Jim S. Wu

Mei-S332, a drosophila protein required for sister-chromatid cohesion, can localize to meiotic centromere regions

Mutations in the Drosophila mei-S332 gene cause premature separation of the sister chromatids in late anaphase of meiosis I. Therefore, the mei-S332 protein was postulated to hold the centromere regions of sister chromatids together until anaphase II. The mei-S332 gene encodes a novel 44 kDa protein. Mutations in mei-S332 that differentially affect function in males or females map to distinct domains of the protein. A fusion of mei-S332 to the green fluorescent protein (GFP) is fully functional and localizes specifically to the centromere region of meiotic chromosomes. When sister chromatids separate at anaphase II, mei-S332-GFP disappears from the chromosomes, suggesting that the destruction or release of this protein is required for sister-chromatid separation.

Soft-Tissue Tumors and Tumorlike Lesions: A Systematic Imaging Approach

Soft-tissue lesions are frequently encountered by radiologists in everyday clinical practice. Characterization of these soft-tissue lesions remains problematic, despite advances in imaging. By systematically using clinical history, lesion location, mineralization on radiographs, and signal intensity characteristics on magnetic resonance images, one can (a) determine the diagnosis for the subset of determinate lesions that have characteristic clinical and imaging features and (b) narrow the differential diagnosis for lesions that demonstrate indeterminate characteristics. If a lesion cannot be characterized as a benign entity, the lesion should be reported as indeterminate, and the patient should undergo biopsy to exclude malignancy.

Bone and Soft-Tissue Lesions: What Factors Affect Diagnostic Yield of Image-guided Core-Needle Biopsy?

PURPOSE To assess lesion-related and technical factors that affect diagnostic yield in image-guided core-needle biopsy (CNB) of bone and soft-tissue lesions. MATERIALS AND METHODS Institutional review board approval and verbal informed consent were obtained for a HIPAA-compliant prospective study of 151 consecutive CNBs of bone (n = 88) and soft-tissue (n = 63) lesions. Each CNB specimen was reported separately in the final pathology report. Diagnostic yield (total number of biopsies that yield a diagnosis divided by total number of biopsies) was calculated for all lesions and subgroups on the basis of lesion composition (lytic, sclerotic, soft tissue), lesion size (< or = 2, > 2 to 5, or > 5 cm), biopsy needle gauge, image guidance modality, number of specimens obtained, and specimen length (< 5, 5-10, or > 10 mm). The minimum number of specimens required to obtain a diagnosis was determined on the basis of the specimen number at which the diagnostic yield reached a plateau. Chi(2) And Wilcoxon rank-sum tests were performed in bivariate analyses to evaluate associations between each factor and diagnostic yield. Significant factors were evaluated with multivariate logistic regression. RESULTS Diagnostic yield was 77% for all lesions. Yield was 87% for lytic bone lesions and 57% for sclerotic bone lesions (P = .002). Diagnostic yield increased with larger lesions (54% for lesions < or = 2 cm, 75% for lesions > 2 to 5 cm, and 86% for lesions > 5 cm [P = .006]). There was no difference in diagnostic yield for bone versus soft-tissue lesions or according to needle gauge or image guidance modality. Diagnostic yield was 77% for bone lesions and 76% for soft-tissue lesions (P = .88). Yield was 83%, 72%, 77%, and 83% for biopsies performed with 14-, 15-, 16-, and 18-gauge needles, respectively (P = .57). Yield was 77% with computed tomographic guidance and 78% with ultrasonographic guidance (P = .99). Diagnostic yield increased with number of specimens obtained and with longer specimen length; it reached a plateau at three specimens for bone lesions and four specimens for soft-tissue lesions. CONCLUSION Diagnostic yield is higher in lytic than in sclerotic bone lesions, in larger lesions, and for longer specimens. Obtaining a minimum of three specimens in bone lesions and four specimens in soft-tissue lesions optimizes diagnostic yield.

Liver Involvement in Hereditary Hemorrhagic Telangiectasia: CT and Clinical Findings Do Not Correlate in Symptomatic Patients

OBJECTIVE The purpose of our study was to report the multiphasic CT findings in patients with symptomatic liver involvement by hereditary hemorrhagic telangiectasia (HHT) and to correlate the CT findings with the type of clinical presentation. CONCLUSION Patients with symptomatic HHT liver disease have diffuse hepatic telangiectases, a dilated common hepatic artery, and a high incidence of biliary abnormalities. Multiphasic CT is useful in diagnosing liver involvement due to HHT; however, no strong correlation was seen between CT findings and the clinical subtype of HHT liver disease.

