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2.
Chemosphere ; 45(1): 91-9, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11572596

ABSTRACT

The objective of this research was to evaluate three extraction tests, i.e., toxicity characteristic leaching procedures (TCLP), extraction procedure (EP), and American Society for Testing and Materials (ASTM) methods, for their ability to extract metals in chemical sludge and incineration bottom ash, in terms of the precision of analytical results. Typical chemical sludges, including the electroplating and dye-stuff sludges, the municipal solid waste incineration bottom ash, the leather debris, and the steel-mill bottom residue containing Cd, Cr, Cu, Pb, and Zn were prepared for the lysimetry test (dynamic testing) to compare with the extraction results. Results show that for bottom residue and dye-stuff sludge, the concentration of metal leached was almost the same between the lysimetry leaching and the TCLP tests. The metal concentration followed the order: TCLP approximately = EP > ASTM. TCLP and EP exhibited almost the same relative standard deviation (RSD) value. Therefore, the results of the TCLP tests for bottom residue and dye-stuff sludge, which have a low metal content and alkalinity, can be used to estimate the metal concentration leached by typical acid rain in Taiwan; whereas the ASTM extraction test may be a better indicator of the lysimetry test.


Subject(s)
Metals, Heavy/chemistry , Refuse Disposal/methods , Chemistry Techniques, Analytical/methods , Coloring Agents , Environmental Monitoring , Hydrogen-Ion Concentration , Incineration , Industrial Waste , Metals, Heavy/adverse effects , Metals, Heavy/analysis , Solubility , Toxicity Tests
3.
Chemosphere ; 44(5): 1231-6, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11513412

ABSTRACT

The molecular weight distribution and chemical composition of precursors and their relationship with disinfection by-products (DBPs) were investigated. Most of the organic matter responsible for the major DBP precursors in the Pan-Hsin water are small compounds with a molecular weight less than 1 kDa. The hydrophobic acids display the greatest ability to produce DBP. Therefore, effective removal of small molecules or hydrophobic acidic organics prior to disinfection process will significantly reduce the DBP concentration in the finished water. Although the coagulation process is effective in removing large organic precursors and the removal efficiencies of CHCl3 formation potential and organic carbon increase proportionally to the molecular weight of the precursors, the conventional treatment methods have limited efficiency in eliminating small precursors, which have high DBP formation potential.


Subject(s)
Disinfectants/chemistry , Water Pollutants, Chemical/analysis , Disinfectants/analysis , Molecular Weight , Organic Chemicals/analysis , Solubility , Water Purification
4.
Leuk Res ; 25(9): 757-67, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11489469

ABSTRACT

AC133 is a novel 5-transmembrane antigen present on a CD34((bright)) subset of human hematopoietic stem cells (HSCs) and it is also expressed on the subset of CD34 positive (CD34(+)) leukemias. But the clinical significance of AC133 expression on leukemic blasts is not yet known. We investigated the expression of AC133 antigen on blast cells of acute leukemia. Forty-one cases of acute leukemia were examined for expression of AC133, CD34, and other antigens using multicolor flow-cytometry. Samples were considered positive if at least 20% of the cells specifically stained with monoclonal antibodies (MoAbs) revealed a higher fluorescence intensity compared to cells of corresponding negative control samples (=20% cut-off level). 14/36 (38.9%) acute myelogenous leukemia (AML) samples and 6/20 (30%) acute lymphoblastic leukemia (ALL) samples were positive for AC133, the difference was not significant. All AC133 positive (AC133(+)) leukemias expressed CD34, whereas 13 of 33 CD34(+) leukemias were negative for AC133, and AC133(+)/CD34(-) leukemia was not found. Expression rates of CD31, CD62L, CD62E, CD105 and CD144 were significantly higher in AC133(+) leukemia compared to those of AC133(-) leukemia (P=0.045, P<0.001, P<0.001, P<0.001, P=0.003, respectively), but bcl-2, CXCR-1, CXCR4, VLA-4, CD106 expression rates were not significantly different between AC133(+) and AC133(-) leukemias. None of the clinical prognostic markers such as age, hemogram, lactate dehydrogenase, and chromosomal aberration were significantly different between AC133(+) and AC133(-) leukemias. CR rates of AC133(+) AML and AC133(-) AML were not significantly different, although there was a trend toward higher CR rates in AC133(-) AML (18/22[81.8%] AC133(-) AML versus 9/14[64.3%] AC133(+) AML), but the 1-year relapse rate of AC133(+) AML was significantly higher than that of AC133(-) AML (8/9 (88.9%) versus 7/19 (36.8%), P=0.016). Median disease-free survival (DFS) times of AC133(+) and AC133(-) AML were significantly different (11 and 18 months, respectively, P=0.006), although overall survival (OS) times were not significantly different (AC133(+) 15 months versus AC133(-) 20 months, respectively, P=0.06). Similar results regarding clinical outcomes were found when AC133(+)/CD34(+) and AC133(-)/CD34(+) were analyzed separately, but the difference did not attain statistical significance. In ALL, 9/11 (81.8%) AC133(-) and 2/4 (50%) AC133(+) cases achieved CR, but the difference was not significant. Four of 11 AC133(-) ALL (36.4%) and 2 of 3 AC133(+) ALL (66.7%) relapsed within 1 year. In survival analysis, median DFS time and OS time of the AC133(+) group were 7 and 18 months, respectively, and these were not significantly different from those of the AC133(-) group (median DFS 15, OS 22 months, respectively). Our results demonstrate that AC133 expression in AML blasts is associated with poor clinical outcomes in terms of higher early relapse and shorter disease-free survival, suggesting that the AC133 antigen might provide the prognostic stratification of acute leukemia. However, to verify the effect of AC133 expression on the therapeutic outcomes of adult acute leukemia, further study including more cases is needed.


