Search PubMed⌕ Search

Biomedical subjects

C C Chao

Publications and source records attributed to C C Chao.

At least 127 records · Page 7Linked to original sources
PubMed1994

Anti-human immunodeficiency virus type 1 activities of U-90152 and U-75875 in human brain cell cultures.

Antiviral activities of the reverse transcriptase inhibitors U-90152 and 3'-azido-2',3'-dideoxythymidine and the protease inhibitor U-75875 were compared in two culture models of human immunodeficiency virus type 1 brain infection. In a model involving acutely infected microglial cells, U-90152 was the most active, whereas in a model using chronically infected promonocytes, U-75875 was the most active.

Antiviral Agents↗
PubMed1994

Transforming growth factor beta in Alzheimer's disease.

Alzheimer's disease (AD) has been hypothesized to be an inflammatory condition. We hypothesized that anti-inflammatory cytokines, such as transforming growth factor beta (TGF-beta), counteract the inflammatory process. In the present study, we found that TGF-beta levels were elevated in both cerebrospinal fluid and serum samples obtained from AD patients < 6 h after death. Serum TGF-beta levels were also markedly elevated before death. These results suggest that elevated TGF-beta levels in AD may represent a protective host response to immunologically mediated neuronal injury.

Aged↗
PubMed1994

Effects of mild exercise on cytokines and cerebral blood flow in chronic fatigue syndrome patients.

Chronic fatigue syndrome (CFS) is an idiopathic disorder characterized by fatigue that is markedly exacerbated by physical exertion. In the present study, we tested the hypothesis that mild exercise (walking 1 mph [1 mile = 1.609 km] for 30 min) would provoke serum cytokine and cerebral blood flow abnormalities of potential pathogenic importance in CFS. Interleukin-1 beta, interleukin-6, and tumor necrosis factor alpha were nondetectable in sera of CFS patients (n = 10) and healthy control subjects (n = 10) pre- and postexercise. At rest, serum transforming growth factor beta (TGF-beta) levels were elevated in the CFS group compared with the control group (287 +/- 18 versus 115 +/- 5 pg/ml, respectively; P < 0.01). Serum TGF-beta and cerebral blood flow abnormalities, detected by single-photon emission-computed tomographic scanning, were accentuated postexercise in the CFS group. Although these findings were not significantly different from those in the control group, the effect of exercise on serum TGF-beta and cerebral blood flow appeared magnified in the CFS patients. Results of this study encourage future research on the interaction of physical exertion, serum cytokines, and cerebral blood flow in CFS that will adopt a more rigorous exercise program than the one used in this study.

Adult↗
PubMed1994

Serum cytokine levels in patients with Alzheimer's disease.

Alzheimer's disease (AD) has been proposed to be an inflammatory disorder. In a recent study, markedly elevated levels of the anti-inflammatory cytokine transforming growth factor beta (TGF-beta) in the serum and cerebrospinal fluid of patients with advanced AD suggested a potential predictive value of this cytokine in patients with AD. In the present prospective study, we tested the hypothesis that the levels of TGF-beta in serum would be increased in patients with AD and could thereby serve as a diagnostic marker. We found that serum TGF-beta levels but not proinflammatory cytokine levels were significantly (P < 0.05) elevated in patients with AD (n = 22) in comparison with the levels in their healthy spousal controls. Also, serum TGF-beta levels were positively correlated (r = 0.45; P < 0.05) with disease severity. Nevertheless, the elevation in serum TGF-beta levels in patients with Ad was modest, and considerable overlap with the control values suggests that the diagnostic usefulness of this cytokine for AD is limited.

Aged↗
PubMed1994

Tumor necrosis factor-alpha potentiates glutamate neurotoxicity in human fetal brain cell cultures.

