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Biomedical subjects

J Feng

Publications and source records attributed to J Feng.

At least 199 records · Page 11Linked to original sources

Transient ischemia inhibits nonexocytotic release of norepinephrine following sustained ischemia in rat heart: is bradykinin involved?

Previous studies have demonstrated that transient ischemia inhibits the release of norepinephrine (NE) following a sustained ischemia. However, the mechanism underlying this inhibition is unknown. Therefore, this study was designed to investigate whether bradykinin (BK) may be involved in the inhibition of NE release following ischemic preconditioning. The effects of transient ischemia, exogenous BK, and kinin receptor blockers on NE release after a prolonged ischemia were tested in the isolated rat heart preparation. Three cycles of 5-min ischemia and reperfusion resulted in the reduction of NE release from 115.3 +/- 14.5 to 51.6 +/- 9.3 pmol.g-1 (p < 0.05) after 30 min of subtotal global ischemia. This effect was not prevented by the administration of either Lys-[Leu8]-des-Arg9-BK (1 mumol.L-1), a B1 antagonist, or HOE-140 (1 mumol.L-1), a B2 antagonist. Three cycles of 5-min BK or des-Arg9-BK infusion also resulted in a dose-dependent inhibition of NE release after 30 min of ischemia. The inhibitory effects of BK (1 mumol.L-1) or des-Arg9-BK (0.5 mumol.L-1) were blocked by Lys-[Leu8]-des-Arg9-BK (1 mumol.L-1), but not by HOE-140 (1 mumol.L-1). The results show that transient ischemia and BK protect sympathetic nerve endings in the isolated rat heart. The inhibition of NE release by pretreatment with BK is mediated by the activation of B1 receptors, whereas preconditioning provided by transient ischemia may be mediated by a different, yet unknown, mechanism in the rat heart.

Animals↗

Amidative peptide processing and vascular function.

Substance P (SP), an amidated peptide present in many sensory nerves, is known to affect cardiovascular function, and exogenously supplied SP has been shown to activate nitric oxide synthase (NOS) in endothelial cells. We now report that SP-Gly, the glycine-extended biosynthetic precursor of SP (which is enzymatically processed to the mature amidated SP), causes relaxation of rat aortic strips with an efficacy and potency comparable to that of SP itself. Pretreatment of the aortic strips with 4-phenyl-3-butenoic acid (PBA), an irreversible amidating enzyme inactivator, results in marked inhibition of the vasodilation activity induced by SP-Gly but not of that induced by SP itself. Isolated endothelial cell basal NOS activity is also decreased by pretreatment with PBA, with no evidence of cell death or direct action of PBA on NOS activity. Both bifunctional and monofunctional forms of amidating enzymes are present in endothelial cells, as evidenced by affinity chromatography and Western blot analysis. These results provide evidence for a link between amidative peptide processing, NOS activation in endothelial cells, and vasodilation and suggest that a product of amidative processing provides intrinsic basal activation of NOS in endothelial cells.

Amino Acid Sequence↗

Antisense oligodeoxynucleotides directed against Kv1.5 mRNA specifically inhibit ultrarapid delayed rectifier K+ current in cultured adult human atrial myocytes.

Several cloned K+ channel subunits are candidates to underlie macroscopic currents in the human heart, but direct evidence bearing on their role is lacking. The Kv1.5 K+ channel subunit has been suggested to play a potential role in human cardiac ultrarapid delayed rectifier (IKur) and transient outward (Ito) currents. To evaluate the role of proteins encoded by the Kv1.5 gene, we incubated cultured human atrial myocytes for 48 hours in medium containing antisense phosphorothioate oligodeoxynucleotides directed against octodecameric segments of the Kv1.5 mRNA coding sequence, the same concentration of homologous oligodeoxynucleotides with four mismatch mutations, or vehicle (control group). Cells exposed to antisense showed a highly significant (approximately 50%) reduction in IKur whether measured by step current at the end of a 400-millisecond depolarizing pulse, tail current at -20 mV, or current sensitive to a concentration of 4-aminopyridine (50 mumol/L) that is highly selective for IKur compared with control cells or cells exposed to mismatch oligodeoxynucleotides. In contrast, Ito was not different among the three experimental groups. When cultured human ventricular myocytes were exposed to Kv1.5 antisense oligodeoxynucleotides with the same controls, no changes occurred in either Ito or the sustained current at the end of a depolarizing pulse. We conclude that Kv1.5 channel subunits are essential to the expression of IKur and do not play a role in Ito in cultured human atrial myocytes. These studies provide the first direct evidence with an antisense approach for the equivalence between a macroscopic cardiac K+ current and a cloned K+ channel subunit and offer insights into the molecular electrophysiology of the human heart.

