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Biomedical subjects

Li Ma

Publications and source records attributed to Li Ma.

At least 73 records · Page 4Linked to original sources
PubMed2005

In vitro procoagulant activity induced in endothelial cells by chemotherapy and antiangiogenic drug combinations: modulation by lower-dose chemotherapy.

One of the emerging problems concerning the use of antiangiogenic drugs, when used in combination with certain chemotherapy regimens, is enhanced rates and severity of adverse clotting events. For as yet unknown reasons, certain drugs and particular combinations can induce an elevated incidence of thromboembolic events in treated cancer patients [e.g., SU5416, a vascular endothelial cell growth factor receptor-2 (VEGFR-2) antagonist, when combined with gemcitabine and cisplatin (CDDP)]. Such results highlight the need to develop assays capturing the essence of enhanced clot formation under such combination treatment and which may have predictive potential as well. Here, we report the possibility of such an assay (i.e., the ratio of tissue factor over tissue factor pathway inhibitor expression or activity in cultured human endothelial cells calculated as a coagulation index). A marked increase in coagulation index was observed after exposure to SU5416 and the CDDP/gemcitabine chemotherapy combination in contrast to either of these treatments used alone. Substitution of SU5416 with any one of ZD6474, SU6668, IMC-1121, a monoclonal antibody to VEGFR-2, or an antibody to VEGF (bevacizumab) did not cause a marked increase in the coagulation index, nor did the combination of SU5416 with 5-fluorouracil and leucovorin. Finally, we noted that reducing the concentrations of gemcitabine and CDDP (i.e., use of "metronomic dosing" in vitro) significantly attenuated the coagulation index increase induced by these drugs, suggesting that use of low-dose chemotherapy regimens might be an approach to consider for reducing the incidence of adverse clotting events associated with chemotherapy alone or in conjunction with antiangiogenic drug combination therapies.

Angiogenesis Inhibitors↗
PubMed2005

Effect of angiotensin converting enzyme inhibitor on the calcium transients and calcium handling proteins in ventricular myocytes from rats with heart failure.

BACKGROUND: Chronic heart failure (CHF) is associated with calcium transients and calcium handling proteins. Angiotensin converting enzyme (ACE) inhibitor has been demonstrated to have beneficial effect on CHF. Yet studies addressed to the relationship between ACE inhibitor and calcium transients in CHF are rare. The aim of this study was to investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transients and calcium handling proteins in ventricular myocytes from rats with experimental heart failure. METHODS: Male Wistar rats were randomized to heart failure group treated with perindopril [CHF-T, 3 mg.kg(-1).d(-1)], heart failure group without treatment (CHF-C) and sham-operated group (PS). Heart failure was induced by abdominal aortic constriction. All groups were further followed up for 12 weeks. Left ventricular myocytes were then isolated. Single cell shortening fraction and [Ca(2+)]i were simultaneously measured by laser scanning confocal microscope under the field stimulation (1.0 Hz). Reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot were performed to evaluate the changes of mRNA and protein of Na(+)-Ca(2+) exchanger (NCX1), sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2) and phospholamban (PLB). RESULTS: The fraction of cell shortening (FS%) and [Ca(2+)]imax (nmol/L) were significantly reduced in group CHF-C compared with group PS (FS%: 7.51 +/- 1.15 vs 13.21 +/- 1.49; [Ca(2+)]i max: 330.85 +/- 50.05 vs 498.16 +/- 14.07; both P < 0.01), and restored at least partially in CHF-T group. In CHF-C group, the left ventricular mRNA of NCX1 and PLB were significantly upregulated in comparing with PS group (RNCX1/beta-Actin: 0.51 +/- 0.12 vs 0.19 +/- 0.06, P < 0.01; RPLB/beta-Actin: 0.26 +/- 0.12 vs 0.20 +/- 0.08, P < 0.05), while SERCA2 mRNA was downregulated (0.48 +/- 0.10 vs 0.80 +/- 0.11, P < 0.01). The mRNA levels of NCX1 and SERCA2 in CHF-T group were between the CHF-C and PS group, and the differences of the latter two groups were significant (all P < 0.05). In CHF-C and CHF-T groups, the protein expression of NCX1 were 1.141 +/- 0.047 and 1.074 +/- 0.081 times of that in PS group respectively (both P < 0.05), and SERCA2 protein levels were 0.803 +/- 0.100 and 0.893 +/- 0.084 times of that in PS group respectively (both P < 0.05). The protein expression of NCX1 and SERCA2 in the CHF-C and CHF-T groups is significantly different (both P < 0.05). CONCLUSION: ACE inhibitor could improve cardiac function of failing heart through directly enhancing the contractility of single cardiomyocyte, and these effects are probably mediated by its roles in preventing the deleterious changes of calcium transients and calcium handling proteins in CHF.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2005

Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis.

Tuberous sclerosis (TSC) is a tumor syndrome caused by mutation in TSC1 or TSC2 genes. TSC tumorigenesis is not always accompanied by loss of heterozygosity (LOH). Recently, extracellular signal-regulated kinase (Erk) has been found activated in TSC lesions lacking TSC1 or TSC2 LOH. Here, we show that Erk may play a critical role in TSC progression through posttranslational inactivation of TSC2. Erk-dependent phosphorylation leads to TSC1-TSC2 dissociation and markedly impairs TSC2 ability to inhibit mTOR signaling, cell proliferation, and oncogenic transformation. Importantly, expression of an Erk nonphosphorylatable TSC2 mutant in TSC2+/- tumor cells where Erk is constitutively activated blocks tumorigenecity in vivo, while wild-type TSC2 is ineffective. Our findings position the Ras/MAPK pathway upstream of the TSC complex and suggest that Erk may modulate mTOR signaling and contribute to disease progression through phosphorylation and inactivation of TSC2.

Amino Acid Sequence↗
PubMed2005

Efficient production, purification, and application of egg yolk antibodies against human HLA-A*0201 heavy chain and light chain (beta2m).

The importance of eggs as a source of specific antibodies is well recognized. Egg yolk contains 8--20mg immunoglobulins (IgY) per milliliter. However, the major problem in separating IgY is to remove the high concentrations of lipids in egg yolk. We first used water dilution method to get the supernatant containing IgY, then purified the antibody by caprylic acid-ammonium sulfate method, and obtained specific antibody with satisfactory purity and activity. By comparison of these several methods, each has its advantages, one can be chosen to purify IgY according to practical need. The purified IgY produced by the immunized chickens can stain the human peripheral blood mononuclear cell effectively when labeled with fluorescent FITC.

Animals↗
PubMed2005

Apoptosis of human gastric cancer SGC-7901 cells induced by mitomycin combined with sulindac.

AIM: To investigate the effects of mitomycin (MMC) combined with sulindac on cell viability, apoptotic induction and expression of apoptosis-related gene Bcl-2 and cyclooxygenase-2 (COX-2) in gastric cancer SGC-7901 cells. METHODS: Human gastric cancer SGC-7901 cells were divided into three treatment groups,namely sulindac treatment group, MMC treatment group and combined sulindac with MMC treatment group. After being treated with drugs, cell viability was examined by MTT assay. Flow cytometry was used to evaluate the cell cycle distribution and apoptotic rates. Morphology of the cells was observed under light microscope and interactive laser microscope. Expression of COX-2 and Bcl-2 was determined by immunocytochemical method. RESULTS: After exposure for 12 h to three kinds of drugs, gastric cancer SGC-7901 cells presented some morphological features of apoptosis, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apoptotic bodies. Growth inhibition was more obvious in combined sulindac with MMC treatment group and sulindac treatment group than in MMC treatment group. The apoptotic rates in co-treated cells and MMC-treated cells 24 h after treatment were 12.0% and 7.2%, respectively. After exposure for 24 h to MMC, the expression of COX-2 and Bcl-2 protein was up-regulated, COX-2 levels were down-regulated but Bcl-2 gene expression was not changed significantly in combined treatment group. CONCLUSION: MMC-induced apoptosis is reduced by up-regulating the expression of COX-2 and Bcl-2 genes. MMC combined with sulindac can suppress the growth of gastric cancer cells through induction of apoptosis mediated by down-regulation of apoptosis-related Bcl-2 and COX-2 gene.

