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Biomedical subjects

H Sun

Publications and source records attributed to H Sun.

At least 145 records · Page 8Linked to original sources
PubMed2000

Supraspinal cholecystokinin may drive tonic descending facilitation mechanisms to maintain neuropathic pain in the rat.

Complete or partial spinal section at T(8) has been shown to block tactile allodynia but not thermal hyperalgesia following L(5)/L(6) spinal nerve ligation (SNL), suggesting the supraspinal integration of allodynia in neuropathic pain. In the present study, the possibility of mediation of nerve injury-associated pain through tonic activity of descending nociceptive facilitation arising from the rostroventromedial medulla (RVM) was investigated. Specifically, the actions of brainstem cholecystokinin and the possible importance of sustained afferent input from injured nerve fibers were determined using pharmacological and physiological approaches in rats with SNL. Lidocaine given bilaterally into the RVM blocked tactile allodynia and thermal hyperalgesia in SNL rats and was inactive in sham-operated rats. Bilateral injection of L365,260 (CCK(B) receptor antagonist) into the RVM also reversed both tactile allodynia and thermal hyperalgesia. Microinjection of CCK-8 (s) into the RVM of naive rats produced a robust tactile allodynic effect and a more modest hyperalgesia. CCK immunoreactivity was not significantly different between SNL and sham-operated rats. The anti-nociceptive effect of morphine given into the ventrolateral periaqueductal gray region (PAG) was substantially reduced by SNL. The injection of L365,260 into the RVM or of bupivacaine at the site of nerve injury restored the potency and efficacy of PAG morphine in SNL rats. These results suggest that changes in supraspinal processing are likely to contribute to the observed poor efficacy of opioids in clinical states of neuropathic pain. These data also indicate that the activation of descending nociceptive facilitatory pathways is important in the maintenance of neuropathic pain, appears to be dependent on CCK release, and may be driven from sustained afferent input from injured nerves to brainstem sites. Collectively, these data support the hypothesis that abnormal tonic activity of descending facilitation mechanisms may underlie chronic pain from peripheral nerve injury.

Anesthetics, Local↗
PubMed2000

Activation effects of single-site and dual-site right atrial pacing in canine.

Medical therapy for managing atrial fibrillation remains less than satisfactory. Electrical therapy such as right atrial (RA) pacing was shown to reduce rate of recurrence of atrial fibrillation, while evidently dual-site pacing was more effective than single-site pacing. However, similarities and/or differences in the electrophysiological consequences of single-site and dual-site RA pacing are unclear. Our objective was to simultaneously map RA and left atrial (LA) activation patterns and compare intra-atrial and interatrial activation properties during single-site and dual-site RA pacing in the normal canine heart. Basket-shaped catheters carrying 64 electrodes were deployed under the guidance of fluoroscopy and echocardiography into both the RA and LA of 7 dogs. Basket unipolar electrograms were simultaneously recorded while pacing at high lateral RA (HRA) alone, at inferior RA septum (RAS) alone, and at both sites simultaneously. We found that pacing at HRA alone resulted in the longest interatrial conduction time (47+/-6 ms). Pacing at RAS alone significantly shortened interatrial conduction time (29+/-5 ms) and completely activated both the RA and LA simultaneously (70+/-6 ms and 69+/-8 ms, respectively). Dual-site pacing at HRA and RAS significantly abbreviated RA complete activation time (52+/-7 ms), but did not alter interatrial conduction time or LA activation pattern compared to pacing at RAS alone. In conclusion, single-site pacing at RAS shortened interatrial conduction time compared to HRA and completely activated both atria simultaneously in canines with normal atria. In addition to shortening interatrial conduction time, dual-site pacing at HRA and RAS abbreviated RA complete activation time.

Analysis of Variance↗
PubMed2000

Biochemical defects in ABCR protein variants associated with human retinopathies.

