M Higashigawa

Social Insurance Chukyo Hospital, Nagoya, Aichi, Japan

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Publications (57)107.95 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To clarify the clinical manifestations of pediatric Japanese spotted fever (JSF), which remain unclear, we retrospectively reviewed the records of 9 consecutive hospitalized children 5 boys and 4 girls aged 0-15 years (median: 2.3) whose diagnosis was patients with JSF who were serologically confirmed from April 2008 to October 2009. We initially studied the polymerase chain reaction (PCR) assay validity for specific Rickettsia japonica DNA in the blood. We also studied febrile duration, the history of contact with tick-infested areas, body temperature, eschars at tick bite sites, skin rash, treatment drugs, and laboratory data. Five of the 9 (56%) had positive PCR tests. Prehospitalization febrile duration was 1-5 days. Five had had contact with tick-infested areas and 4 had not despite living near such areas. Body temperature was 40 degrees C in 7. Only 4 had eschars at bite sites. Characteristic spotted palmar and/or plantar erythema seen in 8 was useful in diagnosis. Laboratory studies showed typical hyponatremia of < 135mEq/L in 6 JSF was diagnosed easily at hospitalization in 7. Diagnosis in a 2-month-old infant proved difficults, however, worsening the child's condition and causing hepatosplenomegaly, thrombocytopenia, anemia, and hyperferritinema. The infant was treated with high-dose gamma-globulin and azithromycin (AZM) followed by minocycline (MINO). Another case was difficult to diagnose due to clinical manifestations consistent with Kawasaki disease. The child was treated with high-dose gamma-globulin and AZM. Three of the 9 were treated with MINO alone and 4 with combined MINO and new quinolones. Fever was resolved within 2 days of treatment in all cases. Our findings show that children with high fever and spotted palmar and/or plantar erythema should be treated immediately for JSF in prevalent areas, even in the absence of eschars.
    Kansenshogaku zasshi. The Journal of the Japanese Association for Infectious Diseases 11/2011; 85(6):638-43.
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    ABSTRACT: Guillain-Barré syndrome (GBS) is well known as presenting with acute immune-mediated polyneuropathies, with strong associations with antecedent infections. Several variant forms of GBS have been described, including acute inflammatory demyelinating polyneuropathy, acute motor axonal neuropathy, acute motor-sensory axonal neuropathy, and sensory GBS. We present a rare case of 2-year-old boy with acute motor and sensory polyneuropathy and left-sided facial nerve paralysis after rotavirus infection. He received immunoglobulin i.v. with subsequent satisfactory recovery.
    Journal of Infection and Chemotherapy 09/2011; 18(1):119-23. · 1.55 Impact Factor
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    ABSTRACT: Practice guidelines for childhood idiopathic thrombocytopenic purpura (ITP) were proposed in 1998 and 2004 in Japan. It is important to evaluate the feasibility and validity of the guidelines because the guidelines are based not on evidence but on opinion. Records of 30 consecutive hospitalized patients aged 0-15 years (median, 3 years; 17 boys, 13 girls) were retrospectively reviewed. The feasibility and validity of the 2004 guidelines were evaluated by calculating an implementation rate, a response rate to first treatments, and a final clinical outcome. Deviation from the guidelines was found in two patients. Management of the other 28 patients followed the guidelines. The implementation rate was 93.3%. Twenty-one of the 28 eligible patients (75%) responded to the first treatment, whereas seven patients (25%) required additional treatment. In 23 patients (76.7%) platelet counts returned to normal within 6 months. Seven patients (23.3%) developed chronic conditions. All patients had no complications and achieved a platelet count >150 000/µL within 6 years. The 2004 Japanese guidelines are feasible and valid for the management of newly diagnosed childhood ITP patients.
    Pediatrics International 01/2011; 53(5):701-5. · 0.88 Impact Factor
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    ABSTRACT: The authors report a case of concurrent moyamoya disease and glycogen storage disease Type 1a that was successfully managed with bypass surgery. This 7-year-old Japanese girl, diagnosed with glycogen storage disease Type 1a at the age of 2 years, presented with repeated transient ischemic attacks. Cerebral angiography revealed severe stenosis at the terminal portions of the bilateral internal carotid arteries, with typical moyamoya vessels. The patient underwent superficial temporal artery-middle cerebral artery anastomosis and encephalomyosynangiosis bilaterally, in 2 staged procedures at an interval of 4 months. Despite perioperative administration of glucose, hypoglycemia and metabolic acidosis occurred after both surgeries. The symptoms were milder after the second surgery, in which an increased dose of glucose was used. The patient tolerated the perioperative conditions well under intensified medical treatment, and no further ischemic symptoms occurred.
