Latest Issue
Volume 0 ， Issue 4 ， 2004
- Abstract：Objective To explore the effects of mifepristone on the growth of human gastric cancer cell line MKN-45 and its possible mechanisms. Methods In situ hybridization was used to detect the expression of progesterone receptor （PR） mRNA in MKN-45 cells. Proliferation, cell cycle distribution, and the expression of Bcl-xL and vascular endothelial growth factor （VEGF） of MKN-45 cells incubated with various concentrations of mifepristone （1, 5, 10, and 20 μmol/L） were analyzed using MTT reduction assay, flow cytometry, reverse transcription-polymerase chain reaction （RT-PCR）, and enzyme-linked immunoab-sorbent assay （ELISA）, respectively. After transplantation of MKN-45 cells underneath the skin of athymic mice, mifepristone was administrated with the dose of 50 mg/（kg·d） for 6 weeks to evaluate the tumor growth. Apoptosis and the expression of proliferating cell nuclear antigen （PCNA） in xenografted tumors were detected using transmission electron microscopy and immunohistochemical staining, respectively. Results PR mRNA was highly expressed in cultured MKN-45 cell. Mifepristone dose-dependently inhibited the pr-oliferation of MKN-45 cells, and the inhibitory rate was dramatically increased from 7.21% to 47.23%. The inhibitory effect was accompanied by a dose-dependent increase in the percentage of cells in G 0 /G 1 phase, and with a concurrent decrease in the proportion of S- and G 2 /M-phase cells and the proliferative index from 57.65% to 24.54%. Meanwhile, mifepristone down-regulated the expression of Bcl-xL and VEGF in a dose-dependent manner. In vivo, mifepristone effectively inhibited the growth of xenografted tumors in nude mice （55.14% for inhibitory rate）, induced apoptosis, and down-regulated PCNA expression in gastric cancer. Conclusion Mifepristone exerts significant growth inhibitory effects on PR-positive human MKN-45 gastric cancer cells via multiple mechanisms, and may be a beneficial agent against the tumor.Keywords：mifepristone;gastric neOplasm;proliferation4|14|3Updated：2024-04-10
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- Abstract：Objective To investigate the effect of peroxisome proliferator-activated receptor-α（PPARα） and PPARγactivators on tumor necrosis factor-α（TNFα） expression in neonatal rat cardiac myocytes. Methods Primary cultures of cardiac myocytes from 1- to 3-day-old Wistar rats were prepared, and myocytes were ex-posed to lipopolysaccharide （LPS） and varying concentrations of PPARαor PPARγactivator （fenofibrate or pioglitazone）.RT-PCR and ELISA were used to measure TNFα, PPARα, and PPARγexpression in cultured cardiac myocytes. Transient tr-ansfection of TNFαpromoter with or without nuclear factor-kappaB （NF-κB） binding site to cardiac myocytes was performed. Results Pretreatment of cardiac myocytes with fenofibrate or pioglitazone inhibited LPS-induced TNFαmRNA and protein expression in a dose-dependent manner. However, no significant changes were observed on PPARαor PPARγmRNA expression when cardiac myocytes were pretreated with fenofibrate or pioglitazone. Proportional suppression of TNFαpromoter activity was observed when myocytes was transiently transfected with whole length of TNFαpromoter （-721/+17） after being stimulated with LPS and fenofibrate or pioglitazone, whereas no change of promoter activity was observed with transfection of TNFαreporter construct in deletion of NF-κB binding site （-182/+17）. Conclusions PPARαand PPARγactivators may inhibit cardiac TNFαexpression but not accompanied by change of PPARαor PPARγmRNA expression. Therefore PPARαand PPARγactivators appear to play a role in anti-inflammation. The mechanism may partly be involved in suppression of the NF-κB pathway.Keywords：peroxisome proliferator-activated receptors;tumor necrosis factor-α;cardiac myocytes;activators4|27|8Updated：2024-04-10
- Abstract：Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing. Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years. Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teena-gers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers （12.7±12.1 mmHg vs. 2.8 ±5.2 mmHg, P< 0.01; 12.2% ±12.0% vs. 2.5% ±4.4%, P< 0.001, respectively）. There was a similar trend for diastolic blood pressure （8.4 ±6.4 mmHg vs. 3.7 ±6.4 mmHg, P= 0.052; 13.2% ±10.6 % vs. 6.8% ±10.1%, P= 0.053, respectively）. Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.Keywords：salt sensitivity;reproducibility;blood pressure;teenagers4|18|0Updated：2024-04-10
