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Biomedical subjects

C Li

Publications and source records attributed to C Li.

At least 847 records · Page 47Linked to original sources
PubMed1997

Therapeutic modification of nuclear factor kappa B binding activity and tumor necrosis factor-alpha gene expression during acute biliary pancreatitis.

The role of cytokines has been well documented in the pathogenesis of acute pancreatitis. Antibodies against specific cytokines have been used to treat pancreatitis, with mixed results. The transcription factor nuclear factor (NF)-kappa B is a pleiotropic regulator of many genes involved in stress and inflammatory responses. The aim of this study was to prevent the NF-kappa B binding activity and tumor necrosis factor (TNF)-alpha gene overexpression as a possible therapeutic intervention for acute pancreatitis. Reversible acute biliary pancreatitis was induced in male Sprague Dawley rats as established in this laboratory. The animals were sacrificed at 0, 5, 15, 30 min and 1, 2, 3, 4, 6, 8, 10, 12, and 24 hours after the induction of pancreatitis. NF-kappa B binding activity was determined by electrophoretic mobility shift assay, and TNF-alpha gene expression was assayed by reverse transcription-PCR. NF-kappa B binding activity was markedly higher around 4 hours and persisted up to 24 hours after pancreatitis induction in animals with acute pancreatitis, whereas TNF-alpha mRNA levels peaked at 24 hours. When amobarbital (to block NF-kappa B activation) was given (60 mg/kg body weight, I.P.) 3 hours before induction of pancreatitis, the activation of NF-kappa B and the overexpression of TNF-alpha gene was prevented, with significantly decreased severity of pancreatitis as assessed by amylase and clinical recovery. We conclude that 1) preventing the activation of NF-kappa B eliminates the induced overexpression of inflammatory cytokines (TNF-alpha) in acute pancreatitis, 2) such intervention correlates with clinical improvement in pancreatitis, and 3) this genetic modification offers a possible therapeutic intervention in acute pancreatitis.

Acute Disease↗
PubMed1997

Regulation of the laminin beta 1 (LAMB1), retinoic acid receptor beta, and bone morphogenetic protein 2 genes in mutant F9 teratocarcinoma cell lines partially deficient in cyclic AMP-dependent protein kinase activity.

We stably transfected a gene encoding a dominant negative regulatory subunit of cyclic AMP (cAMP)-dependent protein kinase A (PKA) into F9 cells and generated cell lines partially deficient in PKA activity (DN16 and DN19). In these cell lines, the retinoic acid (RA) receptor beta and laminin beta(1) chain (LAMB1) genes were regulated normally by RA alone, indicating that in the absence of exogenous modulation of cAMP levels, the PKA signaling pathway does not seem to play a major role in the RA-associated regulation of these genes. However, alterations in gene regulation were observed when the mutant cell lines were treated with a combination of RA and cAMP analogues. Moreover, in the DN16 cell line, which exhibits the lowest PKA activity among the mutant cell lines [22% of wild type (WT) at 1 microM cAMP], there was a significant decrease in the cAMP-associated activation of the LAMB1 gene DNase I hypersensitivity site 2 enhancer, as measured by chloramphenicol acetyl transferase assays. Using electrophoretic mobility shift assays, less protein binding was observed at one of the motifs (C2) within this enhancer region in the DN16 cells as compared to the F9 WT cells after treatment of the cells with RA and cAMP analogues for 24 h. Furthermore, no increase in C2 binding was observed when extracts from RA-treated F9 ST or DN16 cells were subjected to in vitro phosphorylation, suggesting that PKA is involved in the induction of the C2-binding protein in RA-treated cells. In contrast to the results with RA receptor beta and LAMB1, the effects of cAMP analogues on the RA-associated regulation of the bone morphogenetic protein 2 gene were not altered in the cell lines that exhibited reduced PKA activity. These results suggest that a partial reduction in PKA activity is not sufficient to abrogate the effects of cAMP analogues on all of the genes regulated by RA.

Animals↗
PubMed1997

Frequency of the CCR5 delta 32 mutant allele in HIV-1-positive patients, female sex workers, and a normal population in Taiwan.

