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Biomedical subjects

J Ding

Publications and source records attributed to J Ding.

At least 37 records · Page 2Linked to original sources
PubMed2002

Mechanisms of bradykinin-induced glucagon release in clonal alpha-cells In-R1-G9: involvement of Ca(2+)-dependent and -independent pathways.

The mechanisms by which bradykinin (BK) increases glucagon release were investigated. BK (0.1-10 microM) increased [Ca(2+)](i) and glucagon release in clonal alpha-cells In-R1-G9. BK-induced glucagon release was lower in the absence than in the presence of extracellular Ca(2+), but it still increased glucagon release while [Ca(2+)](i) was stringently deprived. Depletion of intracellular Ca(2+) store with thapsigargin abolished both the BK-induced Ca(2+) peak and sustained plateau. Microinjection of heparin abolished BK-induced Ca(2+) release. Pertussis toxin (PTX) did not block BK-induced [Ca(2+)](i) increase or glucagon release. U-73122 (8 microM), a phospholipase C (PLC) inhibitor, abolished BK-induced increases in [Ca(2+)](i), but only reduced BK-induced glucagon release by 40%. A phospholipase D (PLD) inhibitor zLYCK reduced BK-induced glucagon release by 60%. The combination of U-73122 and zLYCK abolished BK-induced glucagon release. Both SK&F 96365, a receptor-operated Ca(2+) channel (ROC) blocker and nimodipine, an L-type Ca(2+) channel blocker, reduced BK-induced [Ca(2+)](i) increase and glucagon release. These findings suggest that BK increase glucagon release through a PTX-insensitive G protein and both Ca(2+)-dependent and -independent pathways. The Ca(2+)-dependent pathway is attributable to PLC activation. PLC catalyzes IP(3) formation, inducing Ca(2+) release from the endoplasmic reticulum, which, in turn, triggers Ca(2+) influx via both ROCs and L-type channels. PLD activation may be involved in Ca(2+)-dependent and/or -independent pathway.

Animals↗
PubMed2002

A concentration-dependent mechanism by which serum albumin inactivates replacement lung surfactants.

Endogenous lung surfactant, and lung surfactant replacements used to treat respiratory distress syndrome, can be inactivated during lung edema, most likely by serum proteins. Serum albumin shows a concentration-dependent surface pressure that can exceed the respreading pressure of collapsed monolayers in vitro. Under these conditions, the collapsed surfactant monolayer can not respread to cover the interface, leading to higher minimum surface tensions and alterations in isotherms and morphology. This is an unusual example of a blocked phase transition (collapsed to monolayer form) inhibiting bioactivity. The concentration-dependent surface activity of other common surfactant inhibitors including fibrinogen and lysolipids correlates well with their effectiveness as inhibitors. These results show that respreading pressure may be as important as the minimum surface tension in the design of replacement surfactants for respiratory distress syndrome.

Biophysical Phenomena↗
PubMed2002

Retroperitoneal subpancreatic ectopic pregnancy following in vitro fertilization in a patient with previous bilateral salpingectomy: how did it get there?

An unusual case of retroperitoneal ectopic pregnancy is reported. The patient, a 34 year old nulligravida, underwent IVF/ET following bilateral salpingectomy. A small, degenerating, intrauterine gestational sac suggested failing intrauterine pregnancy. There was no intraperitoneal free fluid. On Day 41 after ET, the patient was hospitalized because of acute epigastric pains. A pseudocyst of the head of pancreas was demonstrated by CT scan. A day later, exploratory laparotomy, because of a precipitous drop in the hemoglobin, revealed a massive retroperitoneal hematoma and an embryo in the gestational sac attached to the head of pancreas and major blood vessels. The patient did well following surgery. The mechanisms of retroperitoneal embryo migration are discussed and literature is reviewed.

Adult↗
PubMed2002

Mining MEDLINE: abstracts, sentences, or phrases?

A growing body of works address automated mining of biochemical knowledge from digital repositories of scientific literature, such as MEDLINE. Some of these works use abstracts as the unit of text from which to extract facts. Others use sentences for this purpose, while still others use phrases. Here we compare abstracts, sentences, and phrases in MEDLINE using the standard information retrieval performance measures of recall, precision, and effectiveness, for the task of mining interactions among biochemical terms based on term co-occurrence. Results show statistically significant differences that can impact the choice of text unit.

Abstracting and Indexing↗
PubMed2002

The value of MG7 antigen in predicting cancerous change in dysplastic gastric mucosa.

The aim of this study was to ascertain whether MG7Ag is a useful predictor of evolution of gastric dysplasia to carcinoma. A total of 1090 patients with confirmed dysplasia were stained immunohistochemically with MG7 monoclonal antibody by the ABC method. A prospective follow-up study was undertaken on 19 patients with MG7Ag positive staining and 16 with MG7 negative staining over a period of 10-78 months. The expression of MG7Ag was also compared in another two groups by conducting retrospective studies. One group showed an evolution into gastric cancer over 2-4 years, the other did not. Quantitative analysis of MG7Ag expression was carried out on the last two groups. The receiver operating characteristic curve and Youden index were used to assess the best critical value for MG7Ag. MG7Ag was found positive in 456/1090 cases (41.8%) with dysplasia. Prospective follow-up of 35 patients showed that 6/19 patients with MG7Ag positive staining developed gastric cancer, but there were no carcinomatous changes in 16 patients with MG7 negative staining. The results of MG7Ag expression in 72 cases with retrospective follow-up showed there were 24 with positive immunostaining among 34 cancerous cases (70.6%), and only 7 in 38 non-cancerous cases (18.4%) (p<0.01). Image analysis showed that an average MG7Ag density index ++0.19 could be regarded as the critical value for high risk of gastric mucosa with dysplasia evolving to cancer. Positive MG7Ag expression in gastric mucosa of patients with dysplasia, especially in cases with a density index ++0.19, was an indicator of high risk of malignant change.

Adult↗
PubMed2001

Effect of resynchronization therapy stimulation site on the systolic function of heart failure patients.

BACKGROUND: Cardiac resynchronization therapy (CRT) improves systolic function in heart failure patients with ventricular conduction delay by stimulating the left ventricle (LV) or both ventricles (biventricular, BV). Optimal LV site selection is of major clinical interest for CRT device implantation; however, the dependence of hemodynamics on LV stimulation site has not been established. Thus, the objective of this study was to compare the hemodynamic response to CRT for 2 LV coronary vein sites: the free wall and anterior wall. Methods and Results- A total of 30 patients (mean NYHA class, 2.7; mean QRS interval, 152 ms; mean PR interval, 194 ms) enrolled in the PATH-CHF-II trial were studied. CRT was administered with LV and BV stimulation in VDD mode at 4 AV delays. LV stimulation was at the lateral free wall or anterior wall, whereas right ventricular stimulation was fixed near the apex. LV+dP/dt(max) and aortic pulse pressure changes from baseline during CRT were compared for LV sites. Free wall sites with LV and BV stimulation yielded significantly larger LV+dP/dt(max) (14% versus 6%, P<0.001 for LV; 12% versus 5%, P<0.001 for BV) and pulse pressure (8% versus 4%, P<0.001 for LV; 9% versus 5%, P<0.001 for BV) compared with anterior sites. In one third of patients, CRT at free wall sites increased LV+dP/dt(max), whereas it decreased at anterior sites over most AV delays. CONCLUSION: CRT with LV free wall stimulation produced significantly better LV systolic performance compared with anterior stimulation. Further studies are warranted to prove the clinical superiority of the LV free wall as a site for long-term CRT.

Aged↗
PubMed2001

Filler-coupling agent-matrix interactions in silica/polymethylmethacrylate composites.

The interactions of the silane coupling agent methacryloxypropyltrimethoxysilane (MPS) with both fumed silica and a polymethylmethacrylate (PMMA) resin matrix were investigated using thermogravimetric analysis and Fourier transform infrared spectroscopy. OX 50 fumed silica was silanated with MPS at concentrations of 1% and 5% in aqueous ethanol (95%), acetone, and anhydrous toluene. Methyl methacrylate was polymerized with the silanated fumed silica (5% wt/wt) to form composites. The amount of MPS adsorption on the fumed silica and the amount of PMMA attached to the silanated fumed silica were determined by thermogravimetric analysis. MPS could be removed from the fumed silica after washing with methanol, but not after it underwent a drying process at 25 degrees C under vacuum. After vacuum drying at 25 degrees C, two types of adsorbed silane were found, i.e., firmly adsorbed and loosely adsorbed silane. The loosely adsorbed silane could desorb from silica and be incorporated into the polymer matrix through copolymerization with monomeric methyl methacrylate, resulting in crosslinking of the matrix. When the silanated silica was dried at 110 degrees C for 2 h, the loosely adsorbed silane was removed and the amount of firmly adsorbed silane increased. There was a positive correlation between the amount of firmly adsorbed MPS and the amount of PMMA attachment. The highest efficiency for PMMA attachment was found when MPS was adsorbed as a monolayer, because the loosely adsorbed silane did not contribute to the bonding of PMMA, and this suggested that not all of the double bonds of the MPS were accessible for reaction with the methacrylate monomer. Drying at 110 degrees C may also decrease the number of unsaturated double bonds of MPS.

Absorption↗
PubMed2001

Molecular dynamics of HIV-1 reverse transcriptase indicates increased flexibility upon DNA binding.

HIV-1 reverse transcriptase (RT) is one of the main targets for drugs used in the treatment of AIDS, among them, the non-nucleoside RT inhibitors (NNRTIs). The flexibility of RT unliganded and complexed to double-stranded DNA (RT/dsDNA), in water, has been studied by means of molecular dynamics. The simulations show that RT flexibility depends on its ligation state. The RT/dsDNA trajectories show larger fluctuations in the atomic positions than uncomplexed RT, particularly at the tips of the p66 fingers and thumb subdomains. This increased flexibility is consistent with the ability of the p66 fingers of the RT/dsDNA complex to close down after the binding of a deoxynucleoside triphosphate (dNTP) molecule, as observed in the crystal structures of RT/dsDNA bound to dNTP. The two complexation states present different patterns of concerted motions, indicating that the bound dsDNA alters RT flexibility. The motions of amino acid residues that form the non-nucleoside RT inhibitor binding pocket upon complexation with a NNRTI are anticorrelated with the p66 fingers (in RT/dsDNA) and correlated to the RNase H subdomain (unliganded RT). These concerted motions indicate that binding of a NNRTI could alter the flexibility of the subdomains whose motions are correlated to those of the binding pocket.

Binding Sites↗
PubMed2001

Syk expression in endothelial cells and their morphologic defects in embryonic Syk-deficient mice.

Mice deficient in the Syk tyrosine kinase showed severe petechiae in utero and died shortly after birth. The mechanism of this bleeding, however, remains unknown. Here it is shown that this bleeding is caused by morphologic defects of Syk-deficient endothelial cells during embryogenesis. Immunoblot and reverse transcriptase-polymerase chain reaction Northern blot analysis indicated that Syk is expressed in several endothelial cell lines. Immunocytochemical analysis also confirmed that Syk is expressed in the normal embryonic endothelial cells and is absent in Syk-deficient mice. Furthermore, electron microscopic analysis of Syk-deficient mice revealed an abnormal morphogenesis and a decreased number of endothelial cells. The results indicate a critical role for Syk in endothelial cell function and in maintaining vascular integrity in vivo.

Animals↗
PubMed2001

Salvicine, a novel DNA topoisomerase II inhibitor, exerting its effects by trapping enzyme-DNA cleavage complexes.

Salvicine, a structurally modified diterpenoid quinone derived from Salvia prionitis, is a novel anticancer drug candidate. The compound has significant in vitro and in vivo activity against malignant tumor cells and xenografts, especially some human solid tumor models. This anticancer activity of salvicine is associated with its ability to induce tumor cell apoptosis. Salvicine was also found to have a profound cytotoxic effect on multidrug-resistant (MDR) cell lines by down-regulating the expression of MDR-1 mRNA of MDR cells. Salvicine acted as a topoisomerase II (Topo II) poison through its marked enhancement effect on Topo II-mediated DNA double-strand breaks as observed in the DNA cleavage assay. Strong inhibitory activity of salvicine against Topo II was observed in a kDNA decatenation assay, with an approximate IC(50) value of 3 microM. A similar result was obtained by a Topo II-mediated supercoiled DNA relaxation assay. In contrast, no inhibitory activity was observed against the catalytic activity of Topo I. When the effects of salvicine on individual steps of the catalytic cycle of Topo II were dissected, it was found that the mechanism by which salvicine inactivates Topo II is different from that by other anti-Topo II agents. Salvicine greatly promoted Topo II-DNA binding and inhibited pre- and post-strand Topo II-mediated DNA religation without interference with the forward cleavage steps. In addition, salvicine was not a DNA intercalative agent, as demonstrated by DNA unwinding assays. The results of this study indicate that the inhibitory activity of salvicine against Topo II was derived from its ability to stabilize DNA strand breaks through interactions with the enzyme alone or with the DNA-enzyme complex. It is therefore postulated that salvicine acts on Topo by trapping the DNA-Topo II complex, which in turn produces anticancer effects.

Animals↗
PubMed2001

Relative androgen excess and increased cardiovascular risk after menopause: a hypothesized relation.

Many studies have investigated the role of estrogen during menopause; however, less attention has been paid to the role of androgen. Given the possible opposite effects of estrogen and androgen on cardiovascular disease risk, it is suggested that relative androgen excess may better predict the increased risk of cardiovascular disease in women over the age of 50 years than estrogen levels alone. Three phases of hormonal milieu changes are hypothesized as a better way to identify the hormone-cardiovascular disease risk association. A first phase, prepause, occurs before estrogen levels decline (approximately 2 years before menopause). A second phase, interpause, occurs from the end of prepause until approximately age 55. A third phase, postpause, occurs after interpause. The duration of the interpause phase, characterized by relative androgen excess, may be an independent risk factor of cardiovascular disease. This hypothesis could provide a basis for further clinical and epidemiologic research, and it could have important implications for establishing the initiation and duration of estrogen replacement therapy use as a means to prevent cardiovascular disease.

Aged↗
PubMed2001

Antiangiogenic potential of 10-hydroxycamptothecin.

To investigate the antiangiogenic potential of 10-hydroxycamptothecin (HCPT), the proliferation of human microvascular endothelial cells (HMEC) and seven human tumor cell lines were detected by SRB assay, and the endothelial cell migration and tube formation were assessed using two in vitro model systems. Also, inhibition of angiogenesis was determined with a modification of the chick embryo chorioallantoic membrane (CAM) assay in vivo. Morphological assessment of apoptosis was performed by fluorescence microscope. HCPT 0.313-5 micromol x L(-1) treatment resulted in a dose-dependent inhibition of proliferation, migration and tube formation in HMEC cells, and HCPT 6.25-25 nmol x egg(-1) inhibited angiogenesis in CAM assay. HCPT 1.25-5 micromol x L(-1) elicited typical morphological changes of apoptosis including condensed chromatin, nuclear fragmentation, and reduction in volume in HMEC cells. HCPT significantly inhibited angiogenesis both in vitro and in vivo at relatively low concentrations, and this effect was related with induction of apoptosis in HMEC cells. These results taken collectively suggest that HCPT may be a potent antiangiogenetic and cytotoxic drug and further investigation is warranted.

Angiogenesis Inhibitors↗
PubMed2001

[Epitope mapping of anti-glomerular basement membrane antibodies].

OBJECTIVE: To map the epitopes of anti-glomerular basement membrane (GBM) antibodies and to study their clinical relevance. METHODS: 33 sera from patients with anti-GBM antibody mediated diseases were applied to inhibit monoclonal antibody against alpha 3 (IV) NC1 (Mab3), monoclonal antibody against alpha 5 (IV) NC1 (Mab5) and affinity purified, horseradish peroxidase conjugated, human anti-GBM antibodies (APab-HRP) in competitive inhibitory ELISA system using soluble human GBM proteins as solid phase ligands. The inhibition rates were evaluated in epitope mapping and used in comparison for patients with different clinical manifestations. RESULTS: All 33 sera inhibited Mab3, 30/33 sera inhibited APab-HRP, and 11/33 inhibited Mab5. However, the inhibition rates were not parallel. The mean inhibition rate for APab-HRP was 55% in 27 patients with anti-GBM antibody only and was 32% in 6 patients with both anti-GBM antibody and ANCA with a significant difference (P = 0.01). For patients with or without pulmonary hemorrhage, no significant differences could be found in the mean inhibition rates for Mab3, Mab5 or APab-HRP (P < 0.05). CONCLUSION: The anti-GBM antibodies from all patients in the present study recognize the common major epitopes on alpha 3 (IV) NC1, however, the epitopes recognized by different anti-GBM antibodies were not exactly the same. Only a small number of anti-GBM antibody positive sera recognizes alpha 5 (IV) NC1. The epitopes recognized by sera from patients with or without ANCA might be different.

Antibodies↗
PubMed2001

Induction of bulk and c-myc P2 promoter-specific DNA damage by an anti-topoisomerase II agent salvicine is an early event leading to apoptosis in HL-60 cells.

Salvicine is a novel diterpenoid quinone derivative possessing strong antitumor activities and was demonstrated to stabilize the DNA topoisomerase II (Topo II) cleavage complex in vitro and in vivo. In the present work we investigated the possible mechanism through which disturbance of Topo II by salvicine led to cell death. We found that salvicine induced DNA strand breaks in human promyelocytic leukemia HL-60 cells and DNA damage correlated with cell growth inhibition. DNA damage induced by brief exposure to salvicine could be partially reversed, but early DNA breaks triggered the process of apoptosis. Preferential damage in the P2 promoter region of the oncogene c-myc was detected, whereas no obvious DNA damage was found in the 3' region of the same gene. Furthermore, the expression of some protooncogenes such as c-myc, c-fos and c-jun was examined, showing that salvicine produced a reduction in the transcription rate of c-myc in a dose-dependent manner and a marked induction of c-fos and c-jun expression was observed. It appears possible that DNA damage within such genomic regions is an early event, which could lead to growth inhibition mediated by alterations of the expression of selected proliferation regulatory genes, such as c-myc, c-fos and c-jun, and ultimately cell death.

Antineoplastic Agents, Phytogenic↗
PubMed2001

The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance.

Inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT) are widely used in the treatment of HIV infection. Loviride (an alpha-APA derivative) and HBY 097 (a quinoxaline derivative) are two potent non-nucleoside RT inhibitors (NNRTIs) that have been used in human clinical trials. A major problem for existing anti-retroviral therapy is the emergence of drug-resistant mutants with reduced susceptibility to the inhibitors. Amino acid residue 103 in the p66 subunit of HIV-1 RT is located near a putative entrance to a hydrophobic pocket that binds NNRTIs. Substitution of asparagine for lysine at position 103 of HIV-1 RT is associated with the development of resistance to NNRTIs; this mutation contributes to clinical failure of treatments employing NNRTIs. We have determined the structures of the unliganded form of the Lys103Asn mutant HIV-1 RT and in complexes with loviride and HBY 097. The structures of wild-type and Lys103Asn mutant HIV-1 RT in complexes with NNRTIs are quite similar overall as well as in the vicinity of the bound NNRTIs. Comparison of unliganded wild-type and Lys103Asn mutant HIV-1 RT structures reveals a network of hydrogen bonds in the Lys103Asn mutant that is not present in the wild-type enzyme. Hydrogen bonds in the unliganded Lys103Asn mutant but not in wild-type HIV-1 RT are observed between (1) the side-chains of Asn103 and Tyr188 and (2) well-ordered water molecules in the pocket and nearby pocket residues. The structural differences between unliganded wild-type and Lys103Asn mutant HIV-1 RT may correspond to stabilization of the closed-pocket form of the enzyme, which could interfere with the ability of inhibitors to bind to the enzyme. These results are consistent with kinetic data indicating that NNRTIs bind more slowly to Lys103Asn mutant than to wild-type HIV-1 RT. This novel drug-resistance mechanism explains the broad cross-resistance of Lys103Asn mutant HIV-1 RT to different classes of NNRTIs. Design of NNRTIs that make favorable interactions with the Asn103 side-chain should be relatively effective against the Lys103Asn drug-resistant mutant.

Acetamides↗
PubMed2001

PEGylated polycyanoacrylate nanoparticles as tumor necrosis factor-alpha carriers.

The aim of this study was to find an effective carrier for recombinant human tumor necrosis factor-alpha (rHuTNF-alpha). The influence of solvent systems containing poly(methoxy-polyethyleneglycol cyanoacrylate-co-n-hexadecyl cyanoacrylate) (PEGylated PHDCA) on the biological activity of rHuTNF-alpha was investigated. The PEGylated PHDCA nanoparticles loading rHuTNF-alpha were prepared with the double emulsion method. The influence of main experimental factors on the entrapment efficiency was evaluated by the Uniform Design. The physicochemical characteristics and in vitro release of rHuTNF-alpha from the nanoparticles were determined. The results showed that serum albumin such as human serum albumin (HSA) or bovine serum albumin (BSA) could play a protective action on rHuTNF-alpha in the preparation process. At > or =2.0% (w/v) HSA concentration, more than 85% of rHuTNF-alpha activity remained and the role of HSA was not affected by copolymer concentrations from 0.5 to 3.0% (w/v). The entrapment efficiency of the nanoparticles was about 60% and the nanoparticle size was about 150 nm. The nanoparticles were spherical in shape and uniform with the value of the zeta potential about -9 mV. The rHuTNF-alpha release from the nanoparticle showed an initial burst and then continued in a sustained fashion. The results showed that the PEGylated PHDCA nanoparticles could be an effective carrier for rHuTNF-alpha.

Chemical Phenomena↗