Biomedical subjects

Y L Shen

Publications and source records attributed to Y L Shen.

At least 19 recordsLinked to original sources

PubMed2003

Influence of interleukin-2 on Ca2+ handling in rat ventricular myocytes.

In the present study, we examined the effect of interleukin-2 (IL-2) on cardiomyocyte Ca(2+) handling. The effects of steady-state and transient changes in stimulation frequency on the intracellular Ca(2+) transient were investigated in isolated ventricular myocytes by spectrofluorometry. In the steady state (0.2 Hz) IL-2 (200 U/ml) decreased the amplitude of Ca(2+) transients induced by electrical stimulation and caffeine. At 1.25 mM extracellular Ca(2+) concentration ([Ca(2+)](o)), when the stimulation frequency increased from 0.2 to 1.0 Hz, diastolic Ca(2+) level and peak intracellular Ca(2+) concentration ([Ca(2+)](i)), as well as the amplitude of the transient, increased. The positive frequency relationships of the peak and amplitude of [Ca(2+)](i) transients were blunted in the IL-2-treated myocytes. The effect of IL-2 on the electrically induced [Ca(2+)](i) transient was not normalized by increasing [Ca(2+)](o) to 2.5 mM. IL-2 inhibited the frequency relationship of caffeine-induced Ca(2+) release. Blockade of sarcoplasmic reticulum (SR) Ca(2+)-ATPase with thapsigargin resulted in a significant reduction of the amplitude-frequency relationship of the transient similar to that induced by IL-2. The restitutions were not different between control and IL-2 groups at 1.25 mM [Ca(2+)](o), which was slowed in IL-2-treated myocytes when [Ca(2+)](o) was increased to 2.5 mM. There was no difference in the recirculation fraction (RF) between control and IL-2-treated myocytes at both 1.25 and 2.5 mM [Ca(2+)](o). The effects of IL-2 on frequency relationship, restitution, and RF may be due to depressed SR functions and an increased Na(+)-Ca(2+) exchange activity, but not to any change in L-type Ca(2+) channels.

Adenosine Triphosphatases↗

PubMed2001

[Effects of interleukin-2 on the isolated rat heart and the mechanism].

The purpose of the present study was to explore the biological effects and mechanism of interleukin-2 (IL-2) on the isolated rat heart. The results showed that hrIL-2 increased the number of premature ventricular contraction, heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow in the isolated perfused rat heart. Heat inactivated hrIL-2 had no effect on the heart. Pretreatment with ryanodine canceled the positive effects of hrIL-2 on left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow but had no effects on arrhythmogenesis and tachycardia by hrIL-2. Pretreatment with nifedipine or low extracellular calcium abolished the arrhythmogenic effect of hrIL-2 and attenuated partially the augment of heart rate, left ventricular developed pressure, left ventricular end-diastolic pressure and coronary flow. It suggests that the cardiac activity of hrIL-2 depended on the integrity of its spatial structure and transmembrane influx Ca2+ and intracellularly stored Ca2+ were involved in the cardiac activity of hrIL-2.

Animals↗

PubMed2001

[Hydrogen peroxide augments the injury effect of iron on the isolated rat heart and cardiomyocytes].

By using Langendorff perfused rat heart and enzymatically isolated cardiomyocytes, we investigated the augmented injury effect of iron on the myocardium by hydrogen peroxide and the underlying mechanisms. Cell-permeable iron (Fe-HQ) decreased the contractile amplitude, velocity and end-diastolic cell length of the cardiomyocyte but increased the contents of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the myocardial malondialdehyde (MDA) while the left ventricular developed pressure (LVDP), +/-dp/dt(max), heart rate and coronary flow showed biphasic alterations. Hydrogen peroxide augmented the injury effect of iron accompanied by increases of coronary LDH, CK release and myocardial MDA content and decreases of LVDP, +/-dp/dt(max), and heart rate. Reduced glutathione could antagonize the injury effect of iron and hydrogen peroxide on the myocardium while dimethyl sulfoxide had no injury effect on the isolated heart. It is suggested that the functional injury of sulfhydryl group containing proteins may be involved in the augmentation of myocardial injury due to the increase of intracellular iron by hydrogen peroxide, but hydroxyl radicals may not.

