It takes a PHD to interpret histone methylation.
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Chromatin↗
Biomedical subjects
Yi Zhang
Publications and source records attributed to Yi Zhang.
Delayed cutaneous wound healing in mice lacking solute carrier 11a1 (formerly Nramp1): correlation with decreased expression of secretory leukocyte protease inhibitor.
Control of macrophage functions by natural resistance-associated macrophage protein 1 (NRAMP1) has proven to be important for murine resistance to several intracellular pathogens, including Mycobacterium bovis BCG and Salmonella typhimurium, although the exact molecular mechanism of its action remains unknown. We identified secretory leukocyte protease inhibitor (SLPI) as a novel candidate gene whose expression is dependent on Nramp1 gene expression using B10A.Nramp1+/+ and B10A.Nramp1-/- macrophage cell lines in vitro, as well as mice bearing the resistance alleles (wild type (WT)) of the Nramp1 and mice with an ablated Nramp1 gene (knockout (KO)). We established that B10A.Nramp1+/+ cells spontaneously expressed a 10-fold higher level of SLPI messenger RNA (mRNA) compared to B10A.Nramp1-/- expression. Similarly, protein secretion was detected only in supernatants from B10A.Nramp1+/+ macrophages. Induction of SLPI in excisional cutaneous wounds and, most importantly, in macrophages infiltrating these wounds was significantly higher in Nramp1 WT mice compared to KO mice. These differences in SLPI expression in vivo correlated with a significant delay in the kinetics of wound healing in Nramp1 KO mice compared to WT controls. Taken together, these results suggest for the first time that Nramp1 controls macrophage SLPI mRNA and protein expression, and can also have an important effect on the kinetics of wound healing.
Animals↗
Factors influencing route of administration for epoetin treatment among hemodialysis patients in the United States.
BACKGROUND: Published clinical guidelines advocate subcutaneous (SC) administration for epoetin therapy, although this is practiced among only 7% of all hemodialysis patients. Despite this disparity, few studies have examined factors associated with route of epoetin administration in hemodialysis patients. METHODS: Data from the Centers for Medicare & Medicaid Services End-Stage Renal Disease Clinical Performance Measures Project were used to identify 13,854 patients receiving hemodialysis in 3,069 dialysis facilities from October to December in 1999 and 2000. Unadjusted associations were examined by using t-test and chi-square test. Adjusted associations were estimated by using generalized estimating equations to control for clustering of patients within the same dialysis facility. RESULTS: In the United States, use of the SC route of epoetin administration varies widely across the country. After adjusting for patient sociodemographics and comorbidities, the greatest rates of SC therapy are found in the Midwest and West, in providers not affiliated with chains, and in hospital-based and not-for-profit freestanding units. Previous exposure to SC administration (as a predialysis or peritoneal dialysis patient) predicted subsequent SC use, for-profit and large chains were significantly less likely to use SC administration, and increased use of injectable drugs overall (to maximize income) was associated with less SC use. CONCLUSION: In addition to regional variation in SC use, study findings indicate that physician decision making for epoetin administration route is influenced primarily by type of ownership and financial incentives. Adherence to published clinical guidelines was not a consistent predictor of SC use. Given the similar effectiveness, but significantly decreased dose associated with SC epoetin, these findings suggest an enormous opportunity for cost savings for the Medicare program.
Adult↗
N-acetylcysteine antagonizes the development but does not reverse ACTH-induced hypertension in the rat.
We investigated the effect of antioxidant N-acetylcysteine (NAC) on adrenocorticotropic hormone (ACTH)-hypertension. Male Sprague-Dawley rats received NAC (10 mg/L) or water 4 days before ACTH/saline treatment for 13 days (prevention study). In a reversal study, NAC commenced on day 8 of ACTH/saline treatment and continued for 5 days. ACTH increased systolic blood pressure (SBP) in water drinking rats (111 +/- 1 to 131 +/- 3 mmHg, p < 0.001). In the prevention study, NAC + ACTH increased SBP (108 +/- 2 to 120 +/- 2 mmHg, p < 0.001) but less than ACTH alone (p' < 0.05). In the reversal study, NAC had no significant effect (132 +/- 4 to 124 +/- 3 mmHg, ns). Thus, NAC partially prevented but did not reverse ACTH-induced hypertension.
Acetylcysteine↗
Identification of a submicroscopic deletion of SHH associated with the holoprosencephaly spectrum by array-based CGH.
