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Biomedical subjects

Y Bae

Publications and source records attributed to Y Bae.

18 recordsLinked to original sources
PubMed2001

Differential regulation of cell cycle-related proteins by CD95 engagement in thymocytes and T cell leukemic cell line, Jurkat.

CD95 engagement results in apoptosis in thymocytes and in the Jurkat human leukemic T cell line. Biochemical analyses in CD95-engaged thymocytes and Jurkat cells revealed dysregulation of the G1/S cell cycle control point. Cyclin E was upregulated upon CD95 engagement, suggesting G1-to-S progression, but there was no upregulation of cyclin A. Instead, cyclin E was degraded by caspases. In addition, c-myc that normally acts on S-phase progression through the activation of cdc25A appeared to be involved in the inhibition of S-phase progression after CD95 ligation. This implies that G1-->S progression and apoptosis are intimately linked in cells undergoing CD95 ligation. Furthermore, our data suggest that CD95-induced apoptosis occurs at the G1/S phase transition. We therefore suggest that CD95 engagement not only triggers death signals but also affects the G1/S checkpoint.

Amino Acid Chloromethyl Ketones↗
PubMed2001

Characterization of microsatellite markers adjacent to AP-4 on chromosome 16p13.3.

The 1400 kb genomic sequence between the markers D16S406 and D16S423 on chromosome 16p13.3 has been recently sequenced and the interval contains a transcription factor, AP-4, that was identified as a ligand for immunoglobulin-kappa promoter E-box elements,(1)suggesting that AP-4 may be related to immunodeficiency diseases. In addition, chromosome 16p13.3 includes a number of genes including the PKD1 gene,(2,3)the autosomal dominant polycystic kidney disease (ADPKD) gene. ADPKD is characterized by progressive development and enlargement of renal cysts.(4)The size and genomic complexity of the PKD1 gene makes it impractical to detect mutations for prenatal diagnosis. Therefore, pedigree-based linkage analysis remains useful for diagnosis of ADPKD. To increase the number of polymorphic markers in the region around AP-4 gene, we performed database searches of 1400 kb of genomic sequence (from contig NT000677 to NT001573: http://www.ncbi.gov/genome/seq.cgi) across the 16p13.3. A number of dinucleotide or tetranucleotide repeats were found, and 20 microsatellites that contain more than 15 contiguous repeats were chosen for further investigation.

Adult↗
PubMed2001

T-T interaction during thymic selection.

During thymic development, immature thymocytes are selected through the interaction with self peptides loaded on self MHC molecules. Although there is a great deal of debates on how specifically thymocytes recognize self peptides during thymic selection, recent data suggest an important role of peptide diversity in selecting an adequate T-cell repertoire in the thymus. The findings that human T-cells, unlike mouse T-cells, express MHC class II molecules on their surfaces and can play as antigen presenting cells suggesting possible peripheral T-T interaction network has not been intensively studied so far. However, the facts that human thymocytes have surface expression of MHC class II molecules and thymocytes can be selected by thymocytes in in vitro re-aggregation culture system led us to propose a novel hypothesis - "T-T interaction during thymic selection". Our proposition is that peripheral T-T interaction through TCR-derived peptides might reflect the selection process in the thymus and that T-T interaction also plays an important role in thymic selection. This review deals with our thymic T-T interaction hypothesis and its implications on human T-cell development.

Animals↗
PubMed2000

Costimulatory effect of Fas in mouse T lymphocytes.

To induce proper immune responses, T lymphocytes require two types of stimuli, antigen-specific and costimulatory signals. Among costimulatory molecules, CD28-engagement promotes the survival and proliferation of both naive and memory T cells. In addition, it is now believed that Fas may play a role in T cell activation in the human system. It is, however, controversial whether Fas can act as a costimulatory signal in the murine system. Thus, we investigated fundamental differences in the capacity to induce proliferation of T cells between Fas and CD28 in mice. Fas-mediated T cell proliferation was observed only with a full mitogenic dose of anti-CD3 antibodies, whereas CD28 engagement was able to enhance T cell proliferation in the presence of a suboptimal level of anti-CD3 antibody. Furthermore, Fas-engaged T cells showed faster response in the upregulation of CD25 and CD69 expression than CD28-engaged ones. Here, we report that Fas might play a role in mature T cell activation in the mouse system through a different mechanism from that in CD28 costimulation.

Animals↗
PubMed2000

CD95/Fas signaling in T lymphocytes induces the cell cycle control protein p21cip-1/WAF-1, which promotes apoptosis.