Animals↗

PubMed2000

Operant performance following tail-pinch in the rat: effects of d-amphetamine.

To extend the investigation of tail-pinch induced behavioral changes, rats performing on a differential reinforcement of low rates of 10 sec (DRL10), a fixed-interval of 60 sec (F160), and a fixed-ratio of 20 (FR20) schedules were exposed to a paper clip applied to the tail. While a 10 min tail-pinch conducted 1 hr before operant sessions significantly altered the DRL10 behavior, this stressor had little effect on either F160 or FR20 responding. Marked DRL10 behavior performance changes following tail-pinch included increases in the number of lever presses, decreases in the number of the reinforcers, and disruption in the frequency distribution of inter-response times (IRT). These DRL10 operant deficits were diminished when the subject received a tail-pinch pretreatment followed by d-amphetamine treatment (0.2 and 2.0 mg/kg). In combination with biochemical data from others, the present results suggest that catecholamine systems are involved in modulation of DRL10 behavior following tail-pinch.

Animals↗

PubMed2000

Arsenic trioxide-induced apoptosis and differentiation are associated respectively with mitochondrial transmembrane potential collapse and retinoic acid signaling pathways in acute promyelocytic leukemia.

Recent studies showed that arsenic trioxide (As2O3) could induce apoptosis and partial differentiation of leukemic promyelocytes. Here, we addressed the possible mechanisms underlying these two different effects. 1.0 microM As2O3-induced apoptosis was associated with condensation of the mitochondrial matrix, disruption of mitochondrial transmembrane potentials (DeltaPsim) and activation of caspase-3 in acute promyelocytic leukemia (APL) cells regardless of their sensitivity to all-trans retinoic acid (ATRA). All these effects were inhibited by dithiothreitol (DTT) and enhanced by buthionine sulfoximine (BSO). Furthermore, BSO could also render HL60 and U937 cells, which had the higher cellular catalase activity, sensitive to As2O3-induced apoptosis. Surprisingly, 1.0 microM As2O3 did not induce the DeltaPsim collapse and apoptosis, while 0.1 microM As2O3 induced partial differentiation of fresh BM cells from a de novo APL patient. In this study, we also showed that 0.2 mM DTT did not block low-dose As2O3-induced NB4 cell differentiation, and 0. 10.5 microM As2O3 did not induce differentiation of ATRA-resistant NB4-derived sublines, which were confirmed by cytomorphology, expression of CD11b, CD33 and CD14 as well as NBT reduction. Another interesting finding was that 0.10.5 microM As2O3 could also induce differentiation-related changes in ATRA-sensitive HL60 cells. However, the differentiation-inducing effect could not be seen in ATRA-resistant HL60 sublines with RARalpha mutation. Moreover, low-dose As2O3 and ATRA yielded similar gene expression profiles in APL cells. These results encouraged us to hypothesize that As2O3 induces APL cell differentiation through direct or indirect activation of retinoic acid receptor-related signaling pathway(s), while DeltaPsim collapse is the common mechanism of As2O3-induced apoptosis.

Antineoplastic Agents↗

PubMed1999

Diuretics and risk of arrhythmic death in patients with left ventricular dysfunction.

Background-Treatment with diuretics has been reported to increase the risk of arrhythmic death in patients with hypertension. The effect of diuretic therapy on arrhythmic death in patients with left ventricular dysfunction is unknown. Methods and Results-We conducted a retrospective analysis of 6797 patients with an ejection fraction <0.36 enrolled in the Studies Of Left Ventricular Dysfunction (SOLVD) to assess the relation between diuretic use at baseline and the subsequent risk of arrhythmic death. Participants receiving a diuretic at baseline were more likely to have an arrhythmic death than those not receiving a diuretic (3.1 vs 1.7 arrhythmic deaths per 100 person-years, P=0.001). On univariate analysis, diuretic use was associated with an increased risk of arrhythmic death (relative risk [RR] 1.85, P=0.0001). After controlling for important covariates, diuretic use remained significantly associated with an increased risk of arrhythmic death (RR 1.37, P=0.009). Only non-potassium-sparing diuretic use was independently associated with arrhythmic death (RR 1.33, P=0.02). Use of a potassium-sparing diuretic, alone or in combination with a non-potassium-sparing diuretic, was not independently associated with an increased risk of arrhythmic death (RR 0.90, P=0.6). Conclusions-In SOLVD, baseline use of a non-potassium-sparing diuretic was associated with an increased risk of arrhythmic death, whereas baseline use of a potassium-sparing diuretic was not. These data suggest that diuretic-induced electrolyte disturbances may result in fatal arrhythmias in patients with systolic left ventricular dysfunction.

