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Biomedical subjects

H Yang

Publications and source records attributed to H Yang.

At least 253 records · Page 14Linked to original sources
PubMed2001

[The intraoperative application of neural response telemetry with the nucleus CI24M cochlear implant].

OBJECTIVE: To test device integrity and objective auditory reaction for cochlear implant patients intraoperatively. METHODS: Our protocol for intraoperative testing of the implant device includes device electrode impedance test and neural response telemetry (NRT), which measures the electrically evoked auditory nerve compound action potentials (ECAP). RESULTS: We completed electrode integrity tests and NRT intraoperatively on 40 patients with the Nucleus CI24M cochlear implant. We have measured normal implant function on all 40 patients and obtained ECAP results from 39 patients. Out of 33 patients with normal inner ear, typical ECAPs were recorded in 195 electrodes in all 198 testing electrodes(98.5%). In 7 patients with inner ear Mondini dysphasia, affirmative ECAP waveforms were recorded in 26 electrodes in all 42 testing electrodes. The basal electrode ECAP threshold was higher than that of the epical one. CONCLUSIONS: The intraoperative measurements of device function and NRT are quite simple, quick and with high accuracy. Inner ear malformation is an important factor that may affect NRT results.

Action Potentials↗
PubMed2001

[Combined interleukin-2 and herpes simplex virus thymidine kinase gene therapy for head and neck squamous cell carcinoma].

OBJECTIVE: To assess the efficacy of combined interleukin-2 (IL-2) and herpes simplex virus thymidine kinase (HSV-TK) gene therapy for murine head and neck squamous cell carcinoma (HNSCC). METHODS: Ad IL-2 or/and Ad HSV-TK were injected into the tumor tissues directly after the murine HNSCC model was established. DL312 or PBS was used as control and ganciclovir (GCV) was used at 25 mg/kg for 7 days in Ad HSV-TK gene treatment groups. Tumor size was measured before and after treatment to evaluate the response to treatment. Cytotoxic T-lymphocyte (CTL) and natural killer (NK) assays were performed and IL-2 expressions were also measured after IL-2 gene transfection. RESULTS: HNSCC tumor growth was significantly inhibited following combined IL-2 and HSV-TK gene therapy as compared to other groups (P < 0.05). Increased levels of IL-2 protein expression was found in combined and single IL-2 treated groups. The combination and IL-2 treated groups produced greater activities of CTL and NK than that of the controls. CONCLUSION: IL-2 gene therapy can efficiently induce antitumor immunity of the host and enhance antitumor effects of HSV-TK. Combined IL-2 and HSV-TK gene therapy could significantly inhibit HNSCC tumor growth in the murine model.

Animals↗
PubMed2001

[Expression of P21 WAF1/CIP1 in human astrocytomas in correlating with P53, MDM2, and cellular proliferation index].

OBJECTIVE: To study the correlation between the expression of p21, p53, MDM2 gene products and the initiation and progression of human astrocytomas. METHODS: The expression of P21, P53, MDM2, and proliferative cell nuclear antigen (PCNA) labeling index using immunohistochemistry in 41 paraffin embedded human astrocytoma samples. As well as the expression of p21 mRNA using mRNA in situ hybridization in 24 fresh human astrocytoma samples stored at -70 degrees C were investigated. In immunohistochemistry, we divided whole tumor cells by positive tumor cell nuclei to obtain labeling index (LI), in this way we could understand the protein product expression of gene in astrocytoma in different patients. In mRNA in situ hybridization, the expression of p21 mRNA was scored according to the rough percentage of positive cells. RESULTS: In p21 mRNA in situ hybridization, the positive staining was present in 87.5%. In immunohistochemistry, positive P21, P53, MDM2, and PCNA staining were presented in 75.6%, 68.3%, 65.9%, 100% respectively. Higher levels of P21 protein expression were seen in higher histological grade (P = 0.001). The association between P21 expression positively correlated with proliferation index. But not with P53 expression and MDM2 expression. The association between P53 expression and proliferation indices were statistically significant, but the expression of P53 was not related to tumor grade. There was no association between MDM2 expression and grade, or cellular proliferation index. Linear stepwise regression analysis showed the parameters affecting tumor grade were PCNA LI (P = 0.000) and P21 LI (P = 0.001). CONCLUSIONS: (1) Both p21 mRNA and P21 protein were overexpressed in human astrocytomas, the overexpression was related to cellular proliferation index, but was not related to P53 expression, suggesting there could be P53-independent pathway to induce the P21 expression, in addition, the overexpression of P21 alone appeared insufficient to suppress tumor growth, provided the participation of PCNA. (2) The expression of P53 protein was associated with proliferation indices, but was not with the tumor malignancy, this indicated that the inactivation of P53 might be the early event in the growth of human astrocytomas. (3) P21 labeling index and cellular proliferation index influenced the tumor histological grade, our data indicated that p21 gene might play a role in the progression of human astrocytomas.

