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Biomedical subjects

C Chen

Publications and source records attributed to C Chen.

At least 307 records · Page 17Linked to original sources
PubMed2000

N-terminal determinants of I kappa B alpha necessary for the cytoplasmic regulation of c-Rel.

I kappa B alpha is a dual regulator of Rel/NF-kappa B transcription factors. I kappa B alpha retains inactive NF-kappa B dimers in the cytoplasm, and inhibits their DNA-binding and transcriptional activities in the nucleus. Our previous studies identified discrete functional domains in I kappa B alpha responsible for the cytoplasmic and nuclear regulation of c-Rel. Determinants necessary for regulating c-Rel in the nucleus mapped to the central ankyrin domain of I kappa B alpha and a few negatively-charged amino acids that follow in the C-terminal PEST region. In contrast, sequences involved in the cytoplasmic regulation of c-Rel reside in the N-terminal and central ankyrin domains of I kappa B alpha. Here, we present a refined mapping of the N-terminal determinants of I kappa B alpha necessary for the cytoplasmic regulation of c-Rel homodimers. We demonstrate that amino acids 48 - 58 in p40/I kappa B alpha are essential to block the nuclear localization of c-Rel dimers. These data define a region of I kappa B alpha that may be required for optimal masking of the c-Rel NLS, or for the nuclear export of c-Rel/I kappa B alpha complexes. These findings highlight a novel function for the N-terminus of I kappa B alpha in the control of the subcellular localization of Rel/NF-kappa B dimers. Given the implication of deregulated NF-kappa B activity in hematopoietic and solid tumors, our findings predict that certain alterations in this domain of I kappa B alpha may have severe biological repercussions.

Animals↗
PubMed2000

Production and characterization of simian--human immunodeficiency virus-like particles.

We have produced and characterized, in a baculovirus expression system, simian-human immunodeficiency virus-like particles (SHIV VLPs) containing SIV Gag and HIV envelope (Env) proteins. Recombinant SIV gag (SIVmac239) and full-length or cytoplasmic domain-truncated HIV env from either HIV BH10 or HIV 89.6 virus were coexpressed in insect cells and Env incorporation into released SHIV VLPs was characterized. The expression level of the Env protein was found to be about 20-50% higher in both strains producing the truncated Env. Cell surface expression of the truncated Env proteins was found to be about eightfold higher than that of the full-length Env proteins. Furthermore, the truncated Env proteins exhibited higher levels of cleavage into gp120 and gp41 compared with the full-length Env. The SHIV VLPs produced by the coexpression of SIV gag and truncated HIV env contained both precursor (gp160) and gp120, while predominantly gp160 was found in the VLPs containing full-length Env. Coinfection of a recombinant virus expressing the protease furin also resulted in more efficient cleavage of gp160 to gp120. Both full-length and truncated Env were found to induce CD4+ cell fusion. Analysis of VLPs by immunoelectron microscopy demonstrated the incorporation of both full-length and truncated Env on the surface of VLPs. Truncated Env also was incorporated at higher levels on the surfaces of VLPs than full-length Env. The assembly of VLPs containing biologically active Env proteins may be useful in vaccine development and in functional studies of the HIV envelope protein.

Animals↗
PubMed2000

Photoelectron diffraction imaging for C2H2 and C2H4 chemisorbed on Si(100) reveals a new bonding configuration

A new adsorption site for adsorbed acetylene on Si(100) is observed by photoelectron imaging based on the holographic principle. The diffraction effects in the carbon 1s angle-resolved photoemission are inverted (including the small-cone method) to obtain an image of the atom's neighboring carbon. The chemisorbed acetylene molecule is bonded to four silicon surface atoms. In contrast to the C2H2 case, the image for adsorbed C2H4 shows it bonded to two Si surface atoms.

Journal Article↗
PubMed2000

Regulatory science: a special update from the United States Food and Drug Administration: Preclinical issues and status of investigation of botanical drug products in the United States.

