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Biomedical subjects

W Yu

Publications and source records attributed to W Yu.

At least 235 records · Page 13Linked to original sources

RRR-alpha-tocopheryl succinate inhibits EL4 thymic lymphoma cell growth by inducing apoptosis and DNA synthesis arrest.

RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) treatment of murine EL4 T lymphoma cells induced the cells to undergo apoptosis. After 48 hours of VES treatment at 20 micrograms/ml, 95% of cells were apoptotic. Evidence for the induction of apoptosis by VES treatments is based on staining of DNA for detection of chromatin condensation/fragmentation, two-color flow-cytometric analyses of DNA content, and end-labeled DNA and electrophoretic analyses for detection of DNA ladder formation. VES-treated EL4 cells were blocked in the G1 cell cycle phase; however, apoptotic cells came from all cell cycle phases. Analyses of mRNA expression of genes involved in apoptosis revealed decreased c-myc and increased bcl-2, c-fos, and c-jun mRNAs within three to six hours after treatment. Western analyses showed increased c-Jun, c-Fos, and Bcl-2 protein levels. Electrophoretic mobility shift assays showed increased AP-1 binding at 6, 12, and 24 hours after treatment and decreased c-Myc binding after 12 and 24 hours of VES treatment. Treatments of EL4 cells with VES+RRR-alpha-to-copherol reduced apoptosis without effecting DNA synthesis arrest. Treatments of EL4 cells with VES+rac-6-hydroxyl-2, 5,7,8-tetramethyl-chroman-2-carboxylic acid, butylated hydroxytoluene, or butylated hydroxyanisole had no effect on apoptosis or DNA synthesis arrest caused by VES treatments. Analyses of bcl-2, c-myc, c-jun, and c-fos mRNA levels in cells receiving VES + RRR-alpha-tocopherol treatments showed no change from cells receiving VES treatments alone, implying that these changes are correlated with VES treatments but are not causal for apoptosis. However, treatments with VES + RRR-alpha-tocopherol decreased AP-1 binding to consensus DNA oligomer, suggesting AP-1 involvement in apoptosis induced by VES treatments.

Animals↗

Evidence for role of transforming growth factor-beta in RRR-alpha-tocopheryl succinate-induced apoptosis of human MDA-MB-435 breast cancer cells.

MDA-MB-435 human breast cancer cells treated with 10 micrograms/ml of RRR-alpha-tocopheryl succinate (vitamin E succinate, VES) for one, two, three, and four days exhibit 9%, 19%, 51%, and 73% apoptotic cells, respectively. Likewise, cells cultured for one, two, and three days with conditioned media (CM) obtained from MDA-MB-435 cells treated with VES exhibit 10%, 36%, and 74% apoptosis, respectively. A quantitative luciferase-based assay showed CM from VES-treated cells collected at 24 and 48 hours after treatment initiation to contain 75 and 32 pg of active transforming growth factor-beta (TGF-beta), respectively, per 10(6) cells. Although purified TGF-beta 1 is not an effective apoptotic agent for MDA-MD-435 cells, cotreatment of the cells for three days with suboptimal levels of VES (2.5 and 5 micrograms/ml) + 10 ng/ml of purified TGF-beta 1 enhanced apoptosis by 66% and 68%, respectively. Interference of the TGF-beta-signaling pathway by transient transfection of MDA-MB-435 cells with antisense oligomers to TGF-beta type II receptor (TGF-beta R-II) blocked VES-induced apoptosis. Likewise, addition of neutralizing antibodies to TGF-beta 1 or to all three mammalian isoforms of TGF-beta (TGF-beta 1, -beta 2, -beta 3) blocked VES- and CM-induced apoptosis. Furthermore, inhibitors of TGF-beta conversion from an inactive latent form to a biologically active form inhibited VES-induced apoptosis. In summary, the ability to reduce apoptosis by blocking TGF-beta or the TGF-beta receptor-signaling pathway with antisense oligomers or ligand-neutralizing antibodies or prevention of activation of TGF-beta indicates a role for TGF-beta signaling in VES-induced apoptosis.

Antibodies↗

Large-scale concatenation cDNA sequencing.