- Abstract：Objective To study endothelial damage by observing changes of circulating endothelial cells （CECs） in blood, coagula-tion and fibrinolysis index in patients with acute respiratory distress syndrome. Methods CECs were separated by isopycnic centrifugation method in 14 patients with acute lung injury （ALI）, 7 patients with acute respiratory distress syndrome （ARDS）, 10 intensive care unit （ICU） controls, and 15 healthy controls. Plasma prothrombin time （PT）, activated partial thromboplastin time （APTT）, fibrinogen （FG）, fibrin degradation products （FDP）, and D-dimer were examined simultaneously. Acute physiology and chronic health evaluation （APACHE）Ⅱand lung injury score （LIS） were recorded to evaluate severity of illness and lung injury. Results （1） The number of CECs in ALI （10.4 ±2.3） and ARDS groups （16.1 ±2.7） was higher than that in the healthy （1.9 ±0.5） （P< 0.01）. In both ALI and ARDS, the number of CECs correlated with APACHEⅡ（r=0.55, P< 0.05 and r=0.62, P< 0.05, respectively）and LIS （r=0.60, P< 0.05 and r=0.53, P< 0.05, respectively）. CEC number was negatively correlated with PaO 2 in ALI and ARDS （r=-0.49, P< 0.05 and r=-0.64, P< 0.05, respectively）. （2） The level of FDP and D-dimer were higher in ALI and ARDS patients than that in ICU and healthy control groups （P< 0.05）. The level of FG in ARDS group was significantly higher than in the ICU and healthy control groups （P< 0.05）. But in ALI group, the level of FG was significantly higher than only healthy control group （P< 0.05）. Conclusions Endothelial cell damage occurs in ARDS patients, which may play a major role in the pathophysiology of ARDS. Changes of endothelial cell activation and damage markers, such as CECs, plasma coagulation and fibrinolysis index, to some extent reflect severity of illness and lung injury in ARDS.Keywords：acute respiratory distress syndrome;endothelial cell;fibrinogen;fibrin;D-dimer4|17|12Updated：2024-04-10
- Abstract：Objective To confirmed reliability and feasibility of intranasal nerve growth factor （NGF） bypassing the blood-brain barrier and its potential neuroprotective effects on acute cerebral ischemia. Methods （1） To assay NGF concentrations in different brain regions after middle cerebral artery occlusion （MCAO）.Rats were randomly divided into intranasal （IN） NGF, intravenous （IV） NGF, and untreated group （n= 4）. The concentra-tions of NGF of different brain regions in the three groups after MCAO were measured by ELISA. （2） To observe neuro-protective action of NGF on focal cerebral ischemic damage. Rats were randomly assigned to 4 groups: IN vehicle, IN NGF, IV vehicle, IV NGF （n= 8）. Treatment was initiated 30 minutes after onset of MCAO and given again 24 hours later. Three neurologic behavioral tests were performed 24 and 48 hours following onset of MCAO. Corrected infarct volumes were determined 48 hours after onset of MCAO. Results The olfactory bulb in IN NGF group obtained the highest concentration （3252 pg/g） of NGF among all regions, followed by the hippocampus. The NGF concentrations in the olfactory bulb and hippocampus in IN NGF group were markedly higher than that in IV NGF and control groups. The infarct volume in IN NGF group was markedly reduced by 38.8% compared with IN vehicle group. IN NGF group vestibulum function markedly improved compared with IN vehicle group at 24 and 48 hours after onset of MCAO （P 24 h = 0.02 and P 48 h = 0.04, respectively）. Conclusion Intranasal NGF could pass through the blood-brain barrier, reach the central nervous system, reduce infarct volume, and improve neurologic function in rats following MCAO. Intranasal delivery of NGF may be a promising treat-ment for stroke.Keywords：nerve growth factor;middle cerebral artery occlusion;intranasal delivery;cerebral ischemia4|34|16Updated：2024-04-10