Adult↗

Ionic remodeling underlying action potential changes in a canine model of atrial fibrillation.

Rapid electrical activation, as occurs during atrial fibrillation (AF), is known to cause reductions in atrial refractoriness and in adaptation to heart rate of the atrial refractory period, which promote the maintenance of AF, but the underlying ionic mechanisms are unknown. In order to determine the cellular and ionic changes caused by chronic atrial tachycardia, we studied right atrial myocytes from dogs subjected to 1, 7, or 42 days of atrial pacing at 400/min and compared them with myocytes from sham-operated dogs (pacemaker inserted but not activated). Rapid pacing led to progressive increases in the duration of AF induced by bursts of 10-Hz stimuli (from 3 +/- 2 seconds in sham-operated dogs to 3060 +/- 707 seconds in dogs after 42 days of pacing, P < .001) and reduced atrial refractoriness and adaptation to rate of the atrial refractory period. Voltage-clamp studies showed that chronic rapid pacing did not alter inward rectifier K+ current, rapid or slow components of the delayed rectifier current, the ultrarapid delayed rectifier current, T-type Ca2+ current, or Ca(2+)-dependent Cl- current. In contrast, the densities of transient outward current (Ito) and L-type Ca2+ current (ICa) were progressively reduced as the duration of rapid pacing increased, without concomitant changes in kinetics or voltage dependence. In keeping with in vivo changes in refractoriness, action potential duration (APD) and APD adaptation to rate were decreased by rapid pacing. The response of the action potential and ionic currents flowing during the action potential (as exposed by action-potential voltage clamp) to nifedipine in normal canine cells and in cells from rapidly paced dogs suggested that the APD changes in paced dogs were largely due to reductions in ICa. We conclude that sustained atrial tachycardia reduces Ito and ICa, that the reduced ICa decreases APD and APD adaptation to rate, and that these cellular changes likely account for the alterations in atrial refractoriness associated with enhanced ability to maintain AF in the model.

Action Potentials↗

Elevated intakes of supplemental chromium improve glucose and insulin variables in individuals with type 2 diabetes.

Chromium is an essential nutrient involved in normal carbohydrate and lipid metabolism. The chromium requirement is postulated to increase with increased glucose intolerance and diabetes. The objective of this study was to test the hypothesis that the elevated intake of supplemental chromium is involved in the control of type 2 diabetes. Individuals being treated for type 2 diabetes (180 men and women) were divided randomly into three groups and supplemented with: 1) placebo, 2) 1.92 micromol (100 microg) Cr as chromium picolinate two times per day, or 3) 9.6 micromol (500 microg) Cr two times per day. Subjects continued to take their normal medications and were instructed not to change their normal eating and living habits. HbA1c values improved significantly after 2 months in the group receiving 19.2 pmol (1,000 microg) Cr per day and was lower in both chromium groups after 4 months (placebo, 8.5 +/- 0.2%; 3.85 micromol Cr, 7.5 +/- 0.2%; 19.2 micromol Cr, 6.6 +/- 0.1%). Fasting glucose was lower in the 19.2-micromol group after 2 and 4 months (4-month values: placebo, 8.8 +/- 0.3 mmol/l; 19.2 micromol Cr, 7.1 +/- 0.2 mmol/l). Two-hour glucose values were also significantly lower for the subjects consuming 19.2 micromol supplemental Cr after both 2 and 4 months (4-month values: placebo, 12.3 +/- 0.4 mmo/l; 19.2 micromol Cr, 10.5 +/- 0.2 mmol/l). Fasting and 2-h insulin values decreased significantly in both groups receiving supplemental chromium after 2 and 4 months. Plasma total cholesterol also decreased after 4 months in the subjects receiving 19.2 micromol/day Cr. These data demonstrate that supplemental chromium had significant beneficial effects on HbA1c, glucose, insulin, and cholesterol variables in subjects with type 2 diabetes. The beneficial effects of chromium in individuals with diabetes were observed at levels higher than the upper limit of the Estimated Safe and Adequate Daily Dietary Intake.

