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Biomedical subjects

C C Chen

Publications and source records attributed to C C Chen.

At least 325 records · Page 18Linked to original sources

ATP-evoked inositol phosphates formation through activation of P2U purinergic receptors in cultured astrocytes: regulation by PKC subtypes alpha, delta, and theta.

ATP-induced phosphoinositide (PI) hydrolysis was studied in cultured astrocytes. To characterize the P2 purinergic receptor-mediated effects of ATP, the subtype-specific agonists 2-methylthio ATP (2-MeSATP), UTP, and alpha, beta-methylene ATP were compared. ATP, UTP, or 2-MeSATP induced a dose-dependent increase of inositol phosphates (IP) accumulation; alpha, beta-methylene ATP and adenosine had no effect. The order of potency was ATP > or = UTP >> 2-MeSATP. Cross-desensitization experiments indicated that ATP interacted with both P2U and P2Y receptors. P2U was the predominant P2 receptor in mediating PI hydrolysis in astrocytes. The effect of ATP, UTP, or 2-MeSATP was markedly inhibited by pretreatment of cells with pertussis toxin (PTX), indicating that both P2U and P2Y receptors coupled to phospholipase C through PTX-sensitive G protein. Short-term (10 min) treatment of cells with 1 microM TPA attenuated ATP, UTP, and 2-MeSATP-induced PI breakdown; however, long-term (24 h) pretreatment resulted in marked potentiation of both ATP and UTP, and restoration of 2-MeSATP responses. In a further analysis of the effect of TPA, 10 min and 1.5 h pretreatment attenuated ATP-and UTP-induced PI breakdown, but this inhibitory action was lost after 3 h of treatment. Both 6 and 24 h pretreatments resulted in a potentiation. Western blot analysis showed translocation of protein kinase C (PKC) alpha, -delta, and -theta from the cytosol to the membrane following 10 min and 1.5 h treatments, and restoration to basal levels in the membrane fraction was seen after 3 h of treatment. On the other hand, partial and complete down-regulation of these three isoforms was seen after 6 and 24 h of treatment, respectively. PKC eta was translocated but not down-regulated by TPA. These results suggested that PKC alpha, -delta, and -theta, not -eta may exert tonic inhibition on P2U receptor-mediated PI turnover in unstimulated astrocytes.

Adenosine Triphosphate↗

Preoperative cardiac risk assessment with adenosine stress dual-isotope myocardial single-photon emission computed tomography.

BACKGROUND: Previous studies have demonstrated that pharmacologic stress thallium-201 (201Tl) myocardial scintigraphy is a useful tool to evaluate preoperative cardiac risk. HYPOTHESIS: The purpose of this study was to assess the utility of adenosine stress dual-isotope [rest 201Tl/stress technetium-99m (99mTc) sestamibi] myocardial single-photon emission computed tomography (SPECT) in predicting the risk of perioperative cardiac events (unstable angina, myocardial infarction, cardiac death) in patients undergoing major noncardiac surgery. METHODS: We evaluated 43 consecutive patients (20 men, 23 women, mean age 64 years, range 30-83 years) within 8 weeks prior to major noncardiac surgery requiring general anesthesia. SPECT imaging was performed with 111 MBq (3 mCi) 201Tl at rest and 925 MBq (25 mCi)99mTc sestamibi during adenosine stress. RESULTS: Of the 43 patients, 15 (35%) had stress-induced ischemia and 28 (65%) did not. Perioperative cardiac events occurred in 4 (27%) of the 15 patients with stress-induced ischemia (2 unstable angina, 2 nonfatal myocardial infarctions) and in none of the 28 patients without inducible ischemia (p = 0.02). CONCLUSION: Adenosine stress dual-isotope myocardial SPECT is useful in determining the preoperative cardiac risk of patients undergoing major noncardiac surgery.

Adenosine↗

Osthole increases glycosylation of hepatitis B surface antigen and suppresses the secretion of hepatitis B virus in vitro.