    Journal of Neurosurgery Pediatrics 01/2011; 7(1):11-4. · 1.63 Impact Factor
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    ABSTRACT: We describe a case of vaccine-associated paralytic poliomyelitis (VAPP) in a 7-month-old infant with perianal abscesses. The infant had suffered from perianal abscesses from 3 weeks after birth. The abscesses repeatedly developed and spontaneously drained through the orifice. Twenty-seven days before admission, a live attenuated oral poliovirus vaccine (OPV) was given to the infant for the first time for routine immunization. His body temperature rose to 38°C 19 days after receiving the OPV and fell 4 days later. Flaccid paralysis of the right leg appeared 26 days after receipt of the OPV. A Sabin type 3 poliovirus was isolated from a stool obtained at admission. The DNA sequences of the VP1 region of the isolated virus were more than 99% identical with those of the vaccine strain. Mild muscle atrophy with moderate motor impairment in the right leg persisted at 18 months of age. One VAPP case provoked by a perianal abscess has been reported from the United Kingdom. Database search revealed that one of nine VAPP cases reported during 2003-2008 in Japan had a perianal abscess. Taken together, these reports and our case imply that we should give OPV with caution to infants with a perianal abscess.
    Journal of Infection and Chemotherapy 05/2010; 16(5):356-9. · 1.55 Impact Factor
  • Pediatrics International 05/2009; 51(2):297-9. · 0.88 Impact Factor
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    ABSTRACT: Few data are available for the recent occurrence of Mycoplasma infections in children in Japan. The purpose of the present study was therefore to identify the prevalence of Mycoplasma infections in children in Japan. IgM antibodies to M. pneumoniae were prospectively determined using the Meridian ImmunoCard Mycoplasma test in hospitalized patients with lower respiratory tract infections between January 2004 and June 2007. A total of 858 hospitalized patients aged 0-15 years (445 male, 413 female), diagnosed as having acute pneumonia or bronchitis, were enrolled. The number of patients with pneumonia or bronchitis was 331 (male/female, 167/164) and 527 (male/female/ 278/249), respectively. Two hundred and five of the 858 patients (23.9%) were ImmunoCard positive. Of the 205 patients, 121 children and 84 children were diagnosed as having pneumonia and bronchitis, respectively. One hundred and forty-three of the 727 patients (19.7%) <5 years of age were ImmunoCard test positive. M. pneumoniae infection is not rare in children aged <5 years in Japan.
    Pediatrics International 04/2009; 51(5):684-6. · 0.88 Impact Factor
  • Journal of Nihon University Medical Association. 01/2009; 68(1):21-24.
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    ABSTRACT: We investigated the combined effect of cyclophosphamide (CPA) and 5-bromo-2'-deoxyuridine (BrdUrd) both in mice bearing L1210 ascites tumors and in L1210 leukemic cells in vitro. Administration of BrdUrd (100 mg/kg) for 5 consecutive days before a single dose (80 mg/kg) of CPA significantly extended the survival of mice by 158%, compared with CPA alone. BrdUrd administered at daily doses of 100 or 200 mg/kg for 5 consecutive days did not extended the survival of mice. An in vitro MTT assay revealed that BrdUrd enhanced the cytotoxic effect of 4-hydroxycyclophosphamide, an active form of CPA, in the L1210 cells. These results indicate that BrdUrd enhanced the antitumor effect of CPA both in vivo and in vitro.
    Biological & Pharmaceutical Bulletin 02/2008; 31(1):57-61. · 1.85 Impact Factor
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    ABSTRACT: A 2-year-old boy developed acute myositis associated with rotavirus gastroenteritis. He had remarkable swelling and subcutaneous edema, mostly in the legs, 4 days after the onset of gastroenteritis. Marked elevation of creatine kinase was observed while serum albumin, immunoglobulin, and complement were decreased.