A specific 32-nucleotide deletion mutant of the CCR5 gene (Accr5), the coreceptor gene for human immunodeficiency virus type 1 (HIV-1), can effectively suppress the transmission and pathogenesis of the virus. Individuals homozygous for the delta ccr5 allele resist primary macrophage-tropic HIV-1 infection, despite multiple high-risk sexual exposures. This gene deletion is relatively common among Caucasians but uncommon among Africans, Asians, and South Americans. We used polymerase chain reaction (PCR) technology to determine the frequency of the delta ccr5 allele in a Taiwanese population with diverse health status and social backgrounds. Subjects included 24 HIV-1-infected persons in the northern and southern parts of Taiwan; 131 HIV-1 high-risk, licensed female sex workers in the northern part of the island (21% of whom were aborigines); and 187 unrelated, healthy, HIV-1-negative individuals in southern Taiwan. PCR with primers encompassing the entire CCR5 gene was used to explore possible deletions at regions other than the 32-nucleotide area in the female sex workers. No ccr5 deletions were detected, indicating that they are rare or absent in the Taiwanese population. This finding implies that delta ccr5 is not likely to be part of the defense against the spread of HIV-1-infection in Taiwanese.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Human cytomegalovirus matrix protein PP150 is efficiently presented as one of target antigens for cytotoxic T lymphocyte recognition.

OBJECTIVE: To determine whether human cytomegalovirus (CMV) matrix protein PP150 is efficiently presented for CMV-specific CTL recognition. METHODS: Recombinant vaccinia virus (Vac. PP150) encoding human CMV structural matrix protein PP150 was constructed with vaccinia vector PSC11 and it was used to stimulate peripheral blond mononuclear cells from 5 CMV seropositive individuals. RESULTS: PP150-specific CTLs could be generated in all of them, which not only lysed Vac. PP150-infected fibroblasts, but also lysed CMV-infected targets. In the presence of RNA synthesis inhibitor Actinomycin D (Act D) or at very early stage of infection, PP150-specific CTL lysed CMV-infected targets as efficiently as in the absence of Act D or at late stage of infection. CONCLUSIONS: PP150 exogenously introduced with the virus infection could be efficiently presented prior to viral DNA replication and PP150 is one of the major target antigens for CTL recognition.

Antigens, Viral↗
PubMed1997

[Clinical and experiment study of cooling therapy on burned wound].

OBJECTIVE: To observe the subjective benefit of pain relief by cooling therapy when wound temperature drops to below 28 degrees C (threshold for pain). METHOD: 22 patients with partial-thickness burns who received cooling therapy showed 2 days early healing as compared with untreated burn wounds. As a first aid measure, prolonged cooling therapy (up to 30') was recommended. In experimental study, the protective effects with cooling therapy were observed in wistar rats with deep second degree burns. RESULTS: Lower epithelial cell activity and higher schiff alkaline values were seen in the wound skin tissue in the non cooling therapy than in early cooling therapy groups and healthy controls. The groups with early cooling therapy (at once, 10', 20' after scalded injuries) the epithelial cell activity maintained at 83%, 80%, 65%. CONCLUSION: The results suggest that cooling therapy can protect the epithelial cell activity to some extent after scalded injuries which may be associated with inhibition of lipid peroxide.

Adult↗
PubMed1997

[Construction, expression and activity of a single chain antibody to gastric cancer cells].

OBJECTIVE: To construct single chain antibody from McAb 3H11, which has been successfully used in clinical radioimmunoimage, for its widel application in biological treatment of human cancer. METHOD: Reversetranscription and polymerize chain reaction (RT-PCR) were used to clone the V region genes of McAb 3H11 (VH, VL). The cloned VH and VL were sequenced and recombined through a (Gly4Ser) 3 linker. The constructed single chain antibody gene was joined with glutathione-S-transferase gene (gst) and its fusion proteins (GS3H11) were expressed in E. coli. The activity of GS3H11 was characterized with competition experiments after its denature and renature treatment. RESULTS: The recombinant GS3H11 was highly produced in inclusion bodies and the activity was recovered after being renatured. The competition experiments showed that GS3H11 could competitively inhibit the McAb 3H11 binding to gastric tumor cells MGC803. The inhibition was complete when the molecular ratio of GS3H11 to McAb 3H11 reached to 30:1. However, the GS3H11 did not interfere in binding of McAb PD4 and 3G9 to MGC803. CONCLUSION: The specific binding activity of McAb 3H11 is retained in single chain antibody which is potentially useful for therapeutic application.

