Cinnamyl alcohol (CAL) is known as an antipyretic, and a recent study showed its vasodilatory activity without explaining the mechanism. Here we demonstrate the vasodilatory effect and the mechanism of action of CAL in rat thoracic aorta. The change of tension in aortic strips treated with CAL was measured in an organ bath system. In addition, vascular strips or human umbilical vein endothelial cells (HUVECs) were used for biochemical experiments such as Western blot and nitrite and cyclic guanosine monophosphate (cGMP) measurements. CAL attenuated the vasoconstriction of phenylephrine (PE, 1 microM)-precontracted aortic strips in an endothelium-dependent manner. CAL-induced vasorelaxation was inhibited by pretreatment with NG-nitro-L-arginine methyl ester (L-NAME; 10(-4) M), methylene blue (MB; 10(-5) M) and 1 H-[1,2,4]-oxadiazolole-[4,3-a] quinoxalin-10one, (ODQ; 10(-6) or 10(-7) M) in the endothelium-intact aortic strips. Atrial natriuretic peptide (ANP; 10(-8) or 10(-9) M) did not affect the vasodilatory effect of CAL. The phosphorylation of endothelial nitric oxide synthase (eNOS) and generation of nitric oxide (NO) were stimulated by CAL treatment in HUVECs and inhibited by treatment with L-NAME. In addition, cGMP and PKG1 activation in aortic strips treated with CAL were also significantly inhibited by L-NAME. Furthermore, CAL relaxed Rho-kinase activator calpeptin-precontracted aortic strips, and the vasodilatory effect of CAL was inhibited by the ATP-sensitive K+ channel inhibitor glibenclamide (Gli; 10(-5) M) and the voltage-dependent K+ channel inhibitor 4-aminopyridine (4-AP; 2 x 10(-4) M). These results suggest that CAL induces vasorelaxation by activating K+ channels via the NO-cGMP-PKG pathway and the inhibition of Rho-kinase.
Animals ; Aorta/drug effects/metabolism/physiology ; Atrial Natriuretic Factor/pharmacology ; Cyclic GMP/*metabolism ; Cyclic GMP-Dependent Protein Kinases/*metabolism ; Dipeptides/pharmacology ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Humans ; Male ; Methylene Blue/pharmacology ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/*metabolism ; Nitric Oxide Synthase/metabolism ; Oxadiazoles/pharmacology ; Phenylephrine/pharmacology ; Phosphorylation ; Potassium Channel Blockers/pharmacology ; Potassium Channels/*agonists ; Propanols/*pharmacology ; Quinoxalines/pharmacology ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Vasoconstriction/*drug effects ; Vasodilation/drug effects ; rho-Associated Kinases/antagonists & inhibitors/*metabolism

PURPOSE: The needs of stem cell transplantation are increasing in Korea under the circumstance of medical insurance coverage since 1996. But allogeneic bone marrow transplants have the limitation in acquisition of matched donor because of small number of siblings in modern society. Although unrelated stem cell transplantations were made possible in Korea with the establishment of Korean Marrow Donor Program, less than one third of patients who need stem cell transplantation are seeking the matched donors through this program and it still takes too much time and efforts. In this clinical setting, cord blood offers an exciting alternative to traditional sources of stem cells. To implement the widespread clinical use of cord blood stem cells, it is necessary to establish the cord blood bank from which stem cell specimens are obtained. METHODS: To establish the cord blood bank in Korea, we started to develop the proper methods to obtain the cord bloods. Various ways of collecting the cord bloods, separation of red blood cells and storage methods were tried and the standard recommendations were made. RESULTS: Mean volume of collected umbilical cord blood was above 70mL by open or closed method in vaginal delivery and cesarean section. Among the RBC depletion methods by using 3% gelatin, Ficoll-Hypaque, or modified Ficoll-Hypaque method, 3% gelatin sedimentation showed the best result in viability and number of mononuclear cells(MNC), CD34+ cell, and day 14 CFU-GM. The recovery rate after freezing-thawing MNC was higher in the group of using 10% DMSO and programmed freezer starting from 4degrees C than in the group of using mixed with DMSO and hydroxyethyl starch and without programmed freezer. Nine patients underwent cord blood transplantation until December 1998. Among them, 6 patients showed the long-term successful engraftment. CONCLUSION: We have developed simple, efficient, and reproducible methods for collection, processing, and storage of cord blood to establish the cord blood bank. There are some administrative issues including the legal and financial problems that possibly will be resolved by the support of the government and the medical team.
