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Biomedical subjects

R Yu

Publications and source records attributed to R Yu.

At least 73 records · Page 4Linked to original sources
PubMed1999

Docosahexaenoic acid ingestion inhibits natural killer cell activity and production of inflammatory mediators in young healthy men.

The purpose of this study was to examine the effects of feeding docosahexaenoic acid (DHA) as triacylglycerol on the fatty acid composition, eicosanoid production, and select activities of human peripheral blood mononuclear cells (PBMNC). A 120-d study with 11 healthy men was conducted at the Metabolic Research Unit of Western Human Nutrition Reach Center. Four subjects (control group) were fed the stabilization diet throughout the study; the remaining seven subjects were fed the basal diet for the first 30 d, followed by 6 g DHA/d for the next 90 d. DHA replaced an equivalent amount of linoleic acid; the two diets were comparable in their total fat and all other nutrients. Both diets were supplemented with 20 mg D alpha-tocopherol acetate per day. PBMNC fatty acid composition and eicosanoid production were examined on day 30 and 113; immune cell functions were tested on day 22, 30, 78, 85, 106, and 113. DHA feeding increased its concentration from 2.3 to 7.4 wt% in the PBMNC total lipids, and decreased arachidonic acid concentration from 19.8 to 10.7 wt%. It also lowered prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) production, in response to lipopolysaccharide, by 60-75%. Natural killer cell activity and in vitro secretion of interleukin-1beta and tumor necrosis factor alpha were significantly reduced by DHA feeding. These parameters remained unchanged in the subjects fed the control diet. B-cell functions as reported here and T-cell functions that we reported previously were not altered by DHA feeding. Our results show that inhibitory effects of DHA on immune cell functions varied with the cell type, and that the inhibitory effects are not mediated through increased production of PGE2 and LTB4.

Administration, Oral↗
PubMed1999

Pharmacodynamics and toxicodynamics of drug action: signaling in cell survival and cell death.

In therapeutic response to drugs, the plasma concentration range leads to the establishment of a safe and effective dosage regimen. Our hypothesis is that by studying drug concentration-dependent effect on signal transduction mechanisms, a better understanding of the beneficial pharmacodynamic and adverse toxicodynamic responses elicited by the drug may be achieved. Using two classes of chemopreventive compounds (phenolic antioxidants and isothiocyanates), we illustrate the potential utility of two signal transduction pathways elicited by these agents to predict the pharmacodynamic effect (induction of Phase II drug metabolizing enzymes) and the potential toxicodynamic response (stimulation of caspase activity and cytotoxic cell death). At lower concentration, phenolic antioxidants and isothiocyanates activate mitogen-activated protein kinase (MAPK; extracellular signal-regulated protein kinase 2, ERK2; and c-Jun N-terminal kinase 1, JNK1) in a concentration-and time-dependent manner. The activation of MAPK by these compounds may lead to the induction of cell survival/protection genes such as c-jun, c-fos, or Phase II drug metabolizing enzymes. However, at higher concentrations, these agents activate another signaling molecule, ICE/Ced3 cysteine protease enzymes (caspases) leading to apoptotic cell death. The activation of these pathways may dictate the fate of the cells/tissues upon exposure to drugs or chemicals. At lower concentrations, these compounds activate MAPK leading to the induction of Phase II genes, which may protect the cells/tissues against toxic insults and therefore may enhance cell survival. On the other hand, at higher concentrations, these agents may activate the caspases, which may lead to apoptotic cell death, and have toxicity. Understanding the activation of these and other signal transduction events elicited by various drugs and chemicals may yield insights into the regulation of gene expression of drug metabolizing enzymes and cytotoxicity. Thus, the study of signaling events in cell survival (hemeostasis) and cell death (cytotoxicity) may have practical application during pharmaceutical drug development.

Animals↗
PubMed1999

Phase I clinical/pharmacokinetic and pharmacodynamic trial of the c-raf-1 antisense oligonucleotide ISIS 5132 (CGP 69846A).

