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Biomedical subjects

K He

Publications and source records attributed to K He.

At least 37 records · Page 2Linked to original sources
PubMed2000

[The role of bcl-2 gene family in taxol-mediated apoptosis in BJAB B cell lymphoma cell line].

OBJECTIVE: To study the apoptosis-inducing effect of taxol on BJAB B cell lymphoma cell line and the role of bcl-2 gene family. METHODS: BJAB cells were treated with taxol and examined for morphologic changes under light and electron microscopes. Flow cytometry assays and DNA gel electrophoresis were used to demonstrate changes in nuclear DNA contents and DNA fragmentations. Changes in bcl-2 gene family at mRNA and protein levels were studied by immunohistochemistry and semi-quantitative RT-PCR technique. RESULTS: Taxol inhibited growth of BJAB cells. The cells initially showed G2/M arrest, followed by apoptosis, in a time and dose dependent manner. The expression of bcl-2 at mRNA and protion level was decreased while that of bcl-xs transcription was increased after taxol treatment. CONCLUSION: Taxol induces apoptosis of BJAB cells. Bcl-2 and bcl-xs are involved in the regulation of taxol-induced apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2000

[The effects of taxol on different types of lymphoma cell lines].

OBJECTIVE: To observe the effects of new anticancer drug taxol on different types of lymphoma cells and to explore the value of its clinical application. METHODS: Inverted microscope, light microscope, electron microscope, FCM and DNA gel electrophoresis were used to observe the effects of taxol on three different types of lymphoma cell lines, including Jurkat (T cell lymphoma), BJAB (B cell lymphoma, EBV negative) and Raji (B cell lymphoma, EBV positive). RESULTS: Taxol can inhibit the growth and induce the apoptosis of all the three cell lines, while different sensitivities and apoptosis extent. Jurkat cells were most sensitive, mainly showing apoptosis; BJAB cells were last sensitive, showing G(2)/M arrest before apoptosis; Raji cells were last sensitive, mainly showing G(2)/M arrest and only part of cells going to apoptosis. CONCLUSION: Taxol is a valuable chemotherapeutic agent for lymphoma. Its sensitivity differed with the types of lymphoma, EBV infection and the extent of induced apoptosis.

Antineoplastic Agents, Phytogenic↗
PubMed2000

[Taxol-induced apoptosis in Jurkat T cell lymphoma cell line and its molecular mechanisms].

OBJECTIVE: To observe whether antimicrotubular drug taxol can induce apoptosis in Jurkat T cell lymphoma cell line and the role of bcl-2 gene family in this process. METHODS: Different concentrations of taxol were used to treat Jurkat cells. Cell morphology was observed under light and electron microscope. Flow cytometry and electrophoresis were used to analyze DNA contents and DNA fragments. bcl-2 gene family proteins and mRNAs were studied by immunohistochemistry and semi-quantitative RT-PCR technique. RESULTS: Taxol could inhibit Jurkat cell growth. Within a certain range of treating time and dose, cells were induced apoptosis with a time and dose related manner. The expressions of bax protein and mRNA were increased and bcl-x(s) mRNA became detectable after taxol treatment. CONCLUSION: Taxol can specifically induce Jurkat cell apoptosis. It might provide a theoretical basis for clinical treatment and a good model for studying apoptotic gene modulation. Bax and bcl-x(s) participate in the taxol induced apoptosis of Jurkat cells.

Antineoplastic Agents, Phytogenic↗
PubMed1999

Maspin plays an important role in mammary gland development.

Maspin is a unique member of the serpin family, which functions as a class II tumor suppressor gene. Despite its known activity against tumor invasion and motility, little is known about maspin's functions in normal mammary gland development. In this paper, we show that maspin does not act as a tPA inhibitor in the mammary gland. However, targeted expression of maspin by the whey acidic protein gene promoter inhibits the development of lobular-alveolar structures during pregnancy and disrupts mammary gland differentiation. Apoptosis was increased in alveolar cells from transgenic mammary glands at midpregnancy. However, the rate of proliferation was increased in early lactating glands to compensate for the retarded development during pregnancy. These findings demonstrate that maspin plays an important role in mammary development and that its effect is stage dependent.

Animals↗
PubMed1999

Synthesis of 5-substituted 2'-deoxycytidine 5'-(alpha-P-borano)triphosphates, their incorporationinto DNA and effects on exonuclease.

Direct PCR sequencing with boronated nucleotides provides an alternative to current PCR sequencing methods. The positions of boranophosphate-modified nucleotides incorporated randomly into DNA during PCR can be revealed directly by exonuclease digestion to give sequencing ladders. Cytosine nucleotides, however, are especially sensitive to exonuclease digestion and provide suboptimal sequencing ladders. Therefore, a series of 5-substituted analogs of 2'-deoxycytidine 5'-(alpha-P-borano)triphosphates (dCTPalphaB) were synthesized with the hope of increasing the nuclease resistance of deoxycytosine residues and thereby enhancing the deoxycytosine band intensities. These dCTP analogs contain a boranophosphate modification at the alpha-phosphate group in 2'-deoxycytidine 5'-triphosphate (dCTP) as well as a 5-methyl, 5-ethyl, 5-bromo or 5-iodo substitution for the 5-hydrogen of cytosine. The two diastereomers of each new dCTP derivative were separated by reverse phase HPLC. The first eluted diastereomer (putatively Rp) of each dCTP analog was a substrate for T7 DNA polymerase (Sequenase) and had an incorporation efficiency similar to normal dCTP and dCTPalphaB, with the 5-iodo-dCTPalphaB analog being the least efficient. Substitution at the C-5 position of cytosine by alkyl groups (ethyl and methyl) markedly enhanced the dCTPalphaB resistance towards exonuclease III (5-Et-dCTPalphaB >5-Me-dCTPalphaB >dCTPalphaB approximately 5-Br-dCTPalphaB >5-I-dCTPalphaB), thereby generating DNA sequences that better define the deoxycytosine positions. The introduction of modified dCTPalphaB should increase the utility of direct DNA sequencing with boronated nucleoside 5'-triphosphates.

Boron Compounds↗
PubMed1999

Protein carbonyl formation and tyrosine nitration as markers of oxidative damage during ischaemia-reperfusion injury to rat sciatic nerve.

We have investigated the role of oxidative damage in peripheral nerve ischaemia-reperfusion injury using a rat sciatic nerve model. After 5 h ischaemia blood flow to the sciatic nerve was restarted and markers of oxidative damage measured after various times of reperfusion. As a marker of protein oxidative damage, protein carbonyl formation was measured using a sensitive enzyme-linked immunosorbent assay. Protein carbonyl content was unaffected by ischaemia alone, but increased by 55% after 12-18 h reperfusion, correlating with the onset of nerve pathology. Pretreatment with the xanthine oxidase inhibitor allopurinol prevented these abnormalities, suggesting that xanthine oxidase activity is proximal to oxidative damage during reperfusion injury. To determine whether formation of the potent oxidant peroxynitrite from nitric oxide and superoxide contributed to ischaemia-reperfusion injury, we measured the accumulation of 3-nitrotyrosine residues in proteins. Only one protein of 49,000 mol. wt contained significant amounts of 3-nitrotyrosine residues which was shown to be glial fibrillary acidic protein, an abundant cytoskeletal protein in Schwann cells. However glial fibrillary acidic protein contained 3-nitrotyrosine residues prior to ischaemia-reperfusion, and the amount of nitrated tyrosine residues in total glial fibrillary acidic protein did not increase significantly during reperfusion, therefore it was not possible to draw conclusions about the role of peroxynitrite in nerve reperfusion injury.

Animals↗
PubMed1999

Trapped to free: a mechanism to spatiotemporal chaos.

