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Biomedical subjects

Y Wu

Publications and source records attributed to Y Wu.

At least 649 records · Page 36Linked to original sources

Differential regulation of sugar-sensitive sucrose synthases by hypoxia and anoxia indicate complementary transcriptional and posttranscriptional responses

The goal of this research was to resolve the hypoxic and anoxic responses of maize (Zea mays) sucrose (Suc) synthases known to differ in their sugar regulation. The two maize Suc synthase genes, Sus1 and Sh1, both respond to sugar and O2, and recent work suggests commonalities between these signaling systems. Maize seedlings (NK508 hybrid, W22 inbred, and an isogenic sh1-null mutant) were exposed to anoxic, hypoxic, and aerobic conditions (0, 3, and 21% O2, respectively), when primary roots had reached approximately 5 cm. One-centimeter tips were excised for analysis during the 48-h treatments. At the mRNA level, Sus1 was rapidly up-regulated by hypoxia (approximately 5-fold in 6 h), whereas anoxia had less effect. In contrast, Sh1 mRNA abundance increased strongly under anoxia (approximately 5-fold in 24 h) and was much less affected by hypoxia. At the enzyme level, total Suc synthase activity rose rapidly under hypoxia but showed little significant change during anoxia. The contributions of SUS1 and SH1 activities to these responses were dissected over time by comparing the sh1-null mutant with the isogenic wild type (Sus+, Sh1+). Sh1-dependent activity contributed most markedly to a rapid protein-level response consistently observed in the first 3 h, and, subsequently, to a long-term change mediated at the level of mRNA accumulation at 48 h. A complementary midterm rise in SUS1 activity varied in duration with genetic background. These data highlight the involvement of distinctly different genes and probable signal mechanisms under hypoxia and anoxia, and together with earlier work, show parallel induction of "feast and famine" Suc synthase genes by hypoxia and anoxia, respectively. In addition, complementary modes of transcriptional and posttranscriptional regulation are implicated by these data, and provide a mechanism for sequential contributions from the Sus1 and Sh1 genes during progressive onset of naturally occurring low-O2 events.

Journal Article↗

An Arabidopsis brassinosteroid-dependent mutant is blocked in cell elongation.

Cell elongation is a developmental process that is regulated by light and phytohormones and is of critical importance for plant growth. Mutants defective in their response to light and various hormones are often dwarfs. The dwarfed phenotype results because of a failure in normal cell elongation. Little is known, however, about the basis of dwarfism as a common element in these diverse signaling pathways and the nature of the cellular functions responsible for cell elongation. Here, we describe an Arabidopsis mutant, dwarf4 (dwf4), whose phenotype can be rescued with exogenously supplied brassinolide. dwf4 mutants display features of light-regulatory mutants, but the dwarfed phenotype is entirely and specifically brassinosteroid dependent; no other hormone can rescue dwf4 to a wild-type phenotype. Therefore, an intact brassinosteroid system is an absolute requirement for cell elongation.

Arabidopsis↗

A cepstral method for analysis of acoustic transmission characteristics of respiratory system.

The generation and transmission process of transmitted sound signals (TSS) is analyzed and a mathematical model of TSS is established in this paper. The power cepstral characteristics of TSS are studied based on the mathematical model and a new analysis method of acoustic transmission of respiratory system using homomorphic processing technique is proposed. The experimental results show that the normal respiratory system has only one formant, while the abnormal respiratory system presenting lung consolidation has two formants and the second formant plays important role in that system. This new method is a simple and effective one.

Adult↗

S-1153 inhibits replication of known drug-resistant strains of human immunodeficiency virus type 1.

S-1153 is a new imidazole compound that inhibits human immunodeficiency virus (HIV) type 1 (HIV-1) replication by acting as a nonnucleoside reverse transcriptase inhibitor (NNRTI). This compound inhibits replication of HIV-1 strains that are resistant to nucleoside and nonnucleoside reverse transcriptase inhibitors. S-1153 has a 50% effective concentration in the range of 0.3 to 7 ng/ml for strains with single amino acid substitutions that cause NNRTI resistance, including the Y181C mutant, and also has potent activity against clinical isolates. The emergence of S-1153-resistant variants is slower than that for nevirapine, and S-1153-resistant variants contained at least two amino acid substitutions, including F227L or L234I. S-1153-resistant variants are still sensitive to the nucleoside reverse transcriptase inhibitors zidovudine (AZT) and lamivudine. In a mouse and MT-4 (human T-cell line) in vivo HIV replication model, S-1153 and AZT administered orally showed a marked synergy for the inhibition of HIV-1 replication. S-1153 shows a significant accumulation in lymph nodes, where most HIV-1 infection is thought to occur. S-1153 may be an appropriate candidate for two-to three-drug combination therapy for HIV infection.

