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Biomedical subjects

D J Wang

Publications and source records attributed to D J Wang.

At least 55 records · Page 3Linked to original sources

The reappraisal of the association of glycosylated hemoglobin A1c (HbA1c) and blood pressure: a hypertension and diabetes study in a Taiwan rural area.

The association of age, body weight, body mass index (BMI) and glycosylated hemoglobin A1c (HbA1c) to blood pressure in the general population of the Ho-long area in Taiwan was examined. A total of 1341 subjects, 746 men and 595 women, aged 40-90 years, were studied. Sex-specific multiple regression analyses were carried out on variables both univariately and significantly associated with blood pressure. Results show HbA1c to be significantly associated with SBP in both males and females before age, weight and/or BMI are adjusted (p < 0.05). After controlling for these confounders, the strength of SBP-HbA1c association was slightly reduced in males, but remained significant. In contrast, there was no significance in females. Moreover, no significant relationship in DBP-HbA1c was found in either sex group. These findings suggest that although a positive correlation was found between HbA1c and SBP, HbA1c or glucose status appeared to be a less important contributing factor in hypertension than age or body weight.

Age Factors↗

Effect of nicardipine treatment on carbohydrate and lipoprotein metabolism in patients with hypertension.

This study evaluated the effect of nicardipine, calcium channel blocker, monotherapy on blood pressure and metabolic changes. Various aspect of carbohydrate and lipoprotein metabolism were studied before and after 12 weeks of nicardipine treatment in 23 patients with mild to moderate essential hypertension. Nicardipine was well tolerated and induced a significant decrease (p < 0.001) in both systolic and diastolic blood pressure without any changes in heart rate. Plasma levels of fasting glucose, insulin, C-peptide and hemoglobin A1c, hepatic extraction of insulin were similar following nicardipine treatment. Plasma glucose and insulin responses to an oral glucose challenge did not change in association with nicardipine therapy. Although high density lipoprotein (HDL) cholesterol concentration increased slightly, it did not reach statistical significance. Total cholesterol and low density lipoprotein (LDL) cholesterol levels also increased insignificantly. LDL triglyceride and very low density lipoprotein (VLDL) triglyceride concentrations were higher marginally, which resulted in slightly but insignificantly increase in total triglyceride concentration in association with nicardipine monotherapy for 12 weeks. In conclusion, treatment of patients with mild to moderate hypertension with nicardipine led to lower blood pressure effectively while had no significant influence on carbohydrate and lipoprotein metabolism.

Adult↗

[Rotundium in the treatment of atrial fibrillation].

L-tetrahydropalmatine (Rotundium) is an alkaloid of Corydalis turtschaninovii. Some animal experiments had demonstrated that Rotundium had a good antiarrhythmic effect in blocking the calcium channel and that it was a class IV antiarrhythmic agent, similar to that of Bepridil in literatures. This is a clinical report of Rotundium (oral given) on an atrial fibrillation (AF) patients. The therapeutical results were evaluated by 24 hours ambulatory electrocardiographic monitoring and ECG. The results showed that the effective rate of Rotundium on paroxysmal atrial fibrillation and sustained atrial fibrillation of 45 mm (left atrium diameter) or more was 30%, while LAD of less than 45 mm was 80% (P < 0.01). Among 8 cases' duration of AF were 6 months or more, 3 cases were effective, the effective rate 37.5%, while among 10 cases' duration of AF were less than 3 weeks, 3 cases were converted to sinus rhythm, 5 cases were effective. There was a significant difference between two groups. Age and sex exerted no effect on efficacy. During taking Rotundium, blood pressure had no apparent changes and no severe side effects were found. The results showed that Rotundium is an effective, safe new drug to treat AF, especially in paroxysmal atrial fibrillation. The antiarrhythmic mechanism of Rotundium might be related to its prolonging of the effective refractory period of atrial and atrioventricular node.

Adult↗

[Effects of rotundium on clinical electrophysiology in patients with pre-excitation syndrome].

