Studies on Physical and Mental Growth of Prematurely Born Children

The present paper described the results of somatotype for prematurely born children at consecutive ages from primary school to junior high school in our follow-up study. The somatotypy according to the composite assessment of WETZEL\u27 S developmental level and leg length-height ratio was used for this study. The prematurely born children were over-represented among the inferior somatotype and under-represented among the superior somatotype when compared with the matched control group of maturely born children

Subcutaneous injection, from birth, of epigallocatechin-3-gallate, a component of green tea, limits the onset of muscular dystrophy in mdx mice: a quantitative histological, immunohistochemical and electrophysiological study

Dystrophic muscles suffer from enhanced oxidative stress. We have investigated whether administration of an antioxidant, epigallocatechin-3-gallate (EGCG), a component of green tea, reduces their oxidative stress and pathophysiology in mdx mice, a mild phenotype model of human Duchenne-type muscular dystrophy. EGCG (5mg/kg body weight in saline) was injected subcutaneously 4× a week into the backs of C57 normal and dystrophin-deficient mdx mice for 8weeks after birth. Saline was injected into normal and mdx controls. EGCG had almost no observable effects on normal mice or on the body weights of mdx mice. In contrast, it produced the following improvements in the blood chemistry, muscle histology, and electrophysiology of the treated mdx mice. First, the activities of serum creatine kinase were reduced to normal levels. Second, the numbers of fluorescent lipofuscin granules per unit volume of soleus and diaphragm muscles were significantly decreased by about 50% compared to the numbers in the corresponding saline-treated controls. Third, in sections of diaphragm and soleus muscles, the relative area occupied by histologically normal muscle fibres increased significantly 1.5- to 2-fold whereas the relative areas of connective tissue and necrotic muscle fibres were substantially reduced. Fourth, the times for the maximum tetanic force of soleus muscles to fall by a half increased to almost normal values. Fifth, the amount of utrophin in diaphragm muscles increased significantly by 17%, partially compensating for the lack of dystrophin expressio

低出生体重児を対象としたブラゼルトン新生児行動評価による精神発達遅滞児の判別

ブラゼルトン新生児行動評価法（Neonatal Behavioral Assessment Scale；NBAS）による精神発達遅滞児の鑑別診断の有効性を確認するため，追跡調査の結果を用いた判別分析による検討を行った．対象は新生児期にNBASを行い，3才までの発達経過を確認した低出生体重児86例である．これらの対象児を修正3才時のマッカーシー知能発達検査の結果から，境界値を含む一般知能指数90未満の17例（遅滞群）と，一般知能指数90以上の69例（正常群）の2群に分類し，この2群が胎齢44週時のNBASの結果から既知のグループに正しく区別されるかどうかについて，フィッシャーの線型判別式を用いた判別分析を行った．その結果，胎齢44週時のNBASの結果から正常群では69例中61例（88.5％）が，遅滞群では17例中12例（70.6％）が既知のグループに正しく分類され，その全体に対する割合は84.9％であった．また，一般知能指数と判別結果では指数70～79の遅滞域の4例中1例（25.0％），指数80～89の境界域の9例中4例（44.4％），指数90～120未満の正常域の69例中8例（13.0％）が誤判別であった．次に，関数値と各変数値とのグループ内相関を算出した結果，NBASのクラスターのうち「意識状態の幅」，「運動の調整」，「補足項目値」，「意識状態の調整」，「方位反応」のクラスターが順に統計的に影響力が強く，新生児期の行動評価の必要性を示した．以上より，胎齢44週時のNBASから低体重出生の精神発達遅滞児の判別は高い精度で可能で，早期診断と介入，療育の適応決定に有効であると考えられた．また，より長期的なフォローの必要性も示唆した．The results of a follow-up study were reviewed by discriminant analysis to verify the effectiveness of differential diagnosis for mentally retarded infants by the Brazelton Neonatal Behavioral Assessment Scale (NBAS). The subjects were 86 low birthweight infants for whom the NBAS was performed in the neonatal period and whose developmental progress through age 3 years was confirmed. These infants were divided into 2 groups according to the results of the McCarthy Scales at revised age 3 years, i.e., 17 cases of intelligence quotient (IQ) of less than 90 including borderline area (retarded group) and 69 cases of IS 90 or more (normal group). Fisher\u27s linear discriminant analysis was performed to see if these 2 groups are properly distinguished to the known groups in reference to the results of the NBAS at gestational age 44 weeks. As the result, 61 of the 69 cases in the normal group (88.5%) and 12 of the 17 cases in the retarded group (70.6%) were found to be properly classified in the known groups. The overall rate of proper classification was 84.9%. False discrimination was found in 1 of the 4 cases (25.0%) in the retarded area of IQ 70-79, in 4 of the 9 cases (44.4%) in the borderline area of IQ 80-89, and in 8 of the 69 cases (13.0%) in the normal area of IQ 90-<120. Then, the pooled within-groups correlations between discriminating variables and canonical discriminant functions were calculated. The results showed statistical influences by such NBAS clusters as state range, motor performance, supplemental items, state regulation and orientation, in descending order, indicating the necessity of behavioral assessment in the neonatal period. From the above, it was considered that discrimination of mental retardation in low birthweight infants in reference to the NBAS at gestational age 44 weeks is available at a high accuracy, and that the NBAS is effective on early diagnosis and on determining the application of early intervention and care. It was also indicated that follow-up for a longer period is necessary

