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Biomedical subjects

Y Z Huang

Publications and source records attributed to Y Z Huang.

At least 19 recordsLinked to original sources
PubMed2005

Theta-burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex.

In four conscious patients who had electrodes implanted in the cervical epidural space for the control of pain, we recorded corticospinal volleys evoked by single-pulse transcranial magnetic stimulation (TMS) over the motor cortex before and after a 20 s period of continuous theta-burst stimulation (cTBS). It has previously been reported that this form of repetitive TMS reduces the amplitude of motor-evoked potentials (MEPs), with the maximum effect occurring at 5-10 min after the end of stimulation. The present results show that cTBS preferentially decreases the amplitude of the corticospinal I1 wave, with approximately the same time course. This is consistent with a cortical origin of the effect on the MEP. However, other protocols that lead to MEP suppression, such as short-interval intracortical inhibition, are characterized by reduced excitability of late I waves (particularly I3), suggesting that cTBS suppresses MEPs through different mechanisms, such as long-term depression in excitatory synaptic connections.

Aged↗
PubMed2005

Cationic niosomes as gene carriers: preparation and cellular uptake in vitro.

Cationic niosomes of sorbitan monoesters were prepared using film hydration method and tested for their effect on delivery of antisense oligonucleotides (OND) in a COS-7 cell line. These formulations showed positive results on cellular uptake of antisense oligonucleotides. Especially, cationic niosomes of Span 40 and 60 have a more significant effect.

Animals↗
PubMed2005

Relevance of ventricular electrical dispersion to arrhythmogenesis in ischemic myocardium--a simulation study.

A computer simulation method was used to study the possible role of electrical dispersion induced by regional ischemia in the mechanisms underlying cardiac arrhythmias. Ischemic cells were simulated by considering the three major component conditions of acute ischemia (elevated extracellular K+ concentration, acidosis and anoxia) at the level of ionic currents and ionic concentrations. An ischemic area was introduced into a homogeneous healthy tissue to create a localized inhomogeneity. The constructed models were solved using the operator splitting and adaptive time step methods. The numerical experiments showed that action potential durations (APDs) of ischemic cells did not change with beats of shorter or longer cycle length. The smaller percentage increase of slow component of the delayed rectifier K+ current, I(ks), and smaller outward Na+-Ca2+ exchange current were found to be the ionic mechanisms underlying the decreased rate dependence in ischemic cells. The results suggest that ischemia flattens the APD restitution curve; however, the dispersion of refractory period can be greatly increased by a premature beat in the constructed inhomogeneous sheet. This demonstrates that the dispersion of refractoriness rather than APD by a premature beat contributes to reentrant tachyarrhythmias in the locally ischemic tissue.

Action Potentials↗
PubMed2003

Physiological studies in carriers of the DYT1 gene mutation.

The DYT1 gene mutation is associated with early onset generalised dystonia. However, only 30-40 per cent of gene carriers develop symptoms. We have used electrophysiological tests to search for subclinical effects of the presence of the mutation in non-manifesting cases and compared these with those seen in clinically affected cases and healthy controls. Clinically affected patients had the same pattern of abnormalities in spinal and motor cortical circuits as described previously in non-genetically characterised patients. Non-manifesting cases had some but not all of these defects, suggesting that additional genetic or environmental factors may be needed to produce the full range of physiological deficiencies needed to give rise to clinical symptoms.

Carrier Proteins↗
PubMed2002

Preparation of transmission electron microscopy cross-section specimens of crack tips using focused ion beam milling.

The preparation of transmission electron microscope (TEM) thin foil specimens from metal alloys containing cracks is usually thwarted by the difficulty in preventing preferential erosion of material along the flanks and at the tips of cracks. Recent developments in focused ion beam (FIB) micromachining methods have the potential to overcome this inherent problem. In this article we describe the development of new procedures, one using FIB alone and the other using a combination of FIB with more conventional ion milling to generate TEM specimens that largely retain the microstructural information at stress corrosion cracks in austentic alloys. Examples of corrosion product phase identification and interfacial segregation are included to verify that detailed information is not destroyed by ion bombardment during specimen preparation.

Journal Article↗
PubMed2001

Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway.

