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Biomedical subjects

Nobuo Matsuura

Publications and source records attributed to Nobuo Matsuura.

At least 19 recordsLinked to original sources
PubMed2006

Haplotype analysis reveals founder effects of thyroglobulin gene mutations C1058R and C1977S in Japan.

CONTEXT: Thyroglobulin (Tg) mutations were previously believed to be rare, resulting in congenital goitrous hypothyroidism. However, an increasing number of patients with Tg mutations, who are euthyroid to mildly hypothyroid, have been identified in Japan. OBJECTIVES: The purpose of this study was to investigate whether the three frequently found Tg mutations, namely C1058R, C1245R, and C1977S, were caused by a founder effect. RESULTS: We found 26 different mutations within the Tg gene in 52 patients from 41 families. Thirty-five patients were homozygous for the mutations, whereas the others were compound heterozygous. The occurrence of Tg mutation within the general Japanese population is one in 67,000. Patients with the C1245R mutation were found throughout Japan, whereas those with the C1058R mutation were confined to a small village on a southern island, and those with the C1977S mutation were restricted to a city. The eight patients with the C1058R mutation and the seven patients with the C1977S mutation all showed the same combinations of 18 single-nucleotide polymorphisms in the coding region of the Tg gene, which would appear in one in 810 million and one in 37 billion, respectively, control subjects. CONCLUSIONS: The frequently found mutations, C1058R and C1977S, were caused by founder effects. This result suggests that Tg mutations may provide a genetic basis for the cause of familial euthyroid goiter.

Founder Effect↗
PubMed2006

A sensitive radioimmunoassay of insulin autoantibody: reduction of non-specific binding of [125I]insulin.

There has been a lack of consensus among results of assays for insulin autoantibody (IAA) carried out by different laboratories, despite a reduction in the non-specific effect using a cold insulin competitor in radioimmunoassays (RIAs) for IAA in type I diabetes. We speculated that the discrepancies are partly a result of the non-specific binding (NSB) of [125I]insulin to unidentified molecules in serum on polyethylene glycol separation, and tried to improve IAA RIAs. The molecular weight of a candidate for the factor causing NSB was estimated to be about 700 kDa by gel filtration analysis, resembling that of alpha 2-macroglobulin (a2M). Further, the addition of purified a2M to the assay resulted in an increase in NSB. Screening revealed that heterocyclic compounds, such as isothiazolinone derivatives (ProClin300), were greatly effective at reducing NSB in control subjects from 2.904+/-0.909% to 1.347+/-0.254% (n=283, mean+/-SD, p<0.0001). Using our newly developed IAA RIA with ProClin300, the sensitivity for newly diagnosed type I diabetes patients (n=55) was 32.7% and 30.9% with or without insulin competition, respectively, whereas that of the former assay without ProClin300 was only 20.0%.

Adolescent↗
PubMed2006

Parent and health professional perspectives in the management of adolescents with diabetes: development of assessment instruments for international studies.

OBJECTIVE: Assessment of quality of life (QOL) in adolescents with diabetes requires patient, parent and health professional input. Psychometrically robust instruments to assess parent and professional perspectives are required. RESEARCH DESIGN AND METHODS: Questionnaires concerning adolescent QOL were developed for completion by parents and health professionals. In an international study assessing QOL in 2,101 adolescents with diabetes (median age 14 years, range 10-18; from 17 countries including Europe, Japan and North America), parents and health professionals completed their respective questionnaires between March and August 1998. RESULTS: Feasibility and acceptability of the new questionnaires were indicated by high questionnaire completion rates (adolescents 92%; parents 89%; health professionals 94%). Internal consistency was confirmed (Cronbach's alpha coefficients 0.80 parent; 0.86 health professional). Correlations of Diabetes Quality of Life Questionnaire for Youths (DQOLY) scores with parent and health professional global QOL ratings were generally low (r ranging from 0.12 to 0.36). Parent-rated burden decreased incrementally across adolescence, particularly for girls. Professional-rated burden followed a similar profile but only after age 15 years. Until then, burden was rated as uniformly high. Clinically relevant discrepancies in parent and professional burden scores were noted for one-parent families and families where adolescents had been referred for psychological help. In both cases, health professionals but not one-parent families perceived these as high burden situations. The clinical significance of this relates to the significantly poorer metabolic control recorded for adolescents in both situations. CONCLUSIONS: Parent and health professional questionnaires were found to have adequate internal consistency, and convergent and discriminant validity in relation to key clinical and QOL outcomes. The questionnaires are brief, easy to administer and score. They may also enable comparisons across countries and languages to facilitate development of international health outcome parameters. The inclusion of the parent and health professional perspectives completes a comprehensive assessment of adolescent QOL relevant to diabetes.