    Pediatrics International 10/2007; 40(1):82 - 84. · 0.88 Impact Factor
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    ABSTRACT: The endonuclease which causes antibody-induced apoptotic cell death in B cells is not completely understood. We previously established a B-cell line (MBC-1) from a patient with Burkitt's lymphoma at the leukaemic stage which demonstrated the typical morphology and internucleosomal DNA fragmentation of apoptotic cell death when treated with anti-IgM antibody. FK506, an immunosuppressive agent and calcineurin inhibitor, partially rescued the anti-IgM antibody-induced cell death in these MBC-1 cells. DNA SDS-PAGE nuclease activity assay demonstrated that a 17 kD protein exhibited endonuclease activity. Active gel assay showed nuclease activity in the cellular nuclear extract not treated with anti-IgM antibody. This nuclease activity was inhibited by FK506 at concentrations of 10–200 ng/ml in the active gel assay. These results raise the possibility that the 17 kD endonuclease is one of the nuclear members of the immunophilin family, which may function as an endogenous endonuclease in MBC-1 cells.
    British Journal of Haematology 10/2003; 99(4):908 - 913. · 4.94 Impact Factor
  • Masamune Higashigawa, Yoshihiro Komada
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    ABSTRACT: The role of Ca2+ in the intracellular signal transduction process that causes antibody-induced apoptotic cell death in B-cells is not completely understood. We previously established a B-cell line (MBC-1) from a patient with Burkitt lymphoma at the leukemic stage that demonstrated the typical morphology and internucleosomal DNA fragmentation of apoptosis when treated with anti-immunoglobulin (Ig)M antibody. This antibody-induced cell death was partially inhibited by pretreatment with ethyleneglycol-bis-tetraacetic acid (EGTA) and actinomycin-D. FK506, an immunosupressive agent and calcineurin inhibitor, also partially rescued the anti-IgM antibody-induced death of MBC-1 cells. These results show that the calcium signaling pathway, which leads to a change in gene expression, plays an important role in anti-IgM-induced apoptosis in MBC-1 cells. Flow cytometric measurement of the cytosolic free Ca2+ concentration ([Ca2+]i) showed that nontoxic concentrations of 4-bromo-calcium ionophore A23187 (Ca2+ IP) increased [Ca2+]i more than did the anti-IgM antibody. A brief Ca2+ spike was observed on anti-IgM antibody treatment, but a gradual increase and decrease were observed when the cells were treated with Ca2+ IP at a nontoxic concentration of 1 microg/mL. These findings suggest that interpretations differ for the 2 patterns of calcium signaling and that the brief spiked elevation of Ca2+ produces distinct biological and cellular responses compared to the gradual increase and decrease of [Ca2+]i. Our results support the hypothesis that Ca2+ plays a significant role as a multifunctional second messenger providing specific information to the nucleus in anti-IgM antibody-induced apoptosis in MBC-1 cells.
    International Journal of Hematology 08/2002; 76(1):44-9. · 1.68 Impact Factor
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    ABSTRACT: Several 5-fluorouracil (5-FU) derivatives, 1-hexylcarbamoyl-5-fluorouracil (HCFU), 5'-deoxy-5-fluorouridine (5'-DFUR) and UFT (mixed compound of tegafur and uracil), have been developed and clinically widely used. However, comparative pharmacokinetic studies of the parent compound and other fluorinated drivatives have not been precisely reported. The dosage of the oral clinical use for human cancer of 5-FU, HCFU, 5'-DFUR and UFT as tegafur (FT) is 200-300mg/d, 600mg/d, 800-1,200mg/d and 300-600mg/d respectively. These amounts of the drugs are almost equimolar. Previously, we reported the effect of oral equimolar administration of each four drugs on thymidilate synthase activity, deoxyribonucleotide metabolism and cell cycle progression in L1210 ascites tumor. (1,2) In this study, we examined the antitumor effect and 5-FU concentration in the plasma, intestine and tumor after oral equimolar administrations of each drug using BDF1 mice bearing L1210 ascites tumor. In our study, UFT showed the best life prolongation among these four drugs. The intestine 5-FU level was highest by treatment with 5-FU during the initial 4 h. The plasma 5-FU level was highest by treatment with HCFU for 4 h. But the tumor 5-FU level was highest by treatment with UFT over the 24 h. In spite of the high plasma 5-FU concentration after the treatment with HCFU, the 5-FU concentration in the tumor was below the detectable level until 24 h. These findings suggested that the highest specific accumulation of 5-FU in tumor cells may explain the best therapeutic results of UFT.