During screening of Chinese herbal medicines for the activities against hepatitis B virus (HBV), a known pure compound, osthole, was found to inhibit the secretion of HBV surface antigens in vitro. The secretion of hepatitis B surface antigen (HBsAg) in culture medium of MS-G2 and HuH-7 cells transfected with HBV DNA decreased by 60% to 70% after osthole treatment, without any detectable cytotoxic effects. Both 42-nm Dane particles and 22-nm subviral HBsAg particles were significantly reduced as revealed by density gradient analysis of viral particles and the endogenous; HBV DNA polymerase assay. The production of naked HBcAg particles was not changed by osthole treatment. The steady-state level of HBV-specific messenger RNA (mRNA) was not altered by osthole treatment, as revealed by Northern blot analysis, Immunoprecipitation of culture medium showed that the ratio of glycosylated versus nonglycosylated HBsAg increased after osthole treatment. Kinetic studies revealed that osthole increased the glycosylation rate of HBsAg, thus altering the ratio of glycosylated to unglycosylated HBsAg. The increase of glycosylation of HBsAg by osthole was blocked by tunicamycin, an inhibitor of protein glycosylation. We conclude that osthole suppresses the secretion of HBV in cell culture probably because of its novel function in increasing the glycosylation of HBsAg.

Antiviral Agents↗

TGF-beta 1, IL-10 and IL-4 differentially modulate the cytokine-induced expression of IL-6 and IL-8 in human endothelial cells.

Multiple cytokines and growth factors are present at sites of inflammation, and each of these can potentially influence the nature of the inflammatory response. Vascular endothelial cells (ECs) must integrate the signals generated by these multiple factors to effectively regulate the immune response and homeostasis. IL-6 and IL-8 and endothelial-derived products which play an important role as regulators of these processes. As a model for how ECs respond to signals from multiple cytokines, we have examined the effects of pretreatment with TGF-beta 1, IL-10 or IL-4 on TNF-alpha, IL-1 beta- or LPS-induced expression of IL-6 and IL-8 in human umbilical vein endothelial cells (HUVEC). Treatment of HUVEC with TGB-beta 1 or IL-10 significantly inhibited, but did not completely abolish, the TNF-alpha-, IL-1 beta- or LPS-induced expression of IL-6 and IL-8 protein. Maximal inhibition was achieved with physiologically relevant doses (1-2 ng/ml) of either TGF-beta 1 or IL-10. The inhibitory effects of TGF-beta and IL-10 were additive in nature. In contrast, pretreatment with IL-4 amplified the production of IL-6 in TNF-alpha-, IL-1 beta- or LPS-activated ECs, but inhibited IL-8 expression. Addition of TGF-beta 1 completely reversed the effects of IL-4 on IL-6 expression, whilst augmenting inhibition of IL-8. These studies demonstrate that multiple cytokines can act in concert to differentially regulate the endothelial expression of cytokines important to the inflammatory response. Modulation of endothelial cytokine production may contribute to the progression or resolution of the inflammatory response.

Cell Division↗

Phantom evaluation of simultaneous thallium-201/technetium-99m aquisition in single-photon emission tomography.

This study investigated downscatter effects in cardiac single-photon emission tomographic studies with simultaneous thallium-201/technetium-99m acquisition, and evaluated a previously proposed subtraction technique for downscatter compensation. Ten studies were carried out with different defect sizes and locations and varying activity distributions using four energy windows: 70+/-10% keV, 140+/-10% keV, 100+/-10% KeV, and 103+/-16% keV. The subtraction technique used the 100- or 103-keV data to remove scattered 99mTc counts from the 70-keV data. The size and contrast of infarcts in the dual-isotope 70-keV image were artificially decreased compared to those in the 140-keV image, caused by scattered 99mTc counts that were comparable to the primary 201Tl counts in the 70-keV window. The subtraction technique produced larger defects and more heterogeneous activity in the myocardial wall in dual-isotope 70-keV images compared to the corresponding 201Tl-only images. These artifacts were caused by the markedly different spatial distributions of scattered 99mTc counts in the 100-keV (or 103-keV) window as compared with the 70-keV window. It is concluded that scattered 99mTc photons may cause overestimation of ischemia and myocardial viability in simultaneous dual-isotope patient studies. The proposed subtraction technique was inaccurate and produced image artifacts. Adequate downscatter compensation methods must be developed before applying simultaneous 201Tl/99mTc acquisition in clinical practice.

Artifacts↗

Coping strategies and psychiatric morbidity in women attending breast assessment clinics.