Adult↗

[The role of opioid receptors of arcuate nucleus in cytokine-induced hyperthermia].

The present study is to define the role played by the opioid receptors of ARH in the regulation of body temperature. 1 microliter of IL-1 beta (as pyrogen) was injected into the ARH of male Sprague-Dawley rat with an automatic micromanipulator to induce hyperthermia. 30 minutes prior to the injection of pyrogen, the experimental groups were pre-treated with general opioid receptor antagonist naloxone (Nal), selective mu, delta, kappa receptor antagonists CTAP, NTI, nor-BNI respectively. Controls were pre-treated with saline. The results showed that IL-1 beta-induced hyperthermia was blocked by Nal and CTAP, suggesting the involvement of, or mediation by, ARH opioid receptors (mainly the mu type) in IL-1 beta-induced hyperthermia. The blockade by delta and kappa antagonists was not remarkable. Thus their participation in this process is less likely. The similarity between the roles of opioid receptors of ARH and POAH in IL-1 beta-induced hyperthermia strongly supports the view that ARH may be an important component of the thermoregulatory center.

Animals↗

[The development and application of an hand-held gamma detecting probe].

A new device for tumor to perform radioimmunoguided surgery (RIGS) was described, The instrument was based on the inverse square law that the sensitive and specificity of the detector increase as the distance between the source and the detector shorted. The experimental results showed that the hand-held gamma detecting probe was practical to perform radioimmuoguided surgery for tumor in vivo.

Animals↗

[Study on the direct determination of Pb and Cd in milk powder by GFAAS].

The paper reports the direct determination of Pb and Cd in milk powder by GFAAS. The mothed does not need any pre-treatment to the samples and fully use some function of pre-treatment which the Graphite Furnace have. The result indicates that the method is simple, rapid and accurate, and the false result from any pre-treatment to the samples can be reduced. The recover rate of Pb is 100.1%, CV =2.7 ; and Cd is 98.6%, CV = 3.1 %. This method is also applied to the rapid determination of Pb and Cd in soluble samples with satisfactory results.

Analytic Sample Preparation Methods↗

Effects of class III antiarrhythmic drugs on transient outward and ultra-rapid delayed rectifier currents in human atrial myocytes.

A variety of class III antiarrhythmic agents have been shown to block the delayed rectifier current, but their effects on other K+ currents, particularly in human tissues, are less clear. We studied the concentration-dependent actions of the class III compounds d-sotalol, E-4031 and ambasilide on the transient outward current (I(to)) and the ultra-rapid delayed rectifier current (I(Kur)) in human atrial myocytes. d-Sotalol and E-4031 failed to alter I(to) or I(Kur) at concentrations up to 500 and 50 microM, respectively. In contrast, ambasilide produced a concentration-dependent inhibition of I(to) and I(Kur), with statistically significant effects at 10 microM and maximum effects at 100 microM. The 50% inhibitory concentration of ambasilide averaged 23 +/- 2 microM and 34 +/- 3 microM for I(to) and I(Kur) respectively. Ambasilide did not alter the voltage-dependence of activation or inactivation of I(to), or the voltage-dependence of I(Kur), and it did not affect I(to) recovery from inactivation. On the other hand, ambasilide accelerated I(to) inactivation, by introducing a more rapid component that accelerated with increasing drug concentration. Furthermore, block of both I(to) and I(Kur) developed over time after the onset of depolarization, with time constants of 5.8 +/- 0.8 msec and 2.5 +/- 0.4 msec at concentrations of 10 and 50 microM for I(to) and 6.1 +/- 0.8 msec and 2.1 +/- 0.3 msec at 10 and 50 microM for I(Kur). We conclude that neither d-sotalol nor E-4031 affects I(to) or I(Kur), whereas ambasilide produces efficacious open-channel block of both currents, in human atrial myocytes.

Aminobenzoates↗

[Improving the human iodine supply by iodination of swine feed].

