-
Tri Budi Hartomo,
Aiko Kozaki,
Daiichiro Hasegawa,
Thi Van Huyen Pham,
Nobuyuki Yamamoto,
Atsuro Saitoh,
Toshiaki Ishida,
Keiichiro Kawasaki,
Yoshiyuki Kosaka,
Hiroki Ohashi, [......],
Satoshi Hirase,
Ikuko Kubokawa,
Takeshi Mori,
Tomoko Yanai, Akira Hayakawa,
Yasuhiro Takeshima,
Kazumoto Iijima,
Masafumi Matsuo,
Hisahide Nishio,
Noriyuki Nishimura
[show abstract]
[hide abstract]
ABSTRACT: Minimal residual disease (MRD) is derived from tumor-initiating cells (TICs) and is responsible for tumor relapse. Neuroblastoma is characterized by extreme tumor heterogeneity, and more than half of high-risk patients experience tumor relapse. To overcome tumor heterogeneity and achieve more sensitive detection of MRD, several sets of real-time RT-PCR markers have been reported for MRD monitoring in neuroblastoma patients from different centers. However, these markers vary across centers and are still being validated. In the present study, we validated the ability of 14 commonly used real-time RT-PCR markers to detect MRD based on their expression in neuroblastoma TICs, and we developed a novel MRD detection protocol, which scored the samples as MRD-positive when the expression of one of the 11 real-time RT-PCR markers (CHRNA3, CRMP1, DBH, DCX, DDC, GABRB3, GAP43, ISL1, KIF1A, PHOX2B and TH) exceeded the normal range. By using this protocol, we prospectively monitored MRD in 73 bone marrow (BM), 12 peripheral blood stem cell and 8 peripheral blood samples from 14 neuroblastoma patients treated at a single center. We scored 100, 56, 56 and 57% BM cytology-positive, elevated vanillylmandelic acid (VMA), elevated homovanillic acid (HVA) and elevated neuron-specific enolase (NSE) samples as MRD-positive, respectively. MRD was also positive in 48, 45, 46 and 43% of the BM cytology-negative and normal VMA, normal HVA and normal NSE samples, respectively. These results suggest that the present MRD detection protocol based on the expression of a set of 11 real-time RT-PCR markers in neuroblastoma TICs achieves sensitive MRD monitoring in neuroblastoma patients.
Oncology Reports 04/2013; 29(4):1629-36. · 1.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Although secondary renal involvement of non-Hodgkin lymphoma is frequently encountered, primary renal lymphoma is quite rare. We present a pediatric case of primary renal diffuse large B-cell lymphoma.
A 12-year-old girl presenting with gross hematuria was referred to our hospital. Abdominal ultrasonography and imaging revealed a mass lesion in the superior pole of the right kidney. Serum creatinine and blood urea nitrogen levels were within normal ranges. Preoperative assessment of the mass indicated unspecified renal tumor. Right nephrectomy was performed and pathological examination showed diffuse large B-cell lymphoma. Postoperative fluorodeoxyglucose-positron emission tomography/computed tomography showed a small high-uptake lesion in the thyroid gland and aspiration cytology of the thyroid tumor demonstrated involvement of lymphoma, so stage III tumor diagnosed. After one course of chemotherapy, the patient achieved complete remission. She remains alive without disease, 3 years after completing a total of six courses of chemotherapy.
Primary renal lymphoma is a very rare entity and preoperative diagnosis may be difficult. However, this entity is often reported to show clinically aggressive characteristics and therefore should be considered among the differential diagnoses for unusual renal tumors in pediatric patients.
The American journal of case reports. 01/2013; 14:34-7.
-
[show abstract]
[hide abstract]
ABSTRACT: Ewing sarcoma family of tumors is the second most common primary bone tumor of childhood. Extraosseous Ewing sarcoma family of tumors is rare. We present a pediatric case of primary endobronchial Ewing sarcoma family of tumors.
