Background: Acute radiation syndrome (ARS) primarily refers to damage to the hematopoietic system, myeloid system, and gastrointestinal (GI) system caused by radiation exposure. Such damage progresses to become life-threatening. In particular, as the syndrome develops very rapidly-within several hours from radiation exposure-prompt and accurate diagnosis and treatment are needed, as is further research into appropriate diagnostic and treatment modalities. Materials and Methods: Minipigs, which display human-like properties, underwent whole-body irradiation at 2 or 4 Gy (doses causing hematopoietic ARS) or at higher doses of 7 or 12 Gy. Changes in the blood cells and clinical symptoms were analyzed and we performed a necropsy when the animals succumbed to ARS. Results and Discussion: The minipig irradiated with 2 Gy showed a decrease in white blood cells, including neutrophils, lymphocytes, and platelets in the early stages. However, the blood cell counts gradually increased and returned to normal values. The minipig irradiated with 4 Gy succumbed due to hematopoietic ARS. In contrast, the minipigs irradiated with 7 or 12 Gy exhibited clinical symptoms of combined GI damage and hematopoietic syndrome. Moreover, a characteristic pattern of platelet changes was observed in the 7 and 12 Gy irradiated minipigs. Conclusion: The changes in the platelet count caused by radiation exposure observed in minipigs, which are hematologically and pathohistologically similar to humans, suggest that they can be used as a novel diagnostic criterion.
Jung, You Jin;Jeon, Yeon Jin;Cho, Won Kyoung;Lee, Jae Wook;Chung, Nack-Gyun;Jung, Min Ho;Cho, Bin;Suh, Byung-Kyu
Clinical and Experimental Pediatrics
/
v.56
no.7
/
pp.298-303
/
2013
Purpose: The purpose of this study was to evaluate short-term thyroid dysfunction and related risk factors in pediatric patients who underwent hematopoietic stem cell transplantation (HSCT) during childhood. Methods: We studied 166 patients (100 boys and 66 girls) who underwent HSCT at the Catholic HSCT Center from January 2004 through December 2009. The mean age at HSCT was $10.0{\pm}4.8$ years. Thyroid function of the patients was tested before and during 3 months of HSCT. Results: Out of 166 patients, 165 (99.4%) underwent allotransplantation. Acute graft-versus-host disease (GVHD, grades II to IV) developed in 76 patients. Conditioning regimens before HSCT include total body irradiation (n=57), busulfan (n=80), and reduced intensity (n=29). Forty-five (27.1%) had thyroid dysfunction during 3 months after HSCT (29 euthyroid sick syndrome [ESS], 6 subclinical hyperthyroidism, 4 subclinical hypothyroidism, 3 hypothyroxinemia, 2 overt hyperthyroidism, and 1 high $T_4$ syndrome). In a univariate logistic regression analysis, age at HSCT (P=0.002) and acute GVHD (P=0.009) had statistically significant relationships with thyroid dysfunction during 3 months after HSCT. Also, in a univariate logistic regression analysis, ESS (P=0.014) showed a strong statistically significant association with mortality. Conclusion: In our study 27.1% patients experienced thyroid dysfunction during 3 months after HSCT. Increase in age and acute GVHD may be risk factors for thyroid dysfunction during 3 months after HSCT. There was a significant association between ESS and mortality.
Journal of The Korean Society of Clinical Toxicology
/
v.9
no.2
/
pp.39-48
/
2011
In mass casualty situation due to radiological accidents, it is important to start aggressive management with rapid triage decisions. External contamination needs immediate decontamination and internal contamination should be treated with special expertise and equipment to prevent the rapid uptake of radionuclides by target organs. Acute radiation syndrome shows a sequence of events that varies with the severity of the exposure. More severe exposures generally lead to more rapid onset of symptoms and severe clinical findings. After the massive exposure, various systems of the body reflect their severe damages that can lead to death within hours or up to several months. The disease progression has classically been divided into four stages: prodromal, latent, manifest illness, and recovery or death. Three characteristic clusters of symptoms including the hematopoietic syndrome, the gastrointestinal syndrome and the cerebrovascular syndrome are all associated with the acute radiation syndrome. The standard medical management of the patients with a potentially survivable radiation exposure includes good medical, surgical and supportive measures. Specific treatment with cytokines and bone marrow transplantation should be considered. The management of internal contamination is much the same as the treatment of poisoning. The standard decontamination should be applied to reduce uptake, and the chelating agents can be administered to enhance the clearance of radioisotopes. Radioactive iodine ($^{131}I$) as one of the nuclear fission products can increase the incidence of thyroid cancer in children. Potential benefit of potassium iodide prophylaxis is greater especially in neonates, infants and small children.