The Slit protein guides neuronal and leukocyte migration through the transmembrane receptor Roundabout (Robo). We report here that the intracellular domain of Robo interacts with a novel family of Rho GTPase activating proteins (GAPs). Two of the Slit-Robo GAPs (srGAPs) are expressed in regions responsive to Slit. Slit increased srGAP1-Robo1 interaction and inactivated Cdc42. A dominant negative srGAP1 blocked Slit inactivation of Cdc42 and Slit repulsion of migratory cells from the anterior subventricular zone (SVZa) of the forebrain. A constitutively active Cdc42 blocked the repulsive effect of Slit. These results have demonstrated important roles for GAPs and Cdc42 in neuronal migration. We propose a signal transduction pathway from the extracellular guidance cue to intracellular actin polymerization.

Actins↗
PubMed2001

Erbin is a protein concentrated at postsynaptic membranes that interacts with PSD-95.

Neuregulin is a factor essential for synapse-specific transcription of acetylcholine receptor genes at the neuromuscular junction. Its receptors, ErbB receptor tyrosine kinases, are localized at the postjunctional membrane presumably to ensure localized signaling. However, the molecular mechanisms underlying synaptic localization of ErbBs are unknown. Our recent studies indicate that ErbB4 interacts with postsynaptic density (PSD)-95 (SAP90), a PDZ domain-containing protein that does not interact with ErbB2 or ErbB3. Using as bait the ErbB2 C terminus, we identified Erbin, another PDZ domain-containing protein that interacts specifically with ErbB2. Erbin is concentrated in postsynaptic membranes at the neuromuscular junction and in the central nervous system, where ErbB2 is concentrated. Expression of Erbin increases the amount of ErbB2 labeled by biotin in transfected cells, suggesting that Erbin is able to increase ErbB2 surface expression. Furthermore, we provide evidence that Erbin interacts with PSD-95 in both transfected cells and synaptosomes. Thus ErbB proteins can interact with a network of PDZ domain-containing proteins. This interaction may play an important role in regulation of neuregulin signaling and/or subcellular localization of ErbB proteins.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Regulation of CDC42 GTPase by proline-rich tyrosine kinase 2 interacting with PSGAP, a novel pleckstrin homology and Src homology 3 domain containing rhoGAP protein.

Proline-rich tyrosine kinase 2 (PYK2), a tyrosine kinase structurally related to focal adhesion kinase (FAK), is implicated in regulating cytoskeletal organization. However, mechanisms by which PYK2 participates in and regulates cytoskeletal organization remain largely unknown. Here we report identification of PSGAP, a novel protein that interacts with PYK2 and FAK and contains multiple domains including a pleckstrin homology domain, a rhoGTPase-activating protein domain, and a Src homology 3 domain. PYK2 interacts with PSGAP Src homology 3 domain via the carboxyl-terminal proline-rich sequence. PSGAP is able to increase GTPase activity of CDC42 and RhoA in vitro and in vivo. Remarkably, PYK2, but not FAK, can activate CDC42 via inhibition of PSGAP-mediated GTP hydrolysis of CDC42. Moreover, PSGAP is localized at cell periphery in fibroblasts in a pleckstrin homology domain-dependent manner. Over expression of PSGAP in fibroblasts results in reorganization of cytoskeletal structures and changes of cellular morphology, which requires rhoGTPase-activating activity. Taken together, our results suggest that PSGAP is a signaling protein essential for PYK2 regulation of cytoskeletal organization via Rho family GTPases.

Amino Acid Sequence↗
PubMed2001

Mechanism of cardioprotection by resveratrol, a phenolic antioxidant present in red wine (Review).

Coronary heart disease (CHD) has been and remains a major contributor to morbidity and mortality in developed countries. The most common form of CHD in the western world is atherosclerosis (AS), especially of the major coronary arteries. Failure to maintain an intact endothelium, as a result of episodic and/or persistent injury and perturbation of the vascular endothelium, promotes formation of fatty streaks which are considered initiation events of AS. Cellular constituents contributing to endothelial injury include endothelial cells, monocytes, platelets, and smooth muscle cells. Individuals diagnosed with AS face complex, enduring clinical complications and enormous medical costs. Simple and easily compliant prevention and treatment measures are therefore strategic considerations in the management of this vascular disease. Based on known risk factors for CHD, priorities in AS prevention should include smoking cessation, blood pressure control, and diet modification. In recent years, the possible benefits of low to moderate consumption of alcoholic beverages, particularly of red wine, in the prevention of heart disease has received increasing attention and debate in the popular media as well as in the scientific community. Such attention has been prompted by research findings supporting a relationship between red wine consumption and the French paradox. This phenomenon refers to people residing in certain parts of France where red wine is customarily consumed during meals having a low CHD mortality, despite living a lifestyle considered to have comparably high CHD risks, as those in the US and many other developed countries. Studies have reported that the cardioprotective effects of red wine are greater than those attributed solely to ethanol and other types of alcoholic beverages. The mechanism(s) underlying the greater CHD protective benefits of red wine have not been elucidated. Recently the polyphenol resveratrol (3,5,4'-trihydroxy-trans-stilbene), known to be abundantly present in red wine, compared to white wine, beer, or spirits, has been demonstrated to elicit a broad spectrum of biological responses in in vitro and in animal studies, including effects that are compatible with the cardioprotective roles proposed for red wine. These recently described effects of resveratrol will be reviewed in this article. We will first summarize published data showing an inverse association between consumption of alcoholic beverages/red wine and risk of CHD. A review of biosynthesis of resveratrol and its presence in food groups and wines will follow. Recent studies relating exposure to wine/resveratrol with reduction in myocardial damage during ischemia-reperfusion, modulation of vascular cell functions, inhibition of LDL oxidation, and suppression of platelet aggregation will be presented. The last section of this review will focus on a discussion of mechanism(s) by which resveratrol acts as a potential cardioprotective agent.