- Abstract：Objective To evaluate the emotional and cognitive status in patients with obstructive sleep apnea syndrome （OSAS）, using neuropsychological tests and evoked-related potential （P3）. Methods Sixteen patients diagnosed of OSAS were tested by Hamilton rating scale for anxiety （HRSA） and Hamilton rating scale for depression （HRSD）. Other three groups, OSAS patient group （n=21）, snoring group （n=21）, and control group （n=21）, were administered polysomnography （PSG）, auditory evoked event-related potential （P3）, and clinic memory test. The results were analyzed using general linear model （GLM） analysis and Post Hoc test. Results Twelve OSAS patients’ scores of HRSA and HRSD were beyond the normal range, 26.42 ±4.48 and 22.08 ±3.97 respectively. The auditory P3 latency in OSAS group was 363.1 ±22.9 ms （Fz）, 368.57 ±28.03 ms （Cz）, in snoring group 336.57 ±31.08 ms （Fz）, 339.81 ±31.76 ms （Cz）, in control group 340.8 ±28.7 ms （Fz）, 338.29 ±29.21 ms （Cz）. There were significant differences between OSAS group and snoring group, as well as control group （P< 0.05）. No significant difference was seen between snoring group and control group. No significant difference was noted in P3 amplitude among three groups. Memory quotient （MQ） reduced in snoring group compared with control group. Conclusions Emotional disturbances are common clinical features in OSAS patients. Abnormal auditory P3 latency indicates the cognitive dysfunction in OSAS patients. Nocturnal hypoxaemia may play an important role on it. Snorers should be monitored because of the tendency to develop cognitive impairment.Keywords：obstructive sleep apnea syndrome;evoked-related potential;cognitive function4|33|23Updated：2024-04-10
- Abstract：Objective To construct a single plasmid vector mediating doxycycline-inducible recombined human insulin gene expr-ession in myotube cell line. Methods An expression cassette of rtTAnls driven by promoter of human cytomegalovirus and a furin-cuttable recom-bined human insulin expression cassette driven by a reverse poly-tetO DNA motif were cloned into a single plasmid vector （prTR-tetO-mINS）. The prTR-tetO-mINS and pLNCX were co-transfected into a myotube cell line （C2C12） and pLNCX vector were used as a control. After selection with G418, the transfected cells were induced with doxycycline at concentra-tions of 0, 2, and 10 μg/mL. RT-PCR was used to determine expression levels of recombinant insulin mRNA at the 5th day. Insulin production in cell cultures medium （at different incubation time） and cell extracts （at the 7th day） were analyzed with human pro/insulin RIA kits. Results Immune reactive insulin （IRI） level in cell medium was found increased at 24 hours of doxycycline incubation, and still increased at the 5th day. After withdrawn of doxycycline, IRI decreased sharply and was at baseline three days later. IRI and human insulin mRNA levels were positively related to different levels of doxycycline. A 25-fold increase in IRI was found against background expression at the 7th day. Conclusion Human insulin expression can be successfully regulated by doxycycline and the background was very low. This single tet-on insulin expression system may provide a new approach to a controlled insulin gene therapy in skeletal muscle.Keywords：doxycycline;tetracycline;insulin gene therapy;diabetes mellitus4|17|0Updated：2024-04-10
- Abstract：Objective To study the role of extracellular signal-regulated kinase （ERK） in cerebral ischemia and the mechanism of protective effects of U0126 （1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio] butadiene） on ischemic brain. Methods Mice underwent left middle cerebral artery occlusion （MCAO） by introducing a suture in the lumen. U0126 was injected intravenously through the internal jugular vein. The immuno-activity of phosphorylated ERK1/2 （pERK1/2）, phos-phorylated mitogen activated protein kinase kinase （pMEK）, and phosphorylated Elk-1 （pElk-1） was assessed by Western blot analysis and immunohistochemistry. Interleukin （IL）-1βmRNA level was measured by ribonuclease protection assay. Results Phosphorylated ERK1/2 in 2 hours MCAO mice was down-regulated after intravenous injection of U0126. The inhibition was dose dependent and treatment time related. pMEK and pElk-1 were also reduced in a similar fashion after U0126 treatment. IL-1βmRNA increased after 1 and 2 hours of MCAO. After injection of U0126, it was down-regulated during 1 to 4 hours after MCAO. Conclusion Intravenous administration of the MEK inhibitor U0126 inhibits pMEK, pERK1/2, and pElk-1 up-regulation induced by cerebral ischemia. The protective effect of U0126 against ischemic injury is probably resulted from the reduction of IL-1βmRNA via the inhibition of ERK pathway.Keywords：cerebral ischemia;mitogen activated protein kinases;interleukin-14|75|28Updated：2024-04-10