We further investigate the crisis-induced transition from temporal chaos (TC) to spatiotemporal chaos (STC) due to collision between the unstable orbit of a carrier saddle steady wave (SSW) and the attractor of its perturbation wave (PW) [Kaifen He, Phys. Rev. Lett. 80, 696 (1998)]. In the present work, the influence of the SSW on its PW is studied in different dimensions. It is found that in our case, as a result of mode-mode couplings only one dimension becomes crucial in the onset of crisis. The state transition of the PW mode phase in this dimension at the crisis is emphasized. Before the crisis, all the PW partial waves are trapped in the SSW state. After the crisis, the PW partial wave in this dimension is free from the trapping of the SSW partial wave; it experiences on-off resonance with the latter, which is responsible for the transition to STC.

Journal Article↗
PubMed1999

The induction of liver microsomal cytochrome P450 by Glycyrrhiza uralensis and glycyrrhetinic acid in mice.

The effect of Glycyrrhiza uralensis Fisch (GRZ) aqueous extract and one of its active principles Glycyrrhetinic acid (GRT) on hepatic cytochrome P450 in mice were investigated. Oral administration of GRZ at 10 g/kg/d or GRT at 50 mg/kg/d for 7 days was found to increase the P450 contents up to 4.6 fold compared with the controls. The activities of aryl hydrocarbon hydroxylase (AHH, 3.1 and 3.3 fold), aminopyrine N-demethylase (ADM, 4.2 and 3.2 folds), and 7-ethoxycumarin O-deethylase (ECOD, 2.8 and 2.5 fold) were also shown to be increased. Western blot analysis showed that the subtypes of P450 isoforms induced selectively by GRZ and GRT included CYP1A1 (1.8 and 1.5 fold over that of the control, respectively), CYP2B1 (both 1.3 fold), and CYP2C11 (3.2 and 3.0 fold). Moreover, significant positive correlation between the P450 content or the isoforms and the corresponding enzyme activities mentioned above was observed.

Animals↗
PubMed1999

Effect of aerobic exercise and ginsenosides on lipid metabolism in diet-induced hyperlipidemia mice.

AIM: To study the effect of aerobic exercise and its combination with Gin (ginsenosides from stems and leaves of ginseng) on lipid metabolism in diet-induced hyperlipidemia mice. METHODS: The mouse hyperlipidemia model was set up by feeding high cholesterol diet. Unloaded swimming was designed to be a manner of aerobic exercise. The effects of aerobic exercise and its combination with Gin on total cholesterol (TC), triglycerides (TG), high density lipoprotein cholesterol (HDL-c) in serum, malondialdehyde (MDA), and superoxide dismutase (SOD) in liver tissue were measured; the thymus and liver were weighed. RESULTS: (1) The mouse hyperlipidemia model was set up successfully: TC and MDA increased (P < 0.05) but HDL-c and SOD decreased (P < 0.05); the liver weight increased and the thymus weight reduced; fatty liver was found; (2) aerobic exercise reduced TC but increased MDA and HDL-c in cholesterol-rich diet mice; the liver weight did not reduce, and fatty liver did not clear up; and (3) when aerobic exercise combined with Gin, TC and TG decreased markedly (P < 0.01), and MDA also decreased (P < 0.05); SOD and HDL-c increased markedly (P < 0.01); the thymus weight increased and the liver weight decreased to normal level; fatty liver cleared up. CONCLUSION: Aerobic exercise could lower serum lipid to some extent but could not satisfactorily regulate lipid metabolism. When combined with Gin, aerobic exercise could better lower serum lipid, regulate lipid metabolism, promote antioxidation, and enhance immune activity.

Animals↗
PubMed1999

[Modulation of multiple drug resistance by nomegestrol acetate and droloxifene in K562/A02].

