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1.
Article in Chinese | MEDLINE | ID: mdl-37667153

ABSTRACT

Objective: To explore the moderating mechanism of mindfulness on perceived stress and job burnout of medical staff. Methods: From November 2020 to March 2022, 1626 medical staff were investigated by questionnaires. Chinese Version Perceived Stress Scale (CPSS), Maslach Burnout Inventory-Human Service Survey (MBI-HSS) and Mindful Attention Awareness Scale (MAAS) were used to evaluate the perceived stress, three dimensions of job burnout[depersonalization (DP), emotional exhaustion (EE), personal accomplishment (PA) ], and mindfulness level of medical staff. The Spearman rank correlation analysis was used to analyze the correlation between mindfulness and perceived stress, job burnout of medical staff. And the SPSS PROCESS macro program was used to test the moderating effect of mindfulness on perceived stress and job burnout. Results: Among the 1626 medical staff, 57.38% had perceived stress with health risk (933/1626), and 63.84% (1038/1626) had job burnout, among them, with 618 (38.01%), 274 (16.85%), and 146 (8.98%) experiencing mild, moderate and severe job burnout, respectively. The scores of mindfulness among medical staff were significantly correlated with perceived stress and various dimensions of job burnout (EE, DP and PA) (r(s)=-0.155, -0.351, -0.315, 0.307, P<0.001). Mindfulness had a moderating effect between perceived stress and job burnout, which was achieved through three moderating pathways: perceived stress-mindfulness-EE, perceived stress-mindfulness-DP and perceived stress-mindfulness-PA (ΔR(2)=0.073, 0.06, 0.006, P<0.001) . Conclusion: Medical staff have a high level of job burnout, mindfulness plays a moderating role between perceived stress and job burnout. Specific measures can be taken to improve the level of mindfulness in medical staff, so as to prevent and alleviate job burnout of medical staff.


Subject(s)
Burnout, Professional , Medical Staff , Mindfulness , Humans , Emotions , Medical Staff/psychology , Burnout, Professional/prevention & control
2.
Zhonghua Yi Xue Za Zhi ; 101(25): 1985-1990, 2021 Jul 06.
Article in Chinese | MEDLINE | ID: mdl-34225420

ABSTRACT

Objective: To investigate the efficacy and tolerability of Polatuzumab vedotin+rituximab±bendamustine (Pola-(B)R) in relapse/refractory diffuse large B cell lymphoma (R/R DLBCL) patients. Methods: The clinical data of 21 patients enrolled in Chinese Pola compassionate use program (CUP) in 4 centers from November 2019 to August 2020 were collected. There were 15 males and 6 females, and the median age was 56 years (ranged 25-76 years). Of the patients, 10 cases received Pola-BR regimen and the other 11 received Pola-R. Their clinical features, regimens, efficacy, and adverse events (AEs) were retrospectively analyzed. Results: Twenty-one patients with at least one efficacy evaluation were included. At data analysis cut-off point (12 Aug. 2020), the best overall response (BOR) rate was 81.0% (17/21) and the complete response (CR) rate was 19.0% (4/21). Kaplan-Meier survival estimation was performed, at a median follow-up of 54 days, three patients (14.3%) had disease progressed, and 18 patients (85.7%) were censored; the median progression-free survival (mPFS) was estimated to be 148 days. The incidence of adverse effects (AEs) of any grade was higher in Pola-BR group than Pola-R group (80.0% vs 63.6%). However, the incidence of grade 3-4 AEs were close in the two groups (30.0% vs 29.3%). The most common hematological toxicities were thrombocytopenia (28.6%, 6/21), neutropenia (28.6%, 6/21) and anemia (14.3%, 3/21), respectively. One patient with pneumonia and 1 patient with hemophagocytic syndrome recovered after symptomatic treatment. No peripheral neuropathy of grade≥2 was observed. Conclusions: The preliminary data suggested that, for heavily treated Chinese R/R DLBCL, the Pola-(B)R regimen still achieves promising efficacy and tolerable safety.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Large B-Cell, Diffuse , Adult , Aged , Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cohort Studies , Female , Humans , Immunoconjugates , Lymphoma, Large B-Cell, Diffuse/drug therapy , Male , Middle Aged , Neoplasm Recurrence, Local , Retrospective Studies , Rituximab/therapeutic use , Treatment Outcome
6.
Genet Mol Res ; 15(2)2016 Apr 04.
Article in English | MEDLINE | ID: mdl-27173182

