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J S Hahn

Publications and source records attributed to J S Hahn.

At least 37 records · Page 2Linked to original sources
PubMed1999

Constitutive activation of extracellular signal-regulated kinase in human acute leukemias: combined role of activation of MEK, hyperexpression of extracellular signal-regulated kinase, and downregulation of a phosphatase, PAC1.

Extracellular signal-regulated kinase (ERK) is an important intermediate in signal transduction pathways that are initiated by many types of cell surface receptors. It is thought to play a pivotal role in integrating and transmitting transmembrane signals required for growth and differentiation. Constitutive activation of ERK in fibroblasts elicits oncogenic transformation, and recently, constitutive activation of ERK has been observed in some human malignancies, including acute leukemia. However, mechanisms underlying constitutive activation of ERK have not been well characterized. In this study, we examined the activation of ERK in 79 human acute leukemia samples and attempted to find factors contributing to constitutive ERK activation. First, we showed that ERK and MEK were constitutively activated in acute leukemias by in vitro kinase assay and immunoblot analysis. However, in only one half of the studied samples, the pattern of ERK activation was similar to that of MEK activation. Next, by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and immunoblot analysis, we showed hyperexpression of ERK in a majority of acute leukemias. In 17 of 26 cases (65.4%) analyzed by immunoblot, the pattern of ERK expression was similar to that of ERK activation. The fact of constitutive activation of ERK in acute leukemias suggested to us the possibility of an abnormal downregulation mechanism of ERK. Therefore, we examined PAC1, a specific ERK phosphatase predominantly expressed in hematopoietic tissue and known to be upregulated at the transcription level in response to ERK activation. Interestingly, in our study, PAC1 gene expression in acute leukemias showing constitutive ERK activation was significantly lower than that in unstimulated, normal bone marrow (BM) samples showing minimal or no ERK activation (P =.002). Also, a significant correlation was observed between PAC1 downregulation and phosphorylation of ERK in acute leukemias (P =.002). Finally, by further analysis of 26 cases, we showed that a complementary role of MEK activation, ERK hyperexpression, and PAC1 downregulation could contribute to determining the constitutive activation of ERK in acute leukemia. Our results suggest that ERK is constitutively activated in a majority of acute leukemias, and in addition to the activation of MEK, the hyperexpression of ERK and downregulation of PAC1 also contribute to constitutive ERK activation in acute leukemias.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1999

Dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha induced by guanidine hydrochloride.

The dynamic equilibrium unfolding pathway of human tumor necrosis factor-alpha (TNF-alpha) during denaturation at different guanidine hydrochloride (GdnHCl) concentrations (0-4.2 M) was investigated by steady-state fluorescence spectroscopy, potassium iodide (KI) fluorescence quenching, far-UV circular dichroism (CD), picosecond time-resolved fluorescence lifetime, and anisotropy decay measurements. We utilized the intrinsic fluorescence of Trp-28 and Trp-114 to characterize the conformational changes involved in the equilibrium unfolding pathway. The detailed unfolding pathway under equilibrium conditions was discussed with respect to motional dynamics and partially folded structures. At 0-0.9 M [GdnHCl], the rotational correlation times of 22-25 ns were obtained from fluorescence anisotropy decay measurements and assigned to those of trimeric states by hydrodynamic calculation. In this range, the solvent accessibility of Trp residues increased with increasing [GdnHCl], suggesting the slight expansion of the trimeric structure. At 1.2-2.1 M [GdnHCl], the enhanced solvent accessibility and the rotational degree of freedom of Trp residues were observed, implying the loosening of the internal structure. In this [GdnHCl] region, TNF-alpha was thought to be in soluble aggregates having distinct conformational characteristics from a native (N) or fully unfolded state (U). At 4.2 M [GdnHCl], TNF-alpha unfolded to a U-state. From these results, the equilibrium unfolding pathway of TNF-alpha, trimeric and all beta-sheet protein, could not be viewed from the simple two state model (N-->U).

Anisotropy↗
PubMed1999

Reduced erythropoietin responsiveness to anemia in diabetic patients before advanced diabetic nephropathy.

