Biomedical subjects

C J Hu

Publications and source records attributed to C J Hu.

At least 37 records · Page 2Linked to original sources

PubMed1998

Rapid detection of a recombinant hotspot associated with Charcot-Marie-Tooth disease type IA duplication by a PCR-based DNA test.

A 1.5-Mb duplication on chromosome 17p11.2-p12 (CMT1A duplication) caused by a misalignment of the CMT1A repeat sequences (CMT1A-REPs) is associated with Charcot-Marie-Tooth disease type 1A (CMT1A). A hotspot of crossover breakpoints located in a 3.2-kb region of the CMT1A-REPs accounts for three-quarters of the rearrangements in CMT1A patients. We developed a PCR-based diagnostic method to detect a recombination hotspot associated with the CMT1A duplication. Thirty-one CMT1A Chinese patients from different families and 50 healthy people over 65 years of age were studied. Twenty-seven of the 31 cases demonstrated the 3.2-kb hotspot crossover, of which there were two subgroups. The type 1 crossover breakpoint was located at the distal CMT1A-REP around the PmeI site, and accounted for 24 of the 27 cases with a 3.2-kb hotspot crossover in CMT1A duplication patients. The type 2 crossover breakpoint was located at the distal CMT1A-REP around the base 3625 region, accounting for 3 of the 27 cases. The results correlated very well with the results of Southern transfer analysis. This study has a potentially important role in the diagnosis of CMT1A disease.

Charcot-Marie-Tooth Disease↗

PubMed1997

Traumatic brainstem deafness with normal brainstem auditory evoked potentials.

A 48-year-old woman became totally deaf after a head injury. Magnetic resonance imaging showed bilateral contusions around the inferior colliculi and the brainstem auditory evoked potentials (BAEP) failed to show any abnormality. This case demonstrates that small, symmetrical, bilateral lesions around the inferior colliculi may cause deafness and may still be associated with a normal BAEP.

Auditory Pathways↗

PubMed1997

Effects of dauricine, quinidine, and sotalol on action potential duration of papillary muscles in vitro.

AIM: To compare the characteristics of dauricine, sotalol, and quinidine on action potential duration (APD). METHODS: Using intracellular microelectrode method to record APD in guinea pig papillary muscles. RESULTS: Dauricine 20 mumol.L-1 prolonged action potential at 90% repolarization, the percent of APD prolongation were 22 +/- 8, 11 +/- 6, 9 +/- 5, 7 +/- 5, 6 +/- 3, 4.3 +/- 2.8, 4.5 +/- 2.8 at the cycle lengths of 200-2000 ms, dauricine became more effective in lengthening APD at short cycle lengths. The effect of dauricine on prolonging APD exhibited normal use-dependence, whereas quinidine 1 mumol.L-1 and sotalol 10 mumol.L-1 were less effective in lengthening APD at short cycle lengths. The effect of quinidine and sotalol on APD exhibited reverse use-dependence. CONCLUSION: [corrected] The effect of dauricine on APD depends on activation frequency.

Action Potentials↗

PubMed1997

Dauricine inhibited L-type calcium current in single cardiomyocyte of guinea pig.

AIM: To study the effect of dauricine (Dau) on L-type calcium current in guinea pig ventricular myocytes. METHODS: Using whole-cell recording method to record L-type calcium current (ICa) in single ventricular cell of guinea pig. RESULTS: Dau 1, 10, and 100 mumol.L-1 markedly reduced ICa by 15.2% +/- 2.2%, 41% +/- 5%, and 82% +/- 8%, respectively. After washing out, ICa partially recovered. Dau inhibited ICa at 3 Hz and 1 Hz to a similar extent, its effect on ICa appeared to be not frequency-dependent. CONCLUSION: Dau had a calcium channel blocking effect.

Alkaloids↗

PubMed1996

Effects of daurisoline on intracellular Ca2+ activity in myocardium.

AIM: To explain the effect of daurisoline (DS) on delayed afterdepolarization (DAD). METHODS: Ca(2+)-sensitive microelectrode technic was used to record intracellular Ca2+ activity (alpha Cai) and triggered activity (TA) arising from DAD in myocardium. RESULTS: Strophantin G 3 mumol.L-1 yielded an increase in resting myocardial alpha Cai by 0.19 +/- 0.11 mumol.L-1 and transient elevations of alpha Cai by 1.48 +/- 0.55 and 4.96 +/- 1.81 mumol.L-1, respectively during the development of DAD and TA. By pretreatment with DS or verapamil, strophantin G-caused elevations of the alpha Cai in resting and provoked myocardia were eliminated and TA disappeared. DS 50 mumol.L-1 reduced Na(+)-free medium-induced elevation of dog Purkinje fibrous alpha Cai and abolished caffeine-induced increase of dog myocardial alpha Cai. CONCLUSIONS: DS inhibited DAD and TA by preventing an increase of alpha Cai via transmembrane Ca2+ entry and Ca2+ release from the reticulum.

