PubMed Health⌕ Search

Biomedical subjects

T D Kim

Publications and source records attributed to T D Kim.

At least 19 recordsLinked to original sources
PubMed2006

Inhibition of retinoic acid receptor signaling by Ski in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease with multiple different cytogenetic and molecular aberrations contributing to leukemic transformation. We compared gene expression profiles of 4608 genes using cDNA-arrays from 20 AML patients (nine with -7/del7q and 11 with normal karyotype) with 23 CD34+ preparations from healthy bone marrow donors. SKI, a nuclear oncogene, was highly up regulated. In a second set of 183 AML patients analyzed with real-time PCR, the highest expression level of SKI in AML with -7/del7q could be confirmed. As previously described, Ski associates with the retinoic acid receptor (RAR) complex and can repress transcription. We wanted to investigate the interference of Ski with RARalpha signaling in AML. Ski was co-immunoprecipitated and colocalized with RARalpha. We also found that overexpression of wild-type Ski inhibited the prodifferentiating effects of retinoic acid in U937 leukemia cells. Mutant Ski, lacking the N-CoR binding, was no more capable of repressing RARalpha signaling. The inhibition by wild-type Ski could partially be reverted by the histone deacetylase blocking agent valproic acid. In conclusion, Ski seems to be involved in the blocking of differentiation in AML via inhibition of RARalpha signaling.

Acute Disease↗
PubMed2004

Eight novel MICB alleles, including a null allele, identified in gastric MALT lymphoma patients.

MICA and MICB, as members of the major histocompatibility complex (MHC) class I-chain-related genes (MIC), encode stress-inducible glycoproteins that act as activating ligands for NKG2D and gammadelta T-cell receptor-bearing cells. We here describe the identification of eight novel MICB variants, including a null allele, which were identified in peripheral blood leukocytes of gastric MALT lymphoma patients. Only two of the novel alleles are characterized by point mutations, whereas the other variants display a recombination of known exonic MICB sequences that may be best explained by intragenic conversions. The novel MICB null allele is characterized by a Cytosin (C) deletion in a stretch of four Cs beginning from nucleotide 135 of exon 2 that leads to a premature stop codon (TGA) at codon 66.

Alleles↗
PubMed2003

Etiology and therapy of Helicobacter pylori-associated gastric lymphomas.

The WHO separates marginal zone B-cell lymphomas (MZBL) of nodal and extranodal type. Both arise from memory B cells of the marginal zone. Extranodal MZBL of the mucosa-associated lymphatic tissue (MALT) have characteristic features such as homing in epithelial tissue, lymphoepithelial destruction, and a very indolent clinical course. They arise in epithelial tissues normally devoid of lymphatic cells, where the lymphatic tissue was acquired after, for instance, a chronic infection. The best example here is infection of the stomach with Helicobacter pylori ( Hp). Besides the classical association with gastric MALT lymphomas, there have been reports in which an association between Hp and diffuse large B-cell lymphoma (DLBCL) has been observed as well. Consequently, cure of Hp infection resulted in remission induction not only in gastric MALT lymphomas, but also in some patients with very limited stages of DLBCL of the stomach. In addition to the association with Hp, progress has been made with regard to MALT lymphoma biology. Translocation t(1;14) involving the Bcl-10 gene, and translocation t(11;18) involving a novel gene called MLT1, both result in activation of the crucial transcription factor NF-kappaB. These genetic events seem specific in that they have been observed only in MALT lymphomas. Once present, at least the more frequently observed translocation t(11;18) renders cells resistant to cure of Hp infection. Another clinically important question is that in many patients in complete remission after cure of Hp infection, detection of minimal residual disease is positive. Whether these cells are normal memory B cells (with the identical B-cell rearrangement as the original lymphoma clone), or dormant lymphoma cells, is unclear at present. In patients not responding to cure of Hp infection, several treatment options are discussed. MALT lymphomas have opened up a new discussion of lymphoma biology and have thus been called a model disease.