ABSTRACT

Monomethoxypolyethylene glycol-chitosan (mPEG-CS) nanoparticles were used as interfering RNA carriers to transfect human prostate cancer PC-3M cells to evaluate the effects of livin and survivin gene silencing on the proliferation and apoptosis. mPEG-CS nanoparticles with sizes of approximately 60 nm were first synthesized by ionic crosslinking. Through electrostatic adsorption, mPEG-CS-livin short hairpin RNA (shRNA), mPEG-CS-survivin shRNA, and mPEG-CS-(livin shRNA + survivin shRNA) nanoparticles were then prepared to transfect PC-3M cells. The mRNA and protein expression levels of livin and survivin were measured by reverse transcription-PCR and western blotting, respectively. The inhibitory effects of down-regulated livin and survivin gene expression on the cell proliferation were evaluated by MTT assay. Cell apoptosis was assessed visually using Hoechst staining. Livin and survivin expression levels in all shRNA interference groups were effectively down-regulated at both the mRNA and protein levels. Dual silencing of livin and survivin genes markedly inhibited cell proliferation and facilitated apoptosis, with better outcomes than those of individual shRNA treatments. mPEG-CS nanoparticle-mediated dual shRNA interference of livin and survivin genes significantly reduced the expression levels in PC-3M cells, inhibited proliferation, and promoted apoptosis. As these effects were superior to single interference, this method may have synergistic effects.


Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Inhibitor of Apoptosis Proteins/genetics , Nanoparticles/chemistry , Neoplasm Proteins/genetics , Prostatic Neoplasms/metabolism , RNA Interference , Adaptor Proteins, Signal Transducing/metabolism , Apoptosis , Cell Line, Tumor , Cell Proliferation , Chitosan , Glutamic Acid , Humans , Inhibitor of Apoptosis Proteins/metabolism , Male , Neoplasm Proteins/metabolism , Polyethylene Glycols , Survivin
7.
Genet Mol Res ; 15(1): 15017326, 2016 Mar 04.
Article in English | MEDLINE | ID: mdl-26985934

ABSTRACT

5-Fluorouracil (5-FU) is widely used in chemotherapy for treatment of colorectal cancer. Leucine-rich repeat-containing G protein-coupled receptor (LGR) is known to participate in the occurrence and development of breast cancer by regulating the rebirth of tumor vessels. This study aimed to explore the proliferation and apoptosis of HCT116 colorectal cancer cells treated with 5-FU and related molecular mechanisms. 5-FU (20 µg/mL) was used to treat cultured HCT116 cells. An MTT test, flow cytometry, and colony formation assays were used to examine the proliferation and apoptosis of HCT116 cells. Western blotting was applied to detect the expression of the LGR4 protein in HCT116 cells. Small interference RNA or over-expression techniques were used to manipulate LGR4 expression in HCT116 cells and describe the proliferation and apoptosis of HCT116 treated with 5-FU. A dosage of 20 µg/mL 5-FU resulted in a significant decrease in the proliferation and apoptosis of HCT116 cells and significantly decreased expression levels of LGR4. The specific gene silence or over-expression of LGR4 in HCT116 cells increased and decreased the levels of apoptosis in HCT116, respectively. 5-FU induces apoptosis of colorectal cancer cells and inhibits proliferation by suppressing LGR4 proteins.


Subject(s)
Antimetabolites, Antineoplastic/pharmacology , Colorectal Neoplasms/metabolism , Fluorouracil/pharmacology , Receptors, G-Protein-Coupled/metabolism , Apoptosis , Cell Proliferation/drug effects , Gene Expression Regulation, Neoplastic/drug effects , HCT116 Cells , Humans , RNA, Small Interfering/pharmacology , Receptors, G-Protein-Coupled/genetics
8.
Sci Rep ; 4: 5477, 2014 Jun 27.
Article in English | MEDLINE | ID: mdl-24969627

ABSTRACT

Density functional theory calculations of NdAlO3/SrTiO3 heterostructure show that two-dimensional electron gas (2-DEG) is produced at the interface with a built-in potential of ~0.3 eV per unit cell. The effects of surface defects on the phase stability and electric field of 2-DEG have been investigated. It is found that oxygen vacancy is easily to form on the NdAlO3(001) surface, with a low threshold displacement energy and a low formation energy. This point defect results in surface reconstruction and the formation of a zigzag -Al-O-Al- chain, which quenches the built-in potential and enhances the carrier density significantly. These results will provide fundamental insights into understanding how surface defects influence the electronic behavior of 2-DEG and tuning their electronic properties through surface modification.