Ligation of CD95 on T lymphocytes resulted in the up-regulation of a cell cycle control protein, p21cip-1/WAF-1, an inhibitor of cyclin-dependent kinases. This up-regulation was completely blocked by the cysteine protease inhibitor Z-VAD-fmk (benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone), whereas DEVD-CHO (succinyl-Asp-Glu-Val-Asp-aldehyde), a caspase 3 inhibitor, had no effect. In Faslpr-cg mice, a point mutation in the death domain of CD95 results in failure to recruit FADD (Fas-associated death domain), and in the present study this mutation prevented both CD95-mediated apoptosis and p21cip-1/WAF-1 induction. During apoptotic cell death due to irradiation, p21cip-1/WAF-1 is up-regulated by a p53-dependent pathway that responds to DNA damage. However, CD95-induced up-regulation of p21cip-1/WAF-1 in T cells was p53-independent. T cells deficient in p21cip-1/WAF-1 were less susceptible to CD95-induced apoptosis. We conclude that in T cells, ligation of CD95 and activation of caspases cause the induction of p21cip-1/WAF-1, which acts to promote cell death.

3T3 Cells↗
PubMed2000

Expression of the zinc finger gene fez-like in zebrafish forebrain.

Anterior-posterior (A-P) patterning in the neuroectoderm is established during gastrulation in zebrafish and amphibians. We isolated a novel zinc-finger gene fez-like (fezl) from zebrafish, which displays sequence similarities to Xenopus Fez. The fezl transcripts were detected in the anterior edge of neuroectoderm, the prospective dorsal forebrain, from the late gastrula (80% epiboly stage) to the mid-segmentation period. fezl was also expressed in the ventral forebrain overlying the prechordal plate at these stages. The expression of fezl was enhanced in embryos expressing the Wnt inhibitor Dkk1 and reduced in embryos expressing Wnt8b. The expression in the ventral forebrain was eliminated in the one-eyed pinhead mutant and the antivin RNA-injected embryos, which lack the prechordal plate. Radiation hybrid mapping revealed that the fezl gene is localized to linkage group 11.

Amino Acid Sequence↗
PubMed2000

Successful management of intractable coronary spasm with a coronary stent.

Although the long-term survival of patients suffering from coronary spasm is usually excellent, serious complications can develop, such as disabling pain, myocardial infarction, ventricular tachyarrhythmias, atrioventricular block and sudden cardiac death. A 40-year-old man who had intractable chest pain from coronary artery spasm suffered ventricular fibrillation and an acute anterior myocardial infarction upon first admission. The patient underwent a coronary angiogram, which revealed a spontaneous focal spasm at the proximal left anterior descending coronary artery (LAD). He was treated by the combination of nitrate and calcium channel blocker, but continued to complain of severe chest pain despite intensive medical therapy and he had to be treated in the emergency room 5 times during an 8-month follow-up period. An ergonovine coronary angiogram was performed and an intracoronary ultrasound examination, which revealed a focal spasm at the same site of the proximal LAD with a small amount of localized eccentric atheromatous plaque. A coronary artery stent was placed in the proximal LAD and his symptoms resolved. A follow-up coronary angiogram was performed 3 years after stenting and the stent remained patent without any in-stent restenosis or spasm.

Adult↗
PubMed2000

A case of myasthenia gravis proven by ultrastructural study.

Although light microscopic features of muscle are not pathognomonic in most cases of myasthenia gravis (MG), careful examination of neuromuscular junction by electron microscopy (EM) can reveal important clues for this disease. We report here a case of MG confirmed by EM study to emphasize that tissue diagnosis is still the best adjuvant to confirm the diagnosis. An 18-year-old female visited our hospital complaining of progressive muscle weakness for 3 years. She had difficulty in running, going upstairs and doing routine activities. Symptoms were aggravated with continuous work and resolved after rest. She had weakness of bilateral masseter and facial muscles and proximal portions of extremities without definite diurnal variation. Electromyography showed myopathic changes in proximal muscles of extremities. MG was considered but tensilon test was equivocal. Repetitive nerve stimulation tests revealed 20-30 percent decrease in responses to low and high rate stimulation. Muscle biopsy revealed selective type 2 atrophy. Ultrastructurally, abnormalities of neuromuscular junctions, i.e., wide primary synaptic cleft, and wide and shallow secondary synaptic clefts with mild myopathic features were present. These findings were pathognomonic for MG. Later, her symptoms were improved completely 3 months after thymectomy. The histologic finding of thymus was follicular hyperplasia.