Chromosomes, Human, Pair 1↗
PubMed2001

Structural basis of non-specific lipid binding in maize lipid-transfer protein complexes revealed by high-resolution X-ray crystallography.

Non-specific lipid-transfer proteins (nsLTPs) are involved in the movement of phospholipids, glycolipids, fatty acids, and steroids between membranes. Several structures of plant nsLTPs have been determined both by X-ray crystallography and nuclear magnetic resonance. However, the detailed structural basis of the non-specific binding of hydrophobic ligands by nsLTPs is still poorly understood. In order to gain a better understanding of the structural basis of the non-specific binding of hydrophobic ligands by nsLTPs and to investigate the plasticity of the fatty acid binding cavity in nsLTPs, seven high-resolution (between 1.3 A and 1.9 A) crystal structures have been determined. These depict the nsLTP from maize seedlings in complex with an array of fatty acids.A detailed comparison of the structures of maize nsLTP in complex with various ligands reveals a new binding mode in an nsLTP-oleate complex which has not been seen before. Furthermore, in the caprate complex, the ligand binds to the protein cavity in two orientations with equal occupancy. The volume of the hydrophobic cavity in the nsLTP from maize shows some variation depending on the size of the bound ligands. The structural plasticity of the ligand binding cavity and the predominant involvement of non-specific van der Waals interactions with the hydrophobic tail of the ligands provide a structural explanation for the non-specificity of maize nsLTP. The hydrophobic cavity accommodates various ligands from C10 to C18. The C18:1 ricinoleate with its hydroxyl group hydrogen bonding to Ala68 possibly mimics cutin monomer binding which is of biological importance. Some of the myristate binding sites in human serum albumin resemble the maize nsLTP, implying the importance of a helical bundle in accommodating the non-specific binding of fatty acids.

Binding Sites↗
PubMed2001

Analysis of Fc gammaRIII and IgG Fc polymorphism reveals functional and evolutionary implications of protein-protein interaction.

Fc gamma receptor III (Fc gammaRIII), a low-affinity receptor for the Fc portion of immunoglobulin G (IgG Fc), targets antigen-antibody complexes in a variety of effector cells of the immune system. We have investigated Fc gammaRIII and IgG Fc polymorphism and made comparative analysis of the functional and evolutionary implications of the interaction between these two molecules. Sequence analysis and comparison of the three-dimensional structure suggest that the C-terminal Ig domain of Fc gammaRIII is associated with the binding of IgG. The polymorphic residues of Fc gammaRIII are mainly located in the region of the C-terminal Ig domain that might be involved in IgG binding. Therefore, polymorphism and functional binding affinity seems to be related to each other as has been increasingly implicated in clinical observations. IgG Fcs, the natural ligand of Fc gammaRs, also exhibit significant polymorphism. Three regions have been identified where polymorphism frequently occurs: the putative FcR binding site, the linker region, and the intermolecular domain-domain interface of the second Ig domain. The putative Fc gammaR binding sites where polymorphic, and isotype-specific residues cluster are consistent with the regions that have been identified by mutagenesis and molecular modeling studies. The polymorphic residues of IgG Fc were mainly located in the molecular surface, which could be used in the recognition of other binding molecules. These observations suggest that polymorphic and isotype-specific residues in IgG Fc are closely related to their function and protein-protein interaction. Therefore, the colocalization of the polymorphic residues of Fc gammaRIII and IgG Fcs at their docking sites implies that the polymorphic residues would affect the IgG-Fc gammaRIII binding interactions to optimize their signaling through evolution.

Amino Acid Sequence↗
PubMed2001

Pharmacological characterization of adenosine receptors in PGT-beta mouse pineal gland tumour cells.