A total of 100 kb of DNA derived from 69 individual human brain cDNA clones of 0.7-2.0 kb were sequenced by concatenated cDNA sequencing (CCS), whereby multiple individual DNA fragments are sequenced simultaneously in a single shotgun library. The method yielded accurate sequences and a similar efficiency compared with other shotgun libraries constructed from single DNA fragments (> 20 kb). Computer analyses were carried out on 65 cDNA clone sequences and their corresponding end sequences to examine both nucleic acid and amino acid sequence similarities in the databases. Thirty-seven clones revealed no DNA database matches, 12 clones generated exact matches (> or = 98% identity), and 16 clones generated nonexact matches (57%-97% identity) to either known human or other species genes. Of those 28 matched clones, 8 had corresponding end sequences that failed to identify similarities. In a protein similarity search, 27 clone sequences displayed significant matches, whereas only 20 of the end sequences had matches to known protein sequences. Our data indicate that full-length cDNA insert sequences provide significantly more nucleic acid and protein sequence similarity matches than expressed sequence tags (ESTs) for database searching.

DNA Transposable Elements↗

Photomodulation of oxidative metabolism and electron chain enzymes in rat liver mitochondria.

Low-level laser irradiation has been applied in a variety of laboratory studies and clinical trials for photobiostimulation over the last three decades. Considerable skepticism exists regarding the concept of photostimulation within the medical community. One of the major difficulties with photoirradiation research is that it lacks experimentally supportable mechanisms for the alleged photobiostimulatory effects. This study was undertaken to determine whether oxidative metabolism and electron chain enzymes in rat liver mitochondria can be modulated by photoirradiation. Oxygen consumption, phosphate potential, and energy charge of rat liver mitochondria were determined following photoirradiation. Activities of mitochondrial enzymes were analyzed to assess the specific enzymes that are directly involved with the photostimulatory process. An argon-dye laser at a wave-length of 660 nm and at a power density of 10 mW/cm2 was used as a photon source. Photoirradiation significantly increased oxygen consumption (0.6 J/cm2 and 1.2 J/cm2, P < 0.05), phosphate potential, and the energy charge (1.8 J/cm2 and 2.4 J/cm2, P < 0.05) of rat liver mitochondria and enhanced the activities of NADH: ubiquinone oxidoreductase, ubiquinol: ferricytochrome C oxidoreductase and ferrocytochrome C: oxygen oxidoreductase (0.6 J/cm2, 1.2 J/cm2, 2.4 J/cm2 and 4.8 J/cm2, P < 0.05). The activities of succinate ubiquinone oxidoreductase, ATPase, and lactate dehydrogenase were not affected by photoirradiation.

Adenosine Triphosphatases↗

V(D)J recombination: in vitro coding joint formation.

Antigen receptor genes are assembled through a mechanism known as V(D)J recombination, which involves two different joining reactions: signal and coding joining. Formation of these joints is essential for antigen receptor assembly as well as maintaining chromosomal integrity. Here we report on a cell-free system for coding joint formation using deletion and inversion recombination substrates. In vitro coding joint formation requires RAG1, RAG2, and heat-labile factors present in the nuclear extract of nonlymphoid cells. Both inversion- and deletion-mediated coding joint reactions produce diverse coding joints, with deletions and P nucleotide addition. We also show that deletion-mediated coding joint formation follows the 12/23 rule and requires the catalytic subunit of DNA-dependent protein kinase.

Cell Nucleus↗

Endoleak as a complication of endoluminal grafting of abdominal aortic aneurysms: classification, incidence, diagnosis, and management.

The inability to obtain or maintain a secure seal between a vessel wall and a transluminally implanted intra-aneurysmal graft is a complication unique to the evolving technique of endovascular aneurysm exclusion. Because the term "leak" has long been associated with aneurysm rupture, the term "endoleak" is proposed as a more definitive description of this phenomenon. Embracing both persistent blood flow into the aneurysmal sac from within or around the graft (graft related) and from patent collateral arteries (nongraft related), endoleak can be classified as primary or secondary depending on the time of occurrence (within 30 days of implantation or following apparent initial seal, respectively). Diagnostic techniques to detect endoleak include arteriography, intraprocedural pressure monitoring, contrast-enhanced computed tomography, abdominal X ray, and duplex scanning. Management strategies for endoleak range from observation with periodic imaging surveillance to correction by additional endoluminal or surgical procedures. Standardization of the terminology describing this important sequela to endovascular aneurysm exclusion should facilitate uniform reporting of clinical trial data vital to the evaluation of this emerging technique.

Aortic Aneurysm, Abdominal↗

Three-year experience with the White-Yu Endovascular GAD Graft for transluminal repair of aortic and iliac aneurysms.