A 12-year-old boy presented with dyspnea and chest radiography showed right pulmonary atelectasis. Chest computed tomography demonstrated tumor in the right main bronchus. Histopathological examination of the resected tumor demonstrated Ewing sarcoma family of tumors. No other lesions were detected throughout the body and the right main bronchus was thought to be the primary site. As of 1 year and 6 months after further resection of residual tumor followed by chemotherapy and radiotherapy, the patient remains disease-free.
Extraosseous Ewing sarcoma family of tumors arises in soft tissues of the trunk or extremities, but primary endobronchial Ewing sarcoma family of tumors has rarely been reported. Although quite rare, Ewing sarcoma family of tumors should be considered among the differential diagnoses for pediatric bronchial tumor.
The American journal of case reports. 01/2013; 14:67-9.
-
Thi Van Huyen Pham,
Tri Budi Hartomo,
Myeong Jin Lee,
Daiichiro Hasegawa,
Toshiaki Ishida,
Keiichiro Kawasaki,
Yoshiyuki Kosaka,
Tomoto Yamamoto,
Satoru Morikawa,
Nobuyuki Yamamoto,
Ikuko Kubokawa,
Takeshi Mori,
Tomoko Yanai, Akira Hayakawa,
Yasuhiro Takeshima,
Kazumoto Iijima,
Masafumi Matsuo,
Hisahide Nishio,
Noriyuki Nishimura
[show abstract]
[hide abstract]
ABSTRACT: Neuroblastoma is an aggressive pediatric tumor that accounts for 15% of cancer-related deaths in children. More than half of high-risk neuroblastoma patients develop tumor relapse that is lethal in most cases. A small population of tumor-initiating cells (TICs), recently identified from high-risk neuroblastoma patients as spheres, is believed to be responsible for tumor relapse. Rab family small G proteins are essential in controlling membrane traffic and their misregulation results in several cancers. Rab15 was originally isolated as a brain-specific Rab protein regulating the endocytic recycling pathway and was recently identified as a downstream target of the neural transcription factor Atoh1. Previously, we identified two alternatively spliced Rab15 isoforms in neuroblastoma cells and showed a significant correlation between Rab15 expression and neuronal differentiation. As aberrant alternative splicing is intimately associated with an increasing number of cancers, its use as a new diagnostic and/or prognostic biomarker has attracted considerable attention. In the present study, we explored cancer-associated changes of Rab15 alternative splicing in neuroblastoma TICs. We found that Rab15 alternative splicing generated two novel isoforms designated as Rab15(AN2) and Rab15(AN3) in addition to two known isoforms designated as Rab15(CN) and Rab15(AN1). Although both Rab15(AN2) and Rab15(AN3) contained premature termination codons, they were detected in not only neuroblastoma cells but also in normal human tissues. One isoform was predominantly expressed in the brain and testis, while the other isoform was more specifically expressed in the brain. In neuroblastoma, Rab15 isoform balance measured by the Rab15(CN)/Rab15(AN1+AN2+AN3) ratio was significantly decreased in spheres compared to parental cells. These results suggest that Rab15 alternative splicing may serve as a biomarker to discriminate TICs from non-TICs in neuroblastoma.
