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Z Fan

Publications and source records attributed to Z Fan.

At least 19 recordsLinked to original sources
PubMed1992

Multiple ionic mechanisms of early afterdepolarizations in isolated ventricular myocytes from guinea-pig hearts.

Ionic mechanisms of early afterdepolarization (EAD) induced by the K(+)-free solution or veratridine were studied with guinea-pig ventricular myocytes using the patch-clamp technique of whole-cell and cell-attached patch configurations. In the K(+)-free solution, myocytes exhibited prolonged action potential duration with humps on the final repolarization phase, which eventually turned into EAD starting around -70 mV and induced triggered activity. Application of 0.5 mM Cd2+ inhibited the development of EAD and caused depolarization of maximum diastolic potentials around -30 mV, although Cd2+ did not prevent prolongation of the action potential. Application of 50-100 microM Ni2+ or 30 microM tetrodotoxin had little effects on EAD and diastolic potentials. The background current-voltage relation examined by a ramp voltage clamp showed inhibition of the inward rectifier K+ current, induction of steady inward current between -40 and -10 mV, and increase in the outward tail current upon repolarization in the K(+)-free solution. Cd2+ completely blocked the steady inward current at the plateau level and partially depressed the delayed outward K+ current, while Ni2+ had no effects on the background I-V relation. Tetrodotoxin showed a mild inhibitory effect on the inward component of the background current negative to -50 mV, but left the steady inward current at the plateau level. Therefore, EAD in the K(+)-free condition is mainly formed by decreased inward rectifier K+ current, activation of the L-type Ca2+ current, and time-dependent decay of the delayed outward K+ current upon repolarization. Application of 25-100 microM veratridine caused marked prolongation of action potential with appearance of regenerative EADs. Action potential prolongation and EADs were partially abolished by Cd2+ and completely eliminated by tetrodotoxin. The single channel current recordings showed a decreased current amplitude, and prolonged and delayed openings of the Na+ channel currents by veratridine. Thus, an ensemble average current showed markedly prolonged decay time constant of 609 msec in veratridine from 3.6 msec in the control. These results indicate that veratridine-induced EAD is mainly formed by altered properties of the Na+ channel current and partly by the L-type Ca2+ current due to slowed repolarization. Thus, EAD can be induced by different ionic mechanisms depending on the basal conditions.

Action Potentials↗
PubMed1992

Aromatic aldehydes and aromatic ketones open ATP-sensitive K+ channels in guinea-pig ventricular myocytes.

Patch-clamp techniques were used to study the effects of three carbonyl compounds, 3,4-dihydroxybenzaldehyde, 2,3-dihydroxybenzaldehyde, and 2,4-dihydroxyacetophenone, on the adenosine-5'-triphosphate(ATP)-sensitive K+ channel current (IK.ATP) in guinea-pig ventricular myocytes. 3,4-Dihydroxybenzaldehyde (0.5-1 mM) shortened the action potential duration, and this effect was inhibited by application of a specific blocker of IK.ATP, glibenclamide. The shortening of the action potential duration was shown to be caused by a time-independent outward current. In the cell-attached patch configuration, all three compounds activated a kind of single-channel current, which showed an inward rectification at positive potentials and which had a linear current/voltage relation at negative potentials, having a conductance of 90 pS. The current reversed at about 0 mV in symmetrical K+ concentrations on both sides of the membrane. In excised patches this current was blocked by internal application of ATP. Thus we identified this channel as IK.ATP. The activation effects of two aromatic aldehydes were stronger than that of the aromatic ketone. The effect of these compounds on IK.ATP was not reduced by addition of cysteine (10 mM). In inside-out patches, 3,4-dihydroxybenzaldehyde increased the activity of IK.ATP, which had been blocked by 0.5 mM MgATP in the presence of 0.5 mM ADP, but the activation effect was variable and much weaker than that in the cell-attached configuration, and was completely eliminated in the absence of ADP.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetophenones↗
PubMed1992

Radioiodinated anti-hepatocellular carcinoma (HCC) ferritin. Targeting therapy, tumor imaging and anti-antibody response in HCC patients with hepatic arterial infusion.

