CD40 activation mediates p53-dependent cell cycle regulation in human multiple myeloma cell lines

It has been reported that the activation of multiple myeloma (MM) cells by CD40 induces proliferation, growth arrest, and apoptosis. To determine whether the biologic sequelae of CD40 activation in MM cells depends on p53 function, we identified temperature-sensitive p53 mutations in the RPMI 8226 (tsp53E285K) and the HS Sultan (tsp53Y163H) MM cell lines. These cells were then used as a model system of inducible wtp53-like function because wild-type-like p53 is induced at permissive (30 degrees C) but not at restrictive (37 degrees C) temperatures. Using p21-luciferase reporter assays, we confirmed that CD40 induces p53 transactivation in RPMI 8226 and HS Sultan cells cultured under permissive, but not restrictive, conditions. Furthermore, CD40 activation of these MM cells under permissive, but not restrictive, temperatures increased the expression of p53 and p21 mRNA and protein. Importantly, CD40 activation induced the proliferation of RPMI 8226 and HS Sultan cells at restrictive temperatures and growth arrest and increased subG1 phase cells at permissive temperatures. These data confirmed that CD40 activation might have distinct biologic sequelae in MM cells, depending on their p53 status.     

Acquired immune hemolytic anemia associated with IgA erythrocyte coating: investigation of hemolytic mechanisms

We have investigated the hemolytic mechanisms in a patient with acquired immune hemolytic anemia whose red cells appeared to be coated with IgA alone. The clinical course was similar to that of patients with hemolytic anemia mediated by warm-reacting IgG antibody. Splenic sequestration of red cells was demonstrated, and marked reduction of hemolysis occurred after corticosteroid therapy. Antibody was eluted from the patient's red cells and used to sensitize normal red cells in vitro. These sensitized red cells were not lysed by fresh autologous serum, nor did they fix detectable amounts of C3. However, red cells sensitized by eluted antibody were lysed by normal human peripheral blood monocytes in a system designed to demonstrate antibody-dependent cell-mediated cytotoxicity. Monocyte-mediated hemolysis of sensitized red cells was inhibited by the addition of low concentrations of normal serum IgA to the system, but not by IgG. The ability of the eluate to induce monocyte-mediated hemolysis was abolished by its adsorption on Sepharose-bound anti-IgA, but not by preincubation with Sepharose-bound anti-IgG. In addition, normal human monocytes were demonstrated to ingest eluate-sensitized red cells. These data demonstrate an in vitro interaction of IgA-sensitized red cells with leukocytes and suggest a possible mechanism for the patient's hemolysis.     

Comparison of the EUCAST and CLSI Broth Microdilution Methods for Testing Isavuconazole,Posaconazole, and Amphotericin B against Molecularly Identified Mucorales Species

We compared EUCAST and CLSI antifungal susceptibility testing (AFST) methods for triazoles and amphotericin B against 124 clinical Mucorales isolates. The EUCAST method yielded MIC values 1- to 3-fold dilutions higher than those of the CLSI method for amphotericin B. The essential agreements between the two methods for triazoles were high, i.e., 99.1% (voriconazole), 98.3% (isavuconazole), and 87% (posaconazole), whereas it was significantly lower for amphotericin B (66.1%). Strategies for harmonization of the two methods for Mucorales AFST are warranted.     

Prosthetic Rehabilitation Following Socket Reconstruction with Blair‐Brown Graft and Conformer Therapy for Management of Severe Post‐Enucleation Socket Syndrome – A Clinical Report

One of the most common tumors of the eye diagnosed in childhood is retinoblastoma, which mandates enucleation with adjunctive chemotherapy and radiotherapy to save the patient's life. The most common late enucleation complication is post‐enucleation socket syndrome (PESS), which poses a management dilemma for the prosthodontist and surgeon, along with being a major esthetic concern for the patient. The reconstruction of such sockets is complex. The purpose of this clinical report is to describe the rehabilitation of such a pediatric patient with severe PESS. The patient was successfully rehabilitated by presurgical conformer therapy, socket reconstruction surgery with non‐meshed intermediate split thickness skin graft (STSG)/Blair‐Brown graft, and postsurgical conformer stent. This was followed by fabrication of a custom ocular prosthesis, to achieve favorable functional, physical, and psychological effects.     

