m-CCCP or valinomycin at concentrations which had only minimal effects on P450scc activity. m-CCCP also inhibited import and processing of both StAR and the truncated StAR mutants, N-19 and C-28, in transfected COS-1 cells. Steroidogenesis induced by StAR and N-47, an active N-terminally truncated StAR mutant, was reduced in transfected COS-1 cells when treated with m-CCCP. This study shows that StAR action requires a membrane potential, which may reflect a functional requirement for import of StAR into the mitochondria, or more likely, an unidentified factor which is sensitive to ionophore treatment. Furthermore, the ability of N-47 to stimulate steroidogenesis in nonsteroidogenic HepG2 liver tumor cells, suggests that the mechanism by which StAR acts may be common to many cell types.

Animals↗
PubMedDate not supplied

Planar imaging of 99mTc-labeled (bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium[V]) can detect resting ischemia.

BACKGROUND: (99m)Tc-labeled (bis(N-ethoxy, N-ethyl dithiocarbamato) nitrido technetium(V)) ([99m]TcN-NOET) is a new lipophilic, neutral-charge cardiac perfusion imaging agent that demonstrates apparent redistribution in animal models and humans. The purpose of this study was to determine whether the kinetics of (99m)TcN-NOET are suitable for the detection of resting ischemia. METHODS AND RESULTS: Microspheres were injected at baseline and simultaneously with (99m)TcN-NOET after a 90% reduction in resting flow in the left circumflex coronary artery in six open-chest canine experiments. The relationship of flow and activity early after injection was determined in one experiment by termination at 10 minutes. The flow ratio (left circumflex/left anterior descending coronary artery) after stenosis fell significantly (0.87 +/- 0.04 vs 0.46 +/- 0.04; p < 0.05). The end-tissue (99m)Tc ratio (0.78 +/- 0.05) was significantly higher than the flow ratio at injection (0.46 +/- 0.04; p < 0.05), indicating substantial redistribution. In vivo imaging was conducted during 2 hours in five experiments, followed by ex vivo imaging. Myocardial clearance from 10 minutes onward was biphasic in left anterior descending and monophasic in left circumflex coronary arteries. Myocardial clearance from 10 to 60 minutes was delayed in left circumflex (35.5% +/- 8.1%) versus left anterior descending coronary arteries (49.2% +/- 8.6%; p < 0.05). No significant difference was observed from 60- to 120-minute clearance. Five of five experiments demonstrated initial defects and complete fill-in at 90 to 120 minutes by qualitative assessment. Quantitation of ex vivo images confirmed significant redistribution. CONCLUSIONS: Resting ischemia caused by moderate to severe stenosis can be detected on scans with (99m)TcN-NOET. Redistribution was near complete in this model by 90 to 120 minutes. (99m)TcN-NOET is a promising new agent for the detection of coronary artery disease in viable myocardium and warrants further investigation.

Animals↗
PubMedDate not supplied

Technetium 99m-HL-91: a potential new marker of myocardial viability assessed by nuclear imaging early after reperfusion.

OBJECTIVE: 99mTc-HL-91 (Prognox) is a potential new hypoxia-avid myocardial imaging agent. The purpose of this study was to determine whether this tracer would demonstrate increased activity in nonviable myocardium in vivo. METHODS AND RESULTS: A 3-hour left circumflex artery (LCx) occlusion was followed by 1 hour of reperfusion, injection of 99mTc-HL-91 (185 MBq), and 2 hours of gamma camera imaging in 6 open-chest canine experiments. Microspheres were injected during baseline, at occlusion, at the time of tracer injection, and at the end of the experiment. After the animals were killed, heart slices were imaged. Blood flow and tracer activity were determined by well counting. Mean infarct size was 19.2% +/- 2.2% (SEM). All six dogs demonstrated no increased 99mTc-HL-91 myocardial activity other than small foci on in vivo and ex vivo gamma camera images. The mean large region of interest (ROI)-determined LCx/LAD (left anterior descending) ratio was 1.10 +/- 0.03 in vivo, and 1.0 +/- 0.02 ex vivo. Mean clearance curves from LCx and LAD ROI were not significantly different, and 2-hour retention was 15.2% +/- 2.1% for the LCx and 18.6% +/- 2.7% for the LAD (p = NS). ROI clearance curves demonstrated biexponential clearance over the first hour and linear clearance over the second hour. Myocardial blood flow (microspheres) versus well-counted tracer uptake curves were linear with near-zero slopes for viable tissue, nonviable tissue, and mosaic tissue. Blood clearance was triexponential with a 2-hour retention of 7.8% +/- 1.1%. CONCLUSIONS: In contrast to viable ischemic tissue, normal and nonviable myocardium demonstrate similar 99mTc-HL-91 uptake and retention kinetics. This agent warrants further clinical studies in situations where there is a need to differentiate ischemic viable from nonviable myocardium.

