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Biomedical subjects

S Dong

Publications and source records attributed to S Dong.

At least 91 records · Page 5Linked to original sources
PubMed1997

Leukemia-associated retinoic acid receptor alpha fusion partners, PML and PLZF, heterodimerize and colocalize to nuclear bodies.

In acute promyelocytic leukemia (APL), the typical t(15;17) and the rare t(11;17) translocations express, respectively, the PML/RARalpha and PLZF/RARalpha fusion proteins (where RARalpha is retinoic acid receptor alpha). Herein, we demonstrate that the PLZF and PML proteins interact with each other and colocalize onto nuclear bodies (NBs). Furthermore, induction of PML expression by interferons leads to a recruitment of PLZF onto NBs without increase in the levels of the PLZF protein. PML/RARalpha and PLZF/RARalpha localize to the same microspeckled nuclear domains that appear to be common targets for the two fusion proteins in APL. Although PLZF/RARalpha does not affect the localization of PML, PML/RARalpha delocalizes the endogenous PLZF protein in t(15;17)-positive NB4 cells, pointing to a hierarchy in the nuclear targeting of these proteins. Thus, our results unify the molecular pathogenesis of APL with at least two different RARalpha gene translocations and stress the importance of alterations of PLZF and RARalpha nuclear localizations in this disease.

Animals↗
PubMed1997

Mapping the regions of the complement inhibitor CD59 responsible for its species selective activity.

CD59 is a widely distributed membrane-bound glycoprotein that inhibits the formation of the cytolytic membrane attack complex (MAC) of complement on host cells. CD59 from different species varies in its capacity to inhibit heterologous complement, and this species selective function of CD59 contributes to the phenomenon of homologous restriction. Here, we demonstrate that human CD59 is not an effective inhibitor of rat complement, although rat CD59 inhibits rat and human complement equally well. By constructing human-rat CD59 chimeric proteins, we have mapped the residues important in conferring human CD59 species selectivity to two regions; 40-47 and 47-66 in the primary structure. Analysis of a model of the molecular surface of human CD59 revealed that residues 40-66 mapped to a region in the three-dimensional structure that surrounds residues previously identified as important for CD59 function.

Amino Acid Sequence↗
PubMed1997

Mapping the active site of CD59.

CD59 is a widely distributed membrane-bound inhibitor of the cytolytic membrane attack complex (MAC) of complement. This small (77 amino acid) glycoprotein is a member of the Ly6 superfamily of proteins and is important in protecting host cells from the lytic and proinflammatory activity of the MAC. CD59 functions by binding to C8 and/or C9 in the nascent MAC and interfering with C9 membrane insertion and polymerization. We present data obtained from a combination of molecular modeling and mutagenesis techniques, which together indicate that the active site of CD59 is located in the vicinity of a hydrophobic groove on the face of the molecule opposite to a "hydrophobic strip" suggested earlier. In addition, removal of the single N-linked glycosylation site at Asn18 of CD59 resulted in an enhancement of complement inhibitory activity.

Amino Acid Sequence↗
PubMed1997

MLL self fusion mediated by Alu repeat homologous recombination and prognosis of AML-M4/M5 subtypes.

Fifty-six patients with de novo acute myeloid leukemia M4/M5 subtypes were studied for rearrangements of the mixed lineage leukemia gene, MLL (also called HRX, Htrx-1, or ALL-1). Ten patients (18%) showed rearrangements of the MLL gene, 9 in a major breakpoint cluster region within a centromeric 8.3-kb BamHI fragment, whereas rearrangement in one patient was the result of a direct tandem duplication of exons 2-6 of MLL. Analysis of sequences at the duplication junction revealed that the points of MLL fusion within introns 6 and 1 both lie within Alu elements. This suggests the involvement of Alu repeat mediated homologous recombination in MLL self fusion. For the 10 rearranged samples, cytogenetics analysis revealed a normal karyotype in 3, and 3 had abnormalities other than 11q23. Survival analysis of patients revealed no difference between those with rearrangement of MLL and those showing the germ-line configuration.

Adult↗
PubMed1997

Comparison of total versus partial laparoscopic fundoplication in the management of gastroesophageal reflux disease.