Adolescent↗
PubMed2006

Effects of dioxins on the quantitative levels of immune components in infants.

Dioxins (polychlorinated dibenzo-p-dioxin (PCDD)+polychlorinated dibenzofuran (PCDF)) and polychlorinated biphenyls (PCBs) are potentially hazardous compounds and have structural similarity with thyroid hormones. Animal studies have demonstrated that PCDDs, PCDFs and PCBs can alter immune functions. However, in humans it is not yet elucidated whether dioxins contained in breast milk have any effects on the immune functions in infants. To investigate the effects of dioxins on the immune system, we compared the quantitative levels of immune components between a breast-fed group and bottle-fed group, in which dioxin concentration is almost zero. Ratios of immune cells, such as CD4+ and CD8+ T-lymphocytes, as well as B-lymphocytes (CD19+ and/or CD20+) and NK cells (CD16+, CD56+) in peripheral blood lymphocytes, serum immunoglobulin level, and level of specific IgE antibody to allergens in the venous blood at 12 months of age were assessed in a subgroup of 281 infants. The relationship of post-natal dioxin exposure via breast feeding with the ratio of immunological markers and the level of humoral antibodies up to 12 month of age was not demonstrated. In conclusion, it would appear that the content of dioxins in breast milk in the Japanese general population is not enough to induce any change in theses-examined immunological parameters during the first year of life, although long-term effects remain to be evaluated.

Adult↗
PubMed2006

[Development of neonatal Graves' disease--prediction, prevention and treatment].

It is well known that neonatal hyperthyroidism or neonatal Graves' disease is caused by trans-placental transfer of TSH receptor antibodies. The antibodies stimulate the thyroid gland in the fetal and neonatal stages, which induces hyperfunction of the thyroid gland and increased thyroid hormone production. In this paper, I would like to focus on four clinically interesting issues related neonatal hyperthyroidism. 1. High risk of mothers whose infants develop neonatal Graves' disease. 2. How to predict for development of neonatal Graves' disease. 3. How to prevent for development of neonatal Graves' disease. 4. How to treat the infants with Graves' disease. I also mention on the neonatal thyrotoxicosis and fetal hyperthyroidism.

Autoantibodies↗
PubMed2005

Human milk survey for dioxins in the general population in Japan.

BACKGROUND: Much attention has been paid to the level of dioxins in breast milk in Japan but few large-scale studies have been conducted on the subject. METHODS: From 1997 to 2002, we collected 839 samples of breast milk from primiparas residing throughout Japan. Starting in 1999, breast milk was also collected from secundiparas. Seven isomers of polychlorinated dibenzo-p-dioxins (PCDDs), 10 of polychlorinated dibenzofurans (PCDFs), 4 of coplanar polychlorinated biphenyls (Co-PCBs) and 8 of mono-orthochlorinated polychlorinated biphenyls (mono-ortho PCBs) were analyzed by employing gas chromatography and mass spectrometry. A correlation between the level of dioxins in human milk and the age of the mothers was noted for the primiparas and the secundiparas; and the levels were compared between the first and the second deliveries. Grouped by parity and prefecture in each year, observations were also made on the trends in these levels. Dioxin levels are shown by using geometric means because their distributions were skewed to the left. RESULTS: The sum of PCDDs and PCDFs, Co-PCBs, mono-ortho PCBs, and total dioxins in the breast milk of primiparas were 13.9, 5.4, 3.4, and 22.7 pg TEQ/g fat, respectively. In the samples obtained from secundiparas, these levels were 63-68 percents of those taken from the primiparas. The correlation coefficients between the PCDDs/DFs, Co-PCBs, mono-ortho PCBs, and total dioxins and the age of the primiparas were 0.19, 0.17, 0.36, and 0.24, respectively. All these correlations were statistically significant (p < 0.001). The positive correlations between these contaminants and the age of the secundiparas were also examined. The total dioxins as well as PCDDs/DFs, Co-PCBs, and mono-ortho PCBs in the breast milk of the primiparas declined significantly between 1998 and 2002 (regression coefficients: -0.04, -0.05, -0.03, and -0.03, respectively). However, no significant decline in these levels was observed when sorted by prefectures. CONCLUSIONS: Much attention should be paid to the age and parity of nursing mothers when investigating the relationship between the level of dioxins in breast milk and the body burden of infants.

