Biomedical subjects

W Shen

Publications and source records attributed to W Shen.

At least 55 records · Page 3Linked to original sources

PubMed2001

[Application of computer image process to the research on the contact characteristics of subtalar joint].

With the use of computer image processing technology, a new method was proposed for studying the contact characteristics of the subtalar joint. The results showed the total subtalar articulation area was 9.52 +/- 0.40 cm2. On neutral position and under 600 N load, the contact area of the subtalar joint was 2.00 +/- 0.11 cm2. The contact area of the posterior articulation was significantly larger than that of the anterior and medial articulation (p < 0.01). The average contact pressure was 19.3 +/- 1.38 N, the force transmitted by the subtalar was 389.16 +/- 28.75 N, which accounted for about 64.86% of the applied shank load (600 N), and 69.39% of the force was transmitted by the posterior articulation. The posterior articulation plays an important role in the load. The fracture line of the calcaneus often appears in this area.

Adult↗

PubMed2001

Effects on gamma-aminobutyric acid (GABA)(A) receptors of a neuroactive steroid that negatively modulates glutamate neurotransmission and augments GABA neurotransmission.

Neurosteroids positively and negatively modulate gamma-aminobutyric acid (GABA)(A) receptors and glutamate receptors, which underlie most fast inhibition and excitation in the central nervous system. We report the identification of a neuroactive steroid, (3 alpha,5 beta)-20-oxo-pregnane-3-carboxylic acid (3 alpha 5 beta PC), with unique cellular actions. 3 alpha 5 beta PC positively modulates GABA(A) receptor function and negatively modulates N-methyl-D-aspartate (NMDA) receptor function, a combination that may be of particular clinical benefit. 3 alpha 5 beta PC promotes net GABA(A) potentiation at low steroid concentrations (<10 microM) and at negative membrane potentials. At higher concentrations, the steroid also blocks GABA receptors. Because this block would presumably counteract the NMDA receptor blocking actions of 3 alpha 5 beta PC, we characterize the GABA receptor block in some detail. Agonist concentration, depolarization, and high extracellular pH increase the block. The apparent pK for both potentiation and block was 6.4 to 6.9, substantially higher than expected from carboxylated steroid in an aqueous environment. Block is not dependent on the stereochemistry of the carboxylic acid at carbon 3 and is relatively insensitive to placement of the carboxylic acid at the opposite end of the steroid (carbon 24). Potentiation is critically dependent on the stereochemistry of the carboxylic acid group at carbon 3. Consistent with the pH dependence of potentiation, effects of the amide derivative (3 alpha,5 beta)-20-oxo-pregnane-3-carboxamide, suggest that the un-ionized form of 3 alpha 5 beta PC is important for potentiation, whereas the ionized form is probably responsible for block. Further refinement of the neuroactive steroid to promote GABA potentiation and NMDA receptor block and diminish GABA receptor block may lead to a clinically useful neuroactive steroid.

Animals↗

PubMed2001

[Clinical study on treatment 82 cases of chronic primary glomerulopathy with deficiency of yin with damp-heat symptom with dan shao tang].

OBJECTIVE: To investigate the treatment effect of Dan Shao Tang on chronic primary glomerulopathy with deficiency of Yin with damp-heat symptom. METHODS: 132 cases of chronic glomerulopathy with deficiency of Yin with damp-heat symptom, which divided into two groups at random, the 82 cases which were the therapy group using Dan Shao Tang and west medicine, and the other 50 cases which treated only by west medicine. We observed the effect and indexes change including renal function, proteinuria, hematuria. RESULTS: The effective rate of the therapy group is 90.24%, and the effective rate of the control group is 66% (P < 0.05), The therapy group is superior to the control group in improving renal function, decreasing proteinuria and hematuria in evidence(P < 0.05). CONCLUSION: Dan Shao Tang is effective to treatment on chronic primary glomerulopathy with deficiency of Yin with damp-heat symptom.

