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Y C Zhang

Publications and source records attributed to Y C Zhang.

At least 37 records · Page 2Linked to original sources
PubMed2000

Antisense inhibition of beta(1)-adrenergic receptor mRNA in a single dose produces a profound and prolonged reduction in high blood pressure in spontaneously hypertensive rats.

BACKGROUND: beta-Blockers are the first line of therapy for hypertension. However, they are associated with side effects because of central nervous system (CNS) effects and beta(2)-adrenergic antagonism. To overcome these problems and provide a long-term beta(1)-blockade, antisense oligonucleotides against rat beta(1)-adrenergic receptor (beta(1)-AR) mRNA (beta(1)-AS-ODN) were designed and tested for the ability to inhibit cardiac beta(1)-ARs as well as lower blood pressure in spontaneously hypertensive rats (SHRs). METHODS AND RESULTS: Radioligand binding assay showed that a single intravenous injection of beta(1)-AS-ODN delivered in cationic liposomes significantly decreased cardiac beta(1)-AR density by 30% to 50% for 18 days (P<0.01), with no effect on beta(2)-ARs. This was accompanied by marked attenuation of beta(1)-AR-mediated positive inotropic response in isolated perfused hearts in vitro (P<0.02) and in conscious SHRs monitored by telemetry in vivo (P<0.02). Furthermore, the blood pressure of SHRs was reduced for 20 days, with a 38 mm Hg maximum drop. Heart rate was not significantly decreased. Quantitative autoradiography was performed to assess beta(1)-AS-ODN effects on the CNS, which demonstrated no changes in beta(1)-ARs in brain, in contrast to a significant reduction in heart and kidney (P<0.05). For comparison with beta-blockers, the effects of atenolol on cardiovascular hemodynamics were examined, which lowered blood pressure for only 10 hours and elicited appreciable bradycardia in SHRs. CONCLUSIONS: These results indicate that beta(1)-AS-ODN, a novel approach to specific beta(1)-blockade, has advantages over currently used beta-blockers in providing a profound and prolonged reduction in blood pressure without affecting heart rate, beta(2)-ARs, and the CNS. Diminished cardiac contractility resulting from less beta(1)-AR expression contributes to the antihypertensive effect.

Adrenergic beta-1 Receptor Antagonists↗
PubMed2000

Protection against myocardial dysfunction induced by global ischemia-reperfusion by antisense-oligodeoxynucleotides directed at beta(1)-adrenoceptor mRNA.

Plasma catecholamine levels rise, and myocardial beta(1)-adrenoceptor (beta(1)-AR) sensitivity increases during ischemia. These factors enhance myocardial injury and cardiac dysfunction. beta(1)-AR blockers are clinically used to protect heart against ischemia and to improve cardiac dysfunction in patients with ischemic heart disease, but these agents often cause intolerable side effects. To examine the potential cardioprotective effect of therapy with antisense-oligodeoxynucleotides directed at beta(1)-AR mRNA (beta(1)-AS-ODNs) during myocardial ischemia-reperfusion, Sprague-Dawley rats were treated with beta(1)-AS-ODNs or inverted-oligodeoxynucleotides (IN-ODNs), each 200 microg/rat. Hearts were excised, perfused, and subjected to global ischemia (30 min) followed by reperfusion (30 min). Other rats were given selective beta(1)-AR blocker atenolol (2 mg/kg) or saline before excising the hearts. Ischemia-reperfusion resulted in cardiac dysfunction, indicated by an increase in coronary perfusion pressure and left ventricular end-diastolic pressure and a decrease in developed left ventricular pressure, as well as evidence of lipid peroxidation in saline-treated rats (all P <.05 versus control values). Administration of AS-ODNs or atenolol, but not IN-ODNs, protected hearts against functional deterioration and lipid peroxidation (P <.05 versus saline or IN-ODNs treatment). AS-ODNs therapy appeared to be equivalent to atenolol in these effects. Expression of beta(1)-AR protein as well as mRNA in the myocardium were markedly up-regulated after ischemia-reperfusion, and treatment with beta(1)-AS-ODNs, but not atenolol, decreased the rise in enhanced expression of beta(1)-AR. These observations imply that beta(1)-AS-ODNs can ameliorate cardiac dysfunction after ischemia-reperfusion by reducing the expression of beta(1)-AR in the ischemic-reperfused myocardium.

Animals↗
PubMed2000

Adaptive response of thymocyte apoptosis and cell cycle progression induced by low dose X-ray irradiation in mice.

