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Biomedical subjects

L Gong

Publications and source records attributed to L Gong.

At least 19 recordsLinked to original sources

Muscle-specific creatine kinase gene polymorphism and running economy responses to an 18-week 5000-m training programme.

OBJECTIVE: To investigate the association between muscle-specific creatine kinase (CKMM) gene polymorphism and the effects of endurance training on running economy. METHODS: 102 biologically unrelated male volunteers from northern China performed a 5000-m running programme, with an intensity of 95-105% ventilatory threshold. The protocol was undertaken three times per week and lasted for 18 weeks. Running economy indexes were determined by making the participants run on a treadmill before and after the protocol, and the A/G polymorphism in the 3' untranslated region of CKMM was detected by polymerase chain reaction-restricted fragment length polymorphism (NcoI restriction enzyme). RESULTS: Three expected genotypes for CKMM-NcoI (AA, AG and GG) were observed in the participants. After training, all running economy indexes declined markedly. Change in steady-state consumption of oxygen, change in steady-state consumption of oxygen by mean body weight, change in steady-state consumption of oxygen by mean lean body weight and change in ventilatory volume in AG groups were larger than those in AA and GG groups. CONCLUSIONS: The findings indicate that the CKMM gene polymorphism may contribute to individual running economy responses to endurance training.

Adolescent↗

Protein serine/threonine phosphatase-1 dephosphorylates p53 at Ser-15 and Ser-37 to modulate its transcriptional and apoptotic activities.

We have previously demonstrated that the serine/threonine protein phosphatase-1 (PP-1) plays an important role in promoting cell survival. However, the molecular mechanisms by which PP-1 promotes survival remain largely unknown. In the present study, we provide evidence to show that PP-1 can directly dephosphorylate a master regulator of apoptosis, p53, to negatively modulate its transcriptional and apoptotic activities, and thus to promote cell survival. As a transcriptional factor, the function of p53 can be greatly regulated by phosphorylation and dephosphorylation. While the kinases responsible for phosphorylation of the 17 serine/threonine sites have been identified, the dephosphorylation of these sites remains largely unknown. In the present study, we demonstrate that PP-1 can dephosphorylate p53 at Ser-15 and Ser-37 through co-immunoprecipitation, in vitro and in vivo dephosphorylation assays, overexpression and silence of the gene encoding the catalytic subunit for PP-1. We further show that mutations mimicking constitutive dephosphorylation or phosphorylation of p53 at these sites attenuate or enhance its transcriptional activity, respectively. As a result of the changed p53 activity, expression of the downstream apoptosis-related genes such as bcl-2 and bax is accordingly altered and the apoptotic events are either largely abrogated or enhanced. Thus, our results demonstrate that PP-1 directly dephosphorylates p53, and dephosphorylation of p53 has as important impact on its functions as phosphorylation does. In addition, our results reveal that one of the molecular mechanisms by which PP-1 promotes cell survival is to dephosphorylate p53, and thus negatively regulate p53-dependent death pathway.

Amino Acid Substitution↗

Genomic instability in phenotypically normal regenerants of medicinal plant Codonopsis lanceolata Benth. et Hook. f., as revealed by ISSR and RAPD markers.

