Endocrinology and Metabolism Group

• Studies on steroid metabolism in patients with various illnesses/pathologic conditions
  • Steroid metabolism in Kawasaki's disease: Clinical research is being conducted for the development of effective steroid-based therapies for Kawasaki's disease.
  • Physiological functions of glucocorticoids in obesity and mast cells: Basic research using mast cell cultures is being conducted, focusing on the enzymes involved in glucocorticoid metabolism.
  • Identification of factors determining steroid sensitivity: Although glucocorticoids have been used in various fields, there are many open questions about the mechanisms underlying their pharmacological activities. We are conducting basic research using leukemia cells to identify the factor(s) determining steroid sensitivity.

• Basic research on the mechanism for disease development beginning with the intrauterine period
  Recent epidemiological studies have pointed out the possibility that the nutritional environments from the intrauterine period to infancy/early childhood could affect the risk of onset of chronic lifestyle-related illnesses in adults and the elderly, and the concept of "Developmental Origins of Health and Disease (DOHaD)" has been proposed. Concerning the relationships of the maternal nutritional state, maternal complications, etc., during the intrauterine period to postnatal disease development, we are engaged in basic research, focusing on epigenetic modifications.

• Clinical research concerning effective interventions for metabolic syndrome during childhood
  • By means of group health checkups at schools and outpatient endocrinology practices, we have been following up children with obesity or metabolic syndrome and studying effective interventions for such cases.
  • Using urinary myo-inositol as a new indicator, we have been collecting data on the benefits of testing methods designed to enable early detection of diabetes-precursory conditions among children.

• Basic research on the physiological activities and functions of maternal milk
  Although breastfeeding is recommended as the best means of nourishing children during early infancy, several open questions remain. Through basic research with the use of cell cultures, we are attempting to clarify the physiological functions of maternal milk in relation to pediatric obesity and from the viewpoint of finding an effective means to prevent progression of pediatric obesity to obesity/metabolic syndrome in adulthood.

• Endocrinological research and research on therapeutic interventions in the field of pediatric cancer
  • We are attempting to improve the quality of life of individuals who have had pediatric cancers, through assessment of and providing interventions for their late complications in these patients, including from the endocrinological point of view.
  • Anticancer agents can exert remarkable effects but, at the same time, they also evoke various adverse reactions. We are conducting basic research using cell cultures concerning the adverse effects of anticancer agents on the endocrine system.

• Clinical genetics
  Clinical genetics has two aspects. First, it pertains to conditions conventionally expressed by the term "congenital malformation syndrome." For many years, this has tended to be viewed as a niche field, in which research has been conducted only by those with special interest in the field. However, following cloning of the genes responsible for numerous illnesses in recent years, clarification of the pathogenesis of diseases at the molecular level has been advancing in this field. Because congenital malformation syndrome is a disease often involving diverse fields, clarification of its characteristics and pathogenesis may be expected to have an impact in diverse fields. Second, clinical genetics, from the aspect of genetics in the broader sense of the term, encompasses pediatrics and all other fields of medicine. Because genetics pertains to the gene and genome, which are shared in all fields of medicine, it is important in every specialty of medicine. In this connection, the Hamamatsu University School of Medicine has published numerous findings, not reported before in the world, revealed by analysis of pediatric endocrine diseases (related to child growth and maturation), not only from the viewpoint of endocrinology, but also from the viewpoint of genetics.

Hematology and Oncology Group

• Participation in multicenter studies related to the treatment of pediatric hematological diseases and tumors
  Nowadays, research on hematological diseases and tumors in children is often conducted in the form of multicenter studies. We have been participating in such studies to treat these diseases.

• Resistance of leukemia cells to anticancer agents and the mechanism of development of resistance
  It is inevitable that development of resistance of leukemia cells to anticancer agents has a great impact on the outcome of treatment. We are attempting to prevent the development of such resistance, and thereby improve the treatment outcomes, through elucidation of the mechanism of development of resistance. Many samples obtained from children with leukemia have been sent to our facility from across the country, requesting us to conduct anticancer agent susceptibility testing. By anticancer agent susceptibility testing of such samples, we have collected valuable data. We have presented our findings obtained through such testing at professional society meetings or in professional journals. We will continue to engage in this research, towards the goal of improving the treatment of pediatric leukemia.
  If you desire anticancer agent susceptibility testing, please contact our staff in charge in advance.
  Staff in charge: Kimiyoshi Sakaguchi
  TEL: 053-435-2312