Adolescent↗
PubMed2001

[Raman spectra of Cu/Zn superoxide dismutase and L-cysteine used as an electron transfer promoter].

In author's laboratory, it has been demonstrated with electrochemical techniques that L-cysteine can be used as an effective electron transfer promoter to accelerate the electron transfer process of Cu/Zn superoxide dismutase on gold electrode. In order to reveal the mechanism of this promotion, confocal microscopic Raman spectroscopic technique is employed here to obtain Raman spectra of solid state SOD and L-cysteine modified gold electrode. Moreover, Raman spectra of L-cysteine modified gold electrode with two different approaches are also obtained. Analysis and discussion for these Raman spectra are reported.

Cysteine↗
PubMed2001

[Maximal entropy principle wavelet denoising].

In the filed of wavelet denoising, an essential problem is how to determine the cutting threshold of wavelet coefficients that divides the coefficients corresponding to signal and noise respectively. The wavelet denoising method discussed here determines this threshold by using the maximal entropy principle (MEP) of information theory. From the basic principle of probability theory, it can be deduced that the detailed wavelet coefficients sequence of an arbitrary distributed random noise sequence satisfies a normal distribution. Based on this conclusion, an optimal threshold is determined using MEP. Such that the coefficients whose absolute values are less than the threshold satisfies a normal probabilistic distribution. This threshold is an optimal value that distinguishes the wavelet coefficients of signal and noise in view of statistics. The simulation analysis using spectral data and the comparison with other methods showed that this method provides a best improvement of signal-to-noise ratio, and its performance is least sensitive to the change of signal-to-noise ratio.

Algorithms↗
PubMed2001

[Clinical study on the efficacy of tranexamic acid in reducing postpartum blood lose: a randomized, comparative, multicenter trial].

OBJECTIVE: To study the efficacy and safety of Transamin (tranexamic acid) in reducing postpartum blood loss. METHODS: Four hundred primipara with term singleton pregnancy, vertex presentation, spontaneous delivery were enrolled. Ten U Oxytocin was injected intravenously immediately after the delivery of fetal shoulders in the second stage of labor. Then all the puerperants were randomly assigned to 4 groups. Group I (n = 94): Transamin 1.0 g was injected i.v.; Group lI (n = 92): Transamin 0.5 g i.v.; Group III (n = 92): aminomethylbenzoic acid 0.5 g i.v. was given; Group IV (n = 87): no treatment. Vaginal bleeding was precisely collected, and examined immediately after the expulsion of placenta and from placenta expulsion till 2 hours after delivery. The amount of blood loss was measured by both methods of weight and volume. RESULTS: There were no significant differences of blood loss immediately after the expulsion of placenta among the 4 groups (P > 0.05). For the average blood loss at 2 hour postpartum, it was 129.7 ml, 133.9 ml, 168.5 ml and 178.2 ml for group I, II, II and IV respectively, while the total blood loss for the 4 groups was 243.3 ml, 242.9 ml, 308.1 ml, and 314.8 ml respectively. The average blood loss of group I and II was significantly less than group III and IV (P < 0.01), however, there was no significant difference between group I and group II (P > 0.05). The occurrences of postpartum hemorrhage (blood lose > or = 400 ml) were 6.4%, 13.3%, 20.7% and 25.3% for group I, II, III and IV respectively. There was no major adverse effects appeared. CONCLUSIONS: Transamin is efficient and safe in reducing the postpartum blood loss. 1.0 g of Transamin has the best efficacy, and 0.5 g of Transamin followed.