PURPOSE: Raf-1 is a protein kinase that plays a broad role in oncogenic signaling and acts as a downstream effector of Ras in the mitogen-activated protein kinase pathway. The present study was designed to determine the maximum-tolerated dose (MTD), toxicity profile, pharmacokinetics, and antitumor activity of the c-raf-1 antisense oligodeoxynucleotide ISIS 5132 (CGP 69846A; ISIS Pharmaceuticals Inc, Carlsbad, CA). The effect of ISIS 5132 on c-raf-1 gene expression in peripheral-blood mononuclear cells (PBMCs) of treated patients was studied using a reverse transcriptase polymerase chain reaction assay. PATIENTS AND METHODS: Patients with refractory malignancies received ISIS 5132 as a 2-hour intravenous infusion three times weekly for 3 consecutive weeks. Pharmacokinetic sampling was performed during the first cycle in all patients; PBMCs for c-raf-1 mRNA analysis were collected at baseline and on days 3, 5, 8, and 15 of cycle 1 and on day 1 of each cycle thereafter. RESULTS: Thirty-one patients received ISIS 5132 at one of nine dose levels ranging from 0.5 mg/kg to 6.0 mg/kg. Clinical toxicities included fever and fatigue, but these were not dose limiting. A clinically defined MTD was not reached. The harmonic mean half-life of ISIS 5132 was 59.8 minutes (range, 35.5 to 107.3 minutes). The area under the concentration-time curve increased linearly with dose, and mean plasma clearance was 1.86 mL/kg/min (range, 1.21 to 2.41 mL/kg/min). Two patients experienced prolonged stable disease lasting more than 7 months, which was associated with persistent reduction in c-raf-1 expression in PBMCs. Significant decreases in c-raf-1 expression were identified at time points after the baseline value (P <.05) at doses >/= 2.5 mg/kg. CONCLUSION: ISIS 5132 is well tolerated at doses up to 6.0 mg/kg when administered as a thrice weekly 2-hour infusion for 3 consecutive weeks. The pharmacokinetic behavior of the drug is reproducible, and suppression of target gene expression is observed in circulating PBMCs.

Adult↗
PubMed1999

Studies on the callus cultures of Ginkgo biloba and its metabolites-ginkgolides.

The production of ginkgolides in callus culture of Ginkgo biloba was reported. The affection of some physical factors and chemical substances on the induction and growth of calli was also investigated. A biologically quantitative method (platelet aggregation induced by PAF) and HPLC were successfully used for the determination of Ginkgolides A and B in all kinds of callus cultures. The result showed that the content of Ginkgolides B in the callus cultures varies from 0.005% to 0.01%, which is one of the best results for the callus culture of G.biloba in the world.

2,4-Dichlorophenoxyacetic Acid↗
PubMed1999

[In vitro study on cellular and molecular mechanism of tripterine treating leukemic mast cells].

OBJECTIVE: To explore the effect of tripterine on leukemic mast cells. METHODS: The human leukemic mast cell line (HMC-1) was used as target cells for the tripterine's effect. RESULTS: 1. Apoptosis of HMC-1 cells could be efficiently induced by tripterine (0.125-1.0 mumol/L), showing the apoptotic changes in morphology, DNA ladder on argarose gel electrophoresis and apoptotic peak before G1 phase of cell cycle on flowcytometry. 2. The magnitude of apoptosis increased with the augmentation of tripterine concentration and duration of exposure; 3. With G1 phase cells decreasing, S phase cells were increased, and then apoptotic cells increased with a diminution of S phase cells. They bored significant negative relation (P < 0.01); 4. Tripterine could upregulate Bax, c-myc expression and downregulate bcl-2 expression at protein level. CONCLUSION: Tripterine can efficiently induce HMC-1 cell apoptosis, occurring mainly in S phase, which is correlated with upregulating Bax, c-myc expression and downregulating bcl-2 expression.

Antineoplastic Agents, Phytogenic↗
PubMed1999

[Effect of Yiqi Zishen granule on ultrastructure of glomeruli of IgA nephropathy in mice].