The radioprotective effects of Melatonin and Ge-132 on acute hematopoietic injury was investigated in mice exposed to an acute whole-body radiation dose of 8 Gy. Melatonin was administered intraperitoneally 1 hour before irradiation at a dose of 200 mg/kg, and Ge-132 was administered orally from days 5 to 20 after irradiation at a dose 130 - 150 mg/kg/d. The radioprotective effects were evaluated for spleen using TUNEL assay, and in peripheral blood by counting lymphocyte & WBC. The 4 experimental groups (irradiation-only, melatonin pretreatment, Ge-132 posttreatment, and melatonin pretreatment plus Ge-132 posttreatment) were observed for survival analysis up to 30 days following irradiation. The apoptotic index (47.8% vs 45.9%, p=0.385), and the number of lymphocytes ($97/{\mu}{\ell}\;vs\;101/{\mu}{\ell}$, p=0.898) were not significantly different between the irradiation-only and the melatonin pretreatment group, But the number of WBCs ($147/{\mu}{\ell}\;vs\;306/{\mu}{\ell}$, p=0.010) was higher in the melatonin pretreatment group. The irradiation-only, melatonin, Ge-132, and melatonin plus Ge-132 treatments resulted in survival rate at 30 days of 21.4%, 100%, 35.7%, and 85.7%, respectively. The melatonin pretreatment group in survival analysis between groups was showed significantly higher survival than the irradiation-only(p=0.000), or Ge-132 posttreatment group(p=0.0003). These results indicate that the melatonin may have a potential as an effective radioprotector on acute hematopoietic syndrome following radiation exposure.
Beginning in the summer of 1993, a serious mortality among cultured penaeid shrimp occurred in the western sea of Korea. The typical sign of this disease was white spots inside the surface of the carapace. Cytopathic effect (CPE) were not observed by virus in CHSE-214, RTG-2, but not by pH 11. A nonoccluded rod-shaped form virus was observed by electron microscopy in the lymphoid organ. The virion was bacilliform virus and sourrounded by a virion envelope. Its virion protein was found to be similar to hypodermal and hematopoietic necrosis virus (HHNBV) by analysis of virion proteins in SDS-PAGE. The genome of virus is double stranded DNA molecule whose full length was about 114kb. It was similar to penaeus acute viremia (PAV) of Japan.
Chaudhary, Ajay K;Chaudhary, Shruti;Ghosh, Kanjaksha;Shanmukaiah, Chandrakala;Nadkarni, Anita H
Asian Pacific Journal of Cancer Prevention
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v.17
no.3
/
pp.1519-1529
/
2016
Background: Matrix metalloproteinase -2 (gelatinase-A, Mr 72,000 type IV collagenase, MMP-2) and -9 (gelatinase-B, Mr 92,000 type IV collagenase, MMP-9) are key molecules that play roles in tumor growth, invasion, tissue remodeling, metastasis and stem-cell regulation by digesting extracellular matrix barriers. MMP-2 and -9 are well known to impact on solid cancer susceptibility, whereas, in hematological malignancies, a paucity of data is available to resolve the function of these regulatory molecules in bone marrow mononuclear cells (BM-MNCs) and stromal cells of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Objectives: The present study aimed to investigate mRNA expression and gelatinase A and B secretion from BM-MNCs in vitro and genotypic associations of MMP-2 (-1306 C/T; rs243865), MMP-9 (-1562 C/T; rs3918242), tissue inhibitor of metalloproteinase -1 (TIMP-1) (372T/C; rs4898, Exon 5) and TIMP-2 (-418G/C; rs8179090) in MDS and AML. Results: The study covered cases of confirmed MDS (n=50), AML (n=32) and healthy controls (n=110). MMP-9 mRNA expression revealed 2 fold increased expression in MDS-RAEB II and 2.5 fold in AML M-4 (60-70% blasts). Secretion of gelatinase-B also revealed the MMP-9 mRNA expression and ELISA data also supported these data. We noted that those patients having more blast crises presented with more secretion of MMP-9 and its mRNA expression. In contrast MMP-9 (-1562 C/T) showed significant polymorphic associations in MDS (p<0.02) and AML (p<0.02). MMP-9 mRNA expression of C/T and T/T genotypes were 1.5 and 2.5 fold increased in MDS and AML respectively. In AML, MMP-2 C/T and T/T genotypes showed 2.0 fold mRNA expression. Only MMP-9 (-1306 C/T) showed significant 4 fold (p<0.001) increased risk with chemical and x-ray exposed MDS, while tobacco and cigarette smokers have 3 fold (p<0.04) risk in AML. Conclusions: In view of our results, MMP-9 revealed synergistic secretion and expression in blast crises of MDS and AML with 'gene' polymorphic effects and is significantly associated with increased risk with tobacco, cigarette and environmental exposure. Release and secretion of these enzymes may influence hematopoietic cell behavior and may be important in the clinical point of view. It may offer valuable tools for diagnosis and prognosis, as well as possible targets for the treatments.