Germany and several other countries are areas of severe iodine deficiency. In addition to iodized salt additional strategies to fight iodine deficiency exist. A promising possibility is the supplementation of feed with iodine, in order to increase its content in food of animal origin. In a feeding experiment 24 male castrated and female piglets of the cross breed Deutsche Landrasse x Pietrain were fed a high iodine supplemented diet. At a body weight of 100 kg the animals were slaughtered and the effect of the iodine supplementation on iodine content in the organs was studied. Animals receiving 30 mg iodine/kg feed showed significantly higher iodine contents in muscle, heart, kidney, liver, serum, fat and in the thyroidea than animals receiving no iodine supplementation. The iodine content in muscle and organs increased by a factor three to seven. Concerning meat quality and other slaughter parameters there was no difference between the two groups. This demonstrates that this strategy is in addition to iodized salt a possibility to reduce iodine deficiency.

Abattoirs↗

A self-assembled antibody electrode for HT29 tumour cells.

The present paper describes a self-assembled monoclonal-antibody immunosensor for HT29 tumour cells. This immunosensor is composed of two parts. One is a three-electrode system and the other is a layer of anti-(human colonic tumour) monoclonal antibody DF-I, which self-assembled on to the gold electrode. Two kinds of cells, HT29 tumour cells and normal fibroblast cells, were compared using the antibody electrode. The result was the same as that obtained by using immune luminescence. The HT29 cells can be captured specifically by the assembled anti-HT29 monoclonal-antibody electrode and can be measured by an electrochemical method.

Antibodies, Monoclonal↗

Promotion of osteogenesis by a piezoelectric biological ceramic.

Hydroxyapatite (HA) ceramic and piezoelectric biological ceramic, hydroxyapatite and barium titanate (HABT), were implanted in the jawbones of dogs. Histological observation showed that, compared with HA ceramics, HABT promoted the growth and repair of the bone significantly, the tissue growth around the HABT ceramic was direction-dependent, the collagen arranged orderly and the bone grew orderly. The order growth of the bone increased the efficiency of osteogenesis on the surface of the implanted HABT ceramics.

Animals↗

Vaccination with monoclonal anti-idiotypic antibody on immunocompetent mice bearing human ovarian carcinoma.

OBJECTIVE: To observe the effects of anti-idiotypic monoclonal antibody 6B11 against ovarian carcinoma SKOV3 on immunocompetent mice BCF1 both in vivo and in vitro, so as to investigate the possibility of using it as a tumor vaccine. METHODS: After immunization with 6B11 and normal mice (NM) IgG respectively on 2 groups of BCF1, blood, lymphocytes and tumor tissues were taken every other day. Ab3 was tested from blood samples. Subpopulations of lymphocytes were examined by FCM. The lymphocytes from immunized BCF1 were also cultured with SKOV3 to observe the chemotaxis and killing effects. Serial tissue sections were taken from BCF1 after immunization by SRCA implantation of SKOV3. TIL and visible cancer cells were examined carefully and compared with those in the controls. RESULTS: Ab3 rose quickly after immunization with 6B11 but lowered down gradually till the 9th week. The CD4+/ CD8+ ratio of BCF1 changed markedly after immunization with 6B11. The immunized lymphocytes showed a beautiful chemotaxis with and killing effect on SKOV3. During in vivo examinations, TIL were found significantly earlier in the immunized BCF1 than in the controls and reached the peak earlier in the former (on the 6th day) than in the latter, while the viability of tumor cells was vice versa between the two groups. CONCLUSION: 6B11 may be used as a vaccine for not only active immunization but also prevention of ovarian carcinoma.

Animals↗

[Preparation of F(ab')2 fragment of monoclonal antibody COC166-9 and its experimental study of radioimmunoimaging for ovarian carcinoma].

OBJECTIVES: To obtain F(ab')2 fragment of monoclonal antibody (McAb) COC166-9 and to perform its radioimmunoimaging (RII) for ovarian carcinoma. METHODS: McAb COC166-9 was digested into F(ab')2 by ficin and tested by SDS-PAGE. After purification by DEAE-32, F(ab')2, COC166-9 and normal murine IgG (nMIgG) were labelled by 131I and injected intraperitoneally into three groups of nude mice bearing human ovarian cancer xenografts respectively. 72 hours after injection, RII was performed in three groups of mice. RESULTS: The yield of F(ab')2 was 54%, about 80% of the maximal theoretical yield. Good immunoreactivity of F(ab')2 retained with higher ratio of tumor to normal tissue radioactivity (T/NT) than that of intact COC166-9. RII showed better result with lower nonspecific background than the latter. CONCLUSION: F(ab')2 could be obtained by ficin digestion with good yield and immunoactivity as well as better RII than intact monoclonal antibody.