Mutations in the gene encoding ABCR (ABCA4), a photoreceptor-specific ATP-binding cassette (ABC) transporter, are responsible for autosomal recessive Stargardt disease (STGD), an early onset macular degeneration, and some forms of autosomal recessive cone-rod dystrophy and autosomal recessive retinitis pigmentosa. Heterozygosity for ABCA4 mutations may also represent a risk factor for age-related macular degeneration (AMD), although this idea is controversial. An ongoing challenge in the analysis of ABCA4-based retinopathies arises from the observation that most of the ABCA4 sequence variants identified so far are missense mutations that are rare in both patient and control populations. With the current sample size of most sequence variants, one cannot determine statistically whether a particular sequence variant is pathogenic or neutral. A related challenge is to determine the degree to which each pathogenic variant impairs ABCR function, as genotype-phenotype analyses indicate that age of onset and disease severity correlate with different ABCA4 alleles. To address these questions, we performed a functional analysis of human ABCR and its variants. These experiments reveal a wide spectrum of biochemical defects in these variants and provide insight into the transport mechanism of ABCR.

ATP-Binding Cassette Transporters↗
PubMed2000

Interaction of antimony tartrate with the tripeptide glutathione implication for its mode of action.

The tripeptide glutathione (gamma-L-Glu-L-Cys-Gly, GSH) is thought to play an important role in the biological processing of antimony drugs. We have studied the complexation of the antileishmanial drug potassium antimony(III) tartrate to GSH in both aqueous solution and intact red blood cells by NMR spectroscopy and electrospray ionization mass spectrometry. The deprotonated thiol group of the cysteine residue is shown to be the only binding site for Sb(III), and a complex with the stoichiometry [Sb(GS)3] is formed. The stability constant for [Sb(GS)3] was determined to be log K 25 (I = 0.1 M, 298 K) based on a competition reaction between tartrate and GSH at different pH* values. In spite of being highly thermodynamically stable, the complex is kinetically labile. The rate of exchange of GSH between its free and Sb-bound form is pH-dependent, ranging from slow exchange on the 1H-NMR timescale at low pH (2 s-1 at pH 3.2) to relatively rapid exchange at biological pH (> 440 s-1). Such facile exchange may be important in the transport of Sb(III) in various biofluids and tissues in vivo. Our spin-echo 1H-NMR data show that Sb(III) rapidly entered red blood cell walls and was complexed by intracellular glutathione.

Antimony Potassium Tartrate↗
PubMed2000

Spatial regularization of the electrocardiographic inverse problem and its application to endocardial mapping.

Numeric regularization methods for solving the inverse problem of electrocardiography in realistic volume conductor models have been mostly limited to uniform regularization in the spatial domain. A method of spatial regularization (SR) was developed and tested in canine, where each spatial spectral component of the volume conductor model was considered separately, and a SR operator was selected based on explicit a posteriori criterion at each time instant through the heartbeat. The inverse problem was solved in the left ventricle by reconstructing endocardial surface electrograms based on cavitary electrograms measured with the use of a noncontact, multielectrode probe. The results were validated based on electrograms measured in situ at the same endocardial locations using an integrated, multielectrode basket-catheter. A probe-endocardium three-dimensional model was determined from multiplane fluoroscopic images. The boundary element method was applied to solve the boundary value problem and derive the relationship between endocardial and probe potentials. Endocardial electrograms were reconstructed during both normal and paced rhythms using SR as well as standard, uniform, zeroth-order Tikhonov (ZOT) regularization. Compared to endocardial electrograms measured by the basket, electrograms reconstructed using SR [relative error (RE) = 0.32, correlation coefficient (CC) = 0.97, activation error = 3.3 ms] were superior to electrograms reconstructed using ZOT regularization (RE = 0.59, CC = 0.79, activation error = 4.9 ms). Therefore, regularization based on spatial spectral components of the model improves the solution of the inverse problem of electrocardiography compared to uniform regularization.

Animals↗
PubMed2000

X-Ray crystal structure and molecular dynamics simulations of silver hake parvalbumin (Isoform B).

