Refractory anemia with ringed sideroblasts associated with marked thrombocytosis harbors JAK2 mutation and shows overlapping myeloproliferative and myelodysplastic features.
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Adult↗
Biomedical subjects
S Hao
Publications and source records attributed to S Hao.
Epigenetic transfer of metastatic activity by uptake of highly metastatic B16 melanoma cell-released exosomes.
AIM: To investigate potential role of highly metastatic BL6-10 tumor cell-released exosomes (EXO) in transfer of metastatic activity into poorly metastatic tumor cell line F1. METHODS: The highly metastatic B16 melanoma cell line (BL6-10) was generated in our laboratory. EXO from this cell line were isolated and amount of exosomal recovered proteins was measured using Bradford assay. For phenotypic analysis BL6-10 and F1 melanoma cells were stained with FITC-conjugated anti-MHC I (H-2K(b)), MHC II (Ia(b)) and Met 72 antibodies and analyzed by flow cytometry. C57BL/6 mice (8 per group) were injected (i. v.) with 0.5 x 10(6) F1, BL6-10 and F1(EXO) melanoma cells. Lungs were removed 4 weeks after tumor cell injection, fixed in 10% neutral buffered formaldehyde and embedded in paraffin for histological analysis. RESULTS: Data revealed that BL6-10 cells expressed metastasis marker (Met 72 tumor antigen), while F1 cells did not display this cell surface marker. All mice inoculated with BL6-10 melanoma cells had numerous lung tumor colonies, while mice injected with F1 tumor cells were free of lung metastatic colonies. BL6-10 tumor cells-released EXO also expressed Met 72 tumor antigen as BL6-10 tumor cells, but in less amount. F1 tumor cells can uptake EXO from BL6-10 tumor cells and express acquired exosomal Met 72 tumor antigen. CONCLUSION: The metastatic activity of highly metastatic BL6-10 tumor cells can be transferred to poorly metastatic F1 tumor cells by uptake of highly metastatic BL6-10 tumor-released EXO.
Animals↗
Activation of a rice endogenous retrotransposon Tos17 in tissue culture is accompanied by cytosine demethylation and causes heritable alteration in methylation pattern of flanking genomic regions.
Tos17 is a copia-like, cryptic retrotransposon of rice, but can be activated by tissue culture. To study possible epigenetic mechanism controlling activity of Tos17, we subjected three rice lines (the parental line cv. Matsumae and two introgression lines, RZ2 and RZ35) that harbor different copies of the element to tissue culture. For each line, we investigated transcription and transposition of Tos17 in seed plants, calli and regenerated plants, cytosine-methylation status at CG and CNG positions within Tos17, effect of 5-azacytidine on methylation status and activity of Tos17, and cytosine-methylation states in genomic regions flanking original and some newly transposed copies of Tos17 in calli and regenerated plants. We found that only in introgression line RZ35 was Tos17 transcriptionally activated and temporarily mobilized by tissue culture, which was followed by repression before or upon plant regeneration. The activity and inactivity of Tos17 in calli and regenerated plants of RZ35 are accompanied by hypo- and hyper-CG methylation and hemi- and full CNG methylation, respectively, within the element, whereas immobilization of the element in the other two lines is concomitant with near-constant, full hypermethylation. Treatment with 5-azacytidine induced both CG and CNG partial hypomethylation of Tos17 in two lines (Matsumae and RZ35), which, however, was not accompanied by activation of Tos17 in any line. Heritable alteration in cytosine-methylation patterns occurred in three of seven genomic regions flanking Tos17 in calli and regenerated plants of RZ35, but in none of the five regions flanking dormant Tos17 in the other two lines.
Azacitidine↗
Mobilized retrotransposon Tos17 of rice by alien DNA introgression transposes into genes and causes structural and methylation alterations of a flanking genomic region.