Animals↗
PubMed2001

[Neuregulin/ErbB signal transduction pathway in the development of nervous system].

Neuregulins are a family of structurally-related polypeptides encoded by four distinct genes. Three isoforms of neuregulin (NRG1, 2, and 3) are highly expressed in the developing and adult brain, among which NRG1 is best characterized. NRG1 has multiple functions essential for the development of the nervous system. It promotes growth and differentiation of glial cells and regulates the migration of cerebellar granule cells along radial glial fibers. During synaptogenesis, NRG1 induces the expression of acetylcholine receptor at the neuromuscular junction and in CNS, and expression of the NMDA receptor NR2C subunit and GABAA receptors in cerebellar granule cells. Recent studies indicate that NRG receptors are densely distributed in the postsynaptic membrane, suggesting that NRGs may play an important role in synaptic plasticity. We review recent progress in studies of NRG, their functions, and signaling mechanisms.

Animals↗
PubMed2000

Expression of PSD-95/SAP90 is critical for N-methyl-D-aspartate receptor-mediated thermal hyperalgesia in the spinal cord.

PSD-95/SAP90, a molecular scaffold protein, attaches the N-methyl-D-aspartate receptor to cellular signaling pathways through PSD-95/DLG/Z0-1 domain interactions at neuronal synapses.(5,9) This suggests that PSD-95/SAP90 might be involved in many physiological and pathophysiological actions triggered via the N-methyl-D-aspartate receptor in the central nervous system. Here, we present evidence that suppression of the expression of PSD-95/SAP90 in the spinal cord significantly attenuated facilitation of the tail-flick reflex triggered through N-methyl-D-aspartate receptor activation but not baseline tail-flick reflex latency. Moreover, PSD-95/SAP90's messenger RNA and protein were enriched in the spinal cord and selectively distributed in the superficial dorsal horn, where PSD-95/SAP90 overlapped with the N-methyl-D-aspartate receptor. In spinal cord neurons, PSD-95/SAP90 interacted with the N-methyl-D-aspartate receptor subunits 2A/2B. It is indicated that activation of the N-methyl-D-aspartate receptor in spinal hyperalgesia results in association of the N-methyl-D-aspartate receptor with PSD-95/SAP90 and that PSD-95/SAP90 is required for noxious thermal hyperalgesia triggered via the N-methyl-D-aspartate receptor at the spinal cord level. The present findings may provide novel insights into the mechanisms for persistent sensitization of the somatosensory system.

Animals↗
PubMed2000

Regulation of neuregulin signaling by PSD-95 interacting with ErbB4 at CNS synapses.

Neuregulins (NRGs) and their receptors, the ErbB protein tyrosine kinases, are essential for neuronal development, but their functions in the adult CNS are unknown. We report that ErbB4 is enriched in the postsynaptic density (PSD) and associates with PSD-95. Heterologous expression of PSD-95 enhanced NRG activation of ErbB4 and MAP kinase. Conversely, inhibiting expression of PSD-95 in neurons attenuated NRG-mediated activation of MAP kinase. PSD-95 formed a ternary complex with two molecules of ErbB4, suggesting that PSD-95 facilitates ErbB4 dimerization. Finally, NRG suppressed induction of long-term potentiation in the hippocampal CA1 region without affecting basal synaptic transmission. Thus, NRG signaling may be synaptic and regulated by PSD-95. A role of NRG signaling in the adult CNS may be modulation of synaptic plasticity.