Oncology Reports 03/2012; 27(6):2045-9. · 1.84 Impact Factor
-
Tomoko Yanai,
Satoshi Hirase,
Natsuki Matsunoshita,
Nobuyuki Yamamoto,
Takeshi Ninchoji,
Ikuko Kubokawa,
Takeshi Mori, Akira Hayakawa,
Yasuhiro Takeshima,
Kazumoto Iijima,
Masafumi Matsuo
[show abstract]
[hide abstract]
ABSTRACT: Place of death is an important issue at the end-of-life. It is poorly understood in pediatric cancer patients in Japan. This study aimed to clarify place of death of children with cancer as well as variables associated with place of death. Study population was pediatric cancer patients who died in the Department of Pediatrics at Kobe University Hospital during the last 7 years. The medical records were retrospectively reviewed regardless of cause of death to derive data relating to patients' characteristics and disease. 18 patients were included. Median age at death was 12.2 years old. 6 patients including 5 children in complete remission had hematological disease and 12 patients suffered from solid tumors. 4 patients (22.2%) died at home, whereas 14 patients (77.8%) died in the hospital including 6 ICU deaths. No one died in hospices. Preference of patients was unavailable due to the lack of inquiry. Factors influencing place of death (home, ICU, non-ICU) were disease (hematological disease vs. solid tumor, p=0.010, brain tumor vs. non-brain tumor, p=0.023), disease status (complete remission vs. non-complete remission, p=0.0014) and preference of families (p=0.029). Among 6 families who expressed preference, no disparity was observed between actual and preferred place of death. This is the first English publication of place of death of pediatric cancer patients in Japan. The low percentage of home death, factors influencing place of death and the lack of disparity between actual and preferred place of death were indicated. Further studies are required to better understand place of death.
The Kobe journal of medical sciences 01/2012; 58(2):E33-40.
-
Noriyuki Nishimura,
Tri Budi Hartomo,
Thi Van Huyen Pham,
Myeong Jin Lee,
Tomoto Yamamoto,
Satoru Morikawa,
Daiichiro Hasegawa,
Hiroki Takeda,
Keiichiro Kawasaki,
Yoshiyuki Kosaka,
Nobuyuki Yamamoto,
Ikuko Kubokawa,
Takeshi Mori,
Tomoko Yanai, Akira Hayakawa,
Yasuhiro Takeshima,
Kazumoto Iijima,
Masafumi Matsuo,
Hisahide Nishio
[show abstract]
[hide abstract]
ABSTRACT: A growing number of epidemiological studies have demonstrated that the consumption of green tea inhibits the growth of a variety of cancers. Epigallocatechin gallate (EGCG), the most abundant catechin in green tea, has been shown to have an anti-cancer effect against many cancers. Most cancers are believed to be initiated from and maintained by a small population of tumor-initiating cells (TICs) that are responsible for chemotherapeutic resistance and tumor relapse. In neuroblastoma, an aggressive pediatric tumor that often relapses and has a poor prognosis, TICs were recently identified as spheres grown in a serum-free non-adherent culture used for neural crest stem cell growth. Although EGCG has been reported to induce growth arrest and apoptosis in neuroblastoma cells, its effect on neuroblastoma TICs remains to be defined.
Gene expression was analyzed by real-time reverse transcription polymerase chain reaction (RT-PCR). The effects of EGCG on cell proliferation, apoptosis, and sphere formation were determined by cell counting, propidium iodide staining, and sphere (>100 μm in diameter) counting, respectively.
Neuroblastoma BE(2)-C cells showed increased expression of stem cell markers (nanog homeobox [NANOG] and octamer-binding transcription factor 4 [OCT4]), as well as decreased expression of neuronal differentiation markers (Cu(2+)-transporting ATPase alpha polypeptide [ATP7A] and dickkopf homolog 2 [DKK2]) in spheres grown in serum-free non-adherent culture, compared to parental cells grown in conventional culture. Although EGCG induced growth arrest and apoptosis in the parental cells in a dose-dependent manner, it was not effective against spheres. However, EGCG potently inhibited sphere formation in the BE(2)-C cells.
The present results suggest that EGCG may inhibit the development of TICs in BE(2)-C cells.
Environmental Health and Preventive Medicine 09/2011; 17(3):246-51.