10.
Plant Dis ; 95(11): 1483, 2011 Nov.
Article in English | MEDLINE | ID: mdl-30731748

ABSTRACT

In Guangxi Province of southwest China, diseases caused by Tospoviruses (family Bunyaviridae) pose a serious threat to tobacco (Nicotiana tobacum) production. During surveys conducted annually at Xinrong Village in Jingxi County from 2008 to 2010, more than 130 ha of fields were found to have 10 to 50% of plants exhibiting symptoms similar to spotted wilt caused by Tomato spotted wilt virus (TSWV). During this period, disease symptoms at similar prevalence and incidence were also found at Fushan, Debao County in most of the cultivars produced in these areas, including Yunyan 85, 87, 92, 97, and K326. Symptoms on tobacco varied but commonly included dwarfing, midrib browning, distorted apical buds, and concentric ringspots that coalesced to form large areas of dead leaf tissue. Mechanical inoculation from diseased tobacco leaves with concentric ringspots back to tobacco cv. Yunyan 85 or 87, resulted in 12 of 16 plants with symptoms similar to those observed in the field. No symptoms on plants developed following inoculation with buffer only. Symptoms found in the field resembled those caused by TSWV. However, testing using TSWV-specific antiserum was shown to be negative by double-antibody sandwich-ELISA (Agdia, Elkhart, IN). Total RNA was extracted from 27 diseased tobacco plants collected from different regions in Guangxi using Trizol reagent (Invitrogen, Carlsbad, CA) according to the manufacturer's instructions. RNA extracts were amplified by reverse transcription (RT)-PCR using the degenerate primers T2740 (ATGGGDATNTTTGATTTCATG) and T3920c (TCATGCTCATSAGRTAAATYTCTCT) designed to target the partial RNA-dependent RNA polymerase (RdRp) sequence of members in the genus Tospovirus (3). Amplification was performed at 42°C for 60 min, followed by 35 cycles of PCR (30 s denaturation at 94°C, 45 s annealing at 55°C, and 30 s extension at 72°C) and a 7-min final extension at 72°C. A PCR product of approximately 1.2 kb was amplified from 21 diseased plants. RT-PCR amplicons were cloned into the pUC19-T Simple Vector (TaKaRa, Dalian, China) and sequenced in both directions. Sequences were assembled and analyzed by DNAStar 5.01 (DNASTAR, Madison, WI). Sequences of representative isolates were deposited in GenBank (Accession Nos. JN020022 to JN020027). The 1.2-kb partial RdRp sequences of these isolates were shown to have 94.4 to 95.3% nucleotide identity and 96.5 to 97.5% amino acids identity to Tomato zonate spot virus (TZSV) (GenBank Accession No. NC_010491) (1). Among these TZSV isolates from Guangxi, the partial RdRp sequences have 98.0 to 99.4% nucleotide identity and 98.8 to 100% amino acids identity with each other. The presence of TZSV was further confirmed in diseased tobacco plants by indirect ELISA using antiserum of TZSV (provided by Prof. Zhongkai Zhang, Agricultural Academy of Yunnan, China). TZSV has been characterized as a novel tospovirus on various hosts including tobacco in Yunnan province (1,2). To our knowledge, this is the first report of TZSV-associated disease on tobacco in Guangxi Province, southwest China. Further work is necessary to study the epidemiology and management of the disease. References: (1) J. Dong et al. Arch. Virol. 153:855, 2008. (2) J. Dong et al. J. Insect Sci. 10:166, 2010. (3) Y. Lin. Master Thesis. National Chung Hsing University, Taichung, Taiwan, Republic of China, 2007.

11.
J Int Med Res ; 39(6): 2414-20, 2011.
Article in English | MEDLINE | ID: mdl-22289561

ABSTRACT

This study compared the clinical results of surgical treatment of high complex anal fistula with a conventional seton and a new type of seton consisting of an elastic sheath and alloy core tube for irrigation of the wound track. A total of 438 patients were included in the study; 215 were treated with a conventional seton and 223 with the new-type seton. In patients treated with the new-type seton, the wound track was irrigated daily with 100 ml physiological saline, 100 ml hypertonic saline and 0.5 g metronidazole gel from the second postoperative day until seton removal. The new-type seton was associated with significant reductions in recurrence rate, length of stay and healing time compared with the conventional seton, but there were no significant differences in operation time or postoperative incontinence rates. It is concluded that the new-type seton with irrigating tube can improve the treatment of high complex anal fistula.