Molecular phylogeny of the higher and lower taxonomy of the Fusarium genus and differences in the evolutionary histories of multiple genes

<p>Abstract</p> <p>Background</p> <p>Species of the <it>Fusarium </it>genus are important fungi which is associated with health hazards in human and animals. The taxonomy of this genus has been a subject of controversy for many years. Although many researchers have applied molecular phylogenetic analysis to examine the taxonomy of <it>Fusarium </it>species, their phylogenetic relationships remain unclear only few comprehensive phylogenetic analyses of the <it>Fusarium </it>genus and a lack of suitable nucleotides and amino acid substitution rates. A previous stugy with whole genome comparison among <it>Fusairum </it>species revealed the possibility that each gene in <it>Fusarium </it>genomes has a unique evolutionary history, and such gene may bring difficulty to the reconstruction of phylogenetic tree of <it>Fusarium</it>. There is a need not only to check substitution rates of genes but also to perform the exact evaluation of each gene-evolution.</p> <p>Results</p> <p>We performed phylogenetic analyses based on the nucleotide sequences of the rDNA cluster region (rDNA cluster), and the β-tubulin gene (<it>β-tub</it>), the elongation factor 1α gene (<it>EF-1α</it>), and the aminoadipate reductase gene (<it>lys2</it>). Although incongruence of the tree topologies between <it>lys2 </it>and the other genes was detected, all genes supported the classification of <it>Fusarium </it>species into 7 major clades, I to VII. To obtain a reliable phylogeny for <it>Fusarium </it>species, we excluded the <it>lys2 </it>sequences from our dataset, and re-constructed a maximum likelihood (ML) tree based on the combined data of the rDNA cluster, <it>β-tub</it>, and <it>EF-1α</it>. Our ML tree indicated some interesting relationships in the higher and lower taxa of <it>Fusarium </it>species and related genera. Moreover, we observed a novel evolutionary history of <it>lys2</it>. We suggest that the unique tree topologies of <it>lys2 </it>are not due to an analytical artefact, but due to differences in the evolutionary history of genomes caused by positive selection of particular lineages.</p> <p>Conclusion</p> <p>This study showed the reliable species tree of the higher and lower taxonomy in the lineage of the <it>Fusarium </it>genus. Our ML tree clearly indicated 7 major clades within the <it>Fusarium </it>genus. Furthermore, this study reported differences in the evolutionary histories among multiple genes within this genus for the first time.</p

ブラゼルトン新生児行動評価の臨床活用

我々はこれまでブラゼルトン新生児行動評価法（NBAS）を未熟児やリスクを有する成熟児の早期発達評価と介入手段として応用してきた。今回は未熟児を対象にNBASの評価結果から発達障害を予測された児の新生児行動上の特性を4つの行動系に分けて整理し，我々の実施している早期療育プログラムについて報告した。また，これまでフォローした児について発達経過を加えた。We have applied the Brazelton\u27s Neonatal Behaviour Assessment Scale (NBAS) for the evaluation of early development stages in both premature infants, and mature risk infants, as well as for the clinical application of early intervention method. This paper reports the neonatal behaviour peculiarities of premature infants forecast by NBAS to have mental-motor delays. This paper also report on our practical application of the early intervention program. Finally, we conclude with the progress made in these infant\u27s developments

spERt Technology: A novel strategy to improve productivity through enhanced polyribosome assembly on the endoplasmic reticulum in CHO cells

In cell line development process, it is frequently observed that increased mRNA levels do not always correlate with protein expression levels in CHO cells. In line with this gap, the endoplasmic reticulum (ER) in CHO cells is much less proliferated as compared with that in terminally differentiated (i.e., professional) secretory cells, suggesting that there is still room to improve their specific productivity if translational efficiency on the ER can be up-regulated. Here we present a novel engineering approach (spERt Technology) to improve specific production rates by mimicking the ER translational apparatus of professional secretory cells. In spERt Technology, we exploit the unique factors that are required for translationally active polyribosome formation on the ER to directly enhance the translational efficiency (1, 2). A high antibody (Ab) producing clone generated by a novel screen using flow cytometry (3) was used as a model cell line. The factors were introduced into the high producer and a series of the spERt Technology - introduced cell lines were generated Among these cell lines, we selected one of the best clones (spERt-f9) having stable and high productivity. Polyribosome analysis of these cell lines revealed that enhanced assembly of the ER polyribosomes as expected (1). Consistent with the highly developed polyribosomes, the spERt-introduced cell lines produced higher levels of Ab than that of parental cells, and showed prominent increase of specific production rates. Further optimization of feeding process resulted in remarkable increase of productivity in spERt-f9 cells: Ab titers of 7.6 g/L and 9.5 g/L on day 14 and 17, respectively, were achieved in shake flask fed-batch cultures by using chemically defined media. Importantly, high cell viabilities were maintained in spERt-f9 cells throughout the culture periods. In addition, lower glucose consumption and reduced accumulation of ammonia were observed. Product quality in these cells were analyzed and compared with that in the parental cells. In conclusion, spERt Technology enables to improve productivity of high Ab producers, associated with reduced accumulation of waste metabolites and high cell viabilities

DNA Lesions Induced by Replication Stress Trigger Mitotic Aberration and Tetraploidy Development

During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress