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M Sung

Publications and source records attributed to M Sung.

At least 19 recordsLinked to original sources
PubMed2006

The influence of exogenous progestin on the occurrence of proestrous or estrous signs, plasma concentrations of luteinizing hormone and estradiol in deslorelin (GnRH agonist) treated anestrous bitches.

UNLABELLED: The objectives of this study were to confirm: (i) whether progestin treatment suppressed GnRH agonist-induced estrus in anestrous greyhound bitches; and (ii) the site of progestin action (i.e. pituitary, ovary). All bitches received a deslorelin implant on Day 0 and blood samples were taken from -1 h to +6 h. Five bitches were treated with megestrol acetate (2 mg/kg orally once daily) from -7 d to +6 d (Group 1) and 10 bitches were untreated controls (Group 2). Proestrous or estrous signs were observed in 4 of 5 bitches in Group 1, and 4 of 10 bitches in Group 2 (P = 0.28). The plasma LH responses (area under the curve from 0 to 6h after implantation) were higher (P = 0.008) in Group 2 than in Group 1. Plasma LH responses were similar (P = 0.59) in bitches showing signs of proestrus or estrus (responders) and in non-responders. The plasma estradiol responses (calculated as for LH response) were greater in Group 1 than in Group 2 (P = 0.048), and in responders than in non-responders (P = 0.02). IN CONCLUSION: (i) progestin treatment (a) did not suppress the incidence of bitches showing deslorelin-induced proestrus or estrus, and (b) was associated with a reduced pituitary responsiveness and an increased ovarian responsiveness to deslorelin treatment; (ii) the occurrence of proestrous or estrous signs reflected increased ovarian responsiveness to induced gonadotrophin secretion and not increased pituitary responsiveness to deslorelin.

Anestrus↗
PubMed2004

Search for pi(0)-->nu(mu)nu(mu) decays in the LSND detector.

We observe a net beam excess of 8.7+/-6.3(stat)+/-2.4(syst) events, above 160 MeV, resulting from the charged-current reaction of nu(micro) and/or nu;(mu) on C and H in the LSND detector. No beam-related muon background is expected in this energy regime. Within an analysis framework of pi(0)-->nu(mu)nu;(mu), we set a direct upper limit for this branching ratio of Gamma(pi(0)-->nu(mu)nu;(mu))/Gamma(pi(0)-->all)<1.6 x 10(-6) at 90% confidence level.

Journal Article↗
PubMed2001

DA-125, a novel anthracycline derivative showing high-affinity DNA binding and topoisomerase II inhibitory activities, exerts cytotoxicity via c-Jun N-terminal kinase pathway.

PURPOSE: DA-125 [(8S,10S)-8-(3-Aminopropanoyloxyacetyl)-10-[(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) oxy]-7,8,9,10-tetrahydro-6,8,11-trihydroxy-1-methoxy-5,12-naphthacene-dione hydrochloride] is a novel anthracycline derivative with anticancer activity. In the present study, we compared the cytotoxicity of DA-125 with that of doxorubicin in H4IIE rat hepatoma cells and investigated the mechanistic basis. Because activation of MAP kinases, in particular c-Jun N-terminal kinase (JNK), is implicated in apoptotic cell death, the signaling pathways responsible for DA-125-induced apoptosis were studied. METHODS: Cytotoxicity and apoptosis were measured in H4IIE cells and cells were stably transfected with a dominant-negative mutant of JNK1 (JNK1-) by MTT and TUNEL assays. Inhibition of topoisomerase II activity was determined in vitro. Drug accumulation and DNA binding affinity were determined by fluorescence spectroscopy. RESULTS: The cytotoxicity of DA-125 was greater than that of doxorubicin (IC50 11.5 vs 70 microM). DA-125 induced apoptosis with 30-fold greater potency than doxorubicin. Inhibition of topoisomerase II by DA-125 was fourfold greater. The presence of excess beta-alanine, a DA-125 moiety, failed to alter cytotoxicity and accumulation of DA-125, indicating that the improved cytotoxicity of DA-125 did not result from the beta-alanine moiety. Greater cellular accumulation of DA-125 correlated with its high-affinity DNA binding. Although neither PD98059 nor SB203580 altered the degree of cytotoxicity induced by DA-125, JNK1 cells exhibited about a twofold greater viability than control cells. DA-125-induced apoptosis was also decreased in JNK1- -transfected cells. CONCLUSIONS: DA-125 potently inhibited topoisomerase II activity and induced apoptosis by a high rate of prooxidant production. DA-125 exhibited high-affinity DNA binding with improved cellular drug accumulation. Apoptosis induced by DA-125 involved the pathway of JNK1, but not ERK1/2 or p38 kinase.