This study examined the role of coping strategies and personality characteristics in mediating psychiatric morbidity in subjects facing possibly serious breast disease. Participating were 121 women aged 20 to 65 undergoing breast fine needle biopsy for a suspicious lesion on mammography. All subjects received psychosocial assessments including the 12-item General Health Questionnaire (GHQ-12), the Eysenck Personality Inventory (EPI) and the Coping Strategies Inventory. The results show that neuroticism was the only EPI subscore significantly correlated with GHQ-12 score. A habitual method of coping with adversity known as 'engagement' has a negative correlation with GHQ-12 score; that is, patients who actively confront their illness and the uncertainty that surrounds it show better psychological health. Stepwise multiple regression reveals that neuroticism and an engagement coping strategy are the most significant predictors towards GHQ-12 score prior to the diagnosis of breast cancer.

Adaptation, Psychological↗

Pharmacokinetics of osthole in rat plasma using high-performance liquid chromatography.

A simple high-performance liquid chromatographic method was developed to study the pharmacokinetics of osthole in rat plasma. After addition of an internal standard (paeonol), plasma was deproteinized by acetonitrile for sample clean-up. The drugs were separated on a reversed-phase column and detected by UV absorption at 323 nm. Acetonitrile-water-diethylamine (50:50:0.1, v/v/v) (pH 3.0, adjusted with orthophosphoric acid) was used as the mobile phase. It was applied to the pharmacokinetic study of osthole in rats after a dose of 10 mg kg-1 by intravenous administration. A biphasic phenomenon with a rapid distribution followed by a slower elimination phase was observed from the plasma concentration-time curve.

Adjuvants, Immunologic↗

Arachidonic acid stimulates the intrinsic activity of ubiquitous glucose transporter (GLUT1) in 3T3-L1 adipocytes by a protein kinase C-independent mechanism.

Exposure of adipocytes to arachidonic acid rapidly enhanced basal 2-deoxyglucose uptake, reaching maximal effect at approximately 8 hr. Insulin-stimulated 2-deoxyglucose uptake was not altered over the experimental period. While the short-term (2-h exposure) effect of arachidonic acid was negligibly influenced by cycloheximide, the enhancement of glucose transport by long-term (8-h) exposure to arachidonic acid was markedly decreased by the simultaneous presence of protein-synthesis inhibitors, implying that the short-term and long-term effects of arachidonic acid may involve distinct mechanisms. Immunoblot analysis revealed that 8-h but not 2-h exposure to arachidonic acid increased the content of the ubiquitous glucose transporter (GLUT1) in both total cellular and plasma membranes. The insulin-responsive glucose transporter (GLUT4), on the other hand, was not affected. Following 2-h exposure to arachidonic acid, kinetic studies indicated that the apparent Vmax of basal 2-deoxyglucose uptake was more than doubled, while the apparent Km for 2-deoxyglucose remained unchanged. Protein kinase C (PKC) depletion by pretreating cells with 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) for 24 h had little influence on the subsequent enhancing effect of arachidonic acid on 2-deoxyglucose uptake. In addition, PMA was able to stimulate 2-deoxyglucose uptake in arachidonic-acid-pretreated cells with similar increments as in non-treated cells. Thus, our data seem to suggest that arachidonic acid may enhance the intrinsic activity of GLUT1 by a PKC-independent mechanism.

3T3 Cells↗

Cloning and characterization of cDNAs encoding the antibacterial peptide, defensin A, from the mosquito, Aedes aegypti.

Insect defensins are cationic, inducible antibacterial peptides. Four full-length cDNAs encoding defensin A from the mosquito Aedes aegypti were cloned using polymerase chain reaction (PCR) and sequenced. All four cDNAs are 473 base pairs long, bearing an open reading frame of 98 amino acids with a few substitutions in the signal peptide domain. The deduced amino acid sequence of Aedes aegypti defensin (AaDef) contains a signal peptide sequence of 18 amino acids followed by a 40-amino acid putative propeptide domain and a 40-amino acid mature peptide domain. The mature peptide, with a predicted M(r) of 4148, shows 80% identity and 93% similarity to Phormia defensin A, and is identical to the peptide sequencing data for mosquito defensin A of Lowenberger et al. (1995) and B of Chalk et al. (1995). There are three potential phosphorylation sites but no glycosylation sites detected in AaDef. Three putative disulfide linkages between cysteines, characteristic of insect defensins, are conserved in AaDef. Aedes aegypti defensin mRNA is produced in response to a bacterial challenge; it is dramatically enhanced 6 h after bacterial injection, continues to increase through 24 h, and is maintained at high levels until at least 30 h post-bacterial injection.