Announcement of a planned clinical study

To patients who have received outpatient or inpatient care at the Department of Pediatrics
To patients whose samples have been sent to our Pediatrics Department for drug susceptibility testing

Request for Cooperation with the Study for "Exploration of Genetic Predisposition to Apoptosis of Cancer Cells in Children with Cancer"

Past performance

1. Fujii Y, Hongo T, Nakagawa Y, et al. Cell culture of small round cell tumor originating in the thoracopulmonary region. Evidence for derivation from a primitive pluripotent cell. Cancer, 64:43-51, 1989
2. Fujii Y, Matui Y, Nakagawa Y, et al. Translocation t(12;16)(q13;p11) in myxoid liposarcoma of a child and implication of the human int-1 gene in tumorigenesis. Jpn J Cancer Res, 80:958-962, 1989
3. Fujii Y, Nakagawa Y, Hongo T, et al. [Cell line of small round cell tumor originating in the chest wall: W-ES]. Hum Cell, 2:190-191, 1989
4. Hongo T, Fujii Y, Igarashi Y. An in vitro chemosensitivity test for the screening of anti-cancer drugs in childhood leukemia. Cancer, 65:1263-1272, 1990
5. Fujii Y, Hongo T, Masui H, et al. Angiotensin-induced hypertension chemotherapy in children with advanced solid tumors. Acta Paediatr Jpn, 33:381-383, 1991
6. Hongo T, Fujii Y. In vitro chemosensitivity of lymphoblasts at relapse in childhood leukemia using the MTT assay. Int J Hematol, 54:219-230, 1991
7. Hongo T, Fujii Y, Fukuoka T, et al. Long-term treatment in infantile choriocarcinoma. Acta Paediatr Jpn, 34:52-59, 1992
8. Fujii Y, Hongo T, Hayashi Y. Chromosome analysis of brain tumors in childhood. Genes Chromosomes Cancer, 11:205-215, 1994
9. Hongo T, Fujii Y, Yajima S, et al. Analysis of the circumstances of death of 56 children suffering from cancer: proposal for the development of terminal medicine in Japan. Acta Paediatr Jpn, 37:604-609, 1995
10. Hongo T, Yajima S, Sakurai M, et al. In vitro drug sensitivity testing can predict induction failure and early relapse of childhood acute lymphoblastic leukemia. Blood, 89:2959-2965, 1997
11. Hongo T, Yamada S, Yajima S, et al. Biological characteristics and prognostic value of in vitro three-drug resistance to prednisolone, L-asparaginase, and vincristine in childhood acute lymphoblastic leukemia. Int J Hematol, 70:268-277, 1999
12. Watanabe C, Yajima S, Taguchi T, et al. Successful unrelated bone marrow transplantation for a patient with chronic granulomatous disease and associated resistant pneumonitis and Aspergillus osteomyelitis. Bone Marrow Transplant, 28:83-87, 2001
13. Yamada S, Hongo T, Okada S, et al. Clinical relevance of in vitro chemoresistance in childhood acute myeloid leukemia. Leukemia, 15:1892-1897, 2001
14. Yamada S, Hongo T, Okada S, et al. Distinctive multidrug sensitivity and outcome of acute erythroblastic and megakaryoblastic leukemia in children with Down syndrome. Int J Hematol, 74:428-436, 2001
15. Hongo T, Okada S, Inoue N, et al. Two groups of Philadelphia chromosome-positive childhood acute lymphoblastic leukemia classified by pretreatment multidrug sensitivity or resistance in in vitro testing. Int J Hematol, 76:251-259, 2002
16. Hongo T, Okada S, Ohzeki T, et al. Low plasma levels of hemostatic proteins during the induction phase in children with acute lymphoblastic leukemia: A retrospective study by the JACLS. Japan Association of Childhood Leukemia Study. Pediatr Int, 44:293-299, 2002
17. Fujii Y, Watanabe C, Okada S, et al. Analysis of the circumstances at the end of life in children with cancer: a single institution's experience in Japan. Pediatr Int, 45:54-59, 2003
18. Hongo T, Watanabe C, Okada S, et al. Analysis of the circumstances at the end of life in children with cancer: symptoms, suffering and acceptance. Pediatr Int, 45:60-64, 2003
19. Okada S, Hongo T, Yamada S, et al. In vitro efficacy of l-asparaginase in childhood acute myeloid leukaemia. Br J Haematol, 123:802-809, 2003
20. Okada S, Hongo T, Sakaguchi K, et al. Pilot study of ifosfamide/carboplatin/etoposide (ICE) for peripheral blood stem cell mobilization in patients with high-risk or relapsed medulloblastoma. Childs Nerv Syst, 23:407-413, 2007
21. Sai S, Nakagawa Y, Sakaguchi K, et al. Differential regulation of 11beta-hydroxysteroid dehydrogenase-1 by dexamethasone in glucocorticoid-sensitive and -resistant childhood lymphoblastic leukemia. Leuk Res, 33:1696-1698, 2009
22. Sai S, Nakagawa Y, Yamaguchi R, et al. Expression of 11beta-hydroxysteroid dehydrogenase 2 contributes to glucocorticoid resistance in lymphoblastic leukemia cells. Leuk Res, 35:1644-1648, 2011
23. Takahashi H, Koh K, Kato M, et al. Acute myeloid leukemia with mediastinal myeloid sarcoma refractory to acute myeloid leukemia therapy but responsive to L-asparaginase. Int J Hematol, 96:136-140, 2012
24. Takahashi H, Nagatoshi Y, Kato M, et al. Multifocal skin lesions and melena with thrombocytopenia in an infant. J Pediatr, 160:524-524 e521, 2012
25. Takahashi H, Koh K, Kato M, et al. The feasibility of Erwinia asparaginase for pediatric patients who developed an allergic reaction to E.coli asparaginase during treatment of acute lymphoblastic leukemia. Rinsho Ketsueki, 54:370-377, 2013
26. Takahashi H, Kato M, Kikuchi A, et al. Delayed short-term administration of granulocyte colony-stimulating factor is a good mobilization strategy for harvesting autologous peripheral blood stem cells in pediatric patients with solid tumors. Pediatr Transplant, 17:688-693, 2013