Dioxins↗
PubMed2005

Domain-specific function of ShcC docking protein in neuroblastoma cells.

ShcC is a family member of the Shc docking proteins that possess two different phosphotyrosine-binding motifs and conduct signals as Grb2-binding substrates of various receptor tyrosine kinases. We have recently shown that some neuroblastoma cell lines, such as NB-39-nu cells, express a protein complex of hyperphosphorylated ShcC and anaplastic lymphoma kinase (ALK), which is self-activated by gene amplification. Here, we demonstrate that the expression of a mutant ShcC lacking Grb2-binding sites, 3YF-ShcC, significantly impaired the survival, differentiation and motility of NB-39-nu cells by blocking the ERK and Akt pathways. On the other hand, cells overexpressing ShcC or 3YF-ShcC, but not a mutant ShcC that lacks SH2, showed decreased anchorage independency and in vivo tumorigenicity, suggesting a novel ShcC-specific suppressive effect through its SH2 domain on cell transformation. Notably, overexpression of ShcC suppressed the sustained phosphorylation of Src family kinase after cell detachment, which might be independent of phosphorylation of Grb2-binding site. It was indicated that the Src/Fyn-Cas pathway is modulated as a target of these suppressive effects by ShcC. Reciprocal change of ShcC expression and phosphorylation observed in malignant neuroblastoma cell lines might be explained by these phosphotyrosine-dependent and -independent functions of ShcC.

Agar↗
PubMed2005

Past 10-year status of insulin therapy for preschool-age Japanese children with type 1 diabetes.

The aim of this study was to evaluate the past 10-year status of insulin therapy for preschool-age children with type 1 diabetes in Japan. One-hundred and forty-two patients who had been diagnosed at less than 5 years of age within the past 10 years (1993-2002) at 36 hospitals were registered in this study on April 2003. The methods of daily insulin therapy and episodes of severe hypoglycemia during the preschool period were investigated. Eighty-six (60.6%) children were treated with a pen-type device and 56 (39.4%) were treated with a syringe-type device. The once-a-day insulin regimen was used for 2, a twice-a-day regimen for 104, a three-times-a-day for 28 and a four-times-a-day for 8. Episodes of severe hypoglycemia were recorded in nearly half of the subjects, and one-fourth of the subjects had repeated episodes. One hundred and eleven of their parents were questioned regarding the degree of psychosocial stress experienced during the care of their children. Most parents worried about the glycosylated hemoglobin value at each hospital visit. They were next very afraid of nocturnal severe hypoglycemia, independent of any actual experience. These results suggest that although insulin therapy can involve various methods, the important point is to simultaneously provide good glycemic control and prevent severe hypoglycemia, especially during this age.

Child, Preschool↗
PubMed2005

Slowly progressing form of type 1 diabetes mellitus in children: genetic analysis compared with other forms of diabetes mellitus in Japanese children.

