Search PubMed⌕ Search

Biomedical subjects

R Wu

Publications and source records attributed to R Wu.

At least 199 records · Page 11Linked to original sources
PubMed1997

[Vertical transmission of hepatitis C virus].

To study the transmission of hepatitis C virus (HCV) from infected mother to their infants, out of 1047 mothers studied, 8 were anti-HCV antibody and 6 were HCV RNA positive as well as 2 mothers who were anti-HCV antibody and HCV RNA positive. 12 mothers and their 12 babies were followed up for 12 months. Only one of 12 infants showed persistently positive for anti-HCV antibody and HCV RNA at 1, 6 and 12 months of age. His HCV type was identical to his mother. These results suggest that vertical transmission is present but not an important route for HCV infection.

Adult↗
PubMed1996

Oxidative DNA damage in human respiratory tract epithelial cells. Time course in relation to DNA strand breakage.

When human respiratory tract epithelial cells were exposed to 100 microM H2O2, there was rapid induction of DNA strand breakage and chemical modifications to all 4 DNA bases suggestive of attack by OH.. The major products were FAPy-adenine, FAPy-guanine, and 8-OH-guanine. Some of the base modifications were removed very quickly from the DNA (e.g., 8-OH-guanine), whereas others persisted for longer (e.g., thymine glycol), probably due to differential activity of different repair enzymes. By contrast, strand breaks continued to increase over the time course of the experiment, perhaps because strand breakage is also implicated in the repair process. One should therefore be cautious in using strand breakage as a sole measure of oxidative DNA damage, and when drawing conclusions about the pattern and biological significance of oxidative DNA damage in cells the relative persistence of different lesions must be considered.

Bronchi↗
PubMed1996

Specificity of LIM domain interactions with receptor tyrosine kinases.

LIM domains, Cys-rich motifs containing approximately 50 amino acids found in a variety of proteins, are proposed to direct protein*protein interactions. To identify structural targets recognized by LIM domains, we have utilized random peptide library selection, the yeast two-hybrid system, and glutathione S-transferase fusions. Enigma contains three LIM domains within its carboxyl terminus and LIM3 of Enigma specifically recognizes active but not mutant endocytic codes of the insulin receptor (InsR) (Wu, R. Y., and Gill, G. N. (1994) J. Biol. Chem. 269, 25085-25090). Interaction of two random peptide libraries with glutathione S-transferase-LIM3 of Enigma indicated specific binding to Gly-Pro-Hyd-Gly-Pro-Hyd-Tyr-Ala corresponding to the major endocytic code of InsR. Peptide competition demonstrated that both Pro and Tyr residues were required for specific interaction of InsR with Enigma. In contrast to LIM3 of Enigma binding to InsR, LIM2 of Enigma associated specifically with the receptor tyrosine kinase, Ret. Ret was specific for LIM2 of Enigma and did not bind other LIM domains tested. Mutational analysis indicated that the residues responsible for binding to Enigma were localized to the carboxyl-terminal 61 amino acids of Ret. A peptide corresponding to the carboxyl-terminal 20 amino acids of Ret dissociated Enigma and Ret complexes, while a mutant that changed Asn-Lys-Leu-Tyr in the peptide to Ala-Lys-Leu-Ala or a peptide corresponding to exon16 of InsR failed to disrupt the complexes, indicating the Asn-Lys-Leu-Tyr sequence of Ret is essential to the recognition motif for LIM2 of Enigma. We conclude that LIM domains of Enigma recognize tyrosine-containing motifs with specificity residing in both the LIM domains and in the target structures.

3T3 Cells↗
PubMed1996

Comparison of methaqualone excretion patterns using Abuscreen ONLINE and EMIT II immunoassays and GC/MS.

