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Biomedical subjects

Z Chen

Publications and source records attributed to Z Chen.

At least 973 records · Page 54Linked to original sources
PubMed1997

Human immunodeficiency virus type 2 (HIV-2) seroprevalence and characterization of a distinct HIV-2 genetic subtype from the natural range of simian immunodeficiency virus-infected sooty mangabeys.

The extent of zoonotic infections in rural Sierra Leone, where both feral and pet sooty mangabeys harbor divergent members of the human immunodeficiency virus type 2 (HIV-2)-sooty mangabey simian immunodeficiency virus (SIVsm) family, was tested in blood samples collected from 9,309 human subjects in 1993. Using HIV-1- and HIV-2-specific enzyme immunoassays and confirmatory Western blot analysis to test for antibodies to SIVsm-related lentiviruses, we found only nine subjects (0.096%) who tested positive for HIV: seven tested positive for HIV-1 and two tested positive for HIV-2. Compared with other rural West African communities, Sierra Leone displayed the lowest seroprevalence (0.021%) of HIV-2 infection yet reported, much lower than the previously reported seroprevalence in SIVsm-infected feral and household pet sooty mangabeys. Heteroduplex analysis demonstrated that two of the newly found HIV-1 strains belonged to subtype A, the most common HIV-1 subtype in Africa, but this is the first report of subtype A in Sierra Leone. The two HIV-2-infected individuals harbored two distinct HIV-2 strains, designated 93SL1 and 93SL2. Phylogenetic analysis indicated that HIV-2 93SL1 is a member of HIV-2 subtype A, the first strain of this HIV-2 subtype found in Sierra Leone. In contrast, HIV-2 93SL2 belongs to none of the five previously characterized HIV-2 subtypes (A to E) but is a new subtype, herein designated F, having the most divergent transmembrane sequences yet reported for HIV-2. The fact that both of the two most divergent HIV-2 subtypes known, E and F, are rare and found as single occurrences in persons from Sierra Leone may be related to the fact that this small region of West Africa also contains free-living and household pet sooty mangabeys with highly divergent variants of SIVsm. This finding provides support for the hypotheses that new HIV-2 subtypes result from independent cross-species transmission of SIVsm to the human population and that these single-occurrence transmission events had not spread widely into the population by 1993.

Adolescent↗
PubMed1997

Kinase-deficient Pak1 mutants inhibit Ras transformation of Rat-1 fibroblasts.

Among the mechanisms by which the Ras oncogene induces cellular transformation, Ras activates the mitogen-activated protein kinase (MAPK or ERK) cascade and a related cascade leading to activation of Jun kinase (JNK or SAPK). JNK is additionally regulated by the Ras-related G proteins Rac and Cdc42. Ras also regulates the actin cytoskeleton through an incompletely elucidated Rac-dependent mechanism. A candidate for the physiological effector for both JNK and actin regulation by Rac and Cdc42 is the serine/threonine kinase Pak (p65pak). We show here that expression of a catalytically inactive mutant Pak, Pak1(R299), inhibits Ras transformation of Rat-1 fibroblasts but not of NIH 3T3 cells. Typically, 90 to 95% fewer transformed colonies were observed in cotransfection assays with Rat-1 cells. Pak1(R299) did not inhibit transformation by the Raf oncogene, indicating that inhibition was specific for Ras. Furthermore, Rat-1 cell lines expressing Pak1(R299) were highly resistant to Ras transformation, while cells expressing wild-type Pak1 were efficiently transformed by Ras. Pak1(L83,L86,R299), a mutant that fails to bind either Rac or Cdc42, also inhibited Ras transformation. Rac and Ras activation of JNK was inhibited by Pak1(R299) but not by Pak1(L83,L86,R299). Ras activation of ERK was inhibited by both Pak1(R299) and Pak1(L83,L86,R299), while neither mutant inhibited Raf activation of ERK. These results suggest that Pak1 interacts with components essential for Ras transformation and that inhibition can be uncoupled from JNK but not ERK signaling.

Animals↗
PubMed1997

Estimation of nonmechanical VO2 in isolated rabbit heart: comparison of mechanical unloading and BDM method.

