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J Ding

Publications and source records attributed to J Ding.

At least 145 records · Page 8Linked to original sources
PubMed1999

In vitro cytotoxicity of salvicine, a novel diterpenoid quinone.

AIM: To study the in vitro cytotoxicity of 4,5-seco-5,10-friedo-abieta-3,4-dihydroxy-5(10),6,8,13-tetraene-11, 12-dione (salvicine), a novel diterpenoid quinone compound on human tumor cell lines and its effect on cell cycle progression. METHODS: Growth inhibition of human tumor cells was measured by microculture tetrazolium assay (MTT). Cell cycle was analyzed by flow cytometry. RESULTS: Exposing tumor cell lines tested to salvicine for 72 h, in comparison with reference drugs vincristine (VCR) and etoposide (VP-16), salvicine was as cytotoxic as VP-16 and weaker than VCR in 3 leukemia cell lines. For 12 solid tumor cell lines, salvicine exhibited cytotoxic activities and was over 5.41- and 4.15-fold stronger than VCR and VP-16, respectively. Salvicine presented better activities especially against gastric and lung carcinoma cell lines. Exposing K562 leukemia cells to 9 graded concentrations of salvicine (from 0.39 to 100 mumol.L-1) for 24 h and to salvicine 10 mumol.L-1 for 7 different periods (from 1 to 48 h), the growth inhibition of cells was enhanced along with increased concentration or prolonged exposure. Cell cycle analysis demonstrated that salvicine arrested K562 cells in G1 phase and this effect was also heightened with increased concentration or extended exposure. CONCLUSION: Salvicine exhibited potent cytotoxic activities against various human tumor cell lines, and blocked K562 leukemia cells in G1 phase of cell cycle.

Antineoplastic Agents, Phytogenic↗
PubMed1999

[Study on seroprevalence of Helicobacter pylori infection among upper digestive tract cancer patients and their kindreds].

OBJECTIVE: In order to analyse the association between Hp infection and the risk of upper-digestive tract cancer. METHODS: In Huaian and Pizhou cities, Jiangsu province, Hp IgG quantitative-enzyme-immunoassay methods was used to identify IgG to H.pylori in the serum of 312 cases of upper-digestive tract cancer patients and their kindreds. RESULTS: (1) The level of IgG to H. pylori and the IgG positive rate (50.0%) in gastric cancer patients were both higher than that of cardia and esophageal cancer patients (P > 0.05, chi 2 test) but no significant differences were observed between cardia and esophageal cancer patients, 3 types of cancer patients and their kindreds; (2) the overall positive rates of both patients and kindreds in gastric cancer families (27.1%) were significantly higher than that of cardia or esophageal cancer families (P < 0.05) but no significant differences were observed between cardia and esophageal groups. CONCLUSION: H.pylori infection was not thought to be correlated with the development of gastric cancer, although higher clustering of Hp infection in families afflicted with gastric cancer was noticed.

Adult↗
PubMed1999

[The relation between placental pathologic changes and serum nitric oxide levels of maternal and umbilical blood in intrauterine growth retardation].

OBJECTIVE: To study the relation between placental pathologic changes and levels of maternal and umbilical serum nitric oxide (NO) in intrauterine growth retardation (IUGR). METHODS: 38 patients with IUGR (IUGR group) and 30 healthy pregnant women in their late trimester (control group) were studied from Nov. 1997 to Oct. 1998. The placenta and the appendages of fetus were studied after delivery. The concentration of serum NO were determined with cortas' method. RESULTS: Placental pathological changes were found in 26 cases of IUGR group (68.42%), and the main pathological changes were growth retardation of villi and villositis. In the control group, 5 out of 30 cases had placental pathological findings (16.67%). There was statistically significant difference between the 2 groups (P < 0.01). In IUGR group, the maternal and umbilical NO concentration in the 26 cases with placental pathological changes decreased significantly when compared with that in 12 cases without obvious pathological findings of placenta (P < 0.05, P < 0.05); NO levels of umbilical cord were higher than that of maternal serum in both groups(P < 0.01, P < 0.05); There was correlation about serum NO concentration between mother and her fetus in both groups (r = 0.5475, r = 0.8506); but umbilical serum NO level was not related to the weight of the newborn (r = 0.2838). CONCLUSION: The obvious placental pathologic changes occurred in patient with IUGR caused noticeably lower NO levels in maternal and umbilical serum.

Adult↗
PubMed1999

[A study on the mechanism of the resistance of Shigellae to fluoroquinolones].