A recent survey was conducted across the therapeutic divisions within the CDER, U.S. FDA regarding the number of submissions related to botanical drug products over the past ten years. The overall number of botanical submissions as expressed in the parenthesis are as follows: 1990 (1), 1991 (4), 1992 (4), 1993 (5), 1994 (6), 1995 (5), 1996 (13), 1997 (16), 1998 (10). In the total of 64 counted, 50 of them are submitted in original IND and the rest (14) in pre-IND format. The therapeutic categories are focused on dermatological and topical (19), anti AIDS/antiviral (12), oncologic (13), neuropharmacologic (8), endocrine and metabolic (3), urologic (2), tobacco (2), and cardio-renal products (1). The regulatory actions taken on these submissions showed that 68% of them are evaluated as safe to proceed for the human trials, while the rest (32%) of submissions required agency's regulatory guidance. Among the submissions that required further guidance, 81% were deficient in preclinical pharmacology/toxicology information and the rest (19%) lacks information in other areas (chemistry, clinical protocols). Following agency's guidance, 93% of the submissions that were put on hold were allowed to proceed. In summary, a total of 94% of all the botanical INDs submitted to the agency were allowed to proceed without additional animal toxicity studies conducted. In conclusion, this survey indicates that the growing public interest in botanical supplements has prompted more formal evaluation of the efficacy/safety claims of these products.

Databases, Factual↗
PubMed2000

Body mass index and cardiovascular risk factors in a rural Chinese population.

The metabolic consequences of obesity are well-documented in Western populations. However, limited data are available on the association between body mass index (BMI) and cardiovascular risk factors in developing countries. The authors therefore examined the association between BMI and cardiovascular risk factors in a very lean population in China. A total of 2,542 subjects aged 20-70 years from a rural area of Anqing, China, participated in a cross-sectional survey, and 1,610 provided blood samples in 1993. Mean BMI (kg/m2) was 20.7 for men and 20.9 for women. After adjustment for age, sex, education level, occupation, current alcohol use, and cigarette smoking, BMI was significantly associated with systolic and diastolic blood pressures (p < 0.0001). The adjusted odds ratio for hypertension (systolic pressure > or =140 mmHg or diastolic pressure > or = 90 mmHg) across quintiles of BMI (quintile medians: 18.0, 19.4, 20.6, 21.8, and 24.0) were 1.0, 1.34, 2.46, 2.61, and 4.90 (95% confidence interval: 3.20, 7.50). A higher BMI was directly associated with higher levels of serum total cholesterol, triglycerides, and fasting glucose and lower levels of high density lipoprotein cholesterol. These data from a very lean Chinese population confirm independent relations between body mass and cardiovascular risk factors observed in predominantly overweight Western populations and extend the range of associations to lower BMI levels than do previous studies.

Adult↗
PubMed2000

LEUNIG has multiple functions in gynoecium development in Arabidopsis.

The Arabidopsis gene LEUNIG was previously found to regulate floral organ identity. In this work we describe gynoecial phenotypes of newly isolated strong leunig alleles, leunig-101, leunig-102, and leunig-103. Gynoecia of these strong leunig mutants are united only at the basal part, leaving four unfused parts at the apex. Among them two medial ones are styles capped with stigmas, and two lateral ones are protrusions from valves. The gynoecium with unfused apex in leunig arises as a unit from a basal meristematic zone, suggesting that LEUNIG is required for normal congenital gynoecium fusion. The epidermal cells on growing inner surfaces of leunig gynoecium failed to fuse after they contact each other, indicating that LEUNIG is essential for the proper postgenital fusion. The epidermal cells at the very distal portion of protruded valves mimic those on wild-type styles, and those valves occasionally also have stigma-like tissues, indicating that LEUNIG function is required for the valve identity determination. We have also analyzed clavata1-4 leunig-101, clavata2-1 lug-101, fruitfull-1 leunig-101, and pinoid-1 leunig-101 double mutants. clavata1-4 leunig-101 and clavata2-1 leunig-101 exhibited additive phenotypes of single mutants, suggesting that LEUNIG and CLAVATA genes function in different pathways. In contrast, FRUITFULL and PINOID genes interact with LEUNIG to regulate gynoecium development. genesis 26:42-54, 2000.