Analysis of Variance↗

PubMed1999

Apoptosis and growth inhibition in malignant lymphocytes after treatment with arsenic trioxide at clinically achievable concentrations.

BACKGROUND: Arsenic trioxide (As2O3) can induce clinical remission in patients with acute promyelocytic leukemia via induction of differentiation and programmed cell death (apoptosis). We investigated the effects of As2O3 on a panel of malignant lymphocytes to determine whether growth-inhibitory and apoptotic effects of As2O3 can be observed in these cells at clinically achievable concentrations. METHODS: Eight malignant lymphocytic cell lines and primary cultures of lymphocytic leukemia and lymphoma cells were treated with As2O3, with or without dithiothreitol (DTT) or buthionine sulfoximine (BSO) (an inhibitor of glutathione synthesis). Apoptosis was assessed by cell morphology, flow cytometry, annexin V protein level, and terminal deoxynucleotidyl transferase labeling of DNA fragments. Cellular proliferation was determined by 5-bromo-2'-deoxyuridine incorporation into DNA and flow cytometry and by use of a mitotic arrest assay. Mitochondrial transmembrane potential (delta psi(m)) was measured by means of rhodamine 123 staining and flow cytometry. Protein expression was assessed by western blot analysis or immunofluorescence. RESULTS: Therapeutic concentrations of As2O3 (1-2 microM) had dual effects on malignant lymphocytes: 1) inhibition of growth through adenosine triphosphate (ATP) depletion and prolongation of cell cycle time and 2) induction of apoptosis. As2O3-induced apoptosis was preceded by delta psi(m) collapse. DTT antagonized and BSO enhanced As2O3-induced ATP depletion, delta psi(m) collapse, and apoptosis. Caspase-3 activation, usually resulting from delta psi(m) collapse, was not always associated with As2O3-induced apoptosis. As2O3 induced PML (promyelocytic leukemia) protein degradation but did not modulate expression of cell cycle-related proteins, including c-myc, retinoblastoma protein, cyclin-dependent kinase 4, cyclin D1, and p53, or expression of differentiation-related antigens. CONCLUSIONS: Substantial growth inhibition and apoptosis without evidence of differentiation were induced in most malignant lymphocytic cells treated with 1-2 microM As2O3. As2O3 may prove useful in the treatment of malignant lymphoproliferative disorders.

Adenosine Triphosphate↗

PubMed1999

Grandparents in the United States and the Republic of China: a comparison of generations and cultures.

Grandparent behaviors in the United States and the Republic of China are examined to identify curriculum themes for helping them adjust to their changing role. The 3,286 non-consanguineous subjects included Chinese (n = 751), African Americans (n = 777), Caucasian Americans (n = 1,086), and Mexican Americans (n = 672). Analyses were performed using 1) Generation with three levels (grandparent, parent, and grandchild) and 2) Culture with four levels (Chinese, African American, Caucasian American, and Mexican American). The results revealed significant differences in perceptions about grandparents across cultures as well as between generations within cultures. All three generations reported grandparent strengths and needs. Specific guidelines and curriculum topics are recommended for education to support grandparent development.

Aged↗

PubMed1999

[HRV analysis system based on Windows 95 and its preliminary application].