Subject(s)
Biomarkers, Tumor/analysis , Glycoproteins/analysis , Leukemia/diagnosis , Peptides/analysis , AC133 Antigen , Acute Disease , Adolescent , Adult , Aged , Antigens, CD , Antigens, CD34/analysis , Disease Progression , Female , Humans , Leukemia/metabolism , Leukemia/mortality , Leukemia/physiopathology , Male , Middle Aged , Prognosis , Treatment Outcome
5.
Yonsei Med J ; 42(2): 258-63, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11371117

ABSTRACT

Sjögren's syndrome (SS) is an autoimmune disease characterized by a lymphocytic infiltration of the salivary and lacrimal glands leading to a progressive destruction of these glands due to the production of autoantibodies. This disorder is either isolated (primary SS) or associated with other systemic diseases (secondary SS). The occurrence of B-cell non-Hodgkin's lymphoma (NHL) represents the major complication in the evolution of SS patients. The risk of developing NHL, which is equivalent for both primary and secondary SS, was estimated to be 44 times greater than that observed in a comparable normal population. NHLs in SS patients occur preferentially in the salivary glands and in other mucosa-associated lymphoid tissues (MALT). However, it can also occur in the lymph nodes or bone marrow. We documented a case of low-grade B-cell lymphoma of MALT in the right eyelid and primary biliary cirrhosis (PBC) of a patient with SS. To the best of our knowledge, this is the first case reported in Korea.


Subject(s)
Eyelid Neoplasms/etiology , Liver Cirrhosis, Biliary/complications , Lymphoma, B-Cell, Marginal Zone/etiology , Sjogren's Syndrome/complications , Eyelid Neoplasms/pathology , Female , Humans , Liver Cirrhosis, Biliary/pathology , Lymphoma, B-Cell, Marginal Zone/pathology , Middle Aged , Sjogren's Syndrome/pathology
6.
Yonsei Med J ; 42(1): 65-73, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11293503

ABSTRACT

The purpose of this study was to evaluate the feasibility and efficacy of autologous transplantation of peripheral blood stem cells (PBSC) mobilized with high-dose consolidation chemotherapy and granulocyte colony-stimulating factor in patients with acute myelogenous leukemia (AML). Twenty patients received myeloablative chemotherapy or chemo-radiotherapy including total body irradiation followed by the infusion of PBSC. PBSC were collected by large-volume leukaphereses. The mean number of mononuclear cells and CD34-positive cells infused were 7.2 x 10(8)/kg (range, 2.2-16.6), and 6.6 x 106/kg (range, 2.1-27.7), respectively. Engraftment failure was not seen in the enrolled patients. The median time to neutrophil (> or = 500/microL) and platelet recovery (> or = 50,000/microL) from the transplant was 12 days (range, 8-20) and 28 days (range, 10-600), respectively. The 2-year probability of disease-free survival (DFS) and relapse were 43% and 57% for patients with AML transplanted in first complete remission (CR1). The outcome of the patients transplanted in the advanced status was significantly worse than the patients transplanted in CR1 (P=0.04). Most relapses occurred within 1 year after transplantation. Fatal hepatic veno-occlusive disease was observed in one case. Other transplantation-related toxicities were mild. Our results demonstrated that autologous transplantation of high-dose consolidation chemotherapy-mobilized peripheral blood progenitor cells is feasible in the patients with AML in CR1. To further reduce the risk of leukemia relapse, much effort should be contributed to the field of ex vivo purging and post-transplant immunotherapy.