Alleles↗
PubMed2000

Short-chain fatty acids inhibit the release and content of growth hormone in anterior pituitary cells of the goat.

The effects of short-chain fatty acids (SCFA: acetate, propionate, and butyrate) on growth hormone (GH)-releasing hormone (GHRH)-induced GH secretion from pituitary somatotrophs were assessed on isolated anterior pituitary cells of goats. Cells were cultured in Dulbecco's modified Eagle's medium for 3 days, either in the presence (1, 3, or 10 mM) or in the absence of each SCFA, and then stimulated with GHRH (10(-12) to 10(-7) M) for 30 min, again in the presence of and at the concentration of SCFA used over the previous 3 days. In the cells cultured in the absence of SCFA, the addition of SCFA to the medium during the GHRH stimulation period did not significantly change GHRH-induced GH release. However, in cells cultured in the presence of either propionate (3 or 10 mM) or butyrate (1, 3, or 10 mM), the addition of SCFA to the medium during GHRH stimulation significantly reduced the GHRH-induced GH release. The inhibitory effects of SCFA were dependent on the concentrations of SCFA and were greater for butyrate than for propionate. In the cells cultured in the presence of butyrate, but not in the absence, the total GH production (the sum of the released GH and the remaining GH after stimulation) was also significantly reduced. The GHmRNA expression was reduced in the cells cultured with 10 mM butyrate, whereas it was enhanced by the stimulation with 10(-7) M GHRH. These findings suggest that propionate and butyrate may inhibit GHRH-induced GH release and GH production by caprine anterior pituitary cells.

Acetates↗
PubMed2000

Fluorescence Excitation Spectrum of a (2)Pi(3/2)-(2)Pi(3/2) Transition of NiF.

In this study, a supersonic beam of NiF was produced by the reaction of SF(6) with a dc discharge-sputtering source of nickel atoms. The laser-induced fluorescence excitation spectrum of a (2)Pi(3/2)-(2)Pi(3/2) transition has been recorded in the range of 500-520 nm and rotational structure of 506.5-nm band analyzed under the 30 K rotational temperature. Our data are consistent with a (2)Pi(3/2) ground state for NiF. The lifetime of this band is measured. Copyright 2000 Academic Press.

Journal Article↗
PubMed2000

Effects of homocysteine on smooth muscle cell proliferation in both cell culture and artery perfusion culture models.

BACKGROUND: Hyperhomocysteinemia is associated with increased risk for vascular disease. However, the pathogenic mechanisms of homocysteine are largely unknown. We evaluated the effects of homocysteine on smooth muscle cell (SMC) and endothelial cell proliferation in cell culture and on SMC proliferation of balloon angioplasty-injured arteries in a perfusion culture model. METHODS: Human and pig SMCs and endothelial cells were cultured with variable amounts of homocysteine for 72 h and the total cells were counted using a hemocytometer. Fresh pig carotid arteries were harvested from a local slaughterhouse and cultured in a newly designed artery perfusion culture system. Five groups of arteries (six per group) were cultured for 48 h under different conditions: normal control, balloon angioplasty injury alone, and injury with three different doses of homocysteine. Vessel viability was evaluated. SMC proliferation was assayed by bromodeoxyuridine (BrdU) DNA labeling. RESULTS: At concentrations equivalent to those in human hyperhomocysteinemia, homocysteine significantly stimulated both cultured human and pig SMC proliferation with a dose-dependent effect, while it inhibited cultured endothelial cell growth. Perfusion-cultured pig carotid arteries remained contractile in response to norepinephrine and relaxant to nitroglycerine, and viable cells were also isolated from the cultured arteries. SMC proliferation (BrdU index) showed significant differences among the groups. SMC proliferation was stimulated by vascular injury and further enhanced by homocysteine in a dose-dependent manner. The proliferative response occurred strongly on the luminal side of the vessel wall, with the effects tapering toward the adventitia. CONCLUSIONS: Homocysteine had a mitogenic effect on vascular SMCs and a cytotoxic effect on endothelial cells. This differential effect of homocysteine on vascular cells may represent a pathogenic mechanism of vascular lesion formation in patients with hyperhomocysteinemia.

