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ABSTRACT Dynamic sensitivities are useful to characterize time-varying systems efficiently. In metabolic reaction systems, however, analysis using these values is not so popular. This is mainly due to the following two reasons. One is that the calculation of dynamic sensitivities requires us to derive differential equations for sensitivities from those for metabolite concentrations by partial differentiation, and it is not easy for experimentalists to perform this mathematical operation. The other is that the metabolic reaction systems are mostly described by stiff differential equations, from which it may not be easy to obtain reliable numerical solutions. We have previously developed software for calculation of dynamic sensitivities ( softcads), in which one can calculate dynamic sensitivities with high accuracy by setting only differential equations for metabolite concentrations. This paper further improves the algorithm of softcads to enhance its performance. The results clearly show that regardless of the degree of stiffness, the improved softcads provides dynamic sensitivities with the super high accuracy that is comparable to the machine accuracy and also completes the calculation in a shorter time. © 2011 Curtin University of Technology and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim: The effect that intrauterine or extrauterine growth restriction (EUGR) had on the build of very low birthweight (VLBW) infants was investigated before Japanese children started school., Method: Between 2005 and 2017, the National Hospital Organization, Saga, Japan, carried out preschool checks on 322 children born with a VLBW at approximately six years of age. Growth restriction was defined as being born small for gestational age (SGA) or EUGR if they were born at term. The prevalence of short stature, thinness and obesity was determined, and associations between SGA or EUGR and subsequent body build were investigated., Results: In this study, 77 of 322 (23.9%) infants were SGA and 153 of 322 (47.5%) were EUGR: 14 of 77 (18.2%) SGA infants caught up in growth to the 169 non-EUGR infants, while 90 of 245 (36.7%) appropriate for gestational age infants subsequently demonstrated EUGR. There were 38 (11.8%) short stature, 38 (11.8%) thin and six (1.9%) obese subjects in the total cohort and growth hormone deficiencies in nine (2.8%) cases. We found significant associations between EUGR and both short stature and thinness., Conclusion: Extrauterine growth restriction was significantly associated with short stature and thinness in VLBW infants at around six years, irrespective of the degree of SGA., (©2018 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

In order to evaluate the contribution of FBN1, FBN2, TGFBR1, and TGFBR2 mutations to the Marfan syndrome (MFS) phenotype, the four genes were analyzed by direct sequencing in 49 patients with MFS or suspected MFS as a cohort study. A total of 27 FBN1 mutations (22 novel) in 27 patients (55%, 27/49), 1 novel TGFBR1 mutation in 1 (2%, 1/49), and 2 recurrent TGFBR2 mutations in 2 (4%, 2/49) were identified. No FBN2 mutation was found. Three patients with either TGFBR1 or TGFBR2 abnormality did not fulfill the Ghent criteria, but expressed some overlapping features of MFS and Loeys-Dietz syndrome (LDS). In the remaining 19 patients, either of the genes did not show any abnormalities. This study indicated that FBN1 mutations were predominant in MFS but TGFBRs defects may account for approximately 5-10% of patients with the syndrome.

We examined the effectiveness of various anti-tumour agents to natural killer (NK)-cell tumour cell lines and samples, which are generally resistant to chemotherapy, using flow cytometric terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labelling (TUNEL) assay. Although NK-YS and NK-92 were highly resistant to various anti-tumour agents, l-asparaginase induced apoptosis in these two NK-cell lines. NK-cell leukaemia/lymphoma and acute lymphoblastic leukaemia (ALL) samples were selectively sensitive to l-asparaginase and to doxorubicin (DXR) respectively. Samples of chronic NK lymphocytosis, an NK-cell disorder with an indolent clinical course, were resistant to both drugs. Our study clearly separated two major categories of NK-cell disorders and ALL according to the sensitivity to DXR and l-asparaginase. We examined asparagine synthetase levels by real-time quantitative polymerase chain reaction (RQ-PCR) and immunostaining in these samples. At least in nasal-type NK-cell lymphoma, there was a good correlation among asparagine synthetase expression, in vitro sensitivity and clinical response to l-asparaginase. In aggressive NK-cell leukaemia, although asparagine synthetase expression was high at both mRNA and protein levels, l-asparaginase induced considerable apoptosis. Furthermore, samples of each disease entity occupied a distinct area in two-dimensional plotting with asparagine synthetase mRNA level (RQ-PCR) and in vitrol-asparaginase sensitivity (TUNEL assay). We confirmed rather specific anti-tumour activity of l-asparaginase against NK-cell tumours in vitro, which provides an experimental background to the clinical use of l-asparaginase for NK-cell tumours.

In the normal developmental pathway of natural killer (NK) cells, pre-NK cells express CD161, immature NK cells express CD161 and CD56, and mature NK cells express CD161, CD56 and CD94. To identify the normal counterpart of NK cells from which neoplastic cells originate, surface antigens were analysed. Blastic NK-cell lymphoma/leukaemia lacked CD94 and CD161 but had CD56. Aggressive NK-cell leukaemia/lymphoma and nasal NK-cell lymphoma, although morphologically immature, expressed both CD56 and CD94 and strong NK activity. Cells from chronic NK lymphocytosis expressed CD56 and CD94.