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Biomedical subjects

R Y Wu

Publications and source records attributed to R Y Wu.

At least 19 recordsLinked to original sources

The effect of 50 Hz magnetic field on GCSmRNA expression in lymphoma B cell by mRNA differential display.

Magnetic fields (MFs) of various characteristics can lead to plethora effects in biological system. From a molecular point of view, we hypothesized that there must be a fundamental difference in gene expression between the MF exposed and the unexposed cell. To identify the classes of genes that are regulated, 0.8 mT 50 Hz MF-induced changes in gene expression were examined in a Daudi cell culture using differential display and reverse transcriptase-polymerase chain reaction. A candidate cDNA (signatured as MF-CB) that was observed in the sham-exposed but not in MF-exposed cultures was recovered and reamplified. After verification by Northern blot, the cDNA was cloned and sequenced. It was found that 254-base pair of 5'-end MF-CB cDNA clone was identical to gcs in open reading frame (ORF) range. Based on the preliminarily sequence, the prolonged length of 5'-end MF-CB cDNA was obtained by PCR amplification and its sequence analysis showed the same results as its original fragment. In order to further determine whether MF-CB cDNA is from gcs, two Northern blots were probed with gcs and MF-CB cDNA, respectively, and the data revealed signals of the same size and expression pattern on the two probe filters, which demonstrated that MF-CB is an EST (expression sequence tag) of gcs. gcs is a gene, identified recently (GenBank accession number D89866), encoding ceramide glucosyltransferase (GCS), which has been implicated as a causal element in human cell growth and differentiation. In an additional experiment, time-dependent changes in the transcription of gcs induced by 0.8 mT MF were observed by Northern blot with a sharp and reproducible inhibition effect after 20 min exposure and a reduction after 20-24 h exposure. The study demonstrates for the first time that 50 Hz MF can lead to changes in gcs transcription, which provides a new clue to elucidate the mechanism by which MF influence cell growth and differentiation.

Amino Acid Sequence↗

Automatic prostate boundary recognition in sonographic images using feature model and genetic algorithm.

This paper describes the development of a model-based boundary recognition system for transrectal prostate ultrasonographic images. It consists of two techniques: boundary modeling and boundary searching with model constraints. To achieve higher specificity of the model, a method called feature modeling is derived from the existing point distribution modeling method. To improve the robustness of the searching technique, the genetic algorithm is used. Incremental genetic algorithm with crowding replacement and binary string chromosome type was found experimentally to give good search results. It was shown that the system could recognize the boundary with considerable accuracy and consistency within a few minutes in transrectal ultrasonographic images taken from approximate middle position of the prostate.

Algorithms↗

The tumor suppressor Smad4/DPC4 and transcriptional adaptor CBP/p300 are coactivators for smad3 in TGF-beta-induced transcriptional activation.

Smads regulate transcription of defined genes in response to TGF-beta receptor activation, although the mechanisms of Smad-mediated transcription are not well understood. We demonstrate that the TGF-beta-inducible Smad3 uses the tumor suppressor Smad4/DPC4 and CBP/p300 as transcriptional coactivators, which associate with Smad3 in response to TGF-beta. The association of CBP with Smad3 was localized to the carboxyl terminus of Smad3, which is required for transcriptional activation, and a defined segment in CBP. Furthermore, CBP/p300 stimulated both TGF-beta- and Smad-induced transcription in a Smad4/DPC4-dependent fashion. Smad3 transactivation and TGF-beta-induced transcription were inhibited by expressing E1A, which interferes with CBP functions. The coactivator functions and physical interactions of Smad4 and CBP/p300 with Smad3 allow a model for the induction of gene expression in response to TGF-beta.

Adenovirus E1A Proteins↗

Heteromeric and homomeric interactions correlate with signaling activity and functional cooperativity of Smad3 and Smad4/DPC4.

Homologs of Drosophila Mad function as downstream mediators of the receptors for transforming growth factor beta (TGF-beta)-related factors. Two homologs, the receptor-associated Smad3 and the tumor suppressor Smad4/DPC4, synergize to induce ligand-independent TGF-beta activities and are essential mediators of the natural TGF-beta response. We now show that Smad3 and Smad4 associate in homomeric and heteromeric interactions, as assessed by yeast two-hybrid and coimmunoprecipitation analyses. Heteromeric interactions are mediated through the conserved C-terminal domains of Smad3 and Smad4. In Smad3, the homomeric interaction is mediated by the same domain. In contrast, the homomeric association of Smad4 requires both the N-terminal domain and the C-terminal domain, which by itself does not homomerize. Mutations that have been associated with impaired Mad activity in Drosophila or decreased tumor suppressor activity of Smad4/DPC4 in pancreas cancer, including a short C-terminal truncation and two point mutations in the conserved C-terminal domains, impair the ability of Smad3 and Smad4 to undergo homo- and heteromeric associations. Analyses of the biological activity of Smad3 and Smad4 and their mutants show that full signaling activity correlates with their ability to undergo efficient homo- and heteromeric interactions. Mutations that interfere with these interactions result in decreased signaling activity. Finally, we evaluated the ability of Smad3 or Smad4 to induce transcriptional activation in yeast. These results correlate the ability of individual Smads to homomerize with transcriptional activation and additionally with their biological activity in mammalian cells.