Antibiotics, Antineoplastic↗
PubMed2005

[Screening for congenital hypothyroidism in 106 224 neonates in Hunan Province].

OBJECTIVE: Diagnosing congenital hypothyroidism (CH) early was studied in this paper through neonatal screening to prevent children's mental retardation. METHODS: The first step is mensurating the concentration of thyroid stimulating hormone (TSH) with the method of time-distinguished fluorometry immunoassay. If the result is positive, then it is necessary to mensurate the serum TSH, free triiodothyronine (FT3),free thyroxin (FT4) with chemiluminescence immunoassay (CLIA) and execute clinical diagnosis. RESULTS: There were 68 confirmed congenital hypothyroidism patients among the 106,224 samples from Apr.1997 to Dec.2003 in Hunan province. The positive rate was 1/1,562, which was obviously higher than the national average value (1/3,009). CONCLUSION: First, neonatal screening is the key to prevent mental retardation through early diagnosing and treating CH. Second, the probability of suffering CH is high in Hunan province. Third, the positive rate is relative to the development of science and technology, while the accumulated rate is better to reflect the real incidence of the disease. Fourth, selecting proper critical value will help to prevent missing screening.

China↗
PubMed2005

In vivo effects of Chinese herbal recipe, Danshaohuaxian, on apoptosis and proliferation of hepatic stellate cells in hepatic fibrotic rats.

AIM: To investigate the effects of Danshaohuaxian (DSHX), a Chinese herbal recipe, on the apoptosis and cell cycles of hepatic stellate cells (HSCs) in rat hepatic fibrosis and its possible mechanisms. METHODS: Seventy-six male Wistar rats were randomly divided into normal control group, hepatic fibrosis group, non-DSHX-treated group and DSHX-treated group. Except for the normal control group, rat hepatic fibrotic models were induced by subcutaneous injection of carbon tetrachloride (CCl4), drinking alcohol, giving diet of hyperlipid and hypoprotein for 8 wk. When the hepatic fibrotic models were produced, 12 rats of hepatic fibrosis group (15 rats survived, others died during the 8 wk) were sacrificed to collect blood and livers. HSCs were isolated from the other 3 rats to detect the apoptotic index (AI) and cell cycles by flow cytometry. DSHX was then given to the DSHX-treated group (1.0 g/kg, PO, daily) for 8 wk. At the same time, normal control group and non-DSHX-treated group were given normal saline for 8 wk. At end of the experiment, some rats in these three groups were sacrificed to collect blood and livers, the other rats were used for HSC isolation to detect the apoptotic index (AI) and cell cycles. Then the liver index, serum hyaluronic acid (HA) and alanine aminotransferase (ALT), degree of hepatic fibrosis, urinary excretion of hydroxyproline (Hyp) and expression of collagen types I and III (COL I and III) in these four groups were detected respectively. RESULTS: Compared with the indexes of the hepatic fibrosis group and non-DSHX-treated group, the DSHX-treated group revealed a liver index of (0.0267+/-0.0017 vs 0.0423+/-0.0044, 0.0295+/-0.0019, P<0.05), levels of serum HA (200.78+/-31.71 vs 316.17+/-78.48, 300.86+/-72.73, P<0.05) and ALT (93.13+/-5.79 vs 174.5+/-6.02, 104.75+/-6.54, P<0.01), and stage of hepatic fibrosis (1.30 vs 4.25, 2.60, P<0.01) all reduced. The urinary excretion of Hyp increased (541.09+/-73.39 vs 62.00+/-6.40, 182.44+/-30.83, P<0.01), the COL I and III expression decreased (COL I: 1.07+/-0.96 vs 4.18+/-2.26, 3.22+/-1.44, P<0.01; COL III: 1.09+/-0.58 vs 3.04+/-0.62, 2.23+/-0.58, P<0.01), the HSCs apoptotic index of HSCs (7.81+/-0.47 vs 1.63+/-0.25, 1.78+/-0.4, P<0.05) and the ratio of G0-G1 phase cells increased (94.30+/-1.33 vs 62.27+/-17.96, 50.53+/-2.25, P<0.05). The ratios of S-phase cells (3.11+/-1.27 vs 9.83+/-1.81, 11.87+/-1.9, P<0.05) and G2-M phase cells (2.58+/-0.73 vs 23.26+/-10.95, 13.60+/-1.15, P<0.01) declined. CONCLUSION: DSHX capsule shows certain therapeutic effects on hepatic fibrosis in rats and inhibits abnormal deposition of COL I and III in rat livers by promoting the apoptosis of HSCs and preventing their proliferation.

