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Biomedical subjects

Y Feng

Publications and source records attributed to Y Feng.

At least 433 records · Page 24Linked to original sources
PubMed1989

Proton resonance assignments of horse ferricytochrome c.

Two-dimensional nuclear magnetic resonance spectroscopy (2D NMR) was used to obtain extensive resonance assignments in the 1H NMR spectrum of horse ferricytochrome c. Assignments were made for the main-chain and C beta protons of 102 residues (all except Pro-44 and Gly-84) and the majority of side-chain protons. As starting points for the assignment of the oxidized protein, a limited set of protons was initially assigned by use of 2D NMR magnetization transfer methods to correlate resonances in the oxidized form with assigned resonances in the reduced form [Wand, A. J., Di Stefano, D. L., Feng, Y., Roder, H., & Englander, S. W. (1989) Biochemistry (preceding paper in this issue)]. Given the complexity of the spectrum due to the size of this protein (104 residues) and its paramagnetic center, the initial search for side-chain spin systems in J-correlated spectra was successful only for the simplest side chains, but the majority of NH-C alpha H-C beta H subspin systems (NAB sets) could be identified at this stage. The subsequent search for sequential NOE connectivities focused on NAB sets, with use of previously assigned residues to place NOE-connected segments within the amino acid sequence. Selective proton labeling of either the slowly or the rapidly exchanging amide sites was used to simplify the spectra, and systematic work at two temperatures was used to resolve ambiguities in the 2D NMR spectra. These approaches, together with the use of magnetization transfer methods to correlate reduced and oxidized cytochrome c spectra, provide multiple cross-checks to verify assignments.

Amino Acid Sequence↗
PubMed1988

The YYRR box: a conserved dipyrimidine-dipurine sequence element in Drosophila and other eukaryotes.

We have discovered a novel DNA sequence element in Drosophila which is based upon a CTGA tandem repeat. This element has been named the YYRR box to emphasize its dipyrimidine-dipurine nature which is predicted to have unusual structural features. Southern hybridization analysis of genomic DNA indicates the presence of 25-30 copies of the YYRR box in each of three Drosophila species (melanogaster, pseudoobscura, and virilis) and conservation of genomic location within species. Similar analysis of human and rat DNA indicates the presence of YYRR related sequences in mammals as well. YYRR boxes have been localized to two genetic loci in Drosophila: Gld and a gene tentative identified as ted. These two genes exhibit correlated patterns of developmental expression and an identical mutant phenotype. Sequence analysis of the Gld YYRR box in three Drosophila species revealed a high degree of conservation despite its intronic location.

Animals↗
PubMed1988

Effect of continuous infusion of bleomycin on the time for completion of repair of sublethal radiation damage in mouse lip mucosa during fractionated irradiation.

The influence of a simultaneous continuous infusion of bleomycin on the time necessary for repair of sublethal radiation damage during fractionated irradiation of mouse lip mucosa was studied. Although there are strong indications that bleomycin interferes with the accumulation and repair of sublethal radiation damage, no significant change in the time course of these repair processes could be demonstrated following various analyses of the experimental results. An interval of at most 4 h between successive irradiations was sufficient to allow for a similar amount of repair of sublethal damage as compared with either 24 h (2 fractions) or 6 h (10 fractions), whether or not radiation was combined with bleomycin infusion.

Animals↗
PubMed1988

Effect of simultaneous administration of bleomycin on the acute skin reactions of mice after single and fractionated doses of radiation.

The effect of bleomycin on the acute mouse foot skin reactions, occurring after irradiation, was investigated. Bleomycin was delivered simultaneously with the irradiation treatment, either by intraperitoneal injection or by subcutaneous continuous infusion. Experiments were carried out to investigate (a) the modification by bleomycin of the response to single doses of radiation (b) the effect of total drug dose on this modification (c) the influence of the drug on repair of sublethal radiation damage and (d) the interference by the drug with compensatory repopulation after irradiation. In none of the experiments could any influence of the drug on these radiation induced reactions and recovery processes be demonstrated. These results are in direct contrast to what we have observed previously for similar types of experiments in another epithelial system, the mouse lip mucosa.