The dose-effect of adaptive response of thymocyte apoptosis and cell cycle progression induced by whole-body X-ray irradiation (WBI) was studied in male Kunming mice. The inductive doses (D1) were 25, 50, 75, 100 or 200 mGy 6 h before the challenging doses (D2) of 1.0, 1.5 or 2.0 Gy. The changes in the percentages of the thymocyte apoptotic bodies (TAB) and the cells in different phases of cell cycle were measured with flow cytometry. The percentages of TAB decreased, the arrests of G1 and G2 + M phases diminished, and the cells of DNA synthesis of S phase increased when the D1 + D2 groups was compared with the D2 groups. When D1 was 200 mGy, the adaptive response of thymocyte apoptosis and cell cycle progression were no longer induced by low dose radiation (LDR). In addition, the extracellular fluid from the splenocytes were cultured with Con A for 48 h in vitro 24 h after 75 mGy WBI was placed in the murine thymocyte suspension from mice irradiated with 2.0 Gy WBI and co-incubated. The thymocyte apoptosis decreased. Especially, noteworthy was that the percentages of TAB after the incubation for 72 h were significantly lower than those in 2.0 Gy irradiated thymocytes (P < 0.05). These results indicate that when the mice were irradiated with 25-100 mGy (D1, 12.5 mGy/min) 6 h before 1.0-2.0 Gy (D2, 0.287 Gy/min) exposure, an adaptive response of thymocyte apoptosis and cell cycle progression may be induced under the condition of WBI, and LDR (75 mGy) may change the microenvironment of immune cells and decrease the thymocyte apoptosis.

Animals↗
PubMed1999

Upregulation of endothelial receptor for oxidized low-density lipoprotein (LOX-1) in cultured human coronary artery endothelial cells by angiotensin II type 1 receptor activation.

Cross talk between oxidized LDL (ox-LDL) and angiotensin II (Ang II) may be relevant in atherosclerosis. In this study, we examined the presence of a specific endothelial receptor for ox-LDL (LOX-1) and Ang II receptors in human coronary artery endothelial cells (HCAECs). In addition, we studied the effect of Ang II on LOX-1 gene and protein expression. LOX-1 was consistently identified in HCAECs by reverse transcriptase-polymerase chain reaction (RT-PCR), cDNA sequence, Western blot, and 125I-labeled ox-LDL binding assay (Bmax, 29.7 ng/mg protein). The HCAECs also exhibited Ang II receptors (AT1>AT2), as determined by RT-PCR and 125I-labeled Ang II binding assay (Bmax, 2.21 and 1.19 fmol/mg protein, respectively). Incubation of HCAECs with Ang II markedly increased LOX-1 mRNA (RT-PCR) and protein (Western blot) expression. The increase in LOX-1 expression was dependent on Ang II concentration (10(-12) to 10(-6) mol/L). Ang II caused a concentration-dependent increase in 125I-labeled ox-LDL uptake by HCAECs and enhanced ox-LDL-mediated cell injury, as evident from an increase in LDH release and a decrease in cell viability. These effects of Ang II were completely blocked by pretreatment of HCAECs with losartan, a specific AT1 blocker, but not by PD123319, a specific AT2 blocker. These observations indicate the following: (1) HCAECs possess abundant LOX-1 as well as Ang II (AT1>AT2) receptors, (2) Ang II upregulates LOX-1 receptor and ox-LDL uptake, (3) the effects of Ang II are mediated by AT1 activation, and (4) Ang II enhances ox-LDL-mediated injury to HCAECs.

Angiotensin II↗
PubMed1999

Intravenous angiotensinogen antisense in AAV-based vector decreases hypertension.

Angiotensinogen (AGT) has been linked to hypertension. Because there are no direct inhibitors of AGT, we have developed antisense (AS) inhibition of AGT mRNA delivered in an adeno-associated virus (AAV)-based plasmid vector. This plasmid, driven by the cytomegalovirus promoter, contains a green fluorescent protein reporter gene and AS cDNA for rat AGT. Transfection of the plasmid into rat hepatoma cells brought a strong expression of the transgenes and a significant reduction in the level of AGT. In the in vivo study, naked plasmid DNA was intravenously injected into adult spontaneously hypertensive rats at different doses (0.6, 1.5, and 3 mg/kg). Expression of AGT AS mRNA was present in liver and heart, and it lasted longer in the liver. All three doses produced a significant decrease in blood pressure (BP). BP decreased for 2, 4, and 6 days, respectively. The lowest dose decreased BP by 12 +/- 3.0 mmHg, whereas the higher doses decreased BP by up to 22.5 +/- 5.2 mmHg compared with the control rats injected with saline (P < 0.01). The injection of the plasmid with liposomes produced a more profound and longer reduction (8 days) in BP. Consistent changes in plasma AGT level were observed. Sense plasmid had no effect. No liver toxicity was observed after injection of AS plasmid with or without liposomes. Our results suggest that the systemic delivery of AS against AGT mRNA by AAV-based plasmid vector, especially with liposomes, may have potential for gene therapy of hypertension and that further studies with the plasmid packaged into a recombinant AAV vector for a longer-lasting AS effect are warranted.