Parvalbumins constitute a class of calcium-binding proteins characterized by the presence of several helix-loop-helix (EF-hand) motifs. In a previous study (Revett SP, King G, Shabanowitz J, Hunt DF, Hartman KL, Laue TM, Nelson DJ, 1997, Protein Sci 7:2397-2408), we presented the sequence of the major parvalbumin isoform from the silver hake (Merluccius bilinearis) and presented spectroscopic and structural information on the excised "EF-hand" portion of the protein. In this study, the X-ray crystal structure of the silver hake major parvalbumin has been determined to high resolution, in the frozen state, using the molecular replacement method with the carp parvalbumin structure as a starting model. The crystals are orthorhombic, space group C2221, with a = 75.7 A, b = 80.7 A, and c = 42.1 A. Data were collected from a single crystal grown in 15% glycerol, which served as a cryoprotectant for flash freezing at -188 degrees C. The structure refined to a conventional R-value of 21% (free R 25%) for observed reflections in the range 8 to 1.65 A [1 > 2sigma(I)]. The refined model includes an acetylated amino terminus, 108 residues (characteristic of a beta parvalbumin lineage), 2 calcium ions, and 114 water molecules per protein molecule. The resulting structure was used in molecular dynamics (MD) simulations focused primarily on the dynamics of the ligands coordinating the Ca2+ ions in the CD and EF sites. MD simulations were performed on both the fully Ca2+ loaded protein and on a Ca2+ deficient variant, with Ca2+ only in the CD site. There was substantial agreement between the MD and X-ray results in addressing the issue of mobility of key residues in the calcium-binding sites, especially with regard to the side chain of Ser55 in the CD site and Asp92 in the EF site.

Animals↗
PubMed2000

Excitotoxic effect of kainic acid on chicken otoacoustic emissions and cochlear potentials.

Kainic acid (KA) is a potent glutamate analog that can temporarily or permanently damage glutamatergic neurons. The purpose of the present study was to determine the short- and long-term effects of KA on chicken otoacoustic emissions and cochlear potentials. A chronic electrode was used to record the compound action potential (CAP), cochlear microphonic (CM), and the slow, positive neural potential (SPNP), a predominantly dc response. The CM, CAP, SPNP, and distortion product otoacoustic emissions (DPOAEs) were recorded before and after infusing 10 microl of a low dose (KA-L, 0.3 mM) or high dose (KA-H, 5 mM) of KA into scala tympani. KA caused a rapid and large reduction in CAP and SPNP amplitude in both the KA-H and KA-L groups; however, the CM and DPOAEs were largely unchanged. The amplitude of the CAP and SPNP in the KA-L group began to recover around 1 week post-KA, but was approximately 50% below normal at 4 weeks post-KA. In contrast, the CAP and SPNP showed no signs of recovery in the KA-H group. The results suggest that KA has no effect on the CM and DPOAEs generated by the hair cells, but selectively damages the CAP generated by the cochlear ganglion neurons. The reduction in the avian SPNP suggests that the response originates in the cochlear afferent neurons, unlike the summating potential (SP) in mammals that is generated in hair cells.

Action Potentials↗
PubMed2000

Multiple splicing defects in an intronic false exon.