    Biological & Pharmaceutical Bulletin 12/2001; 24(11):1329-31. · 1.85 Impact Factor
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    ABSTRACT: Renal tubular acidosis (RTA) was observed in a preterm boy shortly after birth. His mother had glaucoma and had been treated during pregnancy with oral acetazolamide, a carbonic anhydrase inhibitor. When RTA developed, acetazolamide was detected in his serum demonstrating transplacental acetazolamide passage.
    European Journal of Pediatrics 06/2001; 160(5):321-2. · 1.91 Impact Factor
  • Biological & Pharmaceutical Bulletin - BIOL PHARM BULL. 01/2001; 24(11):1329-1331.
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    ABSTRACT: Many protocol studies have shown that low dose 6-mercaptopurine (6MP) in maintenance chemotherapy for childhood acute lymphoblastic leukemia (ALL) can be utilized to cure the disease. Mitotic or reproductive cell death has been recognized after G2 arrest when cells are treated with antitumor agents. The precise mechanism of mode of action of 6MP still remains unclear. We found delayed cytotoxic effect of 6MP in P388 murine leukemic cells. Morphological study showed that 6MP induced delayed death was characterized by an enlargement of cell size and multinucleated nuclei. Agarose gel electrophoresis of fragmented DNA from cells treated with 6MP showed the typical ladder pattern. These findings were compatible with mitotic death. Our results make us hypothesize that the delayed cytotoxicity of 6MP is one of the drug induced mitotic deaths caused by DNA damage due to incorporation of 6-thioguanine (6TG) into DNA as thioguanine nucleotide (TGN). Mitotic death may be a mechanism for killing the cycling cells from residual leukemic cells in G0 or long G1 phases in the treatment of childhood ALL.
    Journal of experimental & clinical cancer research: CR 10/1999; 18(3):417-24. · 1.50 Impact Factor
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    ABSTRACT: Eradication of contaminated tumor cells in bone marrow is a matter of utmost concern in the setting of autologous bone marrow transplantation. 4-Hydroperoxycyclophosphamide (4-HC) is often used for ex vivo chemical purging of contaminated tumor cells in bone marrow. The marrow from patients pretreated with 5-fluorouracil (5-FU) is enriched with multifactor-responsive high proliferative potential colony-forming cells. To develop an efficient ex vivo chemical purging system, we evaluated interaction between 4-HC and 5-FU. We investigated the antitumor effect of cyclophosphamide, a mother compound of 4-HC, and 5-FU against L1210 ascites tumor in B6D2F1 mice. The median lifespan of the mice treated with 4-HC or 5-FU alone was 8 and 12 days, respectively. The combination of both drugs significantly extended the median lifespan to 18.5 days. The median effect plot analysis indicated a synergistic cytotoxic interaction between 5-FU and 4-HC in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl terazolium bromide (MTT) assay. Clonogenic assay also showed that combination of 4-HC and 5-FU significantly reduced L1210 leukemic colonies to 20% of untreated control. Bone marrow cells from the mice treated with 5-FU at 150 mg/kg body weight was resistant to 4-HC at concentrations as high as 0.2 microgram/ml, which was more than 70% inhibitory concentration for colony formation in L1210 leukemic cells. Findings suggest that sequential treatment with in vivo 5-FU followed by ex vivo 4-HC could selectively enhance antitumor effects of 4-HC in tumor cells remaining in bone marrow.
    Cancer Investigation 02/1999; 17(7):486-93. · 2.24 Impact Factor
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    ABSTRACT: It has been reported that aclarubicin inhibits etoposide (VP-16) induced cytotoxicity in human lung cancer cell lines (1, 2). However, it still remains unclear how aclarubicin (ACR) inhibits etoposide-induced cytotoxicity. We report here that the combination of ACR and VP-16 showed antagonistic cytotoxic effect in P388 murine leukemic cells. DNA unwinding assay showed that 1000 ng/ml ACR significantly reduced VP-16 induced early DNA double strand(ds) breaks compared to that of VP-16 alone at a concentration of 10 microM. However, ACR did not inhibit VP-16 induced early DNA double strand breaks at a concentration of 100 ng/ml, a clinically achievable concentration. Furthermore, DNA repair occurred within two hours after removing VP-16 even if ACR was co-cultured at concentrations of 100 and 1000 ng/ml. DNA agarose gel electrophoresis and detection of sub-G1 fraction by flowcytometer showed that 100 ng/ml of ACR inhibited VP-16 induced DNA ladder formation and formation of sub-G1 fraction. Radioactive precursor incorporation studies showed that VP-16 inhibited DNA synthesis rather than RNA synthesis. On the other hand, ACR selectively inhibited RNA synthesis at a concentration of 100 ng/ml. The VP-16 induced increment of [3H]-L-leucine uptake was canceled by addition of 100 ng/ml of ACR. These data suggest that ACR inhibited VP-16 induced apoptosis by the inhibition of RNA synthesis along with protein synthesis, but not early DNA double strand breaks and DNA repair at a concentration of 100 ng/ml in P388 murine leukemic cells.