高黏度与低黏度骨水泥在经皮椎体后凸成形术中的应用比较

目的对比高黏度与低黏度骨水泥经皮椎体后凸成形术(PKP)治疗骨质疏松性椎体压缩性骨折(OVCF)的疗效差异。方法将2013年3月至2014年9月高要市人民医院收治的60例OVCF患者采用随机抽签法分为低黏度组(低黏度骨水泥PKP治疗)和高黏度组(高黏度骨水泥PKP治疗),每组各30例。对比两组手术前后伤椎椎体高度和后凸Cobb角;采用视觉模拟量表(VAS)评分、Oswestry功能障碍指数(ODI)、36项健康调查简表(SF-36)评分对患者疼痛程度、功能障碍和生活质量等主观感受进行评价;统计骨水泥渗漏、近期肺栓塞等并发症发生情况。结果低黏度组和高黏度组骨水泥注入量分别为(3.1±0.6)m L和(3.6±0.8)m L,两组比较,差异有统计学意义(P0.05)。术后随访3~6个月(平均4个月),两组术后1 d、3个月VAS评分、ODI、SF-36评分、伤椎椎体高度和后凸Cobb角均优于术前(P0.05),其中高黏度组术后1 d、3个月上述指标均优于低黏度组(P0.05)。低黏度组和高黏度组术后发生骨水泥渗漏、近期肺栓塞分别为6、2例和1、0例,两组并发症发生率比较,差异有统计学意义(P0.05)。结论与低黏度骨水泥比较,高黏度骨水泥PKP治疗OVCF近期疗效更为理想,骨水泥渗漏、近期肺栓塞等并发症发生率相对较低,值得临床推广应用。     

Randomized, Double-Blind Placebo-Controlled Trial of Coenzyme Q10 in Patients with Acute Myocardial Infarction

The effects of oral treatment with coenzyme Q10 (120 mg/d) were compared for 28 days in 73 (intervention group A) and 71 (placebo group B) patients with acute myocardial infarction (AMI). After treatment, angina pectoris (9.5 vs. 28.1), total arrhythmias (9.5% vs. 25.3%), and poor left ventricular function (8.2% vs. 22.5%) were significantly (P < 0.05) reduced in the coenzyme Q group than placebo group. Total cardiac events, including cardiac deaths and nonfatal infarction, were also significantly reduced in the coenzyme Q10 group compared with the placebo group (15.0% vs. 30.9%, P < 0.02). The extent of cardiac disease, elevation in cardiac enzymes, and oxidative stress at entry to the study were comparable between the two groups. Lipid peroxides, diene conjugates, and malondialdehyde, which are indicators of oxidative stress, showed a greater reduction in the treatment group than in the placebo group. The antioxidants vitamin A, E, and C and beta-carotene, which were lower initially after AMI, increased more in the coenzyme Q10 group than in the placebo group. These findings suggest that coenzyme Q10 can provide rapid protective effects in patients with AMI if administered within 3 days of the onset of symptoms. More studies in a larger number of patients and long-term follow-up are needed to confirm our results.     

National Trends and Outcomes in Dialysis-Requiring Acute Kidney Injury in Heart Failure: 2002–2013

Background

Dialysis-requiring acute kidney injury (D-AKI) is a serious complication in hospitalized heart failure (HF) patients. However, data on national trends are lacking after 2002.

Goldenhar Syndrome with Tessier’s 7 Cleft: Report of a Case

Goldenhar syndrome, a variant of hemifacial microsomia, is a well-known developmental anomaly of maxillofacial skeleton that is apparent at birth. The first and second branchial arch involvement during early embryonic development results in a wide spectrum of anomalies that may include macrostomia and lateral facial clefts. Though clefts of the orofacial region are among the most common congenital facial defects, the occurrence of lateral facial clefts (Tessier 7 cleft) in conditions such as the Goldenhar syndrome, is very rare (<5%). The lateral facial cleft, which results because of improper development of the perioral muscles of the face, gives an appearance of macrostomia giving rise to potential psychological, aesthetic and feeding problems. This clinical report describes the closure of a Tessier 7 cleft and the use of distraction osteogenesis to treat mandibular asymmetry in an 11-year-old female patient with Goldenhar’s syndrome.