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Biomedical subjects

Y Fu

Publications and source records attributed to Y Fu.

At least 37 records · Page 2Linked to original sources

Identification of a novel HLA-DPB1 allele--DPB1*0102.

In this report, we describe the identification of a novel HLA-DPB1 allele, DPB1*0102, which was first found in a 27-year-old woman and was later detected again in another person, from the Han population of China. According to the nucleotide alignment, DPB1*0102 was the most similar to DPB1*0202, with only one nucleotide substitution from A to G at position 192 among three closely related alleles--DPB1*0202, DPB1*2401 and DPB1*0501. This substitution was a non-synonymous one, which caused a change of amino acid from E to K at codon 69 of DP beta-chain in the mature protein.

Adult↗

First results from KamLAND: evidence for reactor antineutrino disappearance.

KamLAND has measured the flux of nu;(e)'s from distant nuclear reactors. We find fewer nu;(e) events than expected from standard assumptions about nu;(e) propagation at the 99.95% C.L. In a 162 ton.yr exposure the ratio of the observed inverse beta-decay events to the expected number without nu;(e) disappearance is 0.611+/-0.085(stat)+/-0.041(syst) for nu;(e) energies >3.4 MeV. In the context of two-flavor neutrino oscillations with CPT invariance, all solutions to the solar neutrino problem except for the "large mixing angle" region are excluded.

Journal Article↗

Does the discharge ECG provide additional prognostic insight(s) in non-ST elevation ACS patients from that acquired on admission?

BACKGROUND: Although the prognostic value of admission ST changes in patients with non-ST elevation acute coronary syndrome (ACS) is established, the utility of the discharge ECG is unknown. Accordingly, using the PARAGON-B Troponin substudy, we assessed the prevalence of ST depression on both admission and discharge ECG, the likelihood of developing new Q-waves at discharge and the additional prognostic value of these changes. METHODS AND RESULTS: Nine hundred and eighteen patients were studied; 542 patients (59%) had admission ST downward arrow > or =1mm and 376 patients (41%) did not and their 6-month mortality was 4.4 vs 0.8%, P=0.002, respectively. Of patients with ST downward arrow on admission, 320 (59%) normalized their ST segment at discharge. Of patients without ST downward arrow on admission, 35 (9.3%) developed new ST downward arrow at discharge. Patients with persistent ST downward arrow on discharge had a higher 6-month mortality (6.0 vs 0.9%), (re)MI (16.3 vs 7.4%), and death/(re)MI (20.0 vs 8.3%) than those who never had ST downward arrow (all P< or =0.002). Two hundred and fifty-six patients had Q-waves on admission whereas by discharge 320 had Q-waves. Patients with Q-waves on discharge vs those without had a higher mortality (4.8 vs 1.9%), (re)MI (13.8 vs 8.3%), and death/(re)MI (16.4 vs 9.6%) at 6 months (all P< or =0.021). CONCLUSIONS: This study highlights that the dynamic ECG changes which occur between admission and discharge in non-ST elevation ACS patients allows further risk stratification in determining the likelihood of 6-month death and/or re(MI).

Acetates↗

HLA-DRB1, DQB1 and DPB1 polymorphism in the Naxi ethnic group of South-western China.

Polymorphism of HLA-DRB1, DQB1 and DPB1 was revealed with a sequencing-based typing (SBT) method in unrelated healthy volunteers from the Naxi ethnic group. Among the 43 DRB1 alleles detected, the most common allele was DRB1*12021 with a frequency of 17%, followed by DRB1*08032, DRB1*09012 and DRB1*1404 with frequencies of 8.5%, 7.4% and 7.4%, respectively. Among 23 DQB1 alleles detected, the most frequent DQB1 allele was DQB1*03011/0309 (21.9%), followed by DQB1*0502 (16.4%) and DQB1*05031 (9.6%). For the DPB1 locus, the most common alleles were DPB1*0501 (25.5%), DPB1*0402 (14.6%) and DPB1*02012 (12.0%). The most common DRB1-DQB1-DPB1 haplotype was DRB1*1404-DQB1*05031-DPB1*0402 with a frequency of 5.26%, followed by the DRB1*08032-DQB1*06011-DPB1*1301 (3.51%). The distribution characteristics of the HLA class II alleles revealed that the Naxi ethnic group belonged to the Southern group of Chinese.

