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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
PubMed2000

[Effect of extract from overground part of Tripterygium wilfordii Hook. f. on Masugi nephritis in rabbits].

OBJECTIVE: To observe the effect of extract from overground part of Trpterygium wilfordii on Masugi nephritis in rabbits. METHOD: Masugi nephritis was made by giving i.v. the rabbit an injection of sheep antirabbit serum. RESULT: The extract could effectively inhibit the increase of uric protein, serum BUN, creatinine and glomerulus cells in rabbits. CONCLUSION: The extract from overground part of Tripterygium wilfordii has better curative effect on Masugi nephritis in rabbits.

Albuminuria↗
PubMed2000

[An experimental study on traumatic brain injury for inducing neuronal apoptosis in rats].

This study was designed to explore the effect of traumatic brain injury and its mechanism for inducing neuronal apoptosis. The model of experimental traumatic brain injury was used. The rats were dispatched at different times(3 h, 12 h, 24 h, 48 h, 72 h) after traumatic brain injury, and the neuronal apoptosis was evaluated with microscope (HE staining), TUNEL method, flow cytometry, gel electrophoresis and immunohistochemistry assay. The results showed that the brain tissue neurons treated by traumatic brain injury underwent morphological changes of apoptosis, the DNA presented "ladder" break, the rate of neuronal apoptosis at different times ranged from 9.8% to 14.0%, but that of the control group was 1.7% and the expressions of related apoptosis genes(c-myc, fas and fasL) were increased. The findings of this study indicate that traumatic brain injury can induce neuronal apoptosis, and its molecular mechanism might be related to the expression of some apoptosis genes.

Animals↗
PubMed2000

[Effectiveness of recombinant human growth hormone treatment for severe burn injury].

In order to investigate the effectiveness and safety of recombinant human growth hormone(rhGH) treatment for severe burn injury, we designed a randomized prospective study. The patients in rhGH group were given rhGH in a dose of 0.5 IU/(kg.d) subcutaneously between days 3-17 post-burn. Indices about protein metabolism, wound healing, hepatic and renal function and blood were measured regularly. Patients were monitored until their wound healed sufficiently so that they could be discharged for rehabilitation. The results showed: all patients survived; the rhGH group had less weight loss, increased level of serum albumin and shorter healing time of deep partial-thickness burn and donor site. The hospital stay time decreased from the control value of 45 +/- 17 days to 37 +/- 12 days for rhGH treated patients, i.e. a significant improvement. Resistant hyperglycemia was present in 2 patients in the rhGH group and disappeared after transient insulin administration. This study demonstrates that rhGH treatment for severe burn injury has obvious beneficial effects with slight side-effects.

Adult↗
PubMed2000

[The analysis of the axises of corneal astigmatism and total astigmatism in astigmatic patients].

PURPOSE: The axial amount and the relationship between the axises of corneal astigmatism and total astigmatism were statistically analyzed in ametropic patients, for the purpose of selecting the refractive correction, the base curve of contact lens, the axis of astigmatic contact lens, and providing the reference of operational amount of ecimer laser keratoplasty. METHODS: The refractive state and the corneal curvature of ametropic patients were measured and consecutvely repeated 3 times in the same eye at the same state with the same autorefractometer in 107 cases. The detected axises of total astigmatism and corneal astigmatism were statistically analyzed through the computerized recording. RESULTS: The mean angle between the axis of corneal astigmatism and the axis of total astigmatism was 5.73 degrees +/- 3.97 degrees in myopic patients, 3.13 degrees +/- 2.49 degrees in mixture astigmatism patients and 6.35 degrees +/- 4.20 degrees in hyperopic patients. CONCLUSION: The angle between the axis of corneal astigmatism and the axis of total astigmatism in the refractive state was mainly caused by the difference of the axises of surface astigmatism of lens and cornea.

Adolescent↗
PubMed1999

Role of a mitogen-activated protein kinase pathway in the induction of phase II detoxifying enzymes by chemicals.

Mitogen-activated protein kinase (MAPK) cascades are activated by diverse extracellular signals and participate in the regulation of an array of cellular programs. In this study, we investigated the roles of MAPKs in the induction of phase II detoxifying enzymes by chemicals. Treatment of human hepatoma (HepG2) and murine hepatoma (Hepa1c1c7) cells with tert-butylhydroquinone (tBHQ) or sulforaphane (SUL), two potent phase II enzyme inducers, stimulated the activity of extracellular signal-regulated protein kinase 2 (ERK2) but not c-Jun N-terminal kinase 1. tBHQ and SUL also activated MAPK kinase. Inhibition of MAPK kinase with its inhibitor, PD98059, abolished ERK2 activation and impaired the induction of quinone reductase, a phase II detoxifying enzyme, and antioxidant response element (ARE)-linked reporter gene by tBHQ and SUL. Overexpression of a dominant-negative mutant of ERK2 also attenuated tBHQ and SUL induction of ARE reporter gene activity. Interestingly, although expression of Ras and its mutant forms showed distinct effects on basal ARE reporter gene activity, they did not affect the activation of reporter gene by the inducers. Furthermore, a dominant-negative mutant of Ras had little effect on ERK2 activation by tBHQ and SUL, implicating a Ras-independent mechanism. Indeed, both tBHQ and SUL were able to stimulate Raf-1 kinase activity in vivo as well as in vitro. Thus, our results indicate that the induction of ARE-dependent phase II detoxifying enzymes is mediated by a MAPK pathway, which may involve direct activation of Raf-1 by the inducers.

Animals↗
PubMed1999

Effects of capsaicin on induction of c-jun proto-oncogene expression in Fisher-344 rats by N-methyl-N'-nitro-N-nitrosoguanidine.