Tos17 is a copia-like endogenous retrotransposon of rice, which can be activated by various stresses such as tissue culture and alien DNA introgression. To confirm element mobilization by introgression and to study possible structural and epigenetic effects of Tos17 insertion on its target sequences, we isolated all flanking regions of Tos17 in an introgressed rice line (Tong35) that contains minute amount of genomic DNA from wild rice (Zizania latifolia). It was found that there has been apparent but limited mobilization of Tos17 in this introgression line, as being reflected by increased but stable copy number of the element in progeny of the line. Three of the five activated copies of the element have transposed into genes. Based on sequence analysis and Southern blot hybridization with several double-enzyme digests, no structural change in Tos17 could be inferred in the introgression line. Cytosine methylation status at all seven CCGG sites within Tos17 was also identical between the introgression line and its rice parent (Matsumae)-all sites being heavily methylated. In contrast, changes in structure and cytosine methylation patterns were detected in one of the three low-copy genomic regions that flank newly transposed Tos17, and all changes are stably inherited through selfed generations.
3' Flanking Region↗
Molecular cytogenetic characterization of a familial balanced reciprocal translocation t(11;18) (q13.3; q23) associated with pregnancy wastage.
A new male patient associated with a pregnancy wastage was detected in China. Cytogenetic analyses including G-banding, chromosome painting and observation of synaptonemal complexes (SCs) demonstrated that the pregnancy wastage was associated with a balanced reciprocal translocation t(11;18) (q13.3; q23). The proband was the carrier of the translocation and his karyotype was 46,XY,t(11;18)(11pter-->11q13.3:: 18q23-->18qter; 18pter-->18q23::11q13.3-->11qter). The pedigree was analyzed based on a G-banded karyotype of the nine familial members. The translocation chromosomes came from the proband's mother. The result of the SC observation in the proband showed that each of the spermatocytes displayed one quadrivalent during their pachytene stages. In the quadrivalents, there existed homologous and nonhomologous synapses and the latter occurred widely during early, middle and late pachytene stages. The reasons and genetic basis of the pregnancy wastage are discussed.
Abortion, Spontaneous↗
The role of zinc binding in the biological activity of botulinum toxin.
Botulinum toxin is a zinc-dependent endoprotease that acts on vulnerable cells to cleave polypeptides that are essential for exocytosis. To exert this poisoning effect, the toxin must proceed through a complex sequence of events that involves binding, productive internalization, and intracellular expression of catalytic activity. Results presented in this study show that soluble chelators rapidly strip Zn(2+) from its binding site in botulinum toxin, and this stripping of cation results in the loss of catalytic activity in cell-free or broken cell preparations. Stripped toxin is still active against intact neuromuscular junctions, presumably because internalized toxin binds cytosolic Zn(2+). In contrast to soluble chelators, immobilized chelators have no effect on bound Zn(2+), nor do they alter toxin activity. The latter finding is because of the fact that the spontaneous loss of Zn(2+) from its coordination site in botulinum toxin is relatively slow. When exogenous Zn(2+) is added to toxin that has been stripped by soluble chelators, the molecule rebinds cation and regains catalytic and neuromuscular blocking activity. Exogenous Zn(2+) can restore toxin activity either when the toxin is free in solution on the cell exterior or when it has been internalized and is in the cytosol. The fact that stripped toxin can reach the cytosol means that the loss of bound Zn(2+) does not produce conformational changes that block internalization. Similarly, the fact that stripped toxin in the cytosol can be reactivated by ambient Zn(2+) or exogenous Zn(2+) means that productive internalization does not produce conformational changes that block rebinding of cation.
Animals↗
Distribution and transcription activity of nucleolar DNA in higher plant cells.
By using the NAMA-Ur DNA selective staining method, we have observed in situ the location of nucleolar DNA in onion cells and found it at the boundary between fibrillar centres (FC) and dense fibrillar component (DFC) in transcriptionally active nucleolus. We have also used anti-NOR serum, which is identified as the RNA Polymerase I transcription factor (UBF) antibody, to study its reactivity with higher plant cells and demonstrated this factor associated to the DFC but not present at the interior of FC. Finally, by employing anti-DNA/RNA hybrid antibodies, we labeled the transcriptionally active rRNA genes in active nucleolus and testified that at the boundary between FC and DFC. The results provide the evidence that the boundary between FC and DFC is the genuine transcription site of rRNA genes in nucleolus.
Cell Nucleolus↗
Separation-induced body weight loss, impairment in alternation behavior, and autonomic tone: effects of tyrosine.
We have investigated the effects of tyrosine on alternation behavior and hippocampal adrenergic and cholinergic tone in a model of self-induced weight loss caused by separation stress. Separation decreased body weight in mice (P < .001) and spontaneous alternations in the T-maze (P < .001). This impairment was associated with depletion of both norepinephrine (NE, P < .001) and dopamine (P < .01) while increasing MHPG (P < .05) and the ratio of MHPG/NE (P < .05). Increasing tyrosine availability restored performance to control levels (P < .001) and repleted dopamine (P < .05) and presumably also NE (indicated by increases in both MHPG, P < .001, and MHPG/NE, P < .05). Stress increased adrenergic alpha(2)-receptor density (P < .001) without changing its K(d) and the B(max) and K(d) of beta-receptors, suggesting that it decreased NE transmission through action on alpha(2)-receptors. The balance between beta- and alpha(2)-receptors appeared to be related to alternation behavior as shown by the decrease (P < .01) and increase (P < .05) in their ratios induced by stress and tyrosine, respectively. With regard to cholinergic tone, separation stress increased M1 receptor density (P < .05) and its mRNA signal (P < .001). Tyrosine further increased M1 receptor density of stressed mice (P < .05). Tyrosine might be a potential therapy for cognitive and mood problems associated with the maintenance of a reduced body weight in the treatment of obesity and in the extreme case of anorexia nervosa.
Animals↗
Structural components of the nuclear body in nuclei of Allium cepa cells.
Nuclear bodies have long been noted in interphase nuclei of plant cells, but their structural component, origin and function are still unclear by now. The present work showed in onion cells the nuclear bodies appeared as a spherical structure about 0.3 to 0.8 microm in diameter. They possibly were formed in nucleolus and subsequently released, and entered into nucleoplasm. Observation through cytochemical staining method at the ultrastructural level confirmed that nuclear bodies consisted of ribonucleoproteins (RNPs) and silver-stainable proteins. Immunocytochemical results revealed that nuclear bodies contained no DNA and ribosomal gene transcription factor (UBF). Based on these data, we suggested that nuclear bodies are not related to the ribosome or other gene transcription activities, instead they may act as subnuclear structures for RNPs transport from nucleolus to cytoplasm, and may also be involved in splicing of pre-mRNAs.
Cell Nucleolus↗
Diet restriction in mice causes a decrease in hippocampal choline uptake and muscarinic receptors that is restored by administration of tyrosine: interaction between cholinergic and adrenergic receptors influencing cognitive function.
We have studied the effects of diet restriction (DR) to 60% and 40% of daily requirements, and tyrosine administration on cognitive function in mice, to define the nutritional-neurochemical interactions on autonomic tone involved in behavior and energy regulation. Cognitive function in the Morris Water maze was significantly impaired after 40% DR compared to both control and 60% DR. It was restored after tyrosine in association with increased M1 cholinergic and beta-adrenergic receptor function, and decreased alpha-adrenergic function. DR to 40% significantly decreased choline uptake (p <.05) and M1 receptor number (Bmax) (p <.05), without changes in affinity (Kd), choline acetyl transferase (ChAT) or acetyl cholinesterase (AChE) activity. Tyrosine administration significantly increased choline uptake (Bmax) (p <.05) and M1 density in the 40% DR (p <.01) without changes in affinity. ChAT activity was decreased after tyrosine--significantly after 40% DR (p <.05) while AChE was not affected. Both M1 mRNA and protein were not influenced by DR or tyrosine administration. Tyrosine hydroxylase mRNA was decreased significantly by 40% DR (p <.01). The effect of DR and tyrosine appeared to be both pre- and post-synaptic, indicating modulation of cholinergic activity by adrenergic tone. Nutritional effect on behavior and autonomic tone may have implications for the treatment of mood changes associated with weight loss and semi-starvation.