Cytokines may play a pathogenetic role in the brain. Using human fetal brain cell cultures, we investigated whether cytokines released during inflammation modulate neuronal injury. Exposure of human fetal neuronal cells to the excitatory amino acid neurotransmitter, glutamate, for 6 days resulted in a dose-dependent cell loss. Tumor necrosis factor (TNF)-alpha potentiated glutamate neurotoxicity. This TNF alpha-potentiated glutamate neurotoxicity was blocked by the glutamate receptor antagonists, 2-APV and MK-801, suggesting that the potentiating effect of TNF alpha is predominantly mediated by a glutamate receptor mechanism. Exposure of neuronal cultures to TNF alpha for 5 days resulted in a 27% decrease in astrocyte glutamine synthetase and in a 50% inhibition of 3H-glutamate uptake, suggesting that the effect of TNF alpha indirectly involves glutamate metabolism. These findings suggest that under pathologic conditions, TNF alpha may impair embryonic development of the brain by exacerbating excitotoxicity.

2-Amino-5-phosphonovalerate↗
PubMed1994

Decreased accumulation as a mechanism of resistance to cis-diamminedichloroplatinum(II) in cervix carcinoma HeLa cells: relation to DNA repair.

We previously described a cisplatin-resistant HeLa variant cell line that also exhibited cross-resistance to UV radiation and an enhancement in repair of UV-DNA adducts. In this study, excision repair of cisplatin-DNA adducts in the resistant cell line was investigated by different methods. Using a monoclonal antibody specific for cisplatin-DNA adducts, we found a 2-3-fold decrease in the accumulation of cisplatin-DNA adducts in the resistant cells. This was supported by the direct measurement of the number of cisplatin molecules in cells by atomic absorption spectrophotometry. The repair kinetic curves were composed of two phases, i.e., a rapid phase within the first 4 hr of repair incubation, followed by a slow phase for the cisplatin-DNA adducts. There was a 2.6-fold enhancement in the rapid repair rate in the resistant cells. Dose-response curves from these direct measurements indicated a 2.3-fold reduction in adduct accumulation in the resistant cells. In addition, repair-associated DNA strand breaks, measured using alkaline elution, showed a 1.6-fold increase in the resistant cells. Indirect detection of DNA excision repair, using host cell reactivation of transfected plasmid DNA carrying cisplatin damage, also showed 2.4-fold enhancement in the resistant cells. A phenotypic revertant of the cisplatin-resistant cells displayed reduced DNA repair, compared with the resistant cells. Furthermore, immediately after cisplatin treatment the resistant cells accumulated only 50-60% of the cisplatin-DNA adducts of the parental cells. The results suggest multifactorial mechanisms in cisplatin resistance, including reduced adduct formation and improved excision repair. The findings are also consistent with the notion that the early stage of DNA excision repair is a rate-limiting step in drug resistance.

Antibodies, Monoclonal↗
PubMed1994

Recovery from propofol anesthesia: a quantitative electroencephalographic analysis.

Four numerical descriptors (median frequency, spectral edge frequency-95%, total power, and delta-ratio) derived from the computer-processed electroencephalogram (Neurometrics Lifescan) were analyzed for their ability to predict imminent arousal from total intravenous anesthesia with propofol. Fifteen patients undergoing minor surgical procedures without intubation were enrolled in the study. Arousal was defined as eye opening in response to verbal stimuli. During emergence from propofol, there were no significant changes among the descriptors except the delta-ratio. Significant change of delta-ratio occurred 210 seconds before patients' arousal and thereafter. An increase of delta-ratio value indicates that patients shifted from anesthetic to arousal state. It is concluded that the degree of delta-ratio change may be used for predicting patients' arousal from propofol anesthesia.

Adult↗
PubMed1994

Priming effect of morphine on the production of tumor necrosis factor-alpha by microglia: implications in respiratory burst activity and human immunodeficiency virus-1 expression.

