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Biomedical subjects

S T Park

Publications and source records attributed to S T Park.

16 recordsLinked to original sources
PubMed1999

Growth inhibition and apoptosis due to restoration of E2A activity in T cell acute lymphoblastic leukemia cells.

Two models have been proposed for the molecular mechanism by which the Tal1 oncogene causes T cell acute lymphoblastic leukemia (T-ALL). The activation model suggests that Tal1 as heterodimers with the E2A transcription factor activates the expression of oncogenes. The inhibition model postulates that Tal1 interferes with the tumor-suppressing function of E2A. In the Jurkat T cell line, originally derived from a patient with T-ALL, Tal1 is complexed with E2A proteins and the transcriptional activity of E2A is very low. When E2A activity was restored by expressing an E2A-Tal1 fusion protein, E-T/2, the Jurkat cells underwent growth arrest and subsequently apoptosis, thus supporting the inhibition model and suggesting that E2A loss may contribute to leukemic progression.

Apoptosis↗
PubMed1999

Effect of Korean folk medicine 'Chung-Dae-San' on mast cell-dependent anaphylactic reaction.

We investigated the effect of the herbal formulation 'Chung-Dae-San' (CDS) on anaphylactic reactions. CDS inhibited compound 48/80-induced anaphylactic shock 100% with the dose of 10(0) g/kg body weight (BW). When CDS was given as pretreatment at concentrations ranging from 10(-4) to 10(0) g/kg BW, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. We also investigated the effect of CDS on mast cell-dependent passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE antibody. CDS potently inhibited PCA when administered orally, topically, intraperitoneally or intradermally. However, it did not show inhibitory activity when administered intravenously. CDS dose-dependently inhibited the histamine release from the rat peritoneal mast cells (RPMC) by compound 48/80 and anti-DNP IgE. Moreover, the level of cAMP in RPMC, when CDS was added, significantly increased about 4-fold at 4 min compared with that of basal cells. These results indicate that CDS may possess strong antianaphylactic activity and also suggest the differential activity following administration routes may be caused by difference in bioavailability.

Anaphylaxis↗
PubMed1998

The Tal1 oncoprotein inhibits E47-mediated transcription. Mechanism of inhibition.

The Tal1 oncogene is a class II basic helix-loop-helix (bHLH) transcription factor, overexpressed in as much as 60% of T cell acute lymphoblastic leukemia cases. Like other class II bHLH proteins, Tal1 can heterodimerize with the class I bHLH proteins, such as E47, and bind to a DNA recognition sequence termed E box. Therefore, it is believed that the oncogenic capacity of Tal1 lies in its ability, as a heterodimer with E47, to activate aberrantly a set of "leukemogenic" genes in T cells. However, compared with E47 homodimers, Tal1/E47 heterodimers are very poor transactivators. Thus the effect of Tal1 is actually to inhibit E47 homodimer activity. Here we propose that the transforming properties of Tal1 are the result of its ability to inhibit E47 activity. We address the mechanism of Tal1 inhibition and demonstrate that Tal1/E47 heterodimers cannot activate transcription because their respective activation domains are incompatible. Furthermore, we present data showing that Tal1 can inhibit E47-mediated activation of the CIP1 gene. Finally, we demonstrate that Tal1 inhibits E47 activity in leukemic T cells.

Basic Helix-Loop-Helix Proteins↗
PubMed1998

Immunohistochemical study of 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase in the rat cardiovascular system.

The enzyme complex 3beta-hydroxysteroid dehydrogenase (3beta-HSD) is involved in the biosynthesis of all classes of active steroids. It is known that the enzymatic activity of 3beta-HSD is present not only in classical steroidogenic tissues, but also in many peripheral tissues including cardiac tissue. To determine whether 3beta-HSD is present in rat non-steroidogenic tissues, we examined cardiovascular tissues including the ventricle, atrium, aortic arch, abdominal aorta, and inferior vena cava by immunohistochemistry and Western blotting using polyclonal antibody raised against a synthetic peptide of human placental 3beta-HSD. By Western blotting, protein bands immunoreactive for anti-3beta-HSD were detected at molecular weights of 42 and 37 kDa in both the ventricle and atrium, whereas only a 37 kDa band was recognized in both the aortic arch and abdominal aorta. By immunohistochemistry, immunoreactivity for 3beta,-HSD was detected in both the ventricular and atrial cardiocytes, while immunostaining was also found, though faintly, in the smooth muscles of the aortic arch, abdominal aorta, and inferior vena cava. These results suggest that cardiocytes may synthesize the steroidogenic 3beta,-HSD enzyme.