Alleles↗

Intercontinental genetic divergence of Castanea species in eastern Asia and eastern North America.

Castanea is one of the many plant genera with a disjunct distribution pattern between eastern Asia and eastern North America. Five species from three sections of the genus were investigated to examine genetic divergence between eastern Asian and eastern North American species. A total of 62 native populations were sampled for allelic variation at isozyme loci. The Chinese chestnut C. mollissima had the highest genetic variability, while the American C. dentata had the lowest genetic variability. The highest intracontinental genetic identities were observed between the Allegheny and Ozark chinkapins (0.931) and between C. mollissima and C. seguinii (0.870), while lower identities were detected between the American C. pumila and C. dentata (0.720-0.729). In intercontinental comparisons, genetic identities of 0.505, 0.495 and 0.507 were observed between the American chestnut and the Chinese C. mollissima, C. seguinii and C. henryi, respectively, whereas the Ozark chinkapin C. pumila var. ozarkensis had lower identities of 0.469, and 0.435 with C. mollissima and C. seguinii, respectively, but a slightly higher identity of 0.520 with C. henryi, the Chinese chinkapin. Divergence times were estimated at 10-13 million years before present between C. dentata and C. mollissima, and C. pumila var. ozarkensis and C. henryi.

Biological Evolution↗

Epitope analysis for human sperm-immobilizing monoclonal antibodies, MAb H6-3C4, 1G12 and campath-1.

Human monoclonal antibody, MAb H6-3C4, possesses strong sperm immobilizing activity. MAb H6-3C4 has been suggested by several research groups to react with a carbohydrate moiety of male reproductive tract CD52 (mrtCD52). In the present study, we analysed the epitope on mrtCD52 for MAb H6-3C4 and found that it was polymorphic in Western blot analysis and disappeared after enzymatic removal of the N-linked carbohydrate moiety. Two other monoclonal antibodies (1G12, campath-1) with sperm-immobilizing activity recognized mrtCD52 in a polymorphic manner similar to MAb H6-3C4. Further analysis showed that 1G12 recognized a structure formed by the peptide and/or a glycosylphosphatidylinositol (GPI) anchor portion as does campath-1. Results of a lectin binding assay suggested the presence of O-linked carbohydrates on mrtCD52. Our results also indicated that the peptide portion of CD52 could serve as an epitope for sperm-immobilizing antibodies. It was concluded that the epitope of MAb H6-3C4 is similar to, but distinct from, those of 1G12 and campath-1, and that mrtCD52 contains different antigenic epitopes.

Antibodies, Monoclonal↗

A novel DRB1*09 allelic sequence in the Jing ethnic minority of China.

A new DRB1 allele, DRB1*0902, has been identified in an individual of the Jing ethnic minority. Its sequence was confirmed by sequencing of PCR products and clones. This allele differed by three nucleotides from DRB1*09012 at positions 157, 161 and 166, and resulted in amino acid motif substitution from VAES to DAEY.

Amino Acid Motifs↗

[Protective effect of human decay accelerating factor on mouse cells].

OBJECTIVE: To observe the protective effect of human decay accelerating factor (DAF) expressed in mouse myeloma cells against the injury of human serum complement. METHODS: Mouse myeloma cells were transfected with human DAF cDNA and then put into normal human serum culture to observe if they were injured. RESULTS: The mouse cells containing human DAF cDNA and expressing human DAF survived for more than 48 hours and passed on from generation to generation in the culture medium containing human normal serum. However, the control mouse cells died in 1 - 4 hours. CONCLUSION: Human DAF protects mouse cells from injuring by human complement.

Animals↗

Endothelin-1 gene variant associates with blood pressure in obese Japanese subjects: the Ohasama Study.