Subject(s)
Rectal Fistula/surgery , Suture Techniques/instrumentation , Therapeutic Irrigation/instrumentation , Adolescent , Adult , Fecal Incontinence/etiology , Female , Humans , Male , Middle Aged , Suture Techniques/adverse effects , Therapeutic Irrigation/adverse effects , Treatment Outcome , Young Adult
12.
J Nanosci Nanotechnol ; 10(3): 2023-7, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20355620

ABSTRACT

A large quantity of uniform ZnO nanoneedles has been synthesized by thermal evaporation method. Both single and double tip ZnO nanoneedles were found coexistence in the as-synthesized products. The single tip nanoneedles are major products in the synthesis and a few double tip nanoneedles were also observed. The polarity of the nanoneedles was characterized by convergent beam electron diffraction (CBED) and the simulation results reveal that the polarity of the ZnO (0001) surface directs the preferential growth of the nanoneedles. It is also found that most of the double tip nanoneedles are originated from the joint growth of two single tip nanoneedles with a kink in the middle and smooth ones might be generated from forming thin layer of cubic structures in the double nanoneedle tips. A large quantity of ZnO nanorod building blocks without tips was also achieved by fast cooling. The formation of the nanoneedles and nanorods can be attributed to different cooling speeds in our experiments. The sharp single nanoneedle tip can be potentially used as scanning probe microscope or field-emission tips.

13.
J Phys Condens Matter ; 18(26): 6001-7, 2006 Jul 05.
Article in English | MEDLINE | ID: mdl-21690814

ABSTRACT

Rutile-type Co-doped SnO(2) nano-crystal powders are prepared by the wet chemical method. The magnetic moment is found to decrease with increasing Co content. There is hysteresis between field cooled (FC) and zero field cooled (ZFC) magnetization when the temperature is below 70 K. These magnetic behaviours represent antiferromagnetic interaction between Co ions. By measuring the magnetization as a function of temperature, the magnetic interaction between Co ions is evaluated qualitatively using the Curie-Weiss law. The value of the effective exchange integral J(1)/k(B) is about -62 K, indicating a very strong antiferromagnetic superexchange interaction between Co ions.

14.
Infection ; 29(4): 228-31, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11545486

ABSTRACT

BACKGROUND: This study analyzes the prevalence of hospital and community-acquired infections caused by Escherichia coli. PATIENTS AND METHODS: The antibiotic resistance pattern was used to characterize the isolates, and a retrospective observational study was performed to assess the relationship between antimicrobial use and bacterial resistance. The study was conducted during a 1-year and 7-month period in a 1,500-bed tertiary care hospital in Anhui, China. RESULTS: An E. coli infection was diagnosed in 1.4% of patients (519/36,179) admitted to the hospital between March 1, 1999 and August 31, 2000. Of the 519 isolates, 489 (94.2%) were resistant to at least one antimicrobial; 86% were resistant to ampicillin, 85% to cephalothin, 83% to piperacillin, 77% to ampicillin/sulbactam, 72% to trimethoprim/sulfamethoxazole (TMP-SMZ), 70% to ciprofloxacin, 61% to cefoperazone, 58% to tobramycin, 56% to gentamicin, 48% to ticarcillin-clavulanate, 44% to cefazolin, 43% to cefuroxime, 36% to cefoxitin, 32% to cefepime, 29% to aztreonam, cefetaxime and ceftriaxone, 28% to ceftazidime, 19% to piperacillin/tazobactam, 10% to amikacin, while all strains tested were susceptible to imipenem. CONCLUSION: Prior receipt of amtimicrobial therapy was significantly associated with infection caused by a resistant organism.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Escherichia coli Infections/drug therapy , Escherichia coli Infections/epidemiology , Escherichia coli/isolation & purification , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , China/epidemiology , Community-Acquired Infections/epidemiology , Community-Acquired Infections/microbiology , Cross Infection/epidemiology , Cross Infection/microbiology , Drug Resistance, Multiple, Bacterial , Female , Humans , Infant , Infant, Newborn , Male , Middle Aged , Multivariate Analysis , Prevalence , Retrospective Studies , Risk Factors
15.
Inorg Chem ; 40(4): 710-4, 2001 Feb 12.
Article in English | MEDLINE | ID: mdl-11225113