Animals↗
PubMed1998

Parathyroid carcinoma: report of three cases and review of the literature.

Parathyroid carcinoma is a rare endocrine malignancy characterized by the exaggerated metabolic effects of the parathyroid glands. The preoperative differential diagnosis between parathyroid carcinoma and primary hyperparathyroidism is often difficult because many of the signs and symptoms are very similar. Intraoperative differentiation is obscured by the strict anatomic and histologic criteria required for diagnosis of parathyroid carcinoma. We have encountered three patients with parathyroid carcinoma during the last 10 years and managed them successfully. Two of them presented with recurrence of hypercalcemia, one 11 years after and the other 3 years after the primary operation for hyperparathyroidism; both patients were eventually diagnosed with parathyroid carcinoma. The third case was suspected as primary hyperparathyroidism preoperatively but confirmed as carcinoma subsequent to histologic examination.

Adult↗
PubMed1997

Stereotactic breast biopsy as an alternative to excisional biopsy.

The current widespread use of modern mammography has increased the detection of suspicious mammographic lesions, which has led to a greater number of diagnostic surgical biopsies. Most of these lesions referred for surgical biopsy have been benign. The reduction in the number of benign surgical biopsies can reduce medical costs and unnecessary invasive breast surgery. Stereotactic large-core needle biopsies in patients with suspicious mammographic lesions can preselect the breast lesions that need further evaluation with surgical excisional biopsy. Our results with stereotactic large-core needle biopsies support this alternative approach to the workup of suspicious mammographic lesions.

Adult↗
PubMed1997

Regulation of the expression of cyclin-dependent kinase inhibitor p21 by E2A and Id proteins.

The helix-loop-helix transcription factor E2A plays important roles not only in promoting cellular differentiation but also in suppressing cell growth. Id proteins, the inhibitors of E2A, have opposite effects on cell differentiation and growth. To understand the mechanisms by which E2A suppresses cell growth, we examined the role of E2A in regulating the expression of the cyclin-dependent kinase inhibitor p21CIP1/WAF1/SD11, which prevents cell cycle progression upon overexpression. By using transient-cotransfection assays of luciferase reporter constructs in HeLa cells, we have found that overexpression of E2A can transcriptionally activate the p21 gene. To identify the sequences that mediate this activation in the promoter of the p21 gene, we carried out mutational analyses. Out of the eight putative E2A-binding sequences (E1 to E8) in the promoter, the E1 to E3 sequences located close to the transcription start site are found to be essential. In addition, loss of the E boxes in the promoter also reduces p21 expression without cotransfection with E2A in HIT pancreatic cells, where the endogenous E2A-like activity is high. Furthermore, we have also shown that overexpression of E2A in 293T cells activates expression of the endogenous p21 gene at both the levels of mRNA and protein. In correlation with the finding that E47 overexpression leads to growth arrest in NIH 3T3 cells, we have shown that Id1 overexpression in NIH 3T3 cells accelerates cell growth and inhibits p21 expression. Taken together, these results provide insight into the mechanisms by which E2A and Id proteins control cell growth.

3T3 Cells↗
PubMed1997

Management of ductal carcinoma in situ of the breast--experiences from National Naval Medical Center during last 10 years.

Seventy-one ductal carcinoma in situ (DCIS) patients were reported to the tumor registry at the National Naval Medical Center between 1986 and 1995. This number represents 6.5% of all breast cancer patients. We did not include the patients with microinvasion or infiltrating ductal carcinoma with extensive DCIS in this study. After excluding 16 cases because of inaccessable clinical records, 55 cases of pure DCIS were analyzed. The mean age at presentation was 52.0 years (32 year-old to 74 year-old) and the most common clinical feature was an abnormal mammographic finding (40 cases, 73%). Family history of breast cancer was positive in 14 cases among the 39 cases with DCIS (35.9%) according to the medical records. Total mastectomy was the most common form of treatment for DCIS (19 cases, 34.5%) during this period, followed by modified radical mastectomy, lumpectomy only, lumpectomy with radiation therapy. Three hundred and two axillary lymph nodes were examined but revealed no nodal metastasis. Comedo type DCIS was the most common subtype (21 cases, 38.2%). There were no local recurrences or DCIS related deaths reported to the tumor registry during this period (mean follow-up interval of 51 months).