OBJECTIVE: To study the effect and therapeutical mechanism of Yiqi Zishen granule (YQZSG) in treating IgA nephropathy. METHODS: One hundred and fifty mice were divided into 5 groups randomly, in every treatment group, the relevant drugs were given. Their kidney tissues were observed with light microscope and electron microscope in batches at the 3rd, 6th, 9th and 12th week. RESULTS: The glomerular mesangial cells and mesangial matrix were proliferative in the model group at the 6th, 9th and 12th week. The light density of glomeruli, the mesangial area, the numeral density of mesangial cells and the light density of mesangial matrix in the model group were obviously higher, the change of large and small dosage YQZSG group and positive Chinese drug group were similar, but milder in pathological degree. The light density of glomerulus area, the mesangial area, the numeral density of mesangial cells and the light density of mesangial matrix in large dosage YQZSG group were significantly lower than those in the model group (P < 0.05 or P < 0.01). CONCLUSION: YQZSG could inhibit the proliferation of mesangial cells and the mesangial matrix in IgA nephropathy.

Animals↗
PubMed1999

[Detection of TNF-alpha and NCF in the serum and BALF of patients with sarcoidosis and evaluate their clinical significance].

OBJECTIVE: To evaluate the role of cytokines released by the inflammatory cells and immunocytes from patients in pathogenesis of developing sarcoidosis. METHODS: With well- microchemotaxis and allergy immunology, the level of tumor necrosis factor-alpha (TNF-alpha) and neutrophil chemotactic factor (NCF) was measured in the serum and BALF of 11 sarcoidosis and 7 IPF and 8 normal subjects (non-smokers). RESULTS: The levels of TNFalpha (11.9 +/- 3.2, 11.7 +/- 3.0 ng x L(-1)) and NCF (191 +/- 51, 203 +/- 44 cell x 10HP(-1)) of BALF in the patients with sarcoidosis and IPF were significantly higher than these in control group (P < 0.01) and were higher than those in serum. The level of TNF-alpha in the BALF of patients with sarcoidosis was positively correlated with the percentage of lymphocytes (r = 0.73, P < 0.01). The activity of NCF in the BALF of patients with IPF was positively correlated with the percentage of neutrophils (r = 0.89, P < 0.01). CONCLUSIONS: It indicated that TNF-alpha and NCF might play an important role in the pathogenetic process of the sarcoidosis and IPF, and can act as the marker of activity of these diseases.

Adult↗
PubMed1999

[In vitro studies on the bioactive materials released by lung fibroblasts in experimental pulmonary fibrosis].

OBJECTIVES: The purpose of the present study was to clarify the consecutive changes and roles of hyaluronan (HA), interleukin-8 (IL-8) and collagen production by lung fibroblasts in the course of pulmonary fibrosis. METHODS: Quantitative and comparative assessments of the HA, IL-8 and collagen (presented by hydroproline; HYP) levels in lung fibroblast-conditioned media were made at various stages during the development of bleomycin-induced pulmonary fibrosis in rats. RESULTS: In lung fibroblast-conditioned media of bleomycin-treated animals: (1) The HA levels increased significantly on day 1, peaked on day 3, and then gradually declined and returned to control values on days 14 - 28. (2) The IL-8 levels strikingly increased on day 1, reached the peak values on day 7, thereafter, gradually decreased, regained control values by day 28. (3) The collagen levels increased significantly on day 7, peaked on day 14, and then gradually declined, However, remained significantly above normal values on day 28. (4) In bleomycin group, the HA and IL-8 levels both significantly correlated to cell components in BALF. CONCLUSIONS: The lung fibroblasts were activated, produced increased HA and IL-8, and were the main source of HA and IL-8 within the lung in the early stage of pulmonary fibrosis; increased HA and IL-8 synthesis of lung fibroblasts might reflect the intensity of alveolitis and the disease activity; The excessive collagen deposition within the lung primarily occurred at the middle stage of pulmonary fibrosis.

Animals↗
PubMed1999

[Synthetic assessment of health impact of cerebrovascular diseases on potential health days of life lost].