- Abstract：Objective To investigate the role of cytoplasmic domain of integrin alphaⅡb in platelet signal transduction. Methods Binding capacity of integrin alphaⅡb R995A to antibody platelet activation complex-1 （PAC-1） and pp125 focal adhesion kinase （FAK） phosphorylation of cells were detected by flow cytometry, immune precipitation, and Western blotting. Results Without activation, wild-type alphaⅡbbeta3 Chinese hamster ovary （CHO） cells failed to bind to PAC-1, but mutant chimera alphaⅡb R995A beta3 CHO cells were able to bind with PAC-1. Furthermore, phosphorylation of pp125 （FAK） in wild-type alphaⅡbbeta3 CHO cells occured only when cells were adhered to fibrinogen, but could not be detected in bovine serum albumin suspension. However in the mutant chimera group, it could be detected in both conditions. Conclusion The mutation in integrin alphaⅡb R995A alters its affinity state as a receptor, thus also mediating cytoplasmic signal transduction leading to the phosphorylation of pp125 （FAK） without ligand binding.Keywords：integrin alphaⅡbbeta3;signal transduction;pp125 focal adhesion kinase;phosphorylation4|21|0Updated：2024-04-10
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- Abstract：Objective To investigate the roles of sympathetic and vagus nerves in hypotension and bradycardia induced by fentanyl. Methods Fourteen rabbits were divided into 2 groups: normal and vagotomized rabbits. Rabbits were anesthetized, paralyzed, and artificial ventilated. Right renal sympathetic nerve was exposed and prepared for recording electrical activity. Fentanyl was injected intravenously in incremental doses of 1, 4, 15, 30, and 50 μg/kg at 10 minutes intervals. Results Fentanyl significantly reduced the spontaneous activity of renal sympathetic nerve, mean arterial pressure, and heart rate above a total dose of 20 μg/kg in both normal and vagotomized rabbits. However, normal rabbits spontaneous sympathetic nerve activity and mean arterial pressure were more depressed than vagotomized rabbits at total doses of 50 and 100 μg/kg. There were no significant difference in the reduction of heart rate between normal and vagotomized rabbits. Conclusion Fentanyl induction of bradycardia and hypotension in rabbits is mainly due to depression of sympathetic nerve activity.Keywords：fentanyl;sympathetic nerve;vagus nerve4|8|0Updated：2024-04-10
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- Abstract：Objective To test whether in the absence of actin, actin-binding proteins such as caldesmon, calponin, and tropomyosin interact with the myosin of unphosphorylation, Ca 2+ -dependent phosphorylation （CDP）, and Ca 2+ -independent phosphorylati-on （CIP） and stimulate myosin Mg 2+ -ATPase activities. Methods Mg 2+ -ATPase activities were measured to evaluate the effects of caldesmon, calponin, and tropomyosin on the myosin in unphosphorylation, CDP by myosin light chain kinase （MLCK）, and CIP by MLCK. Results （1） At different incubation-time, i.e., 5, 10, 20, 40, and 60 minutes, the highest Mg 2+ -ATPase activity was ob-served when myosin was in the state of CDP, the medium was CIP of myosin, and the lowest was the unphosphorylated myosin. （2） In the absence of caldesmon, calponin, and tropomyosin, the Mg 2+ -ATPase activities from high to low were in the following order: CDP, CIP, and unphosphorylated myosin. However, in the presence of caldesmon, calponin, and tropo-myosin, the order of relative value of Mg 2+ -ATPase activities from high to low was unphosphorylated, CIP, and CDP of myosin respectively compared to the corresponding controls. Conclusions The results propose that caldesmon, calponin, and tropomyosin are capable of stimulating Mg 2+ -ATPase activity of smooth muscle myosin in Ca 2+ -independent manner, since Ca 2+ is not obligating for the stimulating effects of the three proteins. The common characteristic of the three proteins is that when myosin activities are low, their activations are relatively strong and this property might be involved in smooth muscle tension keeping.Keywords：actin-binding proteins;myosin Mg 2+ -ATPase activity;Ca 2+ -independent phosphorylation;Ca 2+ -dependent phosphorylation4|54|3Updated：2024-04-10