1. The adenosine receptor in mouse pinealocytes was identified and characterized using pharmacological and physiological approaches. 2. Expression of the two adenosine receptor subtypes A2B and A3 was detected in mouse pineal glands and PGT-beta cells by polymerase chain reaction and nucleotide sequencing. 3. Adenosine and 5'-N-ethylcarboxamidoadenosine (NECA) evoked cyclic AMP generation but the A2)-selective agonist 2-(4-(2-carboxyethyl)phenylethylamino)adenosine-5'-N-ethylcarboxamideadenosine (CGS 21680) and the A1-specific agonists R-N(6)-(2-phenylisopropyl)adenosine (R-PIA) and N(6)-cyclopentyladenosine (CPA) had little effect on intracellular cyclic AMP levels. The A2B receptor selective antagonists alloxazine and enprofylline completely blocked NECA-mediated cyclic AMP accumulation. 4. Treatment of cells with the A3-selective agonist N(6)-(3-iodobenzyl)-5'-(N-methylcarbamoyl)adenosine (IB-MECA) inhibited the elevation of the cyclic AMP level induced by NECA or isoproterenol in a concentration-dependent manner with maximal inhibition of 40 - 50%. These responses were blocked by the specific A3 adenosine receptor antagonist MRS 1191. Pretreatment of the cells with pertussis toxin attenuated the IB-MECA-induced responses, suggesting that this effect occurred via the pertussis toxin-sensitive inhibitory G proteins. 5. IB-MECA also caused a concentration-dependent elevation in [Ca(2+)]i and IP3 content. Both the responses induced by IB-MECA were attenuated by treatment with U73122 or phorbol 12-myristate 13-acetate. 6. These data suggest the presence of both A2B and A3 adenosine receptors in mouse pineal tumour cells and that the A2B receptor is positively coupled to adenylyl cyclase whereas the A3 receptor is negatively coupled to adenylyl cyclase and also coupled to phospholipase C.

4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone↗
PubMed2000

Thermal behavior of proteins: heat-resistant proteins and their heat-induced secondary structural changes.

Most proteins are denatured by heat treatment, and the process is usually irreversible. However, some proteins, such as hyperthermophilic proteins are known to be stable even at the boiling temperature of water. We here describe a systematic investigation of thermal behavior of proteins by purifying and characterizing some heat-resistant proteins (HRPs) that are not aggregated upon heat treatment. Although most proteins were precipitated by boiling in a water bath, about 20 and 70 wt % of total proteins appeared to be heat-resistant in Jurkat T-cell lysates and human serum, respectively. We identified major HRPs from Jurkat T-cells and human serum by N-terminal amino acid sequencing and Western blot analysis. HRPs of 20 and 45 kDa (HRP20 and HRP45) were identified as alpha-synuclein and calreticulin, respectively, and HRPs of 60, 27, and 16 kDa (HRP60, HRP27, and HRP16) were identified as human serum fetuin, apolipoprotein A-I, and transthyretin, respectively. By a systematic investigation of the effect of heat on the secondary structure of the purified HRPs by circular dichroic spectroscopy, we observed four major types of thermal behavior, suggesting that the proteins could protect themselves through these pathways. Although our analysis is restricted to protein secondary structural changes, our data indicate that heat resistance of protein can be achieved in several different ways depending on the thermodynamic stability of native (N), unfolded (U), denatured (D), and intermediate (I) states.

Amino Acid Sequence↗
PubMed2000

Differential regulation of P2Y(11) receptor-mediated signalling to phospholipase C and adenylyl cyclase by protein kinase C in HL-60 promyelocytes.