Animals↗

Zinc deficiency decreases plasma level and hepatic mRNA abundance of apolipoprotein A-I in rats and hamsters.

The influence of Zn deficiency on the plasma level as well as the hepatic and intestinal gene expression of apolipoprotein (apo) A-I was examined in rats and hamsters. Male Sprague-Dawley rats (8 wk old) and Golden Syrian hamsters (7 wk old) were assigned to three dietary treatments: Zn adequate (ZA, 30 mg Zn/kg diet), Zn deficient (ZD, <0.5 mg Zn/kg diet), and Zn replete (ZDA, ZD animals fed the ZA diet for the last 2 days). The dietary treatments lasted for 18 days for rats or 6 wk for hamsters. For the measurement of apoA-I mRNA abundance, hamster apoA-I cDNA was cloned from the small intestine. The full-length 905-base pair cDNA shared approximately 80% similarity with the human, rat, and mouse apoA-I cDNAs. Hepatic and plasma Zn levels were reduced in ZD animals but normalized in ZDA rats and increased in ZDA hamsters compared with ZA animals. Zn deficiency reduced plasma apoA-I and hepatic apoA-I mRNA levels 13 and 38%, respectively, in ZD rats. The 2 days of Zn replenishment raised plasma apoA-I and hepatic apoA-I mRNA levels in ZDA rats by 34 and 28%, respectively, higher than ZA rats. Similarly, these levels were decreased by 18 and 25%, respectively, in ZD hamsters but normalized in ZDA hamsters compared with ZA hamsters. In contrast to the alterations of hepatic apoA-I mRNA levels, neither Zn deficiency nor subsequent Zn repletion produced alterations in the intestinal apoA-I mRNA abundance. Data from this study demonstrated that Zn deficiency specifically decreases hepatic apoA-I gene expression, which may at least be partly responsible for the reduction of plasma apoA-I levels.

Amino Acid Sequence↗

Myocardial contractile depression from high-frequency vibration is not due to increased cross-bridge breakage.

Experiments were conducted in 10 isolated rabbit hearts at 25 degrees C to test the hypothesis that vibration-induced depression of myocardial contractile function was the result of increased cross-bridge breakage. Small-amplitude sinusoidal changes in left ventricular volume were administered at frequencies of 25, 50, and 76.9 Hz. The resulting pressure response consisted of a depressive response [delta Pd(t), a sustained decrease in pressure that was not at the perturbation frequency] and an infrequency response [delta Pf(t), that part at the perturbation frequency]. delta Pd(t) represented the effects of contractile depression. A cross-bridge model was applied to delta Pf(t) to estimate cross-bridge cycling parameters. Responses were obtained during Ca2+ activation and during Sr2+ activation when the time course of pressure development was slowed by a factor of 3. delta Pd(t) was strongly affected by whether the responses were activated by Ca2+ or by Sr2+. In the Sr(2+)-activated state, delta Pd(t) declined while pressure was rising and relaxation rate decreased. During Ca2+ and Sr2+ activation, velocity of myofilament sliding was insignificant as a predictor of delta Pd(t) or, when it was significant, participated by reducing delta Pd(t) rather than contributing to its magnitude. Furthermore, there was no difference in cross-bridge cycling rate constants when the Ca(2+)-activated state was compared with the Sr(2+)-activated state. An increase in cross-bridge detachment rate constant with volume-induced change in cross-bridge distortion could not be detected. Finally, processes responsible for delta Pd(t) occurred at slower frequencies than those of cross-bridge detachment. Collectively, these results argue against a cross-bridge detachment basis for vibration-induced myocardial depression.

Animals↗

Regression of LV hypertrophy with captopril normalizes membrane currents in rabbits.

Recent studies indicate that regression of left ventricular hypertrophy (LVH) normalizes the in situ electrophysiological abnormalities of the left ventricle. This study was designed to determine whether regression of LVH also normalizes the abnormalities of individual membrane currents. LVH was induced in rabbits by renal artery banding. Single ventricular myocytes from rabbits with LVH at 3 mo after renal artery banding demonstrated increased cell membrane capacitance, prolonged action potential duration, decreased inward rectifier K+ current density, and increased transient outward K+ current density compared with myocytes from age-matched controls. Additional rabbits were randomized at 3 mo after banding to treatment with either vehicle or captopril for an additional 3 mo. Myocytes from LVH rabbits treated with vehicle showed persistent membrane current abnormalities. However, myocytes isolated from LVH rabbits treated with captopril had normal cell membrane capacitance, action potential duration, and membrane current densities. Captopril had no direct effect on membrane currents of either control or LVH myocytes. These data support the hypothesis that the action potential prolongation and membrane current abnormalities of LVH are reversed by regression. Normalization of membrane currents probably explains the reduced vulnerability to ventricular arrhythmia observed in this LVH model after treatment with captopril.