BACKGROUND AND METHODS: A comparison of total vs. partial laparoscopic fundoplication was conducted in 89 patients from July 92 to June 96. Parameters examined were operating room (OR) times, conversion rates, and perioperative complications. Patient satisfaction, control of symptoms, and late complications were assessed by follow-up at a mean of 6 and 15.4 months. RESULTS: There were six conversions to open surgery resulting in 48 laparoscopic total (LTF) and 35 laparoscopic partial (25 anterior and 10 Toupet) fundoplications (LPF). The following results were obtained for each respectively: preop Demeester score 44 vs. 39; OR time 2.9 vs. 2.5 hours; length of stay 3.6 vs. 4.1 days; early morbidity 25% vs. 1%. There were no mortalities. At a mean follow-up of 6 months, new-onset dysphagia was present in 8 (17%) vs. 2 (8%), respectively (NS), and both total and partial fundoplications appeared successful in controlling symptoms (98% vs. 97%). At a mean follow-up of 15.4 months, heartburn was resolved or improved in 76% vs. 87% (NS); regurgitation was improved or resolved in 93% vs. 93%; and patient satisfaction with the procedure was present in 93% vs. 97% (NS). Persistent dysphagia was present in 7.3% vs. 10.3% (NS) of patients. Early satiety was present more often in the partial fundoplication group (56% vs. 83% P = .03). CONCLUSIONS: Early follow-up suggests equal efficacy in controlling symptoms and in achieving patient satisfaction. A 6-month follow-up suggested a higher incidence of new dysphagia in the total fundoplication group; however, at 15-month follow-up there was no significant difference.

Female↗
PubMed1997

Scanning tunnelling microscopy observation of cytochrome-c denaturation induced by bromopyrogal red on highly oriented pyrolytic graphite.

The denaturation of cytochrome-c (cyt-c) induced by bromopyrogal red (BPR) was studied by scanning tunnelling microscopy (STM) on the electrochemically pretreated highly oriented pyrolytic graphite (HOPG) surface. STM images reveal that denatured cyt-c molecules exist in variable states including aggregates, globular compact, partially unfolded and combined with BPR molecule. The apparently low image contrast of denatured cyt-c observed in this experiment comparing to that of native cyt-c molecules, and the relative low image contrast of the unfolded part comparing with the compact globular part, are ascribed to the unfavourable tunnelling paths for the conformational variations of denatured cyt-c molecules.

Animals↗
PubMed1997

Macrophage surface glycoproteins binding to galectin-3 (Mac-2-antigen).

Galectin-3 (formerly called Mac-2 antigen) is a approximately 30 kDa carbohydrate-binding protein expressed on the surface of inflammatory macrophages and several macrophage cell lines. We have purified from lysates of the murine macrophage cell line WEHI-3 glycoproteins that bind to a galectin-3 affinity column. Several of these receptors are labelled after biotinylation of intact cells showing their location at the cell surface. N-terminal aminoacid sequencing of intact galectin-3-binding glycoproteins isolated from preparative SDS-gels or of chemically derived fragments showed several homologies with known proteins and identification was confirmed by immunoprecipitation with specific antibodies. The glycoproteins were shown to be: the alpha-subunit(CD11b) of the CD11b/CD18 integrin(Mac-1 antigen); the lysosomal membrane glycoproteins LAMPs 1 and 2 which are known in part to be expressed at cell surfaces; the Mac-3 antigen, a mouse macrophage differentiation antigen defined by the M3/84 monoclonal antibody and related immunochemically to LAMP-2; the heavy chain of CD98, a 125 kDa heterodimeric glycoprotein identified by the 4F2/RL388 monoclonal antibodies respectively on human and mouse monocytes/macrophages and on activated T cells. Further studies showed that CD11b/CD18, CD98 and Mac-3 are major surface receptors for galectin-3 on murine peritoneal macrophages elicited by thioglycollate.

Amino Acid Sequence↗
PubMed1997

[The effect of NO-like relaxing factor on vascular reactivity in tourniquet shock rat].

This work was done on rat tourniquet shock (ToS) model. It was found that reactivity of isolated perfused aortic ring to noradrenaline decreased, while cGMP content of the aortic tissue increased. These changes could be potentiated by perfusion with L-arginine (NO-precursor). On the other side, when the aortic ring was perfused with L-NNA (NO-synthesis inhibitor) or methylene blue (soluble cGMPase inhibitor), the changes could be attenuated. The effect of these drugs are independent of the presence of vascular endothelium. The results suggest that non-endothelium-derived NO-like relaxing factor may be one of the factors causing low vascular reactivity of the ToS animals.

Animals↗
PubMed1997

[Measurement and evaluation of radiation dose distribution of gamma-ray altimeter in static test for recovery capsule during simulated landing].

The gamma-ray altimeter, containing a gamma-radioactive source 137Cs with activity of 2.96 x 10(10) Bq, was used to detect the height of the spacecraft recovery capsule during landing. To measure the gamma-dose distribution near to the guidance section, especially at position where the useful load is located in recovery capsule, gamma-dose field at the test-site for one machine test was measured by means of a gamma-dose rate meter FJ-317C and a gamma-dose meter ANRI-01-02. The result showed that the absorbed dose rate at 5 meters from gamma-source on the ground is as low as the radiation protection limit when the altimeter is down to 0.16 m from the ground. The ground reflection effect for gamma-ray decreases as height of the recovery capsule increases. Therefore, the gamma-dose level at useful load in the recovery capsule will meet the requirements of flight safety.