Adult↗
PubMed1996

Association of a novel GTP binding protein, DRG, with TAL oncogenic proteins.

TAL1 is a basic helix-loop-helix (bHLH) protein involved in hematopoietic development. In T cell acute lymphoblastic leukemic cells, TAL1 is aberrantly overexpressed and is thought to contribute to oncogenesis. To identify proteins that interact with TAL1 in mediating leukemogenesis, we used TAL1 as a bait in a two-hybrid interaction screen, and isolated a cDNA clone that encodes a unique GTP binding protein, DRG. The interaction between DRG and TAL1 was confirmed both in vitro and in vivo. DRG was also shown to bind in vitro to two TAL1-related proteins, TAL2 and Lyl1. Mutational analyses showed that the HLH domain of TAL1 was necessary and sufficient for its interaction with the C-terminus of DRG. Furthermore, while DRG and E47 compete to interact with TAL1, TAL1 binds to DRG and E47 in a mutually exclusive manner. In rat embryonic fibroblast transformation assays, DRG stimulated the cotransforming activity of c-myc and ras. Based on these results, DRG appears to be a potential target for TAL-like oncoproteins.

Amino Acid Sequence↗
PubMed1996

NMR functional imaging using a tailored RF gradient echo sequence: a true susceptibility measurement technique.

The tailored radio frequency gradient echo (TRFGE) technique that has been used in venography (Cho et al., Magn. Reson. Med. 28, 25-38, 1992; Ro, Cho, Magn. Reson. Med. 28, 237, 1992) is applied to functional imaging. The TRFGE technique has the advantage that it is sensitive to the field gradient created by the susceptibility effect, thereby enhancing only the signals from the regions with local field gradient. In addition, the method is insensitive to the in-flow effect, especially from the arterial blood. The latter further simplifies the functional MRI data analysis. The TRFGE sequence is, therefore, suitable for functional MR imaging for which true susceptibility effect measurements are of prime importance. To examine the TRFGE functional imaging systematically, experiments with various imaging parameters such as flip angle alpha, repetition time, and echo time were performed and the results were compared with the data obtained from the conventional gradient echo functional MR imaging. The experimental results shown were all obtained from human volunteers with a 2.0T whole body MRI system.

Arousal↗
PubMed1996

FK506-binding protein mutational analysis: defining the active-site residue contributions to catalysis and the stability of ligand complexes.

The 12 kDa FK506-binding protein FKBP12 is a cis-trans peptidyl-prolyl isomerase that binds the macrolides FK506 and rapamycin. We have examined the role of the binding pocket residues of FKBP12 in protein-ligand interactions by making conservative substitutions of 12 of these residues by site-directed mutagenesis. For each mutant FKBP12, we measured the affinity for FK506 and rapamycin and the catalytic efficiency in the cis-frans peptidyl-prolyl isomerase reaction. The mutation of Trp59 or Phe99 generates an FKBP12 with a significantly lower affinity for FK506 than wild-type protein. Tyr26 and Tyr82 mutants are enzymatically active, demonstrating that hydrogen bonding by these residues is not required for catalysis of the cis-trans peptidyl-prolyl isomerase reaction, although these mutations alter the substrate specificity of the enzyme. We conclude that hydrophobic interactions in the active site dominate in the stabilization of FKBP12 binding to macrolide ligands and to the twisted-amide peptidyl-prolyl substrate intermediate.

Amino Acid Isomerases↗
PubMed1996

Methylmercury-induced neurotoxicity in cerebral neuron culture is blocked by antioxidants and NMDA receptor antagonists.

The neurotoxic effects of methylmercury on cerebral neuron cultures derived from neonatal mouse were studied. Exposure of cerebral neurons to methylmercury chloride resulted in significant cell damage and death in a time-dependent manner in cerebral neuron cultures. The methylmercury neurotoxicity was blocked by oxygen radical scavengers such as glutathione, catalase, selenium, and cysteine. Antagonists of the N-methyl-D-aspartate (NMDA) receptor, including MK-801 (a non-competitive NMDA antagonist), D-2-amino-5-phosphonovaleric acid (APV) (a competitive NMDA antagonist), and 7-chlorokynurenic acid (an antagonist at the glycine site associated with the NMDA receptor), similarly blocked methylmercury-induced neurotoxicity in cerebral neuron cultures. These results indicate that both oxygen radicals and excitotixic amino acids are involved in the methylmercury-induced neurotoxicity of cerebral neuron cultures.