Objective. To provide a real useful application system for the HRV research. Method. The acquisition, detection and analysis system of HRV signal was set up based on Windows 95. The system analyzes the HRV signal with statistic method in time domain and power spectrum in frequency domain. And the power spectrum array was also introduced into the analysis. HRV signals of some healthy persons and some patients were detected and analyzed. Result. The HRV characteristic is much more obvious in the diabetics patients. Conclusion. The system is useful in HRV signal analysis and cardiovascular research.

Aerospace Medicine↗

PubMed1998

[Involvement of endogenous opioids in cardioprotective effects of ischemic preconditioning in the isolated rat heart].

In the present study, the relationship between the blockade of kappa-opioid receptor and ischemic preconditioning (IP) was examined and the effect of IP and prolonged ischemia on levels of dynorphin A1-13 (Dyn A1-13) in cardiac muscle in isolated perfused rat heart was investigated. The results are as follows: (1) IP reduced the severity of ischemia/reperfusion arrhythmia (P < 0.05) and infarct size (P < 0.01), but had no significant effect on heart rate and coronary flow (P > 0.05); (2) MR2266, kappa opioid receptor antagonist, reduced the severity of ischemia/reperfusion arrhythmia (P < 0.05) and infarct size (P < 0.01), and also enhanced the recovery of coronary flow, but had no significant effect on heart rate (P > 0.05); and (3) prolonged ischemia decreased the levels of Dyn A1-13 (P < 0.05), which was more marked in the unpreconditioned hearts. The results suggest: (1) MR2266 can "mimic" cardioprotective effect of IP in reducing the severity of arrhythmias and limiting infarct size of cardiac muscle; (2) ischemia causes release of endogenous kappa opioids, which can be attenuated by IP; and (3) the cardioprotective effects of IP in rat heart involves endogenous kappa opioids.

Animals↗

PubMed1996

Decreased affinity of K-receptor binding during reperfusion following ischaemic preconditioning in the rat heart.

The effects of ischaemic preconditioning with three cycles of ischaemia of 3 min and reperfusion of 5 min each cycle on ventricular fibrillation threshold (VFT) and ventricular fibrillation (VF), and binding properties of tritiated U69,593, a selective kappa opioid-receptor (k-receptor) agonist, during subsequent ischaemia and/or reperfusion were studied in the rat heart. It was found that ischaemic preconditioning significantly enhanced the VFT values during ischaemic and reperfusion. VF during the subsequent reperfusion period was also significantly reduced. The Kd of the [3H]U69,593 binding sites in the sarcolemma of the heart at 5 min of reperfusion was significantly increased following ischaemic preconditioning. The Bmax was, however, not altered after the preconditioning. The study provides evidence for the first time suggesting that the cardioprotective effects of ischaemic preconditioning may be related to a reduction in affinity of the K-receptor binding.

Analgesics↗

PubMed1996

Grandparents in Taiwan: a three-generational study.

Grandparents in the Republic of China want to remain influential, but social policy has not provided them with education to fulfill their changing role. The performance of grandparents was examined to determine suitable content for an intervention program. A sample of 751 non-consanguineous participants from urban and rural Taiwan included 234 grandparents, 241 parents, and 276 grandchildren. Each generation was administered a separate version of the Grandparent Strengths and Needs Inventory that was translated into Mandarin. Respondents identified favorable qualities of grandparents as well as aspects of their relationships in which growth was necessary. Multivariate analysis of variance, univariate analysis of variance, Scheffé and t-tests were used to analyze scores, confirm results, and facilitate interpretation. All three generations described aspects of grandparent success and specific realms of learning they should acquire to become more effective. Significant main effects that influenced responses about grandparent performance were generation, gender of grandchild, age of grandchild, frequency of grandchild care by grandparent, generations living together, and amount of time grandparent and grandchild spent together. Considerations were recommended to improve behavior of grandparents and guide the development of educational programs for them.

Aged↗

PubMed1995

Effects of an indene-derivative, TN-871, on synaptic transmission in a sympathetic ganglion: presynaptic actions on neurotransmitter release.