Codonopsis lanceolata Benth. et Hook. f., commonly known as bonnet bellflower, is a high-valued herb medicine and vegetable. In this study, a large number of plants were regenerated via organogenesis from immature seed-derived calli in C. lanceolata by a simple and efficient method. Compared with the mother donor plant, the regenerated plants did not exhibit visible phenotypic variations in six major morphological traits examined at the stage of one-season-maturity under field conditions. To gain insight into the genomic stability of these regenerated plants, 63 individuals were randomly tagged among a population of more than 2,000 regenerants, and were compared with the single mother donor plant by two molecular markers, the inter-simple sequence repeats (ISSR) and randomly amplified polymorphic DNA (RAPD). Apparent genomic variation was detected in the 63 regenerants, whereas preexisting heterozygosiy in the donor plant was deemed minimal by testing 30 seedlings germinated from selfed seeds of the same donor plant. The percentages of polymorphic bands (PPB) in the ISSR and RAPD analysis were respectively 15.7 and 24.9% for the 63 regenerated plants. Cluster analysis indicates that the genetic similarity values calculated on the basis of RAPD and ISSR data among the 64 plants (63 regenerated and one donor) were respectively 0.894 and 0.933, which allow classification of the plants into distinct groups. Nineteen randomly isolated bands underlying the changed RAPD or ISSR patterns were sequenced, and three of them showed significant homology to known-function genes. Detailed pairwise sequence comparison at one locus between the donor plant and a regenerant revealed that insertion of two short (24 and 19 bp) stretches of nucleotides in the regenerated plant relative to the donor plant occurred in an apparently stochastic manner.

Base Sequence↗

Antitumor effect of antisense ODC adenovirus on human prostate cancer cells.

Ornithine decarboxylase (ODC), the first enzyme of polyamine biosynthesis, was found to increase in cancer cells, especially prostate cancers. Some chemotherapeutic agents aimed to decrease ODC expression showed inhibitory effects on cancer cells. In this study, we examined the effect of adenoviral-transduced antisense ODC on prostate cancer cells. An adenovirus carrying antisense ODC (rAd-ODC/Ex3as) was infected to prostate cancer cells PC-3 and LNCap. Expression of ODC and concentration of polyamines in cells were determined by Western blotting and HPLC. MTT (3-(4,5-methylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assay was used to analyze the effect on cell growth. Cell cycle was evaluated by FCM and cellular invasion by Matrigel invasion assay. A nude mouse xenograft model was used to examine tumorigenicity. Expression of ODC in PC-3 and LNCap cells were reduced to 45 and 59%, and three polyamines were also decreased by the rAd-ODC/Ex3as treatment. Consequently, cell growth was substantially inhibited and cell cycle arrested at G1 phase. Matrigel invasion assay showed relatively low invasion. Marked suppression of tumor formation was observed in the xenograft model. This study suggests that rAd-ODC/Ex3as has the antitumor effect on the human prostate cancer cells.

Adenoviridae↗

Potassium channel blocker TEA prevents CA1 hippocampal injury following transient forebrain ischemia in adult rats.

It has been recently reported that potassium channel increases activities in CA1 pyramidal neurons of rat hippocampus following transient forebrain ischemia. To understand the role of the enhanced potassium current in the pathogenesis of neuronal damage after ischemia, we examined the effects of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on the neuronal injury of CA1 region induced by 15 min forebrain ischemia using a four-vessel occlusion model. Adult rats received intracerebroventricular administration of either TEA or 4-AP after ischemia or TEA before ischemia and once each day for 7 days. In the postischemic TEA treated-rats, the neuronal injury in hippocampal CA1 region was significantly less than that of the controls. In contrast, neither preischemic infusion of TEA nor postischemic treatment of 4-AP had any neuroprotective effects. The present study demonstrates that postischemic application of TEA protects hippocampal CA1 pyramidal neurons against ischemic insult, suggesting that potassium channels may play important roles in the pathogenesis of CA1 neuronal death after transient forebrain ischemia.

4-Aminopyridine↗

Development of a novel proteomic approach for the detection of transitional cell carcinoma of the bladder in urine.

Development of noninvasive methods for the diagnosis of transitional cell carcinoma (TCC) of the bladder remains a challenge. A ProteinChip technology (surface enhanced laser desorption/ionization time of flight mass spectrometry) has recently been developed to facilitate protein profiling of biological mixtures. This report describes an exploratory study of this technology as a TCC diagnostic tool. Ninety-four urine samples from patients with TCC, patients with other urogenital diseases, and healthy donors were analyzed. Multiple protein changes were reproducibly detected in the TCC group, including five potential novel TCC biomarkers and seven protein clusters (mass range, 3.3 to 133 kd). One of the TCC biomarkers (3.4 kd) was also detected in bladder cancer cells procured from bladder barbotage and was identified as defensin. The TCC detection rates provided by the individual markers ranged from 43 to 70% and specificities from 70 to 86%. Combination of the protein biomarkers and clusters, increased significantly the sensitivity for detecting TCC to 87% with a specificity of 66%. Interestingly, this combinatorial approach provided sensitivity of 78% for detecting low-grade TCC compared to only 33% of voided urine or bladder-washing cytology. Collectively these results support the potential of this proteomic approach for the development of a highly sensitive urinary TCC diagnostic test.