Action Potentials↗

PubMed1995

Comparison of the in vitro host range of recombinant met-interferon-con1, interferon-alpha 2b, and interferon-beta [corrected].

The antiviral activity of human r-metIFN-con1 was compared with that of IFN-alpha 2b and IFN-beta on a number of human, other primate, rodent, feline, and canine cell lines. Although the specific activities of r-metIFN-con1 and IFN-alpha 2b differed 10-fold, the host range was very similar. The host range of IFN-beta differed from that of r-metIFN-con1 and IFN-alpha 2b in that Vero cells were 100-fold better protected by IFN-beta and MDBK protected at a 100-fold less efficiency. In general, there were only minor differences between the host ranges of the three interferons, human and primate cells being better protected than those of other species. However, the tissue of origin of the cell appears to be more important than the species of origin in defining host range [corrected].

Animals↗

PubMed1994

[Antagonism of daurisoline on arrhythmogenic delayed afterdepolarization].

Standard microelectrode technique was used to study the effect of daurisoline (DS) on delayed afterdepolarization (DAD) and triggered activity (TA) in guinea pig ventricular trabeculae. DS (50 mumol.L-1) abolished TA induced by ouabain or caffeine, inhibited isoprenaline-induced TA, decreased incidence of TA induced by K(+)-free and high-Ca2+ medium or phenylephrine from 100.75% to 9.1% and 22.2% respectively, and significantly suppressed DAD caused by the above induces. It is concluded that DS exert antagonistic action to DAD and TA in guinea pig trabeculae.

Alkaloids↗

PubMed1994

[Measurement of cytoplasmic Ca2+ activity in myocardia with Ca(2+)-sensitive microelectrode].

The improved neutral ligand ETH1001 Ca(2+)-sensitive microelectrodes (Ca-ISE, tip diameter 0.4-0.8 mumol.L-1) are highly ion selective and sensitive and therefore can be reliably used to measure cytoplasmic Ca2+ activity (alpha iCa) in myocardia. The resting alpha iCa in guinea-pig ventricular trabecula, canine ventricular myocardia and Purkinje fibers were respectively 0.19 +/- 0.01, 0.20 +/- 0.02 and 0.46 +/- 0.07 mumol.L-1. Three mumol.L-1 strophantin G increased the resting and dynamic myocardial alpha iCa by 0.18 +/- 0.02 and 6.69 +/- 2.09 mumol.L-1 respectively, as well as engendered triggered activity (TA). When pretreated with 100 mumol.L-1 dauricine (Dau), strophantin G could no longer increase alpha iCa and TA disappeared. It is suggested thus the applicability of Ca-ISE for measurement of myocardia alpha iCa and TA is obvious.

Alkaloids↗

PubMed1993

[First-pass effect of dauricine].

The first-pass effect of dauricine (Dau) was compared with that of lidocaine (Lid) by measuring the ventricular fibrillation threshold (VFT) and dauricine plasma concentration in rats or rabbits. After forelimb or mesenteric vein (imv) infusion of Dau at a rate of 1 mg.kg-1 x min-1 in rats, the VFT were 1.64-3.17 or 1.60-2.11 V, respectively. In the case of Lid at 2.5 mg.kg-1 x min-1, the VFT were 1.69-4.79 or 1.67-2.80 V, respectively, after ear vein (iev) or imv infusion of Dau at a rate of 0.5 mg.kg-1 x min-1 in rabbits, the VFT were 6.50-12.14 or 5.81-7.43 V, respectively. Plasma Dau concentration through iev infusion was significantly higher than that through imv route. As the dose of imv infusion increased, AUC of Dau showed a nonlinear increase. The results suggested that Dau showed a considerable first-pass effect, which was dose-dependent.

Alkaloids↗

PubMed1993

[Hypotensive effect of dihydrolycorine].