Radioimmunoimaging and radioimmunotherapy with radioiodinated anti-(hepatocellular carcinoma ferritin) antibody (131I- or 125I-FtAb) have been applied in patients with primary liver cancer. A total of 41 patients with surgically unresectable hepatocellular carcinoma (HCC) and receiving hepatic artery ligation and cannulation during exploratory laparotomy were treated with this regimen by intrahepatic arterial infusion. Compared with the control group, a decline of serum alpha-fetoprotein (65.7% versus 42.9%) and shrinkage of tumor (68.3% versus 33.9%) were observed in the treated group, and a higher second-look resection rate (31.7% versus 5.1%) and longer survival (1-year: 61.0% versus 37.3%, 3-year: 25.0% versus 6.9%) resulted. The administration of antibody through a hepatic arterial catheter (n = 16) was compared with intravenous injection (n = 17) in terms of the tumor-imaging sensitivity in 33 patients with liver cancer. The results indicated that hepatic arterial infusion was superior to intravenous injection. The sensitivity 7 days after the administration was 100% in the i.a. group and 76.5% in the i.v. group, the uptake ratio of tumor to liver being 1.74 +/- 0.57 in the former and 1.34 +/- 0.29 in the latter. Furthermore, intrahepatic arterial infusion revealed a lower anti-antibody detection rate than intravenous injection (0/14 versus 4/11).

Antibody Formation↗
PubMed1991

Cytoreduction and sequential resection: a hope for unresectable primary liver cancer.

For decades, unresectable primary liver cancer (PLC) determined by operation was incurable. However, a retrospective study of 24 years' materials with unresectable PLC indicated that 5-year survival of unresectable PLC has increased from 0% in 1966-1977 (n = 137) to 16.9% in 1978-1989 (n = 345). This encouraging improvement was mainly a result of cytoreduction therapy followed by sequential resection. Multimodality combination treatment with hepatic artery ligation, plus hepatic artery infusion with chemotherapy, plus radioimmunotherapy (or radiotherapy) yielded the highest sequential resection rate (30.6%) and 5-year survival (28.0%) as compared with double combination and single modality treatment. The 5-year survival of 33 patients receiving sequential resection after cytoreduction therapy was 63.2%. It is suggested that cytoreduction and sequential resection might offer a hope for surgically verified unresectable PLC.

Adolescent↗
PubMed1991

The catalytic subunit of cyclic AMP-dependent protein kinase directly inhibits sodium channel activities in guinea-pig ventricular myocytes.

We investigated the effects of the purified catalytic subunit (C subunit) of the cAMP-dependent protein kinase (A-kinase) on the cardiac Na+ channel currents. Single Na+ channel currents in guinea-pig ventricular myocytes were recorded using the patch clamp technique of the inside-out configuration. Application of C subunit decreased the peak average current and slowed the current decay, effects which were caused by decrease in the open probability of Na+ channels and increase in the first latency, whereas the unitary current amplitude and mean open times were not affected. We conclude that the cardiac Na+ channel is directly modulated by phosphorylation process through A-kinase.

Animals↗
PubMed1991

Augmentation of cellular immune function during the early phase of zidovudine treatment of AIDS patients.

Twenty-five patients with AIDS in AIDS Clinical Trials Group Protocol 002 were treated with either low or high dosages of zidovudine. This resulted in moderate, transient increases by 10 and 20 weeks in lymphocyte blastogenesis and interferon-gamma (IFN-gamma) production in vitro in response to phytohemagglutinin with and without recombinant interleukin-2. Immune responses to cytomegalovirus and herpes simplex virus type 1 antigens were augmented less frequently during therapy. Natural killer (NK) cell lysis of uninfected and human immunodeficiency virus-infected cells was also transiently increased by 10 and 20 weeks. IFN-gamma production, the only immune parameter directly associated with increases in numbers of CD4+ T cells, peaked at 10 weeks of treatment. The limited efficacy of zidovudine treatment in AIDS patients is associated with moderate, temporary increases in nonspecific and herpesvirus-specific T lymphocyte responses and NK cell function.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Action of nicorandil on ATP-sensitive K+ channel in guinea-pig ventricular myocytes.