Adult↗

Risks of smoking in treated and untreated older Chinese patients with isolated systolic hypertension.

OBJECTIVES: To examine the health risks associated with smoking and blood pressure in Chinese hypertensive patients and to compare the benefit of antihypertensive drug treatment with the risk attributable to smoking. METHODS: We used multiple Cox regression to correlate outcome with blood pressure and smoking status in 2284 older (aged > or = 60 years) patients enrolled in the Systolic Hypertension in China (Syst-China) Trial (systolic/diastolic blood pressure > or = 160/< 95 mmHg). RESULTS: Median follow-up was 3.0 years. After adjustment for sex, age, active antihypertensive treatment and various entry characteristics, the relative hazard rates associated with smoking more than 20 cigarettes per day were 2.04 (P = 0.04), 4.66 (P < 0.001) and 4.74 (P = 0.002) for all-cause, noncardiovascular and cancer mortality, respectively. With similar adjustments applied, the relative hazard rates for total (fatal and non-fatal) stroke associated with smoking 10-20 and more than 20 cigarettes per day were 1.78 (P = 0.04) and 2.23 (P = 0.03), respectively. Furthermore, both smoking and systolic blood pressure were associated with higher risk of stroke. Compared with the overall risk in the whole group, treating 1,000 patients for 5 years prevented 40 [95% confidence interval (CI), 5-75] strokes in smokers as well as never smokers. Prognosis in never smokers and past smokers was similar. Quitting smoking had the potential to prevent 51 (95% CI, -21 to 122) strokes in untreated hypertensive patients and to prevent 45 (95% CI, - 14 to 104) additional strokes in treated patients, over and above the effects of antihypertensive treatment. If, in addition to stroke, non-cardiovascular mortality was also accounted for, the estimated absolute benefit of quitting smoking increased to 69 (95% CI, -18 to 155) and 97 (95% CI, 23-171) events in the untreated and the treated group, respectively. CONCLUSIONS: In elderly Chinese patients, smoking was a risk factor for all-cause, non-cardiovascular and cancer mortality, as well as fatal and non-fatal stroke. The potential benefits of antihypertensive treatment and quitting smoking were approximately similar. In our view, these findings are important in terms of public health policies and health economics.

Aged↗

Temperature-sensitive transformation by an Abelson virus mutant encoding an altered SH2 domain.

Abelson murine leukemia virus (Ab-MLV) encodes the v-Abl protein tyrosine kinase and induces transformation of immortalized fibroblast lines and pre-B cells. Temperature-sensitive mutations affecting the kinase domain of the protein have demonstrated that the kinase activity is absolutely required for transformation. Despite this requirement, mutations affecting other regions of v-Abl modulate transformation activity. The SH2 domain and the highly conserved FLVRES motif within it form a phosphotyrosine-binding pocket that is required for interactions between the kinase and cellular substrates. To understand the impact of SH2 alterations on Ab-MLV-mediated transformation, we studied the Ab-MLV mutant P120/R273K. This mutant encodes a v-Abl protein in which the beta B5 arginine at the base of the phosphotyrosine-binding pocket has been replaced by a lysine. Unexpectedly, infection of NIH 3T3 or pre-B cells with P120/R273K revealed a temperature-dependent transformation phenotype. At 34 degrees C, P120/R273K transformed about 10-fold fewer cells than wild-type virus of equivalent titer; at 39.5 degrees C, 300-fold fewer NIH 3T3 cells were transformed and pre-B cells were refractory to transformation. Temperature-dependent transformation was accompanied by decreased phosphorylation of Shc, a protein that interacts with the v-Abl SH2 and links the protein to Ras, and decreased induction of c-Myc expression. These data suggest that alteration of the FLVRES pocket affects the ability of v-Abl to interact with at least some of its substrates in a temperature-dependent fashion and identify a novel type of temperature-sensitive Abelson virus.