To understand the mechaneoenergetics of heart muscle, it is important to be able to accurately partition energy consumption into its two major components, that used for nonmechanical activity [mainly excitation-contraction (E-C) coupling and basal metabolism] and that used for mechanical activity (cross-bridge cycling). In most experiments in the beating heart, this has been accomplished by assuming that the unloaded oxygen consumption (VO2) represents nonmechanical VO2 and subtracting it from total VO2 to yield mechanical VO2. However, unloaded VO2 is "contaminated" by an uncertain amount of energy consumption for cross-bridge cycling under unloaded conditions. We recently, reported an alternative method to estimate nonmechanical VO2 using the negative inotropic drug 2,3-butanedione monoxime (BDM), which, in theory, should not include cross-bridge cycling-related energy consumption. In the present study, we compared changes in unloaded VO2 and the BDM estimate of nonmechanical VO2 as E-C coupling was varied by changing the perfusate Ca2+ concentration ([Ca2+]) in the isolated rabbit heart. An isolated, red blood cell-perfused, isovolumically contracting balloon in left ventricle preparation was employed. In one group (n = 8), contractility (maximal elastance), unloaded VO2, and the BDM estimate of nonmechanical VO2 were assessed at a perfusate [Ca2+] of 2.5 mM and then at 5.0 mM. In a second group (n = 6), perfusate was 1.0 and 2.5 mM. The change in contractility in each group as [Ca2+] was increased was comparable. Unloaded VO2 was systematically greater than the BDM estimate of nonmechanical VO2 under all conditions. However, the absolute change in both estimates was similar in both groups. In conclusion, over the range of perfusate [Ca2+] employed in this study, changes in unloaded VO2 and the BDM estimate of nonmechanical VO2 are similar. These results support the use of unloaded VO2, which is easier to measure and has less estimation error in individual cases than the BDM-derived value for nonmechanical VO2, as an accurate index of change in E-C coupling energy consumption.

Animals↗
PubMed1997

Pulmonary endothelial NO synthase gene expression is decreased in fetal lambs with pulmonary hypertension.

Nitric oxide (NO), produced by endothelial (e) NO synthase (NOS), is critically involved in the cardiopulmonary transition from fetal to neonatal life. We have previously shown that NO-dependent relaxation is attenuated in intrapulmonary arteries from fetal lambs with pulmonary hypertension (PHT) created by prenatal ligation of the ductus arteriosus. In the present study, we determined whether this is due to altered pulmonary eNOS expression. eNOS and neuronal NOS (nNOS) protein expression were assessed in lungs from near-term control lambs and PHT lambs that underwent ductal ligation 10 days earlier. eNOS protein expression was decreased 49% in PHT lung. In contrast, nNOS protein abundance was unchanged. NOS enzymatic activity was also diminished in PHT vs. control lung (60 +/- 3 vs. 110 +/- 7 fmol.mg protein-1.min-1, respectively). Paralleling the declines in eNOS protein and NOS enzymatic activity, eNOS mRNA abundance was decreased 64% in PHT lung. Thus pulmonary eNOS gene expression is attenuated in the lamb model of fetal PHT. Because NO modulates both vasodilation and vascular smooth muscle growth, diminished eNOS expression may contribute to both the abnormal vasoreactivity and the excessive muscularization of the pulmonary circulation in fetal PHT.

Animals↗
PubMed1997

Estrogen acutely stimulates nitric oxide synthase activity in fetal pulmonary artery endothelium.

Estrogen (E) has nitric oxide (NO)-mediated effects in certain vascular beds, and fetal E levels rise acutely with parturition, suggesting that E may be involved in NO-mediated pulmonary vasodilation at birth. We tested the hypothesis that E acutely stimulates NO synthase (NOS) activity in ovine fetal pulmonary artery endothelial cells (PAEC) by measuring L-[3H]arginine conversion to L-[3H]citrulline in intact cells. NOS activity in the presence of 17 beta-estradiol (E2 beta) rose in a dose-dependent manner, increasing 70-100%, with a threshold concentration of 10(-10) M. This effect was detectable within 5 min of E2 beta exposure, and the maximal response was comparable to that obtained with acetylcholine, which had a threshold concentration of 10(-8) M. Ca2+ removal completely inhibited E2 beta-stimulated NOS activity, and activity with E2 beta and the Ca2+ ionophore A-23187 was not additive. In addition, the expression of the endothelial isoform of NOS (eNOS) was not altered, and the inducible and neuronal NOS isoforms were not detected by immunoblot analysis. These findings indicate that E2 beta acutely stimulates eNOS by Ca2+ influx. Furthermore, E2 beta-stimulated NOS activity was fully inhibited by the E receptor (ER) antagonists tamoxifen and ICI-182,780, and ER mRNA expression was evident in reverse transcription-polymerase chain reaction assays. Thus E acutely stimulates eNOS activity in fetal PAEC via the activation of endothelial ER and increases in intracellular Ca2+.

