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Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 415 records · Page 23Linked to original sources
PubMed2000

[Diagnosis and management of gestational trophoblastic tumor with liver metastases].

OBJECTIVE: To evaluate management options and clinical prognosis for women presenting gestational trophoblastic tumor (GTT) with liver metastases. METHODS: We retrospectively analyzed sixteen GTT patients with liver metastases treated in the Peking Union Medical College (PUMC) hospital from 1985 to 1998. All were treated with 5-FU combined chemotherapy or EMA/CO regimen. Eight of them received hepatic artery infusion chemotherapy. Treatment outcome was measured by beta subunit human chorionic gonadotropin assay (beta-hCG) and by imaging studies which included ultrasound and computerized tomography. RESULTS: Of 16 cases, 4 achieved complete remission; biochemical remission was obtained in 2 patients who were alive with residual tumor; 10 patients died of the disease. The overall survival rate was 37.5% (6/16). CONCLUSIONS: The outcome for women presenting with liver metastases from GTT is poor. Early diagnosis and prompt initiation with vigorous multi-agent chemotherapy given through multi-routes are emphasized for improving the treatment outcome.

Adult↗
PubMed2000

[Raman spectra of the serums from cancerous persons].

The serums of different categories, those who are normal people and those who are patient suffering from nasopharyngeal cancer, liver cancer and chronic leukaemia, were determined by laser Raman spectra at the range of 0-2,000 cm-1. The results demonstrated that the serums of those who are suffering from the same disease show different characteristic peak height, but their Raman spectrogram characteristics are almost the same. There exists great difference in the laser Raman spectrogram for the serums of the different kinds of cancerous patients. Near the characteristic peaks of laser Raman spectrograms of serums from the cancerous patients, the normal person's serum has no Raman spectrogram characteristic peak.

Humans↗
PubMed2000

[Study on the infrared spectra of metallic clusters containing R2dtc ligand and V = O group].

This paper reports the features and regularities of the infrared spectra for two kinds of complexes containing R2dtc ligand. The cubane-like clusters containing R2dtc ligand possess weak and wide peaks at 400-500 cm-1 assigned to M-mu 3S vibration, while the peaks at 330-380 cm-1 and 1,470-1,510 cm-1 can be assigned to M-Sdtc and C-N vibrations, respectively. The nu(C-N) and nu(C = S) vibrations for Me2dtc-cubane cluster exhibit blue shift and red shift, respectively, when compared with those of other R2dtc ones. This would be attributed to the strong super-conjugation of the methyl group. The M-mu 3S vibrations for both types of complexes [V2Cu2S4(R2dtc)2(PhS)2]2- and [VCu4S4(R2dtc)n(PhS)4-n]3- (n = 0, 1, 2) occur at 480 and 465 cm-1, respectively. This small difference becomes a useful indication to distinguish the two types of clusters. Cluster complexes containing (R2dtc)2V2O2(mu-S)2 structural unit show the V = O vibration in the range of 844-970 cm-1. It is noted that (Et4N)[V3S2O3(Et2dtc)3] contains two sets of the V = O bonds corresponding to two sets of V = O vibrations at 970 and 844 cm-1. An additional coordination of the V = O bond to another metal atom obviously weakens the V = O bond to give rise to the red shift of the infrared frequency. Similar red shifts were also observed for other complexes and were discussed.

English Abstract↗
PubMed1999

Platelet-activating factor inhibits ionotropic GABA receptor activity in cultured hippocampal neurons.

