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Biomedical subjects

Toshiro Hara

Publications and source records attributed to Toshiro Hara.

At least 37 records · Page 2Linked to original sources
PubMed2006

Reduced gene expression of clustered ribosomal proteins in Diamond-Blackfan anemia patients without RPS19 gene mutations.

Diamond-Blackfan anemia (DBA) is a rare congenital pure red cell aplasia occasionally presenting physical anomalies. Ribosomal protein S19 gene (RPS19) is one of the causative genes for DBA; however, the pathologic mechanism of erythroblastopenia and abnormal morphology has not been clarified. To assess the pathophysiology of DBA, the gene expression profile of 2 representative patients carrying no RPS19 mutations was compared with that of aplastic anemia (AA) patients, assessed by the microarray analyses. The K-mean clustering analysis revealed the significant categorization of 28 ribosomal protein (RP) genes into a small set of group (994 genes) (P=2.39E-17), all of which were expressed at lower levels in DBA than in AA patients. RPS19 was categorized into the set of low expressing genes in DBA patients. No mutations were determined in the promoter and coding sequences of top 10 RP genes expressed at the levels over 1.2 of the AA/DBA ratio, in 3 DBA patients. These results indicated that the lower expression of RP gene group, even without the mutation, was a distinctive feature of DBA from AA, although the study number was small. The reduced RP gene expression, by itself, may suggest an underlying mechanism of the constitutional anemia.

Adult↗
PubMed2006

Unrelated donor cord blood transplantation for childhood severe aplastic anemia after a modified conditioning.

Treatment of severe aplastic anemia (SAA) patients who lack human leukocyte antigen (HLA)-matched donors and failed immunosuppressive therapy (IST) is challenging. Recently, umbilical cord blood transplantation (CBT) after non-myeloablative therapy has been reported in adult but not in childhood SAA. However, most cases resulted in mixed donor chimerism and incomplete hematological recovery. We reported an 11-yr-old girl with recurred SAA 5 yr after IST who underwent unrelated donor CBT after a modified regimen. This patient had renal and cardiac dysfunction, and lacked suitable bone marrow donors. The 3.9 x 10(7)/kg CB cells from an HLA one-locus mismatched unrelated donor were infused after conditioning with total body irradiation (5 Gy), melphalan (120 mg/m(2)), and fludarabin (120 mg/m(2)). Hematological recovery was favorable in complete chimerism. A major complication was only skin graft-versus-host disease (grade I). CB could be an alternate stem cell source for childhood SAA after modified preparative regimen.

Anemia, Aplastic↗
PubMed2006

Moyamoya syndrome in a splenectomized patient with beta-thalassemia intermedia.

We describe a 14-year-old Japanese girl with beta-thalassemia intermedia who developed moyamoya syndrome after splenectomy. This patient had compound heterozygous mutations of the beta-globin gene and received occasional transfusions. After splenectomy at 12 years of age, she transiently required partial exchange transfusions for leukoerythroblastosis but attained transfusion independence. Two years after the splenectomy, transient ischemic attacks occurred repeatedly with right hemiparesis or left paresthesia. Magnetic resonance imaging revealed bilateral stenosis of the internal carotid arteries and dilatation of the perforating branches with the formation of moyamoya vessels but not infarctions. The strict adherence to aspirin and dipyridamole has led to no stroke or progression of the vasculopathy for 8 years. Moyamoya disease has been reported in a patient with beta-thalassemia major. Cerebral vasculopathy can be a rare but grave consequence of the thromboembolic complications in beta-thalassemia major/intermedia. (J Child Neurol 2006;21:75-77).

Adolescent↗
PubMed2005

Serum immunoglobulin levels do not affect antibody responses to influenza HA vaccine in preterm infants.