Angioplasty, Balloon↗
PubMed2000

A new perfusion culture system used to study human vein.

BACKGROUND: Cell culture studies, ring studies, and indirect physiologic studies are the predominant models used to study human vascular tissue. Such studies are limited in their capacity to permit physiologic single-factor changes or to provide the proper mechanical stress or extracellular matrix present in normal tissues. We present a newly devised organ culture system that addresses these issues and permits survival of intact segments of human vascular tissue in a perfused environment. Our experience culturing human saphenous vein with this system is detailed. METHODS: Perfusion culture chambers were designed and constructed in our laboratory. Excess saphenous vein segments were collected from coronary artery bypass graft cases at our hospital and then mounted into our perfusion culture system for 0, 24, 48, 72, or 96 h. Vasomotor assays, hematoxylin and eosin staining, bromodeoxyuridine staining, and factor VIII staining were performed to assess tissue survival. RESULTS: A total of 24 veins were cultured. Average vessel length was 5 cm. The vessels contracted and relaxed the following amounts: time 0 (6.7% contraction, 5.0% relaxation), 24 h (5.7%, 5.3%), 48 h (5.2%, 2.8%), 72 h (4.8%, 5.3%), 96 h (4.8%, 3.8%). Hematoxylin and eosin staining, bromodeoxyuridine staining, and factor VIII staining support the viability of the tissue segments. CONCLUSION: A new perfusion organ culture system has been devised that permits survival of intact human venous tissue for periods up to 96 h. Studies that permit physiologic single-factor changes along with precise control of the hemodynamic environment are possible with this system.

Humans↗
PubMed2000

Hydrogen peroxide-induced oxidative damage and apoptosis in cerebellar granule cells: protection by Ginkgo biloba extract.

The ability of oxidative stress to induce apoptosis and the protective effects of Ginkgo biloba extract (EGb761) against this induction were studied in cultures of rat cerebellar granule cells. Cells were exposed to oxidative stress by treatment with 50 microm hydrogen peroxide+100 microm ferrous sulphate which generates hydroxyl radicals by Fenton reaction. Both morphological observation and biochemical analysis revealed that H(2)O(2)/FeSO(4)treatment induced apoptotic cell death in cerebellar granule cells, which was characterized by chromatin condensation and DNA fragmentation. During this process, the fluidity of the cell membrane decreased markedly, and the conformation of membrane proteins altered significantly. Pretreating cerebellar granule cells with the antioxidant EGb761 (Ginkgo biloba extract) effectively attenuated oxidative damage induced by H(2)O(2)/FeSO(4), and prevented cells from apoptotic cell death. The results suggested that EGb761 might be used as a potential drug for neuronal diseases associated with the excessive production of reactive oxygen species.

Animals↗
PubMed2000

Relationship between the expression of alpha 1-antitrypsinase in bronchioalveolar carcinoma and clinical pathology.

By using immunohistochemistry LSAB method and imaging analysis technique, the expression of alpha 1-antitrypsinase (alpha 1-AT) in 41 cases of bronchioalveolar carcinoma (BAC) was quantitatively detected to explore the relationship between alpha 1-AT expression in BAC tissues and clinical pathology. The results showed that the total positive rate for alpha 1-AT expression was 85.4%. The positive rate for alpha 1-AT expression in alveolar BAC was 100%, with the immunity reactive staining intensity being significantly higher than in papillary BAC, mucinous BAC or sclerosing BAC (P < 0.05). The positive rate in papillary BAC was 93.3%, with the intensity higher mucinous BAC or sclerosing BAC (P < 0.01); The positive rate in both mucinous BAC and sclerosing BAC was 66.7% (P > 0.05); The expression intensity in lymph node metastatic group was obviously lower than that in the group without metastasis (P < 0.01); The patients with mucinous BAC were diagnosed at a younger age than those with other histologic types of BAC (P < 0.05). It was suggested that BAC cells could also produce alpha 1-AT. Detection of alpha 1-AT could be used as a new method to diagnose BAC and might play a role in assessing BAC metastasis.