    Journal of experimental & clinical cancer research: CR 01/1999; 17(4):435-42. · 1.50 Impact Factor
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    ABSTRACT: Transient myeloproliferative disorder (TMD) in neonates with Down syndrome is characterized by increased megakaryoblastic cells in the peripheral blood. Despite their spontaneous regression in weeks, prognosis is not always favorable because of fatal hepatic fibrosis. In this study, blood thrombopoietin (TPO) levels were measured by ELISA in six TMD patients and the expression of c-Mpl, a ligand for TPO, was examined on the blast cells from four patients by flow cytometer. At the onset, TPO level was undetectable in one patient and significantly lower in five patients than six neonatal controls (mean 0.52 fmol/ml, range 0.30-0.93 vs. 3.70, 1.38-8.33, P < 0.001), although platelet counts were similar (mean 321 x 10(9)/l, range 42-1,040 vs. 253 x 10(9)/l, 124-381). Two patients died of hepatic failure. TPO levels were measured in five patients after regression of the blast cells. With regression of blast cells, TPO levels were remarkably increased in four survived patients. In one patient with hepatic failure, TPO level was poorly elevated and relatively lower compared to the others. TPO levels were inversely correlated with blast numbers (r = -0.85, P < 0.001), but not with platelet counts (r = 0.426). Blast cells from four patients were all positive for c-Mpl. Our findings suggest that megakaryocyte mass is a major regulator of TPO levels and hepatic failure may affect the TPO level because liver is a major source of TPO production.
    American Journal of Hematology 09/1998; 58(4):267-72. · 4.00 Impact Factor
  • Source
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    ABSTRACT: Transient myeloproliferative disorder (TMD) in neonates with Down syndrome is characterized by increased megakaryoblastic cells in the peripheral blood. Despite their spontaneous regression in weeks, prognosis is not always favorable because of fatal hepatic fibrosis. In this study, blood thrombopoietin (TPO) levels were measured by ELISA in six TMD patients and the expression of c-Mpl, a ligand for TPO, was examined on the blast cells from four patients by flow cytometer. At the onset, TPO level was undetectable in one patient and significantly lower in five patients than six neonatal controls (mean 0.52 fmol/ml, range 0.30–0.93 vs. 3.70, 1.38–8.33, P < 0.001), although platelet counts were similar (mean 321 × 109/l, range 42–1,040 vs. 253 × 109/l, 124–381). Two patients died of hepatic failure. TPO levels were measured in five patients after regression of the blast cells. With regression of blast cells, TPO levels were remarkably increased in four survived patients. In one patient with hepatic failure, TPO level was poorly elevated and relatively lower compared to the others. TPO levels were inversely correlated with blast numbers (r = −0.85, P < 0.001), but not with platelet counts (r = 0.426). Blast cells from four patients were all positive for c-Mpl. Our findings suggest that megakaryocyte mass is a major regulator of TPO levels and hepatic failure may affect the TPO level because liver is a major source of TPO production. Am. J. Hematol. 58:267–272, 1998. © 1998 Wiley-Liss, Inc.
    American Journal of Hematology 07/1998; 58(4):267 - 272. · 4.00 Impact Factor

Publication Stats

180 Citations
107.95 Total Impact Points

Institutions

  • 1992–2001
    • Social Insurance Chukyo Hospital
      Nagoya, Aichi, Japan
  • 1988–2001
    • Mie University
      • • Department of Hospital Pharmacy
      • • Department of Pediatrics
      Tsu-shi, Mie-ken, Japan
  • 1996
    • Osaka University
      • Division of Neurology
      Suita, Osaka-fu, Japan