Platelet-activating factor (PAF), one of the most potent bioactive lipids, has been implicated in modulating long-term potentiation (LTP) and neurotoxicity. In the CNS, glutamate and GABA are the major excitatory and inhibitory neurotransmitters, respectively. Previous work has focused on the effects of PAF on glutamatergic receptor responses. The purpose of the present study was to investigate the possible actions of PAF on ionotropic GABA receptor responses in primary cultured hippocampal neurons using the whole-cell and single channel patch clamp techniques. Extracellular application of PAF induced a reduction of the GABA gated Cl- current in a majority of cells (29 of 44 cells), while it caused an enhancement in 10 of 44 cells. A similar heterogeneous modulation of PAF on the GABA receptor activities was also observed in outside-out patch recordings. Moreover, the cell-attached single channel recordings showed that PAF decreased the GABA channel activity. Therefore, PAF may modulate synaptic activity by inhibiting GABA receptor channels. During seizures and neural injury, when enhanced synthesis of this lipid mediator takes place, the actions of PAF on inhibitory GABA receptors may contribute to synaptic dysfunction.

Animals↗
PubMed1999

MHC class I-restricted recognition of a melanoma antigen by a human CD4+ tumor infiltrating lymphocyte.

It is generally considered that MHC class I-restricted antigens are recognized by CD8+ T cells, whereas MHC class II-restricted antigens are recognized by CD4+ T cells. In the present study, we report an MHC class I-restricted CD4+ T cell isolated from the tumor infiltrating lymphocytes (TILs) of a patient with metastatic melanoma. TIL 1383 I recognized HLA-A2+ melanoma cell lines but not autologous transformed B cells or fibroblasts. The antigen recognized by TIL 1383 I was tyrosinase, and the epitope was the 368-376 peptide. Antibody blocking assays confirmed that TIL 1383 I was MHC class I restricted, and the CD4 and CD8 coreceptors did not contribute significantly to antigen recognition. TIL 1383 I was weakly cytolytic and secreted cytokines in a pattern consistent with it being a Th1 cell. The avidity of TIL 1383 I for peptide pulsed targets is 10-100-fold lower than most melanoma-reactive CD8+ T cell clones. These CD4+ T cells may represent a relatively rare population of T cells that express a T-cell receptor capable of cross-reacting with an MHC class I/peptide complex with sufficient affinity to allow triggering in the absence of the CD4 coreceptor.

Antigens, Neoplasm↗
PubMed1999

Structure, alternative splicing, and expression of the human RGS9 gene.

An isoform of RGS9 was recently identified as the GTPase activating protein in bovine and mouse rod and cone photoreceptors. To explore the potential role of the RGS9 gene in human retinal disease, we determined its exon/intron arrangement, and investigated its expression in human retina. The results show that the gene, located on 17q24, consists of 19 exons and spans more than 75kb of genomic DNA. The entire gene was found to be contained on a single BAC clone with an insert size of 170kb. The major transcripts of the gene are alternatively spliced into a 9.5kb retina-specific transcript (RGS9-1) and a brain specific 2.5kb transcript (RGS9-2). Exons 1-16 are constitutive and present in both variants. Exon 17 contains the 3' end of the open reading frame and the 3'-UTR of the RGS9-1 variant. In RGS9-2, exon 17 is alternatively spliced and joined to exons 18 and 19 that are not present in the retina variant. Immunolocalization with a monoclonal antibody recognizing the retina and brain variants shows abundant expression in photoreceptors and possibly very low levels in cell types of the inner retina. Owing to the specific expression of RGS9-1 in photoreceptors the RGS9 gene is a candidate gene for RP17, a form of autosomal retinitis pigmentosa, located on the long arm of chromosome 17.

Aged↗
PubMed1999

Human GHRH reduces voltage-gated K+ currents via a non-cAMP-dependent but PKC-mediated pathway in human GH adenoma cells.