Antibodies, Monoclonal↗
PubMed1997

[Immediate and late repair of the midface fracture].

A new method of repairing midface fracture is reported. The authors emphasize that midface fracture should be treated by early open reduction in order to recover good function and external contour. The paper presents the causes, the classification of injury, and the symptoms and diagnosis of midface fracture in 65 cases. Four types of operative approaches were used: 1. hemi-coronal or coronal incision; 2. intraoral incision; 3. transconjunctival approach; and 4. Le-Fort I osteotomy. Postoperative roentgenographic examinations after 1-3 months showed bony healing of all the fractures and good external contour as well. Both functional and cosmetic results were achieved. The indications, advantages, disadvantages of the operation and the operative approaches were discussed.

Adult↗
PubMed1997

[The application of intracoronary stenting to type B and C lesions of coronary arteries].

Intracoronary stenting was introduced to 4 lesions due to coronary arterial dissections and to 2 lesions owing to elastic recoil of coronary arteries and stent placement was directly performed in 6 complex coronary lesions after 12 target lesions from 7 patients with Types B and C lesions of coronary arteries had been pre-dilated with balloon. Coronary angiography showed that dissections and recoils had disappeared. Target lesions were well dilated and blood flow was well improved in all cases, one patient was complicated with hemorrhage which was cured quickly. During the follow-up period of 1 to 24 months, another case had recurrence of angina after 2 months of stenting which could be controlled with anti-angina agents. These indicate that intracoronary stenting had good therapeutic effect and is considered as a safe, fast and effective method in dealing with acute complications of coronary artery after routine PTCA.

Aged↗
PubMed1996

Myelin-associated glycoprotein inhibits neurite/axon growth and causes growth cone collapse.

We have previously shown that myelin-associated glycoprotein (MAG) inhibits neurite growth from a neuronal cell line. In this study we show that 60% of axonal growth cones of postnatal day 1 hippocampal neurons collapsed when they encountered polystyrene beads coated with recombinant MAG (rMAG). Such collapse was not observed with denatured rMAG. Neurite growth from rat embryonic hippocampal and neonatal cerebellar neurons was also inhibited about 80% on tissue culture substrates coated with rMAG. To investigate further the inhibitory activity of MAG in myelin, we purified myelin from MAG-deficient mice and separated octylglucoside extracts of myelin by diethylaminoethyl (DEAE) ion-exchange chromatography. Although there was no significant difference in neurite growth on myelin purified from MAG-/- and MAG+/+ mice, differences were observed in the fractionated material. The major inhibitory peak that is associated with MAG in normal mice was significantly reduced in MAG-deficient mice. These results suggest that although MAG contributes significantly to axon growth inhibition associated with myelin, its lack in MAG-deficient mice is masked by other non-MAG inhibitors. Axon regeneration in these mice was also examined after thoracic lesions of the corticospinal tracts. A very small number of anterogradely labeled axons extended up to 13.2 mm past the lesion in MAG-/- mice. Although there is some enhancement of axon generation, the poor growth after spinal cord injury in MAG-/- mice may be due to the presence of other non-MAG inhibitors. The in vitro studies, however, provide the first evidence that MAG modulates growth cone behavior and inhibits neurite growth by causing growth cone collapse.

Animals↗
PubMed1996

Cu2+ potently enhances ATP-activated current in rat nodose ganglion neurons.

Several lines of evidence suggest a physiological role for Cu2+ in regulating nervous system function. In the present study using whole-cell patch-clamp recording, Cu2+ greatly enhanced current activated by 10 microM ATP in the majority of rat nodose ganglion neurons. The enhancement was concentration-dependent between 1 and 50 microM Cu2+, and had an EC50 of 6.1 microM. Cu2+ shifted the ATP concentration-response curve to the left in a parallel manner. However, Cu2+ did not enhance ATP-activated current in the presence of a maximally-effective concentration of Zn2+. The observations suggest that Cu2+ increases the affinity of the receptor for ATP by acting at the Zn2+ modulatory site. In addition, a subset of neurons in the nodose ganglion express ATP-gated receptor-channels that are insensitive to modulation by physiological concentrations of Cu2+, Zn2+ and protons.

Adenosine Triphosphate↗
PubMed1996

ATPase activity of the cystic fibrosis transmembrane conductance regulator.

The gene mutated in cystic fibrosis codes for the cystic fibrosis transmembrane conductance regulator (CFTR), a cyclic AMP-activated chloride channel thought to be critical for salt and water transport by epithelial cells. Plausible models exist to describe a role for ATP hydrolysis in CFTR channel activity; however, biochemical evidence that CFTR possesses intrinsic ATPase activity is lacking. In this study, we report the first measurements of the rate of ATP hydrolysis by purified, reconstituted CFTR. The mutation CFTRG551D resides within a motif conserved in many nucleotidases and is known to cause severe human disease. Following reconstitution the mutant protein exhibited both defective ATP hydrolysis and channel gating, providing direct evidence that CFTR utilizes ATP to gate its channel activity.

Adenosine Triphosphatases↗
PubMed1996

Reduced arrhythmogenicity of biphasic versus monophasic T-wave shocks. Implications for defibrillation efficacy.

BACKGROUND: Biphasic waveforms defibrillate more effectively than monophasic waveforms; however, the mechanism remains unknown. The "upper-limit-of-vulnerability" hypothesis of defibrillation suggests that unsuccessful defibrillation is due to reinduction of ventricular fibrillation (VF). Thus, VF induction mechanisms may be important for the understanding of defibrillation mechanisms. We therefore compared myocardial VF vulnerability for monophasic versus biphasic shocks. METHODS AND RESULTS: In 10 Langendorff-perfused rabbit hearts, monophasic and biphasic T-wave shocks were randomly administered over a wide range of shock coupling intervals and shock strengths, and the two-dimensional coordinates within which VF was induced were used to calculate the area of vulnerability (AOV) for both shock waveforms. The arrhythmic response to biphasic shocks differed from that to monophasic shocks in three distinct ways: (1) the AOV was smaller (8.9 +/- 4.2 versus 13.9 +/- 6.0 area units, P < .02), (2) the transition zone between VF-inducing and nonarrhythmogenic shocks was narrower (14.7 +/- 4.8 versus 29.9 +/- 6.4 area units, P < .001), and (3) the entire AOV shifted toward longer coupling intervals (by 11.0 +/- 8.8 ms at the left border [P < .005] and 6.0 +/- 5.2 ms at the right border [P = .005] of the AOV). CONCLUSIONS: Biphasic shocks encounter a smaller AOV than monophasic shocks, a narrower transition zone from VF to no arrhythmia induction, and a lesser effectiveness in inducing VF at short coupling intervals. In keeping with the upper-limit-of-vulnerability hypothesis, these waveform-dependent differences in VF inducibility might help explain the lower defibrillation threshold for biphasic shocks.

Animals↗
PubMed1996

Radio-induced modulation of transforming growth factor beta1 sensitivity in a p53 wild-type human colorectal-cancer cell line.

Unlike normal intestinal cells, colorectal-carcinoma cell lines are usually not responsive to transforming growth factor beta1. The cyclin-dependent kinase inhibitor p21 that is induced by X irradiation in cells expressing normal p53 can also be induced by TGF-beta1 by a p53-independent pathway. We have investigated possible interactions between ionizing radiation and TGF-beta1, using a panel of 8 human colorectal-cancer cell lines varying in p53 status and sensitivity to the cyto-inhibitory effect of TGF-beta1. Heterogeneity in the radiosensitivity of these cell lines was observed, with SF2 (surviving fraction after irradiation with 2 Gy) ranging from 0.19 to 0.82. Radioresistance (high SF2 values) was in general associated with abnormal expression of p53. An effect of TGF-beta1 treatment on radiosensitivity was observed with one cell line only (LS513), and manifested by enhancement of the cytotoxic effect of radiation. In an experiment with fractionated irradiation during continuous exposure to TGF-beta1, there was no change in the intrinsic radiosensitivity of LS513 cells, though irradiated cells treated with TGF-beta1 were more sensitive to the first radiation dose. Irradiated LS513 colorectal-cancer and Mv-1-Lu epithelial cells were significantly more sensitive to TGF-beta1 than were unirradiated controls, whereas no change was observed in the TGF-beta1 sensitivity of irradiated LS1034 cells. Radio-induced modulation of TGF-beta1 sensitivity was transitory and declined before the decline to baseline level of p21 mRNA expression. On the basis of these results, we postulate that radiation-induced sensitization to TGF-beta1 occurs in TGF-beta1-sensitive cells expressing wild-type p53.