A study was performed to compare the ONLINE and EMIT II immunoassays with gas chromatographic/mass spectrometric (GC/MS) analysis of methaqualone metabolites on urine using samples obtained from a clinical study. Urine was collected over a 72 h period from six healthy adults (4 male, 2 female) after oral dosing with 200 mg methaqualone (MTQ). Each urine sample was analyzed by ONLINE and EMIT II. The samples were then analyzed by GC/MS, hydrolyzed with beta-glucuronidase and again analyzed by GC/MS. Both immunoassays showed greater than 600 ng/ml concentrations of drug in each sample by the second void and remained highly positive for the rest of the 72 h. Unhydrolyzed samples analyzed by GC/MS showed both low concentrations of MTQ as well as its five major hydroxylated metabolites. The hydrolyzed samples analyzed by GC/MS showed high concentrations of the hydroxylated metabolites with the 2'-hydroxy and 3'-hydroxy metabolites being present at the highest concentrations, the 4'-hydroxy metabolite at a lower amount and the 6-hydroxy and 2-hydroxy metabolites at the lowest concentrations. The GC/MS data coupled with the antibody cross-reactivity data indicate that the major species in clinical samples that cross-react in both immunoassays are the conjugated forms of the hydroxylated metabolites of MTQ. Therefore when confirming by GC/MS after an immunoassay screen it would be prudent to confirm for the major hydroxylated metabolites as glucuronides of MTQ instead of the parent drug.

Adult↗
PubMed1996

Inhibition of TGF-alpha gene expression by vitamin A in airway epithelium.

The autocrine/paracrine growth mechanism has been implicated in the regulation of bronchial epithelial cell proliferation. By inhibiting the expression of the transforming growth factor-alpha (TGF-alpha) gene product, vitamin A is able to suppress the proliferation of tracheobronchial epithelial cells in culture. Similar repressions in TGF-alpha mRNA levels by retinol were observed in airway explant cultures and in a cell line immortalized from normal human bronchial epithelial cells. Both the nuclear run-on transcriptional assay and the transfection study with the chimeric construct of the TGF-alpha promoter and chloramphenicol acetyltransferase reporter gene partly suggest a transcriptional downregulation mechanism of TGF-alpha gene expression by the retinol treatment; however, this inhibition at the transcriptional level cannot account for the total inhibition at the mRNA level. These results suggest that a downregulation of the expression of the TGF-alpha gene at the transcriptional and post-transcriptional levels by vitamin A may precede the essential event associated with the homeostasis of normal conducting airway epithelium.

Animals↗
PubMed1996

Neurofibromatosis type I gene mutation in a patient with features of LEOPARD syndrome.

Multiple lentigines (LEOPARD) syndrome has been delineated as an autosomal dominant disorder with lentigines, cardiac abnormalities, variable mental retardation, and typical craniofacial features as the most characteristic findings. LEOPARD syndrome shows a great clinical overlap with neurofibromatosis type 1 (NF1). In this report we describe a de novo missense mutation (M 1035R) in exon 18 of the NF1 gene in a young woman with a prior diagnosis of LEOPARD syndrome. We hypothesize that some patients now diagnosed with LEOPARD syndrome have in fact a mutation in the NF1 gene, whereas in other patients with LEOPARD syndrome, a different gene might be involved.

Abnormalities, Multiple↗
PubMed1996

Sequence of rice hoja blanca tenuivirus RNA-2.

The sequence of rice hoja blanca tenuivirus RNA-2 is analysed and compared to its counter-part in rice stripe tenuivirus. The RNA encodes two proteins, in an ambisense arrangement. The 94 kD pc2, located in the complementary sense RNA, has several features typical of viral membrane (glyco)proteins, and also has regions of local homology to the glycoproteins of the Phleboviruses (Bunyaviridae). The 23 kD pv2 lies in the viral sense RNA and has two small conserved domains that are almost exclusively found in retro-viral membrane glycoproteins. Its genome location is analogous to the NSm protein of several of the Bunyaviridae species, which is thought to have a membrane-related function. The two open reading frames are separated by a large intergenic region which, in common with the other tenuivirus ambisense RNA segments, has a short region that is highly conserved between RStV and RHBV. The significance of these results with respect to the virus structure and gene expression is discussed.