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Chromosome Deletion↗
Species variability in cardiovascular research: the example of adrenocorticotrophin-induced hypertension.
1. Lawrie Beilin has contributed greatly to international hypertension research through both animal and human studies. 2. Animals are used in biomedical research to gain insights that can be extrapolated ultimately to humans. 3. A simple experimental manipulation, adrenocorticotrophin (ACTH) administration, has a range of different cardiovascular effects in different species. 4. Caution should be exercised in extrapolating data from animals to humans.
Adrenocorticotropic Hormone↗
Clinical significance of human kallikrein 10 gene expression in colorectal cancer and gastric cancer.
BACKGROUND AND AIM: Recent evidence suggests that the human kallikrein 10 (KLK10) gene is differentially regulated in endocrine-related tumors and has potential as diagnostic and/or prognostic marker; however, KLK10 expression has never been investigated in gastrointestinal cancers. The aims of this study were to demonstrate expression and single nucleotide polymorphisms of KLK10 in colorectal cancer (CRC) and gastric cancer (GC), and to correlate the relative KLK10 expression level with clinicopathological factors of CRC and GC. METHODS: Between March 2004 and January 2005, 63 patients with histologically confirmed CRC and 36 with GC were recruited into the study. Using quantitative real-time (qRT) RT-PCR and Western blot, KLK10 expression in tumor and non-tumor colorectal and gastric tissues was determined at the mRNA and protein levels. KLK10 protein was localized by immunohistochemistry. The KLK10 genomic DNA from 16 cases of paired normal/cancerous colorectal tissues was PCR-amplified and examined for single nucleotide polymorphisms by direct sequencing. RESULTS: KLK10 mRNA expression was detected by qRT in 61 of 63 (96.8%) CRC specimens and in all GC specimens. KLK10 expression was much higher in tumor tissue than in the corresponding normal mucosal tissue at the mRNA and protein levels (P<0.01). The KLK10 mRNA expression level significantly correlated with lymphatic invasion (P=0.034) and clinical stage of CRC (P=0.025). The KLK10 mRNA expression level significantly correlated with the depth of GC invasion (P=0.018), clinical stage (P=0.045), patient sex (P=0.027) and Lauren type of gastric cancer (P=0.028). No mutations or polymorphisms were detected in exon 1, 2 and 5 of KLK10 gene in CRC. Single nucleotide polymorphisms were identified in codon 50 of exon 3, GCC (alanine) to TCC (serine). The genetic changes of exon 4 were located at codon 106 [GGC (glysine) to GGA (glysine)], codon 112 [ACG (threonine) to ACC (threonine)], codon 141 [CTA (leucine) to CTG (leucine)], and codon 149 [CCG (proline) to CTG (leucine)]. All were identical in tumor and corresponding normal tissue DNA from the same individuals. CONCLUSION: KLK10 expression is up-regulated in CRC and GC and higher expression of KLK10 closely correlates with advanced disease stage, which predicts a poorer prognosis; however, further follow-up study is needed.
Adult↗
Effect of resveratrol on L-type calcium current in rat ventricular myocytes.
AIM: To study the effect of resveratrol on L-type calcium current (I(Ca-L)) in isolated rat ventricular myocytes and the mechanisms underlying these effects. METHODS: I(Ca-L) was examined in isolated single rat ventricular myocytes by using the whole cell patch-clamp recording technique. RESULTS: Resveratrol (10-40 micromol/L) reduced the peak amplitude of I(Ca-L) and shifted the current-voltage (I-V) curve upwards in a concentration-dependent manner. Resveratrol (10, 20, 40 micromol/L) decreased the peak amplitude of I(Ca-L) from -14.2+/-1.5 pA/pF to -10.5+/-1.5 pA/pF (P<0.05), -7.5+/-2.4 pA/pF (P<0.01), and -5.2+/-1.2 pA/pF (P<0.01), respectively. Resveratrol (40 micromol/L) shifted the steady-state activation curve of I(Ca-L) to the right and changed the half-activation potential (V0.5) from -19.4+/-0.4 mV to -15.4+/-1.9 mV (P<0.05). Resveratrol at a concentration of 40 micromol/L did not affect the steady-state inactivation curve of I(Ca-L), but did markedly shift the time-dependent recovery curve of I(Ca-L) to the right, and slow down the recovery of I(Ca-L) from inactivation. Sodium orthovanadate (Na(3)VO(4); 1 mmol/L), a potent inhibitor of tyrosine phosphatase, significantly inhibited the effects of resveratrol (P<0.01). CONCLUSION: Resveratrol inhibited I(Ca-L) mainly by inhibiting the activation of L-type calcium channels and slowing down the recovery of L-type calcium channels from inactivation. This inhibitory effect of resveratrol was mediated by the inhibition of protein tyrosine kinase in rat ventricular myocytes.