Altitude↗
PubMed1997

[Study of dominant negative effect of the PLZF-RARalpha against the wild-type RARalpha in acute promyelocytic leukemia].

OBJECTIVE: To explore the role of promyelocytic leukemia zinc finger (PLZF) gene on 11q23 and RARalpha gene on 17q21. METHODS: Eight PLZF/RARalpha expression plasmids with deletions of different PLZF motifs were constructed by using PCR based-method. RESULTS AND CONCLUSION: By transient co-transfection, it was confirmed that PLZF/RARalpha had a dominant negative effect against the wild-type RARalpha, the POZ domain of PLZF/RARalpha was responsible for the dominant negative effect and the PLZF/RARalpha may play certain role through a spatial interaction with POZ.

Animals↗
PubMed1997

[Comparative study of two fusion retinoic acid receptor alpha in acute promyelocytic leukemia].

OBJECTIVE: To make a comparison of biological properties between PML-RARalpha and PLZF-RARalpha fusion proteins. METHODS: Receptor radioligand binding assay, receptor DNA binding assay and immunofluorescence methods were used. RESULTS AND CONCLUSION: PML-RARalpha and PLZF-RARalpha had similar ligand-binding affinities. Both could bind in vitro to retinoic acid response elements (RAREs) forming homodimers and to retinoic acid X receptor. However ,they differed in the relative binding affinities to different RAREs,the behavior of forming complex with RXR and the subcellular localization. More importantly, PML-RARalpha and PLZF-RARalpha could block different regulatory pathways mediated by PML or PLZF, through heterocomplex formation with wild-type PML or PLZF. The differences between PML-RARalpha and PLZF-RARalpha may in part explain the apparent resistance of APL with t(11;17) to differentiating effect of all-trans retinoic acid (ATRA).

DNA↗
PubMed1997

[Analysis of vitamin K1 in Cephalanoplos segetum (Bunge) Kitam by high performance liquid chromatography].

A modified method for the analysis of vitamin K1 in Cephalanoplos segetum (Bunge) Kitam, an edible wild herb, is proposed in this paper. The ground herb sample was extracted with CHCl3, followed by evaporation to dryness with nitrogen. The residue was dissolved with methanol, filtered through 0.5microm micropore membrane and then determined on a Novapak C18, 150mm x 3.9mm i.d., column with methanol/isopropanol (70:30) as mobile phase and UV-248nm as detector. Recovery was more than 95% with CV 1.23%. The method is simple and accurate without saponification, extraction and evaporation procedures as those used previously.

Asteraceae↗
PubMed1997

[Determination of chromium, manganese and nickel in six biological agents].

The determination of chromium, manganese and nickel in biological agents has obtained by flame atomic absorption spectrometry. The results show that three trace elements of body necessary are the most rich in ant factor injection liquid. The chromium content is slightly lower in the brain cell activator injection liquid, the nickel content is slightly lower in the shift factor injection liquid and the manganese is the lowest in the marrow factor injection liquid. In this paper, we have studied three trace element contents in six biological agents. It provides, useful data for clinical treatment to some trace-element-lacking diseases.

Chromium↗
PubMed1996

Galectin-3 stimulates uptake of extracellular Ca2+ in human Jurkat T-cells.

Galectin-3, a mammalian galactoside-binding protein, is not expressed in the Jurkat T-lymphoblastoid cell line. However, Jurkat cells express surface glycoprotein receptors for galectin-3, one of which is shown to be the glycosylated heavy chain of CD98 (4F2 antigen), a T-cell activation marker. Addition of galectin-3 to Jurkat cells triggers a sustained influx of extracellular Ca2+ in a concentration dependent manner. The induced increase in cytosolic [Ca2+]i is blocked by sugar hapten inhibitors of galectin-3. The galectin-3-induced effect is insensitive to voltage-gated Ca2+ channel antagonists such as prenylamine, nifedipine and diltiazem and to pertussis toxin but is inhibited by cholera toxin. The results suggest that galectin-3 released by accessory cells such as macrophages may bind in vivo to T-cell activation antigens and also participate in Ca2+ signalling.

Animals↗
PubMed1996

Amino-terminal protein-protein interaction motif (POZ-domain) is responsible for activities of the promyelocytic leukemia zinc finger-retinoic acid receptor-alpha fusion protein.