Alanine Transaminase↗
PubMed2005

Mitosin/CENP-F as a negative regulator of activating transcription factor-4.

Mitosin/CENP-F is a human nuclear matrix protein with multiple leucine zipper motifs. Its accumulation in S-G2 phases and transient kinetochore localization in mitosis suggest a multifunctional protein for cell proliferation. Moreover, its murine and avian orthologs are implicated in myocyte differentiation. Here we report its interaction with activating transcription factor-4 (ATF4), a ubiquitous basic leucine zipper transcription factor important for proliferation, differentiation, and stress response. The C-terminal portion of mitosin between residues 2488 and 3113 bound to ATF4 through two distinct domains, one of which was a leucine zipper motif. Mitosin mutants containing these domains were able to either supershift or disrupt the ATF4-DNA complex. On the other hand, ATF4, but not ATF1-3 or ATF6, interacted with mitosin through a region containing the basic leucine zipper motif. Moreover, overexpression of full-length mitosin repressed the transactivation activity of ATF4 in dual luciferase-based reporter assays, while knocking down mitosin expression manifested the opposite effects. These findings suggest mitosin to be a negative regulator of ATF4 in interphase through direct interaction.

Activating Transcription Factor 4↗
PubMed2005

Imatinib-induced sweet syndrome in a patient with chronic myeloid leukemia.

BACKGROUND: Imatinib mesylate has become one of the main chemotherapeutic agents currently used to treat patients with chronic myeloid leukemia (CML). Although cutaneous reactions to this drug have been documented before, this is the first time that Sweet syndrome has been reported with its use. OBSERVATIONS: We report a case of Sweet syndrome secondary to the administration of imatinib to treat CML. On 2 separate occasions, a 53-year-old African American woman with CML developed neutrophilic dermatosis consistent with Sweet syndrome after chemotherapy with imatinib. CONCLUSION: Greater awareness of the adverse effects of imatinib and the characterization of its cutaneous adverse effects will lead to improved surveillance for and treatment of those adverse effects.

Antineoplastic Agents↗
PubMed2005

Roles of platelets and proteinase-activated receptors in gastric ulcer healing.

Proteinase-activated receptors (PARs) are expressed on the surface of many cells, but those on the platelet have been among the most thoroughly characterized. PARs act as key receptors mediating the proaggregatory and pro-secretory effects of thrombin. In addition to contributing to hemostasis, platelets are increasingly being viewed as important contributors to healing and to tumor growth. This is attributable to the many pro- and anti-angiogenic factors that are stored within platelets, which can be released at the sites of injury and new vessel growth. In this paper, we review the importance of the platelet in gastric ulcer healing, the contribution of platelet-contained angiogenic factors to the healing of gastric ulcers, and the role of PARs in regulating the release of angiogenic factors from platelets. Taken together, our results suggest that PARs, including those expressed on platelets, are a rational therapeutic target for modulating healing processes and tumor growth.

Blood Platelets↗
PubMed2005

Expression, refolding, purification, and bioactivity of recombinant bifunctional protein, hIL-2/GM-CSF.

Interleukin-2 (IL-2) can stimulate T cell proliferation and differentiation when binding to its receptor on T cells. It produces a marked effect by enhancing the cytotoxicity of CD8+ T cells and natural killer cells. Granulocyte-macrophage colony stimulating factor (GM-CSF) is associated with many cells proliferation, such as dendritic cells, macrophages. Here, we report the construction, expression and purification of a bifunctional protein, hIL-2/GM-CSF, which may facilitate interaction between T cells and the antigen presentation cells and improve the efficiency of antigen presentation. We found that the use of chemicals and temperature shift is a peculiar system for induction of the Escherichia coli transformed with an IPTG-regulated hIL-2/GM-CSF expression vector in this research. After renaturation, anion exchange chromatography, metal affinity chromatography, and strict endotoxin-free cation exchange chromatography, the fusion protein devoid of endotoxin showed high purity. Cell proliferation experiments proved that this bifunctional protein retains both hIL-2 and GM-CSF biological activities. These results will facilitate the numerous subsequent studies on this bifunctional molecule.