Animals↗

Mitogenic signaling by Ret/ptc2 requires association with enigma via a LIM domain.

The ret/ptc2 papillary thyroid cancer oncogene, an oncogenic form of the c-Ret receptor tyrosine kinase, is the product of a somatic crossover event fusing the dimerization domain of the type Ialpha regulatory subunit of cyclic AMP-dependent protein kinase (RI) with the tyrosine kinase domain of c-Ret. Mitogenic activity of Ret/ptc2 required dimerization via the N terminus of RI and a tyrosine residue located C-terminal to the kinase core of Ret, Tyr-586 (Durick, K., Yao, V. J., Borrello, M. G., Bongarzone, I., Pierotti, M. A. and Taylor, S. S. (1995) J. Biol. Chem. 270, 24642-24645). Using the yeast two-hybrid system, Ret/ptc2 binding proteins were identified, and the sites of interaction with Ret/ptc2 were mapped. The SH2 domains of phospholipase Cgamma and Grb10 were both identified, and binding depended on phosphorylation of Tyr-539 and Tyr-429, respectively. These interactions, however, were not required for mitogenic signaling. The second of the three LIM domains in Enigma (Wu, R. Y., and Gill, G. N. (1994) J. Biol. Chem. 269, 25085-25090) was also identified as a Ret/ptc2 binding domain. Enigma, a 455-residue protein, was discovered based on its interaction with the insulin receptor through the C-terminal LIM domain. Although the association with Enigma required Tyr-586 of Ret/ptc2, the interaction was phosphorylation-independent. In contrast to the SH2 interactions, disruption of the interaction with Enigma abolished Ret/ptc2 mitogenic signaling, suggesting that LIM domain recognition of an unphosphorylated tyrosine-based motif is required for Ret signal transduction.

3T3 Cells↗

[Inhibitory effects of tachykinin receptor antagonists on leukotriene C4-induced cardiovascular responses in guinea pigs].

This study is to determine whether sensory neuropeptides are involved in the cardiovascular effects of leukotriene C4 (LTC4). LTC4 (0.8 nmol.kg-1, i.v.) caused hypotensive response and increased Evans blue extravasation from the atria and ventricles in anaesthetized guinea pigs. CP-96345 (2.06 mumol.kg-1, i.v.), a tachykinin NK-1 receptor antagonist, and SR-48968 (1.66 mumol.kg-1, i.v.), an NK-2 receptor antagonist, partially inhibited LTC4-induced increase (46.6% and 37.5%, respectively) of dye extravasation from the atria of guinea pigs. Combination of CP-96345 and SR-48968 markedly inhibited LTC4-induced hypotension and increase of microvascular leakage in both atria and ventricles (58.1% and 54.1%, respectively), similar to the inhibition by ONO-1078 (0.06 mumol.kg-1, i.v.), a specific leukotriene antagonist. These results suggest that NK-1 and NK-2 receptors may be involved in the hypotension and the inflammation of heart induced by LTC4.

Animals↗

Pulsed magnetic field from video display terminals enhances teratogenic effects of cytosine arabinoside in mice.

Eighty-nine Swiss Webster mice were randomly divided into four groups: a control group, a pulsed magnetic field (PMF) group, a cytosine arabinoside (ara-C, a teratogen) group, and a combined PMF + ara-C group. Mice in the PMF and PMF + ara-C groups were irradiated with a PMF (a sawtooth waveform with 52 microseconds rise time, 12 microseconds decay time, and 15.6 kHz frequency) at a peak magnetic flux density of 40 microT for 4 hours daily on days 6-17 of gestation. The mice in the ara-C and the PMF + ara-C groups were injected intraperitoneally on day 9 of gestation with 10 mg/kg of ara-C. The incidence of resorption and dead fetuses was not affected by PMF but was increased by ara-C injection. The malformation incidence of cleft palate (CP) and/or cleft lip (CL) was significantly higher in all three of the treated groups than in the control group (P < 0.05). If, however, statistical analyses had been done on litters rather than on individual fetuses, they would show that the incidence of CP and/or CL in the PMF group is not significantly greater than that in the control group. A significantly higher incidence of CP and/or CL was found in the PMF + ara-C group (49%) than the ara-C alone group (26.1%). These data suggest that PMF might enhance the development of ara-C-induced CP and/or CL. The incidence of minor variations in skeletal development, including reduction of skeletal calcification and loss of skeleton, was not statistically significant in the PMF group.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

LIM domain recognition of a tyrosine-containing tight turn.

