Folding of Staphylococcal Nuclease Induced by Binding of Chemically Modified Substrate Analogues Sheds Light on Mechanisms of Coupled Folding/Binding Reactions.

Several proteins have been shown to undergo a shift in the mechanism of ligand binding-induced folding from conformational selection (CS; folding precedes binding) to induced fit (IF; binding precedes folding) with increasing ligand concentration. In previous studies of the coupled folding/binding reaction of staphylococcal nuclease (SNase) in the presence of a substrate analogue, adenosine-3',5'-diphosphate (prAp), we found that the two phosphate groups make important energetic contributions toward stabilizing its complex with the native protein as well as transient conformational states encountered at high ligand concentrations favoring IF. However, the structural contributions of each phosphate group during the reaction remain unclear. To address this question, we relied on fluorescence, nuclear magnetic resonance (NMR), absorption, and isothermal titration calorimetry to study the effects of deletion of the phosphate groups of prAp on the kinetics of ligand-induced folding, using a strategy analogous to mutational ϕ-value analysis to interpret the results. Kinetic measurements over a wide range of ligand concentrations, together with structural characterization of a transient protein-ligand encounter complex using 2D NMR, indicated that, at high ligand concentrations favoring IF, (i) the 5'-phosphate group interacts weakly with denatured SNase during early stages of the reaction, resulting in loose docking of the two domains of SNase, and (ii) the 3'-phosphate group engages in some specific contacts with the polypeptide in the transition state prior to formation of the native SNase-prAp complex.

Risk factors for myopia at 1-year corrected age following laser photocoagulation for retinopathy of prematurity.

BACKGROUND/OBJECTIVES: The prevalence of myopia is higher in preterm infants who underwent laser photocoagulation (LPC) for retinopathy of prematurity (ROP). The aim of this study was to investigate factors associated with myopia in preterm infants who undergo LPC for ROP. SUBJECTS/METHODS: We retrospectively analysed the medical records of preterm infants born at Kyushu University Hospital (October 2008-March 2018) at ≤32 weeks of gestational age or with birth weight ≤1500 g. We evaluated the associations between nine clinical factors and the spherical equivalent at 1-year corrected age by performing multivariable linear regression in LPC-treated ROP patients. RESULTS: Among the 485 infants enroled, 76 developed ROP requiring treatment. Of these, 71 underwent LPC, which was provided to 63 infants as the primary treatment (LPC alone or the combination therapy of LPC and intravitreal injection of bevacizumab [IVB]) and to eight infants as additional LPC after IVB monotherapy. The results of a refractive examination at 1-year corrected age were available for 110 eyes of 56 infants (78.9%). The mean ± standard deviation of the SE value was -0.5 ± 3.0 dioptres (D). Multivariable linear regression analysis revealed a significant association between laser spot count and SE value (ß = -0.081 ± 0.040 D per 100 spots [mean ± standard error], p = 0.045). CONCLUSIONS: Our results suggest that an increased laser spot count observed during ROP treatment associates with myopia.

Neurodevelopmental outcomes following intravitreal bevacizumab injection in Japanese preterm infants with type 1 retinopathy of prematurity.

PURPOSE: The purpose of this study was to evaluate neurodevelopmental outcomes in 18-month old (corrected age) preterm infants who received an intravitreal bevacizumab (IVB) injection for the treatment of type 1 retinopathy of prematurity (ROP). METHODS: In this ten-year retrospective study, we reviewed the medical records of patients who underwent ROP screening at Kyushu University Hospital. Among the patients who received IVB or laser photocoagulation (LPC) for the treatment of type 1 ROP, we included infants whose neurodevelopmental examination (the Kyoto Scale of Psychological Development [KSPD]) results at 18 months corrected age were available. Then, the effect of IVB on the developmental quotient (DQ) in each KSPD domain (Postural-Movement, Cognitive-Adaptive, or Language-Social domain) or the overall DQ was investigated by performing linear regression analysis. RESULTS: Out of the 513 patients reviewed, 53 were included in the study. IVB and LPC were performed for 14 and 39 patients, respectively. Administration of IVB was significantly associated with neurodevelopmental delay in the Language-Social domain (p = 0.01). The observed association remained even after adjusting for gestational age and birth weight (p = 0.03). CONCLUSIONS: Administration of IVB may introduce a risk of developmental impairment of interpersonal relationships, socializations, and/or verbal abilities of preterm children. We recommended that preterm infants who received IVB undergo a neurodevelopmental reassessment during their school years or in adulthood.

A Case Report of Preoperative, Intraoperative, and Postoperative Anterior Chamber Shallowing Resulting from Different Mechanisms.

A 54-year-old woman with an epiretinal membrane in her left eye accompanied by a shallow anterior chamber due to primary angle closure glaucoma underwent vitrectomy and cataract surgery. During the cataract surgery, immediately after the ultrasonic tip had been removed from the anterior chamber, anterior chamber flattening occurred. An intraoperative fundus examination showed the development of acute intraoperative choroidal effusion. Postoperatively, the anterior chamber remained shallow even after the choroidal detachment had subsided; capsular bag distension seen by ultrasound biomicroscopy suggested the development of early postoperative capsular block syndrome. After neodymium:yttrium-aluminium-garnet laser capsulotomy, the anterior chamber deepened. Depending on the perioperative period, the mechanism of a flat anterior chamber can change, and understanding the underlying mechanisms is required for appropriate treatment.

In vivo change of elastic property in polyethylene acetabular components.

Polyethylene is an elastic material. It is known that oxidative degradation of polyethylene occurs after sterilization by means of gamma irradiation. However, there have been few detailed reports with regard to the effects of this degradation on the mechanical property, especially in total hip prostheses. The purpose of this study was to examine the change in mechanical property of irradiated and non-irradiated polyethylene cups after implantation. Fifty-six ultra-high molecular-weight polyethylene (UHMWPE) cups retrieved at revision surgery were evaluated. Thirty-two cups were sterilized by gamma irradiation in air and 24 by ethylene oxide gas (EtO). To evaluate the mechanical property of the cup and its regional distribution, Vickers hardness was measured at nine points at the cross-section of the cups. In the irradiated cups, the hardness increased in proportion to the time from sterilization. This phenomenon was not found in the cups sterilized by EtO. Less change of hardness was observed in the cups sterilized by EtO than in those sterilized by irradiation. The gamma-irradiation in air actually affected the elastic property of cup polyethylene in vivo, although any difference in the wear rate was not detected between two sterilization methods. In cases with accelerated wear of the acetabular cup, other factors affecting wear should also be considered.

Case report: rheumatoid arthritis occurring during observation after surgery for localized pigmented villonodular synovitis.

Abstract In the rare case presented here, arthroscopic resection was performed after a diagnosis of localized pigmented villonodular synovitis (LPVS) of the knee, but the disorder recurred after about 1 year as the diffuse form, and synovectomy was performed through a medial parapatella incision. Subsequently, rheumatoid arthritis (RA) occurred during the postoperative observation period. The course of this case is interesting because of the combination of the two diseases. In cases of PVS, the possibility of RA should always be considered.