Antibody responses to two doses of influenza hemagglutinin (HA) vaccine were evaluated in 45 previously unimmunized preterm infants aged 6-11 months before the 2003/2004 influenza season. Twenty-three (51.1%), 21 (46.6%) and 2 (4.4%) of the subjects acquired protective (>or=1:40) hemagglutination inhibition (HI) antibody titers after vaccination for A/New Caledonia (H1N1), A/Panama (H3N2) and B/Shandong, respectively. Antibody responses to A (H1N1), A (H3N2) appeared to be comparable to those reported on full-term infants of similar ages vaccinated with the identical vaccine. Serum IgG levels at vaccination had no positive association with antibody responses on univariate or multivariate analysis, indicating that prolonged hypogammaglobulinemia after 6 months of age in preterm infants was not a factor to affect antibody responses to influenza HA vaccine.

Antibodies, Viral↗
PubMed2005

A novel transfection method for mammalian cells using gas plasma.

Introduction of foreign genes into target cells is a crucial step for achievement of gene therapy. We have recently developed a novel transfection system for eukaryotic cells, namely the electric pulse-activated gas plasma generator. To measure the transfection efficiency and mortality by flow-cytometry, we employed enhanced green fluorescent protein and propidium iodide staining, respectively. One day after the 1-3s plasma exposures with DNA concentration at 0.5 microg/microl, favorable transfection efficiencies (17.8-21.6%) and mortalities (0.65-2.86%) were obtained for HeLa-S3, HT-1080 and MCF-7 cells. The recipient cells became transiently permeable for plasmid DNA during the plasma exposure, suggesting that plasma-mediated transfection may involve similar mechanisms that accounts for electroporation. The relatively low mortality rates are encouraging in our attempt to apply this system to the various cell lines including the primary cell cultures.

Cell Line, Tumor↗
PubMed2005

Mutations of syntaxin 11 and SNAP23 genes as causes of familial hemophagocytic lymphohistiocytosis were not found in Japanese people.

Although mutations of perforin, MUNC13-4 and syntaxin 11 genes have been found in children with familial hemophagocytic lymphohistiocytosis (FHL), the incidence of each genetic subtype varies in different ethnic groups. We evaluated mutations of syntaxin 11 and SNAP23 genes in 30 Japanese FHL patients. The patients had no mutations and 10% had one polymorphism (146G>A) of syntaxin 11, while no mutation of SNAP23 was observed. Our results indicate that aberrations in the SNARE system may not cause FHL in Japanese families.

Base Sequence↗
PubMed2005

Genetic susceptibility to simple febrile seizures: interleukin-1beta promoter polymorphisms are associated with sporadic cases.

Febrile seizures (FSs) are the commonest form of convulsions. A genetic predisposition to FSs is known, based on family studies, twin studies, and complex segregation analysis. Simple FSs may be more homogenous in their clinical manifestations, and show better agreement with the multifactorial inheritance theory than the complex type. Interleukin-1 (IL-1) beta is one of the pro-inflammatory cytokines that are postulated to be involved in the development of FSs. To determine whether or not function-related polymorphisms of the IL-1beta (IL1B) gene are associated with susceptibility to simple FSs, the genotypes for two biallelic polymorphisms in the promoter region at positions -31 and -511 of the IL1B gene were determined by means of PCR-restriction fragment length polymorphism in 229 FS patients (108 sporadic and 60 familial simple FS, and 61 complex FS patients) and 158 controls. IL1B -31C/T, a TATA box polymorphism, has been found to be in complete linkage disequilibrium with the IL1B -511C/T polymorphism. Sporadic simple FS patients exhibited significantly higher frequencies of IL1B -31C/-511T alleles and homozygotes than controls (uncorrected p = 0.0094 and 0.0029, corrected p = 0.038 and 0.035, respectively), while no differences were observed in patients with all or familial simple FSs versus controls. There were no significant differences in the frequencies of -31C/T and -511C/T in the IL-1beta promoter gene between complex FS patients and controls. The present study suggests that the IL-1beta gene contributes to a genetic susceptibility to the development of simple FSs of sporadic occurrence.

Adolescent↗
PubMed2005

Long-term use of peripherally inserted central venous catheters for cancer chemotherapy in children.

BACKGROUND: Peripherally inserted central venous catheters (PICCs) have been increasingly used in pediatric patients. However, little is known about the incidence and risk of complications when using this device in children with cancer. The purposes of this study are to assess the feasibility of PICCs and to determine the risk factors for PICC-related complications in pediatric patients with various types of malignancies. PATIENTS AND METHODS: We attempted to place PICCs in 53 patients with a median age of 5 years ranging from 2 months to 20 years. PICCs were used to administer fluid, parenteral nutrition, anticancer agents, antibiotics, and blood products and also for the through-line blood sampling. The duration of catheterization and the incidence of PICC-related complications requiring removal were retrospectively evaluated in association with the diagnosis, sex, age and body weight of the patients, size, insertion site and tip location of the catheters, type of treatment, and duration of leukopenia. RESULTS: PICCs were successfully placed in 109 of 112 attempts (97.3%) in 53 patients, and they were followed for a total of 11,797 catheter days (median placement, 87 days; range, 3 to 512 days). Fifty five PICCs (50.5%) were removed as a result of PICC-related complications with a rate of 4.66 per 1,000 catheter days. The most common reasons for catheter removal were occlusion (n=18), breakage/leakage (15), and infection (10). More than 70% of such complications occurred more than 30 days after placement. The catheter tip location in the superior vena cava or the right atrium might decrease the risk of complications. Other parameters did not influence the incidence of complications. CONCLUSIONS: PICCs were found to provide a reliable access for prolonged intravenous administration and blood sampling in children intensively treated for hematologic and solid malignancies, thus leading to a reduction of physical pain and psychological stress in such patients. However, the long-term placement of PICCs may also be related to an increased risk of complications.

Adolescent↗
PubMed2005

Colonic stricture secondary to hemolytic uremic syndrome caused by Escherichia coli O-157.

Shiga toxin-producing Escherichia coli (E. coli) is known to be one of the main causes of hemolytic uremic syndrome (HUS). Of the secondary complications of HUS, colonic stricture is relatively rare. We herein report on a Japanese girl that demonstrated sigmoid colon stricture secondary to HUS caused by an infection of E. coli O-157. Severe HUS occurred after the E. coli O-157 infection, so hemodialysis was performed due to renal failure. However, 1 month after recovery from HUS, abdominal symptoms occurred. A contrast study in the colon revealed a sigmoid colon stricture. The stricture was operatively resected. Thereafter, her postoperative course was uneventful. We also review the occurrence of this complication secondary to HUS in the literature.

Child, Preschool↗
PubMed2005

Magnetic resonance studies of brain lesions in patients with Kawasaki disease.

We evaluated brain lesions in patients with coronary arterial lesions (CAL) as a complication of Kawasaki disease (KD) by magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Among 47 patients who underwent coronary angiography for the evaluation of CAL due to KD at Kyushu University Hospital from April 1996 to September 2004, 24 patients were evaluated prospectively by brain MRI and MRA 0.1-21.2 years after the onset of KD. Although most patients had irritability or lethargy, none of them had significant neurological symptoms or signs during the acute phase, except one who showed neck stiffness. In one patient with no apparent neurological symptoms out of the 24 patients, brain MRI and MRA revealed right cerebellar infarction and obliteration of the right posterior inferior cerebellar artery, respectively. These results revealed the presence of cerebrovascular lesion in one of the 24 KD patients with CAL and suggested the need to consider the possibility of brain lesions in severe cases of KD with or without neurological symptoms.

Adolescent↗
PubMed2005

Severe combined immunodeficiency caused by a splicing abnormality of the CD3delta gene.