Amino Acid Sequence↗
PubMed1996

Sequence of echinochloa hoja blanca tenuivirus RNA-5.

The sequence is presented of RNA-5 of Echinochloa hoja blanca tenuivirus, a second tenuivirus associated with rice cultivation in Latin America (after rice hoja blanca virus). The RNA is 1334 nucleotides long and contains in the complementary sense RNA a single long open reading frame. The deduced amino acid sequence of this open reading frame shows that it encodes a highly basic and hydrophilic 44 kD protein (pc5) with about 50% similarity to the pc5 protein of maize stripe virus (MStV). This and other features of the RNA are discussed.

Amino Acid Sequence↗
PubMed1996

Sequence of Echinochloa hoja blanca tenuivirus RNA-4.

The sequence is presented of RNA-4 of Echinochloa hoja blanca tenuivirus (EHBV), one of two tenuiviruses associated with rice cultivation in Latin America (together with rice hoja blanca virus; RHBV). Analysis of the sequence shows that the coding regions of EHBV RNA-4 are closely related to those of RHBV RNA-4. However, the intergenic region separating the two ambisense open reading frames, are highly distinct for the two viruses. The features of the RNA and the comparisons with the sequences of RNA-4 of RHBV, rice stripe virus (RStV) and maize stripe virus (MStV) are discussed.

Amino Acid Sequence↗
PubMed1996

Sequence of Echinochloa hoja blanca tenuivirus RNA-3.

Analysis of the sequence of the 2336 nucleotide RNA-3 of Echinochloa hoja blanca tenuivirus shows that it is closely related to RNA-3 of rice hoja blanca tenuivirus, the principal virus disease of rice in Latin America. This is especially true for the coding regions, where the viruses are almost 90% similar. However, the non-coding regions of RNA-3 of these viruses, principally the intergenic region separating the two ambisense open reading frames, are only about 50% similar, suggesting that these are distinct viruses. The results closely resemble those obtained for the analysis of RNA-4 of these viruses, both in the absolute and relative percentage similarities of the coding and non-coding regions. This implies a coordinated evolution of the different tenuivirus RNA segments. The features of the RNA and the comparisons with the sequences of RNA-3 of RHBV, rice stripe virus (RStV) and maize stripe virus (MStV) are discussed.

Amino Acid Sequence↗
PubMed1996

A novel intact circular dsDNA supercoil.

A novel intact circular dsDNA supercoil is proposed as an alternative to the conventional DNA supercoil, so that the two complementary strands of ssDNA circles are separable without any covalent bond breakage. This new structure can be visualized by using two tubings: one black and one clear. Twist the black tubing a number of times and connect its two ends. Do the same for the clear tubing. Then wrap the two tubings together. This forms the separable or novel supercoil. On the other hand, the conventional supercoil can be modeled by twisting the black and clear tubings together and then connect their respective ends, so that the two tubings are not separable unless one of them is cut. Experimentally, in the absence of any enzyme, many intact plasmid dsDNA circles give two bands on agarose gel electrophoresis under a certain given condition, while the same plasmid molecules after cutting once by a restriction enzyme give only one band under the same condition. In the case of intact pUC19 plasmids, these two bands can then be recovered and sequenced separately, using two primers in opposite directions. Each band gives mostly one sequence which is complementary to that of the other band. The combination of the above theoretical model and experimental results strongly suggests that there is an alternative structure of DNA which does not have the usual difficulty of unwinding, rewinding and requiring numerous covalent bond breakages and ligations during semiconservative.

Base Sequence↗
PubMed1996

Breast cancer during pregnancy: quantifying the risk of treatment delay.