3T3 Cells↗

Prognostic significance of serum creatinine and uric acid in older Chinese patients with isolated systolic hypertension.

We examined the relation of serum creatinine and uric acid to mortality and cardiovascular disease in older (aged >/=60 years) Chinese patients with isolated systolic hypertension (systolic/diastolic blood pressure >/=160/<95 mm Hg). We used Cox regression to correlate outcome with baseline serum creatinine and uric acid measured in 1880 and 1873, respectively, of the 2394 patients enrolled in the placebo-controlled Systolic Hypertension in China (Syst-China) TRIAL: Median follow-up was 3 years. In multiple Cox regression analysis with adjustment for gender, age, active treatment, and other significant covariates, serum creatinine was significantly associated with a worse prognosis. The relative hazard rates (95% CIs) associated with a 20-micromol/L increase in serum creatinine for all-cause, cardiovascular, and stroke mortality were 1.16 (1.05 to 1.27, P=0.003), 1.15 (1.01 to 1.31, P=0.03), and 1.37 (1.13 to 1.65, P=0.001), respectively. In a similar analysis, which also accounted for serum creatinine, serum uric acid was also significantly and independently associated with excess mortality of cardiovascular disease and stroke. The relative hazard rates associated with a 50-micromol/L increase of serum uric acid were 1.14 (1.02 to 1.27, P=0.02) for cardiovascular mortality and 1.34 (1.14 to 1.57, P<0.001) for fatal stroke. In conclusion, in older Chinese patients with isolated systolic hypertension, serum creatinine and serum uric acid were predictors of mortality.

Age Factors↗

Effect of long-acting isosorbide-5-mononitrate administration on large artery distensibility in patients with essential hypertension.

To evaluate the clinical efficacy of long-acting nitrates, isosorbide-5-mononitrate (IS-5-MN), on large artery distensibility in patients with essential hypertension. Large arterial distensibility was assessed by automatic noninvasive measurement of the carotid-femoral pulse wave velocity (PWV). Seventeen patients aged 62.53+/-7.94 years (mean+/-SD) with essential hypertension undering long-term antihypertensive therapy were studied in this trial. PWV was measured 2 weeks and 4 weeks after oral administration of IS-5-MN (30 mg once daily) with previous therapy. There was no significant difference in systolic blood pressure, diastolic blood pressure, pulse pressure or heart rate at 2 weeks and 4 weeks after treatment compared with baseline. The carotid-femoral PWV decreased significantly at 2 and 4 weeks after treatment (p<0.05, p< 0.05, respectively). Long-acting nitrates have potential value in improving large arterial distensibility in patients with essential hypertension independent of blood pressure alteration. It might be used as an effectively additive drug in hypertension control.

Administration, Oral↗

[Optimization of synthetic culture condition on lignin biodegradation ability of alkaliphilic ligninolytic bacteria using orthogonal experimental design].

The effects of seven single culture factors on lignin biodegradation ability of alkaliphilic ligninolytic bacteria strain 6 in alkaline liquid medium (pH approximately 10.5) with compounded carbons were optimized using orthogonal experiments. The result showed the seven single culture factors promote the activities of Laccase and MnP and the degradation rate of wheat straw lignin in varying degrees. The synthetic result was analysised. The optimal synthetic condition was static culture (10 days culture period), 37 degrees C, the initial pH10.6, 1 g/L sugar (the starting carbons), wheat straw lignin (the second carbons, wheat straw powder 20 g/L, added into on the fourth day after inoculation), 1.2 g/L NH4NO3 (nitrogen), 0.3% detergent T-80, 70 ml medium/250 ml flask.