Antifibrinolytic Agents↗
PubMed2001

[The role of cell junction in hypothermic impairment of tissue].

OBJECTIVE: To investigate the role of cell junction in the hypothermal impairment of tissue without any cryoprotectant. METHODS: Epithelial MDCK cell line which is able to form well-defined cell junctions after confluency, and fibroblast V79 cell line which is unable to be used for graded freezing experiments, either in suspension, single tough attached to flasks or as monolayers on flasks. Then the viability was assessed by WST-1 and MT, respectively. RESULTS: The results of viability of the two types of cells assessed by WST-1 were well-fitted with that of MTT. The recovery of the two types of cells in suspension was higher than that of single tough group and monolayer group. The single tough group of MDCK had a higher recovery than did the monolayer group. At the same time, such tendency was not observed on V79 cells. As compared with V79 monolayers, lower recovery was found on MDCK monolayers. CONCLUSIONS: The junction between cells and the adhesion between cell and matrix have important roles in the hypothermic impairment of tissue. Their existence affect the recovery of cells under hypothermia. The cytoskeleton system may contribute to the impairment caused by junctions.

Animals↗
PubMed2000

Role of vagus nerve signaling in CNI-1493-mediated suppression of acute inflammation.

CNI-1493 is a potent anti-inflammatory agent, which deactivates macrophages and inhibits the synthesis of proinflammatory mediators. The objective of the present study was to identify the role of the central nervous system (CNS) and efferent vagus nerve signaling in CNI-1493-mediated modulation of acute inflammation in the periphery. CNI-1493 was administered either intracerebroventricularly (i.c.v., 0.1-1,000 ng/kg) or intravenously (i.v., 5 mg/kg) in anesthetized rats subjected to a standard model of acute inflammation (subcutaneous (s.c.) injection of carrageenan). I.c.v. CNI-1493 significantly suppressed carrageenan-induced paw edema, even in doses at least 6-logs lower than those required for a systemic effect. Bilateral cervical vagotomy or atropine blockade (1 mg/kg/h) abrogated the anti-inflammatory effects of CNI-1493 (1 microg/kg, i.c.v. or 5 mg/kg, i.v.), indicating that the intact vagus nerve is required for CNI-1493 activity. Recording of the efferent vagus nerve activity revealed an increase in discharge rate starting at 3-4 min after CNI-1493 administration (5 mg/kg, i.v.) and lasting for 10-14 min (control activity=87+/-5.4 impulses/s versus CNI-1493-induced activity= 229+/-6.7 impulses/s). Modulation of efferent vagus nerve activity by electrical stimulation (5 V, 2 ms, 1 Hz) of the transected peripheral vagus nerve for 20 min (10 min before carrageenan administration and 10 min after) also prevented the development of acute inflammation. Local administration of the vagus nerve neurotransmitter, acetylcholine (4 microg/kg, s.c.), or cholinergic agonists into the site of carrageenan-injection also inhibited acute inflammation. These results now identify a previously unrecognized role of efferent vagus nerve activity in mediating the central action of an anti-inflammatory agent.

Acetylcholine↗
PubMed2000

Stabilization and productive positioning roles of the C2 domain of PTEN tumor suppressor.