1. Whole-cell voltage-gated K+ currents and the K+ current response to growth hormone-releasing hormone (GHRH) were characterised in primary cultures of human acromegalic somatotropes. 2. Both delayed rectifier (IK) and transient (IA) K+ currents were recorded from human somatotropes held at -80 mV and bathed in a solution containing Cd2+ (1 mM), TTX (1 microM) and a low concentration of Ca2+ (0.5 mM). Only IK was recorded, however, when a holding potential of -40 mV was used. 3. GHRH (10 nM) immediately and significantly reduced the amplitude of both IA and IK. While the reduction in the amplitude of IA was fully reversed following the removal of GHRH, the amplitude of IK had only partially recovered 10 min after GHRH removal. In addition, GHRH shifted the voltage-dependent inactivation curve of IA by 13.5 mV in the negative direction. 4. In a low Ca2+ and Cd2+-containing solution, the Ca2+-activated K+ channel blockers apamin (100 nM and 1 microM) and charybdotoxin (1 microM) did not alter K+ currents or the effect of GHRH on the recorded K+ currents. 5. The whole-cell K+ currents and their responses to GHRH were unaffected by the application of 8-bromo-cAMP (100 microM), Rp-cAMP (100 microM) or the protein kinase A (PKA) inhibitor H89 (1 microM). In addition, intracellular dialysis of the PKA inhibitory peptide PKI (10 microM) had no effect on the K+ current response to GHRH. 6. While the application of protein kinase C (PKC) inhibitors calphostin C (100 nM) or chelerythrine (1 microM) did not affect the amplitude of the K+ currents, the K+ current response to GHRH was significantly attenuated. Downregulation of PKC with phorbol 12,13-dibutyrate (PDBu, 0.5 microM for 16 h) also abolished the K+ current response to GHRH. In addition, intracellular dialysis of somatotropes with the PKC inhibitory peptide PKC19-36 (1 microM) prevented the GHRH-induced decrease in the amplitude of the voltage-gated K+ currents. Local application of PDBu (1 microM) significantly reduced the amplitude of the voltage-gated K+ currents in a similar manner to that induced by GHRH, but without clear recovery upon removal. 7. This study demonstrates that GHRH decreases voltage-gated K+ currents via a PKC-mediated pathway in human adenoma somatotropes, rather than by the cAMP-PKA pathway that is usually implicated in the actions of GHRH.

Adenoma↗
PubMed1999

Activation of the unfolded protein response pathway induces human asparagine synthetase gene expression.

The gene for the amino acid biosynthetic activity asparagine synthetase (AS) is induced by both amino acid and glucose deprivation of cells. The data reported here document that the human AS gene is induced following activation of the Unfolded Response Pathway (UPR), also known as the Endoplasmic Reticulum Stress Response (ERSR) in mammals. Increased AS transcription occurs in response to glucose deprivation, tunicamycin, or azetidine-2-carboxylate, all known to activate the UPR/ERSR pathway. Previously identified ERSR target genes contain multiple copies of a single highly conserved cis-element. In contrast, the human AS gene does not contain the ERSR element, as it has been described for other responsive genes. Instead, AS induction requires an Sp1-like sequence, a sequence previously shown to be associated with amino acid control of transcription, and possibly, a third region containing no consensus sequences for known transcription factors. Oligonucleotides covering each of these regions form DNA-protein complexes in vitro, and for some the amount of these complexes is greater when nuclear extracts from glucose-starved cells are tested. These results document that a wider range of metabolic activities are activated by the UPR/ERSR pathway than previously recognized and that genomic elements other than those already described can serve to enhance transcription of specific target genes.

Aspartate-Ammonia Ligase↗
PubMed1999

The PPAR activator docosahexaenoic acid prevents acetaminophen hepatotoxicity in male CD-1 mice.