Endocytosis of cell surface receptors requires sequence "codes" consisting of tight turn structures with an essential Tyr or Phe residue. To determine mechanisms through which cells recognize this information, we utilized exon 16 of the human insulin receptor in the two-hybrid system to isolate a novel 455-amino acid cytoplasmic protein that contains two LIM domains within its carboxyl terminus. Mutational analyses indicate that one of the Cys-rich Zn2+ binding LIM domains specifically recognizes active but not inactive endocytic codes contained in exon 16. These findings suggest that LIM domain structures in proteins provide molecular recognition of Tyr-containing tight turn structures.

Amino Acid Sequence↗

Effects of 2.45-GHz microwave radiation and phorbol ester 12-O-tetradecanoylphorbol-13-acetate on dimethylhydrazine-induced colon cancer in mice.

The purpose of this study was to investigate the effects of 2.45 GHz microwave (MW) radiation on dimethylhydrazine (DMH)-induced colon cancer in mice. The subjects were 115 Balb/c mice 4 weeks of age. The animals were divided into group A (control), group B (DMH), group C (DMH+MW), and group D [DMH + 12-O-tetradecanoylphorbol-13- acetate (TPA)]. Radiation (10 mW/cm2) was delivered dorsally with the E field parallel to the mouse's long body axis in an anechoic chamber. Radiations were administered 3 hr daily, 6 days per week, over a period of 5 months. The average SAR was estimated to be 10-12 W/kg. During the course of radiation treatments, DMH was injected once per week. The tumor promoter TPA was administered once per week for 10 weeks, from the third week on, after the initial treatment. The incidence of tumors did not significantly differ between the three test groups (groups B, C, and D; P > 0.25). However, the number of tumors, the size of the tumors, and the incidence of protuberant and infiltrative types in tumor-bearing animals were higher in group D compared to groups B and C (P < 0.05). No difference was found between groups B and C (P > 0.25). The study indicates that 2.45 GHz microwave radiation at 10 mW/cm2 power density did not promote DMH-induced colon cancers in young mice. The study also showed that TPA could accelerate colon tumor production if a tumor was initiated.

Adenomatous Polyps↗

Neihumicin, a new cytotoxic antibiotic from Micromonospora neihuensis. I. The producing organism, fermentation, isolation and biological properties.

A new cytotoxic and antifungal antibiotic, neihumicin, was isolated from the culture broth of a soil isolate identified as Micromonospora neihuensis Wu, sp. nov. Neihumicin shows in vitro cytotoxicity against KB tissue culture cells (ED50 0.94 micrograms/ml) as well as antifungal activity against Saccharomyces cerevisiae ATCC 9763.

Antibiotics, Antineoplastic↗

Neihumicin, a new cytotoxic antibiotic from Micromonospora neihuensis. III. Structure-activity relationships.

Structure-cytotoxicity relationships studies have indicated that the C-3 and C-6 disubstituted piperazine-2,5-diones are structurally required for significant cytotoxicity, and the neihumicin-like C-3 and C-6 disubstituted unsymmetrical piperazine derivatives are, in general, more cytotoxic than the corresponding symmetrical piperazine-2,5-diones. Several synthetic analogs including 3,6-di-(2,4,5-trimethoxybenzylidene)piperazine-2,5- dione, 3,6-dibenzylidene-2-ethoxy-3,6-dihydropyrazine-5-one, 3-benzylidene-6-(m-chlorobenzylidene)-2-methoxy-3,6-dihydropyrazine++ +-5-one, have been shown to be more cytotoxic than neihumicin.

Antibiotics, Antineoplastic↗

[Carcinoembryonic antigen and immunoglobin in gastric juice in the diagnosis of gastric cancer].

Levels of carcinoembryonic antigen (CEA) and immunoglobin (Ig) in gastric juice of 93 patients with benign and malignant gastric diseases were assayed. The CEA level in gastric cancer patients (55.73 +/- 38.26 ng/ml) was obviously higher than that in peptic ulcer (15.51 +/- 12.09 ng/ml) and superficial gastritis (26.96 +/- 20.17 ng/ml). But no significant difference was found between the CEA levels of gastric cancer and chronic atrophic gastritis (48.66 +/- 31.87 ng/ml). Also, elevated CEA was closely correlated to intestinal metaplasia. The positive rate of Ig was significantly higher in gastric cancer (IgG greater than or equal to 185 ug/ml, IgA greater than or equal to 100 ug/ml) than in benign gastric diseases. Although no correlation is present in the CEA and Ig in gastric juice, the combination of these two methods could improve the diagnostic accuracy. We believe that the two assays are worthy for screening gastric cancer from patients with high risk, and for identifying precancerous lesions.

Adult↗