Adult↗

PubMed2001

Percutaneous transluminal stenting in patients with carotid artery stenosis.

OBJECTIVE: To assess the efficacy and safety of percutaneous transluminal stenting for patients with carotid artery stenosis. METHODS: Selective percutaneous transluminal stenting was performed for patients with symptomatic carotid artery stenosis (luminal narrowing > or = 70%). Success rates and complications associated with the procedures were observed. During six months of follow-up, both recurrent symptom and restenosis rates were recorded. RESULTS: There were 17 bifurcating lesions among 27 stenoses in 26 patients, of whom 18 had concomitant coronary artery diseases. The acute procedural success rate was 96.3% (26/27), and the degree of stenosis was reduced from 88.6% +/- 8.9% (range 70-100) to 0.4% +/- 2.0% (range 0-10). Six patients developed severe bradycardia and hypotension, and 3 experienced transient loss of consciousness during balloon dilatation. During hospitalization, 2 patients experienced loss of consciousness and convulsion, respectively, due to hyperperfusion, and both recovered 12 hours later. There were 2 minor stroke cases (7.4%) but no cases of major stroke or death. At the 6-month follow-up, there were no cases of TIA or new onset of stroke. There was no restenosis detected in 16 cases using angiography and in 10 cases using MRI in 6 to 16 months of follow-up. CONCLUSIONS: Percutaneous transluminal stenting for patients with carotid artery stenosis has a high procedural success rate with few and acceptable complications. Few patients suffered from recurrent symptoms or showed restenosis in long-term follow-up.

Aged↗

PubMed2001

Optimal timing of coronary stenting in unstable angina patients.

OBJECTIVE: To assess the efficacy and safety of intracoronary stenting in the acute phase of unstable angina pectoris (UAP). METHODS: Fifty-five patients with UAP were randomized to early (Group I, n = 29) and delayed interventional treatment (Group II, n = 26). Coronary angiography and stenting were performed within 48 hours in Group I and 7-10 days later in Group II. Procedural success rate, time interval from admission to angina relief and duration of hospitalization were recorded. Cardiac events within 30 days were observed as well. RESULTS: Clinical characteristics and angiographic features were similar between the two groups. There was no significant difference in the procedural success rate (93% versus 96%), but the cardiac event rate within 30 days was significantly lower in Group I than in Group II (0% versus 9.2%, P < 0.05). The time interval from admission to angina relief (4.4 +/- 3.1 days versus 5.7 +/- 2.9 days) and the duration of hospitalization (8.8 +/- 3.2 days versus 13.5 +/- 3.1 days) were significantly reduced in Group I (both P < 0.05). CONCLUSIONS: Intracoronary stent implantation is effective and safe in the acute phase of UAP. Early percutaneous coronary intervention results in rapid improvement in symptomatology and a shorter hospitalization. Its long-term effect has to be confirmed in a future randomized study.

Aged↗

PubMed2001

Intracoronary stent implantation under intracoronary ultrasound guidance with aspirin and ticlopidine therapy.

OBJECTIVE: To observe the immediate angiographic and intravascular ultrasound (IVUS) results and their effects on one month clinical outcomes in forty-one patients who submitted to coronary stent deployment with IVUS guidance. METHODS: All patients were allocated to coronary stent implantation with high inflation pressure. After good angiographic results (< 20% residual stenosis), all patients underwent IVUS and higher-pressure dilatation would be necessary if criteria for optimal coronary stent implantation were not met. The optimal criterion of IVUS for stent implantation was the ratio of intrastent lumen cross-sectional area to the average of the proximal and distal reference lumen cross-sectional areas > or = 80%. All patients had aspirin and ticlopidine therapy on the day of angioplasty and during the one month follow-up period. RESULTS: Optimal criteria of IVUS were obtained without any further intrastent dilatation in twenty-five patients but intrastent higher-pressure dilatation was performed in fourteen patients whose ultrasound results did not reach the criteria. In these patients, we increased the minimal intrastent lumen area 25.7% (P < 0.05). Thirty-five patients (90%) had good minimal intrastent lumen area of IVUS. There were no deaths, myocardial infarction, acute stent thrombosis or need for revascularization during the study and the one month follow-up. CONCLUSIONS: Intracoronary stent deployment under IVUS guidance, including combining aspirin and ticlopidine therapy, had beneficial ultrasound results and good clinical outcomes after one month follow-up.