Bone Marrow ; Cesarean Section ; Dimethyl Sulfoxide ; Erythrocytes ; Female ; Fetal Blood* ; Gelatin ; Granulocyte-Macrophage Progenitor Cells ; Humans ; Insurance Coverage ; Korea* ; Pregnancy ; Siblings ; Starch ; Stem Cell Transplantation ; Stem Cells* ; Tissue Donors

BACKGROUND: To standardize the separation method of cord blood and establish the Korean Cord Blood Bank, we analysed the data regarding cord blood separation from 8 different hospitals which involved in cord blood banking project. METHODS: We analysed 306 samples which collected with heparinized syringes and separated within 24 hours by Ficoll-Hypaque density gradient separation method and RBC depletion method with 3% gelatin. We performed the mononuclear cell (MNC) count, viability, CD34+ cell count and CFU-GM count following separation of cord blood. We assessed the yield of hematopoietic stem cells by different separation methods in 9 hospitals and the variability among hospitals which performed cord blood separation by same method. RESULTS: 1) In 204 samples of cord blood separated with Ficoll-Hypaque, there were significant differences in MNC count, viability, CD34+ cell count and CFU-GM count among all engaged hospitals, but not in each individual hospital. 2) In 102 samples of cord blood separated with 3% gelatin, there were significant differences in viability, CFU-GM count and CD34+ cell count among all engaged hospitals, but not in MNC count. 3) The yield of MNCs, CD34+ cells and CFU-GM was higher in the cord blood separated with 3% gelatin than Ficoll-Hypaque. CONCLUSION: We suggest that RBC depletion method with 3% gelatin would be better than Ficoll-Hypaque method in order to increase the yield of hematopoietic stem cells and standardize the method of cord blood separation.
Cell Count ; Fetal Blood* ; Gelatin ; Granulocyte-Macrophage Progenitor Cells ; Hematopoietic Stem Cells ; Heparin ; Syringes

PURPOSE: Acute lymphoblastic leukemia (ALL) accounts for approximately 75% of all cases of childhood leukemia. We investigated epidemiology, clinical and laboratory features and treatment outcome of the children with ALL in Korea during recent 5 years. METHODS: One thousand forty nine patients were enrolled between January 1994 and December 1998 from 37 major hospitals in Korea. The data regarding the clinical and laboratory features including age, WBC counts at diagnosis, immunophenotype, morphology, cytogenetics and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed. The differences between groups analyzed by log-rank test. RESULTS: There were 597 males and 452 females. The distribution between the age 2 and 5 years is most common in 46.1%. The annual incidence rate per 100,000 population varied from 1.6 to 2.2. The 5 year event free survival (EFS) rates according to good prognostic factors were as follows: 67% bet ween 1-9 year of age at diagnosis, 69% in under 10,000/mm3of initial WBC count, 74% in early pre-B cell CALLA ( ) immunophenotype, 65% in L3 morphology, 68% in no CNS invasion. Most of patients were treated by CCG treatment protocol. The 5 year EFS was 63%. Main complications were sepsis (21.8%) and hemorrhage (12.5%). The relapse rate was 15.6%. The common causes of death were sepsis, DIC, pneumonia, relapse. CONCLUSION: Our results could provide the most recent and important information about acute lymphoblastic leukemia of children in Korea.
Cause of Death ; Child ; Clinical Protocols ; Cytogenetics ; Dacarbazine ; Diagnosis ; Disease-Free Survival ; Epidemiology* ; Female ; Hemorrhage ; Humans ; Incidence ; Kaplan-Meier Estimate ; Korea* ; Leukemia ; Male ; Medical Records ; Pneumonia ; Precursor Cell Lymphoblastic Leukemia-Lymphoma* ; Precursor Cells, B-Lymphoid ; Recurrence ; Retrospective Studies ; Sepsis ; Treatment Outcome

PURPOSE: Wilms tumor is the most common malignant renal tumor in children. We investigated the epidemiology, clinical features and treatment outcome of the children with Wilms tumor in Korea during the recent 10 years. METHODS: Two hundred forty six patients were enrolled between January 1991 and December 2000 from 26 major hospitals in Korea. The data regarding the clinical features including sex, age, pathologic type, prognostic factor and treatment outcome of patients were analyzed retrospectively by review of patient's medical records. Kaplan-Meier survival curves were constructed, The differences between groups were analyzed by log-rank test. RESULTS: There were 130 males and 116 females. The incidence between the age of 1~4 years was the highest with 66.2%. The annual incidence rate per 1, 000, 000 population varied from 1.9 to 2.1. The 10 years overall survival rate according to sex, clinical stage, pathologic type and relapse were as follows: 88.6% in male, 90.9% in female, 100% in stage I, 94.7% in stage II, 92.1% in stage III, 63.4% in stage IV, 85.7% in stage V, 95.3% in favorable histology, 64.1% in unfavorable histology, 94.8% in non-relapse, and 40.9% in relapse. The relapse rate was 12%. The 10 years overall survival rate of 246 patients were 89.1%. CONCLUSION: Our results could provide the most recent and important clinical information on Wilms tumor of children in Korea.
