[show abstract][hide abstract] ABSTRACT: Purpose: We evaluated the effect of human parathyroid hormone (hPTH) on the engraftment and/or in vivo expansion of hematopoietic stem cells in an umbilical cord blood (UCB)-xenotransplantation model. In addition, we assessed its effect on the expression of cell adhesion molecules. Materials and Methods: Female NOD/SCID mice received sublethal total body irradiation with a single dose of 250 cGy. Eighteen to 24 hours after irradiation, 1×10(7) human UCB-derived mononuclear cells (MNCs) and 5×10(6) human UCB-derived mesenchymal stem cells (MSCs) were infused via the tail vein. Mice were randomly divided into three groups: Group 1 mice received MNCs only, Group 2 received MNCs only and were then treated with hPTH, Group 3 mice received MNCs and MSCs, and were treated with hPTH. Results: Engraftment was achieved in all the mice. Bone marrow cellularity was approximately 20% in Group 1, but 70-80% in the hPTH treated groups. Transplantation of MNCs together with MSCs had no additional effect on bone marrow cellularity. However, the proportion of human CD13 and CD33 myeloid progenitor cells was higher in Group 3, while the proportion of human CD34 did not differ significantly between the three groups. The proportion of CXCR4 cells in Group 3 was larger than in Groups 1 and 2 but without statistical significance. Conclusion: We have demonstrated a positive effect of hPTH on stem cell proliferation and a possible synergistic effect of MSCs and hPTH on the proportion of human hematopoietic progenitor cells, in a xenotransplantation model. Clinical trials of the use of hPTH after stem cell transplantation should be considered.
Yonsei medical journal 01/2013; 54(1):238-45. · 0.77 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gelsolin and matrix metalloproteinase 12 (MMP12) expression has been reported in Langerhans cell histiocytosis (LCH), but the clinical significance of this expression is unknown. We investigated the associations of these proteins with clinical manifestations in patients diagnosed with LCH.
We performed a retrospective analysis of clinical data from patients diagnosed with LCH and followed up between 1998 and 2008. Available formalin-fixed, paraffin-embedded specimens were used for gelsolin and MMP12 immunohistochemical staining. We analyzed the expression levels of these proteins and their associations with LCH clinical features.
Specimens from 36 patients (20 males, 16 females) with a diagnosis of LCH based on CD1a positivity with clinical manifestations were available for immunohistochemical staining. Median patient age was 62 months (range, 5 to 207). The expression of gelsolin varied; it was high in 17 patients (47.2%), low in 11 patients (30.6%), and absent in 8 patients (22.2%). The high gelsolin expression group had a higher tendency for multi-organ and risk organ involvement, although the trend was not statistically significant. MMP12 was detected only in 7 patients (19.4%) who showed multi-system involvement (P=0.018) and lower event-free survival (P=0.002) in comparison to patients with negative MMP12 staining.
Gelsolin and MMP12 expression may be associated with the clinical course of LCH, and MMP12 expression may be particularly associated with severe LCH. Further studies of larger populations are needed to define the precise role and significance of gelsolin and MMP12 in the pathogenesis of LCH.
The Korean journal of hematology 12/2012; 47(4):267-72.
[show abstract][hide abstract] ABSTRACT: The triad of rash, arthritis, and uveitis seems to be characteristic for early-onset childhood sarcoidosis. We describe an interesting case of early-onset childhood sarcoidosis coexisting enchondromatosis, which clinically masquerade as Langerhans cell histiocytosis. A 33 months old girl presented with skin rash, subcutaneous nodules with polyarthritis, and revealed the involvement of lymph nodes as well as spleen during work-up. She also presented with multiple osteolytic lesions which pathologically proven enchondromatosis. Oral prednisone was prescribed at 2 mg/kg/day for 2 months until when subcutaneous nodules and joint swellings almost disappeared, and then slowly tapered over a period of 5 months. We report an unusual case of early-onset childhood sarcoidosis presented with osteolytic bone lesions which were irrelevant to sarcoidosis.
Journal of Korean medical science 01/2012; 27(1):96-100. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: We analyzed acute neurotoxic problems attributable to chemotherapy or immunosuppression in the context of childhood neoplastic diseases, based on clinical and neuroradiologic findings. This retrospective single-center study reviewed the acute neurologic complications of 62 children receiving conventional chemotherapy or hematopoietic stem cell transplantation from July 2005-July 2008. We excluded patients with central nervous system metastasis and various neurotoxic manifestations not usually requiring cranial magnetic resonance imaging. Of 62 patients, 12 (19.3%) developed acute neurologic complications. The most common complications included posterior reversible encephalopathy syndrome in six of 12 (50%) patients, and Wernicke's encephalopathy in three of 12 (25%) patients. Other complications included chemical arachnoiditis, grey matter injury induced by postchemotherapeutic angiopathy, and leukoencephalopathy. Posterior reversible encephalopathy syndrome was accompanied by hypertensive episodes in most patients (5/6), and Wernicke's encephalopathy was evident with altered mental status in malnourished children. These data indicate that posterior reversible encephalopathy syndrome and Wernicke's encephalopathy are the predominant complications in children undergoing chemotherapy or hematopoietic stem cell transplantation. Early radiologic and clinical evaluation and prompt treatment for these complications are necessary to prevent their progression to irreversible brain damage.
[show abstract][hide abstract] ABSTRACT: Functioning adrenocortical oncocytomas are extremely rare and most reported patients are 40-60 yr of age. To our knowledge, only 2 cases of functioning adrenocortical oncocytomas have been reported in childhood. We report a case of functioning adrenocortical oncocytoma in a 14-yr-old female child presenting with virilization. She presented with deepening of the voice and excessive hair growth, and elevation of plasma testosterone and dehydroepiandrosterone sulfate. She had an adrenalectomy. The completely resected tumor composed predominantly of oncocytes without atypical mitosis and necrosis. A discussion of this case and a review of the literature on this entity are presented.