Subject(s)
Hematopoietic Stem Cell Mobilization , Hematopoietic Stem Cell Transplantation , Leukemia, Myeloid, Acute/therapy , Adult , Female , Hematopoiesis , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Transplantation, Autologous
7.
Am J Hematol ; 68(4): 237-45, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11754412

ABSTRACT

In an effort to develop more effective therapy for patients with refractory or relapsed acute myelogenous leukemia (AML) and high-risk myelodysplastic syndrome (MDS), we investigated the efficacy of a combination chemotherapy consisting of idarubicin, cytarabine, and topotecan. Twenty-seven patients were treated: four with primary refractory AML, nine with AML in first relapse, four with AML in second relapse, and 10 with MDS-RAEB/RAEBT. Patients received as salvage therapy a single course of idarubicin 12 mg/m(2) IV bolus on days 1-3, cytarabine 1 g/m(2) over two hours q 12 hr on days 1-5, and topotecan 1.25 mg/m(2) over 24 hr on days 1-5. Median age was 42 years (range 17-65 years). All patients were evaluable for response: 14 (51.9%) achieved complete remission, 10 with AML (59%) and four with MDS (40%), respectively. Thirteen AML patients (excluding four relapsed after autologous stem cell transplantation) were grouped into four categories to stratify the probability of achieving complete remission (CR): group 1, first CR duration > or = 2 years and receiving first salvage treatment (S1); group 2, first CR duration 1-2 years and receiving S1; group 3, first CR duration 0-1 years and receiving S1; and group 4, first CR duration 0-1 years and receiving S2, S3, or S4 after failing S1. The response rate of each group was as follows: group 1, one of two (50%); group 2, one of one (100%); group 3, four of four (100%); group 4, two of six (33.3%). The median remission duration and survival of patients with AML were six and 12 months, respectively. Median duration of survival in 10 MDS patients was 15 months, and all four MDS patients achieving a CR maintained continuous CR with a median follow-up of 11 months. Severe myelosuppression was observed in all patients, resulting in fever or documented infections in 89% of patients. Median time to recovery of neutrophils > or =0.5 x 10(9)/l was 22 days (11-34) and for platelets > 20 x 10(9)/l 35 days (11-58). Reversible grade 3-4 toxicities included diarrhea (two patients) and mucositis (seven patients). We conclude that combination chemotherapy with intermediate dose cytarabine, idarubicin, and topotecan has significant antileukemic activity and acceptable toxicity in salvage AML and high-risk MDS.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Leukemia, Myeloid, Acute/drug therapy , Myelodysplastic Syndromes/drug therapy , Adolescent , Adult , Aged , Antineoplastic Combined Chemotherapy Protocols/toxicity , Cytarabine/administration & dosage , Cytarabine/toxicity , Disease-Free Survival , Female , Humans , Idarubicin/administration & dosage , Idarubicin/toxicity , Leukemia, Myeloid, Acute/complications , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Myelodysplastic Syndromes/complications , Myelodysplastic Syndromes/mortality , Remission Induction , Salvage Therapy , Survival Rate , Topotecan/administration & dosage , Topotecan/toxicity , Treatment Outcome
8.
Br J Haematol ; 110(2): 385-93, 2000 Aug.
Article in English | MEDLINE | ID: mdl-10971396