We often encounter diabetic patients with anemia in whom the causes of anemia were not clearly identified despite differential hematologic studies. We therefore studied the clinical and biochemical characteristics of diabetic patients with anemia of uncertain cause and measured erythropoietin (Epo) concentrations in 35 diabetic subjects without significant diabetic renal disease. Among 62 medical records of diabetic patients with anemia, showing no evidence of advanced diabetic nephropathy (creatinine clearance > or = 30 mg/kg/1.73 m2), the causes of the anemia were not able to be identified in 28 cases (45.2%). In addition, we enrolled 35 diabetic patients with uncertain causes of anemia in order to evaluate the serum Epo responsiveness to anemia, and compared levels to a group of non-diabetic subjects also with anemia. The serum Epo concentrations of diabetic patients (17.6 +/- 8.1 mIU/ml) were significantly lower than those of non-diabetic patients with similar degree of decrease in hemoglobin concentrations (144.9 +/- 108.0 mIU/ml, P<0.001). The hemoglobin concentrations of diabetic patients correlated with creatinine clearance (r = 0.34, P = 0.03), serum creatinine (r = -0.49, P = 0.003) and albumin excretion rate (r = -0.44, P = 0.009), but showed no relation to age, duration of diabetes, glycated hemoglobin, presence of retinopathy or neuropathy. We concluded that reduced Epo responsiveness to anemia could explain the anemia present in diabetic patient but without advanced diabetic nephropathy. This may reflect early renal interstitial damage.

Aged↗
PubMed1998

Wernicke encephalopathy and beriberi during total parenteral nutrition attributable to multivitamin infusion shortage.

OBJECTIVE: Wernicke encephalopathy (WE) is an acute neurologic disorder characterized by a triad of ophthalmoplegia, ataxia, and mental confusion. WE is attributable to thiamine (vitamin B1) deficiency. Beriberi is the systemic counterpart of thiamine deficiency and often manifests in cardiovascular collapse. WE is usually associated with alcoholism and malnutrition. It has also been seen in people with gastrointestinal diseases with malabsorption. Patients who have received total parenteral nutrition (TPN) without proper replacement of thiamine have also developed WE. Since November 1996, there has been a shortage of multivitamin infusion (MVI). Many patients who were on chronic TPN with MVI ceased to receive the MVI and were converted to an oral form of the multivitamin. As a result, there have been several reports of children and adults on TPN who have developed WE as a result of thiamine deficiency. With this case report, we bring to attention the association of the MVI shortage and WE. Early diagnosis of WE is important, because if it is treated with thiamine in the acute stages, the neurologic and cardiovascular abnormalities can be reversed. CASE REPORT: We report a 20-year-old female patient with Crohn's disease who developed WE as a result of thiamine deficiency. She had Crohn's disease since age 9 years and was on chronic TPN. Two months before admission, MVI was discontinued in the TPN because of the shortage of its supply. An oral multivitamin tablet was substituted instead. She was admitted to the hospital for persistent vomiting. In the hospital, she continued to receive TPN without MVI, but continued taking an oral multivitamin preparation. Two weeks after admission, she developed signs of WE including diplopia, ophthalmoplegia, nystagmus, and memory disturbance. She also developed hypotension that was thought to be caused by beriberi. She was treated with 50 mg of intravenous thiamine. Within hours of the intravenous thiamine, her hypotension resolved. The day after the infusion, she no longer complained of diplopia, and her ophthalmoplegia had improved dramatically. Magnetic resonance imaging showed several areas of abnormally high signal on T2-weighted images in the brainstem, thalamus, and mamillary bodies. The topographic distribution of these changes was typical of WE. After 2 months, her mental status and neurologic status had recovered completely. CONCLUSION: WE and thiamine deficiency should be considered in all patients with malabsorption, malnutrition, and malignancies. WE from thiamine deficiency can occur as a result of cessation of MVI in the TPN infusion. Even if an oral multivitamin preparation is given instead of MVI, patients with malabsorption may not absorb thiamine adequately. Prompt diagnosis of WE is important because it is potentially fatal and readily treatable with thiamine supplementation. Early recognition of WE may be more difficult in children, because the classic triad of symptoms may not develop fully. Magnetic resonance imaging may be useful in these cases to confirm the diagnosis of WE. Because the shortage of MVI is expected to be a long-term, there are likely to be more cases of WE in the pediatric population of TPN-dependent children. Because there is no shortage of intravenous thiamine, it should be administered with TPN even if MVI is not available.