OBJECTIVE: To study the modulation of mdr1, glutathione S-transferase Pi (GST pi), topoisomerase II alpha (Topo II alpha) and multidrug resistance-associated protein (MRP) by nomegestrol acetate (NOM) and droloxifene (DRO) in K562 cell line. METHODS: Adriamycin (ADM)-resistant K562 (K562/A02) and parental K562 cells were treated with NOM and DRO. The alterations of chemosensitivity to ADM were evaluated by MTT assay, mRNA and protein expression of drug-resistant gene by RT-PCR and immunohistochemistry and accumulation of ADM by flow cytometry (FCM). RESULTS: Both NOM and DRO markedly enhanced chemosensitivity to ADM of K562/A02 cells. After 20, 10 and 5 mumol/L of NOM or DRO treatment, the chemosensitivities to ADM were increased by 17.7, 15.1 and 5.1 times, respectively in NOM treated cells and by 12.3, 12.9 and 4.0 times, respectively in DRO treated cells. In both the drugs treated cells the accumulation of ADM was increased by 2-3 times. The MDR reversal activity of NOM was similar to that of VRP, but the modulatory action of DRO on K562/A02 cells was weaker than that of VRP at concentration of 20 mumol/L. After 20 mumol/L of NOM treatment, chemosensitivity to ADM of K562 cells was markedly enhanced (P < 0.05). Both NOM and DRO were found to significantly inhibit mdr1 and GST pi expression and increase Topo II alpha expression at the mRNA and protein level. This modulation of gene expression was time dependent and the maximal effects appeared 5 days after drugs treatment. Both NOM and DRO failed to modulate the MRP expression. In K562 cells, NOM and DRO also inhibited GST pi expression (P < 0.05). CONCLUSION: Both NOM and DRO could markedly reverse the MDR of K562/A02 cells. The reversal activity of NOM was comparable to that of VRP. Both the drugs could modulate mdr1, GST pi and Topo II alpha expression in a time dependent manner.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

[mRNA and protein expression of apoptosis-regulating gene bcl-x in lymphomas].

OBJECTIVE: To observe mRNA and protein expression of bcl-x and explore the role of bcl-x in the regulation of apoptosis and oncogenesis and their value in differential diagnosis of lymphomas. METHODS: Reverse transcription-polymerase chain reaction (RT-PCR) and citric acid-microwave-ABC immunohistochemistry (ICH) were used to observe mRNA transcription forms and protein distributions of bcl-x in 30 frozen tissues and 109 paraffin embedded tissues (both including reactive hyperplasia and common types of lymphoma). RESULTS: RT-PCR revealed that all 30 frozen cases showed bcl-x transcription, of which 29 had bcl-x1 band and 13 had bcl-xs band. Bcl-x1 band was always stronger than bcl-xs band. IHC found that 97/109 cases had fine positive bcl-x granules in the cytoplasm. In lymphoid reactive hyperplasia, bcl-x exhibited weak immunoactivity in cells located in the germinal centers and interfollicular regions of the nodes but not in the mantle zone lymphocytes which surround germinal centers. In lymphomas, bcl-x immunoactivity was always strong and diffuse. The staining fractions in different types of lymphomas were significantly higher than those in lymphoid reactive hyperplasias (P > 0.05), but no significant difference was found between the positive rate and staining fraction of different types of lymphomas. CONCLUSION: Bcl-x shows active mRNA transcription and high protein expression in lymphomas. The long isoform of bcl-x (bcl-xl) is the predominant expression. The characteristics of bcl-x protein expression may be helpful in differential diagnosis of reactive hyperplasia and lymphoma.

Apoptosis↗
PubMed1999

[Phamacognostical identification of medicinal plants of paederia].

OBJECTIVE: To distinguish accurately the dried medicinal plants of Paederia in Guangxi Province. METHOD: Using regular methods for identification of crude drugs. RESULTS: Obvious distinctions were found among leaf quality, presence of hair characteristics, inflorescence morphology, presence of non-glandular hair and scleroid cells along with their sizes, forms and superficial characteristics. Obvious distinctions were also found among cuticular veins of leaf cuticles, projecting of cells' outer walls, development of metaxylem, shapes and separation of crystal cells and wood fibers under microscope. CONCLUSION: All the above-mentioned characteristics can be used for species identification.