Aged↗

PubMed2001

Relationship between age and effect of early and long-term captopril treatment in patients with acute myocardial infarction.

OBJECTIVE: To analyse the relationship between age and treatment with captopril after acute myocardial infarction (AMI). METHODS: In a randomized trial, 822 patients with a first AMI received conventional medical treatment, including intravenous thrombolytic therapy and oral aspirin or metoprolol, and then were randomly allocated to captopril [dosage from the first 6.25 mg to 25 mg/t.i.d, 209 younger patients (< or = 64 years), 269 elderly patients (65-75 years)] or conventional treatment only (131 younger patients, 213 elderly). Survival in the four groups was calculated with the Kaplan-Meier method. Multivariate analysis was performed to understand the degree that multi-variables (including age) affect survival in patients taking captopril in the hospital or during long term follow-up. RESULTS: The survival of patients who took captopril correlated significantly with age (P < 0.001). The survival of the elderly patients on captopril treatment did increase (P < 0.0001), but not of the younger ones (P > 0.05) during hospitalization. During follow-up, the survival of patients who took captopril correlated insignificantly with age (P > 0.05), but both the elderly and the younger patients have good survival rates (all P < 0.01) and lower cardiac events (all P < 0.01) when they took captopril. CONCLUSIONS: Captopril exerts a weak effect on the younger patients but a beneficial effect on the elderly patients during hospitalization after AMI. However, there is no difference between the younger and the elderly in the prognosis, both having good survival and lower cardiac events when they take captopril long term during follow-up.

Adult↗

PubMed2001

Heart rate variability and its response to thyroxine replacement therapy in patients with hypothyroidism.

OBJECTIVE: To analyze heart rate variability (HRV) and its changes with thyroxine treatment in patients with hypothyroidism. METHODS: HRV was analyzed using 24-hour electrocardiographic recording in 38 patients with hypothyroidism and 21 normal controls. The changes in HRV were evaluated for the 18 hypothyroid patients after 3 months of thyroxine therapy. RESULTS: The time domain measurements of HRV in hypothyroid patients were much lower than those in the control group. As to HRV frequency domain, the high frequency power was significantly higher, but the ratio of low frequency power to frequency power for hypothyroid patients was lower than in the controls. These abnormal changes of HRV measurements in hypothyroid patients were improved after treatment with thyroxine and were associated with recovery of serum concentrations of FT3 and FT4. CONCLUSIONS: Patients with hypothyroidism often have autonomic neuropathies with a higher level of vagal tone. These abnormalities could be partly improved by thyoxine therapy.

Adult↗

PubMed2000

Expression of functional formyl peptide receptors by human astrocytoma cell lines.

Activation of astrocytes is important in the pathogenesis of a variety of diseases in the central nervous system, such as infection and neurodegeneration. We found that the bacterial chemotactic peptide, N-formyl-methionyl-leucyl-phenylalanine (fMLF) induced potent migration and Ca(2+) mobilization in human astrocytoma cell lines. The effect of fMLF was pertussis toxin-sensitive, suggesting the involvement of seven transmembrane, G protein-coupled receptor(s) for fMLF. Scatchard analyses revealed that astrocytoma cell lines express both high- and low-affinity binding sites for [3H]fMLF. RT-PCR confirmed the expression of transcripts of fMLF receptors, the high-affinity FPR and the low-affinity FPRL1 by these cells. Both fMLF and F peptide, a synthetic peptide domain of HIV-1 envelope protein which specifically activates FPRL1, increased secretion of IL-6 by astrocytoma cells. Our study demonstrates for the first time that FPR and FPRL1 expressed by astrocytoma cell lines are functional, and suggests a molecular basis for the involvement of these receptors in host defense in the brain.