Acute electrophysiologic effects of rotundium were studied with programmed electrical cardiac stimulation in 14 patients with paroxysmal tachyarrhythmias due to preexcitation syndrome after intravenous infusion of 2 mg/kg. The results showed that the drug depressed the function of the atrioventricular node markedly. Significant lengthening of A-H interval (from 75 +/- 19ms to 88 +/- 21ms, P < 0.01), AVNERP (from 246 +/- 47ms to 290 +/- 45ms, P < 0.01), AVNWCL (from 326 +/- 23ms to 388 +/- 42ms, P < 0.01) were seen. But no significant influence on SNRT, CSNRT and SACT (P < 0.05) were observed. Rotundium lengthened A-delta interval (from 97 +/- 18 ms to 106 +/- 19ms, P < 0.05) and the anterograde effective refractory period (ERP) of the accessory pathway (from 287 +/- 36ms to 320 +/- 43ms P < 0.05). It slightly lengthened V-A interval and the retrograde ERP of the accessory pathway. Rotundium lengthened AERP significantly (from 216 +/- 37ms to 244 +/- 41ms, P < 0.02). The effective rate of prevention of supraventricular tachycardia (SVT) by PES in this study was 77.8% (7/9). Rotundium showed no severe side effect in this study.

Adolescent↗

Extracellular ATP stimulates increases in Na+/K+ pump activity, intracellular pH and uridine uptake in cultures of mammalian cells.

Using 3T3 and 3T6 mouse fibroblasts and A431 epidermoid carcinoma cells, we previously observed that extracellular ATP and ADP were mitogens and they synergized with other growth factors (Huang, N., Wang, D. and Heppel, L. A. (1989) Proc. Natl. Acad. Sci. USA 86, 7904-7908). We now report that ATP and ADP stimulated Na+ entry, intracellular alkalinization and Na+/K+ pump activity, which are early events that had been proposed to play a central role in DNA synthesis. In addition, ATP, ADP and AMPPNP stimulated uridine uptake by a pathway involving arachidonic acid metabolism. In A431 cells, activation of protein kinase C also contributed to ATP-dependent stimulation of uridine uptake. Concentrations of indomethacin and pertussis toxin which inhibited uridine uptake also blocked arachidonic acid metabolism and DNA synthesis. ATP acted as a competence factor. Interestingly, ATP did not have to be continuously present to stimulate uridine uptake. It was equally effective even when it was washed away after brief treatment of cells.

3T3 Cells↗

Extracellular ATP and ADP stimulate proliferation of porcine aortic smooth muscle cells.

The mitogenic effect of extracellular ATP on porcine aortic smooth muscle cells (SMC) was examined. Stimulation of [3H]thymidine incorporation by ATP was dose-dependent; the maximal effect was obtained at 100 microM. ATP acted synergistically with insulin, IGF-1, EGF, PDGF, and various other mitogens. Incorporation of [3H]thymidine was correlated with the fraction of [3H]thymidine-labeled nuclei and changes in cell counts. The stimulation of proliferation was also determined by measurement of cellular DNA using bisbenzamide and by following the increase of mitochondrial dehydrogenase protein. The effect of ATP was not due to hydrolysis to adenosine, which shows synergism with ATP. ATP acted as a competence factor. The mitogenic effect of ATP, but not adenosine, was further increased by lysophosphatidate, phosphatidic acid, or norepinephrine. The inhibitor of adenosine deaminase, EHNA, stimulated the effect of adenosine but not ATP. The adenosine receptor antagonist theophylline depressed adenosine-induced mitogenesis. ADP and the non-hydrolyzable analogue adenosine 5'-[beta, gamma-imido]triphosphate (AMP-PNP) were equally mitogenic. Thus extracellular ATP stimulated mitogenesis of SMC via P2Y purinoceptors. The mechanism of ATP acting as a mitogen in SMC was further explored. Extracellular ATP stimulated the release of [3H]arachidonic acid (AA) and prostaglandin E2 (PGE2) into the medium, and enhanced cAMP accumulation in a dose-dependent fashion similar to ATP-induced [3H]thymidine incorporation. Inhibitors of the arachidonic acid metabolism pathway, quinacrine and indomethacin, partially inhibited the mitogenic effect of ATP but not of adenosine. Pertussis toxin inhibited ATP-stimulated DNA synthesis, AA release, PGE2 formation, and cAMP accumulation. Down-regulation of protein kinase C (PKC) by long-term exposure to phorbol dibutyrate (PDBu) partially prevented stimulation of DNA synthesis and activation of the AA pathway by ATP. The PKC inhibitor, staurosporine, antagonized mitogenesis stimulated by ATP. No synergistic effect was found when PDBu and ATP were added together. Therefore, a dual mechanism, including both arachidonic acid metabolism and PKC, is involved in ATP-mediated mitogenesis in SMC. In addition, ATP acted synergistically with angiotensin II, phospholipase C, serotonin, or carbachol to stimulate DNA synthesis. Finally, the possible physiological significance of ATP as a mitogen in SMC was further studied. The effect of endothelin and heparin, which are released from endothelial cells, on ATP-dependent mitogenesis was investigated. Extracellular ATP acted synergistically with endothelin to stimulate a greater extent of [3H]thymidine incorporation than was seen with PDGF plus endothelin. Heparin, believed to have a regulatory role, partially inhibited the stimulation of DNA synthesis caused both by ATP and PDGF.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Diphosphate↗