-
Keisuke Otsubo,
Hirokazu Kanegane,
Yoshiro Kamachi,
Ichiro Kobayashi,
Ikuya Tsuge,
Masue Imaizumi,
Yoji Sasahara, Akira Hayakawa,
Kandai Nozu,
Kazumoto Iijima,
Shuichi Ito,
Reiko Horikawa,
Yoshinori Nagai,
Kiyoshi Takatsu,
Hisashi Mori,
Hans D Ochs,
Toshio Miyawaki
[show abstract]
[hide abstract]
ABSTRACT: Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is an autoimmune disorder caused by mutations in the FOXP3 gene, which plays a key role in the generation of CD4(+)CD25(+)regulatory T (Treg) cells. We selected CD127 as the surface marker of Treg cells to illustrate the development and function of Treg cells in IPEX syndrome. CD4(+)CD25(+)FOXP3(+) T cells, the putative Treg cells, were almost completely absent in all patients. Importantly, a substantial number of CD4(+)CD25(+)CD127(low) T cells were observed in 3 IPEX patients with hypomorphic mutations in the FOXP3 gene. We demonstrated that CD4(+)CD25(+)CD127(low) T cells isolated from these 3 patients exhibited an appreciable suppressive activity on effector T cell proliferation, although less than that displayed by Treg cells from healthy controls. These results suggest that genetically altered FOXP3 can drive the generation of functionally immature Treg cells, but that intact FOXP3 is necessary for the complete function of Treg cells.
Clinical Immunology 07/2011; 141(1):111-20. · 4.05 Impact Factor
-
Noriyuki Nishimura,
Thi Van Huyen Pham,
Tri Budi Hartomo,
Myeong Jin Lee,
Daiichiro Hasegawa,
Hiroki Takeda,
Keiichiro Kawasaki,
Yoshiyuki Kosaka,
Tomoto Yamamoto,
Satoru Morikawa,
Nobuyuki Yamamoto,
Ikuko Kubokawa,
Takeshi Mori,
Tomoko Yanai, Akira Hayakawa,
Yasuhiro Takeshima,
Hisahide Nishio,
Masafumi Matsuo
[show abstract]
[hide abstract]
ABSTRACT: Neuroblastoma is the most common extracranial solid tumor in children and accounts for 15% of pediatric cancer deaths. Although retinoic acid (RA) is currently used to treat high-risk neuroblastoma patients in the clinic, RA-responsiveness is variable and unpredictable. Since no alterations in the RA-signaling pathway have been found in neuroblastoma cells, molecules correlated with RA-induced differentiation will provide predictive markers of RA-responsiveness for clinical use. The Rab family of small G proteins are key regulators of membrane traffic and play a critical role in cell differentiation and cancer progression. Although an increasing number of cancer-associated alternative splicing events have been identified, alternative splicing of Rab proteins remains to be characterized in neuroblastoma. In the present study, we focused on Rab15 that was originally identified as a brain-specific Rab protein and regulates the endocytic recycling pathway. We identified alternatively spliced Rab15 isoforms designated as Rab15CN and Rab15AN in neuroblastoma cells. Rab15CN was composed of 7 exons encoding 212 amino acids and showed brain-specific expression. Alternative splicing of exon 4 generated Rab15AN that was predicted to encode 208 amino acids and was predominantly expressed in testis. RA induced neuronal differentiation of neuroblastoma BE(2)-C cells and specifically up-regulated Rab15CN expression. Reciprocally, RA-induced differentiation was observed in Rab15CN-expressing BE(2)-C cells in preference to Rab15AN-expressing BE(2)-C cells. Furthermore, Rab15CN expression was also specifically up-regulated during RA-induced differentiation of newly established neuroblastoma cells from high-risk patients. These results suggest that Rab15 expression correlates with RA-induced differentiation of neuroblastoma cells.