ABSTRACT

HLA-DM has been known to be largely absent from the cell surface of antigen-presenting cells, accumulating instead in the intracellular compartment. In this study, we demonstrated that a population of HLA-DM-positive (HLA-DM+) dendritic cells (DCs) can be identified in an in vitro culture of CD34+ bone marrow haematopoietic stem cells. CD34+ bone marrow cells of healthy donors were used to generate DCs with the recombinant human cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor alpha (TNF-alpha) and stem cell factor (SCF), both with and without interleukin 4 (IL-4). Flow cytometric analysis demonstrated that HLA-DM+ cells comprised 2.5 +/- 0.9% and 1.8 +/- 0.4% of the CD34+ cell-derived progeny in the presence of GM-CSF, TNF-alpha and SCF after 7 d and 14 d of culture respectively. The number of HLA-DM molecules expressed per HLA-DM+ cell on d 7 was significantly higher than that on d 14 (1410 +/- 47 versus 370 +/- 25, P < 0.05). The addition of IL-4 to the cytokines from the commencement of culture increased the proportion of HLA-DM+ cells and increased the number of HLA-DM molecules per HLA-DM+ cell significantly (P < 0.05). Although most of the HLA-DM+ cells expressed CD1a, CD80 or CD86 antigen, only a small proportion of CD1a+, CD80+ or CD86+ cells expressed HLA-DM. About half the HLA-DM+ cells expressed CD83. The addition of IL-4 resulted in a decrease in the expression of CD83 on the HLA-DM+ cells on d 7. Microscopic evaluations of sorted HLA-DM+ cells revealed the characteristic morphological features of DCs. Primary mixed lymphocyte cultures demonstrated that the HLA-DM+ cells elicited a vigorous proliferation of allogeneic T cells. The level of antigen-specific T-cell activation induced by antigen-pulsed, chloroquine-treated HLA-DM+ cells was substantially higher than that induced by HLA-DM- cells (P < 0.05). These results show that HLA-DM can be used as a useful DC lineage-specific marker, as well as a tool for the characterization of DCs and human immunotherapy.


Subject(s)
Antigens, CD34/immunology , Dendritic Cells/immunology , HLA-D Antigens/immunology , Hematopoietic Stem Cells/immunology , Antigens, CD1/immunology , B7-1 Antigen/immunology , Cell Division , Cells, Cultured , Flow Cytometry , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Humans , Interleukin-4/immunology , Lymphocytes/cytology , Stem Cell Factor/immunology , Tumor Necrosis Factor-alpha/immunology
9.
Fresenius J Anal Chem ; 366(3): 244-8, 2000 Feb.
Article in English | MEDLINE | ID: mdl-11225667

ABSTRACT

An extraction technique using MTBE (methyl tert. butyl ether) and reagent water in combination with ion chromatography and conductivity determination was developed to quantify dichloroacetic acid (DCAA) and trichloroacetic acid (TCAA) concentrations in raw water after chlorination. The detection limit of the method was 0.45 and 1.50 microg/L for DCAA and TCAA, respectively. Mean values of recovery ranged from 90 to 96% for DCAA and 95 to 108% for TCAA. The evaluation of recovery and precision of the method indicates that the performance characteristics are comparable with gas chromatographic (GC) methods reported in literature. In addition, the procedure is simple, fast, and does not need any derivatization step. Application of the analytical method to the determination of DCAA and TCAA in real samples is shown.


Subject(s)
Dichloroacetic Acid/analysis , Trichloroacetic Acid/analysis , Chlorine , Chromatography, Ion Exchange/methods , Disinfectants
10.
Blood ; 93(11): 3893-9, 1999 Jun 01.
Article in English | MEDLINE | ID: mdl-10339498

ABSTRACT

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.


Subject(s)
Calcium-Calmodulin-Dependent Protein Kinases/metabolism , Leukemia/enzymology , MAP Kinase Kinase Kinase 1 , Protein Serine-Threonine Kinases/metabolism , Protein Tyrosine Phosphatases/metabolism , Down-Regulation , Dual Specificity Phosphatase 2 , Enzyme Activation , Gene Expression Regulation, Neoplastic , Humans , Protein Phosphatase 2 , Protein Serine-Threonine Kinases/genetics , Protein Tyrosine Phosphatases/genetics , Tumor Cells, Cultured , Up-Regulation
11.
Yonsei Med J ; 40(6): 578-82, 1999 Dec.
Article in English | MEDLINE | ID: mdl-10661035

ABSTRACT

Laparoscopic surgery has recently extended its indications and it has also become an acceptable surgical approach for splenectomy. In the last five years, we have performed 40 laparoscopic splenectomies for immune thrombocytopenic purpura. Thirty-five patients were female and 5 patients were male. The mean age was 34, varying from 17 to 56. After learning to perform laparoscopic splenectomy with five ports, we are now usually using three or four ports in a right lateral kidney position. There was no case of conversion to exploratory laparotomy. The mean hospital stay was 7 days. There was no perioperative mortality; but in 2 cases we had postoperative subphrenic abscesses which were successfully managed by catheter drainage. Since undergoing laparoscopic splenectomy, 28 patients (70%) were weaned effectively from their steroid medications. Eight patients (20%) have been on small doses of steroid, and 4 patients (10%) have been on the same doses of steroid with no response. The patient group with rapidly increasing platelet count after splenectomy showed a statistically significant relation with the complete response group (p < 0.001). Laparoscopic splenectomy is a safe and reasonable operative procedure for patients with immune thrombocytopenic purpura.