Dihydrolycorine-HCL(DL) is a derivative of lycorine, an alkaloid isolated from Lycoris radiata Herb. DL iv 20, 40, and 80 mg.kg-1 lowered the mean arterial pressure in pentobar-bitone-anesthetized normotensive rats, cats, and conscious rats either normotensive or renovascular hypertensive. In pithed rats DL depressed the hypertensive effect of reaction to electric stimulation to the T7-9 segments of spinal cord. DL also depressed the hypertensive effect of phenylephrine. In rabbit aorta ring and rat anococcygeus muscle, DL antagonized the contractile effect of methoxamine, with pA2 values of 5.93 and 6.35, respectively. These results suggest that DL can block alpha 1-adrenoceptors.

Alkaloids↗

PubMed1992

Aggregation of washed platelets by plasminogen and plasminogen activators is mediated by plasmin and is inhibited by a synthetic peptide disulfide.

Plasmin is known to activate platelets. However, it is not clear whether plasminogen activators as used in thrombolytic therapy can aggregate platelets and how this relates to the ability of each activator to convert plasminogen to plasmin. Urokinase (UK) and streptokinase (SK) activated purified plasminogen (2 microM) in a concentration-dependent manner. The rates of aggregation of washed platelets by the above plasminogen activators and plasminogen were similar to the extent of activation of plasminogen to plasmin in the absence of platelets. UK or SK (0.2 microM) and plasminogen (2 microM) aggregated platelets modified by an ADP affinity analog, 5'-p-fluorosulfonylbenzoyladenosine (FSBA), and cleaved aggregin, a putative ADP receptor, in [3H]FSBA-modified platelets. These results suggest that the effect was independent of ADP. In contrast, incubation mixtures containing only plasminogen (2 microM) and single chain tissue plasminogen activator (sc-tPA) (less than or equal to 0.12 microM) neither activated the zymogen to an appreciable extent nor aggregated platelets. But, in the presence of fibrin(ogen) fragments (tPA-stimulator), a mixture of plasminogen and sc-tPA aggregated unmodified and FSBA-modified platelets, and cleaved aggregin. The results imply that platelets, in the presence of t-PA stimulator, potentiate activation of plasminogen to plasmin by t-PA, as previously reported. P1, Phe-Gln-Val-Val-Cys-(NpyS)-Gly-NH2, (NpyS = 3-nitro-2-thiopyridine), a synthetic hexapeptide capable of binding to and inhibiting calpain, has been shown to inhibit platelet aggregation induced by purified plasmin. P1 inhibited platelet aggregation by plasminogen and any of the three plasminogen activators. Our results show that at plasma concentrations of plasminogen and at levels of UK and SK attained after infusion of these agents during thrombolysis, these mixtures can cause maximum aggregation which may contribute to reocclusion and stenosis following infarct therapy. P1 can effectively inhibit platelet aggregation under such conditions.

Amino Acid Sequence↗

PubMed1992

Clopidogrel inhibits the binding of ADP analogues to the receptor mediating inhibition of platelet adenylate cyclase.

Clopidogrel, like the homologous thienopyridine derivative ticlopidine, selectively inhibits platelet aggregation induced by ADP. We have previously described two nucleotide-binding sites on platelets related to ADP-mediated platelet responses. The first is a high-affinity binding site for 2-methylthio-ADP (2-MeSADP) that is linked to the inhibition of stimulated adenylate cyclase. The second is the 100-kd exofacial membrane protein aggregin, which is labeled by the reactive ADP analogue 5'-p-fluorosulfonylbenzoyl adenosine (FSBA) that is related to shape change and aggregation. We set out to determine if either of these sites is blocked in vivo by clopidogrel or its active metabolite. Six subjects were given clopidogrel (75 mg/day for 10 days) in a double-blind crossover experiment. All of the subjects developed prolonged bleeding times while taking the drug. The rate of onset of the effect on bleeding time varied among subjects. Platelet aggregation induced by ADP or thrombin was significantly impaired by the drug treatment, but no effect was detected on shape change. The incorporation of [3H]FSBA into aggregin was also unaffected. Inhibition of adenylate cyclase by ADP or by 2-MeSADP was greatly reduced in all subjects, and in the case of 2-MeSADP, there was evidence for a noncompetitive effect. Inhibition of adenylate cyclase by epinephrine was unaffected. In the three subjects for whom binding measurements were made, the number of binding sites for [32P]2-MeSADP was reduced from 534 +/- 44 molecules per platelet during control and placebo periods (11 determinations) to 199 +/- 78 molecules per platelet during drug treatment (three determinations). There was no consistent change in the binding affinity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1992

Protective and anti-arrhythmic effects of dauricine and verapamil on acute myocardial infarction in anesthetized dogs.