Animals↗
PubMed2000

Time-course analysis of stretch reflexes in hemiparetic subjects using an on-line spasticity measurement system.

Spasticity after a stroke is usually assessed in a score form by subjectively determining the resistance of a joint to an externally imposed passive movement. This work presents a spasticity measurement system for on-line quantifying the stretch reflex of paretic limbs. Four different constant stretch velocities in a ramp-and-hold mode are used to elicit the stretch reflex of the elbow joint in spastic subjects. The subjects are tested at supine position with the upper limb stretched towards the ground, in contrast with the horizontally stretched movement used in other studies. By subtracting the baseline torque, reflex torque measured at a selected low stretch velocity of 5 deg/sec, the influence of gravity torque and inertial in vertical stretching mode can be minimized. The averaged speed-dependent reflex torque (ASRT), defined as the measured torque deviated from the baseline torque, is used for quantifying the spastic hypertonia. Four subjects having incurred cerebrovascular accident (CVA) are recruited for time-course study in which the measurements are taken at 72 hours, one week, one month, three months, and six months after onset of stroke. During the development of spasticity, the changes of ASRT and velocity sensitivity of ASRT of the involved and the intact elbow joints are discussed.

Elbow Joint↗
PubMed2000

[Isolation and verification of Triticum aestivum-Eremopyrum orientale addition lines and substitution lines by GISH].

Eremopyrum is a potential genus in wheat improvement. To breed T. aestivum-Er. orientale additional and substitutional lines, chromosome number of 96 BC2F3 individuals were accounted. Fifteen plants with 2n = 43 and eight plants with 2n = 44 were checked out. GISH results of the individuals with 43 chromosomes showed that they blonged to three different monosomic additions. Two disomic additions, one double-monosomic addition, one trible-monosomic addition and one monosomic addition were found in the 2n = 44 individuals. One double-monosomic substitution and one monosomic substitution were obtained. We also proved that it is relatively easier to obtain addition lines in the selfing population than to obtain double-monosomic additions.

In Situ Hybridization↗
PubMed2000

[Flavonoids from Shuteria pampaninianna Hand.-Mazz].

OBJECTIVE: To investigate the chemical constituents of the herbs of Shuteria pampaninianna. METHOD: Using polyamide columine chromatography and NMR spectra to isolate pure flavonods and determine their structures. RESULT: Two flavonoids have been isolated from whole plant of S. pampaninianna and identified as myricetin(1) and ampelopsin(2) respectively. CONCLUSION: Both 1 and 2 were obtained from this plant for the first time.

Fabaceae↗
PubMed1999

Grafting of genetically modified human fetal fibroblasts to produce human butyrylcholinesterase in mice.

Human diploid fibroblast cultures were established from fetal skin tissue. Enzymic dissociation yielded cultures of higher growth capacity of fibroblasts than those prepared by mechanical dissociation followed by spontaneous outgrowth of cells. Transfer of recombinant human butyrylcholinesterase (BChE, EC 3.1.1.8) gene into primary human fibroblasts was achieved successfully using lipofection and retrovirus-mediated transfection. The analysis of drug-resistant colonies suggested the presence of the transcripted BChE mRNA in the cytoplasm of transfected cells. The secreted BChE protein in culture medium was assayed for enzyme activity using butyrylthiocholine as substrate. The genetically modified fibroblasts were mixed with rat tail collagen and transplanted subcutaneously and intraperitoneally to mice. Immunoreactive human BChE appeared in the plasma from the transplanted mice. reaching the top level at day 13. It was not present any longer in most of the mice 20 days later.

Animals↗
PubMed1999

Resveratrol inhibits copper ion-induced and azo compound-initiated oxidative modification of human low density lipoprotein.

To investigate whether resveratrol, a polyphenolic compound in red wine, affects the oxidation of human low density lipoprotein (LDL), LDL purified from normolipidemic subjects was subjected to Cu(2+)-induce and azo compound-initiated oxidative modification, with and without the addition of varying concentrations of resveratrol. Modification of LDL was assessed by the formation of thiobarbituric acid reactive substances (TBARS) and changes in the relative electrophoretic mobility (REM) of LDL on agarose gels. Resveratrol (50 microM) reduced TBARS and REM of LDL during Cu(2+)-induced oxidation by 70.5% and 42.3%, respectively (p < 0.01), and prolonged the lag phase associated with the oxidative modification of LDL by copper ion or azo compound. These in vitro results suggest that resveratrol may afford protection of LDL against oxidative damage resulting from exposure to various environmental challenges, possibly by acting as a free radical scavenger.

Amidines↗