Animals↗
PubMed1988

Effect of protein synthesis inhibition on gene expression during early development of Dictyostelium discoideum.

Several genes which are deactivated on the initiation of development of Dictyostelium discoideum were identified by differential screening of various cDNA libraries. These genes have in common a decrease in the steady-state levels of their corresponding mRNAs on the onset of development and as development proceeds. When development was carried out in the absence of protein synthesis by inhibition with cycloheximide, the decrease in mRNA levels for most genes (V genes) was normal or slightly accelerated. For about 5% of the genes (H genes), however, cycloheximide caused an apparent induction of expression, as revealed by a slight or dramatic increase in mRNA levels, instead of the normal decrease. This effect was due to inhibition of protein synthesis and not to cycloheximide per se. The induction was found to be due to an enhancement of the transcription rate; normal rates of transcription for the H genes were dependent on continued protein synthesis during vegetative growth and development. Thus, two general regulatory classes exist for deactivation of gene expression on initiation of development, one of which is dependent on and one of which is independent of protein synthesis. Analysis of expression of these genes in mutant strains which are aggregation deficient allowed the classes to be subdivided further. Taken together, these characterizations allow several distinct regulatory mechanisms to be identified that are involved in the deactivation of gene expression on the onset of development in D. discoideum.

Cell Aggregation↗
PubMed1988

Effect of continuous infusion of bleomycin on repopulation in mouse lip mucosa during fractionated irradiation.

The effect of the administration of bleomycin on repopulation in mouse lip mucosa during fractionated irradiation was studied. Two equal-sized irradiation fractions were delivered with 1-, 7-, or 10-day intervals, with and without simultaneous administration of 40 mg bleomycin/kg in a continuous sc infusion, given over 7 days. In the experiments with irradiation only, the prolongation of the interval from 1 day to 7 days resulted in a net increase of the isoeffective dose due to compensatory proliferation. This effect was even more pronounced with the 10-day treatment interval. The addition of bleomycin, however, nearly completely suppressed this proliferative activity.

Animals↗
PubMed1986

The combined effect of bleomycin and irradiation on mouse lip mucosa. 1. Influence of timing, sequence and mode of drug administration with single dose irradiation.

The effect of the combination of single dose irradiation and bleomycin on the mucosa of the mouse lip was investigated. Bleomycin was administered either by IP injection or by subcutaneous continuous infusion. With the combined treatment an increased effect was observed compared to irradiation alone. The effect was drug-dose dependent in the range of doses used (5-80 mg/kg) and was similar for both ways of drug administration. There was only a limited influence of timing and sequence of the two agents within a period of 4 days. Since the dose-response curves were shifted in a parallel way, a constant cell killing effect by bleomycin is suggested for all irradiation doses used. This could be due to independent cell kill by the drug, although some mechanism of interaction, such as interference with accumulation of sublethal radiation damage or a true dose modification can not be excluded.

Animals↗
PubMed1986

The combined effect of bleomycin and irradiation on mouse lip mucosa. 2. Influence on the accumulation and repair of sublethal damage during fractionated irradiation.

The effect on the mouse lip mucosa of different fractionated irradiation schedules (with respectively 1, 2, 4 10 and 20 equal fractions) with and without a simultaneous constant drug regimen (bleomycin 40 mg/kg in a continuous subcutaneous infusion over seven days) was investigated. Lowering the fraction size resulted in a progressive increase of both the dose modification factors (DMF) and the absolute dose reduction (ADR), i.e. from 1.19 and 2.8 Gy respectively for single doses to 1.86 and 21.5 Gy respectively for 20 fractions (at isoeffect level 3.5). The mechanisms involved are most probably a direct cell kill by bleomycin, together with a reduced capacity to accumulate and/or to repair sublethal damage, although the influence of redistribution in the cell cycle during bleomycin infusion can not be excluded. Such large differences in the interaction between chemotherapy and irradiation as a function of the fractionation schedule could lead to a significant underestimate of response if data from single dose or 2-fraction experiments are extrapolated to regimens used in clinical practice.