Dauricine (Dau) 5 mg.kg-1 and verapamil (Ver) 0.15 mg.kg-1 iv followed by infusions of 0.1 and 0.01 mg.kg-1.min-1, respectively, for 30 min, depressed the elevated coronary venous blood LDH and CPK after LAD occlusion. Dau produced antagonistic effects on acute myocardial ischemia-induced ventricular ectopic activities (VE) and ventricular tachycardia (VT). The incidences of VE and VT in Ver group and ventricular fibrillation (VF) in both groups tended to descend. The results suggested that Dau and Ver produced marked protective effects on myocardial infarction and antagonized the acute ischemic arrhythmia.

Alkaloids↗

PubMed1991

High molecular weight kininogen inhibits thrombin-induced platelet aggregation and cleavage of aggregin by inhibiting binding of thrombin to platelets.

In this study we show that high molecular weight kininogen (HK) inhibited alpha-thrombin-induced aggregation of human platelets in a dose-dependent manner with complete inhibition occurring at plasma concentration (0.67 mumol/L) of HK. HK (0.67 mumol/L) also completely inhibited thrombin-induced cleavage of aggregin (Mr = 100 Kd), a surface membrane protein that mediates adenosine diphosphate (ADP)-induced shape change, aggregation, and fibrinogen binding. The inhibition of HK was specific for alpha- and gamma-thrombin-induced platelet aggregation, because HK did not inhibit platelet aggregation induced by ADP, collagen, calcium ionophore (A23187), phorbol myristate acetate (PMA), PMA + A23187, or 9,11-methano derivative of prostaglandin H2 (U46619). These effects were explained by the ability of HK, at physiologic concentration, to completely inhibit binding of 125I-alpha-thrombin to washed platelets. As a result of this action of HK, this plasma protein also completely inhibited thrombin-induced secretion of adenosine triphosphate, blocked intracellular rise in Ca2+ in platelets exposed to alpha- and gamma-thrombin, inhibited thrombin-induced platelet shape change, and blocked the ability of thrombin to antagonize the increase in intracellular cyclic adenosine monophosphate (cAMP) levels induced by iloprost. Because elevation of cAMP is known to inhibit binding of thrombin to platelets, we established that HK did not increase the intracellular concentration of platelet cAMP. Finally, HK did not inhibit enzymatic activity of thrombin. To study the role of HK in the plasma environment, we used gamma-thrombin to avoid fibrin formation by alpha-thrombin. Platelet aggregation induced by gamma-thrombin was also inhibited by HK in a dose-dependent manner. The EC50 (concentration to produce 50% of the maximum rate of aggregation) of gamma-thrombin for washed platelets was 7 nmol/L and increased to 102 nmol/L when platelets were suspended in normal human plasma. The EC50 for platelet aggregation induced by alpha-thrombin in plasma deficient in total kininogen was 40 nmol/L. When supplemented with HK at plasma concentration (0.67 mumol/L), the EC50 increased to 90 nmol/L, a value similar to that for normal human plasma. These results indicate that (1) HK inhibits thrombin-induced platelet aggregation and cleavage of aggregin by inhibiting binding of thrombin to platelets; (2) HK is a specific inhibitor of platelet aggregation induced by alpha- and gamma-thrombin; and (3) HK plays a role in modulating platelet aggregation stimulated by alpha-thrombin in plasma.

Adenosine Triphosphate↗

PubMed1990

Effects of dauricine and lidocaine alone or combined on electrophysiological properties of canine Purkinje fibers.

Dauricine (Dau) 1 to 30 mumol/L produced the concentration-dependent depressions in the APA, Vmax, MDP, and prolongations of APD50 and APD90 as well as ERP of the isolated canine cardiac Purkinje fibers (PF). The automaticity and excitation were significantly reduced at concentration of 30 mumol/L. The effects of Dau on all action potential parameters of PF were observed at all stimulation frequencies (60, 75, 100, 150 beats/min). Lidocaine (Lid) markedly shortened APD50 of PF at concentration of 30 mumol/L and also shortened APD90, ERP and significantly depressed APA, Vmax at 100 mumol/L. When perfused in combination with Dau, Lid appreciably shortened APD50 and APD90, and lightly abbreviated ERP prolonged by Dau.

Action Potentials↗

PubMed1990

Effects of dauricine on transmembrane potential of ischemic and non-ischemic Purkinje fibers and ventricular muscles from infarcted canine hearts.