1. Patch-clamp techniques were used to study the effects of nicorandil (2-nicotinamiodethyl nitrate) on the adenosine 5'-triphosphate (ATP)-sensitive K+ channel current (IK.ATP) in guinea-pig ventricular myocytes. 2. Nicorandil activated the time-independent outward current. This effect was dependent on intracellular ATP concentration ([ATP]i) showing a larger effect at 2 mM than at 10 mM [ATP]i. The nicorandil-induced outward current was inhibited by application of 0.3 microM glibenclamide. 3. In the inside-out patch configuration, 0.3-1.0 mM nicorandil increased the open-stage probability of IK.ATP without a change in its conductance value (about 90pS). This effect was inhibited by glibenclamide. Analysis of the open and closed time distributions showed that nicorandil had no effect on open and closed distributions shorter than 5 ms. On the other hand, nicorandil increased the life time of bursts and decreased the interburst intervals. 4 The inward rectifier K+ channel current was not influenced by internal application of nicorandil. 5 Therefore, we conclude that IK.ATP is the only K+ current activated by nicorandil, and the main effect of nicorandil is on the kinetics of the IK.ATP bursting behaviour. These actions are similar to that of pinacidil on this preparation.

Adenosine Triphosphate↗
PubMed1991

Depression of delayed outward K+ current by Co2+ in guinea pig ventricular myocytes.

Effects of Co2+ on the delayed outward K+ current (IK) in guinea pig ventricular myocytes were studied using the whole cell patch-clamp technique. IK was activated by depolarizing voltage pulses positive to -30 mV and reached half-maximal activation at +24 mV. Co2+ shifted the activation curve to a more depolarized voltage range in a concentration-dependent manner, with a Co2+ concentration at which half-maximal response occurs (IC50) of 8 mM and a saturation value of +38 mV. The voltage dependency of IK gatings showed a shift similar to that of activation. In both cases the shift could be explained by screening of surface potential. The density of total negative surface charges sensed by Co2+ was estimated to be 1 e/225 A2. Co2+ also reduced the fully activated IK [IK(full)], and the dose-response curve had a Hill coefficient of 0.5 and an IC50 of 1 mM at 0 mV. Depression of IK(full) was mainly voltage independent. The single-channel unitary current estimated by fluctuation analysis was approximately 0.1 pA at -30 mV either in the absence or presence of Co2+. Therefore, the depression of IK(full) is due to an equivalent reduction in the number of functional channels. It is concluded that Co2+ depressed IK through multiple mechanisms.

Animals↗
PubMed1991

Two components of use-dependent block of Na+ current by disopyramide and lidocaine in guinea pig ventricular myocytes.

We studied the kinetics of the use-dependent block of the Na+ current (INa) by disopyramide and lidocaine. INa was recorded from isolated guinea pig ventricular myocytes by using the whole-cell patch-clamp technique. The use-dependent block of INa by disopyramide with 20- and 200-msec depolarizing pulses developed in two exponential functions. The degree of the use-dependent block and the amplitude of the fast (Af) and slow (As) components with the short (20-msec) pulse protocol were comparable to those with the long (200-msec) pulse protocol. When pH was raised from 7.3 to 8.0, disopyramide increased Af without a change in As. At pH 6.5, INa block developed with a single exponential function revealing only the slow component. The fast and slow components of INa block by disopyramide could be explained by binding of the uncharged and charged forms, respectively, to the activated state of the channel. Development of INa block by lidocaine also was expressed by two exponentials at all pulse durations (5-200 msec). As pulse durations were prolonged or holding potentials were depolarized, the degree of the use-dependent block and Af increased. When pH was lowered to 6.5, the short pulse produced only the slow component, whereas the long pulse caused two exponentials with decreased Af and increased As. Internal application of QX-314, a permanently charged lidocaine analogue, produced a single exponential block of INa with a very slow onset rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Establishment and preliminary application of spermidine radioimmunoassay with 125I-labelled monoclonal antibody and solid phase antigen.