Intracellular recordings were made from bullfrog sympathetic ganglion cells to elucidate effects of 2-n-butyl-1-(4-methylpiperazinyl)-5,6-methylenedioxyindene.2 HCl (TN-871) on synaptic transmission. TN-871 at 30 nM augmented cholinergic nicotinic fast excitatory postsynaptic potentials (fast EPSPs), whereas the drug at 3 microM reversibly depressed them, without affecting acetylcholine-induced depolarizations. TN-871 did not affect active and passive electrical properties of the ganglion cells. The quantal analysis method was applied to the fast EPSPs in a 0.54 mM Ca2+/7.56 mM Mg2+ Ringer's solution. The mean quantal content was significantly increased by TN-871 at 30 nM but significantly decreased at 3 microM. TN-871 at 300 nM either increased or decreased the mean quantal content. The mean quantal size of the fast EPSPs was not changed by TN-871 at the concentrations examined. Fast EPSPs in a 0.99 mM Ca2+/4.86 mM Mg2+ Ringer's solution were not affected by nicardipine, but were inhibited in amplitude by omega-conotoxin in a concentration-dependent manner. It is likely that TN-871, in high concentrations, might block omega-conotoxin-sensitive N-type calcium channels in the presynaptic terminals. These results indicate that TN-871 modulates transmitter release from preganglionic nerve terminals without changing the postsynaptic sensitivity of the ganglion cells to ACh.

Animals↗

PubMed1994

[Extracellular adenosine-5'-triphosphate increases intracellular calcium concentration of the rabbit eye suprachoroid via activation of the intracellular signal transduction].

Intracellular calcium concentration ([Ca2+]i) of the rabbit eye suprachoroid was measured with microfluorophotometry using fura-2. Adenosine-5'-triphosphate (ATP) 1-100 microM, added to a perfusing solution, elicited an increase in [Ca2+]i of the suprachoroid. This action of ATP was inhibited when preparations were perfused with a nominally zero Ca2+ Krebs solution or a high magnesium Krebs solution. The [Ca2+]i-increasing action of ATP was attenuated either by lowering temperature or by a phospholipase C inhibitor, compound 48/80. These results indicate that extracellular Ca2+ is necessary to the ATP action and also suggest that the ATP action may be mediated by the intracellular signal transduction which exerts a Ca(2+)-release from intracellular Ca(2+)-store sites. The potency order of ATP-related purine nucleotides was ATP > or = ATP-gamma-S > adenosine-5'-diphosphate (ADP). Adenosine-5'-monophosphate (AMP) and adenosine were not effective. It is concluded that P2-purinoceptors exist on the surface of the suprachoroid and are involved in mechanisms underlying the ATP-induced increase in [Ca2+]i of the suprachoroid.

Adenosine Triphosphate↗

PubMed1994

Short-term, within-person variability in clinical chemistry test results. Experience from the Atherosclerosis Risk in Communities Study.

We report the within-person, between-person, and methodological variances of a number of chemical analytes for free-living, middle-aged adults who participated in the Atherosclerosis Risk in Communities Study's Intraindividual Variability Study. The Atherosclerosis Risk in Communities Study is a National Institutes of Health-sponsored multicenter study of atherosclerotic risk factors. In the Atherosclerosis Risk in Communities Study and its Intraindividual Variability Study, concentrations of the following 12 chemical analytes were measured in serum from fasting individuals: sodium, calcium, potassium, creatinine, albumin, total protein, magnesium, phosphorus, urea, insulin, glucose, and urate. The analytes are listed in order of the increasing reliability coefficient (ie, the fraction that between-person variance represents of the total observed population variance), which ranged from .59 for sodium to .91 for urate. The reliability coefficient is a strong predictor of the possibility of finding statistical correlations between measured analyte concentrations and disease occurrence in an epidemiological study like the Atherosclerosis Risk in Communities Study. The within-person variance and methodological variance are also useful in computing confidence intervals for sequential laboratory test results in patients and evaluating limits for internal quality control and proficiency testing programs.

Aged↗

PubMed1992

Short-term intraindividual variability in lipoprotein measurements: the Atherosclerosis Risk in Communities (ARIC) Study.