Angiotensinogen↗
PubMed1998

Critical role of AT1 receptor expression after ischemia/reperfusion in isolated rat hearts: beneficial effect of antisense oligodeoxynucleotides directed at AT1 receptor mRNA.

To examine the relevance of angiotensin II type 1 receptor (AT1R) expression in the determination of myocardial function after ischemia/reperfusion, Sprague-Dawley rats were treated intravenously with antisense oligodeoxynucleotides (AS-ODNs) directed at AT1R mRNA (100 microg/rat, n=9) or scrambled antisense oligodeoxynucleotides (Scr-ODNs, 100 microg/rat, n=6). Both AS-ODNs and Scr-ODNs were given along with 300 microg/rat of liposome DOTAP/DOPE, a positive electron carrier (wt:wt= 1:1). The hearts from AS-ODN- or Scr-ODN-treated rats were excised 24 hours later, perfused in vitro, and subjected to 25 minutes of global ischemia followed by 30 minutes of reperfusion. Parallel groups of rats were given the specific AT1R antagonist losartan (10 mg/kg IV, n=6) or saline (n=7) 4 to 6 hours before excising the hearts. Ischemia/reperfusion resulted in a significant increase in myocardial AT1R expression (autoradiography and binding assay) and myocardial dysfunction, indicated by increases in coronary perfusion pressure and left ventricular end-diastolic pressure and a decrease in developed left ventricular pressure (all P<0.01 versus baseline) in the saline-treated group. AT1R protein and mRNA levels also increased in ischemic/ reperfused myocardial tissues. Administration of AS-ODNs or losartan, but not Scr-ODNs, preserved myocardial function and blocked the increased AT1R binding after ischemia/reperfusion (both P<0.01). Myocardial AT1R mRNA levels were not affected by either AS-ODNs or losartan, and the AT1R protein levels were significantly reduced by AS-ODN, but not losartan, treatment. Plasma angiotensin II levels increased after administration of losartan but not after administration of AS-ODNs. These observations imply a critical role of AT1R upregulation in determining myocardial function immediately after ischemia/reperfusion. AS-ODNs to AT1R mRNA may be more beneficial than losartan, because losartan does not affect the plasma angiotensin II level. The sustained increase in AT1R mRNA, but diminished protein expression, in rat hearts treated with AS-ODNs suggests that AS-ODNs block AT1R at the translational level.

Analysis of Variance↗
PubMed1998

Artemisinin blocks activating and slowly activating K+ current in guinea pig ventricular myocytes.

AIM: To study the effect of artemisinin (Art) on outward rectifier potassium current in ventricular myocytes. METHODS: In isolated guinea pig ventricular myocytes, the effects of Art on the two components of delayed outward rectifier K+ current (IK), the rapidly activating inward K+ current (IKr), and the slowly rectifying outward K+ current (IKs) were observed by the whole cell patch-clamp technique. RESULTS: Art decreased IK in a concentration-dependent manner. The IKstep and IKtail were reduced from 387 +/- 46 pA to 240 +/- 48 pA and from 299 +/- 30 pA to 130 +/- 38 pA, respectively at holding potential of +40 mV by Art 50 mumol.L-1. The envelope of tail analysis suggested that both IKr and IKs were inhibited. CONCLUSION: Art blocked the two components of delayed outward rectifier K+ current (IKr and IKs) in guinea pig ventricular cells.

Animals↗
PubMed1998

Comparative study on 4 EIA kits for screening antibody to hepatitis C virus in pooled sera.