OBJECTIVE: To study the mechanism of the resistance of Shigellae to fluoroquinolones. METHODS: A total of 157 clinical isolates were collected. Antibiotic susceptibility testing, reserpine reverse reaction and plasmid conjugation experiment were performed. Accumulation of norfloxacin by shigellae was determined. The N-terminal coding region of gyrA gene was amplified by polymerase chain reaction (PCR), cloned and sequenced in eight fluoroquinolone-resistant isolates and one fluoroquinolone-sensitive isolate as well as in Shigella 51573 (the standard strain). RESULTS: The positive rate of norfloxacin-resistant isolates was 51.2% in the R plasmid conjugation experiment. R plasmid could not mediate resistance to fluoroquinolones. Reserpine could not decrease the minimum inhibition concentration of fluoroquinolones to Shigellae. Norfloxacin uptake by fluoroquinolone-resistant isolates was the same as that by the sensitive one. DNA sequence analysis of gyrA gene from fluoroquinolone-resistant isolates revealed five point mutations that resulted in amino acid change: Gly-81-->Ser, Ser-83-->Leu, Asp-87-->Asn, Asp-87-->Gly, Met-92-->Lys. CONCLUSION: The mutations of gyrA gene were implicated in the resistance of Shigellae to fluoroquinolones.

Anti-Infective Agents↗
PubMed1999

[Advances in the study of mechanisms of the tumor angiogenesis inhibitors].

Tumor angiogenesis inhibitor is the drugs which can destroy or inhibit neovascularization, and block the growth and metastasis of cancer. For clinical applications it may be useful to divide the antiangiogenic drugs into two categories: class 1(specific inhibitors) and class 2 (non-specific inhibitors). This review intends to provide the recent progress of the mechanisms of antiangiogenic drugs (1) Regulation of angiogenesis growth factors; (2) Inhibition of basement membrane degradation; (3) Mediating signal transduction pathway; (4) Effect of cell cycle; (5) Regulation of tumor-related gene.

Angiogenesis Inhibitors↗
PubMed1999

[Studies on allozyme of Gammatricula].

AIM: To furnish molecular genetic evidences for taxonomy of Gammatricula. METHODS: A total of 24 enzymes of 6 populations of Gammatricula songi and 1 population of Gammatricula chinensis collected from Kaihua County and Chunan County of Zhejiang Province were studied using horizontal starch gel electrophoresis. RESULTS: 29 loci were found. The percentages of polymorphic loci of G. songi populations were 6.9%-13.8%. All loci of G. chinensis were monomorphic. The Nei's distance among G. songi populations did not exceed 0.12. The Nei's distance between G. songi and G. chinensis was 0.73. CONCLUSION: The allozyme variations of inter-G. songi are limited, but the allozyme variation between G. songi and G. chinensis is significant.

Alleles↗
PubMed1999

[Construction and in vivo expression of the recombinant adenovirus containing human pro-UK cDNA].

OBJECTIVE: To construct the recombinant adenovirus which contained human pro-UK cDNA and to provide experimental basis for clinical gene therapy. METHODS: The recombinant plasmid pCA14-pro-UK and the plasmid pJM17 were cotransfected into cultured 293 cells and the replication-deficient adenovirus were harvested, identified, propagated and titered. The recombinant virus were then transferred into balloon-injured femoral arteries of rabbits and the pro-UK expression was detected by immunohistochemistry and Western Blot. RESULTS: PCR amplification and in vitro transfection of A549 cells confirmed that pro-UK had been inserted into adenovirus genome correctly, and immunohistochemistry and Western blot analysis showed that pro-UK expressed evidently in the balloon-injured sites of the rabbit femoral arteries. CONCLUSIONS: The recombinant adenovirus that constructed could express pro-UK cDNA in vivo successfully.

Adenoviridae↗
PubMed1999

Peripheral tissue distribution of orphanin FQ precusor mRNA in stroke-prone spontaneously hypertensive rats.

