Two novel mutations of Wiskott–Aldrich syndrome: the molecular prediction of interaction between the mutated WASP L101P with WASP-interacting protein by molecular modeling

AbstractWiskott–Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and increased susceptibility of infections, with mutations of the WAS gene being responsible for WAS and X-linked thrombocytopenia. Herein, two novel mutations of WAS at T336C on exon 3, and at 1326–1329, a G deletion on exon 10, resulting in L101P missense mutation and frameshift mutation 444 stop, respectively, are reported. The affected patients with either mutation showed severe suppression of WAS protein (WASP) levels, T cell proliferation, and CFSE-labeled T cells division. Because WASP L101 have not shown direct nuclear Overhauser effect (NOE) contact with the WASP-interacting protein (WIP) in NMR spectroscopy, molecular modeling was performed to evaluate the molecular effect of WASP P101 to WIP peptide. It is presumed that P101 induced a conformational change in the Q99 residue of WASP and made the side chain of Q99 move away from the WIP peptide, resulting in disruption of the hydrogen bond between Q99 WASP and Y475 WIP. A possible model for the molecular pathogenesis of WAS has been proposed by analyzing the interactions of WASP and WIP using a molecular modeling study

EFFECTS OF THREE PREPARATORY MOVEMENTS ON SIDEWARD PROPULSIVE MOVEMENT

This study investigated the effects of three preparatory movements (squat, countermovement and hopping) on the sideward propulsive movement. Seven subjects were analyzed in 3-D to determine how fast they reacted to external signals, using three techniques, to reacl1 an aIming spot. The hopping and the countermovement types were considered better than the squat type in the propulsion. The hopping particularly showed the shortest duration from the external signal to take-off and also recorded high extension moments due to the pre-stretch mechanism for the push-off phase

Cell type–dependent variation in paracrine potency determines therapeutic efficacy against neonatal hyperoxic lung injury

AbstractBackground aimsThe aim of this study was to determine the optimal cell type for transplantation to protect against neonatal hyperoxic lung injury. To this end, the in vitro and in vivo therapeutic efficacies and paracrine potencies of human umbilical cord blood–derived mesenchymal stromal cells (HUMs), human adipose tissue–derived mesenchymal stromal cells (HAMs) and human umbilical cord blood mononuclear cells (HMNs) were compared.MethodsHyperoxic injury was induced in vitro in A549 cells by challenge with H2O2. Alternatively, hyperoxic injury was induced in newborn Sprague-Dawley rats in vivo by exposure to hyperoxia (90% oxygen) for 14 days. HUMs, HAMs or HMNs (5 × 105 cells) were given intratracheally at postnatal day 5.ResultsHyperoxia-induced increases in in vitro cell death and in vivo impaired alveolarization were significantly attenuated in both the HUM and HAM groups but not in the HMN group. Hyperoxia impaired angiogenesis, increased the cell death and pulmonary macrophages and elevated inflammatory cytokine levels. These effects were significantly decreased in the HUM group but not in the HAM or HMN groups. The levels of human vascular endothelial growth factor and hepatocyte growth factor produced by donor cells were highest in HUM group, followed by HAM group and then HMN group.ConclusionsHUMs exhibited the best therapeutic efficacy and paracrine potency than HAMs or HMNs in protecting against neonatal hyperoxic lung injury. These cell type-dependent variations in therapeutic efficacy might be associated or mediated with the paracrine potency of the transplanted donor cells

Pulsed Radiofrequency Treatment of Pain Relieving Point in a Soft Tissue

Pulsed radiofrequency (PRF) treatment of nervous tissue has been proposed as a less neurodestructive technique alternative to continuous RF heat lesioning. Recently, clinical reports using PRF have shown favorable effects in the treatment of a variety of focal pain areas, even in non-nervous tissues; however, the mechanism of effect underlying this treatment to non-nervous tissue remains unclear. We report the case of a 67-year-old male who presented with pain reliving point in the posterior neck. The patient had pain in the posterior neck for 3 years. The pain subsided with pressure applied to a point in the posterior neck. There were no specific abnormal findings on laboratory testing and radiologic examinations. After PRF treatment to the pain-relieving point, he had pain relief which lasted more than 5 months

A KINEMATIC ANALYSIS OF ELDERLY GAIT WHILE STEPPING OVER OBSTACLES OF VARYING HEIGHT

The purpose of this study was to investigate the kinematics of elderly people who had experienced a fall stepping over obstacles of varying height. Six elderly non-fallers and six elderly fallers stepped over obstacles of height 0, 2.5, 5.1, 15.2cm. The longest stance duration was found in the highest obstacle 15.2cm, which might reflect relatively fast degrading gait function of the faller group. It was found that fallers took a longer time to cross the obstacles, which resulted in slower crossing speeds than when non-fallers stepped over the obstacles. We concluded that elderly persons who had experienced falling tend to step over obstacles conservatively as characterized