The regulatory mode of the P2Y(11) purinoceptor-mediated signalling cascades towards phospholipase C and adenylyl cyclase was studied in HL-60 promyelocytes. Treatment with the potent P2Y(11) receptor activator dATP evoked an elevated intracellular Ca(2+) concentration ([Ca(2+)](i)) and inositol 1,4,5-trisphosphate (IP(3)) production that was sustained for longer than 30 min. However, the dATP-induced responses were significantly inhibited by the activation of protein kinase C after a short exposure to phorbol 12-myristate 13-acetate (PMA). dATP also potently stimulated cyclic AMP production with half maximum effect seen at 23+/-7 microM dATP. In addition, a 5-min pretreatment with PMA enhanced the dATP-stimulated cyclic AMP accumulation. PMA potentiated the cyclic AMP production when adenylyl cyclase was activated directly by forskolin or indirectly by G protein activation after cholera toxin treatment. dATP also enhanced the forskolin-mediated cyclic AMP generation. Treatment of the cells with 10 microM U-73122, which almost completely blocked the dATP-stimulated IP(3) production and [Ca(2+)](i) rise, had no effect on cyclic AMP accumulation, while 10 microM 9-(tetrahydro-2-furyl)adenine (SQ 22536), which inhibited the adenylyl cyclase activation, did not effect the dATP-stimulated phosphoinositide turnover. Taken together, the results indicate that P2Y(11) receptor-mediated activation of phospholipase C and adenylyl cyclase occurs through independent pathways and is differentially regulated by protein kinase C in HL-60 cells.

Adenylyl Cyclases↗
PubMed2000

Structural changes in alpha-synuclein affect its chaperone-like activity in vitro.

Alpha-synuclein, a major constituent of Lewy bodies (LBs) in Parkinson's disease (PD), has been implicated to play a critical role in synaptic events, such as neuronal plasticity during development, learning, and degeneration under pathological conditions, although the physiological function of alpha-synuclein has not yet been established. We here present biochemical evidence that recombinant alpha-synuclein has a chaperone-like function against thermal and chemical stress in vitro. In our experiments, alpha-synuclein protected glutathione S-transferase (GST) and aldolase from heat-induced precipitation, and alpha-lactalbumin and bovine serum albumin from dithiothreitol (DTT)-induced precipitation like other molecular chaperones. Moreover, preheating of alpha-synuclein, which is believed to reorganize the molecular surface of alpha-synuclein, increased the chaperone-like activity. Interestingly, in organic solvents, which promotes the formation of secondary structure, alpha-synuclein aggregated more easily than in its native condition, which eventually might abrogate the chaperone-like function of the protein. In addition, alpha-synuclein was also rapidly and significantly precipitated by heat in the presence of Zn2+ in vitro, whereas it was not affected by the presence of Ca2+ or Mg2+. Circular dichroism spectra confirmed that alpha-synuclein underwent conformational change in the presence of Zn2+. Taken together, our data suggest that alpha-synuclein could act as a molecular chaperone, and that the conformational change of the alpha-synuclein could explain the aggregation kinetics of alpha-synuclein, which may be related to the abolishment of the chaperonic-like activity.

Albumins↗
PubMed1997

Correlating Ca2+ responses and secretion in individual RBL-2H3 mucosal mast cells.

The role of Ca2+ in stimulus-response coupling in nonexcitable cells is still not well understood. The Ca2+ responses of individual cells are extremely diverse, often displaying marked oscillations, and almost nothing is known about the specific features of these Ca2+ signals that are important for the functional response of a cell. Using the RBL-2H3 mucosal mast cell as a model, we have studied the temporal relationship between changes in intracellular Ca2+ and serotonin secretion at the single-cell level using simultaneous indo-1 photometry and constant potential amperometry. Secretion in response to antigen never occurs until intracellular Ca2+ is elevated, nor is it seen during the first few oscillations in Ca2+. Exocytotic events tend to be clustered around the peaks of oscillations, but excellent secretion is also seen in cells with sustained elevations in Ca2+. Ca2+ release from stores in the absence of influx fails to elicit secretion. If refilling and continued release of Ca2+ from stores is prevented with thapsigargin, Ca2+ influx can still trigger secretion, suggesting that store-associated microdomains of Ca2+ are not required for exocytosis. Our findings demonstrate the importance of an amplitude-encoded Ca2+ signal and Ca2+ influx for stimulus-secretion coupling in these nonexcitable cells.

Animals↗
PubMed1994

Identification and partial purification of an endogenous inhibitor of soluble guanylyl cyclase from bovine lung.