Administration, Oral↗
PubMed1998

Primary lymphoma of the eye.

Lymphomas in the eye tend to be localized and to have a better prognosis. We reviewed the clinical presentation, treatment outcome and complications of primary lymphomas of the eye at a single institute focusing on the clinical significance of adequate staging and the prognostic value of pathological subtypes. Twenty-four patients with lymphoproliferative lesion of the eye were treated and followed up. The orbit was the most commonly involved site. Twenty-one patients had unilateral diseases and three patients had bilateral. Histological findings revealed 22 malignant lymphomas, one inflammatory pseudotumor and one atypical lymphoid hyperplasia. Using the NCI Working Formulation, most of the malignant lymphomas were primarily low grade: diffuse small lymphocytic, 15; diffuse small cleaved three; diffuse large cell, three; and diffuse mixed, one. The stages of lymphoma were IAE in 21 patients, IBE in one patient, and IIAE in two patients. Twenty-five of the 27 treated eyes remained disease-free during the median follow-up period of 16 months. Nineteen patients received radiotherapy, five patients received chemo-radiotherapy and one patient received only surgical excision. Two patients relapsed outside the treated field. None of the patients complained of severe dry eye syndrome or cataract formation. In conclusion, after complete staging work-up, locally-confined low grade orbital lymphomas can be up to 90% controlled with radiotherapy alone. By contrast, combined treatment is advised in patients with intermediate and high grade lesions.

Adolescent↗
PubMed1998

Ex vivo generation of functional dendritic cells from mobilized CD34+ hematopoietic stem cells.

The ability to generate dendritic cells (DCs) in sizeable numbers has enormous implications for the development of clinically-effective antigen presentation procedures for cancer immunotherapy. We evaluated the generation of immunostimulatory DCs from peripheral blood CD34+ cells collected from healthy donors. CD34+ cells purified from leukapheresis product were seeded at 1 x 10(4) cells/mL in complete medium supplemented with GM-CSF, TNF alpha, IL-4, c-kit ligand, and flt3 ligand (FL). By day 14 of culture in the presence of GM-CSF + TNF alpha, the total cell number increased by 23.4 +/- 5.4-fold compared to the starting number of CD34+ cells. When the c-kit and FL were added to GM-CSF and TNF alpha, the cell number increased by 109.8 +/- 11.2-fold without affecting the immunophenotype of recovered cells. Flow cytometric analysis indicated that cells with the markers of mature dendritic cells, i.e., CD1a +CD14 -HLA-DR+, and CD80+CD86+HLA-DR+, constituted 49.0% +/- 7.5%, and 38.9% +/- 6.5%, respectively. This pattern of expression of surface antigen was unchanged whether the c-kit ligand and/or FL was added. The irradiated CD1a+HLA-DR+ cells recovered from in vitro cultures elicit a vigorous proliferation of allogeneic peripheral blood T-cells, irrespective of cytokine combinations. These findings provide advantageous tools for the large-scale generation of DCs that are potentially usable for clinical protocols of immunotherapy or vaccination in patients undergoing cancer treatment.

Antigens, CD34↗
PubMed1998

A case of primary bone lymphoma associated with acquired immunodeficiency syndrome.

A 33-year old man with acquired immunodeficiency syndrome was admitted to Severance hospital following 1 year of diarrhea and 2 to 3 months of low sternal pain. The patient had progressive generalized lymphadenopathy for the previous 3 years. Whole body bone scan for evaluation of bone pain showed multiple abnormal hot uptakes at the low sternal body and T8 and T10 vertebra. Chest CT showed multifocal cortical erosion of the bone with soft tissue mass at the low sternal body and spine MRI showed multiple low-signal density in T1WI and high-signal density in T2WI at the T8 and T10 vertebral body. Biopsy was performed at the sternochondral junction and it showed high-grade malignant lymphoma of the large cell immunoblastic type. Immunostaining showed positive for the B-cell markers (CD79a and L26) and negative for the T-cell marker (UCHL1). Radiotherapy of 3,000 cGy was delivered to the sternum and vertebra. Since then, systemic chemotherapy with m-BACOD regimen (except dexamethasone) and anti-retroviral therapy with a combination of 3 drugs (didanosine, lamivudine, indinavir) has been performed. This is the first case report of primary bone lymphoma associated with acquired immunodeficiency syndrome in Korea.