Promyelocytic leukemia zinc finger-retinoic acid receptor a (PLZF-RARalpha), a fusion receptor generated as a result of a variant t(11;17) chromosomal translocation that occurs in a small subset of acute promyelocytic leukemia (APL) patients, has been shown to display a dominant-negative effect against the wild-type RARalpha/retinoid X receptor alpha (RXRalpha). We now show that its N-terminal region (called the POZ-domain), which mediates protein-protein interaction as well as specific nuclear localization of the wild-type PLZF and chimeric PLZF-RARalpha proteins, is primarily responsible for this activity. To further investigate the mechanisms of PLZF-RARalpha action, we have also studied its ligand-receptor, protein-protein, and protein-DNA interaction properties and compared them with those of the promyelocytic leukemia gene (PML)-RARalpha, which is expressed in the majority of APLs as a result of t(15;17) translocation. PLZF-RARalpha and PML-RARalpha have essentially the same ligand-binding affinities and can bind in vitro to retinoic acid response elements (RAREs) as homodimers or heterodimers with RXRalpha. PLZF-RARalpha homodimerization and heterodimerization with RXRalpha were primarily mediated by the POZ-domain and RARalpha sequence, respectively. Despite having identical RARalpha sequences, PLZF-RARalpha and PML-RARalpha homodimers recognized with different affinities distinct RAREs. Furthermore, PLZF-RARalpha could heterodimerize in vitro with the wild-type PLZF, suggesting that it may play a role in leukemogenesis by antagonizing actions of not only the retinoid receptors but also the wild-type PLZF and possibly other POZ-domain-containing regulators. These different protein-protein interactions and the target gene specificities of PLZF-RARalpha and PML-RARalpha may underlie, at least in part, the apparent resistance of APL with t(11;17) to differentiation effects of all-trans-retinoic acid.

Animals↗
PubMed1996

Reduced and altered DNA-binding and transcriptional properties of the PLZF-retinoic acid receptor-alpha chimera generated in t(11;17)-associated acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) associated with chromosomal rearrangement t(11;17) is a distinct syndrome which, unlike typical t(15;17) APL, fails to respond to all-trans retinoic acid (ATRA) therapy. In t(11;17) the PLZF gene, encoding a Krüppel-like zinc finger protein, is fused to the retinoic acid receptor-alpha (RAR alpha) gene, yielding two classes of chimeric proteins. PLZF protein was found in the nucleus in a punctate speckled pattern that differed from the nuclear body expression pattern of the PML protein affected in t(15;17) APL. The reciprocal PLZF-RAR alpha and RAR alpha-PLZF fusion proteins were localized to the nucleus both in the presence and absence of ATRA. PLZF-RAR alpha, in combination with the retinoid X receptor (RXR) bound to a retinoic acid-responsive element (RARE) less efficiently than RAR alpha and formed multimeric DNA-protein complexes. PLZF-RAR alpha stimulated ATRA-dependent transcription of RARE-containing reporter genes with diminished activity compared to wild-type RAR alpha. In addition, PLZF-RAR alpha antagonized the function of coexpressed wild-type RAR alpha, an effect relieved by over-expression of RXR. Leukemogenesis in t(11;17) APL may be related to interference with ATRA-mediated differentiation due to sequestration of RXR by the PLZF-RAR alpha chimera. However, disruption of the function of the myeloid-specific PLZF protein may also play an important role.

Base Sequence↗
PubMed1996

Retinoic acid regulatory pathways, chromosomal translocations, and acute promyelocytic leukemia.

Retinoic acids (RAs) exert a broad range of physiologic actions during embryonic development and adult life. Two families of RA receptors, retinoic acid receptor (RAR) and retinoid X receptor (RXR), have been identified. The therapeutic effect of all-trans-RA (ATRA) in induction of remission for acute promyelocytic leukemia (APL) has largely been proved, and this has, over the past 10 years, greatly stimulated research on oncogenesis and RA-regulated differentiation pathways. In APL, one of the RAR genes, RARA, is fused to PML in the great majority of patients as a result of the chromosomal translocation t(15; 17). However, a small subset of APL patients have a different fusion gene, PLZF-RARA, resulting from the variant translocation t(11;17). A third translocation, t(5;17), in which the NPM gene is fused to RARA, has been described. Current data suggest that PML-RAR alpha and PLZF-RAR alpha fusion receptors may play an important role in the development of APL and that PML-RAR alpha could be the target of ATRA differentiation therapy. Characterization of the genes regulated by retinoic acid may open up new prospects for an understanding of the mechanisms of ATRA differentiation therapy for APL and may help to extend the concept of cancer-targeting treatment to other types of leukemias or solid tumors.

Adult↗