Sensitivity of in vivo MRS of the N-delta proton in proximal histidine of deoxymyoglobin.

The sensitivity of in vivo MRS of the N-delta proton of the proximal histidine of deoxymyoglobin in human skeletal muscles is discussed. Longitudinal relaxation time T1 of this deoxymyoglobin signal was measured in cuffed human forearms at 1.5 T and found to be 9.9 ms. Deoxymyoglobin spectra can be obtained from a forearm in seconds. The detection sensitivity of deoxymyoglobin in fully ischemic skeletal muscles and that of 31P MRS of PCr in normal resting muscles are compared.

Adult↗

Beneficial effects of prewarming the donor liver for rat liver transplantation.

Cold preservation of donor liver can injure the microcirculation enough to impair the function and survival of the transplanted liver. In this study, prewarming the donor liver to 10 degrees C to 12 degrees C after cold storage prior to implantation significantly increased survival rates in rats 1 week after surgery. Following 6, 8, or 9 hours of cold storage in chilled normal saline, prewarming increased survival rates from 40% to 78.6%, from 0% to 35.7%, and from 0% to 14.3%, respectively. The results suggest that pretreatment of the donor liver with warmth following cold storage and before implantation will improve the survival rate of liver transplanted rats.

Animals↗

Transesophageal color Doppler flow imaging in the evaluation of prosthetic cardiac valves.

To determine the value of transesophageal echocardiography in the assessment of prosthetic cardiac valves, 11 patients with clinically suspected cardiac prosthetic valve dysfunction were studied by transesophageal two-dimensional imaging, as well as by color Doppler flow mapping. Among these 11 patients, there were 10 with biological tissue valves and 3 with metallic valves (1 Bjork-Shiley, 2 St. Jude). Nine patients had replacement of mitral valves alone. The remaining two had received both mitral and aortic prostheses. The degree of mitral regurgitation was graded by transesophageal color Doppler according to the area of the regurgitant jet visualized. The degree of aortic regurgitation was graded by the jet height/left ventricular outflow height ratio method. All transesophageal studies were performed without complication and all were well tolerated. The pathological morphology of the cardiac prosthesis was clearly visualized by transesophageal two-dimensional imaging and subsequently proven at surgery. Of those tested, one patient was found to have a torn leaflet, one had a dislodged leaflet, one patient had paravalvular leakage, four had cusp vegetations, and five patients had prosthetic degeneration for other reasons. Mitral regurgitation was graded as absent in one patient, mild in two patients, moderate in two patients, and severe in six patients. Aortic regurgitation was graded as severe in both patients with aortic prostheses. We conclude that in patients with clinically suspected cardiac prosthetic dysfunction, transesophageal two-dimensional imaging combined with color Doppler can provide reliable information that corresponds to surgical findings.

Adult↗

Multiple signal transduction pathways lead to extracellular ATP-stimulated mitogenesis in mammalian cells: I. Involvement of protein kinase C-dependent and -independent pathways.