Adenocarcinoma↗
PubMed2000

Correlative expression of glutathione S-transferase-pi and multidrug resistance associated protein in bladder transitional cell carcinoma.

In order to elucidate the mechanisms of multidrug resistance (MDR) in bladder cancer, the expression of glutathione S-transferase-pi (GST-pi) and multidrug resistance associated protein (MRP) in tissue samples resected from 44 patients and 6 normal bladder mucosa as control was detected by using immunohistochemical method, and the results were analyzed by computer-assisted image analyzing system (IAS) to achieve semi-quantitative data. In addition, correlation between the expression of both factors was studied. The results showed that the positive expression rate of GST-pi and MRP in bladder cancer was 72.7% (32/44) and 68.2% (30/44) respectively, significantly higher than those in normal bladder mucosa, being 16.7% and 33.3% respectively. The rate of GST-pi positive staining was increased correspondingly with tumor grade and stage elevated, being higher in recurrent tumors treated by chemotherapy, but not significantly (P > 0.05). There was no significant differences between the expression of MRP and tumors' behaviors and clinical characters. However, the results demonstrated that the correlation between the expression of both resistant factors was very evident (r = 0.695, P < 0.0025). It was suggested that the activation of GST-pi and MRP might occur during malignant transformation of normal mucosa, but tumors' differentiation and progression could not be the unique factors that influenced both overexpression. Chemotherapy might be another important reason. The correlation of both indicated that there was a common mechanism regulating their expression probably, which made them play a pivotal role in chemotherapy drug resistance of bladder cancers.

Adult↗
PubMed2000

Activation of antioxidant-response element (ARE), mitogen-activated protein kinases (MAPKs) and caspases by major green tea polyphenol components during cell survival and death.

Green tea polyphenols (GTP) have been demonstrated to suppress tumorigenesis in several chemical-induced animal carcinogenesis models, and predicted as promising chemopreventive agents in human. Recent studies of GTP extracts showed the involvement of mitogen-activated protein kinases (MAPKs) in the regulation of Phase II enzymes gene expression and induction of apoptosis. In the current work we compared the biological actions of five green tea catechins: (1) induction of ARE reporter gene, (2) activation of MAP kinases, (3) cytotoxicity in human hepatoma HepG2-C8 cells, and (4) caspase activation in human cervical squamous carcinoma HeLa cells. For the induction of phase II gene assay, (-)-epigallocatechin-3-gallate (EGCG) and (-)-epicatechin-3-gallate (ECG) potently induced antioxidant response element (ARE)-mediated luciferase activity, with induction observed at 25 microM with EGCG. The induction of ARE reporter gene appears to be structurally related to the 3-gallate group. Comparing the activation of MAPK by the five polyphenols, only EGCG showed potent activation of all three MAPKs (ERK, JNK and p38) in a dose- and time-dependent manner, whereas EGC activated ERK and p38. In the concentration range of 25 microM to 1 mM, EGCG and ECG strongly suppressed HepG2-ARE-C8 cell-growth. To elucidate the mechanisms of green tea polyphenol-induced apoptosis, we measured the activation of an important cell death protein, caspase-3 induced by EGCG, and found that caspase-3 was activated in a dose- and time-dependent manner. Interestingly, the activation of caspase-3 was a relatively late event (peaked at 16 h), whereas activation of MAPKs was much earlier (peaked at 2 h). It is possible, that at low concentrations of EGCG, activation of MAPK leads to ARE-mediated gene expression including phase II detoxifying enzymes. Whereas at higher concentrations of EGCG, sustained activation of MAPKs such as JNK leads to apoptosis. These mechanisms are currently under investigation in our laboratory. As the most abundant catechin in GTP extract, we found that EGCG potently induced ARE-mediated gene expression, activated MAP kinase pathway, stimulated caspase-3 activity, and induced apoptosis. These mechanisms together with others, may contribute to the overall chemopreventive function of EGCG itself as well as the GTP