PTEN is a tumor suppressor frequently inactivated in brain, prostate, and uterine cancer. It acts as a phosphoinositide phosphatase and consists of an amino-terminal phosphatase domain tightly linked to a COOH-terminal C2 domain involved in lipid membrane-binding. We investigated the functions of the C2 domain and their relevance for tumor growth. To discriminate between PTEN C2 domain ability to recruit or to position the active site to the membrane, we artificially membrane-targeted PTEN by a myristoylation signal. This modification increased wild-type PTEN growth inhibition but did not rescue a C2 mutant defective in lipid-binding, suggesting a model in which PTEN C2 domain positions the active site productively with respect to the membrane-bound phosphoinositide substrate. When tumor-derived mutations in the loops that connect the C2 beta-strands were analyzed, we found that these generally destabilized the protein but had variable effects on the phosphatase activity and tumor growth. The magnitude of these effects was dependent on the presence of the COOH-terminal PEST sequences and on the cell type where the mutant proteins were expressed, suggesting the existence of fluctuating structural defects of the mutant protein. One of the C2 loop mutants induced a total loss of PTEN tumor-suppressor function, most likely by affecting both the membrane binding and the protein stability. These data support a double role for PTEN C2 domain in protein stability and in productive orientation of the catalytic site.

Binding Sites↗
PubMed2000

Region-specific differentiation of neural tube-derived neuronal restricted progenitor cells after heterotopic transplantation.

Spinal cord neuronal restricted progenitor (NRP) cells, when transplanted into the neonatal anterior forebrain subventricular zone, migrate to distinct regions throughout the forebrain including the olfactory bulb, frontal cortex, and occipital cortex but not to the hippocampus. Their migration pattern and differentiation potential is distinct from anterior forebrain subventricular zone NRPs. Irrespective of their final destination, NRP cells do not differentiate into glia. Rather they synthesize neurotransmitters, acquire region-specific phenotypes, and receive synapses from host neurons after transplantation. Spinal cord NRPs express choline acetyl transferase even in regions where host neurons do not express this marker. The restricted distribution of transplanted spinal cord NRP cells and their acquisition of varied region-specific phenotypes suggest that their ultimate fate and phenotype is dictated by a combination of intrinsic properties and extrinsic cues from the host.

Animals↗
PubMed2000

A highly specific monomeric isocitrate dehydrogenase from Corynebacterium glutamicum.

The monomeric isocitrate dehydrogenase (IDH) of Corynebacterium glutamicum is compared to the topologically distinct dimeric IDH of Escherichia coli. Both IDHs have evolved to efficiently catalyze identical reactions with similar pH optimum as well as striking specificity toward NADP and isocitrate. However, the monomeric IDH is 10-fold more active (calculated as kcat/Km.isocitrate/Km.NADP) and 7-fold more NADP-specific than the dimeric enzyme, favoring NADP over NAD by a factor of 50,000. Such an extraordinary coenzyme specificity is not rivaled by any other characterized dehydrogenases. In addition, the monomeric enzyme is 10-fold more specific for isocitrate. The spectacular substrate specificity may be predominantly attributed to the isocitrate-assisted stabilization of catalytic complex during hydride transfer. No significant overall sequence identity is found between the monomeric and dimeric enzymes. However, structure-based alignment leads to the identification of three regions in the monomeric enzyme that match closely the three motifs located in the central region of dimeric IDHs and the homologous isopropylmalate dehydrogenases. The role of Lys253 as catalytic residue has been demonstrated by site-directed mutagenesis. Our results suggest that monomeric and dimeric forms of IDHs are functionally and structurally homologous.

Alcohol Oxidoreductases↗
PubMed2000

Mechanism and significance of increased glutathione level in human hepatocellular carcinoma and liver regeneration.