Animals↗
Human acyl-CoA:cholesterol acyltransferase (ACAT) and its potential as a target for pharmaceutical intervention against atherosclerosis.
Acyl-CoA:cholesterol acyltransferase (ACAT) catalyzes the formation of cholesteryl esters from cholesterol and long-chain fatty-acyl-coenzyme A. At the single-cell level, ACAT serves as a regulator of intracellular cholesterol homeostasis. In addition, ACAT supplies cholesteryl esters for lipoprotein assembly in the liver and small intestine. Under pathological conditions, the accumulation of cholesteryl esters produced by ACAT in macrophages contributes to foam cell formation, a hallmark of the early stage of atherosclerosis. Several reviews addressing various aspects of ACAT and ACAT inhibitors are available. This review briefly outlines the current knowledge on the biochemical properties of human ACATs, and then focuses on discussing the merit of ACAT as a drug target for pharmaceutical interventions against atherosclerosis.
Acyl Coenzyme A↗
Disruption of the operon encoding Ehb hydrogenase limits anabolic CO2 assimilation in the archaeon Methanococcus maripaludis.
Methanococcus maripaludis is a mesophilic archaeon that reduces CO2 to methane with H2 or formate as an energy source. It contains two membrane-bound energy-conserving hydrogenases, Eha and Ehb. To determine the role of Ehb, a deletion in the ehb operon was constructed to yield the mutant, strain S40. Growth of S40 was severely impaired in minimal medium. Both acetate and yeast extract were necessary to restore growth to nearly wild-type levels, suggesting that Ehb was involved in multiple steps in carbon assimilation. However, no differences in the total hydrogenase specific activities were found between the wild type and mutant in either cell extracts or membrane-purified fractions. Methanogenesis by resting cells with pyruvate as the electron donor was also reduced by 30% in S40, suggesting a defect in pyruvate oxidation. CO dehydrogenase/acetyl coenzyme A (CoA) synthase and pyruvate oxidoreductase had higher specific activities in the mutant, and genes encoding these enzymes, as well as AMP-forming acetyl-CoA synthetase, were expressed at increased levels. These observations support a role for Ehb in anabolic CO2 assimilation in methanococci.
Acetate-CoA Ligase↗
Do dopamine receptors mediate part of MAC?
BACKGROUND: Depletion of central nervous system catecholamines, including dopamine, can decrease MAC (the minimum alveolar concentration of an inhaled anesthetic required to suppress movement in response to a noxious stimulus in 50% of test subjects); release of central nervous system catecholamines, including dopamine, can increase MAC; and increased free dopamine concentrations in the striatum can decrease MAC. Such findings suggest that dopamine receptors might mediate part of the capacity of inhaled anesthetics to provide immobility in the face of noxious stimulation. METHODS: We measured the effect of blockade of D2 dopamine-mediated transmission with 0.3 mg/kg or 3.0 mg/kg droperidol on the MAC of cyclopropane, desflurane, halothane, isoflurane, or sevoflurane in rats, and the effect of 3.0 mg/kg droperidol on the dose or concentration of etomidate (an anesthetic known to act principally by enhancing the response of gamma-aminobutyric acid(A) receptors to gamma-aminobutyric acid) required to suppress movement in response to noxious stimulation. RESULTS: Blockade of D2 dopamine-mediated transmission with droperidol does not decrease the MAC of cyclopropane, desflurane, halothane, isoflurane, or sevoflurane or its equivalent for etomidate in rats. CONCLUSIONS: These data, plus data from studies by others about D1 dopamine receptors, indicate that dopamine receptors do not mediate the immobility produced by inhaled anesthetics.
Anesthetics, Inhalation↗
MES-4: an autosome-associated histone methyltransferase that participates in silencing the X chromosomes in the C. elegans germ line.