Animals↗
Antinociceptive interaction between spinal clonidine and lidocaine in the rat formalin test: an isobolographic analysis.
UNLABELLED: Clinical and basic science studies suggest that spinal alpha-2-adrenergic receptor agonists and local anesthetics produce analgesia, but interaction between alpha-2-adrenergic receptor agonists and local anesthetics in the persistent pain model has not been examined. In the present study, using isobolographic analysis, we investigated the antinociceptive interaction of intrathecal clonidine and lidocaine in the rat formalin test. Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters, and were tested for paw flinch by formalin injection. Biphasic painful behavior was counted. Intrathecal clonidine (3-12 nmol) was administered 15 min before formalin, and intrathecal lidocaine (375-1850 nmol) was administered 5 min before formalin. To examine the interaction of intrathecal clonidine and lidocaine, an isobolographic design was used. Spinal administration of clonidine produced dose-dependent suppression of the biphasic responses in the formalin test. Spinal lidocaine resulted in dose-dependent transient motor dysfunction and the motor dysfunction recovered to normal at 10-15 min after administration. Spinal lidocaine produced dose-dependent suppression of phase-2 activity in the formalin test. Isobolographic analysis showed that the combination of intrathecal clonidine and lidocaine synergistically reduced Phase-2 activity. We conclude that intrathecal clonidine synergistically interacts with lidocaine in reducing the nociceptive response in the formalin test. IMPLICATIONS: Preformalin administration of intrathecal clonidine and lidocaine dose-dependently produced antinociception in the formalin test. The combination of clonidine and lidocaine, synergistically produced suppression of nociceptive response in the persistent pain model.
Adrenergic alpha-Agonists↗
Tyrosine improves appetite, cognition, and exercise tolerance in activity anorexia.
PURPOSE: We have modified for mice the activity wheel model of Routtenberg to study the effects of tyrosine on exercise tolerance, behavior, and brain neurochemistry. METHODS: Mice were fed for 2 h.d(-1) over a 2-wk period. During the second week, each group was injected daily with either saline or tyrosine (100 mg.kg(-1).d(-1)) and exercised on a running wheel. Controls were in cages with inactivated wheels and received the same treatment and feeding protocols as the experimental groups. Food consumption and cognitive function (eight-arm maze) were evaluated for 1 wk. Brains were then assayed for adrenergic and serotonergic metabolites. RESULTS: Activity together with a restricted diet caused extreme weight loss (27%) (P < 0.001) together with decreased food consumption (22%) (P < 0.001). Tyrosine restored food consumption to that of the controls (P < 0.001) with no effect on weight, since there was a 22% increase in activity (P < 0.001). Saline injections caused an 18% decrease in activity (P < 0.001). Both activity and tyrosine improved maze performance (P < 0.05). In the hypothalamus, activity caused a significant increase in 5-hydroxytryptamine (5-HT) (P < 0.001), 5-hydroxyindoleacetic acid (5-HIAA) (P < 0.01), and dopamine (P < 0.05); tyrosine prevented the increase in 5-HT (P < 0.05) and increased 5-HIAA in the controls (P < 0.01). With regard to hippocampal 5-HT, there was a significant increase in 5-HIAA following activity (P < 0.05), whereas tyrosine caused significant increase in 5-HIAA in the controls (P < 0.01). Activity significantly decreased the level of hippocampal 3,4-dihydroxyphenylacetic acid (DOPAC), whereas tyrosine decreased its level only in the controls (both at P < 0.0001). The level of tyrosine hydroxylase increased with activity (P < 0.05), and tyrosine decreased it significantly (P < 0.05). CONCLUSION: Activity anorexia is associated with increased hypothalamic 5-HT concentrations. Tyrosine administration reverses this, and significantly improves food consumption, cognitive behavior, and activity performance. Such nutritional modulations may have implications for the treatment of eating disorders and, in normal circumstances, tyrosine may improve exercise tolerance and delay fatigue.