Animals↗
PubMedDate not supplied

Imidazoline receptor proteins are regulated in platelet-precursor MEG-01 cells by agonists and antagonists.

The I1-imidazoline receptor is a novel brainstem modulator of sympathetic outflow that is elevated on platelets and in brains of depressed patients. A positive correlation has been reported (accompanying manuscript) between plasma norepinephrine (NE) concentrations and the densities (Bmax) of platelet I1 binding sites (I1 sites). I1-candidate proteins of 33 kDa and 85 kDa are now identified on Western blots probed with anti-imidazoline receptor antiserum (IRBP antiserum), that correlate with Bmax values for I1 sites. Furthermore, a human megakaryoblastoma cell line (MEG-01) has been used to study the regulation of these proteins on megakaryocytic cells, while bovine adrenal chromaffin cells provide a standard I1 cell type for comparison. Both the 33 kDa and 85 kDa IRBP-immunoreactive bands were enriched in plasma membrane fractions. IRBP antiserum did not cross-react with I2 imidazoline binding sites located on platelet mitochondrial membranes. The 85 kDa band was enhanced under conditions lacking fetal bovine serum (FBS) from the culture medium 6 h prior to harvesting. Conversely, 33 kDa protein was enhanced on MEG-01 cells grown in the presence of 10% FBS; suggesting that a precursor (85 kDa) and product (33 kDa) relationship might be induced by serum. The 85 kDa band was robustly up-regulated in response to imidazoline receptor-sensitive ligands; moxonidine, idazoxan and agmatine (10 microM each for 6 h). NE also up-regulated the 85 kDa IRBP-immunoreactive protein on MEG-01 membranes, but to a lesser extent. Idazoxan, an imidazoline alpha 2-antagonist, off-set its induction of 85 kDa protein by reducing the 33 kDa band. Yohimbine, a non-imidazoline alpha 2-antagonist, was ineffective alone, or in combination with moxonidine (up to 40 microM), but yohimbine blocked NE's induction of the 85 kDa band. Therefore, a rise in either plasma NE and/or endogenous I-site ligands (i.e. agmatine) could explain an elevation of imidazoline receptors observed in depression.

Agmatine↗
PubMedDate not supplied

Neuronal polo-like kinase in Alzheimer disease indicates cell cycle changes.

Neurons of adults apparently lack the components necessary to complete the cell division process. Therefore, in Alzheimer disease, the increased expression of cell cycle-related proteins in degenerating neurons likely leads to an interrupted mitotic process associated with cytoskeletal abnormalities and, ultimately, neuronal degeneration. In this study, to further delineate the role of mitotic processes in the pathogenesis of Alzheimer disease, we undertook a study of polo-like kinase (Plk), a protein that plays a crucial role in the cell cycle. Our results show disease-related increases in Plk in susceptible hippocampal and cortical neurons in comparison to young or age-matched controls. An increase in neuronal Plk further implicates aberrations in cell cycle control in the pathogenesis of Alzheimer disease and provides a novel mechanistic basis for therapeutic intervention.

Adolescent↗
PubMedDate not supplied

Necessity of carnitine supplementation in semistarved rats fed a high-fat diet.

We investigated the effects of carnitine supplementation on lipid metabolism in semistarved rats. The semistarved rats were fed a high-fat diet and half the normal energy intake for 2 wk. Carnitine was supplied daily at a dose of 250 mg/kg of body weight. The results showed that the concentration of plasma free carnitine increased significantly in semistarved and carnitine-supplemented rats compared with normal and semistarved rats. The activities of muscle carnitine palmitoyltransferase I and preheparin plasma lipoprotein lipase also were significantly increased in semistarved and carnitine-supplemented rats. The plasma triacylglycerol secretion rate was restored to normal by carnitine supplementation in semistarved rats. Urinary excretion of ketone bodies was reduced significantly after carnitine supplementation. We concluded that supplementation of carnitine can significantly increase the concentration of plasma free carnitine and improve lipid metabolism in semistarved rats fed a high-fat diet.

Animals↗