Germ cell development in C. elegans requires that the X chromosomes be globally silenced during mitosis and early meiosis. We previously found that the nuclear proteins MES-2, MES-3, MES-4 and MES-6 regulate the different chromatin states of autosomes versus X chromosomes and are required for germline viability. Strikingly, the SET-domain protein MES-4 is concentrated on autosomes and excluded from the X chromosomes. Here, we show that MES-4 has histone H3 methyltransferase (HMT) activity in vitro, and is required for histone H3K36 dimethylation in mitotic and early meiotic germline nuclei and early embryos. MES-4 appears unlinked to transcription elongation, thus distinguishing it from other known H3K36 HMTs. Based on microarray analysis, loss of MES-4 leads to derepression of X-linked genes in the germ line. We discuss how an autosomally associated HMT may participate in silencing genes on the X chromosome, in coordination with the direct silencing effects of the other MES proteins.
Animals↗
New approach to the total synthesis of (-)-zeylenone from shikimic acid.
The natural antitumor product (-)-zeylenone was prepared for the first time in a stereoselective synthesis from shikimic acid.
Cyclohexanes↗
Comparing cytotoxicity and genotoxicity in HaCaT cells caused by 6-aminochrysene and 5,6-chrysenequinone under ultraviolet A irradiation.
Chrysene is one of the basic polycyclic aromatic hydrocarbons that are toxic environmental pollutants. The photoproducts of 6-aminochrysene (6AC) include 5,6-chrysenequinone (5,6-CQ) along with some minor products. In this study, cytotoxicity and genotoxicity of 6AC and 5,6-CQ to a human skin cell line, HaCaT, were measured with the fluorescein diacetate uptake (FDA) test and comet assay, respectively, in the presence or absence of ultraviolet A (UVA) irradiation. The FDA test result showed that HaCaT cell viability decreased dose dependently after exposure to UVA irradiation in both 6AC (0, 0.1, 0.5, 1, 5, 10, 50 microM) and 5,6-CQ (0, 0.05, 0.25, 0.5, 2.5, 5, 25 microM) groups, with the 6AC group having lower cell viability at the same substrate concentrations; therefore, 6AC was more cytotoxic. Results of the comet assay showed that the extent of DNA damage was also dose dependent after the combined UVA and 6AC treatment (0, 0.05, 0.1, 0.5, 1 microM), although no DNA damage was detectable in the 6AC group without UVA irradiation. In addition, no DNA damage was found in the 5,6-CQ group with or without UVA irradiation. Our study indicated that 5,6-CQ, the major photoproduct of 6AC, was less photocytotoxic than the parent compound and was not photogenotoxic to HaCaT cells under the experimental conditions.
Cell Line, Tumor↗
Prognostic gene expression signatures can be measured in tissues collected in RNAlater preservative.
Gene expression signatures have the ability to serve in both prognostic and predictive capacities in patient management. The use of RNA as the starting material and the lability of this analyte, however, dictate that tissues must be snap-frozen or stored in a solution that can maintain the integrity of the RNA. We compared pairs of snap-frozen and RNAlater preservative-suspended tissue from 30 such paired lymph node-negative breast tumors and 21 such paired Dukes' B colon tumors. We assessed the correlation of gene expression profiles and prediction of recurrence based on two prognostic algorithms. Tissues stored in RNAlater preservative generated expression profiles with excellent correlation (average Pearson correlation coefficients of 0.97 and 0.94 for the breast and colon tumor pairs, respectively) compared to those produced by tissues that were snap-frozen. The correlation in the prediction of recurrence was 97% and 95% for the breast and colon tumor pairs, respectively, between these two types of tissue handling protocols. This novel finding demonstrates that prognostic signatures can be obtained from RNAlater preservative-suspended tissues, an important step in bringing gene expression signatures to the clinic.
Algorithms↗
[Reactivity of a novel monoclonal antibody ZCH-7-2D3 on leukemia cells and its clinical significance].
OBJECTIVE: To analyze the reactive pattern and its clinical significance of ZCH-7-2D3 monoclonal antibody on leukemia cells. METHODS: Bone marrow samples from 100 leukemia patients (male 59: female 41, 34 cases of children and 66 adults, aged 11 months - 77 year) were collected. A CD45 gating strategy and multi-parameter flow cytometry were used to analyze the leukemia cells. RESULT: The positive rate (10/31) of 2D3 antibody on acute lymphocytic leukemia (ALL) patients was significantly lower than that (39/55) of acute myelogeneous leukemia (AML) (P <0.01). 2D3 was positive for all three cases of B/myeloid mixed lineage leukemia, but negative in 6 cases of chronic myelogeneous leukemia (CML), significantly lower than that in AML (39/55, P<0.01) patients. There was no difference between the positive rates of chronic lymphocytic leukemia (CLL, 3/5) and B lineage ALL (9/28, P = 0.2389). The antibody was not found to recognize the differentiation stages of either ALL and AML subtypes. CONCLUSION: 2D3 monoclonal antibody primarily recognizes AML cases. Further studies on cloning of gene encoding the antigen protein and its biological functions are warranted.