OBJECTIVE: To assess synthetically the impact on population health caused by cerebrovascular diseases. METHODS: Incidence, duration of disease, disabilities and deaths of cerebrovascular diseases were analyzed with potential health days of life lost (PHDLL) as an indicator in urban areas of Changsha, Hunan Province. RESULTS: The PHDLL caused by cerebrovascular disease totaled 2 624.94 days per thousand of population, 33.01% of them attributed to deaths and 53.44% to chronic disability. CONCLUSION: Hemorrhagic cerebrovascular disease mainly lead to death and ischemic one caused chronic disability.

Adolescent↗
PubMed1999

[A study on family aggregation of type 2 diabetes mellitus].

OBJECTIVE: To estimate the genetic susceptibility and its relative risk (RR) in the first degree relatives of type 2 diabetes mellitus (DM) through family aggregation analysis. METHODS: A population-based case-control study including 654 pedigrees (363 index cases and 291 controls) was carried out. RESULTS: The prevalence rate in the first degree relatives of DM probands was 3.94%, significantly higher than that in the controls (1.09%), with a relative risk of 3.62 (chi(2) = 36.5, P < 0.001). The RRs in different consanguineal relatives were all higher than 3.0. The younger was the probands at diagnosis for DM, the higher its prevalence rates and RRs among their relatives was and the more likelihood that more than one case of DM occurred in them. CONCLUSION: Significant family aggregation and higher genetic susceptibility were found in the first degree relatives of DM, on whom prevention and treatment for DM should be focused.

Adult↗
PubMed1998

Individual sex preferences and the population sex ratio of newborns.

This paper proposes the hypothesis that countries with stronger sex preferences are more likely to have a negative relationship between crude birth rates and male/female ratios of newborn babies. Conversely, the existence of a significantly negative relationship in any country may also be a supportive evidence of its preferences for sons. Our hypothesis is both behavioral and biological: on the behavioral side, parents with strong sex preferences are inclined to continue to bear children if the existing sex ratio of children is less than desirable. On the biological side, parents with many girls are more likely to be "girl producers", who with individual-specific biological characteristics tend to generate higher female births. We use the macro data in the United Nations Demographic Yearbook to verify and test our hypothesis. For developing countries which do not have reliable micro data on fertility, our approach using macro data is a useful and interesting alternative.

Female↗
PubMed1998

Autofluorescence bronchoscopy in the detection of squamous metaplasia and dysplasia in current and former smokers.

BACKGROUND: New methods are needed to detect precancerous lesions in lung tissue. We conducted a study to determine the utility of LIFE (laser-induced fluorescence emission) autofluorescence bronchoscopy for the detection of squamous metaplasia and dysplasia in current and former smokers. METHODS: In this prospective, single-center study, 53 participants underwent standard white-light bronchoscopy and 39 underwent both white-light and LIFE bronchoscopy. Bronchial biopsy specimens were obtained from all participants at six pre-determined sites using white-light bronchoscopy and from all other sites that appeared to be abnormal in participants who underwent LIFE bronchoscopy. Relationships between LIFE imaging and histologic findings were examined for 245 biopsy specimens obtained from those participants who had undergone LIFE bronchoscopy. RESULTS: LIFE imaging revealed abnormalities designated as either class II or class III in 89 (36.3%) and 16 (6.5%) of the 245 sites examined, respectively, and histopathologic examination showed dysplasia and metaplasia in eight (3.3%) and in 52 (21.2%) of the 245 specimens, respectively. Among the 105 biopsy specimens obtained from sites with abnormal LIFE imaging, only 26 (24.8%) exhibited squamous metaplasia and/or dysplasia, similar to the findings for sites with normal LIFE imaging (34 [24.3%] of 140). Comparison of individuals examined by LIFE imaging with those who underwent white-light bronchoscopy alone revealed no increase in the detection of dysplasia or metaplasia with LIFE bronchoscopy. CONCLUSION: In this population of current and former smokers, abnormalities detected by LIFE bronchoscopy did not improve the detection of squamous metaplasia or dysplasia.