Action Potentials↗

Expression of IGF-I and IGF-II receptors in rat C6 glioma cells as a function of the growth phase.

In the present study, we examined the specific binding of IGF-I and IGF-II to their receptors in C6 glioma cells taken during different growth phases in culture: phase A, early stage of the exponential growth (48 h after seeding); phase B, late stage of the exponential phase (96 h after seeding); phase C, confluent phase (at 144 h after seeding); and phase D, stopped at 48 h post-confluence. Scatchard analysis revealed higher Ka values for the IGF-IR during the exponential phases (A and B). The affinity of IGF-I for its receptor during the post-confluent phase (D) decreased to about half that at phase A (p < 0.01). Although lower at the later phase (D), the number of binding sites of the IGF-IR in the different tested growth stages in culture (A, B, and C) was not statistically different (p > 0.05). Conversely, the number of binding sites of the IGF-II/mannose-6-phosphate receptor appeared to increase during time in culture. The Ka values of the IGF-II/mannose-6-phosphate receptor decreased significantly during the culture time, phase D showing the largest decrease (50%) as compared with phase A (p < 0.005). These binding data suggest that IGF-I and IGF-II receptors are differentially expressed in rat C6 glioma cells in culture and are a function of the growth phase.

Animals↗

Protein-protein interaction domains and the heterodimerization of thyroid hormone receptor variant alpha2 with retinoid X receptors.

Heterodimerization between thyroid hormone receptors (TRs) and retinoid X receptors (RXRs) is mediated by a weak dimerization interface within the DNA- binding domains (DBDs) and a strong interface within the C-terminal ligand- binding domains of the receptors. Previous studies have shown that the conserved ninth heptad in the TR ligand-binding domain appears to play a critical role in heterodimerization with RXR. However, despite lacking the full ninth heptad, TR variant alpha2 (TRv alpha2) can heterodimerize with RXR on specific direct repeat response elements, but not on palindromic elements or in solution. Two possibilities may account for TRv alpha2-RXR heterodimerization on direct repeats. First, the DBD of TRv alpha2 may play a critical role in heterodimerization with RXR. Second, a specific sequence within the unique C terminus of TRv alpha2 may promote the formation of TRv alpha2-RXR heterodimers. In this study, we used receptor chimeras in which the DBD of RXR was replaced by either the TR DBD or an unrelated DBD from the metalloregulatory transcription factor AMT1 to address the role of the DBD dimerization interface in TRv alpha2-RXR heterodimerization. Gel mobility shift analyses showed that whereas TR alpha1 formed heterodimers with these chimeras, TRv alpha2 failed to do so. Deletion of the unique C terminus of TRv alpha2 had only a marginal effect on heterodimerization with RXR. Mutations within the DBD dimerization interface abolished heterodimerization of full-length TRv alpha2 with RXR but only marginally affected heterodimerization of full-length TR alpha1 with RXR. These data support the hypothesis that the TR-RXR DBD dimerization interface plays a critical role in TRv alpha2-RXR heterodimerization. Additional data show that the amino acid residues that make direct TR-RXR contacts within the DBDs also may play a role in receptor monomer binding to DNA, since mutations within these residues severely impair this interaction.

Amino Acid Sequence↗

Presence of antibodies to heat stress proteins in workers exposed to benzene and in patients with benzene poisoning.

Heat shock or stress proteins (Hsps) are a group of proteins induced by a large number of xenobiotics, many of which are common in the working and living environment. The biological significance of the presence of antibodies against Hsps in humans is presently unknown. In the present study, 112 workers were selected and divided into four groups on the basis of their level of occupational exposure to benzene: a control group, two groups of workers exposed to either low (< 300 mg/m3) or high concentrations of benzene (> 300 mg/m3) and a group of workers who had experienced benzene poisoning. Blood samples from these workers were assayed for the number of peripheral white blood cells, concentration of hemoglobin, activities of serum superoxide dismutase (SOD), lymphocyte DNA damage and finally for the presence of antibodies to different human heat-shock proteins (Hsp27, Hsp60, Hsp71 and Hsp90). Benzene-poisoned workers showed a high incidence of antibodies against Hsp71 (approximately 40%) which was associated with a decrease in white blood cells (3.84+/-1.13 x 10(9)versus 7.68+/-1.84 x 10(9) in controls) and with an increase in activities of serum SOD (138.43+/-23.15 micro/ml) and lymphocyte DNA damage (18.7%). These data suggest that antibodies against Hsps can potentially be useful biomonitors to assess if workers are experiencing or have experienced abnormal xenobiotic-induced stress within their living and working environment.