Blotting, Western↗
PubMed2005

Histamine ameliorates spatial memory deficits induced by MK-801 infusion into ventral hippocampus as evaluated by radial maze task in rats.

AIM: To investigate the role of histamine in memory deficits induced by MK-801 infusion into the ventral hippocampus in rats. METHODS: An 8-arm radial maze (4 arms baited) was used to assess spatial memory. RESULTS: Bilateral ventral intrahippocampal (ih) infusion of MK-801 (0.3 microg/site), an N-methyl-D-aspartate (NMDA) antagonist, impaired the retrieval process in both working memory and reference memory. Intrahippocampal injection of histamine (25 or 50 ng/site) or intraperitoneal (ip) injection of histidine (25, 50 or 100 mg/kg) markedly ameliorated the spatial memory deficits induced by MK-801. Both the histamine H1 antagonist pyrilamine (0.5 or 1.0 microg/site, ih) and the H2 antagonist cimetidine (2.5 microg/site, ih) abolished the ameliorating effect of histidine (100 mg/kg, ip) on reference memory deficits, but not that on working memory deficits induced by MK-801. CONCLUSION: The results indicate that histamine in the ventral hippocampus can ameliorate MK-801-induced spatial memory deficits, and that histamine's effect on reference memory is mediated by postsynaptic histamine H1 and H2 receptors.

Animals↗
PubMed2005

[Investigation of single nucleotide polymorphisms in the promoter region of mannan-binding lectin gene in Bais, Uars and Lahus ethnics from China].

AIM: To investigate the single nucleotide polymorphisms(SNP) in the promoter region of mannan-binding lectin (MBL) gene in Bais, Uars and Lahus ethnics. METHODS: 71, 73 and 94 blood samples were obtained from Bais, Uars and Lahus subjects, respectively from Yunnan province. Genomic DNA was isolated from leucocytes. Polymorphism alleles -550(G/C, named H/L alleles), -220(G/C, X/Y alleles) and +4(C/T, P/Q alleles) in the promoter region of MBL gene were detected by sequence-specific primer-PCR and molecular beacon real-time PCR, and the frequencies of haplotypes and genotypes were analyzed. RESULTS: The frequencies of genotypes in Bais, Uars and Lahus ethnics were as follows: LYP/LYP 4(5.6%), 4(5.5%)and 2(2.1%); HYP/LYQ 6(8.5%), 11(15.1%) and 12(12.8%); LYP/LYQ 21(29.6%), 14(19.2%) and 51(54.3%); LXP/LXP 1(1.4%), 2(2.7%)and 0,LYQ/LYQ 10(14.1%); 14(19.2%), 7(7.4%), LXP/LYQ 10(14.1%), 13(17.8%) and 15(16.0%); HYP/LYP 4(5.6%), 3(4.1%) and 4(4.3%); HYP/LXP 3(4.2%), 1(1.4%) and 0; HYP/HYP 12(16.9%), 11(15.1%) and 3(3.2%). CONCLUSION: The distribution of alleles L/H is statistically different among Uars, Bais and Larhus(P<0.01), while X/Y and P/Q are not statistically significant(P>0.05). All studied haplotypes and genotypes are statistically different among the 3 ethnics(P<0.01). Genotypes LYP/LYQ and LXP/LYQ are common in all the 3 ethnics.

Asian People↗
PubMed2005

[High cell density fed-batch culture of E.coli expressing rhVEGF121].