Splice site consensus sequences alone are insufficient to dictate the recognition of real constitutive splice sites within the typically large transcripts of higher eukaryotes, and large numbers of pseudoexons flanked by pseudosplice sites with good matches to the consensus sequences can be easily designated. In an attempt to identify elements that prevent pseudoexon splicing, we have systematically altered known splicing signals, as well as immediately adjacent flanking sequences, of an arbitrarily chosen pseudoexon from intron 1 of the human hprt gene. The substitution of a 5' splice site that perfectly matches the 5' consensus combined with mutation to match the CAG/G sequence of the 3' consensus failed to get this model pseudoexon included as the central exon in a dhfr minigene context. Provision of a real 3' splice site and a consensus 5' splice site and removal of an upstream inhibitory sequence were necessary and sufficient to confer splicing on the pseudoexon. This activated context also supported the splicing of a second pseudoexon sequence containing no apparent enhancer. Thus, both the 5' splice site sequence and the polypyrimidine tract of the pseudoexon are defective despite their good agreement with the consensus. On the other hand, the pseudoexon body did not exert a negative influence on splicing. The introduction into the pseudoexon of a sequence selected for binding to ASF/SF2 or its replacement with beta-globin exon 2 only partially reversed the effect of the upstream negative element and the defective polypyrimidine tract. These results support the idea that exon-bridging enhancers are not a prerequisite for constitutive exon definition and suggest that intrinsically defective splice sites and negative elements play important roles in distinguishing the real splicing signal from the vast number of false splicing signals.

Animals↗
PubMed2000

Existence of a transient outward K(+) current in guinea pig cardiac myocytes.

A novel transient outward K(+) current that exhibits inward-going rectification (I(to.ir)) was identified in guinea pig atrial and ventricular myocytes. I(to.ir) was insensitive to 4-aminopyridine (4-AP) but was blocked by 200 micromol/l Ba(2+) or removal of external K(+). The zero current potential shifted 51-53 mV/decade change in external K(+). I(to.ir) density was twofold greater in ventricular than in atrial myocytes, and biexponential inactivation occurs in both types of myocytes. At -20 mV, the fast inactivation time constants were 7.7 +/- 1.8 and 6.1 +/- 1.2 ms and the slow inactivation time constants were 85.1 +/- 14.8 and 77.3 +/- 10.4 ms in ventricular and atrial cells, respectively. The midpoints for steady-state inactivation were -36.4 +/- 0.3 and -51.6 +/- 0.4 mV, and recovery from inactivation was rapid near the resting potential (time constants = 7.9 +/- 1.9 and 8.8 +/- 2.1 ms, respectively). I(to.ir) was detected in Na(+)-containing and Na(+)-free solutions and was not blocked by 20 nmol/l saxitoxin. Action potential clamp revealed that I(to.ir) contributed an outward current that activated rapidly on depolarization and inactivated by early phase 2 in both tissues. Although it is well known that 4-AP-sensitive transient outward current is absent in guinea pig, this Ba(2+)-sensitive and 4-AP-insensitive K(+) current has been overlooked.

4-Aminopyridine↗
PubMed2000

Truncated activin type I receptor Alk4 isoforms are dominant negative receptors inhibiting activin signaling.

Activin, a member of the transforming growth factor beta (TGFbeta) superfamily of cytokines, inhibits cell proliferation in a variety of cell types. The functions of activin are mediated by type I and type II serine/threonine kinase receptors. The main type I receptor mediating activin signaling in human cells is ActRIB, also called Alk4. We have previously reported that several truncated Alk4 receptor isoforms are exclusively expressed in human pituitary tumors, and that the majority of such tumors did not exhibit activin-induced growth arrest in culture. We therefore studied the function of these truncated receptor isoforms. Transient expression of these truncated receptors inhibited activin-activated transcription from an activin-responsive reporter construct, 3TPLux. When each of these truncated Alk4 receptors was stably transfected into K562 cells, activin-induced expression of an endogenous gene, junB, was blocked, indicating that inhibition of gene expression also occurred at the chromosomal level. Furthermore, activin administration failed to cause growth inhibition and an increase of the G1 population in these cells. Coimmunoprecipitation experiments showed that the truncated Alk4 receptors formed complexes with type II activin receptors, but were not phosphorylated. These data indicate that the truncated activin type I receptors, predominantly expressed in human pituitary adenomas, function as dominant negative receptors to interfere with wild-type receptor function and block the antiproliferative effect of activin. This may contribute to uncontrolled pituitary cell growth and the development of human pituitary tumors.