Adult↗

Mutagenicity of microcystin-LR in human RSa cells.

Microcystin-LR (MCLR) is a potent cyclic heptapeptidic hepatotoxin produced by bloom-forming cyanobacteria. The mutagenicity induced by this compound in cultured human RSa cells was found by determination of ouabain-resistant (OuaR) mutation, with the highest frequency at the concentration of 15 microgram/ml. Moreover, base substitution mutations at K-ras codon 12 in genomic DNA, assessed by polymerase chain reaction (PCR) and differential dot-blot hybridization using digoxigenin-labeled probes, were detected in RSa cells 6 days after exposure to MCLR (7.5-15 microgram/ml).

Cells, Cultured↗

Exaggerated precocious centromere separation in cells of a human breast cancer line treated with a green tea extract.

In a breast cancer cell line, MDA-MB-468, established in our laboratory, an average of 3% of the mitotic cells exhibited a phenomenon known as centromere splaying, which is a characteristic feature of cells of patients with Roberts syndrome. However, centromere splaying in cells of Roberts syndrome patients is limited to i) the centromere region and ii) chromosomes with large amounts of heterochromatin. When the breast cancer cells were treated with an extract of green tea GTE-TP91, up to 45% of the metaphases were observed to exhibit this behavior; and the precocious centromere separation was highly exaggerated, affecting all chromosomes in such metaphases. Apparently, as the sister centromeres continued to pull apart, they carried the chromatids with them, except for the telomere regions, giving a ring-like configuration. Eventually, the sister chromatids became completely separated. Whether this bizarre phenomenon was induced by the polyphenols contained in this green tea extract GTE-TP91 is not known, but this phenomenon, upon further investigation, may throw some light on chromosomal proteins, centromere behavior, telomere behavior and related questions.

Breast Neoplasms↗

Activation of MAP kinases by 5-fluorouracil in a 5-fluorouracil-resistant variant human cell line derived from a KT breast cancer cell line.

To investigate the mechanism of the acquired resistance of human cells to an anticancer drug, 5-fluorouracil (5-FU), a drug-resistant clone, KTFU-4, was isolated from a human KT breast carcinoma cell line, treated with ethylmethanesulfonate and then with 5-FU. The viability of the KT cells, analyzed using an MTT assay, was suppressed by 5-FU in a dose-dependent manner, while that of the KTFU-4 cells was enhanced by it at concentrations between 0.1 and 1.0 microgram/ml. Treatment of KTFU-4 cells with 5-FU resulted in increased amounts of activated phosphorylated ERK1/2 and p38 MAP kinases, but not in the parent KT cells. It is thus possible that 5-FU stimulated the proliferation of KTFU-4 cells by activating a signal transduction pathway leading to cell growth.

Antimetabolites, Antineoplastic↗

[Dynamic variation of incidence of neural tube defects during 1988 to 1992 in China].

OBJECTIVE: To study the variation trend in incidence of neural tube defects (NTDs) during 1988 to 1992 in China. METHODS: Data were collected by hospital-based monitoring, with women of gestation of 28 weeks to seven days after birth as study subjects. And, 3,246,408 perinates were monitored in the National Birth Defect Monitoring Network in 30 provinces, municipalities and autonomous regions all over the country, and 7,778 cases of NTDs during 1988 to 1992 were recorded and analyzed. RESULTS: Incidence of NTDs was 18.0 per ten thousand in 1992, 28.9% reduction from 25.3 per ten thousand in 1988, and yearly average reduction of 8.2%. Incidence of NTDs decreased by 30.5% and 34.2% in rural and urban areas, respectively, by 30.5% and 27.8% in the north and the south, respectively, and incidence of anencephaly and encephalocele fell by 34.2% and 48.5%, respectively. CONCLUSION: Incidence of NTDs showed a falling trend in China, more decrease in rural area and in the north than in urban areas and in the south, respectively, and incidence of anencephaly and encephalocela fell faster.

Anencephaly↗

Are the reductions in nematode attack on plants treated with seaweed extracts the result of stimulation of the formaldehyde cycle?