Animals↗
PubMed1992

PPIase catalysis by human FK506-binding protein proceeds through a conformational twist mechanism.

FK506-binding protein (FKBP) catalyzes the cis-trans isomerization of the peptidyl-prolyl amide bond (the PPIase reaction) and is the major intracellular receptor for the immunosuppressive drugs FK506 and rapamycin. One mechanism proposed for catalysis of the PPIase reaction requires attack of an enzyme nucleophile on the carbonyl carbon of the isomerized peptide bond. An alternative mechanism requires conformational distortion of the peptide bond with or without assistance by an enzyme hydrogen bond donor. We have determined the kinetic parameters of the human FKBP-catalyzed PPIase reaction. At 5 degrees C, the isomerization of Suc-Ala-Leu-Pro-Phe-pNA proceeds in 2.5% trifluorethanol with kcat = 600 s-1, Km = 0.5 mM and kcat/Km = 1.2 x 10(6) M-1s-1. The kcat/Km shows little pH dependence between 5 and 10. A normal secondary deuterium isotope effect is observed on both kcat and kcat/Km. To investigate dependence on enzyme nucleophiles and proton donors, we have replaced eight potential catalytic residues with alanine by site-directed mutagenesis. Each FKBP variant efficiently catalyzes the PPIase reaction. Taken together, these data support an unassisted conformational twist mechanism with rate enhancement due in part to desolvation of the peptide bond at the active site. Fluorescence quenching of the buried tryptophan 59 residue by peptide substrate suggests that isomerization occurs in a hydrophobic environment.

Amino Acid Isomerases↗
PubMed1985

Co-carcinogenic effects of several Korean foods on gastric cancer induced by N-methyl-N'-nitro-N-nitrosoguanidine in rats.

In study I, 48 ACI and Fisher inbred rats were given MNNG 100 micrograms/ml, with or without 1 per cent or 3 per cent red pepper diet; in study II, 164 Sprague-Dawley rats given MNNG 100 micrograms/ml, with or without 5 per cent or 10 per cent NaCl; in study III, 181 Wistar rats given MNNG 83 micrograms/ml with or without maejoo 10 gm per cent/diet; in study IV, 78 Wistar rats given MNNG 83 micrograms/ml with or without ginseng extract 150 micrograms/ml; in study V, 120 Wistar rats given MNNG 83 micrograms/ml with or without retinyl palmitate 150,000 IU/kg. Except for study II (28 weeks), all rats were fed the diets for 37 weeks and were examined at 38 weeks or 40 weeks. In study I, tumor incidence in rats fed a red pepper diet and MNNG solution were 57 per cent (ACI rats, 1 per cent red pepper) and 63 per cent (Fisher rats, 1 per cent or 3 per cent red pepper) which were higher than control group (44 per cent, 43 per cent); in study II, gastric cancer, 61.9 per cent (10 per cent NaCl-MNNG), 27.3 per cent (control); in study III, gastric cancer, 14.8 per cent (maejoo-MNNG), 24 per cent (control); in study IV, malignant tumor of gastroduodenum, 3.4 per cent (ginseng-MNNG), 32.1 per cent (control); in study V, forestomach papilloma, 10.7 per cent (retinoid-MNNG), 29.4 per cent (control), and cancer in duodenum and small intestine, 50.0 per cent (retinoid-MNNG), 17.6 per cent (control). Thus, gastric carcinogenesis was enhanced by red pepper and a high salt diet, was inhibited by a maejoo and ginseng diet and was not effected by vitamin A.

Animals↗
PubMedDate not supplied

Radiological prediction of the depth of invasion and histologic type in early gastric cancer.

In cases of early gastric cancer (EGC), the depth of tumor invasion and histologic type are important factors in its prognosis. To predict the depth of invasion and histologic type by a double-contrast barium study of the stomach, 304 consecutive patients with EGC were analyzed, comparing barium study with pathologic findings. We predicted the depth of invasion and histologic type according to the lesion size, surface pattern, and surrounding mucosal pattern. The depth of tumor invasion was correctly diagnosed in 65.3% (66 of 101) of cancers limited to the mucosal layer (m), and in 59.1% (110 of 186) of cancers which have invaded to the submucosal layer (sm). The histologic type was correctly predicted in 78.9% (56 of 71) of a differentiated adenocarcinoma, and 73.1% (57 of 78) of an undifferentiated adenocarcinoma. Prediction of the depth of tumor invasion and histologic type was promising and showed good correlation to the pathologic findings.

Adenocarcinoma↗