Child ; Epidemiology* ; Female ; Humans ; Incidence ; Kaplan-Meier Estimate ; Korea* ; Male ; Medical Records ; Recurrence ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Wilms Tumor*

PURPOSE: Malignant lymphoma is the primary malignant tumor derived from lymphoid organs. It is composed of Hodgkin's disease and non-Hodgkin lymphoma. Recently, survival rate is on the rise due to improved combination chemotherapy, radiotherapy and high dose chemotherapy followed by hematopoietic stem cell transplantation. In South Korea, no epidemiologic studies concerning malignant lymphoma in the pediatric age group has been performed. Therefore, the Korean Society of Pediatric Hematology-Oncology retrospectively analyzed the incidence, pathologic subtypes, treatment strategies, and survival rates of pediatric malignant lymphomas in South Korea. METHOD: Questionnaires were made and sent to a group of training hospitals, with a return of 580 questionnaires from 24 hospitals. Among them, 517 reports were suitable for analysis. RESULTS: Among the 517 cases, Hodgkin's disease accounted for 58 cases and non-Hodgkin's lymphoma for 459 cases. Male to female ratio for malignant lymphoma was 2.7. Mean age at diagnosis was 8.3 years. Among the pathologic subtypes, mixed cellularity was the most frequent subtype for Hodgkin's disease. Most (70.7%) cases of non-Hodgkins lymphoma belonged to high grade NHL. Burkitt lymphoma accounted for 102 cases, and lymphoblastic lymphoma was found in 58 cases. Peripheral lymphadenopathy was the most common presenting sign upon diagnosis. B symptoms were significantly more frequent in Hodgkin's disease patients than in non-Hodgkin lymphoma patients. The Complete response rate was 62.1% for non-Hodgkin's lymphoma, and 82.8% for Hodgkin's disease. Overall 5 year survival rate was 60.0% in non-hodgkin's lymphoma, and 84.8% in Hodgkin's disease. CONCLUSION: The annual incidence of malignant lymphoma in Korea is 4.7 per million. In cases of chemotherapy-sensitive, refractory or relapsed malinant lymphoma, high dose chemotherapy followed by hematopoietic stem cell transplantation is vital for improved survival. For more systematic analysis of epidemiology on malignant lymphomas, better surveillance mechanisms on the occurrence of malignant lymphomas are crucial, and establishment of standardized treatment protocol for malignant lymphoma is required.