Soil application to the roots of tomato plants (Lycopersicon esculentum) of a commercially-available alkaline extract of the brown alga, Ascophyllum nodosum, resulted in a significant reduction in the number of second-stage juveniles of both Meloidogynejavanica and M. incognita invading the roots, compared to those of plants treated with water alone. Egg recovery from the seaweed extract treated plants was also significantly lower. The three major betaines found in the seaweed extract (gamma-aminobutyric acid betaine, delta-aminovaleric acid betaine and glycinebetaine) also led to significant reductions in both the nematode invasion profile and egg recovery when applied at concentrations equivalent to those present in the extract. This led to the conclusion that the betaines present in the seaweed extract play a major role in bringing about the observed effects. Treatment of Arabidopsis thaliana plants with seaweed extract also resulted in a significant decrease in the number of females of M. javanica which developed in the roots. Significant reductions in egg recovery were also achieved from plants treated with the seaweed extract and similar effects were produced with the betaines found in the seaweed extract. As the experiments were conducted under monoxenic conditions, it can be concluded that the results obtained with the application of either the seaweed extract or betaines are not dependent on microorganisms associated with the rhizosphere.

Animals↗

[Relationship between plasma D(-)-lactate levels and acute intestinal injury in rats following ischemia-reperfusion].

OBJECTIVE: To determine the kinetics of plasma D(-)-lactate levels in both portal and systemic circulations, and to examine whether elevated plasma D(-)-lactate would correlate to intestinal injury in rats subjected to acute intestinal ischemia-reperfusion. METHODS: Anesthetized rats underwent 75 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion. Plasma D(-)-lactate levels were measured by an enzymatic spectrophotometric assay. RESULTS: It showed that intestinal ischemia for 75 minutes resulted in a significant elevation in D(-)-lactate levels in portal vein blood compared to baseline values (P < 0.05). Plasma D(-)-lactate levels had a tendency to further increase after reperfusion up to 6 hours. Similar alterations in D(-)-lactate were also found in systemic circulation, there were no significant differences between the portal and systemic circulation at any time point. Moreover, the histopathological evaluation scores were significantly correlated to the portal D(-)-lactate levels in animals at various time points (r = 0.415, P < 0.01). In addition, a remarkable rise of endotoxin concentration within portal vein was already found at the end of 75-minute ischemia (P < 0.05), reaching a peak at 2 hours post-reperfusion. CONCLUSION: These data suggest that acute intestinal ischemia is associated with failure of mucosal barrier resulting in increased plasma D(-)-lactate levels in both portal and systemic blood. The subsequent reperfusion might cause further increase in D(-)-lactate levels, which correlated to the histopathological alterations. Plasma D(-)-lactate may be a useful marker of intestinal injury following both ischemia and reperfusion insults.

Animals↗

[Mifepristone in the treatment of 47 ectopic pregnancy patients].

OBJECTIVE: To investigate the effect and indication of mifepristone in treating ectopic pregnancy, 47 patients were divided into three groups. RESULTS: Twenty-nine cases were effective; 18 cases were ineffective and operated on in which we observed the gestational termination, bleeding capacity, and pathological changes in fallopian tube. We found that the effect was related to the drug dosage, levels of beta-hCG in blood and the operating time. CONCLUSION: High dosage of mifepristone in treating ectopic pregnancy is convenient, safe, and has no side-effects. It is suitable for patients with early ectopic pregnancy who have smooth life-sign, beta-hCG < 10 ng.ml-1, the mass in pelvic cavity < or = 5 cm, without acute belly-ache and pulsation of fetal heart in fallopian tube and who ask for the conservative treatment.

Abortifacient Agents, Steroidal↗

[Expression of telomerase in acute leukemia].

To understand the expression patterns of telomerase activity in different types of acute leukemia(AL) and during remission state, the mono-nuclear cells of different bone marrow samples were isolated by desity gradient centrifugation. Telomerase activity of the samples was assayed by telomeric repeat amplification protocol(TRAP) with the cell extracts and the TRAP products were resolved in PAGE. The results showed that the telomerase activity was at higher levels in the acute leukemia compared with the normal controls. Of the acute nonlymphocytic leukemia(ANLL), the telomerase activity presented as M2a > M5b > M1 > M3b. Of the acute lymphocytic leukemia(ALL), the activity presented as L1 > L2. The activity assayed in M2a and L2 remission was as high as that in the normal group. It indicated that the expression of telomerase was enhanced differently among the subtypes of ANLL and ALL, and was down-regulated during the AL remission. It implicates that the expression patterns of telomerase activity in AL is associated with the different proliferation states and differentiation properties of the AL cells.

Adolescent↗