Journal of Korean medical science 07/2010; 25(7):1077-9. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hyponatremia is a common metabolic disorder in cancer patients. However, little information is available for patients receiving chemotherapy or stem cell transplantation (SCT). We analyzed the frequency, characteristics, and various causes of hyponatremia including routine use of hypotonic fluids in children following chemotherapy or SCT.
We reviewed the clinical and laboratory data of 63 children who received chemotherapy or SCT at the Department of Pediatrics, Hanyang University Medical Center from July 2005 to July 2008.
All 63 patients at admission received routine parenteral fluids of 0.25% or 0.45% NaCl and 82 episodes of hyponatremia were observed in 40 (63.5%) patients. Of these 82 episodes, 50 episodes of hyponatremia developed in 29 children following chemotherapy and 32 episodes in 16 children following SCT. Seventy-six out of 82 episodes (92.7%) of hyponatremia developed in 37 patients receiving hypotonic fluids with NaCl concentrations between 30 and 150 mEq/L. The frequency of SIADH in the SCT setting was more frequent (14/21, 66.6%) than in the chemotherapy setting (18/58, 31.0%) (P = 0.02), even though the leading cause of hyponatremia was SIADH in both settings.
SIADH is a leading cause of hyponatremia in children following chemotherapy or SCT, and more frequent in SCT settings than in chemotherapy settings. Furthermore, the routine use of hypotonic fluids which could aggravate the development of hyponatremia for these patients should be avoided and then switched to isotonic fluids.
Pediatric Blood & Cancer 03/2010; 54(5):734-7. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: Drug-induced neutropenia (DIN), particularly that in which antibiotic-dependent antineutrophil antibodies have been detected, is a rare disorder. We report the case of a child with pneumococcal pneumonia, who experienced severe neutropenia during various antibiotic treatments. We detected 4 kinds (cefotaxim, augmentin, vancomycin, and tobramycin) of antibiotic-dependent antineutrophil antibodies by using the mixed passive hemagglutination assay (MPHA) technique with this child.
Journal of Korean medical science 10/2009; 24(5):975-8. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: We present two cases of Wiskott-Aldrich syndrome (WAS), in which nonsense mutations in the WASP gene were corrected phenotypically as well as genotypically by unrelated cord blood stem cell transplantation (CBSCT). Two male patients were diagnosed with WAS at the age of 5-month and 3-month and each received unrelated CBSCT at 16-month and 20-month of age, respectively. The infused cord blood (CB) units had 4/6 and 5/6 HLA matches and the infusion doses of total nucleated cells (TNC) and CD34+ cells were 6.24x10(7)/kg and 5.08x10(7)/kg for TNC and 1.33x10(5)/kg and 4.8x10(5)/kg for CD34+ cells, for UPN1 and UPN2, respectively. Complete donor cell chimerism was documented by variable number tandem repeat (VNTR) with neutrophil engraftment on days 31 and 13 and platelets on days 58 and 50, respectively. Immunologic reconstitution demonstrated that CBSCT resulted in consistent and stable T-, B-, and NK-cell development. Flow cytometric analysis for immunologic markers and sequence analysis of the WASP gene mutation revealed a normal pattern after CBSCT. These cases demonstrate that CBs can be an important source of stem cells for the phenotypical and genotypical correction of genetic diseases such as WAS.
Journal of Korean medical science 09/2009; 24(4):751-4. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: A 14-year-old male, who completed chemotherapy following limb salvage surgery for osteosarcoma approximately 2 years ago, was seen for routine follow-up. A CT scan revealed new scattered multifocal nodular lesions. An ultrasonography-guided percutaneous needle biopsy was done to confirm pulmonary metastasis of the underlying osteosarcoma. The lung biopsy showed findings of eosinophilic pneumonia with no evidence of malignancy. Peripheral eosinophilia was also noted. When a more thorough history revealed frequent intake of raw cow liver, we diagnosed pulmonary toxocariasis by ELISA for specific serum IgG antibody.
Pediatric Blood & Cancer 08/2009; 53(7):1343-5. · 2.35 Impact Factor
[show abstract][hide abstract] ABSTRACT: The clinical findings of fever and skin rash with or without evidence of fluid retention, which mimic engraftment syndrome, have been observed during the pre-engraftment period in patients undergoing hematopoietic stem cell transplantation. In order to characterize this newly observed clinical syndrome called pre-engraftment syndrome (pES), we retrospectively analyzed the clinical records of 50 patients. Three out of 14 patients (23.1%) who underwent cord blood stem cell transplantation developed non-infectious fever, skin rash, and tachypnea 4-15 days prior to neutrophil engraftment. Two patients spontaneously recovered with fluid restriction and oxygen inhalation. One patient died of a complicated pulmonary hemorrhage in spite of aggressive supportive therapy and steroid treatment. Four out of 23 patients (17.4%) who underwent allogeneic bone marrow transplantation developed non-infectious fever and skin rash 4 to 5 days prior to neutrophil engraftment. All four of these patients recovered with only steroid treatment. These characteristic findings were not observed in patients who had undergone autologous peripheral blood stem cell transplantation. Interestingly, the speed of neutrophil engraftment was significantly faster for the patients suffering from pre-engraftment syndrome. The close observation and further pathophysiological research are required to better understand this syndrome.
Journal of Korean Medical Science 03/2008; 23(1):98-103. · 1.25 Impact Factor