Bacteria↗

Relationship between age and effect of early and long-term captopril treatment in patients with acute myocardial infarction.

OBJECTIVE: To analyse the relationship between age and treatment with captopril after acute myocardial infarction (AMI). METHODS: In a randomized trial, 822 patients with a first AMI received conventional medical treatment, including intravenous thrombolytic therapy and oral aspirin or metoprolol, and then were randomly allocated to captopril [dosage from the first 6.25 mg to 25 mg/t.i.d, 209 younger patients (< or = 64 years), 269 elderly patients (65-75 years)] or conventional treatment only (131 younger patients, 213 elderly). Survival in the four groups was calculated with the Kaplan-Meier method. Multivariate analysis was performed to understand the degree that multi-variables (including age) affect survival in patients taking captopril in the hospital or during long term follow-up. RESULTS: The survival of patients who took captopril correlated significantly with age (P < 0.001). The survival of the elderly patients on captopril treatment did increase (P < 0.0001), but not of the younger ones (P > 0.05) during hospitalization. During follow-up, the survival of patients who took captopril correlated insignificantly with age (P > 0.05), but both the elderly and the younger patients have good survival rates (all P < 0.01) and lower cardiac events (all P < 0.01) when they took captopril. CONCLUSIONS: Captopril exerts a weak effect on the younger patients but a beneficial effect on the elderly patients during hospitalization after AMI. However, there is no difference between the younger and the elderly in the prognosis, both having good survival and lower cardiac events when they take captopril long term during follow-up.

Adult↗

[Expression of vascular endothelial growth factor and nm23 as prognostic factors in nasopharyngeal carcinoma].

OBJECTIVE: To evaluate the prognostic significance of vascular endothelial growth factor (VEGF) and nm23 expression for patients with nasopharyngeal carcinoma(NPC). METHODS: From Jan. 1991 to Dec. 1995, 75 NPC patients treated in Department of Radiotherapy & Chemotherapy, Zhongnan Hospital of Wuhan University, with follow-up of more than 4 yrs, were selected to enter this study. Specimens of 75 NPC were studied by immunohistochemical staining for VEGF and nm23. The immunohistochemical data were correlated with development of locoregional failure, distant metastasis and survival. RESULTS: Positive expression of VEGF and negative expression of nm23 were found in 54.7% and 56% of NPC specimens. Positive expression of VEGF and negative expression of nm23 correlated with the development of distant metastasis (P = 0.0181; P = 0.0091) and shorter survival (P = 0.0136; P = 0.0207). No association was observed with locoregional failure. No association was observed between the expression of VEGF and the expression of nm23.Cox proportional hazard model was used to compare the various factors and found the VEGF and nm23 expression were significant prognostic factors for patients with NPC. CONCLUSION: The results of the study show that the VEGF and nm23 expression are significant prognostic factors for patients with NPC and indicate that expression of VEGF and nm23 may be useful in identifying patients who may benefit from systemic chemotherapy or other novel treatment strategies.

Adolescent↗

Enhancement in activities of large conductance calcium-activated potassium channels in CA1 pyramidal neurons of rat hippocampus after transient forebrain ischemia.

It has been reported previously that the neuronal excitability persistently suppresses and the amplitude of fast afterhyperpolarization (fAHP) increases in CA1 pyramidal cells of rat hippocampus following transient forebrain ischemia. To understand the conductance mechanisms underlying these post-ischemic electrophysiological alterations, we compared differences in activities of large conductance Ca(2+)-activated potassium (BK(Ca)) channels in CA1 pyramidal cells acutely dissociated from hippocampus before and after ischemia by using inside-out configuration of patch clamp techniques. (1) The unitary conductance of BK(Ca) channels in post-ischemic neurons (295 pS) was higher than that in control neurons (245 pS) in symmetrical 140/140 mM K(+) in inside-out patch; (2) the membrane depolarization for an e-fold increase in open probability (P(o)) showed no significant differences between two groups while the membrane potential required to produce one-half of the maximum P(o) was more negative after ischemia, indicating no obvious changes in channel voltage dependence; (3) the [Ca(2+)](i) required to half activate BK(Ca) channels was only 1 microM in post-ischemic whereas 2 microM in control neurons, indicating an increase in [Ca(2+)](i) sensitivity after ischemia; and (4) BK(Ca) channels had a longer open time and a shorter closed time after ischemia without significant differences in open frequency as compared to control. The present results indicate that enhanced activity of BK(Ca) channels in CA1 pyramidal neurons after ischemia may partially contribute to the post-ischemic decrease in neuronal excitability and increase in fAHP.