Oncology Reports 07/2011; 26(1):145-51. · 1.84 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Febrile neutropenia (FN) is a life-threatening complication, and the primary cause of FN is considered to be microbial infection. Therefore, prompt and appropriate antimicrobial therapy is crucial. Clinicians usually prescribe antimicrobial therapy on the basis of presumptive and empirical data. This is because the causative pathogen for FN in blood culture (BC) analysis is detected several days after sampling. Polymerase chain reaction (PCR) analysis has been used for detecting the causative bacteria of infections. Here, we examined whether multiplex PCR is useful for detecting the causative pathogens for FN patients. We extracted DNA from the patients' whole blood and performed multiplex PCR. In total, 128 samples of 40 patients clinically diagnosed with FN were used in this study. Multiplex PCR analysis revealed the causative pathogen in 3 patients with FN; the DNA fragments amplified were those of Pseudomonas aeruginosa in 2 cases and Psedomonas putida in 1 case. These patients could be started on appropriate antimicrobial therapy a few hours after sampling. However, the DNA fragment of the causative pathogen could not be amplified by PCR in 2 patients, although BC analysis did detect the causative bacteria. Thus, we conclude that multiplex PCR is serviceable in case of FN because of its rapidness. However, BC is also indispensable to treating FN owing to its high sensitivity.
The Kobe journal of medical sciences 01/2011; 57(2):E32-7.
-
Takeshi Mori,
Noriyuki Nishimura,
Daiichiro Hasegawa,
Keiichiro Kawasaki,
Yoshiyuki Kosaka,
Kazuko Uchide,
Tomoko Yanai, Akira Hayakawa,
Yasuhiro Takeshima,
Hisahide Nishio,
Masafumi Matsuo
[show abstract]
[hide abstract]
ABSTRACT: Most chromosomal rearrangements including the mixed lineage leukemia (MLL) gene are manifested as leukemia and predict a poor prognosis. Although more than 50 MLL-rearrangement partners are characterized, MLL-related leukemogenesis remains to be understood. Here we report a case of a 3-year old boy bearing a novel MLL-rearrangement with the suppressor of actin mutations 1-like (SACM1L) gene in the absence of leukemia. Bone marrow cells harboring the MLL-SACM1L rearrangement appeared during chemotherapy for acute lymphoblastic leukemia with hyperdiploidy and were continuously detected over 7 years without clonal expansion.
Leukemia research 10/2010; 34(10):1398-401. · 2.36 Impact Factor
-
Masanori Horinouchi,
Mariko Yagi,
Hiroyuki Imanishi,
Takeshi Mori,
Tomoko Yanai, Akira Hayakawa,
Yasuhiro Takeshima,
Michiyo Hijioka,
Noboru Okamura,
Toshiyuki Sakaeda,
Masafumi Matsuo,
Katsuhiko Okumura,
Tsutomu Nakamura
[show abstract]
[hide abstract]
ABSTRACT: The objective of this study was to identify novel pharmacogenetic determinants of treatment-related hepatotoxicity during the maintenance phase in children with acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL). Although the authors first determined whether genotypes of drug-metabolizing enzymes and transporters--glutathione S-transferase (GST) genes, GSTM1 positive/null, GSTT1 positive/null and GSTP1 A313G, methylenetetrahydrofolate reductase (MTHFR) C677T, reduced folate carrier 1 (RFC1) G80A, and breast cancer resistant protein (BCRP) C421A--were associated with hepatotoxicity for 24 patients, no significant difference was detected for genotype and allelic frequencies between the patients with and those without severe treatment-related hepatotoxicity. Therefore, the authors explored potential candidate polymorphisms associated with hepatotoxicity using the Illumina Infinium HumanHap300, encompassing more than 318,000 tag single-nucleotide polymorphisms (SNPs), for 8 of 24 patients with or without severe hepatotoxicity. Genome-wide genotyping uncovered a total of 28 candidate SNPs. rs1966862, in Rho GTPase-activating protein 24 (ARHGAP24), was the most significant of the candidates, and the genotypes of rs13424027 (PARD3B), rs1156304 (KCNIP4), rs10255262 (SLC13A1), rs7403531 (RASGRP1), and rs381423 (unidentified gene) were also significantly associated with severe hepatotoxicity. This study suggested rs1966862 (ARHGAP24) and the other SNPs to be predictive factors for drug-induced hepatotoxicity during the maintenance phase in pediatric patients with ALL or LBL.