The heptadecapeptide orphanin FQ (OFQ) is a recently discovered neuropeptide that exhibits structural features reminiscent of the opioid peptides and that is an endogenous ligant to a G protein-coupled receptor sequentially related to the opioid receptors. OFQ was originally isolated from brain, but the presence of OFQ in peripheral tissues, especially in cardiovascular system, has not been clarified. The present study was designed to investigate the peripheral tissue distribution of OFQ precusor mRNA in stroke-prone spontaneously hypertensive rats (SHRSP) and compare the difference of OFQ precusor mRNA expression in aorta or cultured vascular smooth muscle cells (VSMCs) between SHRSP and wistar-Kyoto normotensive (WKY) rats. By using quantitative reverse transcription-polymerase chain reaction (RT-PCR), OFQ precusor mRNA was detected in aorta and ovary at high levels comparable with the amounts found in brain. Moderate expression was found in testis, while a little OFQ precusor mRNA could be detected in atrium. All other peripheral tissues examined from SHRSP, including ventricle, liver, lung and kidney, showed no expression of OFQ precusor mRNA. In the vascular system, OFQ precusor mRNA was expressed in aorta, pulmonary artery, renal artery and vein at high levels comparable with the amounts found in brain. We also found that OFQ precusor mRNA levels were much higher in aorta or cultured VSMCs from SHRSP than those from WKY rats. In conclusion, the present study has shown that OFQ precusor mRNA is present in some peripheral tissues, especially in cardiovascular and reproductive system, suggesting that OFQ possibly involves in the regulation of cardiovascular and reproductive functions.

Animals↗
PubMed1998

Structure and functional implications of the polymerase active site region in a complex of HIV-1 RT with a double-stranded DNA template-primer and an antibody Fab fragment at 2.8 A resolution.

The structure of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) complexed with a 19-mer/18-mer double-stranded DNA template-primer (dsDNA) and the Fab fragment of monoclonal antibody 28 (Fab28) has been refined at 2.8 A resolution. The structures of the polymerase active site and neighboring regions are described in detail and a number of novel insights into mechanisms of polymerase catalysis and drug inhibition are presented. The three catalytically essential amino acid residues (Asp110, Asp185, and Asp186) are located close to the 3' terminus of the primer strand. Observation of a hydrogen bond between the 3'-OH of the primer terminus and the side-chain of Asp185 suggests that the carboxylate of Asp185 could act as a general base in initiating the nucleophilic attack during polymerization. Nearly all of the close protein-DNA interactions involve atoms of the sugar-phosphate backbone of the nucleic acid. However, the phenoxyl side-chain of Tyr183, which is part of the conserved YMDD motif, has hydrogen-bonding interactions with nucleotide bases of the second duplex base-pair and is predicted to have at least one hydrogen bond with all Watson-Crick base-pairs at this position. Comparison of the structure of the active site region in the HIV-1 RT/dsDNA complex with all other HIV-1 RT structures suggests that template-primer binding is accompanied by significant conformational changes of the YMDD motif that may be relevant for mechanisms of both polymerization and inhibition by non-nucleoside inhibitors. Interactions of the "primer grip" (the beta12-beta13 hairpin) with the 3' terminus of the primer strand primarily involve the main-chain atoms of Met230 and Gly231 and the primer terminal phosphate. Alternative positions of the primer grip observed in different HIV-1 RT structures may be related to conformational changes that normally occur during DNA polymerization and translocation. In the vicinity of the polymerase active site, there are a number of aromatic residues that are involved in energetically favorable pi-pi interactions and may be involved in the transitions between different stages of the catalytic process. The protein structural elements primarily responsible for precise positioning of the template-primer (including the primer grip, template grip, and helices alphaH and alphaI of the p66 thumb) can be thought of functioning as a "translocation track" that guides the relative movement of nucleic acid and protein during polymerization.

Amino Acid Sequence↗
PubMed1998

Structures of Tyr188Leu mutant and wild-type HIV-1 reverse transcriptase complexed with the non-nucleoside inhibitor HBY 097: inhibitor flexibility is a useful design feature for reducing drug resistance.

The second generation Hoechst-Bayer non-nucleoside inhibitor, HBY 097 (S-4-isopropoxycarbonyl-6-methoxy-3-(methylthiomethyl)-3, 4-dihydroqui noxalin-2(1H)-thione), is an extremely potent inhibitor of HIV-1 reverse transcriptase (RT) and of HIV-1 infection in cell culture. HBY 097 selects for unusual drug-resistance mutations in HIV-1 RT (e.g. Gly190Glu) when compared with other non-nucleoside RT inhibitors (NNRTIs), such as nevirapine, alpha-APA and TIBO. We have determined the structure of HBY 097 complexed with wild-type HIV-1 RT at 3.1 A resolution. The HIV-1 RT/HBY 097 structure reveals an overall inhibitor geometry and binding mode differing significantly from RT/NNRTI structures reported earlier, in that HBY 097 does not adopt the usual butterfly-like shape. We have determined the structure of the Tyr188Leu HIV-1 RT drug-resistant mutant in complex with HBY 097 at 3.3 A resolution. HBY 097 binds to the mutant RT in a manner similar to that seen in the wild-type RT/HBY 097 complex, although there are some repositioning and conformational alterations of the inhibitor. Conformational changes of the structural elements forming the inhibitor-binding pocket, including the orientation of some side-chains, are observed. Reduction in the size of the 188 side-chain and repositioning of the Phe227 side-chain increases the volume of the binding cavity in the Tyr188Leu HIV-1 RT/HBY 097 complex. Loss of important protein-inhibitor interactions may account for the reduced potency of HBY 097 against the Tyr188Leu HIV-1 RT mutant. The loss of binding energy may be partially offset by additional contacts resulting from conformational changes of the inhibitor and nearby amino acid residues. This would suggest that inhibitor flexibility can help to minimize drug resistance.

