Biomedical subjects

D Yu

Publications and source records attributed to D Yu.

At least 109 records · Page 6Linked to original sources

PubMed2000

Inhibitory effect of fluvastatin on aortic intimal thickening in normocholesterolemic rabbits.

OBJECTIVE: The anti-atherosclerotic effect of fluvastatin at does insufficient to lower serum cholesterol on the catheter-induced intimal thickering and possible mechanism were investigated in abdominal aorta of rabbits. METHODS: Fifty-six rabbits were randomly divided into eight groups (n = 7, each). Fluvastatin was given mixed with food at daily dose of 8 mg/kg starting 5 days before catheterization. Light microscope, immunohistochemistry, transmission electron microscope and RT-PCR assay were applied to assess vascular smooth muscle cell (VSMC) proliferation and apoptosis, as well as oncogene expression in vascular wall. RESULTS: At day 10 and day 15 after catheter induced denudation intima/media (I/M) thickness ratio was obviously higher, and also the percentage of PCNA-positive cells and TUNEL-positive cells in media was significantly higher compared with controls. The intimal hyperplasia was mostly composed of alpha-SM-actin-positive cells. In rabbits given fluvastatin I/M ratio and the percentage of these positive cells significantly decreased compared with those without fluvastatin. The overexpression of proto-oncogene H-ras mRNA and decreased expression of anti-oncogene p53 mRNA were found after vascular injury, whereas fluvastatin significantly reduced H-ras mRNA and increased p53 mRNA expression. CONCLUSION: Proliferation of VSMC in the media and the migration to the intima can be inhibited, and apoptosis of VSMC be induced by short-term use of fluvastatin after balloon catheter denudation, independent of serum lipid change. The underlying mechanism is presumably associated with the influence of fluvastatin on oncogene expression in the injured vascular wall.

Animals↗

PubMed2000

Nitric oxide inhibits a rise of ATP-introduced cytosolic free Ca2+ concentration and release from intracellular stored Ca2+.

OBJECTIVE: The effects of ATP-introduced a rise in cytosolic free Ca2+ concentration and inhibition of nitric oxide were investigated. METHOD: Measurement of free Ca2+ ([Ca2+]i) of cultured rat tail arterial smooth muscle cells using Fura-2/AM dual excitation wavelength spectrofluorometer. RESULTS: There are two components of [Ca2+]i can be evoked by ATP. One part is Ca2+ entry from Ca2+ channel and formed a plateau. The another part is a peak that released from Ca2+ store. Both of them can be inhibited by NO. CONCLUSION: The ATP induced [Ca2+]i rise that release Ca2+ from both Insp3 and ryanochine receptors and Ca2+ entry through calcium channels. The inhibition of NO on ATP induced [Ca2+]i rise that was mediated by cGMP.

Adenosine Triphosphate↗

PubMed2000

[Damage mechanisms of molecule in DNA aqueous solution induced by ultraviolet radiation].

After ultraviolet radiation treated at various time, the Raman spectra of herring sperm DNA in aqueous solution were presented. The analytic results showed that first, the out-ring amino group numeration of cytosine C4 site have reducing in the form of Raman hypochromicity; but C4O ketone group of derivative uracil assumed have not emerge with Raman hyperchromiciuy, in UV-induced DNA only with water molecule join in; second, the electron cloud of the main-groove side in pyrimidine ring have a tendency of slanting toward C6 site, which was beneficial to the deamination of C-->U transition, after some cytosine formed dipyrimidine with another adjacent pyrimidine; and third, with UV radiation, the characteristic peak 616 cm-1 of uracil N3C4 has arisen. Its very important, because the quality of the N3C4 bond have a great difference between cytosine and uracil. The result have not supported the model that cytosine can direct to be come off amino group for form the ketone type uracilo depend on UV-induced, therefore we have found that the process of get involved in imino tautomer state was probable exist by Raman spectroscopic technique.

