Cine CT of the mediastinum in pediatric patients

Cine computed tomographic (CT) examinations of the mediastinum were performed in 83 pediatric patients. Lesions imaged include neoplastic, inflammatory, and vascular abnormalities. The 50-msec scan time of cine CT provides for superb depiction of the heart and airway, minimizes motion artifact, allows examinations to be done with little or no sedation, and permits optimal opacification of all vascular structures with as little as 0.5 mL of intravenously administered contrast medium per kg of body weight. Scanning time for an examination in which images in 20 sections are obtained is approximately 10 seconds. Radiation dose is significantly lower than that in comparable CT or plain radiographic studies. Preliminary experience shows cine CT to be an excellent imaging modality for the examination of the mediastinum in children.     

Magnetic resonance imaging in the diagnosis and staging of renal and perirenal neoplasms

Thirty-one adult patients underwent magnetic resonance (MR) imaging after CT scans had demonstrated findings consistent with renal cell carcinoma. MR images were interpreted prospectively and independently of the CT findings. Because the CT scanning was performed at multiple institutions by many examiners, this study was not a direct comparison of CT versus MR. The preoperative diagnoses and staging of the neoplasms, as judged by MR, were compared with those obtained at laparotomy (n = 28), autopsy (n = 1), or biopsy (n = 2). Correct preoperative diagnoses were rendered in 31 patients (100%) on the basis of MR findings. The anatomic staging of 27 renal cell carcinomas was correctly performed by MR in 26 patients (86%). When compared with results of previous studies of the value of CT in the diagnosis and staging of renal neoplasms, MR appears to have several advantages in determination of the origin of the mass; the evaluation of vascular patency; the detection of perihilar lymph node metastases; and the evaluation of direct tumor invasion of adjacent organs. MR is sensitive in determining the extent of tumor thrombus and in evaluating invasion of the inferior vena caval wall. MR should assume an important role in the diagnosis and staging of renal neoplasms.     

Modeling rare gene variation to gain insight into the oldest biomarker in autism: construction of the serotonin transporter Gly56Ala knock-in mouse

Alterations in peripheral and central indices of serotonin (5-hydroxytryptamine, 5-HT) production, storage and signaling have long been associated with autism. The 5-HT transporter gene (HTT, SERT, SLC6A4) has received considerable attention as a potential risk locus for autism-spectrum disorders, as well as disorders with overlapping symptoms, including obsessive-compulsive disorder (OCD). Here, we review our efforts to characterize rare, nonsynonymous polymorphisms in SERT derived from multiplex pedigrees carrying diagnoses of autism and OCD and present the initial stages of our effort to model one of these variants, Gly56Ala, in vivo. We generated a targeting vector to produce the Gly56Ala substitution in the Slc6a4 locus by homologous recombination. Following removal of a neomycin resistance selection cassette, animals exhibiting germline transmission of the Ala56 variant were bred to establish a breeding colony on a 129S6 background, suitable for initial evaluation of biochemical, physiological and behavioral alterations relative to SERT Gly56 (wildtype) animals. SERT Ala56 mice were achieved and exhibit a normal pattern of transmission. The initial growth and gross morphology of these animals is comparable to wildtype littermate controls. The SERT Ala56 variant can be propagated in 129S6 mice without apparent disruption of fertility and growth. We discuss both the opportunities and challenges that await the physiological/behavioral analysis of Gly56Ala transgenic mice, with particular reference to modeling autism-associated traits.     

Effects of inhibitors of DNA strand break repair on HeLa cell radiosensitivity

The effects of three drugs (hydroxyurea, 1-beta-arabinofuranosylcytosine, and diamide) known to inhibit DNA synthesis on the repair of ionizing radiation-induced DNA single-strand breaks measured by alkaline elution and on cellular radiosensitivity were examined. Inhibition of repair was observed at 10(-2) M hydroxyurea, 10(-4) M 1-beta-D-arabinofuranosylcytosine, and 5 X 10(-5) M diamide, levels causing only 10% cell kill. While the mechanisms by which the drugs inhibit DNA synthesis differ, they are equally effective at inhibiting repair; without drug, cells, after a dose of 10 grays, repair 35% of DNA strand breaks in 3 min and a further 35% in 1 hr; with drug, only 10% is repaired in 3 min, and the deficiency in repair amount remains, even after 60 min. The effect of similar drug treatment on radiation-induced cell killing shows that radiosensitivity is increased; the major effect is reduction in D0 from 1.3 grays to approximately 0.8 grays with smaller effects on Dq. The data are consistent with the hypothesis that radiation produces potential double-strand breaks in DNA which, if not rapidly repaired, are converted into lethal actual double-strand breaks.     

Prostatic carcinoma: staging by clinical assessment, CT, and MR imaging

The sensitivity, specificity, accuracy, and positive and negative predictive values of clinical assessment, computed tomography (CT), and magnetic resonance (MR) imaging were compared in the differentiation of stage B from stage C prostatic carcinoma. Forty-six patients who had undergone radical prostatectomy were included in the study. Surgical-pathologic staging was considered the "truth measure." Clinical staging had an accuracy of 61%, and CT, 65%. Accuracy for MR imaging depended on the instrument parameters and plane of section used. When only transverse T1-weighted images were analyzed, MR accuracy was 61%. However, when transverse T1- and T2-weighted images supplemented by additional T2-weighted coronal or sagittal images were studied, accuracy increased to 83%. At present, MR imaging is the most accurate diagnostic modality for the local staging of carcinoma of the prostate, but for optimal results, multiple sequences and two orthogonal planes of imaging are needed.