To describe clinical and neurodevelopmental phenotypes of Costello syndrome, we performed a retrospective review of the clinical records and findings in 10 children with Costello syndrome. All patients showed significant postnatal growth retardation and severe feeding difficulties leading to failure to thrive from early infancy. All required tube feeding and some needed high‐calorie formulas for variable periods. Developmental quotients/IQs in seven children were 50 or less, and three were in the mildly retarded range. Five had seizures. Remarkable manifestations not previously reported were the characteristic behavior in infancy. Although happy and sociable personality was always emphasized in the genetic literature, all children showed significant irritability, including hypersensitivity to sound and tactile stimuli, sleep disturbance, and excess shyness with strangers in infancy. Those symptoms usually disappeared around age 2–4 years. Other clinical signs included cardiac abnormalities (8), musculoskeletal abnormalities (10), ophthalmological manifestations (5), increased urinary vanillymandelic acid (VMA) and homovanillic acid (HVA) (3), rhabdomyosarcoma (1), laryngomalacia (1), and cryptorchidism (1). Only three girls had papillomata. Family histories were negative for Costello syndrome. In conclusion, we confirm the wide spectrum of mental function in patients with Costello syndrome, which ranges from severe to mild. During infancy Costello syndrome showed remarkable irritability with severe feeding problems, which attributes significant difficulties to the parents of affected children. © 2003 Wiley‐Liss, Inc.

The findings strongly suggested that neutrophil-mediated events are involved in the pathogenesis of RSV bronchiolitis, and the monitoring of UTI concentrations might be useful for evaluating the neutrophil-mediated airway inflammation.

A high electric field was applied cyclically to poly(vinylidene fluoride) films, during which the simultaneous and time-resolved measurements of the two-dimensional wideangle X-ray diffraction (WAXD), small-angle X-ray scattering (SAXS), and transmission-type Fourier transform infrared (FTIR) spectra were performed using a synchrotron X-ray radiation system. The inversion of the CF 2 dipole moments caused by the alternate change of the electric field vector direction was detected to occur around ±80−100 MV/m as estimated by the electricfield-strength dependence of the IR band intensity. On the other hand, the WAXD peaks were found to show the maximal intensities at 0 and ±250−300 MV/m. In these regions, the 001 reflection of the β form and the 002 reflection of the δ form changed the intensities remarkably and periodically. These experimental data were interpreted, not by the idea of a simple inversion motion of the rigid polar chains (the planar zigzag chains of the form β and the TGTG̅ chains of the α and δ forms) but by the more complicated couplings between the rotation and tilting motions of the chain segments, the cooperative T-G conformational exchanges, and the associated inversion motion of the CF 2 dipoles. The idea of the cooperative chain motions was supported by the density functional theory calculations performed under the external electric field. Different from the remarkable changes of the WAXD and FTIR data, the SAXS patterns did not show the detectable changes in these processes, indicating that the above-mentioned cooperative structural changes should occur in the crystalline regions with the stacked lamellar structure kept unchanged.

Coronary microvessel endothelial dysfunction and nitric oxide (NO) depletion contribute to elevated passive tension of cardiomyocytes, diastolic dysfunction and predispose the heart to heart failure with preserved ejection fraction. We examined if diastolic dysfunction at the level of the cardiomyocytes precedes coronary endothelial dysfunction in prediabetes. Further, we determined if myofilaments other than titin contribute to impairment. Utilizing synchrotron microangiography we found young prediabetic male rats showed preserved dilator responses to acetylcholine in microvessels. Utilizing synchrotron X-ray diffraction we show that cardiac relaxation and cross-bridge dynamics are impaired by myosin head displacement from actin filaments particularly in the inner myocardium. We reveal that increased PKC activity and mitochondrial oxidative stress in cardiomyocytes contributes to rho-kinase mediated impairment of myosin head extension to actin filaments, depression of soluble guanylyl cyclase/PKG activity and consequently stiffening of titin in prediabetes ahead of coronary endothelial dysfunction.