Purified anti-spermidine monoclonal antibody was labelled with radioactive iodine by the Iodogen method and spermidine-bovine serum albumin (SPD-BSA) conjugate was used to coat polystyrene beads as solid phase antigen. The new solid phase 125I-labelled spermidine radioimmunoassay (RIA) depends on the competition between spermidine in the sample and the solid phase antigen for the limited amount of 125I-labelled monoclonal antibody. The sensitivity of this assay was 10 ng/ml higher than that of liquid RIA for spermidine with 14C-labelled spermidine. The coefficients of variation (CV) within and among batches were 4% and 13% respectively. The sample-batch capacity was increased from 20 (liquid RIA with 14C-labelled spermidine) to 150-200 by using this method. Because of its simplicity, the solid phase RIA kit is very convenient for population survey. This RIA could be used to determine spermidine in saliva for the diagnosis of precancerous lesions. In a preliminary study saliva spermidine levels in different populations were measured among 130 normal subjects, 202 esophageal epithelial hyperplasia cases treated with anti-tumor B for 5 years, 207 esophageal epithelial hyperplasia cases as control, and 55 esophageal cancer patients. The levels were 1,795 +/- 1,481, 3,470 +/- 6,981, 9,753 +/- 17,641 and 18,090 +/- 21,509 ng/ml, respectively, with the saliva spermidine levels in precancerous and cancer patients being significantly higher than that of normal subjects (P less than 0.001); the level in patients treated with anti-tumor B was significantly lower than that of controls (P less than 0.001). This decreased saliva spermidine content was coincident with the 47.3% reduction of canceration rate seen in precancerous patients after a 5-year treatment with anti-tumor B.

Antibodies, Monoclonal↗
PubMed1990

Pinacidil activates the ATP-sensitive K+ channel in inside-out and cell-attached patch membranes of guinea-pig ventricular myocytes.

Patch-clamp techniques were used to study the effects of pinacidil on the adenosine-5'-triphosphate (ATP)-sensitive K+ channel current in guinea-pig ventricular myocytes. In inside-out patches, the ATP-sensitive K+ channel current could be recorded at an internal ATP concentration of 0.5 mM or less and almost complete inhibition was achieved by raising the concentration to 2 mM. Application of pinacidil (10-30 microM) in the presence of 2 mM ATP restored the current, whereas 5 mM ATP antagonized the effect of pinacidil. The conductance of the channel at symmetrical K+ concentrations of 140 mM was 75 pS with a slight inward rectification at voltages positive to + 40 mV. There was no significant change in the conductance after application of pinacidil. In 0.5 mM ATP, at -80 mV, both the distributions of the open time and the life-time of bursts could be fitted by a single exponential. An increase in ATP concentration decreased the mean life-time of bursts, whereas pinacidil increased it with little increase in the mean open time. Closed time distributions of the channel were fitted by at least two exponentials, with a fast and a slow time constant. An increase in ATP concentration markedly increased the slow time constant associated with a decrease in the number of bursts, whereas the effect of pinacidil was opposite to that of increased ATP. These results indicate that pinacidil increases the open-state probability of the ATP-sensitive K+ channel.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗
PubMed1990

Multiple actions of pinacidil on adenosine triphosphate-sensitive potassium channels in guinea-pig ventricular myocytes.