OBJECTIVE: To investigate the optimal high cell density fermentation conditions of recombinant E.coli BL21/pET- 24a/hVEGF(121) expressing recombinant human vascular endothelial growth factor (rhVEGF(121)). METHODS: The effects of the composition of the fermentation medium, induction time and fed-batch carbon sources on the expression level of rhVEGF(121) and cell output were analyzed. RESULTS AND CONCLUSION: When cultured in modified M9 medium and induced for 4 h in the presence of 0.5 mmol/L IPTG at 37 degrees celsius; with glycerol as the carbon sources by continuous fed-batch mode, the recombinant E.coli expressed rhVEGF(121) at the level up to 23% of the total proteins and the yield reached 68 g/L. The optimized fermentation condition for recombinant E.coli enables high expression level of rhVEGF(121).

Escherichia coli↗
PubMed2005

[Study on the role of angiogenesis and related factors in leukemias].

OBJECTIVE: To observe the bone marrow angiogenesis in leukemia and evaluate the expression and role of endostatin (ES), vascular endothelial growth factor (VEGF) and its receptor (VEGFR) in leukemia patients. METHODS: Bone marrow angiogenesis was assayed by vWF immunohistochemical method. The ES and VEGF concentrations in plasma were detected by ELISA. The expression of VEGFR in leukemia cells was determined by flow cytometry (FCM). RESULTS: The bone marrow microvessel density (MVD) in 26 cases of acute leukemia (AL) [(20.78 +/- 7.75)/high-power field (HP)] and 5 chronic myelogenous leukemia (CML) [(28.67 +/- 7.32)/HP] at newly diagnosed stage was significantly higher than that in the control group [(9.29 +/- 3.53)/HP, P < 0.01]. The bone marrow MVD in the complete remission (CR) groups, (11.33 +/- 5.66)/HP for AL and (17.00 +/- 8.04)/HP for CML, was significantly lower than that of newly diagnosed groups (P < 0.05 and < 0.01). No significant difference was found between the remission groups and the control group (P > 0.05). The plasma ES and VEGF concentrations of newly diagnosed AL and CML groups were significantly higher than those of the control group (P < 0.05). The levels of plasma ES and VEGF in AL CR group and plasma ES in CML CR group decreased to levels comparable to normal values (P > 0.05), but the plasma VEGF in CML CR group was still higher than that in control (P < 0.01). AL bone marrow mononuclear cells had higher expression of VEGFR at various levels whereas CML and control samples had lower levels of VEGFR. CONCLUSIONS: Leukemia patients at newly diagnosed stage had remarkable angiogenesis in bone marrow and elevated plasma ES and VEGF concentrations. VEGFR was expressed at different levels in AL cells.

Acute Disease↗
PubMed2005

[Biologic properties of an anti-human ovarian carcinoma/anti-human CD3 single chain bispecific antibody].

BACKGROUND & OBJECTIVE: Previous routine therapies can' t improve the survival rate of ovarian carcinoma patients. Experimental and pre-clinical data showed that bispecific antibodies could efficiently induce antitumor effect of cytotoxic cells. This study was to investigate the biologic properties of an anti-human ovarian carcinoma/anti-human CD3 single chain bispecific antibody (BHL-I) in vitro, and provide reference for pre-clinical experiment and its application. METHODS: Peripheral blood lymphocytes (PBLs), isolated from peripheral blood of healthy donors, were treated with BHL-I. The conjugation between PBLs and target ovarian carcinoma SKOV3 cells was observed under reverse microscope; the proliferation of peripheral blood mononuclear cells (PBMCs) and cytotoxicity of PBLs to SKOV3 cells were detected by MTT assay; the concentrations of human interferon-gamma (hIFN-gamma) and human tumor necrosis factor-alpha (hTNF-alpha), secreted by PBLs in the process of killing target cells, were detected by ELISA. RESULTS: The rosette (PBL-SKOV3) formation rate was significantly higher in BHL-I group than in control group (15.7% vs. 11.1%, P<0.01). BHL-I significantly enhanced the proliferation of PBLs and cytotoxicity of PBLs to SKOV3 cells in the presence of relative antigen (P<0.01); the cytotoxic rate was positively correlated with the rosette formation rate (r=0.946); the concentrations of hIFN-gamma and hTNF-alpha were significantly increased (P<0.01). CONCLUSION: BHL-I could mediate conjugation between PBLs and SKOV3 cells, and activate the cytotoxicity of PBLs which may relate with up-regulation of hIFN-gamma and hTNF-alpha.

Antibodies, Bispecific↗