Dauricine (Dau) 1-30 mumol/L produced the concentration-dependent depression of APA, Vmax, MDP, and RP, and prolongations of APD90 of Purkinje fibers (PF) and epicardial ventricular muscles (VM) from both infarcted and non-infarcted zones. The ERP was lengthened only in non-ischemic PF and VM, and APD50 in non-ischemic PF, non- and ischemic VM. The prolonging effects of Dau on APD and ERP of ischemic PF were much less than those of non-ischemic ones, and its depressing effect on the Vmax of ischemic VM was markedly greater than that of non-ischemic VM. The results suggest that Dau exerts its anti-arrhythmic effect through further depressing conduction of ischemic zone.

Action Potentials↗

PubMed1990

[Effects of dauricine on His-bundle electrogram and interaction with other drugs in anesthetized rabbits].

Dauricine was shown to prolong the HBE A-H, H-V intervals and the V width of anesthetized rabbits in a dose-dependent manner. Dauricine 2.5, 5 and 7.5 mg/kg iv increased the A-H interval by 11 +/- 6, 21 +/- 12 and 33 +/- 14%; prolonged the H-V interval by 22 +/- 9, 34 +/- 22 and 51 +/- 16%; and widened the V by 14 +/- 6, 22 +/- 12 and 27 +/- 11%, respectively. The effect of dauricine on the H-V interval was greater than on the A-H interval. Influence of lidocaine on the His-bundle electrogram was not significant. The effect of dauricine on the H-V interval was weakened when administered in combination with lidocaine (p less than 0.05). Dauricine 7.5 mg/kg prolonged the A-H interval at all stimulation frequencies (300, 335, 375, 430 beats/min). Dauricine increased the atrial effective refractory period (AERP) and the atrial-ventricular (A-V) node functional refractory period (AVNFRP) of the rabbits in dose-dependent manner. Isoprenaline 10 micrograms/kg iv shortened the A-H, H-V intervals and V width, and atropine 3 mg/kg iv partially reduced the A-H interval prolonged by dauricine.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaloids↗

PubMed1989

Thrombin-induced platelet aggregation involves an indirect proteolytic cleavage of aggregin by calpain.

5'-p-Fluorosulfonylbenzoyl adenosine (FSBA), a nucleotide analog of ADP, has been shown to inhibit ADP-induced shape change, aggregation and exposure of fibrinogen binding sites concomitant with covalent modification of a single surface membrane polypeptide of Mr 100,000 (aggregin). Since thrombin can aggregate platelets which have been modified by FSBA and are refractory to ADP, we tested the hypothesis that thrombin-induced platelet aggregation might involve cleavage of aggregin. At a low concentration of thrombin (0.05 U/ml), platelet aggregation, exposure of fibrinogen receptors and cleavage of aggregin in FSBA-modified platelets did not occur, indicating ADP dependence. In contrast, incubation of [3H]FSBA-labeled intact platelets with a higher concentration of thrombin (0.2 U/ml) resulted in cleavage of radiolabeled aggregin, aggregation, and exposure of fibrinogen binding sites. Under identical conditions, aggregin in membranes isolated from [3H]FSBA-labeled platelets was not cleaved by thrombin. Thrombin-induced platelet aggregation and cleavage of aggregin were concomitantly inhibited by a mixture of 2-deoxy-D-glucose, D-gluconic acid 1,5-lactone, and antimycin A. These results suggest that thrombin cleaves aggregin indirectly by activating an endogeneous protease. Thrombin is known to elevate intracellular Ca2+ concentration and thereby activates intracellular calcium dependent thiol proteases (calpains). In contrast to serine protease inhibitors, calpain inhibitors including leupeptin, antipain, and ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (chelator of Ca2+) inhibited platelet aggregation and cleavage of aggregin in [3H]FSBA-labeled platelets. Leupeptin, at a concentration of 10-20 microM, used in these experiments, did not inhibit the amidolytic activity of thrombin, thrombin-induced platelet shape change, or the rise in intracellular Ca2+. Purified platelet calpain II caused aggregation of unmodified and FSBA-modified platelets and cleaved aggregin in [3H]FSBA-labeled platelets as well as in isolated membranes. The latter is in marked contrast to the action of thrombin on [3H]FSBA-labeled membranes. Thus, thrombin-induced platelet aggregation may involve intracellular activation of calpain which proteolytically cleaves aggregin thus unmasking latent fibrinogen receptors, a necessary prerequisite for platelet aggregation.

Adenosine↗