An endogenous inhibitor of soluble guanylyl cyclase from bovine lung has been partially purified by use of anion exchange, hydrophobic interaction, and gel filtration chromatography. This inhibitor is a protein with a molecular weight of about 149,000 which was estimated from its elution behavior, versus that of a series of standards, on a Sephacryl S-300-HR column. Its activity was measured by comparison of the level of cGMP production from soluble guanylyl cyclase in the presence and absence of the inhibitor protein. Soluble guanylyl cyclase is inhibited by this protein when either Mg2+ or Mn2+ is used as a cofactor. The insensitivity of its inhibitory activity to both isobutylmethylxanthine and the presence of cGMP demonstrates that this new protein is not a phosphodiesterase. This new protein inhibits both activated and unactivated soluble guanylyl cyclase. Because the inhibition was found to be noncompetitive with respect to the substrate, GTP, it appears that this inhibitor may be an allosteric regulator of soluble guanylyl cyclase.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1992

Activation of voltage-dependent calcium channels of mammalian sperm is required for zona pellucida-induced acrosomal exocytosis.

Previous work indicates that antagonists of the L-type voltage-dependent Ca2+ channel (VDCC) prevent the Ca(i) increase in mammalian sperm that is promoted by incubation in alkaline, K(+)-based media. Here, were provide additional evidence that sperm possess VDCC and show that their activation is required for the Ca2+ entry that mediates acrosomal exocytosis in both the presence and the absence of egg agonists. Specifically, we report that: (1) Sperm membrane potential changes, Ca(i) elevation, and acrosomal exocytosis have similar K+ dose dependencies, consistent with a characteristic requirement of a large depolarization for activation of the sperm VDCC; (2) High affinity binding sites (Kd approximately 0.35 +/- 0.03 and 0.45 +/- 0.06 nM; Bmax = 16.0 +/- 1.4 and 5.8 +/- 0.8 fmole/mg protein) for the VDCC antagonist, PN200-110, respectively, are present in membrane preparations from sperm of the ram and bull; (3) PN200-110 and the other VDCC antagonists nitrendipine, nisoldipine, verapamil, diltiazem, Ni2+, or Co2+ inhibit (IC50 = 0.1, 0.4, 0.6, 0.8, 1.0, 60, and 110 microM, respectively) the acrosomal exocytosis produced by combined elevation of pH0 and membrane depolarization; (4) Exocytosis induced by the ZP3 agonist of the mammalian egg also is inhibited by VDCC antagonists with similar dose dependencies; (5) Depolarizing treatments that presumably activate the sperm VDCC bypass the blockade of ZP3-induced exocytosis imposed by pertussis toxin. These results indicate that activation of the sperm VDCC is sufficient to induce sperm acrosomal exocytosis and that VDCC activation is necessary in the ZP3 signal transduction pathway. They also indicate that the presumed G-protein targets of pertussis toxin probably produce a required but indirect activation of the putative sperm VDCC. Possible intervening events include alteration of the voltage sensitivity of the VDCC, membrane depolarization, or both. We suggest that the depolarization-induced acrosome reaction may provide a useful system to investigate subsequent events in the exocytotic process.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Metabolism of liposome-encapsulated heparin.

In order to elucidate the metabolism of liposome encapsulated heparin (LIPO-HEP), LIPO-HEP containing 3H-heparin (3H-HEP) and/or 14C-phosphatidylcholine (14C-PC) was intravenously administered into rats and the radioactivity as well as the biological activity in plasma and certain organs was investigated. The amount of 3H-radioactivity in plasma was significantly higher in rats receiving LIPO-HEP than in those receiving untreated heparin. The amount of 14C-radioactivity in plasma of rats receiving LIPO-HEP, however, was not proportional to the amount of 3H-radioactivity in the same rats, indicating the dissociation of liposome and heparin in plasma. Incorporation of 3H-radioactivity into various organs examined, i.e., liver, spleen, lung, was significantly higher in rats receiving LIPO-HEP than in those receiving untreated heparin, e.g. 4.7 and 11.8 times higher in the liver and the spleen, respectively at 150 min after the injection. Thereby, in contrast to the untreated heparin, LIPO-HEP was selectively incorporated into the reticuloendothelial system (RES) and it may be suggested that prolonged biological activity in LIPO-HEP is due to a gradual release of heparin from the liposomes entrapped in RES, and that it is not due to prolonged circulation in blood.