Antioxidants↗
PubMed2000

Signal transduction events elicited by natural products: role of MAPK and caspase pathways in homeostatic response and induction of apoptosis.

Many natural products elicit diverse pharmacological effects. Using two classes of potential chemopreventive compounds, the phenolic compounds and the isothiocyanates, we review the potential utility of two signaling events, the mitogen-activated protein kinases (MAPKs) and the ICE/Ced-3 proteases (caspases) stimulated by these agents in mammalian cell lines. Studies with phenolic antioxidants (BHA, tBHQ), and natural products (flavonoids; EGCG, ECG, and isothiocyanates; PEITC, sulforaphane), provided important insights into the signaling pathways induced by these compounds. At low concentrations, these chemicals may activate the MAPK (ERK2, JNK1, p38) leading to gene expression of survival genes (c-Fos, c-Jun) and defensive genes (Phase II detoxifying enzymes; GST, QR) resulting in survival and protective mechanisms (homeostasis response). Increasing the concentrations of these compounds will additionally activate the caspase pathway, leading to apoptosis (potential cytotoxicity). Further increment to suprapharmacological concentrations will lead to nonspecific necrotic cell death. The wider and narrow concentration ranges between the activation of MAPK/gene induction and caspases/cell death exhibited by phenolic compounds and isothiocyanates, respectively, in mammalian cells, may reflect their respective therapeutic windows in vivo. Consequently, the studies of signaling pathways elicited by natural products will advance our understanding of their efficacy and safety, of which many may become important therapeutic drugs of the future.

Animals↗
PubMed2000

Efficacy and safety of preoperative lobar or segmental ablation via transarterial administration of ethiodol and ethanol mixture for treatment of hepatocellular carcinoma: clinical study.

Transarterial embolization (TAE) using various thrombotic substances for unresectable hepatocellular carcinoma (HCC) performed on many patients has resulted in a better survival rate. We evaluated the efficacy and clinical safety of using an Ethiodol-ethanol mixture as the embolizer for treatment of HCC and the possibility of a surgical approach for inoperable tumors after TAE. Twenty patients with HCC who underwent TAE and tumor resection were included in the study. Initially, eight had increased retention rate of indocyanine green dye via intravenous injection (0.5 mg/kg) at 15 minutes (ICGR15), and six had an insufficient residual volume that precluded them from undergoing tumor resection. TAE was performed by slowly infusing the mixture of Ethiodol and ethanol into the artery supplying the tumor until dual hepatic artery and portal vein embolization was achieved. Serum levels of alanine aminotransferase increased after embolization, but all biochemistry studies reverted to normal within 2 weeks. A decreased tumor size (n = 15), improved ICG (n = 8), and increased volume of the nonembolized lobe (n = 10) were noted. The operations performed were right lobectomy (n = 11), extended right lobectomy (n = 3), left lobectomy (n = 2), extended left lobectomy (n = 2), and wedge resection (n = 2), which included patients who did not want to undergo major hepatectomy. Complete tumor necrosis was found in seven cases. All patients survived with no associated complications. The 1-year survival rate was 95%. Transarterial Ethiodol and ethanol administration creating dual hepatic artery and portal vein embolization was a safe and efficacious method for treating HCC. It effectively decreases tumor size, causes compensatory hepatic hypertrophy, and improves the ICGR15, which allows a wider range of patients to undergo liver surgery and achieve better survival.

Adult↗