Opiates alter a variety of functional activities of the somatic immune system; within the central nervous system, however, their effects on immune responses are unknown. In the present study, we investigated the effect of morphine on the release of tumor necrosis factor (TNF)-alpha from murine neonatal microglia. Microglial cell cultures did not release TNF-alpha when incubated with morphine alone; however, an enhanced (P < .01) release of TNF-alpha was observed when cultures were first primed with morphine for 24 h and then stimulated with lipopolysaccharide. A bell-shaped dose-response curve was observed for the priming effect of morphine; maximal enhancement of TNF-alpha release (310 +/- 15% of control) was detected at a concentration of 10(-10) M morphine. Pretreatment of microglia for 30 min with opioid receptor antagonists (i.e. naloxone and beta-funaltrexamine) completely blocked the priming effect of morphine. In addition, morphine treatment amplified (P < .01) the priming effect of lipopolysaccharide on phorbol myristate acetate-triggered superoxide anion production by microglial cell cultures, and this effect was abrogated (P < .01) by anti-TNF-alpha antibody. Furthermore, culture supernatants derived from microglial cell cultures that had been treated with morphine before stimulation with lipopolysaccharide had an increased capacity to upregulate human immunodeficiency virus-1 expression in the latently infected promonocytic clone U1. This effect was also blocked by anti-TNF-alpha antibody. These findings suggest that morphine primes microglia for enhanced production of TNF-alpha which could alter several functional activities of these cells within the brain.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Thoracic epidural anesthesia for major abdominal surgery: a retrospective study.

In 1986-1988, the authors had experiences with thoracic epidural anesthesia for a variety of major abdominal operations in 303 patients. It is proved to be reliable and effective. The puncture levels were between T8 to T12. 2% lidocaine, in plain form or with 1:200,000 epinephrine, was used as anesthetic agent. Perioperative complications were carefully managed with satisfactory results. Post-operative conditions were evaluated and seemed to be superior to those of general anesthesia in many aspects. No patient had neurologic deficit as a result of the epidural anesthesia. We concluded that thoracic epidural anesthesia is an excellent alternative technique in major abdominal surgeries.

Abdomen↗
PubMed1993

Lack of DNA enzymatic photoreactivation in HeLa cell-free extracts.

Using a DNA-protein binding assay, we have previously identified and characterized a UV-damaged DNA recognition protein (UVDRP) from HeLa cells [(1991) Nucleic Acids Res. 19, 6413-6418]. In this report, the photoreactivating activity of UVDRP from the yeast, Saccharomyces cerevisiae, and HeLa cells was investigated. Although yeast and human cells are evolutionarily different from each other, both UVDRPs were conserved in the sense of their biochemical characteristics except that the yeast UVDRP also exhibited an enzymatic photoreactivating activity. A mammalian expression vector plasmid DNA carrying the bacterial chloramphenicol acetyltransferase (CAT) gene was UV irradiated in vitro followed immediately by exposure to photoreactivating light, and its transient expression in repair-deficient xeroderma pigmentosum (XP) cells was investigated. More than 80% of the CAT activity was inhibited by UV irradiation, which was partially restored (> 60%) by a partially purified yeast photolyase. In contrast, HeLa cell extracts did not express a photoreactivatable recovery from UV-induced inhibition of the CAT activity tested in the same system. This study has demonstrated the potential use of the DNA-mobility shift assay to investigate enzymatic photoreactivation, and has indicated the absence of the repair mechanism in human cells.

Cell Line↗
PubMed1993

Constitutive over-production of DNA-damage recognition proteins and acquired UV resistance in prolonged culture of F9 teratocarcinoma stem cells.

An ultraviolet (UV)-resistant F9 variant cell line, termed F9Vc, was established from a prolonged culture of murine F9 embryonic stem cells. A 6-fold UV resistance was detected in F9V2 cells compared to the F9 parental cells, as determined by ID50 (36 J/m2 vs. 6 J/m2), the UV dose causing 50% growth inhibition. Using a DNA mobility-shift assay, a nuclear protein (termed UVDRP) that preferentially binds to UV-damaged DNA was detected in F9 and F9Vc cell extracts. The UVDRP in F9Vc cells was present at a 7-fold higher concentration than that of F9 cells. Interestingly, the F9 UVDRP was transiently induced following cellular differentiation by retinoic acid (RA)/cAMP, with optimum induction (15-fold) at 6 days. Although constitutively over-produced, UVDRP also remained inducible in F9Vc cells in response to RA/cAMP. Indirect DNA repair measurement by host cell reactivation of UV-damaged plasmid DNA demonstrated that F9Vc cells exhibited a slight increase or a similarity in repair ability compared to the F9 cells. Parallel experiments using the repair-defective xeroderma pigmentosum (XP) group A fibroblasts and the normal VA13 fibroblasts also indicated that over-production of UVDRP binding activity was associated with enhanced DNA repair and UV resistance. The findings indicate that prolonged culture of F9 cells can establish a condition sufficient to cause constitutive over-production of UVDRP binding activity and UV resistance. The results also suggest that the RA/cAMP-inducible UVDRP in F9 stem cells may be important for the sensitivity or resistance of the cells to UV damage.