China↗
PubMed1999

Effects of ginsenosides on myocardial reperfusion arrhythmia and lipid superoxidation in high cholesterol diet rats.

To explore the effects of GSL on myocardial reperfusion arrhythmia and lipid superoxidation in high cholesterol diet rats. Hyperlipidemia model was set up with administered high cholesterol emulsion 15 ml/kg to rats orally for 14 days. In GSL group, rats were given GSL i.p. 75 mg/kg simultaneously when administered high cholesterol emulsion. The experiment of myocardial ischemia reperfusion was performed on all rats. The results showed: (1) After administration of high cholesterol emulsion to rats orally for 14 days, hyperlipidemia model was set up successfully, simultaneously treatment with GSL. It lowered serum lipid; (2) In hyperlipidemia state, serum MDA increased (p < 0.01, SOD and NO decreased markedly (p < 0.01 and p < 0.05 respectively) after 2 h of myocardial reperfusion; the rate of reperfusion arrhythmia (RPAr) increased within 10 min of reperfusion, four out of nine rats died of ventricular fibrillation (VF); and (3) GSL decreased MDA, increased SOD and NO after 2 h of myocardial reperfusion. All changes were significant (p < 0.01); the rate of RPAr decreased, no VF occurred and all rats survived. Hyperlipidemia aggravated myocardial ischemia reperfusion injury and increased the incidence of RPAr. The results suggested that GSL reduced myocardial ischemia reperfusion injury and RPAr in high cholesterol diet state through antiperoxidating and inducing the production of NO.

Animals↗
PubMed1999

Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486).

Mifepristone (RU486), an 11beta-substituted nor-steroid containing a 17alpha-1-propynyl group used clinically as an antiprogestin agent for medical abortions, was demonstrated to be a selective mechanism-based inactivator of human cytochrome P-450-3A4 (CYP-3A4). The loss of testosterone 6beta-hydroxylation activity was time- and concentration-dependent as well as requiring metabolism of mifepristone in a purified CYP-3A4 reconstituted system. The inactivation exhibited pseudofirst-order kinetics. The values for KI and kinactivation were 4.7 microM and 0.089 min-1, respectively. The reduced-CO spectrum of CYP-3A4 was decreased by 76%, whereas approximately 81% of the activity was lost following incubation with mifepristone in the reconstituted system in the presence of NADPH. However, the Soret peak of the inactivated CYP-3A4 was slightly increased. High-performance liquid chromatography analysis of the incubation mixture showed that the peak containing the heme dissociated from the inactivated CYP3A4 was almost identical with that seen for the -NADPH control. Covalent binding of [3H]mifepristone to apoCYP3A4 was demonstrated by SDS-PAGE and high-pressure liquid chromatography analyses of the reconstituted system containing CYP-3A4, NADPH-CYP reductase, cytochrome b5 and lipids in the presence of NADPH. The stoichiometry was determined to be approximately 1 mol of mifepristone bound per 1 mol of CYP-3A4 inactivated. Therefore, the mechanism of inactivation of CYP-3A4 by mifepristone involves irreversible modification of the apoprotein at the enzyme active site instead of being the result of heme adduct formation or heme fragmentation. Mifepristone exhibits selectivity for CYP-3A4 as evidenced by the fact that it did not show mechanism-based inactivation of CYPs 1A, 2B, 2D6, and 2E1, although a competitive inhibition of CYP 2B1 and 2D6 was observed.

Abortifacient Agents, Steroidal↗
PubMed1998

Identification of the heme-modified peptides from cumene hydroperoxide-inactivated cytochrome P450 3A4.