Acetylcholine↗
PubMed1997

Inputs from upper airway affect firing of respiratory-associated midbrain neurons.

In 16 decerebrated unanesthetized cats, we studied effects of neural inputs from upper airway on firing of 62 mesencephalic neurons that also developed respiratory-associated (RA) rhythmic firing when respiratory drive was high [Z. Chen, F. L. Eldridge, and P.G. Wagner. J. Physiol. (Lond.) 437: 305-325, 1991] and on firing of 16 neurons that did not develop the rhythmic firing (non-RA neurons). Activity in RA neurons increased after mechanical expansion of pharynx (45% of those tested) or larynx (68%) and after stimulation of glossopharyngeal (50%) or superior laryngeal nerves (77%). The increased neuronal firing occurred despite decreases or abolition of respiratory activity (expressed in phrenic nerve). Neuronal firing also increased after mechanical stimulation of nasal mucosa (66%) or by jets of air directed into the nares (48%) and after light brushing of nasal skin ( approximately 40%). Most stimuli led to decreased firing in a smaller number of neurons, and some neurons showed no response. None of the non-RA neurons developed an increase of firing after any of the stimuli, although one had decreased firing after stimulation of the superior laryngeal nerve. We conclude that inputs from the upper airway and nasal skin have independent modulatory effects on the same mesencephalic neurons that are stimulated by ascending rhythmic RA input from the medulla. These findings may have relevance to generation of the sensation of dyspnea.

Animals↗
PubMed1997

Estrogen upregulates endothelial nitric oxide synthase gene expression in fetal pulmonary artery endothelium.

NO, produced by endothelial NO synthase (eNOS), is a key mediator of pulmonary vasodilation during cardiopulmonary transition at birth. The capacity for NO production is maximal at term because pulmonary eNOS expression increases during late gestation. Since fetal estrogen levels rise markedly during late gestation and there is indirect evidence that the hormone enhances nonpulmonary NO production in adults, estrogen may upregulate eNOS in fetal pulmonary artery endothelium. Therefore, we studied the direct effects of estrogen on eNOS expression in ovine fetal pulmonary artery endothelial cells (PAECs). Estradiol-17beta caused a 2.5-fold increase in NOS enzymatic activity in PAEC lysates. This effect was evident after 48 hours, and it occurred in response to physiological concentrations of the hormone (10(-10) to 10(-6) mol/L). The increase in NOS activity was related to an upregulation in eNOS protein expression, and eNOS mRNA abundance was also enhanced. Estrogen receptor antagonism with ICI 182,780 completely inhibited estrogen-mediated eNOS upregulation, indicating that estrogen receptor activation is necessary for this response. In addition, immunocytochemistry revealed that fetal PAECs express estrogen receptor protein. Furthermore, transient transfection assays with a specific estrogen-responsive reporter system have demonstrated that the endothelial estrogen receptor is capable of estrogen-induced transcriptional transactivation. Thus, estrogen upregulates eNOS gene expression in fetal PAECs through the activation of PAEC estrogen receptors. This mechanism may be responsible for pulmonary eNOS upregulation during late gestation, thereby optimizing the capacity for NO-mediated pulmonary vasodilation at birth.

Animals↗
PubMed1997

Fat or lean tissue mass: which one is the major determinant of bone mineral mass in healthy postmenopausal women?

The relative importance of fat and lean tissue mass in determining bone mineral mass among postmenopausal women was examined in this 1-year longitudinal study. Fifty postmenopausal Caucasian women entered the study; 45 of them completed a 1-year follow-up. Dual-energy X-ray absorptiometry was employed for measuring total and regional bone mineral density (BMD) and bone mineral content (BMC), fat tissue mass (FTM), lean tissue mass (LTM), and body weight. Results from linear regression analysis using the cross-sectional data (n = 50) of the study indicated that LTM explained a larger percentage of variation in bone mineral mass than did FTM. FTM and LTM were found to be moderately correlated (r = 0.55); when FTM was entered in the same predicting regression models, LTM was a significant predictor (p < 0.05) of the total and regional BMC, but not BMD. The percent FTM (and inversely %LTM) was correlated with BMD and BMC, but significant correlation was primarily found only for total body BMD (or BMC). Weight was the best predictor of total body BMD and BMC. Longitudinally (n = 45), annual changes in both FTM and weight were significantly associated with annual changes in regional BMD after adjustment for initial bone mineral values (p < 0.05). We conclude that bone mineral mass is more closely related to LTM than to FTM, while annual changes in regional BMD are more closely correlated with changes in FTM in healthy postmenopausal women. Meanwhile, increased body weight is significantly associated with increased bone mineral mass.