Animals↗

GNB1L, a gene deleted in the critical region for DiGeorge syndrome on 22q11, encodes a G-protein beta-subunit-like polypeptide.

CATCH 22 syndromes, which include DiGeorge syndrome and Velocardiofacial syndrome, are the most common cause of congenital heart disease which involve microdeletion of 22q11. Using a strategy including EST searching, PCR amplification and 5'-RACE, we have cloned a 1487 bp cDNA fragment from human heart cDNA library. The cloned GNB1L cDNA encodes a G-protein beta-subunit-like polypeptide, and the GNB1L gene is located in the critical region for DiGeorge syndrome. A comparison of GNB1L cDNA sequence with corresponding genomic DNA sequence revealed that this gene consists of seven exons and spans an approximately 60 kb genomic region. Northern blot analysis revealed GNB1L is highly expressed in the heart.

Amino Acid Sequence↗

Identification and functional expression of four isoforms of ATPase II, the putative aminophospholipid translocase. Effect of isoform variation on the ATPase activity and phospholipid specificity.

ATPase II, a vanadate-sensitive and phosphatidylserine-dependent Mg(2+)-ATPase, is a member of a subfamily of P-type ATPase and is presumably responsible for aminophospholipid translocation activity in eukaryotic cells. The aminophospholipid translocation activity plays an important physiological role in the maintenance of membrane phospholipid asymmetry that is observed in the plasma membrane as well as the membranes of certain cellular organelles. While the preparations of ATPase II from different sources share common fundamental properties, such as substrate specificity, inhibitor spectrum, and phospholipid dependence, they are divergent in several characteristics. These include specific ATPase activity and phospholipid selectivity. We report here the identification of four isoforms of ATPase II in bovine brain. These isoforms are formed by a combination of two major variations in their primary sequences and show that the structural variation of these isoforms has functional significance in both ATPase activity and phosholipid selectivity. Furthermore, studies with the phosphoenzyme intermediate of ATPase II and its recombinant isoforms revealed that phosphatidylserine is essential for the dephosphorylation of the intermediate. Without phosphatidylserine, ATPase II would be accumulated as phosphoenzyme in the presence of ATP, resulting in the interruption of its catalytic cycle.

Amino Acid Sequence↗

Redox modulation of large conductance calcium-activated potassium channels in CA1 pyramidal neurons from adult rat hippocampus.

Redox regulation of BK(Ca) channels was studied in CA1 pyramidal neurons of adult rat hippocampus by using inside-out configuration of patch clamp. Intracellular application of oxidizing agent 5, 5'-dithio-bis(2-nitrobenzoic acid) (DTNB) markedly increased activity of BK(Ca) channels and this stimulating action persisted even after washout. In contrast, the reducing agent dithiothreitol (DTT) had no apparent effects on channel activity but could reverse the pre-exposure of DTNB-induced enhancement. The increase in channel activity produced by DTNB was due to shortened closed time as well as prolonged open time. The effects exerted by another redox couple glutathione disulphide and its reducing form were similar as DTNB and DTT. The present results indicate that BK(Ca) channels in CA1 pyramidal neurons can be modulated by intracellular redox potential, and that augmentation of BK(Ca) channels by oxidative stress might contribute to the postischemic electrophysiological alterations of CA1 pyramidal neurons.

Animals↗