Animals↗
[Study on the form and stability of alpha and beta domain of metallothionein binding to lead (II)].
For studying the actions of metallothionein(MT) binding to lead, the alpha and beta structural domain of metallothionein binding to Cd (Cd7-alpha-MT and Cd7-beta-MT) was extracted and purified from a strain of BL2I by dissolving them in acid to eliminate protein. The apo-alpha-MT and apo-beta-MT were separated by gel Sephadex-G25 to eliminate Cd. Different doses of lead were added to the apo-alpha-MT and apo-beta-MT. The structure of MT metal Cluster with lead was formed after reacting completely, and was then examined by ultraviolet spectrophotometer. The UV spectrum showed that the interaction of lead with alpha domain leading to two kind of products, one binding with 4 lead(Pb4-alpha-MT) and the other binding with 7 lead (Pb7-alpha-MT). Only one product, the beta domain binding with 3 lead(Pb3-beta-MT) was formed. The reaction rate of these products with DTNB was also measured in this study. Results showed that the domain binding to 4 lead was more stable than the others. All these works provide strong evidence that further studies on the mechanism of MT interacting with lead and the function of MT in eliminating lead were needed.
Drug Interactions↗
Electroacupuncture potentiates the antinociceptive effect of intrathecal endomorphin-1 in the rat formalin test.
Endomorphin-1 is a novel endogenous mu-opioid peptide. In this study, we examined the effects of 2 Hz electroacupuncture in the rat tail flick test and the formalin test (a persistent noxious model). Moreover, we investigated if the electroacupuncture potentiated the effect of intrathecal endomorphin-1. The results demonstrated that electroacupuncture alone produced a significant antinociception in the tail flick test, but not in the formalin test, and that intrathecal endomorphin-1 dose-dependently suppressed the biphasic nociceptive behavior in the formalin test. Electroacupuncture enhanced the antinociceptive effect of intrathecal endomorphin-1 in the formalin test, resulting in a significant leftward shift in the dose-response curves for intrathecal endomorphin-1 antinociception. The enhanced effect was antagonized by intraperitoneal naltrexone. The study suggests that electroacupuncture may potentiate the intrathecal endomorphin-1 antinociception partially mediated by opioid receptors.
Analgesics, Opioid↗
Low dose anandamide affects food intake, cognitive function, neurotransmitter and corticosterone levels in diet-restricted mice.
This investigation reports the possible role of the endocannabinoid anandamide on modulating the behavioral and neurochemical consequences of semi-starvation. We studied the effect of very low dose anandamide (0.001 mg/kg) administration on food intake, cognitive function and catecholaminergic and serotonergic pathways in two murine brain areas concerned with appetite (hypothalamus) and learning (hippocampus), and the peripheral corticosterone response to the stress of 40% diet restriction. Anandamide-treated mice consumed 44% more food (P<0.05) during 1 week of 2.5-h feeding each day. In the hypothalamus, there were significantly increased concentrations of norepinephrine (P<0.01), dopamine (P<0.05) and 5-hydroxytryptamine (5-HT) (P<0.001). In the hippocampus, anandamide increased significantly norepinephrine and dopamine, but decreased 5-HT (all at P<0.001). Diet restriction was accompanied in both areas by a significant decrease in all neurotransmitter concentrations that were partially restored by anandamide for dopamine and 5-HT, but not for norepinephrine. In animals on diet restriction, anandamide significantly improved impaired maze performance. Norepinephrine turnover and plasma corticosterone levels were also raised significantly by anandamide. The fact that low dose anandamide improved food intake, cognitive function and reversed some of the neurotransmitter changes caused by diet restriction, might have implications for the treatment of cachexia associated with acquired immunodeficiency syndrome (AIDS) and cancer, for mood changes sometimes associated with dieting, and in the extreme case, of patients with anorexia.