Animals↗
PubMed2001

In vitro thymocyte differentiation in MHC class I-negative Xenopus larvae.

CTX is a surface antigen whose expression in larval and adult Xenopus is primarily restricted to MHC class I-negative immature cortical thymocytes. In adult Xenopus, surface expression of CTX marks a population of MHC class I(-) CD8(+) immature thymocytes that appears to be the equivalent of the mammalian CD4CD8 double positive subset. The present study reveals that transient in vitro exposure of immature CTX(+) thymocytes from MHC class I-negative tadpoles to suboptimal mitogenic concentrations of phorbol ester (PMA) plus ionomycin, induces larval cells to differentiate into more mature T-lymphoblasts that express high level of surface CD5 and CD45. These T-lymphoblasts have downregulated CTX, Rag 1 and TdT genes, whereas TCR-beta genes remain actively transcribed. Signaling induced by PMA/ionomycin modulates both class I and class II expression of MHC class I/II-negative larval thymocytes. This study also reveals that larval T-lymphoblasts are composed of two distinct subsets: CD5(high)CD8(-) and CD5 (high)CD8 (high).

Animals↗
PubMed2001

Purification, crystallization and preliminary X-ray analysis of the Escherichia coli glucose-1-phosphatase.

Encoded by the agp gene, Escherichia coli glucose-1-phosphatase hydrolyzes glucose-1-phosphate in the periplasmic space of the bacterium. It is a potential drug-design target because inositol phosphatases have been identified as important virulence determinants in several human and animal pathogens. The enzyme was isolated and purified to homogeneity from a strain of E. coli CU1867 (an appA-deficient mutant). Crystals were obtained overnight by the equilibrium vapour-diffusion method from a solution containing 10 mg ml(-1) enzyme, 1.2 M ammonium sulfate and 25% polyethylene glycol monomethyl ether 5000 in 0.1 M MES at pH 6.5. The crystals belong to space group R3, with unit-cell parameters a = b = 156.0, c = 92.2 A. The diffraction limit was 2.6 A at a rotating-anode X-ray source; a 2.7 A resolution data set has been collected using light mineral oil as a cryoprotectant. The data set was 95.2% complete, with an R(sym) of 0.058. There were two monomers of glucose-1-phosphatase in the asymmetric unit, which correspond to a V(M) of 2.36 A Da(-1) and 47.5% solvent content. Self-rotation analysis unambiguously shows a twofold non-crystallographic symmetry.

Crystallization↗
PubMed2001

Surrogate markers of antitumor responses: in vitro activation of T cells by autologous tumor peptides.

The increasing ability to augment antitumor immunity in model systems has led to increased numbers of clinical trials. However, progress in detecting immune responses by patients against autologous tumors has been slow. Although a considerable number of tumor antigens, as well as peptides derived from them, and the MHC determinants together with which they are presented have been identified for melanoma, this is not so for the majority of solid tumors. Furthermore, tumor cells themselves are poor stimulators of immunity. Thus, approaches that do not depend upon defined antigens or using tumor cells as stimulators would be desirable. To attempt to measure immune responses in these situations, we tested whether total peptides, prepared from autologous tumor tissue, stimulated cytokine release by T cells. Peripheral blood mononuclear cells (PBMCs) were mixed with antigen-presenting cells (APCs), pulsed with tumor peptides, and tested in the ELISPOT assay for IFN-gamma secretion. Few spots were obtained when PBMCs were cultured with unpulsed APCs or in wells with peptide-pulsed APC alone. In contrast, a strong response was seen when PBMCs were cultured with APCs that had been pulsed with autologous total tumor peptides. This system should help to identify those immunotherapeutic approaches that induce responses against tumor cells in vivo. Because different cytokine profiles are associated with distinct arms of the immune response, testing in the ELISPOT assay may also help us understand the mechanisms responsible.