Astrocytoma↗

PubMed2000

Down-regulation of the chemokine receptor CCR5 by activation of chemotactic formyl peptide receptor in human monocytes.

Interactions between cell surface receptors are important regulatory elements in the complex host responses to infections. In this study, it is shown that a classic chemotactic factor, the bacterial chemotactic peptide N-formyl-methionyl-leucylphenyl-alanine (fMLF), rapidly induced a protein-kinase-C-mediated serine phosphorylation and down-regulation of the chemokine receptor CCR5, which serves as a major human immunodeficiency virus (HIV)-1 coreceptor. The fMLF binding to its receptor, formyl peptide receptor (FPR), resulted in significant attenuation of cell responses to CCR5 ligands and in inhibition of HIV-1-envelope-glycoprotein-mediated fusion and infection of cells expressing CD4, CCR5, and FPR. The finding that the expression and function of CCR5 can be regulated by peptides that use an unrelated receptor may provide a novel approach to the design of anti-inflamatory and antiretroviral agents. (Blood. 2000;96:2887-2894)

Anti-HIV Agents↗

PubMed2000

Gating of inward rectifier K+ channels by proton-mediated interactions of N- and C-terminal domains.

Ion channels play an important role in cellular functions, and specific cellular activity can be produced by gating them. One important gating mechanism is produced by intra- or extracellular ligands. Although the ligand-mediated channel gating is an important cellular process, the relationship between ligand binding and channel gating is not well understood. It is possible that ligands are involved in the interactions of different protein domains of the channel leading to opening or closing. To test this hypothesis, we studied the gating of Kir2.3 (HIR) by intracellular protons. Our results showed that hypercapnia or intracellular acidification strongly inhibited these channels. This effect relied on both the N and C termini. The CO(2)/pH sensitivities were abolished or compromised when one of the intracellular termini was replaced. Using purified N- and C-terminal peptides, we found that the N and C termini bound to each other in vitro. Although their binding was weak at pH 7.4, stronger binding was seen at pH 6.6. Two short sequences in the N and C termini were found to be critical for the N/C-terminal interaction. Interestingly, there was no titratable residue in these motifs. To identify the potential protonation sites, we systematically mutated most histidine residues in the intracellular N and C termini. We found that mutations of several histidine residues in the C but not the N terminus had a major effect on channel sensitivities to CO(2) and pH(i). These results suggest that at acidic pH, protons appear to interact with the C-terminal histidine residues and present the C terminus to the N terminus. Consequentially, these two intracellular termini bound to each other through two short motifs and closed the channel. Thus, a novel mechanism for K(+) channel gating is demonstrated, which involves the N- and C-terminal interaction with protons as the mediator.

Amino Acid Motifs↗

PubMed2000

Synthesis of 1,3-diynes via palladium-catalyzed reaction of 1, 1-dibromo-1-alkenes.

[reaction: see text] Both symmetric and unsymmetric 1,3-diynes were prepared from the palladium-catalyzed reaction of 1,1-dibromo-1-alkenes. The formation of symmetric 1,3-diynes 2 (homocoupling) was catalyzed by a weak ligand, tris(2-furyl)phosphine (TFP), and the addition of catalytic amount of CuI accelerated the reaction. The synthesis of unsymmetric 1,3-diynes 4 (the Sonogashira reaction) required a highly electron rich tris(4-methoxyphenyl)phosphine as the ligand, and CuI promotes the formation of byproduct 1,1-diynyl-1-alkenes 5.

Journal Article↗

PubMed2000

Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH.