Acetaminophen (APAP)-induced hepatocellular necrosis can be prevented by treatment with peroxisome proliferators. This protection is associated with lowered protein arylation and glutathione depletion in mice. Peroxisome proliferators have been shown to activate nuclear receptors. These receptors, termed peroxisome proliferator activated receptors (PPARs), can also be activated by free fatty acids. This study was designed to determine if treatment with the PPAR activator docosahexaenoic acid (DHA) would also lower APAP toxicity. Male CD-1 mice received 250 mg DHA/kg or 500 mg clofibrate (CFB)/kg, i.p., for 5 d. Controls received corn oil vehicle, i.p. After overnight fasting, mice received 800 mg APAP/kg, p.o. At 24 h after APAP, hepatotoxicity was evident in control mice by elevated plasma sorbitol dehydrogenase activity (SDH) and histologic evidence of hepatic degeneration and necrosis. As expected, CFB pretreatment significantly decreased this. Similarly, DHA protected against APAP-induced hepatotoxicity at 24 h after challenge. However, treatment with DHA did not increase hepatic glutathione prior to APAP, as previously shown with CFB. Interestingly, DHA did not increase palmitoyl coenzyme A (CoA) oxidase activity or other biochemical parameters associated with peroxisome proliferation after 5 d of treatment at 250 mg/kg. No significant alterations in microsomal APAP glucuronidation or cytochrome P-450-mediated bioactivation were detected either. Collectively, these results show that DHA also prevents APAP-induced hepatotoxicity at 24 h after challenge. However, the association between resistance against APAP-induced liver injury, PPAR activation, and peroxisome proliferation is not clearly understood.

Acetaminophen↗
PubMed1999

Enhancement of dendrimer-mediated transfection using synthetic lung surfactant exosurf neonatal in vitro.

Pulmonary surfactants enhance adenovirus-mediated gene transfer but inhibit cationic liposome-mediated transfection in lung epithelial cells in vitro. This study examines the effect of the synthetic lung surfactant Exosurf on dendrimer-mediated transfection in eukaryotic cells. Exosurf significantly enhanced dendrimer-luciferase plasmid transfection in a number of cell lines and was very effective in primary cells. Luciferase expression increased up to 40-fold in primary normal human bronchial/tracheal epithelial cells (NHBE). FACScan analysis demonstrated that the transfection rate of the human T cell leukemia Jurkat cell line has significantly improved from 10 to 90% of cells at 24 h after transfection. Analysis of the components of Exosurf revealed that the nonionic surfactant tyloxapol was responsible for the enhancement of dendrimer-mediated gene transfer. The tyloxapol effect was due to increased cell membrane porosity and DNA uptake. Our results demonstrate that Exosurf and its component, tyloxapol, constitute a powerful enhancer for dendrimer-mediated gene transfer in vitro.

Animals↗
PubMed1999

A soluble transforming growth factor beta type III receptor suppresses tumorigenicity and metastasis of human breast cancer MDA-MB-231 cells.

Transforming growth factor beta (TGF-beta) can promote late stage tumor progression in a number of model systems. In the present study, we have examined whether expression of a truncated soluble extracellular domain of TGF-beta type III receptor (sRIII) in human breast cancer MDA-MB-231 cells can antagonize the tumor-promoting activity of TGF-beta by sequestering active TGF-beta isoforms that are produced by the cancer cells. The secretion of sRIII reduced the amount of active TGF-beta1 and TGF-beta2 in the conditioned medium. This led to a significant reduction of the growth-inhibitory activity of the medium conditioned by sRIII-expressing cells on the growth of mink lung epithelial CCL64 cells in comparison with the medium conditioned by the control cells. The tumor incidence and growth rate of all of the three sRIII-expressing clones studied were significantly lower than those of the control cells in athymic nude mice. Four of five control cell-inoculated mice showed spontaneous metastasis in the lung, whereas none of the sRIII-expressing cell-inoculated mice had any lung metastasis. Thus, our results suggest that the sRIII may be used to antagonize the tumor-promoting activity of TGF-beta.

Animals↗
PubMed1999

Glutathione S-transferase M1 genotypes and the risk of squamous carcinoma of the cervix: a population-based case-control study.

The authors determined the GSTM1 genotype of 190 Caucasian women with invasive squamous cell cervical cancer in western Washington State between January 1986 and June 1994 and of 206 controls. It was found that 53% of cases and 57% of controls had the GSTM1 null genotype. The age-adjusted odds ratio associated with GSTM1 null genotype was 0.8 (95% confidence interval 0.6, 1.3). The lack of association between cervical cancer risk and GSTM1 genotype was true both for smokers and nonsmokers of cigarettes and for heavy and light smokers. These data suggest that women with the GSTM1 null genotype are not at increased risk of cervical cancer.