Cumene hydroperoxide-mediated (CuOOH-mediated) inactivation of cytochromes P450 (CYPs) results in destruction of their prosthetic heme to reactive fragments that irreversibly bind to the protein. We have attempted to characterize this process structurally, using purified, 14C-heme labeled, recombinant human liver P450 3A4 as the target of CuOOH-mediated inactivation, and a battery of protein characterization approaches [chemical (CNBr) and proteolytic (lysylendopeptidase-C) digestion, HPLC-peptide mapping, microEdman sequencing, and mass spectrometric analyses]. The heme-peptide adducts isolated after CNBr/lysylendopeptidase-C digestion of the CuOOH-inactivated P450 3A4 pertain to two distinct P450 3A4 active site domains. One of the peptides isolated corresponds to the proximal helix L/Cys-region peptide 429-450 domain and the others to the K-region (peptide 359-386 domain). Although the precise residue(s) targeted remain to be identified, we have narrowed down the region of attack to within a 17 amino acid peptide (429-445) stretch of the 55-amino acid proximal helix L/Cys domain. Furthermore, although the exact structures of the heme-modifying fragments and the nature of the adduction remain to be established conclusively, the incremental masses of approximately 302 and 314 Da detected by electrospray mass spectrometric analyses of the heme-modified peptides are consistent with a dipyrrolic heme fragment comprised of either pyrrole ring A-D or B-C, a known soluble product of peroxidative heme degradation, as a modifying species.

Amino Acid Sequence↗
PubMed1998

Inactivation of cytochrome P450 3A4 by bergamottin, a component of grapefruit juice.

Grapefruit juice has been found to significantly increase oral bioavailability of several drugs metabolized by cytochrome P450 3A4 (P450 3A4) through inhibiting the enzymatic activity and decreasing the content of intestinal P450 3A4. HPLC/MS/MS and HPLC/UV analyses of ethyl acetate extracts from grapefruit juice revealed the presence of several furanocoumarins of which bergamottin (BG) is the major one. BG was shown to inactivate P450 3A4 in a reconstituted system consisting of purified P450 3A4, NADPH-cytochrome P450 reductase, cytochrome b5, and phospholipids. Inactivation was time- and concentration-dependent and required metabolism of BG. The loss of catalytic activity exhibited pseudo-first-order kinetics. The values of kinactivation and KI calculated from the inactivation studies were 0.3 min-1 and 7.7 microM, respectively. While approximately 70% of the erythromycin N-demethylation activity was lost during incubation with BG in the reconstituted system, P450 3A4 retained more than 90% of the heme as determined either by UV-visible spectroscopy or by HPLC. However, approximately 50% of the apoP450 in the BG-inactivated P450 3A4 incubation mixture could not be recovered from a reverse-phase HPLC column when compared with the -NADPH control. The mechanism of the inactivation appears to involve modification of the apoP450 in the active site of the enzyme instead of heme adduct formation or heme fragmentation. These results indicate that BG, the primary furanocoumarin extracted from grapefruit juice, is a mechanism-based inactivator of P450 3A4. BG was also found to inhibit the activities of P450s 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 in human liver microsomes.

Beverages↗
PubMed1998

[Detection of CBF beta-MYH11 fusion transcript and inv(16)(p13;q22) in acute myelomonocytic leukemia(M4) by RT-PCR and FISH].

OBJECTIVE: To study the clinical significance of inv(16) and CBF beta-MYH11 fusion gene in the diagnosis and prognosis for M4Eo. METHODS: CBF beta-MYH11 fusion transcripts and inv (16) were analyzed by reverse-transcriptase polymerase chain reaction(RT-PCR) and fluorescence in situ hybridization(FISH), respectively, in acute myelomonocytic leukemia(M4) with or without eosinophilia. RESULTS: In fifteen cases tested, one case of M4Eo and one of 9 M4 without eosinophilia were found to have CBF beta-MYH11 fusion transcript. Follow-up of the M4Eo patient showed residual PCR positivity 2 months after complete remission. CONCLUSION: The data suggest that screening by both RT-PCR and FISH should be performed in all AML-M4 regardless of morphologic features to allow accurate diagnosis and prognosis of M4 patients.

Adolescent↗