Activin Receptors, Type I↗
PubMed2000

The reovirus project: an application of distributed visualization.

This paper describes a distributed visualization of the operation of a reovirus. This visualization allows several groups of users at different locations to view how the virus behaves in normal and cancer cells. The users at each location can interact with the visualization and the other users. The techniques used to produce this visualization include the reduction of geometrical complexity, user representation and interaction with the visualization. Future work includes improving the explanations of the reovirus and providing users with different views of the animation highlighting various aspects of the virus's behaviour.

Canada↗
PubMed2000

Study on the physiology and degradation of dye with immobilized algae.

Immobilization of chlorella (pyrenoidosa) with calcium alginate was carried out. Both algal growth and physiological activity increased after immobilization. Algal size and initial density have little influence on cell growth and physiological activity. Algal cell division inside the support was restricted without bubbling air containing 2% CO2. Individual algal cell increased and algal distribution inside the support was not homogeneous, indicating that within the support the resistance of mass transfer of CO2 was the limiting factor for the growth and cell division of immobilized algae. After bubbling 2% CO2, algal growth, the cell division considerably increased and individual cell size restored normally. Study of the degradation of dye (direct brown NM) by immobilized algae was better than that of free algae. Bubbling air containing 2% CO2 in the culture solution was more favorable for increasing decolorization rate. Preliminary study of co-immobilization of algae plus bacterium illustrated that the addition of bacterium increased the anabolic activity of algae, thus increased the decolorization capacity if immobilized algae for dye.

Alginates↗
PubMed2000

Long-term survey of outcome in acute promyelocytic leukemia.

OBJECTIVE: To investigate all-trans retinoic acid (ATRA) and As2O3 which were found to be able to selectively induce differentiation and apoptosis in acute promyelocytic leukemia (APL) and recently became standard treatment for de novo or relapsed APL. The results of long-term follow up in 72 APL patients were presented and prognostic factors discussed. METHODS: Seventy-two newly-diagnosed patients with APL entering CR with ATRA were consolidated with chemotherapy alone (31 patients), ATRA + chemotherapy (30 patients) and ATRA alone (11 patients). Univariate analysis was done to identify the potential prognostic factors. A total of 40 cases of patients relapsed after their first complete remission, including 3 groups of patients: group A, patients treated with ATRA and chemotherapy after relapse (8 patients); group B patients treated with As2O3 alone for 2nd CR and consolidation (21 patients); group C patients treated with As2O3 for 2nd CR and both As2O3 and chemotherapy for consolidation (11 patients). Univariate analysis was also done to identify the potential prognostic factors. RESULTS: With a median follow-up of 45 months (5-75 months), the median event-free survival was 21 months and median overall survival was not achieved. The estimated 3- and 5-year event-free survival (EFS) and over-all survival (OS) were 32.5 +/- 10.5%, 18.4 +/- 7.5% and 73.8 +/- 17.5%, 58.5 +/- 15.2%. In denovo patients, the combination of ATRA and chemotherapy in both induction and post-remission treatment was found to be statistically significant for EFS (P = 0.023), and initial peripheral leukocyte count was significantly related to OS. In relapsed patients, only the treatment of As2O3 with or without chemotherapy in consolidation after relapse was statistically significant for CR and both EFS (P = 0.0061) and OS (P = 0.0013). CONCLUSION: ATRA is an effective induction therapy and can be considered as first choice of treatment in denovo APL. Addition of chemotherapy in both induction and post-remission therapy can delay or decrease the possibility of relapse compared to ATRA alone. As2O3 is an effective agent for relapsed APL and remains an important prognostic factor for relapsed APL.

Adolescent↗
PubMed2000

[The in vivo degradation, adsorption and excretion of poly(epsilon-caprolactone)].