1. The patch-clamp method was used to study the effects of pinacidil on the adenosine 5'-triphosphate (ATP)-sensitive K+ channel current in guinea-pig ventricular myocytes. 2. In the inside-out configuration of the patch membranes, the channel activity revealed a nearly fully open state in the absence of ATP, whereas application of ATP (0.1-5 mM) markedly suppressed the channel opening. Addition of pinacidil (0.02-1.0 mM) antagonized the inhibitory action of ATP and induced channel opening without marked change in conductance. An increase in ATP concentration depressed the maximal effect of pinacidil. Consequently, the dose-response relationship of ATP inhibition was shifted to the right, but the shift approached a limiting value as pinacidil concentration was increased. The results indicate that the antagonism between pinacidil and ATP is not competitive. 3. The dose-response curve for activation of the channel by pinacidil examined at -50 mV showed a sigmoidal shape but at +50 mV it had a convex shape, revealing asymmetry in the activating effects of pinacidil at these two voltages. 4. In the absence of ATP, pinacidil produced a voltage-dependent block at positive voltages by decreasing the mean open time and increasing the mean closed time, whereas no such effects were observed at negative voltages. The concentration-block relation at a given voltage was fitted to a first-order Hill saturation function. The Kd (dissociation constant) decreased with depolarization from 2.2 mM at +20 mV to 0.15 mM at + 80 mV. 5. The kinetics of block and unblock by pinacidil were shown to be slow, and were expressed by a first-order transition model. The blocking and unblocking rate constants were voltage dependent. 6. The slow block of single-channel current showed an exponential decay in the ensemble current. The time constant of the decay was voltage dependent, reaching a maximal value at around +50 mV. 7. In the absence of ATP, the channel activity gradually decreased and eventually stopped within 12-20 min, a process known as run-down of channel activity. Calcium accelerated this run-down process. Application of pinacidil partially reactivated the channel. Such channel reactivation by pinacidil during the course of run-down depended upon the conditions of the patch and the time course of the run-down. Pretreatment of the channel with ATP markedly strengthened the reactivation effect of pinacidil. 8. These results indicate that there are multiple sites or processes for interaction of pinacidil with the ATP-sensitive K+ channel.

Action Potentials↗
PubMed1990

Interrelation between pinacidil and intracellular ATP concentrations on activation of the ATP-sensitive K+ current in guinea pig ventricular myocytes.

The patch-clamp technique was used to study the relation between pinacidil and intracellular ATP concentration [( ATP]i) on the activation of the outward K+ current in guinea pig ventricular myocytes. Pinacidil shortened the action potential duration, exhibiting stronger effect at 2 mM [ATP]i than at 5 mM [ATP]i. Pinacidil at 5 microM or higher concentrations activated the time-independent outward current at potentials positive to -80 mV, and the pinacidil-activated current was suppressed by increasing [ATP]i from 2 to 5 mM. The dose-response curve of pinacidil at different [ATP]i showed a shift to the right and a depression of the maximum response at increased [ATP]i. The pinacidil-induced shortening of the action potential duration and outward current were inhibited by application of 0.3-1.0 microM glibenclamide. In single-channel current recordings, pinacidil activated the intracellular ATP-sensitive K+ channel current without changing the unitary amplitude, and increased open probability of the channel, an effect dependent on [ATP]i. The pinacidil-activated single-channel current was blocked by glibenclamide. These results prove the notion that pinacidil activates the ATP-sensitive K+ channel current, which explains the action potential shortening in cardiac cells after application of pinacidil.

Action Potentials↗
PubMed1990

[The blocking effect of ethmozin on sodium current in single myocardial cell].

Effects of ethmozin on sodium current in isolated single ventricular cells were studied using a giga-ohm seal patch electrode and whole cell clamp technique. The results were quite similar with the previous paper on multiple ventricular cell preparation. Further evidences were used to clarify the uncertainty in the previous work of using conventional microelectrode to record action potential. Ethmozin (1-5 mg/L) suppressed phase 0 of action potential recorded in single cell without significant influence on other portions of action potential, which was shown in current clamp mode. In voltage clamp mode, suppress of sodium current (INa) by ethmozin could be recorded through all the physiological voltage range with slight shift of peak (INa) to the positive voltage. Time course of decay of INa was also slowed down by ethmozin. Thus, the mechanism of the slowing down of the rising phase and propagation velocity as well as a rise in threshold of excitability in ventricular muscle reported before was disclosed. Furthermore, ethmozin modified recovery course of INa by decelerating it, which confirmed its use-dependent action discovered before. However, ethmozin promotes its block effect on INa with tonic block stronger than phasic block. Ethmozin has no influence on other membrane current components such as slow inward calcium current and outward potassium current in the present doses. It was concluded that ethmozin is a specified sodium blocker with modification actions on its gating process.

Action Potentials↗
PubMed1990

[Description of six new species of the family Anthomyiidae from Mountain Emei].