- Abstract：Objective To investigate the mechanism of anticoagulation protein defect in the pathogenesis of unexplained recurrent miscarriage. Methods Fifty-seven patients with a history of unexplained abortion were enrolled as the investigation group for tests of protein C, protein S, antithrombinⅢ（AT-Ⅲ）, as well as activated protein C resistance （APC-R）. The control group con-sisted of fifty healthy women with a history of normal pregnancy and delivery. Blood samples were obtained for measuring serum activity of protein C, protein S, AT-Ⅲ, and APC-R. Patients with positive APC-R were tested for factorⅤ（FⅤ） Lei-den gene mutation by PCR-RFLP method. Results Of the 57 patients, 12 （21.1%）, 1 （1.8%）, and 5 （8.8%） cases were found with protein S, protein C, and AT-Ⅲdeficiency respectively, and 13 （22.8%） cases with positive results of APC-R. Of the control group, no protein C or AT-Ⅲdeficiency was ever found, whereas 2 （4.0%） volunteers were presented with protein S deficiency and 3 （6.0%） with positive results of APC-R. No FⅤLeiden gene mutation was identified in all the patients with positive APC-R results. Late spontan-eous abortion cases had higher incidence of anticoagulation protein defect than the early cases. Conclusion Anticoagulation protein defect may play a role in the pathogenesis of fetal loss, especially for those occurr-ing in late stage of pregnancy.Keywords：protein S deficiency;protein C deficiency;activated protein C resistance;spontaneous abortion4|6|1Updated：2024-04-10
- Abstract：Objective To explore the relationship between human cytomegalovirus （HCMV） UL144 sequence variability and clinical disease. Methods HCMV UL144 open reading frame （ORF） was amplified by PCR assay in 72 lowpassage isolates [65 con-genitally infective children and 7 healthy children who were HCMV-DNA positive by quantitative PCR （qPCR）]. All positive PCR products were analyzed by heteroduplex mobility assay and single-stranded conformation polymorphism （HMA-SSCP） and 32 of them were sequenced. Results Fifty-five patient isolates and five healthy children isolates were HCMV-UL144 positive by PCR. Sequencing and HMA-SSCP analysis showed that significant strain-specific variability was present in the UL144 ORF. Phylogenetic analysis indicated that the nucleotide sequences could be separated into 3 major genotypes. Comparing between UL144 se-quences and the corresponding symptoms showed that genotype 2 did not exist in megacolon isolates. And genotype 1 and 3 were the major types among microcephaly and jaundice isolates respectively. Conclusions HCMV-UL144 existed in most of low passage isolates and sequences were hypervariable. The UL144 ORF and its predicted product with the high level of sequence variability in different kinds of isolates suggest that UL144 ORF might play a role in HCMV infectivity and subsequent diseases.Keywords：human cytomegalovirus;UL144 open reading frame;variability10|18|4Updated：2024-04-10
- Abstract：Objective To explore fetal arrhythmia clinical significance and its correlation with fetal prognosis. Methods Twenty-six cases of fetal arrhythmia detected among 12 799 pregnant women recorded over a ten-year period in Peking Uinon Medical College （PUMC） Hospital were reviewed retrospectively. Fetal arrhythmia was diagnosed by fetal auscultation, ultrasonography, electric fetal heart monitoring, and fetal echocardiography. Results Twenty-six fetuses were documented with fetal arrhythmia （3 tachycardia, 4 bradycardia, 19 normal heart rate with irregular fetal cardiac rhythm）. The incidence of fetal arrhythmia in our hospital was 0.2%. They were diagnosed at the average of 35 weeks’ gestation （15 to 41 weeks）. Twenty-two cases were diagnosed by antenatal fetal auscultation, 1 case was diagnosed by ultrasonography, and 3 cases were diagnosed by electric fetal heart monitoring. Fetal echocardiograms were per-formed on 17 fetuses, 6 cases （35.3%） of which showed that ventricular premature beats with normal structure of fetal heart. All neonates survived postnatally and 24 of them （92.3%） were followed up. Echocardiograms were performed for 16 neonates and 2 of them were identified as atrial septal defects with normal heart rhythms. The results of follow-up showed that the two patients had no apparent clinical manifestation. The echocardiogram showed that atrial septal defect obliterated already. Conclusion The prognosis is well for most of the fetuses with arrhythmias, with low incidence of heart deformation.Keywords：fetal arrhythmia;congenital heart disease;fetal echocardiography5|19|0Updated：2024-04-10
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