Purpose : In most cases, myelodysplastic syndrome(MDS) transforms into a more aggressive state or acute myelogenous leukemia; it's prognosis is very poor. It is believed that hematopoietic stem cell transplantation(HSCT) is the only curative treatment of MDS, but available data in children are very sparse. In this report, the short term outcome of HSCT in childhood MDS was analyzed. Methods : Ten children with MDS(CMMoL 5, RAEB 3, RAEBt 2) underwent HSCT(HLA-matched sibling transplantation 4, HLA-matched unrelated transplantation 4, cord blood transplantation 1, HLA-mismatched familial transplantation 1) between November 1995 and January 2001 at St. Mary's Hospital. Median follow-up duration was 11 months. Results : Engraftment was successful in all cases and 8 patients are alive without disease. Three cases of VOD were observed and improved without complication. Four cases of grade II and 1 case of grade III acute GVHD were observed and well controlled with treatment. Three patients relapsed after transplantation. One patient is alive without disease after cytoreduction with allogenic stem cell rescue and 2 patients died of relapse. Conclusion : HSCT is a curative strategy of MDS and the survival rate is relatively higher than that of adults. But there is an obvious need for more studies because of the small number of patients and the short duration of the follow-up.
Background: The complication rate of fungal disease is higher among patients with hematological malignancies. We investigated the clinicobacteriological outcomes of resected pulmonary fungal infections complicating hematological malignancies. Methods: Between 2001 and 2017, 21 patients with pulmonary fungal infections complicating hematological malignancies underwent resection, and their clinical records and survival were retrospectively reviewed. Results: The median age of the patients was 47 years, and 13 were male. The histological diagnoses were pulmonary aspergillosis (19 cases), mucormycosis (1 case), and cryptococcosis (1 case). The indications for surgery were resistance to antifungal therapy and the necessity of surgery before hematopoietic stem cell transplantation in 13 and 8 cases, respectively. The diagnoses of the hematological malignancies were acute myelogenous leukemia (10 cases), acute lymphocytic leukemia (5 cases), myelodysplastic syndrome (3 cases), and chronic myelogenous leukemia, malignant lymphoma, and extramedullary plasmacytoma (1 case each). The surgical procedures were partial resection (11 cases), segmentectomy (5 cases), lobectomy (4 cases), and cavernostomy (1 case). The size of the lesions was 0.9-8.5 cm. Fourteen cases had cavitation. There were no surgical-related deaths or fungal progression. Conclusion: Pulmonary fungal infections are resistant to treatments for hematological malignancies. Since the treatment of the underlying disease is extended and these infections often recur and are exacerbated, surgery should be considered when possible.
Purpose: Lymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT). Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's posttransplant immune reconstitution, and therefore require investigation. Methods: The time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK) cell recovery. The impact of pre- and post-transplant variables, including diagnosis of Epstein-Barr virus (EBV) DNAemia posttransplant, on lymphocyte recovery was evaluated. Results: The lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells, and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of $CD16^+/56^+$ cell recovery. Younger patients showed delayed recovery of both $CD3^+/CD8^+$ and $CD19^+$ cells. EBV DNAemia had a deleterious impact on the recovery of both $CD3^+$ and $CD3^+/CD4^+$ lymphocytes at 1 year post-transplant. Conclusion: In our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells.
Lee, Seon-Ju;Lee, Jae-Wook;Lee, Dae-Hyoung;Kwon, Young-Joo;Park, Young-Shil;Hwang, Hui Sung;Kim, Sun Young;Park, Ji Kyoung;Jang, Pil-Sang;Jung, Min-Ho;Chung, Nak-Gyun;Jeong, Dae-Chul;Cho, Bin;Kim, Hack-Ki;Lee, Byung-Churl
Clinical and Experimental Pediatrics
/
v.49
no.11
/
pp.1211-1215
/
2006
Purpose : In this study, we analyzed the short term changes of thyroid function, incidence and risk factors of thyroid dysfunction soon after allogeneic hematopoietic stem cell transplantation (HSCT) in children. Methods : We enrolled 80 pediatric patients following allogeneic HSCT, at the Catholic HSCT center between January, 2004 and February, 2006. Serum TSH (thyroid stimulating hormone), total serum thyroxine and total serum triiodothyronine levels were systematically measured in 80 patients before the HSCT, and at 1 month, 6 months and 12 months after HSCT. Results : Thyroid function statistically decreased at 1 month after HSCT(P<0.001). Thyroid dysfunction at 1 month was observed in 43 (54 percent) of 80 patients, 31 (39 percent) of whom presented with euthyroid sick syndrome (ETS). Thyroid dysfunction was normalized within 1 year after HSCT. In univariate analysis, malignant disease and the presence of acute graft-versus-host disease (grade ${\geq}II$) were risk factors for ETS (P=0.04, 0.01 respectively). In multivariate analysis, we could not detect an independent risk factor for ETS (P=0.19, 0.06 respectively). Conclusion : The present study suggests that the incidence of thyroid dysfunction is high after allogeneic HSCT. Therefore, regular monitoring of thyroid hormone levels after HSCT is required.
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