Adult↗
PubMed1998

Delayed activation-induced T lymphocytes death in aplastic anemia: related with abnormal Fas system.

OBJECTIVES: To quantitate apoptosis and Fas antigen expression of T lymphocytes by activation in aplastic anemia (AA) and compare with that of normal controls and completely-recovered AA, and to investigate the apoptotic sensitivity to anti-fas antibody of activated T lymphocytes in AA. METHODS: We studied the expression of Fas antigen on fresh T lymphocytes of twenty patients with AA [13 newly diagnosed, 7 recorvered AA after immunosuppressive therapy (IST)], and investigated the activation-induced cell death (AICD) and Fas expression by activation [interleukin-2 (200 U/ml) and phytohemagglutinin (50 micrograms/ml)] in 5 newly-diagnosed AA, 5 normal controls and 5 AA in complete response (CR). Apoptotic sensitivity to anti-Fas antibody was assessed by the time-course kinetics of induction of cell death by anti-Fas antibody (500 ng/ml). RESULTS: There was no significant difference of Fas antigen expression on freshly-isolated T lymphocytes among newly-diagnosed severe AA, normal controls and patients with AA in CR after IST. In normal controls, T lymphocytes death was greatly increased at 3 days of activation, and Fas antigen expression on T lymphocytes was increased above baseline at day 1 of activation. In contrast, in newly-diagnosed AA, T lymphocytes showed delayed cell death, which correlated with a slowed increase of Fas antigen expression by activation. Also, anti-Fas antibody sensitivity of activated T lymphocytes was decreased in newly-diagnosed AA. In completely recovered AA, these abnormal AICD and Fas antigen expressions by activation were recovered to normal range. CONCLUSIONS: Abnormal AICD plays a role in the immune pathophysiology of AA, and defective Fas system is involved in this process.

Anemia, Aplastic↗
PubMed1997

Radiation treatment in patients with recurrent Kimura's disease.

PURPOSE: To assess the benefits of radiotherapy for patients with recurrent Kimura's disease and to document the role of radiation treatment as a successful mode of therapy. METHODS AND MATERIALS: From 1985 to 1991, a total of 26 patients with Kimura's disease were treated by local excision and/or systemic steroids at Yonsei University, Yonsei Cancer Center Hospital. Seventeen patients among them eventually had local recurrence after surgical excision. The 17 patients with recurrent Kimura's disease were divided into two groups on the basis of those who received radiation treatment and those who did not. Eight patients in the nonradiation group were treated by systemic steroids alone with individualized doses and schedules. The remaining nine patients in the radiation group were treated by external beam irradiation. The prescribed radiation doses varied from 21.6 to 45 Gy. A comparative analysis on treatment results between both groups was undertaken retrospectively. RESULTS: The majority of the recurrent cases in the nonradiation group treated by steroids alone experienced rapid rerecurrence of the disease. In contrast, all of the patients except one case in the radiation group achieved excellent local control with moderate doses of radiation. There was a significant difference in the rerecurrence rate between the patients of the radiation group (11%) and the nonradiation group (75%). No clear dose-response relationship could be derived from the patients of the radiation group. No secondary malignancies in the irradiated areas have been observed. CONCLUSION: Our results suggest that radiation treatment is preferable as an alternative option for patients with recurrent Kimura's disease who have failed to achieve local control by other modalities.

Adolescent↗
PubMed1997

Bilateral tonic-clonic epileptic seizures in non-benign familial neonatal convulsions.

We report an electroclinical pattern considered characteristic of benign familial neonatal convulsions (BFNC) in two neonates without BFNC. Both neonates were products of uncomplicated pregnancies, labor, and deliveries. The cause of the seizures was not established. There was no family history of seizures or epilepsy. Seizures started on the second and third days after birth. Ten seizures were captured by continuous video-EEG telemetry. The electroclinical events began with generalized tonic posturing coinciding with the appearance of diffuse attenuation of the EEG activity. After several seconds, bilateral clonic movements accompanied by bilateral repetitive sharp waves or spikes occurred in the EEG. One patient had normal development; the other became autistic. We conclude that the electroclinical pattern occurring in BFNC can occur in other types of neonatal seizures.