ABSTRACT

The construction of two-dimensional (2D) copper halide networks within a variety of perovskite hosts by a low-temperature topochemical method is demonstrated. Ion exchange between some layered perovskite oxides of the type A'[An - 1(M,M')nO3n + 1] (A' = alkali metal, H, NH4; A = alkaline earth, rare earth, or Bi; M,M' = Nb, Ta, Ti; n = 2, 3) with CuX2 (X = Cl, Br) results in the oxyhalides (CuX)[An - 1(M,M')nO3n + 1]. Rietveld refinements from X-ray powder diffraction data show that the structures of these new copper oxyhalides contain edge-sharing CuO2X4 octahedra sandwiched between the M/M'O6 octahedra of the perovskite slabs. The compounds are low-temperature phases that decompose well below 700 degrees C. The copper oxyhalides exhibit antiferromagnetic ordering resulting from the magnetic exchange interactions within the planar Cu-X networks.

16.
Chem Commun (Camb) ; (18): 1872-3, 2001 Sep 21.
Article in English | MEDLINE | ID: mdl-12240356

ABSTRACT

Using a high-temperature organic solution reduction method, highly crystalline and single domain bismuth nanoparticles have been synthesized and self-assembled.

17.
J Neurobiol ; 41(4): 495-504, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10590173

ABSTRACT

Lysophosphatidic acid (LPA) plays various roles in the regulation of cell growth as a lipid mediator. We studied the effect of LPA on intracellular Ca(2+) concentration ([Ca2+]i) with Fura-2 in the neural retina of chick embryo during neurogenesis. Bath application of LPA (1-100 microM) to the embryonic day 3 (E3) chick retina caused an increase in [Ca2+](i) in a dose-dependent manner, with an EC(50) value of 9.2 microM. The Ca(2+) rise was also evoked in a Ca(2+)-free medium, suggesting that release of Ca(2+) from intracellular Ca(2+) stores (Ca(2+) mobilization) was induced by LPA. U-73122, a blocker of phospholipase C (PLC), inhibited the Ca(2+) rise to LPA. Pertussis toxin partially inhibited the Ca(2+) rise to LPA, indicating that G(i)/G(o) protein was at least partially involved in the LPA response. The developmental profile of the LPA response was studied from E3 to E13. The Ca(2+) rise to LPA declined drastically from E3 to E7, in parallel with decrease in mitotic activity of retinal progenitor cells. The signal transduction pathway and developmental profile of the Ca(2+) response to LPA were the same as those of the Ca(2+) response to adenosine triphosphate (ATP), which enhances the proliferation of retinal progenitor cells. The coapplication of LPA with ATP resulted in enhancement of Ca(2+) rise in the E3 chick retina. Our results show that LPA induces Ca(2+) mobilization in the embryonic chick retina during neurogenesis.


Subject(s)
Calcium/metabolism , Lysophospholipids/pharmacology , Retina/embryology , Animals , Chick Embryo , Fluorescent Dyes , Fura-2/analogs & derivatives , In Vitro Techniques , Kinetics , Microscopy, Fluorescence , Neurons/drug effects , Neurons/metabolism , Retina/drug effects , Retina/metabolism
18.
Neurosci Lett ; 272(2): 123-6, 1999 Sep 10.
Article in English | MEDLINE | ID: mdl-10507557

ABSTRACT

Capacitative Ca2+ entry occurs in the neural retina of chick embryo during neurogenesis. We studied the effects of blockers of capacitative Ca2+ entry (SK&F 96365, Zn2+, Ni2+), genistein, a tyrosine kinase inhibitor and vanadate, a protein-phosphotyrosine phosphatase inhibitor in the embryonic chick retina with fura-2 fluorescence measurements. After incubation of the retina in a Ca2+-free solution with or without an inhibitor of Ca2+ pumps of intracellular Ca2+ stores, re-introduction of extracellular Ca2+ caused capacitative Ca2+ entry which was inhibited by SK&F 96365 (10 microM), Zn2+ (1 mM), Ni2+ (5 mM) and genistein (100 microM). On the contrary, vanadate (1 mM) enhanced the Ca2+ entry. These results suggested that tyrosine phosphorylation was involved in the activation of capacitative Ca2+ entry.