Pediatric Hematology and Oncology 08/2010; 27(5):344-54. · 0.89 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Several studies have suggested that T cell-producing permeability factors might lead to proteinuria in minimal change nephrotic syndrome (MCNS). However, it is still unclear whether T-cell abnormalities cause MCNS. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder of the immune regulation system, which leads to severe autoimmune phenomena including autoimmune enteropathy, atopic dermatitis with high levels of serum immunoglobulin E (IgE), type 1 diabetes mellitus (T1DM), and severe infection such as sepsis, which frequently result in death within the first 2 years of life. This disease is caused by mutations in the FOXP3 gene that result in the defective development of regulatory T (Treg) cells. This report describes a 5-year-old boy with IPEX syndrome with a 3 bp deletion in the FOXP3 gene (c.748-750delAAG, p.250K.del) and a paucity of CD4(+) CD25(+) FOXP3(+) T cells. The boy's condition was complicated by MCNS in addition to many IPEX-related manifestations, such as atopic dermatitis, T1DM, enteropathy, sepsis and hemolytic anemia. This is the first report of IPEX syndrome complicated by MCNS, and our findings imply that Treg cell dysfunction may be crucial for the development of MCNS.
Pediatric Nephrology 03/2009; 24(6):1181-6. · 2.52 Impact Factor
-
Katsuyasu Saigo,
Yasuyuki Sakota,
Yukako Masuda,
Kyoko Matsunaga,
Mariko Takenokuchi,
Kunihiro Nishimura,
Takeshi Sugimoto,
Kosuke Sakurai,
Makoto Hashimoto,
Tomoko Yanai, Akira Hayakawa,
Yasuhiro Takeshima,
Tsutomu Nomura,
Yoshitsugu Kubota,
Shunichi Kumagai
[show abstract]
[hide abstract]
ABSTRACT: Immature or reticulated platelets are known as a clinical marker of thrombopoiesis. Recently, an automatic method was established to detect reticulated platelets as immature platelet fraction (IPF) by means of hematology analyzer XE-2100. We assessed the effects of IPF detection after chemotherapy for various pediatric malignant disorders of 16 patients. Our results indicate that IPF should be considered a useful marker of imminent platelet recovery so that unnecessary platelet transfusion can be avoided.
Transfusion and Apheresis Science 05/2008; 38(2):127-32. · 1.25 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Osteosarcoma (OS) remains a life-threatening malignancy and its molecular character is not fully understood. Ezrin is a cytoskeleton linker protein involved in regulating the growth and metastatic capacity of cancer cells. However, the correlation between ezrin mRNA expression and clinical severity has not yet been examined in OS biopsy samples. Furthermore, recent evidence has demonstrated that the level of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression is increased in human cancers of various origins, but this has not yet been examined in OS cells. To clarify the correlation between the clinical severity and the levels of ezrin and GAPDH mRNA expression, we quantified these mRNA levels in 4 pediatric OS biopsy samples using real-time quantitative polymerase chain reaction. Among these 4 samples, ezrin mRNA expression was approximately 5-fold higher in a case with lung metastasis compared with the other cases without metastasis, suggesting an association between the ezrin mRNA expression level and metastasis. On the other hand, the GAPDH mRNA expression level was not related to the clinical severity. This is the first report to demonstrate a high level of ezrin mRNA expression in an OS biopsy sample with lung metastasis.