N-Methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a potent inducer of cellular stress leading to chromosomal aberrations, point mutations, and cell death. To study the effect of capsaicin on c-jun expression when given with MNNG to rats, Fisher-344 rats that had been administered MNNG were treated with capsaicin in their diet and organs were removed for measuring c-jun transcripts. We show that pre- or post-treatment of capsaicin relative to MNNG administration up- or down-regulates (depending on the organ) c-jun expression in a consistent pattern in most organs. In fact, we found in this study that capsaicin inhibits c-jun induction, stimulated by MNNG, in the spleen, heart, stomach and lung. Since MNNG, a methylating agent, is a powerful carcinogen that is very effective in the induction of c-jun mRNA, the results suggest that capsaicin uptake in the diet could play a role in inhibition of tumorigenesis induced by MNNG.

Animals↗
PubMed1999

Signal transduction and hormone-dependent internalization of the thyrotropin-releasing hormone receptor in cells lacking Gq and G11.

The thyrotropin-releasing hormone (TRH) receptor was expressed in embryonic fibroblasts from mice lacking the alpha subunits of Gq and G11 (Fq/11 cells) to determine whether G protein coupling is necessary for agonist-dependent receptor internalization. Neither TRH nor agonists acting on endogenous receptors increased intracellular calcium unless the cells were co-transfected with the alpha subunit of Gq. In contrast, temperature-dependent internalization of [3H]MeTRH in Fq/11 cells was the same whether Gqalpha was expressed or not. A rhodamine-labeled TRH analog and fluorescein-labeled transferrin co-localized in endocytic vesicles in Fq/11 cells, indicating that endocytosis took place via the normal clathrin pathway. Cotransfection with beta-arrestin or V53D beta-arrestin increased TRH-dependent receptor sequestration. Fq/11 cells were co-transfected with the TRH receptor and a green fluorescent protein (GFP)-beta-arrestin conjugate. GFP-beta-arrestin was uniformly distributed in the cytoplasm of untreated cells and quickly translocated to the periphery of the cells when TRH was added. A truncated TRH receptor that lacks potential phosphorylation sites in the cytoplasmic carboxyl terminus signaled but did not internalize or cause membrane localization of GFP-beta-arrestin. These results prove that calcium signaling by the TRH receptor requires coupling to a G protein in the Gq family, but TRH-dependent binding of beta-arrestin and sequestration do not.

Animals↗
PubMed1999

Serum antioxidative vitamin levels and lipid peroxidation in gastric carcinoma patients.

Serum antioxidative vitamin levels and lipid peroxidation in gastric cancer patients were compared with values for age-matched healthy subjects. Blood samples were collected from the stomach of cancer patients scheduled for surgical removal of their tumor. Serum ascorbic acid, alpha-tocopherol, beta-carotene, and retinol in serum were determined by high-performance liquid chromatography, and malondialdehyde levels were analyzed spectrophotometrically. General health characteristics and taste preference for spicy and/or salty food were assessed by a self-administered questionnaire. Significant decreases in serum ascorbic acid and beta carotene were observed in stomach cancer patient as compared to the control group. The levels of ascorbic acid in patients with gastric carcinoma were less than one-fifth of the control. Beta carotene and alpha-tocopherol levels in the serum of the cancer patients were significantly decreased compared to the control group, but there were no differences in retinol between the groups. Serum malondialdehyde levels were significantly higher in the cancer patients than in controls. The levels of ascorbic acid and alpha-tocopherol tend to be lower in the patient with a preference for spicy and salty food than in others without the preference. Our results demonstrate that a correlation existed between the levels of serum ascorbic acid and beta carotene, alpha-tocopherol and lipid peroxidation in gastric carcinoma.

Antioxidants↗
PubMed1999

Differential regulation of mitogen-activated protein kinases by microtubule-binding agents in human breast cancer cells.

Drug design targeted at microtubules has led to the advent of some potent anti-cancer drugs. In the present study, we demonstrated that microtubule-binding agents (MBAs) taxol and colchicine induced immediate early gene (c-jun and ATF3) expression, cell cycle arrest, and apoptosis in the human breast cancer cell line MCF-7. To elucidate the signal transduction pathways that mediate such biological activities of MBAs, we studied the involvement of mitogen-activated protein (MAP) kinases. Treatment with taxol, colchicine, or other MBAs (vincristine, podophyllotoxin, nocodazole) stimulated the activity of c-jun N-terminal kinase 1 (JNK1) in MCF-7 cells. In contrast, p38 was activated only by taxol and none of the MBAs changed the activity of extracellular signal-regulated protein kinase 2 (ERK2). Activation of JNK1 or p38 by MBAs occurred subsequent to the morphological changes in the microtubule cytoskeleton induced by these compounds. Furthermore, baccatine III and beta-lumicolchicine, inactive analogs of taxol and colchicine, respectively, did not activate JNKI or p38. These results suggest that interactions between microtubules and MBAs are essential for the activation of these kinases. Pretreatment with the antioxidants N-acetyl-L-cysteine (NAC), ascorbic acid or vitamin E, blocked H2O2- or doxorubicin-induced JNKI activity, but had no effect on JNKI activation by MBAs, excluding a role for oxidative stress. However, BAPTA/AM, a specific intracellular Ca2+ chelator, attenuated JNK1 activation by taxol but not by colchicine, and had no effect on microtubule changes induced by taxol. Thus, stabilization or depolymerization of microtubules may regulate JNK1 activity via distinct downstream signaling pathways. The differential activation of MAP kinases opens up a new avenue for addressing the mechanism of action of antimicrotubule drugs.

Apoptosis↗
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↗