UNLABELLED: CD3delta deficiency is a recently identified rare form of severe combined immunodeficiency. We analysed the CD3delta gene in a Japanese family with severe combined immunodeficiency. The patients lacked T-cells with normal numbers of B-cells and natural killer cells in peripheral blood. We found a novel homozygous mutation in the splicing acceptor site of intron 2 (IVS2-2A --> G) in these patients. Analysis of patients' mononuclear cells revealed the CD3delta splicing abnormality. Chest X-ray films and computed tomography revealed small sized thymuses in these patients. CONCLUSION: The CD3delta gene should be analysed in patients with severe combined immunodeficiency lacking T-cells with normal B- and natural killer cells irrespective of the thymus size.

Alternative Splicing↗
PubMed2005

Thrombocytosis in preterm infants: a possible involvement of thrombopoietin receptor gene expression.

Transient thrombocytosis is commonly observed in preterm infants after birth, but its physiological mechanism is still unknown. To understand the mechanism of the transient thrombocytosis in preterm infants we firstly evaluated a correlation between platelet counts and thrombopoietin (TPO) levels in preterm infants and next c-mpl mRNA levels on platelets in healthy preterm infants longitudinally during a half-year of life. The mean platelet counts in 45 very low birth weight infants (mean gestational age 27.4+/-1.8 weeks, mean birth weight 1047+/-249 g) was 230+/-71x10(9)/l just after birth and thereafter gradually increased to 579+/-178x10(9)/l by 5 weeks of age. The platelet counts continued this level for about next 8 weeks. Serum TPO levels soon after birth and at 1 month of age were significantly higher than those at the age of 2-6 months. There was a significant negative correlation between platelet counts and serum TPO values. The c-mpl expression levels on platelets at birth and at 1 month of age tended to be lower than those on platelets from adults, and the c-mpl levels gradually increased through 6 months of age, although they were still lower than those of adults. Our results suggest that low expression of TPO receptor on platelets until 1 month after birth cause a decreased TPO clearance and keep a high level of free TPO in blood, thereby promoting platelet production from megakaryocytes or their progenitors in bone marrow, resulting in the subsequent thrombocytosis in preterm infants.

Adult↗
PubMed2005

Genetic subtypes of familial hemophagocytic lymphohistiocytosis: correlations with clinical features and cytotoxic T lymphocyte/natural killer cell functions.

Mutations of the perforin (PRF1) and MUNC13-4 genes distinguish 2 forms of familial hemophagocytic lymphohistiocytosis (FHL2 and FHL3, respectively), but the clinical and biologic correlates of these genotypes remain in question. We studied the presenting features and cytotoxic T lymphocyte/natural killer (CTL/NK) cell functions of 35 patients for their relationship to distinct FHL subtypes. FHL2 (n = 11) had an earlier onset than either FHL3 (n = 8) or the non-FHL2/FHL3 subtype lacking a PRF1 or MUNC13-4 mutation (n = 16). Deficient NK cell activity persisted after chemotherapy in all cases of FHL2, whereas some patients with FHL3 or the non-FHL2/FHL3 subtype showed partial recovery of this activity during remission. Alloantigen-specific CTL-mediated cytotoxicity was deficient in FHL2 patients with PRF1 nonsense mutations, was very low in FHL3 patients, but was only moderately reduced in FHL2 patients with PRF1 missense mutations. These findings correlated well with Western blot analyses showing an absence of perforin in FHL2 cases with PRF1 nonsense mutations and of MUNC13-4 in FHL3 cases, whereas in FHL2 cases with PRF1 missense mutations, mature perforin was present in low amounts. These results suggest an association between the type of genetic mutation in FHL cases and the magnitude of CTL cytolytic activity and age at onset.

Adolescent↗
PubMed2005

Successful umbilical cord blood transplantation for severe chronic active Epstein-Barr virus infection after the double failure of hematopoietic stem cell transplantation.