PURPOSE: To report a > 3-year experience with a modular, balloon-expandable endovascular graft used for aneurysm exclusion in the aorta and other arteries. METHODS: The customized White-Yu Endovascular GAD Graft, a woven polyester prosthesis with an intrinsic Elgiloy wire graft attachment system along the body of the graft, is a flexible endograft design available in straight, tapered, and bifurcated versions that can be delivered transluminally through 18F to 24F sheaths. RESULTS: Since July 1993, 93 patients have received the White-Yu endograft for treatment of 76 abdominal aortic, 3 thoracic aortic, 13 iliac, and 1 popliteal aneurysms. Of the 79 aortic procedures, 39 involved straight tube grafts, 20 were tapered aortoiliac models, and 20 were bifurcated devices. Success rates for tube grafts were 81% in the abdominal aorta and 100% for the thoracic aorta; 5 primary endoleaks (14%) and 2 conversions to surgery (5.6%) occurred with this graft type. Aortoiliac grafts were deployed successfully in 95% (19/20) of cases with 1 conversion (5%) due to thrombosis. Seventy-five percent of the bifurcated endograft procedures were successful, with 4 conversions (20%) for technical failures and 1 graft thrombosis. Four additional endografts were deployed to treat two primary and two secondary endoleaks in tube graft patients. Two access-related arterial injuries were treated surgically. There was one case of embolus to the distal femoral artery but no microembolization. Overall perioperative (30-day) mortality was 3.1%. Over a mean 18-month follow-up (range 2 to 39), no late graft thrombosis, stenosis, or graft migration has been seen on CT scans or X ray. Endoleak has not been detected in any aortoiliac or bifurcated graft. Aneurysm size has diminished consistently in successfully treated cases. CONCLUSIONS: The White-Yu endograft appears to offer a safe, efficacious, and minimally invasive means of excluding aneurysms from the circulation. Improvements in patient selection, surgical techniques, and equipment have reduced the incidence of endoleak and conversion to open repair over the course of the evaluation.

Aortic Dissection↗

Endoluminal repair of abdominal aortic aneurysms: strengths and weaknesses of various prostheses observed in a 4.5-year experience.

PURPOSE: To summarize the results of endovascular abdominal aortic aneurysm (AAA) treatment using several endograft designs over a 4.5-year experience and offer comparisons on the various devices. METHODS: From May 1992 to August 1996, 121 AAA patients meeting the criteria for an endoluminal repair were treated with 1 of 5 endograft designs in three configurations. The endografts were implanted in the operating room under fluoroscopic control. Follow-up included contrast-enhanced computed tomography within 10 days of operation, 6 months postoperatively, and annually thereafter. RESULTS: Endografts were successfully deployed in 106 patients (88%). Fifteen cases were converted to open repair. Six procedure-related deaths occurred within 30 days owing to myocardial infarction (3), combined renal failure and septicemia (2), and multisystem failure (1). There were 36 local/vascular complications (30%) and 18 systemic/remote complications (15%). Of the 121 patients undergoing endoluminal AAA repair, 93 (77%) are currently alive and well with their AAAs excluded from the circulation. CONCLUSIONS: Trends in endoluminal AAA repair and prosthetic design point toward simpler devices and earlier treatment of smaller aneurysms once the long-term outcome of aortic endografting has been determined.

Aortic Aneurysm, Abdominal↗

Mechanisms of formation and function of eosinophil lipid bodies: inducible intracellular sites involved in arachidonic acid metabolism.

Lipid bodies, inducible lipid-rich cytoplasmic inclusions, are characteristically abundant in cells associated with inflammation, including eosinophils. Here we reviewed the formation and function of lipid bodies in human eosinophils. We now have evidence that the formation of lipid bodies is not attributable to adverse mechanisms, but is centrally mediated by specific signal transduction pathways. Arachidonic acid and other cis fatty acids by an NSAID-inhibitable process, diglycerides, and PAF by a 5-lipoxygenase dependent pathway are potent stimulators of lipid body induction. Lipid body formation develops rapidly by processes that involve PKC, PLC, and de novo mRNA and protein synthesis. These structures clearly serve as repositories of arachidonyl-phospholipids and are more than inert depots. Specific enzymes, including cytosolic phospholipase A2, MAP kinases, lipoxygenases and cyclooxygenases, associate with lipid bodies. Lipid bodies appear to be dynamic, organelle-like structures involved in intracellular pathways of lipid mobilization and metabolism. Indeed, increases in lipid body numbers correlated with enhanced production of both lipoxygenase- and cyclooxygenase-derived eicosanoids. We hypothesize that lipid bodies are distinct inducible sites for generating eicosanoids as paracrine mediators with varied activities in inflammation. The capacity of lipid body formation to be specifically and rapidly induced in leukocytes enhances eicosanoid mediator formation, and conversely pharmacologic inhibition of lipid body induction represents a potential novel and specific target for anti-inflammatory therapy.

