Nobuo Matsuura

Kabuki make-up syndrome: A syndrome of mentalretardation, unusual facies, large and protruding ears, and postnatal growth deficiency

A previously unrecognized mental retardation malformation syndrome was observed in five unrelated Japanese children. Consistent clinical features included moderate-to-severe mental retardation, progressive dwarfism of postnatal onset, a peculiar facies characterized by long palpebral fissures, with eversion of the lateral third of the lower eyelids, arched eyebrows, broad and depressed nasal tip, large prominent earlobes, short fifth fingers, abnormal dermatoglyphics including absence of digital triradius c or d, and frequent otitis media in infancy. Inconsistent abnormalities included epicanthal folds, cleft or high-arched palate, widely spaced teeth, low occipital hair line, scoliosis, and dislocation of the hip joint. Neither familial occurrence nor parental consanguinity was noted. The etiology of the malformation syndrome remains unknown.

Familial Neonatal Transient Hypothyroidism Due to Maternal TSH-Binding Inhibitor Immunoglobulins

IN 1960, Sutherland et al.1 reported on children with familial nongoitrous cretinism born of a hypothyroid mother with Hashimotos disease. Subsequently, Goldsmith et al.2 studied this family in de...

Congenital adrenal hyperplasia due to 21-hydroxylase deficiency: Newborn screening and its relationship to the diagnosis and treatment of the disorder

Abstract Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency can be detected by newborn screening. The screening alone in 29 programs from 13 countries resulted in the diagnosis of CAH in 1 2 of affected newborns and expedited the diagnosis in 1 3 of affected newborns clinically suspected to have CAH. The benefits of newborn screening for CAH were prevention of severe adrenal crisis, its sequela, incorrect male sex assignment of severely virilized female newborns, and progressive signs of androgen excess. Screening revealed a higher incidence of CAH worldwide (1:15000 live births) compared with the case survey incidence (1:32000 live births) The false-positive rate (usually found in low birth weight and premature infants) was acceptably low (0.01–0.5%) except for three programs (0.7–2.5%). The false-negative rate of CAH screening was negligible. Prenatal diagnosis of CAH is possible by HLA typing or 21-hydroxylase B gene analysis of cultured fetal cells from chorionic villus biopsy sampling in the first trimester and from amniotic cells or hormonal analysis of amniotic fluid in the second trimester. Prenatal treatment of CAH is possible via maternal dexamethasone therapy beginning early pregnancy. However, efficacy and side effects of maternal dexamethasone therapy require further investigation.

HLA-DQ system and insulin-dependent diabetes mellitus in japanese: does it contribute to the development of IDDM as it does in caucasians?

Fifty-six unrelated Japanese patients with insulin-dependent diabetes mellitus (IDDM) were HLA-typed, and restriction fragment length polymorphism (RFLP) analysis was performed after enzyme digestion with Bam HI and Taq I by using both DR and DQ probes. As previously reported, increased frequencies of Bw54, Cw1, DR4, and DRw53, which are in strong linkage disequilibrium in the Japanese population and make the characteristic Japanese haplotype, were confirmed. DQw4, a new allele of the DQ system recognized by the monoclonal antibody HU-46 and in linkage disequilibrium with this haplotype, presented the highest IDDM association. The RFLP analysis also showed the strongest correlation to IDDM when the DQ probe was applied. These results indicate that HLA-DQ might play the most important role in the development of IDDM in Japanese as well as in Caucasians. The correlation of DQβ amino acid sequences strongly associated with IDDM in Japanese are discussed in this study, and contrasting results were found when such sequences were compared with those of Caucasians.

Immunogenetics of early-onset insulin-dependent diabetes mellitus among the Japanese: HLA, Gm, BF, GLO, and organ-specific autoantibodies — the J.D.S. study

The Japan Diabetes Society (JDS) conducted a multicenter study on the immunogenetics of early-onset insulin-dependent diabetes mellitus (IDDM) of the Japanese. Human leukocyte antigen (HLA), properdin factor B (BF), immunoglobulin heavy-chain complex (Gm), and glyoxalase of erythrocytes (GLO) were typed, and organ-specific autoantibodies, including islet cell antibody (ICA), were assayed in 159 Japanese IDDM patients and their family members and in 258 healthy Japanese controls. The HLA-DRw9 phenotype and HLA-Bw61/DRw9 haplotype were significantly increased among the patients with autoantibodies other than ICA but with no autoimmune diseases (RR = 5.84, cP less than 0.001; and RR = 7.45, P less than 0.001), whereas the HLA-DR4 phenotype and HLA-Bw54/DR4 haplotype were significantly increased in those without either the autoantibodies or autoimmune diseases (RR = 2.64, cP less than 0.001; and RR = 4.55, P less than 0.001). The HLA-DR4 phenotype was significantly increased in the patients with autoimmune thyroid diseases (RR = 6.21, cP less than 0.05). In all groups of patients, the HLA-DR2 phenotype was significantly decreased, and the relative risk of the HLA-DRw9/DR4 genotype was highest among all HLA-DR genotypes. No significant association was found between HLA type and the duration or incidence of ICA. Gm types of g and gft were significantly increased in the patients with the autoantibodies (RR = 2.11, P less than 0.05; and RR = 34.11, P less than 0.05), whereas the BF-F phenotype was significantly decreased in the patients either with or without autoantibodies (RR = 0.43, P less than 0.05; and RR = 0.46, P less than 0.05). There was no association between IDDM and GLO type. These data indicate that immunogenetic bases underlying IDDM of the Japanese are heterogeneous, as are those in Caucasians.