Absorptiometry, Photon↗
PubMed1997

Hepatitis C virus (HCV) specific sequences are demonstrable in the DNA fraction of peripheral blood mononuclear cells from healthy, anti-HCV antibody-negative individuals and cell lines of human origin.

No convincing support has been provided so far for the existence of extrahepatic hepatitis C virus particles that should correspond to the sometimes extremely high concentration of 'HCV-RNA' in serum or plasma. If a naturally occurring HCV-specific DNA were to be found, a concept for at least some phenomena in terms of the pathophysiology of HCV should become conceivable. DNA was extracted from peripheral blood mononuclear cells of eleven healthy, anti-HCV-negative individuals, including five long term blood donors, and cells from different cell lines. DNA was subjected to nested polymerase chain reaction omitting a reverse transcriptase step with primers of the 5'NC as well as part of the core region of HCV. Direct polymerase chain reaction, i.e. without a reverse transcriptase step, revealed HCV-specific sequences in the DNA fraction of peripheral blood mononuclear cells of different origin: healthy anti-HCV negative individuals, furthermore in HeLa and MT2 cells. The fragments found were of expected length as well as of shorter and of longer than expected length with respect to the sequence of the HCV genome framed by the primers applied. The results derived from additional hybridization, restriction endonuclase analysis, and sequencing demonstrated HCV-specific sequences in the expected fragments with both a high degree of homology and deletions, respectively, substitutions, as compared to a prototype strain. However, the longer than expected fragments also contained sequences not specific for HCV.

Base Sequence↗
PubMed1997

[The effects of cardiopulmonary bypass on pulmonary surfactant activity].

OBJECTIVE: To study the effects of cardiopulmonary by pass(CPB) on pulmonary surfactant (PS) activity. METHOD: In 12 children with patent ductus arteriosus(PDA) and 19 patients with ventricular septal defect (VSD), saturated phosphatidylcholine (SatPC), total phospholipids (TPL), total protein (TP) and surfactant protein-A(SP-A) in sequential airway aspirates before and after operation were determined. Tetroxide osmium digestion and neutral alumina column chromatography were used for SatPC, and a modified immunoblot method with a rabbit anti-human SP-A polyclonal antibody for SP-A measurment. RESULTS: In 19 VSD patients with CPB, SatPC/TPL was significantly decreased from 48% to 34% (t = 2.737, P < 0.05), SatPC/TP decreased from 64 to 33 mg/g (t = 3.011, P < 0.01), and SP-A from 23 to 11mg/g (t = 2.987, P < 0.01). In 12 patients without CPB, SatPC/TPL, SatPC/TP, SP-A/TP levels were not changed. CONCLUSIONS: CPB significantly reduces pulmonary surfactant activity.

Cardiopulmonary Bypass↗
PubMed1997

8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate actions on calcium dynamics in cultured vascular smooth muscle cells.

AIM: To study 8-(N,N-Diethylamino)n-octyl-3,4,5-trimethoxybenzoate (TMB), a potent Ca(2+)-antagonist, actions on cellular calcium dynamics in vascular smooth muscle cell (VSMC) cultures. METHODS: A7r5 VSMC were cultured with Fura-2 measurements of intracellular Ca2+ concentration, [Ca2+]i. RESULTS: TMB reduced [Ca2+]i from control levels and blocked [Ca2+]i increase caused by norepinephrine (NE) and 2,5-di (t-butyl)-1,4-benzohydroquinone (BHQ). [Ca2+]i reduction by TMB was further enhanced by ryanodine. CONCLUSION: TMB is an effective agent for blocking the [Ca2+]i increase caused by NE and BHQ and for enhancing the [Ca2+]i reduction caused by ryanodine.

Animals↗
PubMed1997

Actions of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate in vascular smooth muscle cell cultures.