DNA Damage↗

PubMed1999

Site of chemical modifications in CpG containing phosphorothioate oligodeoxynucleotide modulates its immunostimulatory activity.

Phosphorothioate oligodeoxynucleotides containing CpG motifs have immunostimulatory activity. Appropriate substitution of deoxynucleosides in the flanking region of CpG-containing phosphorothioate oligodeoxynucleotides with 2'-O-methylribonucleosides results in significant decreases or increases in their immunostimulatory activities. The results provide insights in how to chemically modify phosphorothioate oligodeoxynucleotides containing CpG motifs to suppress or enhance their immunostimulatory activity for different therapeutic uses.

Adjuvants, Immunologic↗

PubMed1999

Antitumor activity and pharmacokinetics of a mixed-backbone antisense oligonucleotide targeted to the RIalpha subunit of protein kinase A after oral administration.

Overexpression of the RIalpha subunit of cAMP-dependent protein kinase (PKA) has been demonstrated in various human cancers. PKA has been suggested as a potential target for cancer therapy. The goal of the present study was to evaluate an anti-PKA antisense oligonucleotide (mixed-backbone oligonucleotide) as a therapeutic approach to human cancer treatment. The identified oligonucleotide inhibited the growth of cell lines of human colon cancer (LS174T, DLD-1), leukemia (HL-60), breast cancer (MCF-7, MDA-MB-468), and lung cancer (A549) in a time-, concentration-, and sequence-dependent manner. In a dose-dependent manner, the oligonucleotide displayed in vivo antitumor activity in severe combined immunodeficient and nude mice bearing xenografts of human cancers of the colon (LS174T), breast (MDA-MB-468), and lung (A549). The routes of drug administration were intraperitoneal and oral. Synergistic effects were found when the antisense oligonucleotide was used in combination with the cancer chemotherapeutic agent cisplatin. The pharmacokinetics of the oligonucleotide after oral administration of (35)S-labeled oligonucleotide into tumor-bearing mice indicated an accumulation and retention of the oligonucleotide in tumor tissue. This study further provides a basis for clinical studies of the antisense oligonucleotide targeted to the RIalpha subunit of PKA (GEM 231) as a cancer therapeutic agent used alone or in combination with conventional chemotherapy.

Administration, Oral↗

PubMed1999

Brain-specific differentiation of mouse yolk sac endothelial cells.

Vascular endothelial cells exhibit diverse functional and biochemical properties that vary among tissues and organs, suggesting that differentiation of endothelial cells is influenced by their microenvironment. In this study, relatively undifferentiated endothelial cells from 9-day embryonic mouse yolk sac were co-cultured with 12-day embryonic mouse brain rudiments. Organ-specific differentiation of the yolk sac endothelial cells was monitored based on the expression and functional activities of two brain-specific endothelial cell markers, glucose transporter 1 (Glut-1) and P-glycoprotein. Immunochemical staining, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and functional assays demonstrated that yolk sac endothelial cells can acquire brain-specific properties after induction by brain rudiments. This result provides support for the hypothesis that endothelial cell heterogeneity is acquired during organogenesis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed1999

Effects of structure on alpha C-H bond enthalpies of amino acid residues: relevance to H transfers in enzyme mechanisms and in protein oxidation.

The bond dissociation enthalpies (BDE) of all of the amino acid residues, modeled by HC(O)NHCH(R)C(O)NH(2) (PH(res)), were determined at the B3LYP/6-31G//B3LYP/6-31G level, coupled with isodesmic reactions. The results for neutral side chains with phi, psi angles approximately 180 degrees, approximately 180 degrees in ascending order, to an expected accuracy of +/-10 kJ mol(-)(1), are Asn 326; cystine 330; Asp 332; Gln 334; Trp 337; Arg 340; Lys 340; Met 343; His 344; Phe 344; Tyr 344; Leu 344; Ala 345; Cys 346; Ser 349; Gly 350; Ile 351; Val 352; Glu 354; Thr 357; Pro-cis 358; Pro-trans 369. BDEs calculated at the ROMP2/6-31G//B3LYP/6-31G level exhibit the same trends but are approximately 7 kJ mol(-)(1) higher. All BDEs are smaller than those of typical secondary or tertiary C-H bonds due to the phenomenon of captodative stabilization. The stabilization is reduced by changes in the phi,psi angles. As a result the BDEs increase by about 10 kJ mol(-)(1) in beta-sheet and 40 kJ mol(-)(1) in alpha-helical environments, respectively. In effect the alpha C-H BDEs can be "tuned" from about 345 to 400 kJ mol(-)(1) by adjusting the local environment. Some very significant effects of this are seen in the current literature on H-transfer processes in enzyme mechanisms and in oxidative damage to proteins. These observations are discussed in terms of the findings of the present study.

Amino Acids↗

PubMed1999

Heregulin beta1-activated phosphatidylinositol 3-kinase enhances aggregation of MCF-7 breast cancer cells independent of extracellular signal-regulated kinase.

Heregulin (HRG) is a family of polypeptide growth factors derived from alternatively spliced genes. HRG can bind to receptor tyrosine kinases erbB3 and erbB4, thereby inducing erbB3 and erbB4 heterodimerization with erbB2, leading to receptor tyrosine phosphorylation and activating downstream signal transduction. Cell-cell homophilic adhesion (cell aggregation) is important in determining the structural organization and behavior of cells in tissues. In addition, tumor cell homophilic adhesion may affect invasive and metastatic potentials of cells. We report that HRG-beta1 can enhance aggregation of MCF-7 and SKBR3 human breast cancer cells. While investigating the downstream signals involved in HRG-beta1-enhanced cell aggregation, we observed that HRG-beta1 induced tyrosine phosphorylation of erbB2 and crbB3 receptor heterodimers and increased the association of the dimerized receptors with the 85-kDa subunit of phosphatidylinositol 3-kinase (PI3K). HRG-beta also increased the kinase activities of extracellular signal-regulated protein kinase (ERK) and PI3K in these cells. By using the mitogen-activated protein kinase/ERK 1 (MEK1) inhibitor PD98059 and PI3K inhibitors wortmannin and LY294002, we found that blocking the MEK1-ERK pathway had no effect on HRG-pbeta1-enhanced cell aggregation; however, blocking the PI3K pathway greatly inhibited HRG-beta1-mediated cell aggregation. Our study indicated that the HRG-beta1-activated MEK1-ERK pathway has no demonstrable role in the induction of cell aggregation, whereas HRG-beta1-activated PI3K is required for enhancing breast cancer cell aggregation. Because aggregation can contribute to invasion/metastasis phenotype of cancer cells, our results have provided one mechanism by which HRG-beta1-activated signaling of erbB receptors may affect invasive/metastatic properties of MCF-7 and SKBR3 breast cancer cells.

Breast Neoplasms↗

PubMed1999

Relative bioavailability of danazol in dogs from liquid-filled hard gelatin capsules.

Danazol was dissolved in non-aqueous mixtures containing either polyethylene glycol 400 or polysorbate 80, and filled into hard gelatin capsules at 50 mg concentrations. The bioavailability of these formulations was compared with commercial danazol capsules in a two-way crossover study using young female beagle dogs. Both formulations showed greater oral bioavailability when compared with either the 100 or 200 mg commercial brand of danazol. The bioavailability of the polyethylene glycol 400 and polysorbate 80 formulations was enhanced 3.7 and 15.8 times, respectively, when compared at the 100 mg dose level.

Animals↗

PubMed1999

Altered outward K(+) currents in Drosophila larval neurons of memory mutants rutabaga and amnesiac.

K(+) currents in cultured Drosophila larval neurons have been classified into four categories according to their inactivation time constants, relative amplitude, and response to K(+) channel blockers 4-AP and tetraethylammonium. The percentage (65%) of neurons displaying K(+) currents which were reduced to 30% in amplitude by 5 mM cyclic adenosine monophosphate (cAMP) analog 8-bromo-cAMP in both Drosophila memory mutants rutabaga (rut) and amnesiac (amn) was significantly larger than that (50%) in wild type. This initial characterization provides evidence for altered K(+) currents in both rut and amn mutants. Arachidonic acid, a specifical inhibitor of Kv4 family (shal) K(+) channels, was found to inhibit K(+) currents in cultured Drosophila neurons, suggesting the presence of shal channels in these neurons.

4-Aminopyridine↗

PubMed1999

A physiologically based pharmacokinetic model of inorganic arsenic.

This study presents a physiologically based pharmacokinetic model of inorganic arsenic disposition in humans. The model focuses on short-term exposures by the oral route. The model considers the four circulating species (AsIII, AsV, and two metabolites, i.e., monomethylarsenic (MMA) and dimethylarsenic (DMA)) in tissue groups. The model also provides for the reduction of AsV to AsIII via chemical reaction with tissue glutathione and the subsequent transformation of AsIII into two metabolites (MMA and DMA) based on the experimental observations. Effort on the development of the model is directed toward the prediction of the kinetic behavior of inorganic arsenic in the body, following environmental exposure at ambient water concentrations, including tissue and blood concentrations, and especially urinary excretion of arsenic and its methylated metabolites. While it is difficult to estimate some of parameters used in the model at this time, the current model assumptions and predictions seem to be consistent with the experimental observations found in the literature. Therefore, the current model, when more fully developed, is expected to provide insight into the behavior of inorganic arsenic and its methylated metabolites within the body and may help increase the understanding of risk assessment issues associated with inorganic arsenic in drinking water.

Administration, Oral↗

PubMed1999

Clonal growth of human acute leukemia cells in serum-free methylcellulose medium.

The clonal growth of human acute leukemia cell line (K562) and acute myeloid leukemia cells in the serum-free culture (SFC) was studied in order to establish a SFC system which could replace the effects of serum by using semi-solid methylcellulose culture technique. Our results showed that the clonal growth of K562 cells in semi-solid culture was dependent on exogenous serum. The K562 could be grown in SFC supplemented with 4 major replacing substances. The multifactor and multilevel orthogonal experiment demonstrated that the colony formation was statistically influenced by the 4 replacing substances at various concentrations (P < 0.01). Among them, bovine serum albumin had greatest effect on clonal growth of K562 cells with the optimal concentration being 15 mg/L, followed by transferring, cholesterol and insulin with their optimal concentrations being of 150 mg/L, 7.8 mg/L and 7.0 mg/L respectively. SFC system was formed with the 4 substances at their optimal concentrations. Colony formation of the blast cells in 10 patients with acute myeloid leukemia was observed in this SFC system. There was a heterogeneity of acute myeloid leukemia cells among the 10 patients in response to the growth substances. In SFC system, there was a linear relationship between the number of the clonal formation and the count of the added cells, indicating the colony growth of the cells. Primary acute leukemia cells maintained in SFC system in 10 cases could completely form clones. The colony formation number in some cases in SFC system was more than that of the serum-containing culture. The SFC system could partially replace the serum for study of the clonal formation of human leukemia cells.

Cell Division↗

PubMed1999

The comprehensive evaluation on four indices of drug resistance in acute myeloid leukemia.

To study sensitivity of drug resistance indexes and resistance manner in acute myeloid leukemia (AML), MTT drug sensitivity, growth types of CFU-L in vitro, Bcl-2 antigen and Bcl-2/Bax ratio and intracellular fluorescence intensity of daunorubicin (DNR) were determined. In 62 cases of AML, the positive coincidence rate was 73% with MTT test and the negative coincidence rate was 70%. In 3 commonly used drugs, if one drug showed sensitivity, the coincidence remission rate reached 71%. In 51 cases of AML, there were 31 patients in the group of complete remission (CR), in which CFU-L of 29 patients showed independent growth. CFU-L of 2 patients showed no growth. However, there were 20 patients in the group of non-remission (NR), in which CFU-L of 14 patients showed independent growth. CFU-L of 6 patients showed non-growth pattern. Statistical analysis showed significant difference (P < 0.05). In 32 cases of AML, the expression rate of Bcl-2 was 59.55% +/- 19.56% in drug-sensitive group, and one was 77.36% +/- 11.91% in drug-resistant group, respectively (P < 0.05). At the same time, the ratio of Bcl-2/Bax was 7.50 +/- 5.04 in drug-sensitive group and one was 14.32 +/- 8.99 in drug-resistant group, respectively (P < 0.05). In 15 case of clinically drug-resistant AML, the fluorescence histogram of DNR showed left-shift of main peak (LSMP) in 12 patients. They were diagnosed as classical drug resistance. Meanwhile, 1 patient showed right-shift of main peak (RSMP) in 3 patients. They were diagnosed as re-growth drug resistance. It is concluded that MTT and CFU-L might be used for prediction of drug sensitivity or resistance when patients were on treatment. Bcl-2 and ratio of Bcl-2/Bax might be associated with the prognosis. DNR histogram could be employed for identify the pattern drug resistance. The strength and weakness of these techniques were discussed.

Adult↗

PubMed1999

Evaluation of In-111 DTPA-paclitaxel scintigraphy to predict response on murine tumors to paclitaxel.

UNLABELLED: Our goal was to determine whether scintigraphy with 111In-DTPA-paclitaxel could predict the response to chemotherapy with paclitaxel. METHODS: Ovarian carcinoma (OCA 1), mammary carcinoma (MCA-4), fibrosarcoma (FSA) and squamous cell carcinoma (SCC VII) were inoculated into the thighs of female C3Hf/Kam mice. Mice bearing 8 mm tumors were treated with paclitaxel (40 mg/kg). The growth delay, which was defined as the time in days for tumors in the treated groups to grow from 8 to 12 mm in diameter minus the time in days for tumors in the untreated control group to reach the same size, was measured to determine the effect of paclitaxel on the tumors. Sequential scintigraphy in mice bearing 10 to 14 mm tumors was conducted at 5, 30, 60, 120, 240 min and 24 hrs postinjection of 111In-DTPA-paclitaxel (3.7MBq) or 111In-DTPA as a control tracer. The tumor uptakes (% injection dose/pixel) were determined. RESULTS: The growth delay of OCA 1, MCA-4, FSA and SCC VII tumors was 13.6, 4.0, -0.02 and -0.28 days, respectively. In other words, OCa 1 and MCA-4 were paclitaxel-sensitive tumors, whereas FSA and SCC VII were paclitaxel-resistant tumors. The tumor uptakes at 24 hrs postinjection of In-111 DTPA paclitaxel of OCA 1, MCA-4, FSA and SCC VII were 1.0 x 10(-3), 1.6 x 10(-3), 2.2 x 10(-3) and 9.0 x 10(-3) % injection dose/pixel, respectively. There was no correlation between the response to chemotherapy with paclitaxel and the tumor uptakes of 111In-DTPA-paclitaxel. CONCLUSIONS: Scintigraphy with 111In-DTPA-paclitaxel could not predict the response to paclitaxel chemotherapy. Although there was significant accumulation of the paclitaxel in the tumor cells, additional mechanisms must be operative for the agent to be effective against the neoplasm. 111In-DTPA-paclitaxel activity is apparently different from that of paclitaxel with Cremophor.

Animals↗

PubMed1999

Stimulatory guanine nucleotide binding protein subunit 1 mutation in two siblings with pseudohypoparathyroidism type 1a and mother with pseudopseudohypoparathyroidism.

UNLABELLED: Pseudohypoparathyroidism (PHP) type la is characterized by multihormone resistance and a constellation of somatic features referred to as Albright hereditary osteodystrophy. Several mutations in the gene coding for the Gs alpha subunit (GNAS1) have been described. Clinical symptoms are heterogeneous and initially laboratory parameters may be normal. We identified a 4 base pair deletion within GNAS1 in two affected siblings with PHP type la and their mother with presumed pseudo PHP. The female proband was diagnosed after an episode of apnoea and seizures. The younger brother was asymptomatic during infancy and had normal plasma parameters. PHP was diagnosed at the age of 4.4 years. Regular check-ups of siblings in families with index cases are therefore important. Molecular genetic analyses or biochemical screening for stimulatory guanine nucleotide binding protein defects should be performed. CONCLUSION: Different symptoms may be seen in patients with the same mutation causing pseudohypoparathyroidism or pseudopseudohypoparathyroidism. Therefore, clinical and biochemical investigations should be performed in all family members with an index patient.

Adult↗

PubMed1999

Glucagonlike peptide-2 enhances small intestinal absorptive function and mucosal mass in vivo.

PURPOSE: Glucagonlike peptide-2 (GLP-2) is a 33-amino acid peptide that appears to be highly tissue specific for the intestine. This study was designed to examine the effect of systemically administered GLP-2 on intestinal absorptive function and mucosal mass, and determine the in vivo dose-response curves for this new peptide. METHODS: Twenty-five young adult male Sprague-Dawley rats had placement of jugular venous catheters connected to subcutaneously placed osmotic minipumps. The rats were divided into five groups based on the contents in the osmotic pump: group 1 (control, n = 5) normal saline and groups 2, 3, 4, and 5 (n = 5 each) were given GLP-2 at 5, 50, 250, and 500 microg/kg/d, respectively. After a 14-day infusion, [C14] galactose and [C14] glycine absorption were measured in a 10-cm segment of midsmall intestine using an in vivo closed-recirculation technique. Mucosal DNA content and protein content of the same small bowel segment were also determined for each group. Statistical analysis was performed by analysis of variance (ANOVA). RESULTS: GLP-2 significantly increased galactose absorption at a dose of 50 (P<.01), 250 (P<.01), and 500 (P<.05) microg/kg/d and glycine absorption at a dose of 50, 250, and 500 microg/kg/d (P<.01). GLP-2 also significantly increased mucosal DNA content at a dose of 50 (P<.01) and 250 (P<.05) microg/kg/d and protein content at a dose of 50 and 250 microg/kg/d (P<.01). CONCLUSIONS: These data demonstrate that GLP-2 can enhance normal rat small intestine mucosal mass and absorption in vivo with the maximum effect seen at 50 microg/kg/d.

Animals↗

PubMed1999

A pharmacokinetic modeling of inorganic arsenic: a short-term oral exposure model for humans.

This study presents a pharmacokinetic modeling of inorganic arsenic disposition in human body for short-term oral exposures. Effort on the development of the model is directed toward the prediction of the kinetic behavior of inorganic arsenic and its metabolites in the body. The current model considers the 4 circulating species; AsIII, AsV, and two metabolites such as monomethylarsenic (MMA) and dimethylarsenic (DMA) in the blood and tissue groups. While it is difficult to estimate some parameters used in the models at this time, the current model assumptions and predictions seem to be consistent with the experimental observations found in the literature. Hence, the current model, when more fully developed, is expected to provide insight into the behavior of inorganic arsenic and its methylated metabolites within the body, and may help increase the understanding of risk assessment issues associated with inorganic arsenic in drinking water.

Administration, Oral↗

PubMed1999

Skin complications in the intensive care unit.

Critically ill patients usually have multiple risk factors for the development of pressure ulcers. Pressure ulcers involve all levels of tissue from bone to skin, and result from excessive pressure and shearing. Control of incontinence, maintenance of adequate oxygen delivery and nutritional support is the key to minimizing the effects of skin breakdown in the intensive care unit. Consistent assessment and surveillance of skin for early signs of pressure ulcer development are essential, as is an interdisciplinary approach with nursing specialists and surgical consultants for pressure ulcers that have developed.

Critical Illness↗