Adolescent↗
[Transformation of embryogenic Calli of Siberian wildrye grass (Elymus sibiricus L. cv. Chuancao No.2) mediated by agrobacterium].
Formation of embryogenic calli of Siberian wildrye grass (Elymus sibiricus L. cv. Chuancao No.2) was induced from mature seeds as explants, and proliferated on MS medium containing 2,4-D 5.0 mg/L and KT 0.05 mg/L. An effective and stable callus regeneration system was established by optimizing the culture conditions (Tables 1, 2 and Fig.2). After the calli were subcultured 8 weeks, selected the whitish-yellow-coloured compact nodular calli that transformed with plasmid pCAMBIA1304 carrying hygromycin resistance gene (hptII) and Pseudomonas pseudoalcaligenes insecticidal protein gene (ppIP), which was mediated by an Agrobacterium strain EHA105. Resistant plants were obtained after hygromycin selection (Figs.3, 4). Some important factors that affect the transformation efficiency were studied, which included selection pressure, time of embryogenic calli proliferation, OD value of Agrobacterium suspension, temperature, medium and time of co-cultivation, and concentration of antibiotics used for suppressing the overgrowth of Agrobacterium in the course of transformation plant regeneration. This research is the first successful genetic transformation of Elymus sibiricus L. cv. Chuancao No.2 mediated by Agrobacterium.
Culture Media↗
HBsAg loading on dendritic cells in patients with chronic hepatitis B: expressions of phenotypic molecules.
BACKGROUND: The antigen reducing ability of dendritic cells (DCs), a kind of antigen presenting cells (APCs) initiating immune response, is associated with the specific immune tolerance of chronic hepatitis B (CHB) patients. However, the dysfunction of DCs can be possibly reversed by the stimulation of antigen peptides. In this study, DCs were cultured from peripheral blood monocytes (PBMCs) in patients with CHB in vitro, and the expression of phenotypic molecules on DCs loaded by different concentrations of HBsAg was observed. METHODS: Forty patients with CHB were divided randomly into 4 groups (10 patients in each group). PBMCs were isolated, and DCs were cultured after addition of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin 4 (IL-4). On the 9th day, DCs of the experimental groups were loaded at HBsAg concentrations of 2.5 mg/L, 5 mg/L and 10 mg/L for 24 hours, whereas those of the control group were not loaded. An electron microscope was used to analyze the morphological changes of the DCs. The expression of phenotypic molecules on DCs in different groups was detected with flow cytometry. RESULTS: A combination of GM-CSF and IL-4 produced DCs from PBMCs in patients with CHB after being cultured for 9 days, whose morphological changes were tested by an electron microscope. The expression of phenotypic molecules on DCs in the control group was as low as CD83 (8.02+/-3.99)%, CD80 (8.77+/-2.06)%, and MHC-DR (14.05+/-2.66)%. Loaded by different concentrations of HBsAg, the up-regulation of phenotypic molecules on DCs was found, with CD83 (18.35+/-2.93)%, CD80 (42.63+/-7.15)% and MHC-DR (47.49+/-6.59)% in 2.5 mg/L HBsAg loading group, CD83 (17.88+/-3.12)%, CD80 (45.24+/-10.93)% and MHC-DR (47.07+/-8.52)% in 5 mg/L HBsAg loading group and CD83 (16.74+/-2.86)%, CD80 (44.59+/-6.99)% and MHC-DR (48.59+/-7.42)% in 10 mg/L HBsAg loading group, respectively. Compared with the control group, the phenotypic molecules in the experimental groups were all different significantly (P<0.01), but among them, there were no differences (P>0.05). CONCLUSIONS: DCs cultured from PBMCs in the patients with CHB under the conditions of GM-CSF and IL-4 present on the typical dendritic morphology but are immature for expressing low phenotypic molecules. Loaded by different concentrations of HBsAg, the immature DCs can differentiate to mature DCs for expressing increasing phenotypic molecules.
Adolescent↗