Animals↗
PubMed1988

[Lympho- and hemodynamic reactions during the contraction of the skeletal musculature of the hindlimb in dogs].

Alterations in arterial pressure (AP) values, blood and perfusate flow from the thoracic duct, lymph and perfusate flow from the femoral lymphatic vessel during femoral muscle contractions induced by electrical stimulation applied for 1.5 and 3.0 min, were studied: the AP values were decreased by 10-15 mm Hg, the blood flow increased to 293.5 +/- 21.7%, the lymph flow increased to 525.4 +/- 29.8%, the perfusate flow from the thoracic duct raised to 81.8 +/- 4.7%, and the perfusate flow from the lymphatic vessel increased to 650.0 +/- 28.2%. The increase in the lymph flow during 1.5 min stimulation seems to be due to squeezing of lymph out of the lymphatic channel, whereas during 3 min stimulation it was due to enhanced lymph production.

Animals↗
PubMed1986

Studies on liposome-encapsulated heparin.

In order to prolong the anticoagulant activity of heparin in vivo, attempts were made to encapsulate heparin into liposomes. Liposome-encapsulated heparin (lipo-heparin) prepared was large multilamellar vesicles (0.5-4.0 micron in diameter). The activity of lipo-heparin was 1.6-5.2 X 10(3) U/g lipid with recovery rate ranged between 0.4 to 1.3% and stable in saline at 4 degrees C for at least two weeks. When intravenously administered into rats, the anticoagulant activity of lipo-heparin was significantly prolonged (approximately three times), as compared with that of untreated heparin. Furthermore, the activity of lipo-heparin could be neutralized by protamine sulfate. From these observations, it was concluded that liposome-encapsulation of heparin results in the prolonged anticoagulant effect in vivo and lipo-heparin may be applicable for clinical use, after further studies on side effects of liposomes are completed.

Animals↗
PubMed1986

Imaging platelet deposition on Dacron bifurcation grafts in man: quantification by a dual-tracer method using 111In-labeled platelets and 99mTc-labeled human serum albumin.

A dual tracer technique using 111In-labeled platelets and 99mTc-labeled human serum albumin was applied to evaluate the thrombogenicity of Dacron bifurcation arterial grafts. The level of platelet accumulation over the whole of the graft was estimated from the ratio of 111In-platelet radioactivity deposited on the vascular wall to these radioactivity circulating in the blood pool, i.e., the platelet-accumulation index (PAI). Furthermore, the PAI value was calculated for each pixel in digitized images and the PAI distribution image (PAI image) was reconstructed. Eighteen patients with DeBakey knitted Dacron bifurcation grafts and 11 normal volunteers were studied. Of the 18 patients, 11 had no graft occlusion (group I) and the remaining 7 (group II) had occlusion. The mean PAI value (+/- SD) over the whole of the graft in group I was 32.6% +/- 33.7% as compared to -8.8% +/- 4.5% in the control group (P less than 0.01). In group I, the PAI value over the entire graft decreased with the age of the graft (r = -0.763; P less than 0.01). In contrast, in group II, platelet accumulation did not diminish with time and persisted beyond the time of which platelet accumulation was no longer found in group I. Moreover, analysis of the PAI images revealed enhanced platelet accumulation on the proximal part of the graft to be more frequent in group II than in group I (6/7 vs 0/11; chi 2c = 10.55; P less than 0.005). The method used for platelet imaging in the present study may be useful in the study of platelet reactions on Dacron arterial prostheses.

Aged↗