Antiviral Agents↗
PubMed1998

Cripto is required for correct orientation of the anterior-posterior axis in the mouse embryo.

The anterior-posterior axis of the mouse embryo is established by two distinct organizing centres in the anterior visceral endoderm and the distal primitive streak. These organizers induce and pattern the head and trunk respectively, and have been proposed to be localized through coordinate cell movements that rotate a pre-existing proximal-distal axis. Here we show that correct localization of both head- and trunk-organizing centres requires Cripto, a putative signalling molecule that is a member of the EGF-CFC gene family. Before gastrulation, Cripto is asymmetrically expressed in a proximal-distal gradient in the epiblast, and subsequently is expressed in the primitive streak and newly formed embryonic mesoderm. A Cripto null mutation generated by targeted gene disruption results in homozygous Cripto-/- embryos that mostly consist of anterior neuroectoderm and lack posterior structures, thus resembling a head without a trunk. Notably, markers of the head organizer are located at the distal end of the embryo, whereas markers of the primitive streak are absent or localized to the proximal side. Our results indicate that Cripto signalling is essential for the conversion of a proximal-distal asymmetry into an orthogonal anterior-posterior axis.

Animals↗
PubMed1998

Exposure to breast milk in infancy and adult breast cancer risk.

BACKGROUND: There is considerable interest in the possibility of an infectious etiology for human breast cancer. Although studies have shown that certain strains of mice transmit mammary tumor virus via breast milk, few epidemiologic studies have addressed this topic in humans. METHODS: We evaluated the relationship between having been breast-fed as an infant and breast cancer risk among 8299 women who participated in a population-based, case-control study of breast cancer in women aged 50 years or more. Case women were identified through cancer registries in three states (Massachusetts, New Hampshire, and Wisconsin); control women were identified through statewide driver's license lists (age <65 years) or Medicare lists (ages 65-79 years). Information on epidemiologic risk factors was obtained through telephone interview. We used multiple logistic regression to assess having been breast-fed and maternal history of breast cancer in relation to breast cancer occurrence both in premenopausal women (205 case women; 220 control women) and in postmenopausal women (3803 case women; 4071 control women). RESULTS: We found no evidence that having been breast-fed increased breast cancer risk in either premenopausal women (odds ratio [OR] = 0.65; 95% confidence interval [CI] = 0.41-1.04) or postmenopausal women (OR = 0.95; 95% CI = 0.85-1.07). In addition, breast cancer risk was not increased by having been breast-fed by a mother who later developed breast cancer. CONCLUSION: Our results do not support the hypothesis that a transmissible agent in breast milk increases breast cancer risk. Because premenopausal women were not well represented in our study population, our findings with regard to this group may not be generalizable and should be viewed with caution.

Breast Feeding↗
PubMed1998

A deficiency in Syk enhances ceramide-induced apoptosis in DT40 lymphoma B cells.

Syk deficiency significantly enhanced ceramide-induced apoptosis. Ectopic expression of wild-type or kinase-inactive Syk rendered Syk-negative cells resistant to ceramide-induced apoptosis. Furthermore, ceramide could not activate Syk, indicating that Syk protected DT40 cells from ceramide-induced apoptosis, via a mechanism independent of its activity. In addition, a deficiency in Lyn also resulted in the cells becoming susceptible to ceramide-induced apoptosis. However, no difference of Ara-C-induced apoptosis between wild-type and mutant cells was observed. c-Jun N-terminal kinases appeared not to be important in mediating the enhanced apoptosis, as they were still activated in mutant cells following ceramide treatment.

Apoptosis↗
PubMed1998

Antibodies directed against ZAP-70 cross-react with a 66 kDa tyrosine kinase in the rat brain.