THE EFFECTS OF WHEELCHAIR CAMBER AND HANDRIM SIZE IN WHEELCHAIR BASKETBALL MOVEMENT

Improving the wheelchair design can be an important determinant of high performance in the wheelchair basketball. Researchers have focused on increasing the efficiency of the wheelchair, looking at the factors such as the seat position, handrim size, and wheel camber. Most handrim and wheel chamber studies, however, have focused only on the propulsive phase. Quick turn as well as fast propulsion is essential to the success in a wheelchair basketball game and the energy efficiency becomes particularly important in a prolonged wheelchair use. The purpose of this study was to investigate the effects of wheelchair camber and handrim size on the linear propulsion, turn velocity, and efficiency

THE EFFECT OF 12-WEEK STRENGTH TRAINING ON GAIT CHARACTERISTICS IN ADOLESCENT WITH DOWN SYNDROME: A SINGLE CASE STUDY

It has been reported that approximately 80% of individuals with Down syndrome (DS) exhibit abnormal gait characteristics. They are exhibited by flat-footed contact with no heel-strike, excessive abduction of the leg in the swing phase, and abnormal knee and hip flexion throughout the gait cycle (Matteo, 2002). The purpose of this study was to examine the influence of a 12-week strength training program on the gait characteristics during walking by an adolescent with DS

Primary Pulmonary Plasmacytoma Presenting as Multiple Lung Nodules

Extramedullary plasmacytoma is a plasma cell tumor arising outside the bone marrow and usually occurs as a solitary tumor in the upper respiratory tract, such as the pharynx, paranasal sinuses, nasal cavity, or oral cavity [1]. Other cases develop in the lymph nodes, skin, gastrointestinal tract, genitourinary tract, and other regions. Primary pulmonary plasmacytomas are very rare and usually present as solitary lung nodules or masses [2]. Unusual cases manifest as diffuse pulmonary infiltration [3,4]. We describe here a unique case of primary pulmonary plasmacytoma, which presented as multiple lung nodules during regular screening in a patient with systemic lupus erythematosus

Clinical impacts of the concomitant use of L-asparaginase and total parenteral nutrition containing L-aspartic acid in patients with acute lymphoblastic leukemia

IntroductionL-asparaginase (ASNase) depletes L-asparagine and causes the death of leukemic cells, making it a mainstay for the treatment of acute lymphoblastic leukemia (ALL). However, ASNase's activity can be inhibited by L-aspartic acid (Asp), which competes for the same substrate and reduces the drug's efficacy. While many commercially used total parenteral nutrition (TPN) products contain Asp, it is unclear how the concomitant use of TPNs containing Asp (Asp-TPN) affects ALL patients treated with ASNase. This propensity-matched retrospective cohort study evaluated the clinical effects of the interaction between ASNase and Asp-TPN.MethodsThe study population included newly diagnosed adult Korean ALL patients who received VPDL induction therapy consisting of vincristine, prednisolone, daunorubicin, and Escherichia coli L-asparaginase between 2004 and 2021. Patients were divided into two groups based on their exposure to Asp-TPN: (1) Asp-TPN group and (2) control group. Data, including baseline characteristics, disease information, medication information, and laboratory data, were collected retrospectively. The primary outcomes for the effectiveness were overall and complete response rates. Relapse-free survival at six months and one year of treatment were also evaluated. The safety of both TPN and ASNase was evaluated by comparing liver function test levels between groups. A 1:1 propensity score matching analysis was conducted to minimize potential selection bias.ResultsThe analysis included a total of 112 ALL patients, and 34 of whom received Asp-TPN and ASNase concomitantly. After propensity score matching, 30 patients remained in each group. The concomitant use of Asp-TPN and ASNase did not affect the overall response rate (odds ratio [OR] 0.53; 95% confidence interval [CI] = 0.17–1.62) or the complete response rate (OR 0.86; 95% CI = 0.29–2.59) of the ASNase-including induction therapy. The concomitant use of Asp-TPN and ASNase also did not impact relapse-free survival (RFS) at six months and one year of treatment (OR 1.00; 95% CI = 0.36–2.78 and OR 1.24; 95% CI, 0.50–3.12, respectively). The peak levels of each liver function test (LFT) and the frequency of LFT elevations were evaluated during induction therapy and showed no difference between the two groups.ConclusionThere is no clear rationale for avoiding Asp-TPN in ASNase-treated patients