Animals↗
PubMed1993

Neuroprotective role of IL-4 against activated microglia.

Microglia have been proposed to play a pathogenetic role in immunologically mediated neurodegenerative diseases. In our study, using microglial/neuronal cell cocultures primed with IFN-gamma, we found that both LPS and TNF-alpha triggered neuronal cell injury (impairment of gamma-aminobutyric acid uptake and neuronal loss) via a nitric oxide mechanism. Pretreatment of cell cocultures with IL-4, an immunosuppressive cytokine, prevented, in a dose-dependent manner, neuronal cell injury induced by activated microglia. The mechanism by which IL-4 exerts its neuroprotective effect was found to involve the inhibition of IFN-gamma priming of microglia with a subsequent decrease in the production of TNF-alpha and nitric oxide.

Animals↗
PubMed1993

Inhibition of UV-damaged DNA recognition activity in HeLa cells by calcium ionophore A23187: potential involvement of cytosolic proteins.

A UV-damage recognition protein (UVDRP) was detected from HeLa nuclear extracts using an in vitro DNA-binding assay. Treatment of cells with a Ca2+ ionophore (A23187) caused a dramatic inhibition of the UVDRP binding activity from nuclear extracts. In the absence of EDTA, addition of cytosolic extracts to the binding reaction effectively blocked the UVDRP binding activity, associated with an increased nuclease activity. However, pretreatment of cytosolic extracts with proteinase destroyed a majority of the inhibitory effect on UVDRP binding activity. Using extracts from A23187-treated cells, a similar conclusion was drawn except that the inhibitory effect of cytosolic extracts on UVDRP binding was completely diminished by proteinase K. In addition, inclusion of the cytosolic extracts in the binding reaction did not alter the UVDRP binding dissociation pattern by specific competitors. These results suggest the potential involvement of cytosolic proteins, probably through a "all-or-none" action mechanism, in the recognition of UV-damaged DNA of HeLa cells.

Calcimycin↗
PubMed1993

Effects of cytokines on multiplication of Toxoplasma gondii in microglial cells.

Microglia may play a role in host defense against Toxoplasma gondii in the central nervous system. In our study, the antitoxoplasma activity of murine microglia was investigated. T. gondii multiplied readily in cultured microglial cells, and activation of these cells with IFN-gamma plus LPS suppressed (p < 0.01) intracellular growth of this parasite. This antitoxoplasma defense of activated microglia was significantly blocked by neutralizing antibodies against TNF-alpha and transforming growth factor-beta, suggesting that these cytokines play a role in the inhibitory process. Consistent with this hypothesis, activation of microglia with IFN-gamma plus TNF-alpha or transforming growth factor-beta inhibited, in a dose-dependent manner, T. gondii multiplication. Treatment with pentoxifylline or dexamethasone, drugs that suppress production of TNF-alpha, prevented (p < 0.01) the microglia from exerting an anti-T. gondii effect. These findings suggest that the host defense function of microglia against T. gondii is dependent primarily on the activating properties of IFN-gamma and TNF-alpha, and that agents that interfere with cytokine-mediated activation may promote the pathogenesis of this infection.

Animals↗
PubMed1993

Overexpression of a UV-damage recognition protein in a UV-sensitive human colon cancer cell line that features multidrug-resistant phenotype.