Cardiology Group

• Clinical research using ultrasonography has been carried out, and various results have been reported.
• Clinical research on Kawasaki's disease has been carried out jointly with the Department of Cardiovascular Medicine.
• Measurement of the blood levels of drugs used for the treatment of pulmonary hypertension is carried out jointly with the Department of Clinical Pharmacology.

Research focused on the above-mentioned topics has been presented at numerous professional society/study group meetings, such as those of the Japanese Society of Pediatric Cardiology and Cardiac Surgery, and the Tokai Society of Pediatric Cardiology.

Announcement of ongoing epidemiological studies

• Multicenter study on analysis of genes related to Kawasaki's disease
• Online case registration with the Japan Pediatric International Cardiology Database (JPIC-DB)

Neurology Group

• Clinical research, primarily conducted through diagnosis, testing and treatment of cases of growth retardation, neural infections and convulsive diseases including epilepsy.
• Clinical research conducted jointly with other facilities on metabolic diseases, muscle diseases, neuroimmune diseases, etc.
  Examples:
  • Clinical research on new treatment methods for Gaucher's disease and mucopolysaccharidosis and their efficacies
  • Clinical research on the diagnosis and treatment of mitochondrial diseases
  • Research on the associated neurological symptoms and long-term outcomes of xeroderma pigmentosum
  • Research on the neurodevelopmental prognosis in children with congenital cytomegalovirus (CMV) infection.
  • Clinical research on the diagnosis and treatment of neurological diseases manifesting with psychiatric symptoms and/or developmental disorders

• In addition, in linkage with the Hamamatsu Development Healthcare and Welfare Center and other facilities/organizations, we have been conducting investigations, assessment, etc., in connection with the supports needed for the establishment of environments/systems conducive for care and growth/development of children with neuromuscular diseases and developmental disorders.

Nephrology Group

• Clinical research is conducted jointly with other facilities on nephrotic syndrome, chronic glomerulonephritis, etc. Examples are given below:
  • Clinical research on the treatment of intractable nephrotic syndrome
  • Clinical research on the treatment and long-term prognosis of IgA nephropathy
  • Clinical research on the diagnosis and treatment of pediatric hypertension