A recent report based on the results of 2 epidemiological studies, the Etude Cas-Temoin de l'Infarctus Myocarde (ECTIM) and the Glasgow Heart Scan Study, revealed that a G/T polymorphism with an amino acid substitution (Lys-->Asn) at codon 198 in exon 5 of the endothelin-1 gene (ET-1) is associated with blood pressure in overweight people. They suggested that G/T polymorphism of ET-1 strongly interacted with body mass index (BMI) in the determination of BP levels. To examine interaction among G/T polymorphism of ET-1, BMI, and BP, we performed an association study in a general Japanese population. Subjects (n=1250) were recruited from Ohasama, a cohort in a rural community of northern Japan. DNA was extracted from buffy coat of participants, and G/T polymorphism of ET-1 was determined by the TaqMan probe polymerase chain reaction method, a powerful tool for semiautomatic genotype determination of a large number of samples. Frequency of T (Asn 198) allele in Japanese (27%) was slightly but significantly higher than in whites (24%). Baseline characteristics (age, BMI, systolic and diastolic BP, and antihypertensive treatment) of all subjects were not significantly different according to the genotype of G/T polymorphism. However, in obese subjects (> or =25 kg/m(2)) diastolic BPs were significantly associated with G/T polymorphism of ET-1. After adjustment for confounding factors, significant association remained; for overweight subjects, diastolic BP level in those with T allele (GT + TT) was 1.8 mm Hg (P=0.04) higher than in those with GG genotype. That similar results were obtained from subjects of different races suggests that the Lys198Asn polymorphism of ET-1 is involved in determination of BP levels in obese subjects.

Asian People↗

Time to treatment influences the impact of ST-segment resolution on one-year prognosis: insights from the assessment of the safety and efficacy of a new thrombolytic (ASSENT-2) trial.

BACKGROUND: Early ST resolution after reperfusion is a prognostic indicator in acute myocardial infarction. Little information exists regarding the prognostic utility of ST resolution beyond 4 hours after fibrinolysis. Furthermore, the relation between time to treatment, ST resolution at 24 to 36 hours, and 1-year outcome has not been well studied. Accordingly, we undertook a prospective ECG substudy in the Assessment of the Safety and Efficacy of a New Thrombolytic (ASSENT-2) trial to examine this. METHODS AND RESULTS: Patients (n=13 100) were stratified into 3 ST-resolution categories, based on baseline and 24- to 36-hour ECGs: complete resolution (>/=70%) in 6698 (51.1%) patients, partial resolution (30% to 70%) in 4610 (35.2%) patients, and no resolution (<30%) in 1792 (13.7%) patients; 1-year mortality rate was 5.1%, 8.0%, and 9.7%, respectively (P<0.001). Among patients treated <2 hours after symptom onset, 55.6% had complete ST resolution, whereas 52.1% and 43% of patients treated between 2 to 4 hours and 4 to 6 hours, respectively, had complete ST resolution (P<0.001). Within each category of ST resolution, patients treated <2 hours had lower 1-year mortality rates as compared with patients treated between 2 to 4 hours or >4 hours (3.8% versus 5.2% and 6.6%, P=0.002 in complete ST resolution; 5.7% versus 8.4% and 9.9%, P=0.001 in partial ST resolution; 7.1% versus 8.7% and 13%, P=0.006 in no resolution). The extent of ST resolution was closely and inversely correlated with 1-year mortality rates (r=-0.963, P<0.001). CONCLUSIONS: ST resolution at 24 to 36 hours after fibrinolysis is influenced by time to treatment and inversely related to 1-year mortality rates. Time to treatment further differentiates between high- and low-risk patients and further highlights the importance of reducing time delay to initiation of fibrinolysis in acute myocardial infarction.

Aged↗

Norepinephrine secretion in the hypothalamic paraventricular nucleus of rats during unlimited access to self-administered nicotine: An in vivo microdialysis study.

Norepinephrine (NE) secretion within the hypothalamic paraventricular nucleus (PVN) is pivotal to endocrine and behavioral responses. Activation of NE afferents to PVN also is necessary for the hypothalamo-pituitary-adrenal axis response to passively administered nicotine. The mode of drug delivery is a critical determinant of the dynamics of neurotransmitter secretion, yet the PVN NE response to nicotine self-administration (SA) is unknown. Herein, rats housed in operant chambers had unlimited 23 hr access to self-administered nicotine. In vivo microdialysis of PVN NE was performed, collecting consecutive 7 min samples over 9 hr sessions during three phases of nicotine SA: acquisition (day 1); early maintenance, once stable rates of SA were achieved (day 9.2 +/- 0.6); later maintenance (day 18.6 +/- 0.8). On d1, nicotine animals had an increased percentage of SA episodes (SAEs) in which NE levels were elevated (80 vs 30% with saline; p < 0.01). By early maintenance, a fourfold increase in such episodes was observed in nicotine animals (p < 0.01), and the overall NE level was greater (1.30 +/- 0.24 vs 0.63 +/- 0.07 pg/10 microl in saline; p < 0.05); NE increased during the first, but not the last, SAE. The pattern was similar during later maintenance, although NE responsiveness declined (overall NE level, 0.96 +/- 0.19 in nicotine vs 0.52 +/- 0.08 pg/10 microl in saline; p < 0.05). Therefore, nicotine SAEs were associated with sustained increases in NE secretion during all three phases of SA. However, the reduced NE responsiveness observed both within the dialysis session in each phase and by later versus early maintenance is consistent with progression of partial daily desensitization of PVN NE secretion to nicotine SA. Therefore, in rats chronically self-administering nicotine, the drug stimulates sustained PVN NE secretion that may alter neuroendocrine and behavioral responses mediated by the PVN. Compared with studies of chronic human smokers, our nicotine SA model may reflect the CNS noradrenergic responses that occur during human cigarette smoking.