Increased glutathione (GSH) level occurs early during liver regeneration and in many drug and/or radiation-resistant tumors. Whether GSH level is elevated in liver cancer is unknown. GSH levels and expression of GSH synthetic enzymes were measured in hepatocellular carcinoma (HCC) and normal liver. GSH levels doubled in HCC. The mRNA levels of g-glutamylcysteine synthetase heavy subunit (GCS-HS) and GSH synthetase (GS) doubled, whereas the expression of GCS light subunit was unchanged. Nuclear run-on assay showed that the rate of gene transcription doubled for both GCS-HS and GS. In HCC, there is increased binding to anti-oxidant response, AP-1 and NF-kB, three cis-acting elements in the 5'-flanking region of the human GCS-HS important for its transcriptional regulation. The role of GSH in cell growth was examined by using HepG2 cells. Cell GSH level was varied by treating cells with cystine (0 to 0.2 mM) with or without GSH ester or buthionine sulfoximine. Cell GSH level correlated directly with growth rate. Finally, preventing the increase in GSH after two-thirds partial hepatectomy blunted liver regeneration. Thus, GSH level is increased during liver growth as a result of up-regulation of GCS-HS and GS. This increase, in turn, facilitates growth.

Antioxidants↗
PubMed2000

Sexual dysfunction in the elderly patient.

With the aging population, the primary care physician will frequently encounter elderly patients with sexual dysfunction. The majority of older patients desire to maintain their sexual activity without significant decline. Age-related physiologic changes include the slower progression of the sexual response cycle. Medical illnesses and medications, as well as cultural, societal, and psychological factors, also impact sexual function. Reassurance and counseling about modifications in sexual practices are usually well received. Medical and surgical therapies are also available. Because sexual function represents a vital issue in an individual's quality of life, the obstetrician/gynecologist must be well versed in the evaluation and treatment of sexual dysfunction of the elderly patient.

Journal Article↗
PubMed2000

New diarylmethylpiperazines as potent and selective nonpeptidic delta opioid receptor agonists with increased In vitro metabolic stability.

Nonpeptide delta opioid agonists are analgesics with a potentially improved side-effect and abuse liability profile, compared to classical opioids. Andrews analysis of the NIH nonpeptide lead SNC-80 suggested the removal of substituents not predicted to contribute to binding. This approach led to a simplified lead, N, N-diethyl-4-[phenyl(1-piperazinyl)methyl]benzamide (1), which retained potent binding affinity and selectivity to the human delta receptor (IC(50) = 11 nM, mu/delta = 740, kappa/delta > 900) and potency as a full agonist (EC(50) = 36 nM) but had a markedly reduced molecular weight, only one chiral center, and increased in vitro metabolic stability. From this lead, the key pharmacophore groups for delta receptor affinity and activation were more clearly defined by SAR and mutagenesis studies. Further structural modifications on the basis of 1 confirmed the importance of the N, N-diethylbenzamide group and the piperazine lower basic nitrogen for delta binding, in agreement with mutagenesis data. A number of piperazine N-alkyl substituents were tolerated. In contrast, modifications of the phenyl group led to the discovery of a series of diarylmethylpiperazines exemplified by N, N-diethyl-4-[1-piperazinyl(8-quinolinyl)methyl]benzamide (56) which had an improved in vitro binding profile (IC(50) = 0.5 nM, mu/delta = 1239, EC(50) = 3.6 nM) and increased in vitro metabolic stability compared to SNC-80.

Animals↗
PubMed2000

N,N-Diethyl-4-(phenylpiperidin-4-ylidenemethyl)benzamide: a novel, exceptionally selective, potent delta opioid receptor agonist with oral bioavailability and its analogues.