Animals↗

Characterization of an ultrarapid delayed rectifier potassium channel involved in canine atrial repolarization.

1. Depolarizing pulses positive to 0 mV elicit a transient outward current (Ito) and a sustained 'pedestal' current in canine atrial myocytes. The pedestal current was highly sensitive to 4-aminopyridine (4-AP) and TEA, with 50% inhibitory concentrations (EC50) of 5.3 +/- 0.7 and 307 +/- 25 microM, respectively. When the pedestal current was separated from Ito with prepulses or by studying current sensitive to 10 mM TEA, it showed very rapid activation and deactivation. We therefore designated the current IKur,d, for 'ultrarapid delayed rectifier, dog'. IKur,d inactivation was bi-exponential, with mean time constants of 609 +/- 91 and 5563 +/- 676 ms during a 20 s pulse to +40 mV. 2. The reversal potential of IKur,d tail currents are dependent on extracellular potassium concentration ([K+]o; slope, 54.7 mV decade-1). The envelope of tails test was satisfied and the current inwardly rectified at > or = +40 mV. The current was insensitive to E-4031, dendrotoxin and chloride substitution, but was inhibited by barium, with an EC50 of 1.65 mM. Lanthanum ions caused a positive shift in voltage dependence without producing direct inhibition. 3. Single-channel activity was observed in cell-attached, inside-out and outside-out patches. Upon depolarization from -50 to +30 mV, single channels had similar time constants and [K+]o dependence to whole-cell current. Channel open probability (Po) increased with depolarization in a saturable fashion and the Po-voltage relation had a half-activation voltage and slope factor similar to whole-cell IKur,d. 4. Unitary channel current was linearly related to depolarization potential to +40 mV; at more positive potentials, inward rectification occurred. The unitary conductance was 20.3 and 35.5 pS for an [K+]o of 5.4 and 130 mM, respectively. Single-channel activity was strongly inhibited by 50 microM 4-AP or 10 mM TEA. Both 4-AP and TEA decreased open time, suggesting open-channel block. 5. Selective inhibition of IKur,d with 50 microM 4-AP or 0.3-5 mM TEA prolonged canine atrial action potentials, indicating that IKur,d contributes to canine atrial repolarization. The single-channel and macroscopic properties of IKur,d have many similarities to those of currents carried by Kv3.1 cloned channels and our findings thus suggest a possible role for Kv3.1 channels in cardiac repolarization.

4-Aminopyridine↗

Substitution of glutamic 779 with alanine in the Na,K-ATPase alpha subunit removes voltage dependence of ion transport.

The effects of changing Glu-779, located in the fifth transmembrane segment of the Na,K-ATPase alpha subunit, on the phosphorylation characteristics and ion transport properties of the enzyme were investigated. HeLa cells were transfected with cDNA coding the E779A substitution in an ouabain-resistant sheep alpha1 subunit (RD). Steady state phosphorylation stimulated by Na+ concentrations less than 20 mM or by imidazole were similar for RD and E779A enzymes, an indication that phosphorylation and Na+ occlusion were not altered by this mutation. With E779A enzyme, higher Na+ concentrations reduced the level of phosphoenzyme and stimulated Na-ATPase activity in the absence of K+. These effects were a consequence of Na+ increasing the rate of protein dephosphorylation. In voltage-clamped HeLa cells expressing E779A enzyme, a prominent electrogenic Na+-Na+ exchange was observed in the absence of extracellular K+. Thus, increased Na-ATPase activity and Na+-dependent dephosphorylation result from Na+ acting as a K+ congener with low affinity at extracellular binding sites. These data suggest that E779A does not directly participate in ion binding but does affect the connection between extracellular ion binding and intracellular enzyme dephosphorylation. In cells expressing control RD enzyme, Na,K-pump current was dependent on membrane potential and extracellular K+ concentration. However, Na,K-pump current in cells expressing E779A enzyme was voltage independent at all extracellular K+ tested. These results indicate that Glu-779 may be part of the access channel determining the voltage dependence of ion transport by the Na, K-ATPase.

Alanine↗