We have previously hypothesized that the level of UV-damage recognition protein (UVDRP) is a potential indicator of DNA-damage-mediated sensitivity or resistance of human cells to UV radiation [Chao, C.C.-K., Biochem. J. 282, 203-207, 1992]. In this study, we detected a 2-fold increase in the UVDRP binding activity in a UV-sensitive multidrug-resistant (MDR) human colon cancer cells compared to the parental SW620 cells. However, the MDR cells did not display enhanced DNA repair. The data is consistent with the conclusion that DNA excision repair is not the sole determinant of cellular sensitivity to genotoxic agents. The results also suggest that recognition of damaged DNA may be associated with generating a signal which mediates cellular sensitivity to UV radiation.

Cell Division↗
PubMed1993

Characterization of a DNA-damage-recognition protein from F9 teratocarcinoma cells, which is inducible by retinoic acid and cyclic AMP.

A nuclear protein that recognizes u.v.-damaged DNA was detected in extracts from murine F9 embryonic stem cells using a DNA-binding assay. The nuclear-protein-binding activity was increased in cells after treatment with retinoic acid/dibutyryl cyclic AMP (dbcAMP), with optimum induction at 6 days. In vitro treatment of nuclear extracts with agents that affect protein conformation (such as urea, Nonidet P40 and Ca2+) slightly modulated the damage-recognition activity. Furthermore, treatment of nuclear extracts with phosphatase dramatically inhibited the binding activity. In addition, damaged-DNA recognition of the nuclear extracts was effectively inhibited by damaged double- and single-stranded DNA. The expression of the nuclear protein with similar characteristics was abundant in HeLa cells and was increased in drug- or u.v.-resistant cells. The findings suggest that the recognition of a u.v.-DNA adduct is modulated, at least in part, by an activity that is induced during retinoic acid/dbcAMP-induced differentiation. These results also imply that the identified damage-recognition protein may be important for the sensitivity or resistance of mammalian cells to DNA damage.

Animals↗
PubMed1993

Photochemical reduction of ferric iron by chelators results in DNA strand breaks.

The induction of single-strand breaks (SSB) in phi X174 RFI DNA by Fe(III) chelates under cool-white fluorescent (CWF) light or in darkness was investigated. Under CWF light, ferric iron (25 microM) without the addition of a low-molecular-weight (LMW) chelator or with the addition of a LMW chelator, such as citrate, nitrilotriacetate (NTA), or EDTA, generated SSB in 11, 30, 13, or 0% of the treated, closed-circular DNA, respectively. Addition of H2O2 increased the formation of DNA SSB to 93, 75, 62, or 25, respectively. In the dark, DNA SSB were not detected in the absence of H2O2. The addition of H2O2 resulted in 85% (none), 8% (citrate), 18% (EDTA), or 42% (NTA) DNA with SSB. The formation of DNA SSB was completely inhibited by a strong Fe(II)-specific chelator, ferrozine. Various .OH scavengers (e.g., mannitol, 5,5-dimethyl-1-pyrroline-N-oxide, dimethyl sulfoxide) completely inhibited DNA SSB formation in the presence of a LMW chelator, but only partially inhibited in the absence. These results suggest that Fe(II) and .OH or similarly reactive species may be involved in the induction of DNA SSB. The evolution of CO2 from chelators, such as EDTA or citrate, required CWF light and Fe(III), suggesting the participation of chelators in the reaction with Fe(III). Under CWF light, catalase inhibited and superoxide dismutase (SOD) stimulated formation of DNA SSB, indicating H2O2 was generated from O2-. and was required for DNA damage. In the dark, SOD inhibited formation of DNA SSB, suggesting O2-. was required for reaction(s) other than formation of H2O2. These results suggest that in the light the photochemical reduction of Fe(III) by the chelators results in formation of DNA SSB without the addition of H2O2. In the dark, the addition of H2O2 was required for the formation of DNA SSB, suggesting a different mechanism for DNA strand break formation.

Chelating Agents↗