The design, synthesis, and pharmacological evaluation of a novel class of delta opioid receptor agonists, N, N-diethyl-4-(phenylpiperidin-4-ylidenemethyl)benzamide (6a) and its analogues, are described. These compounds, formally derived from SNC-80 (2) by replacing the piperazine ring with a piperidine ring containing an exocyclic carbon carbon double bond, were found to bind with high affinity and exhibit excellent selectivity for the delta opioid receptor as full agonists. 6a, the simplest structure in the class, exhibited an IC(50) = 0.87 nM for the delta opioid receptors and extremely high selectivity over the mu receptors (mu/delta = 4370) and the kappa receptors (kappa/delta = 8590). Rat liver microsome studies on a selected number of compounds show these olefinic piperidine compounds (6) to be considerably more stable than SNC-80. This novel series of compounds appear to interact with delta opioid receptors in a similar way to SNC-80 since they demonstrate similar SAR. Two general approaches have been established for the synthesis of these compounds, based on dehydration of benzhydryl alcohols (7) and Suzuki coupling reactions of vinyl bromide (8), and are herewith reported.

Administration, Oral↗
PubMed2000

Inositol-1-phosphate synthase from Archaeoglobus fulgidus is a class II aldolase.

A gene putatively identified as the Archaeoglobus fulgidus inositol-1-phosphate synthase (IPS) gene was overexpressed to high level (about 30-40% of total soluble cellular proteins) in Escherichia coli. The recombinant protein was purified to homogeneity by heat treatment followed by two column chromatographic steps. The native enzyme was a tetramer of 168 +/- 4 kDa (subunit molecular mass of 44 kDa). At 90 degrees C the K(m) values for glucose-6-phosphate and NAD(+) were estimated as 0.12 +/- 0.04 mM and 5.1 +/- 0.9 microM, respectively. Use of (D)-[5-(13)C]glucose-6-phosphate as a substrate confirmed that the stereochemistry of the product of the IPS reaction was L-myo-inositol-1-phosphate. This archaeal enzyme, with the highest activity at its optimum growth temperature among all IPS reported (k(cat) = 9.6 +/- 0.4 s(-1) with an estimated activation energy of 69 kJ/mol), was extremely heat stable. However, the most unique feature of A. fulgidus IPS was that it absolutely required divalent metal ions for activity. Zn(2+) and Mn(2+) were the best activators with K(D) approximately 1 microM, while NH(4)(+) (a critical activator for all the other characterized IPS enzymes) had no effect on the enzyme. These properties suggested that this archaeal IPS was a class II aldolase. In support of this, stoichiometric reduction of NAD(+) to NADH could be followed spectrophotometrically when EDTA was present along with glucose-6-phosphate.

Aldehyde-Lyases↗
PubMed2000

Inducers of gamma-glutamylcysteine synthetase and their effects on glutathione synthetase expression.

Synthesis of GSH occurs via two enzymatic steps, the first is catalyzed by gamma-glutamylcysteine synthetase (GCS) and the second is catalyzed by GSH synthetase (GS). A heavy (HS) and light subunit (LS) make up GCS; regulation of both subunits have been well characterized, whereas regulation of GS is largely unknown. In this study, we examined the effects of treatments known to influence the gene expression of GCS subunits on GS expression. Insulin and hydrocortisone treatment of rat hepatocytes or ethanol-feeding of rats for 9 weeks, which increased the expression of GCS-HS only, had no influence on GS expression. However, two-thirds partial hepatectomy in rats which increased the expression of GCS-HS only, also increased GS expression. Treatment of hepatocytes or rats with diethyl maleate, buthionine sulfoximine, tert-butylhydroquinone, or thioacetamide, which increased the expression of both GCS subunits, increased the expression of GS. The GSH synthesis capacity increased 50-100% by treatments that increased only the GCS-HS expression, whereas it increased 161-200% by treatments that increased both GCS-HS and GS expression. Thioacetamide treatment of Chang cells increased cell GSH and GS expression by 50%, but had minimal influence on GCS subunits. Thus, GS induction can further increase the cell's GSH synthetic capacity and in some cells may be as important as GCS in determining the rate of GSH synthesis.

Animals↗