Adolescent↗
PubMed1999

Cultures of astrocytes and microglia express interleukin 18.

Interleukin 18 (IL-18 or interferon-gamma inducing factor) is a recently discovered pro-inflammatory cytokine and powerful stimulator of the cell-mediated immune response. IL-18 is produced by several sources including monocytes/macrophages, keratinocytes and the zona reticularis and zona fasciculata of the adrenal cortex. IL-18 occurs in brain but its cellular source in the CNS has never been investigated. The presence of IL-18 and its response to stimulation in the brain was tested with primary cultures of microglia, astrocytes and hippocampal neurons. IL-18 mRNA was present in astrocytes and microglia, but not in neurons. The endotoxin lipopolysaccharide (LPS) did not affect IL-18 in astrocytes, but LPS robustly increased IL-18 mRNA in microglia. IL-18 protein was constitutively expressed in astrocytes and induced in microglia by LPS. The levels of interleukin-1beta converting enzyme (ICE), an activating enzyme, and caspase 3 (CPP32), an inactivating enzyme, were assessed to investigate the presence of the appropriate processing enzymes in the cultured cells. ICE was present at constitutive levels in microglia and astrocytes suggesting that these cell types may produce and secrete matured IL-18. Active forms of CPP32 were not detectable in either cell type indicating the absence of a degradative pathway of IL-18. The present results demonstrate that microglia and astrocytes are sources of brain IL-18 and add a new member to the family of cytokines produced in the brain.

Animals↗
PubMed1999

Blockade of tetrahydrobiopterin synthesis protects neurons after transient forebrain ischemia in rat: a novel role for the cofactor.

The generation of nitric oxide (NO) aggravates neuronal injury. (6R)-5,6,7,8-Tetrahydro-L-biopterin (BH4) is an essential cofactor in the synthesis of NO by nitric oxide synthase (NOS). We attempted to attenuate neuron degeneration by blocking the synthesis of the cofactor BH4 using N-acetyl-3-O-methyldopamine (NAMDA). In vitro data demonstrate that NAMDA inhibited GTP cyclohydrolase I, the rate-limiting enzyme for BH4 biosynthesis, and reduced nitrite accumulation, an oxidative metabolite of NO, without directly inhibiting NOS activity. Animals exposed to transient forebrain ischemia and treated with NAMDA demonstrated marked reductions in ischemia-induced BH4 levels, NADPH-diaphorase activity, and caspase-3 gene expression in the CA1 hippocampus. Moreover, delayed neuronal injury in the CA1 hippocampal region was significantly attenuated by NAMDA. For the first time, these data demonstrate that a cofactor, BH4, plays a significant role in the generation of ischemic neuronal death, and that blockade of BH4 biosynthesis may provide novel strategies for neuroprotection.

Animals↗
PubMed1998

Radiofrequency catheter ablation in familial paroxysmal supraventricular tachycardia due to accessory atrioventricular pathways.

Radiofrequency catheter ablation (RF-CA) has been widely used to cure paroxysmal supraventricular tachycardia (PSVT). However, its use has never been reported in familial PSVT caused by an accessory atrioventricular pathway (AP), which is known as one of the typical familial cardiovascular diseases. Two cases of using RF-CA for familial PSVT due to APs are presented, in a brother and sister, supporting a potential genetic role in the developmental failure to lose the atrioventricular connection during fetal life. The sister, a 24-year-old woman, had intermittent episodes of palpitation accompanied by chest pain for 2 years. An electrophysiologic study (EPS) confirmed her clinical tachycardia was atrioventricular reentrant tachycardia (AVRT) due to a left lateral concealed AP, which was subsequently successfully ablated with RF-CA. The brother, a 22-year-old man, had a 5-year history of paroxysmal palpitation. A resting electrocardiogram showed a right bundle branch block and left axis deviation with a delta wave. During his EPS, AVRT was reproducibly induced and a manifest AP was localized and then ablated at the left posteroseptal site, resulting in disappearance of the delta wave. PSVT, however, recurred 1 month later and during a repeat EPS the tachycardia was proved to be AVRT due to a right anterior concealed AP. The right anterior AP was successfully ablated with RF-CA. Both patients remained asymptomatic for more than 3 years following the successful ablation procedures.