1. Eutrichota (Parapegomyia) tuberifolia Deng, Fan et Li, sp. nov. Male: Body length 6mm. The new species is related to Eutrichota (Parapegomyia) socculata Zett., 1938, both with the posterior lobe of pregonites well extended. But the former differs from the latter by the expanded fore part of posterior twig of pregonite and a deep concaving on anterior part of postgonite beyond the setuta. Holotype male, paratypes 2 male male (kept in Department of Parasitology, West China University of Medical Sciences), Leidongping, Mt. Emei, Sichuan, China, July 1983, coll Deng Anxiao. 2. Pegohylemyia apiciquadrata Deng, Fan et Li, sp. nov. male: Body length 6.5mm. The new species resembles Pegohylemyia spinisternata Suwa, 1974 and is characterized by a quadrately apex of cerci and an eagle-beaked apex of postgonites. Holotype male (kgpt in Shanghai Institute of Entomology), paratypes 4 male male (kept in Department of Parasitology, West China University of Medical Sciences) Jinding Mt. Emei, Sichuan, China, July 1984, coll. Deng Anxiao. 3. Pegohylemyia macrospinigera Deng, Fan et Li, sp. nov. male: Body length 6mm. The new species is similar to Pegohylemyia zhuoniensis Jin, 1983 in shape of the cerci and surstyli, having a round but not pointed apex of postgonite and a rank of much strong bristles on the inner side of 5th sternite. Holotype male, paratypes 4 male male (as is stated above No. 2), Huayanding, Mt. Emei, Sichuan, China, July 1984, coll. Deng Anxiao. 4. Pegohylemyia Pardocephalla Deng, Fan et Li, sp. nov. male: Body length 6mm.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

New observations on the mechanisms of antiarrhythmic actions of disopyramide on cardiac membranes.

Electrophysiologic effects of disopyramide on cardiac membranes were studied using the microelectrode technique applied to papillary muscles and the suction pipette whole-cell clamp method applied to isolated ventricular myocytes from guinea-pig hearts. In contrast to previous reports, the development and recovery from the Vmax blocks of action potentials by disopyramide and lidocaine were best expressed by 2 exponential functions, not 1, suggesting that there might be 2 different processes for the sodium current block. A near-therapeutic concentration (11 microM) of disopyramide depressed Vmax at frequencies of 0.1 to 2.0 Hz decreased action potential amplitude and shortened plateau phase in ventricular myocytes. Action potential duration was prolonged by the drug in most of the preparations but shortened in some. Disopyramide prolonged the refractory period and increased threshold current for excitation. The drug was also shown to depress both the calcium current and the delayed outward potassium current. These multiple actions of disopyramide may explain its variety of antiarrhythmic properties.

Action Potentials↗
PubMed1989

Amantadine-induced afterpotentials and automaticity in guinea pig ventricular myocytes.

The ionic mechanisms of amantadine-induced changes in membrane potential and automatic activity in guinea pig ventricular myocytes were studied using the suction-pipette whole-cell clamp method. While 25-100 microM amantadine decreased the action potential amplitude and duration, 200 and 400 microM amantadine lengthened the action potential duration and decreased the maximum diastolic potential with an appearance of diastolic depolarization and automaticity. In the presence of 25-100 microM amantadine, the preparations developed an afterpotential due to incomplete repolarization and a delayed afterdepolarization that eventually brought about triggered automaticity. The former type of afterpotential was abolished by tetrodotoxin (TTX) and the latter by Co2+. Spontaneous activity from the diastolic depolarization was also abolished by Co2+ but not by Cs+. Amantadine suppressed the calcium current to as much as half of the control at the concentrations used (25-200 microM). The drug also produced a depression of the inward rectifier K+ current. The outward current showing time-dependent decay was activated at the plateau voltages by concentrations lower than 100 microM, whereas the delayed outward K+ current was depressed by the drug in a concentration-dependent manner at more positive potentials. Amantadine activated the TTX-sensitive and TTX-insensitive inward currents on repolarization from depolarized states, without producing the transient inward current. These results indicate that the amantadine-induced diastolic depolarization and afterpotentials are caused by changes in multiple ionic currents and that, therefore, the drug can be used as a unique model for the study of arrhythmogenesis.

Amantadine↗