Animals↗
PubMedDate not supplied

Biomass and aggregation analysis of human embryonic kidney 293 suspension cell cultures by particle size measurement.

A method has been developed to monitor the cell growth of aggregated human embryonic kidney 293 (HEK293) suspension cultures by measuring cumulative particle volume and the particle size distribution. This method employs a particle size analyzer that determines the size of individual particles by detecting their light obscuration (blockage) or scattering. Cell counts derived from the cumulative volume of the cell particle correlate well with manual cell counts from a hemacytometer at different stages of growth. This correlation was further confirmed by quantifying total cellular protein of the samples. Simultaneously, the aggregation state of the samples can also be monitored and mathematically described. Results from this study demonstrate that this simple and reproducible method allows the direct measurement of cumulative cell volume and the degree of cell aggregation, as well as an indirect assessment of cell counts.

Biomass↗
PubMedDate not supplied

Structural basis for binding of Smac/DIABLO to the XIAP BIR3 domain.

The inhibitor-of-apoptosis proteins (IAPs) regulate programmed cell death by inhibiting members of the caspase family of enzymes. Recently, a mammalian protein called Smac (also named DIABLO) was identified that binds to the IAPs and promotes caspase activation. Although undefined in the X-ray structure, the amino-terminal residues of Smac are critical for its function. To understand the structural basis for molecular recognition between Smac and the IAPs, we determined the solution structure of the BIR3 domain of X-linked IAP (XIAP) complexed with a functionally active nine-residue peptide derived from the N terminus of Smac. The peptide binds across the third beta-strand of the BIR3 domain in an extended conformation with only the first four residues contacting the protein. The complex is stabilized by four intermolecular hydrogen bonds, an electrostatic interaction involving the N terminus of the peptide, and several hydrophobic interactions. This structural information, along with the binding data from BIR3 and Smac peptide mutants reported here, should aid in the design of small molecules that may be used for the treatment of cancers that overexpress IAPs.

Amino Acid Sequence↗
PubMedDate not supplied

Detection of myocardial viability in ischemic-reperfused rat hearts by Tc-99m sestamibi kinetics.

BACKGROUND: The purpose of this study was to evaluate technetium 99m sestamibi (MIBI) kinetics in assessing myocardial viability in hearts subjected to different ischemia-reperfusion treatments, resulting in graded severity of injury. METHODS AND RESULTS: Sixteen isolated Krebs-Henseleit-perfused rat hearts were divided into 3 groups: control (flow, 12 mL/min; n = 5), ischemic-reperfused with glucose (IR+G, n = 6), and ischemic-reperfused without glucose (IR-G, n = 5). MIBI (11.1 mBq [300 microCi]) was infused for 60 minutes (uptake), followed by a 60-minute clearance. MIBI uptake (percent injected dose per gram) was significantly decreased in the IR+G (2.07 +/- 0.31) and IR-G groups (2.03 +/- 0.23; P = not significant with IR+G) compared with the control group (3.06 +/- 0.25, P <.05). Fractional washout of MIBI was more rapid in the IR-G group (72.7% +/- 3.9%, P <.05) than in the control (21.9% +/- 1.9%) and IR+G groups (20.3% +/- 1.7%). End retention (percent injected dose per gram) of MIBI in the IR-G (0.60 +/- 0.12) and IR+G groups (1.60 +/- 0.18) was significantly less than in the control group (2.30 +/- 0.11, P <.05), respectively. The retention in the IR-G group was less than in the IR+G group (P <.05). Creatine kinase assay, triphenyltetrazolium chloride staining, and transmission electron microscopy analysis demonstrated more serious myocardial damage in the IR-G group than in the IR+G group. End MIBI activity was highly correlated with myocardial viability determined by triphenyltetrazolium chloride staining (r = 0.94; P <.05) and creatine kinase assay (r = -0.86; P <.05). CONCLUSIONS: Clearance of Tc-99m sestamibi is sensitive to metabolic states and may be used for assessment of ongoing myocardial damage.

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