Subject(s)
Calcium/metabolism , Retina/metabolism , Tyrosine/metabolism , Animals , Chick Embryo , Enzyme Inhibitors/pharmacology , Phosphorylation , Vanadates/pharmacology
19.
Int J Dev Neurosci ; 17(3): 163-72, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10452360

ABSTRACT

Release of Ca2+ from intracellular Ca2+ stores (Ca2+ mobilization) and capacitative Ca2+ entry have been shown to be inducible in neuroepithelial cells of the early embryonic chick retina. Both types of Ca2+ responses decline parallel with retinal progenitor cell proliferation. To investigate their potential role in the regulation of neuroepithelial cell proliferation, we studied the effects of 2,5-di-tert-butylhydroquinone (DBHQ), an inhibitor of the Ca2+ pump of intracellular Ca2+ stores, and of SK&F 96365, an inhibitor of capacitative Ca2+ entry, on DNA synthesis in retinal organ cultures from embryonic day 3 (E3) chicks and in dissociated cultures from E7 and E9 chick retinae. We demonstrate that both antagonists inhibit [3H]-thymidine incorporation in a dose-dependent manner without affecting cell viability or morphology. The inhibition of [3H]-thymidine incorporation by SK&F 96365 occurred in the same concentration range (IC50: approximately 4 microM) as the blockade of capacitative Ca2+ entry in the E3 retinal organ culture. At a concentration of 5 microM SK&F 96365. DNA synthesis was reduced by 71, 40 and 32% in the E3, E7 and E9 cultures, respectively. Application of DBHQ at concentrations which led to depletion of intracellular Ca2+ stores also inhibited [3H]-thymidine incorporation with IC50 values of 20-30 microM in the different cultures. Our results suggest the involvement of Ca2+ mobilization and capacitative Ca2+ entry in the regulation of DNA synthesis in the developing neural retina.


Subject(s)
Calcium Channel Blockers/pharmacology , Calcium-Transporting ATPases/antagonists & inhibitors , Calcium-Transporting ATPases/drug effects , DNA/biosynthesis , Enzyme Inhibitors/pharmacology , Retina/drug effects , Animals , Cells, Cultured , Chick Embryo , Epithelial Cells/cytology , Epithelial Cells/drug effects , Hydroquinones/pharmacology , Imidazoles/pharmacology , Organ Culture Techniques , Retina/cytology , Retina/metabolism , Thymidine/metabolism , Tritium
20.
Mol Cell Biol ; 19(6): 4182-90, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10330158

ABSTRACT

A fungus-derived compound (OSI-2040) which induces fetal globin expression in the absence of erythroid cell differentiation was identified in a high-throughput drug discovery program. We utilized this compound to isolate gamma-globin regulatory genes that are differentially expressed in OSI-2040-induced and uninduced cells in the human erythroleukemia cell line K562. Representational difference analysis (RDA) of cDNA revealed several genes that were significantly up- or down-regulated in OSI-2040-induced cells. One gene whose expression was markedly enhanced was the gene for the helix-loop-helix (HLH) transcription factor Id2. Southern analysis of RDA amplicons demonstrated progressive enrichment of Id2 with each successive subtraction of uninduced cDNA from induced cDNA. Northern analysis of OSI-2040-induced K562 cells confirmed that Id2 expression was directly up-regulated coordinately with gamma-globin. Analysis of other inducers of fetal globin demonstrated up-regulation of Id2 with sodium butyrate but not with hemin. Retrovirus-mediated overexpression of Id2 in K562 cells reproduced the enhancement of endogenous globin expression observed with OSI-2040 induction. Functional assays demonstrated that an E-box element in hypersensitivity site 2 is required for Id2-dependent enhancement of gamma-promoter activity. Protein binding studies suggest that alterations in E-box site occupancy by basic HLH proteins may influence this activity, thus expanding the potential role of these factors in globin gene regulation.


Subject(s)
DNA-Binding Proteins/physiology , Globins/biosynthesis , Repressor Proteins , Transcription Factors , Blotting, Northern , Cell Line , DNA, Complementary/metabolism , Dose-Response Relationship, Drug , Electrophoresis, Polyacrylamide Gel , Gene Expression Regulation, Fungal , Globins/metabolism , Humans , Inhibitor of Differentiation Protein 2 , K562 Cells , Luciferases/metabolism , Models, Genetic , Oligonucleotide Probes , Promoter Regions, Genetic , Retroviridae/metabolism , Sequence Analysis, DNA , Transduction, Genetic , Transfection , Tumor Cells, Cultured , Up-Regulation
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