Antigen-Presenting Cells↗
PubMed2000

IFNgamma secretion following stimulation with total tumor peptides from autologous human tumors.

Several issues remain to be resolved before the efficacy of various approaches to elicit anti-tumor immunity in patients can be evaluated. First, in vitro assays able to detect responses by T cells primed in vivo are needed. Second, a source of tumor antigen to stimulate patients' lymphocytes in vitro is required. The ELISPOT assay is attractive, because it can be performed with a small numbers of cells and requires only short-term culture in vitro. A source of tumor antigen is more problematic, since for most tumors, tumor-associated antigens (TAA) have not been identified and/or cloned. In this report we demonstrate that autologous antigen-presenting cells (APC) pulsed with total tumor peptides from autologous tumor tissue can stimulate IFNgamma release by patients' lymphocytes in the ELISPOT assay. Thus, this approach should be considered for monitoring immune responses in clinical immunotherapy trials.

Antigen Presentation↗
PubMed2000

A review of offenders remanded in a State Psychiatric Hospital.

Patients remanded over a two-year period to Woodbridge Hospital by Court Order were studied retrospectively. Schizophrenia was the most common diagnosis, theft and robbery the most prevalent offences. Males greatly outnumbered females. There were important gender differences, with males tending to commit sexual offences and females, theft and mischief. Males were less likely to be acquainted with their victims but those who caused hurt were more likely to know their victims. Outrage of modesty and theft were more likely to be committed against strangers. The reconviction rate was 26%, with repeat offenders more likely to commit sexual offences and theft. Patients who had previous psychiatric hospitalisation were more likely to be attending follow-up prior to and after release from remand and were more likely to have schizophrenia. Those assessed to be fit to plead were either fined or given jail sentences. Unsoundness of mind and unfitness to plead were associated with further remand in this hospital.

Adult↗
PubMed1999

Asp 280 residue is important in the activity of the Escherichia coli leader peptidase.

Leader peptidase is a novel serine protease in Escherichia coli, which catalyzes the cleavage of amino-terminal signal sequences from exported proteins. It is an integral membrane protein containing two transmembrane segments with its carboxy-terminal catalytic domain residing in the periplasmic space. Recently, the x-ray crystal structure of signal peptidase-inhibitor complex showed that Asp 280, a highly conserved consensus sequence of E. coli leader peptidase is the closest charged residue in the vicinity of two catalytic dyad, Ser 90 and Lys 145, and it is likely held in place by a salt bridge to Arg 282. Possible roles of Asp 280 and Arg 282 in the structure-catalytic function relationship were investigated by the site-directed mutagenesis of Asp 280 substituted with alanine, glutamic acid, glycine, or asparagine and of Arg 282 with methionine. All of mutants purified with nickel affinity chromatography were inactive using in vitro assay. It is surprising to find complete lose of activity by an extension of one carbon units in the mutant where Asp 280 is substituted with glutamic acid. These results suggest that Asp 280 and Arg 282 are in a sequence which constitutes catalytic crevice of leader peptidase and are essential for maintaining the conformation of catalytic pocket.

Aspartic Acid↗
PubMed1996

Cryoablation of unresectable malignant liver tumors.

BACKGROUND: Unresectable malignant liver tumors, particularly metastases of gastrointestinal origin, are rapidly lethal in a vast majority of patients, regardless of treatment. PATIENTS AND METHODS: We evaluated 58 patients by laparoscopy and/or laparotomy. Thirty-nine were treated with cryoablation of liver tumors using a liquid-nitrogen cryoprobe delivering a tumoricidal temperature of -196 degrees C with intraoperative ultrasound monitoring. Histologic evaluation showed that 25 patients had colorectal metastases, 3 had gastric tumors, 4 hepatocellular carcinomas, 6 carcinoids, and 1 gastrinoma. RESULTS: All patients who received complete cryoablation are alive with a mean follow-up of 14 months. Five whose treatment could not be completed died between 3 and 9 months postoperatively. Thirteen patients (28%) have recurrent disease and 20 (51%) have no evidence of disease. There were no operative mortalities. Postoperative transient elevation of liver function tests and thrombocytopenia were noted. All patients received postoperative chemotherapy. CONCLUSION: Cryoablation is an active and safe treatment for advanced liver malignancies.

Adult↗