Adult↗
PubMed1998

A case of AV reentrant tachycardia due to a concealed accessory pathway with retrograde conduction manifested by isoproterenol.

Retrograde conduction of the concealed accessory pathway (AP) is a prerequisite for the induction of atrioventricular reentrant tachycardia (AVRT). In patients with AVRT due to a concealed AP, the absence of retrograde conduction of the AP in the baseline state has rarely been reported. We report a case of AVRT due to a concealed left lateral AP, in which the retrograde conduction was absent in the baseline state and manifested by isoproterenol infusion. A 61-year-old man had suffered from intermittent palpitation for 17 years. A narrow QRS complex tachycardia with a retrograde P wave in the ST segment was recorded in 24-h Holter monitoring. An electrophysiologic study was performed while he was in a nonsedated state. No ventriculoatrial conduction over either the normal atrioventricular conduction system or the AP was demonstrated in the baseline state. Isoproterenol was infused at a rate of 1.0 microg/min. Retrograde conduction over the AP became manifest and AVRT was induced. The AP was ablated with radiofrequency energy at the left free wall. After ablation of the AP, no tachycardia was induced. To the authors'best knowledge, only 1 other similar case has been reported in the literature.

Heart Conduction System↗
PubMed1997

Functional dissection of the Moloney murine leukemia virus envelope protein gp70.

The envelope protein of Moloney murine leukemia virus (Mo-MLV) is a complex glycoprotein that mediates receptor binding and entry via fusion with cell membranes. By using a series of substitution mutations and truncations in the Mo-MLV external envelope surface protein gp70, we have identified regions important for these processes. Firstly, truncations of gp70 revealed that the minimal continuous receptor-binding region is amino acids 9 to 230, in broad agreement with other studies. Secondly, within this region there are two key basic amino acids, Arg-83 and Arg-95, that are essential for receptor binding and may interact with a negatively charged residue(s) or with the pi electrons of the aromatic ring on a hydrophobic residue(s) in the basic amino acid transporter protein that is the Mo-MLV ecotropic receptor. Finally, we showed that outside the minimal receptor-binding region at amino acids 2 to 8, there is a region that is essential for postbinding fusion events.

3T3 Cells↗
PubMed1997

CNS innervation of the urinary bladder demonstrated by immunohistochemical study for c-fos and pseudorabies virus.

The aim of the present study is to verify the functional and anatomical neural pathways which innervate the urinary bladder in the central nervous system of the rat. To identify the functional neural pathway, the urinary bladder was stimulated by infusing formalin for 2 h. Then, brain and spinal cord were dissected out and immunohistochemistry was done by using anti-c-fos antibody. Many c-fos immunoreactive (IR) neurons were identified in the telencephalic cortical areas and in several brainstem nuclei, which are known mostly to be related with urinary bladder. In the spinal cord, a number of c-fos IR neurons were found in the lamina I, IIo, dorsal gray commissure, sacral parasympathetic nucleus. To identify the anatomical neural pathway of the urinary bladder, Pseudorabies virus (PRV) was injected into the wall of urinary bladder and was identified with anti-PRV by using immunohistochemistry. Most PRV labeled neurons were found where c-fos IR neurons were identified and few of them were also in the areas where c-fos IR neurons were not found, e.g., prefrontal cortex, agranular insular cortex, and subfornical organ. In the spinal cord, PRV labeled cells were found all over the gray matter. The present study presents morphological evidence demonstrating the supraspinal areas are related with the neural control of the urinary bladder and most functional neural pathway of the urinary bladder is well consistent with the anatomical neural pathway except in some telencephalic cortical areas.

Animals↗
PubMed1996

Head-up tilt test with isoproterenol provocation in syncope of unknown origin.