Animals↗

Comparative impacts of glutathione peroxidase-1 gene knockout on oxidative stress induced by reactive oxygen and nitrogen species in mouse hepatocytes.

Selenium-dependent glutathione peroxidase-1 (GPX1) protects against reactive-oxygen-species (ROS)-induced oxidative stress in vivo, but its role in coping with reactive nitrogen species (RNS) is unclear. Our objective was to compare the protection of GPX1 against cytotoxicity of superoxide generator diquat (DQ), NO donor S-nitroso-N-acetyl-penicillamine (SNAP) and peroxynitrite generator 3-morpholinosydnonimine (SIN-1). Primary hepatocytes were isolated from GPX1-knockout (KO) and wild-type (WT) mice and cultured in complete Williams's medium E with various levels of these agents alone or in combination for up to 12 h. While the KO cells were more susceptible to cell death, DNA fragmentation and protein carbonyl formation induced by 0.25-1 mM DQ, these cells were as tolerant as the WT cells to cytotoxicity of 0.1-1 mM SNAP or 0.5-2 mM SIN-1. Treating cells with SNAP (0.1 or 0.25 mM) in addition to DQ produced synergistic cytotoxicity that minimized differences in apoptotic cell death and oxidative injuries between the KO and WT cells. Less protein nitrotyrosine was induced by 0.05-0.5 mM DQ+0.25 mM SNAP in the KO than in the WT cells. Total GPX activity in the WT cells was reduced by 65 and 25% by 0.5 mM DQ+0.1 mM SNAP and 0.5 mM DQ, respectively. Decreases in Cu,Zn-superoxide dismutase (SOD) activity and increases in Mn-SOD activity in response to DQ or DQ+SNAP were greater in the KO cells than in the WT cells. In conclusion, GPX1 was more effective in protecting hepatocytes against oxidative injuries mediated by ROS alone than by ROS and RNS together. Knockout of GPX1 did not enhance cell susceptibility to RNS-associated cytotoxicity. Instead, it attenuated protein nitration induced by DQ+SNAP.

Animals↗

Sterically hindered C(alpha, alpha)-disubstituted alpha-amino acids: synthesis from alpha-nitroacetate and incorporation into peptides.

The preparation of sterically hindered and polyfunctional C(alpha,alpha)-disubstituted alpha-amino acids (alpha alpha AAs) via alkylation of ethyl nitroacetate and transformation into derivatives ready for incorporation into peptides are described. Treatment of ethyl nitroacetate with N,N-diisopropylethylamine (DIEA) in the presence of a catalytic amount of tetraalkylammonium salt, followed by the addition of an activated alkyl halide or Michael acceptor, gives the doubly C-alkylated product in good to excellent yields. Selective nitro reduction with Zn in acetic acid or hydrogen over Raney Ni gives the corresponding amino ester that, upon saponification, can be protected with the fluorenylmethyloxycarbonyl (Fmoc) group. The first synthesis of an orthogonally protected, tetrafunctional C(alpha,alpha)-disubstituted analogue of aspartic acid, 2,2-bis(tert-butylcarboxymethyl)glycine (Bcmg), is described. Also, the sterically demanding C(alpha,alpha)-dibenzylglycine (Dbg) has been incorporated into a peptide using solid-phase synthesis. It was found that once sterically congested Dbg is at the peptide N-terminus, further chain extension becomes very difficult using uronium or phosphonium salts (PyAOP, PyAOP/HOAt, HATU). However, preformed amino acid symmetrical anhydride couples to N-terminal Dbg in almost quantitative yield in nonpolar solvent (dichloroethane-DMF, 9:1).