OBJECTIVE: To quantify the risk of axillary nodal metastases due to delayed treatment of breast cancer during pregnancy. METHODS: A mathematical model using recently published data was developed to correlate primary breast tumor size with the percentage of pathologically positive axillary lymph nodes. Using this relationship obtained from pathologic data and the accepted relationship of tumor growth and time, Y2 = Y1e(In2)n/DT, an equation estimating the increased risk of axillary metastases due to each day of treatment delay was derived: delta X = 3.7 n/DT, where X = percent positive axillary lymph nodes, n = number of days delay in treatment, and DT = tumor doubling time. RESULTS: A 1-month delay in treatment for an early-stage primary breast cancer with a 130-day doubling time increases the risk of axillary lymph node involvement by 0.9%. A 3-month delay increases the risk by 2.6%, and a 6-month delay by 5.1%. For breast cancer with a 65-day doubling time, a 1-month delay increases the risk by 1.8%, a 3-month delay by 5.2%, and a 6-month delay by 10.2%. CONCLUSION: Axillary lymph nodes are the most important prognostic indicator for survival in breast cancer. Our mathematical model suggests the daily increased risk of axillary metastases due to treatment delay is 0.028% for tumors with moderate doubling times of 130 days and 0.057% for tumors with rapid doubling times of 65 days. This minimal maternal risk may be acceptable to some third-trimester pregnant women with early breast cancer, who prefer organ-sparing treatment with radiation after delivery to a mastectomy during pregnancy. This model further quantitates the increased risk of mortality borne by pregnant women whose breast cancer diagnosis is delayed.

Axilla↗
PubMed1996

Synthesis and evaluation of a polyamine phosphinate and phosphonamidate as transition-state analogue inhibitors of spermidine/spermine-N1-acetyltransferase.

Polyamine analogues such as bis(ethyl)norspermine and N1-ethyl-N11-[(cyclopropyl)methyl]-4,8-diazaundecane (CPENSpm) act as inhibitors of the enzyme spermidine/spermine-N1-acetyltransferase (SSAT) in vitro and possess impressive antitumor activity against a number of cell lines. However, the propensity of these compounds to superinduce SSAT in intact cells limits their usefulness in studies aimed at elucidating the role of SSAT in cellular metabolism. The recently synthesized alkylpolyamine analogue N1-ethyl-N11-[(cycloheptyl)methyl]-4,8-diazaundecane (CHENSpm, 3) is also an effective inhibitor of SSAT and has potent antitumor activity, but does not appear to superinduce SSAT. These findings suggest that it is possible to synthesize polyamine analogues that can be used for selective inhibition of the enzyme in cellular metabolic studies. Along these lines, the phosphate-based transition state analogues 4 and 5 were synthesized and evaluated as inhibitors of isolated SSAT. Phosphonamidate 4 was rapidly hydrolyzed under the assay conditions, and thus did not inhibit the enzyme. However, the phosphinate analogue 5 was an effective inhibitor of purified human SSAT, with a Ki value of 250 microM. The inhibitory activity of 5 was also compared with that of CHENSpm (IC50 = 13 microM), as well as a series of bis-substituted alkylpolyamine analogues. The unsymmetrically substituted polyamine analogue CHENSpm (3) and the phosphinate transition state analogue 5 represent the first functional, nonsuperinducing inhibitors of human SSAT.

Acetyltransferases↗
PubMed1996

Transgenic rice plants harboring an introduced potato proteinase inhibitor II gene are insect resistant.

We introduced the potato proteinase inhibitor II (PINII) gene (pin2) into several Japonica rice varieties, and regenerated a large number of transgenic rice plants. Wound-inducible expression of the pin2 gene driven by its own promoter, together with the first intron of the rice actin 1 gene (act1), resulted in high-level accumulation of the PINII protein in the transgenic plants. The introduced pin2 gene was stably inherited in the second, third, and fourth generations, as shown by molecular analyses. Based on data from the molecular analyses, several homozygous transgenic lines were obtained. Bioassay for insect resistance with the fifth-generation transgenic rice plants showed that transgenic rice plants had increased resistance to a major rice insect pest, pink stem borer (Sesamia inferens). Thus, introduction of an insecticidal proteinase inhibitor gene into cereal plants can be used as a general strategy for control of insect pests.

Animals↗