Four enzyme immunoassay (EIA) test kits, 1 Canadian product and 3 Chinese products, were used in the comparative study. Each pool consisted of 5 sera, and the 5 single sera were tested as controls. The tests were carried out according to the instructions, keeping the same dilution of each serum in single and pool samples. It was found that with the Canadian kit, the positive and negative results of pooled sera had no difference from that of the controls (P > 0.10). In the case of Chinese Yali and Kehua kits, the positive results of pooled sera showed no difference from the controls (P > 0.10), but the optical density (OD) of negative pools were increased (P < 0.01), though quite distant from the cut-off values. In the case of Changzheng kit, the OD of positive pools were significantly lower than those of the controls (P < 0.05), and weak positive samples missed the detection. However this problem could be overcome by blocking the microwells beforehand. Our experiment demonstrate that not all EIA test kits are suitable for screening pools for antibody to hepatitis C virus, and that it is important to assess the sensitivity of the EIA kit to be used for this purpose.

Antibodies, Viral↗
PubMed1997

A prospective study of a serum-pooling strategy in screening blood donors for antibody to hepatitis C virus.

BACKGROUND: To examine the feasibility and to perform a cost-benefit analysis of a pooling protocol of enzyme immunoassay (EIA) screening for antibody to hepatitis C virus (anti-HCV) under real conditions, a prospective study was carried out using sera from 1875 local blood donors. STUDY DESIGN AND METHODS: In the absence of knowledge of the anti-HCV reactions, the donor's sera were pooled into groups of five consecutive samples for testing by EIA. The dilution and final volume of the serum pool were adjusted to equal those recommended for single-serum EIA by the manufacturer of the test kit. The results obtained were compared with those of single-serum EIA to assess the feasibility of the pooling protocol. By applying probability theory, the percentage of reduction in the number of tests performed (L value) when the serum-pooling strategy was used was calculated for several anti-HCV seroprevalences and for varied sizes of pool. The calculations were performed on a computer using a program compiled by the authors. RESULTS: The results showed that seroprevalence was 2.24 percent (95% CI, 1.57-2.91%); the rate of false negativity was 0 (95% CI, 0-8.4%), the sensitivity of the pooling protocol was 100 percent (95% CI, 91.6-100.0%), the rate of false positivity was 0.8 percent (95% CI, 0-1.8%), and the specificity of the pooling protocol was 99.2 percent (95% CI, 98.2-100.0%). Cost-benefit analysis showed that the pooling protocol could save 69.3 percent of the cost. A table of L values can be used conveniently by serologists to determine the optimum pool size if estimates of seroprevalence are available. CONCLUSION: The pool EIA did not perform worse than individual EIAs, and the pooling strategy was markedly less expansive. The pooling protocol was recommended for screening of anti-HCV-positive subjects from large populations with low seroprevalence.

Adolescent↗
PubMed1996

Thymocyte apoptosis in response to low-dose radiation.

Thymocyte apoptosis was assessed by counting apoptotic bodies with flow cytometry (FCM) and measuring DNA fragmentation with fluorescence spectrophotometry (FSP). J-shaped dose-response curves were obtained after both whole-body irradiation (WBI) of mice and in vitro irradiation of EL4 cells with doses ranging from 0.025 to 4 Gy X-rays. There was a significant reduction of apoptosis rate to below control level with doses within 0.2 Gy, and a dose-dependent increase in apoptosis with doses above 0.5 Gy. When thymocytes were cultured 24 h after WBI with 75 mGy X-rays in complete RPMI 1640 medium, a reduction in apoptosis was observed in the course of incubation for 72 h, and the presence of Con A in the medium accentuated this reduction in a dose- and time-dependent manner. The implications of these observations and the possible molecular mechanisms for future studies are proposed.

Animals↗
PubMed1996

Evidence that disruption of connexon particle arrangements in gap junction plaques is associated with inhibition of gap junctional communication by a glycyrrhetinic acid derivative.

Glycyrrhetinic acid exhibits many pharmacological activities, including the ability to block gap junctional communication. However, the mechanism of glycyrrhetinic action is not clear. Others have shown that glycyrrhetinic acid apparently binds to a single proteinatious binding site in the plasma membrane. We present evidence that while exposure to glycyrrhetinic acid derivatives may not affect protein synthesis or location, it does seem to alter connexon particle packing in gap junction plaques.

Animals↗
PubMed1994

Effect of low dose radiation on intracellular calcium and protein kinase C in lymphocytes.