Acetates↗

Opposite roles of selenium-dependent glutathione peroxidase-1 in superoxide generator diquat- and peroxynitrite-induced apoptosis and signaling.

Oxidative injuries including apoptosis can be induced by reactive oxygen species (ROS) and reactive nitrogen species (RNS) in aerobic metabolism. We determined impacts of a selenium-dependent glutathione peroxidase-1 (GPX1) on apoptosis induced by diquat (DQ), a ROS (superoxide) generator, and peroxynitrite (PN), a potent RNS. Hepatocytes were isolated from GPX1 knockout (GPX1-/-) or wild-type (WT) mice, and treated with 0.5 mm DQ or 0.1-0.8 mm PN for up to 12 h. Loss of cell viability, high levels of apoptotic cells, and severe DNA fragmentation were produced by DQ in only GPX1-/- cells and by PN in only WT cells. These two groups of cells shared similar cytochrome c release, caspase-3 activation, and p21(WAF1/CIP1) cleavage. Higher levels of protein nitration were induced by PN in WT than GPX1-/- cells. Much less and/or slower cellular GSH depletion was caused by DQ or PN in GPX1-/- than in WT cells, and corresponding GSSG accumulation occurred only in the latter. In conclusion, it is most striking that, although GPX1 protects against apoptosis induced by superoxide-generator DQ, the enzyme actually promotes apoptosis induced by PN in murine hepatocytes. Indeed, GSH is a physiological substrate for GPX1 in coping with ROS in these cells.

Animals↗

Lipopolysaccharide and interferon-gamma-induced nitric oxide production and protein oxidation in mouse peritoneal macrophages are affected by glutathione peroxidase-1 gene knockout.

This study investigated the role of glutathione peroxidase-1 (GPX1) in protein oxidation in peritoneal macrophages. Macrophages isolated from both wild-type (WT) and GPX1 knockout (KO) mice were activated by lipopolysaccharide (LPS, 1 microg/ml) and interferon-gamma (IFN, 10 U/ml for 24 or 48 h in the presence or absence of 1 microM diquat (DQ), 250 microM aminoguanidine (AG, an inhibitor of inducible nitric oxide synthase), and (or) 100 microM diethyldithiocarbamate (DETC, an inhibitor of Cu,Zn-SOD). In the KO macrophages, there was no protein band detected by Western blot with anti-GPX1 antibody and 98% reduction in total GPX activity compared with WT cells. Nitric oxide (NO) synthesis was greatly enhanced after 24 h by GPX1 knockout and DQ, but inhibited by AG or DETC. Protein carbonyl formation in total cell extract was clearly associated with NO synthesis as higher levels of protein carbonyl were detected in activated KO than WT macrophages, and DQ enhanced slightly while AG or DETC virtually blocked its formation. A similarly marginal effect of GPX1 KO was observed on protein nitration. The LPS/IFN/DQ-induced DNA fragmentation was blocked by AG, but not by DETC. Cell viability at 48 h was decreased by the LPS/IFN activation and further reduced by the addition of DQ, but restored by AG. In conclusion, GPX1 affects the NO production in activated peritoneal macrophages and protects these cells against NO-associated protein oxidation.

Animals↗

Huperzine A protects rat pheochromocytoma cells against oxygen-glucose deprivation.

The effect of huperzine A (HupA) on oxygen-glucose deprivation (OGD)-induced injury was investigated in the rat pheochromocytoma cell line PC12. OGD for 3 h and reoxygenation for 24 h triggered apoptosis characterized by chromatin condensation, nucleus fragmentation and DNA laddering. The temporal profile of c-jun, p53, bcl-2 and bax mRNA after OGD indicated that these genes played important roles in apoptosis. Pre-incubation of the cells for 2 h with 1 microM HupA significantly attenuated apoptosis. The same treatment also reduced the up-regulation of c-jun and bax as well as the down-regulation of bcl-2. These data suggest the ability of HupA to attenuate apoptosis induced by OGD may result from its capability to alter the expression of apoptosis-related genes.

Alkaloids↗