Animals↗
[Study on the absorption of environmental contaminants in low-level exposure by pharmacokinetic analysis].
A dynamic generating toxic gas system and a nose-only exposure system were used for the pharmacokinetic study of inhaled environmental contaminants for benzene, toluene, xylene, ethylbenzene, chlorobenzene, styrene, isopropyl benzene, tetrachloroethylene, nonane and methylcyclohexane in male guinea pig. The change of these substances in blood with time was determined simultaneously by solid phase micro-extraction(SPME) gas chromatography (GC). The results showed that the fraction of absorption of benzene at low (121 micrograms/m3) exposure was 4.8 times higher than that at high(12.1 mg/m3) exposure. The pharmacokinetics of these substances were evaluated by using linear compartment models. The data showed that more styrene was absorbed than tetrachloroethylene at low-exposure. The metabolic elimination of these compounds at various exposure concentrations was extrapolated by using estimated pharmacokinetic parameters. Moreover, not only should the differences in absorption quantities be considered in evaluation of potential risk assessment, the metabolic elimination rates should also be considered although the exposure concentrations in gas for all chemicals were equal. The data presented in this paper was fundamental data used for risk assessment.
Air Pollutants↗
Intrathecal endomorphin-1 produces antinociceptive activities modulated by alpha 2-adrenoceptors in the rat tail flick, tail pressure and formalin tests.
It is known that spinal morphine produces antinociception that is modulated by alpha 2-adrenoceptors. Endomorphin-1, a newly-isolated endogenous opioid ligand, shows the greatest selectivity and affinity for the mu-opiate receptor of any endogenous substance found to date and may serve as a natural ligand for the mu-opiate receptor. We examined the antinociceptive effects of endomorphin-1 administered intrathecally (i.t.) in the rat tail flick, tail pressure and formalin tests. Intrathecal endomorphin-1 produced dose-dependent antinociceptive effects in the three tests. ED50 (CI95) values for antinociception of i.t. endomorphin-1 in the tail flick test and tail pressure test were 1.9 (0.96-3.76) nmol and 1.8 (0.8-4.2) nmol, respectively. ED50 (CI95) values for phase 1 and phase 2 in the formalin test were 12.5 (7.9-19.8) nmol and 17.5 (10.2-30) nmol, respectively. Pretreatment with i.t. beta-funaltrexamine (a mu-opioid receptor selective antagonist) significantly antagonized the antinociceptive effects of endomorphin-1 in the three tests. Beta-funaltrexamine alone had not effects on the three tests. The antinociceptive effects of endomorphin-1 were also antagonized by i.t. yohimbine (an alpha 2-adrenoceptor selective antagonist). The combination of ineffective doses of i.t. clonidine (an alpha 2-adrenoceptor agonist) and endomorphin-1 produced a significant antinociception in the three tests. The results showed that intrathecal endomorphin-1 produced antinociception in a dose-dependent manner in the rat tail flick, tail pressure and formalin tests, which was mediated by spinal mu-opioid receptors and modulated by alpha 2-adrenoceptors.
Adrenergic alpha-Antagonists↗
[Determination of volatile organic compounds in blood by headspace solid-phase microextraction-gas chromatography].
The headspace solid-phase microextraction (HS-SPME) is a novel extraction technique and has been developed rapidly. It is a fast, simple, solventless and sensitive method for sampling, separating, extracting, injecting and analyzing volatile organic compounds. This paper presents the research work in detecting volatile organic compounds(including ten compounds) in blood. The extraction fiber is made by fused-silica fiber with 100 microns polydimethylsiloxane (PDMS). The extraction time of the method was 10 min. The thermal desorption time was 1 min. It was found that the optimized location of the extraction fiber in the injector of GC was to put the whole needle in the injector. The precision of the method was determined to be less 5% relative standard deviation (RSD). The linear range of the detection was rather wide. The lowest detectin limits (LODs) were all < or = 5 ng/ml.
Animals↗