Much epidemiologic research is based on estimation of an association between a putative risk factor and a health outcome--for example, plasma concentration of lipoproteins and ischemic heart disease. Since the repeatability of a risk factor measurement determines, in part, the ability to ascertain its association in populations, the Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability Study was conducted to estimate various components of variation in analyte data and to estimate the repeatability of these measurements. A total of 40 subjects (17 males and 23 females) from Forsyth County, North Carolina, Minneapolis, Minnesota, Jackson, Mississippi, and Washington County, Maryland, were studied in 1988. Fasting blood was collected three times from each subject, with a 1- to 2-week interval between each visit. The contributions of between-person variability, within-person variability, and processing and assay variability were estimated. From these components, the reliability coefficient, R, the correlation between measures made at repeat visits, was estimated. R was above 0.85 for total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, and lipoprotein(a). Low repeatability was obtained for apolipoprotein A-I (R = 0.60). High density lipoprotein subfractions 2 and 3 were intermediate in repeatability. Reliability coefficients from the ARIC Intraindividual Variability Study are generally higher than those found in other studies, and this is related to relative variability in populations studied, to the time between measurements, and to differences in laboratory variability. Only for apolipoprotein A-I would the findings strongly suggest the need to adjust for measurement variability in estimation using one of these analytes as an independent variable.

Cardiovascular Diseases↗

PubMed1992

Short-term intraindividual variability in hemostasis factors. The ARIC Study. Atherosclerosis Risk in Communities Intraindividual Variability Study.

Recent epidemiologic studies found that there is a strong association of hemostatic factors with ischemic heart disease. The Atherosclerosis Risk in Communities (ARIC) Intraindividual Variability (IIV) Study was conducted to estimate the various components of variation in hemostasis factors measured in the ARIC Study and to estimate the measures of repeatability of these factors. A total of 39 subjects (16 men, 23 women) were studied. Each had blood collected three times, with a 1- to 2-week interval between each visit. The contributions of between-person variability, within-person (biologic) variability, and processing and assay variability were estimated. Then the reliability coefficient R was estimated as the proportion of total variance accounted for by between-person variance. The reliability coefficient can be interpreted as the correlation between measures made at repeat visits. Among the various analytes, the reliability coefficients were quite high for activated partial thromboplastin time and plasma factor VIII (R = 0.92, 0.86, respectively). Low repeatability was obtained for antithrombin III activity and protein C (R = 0.42, 0.56, respectively). The lack of repeatability for these variables derives mostly from the processing (field center and laboratory) variation. Other analytes--fibrinogen, plasma factor VII, and von Willebrand factor--were intermediate in repeatability. In comparing the analyte-specific high-level to low-level groups, no substantial difference of within-person plus method coefficient of variation between the two groups was found for any analyte except for factor VIII, whereas the corresponding variance components for most analytes were higher for the higher analyte level. Reliability coefficients from this ARIC IIV study are generally higher than those found in other studies, and this is related to the relative variations in populations studied and to the time between measurements.

Antithrombin III↗

PubMed1991

Bone remodeling in hypervitaminosis D3. Radiologic-microangiographic-pathologic correlations.

To investigate the mechanism of bone changes in hypervitaminosis D3, we compared contact radiographs, microangiograms by injection of Chinese ink, and corresponding histopathologic macrosections of 66 rabbits that received different doses of vitamin D3. In early stages, radiographs showed subperiosteal bone resorption and porotic cortical bone. The corresponding microangiograms showed proliferating vessels in the periosteum and cortical bone with associated dilatation of the Haversian and Volkmann's canals. When metastatic calcification fills these intracortical caverns or the intertrabecular spaces in the metaphysis and physis, the bone shows a diffuse increased density on radiographs. A dense band in the metaphysis reflects a thickening of calcified chondromatrix due to a hypotrophy of the distal metaphyseal capillaries. Six to 12 weeks after vitamin D3 withdrawal, radiographs showed further increased density of the cortical bone, due to newly formed bone and metastatic calcification. Alternating bands of increased and decreased density in the metaphysis and physis reflect the reinvasion of normal vasculature between growth cartilage and calcified chondromatrix, with normalization of endochondral ossification.

Angiography↗