OBJECTIVES: Head-up tilt test (HUT) has been reported to be useful in the evaluation of syncope of unknown origin (SUO). However, the sensitivity of HUT with no pharmacologic provocation was relatively low and variable, ranging 32 approximately 70%. Therefore, several protocols of HUT with different degrees and durations of the tilt and modes of provocation were proposed. The purpose of this study was to determine the value of the multi-stage head-up tilt test with isoproterenol provocation (HUT-isp) in the evaluation of SUO and drug efficacy. METHODS: Sixty-seven patients presenting with SUO and 30 control subjects with no history of syncope underwent the HUT-isp. Blood pressure (BP) was measured every 2 min and whenever the patient complained of any symptom, and cardiac rhythm was continuously monitored. The HUT-isp consisted of 3 stages: first for 20 min with no provocation, second and third stages with infusion of isoproterenol for 10 min each at a rate of 2 micrograms/min and 5 micrograms/min, respectively. A positive HUT-isp was defined when syncope or presyncope was reproduced, accompanied by hypotension (< 80 mmHg) or bradycardia (< 40/min) or both, and positive responses were classified into vasodepressive, cardioinhibitory and mixed type. RESULTS: The HUT-isp was positive in 56 (83.6%) of 67 patients with SUO and 10 (33.3%) of 30 control subjects. The type of positive responses was vasodepressive in 41 (73.2%), cardioinhibitory in 4 (7.1%) and mixed in 11 (19.6%). The sensitivity of the HUT-isp in diagnosing vasovagal syncope was 83.6%, specificity 66.7% and positive predictive value 84.8%. Positive responses were developed most frequently in the 3rd stage: 76.8% in patients, 70% in controls. The effect of 3 drugs (carteolol, aminophylline and disopyramide) was evaluated in 27 patients with a repeat HUT-isp. Carteolol was effective in 12 (85.7%) of 14 patients, disopyramide in 7 (58. 3%) of 12 and aminophylline in 1 (14.3%) of 7. During the follow-up period of 175 +/- 212 days (26 approximately 623 days), none of the 20 patients with a negative repeat HUT-isp developed a recurrent syncope. CONCLUSION: The HUT-isp is thought safe and useful to evaluate syncope of unknown origin and to guide effective drug therapy.

Adult↗
PubMed1990

Role of brachytherapy in the management of pulmonary and mediastinal malignancies.

Brachytherapy, the permanent or temporary implantation of radioactive sources, has been performed in limited numbers of patients with lung cancer over the last 50 years. Because of renewed interest in this modality, we reviewed our experience with 103 patients treated over a 7-year period. The mean age of this group was 55.5 years (range, 1 to 84 years). Primary lung cancer accounted for 82 patients (79.6%); metastatic lesions to the lung, 13 (12.6%); and mediastinal malignancies, 8 (7.8%). Indications for brachytherapy included mediastinal and chest wall invasion in 42 patients (40.8%), unresectable tumors and mediastinal adenopathy in 30 (29.1%), medical contraindications to extensive pulmonary resection in 20 (19.4%), and irradiation of excised lymph node beds in 11 (10.7%). Seeds labeled with radioactive iodine 125 alone were used in 65 patients (63.1%), afterloading catheters containing iridium 192 sources in 25 (24.3%), and both in 13 (12.6%). There were no operative deaths. With a mean follow-up of 18.6 months, the mean and median survivals for the entire group were 17.3 and 14.0 months, respectively. The 1-year, 2-year, and 3-year survivals for the entire group were 67.9%, 38.7%, and 27.8%, respectively. In summary, brachytherapy offers a useful surgical approach in patients in whom unresectable pulmonary or mediastinal malignancies are found at the time of thoracotomy or in patients previously treated with other modalities for whom limited therapeutic alternatives exist.

Adolescent↗
PubMed1987

Comparison of three treatment strategies for esophageal cancer within a single institution.

Fifty-seven patients with esophageal cancer were treated with curative intent between January 1979 and June 1985. Seventeen were treated with radical radiation therapy alone (TD 4000-6500 cGy in 200-250 cGy fractions). Twenty-five were treated using radiation therapy (3000 cGy in 200 cGy fractions, day 1-19, and 2600-3000 cGy in 200 cGy fractions, day 50-68) and concomitant chemotherapy (5-FU and Cis-platinum). Fifteen were treated preoperatively by radiation therapy (3000 cGy at 200 cGy fractions) and concomitant chemotherapy (5-FU and Cis-platinum) followed by esophagectomy in 2-3 weeks. Chi square tests showed no significant baseline differences between the patients in the three different treatment groups with respect to A.J.C. stage, T status, location of tumor or histology. Median survival and 2-year survival for the three treatment groups were RT alone: 5 months and 0%, RT and chemotherapy: 12 months and 37%, RT, chemotherapy and surgery 13 months and 38%. A Cox multivariate analysis revealed significant predictor variables for increased survival were treatment strategy, RT dose delivered and T status. Increased local control was seen with either multimodality approach compared to radiation therapy alone. Our data suggests that a multimodality approach is superior as a curative treatment strategy, compared to RT alone, in esophageal cancer. In our series no significant differences were seen with respect to treatment outcome between the two multimodality approaches used.

Adenocarcinoma↗