Adult↗
PubMed1998

Induction of apoptosis and activation of interleukin 1beta-converting enzyme/Ced-3 protease (caspase-3) and c-Jun NH2-terminal kinase 1 by benzo(a)pyrene.

Benzo(a)pyrene (BaP), a prototype of polycyclic aromatic hydrocarbons (PAHs), is a potent procarcinogen generated during the combustion of fossil fuels and cigarette smoke. In addition to the carcinogenic and mutagenic effects, BaP and other PAHs, including 7,12-dimethylbenz[a]anthracene and 2,3,7,8-tetrachlorodibenzo[p]dioxin, have been shown to induce programmed cell death or apoptosis. However, the molecular mechanisms by which PAHs such as BaP induce apoptosis are not clear. To investigate the molecular events leading to apoptosis induced by BaP, we studied the involvement of the interleukin 1beta-converting enzyme (ICE)/Ced-3 family of proteases (caspases) and c-Jun NH2-terminal kinase 1 (JNK1), which have been shown to mediate numerous extracellular stimuli-induced apoptosis. On treatment of mouse Hepa 1c1c7 hepatoma cells with BaP, the induction of apoptosis, as determined by genome digestion, was observed at concentrations of 1-30 microM after 24 h of treatments. Importantly, at the apoptosis-inducing concentrations, BaP also induced the activation of an ICE/Ced-3 cysteine protease caspase-3 but not caspase-1 (ICE). The activation of caspase-3 by BaP preceded apoptosis. Furthermore, a specific inhibitor of caspase-3-like proteases, acetyl-Asp-Glu-Val-Asp-aldehyde, significantly blocked caspase-3 activity and attenuated apoptosis induced by BaP. Treatment with BaP also caused a time- and dose-dependent activation of JNK1 activity. Interestingly, a much lower concentration (5 nM), as well as much earlier kinetics, were observed in JNK1 activation as compared with caspase-3 activation or induction of apoptosis by BaP. In summary, our results demonstrate that BaP induced apoptosis in the mouse hepatoma Hepa1c1c7 cell line via a caspase-dependent pathway, which may be independent of JNK activation.

Animals↗
PubMed1998

Chemopreventive isothiocyanates induce apoptosis and caspase-3-like protease activity.

Isothiocyanates exert strong anticarcinogenic effects in a number of animal models of cancer, presumably by modulation of xenobiotic-metabolizing enzymes, such as by inhibition of cytochrome P-450 and/or by induction of phase II detoxifying enzymes. Here, we report that phenethyl isothiocyanate and other structurally related isothiocyanates, phenylmethyl isothiocyanate, phenylbutyl isothiocyanate, and phenylhexyl isothiocyanate, but not phenyl isothiocyanate induced apoptosis in HeLa cells in a time- and dose-dependent manner. Treatment with apoptosis-inducing concentrations of isothiocyanates also caused rapid and transient induction of caspase-3/CPP32-like activity. Furthermore, these isothiocyanates, except phenyl isothiocyanate, stimulated proteolytic cleavage of poly(ADP-ribose) polymerase, which followed the appearance of caspase activity and preceded DNA fragmentation. Pretreatment with a potent caspase-3 inhibitor acetyl-Asp-Glu-Val-Asp-aldehyde inhibited isothiocyanate-induced caspase-3-like activity and apoptosis. These results suggest that isothiocyanates may induce apoptosis through a caspase-3-dependent mechanism. The induction of apoptosis by isothiocyanates may provide a distinct mechanism for their chemopreventive functions.

Anticarcinogenic Agents↗
PubMed1998

Biochemical evidence for a conserved interaction between bacterial transferrin binding protein A and transferrin binding protein B.

