磁共振成像在乳腺癌中的应用：究竟是进了一步还是退了两步？

目前，人们正对乳腺磁共振成像（magnetic resonance imaging，MRI）的应用进行研究，表现在两个不同方面：一是将MRI列为乳腺癌高危妇女（例如BRCA1和BRCA2基因发生突变者）的筛查方法；二是对乳腺癌确诊或可疑患者行乳腺X线的同时辅以MRI以决定是否选用局部疗法。这两种用途的依据迥然不同。有预置性突变（predisposition mutations）的妇女乳腺癌发病年龄通常较低，此时由于乳腺组织较为致密，因而乳腺X线筛查的敏感性有所减低。     

Altered clearance of inhaled 99mTc-pentetate aerosols following exposure to cadmium chloride aerosols in ferrets

The rate of clearance of inhaled 99mTc-pentetate aerosols has been used as an indicator of pulmonary epithelial "permeability" in human and animal studies. In order to evaluate this technique further, groups of eight male ferrets (Mustela putorius furo) were given acute exposures to aerosols of CdCl2 or NaCl via endotracheal tube. Serial evaluations of the thoracic clearance rate of inhaled 99mTc-pentetate aerosols (MMAD = 0.6 microns, sigma g = 1.6) were made before exposure and at fixed time points after toxicant exposure (3 or 6, 24, 48 h, and 5 days after CdCl2). These serial evaluations of 99mTc-pentetate thoracic clearance were conducted at three cadmium intake levels (3, 10, and 30 min exposure to 10 mg/m3 CdCl2) in order to evaluate possible dose-related response relationships. The rate of thoracic clearance of Tc-pentetate was observed to be slowed at 3 h after exposure to CdCl2 aerosol and subsequently increased to well above control rates. The time sequence observed strongly suggests that increased Tc-pentetate clearance rates are indicative of a tissue response or repair process, rather than acute lung injury. Tracheal epithelial penetration of macromolecular tracers was not observed to increase in histological evaluations following serial sacrifice.     

Diminished virucidal activity of kethoxal against vesicular stomatitis virus pretreated with guanidinating reagent and proteases.

The reactivity of vesicular stomatitis virus (VSV) with kethoxal can be appreciably altered by treatment with 1-guanyl-3, 5-dimethyl pyrazole nitrate (GDMP) and proteolytic enzymes. Pretreatment of purified VSV with GDMP or proteolytic enzymes markedly reduced the effectiveness of kethoxal as a virucide. The rate of neutralizability of GDMP- and trypsin-treated viruses by specific antiserum differed from that of controls.     

Beta-defensin genomic copy number is not a modifier locus for cystic fibrosis

Human beta-defensin 2 (DEFB4, also known as DEFB2 or hBD-2) is a salt-sensitive antimicrobial protein that is expressed in lung epithelia. Previous work has shown that it is encoded in a cluster of beta-defensin genes at 8p23.1, which varies in copy number between 2 and 12 in different individuals. We determined the copy number of this locus in 355 patients with cystic fibrosis (CF), and tested for correlation between beta-defensin cluster genomic copy number and lung disease associated with CF. No significant association was found.     

Missense FGFR3 mutations create cysteine residues in thanatophoric dwarfism type I (TD1)

Thanatophoric dwarfism (TD) is a sporadic lethal skeletal dysplasia with micromelic shortening of the limbs, macrocephaly, platyspondyly and reduced thoracic cavity. In the most common subtype (TD1), femurs are curved, while in TD2, straight femurs are associated with cloverleaf skull. Mutations in the fibroblast growth factor receptor 3 (FGFR3) gene were identified in both subtypes. While TD2 was accounted for by a single recurrent mutation in the tyrosine kinase 2 domain, TD1 resulted from either stop codon mutations or missense mutations in the extracellular domain of the gene. Here, we report the identification of FGFR3 mutations in 25/26 TD cases. Two novel missense mutations (Y373C and G370C) were detected in 8/26 and 1/26 TD1 cases respectively. Both mutations created cysteine residues in the juxta extramembrane domain of the receptor. Sixteen cases carried the previously reported R248C (9/26 cases), S249C (2/26 cases) or stop codon FGFR3 mutations (5/26 cases). Our results suggest that TD1 is a genetically homogeneous condition and give additional support to the view that newly created cysteine residues in the extracellular domain of the protein play a key role in the severity of the disease.