Journal of Pediatric Hematology/Oncology 08/2007; 29(7):435-9. · 1.16 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Seven of 11 patients with acute myeloblastic leukemia (AML) had allele(s) in which more than half of 27 CpG sites in the p15 gene were methylated. The p15 CpG island region was surrounded with both the acetylated histone H3 (AcH3) and dimethylated histone H3-lysine 9 (MeH3K9) in bone marrow cells of AML patients, whereas with AcH3 alone in normal marrow cells. The p15 CpG islands of DNA immunoprecipitated with anti-AcH3 antibody and anti-MeH3K9 antibody were not always unmethylated and methylated, respectively, in the patients. These results suggest perturbed modifications of histone H3 around the p15 CpG island region in AML.
Leukemia Research 06/2007; 31(5):611-21. · 2.92 Impact Factor
-
Hiroyuki Imanishi,
Noboru Okamura,
Mariko Yagi,
Yukari Noro,
Yuka Moriya,
Tsutomu Nakamura, Akira Hayakawa,
Yasuhiro Takeshima,
Toshiyuki Sakaeda,
Masafumi Matsuo,
Katsuhiko Okumura
[show abstract]
[hide abstract]
ABSTRACT: Methotrexate is administered in high doses to treat childhood acute lymphoblastic leukemia and malignant lymphoma. Hepatotoxicity and bone marrow suppression often limit its use, however. The objective of this study was to determine the genetic polymorphisms associated with the hepatotoxicity and elimination of methotrexate. Genetic polymorphisms of glutathione S-transferase (GST) genes including GSTT1 positive/null, GSTM1 positive/null, and GSTP1 A313G, and genes for reduced folate carrier 1 G80A (RFC1 G80A), methylenetetrahydrofolate reductase C677T (MTHFR C677T), and breast cancer resistant protein C421A (BCRP C421A) were determined for 26 patients by the polymerase chain reaction (PCR) method or by direct sequencing. A high frequency of hepatotoxicity (P = 0.035) was observed for patients with GSTM1 positive and RFC1 AA(80), and serum concentrations of methotrexate 48 h after the start of infusion were higher for patients with the TT(677) genotype of MTHFR (P = 0.028). In conclusion, GSTM1 positive/null and RFC1 G80A polymorphisms could be predictors for hepatotoxicity, and the MTHFR C677T polymorphism is associated with elimination of methotrexate.
Journal of Human Genetics 02/2007; 52(2):166-71. · 2.57 Impact Factor
-
Journal of Pediatrics 08/2006; 149(1):145-6; author reply 146. · 4.11 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: The aim of the study was to clarify the relationship between current pet ownership, passive smoking, and allergic diseases among the Japanese children. From 1995 to 2001, we distributed the Japanese edition of the questionnaire of the American Thoracic Society and the Division of Lung Diseases (ATS-DLD) to survey allergic diseases among 35,552 6-yr-old children at primary school in the city of Himeji, Japan. We analyzed the data by multiple logistic regression and calculated adjusted odds ratios for environmental factors, including passive smoking and pet (dog and/or cat) ownership. There were no significant relationships between the prevalence of asthma and current pet ownership and passive smoking. However, current cat ownership was related to a significantly lower prevalence of atopic dermatitis [adjusted odds ratio (aOR) 0.79, 95% confidence interval (CI) 0.67-0.93], allergic rhinitis (aOR: 0.71, 95% CI 0.57-0.89) and Japanese cedar pollinosis (aOR 0.57, 95% CI 0.44-0.75). Strikingly, passive smoking was also related to a significantly lower prevalence of allergic rhinitis (aOR 0.83, 95% CI 0.77-0.89) and Japanese cedar pollinosis (aOR 0.81, 95% CI 0.74-0.88). Current cat ownership was associated with a lower prevalence of atopic dermatitis, allergic rhinitis, and Japanese cedar pollinosis. In addition, passive smoking was also associated with a lower prevalence of allergic rhinitis and Japanese cedar pollinosis.
Pediatric Allergy and Immunology 03/2006; 17(1):22-8. · 2.46 Impact Factor