The in vivo degradation of poly(epsilon-caprolactone(PCL) was studied in rats. The results showed that the PCL capsules with an initial molecualr weight of 66,000 stayed intact in vivo for 2 years, although the molecular weight of the capsules gradually declined during the two-year implantation. It then degraded into low molecular wight pieces with the extension of the implantation. Tritium-labeled low molecular weight PCL was subcutaneously implanted in rats to further investigate the absorption and excretion of the material. The radioactivity was first detected in blood 15 days post the implantation. At the same time radioactive excreta were recovered from feces and urine. An accumulative 92% of the implanted radioactive dosage was excreted from feces and urine 135 days post the implantation. In the meanwhile, the blood radioactivity dropped to the background level. Radioactivity in the organs was all close to the background level indicating that the material did not cumulate in body tissue and could be completely excreted.

Absorption↗
PubMed2000

Adverse drug reactions: a review of relevant factors.

We examined some of the factors that contribute to the development of adverse drug reactions (ADRs) and analyzed postmarketing ADR reports for 22 drugs. The role of metabolic-based drug-drug interaction in the development of ADRs can not be overstated. Assessment of the postmarketing ADR data for 22 drugs revealed that drugs with high potential for eliciting clinically significant ADRs are usually detected and either withdrawn from the market or placed on restricted use within the first year or two of marketing. Postmarketing data could be a useful tool for understanding the ADR profile of drugs if reporting can be adequately monitored and verified. It is hoped that early evaluation of the clinically meaningful factors such as metabolism, pharmacogenetics, and effect of physiologic and pathophysiologic states on the clinical effect of a drug during drug development would significantly reduce the incidence and severity of post-marketing ADRs.

Adverse Drug Reaction Reporting Systems↗
PubMed2000

[E-cadherin expression and its clinical significance in cervical cancer].

OBJECTIVE: To study the clinical significance of E-cadherin (E-CD) expression in cervical cancer. METHODS: Specimens of 60 cervical cancer, 10 normal cervical epithelia and 12 cervical intraepithelial neoplasia(CIN) were examined for E-CD expression by immunohistochemical staining. RESULTS: E-CD was expressed in all of 10 specimens of normal cervical epithelia. Positive staining was seen in 66.7% of CIN, 46.7% of cervical cancer. In cervical cancer, the frequency of abnormal E-CD expression was correlated to pathologic grade, lymph node metastasis and clinical stage (P < 0.05). The higher the pathologic grade of tumor, the lower was the expression of E-CD. Negative E-CD expression was significantly more frequent in the advanced stage of cervical cancer with lymph node metastasis. CONCLUSION: Decreased expression of E-CD is a useful parameter of cervical malignancy.

Adult↗
PubMed2000

[Protective effects of SMT on myocardial ultrastructure of ischemia reperfusion injury in heart of rat].

AIM: To Investigate the myocardial ultrastructure effects of SMT on the ischemia reperfusion injury (IRI) in the rat heart. METHODS: Eighteen Spraqua-Dawley rats were randomly divided into three groups: ischemia reperfusion group (IR), subjected to 60 min of o-cclusion and 20 min of reperfusion of the anterior descending branch of left coronary artery; IR + SMT group (SMT), given the selective iNOS inhibitor S-methylisothiourea sulfate (SMT, 5 mg/kg, i.v.) before reperfusion; control group (C), didn't occlude coronary artery after exposing heart and observed 80 min. Electrocardiogram (ECG) was recorded. Nitrite and nitrate content were measured in myocardium and blood serum. The changes of myocardial ultrastructure were observed with electron microscope. RESULTS: Ischemia reperfusion induced ST segment elevation and T waves inversion or tallness in ECG, damaged myocardial ultrastructure, increased nitrite and nitrate content in myocardium and blood serum after IR compared with before IR(P < 0.01). Administration of SMT improved the changes of ECG and the injury of myocardial ultrastructure. Nitrite and nitrate content of myocardium were lower than IR group (P < 0.05). The change of nitrite and nitrate level of blood serum in SMT group was nearly in C group. CONCLUSION: SMT can prevent myocardium injury from reperfusion following ischemia.

Animals↗