Arachidonic Acid↗

Regenerative changes in median nerve defects using various rabbit skeletal muscles.

We examined the morphological changes of median nerve regeneration which situated to pass through degenerative latissimus dorsi and brachial triceps muscles in rabbits. Morphological observation was performed at 7, 14, 28, 45, 60 and 180 days after the creation of defect of the bilateral median nerves. Regenerative nerve fibers were observed in the residual tubes of left degenerative muscle bridges. In this respect the regenerative effect of the latissimus dorsi was better than that of the brachial triceps. These results suggest that regular and longer muscle fibers as those of latissimus dorsi may contribute to the effective regeneration of nerve.

Animals↗

[Comparison of radiographs and magnetic resonance imaging in the detection of sacroiliitis in patients with ankylosing spondylitis].

The role of radiography and magnetic resonance (MR) imaging in the detection of sacroiliitis in patients with ankylosing spondylitis (AS) was compared in this study. Thirty-six sacroiliac joints in 18 patients with AS were examined with radiography and MR scan. MR images were performed with the sequence of the coronal T1 weighted image, T2 weighted image, and T2* weighted image. Images of all patients were graded according to the modified New York criteria. Statistical results showed that significant differences existed between MR imaging and radiography in the detection of sacroiliitis (P < 0.01). MR imaging was superior to plain film radiographs in visualising erosions (P < 0.01). Radiography cannot reveal the cartilage changes and bone marrow oedema, which can only be seen in MR images. In the absence of radiographic changes, MR imaging can provide objective and complementary findings of sacroiliitis in patients with AS. Due to the ability to image cartilage changes and bone marrow oedema directly, MR imaging may be particularly useful in early diagnosis of sacroiliitis. For patients without any changes on sacroiliac joint radiograph, further examination of MR imaging may be advisable.

Adolescent↗

[A study on the cytotoxicity of six filling materials in vitro].

This paper deals with the cytotoxicologic analyses on 6 filling materials with morphology of cells, ultraviolet light spectrophotometry and incorporation test using mouse L-929 fibroblasts labelled 3H-TdR. The results showed that the cytotoxicity of Silver amalgam and the Gallium-Silver alloys, which were produced by mixing the conventional dental alloys powder or high copper alloys powder with Gallium, was significantly stronger than that of light curing composites and the Gallium-Silver alloys that were produced by the spherical amalgam alloys powder and Gallium. It suggested that the level of mercury and copper in the alloys can influence their cytotoxic properties.

Animals↗

[The study of chronobiology of CT features of liver cancer].

OBJECTIVE: To explore the biological cycle of malignant biological behavior of liver cancer, and to provide a research basis for the excepically specific phase of drugs for clinical treatment of liver cancer. METHODS: 24 kinds of CT features reflected varying degree of malignant biological behavior. There were 360 cases altogether from randam sampling 30 cases each month. The analytic method is each CT feature fitting a group data of yearly cycle using cosine curve made the analysis of the cyclic sequence character of each CT feature (cosinor). RESULTS: With 95% confidence, there were 10 CT features which showed biologic rhythm (P < 0.05). The acrophase of CT features for invasive growth concentrated between -60 degrees and -120 degrees (March and April). But for non-invasive growth, the CT features were relatively low and concentrated between -180 degrees and -270 degrees (July and September). No acrophase was shown in between -120 degrees and -180 degrees (May and June) and between -270 degrees and -330 degrees (October and November). CONCLUSION: Between CT features of the invasive and non-invasive growths of liver cancer, a sequential difference in biologic cycles can be observed.

Chronobiology Phenomena↗

Involvement of activator protein-1 (AP-1) in induction of apoptosis by vitamin E succinate in human breast cancer cells.

The purpose of this study was to document induction of apoptosis by vitamin E succinate (VES; RRR-alpha-tocopheryl succinate) in human breast cancer cells in culture and to characterize potential c-jun involvement. VES at 18.8 microM (10 micrograms/mL) induced DNA synthesis arrest, reduced total cell numbers, and induced apoptosis in estrogen receptor-positive and estrogen-responsive MCF-7 human breast cancer cells. VES at 10 micrograms/mL induced apoptosis in greater than 60% of cells within 3 d of treatment. Apoptosis was documented by detection of fragmented or condensed nuclei in 4',6-diamindino-2-phenylindole-stained cells, detection of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeled DNA, and DNA laddering. Analyses of mRNA and protein levels of candidate molecules involved in apoptosis showed that MCF-7 cells treated with VES exhibited elevated and persistent expression of c-jun. MCF-7 cells stably transfected with a dominant-negative interfering mutant c-jun, TAM-67, and expressing high levels of mutant jun exhibited approximately 50% blockage of VES-mediated apoptosis. In addition to increased c-jun expression after VES treatment, VES-treated MCF-7 cells exhibited elevated activator protein-1 (AP-1) binding activity. Comparisons of AP-1 binding factors by super-shift analyses with jun-specific antibodies in cells sensitive to VES-induced apoptosis (empty-vector control 7-1 cells) and cells resistant to VES-induced apoptosis (TAM-67-containing TAM-9 cells) showed that the sensitive cells expressed c-jun and jun D and the resistant cells TAM-67 AP-1 binding proteins after VES treatment. These studies suggested that c-jun may be involved in the apoptotic process initiated by VES treatment of human MCF-7 breast cancer cells.