Adult↗
PubMed1999

Glutathione S-transferase M1 genotypes and the risk of vulvar cancer: a population-based case-control study.

Glutathione S-transferases (GSTs) facilitate the excretion of a variety of potential carcinogens. Some 50-60% of Caucasians are homozygous for the null allele of GSTM1, a gene responsible for the presence of one of these enzymes. The authors examined whether women with the GSTM1 null genotype are at altered risk of vulvar cancer. They obtained peripheral blood specimens from 18- to 79-year-old residents of King, Pierce, and Snohomish counties of western Washington who were diagnosed with vulvar cancer between April 1991 and June 1994. Blood specimens were also obtained from controls identified via random digit telephone dialing of western Washington households. The authors determined the GSTM1 genotype of 137 cases (120 in situ and 17 invasive cases) and 248 controls. The frequency of the GSTM1 null genotype was 46.7% among cases and 57.3% among controls. The age-adjusted odds ratio associated with the GSTM1 null genotype was 0.7 (95% confidence interval: 0.4, 1.0). Among current smokers of cigarettes, the age-adjusted odds ratio associated with the GSTM1 null genotype was 0.5 (95% confidence interval: 0.2, 0.9), differing little between heavy and light smokers. Our data suggest that women with the GSTM1 null genotype are not at increased risk of vulvar cancer.

Adult↗
PubMed1999

AMPA-preferring glutamate receptors in cochlear physiology of adult guinea-pig.

1. The present study was designed to determine which glutamate (Glu) receptors are involved in excitatory neurotransmission at the first auditory synapse between the inner hair cells and the spiral ganglion neurons. 2. The Glu receptors present at the membrane level were investigated on isolated spiral ganglion neuron somata from guinea-pigs by whole-cell voltage-clamp measurements. Glu and AMPA induced a fast onset inward current that was rapidly desensitized, while kainate induced only a non-desensitizing, steady-state current. NMDA induced no detectable current. 3. To further discriminate between the AMPA and kainate receptors present, we used the receptor-specific desensitization blockers, cyclothiazide and concanavalin A. While no effect was observed with concanavalin A, cyclothiazide greatly enhanced the Glu-, AMPA- and kainate-induced steady-state currents and potentiated Glu-induced membrane depolarization. 4. To extrapolate the results obtained from the somata to the events occurring in situ at the dendrites, the effects of these drugs were evaluated in vivo. Cyclothiazide reversibly increased spontaneous activity of single auditory nerve fibres, while concanavalin A had no effect, suggesting that the functional Glu receptors on the somata may be the same as those at the dendrites. 5. The combination of a moderate-level sound together with cyclothiazide increased and subsequently abolished the spontaneous and the sound-evoked activity of the auditory nerve fibres. Histological examination revealed destruction of the dendrites, suggesting that cyclothiazide potentiates sound-induced Glu excitotoxicity via AMPA receptors. 6. Our results reveal that fast synaptic transmission in the cochlea is mainly mediated by desensitizing AMPA receptors.

Animals↗
PubMed1999

Contributions of residual calcium to fast synaptic transmission.

Fast neurotransmitter release is driven by high calcium (10-100 microM) near open channels (Ca(local)), followed by a much smaller (<1 microM), longer-lasting residual calcium (Ca(res)). The most prominent component of release, phasic release, lasts several milliseconds and is thought to be triggered by Ca(local). A transient tail of release then continues over the next 20 msec at 1-10% of peak rates. This transient component of release, which we refer to as TR, is poorly understood, and there is conflicting evidence regarding the role of Ca(local) and Ca(res) in its generation. We used optical methods to monitor Ca(res) and whole-cell voltage-clamp recordings to study TR at synapses between granule cells and stellate cells in rat cerebellar slices. After stimulation the probability of release is elevated greatly, peaking at 500 microseconds and then slowly declining to prestimulus levels after tens of milliseconds. After speeding the decay of Ca(res) levels with EGTA, release is confined to a 3 msec interval, and TR is eliminated. Thus, we find that Ca(res) accounts for a transient tail of release on the millisecond time scale that helps to shape the average synaptic current and accounts for at least 20% of the synaptic charge in the 20 msec interval after stimulation. Ca(res)-dependent TR is likely to contribute significantly to fast synaptic transmission under physiological conditions, particularly during high-frequency bursts that elevate Ca(res).