ZAP-70 is another member of Syk family tyrosine kinases which plays an essential role in growth, differentiation, and function of T lymphocytes. In this study, we report the specific expression of a 66 kDa tyrosine kinase that is specifically cross-reacted with anti-ZAP-70 antibodies in the developing neurons. By immunoblot and immunoprecipitation assay using various anti-ZAP-70 antibodies, a 66 kDa tyrosine kinase was detected in lysates from rat brain. During the development of rat brain, expression levels of this 66 kDa tyrosine kinase were highest around 3 weeks after birth and decreased thereafter in the adult. In addition, immunoblot analysis demonstrated that this 66 kDa tyrosine kinase was expressed almost solely in the nervous system. These results suggest that this ZAP-70-related tyrosine kinase may play an important role in growth and differentiation in the developing neurons. Our observations will provide the clue to approach the regulatory system common to neurogenesis and immune response.

Age Factors↗
PubMed1998

Separation and identification of positively charged and neutral nucleoside adducts by capillary electrochromatography-microelectrospray mass spectrometry.

Capillary electrochromatography (CEC) is shown to be capable of separating mixtures containing both positively charged and neutral styrene oxide-adenosine adducts. In a study of the mechanism of deamination of positively charged 1-(2-hydroxy-1-phenylethyl) adenosine using 18O-labeled water, possible contamination of the chromatographically purified deamination product, 1-(2-hydroxy-1-phenylethyl) inosine, with the positively charged 1-(2-hydroxy-1-phenylethyl) adenosine was observed. Because the deamination product and the presumed contamination have the same molecular weights and similar structures, CEC-microelectrospray mass spectrometry (CEC-microESI/MS) was used to confirm the presence and identity of the suspected impurity. A trace amount of the positively charged 1-(2-hydroxy-1-phenylethyl) adenosine, which could not be observed by either HPLC-UV or CEC-UV, was detected by CEC-microESI/MS. This discriminatory ability of CEC-microESI/MS is attributed to the fact that positive ion mode ESI-MS is a more sensitive detector for a positively charged compound than a UV detector, and that the combination of electroosmotic and electrophoretic flows and hydrophobic interactions with the stationary phase contributes to the separation of the positively charged compound. As a result, the positively charged compound was observed to elute much earlier and with much sharper peaks than the neutral compounds for which electroosmotic flow is the only "pumping" force for the solvent.

Chromatography↗
PubMed1998

Role of nitric oxide in vascular hyper-responsiveness to norepinephrine in hypertensive Dahl rats.

OBJECTIVE: To determine whether the abnormal vascular responses observed in salt-sensitive hypertension are caused by an impairment in vascular nitric oxide function. DESIGN: Isometric tension was measured in aortic rings isolated from Dahl salt-sensitive and salt-resistant rats fed a regular-salt (0.4% NaCl) or a high-salt (8% NaCl) diet, with and without inhibition of endogenous nitric oxide synthesis. METHODS AND RESULTS: Systolic arterial pressure, measured weekly by the tail-cuff method, increased markedly in DS rats with a high-salt diet but did not increase in the other groups. In aortic rings, norepinephrine evoked dose-dependent contractions which were significantly increased in rings from DS rats with a high-salt diet Pretreatment with Nomega-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increased the norepinephrine-induced contraction in all groups and abolished differences in contractile responses between high-salt DS rats and the other groups. Acetylcholine induced endothelium-dependent relaxation, which was significantly depressed in high-salt DS rats. L-NAME attenuated the acetylcholine-induced relaxation in all groups and abolished the difference in relaxation response between high-salt DS rats and the other groups. Sodium nitroprusside-induced relaxation was significantly depressed in high-salt DS rats. CONCLUSIONS: Vascular hypercontractile responses to norepinephrine in DS hypertensive rats can, in part, be explained by an impairment in endothelial nitric oxide production.

Acetylcholine↗
PubMed1998

Two-step, predictive, isometric force model tested on data from human and rat muscles.

Functional electrical stimulation can assist paralyzed individuals to perform functional movements, but muscle fatigue is a major limitation to its practical use. An accurate and predictive mathematical model can facilitate the design of stimulation patterns that optimize aspects of the force transient while minimizing fatigue. Solution nonuniqueness, a major shortcoming in previous work, was overcome with a simpler model. The model was tested on data collected during isometric contractions of rat gastrocnemius muscles and human quadriceps femoris muscles under various physiological conditions. For each condition tested, parameter values were identified using the force response to one or two stimulation trains. The parameterized model was then used to predict forces in response to other stimulation patterns. The predicted forces closely matched the measured forces. The model was not sensitive to initial parameter estimates, demonstrating solution uniqueness. By predicting the force that develops in response to an arbitrary pattern of stimulation, we envision the present model helping identify optimal stimulation patterns for activation of skeletal muscle during functional electrical stimulation.

Animals↗