Burkitt Lymphoma ; Child* ; Clinical Protocols ; Diagnosis ; Drug Therapy ; Drug Therapy, Combination ; Epidemiologic Studies ; Epidemiology* ; Female ; Hematopoietic Stem Cell Transplantation ; Hodgkin Disease ; Humans ; Incidence ; Korea* ; Lymphatic Diseases ; Lymphoma* ; Lymphoma, Non-Hodgkin ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Surveys and Questionnaires ; Radiotherapy ; Retrospective Studies* ; Survival Rate

PURPOSE: The annual incidence of aplastic anemia (AA) in Asian countries is higher than in Western countries. The pathogenesis in AA has been investigated in hematopoiesis and immunology. Recently, the survival rate and the quality of life of the patients with AA have been steadily improved by the development of a variety of treatments such as the immunosuppressive therapy (IST), and hematopoietic stem cell transplantation (HSCT). The Korean Society of Pediatric Hematology-oncology retrospectively investigated the incidence, treatment strategies, survival rate, and time to become independent from transfusion in patients with AA, who were diagnosed from January 1st, 1991 to December 31st, 2000 in Korea. METHODS: All the questionnaires were sent to a group of training hospitals, and we collected about 600 questionnaire forms from 27 hospitals. However, 493 reports were available for data analysis. RESULTS: The male and female ratio in AA is 1.1 (259 males vs. 234 female). The median age at diagnosis is 9 years old (range; 0.8~16 years old). The annual incidence of children with AA in Korea is 4.5 per million on the basis of Korean pediatric population. In etiology, there are 20 cases (4.1%) in congenital and others in acquired AA. In acquired AA, the cause of illness was not identifiable for most of the patients, but 1 patient had hepatitis-associated AA, and 3 patients developed the illness after medication. According to the initial laboratory data at diagnosis, the peripheral blood findings showed that hemoglobin is 7.1+/-2.4 g/dL, white blood cell 3, 200/microL (200~16, 550), absolute neutrophil counts 670/microL (0~12, 487), platelets 19, 000/microL (1, 000~500, 000), and corrected reticulocytes 0.18% (0.0~4.7). The bone marrow examination revealed that cellularity was below 25% in 348 patients, and over 25% in 105 patients. In the available data, 269 patients (54.6%) were diagnosed of severe aplastic anemia (SAA) and 224 patients of non-SAA (NSAA). HSCT were done for 96 patients (19.5%) and others received another treatments such as the IST. The anti-thymocyte globulin (ATG) or anti-lymphocyte globulin (ALG) treatment was done for 263 cases, corticosteroids for 259, cyclosporine A (CSA) for 215, and anabolic steroids for 138. The combination IST including ATG or ALG plus corticosteroid plus CSA were applied to 154 children with AA, and transfusion only in 37, as conservative care. In case of those patients with HSCT, the time from diagnosis to transplantation was 12 months (1~144 months) and the sources of stem cells were bone marrow in 82 cases, growth factor mobilized peripheral blood in five, and cord blood in six. There were 57 patients transfused below 40 units of blood products before HSC transplantation. Graft rejection was identified from 16 patients, and booster transplantations were done for 12 patients among them. In complications of HSCT, the graft versus host disease was developed in 20 patients and viral diseases in 12 cases including the CMV, herpetic infection, and hepatitis. Also, one patient suffered from veno-occlusive disease. The overall survival rate in children with AA is 64.3%. The survival rate in HSCT is better than that IST (76.9% vs. 62.6%, P< 0.05). In IST, overall survival rate in very SAA showed lower than SAA and NSAA, and in SAA lower than NSAA in case of absolute neutrophil count below 200/microL (P< 0.05). There was no significant difference in terms of the sex, age at beginning of treatment. In HSCT, transfusion was not related to the survival rate. However, overall survival rate is better in short interval between diagnosis and HSCT than in long interval (P< 0.05). There was no significant difference in the probability of transfusion independence according to treatment strategies, even though it was 71.0% in HSCT and 12.8% in immunosuppressive therapy at the end point of survey (P=0.47). The response pattern was as follows. There were 155 cases of complete response, 110 of partial response and 120 of no response in spite of various treatments. The relapse after treatment was found in 11 patients after IST, of which 6 patients experienced more than 2nd relapse. The median time between the end of treatment and relapse was 16 months (6~84 months). Only three cases developed into other diseases (1 case into acute myeloid leukemia and 2 cases into myelodysplastic syndrome). The median time from diagnosis to the end of treatment was 62 months (0.5~174 months). In fatal cases, the median time between diagnosis and death was 29 months (0~144 months) despite several therapeutic strategies. CONCLUSION: In Korea, the annual incidence of children with AA is 4.5 per million. This result is similar to the ones reported in other Asian countries, but higher than those in Western countries. Although a lot of children with AA received various therapies including IST or HSCT, new treatment strategies have to be developed to improve the survival rate and the quality of life of children with AA
Adrenal Cortex Hormones ; Allergy and Immunology ; Anemia, Aplastic* ; Antilymphocyte Serum ; Asian Continental Ancestry Group ; Bone Marrow ; Bone Marrow Examination ; Child* ; Cyclosporine ; Diagnosis ; Epidemiology* ; Female ; Fetal Blood ; Graft Rejection ; Graft vs Host Disease ; Hematopoiesis ; Hematopoietic Stem Cell Transplantation ; Hepatitis ; Humans ; Incidence ; Korea* ; Leukemia, Myeloid, Acute ; Leukocytes ; Male ; Neutrophils ; Quality of Life ; Surveys and Questionnaires ; Recurrence ; Reticulocytes ; Retrospective Studies* ; Statistics as Topic ; Stem Cells ; Steroids ; Survival Rate ; Virus Diseases