AIMS: Slowly progressing insulin-dependent diabetes mellitus (SPIDDM, hereafter referred to as IDDMS in this article) is a unique subtype of type 1 diabetes in Japanese children. To clarify the genetic background of IDDMS, we analyzed HLA-DRB1, -DQB1 and -DQA1 alleles, phenotypes, and genotypes and compared them with acute-onset type 1 diabetes, non-insulin-dependent diabetes mellitus (NIDDM), and control subjects. METHODS: HLA-DRB1, -DQA1, and -DQB1 types were defined by DNA analysis using polymerase chain reaction (PCR), and typing for human leukocyte antigen (HLA) was performed by the sequencing-based typing (SBT) method using Match Maker and MT Navigator in combination. HLA-A24 was determined by the PCR-sequence-specific oligo-nucleotide probe (PCR-SSOP) method. The 234 patients with type 1 diabetes were divided into three groups: 32 cases of IDDMS, 137 cases of acute-onset form aged more than 5 yr (IDDMA), and 65 cases of acute-onset form less than 5 yr of age at onset (IDDME). In addition, we studied 55 children with type 2 diabetes (NIDDM) and 97 normal controls. RESULTS: The patients with IDDMS were older at diagnosis and had a greater body mass index (BMI) than those with IDDM (A + E). The prevalence of islet autoantbodies was not significantly different from IDDMA. The allele frequencies of DRB1*0405, DQA1*0302, and DQB1*0401 were significantly increased; however, DRB1*0901, DQA1*03, DQB1*0303, and HLA-A24 were low and not significantly different from control subjects. CONCLUSIONS: HLA phenotypes and genotypes in patients with IDDMS were different from those in NIDDM and control subjects and were closer to those of IDDMA. Together with a low prevalence of HLA-A24, the genetic features are similar to those of SPIDDM and latent autoimmune diabetes in adults (LADA) in adults. In our series, the clinical features such as lack of obesity and lack of responsiveness to oral hypoglycemic agents were most different from those of adults' onset.

Age of Onset↗
PubMed2005

Assays for thyroid-stimulating antibodies and thyrotropin-binding inhibitory immunoglobulins in children with Graves' disease.

Studies on thyrotropin receptor autoantibodies (TRAb) by measurement of both thyroid-stimulating antibodies (TSAb) and thyrotropin-binding inhibitory immunoglobulins (TBII) in serum from children with Graves' disease are limited in number of studies. The aim of this study was to investigate the levels of serum TSAb and TBII in children with Graves' disease, and to evaluate the clinical significance of these antibodies. We measured the serum TSAb and TBII at diagnosis and during management in 65 children with Graves' disease. Patients were divided into four groups according to their metabolic state: those with untreated active Graves' disease, those receiving treatment with antithyroid drugs, those in remission, and those in relapse. At diagnosis, both TSAb and TBII assays had high sensitivities and high specificities. In follow-up, the levels of both TSAb and TBII paralleled the course of the disease. There was a strong positive correlation between TSAb and TBII. TBII levels were significantly higher in the patients with ophthalmopathy than those without ophthalmopathy in untreated Graves' children. It was concluded that TSAb and TBII measurements are valuable in the diagnosis and management of children with Graves' disease.

Adolescent↗
PubMed2004

Identification of a novel type 1 diabetes susceptibility gene, T-bet.

The gene encoding interferon (IFN)-gamma, IFNG, is known as one of the candidate susceptibility genes for type 1 diabetes. In addition, cytokines, including IFN-gamma, play important roles in the pathogenesis of type 1 diabetes. Therefore, we focused on the Th1-specific T-box transcription factor gene (T-bet), which contributes to the induction of the hallmark Th1 cytokine, IFN-gamma. We first screened for polymorphisms in the T-bet gene and detected two microsatellite repeat polymorphisms located in intron 1 and the 3'- flanking region, and two single nucleotide polymorphisms, including a His33Gln substitution within the coding region. By association studies, the Gln-positive phenotype and (CA)14 allele in 3'-flanking region of T-bet were found to be associated with type 1 diabetes in the Japanese population. Furthermore, Gln33 T-bet showed a significantly higher transcriptional activity of the IFNG gene via a dual luciferase reporter assay. Our study suggests the first evidence of an association between type 1 diabetes and polymorphisms in the T-bet gene, and that variation in T-bet transcriptional activity may play a role in the development of type 1 diabetes, possibly through the effect on IFN-gamma production in Th1 cells.