Apoptosis↗

Comparison of five systems for staging lymph node metastasis in gastric cancer.

BACKGROUND: There are several systems for staging lymph node metastasis in gastric cancer. Their relative merits are not clear. METHODS: In this retrospective analysis, the nodal status was classified according to the Union Internacional Contra la Cancrum (UICC) and Japanese staging systems, the number and frequency of lymph node metastasis, and the level of involved nodes. Each staging system was scored as good (+1), fair (0) or poor (-1) with respect to prognostic value, theoretical value, convenience, reproducibility and surgical applicability. RESULTS: There were no differences between the five staging systems in predicting survival. The Japanese staging system was most arbitrary owing to the complexity of the system, although it had an advantage in surgical application. The same disadvantage was found in the UICC system and the level system. Determination of the number and frequency of involved nodes was convenient and reproducible, but the number of lymph nodes dissected must be considered when the number of positive nodes is used for staging. CONCLUSION: The classification of metastasis to the regional lymph nodes as N0 (no nodal metastasis), N1 (metastasis in 1-25 per cent of dissected nodes) and N2 (metastasis in more than 25 per cent of dissected nodes) would be a simple, convenient, reproducible staging system with an ability to predict surgical results.

Humans↗

The construction and expression of deletion mutant of human pro-urokinase cDNA.

The human pro-urokinase mutant deleting 150-156 amino acids was constructed by overlap-extension PCR and other molecular cloning techniques. The mutant was expressed transiently in COS-7 cells and constitutively in CHO cells; the expression level is 450-500 IU/10(6) cells/24 h. SDS-PAGE and Western blotting analysis showed that the molecular weight of the expression product is 54 kDa, which is similar to that of the mature pro-UK and recombinant pro-UK (rPro-UK) expressed by full-length cDNA. Most of the products exist in the form of single chain; the percentage of single chain is much higher than that of rPro-UK. In addition, the mutant product is more resistant to proteinases and its affinity to fibrin is also improved slightly.

Animals↗

The effect of cold stress on lymphocyte proliferation in fetal ethanol-exposed rats.

Prenatal ethanol exposure and stress have each been shown to have significant effects on the immune system. This study examined the possible interactive effects of prenatal ethanol exposure and exposure to stress later in life on the immune system. Differential vulnerability to these challenges in female and male offspring was assessed. At 5 to 6 months of age, female and male offspring from prenatal ethanol-exposed (E), pair-red (PF), and ad libitum-fed control (C) conditions were exposed to 0, 1 or 3 days of cold (4 degrees C). At the end of the cold period, the proliferative response of splenic lymphocytes to the mitogens concanavalin A (Con A) and pokeweed mitogen (PWM) was assessed. The data demonstrate a significant interactive effect between prenatal ethanol exposure and cold stress in female offspring. After 1 day of cold stress, E females had significantly increased PWM-induced lymphocyte proliferation compared with PF and C females, and significantly increased Con A-induced lymphocyte proliferation compared with PF females. There were no differences in PWM or Con A-induced lymphocyte proliferation among E, PF, and C females after 0 or 3 days of cold stress, nor among E, PF, and C males on any test day. Regardless of prenatal treatment, females exposed to 1 or 3 days of cold had significantly greater basal plasma corticosterone levels than females not exposed to cold. In contrast, only E males exposed to 1 or 3 days of cold had significantly increased basal plasma corticosterone levels, compared with E males not exposed to cold; PF and C males showed no significant change in basal corticosterone after cold stress. These data demonstrate that, in response to the challenge of cold stress, changes in lymphocyte proliferation to PWM and Con A may occur selectively in E females. Moreover, the interactive effects of prenatal ethanol and cold stress may result in enhanced rather than suppressed immune responsiveness.

Acclimatization↗