Subject(s)
Laparoscopy , Purpura, Thrombocytopenic, Idiopathic/surgery , Splenectomy , Adolescent , Adult , Female , Humans , Male , Middle Aged
12.
Yonsei Med J ; 39(4): 328-38, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9752799

ABSTRACT

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.


Subject(s)
Antigens, CD34/analysis , Dendritic Cells/physiology , Hematopoietic Stem Cells/physiology , Granulocyte-Macrophage Colony-Stimulating Factor/pharmacology , HLA-DR Antigens/analysis , Humans , Interleukin-4/pharmacology , Tumor Necrosis Factor-alpha/pharmacology
13.
Korean J Intern Med ; 13(1): 41-6, 1998 Feb.
Article in English | MEDLINE | ID: mdl-9538630

ABSTRACT

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.


Subject(s)
Anemia, Aplastic/immunology , T-Lymphocytes/immunology , T-Lymphocytes/pathology , Anemia, Aplastic/pathology , Apoptosis , Case-Control Studies , Humans , In Vitro Techniques , Lymphocyte Activation , Time Factors , fas Receptor/blood
14.
Bone Marrow Transplant ; 20(10): 883-8, 1997 Nov.
Article in English | MEDLINE | ID: mdl-9404931

ABSTRACT

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.


Subject(s)
CD8-Positive T-Lymphocytes/pathology , Graft vs Host Disease/pathology , Membrane Glycoproteins/biosynthesis , T-Lymphocyte Subsets/pathology , fas Receptor/biosynthesis , Acute Disease , Adolescent , Adult , Bone Marrow Transplantation/adverse effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Fas Ligand Protein , Female , Gene Expression Regulation , Graft Survival , Graft vs Host Disease/blood , Graft vs Host Disease/immunology , Humans , Immunophenotyping , Leukemia/therapy , Leukocyte Count , Lymphocyte Count , Male , Membrane Glycoproteins/genetics , T-Lymphocyte Subsets/immunology , T-Lymphocyte Subsets/metabolism , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/metabolism , T-Lymphocytes, Cytotoxic/pathology , Transplantation, Homologous/adverse effects , fas Receptor/genetics
15.
Yonsei Med J ; 38(5): 270-84, 1997 Oct.
Article in English | MEDLINE | ID: mdl-9409190

ABSTRACT

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.


Subject(s)
Lymphoma/pathology , Lymphoma/therapy , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Survival Analysis , Treatment Outcome
16.
Yonsei Med J ; 38(4): 212-9, 1997 Aug.
Article in English | MEDLINE | ID: mdl-9339129

ABSTRACT

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.


Subject(s)
Gene Expression/physiology , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/blood , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Wilms Tumor/genetics , Biomarkers, Tumor , Humans , Neoplasm, Residual , Polymerase Chain Reaction , Transcription, Genetic
17.
Br J Haematol ; 93(4): 928-30, 1996 Jun.
Article in English | MEDLINE | ID: mdl-8703827

ABSTRACT

Flow cytometric immunofluorescent analysis was used to assess Fas antigen (CD95) expression in blasts obtained from the bone marrow of 30 patients with acute myeloid leukaemia. The percentage of positive cells in each sample was highly variable. Fas antigen expression did not correlate with age, FAB subtype, white blood cell counts, or CD34 expression. Low expression of Fas was associated with a low complete remission rate after induction chemotherapy (62.5% in cases with < 20% positive cells v 92.9% in cases with > or = 20% positive cells, P < 0.01). The main cause for not achieving remission was resistant disease. Our results suggest that the quantitation of Fas expression can be predictive of treatment outcome in acute myeloid leukaemia.