Aedes↗

Experience with distal circular myotomy for long-gap esophageal atresia.

From 1980 to 1994, the authors treated 65 cases of esophageal atresia (with or without tracheoesophageal fistula). Among these patients, 15 (23%) underwent pure proximal circular myotomies and five (8%) underwent both proximal and distal circular myotomies. Of the latter five cases, three were Gross type C and two were Gross type A. The gap ranged from 4.5 cm to 6.5 cm (mean, 5 cm). Surgical complications in these five patients included two anastomotic leaks (40%), one anastomotic stricture (20%), and four gastroesophageal refluxes (80%). Three patients eventually underwent fundoplication as an antireflux procedure. Mucosal outpouching was noted in all cases. The myotomy did not adversely affect the esophageal peristalsis and motility on the esophagogram. Esophageal function was similar to that of other children who had esophageal atresia without myotomy. All patients could eat food typical for their age. This limited experience suggests that distal circular myotomy might be a safe adjuvant procedure to achieve primary anastomosis in long-gap esophageal atresia.

Anastomosis, Surgical↗

The rectoanal relaxation reflex and continence in repaired anorectal malformations with and without an internal sphincter-saving procedure.

From 1985 to 1994, 27 patients with high- or intermediate type imperforate anus who underwent anorectoplasty were studied for postoperative function, particularly with respect to the rectoanal relaxation reflex and continence. Fourteen of the patients had a rectourogenital fistula and were treated with posterior sagittal anorectoplasty using the fistular end as the neoanus (internal sphincter-saving). Nine patients had a blind rectal pouch and received posterior sagittal anorectoplasty using the trimmed bowel end for reconstruction of the neoanus (incomplete internal sphincter-saving). The other four had Rehbein's mucosa-stripping endorectal pull-through combined with anterior sagittal anorectoplasty (none internal sphincter-saving). A positive rectoanal relaxation reflex was found in 8 of 14 (57.1%), 7 of 9 (77.8%), and 3 of 4 (75%), respectively. It appears that the internal sphincter-saving procedure is not essential for the development of the rectoanal relaxation reflex. Compensation or adaptation most likely contributes to the presence of the rectoanal relaxation reflex, and perhaps to postoperative continence.

Anal Canal↗

Clonal Epstein-Barr virus associated cholangiocarcinoma with lymphoepithelioma-like component.

Epstein-Barr virus (EBV) has been linked to several undifferentiated carcinomas of the aerodigestive tract, especially the nasopharynx, but has not been reported in the biliary tract. We here presented a case of an unusual cholangiocarcinoma harboring EBV genome in a 47-year-old Chinese woman. Physical examination in 1988 in Taiwan, including abdominal sonography of the liver, was essentially negative. She experienced three episodes of malaria in 1990 when she worked in Ghana, Africa, and felt a tumor mass in the epigastrium in October 1992. She received an extended left lobectomy for a huge hepatic tumor of 12 x 10 x 5.5 cm in February 1993. Light microscopy revealed a cholangiocarcinoma composed of both well-differentiated adenocarcinoma and lymphoepitheliomatous undifferentiated carcinoma components. Abundant EBV EBER1 was shown in both tumor components, but not in the nontumor liver. Southern blot analysis and polymerase chain reaction showed a monoclonal episomal form of EBV, with a genotype characteristic for Chinese EBV strain type 1. This finding suggests that the EBV infection preceded monoclonal EBV-harboring tumor cell expansion in this case.

Base Sequence↗

Utility of lentil lectin affinity of alpha-fetoprotein in the diagnosis of hepatocellular carcinoma.