A separation method for DNA computing based on concentration control

A separation method for DNA computing based on concentration control is presented. The concentration control method was earlier developed and has enabled us to use DNA concentrations as input data and as filters to extract target DNA. We have also applied the method to the shortest path problems, and have shown the potential of concentration control to solve large-scale combinatorial optimization problems. However, it is still quite difficult to separate different DNA with the same length and to quantify individual DNA concentrations. To overcome these difficulties, we use DGGE and CDGE in this paper. We demonstrate that the proposed method enables us to separate different DNA with the same length efficiently, and we actually solve an instance of the shortest path problems.

Pituitary and gonadal function in prepubertal boys with hypospadias.

Luteinizing hormone releasing hormone and human chorionic gonadotropin tests were performed to examine the pituitary gonadal axis in 31 prepubertal boys with hypospadias. Luteinizing hormone and follicle stimulating hormone responses to luteinizing hormone releasing hormone in these boys with hypospadias were significantly higher than those in prepubertal control subjects (luteinizing hormone, p less than 0.01). follicle stimulating hormone, p less than 0.05). Prepubertal boys with hypospadias had remarkably reduced testosterone responses to human chorionic gonadotropin stimulation compared to controls (p less than 0.01). Hormonal milieus were further analyzed in the subtypes of hypospadias depending on their severity (distal vs. proximal). Nine of the 31 boys with hypospadias were classified as the proximal type. Basal luteinizing hormone levels in the proximal type were significantly higher than in the distal type (p less than 0.05). Luteinizing hormone and follicle stimulating hormone responses to luteinizing hormone releasing hormone and responses of testosterone to human chorionic gonadotropin were not significantly different in the 2 types. Seven of the 31 boys with hypospadias had a history of maternal progestin ingestion. Basal luteinizing hormone levels and responses of luteinizing hormone and follicle stimulating hormone to luteinizing hormone releasing hormone were also significantly higher in these subjects than in controls (p less than 0.005), though basal levels and responses of testosterone to human chorionic gonadotropin were not different from those of controls. Tests conducted to determine luteinizing hormone and follicle stimulating hormone and testosterone levels using luteinizing hormone releasing hormone and human chorionic gonadotropin stimulation revealed no statistical differences between the boys with hypospadias who had a history of maternal progestin ingestion and those without such a history. The majority of prepubertal boys with hypospadias had varying degrees of deficient testicular activity. The testicular function of these patients should be evaluated longitudinally at puberty and thereafter in order to insure the completion of secondary sexual development.

Influence of iodine excess due to iodine-containing antiseptics on neonatal screening for congenital hypothyroidism in Hokkaido prefecture, Japan

Abstract Introduction: Iodine excess in newborn infants due to the use of iodine-containing antiseptics (povidone-iodine, PVP-I) has been a substantial cause of transient hypothyroidism, particularly in iodine-deficient areas of the world. However, Japan is an iodine-sufficient area. To evaluate the influence of iodine excess due to PVP-I during the perinatal period on neonatal screening for congenital hypothyroidism (CH) in an iodine-sufficient country such as Japan, we determined the iodide status and thyrotropin (TSH) levels in neonates during exposure and without exposure to perinatal PVP-I. Methods: Dried blood on filter paper was collected for neonatal screening at ages 4–7 days before PVP-I exposure (phase I) and after withdrawal of PVP-I from umbilical cord care (phase II). Voided urine samples from the infants and maternal breast milk samples were collected at the time of neonatal blood collection. Iodide was measured in urine and breast milk using an iodide-specific electrode. TSH was measured in the dried blood specimens by enzyme linked immunosorbent assay (ELISA). Results: Urinary iodide and TSH levels were highest in breast-fed infants on PVP-I for umbilical cord care and born to iodine-overloaded mothers who received PVP-I by vaginal application. During phase II, urinary iodide and TSH decreased in infants born in the same clinics where PVP-I had been used. Good correlation was noted between iodide concentrations in breast Witk and the degree of iodine overload in the mother. Discussion: The direct application of PVP-I to infants and iodide in breast milk are essential pathways of iodine overload to infants. Withdrawal of PVP-I significantly decreased the false-positive rate of neonatal screening for CH. Consequently, PVP-I should not be used in delivery or perinatally, even in iodine-sufficient areas such as Japan.

Associatior of B cell alloantigen with juvenile onset diabetes mellitus in the Japanese

Sixty-four Japanese insulin dependent juvenile onset diabetes mellitus (JOD) were studied in relation to HLA-A, B, and DR. Significant deviations were observed. HLA-Bw54 was increased (PF = 49.2%, RR = 6.4) and HLA-B5 was decreased (PF = 7.9%, RR = 0.19). Using radioimmunoassay, two HLA-DR antigens were investigated. Hon 7 antigen, so-called MT3 (WIA4x7), which has linkage disequilibrium between HLA-BW54, is highly associated (PF = 96.9%, RR = 27.8) with JOD found in the Japanese.

LOCAL SEARCH BY CONCENTRATION-CONTROLLED DNA COMPUTING

Concentration-controlled DNA computing is presented for accomplishing a local search for the solution of a shortest path problem. In this method, the concentrations of DNA representing edges are determined according to the costs on edges, and then the hybridization process is performed. Since the concentrations of hopeless candidate solutions tend to be small after the hybridization process, a local search by concentration-controlled DNA computing is a promising approach. In order to discuss about the relationship between given costs on edges in the graph and concentrations of generated DNA paths, a simulation model of the hybridization process is used and the results of a laboratory experiment are shown.