Temperature-dependent effects of EDTA on the membrane glycoprotein IIb- IIIa complex and platelet aggregability

In agreement with previous studies, we observed that incubation of washed human platelets with EDTA at 37 degrees C for short periods caused an irreversible loss of their aggregation response to adenosine diphosphate and markedly diminished their capacity to bind fibrinogen. AP-2 is a monoclonal antibody that reacts with a determinant specific to the glycoprotein (GP) IIb-IIIa complex. We now report that in a direct binding assay, the number of sites for AP-2 on platelets incubated with EDTA at 37 degrees C fell to approximately 30% of those present on control platelets. This effect of EDTA was not observed at room temperature. Analysis of the treated platelets by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed normal amounts of GP IIb and GP IIIa. However, studies using crossed immunoelectrophoresis with 125I-AP-2, 125I-Tab (anti-GP IIb), or 125I- AP-3 (anti-GP IIIa) in intermediate gels showed that at 37 degrees C, EDTA was inducing an irreversible change in GP IIb-IIIa complexes. A reduction in size and probable dissociation of the GP IIb-IIIa precipitate was accompanied by the appearance of precipitates having the characteristics of those given by free GP IIb and free GP IIIa and the location of a major new cathodal precipitate, which bound Tab and AP-3 but not AP-2. Membrane modifications associated with the loss of antigenic determinants on GP IIb-IIIa may explain EDTA-induced loss of platelet aggregability at 37 degrees C.     

p53 gene mutations in multiple myeloma are associated with advanced forms of malignancy

The frequency and type of p53 gene mutations was investigated in a series of 52 cases of multiple myeloma (MM) representative of the different clinical phases and forms of the disease (indolent, 12 cases; chronic, 24 cases; acute/leukemic, 16 cases). DNAs were analyzed for p53 gene mutations in exons 5 to 9 by polymerase chain reaction (PCR), single-strand conformation polymorphism (SSCP), and direct sequencing of PCR-amplified fragments. Point mutations were detected in 7 of 52 patients (13%) (5 at exon 8; 1 at exon 6; 1 at exon 7), and were specifically associated with the more advanced and clinically aggressive acute/leukemic forms of MM (7 of 16 [43%].) Three of the mutated cases had been evaluated at clinical presentation in earlier phases of the disease (indolent or chronic) and were found to be negative for p53 mutation. Moreover, three patients with p53 mutation had not received chemotherapy at the time of investigation. These results support the notion that the development of MM is a multistep process and suggest that alterations in the p53 gene may represent an important late event in MM tumor progression.     

Synthesis and Initial Evaluation of YM-08, a Blood-Brain Barrier Permeable Derivative of the Heat Shock Protein 70 (Hsp70) Inhibitor MKT-077, Which Reduces Tau Levels

相似文献   

甲状腺相关性眼病伴眼外肌肌腱受累1例

目的：报告1例甲状腺相关性眼病的非典型CT扫描表现。方法：一位64岁的中国女性出现复视3mo,无视力模糊。14a前她曾患甲状腺功能亢进症伴多结节甲状腺肿并行甲状腺切除术。眼科检查发现双眼下斜视并向上注视受限。左眼red desaturation并Ⅰ级相对性瞳孔传入障碍。T3,T4和促甲状腺激素（thyroid stimulating hormone,TSH）正常。TSH受体、抗体水平高,与Graves＇病一致。磁共振成像（magnetic resonance imaging,MRI）显示双下直肌弥漫性增大,肌腱受累。结果：给予几周期静脉注射甲基强的松龙继之以口服强的松后视力无提高,反之继续下降。行左眼眼眶减压术,术后其左眼视力有所改善。结论：有肌腱受累的眼外肌增大不能排除甲状腺相关性眼眶病（thyroid assciated orbitopathy,TAO）的可能。     

Stenotrophomonas maltophilia Pseudo-outbreak at a University Hospital Bronchoscopy Unit in Turkey

Objective:

Stenotrophomonas maltophilia is an opportunistic pathogen found predominantly in the enviroment and hospital setting. Invasive procedures and treatment methods, instruments used for diagnosis and irrational antibiotic use play major roles in the spread of this pathogen. The study aimed to evaluate consecutive S maltophilia isolation from bronchoalveolar lavage samples during bronchoscopy procedure during a week.

Methods:

Four patients consecutively had S maltophilia isolated during bronchoscopy between September 8 and 15, 2012. The identification of the isolates and their antibiotic susceptibility were studied by automated Vitek version 2.0 (Biomerieux, France) system. The clonal relationship between the isolates was studied by enterobacterial repetitive intergenic consensus (ERIC) polymerase chain reaction (PCR).

Results:

Four consecutive S maltophilia isolates had identical band patterns and showed clonal relatedness.

Conclusion:

Bronchoscopy is a common invasive procedure that is utilized in chest diseases departments and intensive care units (ICUs). Contamination may take place due to inappropiate use and cause spread of infectious pathogens. In the current study, we detected consecutive S maltophilia strains with identical band patterns isolated within a week. After appropiate disinfection and cleaning procedures, no further isolation was detected.     

Neonatal respiratory distress in near-term infants—consider surfactant protein B deficiency

Two infants presenting with respiratory distress in the first 24 h of life are described. Both patients underwent extensive investigation before the diagnosis of surfactant protein B-deficiency was reached. Both children died within 2 months of birth. Parental consanguinity was known to be a feature in the first case, who proved to have a previously unrecognized mutation of the surfactant protein B gene. In the second case, a history of parental consanguinity was not sought from the Caucasian family, but was later volunteered by the parents themselves. Case 2 proved to have the "common" surfactant protein B-deficient genotype. The key to diagnosis is having a high index of suspicion in any term or near-term newborn with severe respiratory distress; parental consanguinity must be excluded. Surfactant protein B-deficiency can be readily diagnosed from bronchoalveolar lavage specimens; a simple, inexpensive procedure which is well tolerated in newborns.     

Detection of renal masses: sensitivities and specificities of excretory urography/linear tomography, US, and CT

A prospective blinded study of 201 patients was performed to determine the relative sensitivities and specificities of excretory urography/linear tomography (EU/LT) and ultrasound (US) for the diagnosis of renal parenchymal masses. Computed tomography (CT) was used as a standard. EU/LT permitted detection of 10% of CT-confirmed masses (cystic or solid) less than 1 cm, 21% of lesions greater than or equal to 1 cm but less than 2 cm, 52% of lesions greater than or equal to 2 cm but less than 3 cm, and 85% of lesions 3 cm or more in diameter. US permitted detection of 26% of CT-confirmed lesions less than 1 cm, 60% of lesions greater than or equal to 1 cm but less than 2 cm, 82% of lesions greater than or equal to 2 cm but less than 3 cm, and 85% of lesions 3 cm or more in size. The results confirm the relative insensitivity of EU/LT for masses less than 3 cm in diameter and of US for masses less than 2 cm. Further, they suggest that CT may have a role not only in evaluation of cases in which the urographic or sonographic results are questionable or positive, but also in confirmation of apparently negative urographic findings when clinical suspicion of a lesion is high.