CO2 chemoreception may be related to modulation of inward rectifier K+ channels (Kir channels) in brainstem neurons. Kir4.1 is expressed predominantly in the brainstem and inhibited during hypercapnia. Although the homomeric Kir4.1 only responds to severe intracellular acidification, coexpression of Kir4.1 with Kir5.1 greatly enhances channel sensitivities to CO2 and pH. To understand the biophysical and molecular mechanisms underlying the modulation of these currents by CO2 and pH, heteromeric Kir4. 1-Kir5.1 were studied in inside-out patches. These Kir4.1-Kir5.1 currents showed a single channel conductance of 59 pS with open-state probability (P(open)) approximately 0.4 at pH 7.4. Channel activity reached the maximum at pH 8.5 and was completely suppressed at pH 6.5 with pKa 7.45. The effect of low pH on these currents was due to selective suppression of P(open) without evident effects on single channel conductance, leading to a decrease in the channel mean open time and an increase in the mean closed time. At pH 8.5, single-channel currents showed two sublevels of conductance at approximately 1/4 and 3/4 of the maximal openings. None of them was affected by lowering pH. The Kir4.1-Kir5.1 currents were modulated by phosphatidylinositol-4,5-bisphosphate (PIP2) that enhanced baseline P(open) and reduced channel sensitivity to intracellular protons. In the presence of 10 microM PIP2, the Kir4.1-Kir5.1 showed a pKa value of 7.22. The effect of PIP2, however, was not seen in homomeric Kir4.1 currents. The CO2/pH sensitivities were related to a lysine residue in the NH2 terminus of Kir4.1. Mutation of this residue (K67M, K67Q) completely eliminated the CO2 sensitivity of both homomeric Kir4.1 and heteromeric Kir4.1-Kir5.1. In excised patches, interestingly, the Kir4.1-Kir5.1 carrying K67M mutation remained sensitive to low pHi. Such pH sensitivity, however, disappeared in the presence of PIP2. The effect of PIP2 on shifting the titration curve of wild-type and mutant channels was totally abolished when Arg178 in Kir5.1 was mutated. Thus, these studies demonstrate a heteromeric Kir channel that can be modulated by both acidic and alkaline pH, show the modulation of pH sensitivity of Kir channels by PIP2, and provide information of the biophysical and molecular mechanisms underlying the Kir modulation by intracellular protons.

Animals↗

PubMed2000

Kinetic, thermodynamic, and developmental consequences of deleting creatine kinase isoenzymes from the heart. Reaction kinetics of the creatine kinase isoenzymes in the intact heart.

Creatine kinase (CK) exists as a family of isoenzymes in excitable tissue. We studied isolated perfused hearts from mice lacking genes for either the main muscle isoform of CK (M-CK) or both M-CK and the main mitochondrial isoform (Mt-CK) to determine 1) the biological significance of CK isoenzyme shifts, 2) the necessity of maintaining a high CK reaction rate, and 3) the role of CK isoenzymes in establishing the thermodynamics of ATP hydrolysis. (31)P NMR was used to measure [ATP], [PCr], [P(i)], [ADP], pH, as well as the unidirectional reaction rate of PCr--> [gamma-P]ATP. Developmental changes in the main fetal isoform of CK (BB-CK) were unaffected by loss of other CK isoenzymes. In hearts lacking both M- and Mt-CK, the rate of ATP synthesis from PCr was only 9% of the rate of ATP synthesis from oxidative phosphorylation demonstrating a lack of any high energy phosphate shuttle. We also found that the intrinsic activities of the BB-CK and the MM-CK isoenzymes were equivalent. Finally, combined loss of M- and Mt-CK (but not loss of only M-CK) prevented the amount of free energy released from ATP hydrolysis from increasing when pyruvate was provided as a substrate for oxidative phosphorylation.

Adenosine Triphosphate↗

PubMed2000

Activation of the chemotactic peptide receptor FPRL1 in monocytes phosphorylates the chemokine receptor CCR5 and attenuates cell responses to selected chemokines.