Autistic Disorder↗
PubMed1997

Difference in the expression of Fas/Fas-ligand and the lymphocyte subset reconstitution according to the occurrence of acute GVHD.

Acute graft-versus-host disease (aGVHD) remains a major barrier to a wider application of allogeneic bone marrow transplantation (BMT). Although this complication is mainly dependent on donor-derived T lymphocytes, very little information is available concerning the mechanism of lethality. In this study, we investigated both the expression of Fas/Fas-ligand (FasL) and lymphocyte subset reconstitution in patients who underwent HLA-matched related allogeneic BMT (n = 16) and normal donors (n = 10), and several distinct features were observed. First, the reconstitutions of CD3+ and CD56+ cells were different between the aGVHD+ and aGVHD- group. In particular, the percentage of CD3-CD56+ cells was significantly decreased in patients with aGVHD (P < 0.01). Second, the expansion of CD8+ (P = 0.01) and CD8+ CD28- T cells (P = 0.03) was a characteristic finding in patients with aGVHD. Finally, we found that the percentages of Fas+CD8+, Fas+HLA-DR+ and FasL+ CD8+ cells were significantly increased. Fas antigen was highly coexpressed on most of the lymphocyte subsets, especially on CD8+ cells (P < 0.01), and also, significantly higher coexpression of FasL on CD8+ cells was found in patients with aGVHD (P < 0.01). In summary, an increase in the percentage of CD8+ cells which express Fas and its ligand in patients with aGVHD after BMT points to a possible role for the Fas/FasL pathway in the effector phase of aGVHD.

Acute Disease↗
PubMed1997

Monitoring of WT-1 gene expression in peripheral blood of patients with acute leukemia by semiquantitative RT-PCR; possible marker for detection of minimal residual leukemia.

The expression of the WT-1 gene which is found exclusively in human leukemic blasts frequently disappears from bone marrow of leukemia patients in complete remission (CR). Using semiquantitative RT-PCR, we investigated the expression of the WT-1 gene in peripheral bloods (PBs) of 33 patients with acute leukemia (AML 26; ALL 7) and monitored its expression after achievement of CR. None of the 6 normal controls expressed detectable levels of WT-1 transcripts (< 10(-4), background level), whereas 31 (93.9%) of 33 patients expressed variable levels of WT-1 transcripts (range, 10(-4) to 10(1)) at diagnosis. The level of WT-1 expression was not different between AML and ALL. By monitoring WT-1 gene expression in PB of 31 patients during CR, 5 patients relapsed (two from the 18 patients with undetectable levels of WT-1 gene expression and three from the 13 with WT-1 gene expression in low levels). Three of the 5 relapsed patients showed preceding reappearance or rise of WT-1 gene expression. From these results, we reconfirmed that the WT-1 gene is a pan-acute leukemic marker, which can be used to monitor minimal residual leukemia (MRL) after chemotherapy or in patients with CR.

Biomarkers, Tumor↗
PubMed1997

Eight-year experience of malignant lymphoma--survival and prognostic factors.

Several reports have suggested a geographic difference in the histopathologic characteristics and prognosis of malignant lymphoma around the world. We tried to evaluate the clinical and histopathologic characteristics, therapeutic outcomes, and prognostic features of malignant lymphoma, particularly in Korean patients. Three hundred and seventy-six adult patients with the initial histopathologic diagnosis of malignant lymphoma of Yonsei University College of Medicine over an 8-year period were analyzed, retrospectively, with the following results: 1) There were 47 cases of Hodgkin's disease (HD) (12.5%) and 329 of non-Hodgkin's lymphoma (NHL) (87.5%) with a 1:7 ratio. The most common histopathologic subtype of HD was mixed cellularity (44.7%), and that of NHL was intermediate grade (70.8%), especially diffuse large-cell type (44.1%), whereas follicular type was less common. In regard to the incidence of extranodal presentation, it is rare in HD (4.2%), but occurs in 49.8% of patients with NHL. 2) The complete remission (CR) rate was 91.5% in HD and 63.6% in NHL, and the 5-year and 7-year disease-free survival rates were 71.3% and 57.0% in HD; 67.0% and 49.6% in NHL. The 5-year and 8-year overall survival rates were 90.7% and 68.0% in HD; 65.2% and 60.2% in NHL. 3) By multivariate analysis, we found that age, performance status, histopathologic grade, stage, serum lactate dehydrogenase (LDH) and beta 2-microglobulin were the useful prognostic factors in predicting survival in NHL, while no definite prognostic factors were found in HD. Also, in NHL patients less than 60 years old, stage, serum LDH, and histopathologic grade were closely associated with their therapeutic outcomes. In conclusion, the characteristics of malignant lymphoma in our hospital differ from those in Western countries with respect to the clinical, histopathologic and immunophenotypic patterns, but the prognostic factors and overall therapeutic outcomes were quite comparable to those of other reports from Western countries.