AIMS/METHODS: Frozen sera obtained from 70 patients (35 with hepatocellular carcinoma and 35 with benign chronic liver disease) with serum alpha-fetoprotein > 20 ng/ml were studied to evaluate the diagnostic indices of lentil lectin affinity of alpha-fetoprotein in detecting hepatocellular carcinoma. RESULTS: The proportion of alpha-fetoprotein-L3 was significantly higher in patients with hepatocellular carcinoma than in those with benign chronic liver disease (41.0 +/- 33.6% vs. 16.4 +/- 15.3%, p < 0.001). This difference led to a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 57, 89, 83, 67 and 73%, respectively, in detecting hepatocellular carcinoma using the proportion of alpha-fetoprotein-L3 > 35% as a parameter. Within a 1-year period, 1500 high-risk persons were collaborating, leading to 22 cases with serum total alpha-fetoprotein > 20 ng/ml. These 22 cases included six pregnant women. The parameter, alpha-fetoprotein-L3 > 35% was used along with sonography to detect hepatocellular carcinoma for the remaining 16 cases. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 75, 83, 60, 91 and 81%, respectively, by the proportion of alpha-fetoprotein-L3 > 35%; and 100, 92, 80, 100 and 94%, respectively, by sonography. CONCLUSIONS: Lentil lectin affinity of alpha-fetoprotein provides a moderately high sensitivity and a high specificity in the detection of hepatocellular carcinoma for persons with high alpha-fetoprotein levels. It may be a useful adjuvant tool of sonography and total alpha-fetoprotein level in a mass survey of hepatocellular carcinoma for a high-risk population.

Aged↗

Antiplatelet flavonoids from seeds of Psoralea corylifolia.

The MeOH extract of the seeds of Psoralea corylifolia L. was found to inhibit the aggregation of rabbit platelets induced by arachidonic acid, collagen, and platelet activating factor. Bioassay-directed fractionation led to the isolation of three flavonoids, isobavachalcone (1), neobavaiso-flavone (2), and bavachin (3). Compounds 1 and 2 inhibited platelet aggregation.

Animals↗

New prenylflavones from the leaves of Epimedium saggitatum.

Five new prenylflavones, yinyanghuo A (1), yinyanghuo B (2), yinyanghuo C (3), yinyanghuo D (4), and yinyanghuo E (5), along with six known flavonoids, chrysoeriol, quercetin, apigenin, apigenin 7,4'-dimethyl ether, kaempferol, and luteolin, were isolated from the leaves of Epimedium sagittatum. Their structures were determined from spectral analysis. Compounds 1 and 2 showed significant antiplatelet induced by arachidonic acid.

Arachidonic Acid↗

Antiplatelet arylnaphthalide lignans from Justicia procumbens.

Fractionation of the EtOH extract of Justicia procumbens, guided by antiplatelet bioassay, led to the isolation of nine known arylnaphthalide lignans, neojusticin A (1), justicidin B (2), justicidin A (3), taiwanin E methyl ether (4), neojusticin B (5), chinensinaphthol methyl ether (6), taiwanin E (8), chinensinaphthol (9), and diphyllin (10), and a new arylnaphthalide lignan that was characterized by spectral means as 4'-demethylchinensinaphthol methyl ether (7). Compounds 1, 2, 4, and 8 significantly inhibited platelet aggregation.

Animals↗

Constraining volume by matching the moments of a distance distribution.

The problem of computing a molecular structure from a set of distances arises in the interpretation of NMR data as well as other experimental methods that yield distance information. Techniques for computing structures must find conformations consistent with the distance data. There are often other constraints on the structure that must be satisfied as well. One of the most problematic constraints is the constraint on the total volume occupied by the atoms. In this paper, we use the first two moments (mean and variance) of an estimated distance distribution to constrain the volume of a computed structure. We show that a probabilistic algorithm for matching the first two moments of the estimated distance distribution significantly improves the quality of the solution, especially when the distance information alone is not sufficient to define the structure precisely. We also show that our method is not sensitive to small errors in the estimates of mean and variance of the distance distribution. Finally, we demonstrate the use of this constraint in computing a low-resolution structure of the 30S prokaryotic ribosomal subunit. Quantitative analysis of our results allows us to assess the information content contained in constraints on volume, and to show that in some cases addition of a volume constraint adds information roughly equivalent to doubling the number of input distances. Our results also demonstrate the flexibility of probabilistic representations of structural constraints, and the importance of including volume information to constrain structural computations-especially in the case of sparse data.

Algorithms↗