Adolescent↗
PubMed2004

A questionnaire survey on the use of quick-acting insulin analog in Japanese children and adolescents with type 1 diabetes.

BACKGROUND: The aim of this study was to investigate the actual condition of quick-acting insulin analog (Q) in Japanese children and adolescents with type 1 diabetes. METHODS: Forty-seven physicians who managed 944 patients under 18 years of age with type 1 diabetes, were requested to complete questionnaires in May 2002 regarding the use of Q. RESULTS: Q was administered to 417 out of 944 (44%) patients. The details of the daily insulin regimens were as follows: three doses of Q with basal insulin in 116 of 403 (29%), three doses of Q with more than twice the basal insulin in 69 of 403 (17%), and other modifications using either Q or regular insulin (R) depending on the patients' lifestyles in 213 of 403 (53%). Q dose was equal to R after the change of insulin regimens in 232 of 290 (80%). After switching to Q from R, the basal insulin dosage increased in 113 of 341 (33%) and the number of basal insulin injections increased in 42 of 341 (12%). After the transfer to Q from R, glycemic control was judged to improve in 179 of 372 (48%), to have no significant change in 162 of 372 (44%), and to aggravate in 31 of 372 (8%). The majority of patients, (305/389; 78%), noted an improvement of quality of life (QOL) following the administration of Q. CONCLUSIONS: Q was considered to be useful in flexibility of daily insulin therapy and improvement of QOL in children and adolescents with type 1 diabetes. Insulin therapy for type 1 diabetes during childhood and adolescence should be tailored to meet individual needs.

Adolescent↗
PubMed2004

Population pharmacokinetics of arbekacin, vancomycin, and panipenem in neonates.

Immature renal function in neonates requires antibiotic dosage adjustment. Population pharmacokinetic studies were performed to determine the optimal dosage regimens for three types of antibiotics: an aminoglycoside, arbekacin; a glycopeptide, vancomycin; and a carbapenem, panipenem. Eighty-three neonates received arbekacin (n = 41), vancomycin (n = 19), or panipenem (n = 23). The postconceptional ages (PCAs) were 24.1 to 48.4 weeks, and the body weights (BWs) ranged from 458 to 5,200 g. A one-compartment open model with first-order elimination was applied and evaluated with a nonlinear mixed-effect model for population pharmacokinetic analysis. In the fitting process, the fixed effects significantly related to clearance (CL) were PCA, postnatal age, gestational age, BW, and serum creatinine level; and the fixed effect significantly related to the volume of distribution (V) was BW. The final formulas for the population pharmacokinetic parameters are as follows: CL(arbekacin) = 0.0238 x BW/serum creatinine level for PCAs of <33 weeks and CL(arbekacin) = 0.0367 x BW/serum creatinine level for PCAs of > or = 33 weeks, V(arbekacin) = 0.54 liters/kg, CL(vancomycin) = 0.0250 x BW/serum creatinine level for PCAs of <34 weeks and CL(vancomycin) = 0.0323 x BW/serum creatinine level for PCAs of > or = 34 weeks, V(vancomycin) = 0.66 liters/kg, CL(panipenem) = 0.0832 for PCAs of <33 weeks and CL(panipenem) = 0.179 x BW for PCAs of > or = 33 weeks, and V(panipenem) = 0.53 liters/kg. When the CL of each drug was evaluated by the nonlinear mixed-effect model, we found that the mean CL for subjects with PCAs of <33 to 34 weeks was significantly smaller than those with PCAs of > or = 33 to 34 weeks, and CL showed an exponential increase with PCA. Many antibiotics are excreted by glomerular filtration, and maturation of glomerular filtration is the most important factor for estimation of antibiotic clearance. Clinicians should consider PCA, serum creatinine level, BW, and chemical features when determining the initial antibiotic dosing regimen for neonates.

Aminoglycosides↗