We recently reported that extracellular ATP was mitogenic for Swiss 3T3, 3T6, and A431 cells (Huang et al.: Proc. Natl. Acad. Sci. USA, 86:7904-7908, 1989). Here we examined the possible involvement of activation of the protein kinase C (PKC) signal transduction pathway in the mechanism of action of extracellular ATP. A potent synergistic stimulation of DNA synthesis in quiescent cultures of 3T3 and 3T6 cells was observed when ATP was presented in combination with growth factors that activate PKC, such as bombesin, vasopressin, or tumor-promoting phorbol esters. This finding suggests that ATP and these mitogens do not act through a common mechanism. In contrast, ATP was unable to show synergism with phorbol esters in A431 cells. We discovered striking differences when we examined the kinetics of formation of diacylglycerol (DAG) stimulated by ATP among these cell lines. Thus, ATP stimulated a sustained biphasic increase of DAG in A431 cells, but only a rapid transient increase of DAG formation was observed in 3T3 and 3T6 cells. The breakdown of phosphatidylcholine was stimulated by ATP in A431 cells; however, a significantly reduced effect was displayed in 3T6 cells. Furthermore, we found that the diacylglycerol-kinase inhibitor, 1-monooleoylglycerol, greatly potentiated ATP-stimulated DNA synthesis in A431 cells. Finally, down-regulation of PKC by long-term exposure to phorbol dibutyrate (PDBu) prevented stimulation of DNA synthesis induced by bombesin, vasopressin, or phorbol esters in 3T3 or 3T6 cells, while it had no such effect on ATP-stimulated mitogenesis in the presence of insulin or epidermal growth factor. On the other hand, PDBu-mediated down-regulation of PKC partially inhibited [3H [thymidine incorporation stimulated by ATP in A431 cells. Taken together, we conclude that a protein kinase C-dependent pathway is partially involved in ATP-stimulated DNA synthesis in A431 cells, but a protein kinase C-independent pathway exists in 3T3 and 3T6 cells. Pertussis toxin (PTX) inhibited the sustained phase of DAG formation and the breakdown of phosphatidylcholine stimulated by ATP in A431 cells. This suggests involvement of a PTX-sensitive G protein.

Adenosine Triphosphate↗

Multiple signal transduction pathways lead to extracellular ATP-stimulated mitogenesis in mammalian cells: II. A pathway involving arachidonic acid release, prostaglandin synthesis, and cyclic AMP accumulation.

We have previously shown that extracellular ATP acts as a mitogen via protein kinase C (PKC)-dependent and independent pathways (Wang, D., Huang, N., Gonzalez, F.A., and Heppel, L.A. Multiple signal transduction pathways lead to extracellular ATP-stimulated mitogenesis in mammalian cells. I. Involvement of protein kinase C-dependent and independent pathways in the mitogenic response of mammalian cells to extracellular ATP. J. Cell. Physiol., 1991). The present aim was to determine if metabolism of arachidonic acid, resulting in prostaglandin E2 (PGE2) synthesis and elevation of cAMP levels, plays a role in mitogenesis mediated by extracellular ATP. Addition of ATP caused a marked enhancement of cyclic AMP accumulation in 3T3, 3T6, and A431 cells. Aminophylline, an antagonist of the adenosine A2 receptor, had no effect on the accumulation of cyclic AMP elicited by ATP, while it inhibited the action of adenosine. The accumulation of cyclic AMP was concentration dependent, which corresponds to the stimulation of DNA synthesis by ATP. The maximal accumulation was achieved after 45 min, with an initial delay period of about 15 min. That the activation of arachidonic acid metabolism contributed to cyclic AMP accumulation and mitogenesis stimulated by ATP in 3T3, 3T6, and A431 cells was supported by the following observations: (a) extracellular ATP stimulated the release of [3H]arachidonic acid and PGE2 into the medium; (b) inhibition of arachidonic acid release by inhibitors of phospholipase A2 blocked PGE2 production, cyclic AMP accumulation, and DNA synthesis activated by ATP, and this inhibition could be reversed by adding exogenous arachidonic acid; (c) cyclooxygenase inhibitors, such as indomethacin and aspirin, diminished the release of PGE2 and blocked cyclic AMP accumulation as well as [3H]thymidine incorporation in response to ATP; (d) PGE2 was able to restore [3H]thymidine incorporation when added together with ATP in the presence of cyclooxygenase inhibitors; (e) pertussis toxin inhibited ATP-stimulated DNA synthesis in a time- and dose-dependent fashion as well as arachidonic acid release and PGE2 formation. Other evidence for involvement of a pertussis toxin-sensitive G protein(s) in ATP-stimulated DNA synthesis as well as in arachidonic acid release is presented. In A431 cells, the enhancement of arachidonic acid and cyclic AMP accumulation by ATP was partially blocked by PKC down-regulation, implying that the activation of PKC may represent an additional pathway in ATP-stimulated metabolism of arachidonic acid. In all of these studies, ADP and AMP-PNP, but not adenosine, were as active as ATP.(ABSTRACT TRUNCATED AT 400 WORDS)

Adenosine Triphosphate↗

In vivo mechanisms of myocardial functional stability during physiological interventions.

Metabolic regulatory mechanisms are designed to maintain stable myocardial function during extremes in physiological insult; they can now be studied in vivo and may provide insight into mechanisms of altered myocardial functional decompensation during disease processes. To determine mechanisms of myocardial stability during hypoxia and acute pressure loading, creatine kinase (CK) kinetics (forward rate constant, Kf, and flux of phosphocreatine, PCr, to adenosine triphosphate, ATP), and nicotinamide adenine dinucleotide (NADH) redox state were determined with 31P nuclear magnetic resonance (NMR) and NADH fluorometry, respectively, and correlated with heart work (heart rate x systolic blood pressure, HR x SBP), cardiac output (CO) and O2 consumption (MVO2) in 15 anesthetized open chest dogs. Hypoxia (PaO2 of 30-35 mm Hg) was produced in 6 dogs with an inspired O2/N2 of 200/3,000. Cardiac loading was produced in 9 dogs by administration of norepinephrine (NE, 1 micrograms/kg/min). Each dog acted as its own control. Baseline NADH fluorometry, 31P-NMR saturation transfer and cardiac function measurements were performed simultaneously in each dog, after which the experimental interventions were made. Similar increases in HR x SBP, CO, and MVO2 which occurred during both interventions were associated with different bioenergetic responses. During NE infusion, the Kf of CK increased from control; during hypoxia, the Kf decreased from control (p less than 0.05). Flux of PCr----ATP was significantly lower during hypoxia than during NE infusion (p less than 0.05). PCr was decreased significantly during NE infusion (p less than 0.05). In addition, NADH redox state increased (from baseline of 100%) during hypoxia (140 +/- 10%) and decreased during NE infusion (78 +/- 6%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

Perfusion scan in pulmonary tumor microembolism: report of a case.

A 76-year-old male patient was admitted to our hospital with the chief complaint of dyspnea. A chest CT scan showed pericardial effusion, mediastinal lymphadenopathy and a tumor in the right ventricle with invasion to the main trunk of the pulmonary artery. A 99mTc MAA perfusion lung scan revealed multiple small subsegmental peripheral defects and a "fissure sign", while the 133Xe ventilation scan was normal. After the chest CT scan and scans of both lungs, tumor microembolism was highly suspected. Open chest surgery was performed. A huge tumor in the right ventricle involving the main trunk of the pulmonary artery was found. In addition, multiple tumor thrombi in the pulmonary arteries and veins were also noted. The pathology was metastatic squamous cell carcinoma. Thereafter, the primary lesion was found by bronchoscopy. The final diagnosis was squamous cell carcinoma of the right lower lobe bronchus with metastases to the right ventricle and pulmonary vessels, and in association with pulmonary tumor microembolism. We present this uncommon case and describe the pulmonary perfusion pattern of the tumor microembolism.

Aged↗

[Metabolic effects of chlorothiazide and propranolol on essential hypertension--a double-blind, cross-over design clinical trial].

Several studies have shown that antihypertensive drugs therapy could reduce morbidity and mortality of hypertension related complication such as stroke, congestive heart failure and renal failure, but there was no significant reduction of coronary heart disease. The benefit of the treatment on morbidity and mortality may be counterbalanced by adversed metabolic effects of long-term therapy. The purpose of this study is to evaluate the blood pressure-lowering and adverse metabolic effects of chlorothiazide and propranolol monotherapy. A double-blind, cross-over design clinical trial was performed for 42 cases (22 males and 20 females) with the mean age of 52 (from 30 to 59 years old). After 2 weeks run-in period, the patients were assigned to group A and B with age and sex stratification. Chlorothiazide and propranolol were given for 12 weeks in alternative with 2 weeks placebo washout period. Our studies have shown that, chlorothiazide and propranolol could reduce both systolic and diastolic blood pressure significantly. But they also associated with adverse metabolic effects. Serum uric acid and triglyceride increased and decreased the concentration of high density lipoprotein cholesterol (HDL-C). Those changes could counterbalance the benefit of blood pressure-lowering effect of antihypertension. Carefully monitoring the adverse metabolic effects closely is necessary in therapy with these drugs.

Adult↗

[Clinical and experimental research of the treatment of chronic renal failure with shenshuaifang].

33 cases of chronic renal failure (CRF) patients were treated by coloclysis with Chinese medicine Shenshuaifang (SSF). The effective rate was 60.61%, the total effective rate was 87.88%. It showed significant difference in the total effective rate compared with the control group (P less than 0.05). Animal experiments showed SSF could slow down the rising of the blood Cr and BUN of the mice which suffered with CRF, and reduce their urine protein. Conclusion. SSF had good effect on lowering the blood Cr and BUN of the CRF patients, so it could delay the progress of CRF, and it's effect was better than the general medical conservative treatment.

Administration, Rectal↗

Extracellular ATP shows synergistic enhancement of DNA synthesis when combined with agents that are active in wound healing or as neurotransmitters.

The polypeptides PDGF, TGF alpha, and EGF have previously been shown by others to stimulate proliferation of fibroblasts and keratinocytes in the process of wound healing. Here we demonstrate that extracellular ATP, ADP or AMPPNP caused synergistic enhancement of DNA synthesis in 3T6 mouse fibroblasts and BALB/MK keratinocytes when combined with any of the above polypeptides. TGF beta showed synergistic stimulation with ATP in fibroblasts but it inhibited keratinocytes. ATP acted as a mitogen for NIE-115 neuroblastoma cultures. In 3T6 cells, ATP stimulated thymidine incorporation in combination with carbachol or norepinephrine. The effect of carbachol was sensitive to atropine. We suggest that extracellular ATP and ADP may play a physiological role in wound healing and as a mitogenic neurotransmitter in the nervous system.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗

Activation of early events of the mitogenic response by a P2Y purinoceptor with covalently bound 3'-O-(4-benzoyl)-benzoyladenosine 5'-triphosphate.

3'-O-(4-Benzoyl)benzoyl-ATP (BzATP), a photoaffinity analog of ATP, was used as a ligand for a P2Y purinoceptor (adenine nucleotide receptor) present in intact Swiss 3T3 and 3T6 cells and A-431 epidermoid carcinoma cells. Photolysis of serum-starved cells in the presence of 10-50 microM BzATP, followed by extensive washing to remove unincorporated BzATP, induced the release of arachidonic acid. A trace (less than 0.01%) of photoincorporated BzATP was as effective as when 50 microM BzATP or ATP was contained in the incubation medium during the assay. Photoincorporated BzATP also stimulated the production of prostaglandin E2 and the accumulation of cyclic AMP. In previous studies, we demonstrated that these three events are obligatory early steps in a pathway leading to DNA synthesis in the above cell lines. The evidence indicated that the purinoceptor activated by extracellular ATP or BzATP was linked to a pertussis toxin-sensitive GTP-binding protein. Consistent with these observations, we now find that pertussis toxin inhibits the effect of photoincorporated BzATP on arachidonic acid release. These results indicate that BzATP is an effective agonist for the P2Y purinoceptor concerned with stimulation of DNA synthesis in 3T3, 3T6, and A-431 cells. Furthermore, after photolysis it becomes irreversibly associated with intact cells and promotes the activation of early events required for DNA synthesis.

Adenosine Triphosphate↗