As an adaptation to the iron-restricted environment of the host, some bacterial pathogens possess iron acquisition pathways mediated by surface receptors that specifically bind transferrin from the host. The receptor is composed of two receptor proteins, TbpA and TbpB, which are both capable of binding to transferrin. Previous studies have demonstrated that affinity isolation of TbpB from Neisseria meningitidis or Haemophilus influenzae with immobilized human transferrin required the homologous TbpA, implicating a TbpA-TbpB interaction. In this study, we demonstrated that TbpA from either species can facilitate isolation of either TbpB, indicating that the TbpA-TbpB interaction is conserved within these species. Extension of these studies to veterinary pathogens in which a TbpA-Tf complex is used to affinity isolate heterologous TbpBs, demonstrated an interaction between the receptor proteins from N. meningitidis and Actinobacillus pleuropneumoniae. Further delineation of the TbpA-TbpB-transferrin interaction with recombinant chimeric N. meningitidis/A. pleuropneumoniae TbpBs has identified a region encoded by the first 1/4 of the tbpB gene which is involved in Tf binding.

Actinobacillus pleuropneumoniae↗
PubMed1998

Optical fiber sensor for tetracycline antibiotics based on fluorescence quenching of covalently immobilized anthracene.

A new optical fiber sensor for tetracycline is fabricated with an anthracene-containing copolymer prepared from 9-anthrylmethyl methacrylate, methyl methacrylate and n-butyl acrylate (PAMB). The sensing relies on the fact that the fluorescence of the sensor membrane fabricated with PAMB can be strongly quenched by the tetracycline antibiotics extracted from the sample. The proposed sensor responds linearly in the measuring ranges 2.02 x 10(-7)-2.02 x 10(-4) mol l-1 tetracycline (TC), 2.00 x 10(-7)-2.03 x 10(-4) mol l-1 oxytetracycline (OTC) and 4.05 x 10(-7)-2.03 x 10(-4) mol l-1 doxycycline (DC) and has detection limits of 1.00 x 10(-7) mol l-1 for TC and OTC, and 2.00 x 10(-7) mol l-1 for DC. The leaching of anthracene from the sensor membrane was hindered by covalent immobilization, resulting in a drastically enhanced sensor lifetime. Moreover, the sensor can rapidly respond to the antibiotics of interest (ca. 30s) and exhibits good reproducibility, reversibility, and selectivity in the presence of some common pharmaceutical species as well as alkali and alkali-earth metal salts. The sensor was used for the direct assay of tetracycline antibiotics in commercial pharmaceutical preparations and urine. The results are comparable to those obtained by conventional spectrophotometry. The recovery for tetracycline antibiotics from urine samples is also satisfactory.

Anti-Bacterial Agents↗
PubMed1998

Receptors for thyrotropin-releasing hormone on rat lactotropes and thyrotropes.

Primary cultures of rat pituitary cells were stained with an antibody to the native thyrotropin-releasing hormone (TRH) receptor and with a bioactive, fluorescent analogue of TRH, Rhod-TRH. Rhod-TRH specifically stained 86% of lactotropes and 21% of nonlactotropes from primary pituitary cell cultures. Lactotropes and thyrotropes accounted for 90% of cells that stained with Rhod-TRH, but there were occasional lactotropes and thyrotropes that did not show detectable staining with antireceptor antibodies or with Rhod-TRH. The intensity of staining was generally higher in the GH3 line of tumor cells than in normal pituicytes, and 100% of the tumor cells stained with Rhod-TRH. To determine whether the TRH receptor undergoes ligand-directed endocytosis in normal cells, TRH receptor immunocytochemistry was performed before and after TRH binding. TRH receptors were localized on the surface of cells prior to TRH exposure, and Rhod-TRH fluorescence was confined to the plasma membrane when TRH binding was performed at 0 degrees C, where endocytosis is blocked. When cells were incubated with TRH at 37 degrees C, receptors were found in intracellular vesicles in both lactotropes and thyrotropes, and Rhod-TRH was rapidly internalized into endosomes at elevated temperatures. Internalization of Rhod-TRH was inhibited by hypertonic sucrose, indicating that it occurs through clathrin-coated pits. These findings show that some of the heterogeneity in the secretory and calcium responses of pituicytes to TRH occurs at the level of the TRH receptor.

Amino Acid Sequence↗