Animals↗
PubMed1999

Nucleoside diphosphate kinase associated with membranes modulates mu-opioid receptor-mediated [35S]GTPgammaS binding and agonist binding to mu-opioid receptor.

The role of nucleoside diphosphate kinase (NDKP), which converts GDP to GTP, in the coupling of mu-opioid receptors to G protein was investigated in membranes of Chinese hamster ovary cells stably transfected with the cloned rat mu-opioid receptor (rmor). Endogenous NDPK activity in membranes was determined to be 0.60+/-0.02 micromol/mg protein/30 min UDP (at 10 mM), a competitive substrate of NDPK for GDP with no effect on guanine nucleotide binding to G proteins, reduced basal [35S]GTPgammaS binding and unmasked morphine-stimulated [35S]GTPgammaS binding to pertussis toxin-sensitive G proteins, indicating that [35S]GTPgammaS binding to NDPK accounts for part of its high basal binding. UDP increased the extent of morphine-induced increase in [35S]GTPgammaS binding in the presence of GDP, most likely by reducing basal binding and inhibiting conversion of GDP to GTP. ATP greatly reduced morphine-induced increase in [35S]GTPgammaS binding, whereas AMP-PCP (adenylyl-(beta,gamma-methylene)-diphosphoate tetralithium salt), which cannot serve as the phosphate donor for NDPK, did not, demonstrating that effects of ATP is mediated by the NDPK product GTP. In addition, GDP and ATP increased the Kd and lowered the Bmax of the agonist [3H]DAMGO ([D-Ala2,N-Me-Phe4,Gly5ol]-Enkephalin) for the mu-opioid receptor and GDP alone increased Kd, most likely through their conversion to GTP by NDPK. Addition of exogenous NDPK enhanced the inhibitory effects of GDP and combined GDP and ATP on [3H]DAMGO binding. Thus, NDPK appears to play a role in modulating signal transduction of and agonist binding to mu-opioid receptors.

Adenosine Triphosphate↗
PubMed1999

The gene expression of coagulation factor VIII in mammalian cell lines.

Both the full-length and B domain-deleted cDNA of factor VIII were constructed in plasmid pcDNA3, respectively, and successfully expressed in Cos-7 cells. The yield of recombinant factor VIII-deltaB (0.4 U/mL/10(6) cells/day) was approximately four times higher than that of the recombinant factor VIII. In addition, it was indicated that the gene expression of factor VIII is specific for cells from different tissues. The highest expression level was found in the hepatocellular carcinoma line SMMC-7721, followed by kidney, ovary, and lung cell lines. To compare the efficiency of gene expression of recombinant factor VIII, the factor VIII-deltaB gene was further reconstructed in different forms in the expression plasmid pCMV-dhfr for transient gene expression in Chinese hamster ovary cells. The redundant 5'- and 3'-untranslated sequences of factor VIII-deltaB were deleted. The cDNA encoding the heavy and light chains of factor VIII were constructed, respectively. Among them the high yield of the recombinant factor VIII was found in the coexpression of the heavy and light chain cDNA fragments of factor VIII. The deletion of the redundant 5'-untranslated sequence of factor VIII-deltaB was also beneficial for gene expression. As expected, the gene coexpression of factor VIII-deltaB and von Willibrand Factor cloned by the long-polymerase chain reaction method was also helpful for enhancing the expression level of recombinant factor VIII. A monoclonal antibody raised against factor VIII was prepared and used for the specific assay of recombinant factor VIII by the competitive ELISA method, the assay results were consistent with those determined by the one-stage bioassay.

Animals↗