Subject(s)
Antineoplastic Agents/therapeutic use , Cytarabine/therapeutic use , Daunorubicin/therapeutic use , Leukemia, Myeloid/metabolism , Mitoxantrone/therapeutic use , Thioguanine/therapeutic use , fas Receptor/metabolism , Acute Disease , Adult , Bone Marrow/metabolism , Drug Resistance, Neoplasm , Female , Humans , Leukemia, Myeloid/drug therapy , Male , Middle Aged , Treatment Outcome
18.
Yonsei Med J ; 37(2): 104-11, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8711932

ABSTRACT

The purpose of this study was to compare iron related indices in patients with iron deficiency anemia and chronic causative diseases between geriatric older than 65 years and adult, nongeriatric younger than 65 years groups. Iron deficiency anemia (IDA) cases with chronic disorders from Youngdong Severance hospital from June, 1991 to April, 1994, older than 65 years (17 cases), and younger than 65 years (29 cases) were analysed with iron related indices. Mean hemoglobin was 7.8 +/- 2.2 g/dl in geriatric IDA and 8.0 +/- 1.8 g/dl in adult IDA without significant difference. RDW value was 19.5 +/- 2.6 in geriatric IDA and 18.4 +/- 3.2 in adult IDA with no significant difference. Serum iron and transferrin saturation between geriatric IDA were 22.7 +/- 12.3 ug/dl, 6.7 +/- 4.1% and 28.6 +/- 16.6 ug/dl, 7.1 +/- 4.4% in adult IDA with no significant difference, but TIBC was significantly lower (P = 0.011) in geriatric IDA than in adult IDA patients (357.2 +/- 83.2, 413.6 +/- 54.0 ug/dl). In normal elderly people, serum ferritin was 152.5 +/- 95.4 ng/ml in male and 111.1 +/- 54.1 ng/ml in female with range 19.8 approximately 367.7 ng/ml in male and 11.7 approximately 238.7 ng/ml in female and was higher than that of normal adult in both sexes (147.0 +/- 108.0, 35.3 +/- 20.5 ng/ml) (P = 0.045). Serum ferritin in geriatric IDA was 13.8 +/- 11.8 ng/ml and 5.7 +/- 4.0 ng/ml in adult IDA with significant difference(P = 0.001). The Upper margin for geriatric IDA was 37 ng/ml with 95% confidence interval. In the diagnosis of geriatric IDA with causative diseases, we should consider that TIBC does not increase and the upper margin for serum ferritin is suggested to increases up to 37 ng/ml.


Subject(s)
Anemia, Iron-Deficiency/blood , Aged , Aged, 80 and over , Female , Ferritins/blood , Hemoglobins/analysis , Humans , Iron/blood , Korea , Male
19.
J Korean Med Sci ; 11(1): 64-7, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8703372

ABSTRACT

Ecthyma gangrenosum is a characteristic skin lesion of systemic infection due to Pseudomonas aeruginosa. It has a high incidence in patients with chronic disease and impaired defense mechanisms. Early diagnosis and appropriate systemic antibiotic therapy is crucial since its mortality rate is very high. We report a case of ecthyma gangrenosum in aplastic anemia.


Subject(s)
Anemia, Aplastic/complications , Pseudomonas Infections/complications , Skin Diseases, Bacterial/etiology , Adult , Anemia, Aplastic/pathology , Female , Humans , Opportunistic Infections/microbiology , Opportunistic Infections/pathology , Pseudomonas Infections/microbiology , Pseudomonas Infections/pathology , Skin Diseases, Bacterial/drug therapy , Skin Diseases, Bacterial/pathology
20.
Yonsei Med J ; 36(4): 315-21, 1995 Sep.
Article in English | MEDLINE | ID: mdl-7483674

ABSTRACT

Primary lymphoma presenting in the thyroid gland is uncommon. A review of the Yonsei University Medical Center experience between 1982 and 1994 was performed retrospectively to assess the treatment outcome and prognostic factors. There were four females and one male, and the median age was 65 years. All 5 cases presented with a neck mass. Two of them had co-existing biopsy-proved Hashimoto's thyroiditis and three cases were each in a hypothyroid state. All cases with non-Hodgkin's disease were of intermediate grade. One case was in stage IE and four were in stage IIE. Three cases were treated with surgery alone and two cases with bulky inoperable stage IIB were treated with chemo-radiotherapy. Chemotherapy induced a complete response in one and a partial response in the other with minimal transient toxicity. As the questions regarding justification for extensive surgical intervention increase, combined chemo-radiotherapy can be suggested as an initial treatment even in stage I, and stage II thyroid lymphoma based on prognostic factor evaluation.


Subject(s)
Lymphoma/diagnosis , Lymphoma/therapy , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/therapy , Aged , Biopsy, Needle , Combined Modality Therapy , Female , Humans , Lymphoma/pathology , Male , Middle Aged , Neoplasm Staging , Thyroid Neoplasms/pathology , Treatment Outcome
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