It is first reported in the present paper that whole-body irradiation (WBI) with low dose X-rays could increase intracellular calcium ions ([Ca2+]i) and stimulate protein kinase C (PKC) activity of mouse lymphocytes. Following WBI of male Kunming mice with 75 mGy X-rays at a dose rate of 12.5 mGy/min the mobilization of [Ca2+]i with Con A in CD4+ and CD8+ Cells in the thymus and spleen was potentiated and the amplitude of [Ca2+]i mobilization in thymocytes in response to anti-CD3 monoclonal antibody increased with time from 4 to 24 h following low dose radiation. The PKC activity in the homogenate of spleen was markedly stimulated 12 h after WBI with 75 mGy, reaching its peak value at 24-48 h and coming down to lower than normal on day 7. However, the PKC activity in the separated T lymphocytes reached its peak value at 12 h and that in the B lymphocytes reached its peak value on day 4, both coming down to below control on day 7. The implications of this facilitation of signal transduction in T lymphocytes in the mechanism of immunoenhancement after low dose radiation were discussed.

Animals↗
PubMed1994

Signal transduction in lymphocytes after low dose radiation.

Mice were given whole-body irradiation (WBI) with 75 mGy X-rays which had previously been found to stimulate immunologic functions. This low dose radiation (LDR) potentiated [Ca2+]i mobilization in thymic and splenic lymphocytes in response to Con A and anti-CD3 McAb and activated protein kinase C in T and B lymphocytes of the spleen. The expression of TCR/CD3 molecules on the thymocytes was enhanced after LDR indicating an expedited maturation and differentiation process in the thymus. The changes in TCR/CD3 expression and [Ca2+]i mobilization in response to McAb-CD3 after LDR was found to be highly correlated. Meanwhile the transcription of c-fos and c-jun genes was up-regulated beginning 3 hours after LDR. The expression of IL2R in active thymocytes was potentiated 24 hours after LDR which coincided with the previous finding of increased secretion of IL2 by splenocytes after WBI with 75 mGy X-rays. It is first reported in the present paper that LDR could stimulate immunologic functions through facilitation of the signal transduction process in the lymphocytes.

Animals↗
PubMed1993

[A study on the effect of dynorphin A- (1-13) ICV injection on water, sodium and potassium excretion of rats].

The effect of Kappa-agonist dynorphin A-(1-13) on the urine flow was studied in ethanol-anesthetized rats. Intracerebroventricular injection of dynorphin A- (1-13) (5 micrograms, 10 micrograms) induced a potent diuretic response with insignificant action on mean arterial pressure and heart rate. The diuretic response began to show at about 20 min after injection and lasted 120 min. This diuretic effect could be almost completely blocked by pretreatment with naloxone (20 micrograms) or atropine (10 micrograms).

Animals↗
PubMed1993

An epidemic of encephalitis and meningoencephalitis in children caused by echovirus type 30 in Shanghai.

An outbreak of viral central nervous system infection occurred from May to September, 1991 in Shanghai, China. Totally 376 cases were admitted into our hospital, 54% with encephalitis and 46% with meningoencephalitis. Echovirus type 30 was isolated from CSF and stools of the patients. Only 3 of the patients were under 1 year of age. CSF examination revealed the cell count from 0-1600 x 10(6)/L. Interestingly, 9 had CSF PMNs over 90% and 13 had low sugar levels. EKG was randomly done in 20 patients and 15 demonstrated myocarditis. The outcome was uneventful in all except 1 who had psychological problem at the time of discharge.

Adolescent↗
PubMed1992

Effects of berbamine on contraction and Ca2+ influx of pig basilar artery.

Effects of berbamine (Ber) on KCl- and 5-HT-induced contraction of basilar artery (BA) of pigs were studied in vitro. Ber relaxed markedly KCl-induced contraction of BA (IC50 = 4.63 mumol.L-1) and its effect was antagonized by increasing the concentration of extracellular Ca2+; Ber inhibited 5-HT-induced contraction of BA, showing significant inhibition of sustained tonic contraction (STC) (IC50 = 0.64 mumol.L-1) whereas the initial fast phasic contraction (FPC) was relatively unaffected (IC50 = 19.8 mumol.L-1); the 5-HT-induced contraction of BA was dependent on the concentration of extracellular Ca2+, especially STC. The results of Ca2+ withdrawal and replacement indicated that STC was due to 5-HT-stimulated Ca2+ influx, while 5-HT-induced release of intracellular Ca2+ resulted in FPC. Ber 0.8 mumol.L-1 produced markedly inhibitory effect on Ca2+ influx induced by 5-HT (P < 0.01). The effects of Ber were similar to those of nimodipine (Nim). The present results suggested that Ber has antagonistic effect on the potential sensitive channels (PSC) and the receptor operated channels (ROC).

Alkaloids↗