FPRL1 is a seven-transmembrane (STM), G-protein coupled receptor which was originally identified as a low affinity receptor for the bacterial chemotactic formyl peptide and a high affinity receptor for the lipid metabolite lipoxin A4. We recently discovered that a number of peptides, including several synthetic domains of the HIV-1 envelope proteins and the serum amyloid A, use FPRL1 to induce migration and calcium mobilization in human monocytes and neutrophils. In this study, we report that a synthetic peptide domain of the V3 region of the HIV-1 envelope gp120, activates the FPRL1 receptor in monocytes and neutrophils. Furthermore, monocytes prestimulated with V3 peptide showed reduced response to several chemokines that use multiple cell receptors. This is associated with a rapid phosphorylation of the chemokine receptor CCR5 on the serine residues. Our study suggests that FPRL1, as a classical chemoattractant receptor, may play an important role in modulating monocyte activation in the presence of multiple stimuli.

Amino Acid Sequence↗

PubMed2000

Pregnenolone sulfate modulates inhibitory synaptic transmission by enhancing GABA(A) receptor desensitization.

We examined the effects of the neurosteroid pregnenolone sulfate (PS) on GABA(A) receptor-mediated synaptic currents and currents elicited by rapid applications of GABA onto nucleated outside-out patches in cultured postnatal rat hippocampal neurons. At 10 microm, PS significantly depressed peak responses and accelerated the decay of evoked inhibitory synaptic currents. In nucleated outside-out patches, PS depressed peak currents and speeded deactivation after 5 msec applications of a saturating concentration of GABA. PS also increased the rate and degree of macroscopic GABA receptor desensitization during prolonged GABA applications. In a paired GABA application paradigm, PS slowed the rate of recovery from desensitization. In contrast to its prominent effects on currents produced by saturating GABA concentrations, PS had only small effects on peak currents and failed to alter deactivation after brief applications of the weakly desensitizing GABA(A) receptor agonists taurine and beta-alanine. However, when beta-alanine was applied for a sufficient duration to promote receptor desensitization, PS augmented macroscopic desensitization and slowed deactivation. These results suggest that PS inhibits GABA-gated chloride currents by enhancing receptor desensitization and stabilizing desensitized states. This contention is supported by kinetic modeling studies in which increases in the rate of entry into doubly liganded desensitized states mimic most effects of PS.

Animals↗

PubMed2000

Prestin is the motor protein of cochlear outer hair cells.

The outer and inner hair cells of the mammalian cochlea perform different functions. In response to changes in membrane potential, the cylindrical outer hair cell rapidly alters its length and stiffness. These mechanical changes, driven by putative molecular motors, are assumed to produce amplification of vibrations in the cochlea that are transduced by inner hair cells. Here we have identified an abundant complementary DNA from a gene, designated Prestin, which is specifically expressed in outer hair cells. Regions of the encoded protein show moderate sequence similarity to pendrin and related sulphate/anion transport proteins. Voltage-induced shape changes can be elicited in cultured human kidney cells that express prestin. The mechanical response of outer hair cells to voltage change is accompanied by a 'gating current', which is manifested as nonlinear capacitance. We also demonstrate this nonlinear capacitance in transfected kidney cells. We conclude that prestin is the motor protein of the cochlear outer hair cell.

Amino Acid Sequence↗

PubMed2000

Investigation of the radial compression of carbon nanotubes with a scanning probe microscope

Efforts have been made to characterize the mechanical properties of carbon nanotubes. Previous work has concentrated on the tubes' longitudinal properties, and studies of their radial properties have lagged behind. We have used a scanning probe microscope with an indentation/scratch function to investigate the radial compression of multiwalled carbon nanotubes under an asymmetric stress. In particular, we have determined the radial compressive elastic modulus at different compression levels and have estimated the compressive strength to be well beyond 5.3 GPa.

Journal Article↗