Cell Survival↗
PubMed1996

Dioxabicyclooctanyl naphthalenenitriles as nonredox 5-lipoxygenase inhibitors: structure-activity relationship study directed toward the improvement of metabolic stability.

Naphthalenic lignan lactone 3a (L-702,539), a potent and selective 5-lipoxygenase (5-LO) inhibitor, is extensively metabolized at two different sites: the tetrahydropyran and the lactone rings. Early knowledge of the metabolic pathways triggered and directed a structure-activity relationship study aimed toward the improvement of metabolic stability in this series. The best modifications discovered, i.e., replacement of the lactone ring by a nitrile group, replacement of the tetrahydropyran ring by a 6,8-dioxabicyclo[3.2.1]octanyl moiety, and replacement of the pendant phenyl ring by a 3-furyl ring, were incorporated in a single molecule to produce inhibitor 9ac (L-708,780). Compound 9ac inhibits the oxidation of arachidonic acid to 5-hydroperoxy-eicosatetraenoic acid by 5-LO (IC50 = 190 nM) and the formation of leukotriene B4 in human polymorphonuclear leukocytes (IC50 = 3 nM) as well as in human whole blood (IC50 = 150 nM). The good inhibitory profile shown by naphthalenenitrile 9ac is accompanied by an improved resistance to oxidative metabolism. In addition, 9ac is orally active in the functional model of antigen-induced bronchoconstriction in allergic squirrel monkeys (95% inhibition at 0.1 mg/kg).

Animals↗
PubMed1996

Acid pH augments excitatory action of ATP on a dissociated mammalian sensory neuron.

ATP stimulates nociceptive neurons via an action on ligand-gated ion channels. Since tissue injury and inflammation result in both localized acidosis and release of ATP, we studied the effect of acid pH on ATP-gated ion channels in rat nodose ganglion neurons. Lowering pH dramatically increased membrane depolarization and action potential firing elicited by ATP. ATP-activated current was enhanced by acid pH and suppressed by alkaline pH. A pH of 7.2 produced the half-maximal effect. Acidification increased the apparent affinity of the receptor for ATP, as evidenced by a parallel shift of the ATP concentration-response curve to the left. The observations suggest that the localized acidosis associated with tissue injury may enhance pain perception via an action on ATP-gated ion channels on mammalian sensory neurons.

Action Potentials↗
PubMed1996

Urokinase-type plasminogen activator-induced monocyte adhesion is modulated by kininogen, kallikrein, factor XII, and plasminogen.

Urokinase-type plasminogen activator (u-PA) was found to induce monocyte adhesion through a u-PA receptor (u-PAR)-mediated cAMP-dependent signal transduction pathway (J. Biol. Chem. 270, 30282-30285, 1995). In the present study, the effects of kininogen, kallikrein, factor XII, and plasminogen on u-PA-induced monocyte adhesion were examined since these proteins are abundant in plasma and closely related to u-PA in fibrinolysis and inflammation. Monocyte adhesion to a standard plastic surface by u-PA was shown to be inhibited by the activated, two-chain forms of kininogen (HKa) and kallikrein. The latter occurred only at higher, though physiological, concentrations and was dependent on its catalytic activity. Monocyte adhesion was promoted by factor XII and plasminogen via a noncatalytic mechanism. The findings indicated that u-PA-induced monocyte adhesion was downregulated by HKa and kallikrein and upregulated by factor XII and plasminogen at physiological concentrations. Therefore, these contact system proteins may be important modulators of u-PA-induced monocyte adhesion, a process which is involved in many pathophysiological events.

Blood Coagulation Factors↗