Adolescent↗
PubMed1997

Stroma-free human hemoglobin A decreases R3230Ac rat mammary adenocarcinoma blood flow and oxygen partial pressure.

We examined the effect of a nitric oxide (NO) quencher, stroma-free human hemoglobin A (HbA0; 0.01, 0.05, 0.1, 0.2 g/kg), on the blood flow measured using the Doppler flow technique, tumor oxygen pressure (pO2) and the diameter of the arterioles using R3230Ac mammary adenocarcinoma as the tumor model. In female Fischer 344 rats with 1-cm-diameter tumors implanted in the lateral aspect of the left quadriceps, intravenous infusion of 0.1 and 0.2 g/kg HbA0 decreased both central tumor and peripheral tumor blood flow by 20-30% (P < 0.05). Tumor pO2 decreased 28% with 0.2 g/kg HbA0, from 15 mm Hg (baseline) to 11 mm Hg at 10 min (P = 0.02). Although 0.2 g/kg HbA0 increased blood flow 55% in the left quadriceps muscle proximal to the implanted tumor (P < 0.05), HbA0 had little effect on blood flow in right quadriceps muscle with no tumor implanted, and increased right quadriceps pO2, from 21 mm Hg (baseline) to 23 mm Hg at 10 min (P = 0.03). HbA0 increased mean arterial pressure 5-10% in a manner that was dependent on dose while heart rate concurrently decreased 9-19%. The diameter of the arterioles supplying the tumor was rapidly reduced 10% by 0.2 g/kg HbA0 (P = 0.037) and remained stable through 60 min of observation (P = 0.005). HbA0 selectively reduces tumor blood flow and tumor pO2 through vasoconstriction of the arterioles supplying the tumor. Vascular NO quenching provides an alternative to NO synthase inhibition as a means to achieve the goal of selective tumor hypoxia.

Adenocarcinoma↗
PubMed1996

Predictive value of EEG for outcome and epilepsy following neonatal seizures.

The value of the electroencephalogram in predicting outcome and epilepsy was examined in neonates who had experienced EEG-confirmed neonatal seizures. Electroencephalogram, neuroimaging studies, and other clinical variables were systematically analyzed in 81 consecutive neonates with EEG-confirmed seizures. The surviving subjects were followed for a mean of 17 months to determine if they developed post-neonatal seizures (PNS) and abnormal neurodevelopmental outcome. Several EEG variables were correlated with neurodevelopmental outcome and PNS when analyzed with univariate and multivariate statistical analyses. The EEG background activity and the presence of status epilepticus were strong predictors of outcome, but were not associated with PNS. The presence of rhythmic theta-alpha bursts was highly favorable for both outcome and PNS. In the interictal EEG, the number of negative sharp waves in the temporal region correlated with outcome and PNS. Clinical variables associated with unfavorable outcomes included an abnormal neonatal neurologic exam and certain seizure etiologies (e.g. cerebral dysgenesis and infections). Global abnormalities on neuroimaging studies were invariably associated with an unfavorable outcome and with the development of PNS in 66% of cases. Using multivariate analysis, prediction of outcome (favorable versus unfavorable) was accurately achieved in 85% of cases when combining EEG variables with neuroimaging and clinical findings. In conclusion, in neonates with EEG-confirmed seizures, the EEG is a useful predictor of outcome, but is a less useful predictor of PNS.

Analysis of Variance↗