Immunology and Allergy Group

• The prevalence of allergic diseases has been increasing in Japan, and the number of patients with allergic diseases has been increasing. At the same time, the methods adopted for managing this disease have also been advancing steadily. Our department has been proactively adopting new treatment methods and conducting clinical research to identify optimal methods for diagnosis and treatment based on scientific evidence.
  <Food allergy>
  ・Efficacy of nutritional and diet guidance for patients with food allergy: A retrospective case series study (completed in 2017)
  ・A prospective before/after comparison study of tolerance induction by very low-dose oral immunotherapy (VLOIT) in children with peanut allergy (under way as of 2018)
  ・Influence of the frequency of food consumption on the acquisition of tolerance to food allergy (under way as of 2018)
  ・An attempt at safe food loading test based on blood test and skin prick test (under way as of 2018)
  <Atopic dermatitis>
  ・Proactive therapy for atopic dermatitis: A randomized comparative study (completed in 2012)
  ・Influence of washing with soap on atopic dermatitis (2016 winter session completed/2017 winter session completed)
  <Research on the pathophysiology of allergic march>
  ・Study on the prevention of food allergy onset through early intervention for infantile atopic dermatitis/Multicenter examiner-blinded random-intervention parallel-group comparative study (under way as of 2018, a multicenter study)
  ・Prospective cohort study exploring the allergic march-preventive effects of early intervention and oral immunotolerance induction in infants with atopic dermatitis (under way as of 2018, a multicenter study)

• Latest evidence-based management is applied not only to patients with allergic diseases, but also to patients with collagen diseases, juvenile rheumatoid arthritis, inflammatory bowel diseases, immunodeficiency, etc.

Performance

１．Fukuie T, Nomura I, Horimukai K, Manki A, Masuko I, Futamura M, Narita M, Ohzeki T, Matsumoto K, Saito H, Ohya Y.　Proactive treatment appears to decrease serum immunoglobulin-E levels in patients with severe atopic dermatitis.　Br J Dermatol. 2010 Nov;163(5):1127-9

2． Fukuie T, Hirakawa S, Narita M, Nomura I, Matsumoto K, Tokura Y, Ohya Y.　Potential preventive effects of proactive therapy on sensitization in moderate to severe childhood atopic dermatitis: A randomized, investigator-blinded, controlled study. J Dermatol. 2016; 43: 1283-1292.

3. Ohnishi H, Kishimoto Y, Taguchi T, Kawamoto N, Nakama M, Kawai T, Nakayama M, Ohara O, Orii K, Fukao T. Immunodeficiency in Two Female Patients with Incontinentia Pigmenti with Heterozygous NEMO Mutation Diagnosed by LPS Unresponsiveness. J Clin Immunol. 2017 Aug;37(6):529-538.

4．Natsume O, Kabashima S, Nakazato J, Yamamoto-Hanada K, Narita M, Kondo M, Saito M, Kishino A, Takimoto T, Inoue E, Tang J, Kido H, Wong GW, Matsumoto K, Saito H, Ohya Y; PETIT Study Team. Two- step egg introduction for prevention of egg allergy in high-risk infants with eczema (PETIT): a randomised, double-blind, placebo-controlled trial. Lancet. 2017 Jan 21;389(10066):276-286.

5. Mitsui M, Shoda T, Natsume O, Nomura I, Narita M, Fukuda A, Sakamoto S, Kasahara M, Ohya Y. Factors Associated with Development of Food Allergy in Young Children after Liver Transplantation: A Retrospective Analysis of 10 Years' Experience. J Allergy Clin Immunol Pract. 2017 Nov - Dec;5(6):1698-1706

6. Ohnishi H, Kishimoto Y, Taguchi T, Kawamoto N, Nakama M, Kawai T, Nakayama M, Ohara O, Orii K, Fukao T. Immunodeficiency in Two Female Patients with Incontinentia Pigmenti with Heterozygous NEMO Mutation Diagnosed by LPS Unresponsiveness. J Clin Immunol. 2017; 37: 529-538.

7. Natsume O, Ohya Y. Recent advancement to prevent the development of allergy and allergic diseases and therapeutic strategy in the perspective of barrier dysfunction. Allergol Int. 2018 Jan;67(1):24-31.

8. Yasuoka R, Iwata N, Abe N, Kohagura T, Nakaseko H, Shimizu M, Kawabe S. Risk factors for hypersensitivity reactions to tocilizumab introduction in systemic juvenile idiopathic arthritis. Mod Rheumatol. 2018 Mar 26:1-12.

Neonatal and Perinatal Medicine Group

• Diagnosis and follow-up of congenital malformation syndrome
• Heart/head ultrasound screening of normal neonates
  Clinical research has been conducted primarily about these topics.