AIM: To study the effects of 8-(N,N-diethylamino)-n-octyl-3,4,5-trimethoxybenzoate (TMB-8) on vascular smooth muscle (VSM) cells A7r5. METHODS: The effects of TMB-8 were investigated in A7r5 cell cultures with 45CaCl2. RESULTS: TMB-8 reduced the intracellular free Ca2+ concentration, [Ca2+]i in a Ca(2+)-free medium and blocked Ca2+ entry from the extracellular site in a regular Ca2+ medium. The equilibrated total cellular binding of Ca2+ was increased by TMB-8 whereas 45Ca2+ entry activated by both NE and KCl was inhibited. However, the NE-activated Ca2+ entry was not blocked by TMB-8 if TMB-8 was added together with 45Ca2+ at a later time instead of by pretreatment. Similar to actions of NE and KCl, depletion of Ca2+ from sarcoplasmic reticulum (SR) would also activate Ca2+ entry, which was blocked by TMB-8. When TMB-8 was rinsed out alone or together with NE after pretreatment with NE plus TMB-8 in VSM cells, the inhibitory effect of TMB-8 was not affected. CONCLUSION: TMB-8 not only blocks Ca2+ entry from the extracellular site, but also enhances Ca2+ uptake into SR which, indirectly inhibits Ca2+ entry from the extracellular site.

Animals↗
PubMed1997

[Effect of EBV-LMP and EGF autocrine on proliferation of nasopharyngeal carcinoma cell line CNE and their relationship in action].

EBV-LMP gene transfection, radioimmuno-binding assay (RIA) and colorimetric cell viability assay (MTT) were used to investigate the effect and relationship of EBV-LMP and EGF autocrine on the growth and proliferation of well differentiated nasopharyngeal carcinoma cell line (CNE1). Autocrine EGF was detected in the supernant of CNE1 cells and CNE1 cells could grow in serum-free medium, implicating that the cell proliferation-promoting effect of EGF autocrine was present in the CNE1 cell line. Nevertheless the positive signals of LMP gene polymerase chain reaction and LMP Mab immunohistochemical staining in pCMV alpha-LMP DNA transfected cells, confirmed the successful transfection of LMP gene. EGF autocrine amount and the proliferation of CNE1 cells in serum-free medium were more obvious in post-transfected cells than those in untransfected cells. The present study represents the first report on promotion of EGF autocrine in EBV-LMP-transfected cells, thus promoting cell proliferation.

Autocrine Communication↗
PubMed1997

[The ampullar endolymhatic potential in the guinea pigs].

The purpose of this paper is to understand the physiologic feature of the ampullar endolymphatic potential (AEP) in the guinea pigs (n = 35). The high input impedence microelectrode amplifier was used. The effects of asphyxia, furosemide and ischemia on the AEP were observed. The AEP was 4.55 +/- 1.35 mV, (n = 35) in normal. The potential decreased to 2.8 +/- 0.8 mV from the original level in two minutes of asphyxia. When the respirator was turned on the AEP started to rise abruptly after a latency. In all instances there was an overshoot above the preasphyxia level. When furosemide was administered i.v. at 100 mg/kg, no effects were seen in the AEP. After obstruction of the ascending aorta to cause ischemia, the AEP continued to decline until it reached a minimum of -19.4 +/- 1.7 mV in 52.5 +/- 9.6 minutes and slowly returned to zero line in about 150 minutes. There was no obovious effect after furosemide injection. The results suggest that AEP may deffer from as the positive potential in cochlea. It is produced in the specialized cells (dark cells) of the ampullar and has special electro-physiologic characteristics.

Action Potentials↗
PubMed1997

[A continuous and constant rate administration method--mini-osmotic pump].

Mini-osmotic pump is a delicate administration method. When it is activated by water, mini-osmotic pump can deliver a variety of solutions or suspensions at a constant rate for days even up to several weeks. Since it is drived by osmotic pressure, the pumping rate is independent on the physical and chemical feature of the drugs. The pump from inside to outside consists of a cylindrical reservior, osmotic driving agent and semipermeable membrane.

Animals↗
PubMed1997

[Effect of CRF, AVP and NE on cAMP in cultured rat anterior pituitary cells during hypoxia].

In the study, the effect CRF (corticotropin-releasing factor), AVP (argipressin) and NE (norepinephrine) on cAMP formation in cultured rat anterior pituitary cells in vitro was examined and the effect of cAMP formation between normoxia and hypoxia (8%O2) was compared. CRF stimulated the formation of cAMP levels which was correlated with the concentration of CRF in medium. The cAMP levels in medium increased. The intracellular cAMP in cultured anterior pituitary cells was not changed by AVP. The concentration of intracellular cAMP was decreased by NE, but the content of extracellular cAMP was no changed. Hypoxia decreased the stimulating effects of CRF on the cAMP formation in cultured anterior pituitary cells.

Animals↗