An 11-year-old boy with severe chronic active Epstein-Barr virus infection (CAEBV) underwent successful cord blood transplantation (CBT) after consecutive failure of peripheral blood and bone marrow transplantation from his HLA-mismatched mother. CB cells from an unrelated donor were infused after conditioning with total body irradiation (12 Gy), melphalan (120 mg/m(2)), and etoposide (600 mg/m(2)). Complete remission without circulating EBV-DNA has continued for 15 months after a delayed hematologic recovery. This is the first successful report of CBT for CAEBV. CB may therefore be an alternate source of stem cells for the curative treatment of CAEBV, despite the absence of EBV-specific cytotoxic T lymphocytes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Differential mRNA expression of glucocorticoid receptor alpha and beta is associated with glucocorticoid sensitivity of acute lymphoblastic leukemia in children.

BACKGROUND: Sensitivity of leukemic blasts to glucocorticoid is one of the important prognostic factors for pediatric acute lymphoblastic leukemia (ALL). Alternative splicing of the glucocorticoid receptor (GR) gene results in several isoforms. We examined an association of the expression pattern of GR isoforms in leukemic blasts with their sensitivity to glucocorticoid in childhood ALL. PROCEDURES: The relative mRNA expression of GRalpha, GRbeta, GRgamma, and GR-P was determined in leukemic blasts of 23 childhood ALL at initial presentation and of 14 ALL cell lines by quantitative RT-PCR. Glucocorticoid-sensitivity of leukemic blasts was determined by counting apoptotic cells with flow cytometry after 6-hr incubation with prednisolone (PSL). RESULTS: The relative expression of GRalpha mRNA was significantly higher in blasts of B-precursor ALL than those of others (13.6 vs. 2.24, P = 0.015), while those of GRalpha, GRbeta, and GRgamma showed no difference. GRbeta/GRalpha ratios were significantly lower in B-precursor ALL than others (0.80 vs. 4.64, P = 0.035). The proportions of apoptotic cells after PSL exposure were inversely correlated with the GRbeta/GRalpha ratios in ALL cell lines (r = -0.612, P = 0.020). PSL administration induced apoptosis efficiently in leukemic blasts with low GRbeta/GRalpha ratios compared with those of high ratios (cell lines: 4.93% vs. 1.90%, P = 0.013, primary leukemia: 11.7% vs. 3.6%, P = 0.037). CONCLUSIONS: The amounts of GR isoform mRNA in leukemic blasts were closely correlated with sensitivity to glucocorticoid exposure. The mRNA expression pattern of GR isoforms at initial presentation may provide valuable information for prognosis in children with newly diagnosed ALL.

Adolescent↗
PubMed2005

Immune response after influenza vaccination in children with cancer.

PURPOSE: To assess the immune response to inactivated trivalent split influenza vaccine in children with cancer. PROCEDURES: Forty-four children with various types of malignancies received two doses of influenza vaccine 2-4 weeks apart. Hemagglutinin-inhibition (HI) antibody titers were determined in paired sera obtained just before the first vaccination and 4 weeks after the second vaccination. RESULTS: Influenza vaccine was administered to all children without any serious adverse effects. Protective titer rates (proportion of patients achieving antibody titers > or =40 among those with pre-vaccination titers <40) and response rates (proportion of patients with fourfold or more antibody rise) were 72% and 65% for H1N1, 60% and 40% for H3N2, and 38% and 46% for influenza B, respectively. However, patients on chemotherapy showed a significantly lower immune response to influenza A than those having completed chemotherapy; protection titer rates were 42% versus 90% for H1N1 (P = 0.006) and 25% versus 83% for H3N2 (P = 0.019). For influenza B, patients with low IgG showed a lower response rate than those with high IgG (29% vs. 61%, P = 0.040). Multivariate analysis revealed that factors significantly associated with a lower immune response were low IgG (P < 0.001) and administration of chemotherapy (P = 0.003) for H1N1, administration of chemotherapy (P = 0.008) for H3N2, and low white blood cell (WBC) count (P = 0.030) and low IgG (P = 0.030) for influenza B. CONCLUSIONS: Influenza vaccination given to children with cancer was safe and induced immune reaction comparable to healthy children, although patients on chemotherapy and/or with chemotherapy-related conditions had a limited ability to produce a sufficient immune response.

Adolescent↗