Assessing spinal muscular atrophy with quantitative ultrasound

Objective: To assess the value of quantitative ultrasound in patients with type 2 and 3 spinal muscular atrophy (SMA). Methods: Twenty-five patients with SMA (15 type 2 and 10 type 3) and 21 normal subjects were enrolled for this observational study. Strength of biceps brachii, wrist extensors, quadriceps, and tibialis anterior were measured with hand-held dynamometry. In addition, these 4 muscles were studied with a standard ultrasound system using a 5-MHz probe, and luminosity values for each muscle and the overlying subcutaneous fat were obtained by subsequent image analysis. A luminosity ratio (LR) for each muscle was calculated by dividing the muscle by the subcutaneous fat luminosity. The LR and strength scores for all 4 muscles were averaged to provide a single summary value for each patient. Results: The LRs increased with disease severity: 1.27 ± 0.26 for normal subjects, 2.43 ± 0.78 for type 3 SMA, and 3.85 ± 1.3 for type 2 SMA (p < 0.001). Taking all the normal subject and patient data together, there was a good correlation between strength and LR (r = −0.711, p < 0.001). There was also a moderate relationship between LR and strength in the patients with SMA alone (r = −0.588, p = 0.008), and, as expected, a nonsignificant relationship between LR and strength in normal subjects (r = −0.011). Conclusions: Quantitative ultrasound has the potential of serving as a marker of SMA severity and may be useful in future clinical trials.

Evaluation of skeletal muscle during calf exercise by 31-phosphorus magnetic resonance spectroscopy in patients on statin medications.

Muscle pain is a common side effect of statin medications, but the cause is poorly understood. We characterized phosphocreatine (PCr) exercise recovery kinetics in 10 patients with hypercholesterolemia before and after a 4‐week regimen of statin therapy using 31‐phosphorus magnetic resonance spectroscopy (31P‐MRS). 31P spectra were obtained before, during, and after exercise on a calf flexion pedal ergometer. Creatine kinase (CK) serum levels were drawn before and after statin therapy. The mean metabolic recovery time constant in subjects increased from 28.1 s (SE = 6.5 s) to 55.4 s (SE = 7.4 s) after statin therapy. The unweighted mean of the pre/post‐recovery time difference was −27.3 s (SE = 12.4 s; P = 0.02). Pre‐ and post‐therapy CK levels were not significantly different (P = 0.50). Metabolic recovery time in the calf is prolonged in patients after statin use. This suggests that statins impair mitochondrial oxidative function, and 31P MRS is a potential study model for statin‐associated myopathy. Muscle Nerve, 2011

Calcific Tendinitis: A Pictorial Review

Calcific tendinitis is caused by the pathologic deposition of calcium hydroxyapatite crystals in tendons and is a common cause of joint pain. The disease typically affects the shoulder and hip, with characteristic imaging findings; however, any joint can be involved. Occasionally, calcific tendinitis can mimic aggressive disorders, such as infection and neoplasm, especially on magnetic resonance imaging. Radiologists should be familiar with the imaging findings to distinguish calcific tendinitis from more aggressive processes. Image-guided percutaneous needle aspiration and steroid injection of calcific tendinitis are useful techniques performed by the radiologist for the treatment of symptomatic cases. Familiarity with these procedures and their imaging appearance is an important aspect in the management of this common disease.

The mitotic centromeric protein MEI-S332 and its role in sister-chromatid cohesion

Abstract. Faithful segregation of sister chromatids during cell division requires properly regulated cohesion between the sister centromeres. The sister chromatids are attached along their lengths, but particularly tightly in the centromeric regions. Therefore specific cohesion proteins may be needed at the centromere. Here we show that Drosophila MEI-S332 protein localizes to mitotic metaphase centromeres. Both overexpression and mutation of MEI-S332 increase the number of apoptotic cells. In mei-S332 mutants the ratio of metaphase to anaphase figures is lower than wild type, but it is higher if MEI-S332 is overexpressed. In chromosomal squashes centromeric attachments appear weaker in mei-S332 mutants than wild type and tighter when MEI-S332 is overexpressed. These results are consistent with MEI-S332 contributing to centromeric sister-chromatid cohesion in a dose-dependent manner. MEI-S332 is the first member identified of a predicted class of centromeric proteins that maintain centromeric cohesion.

Cross-sectional Evaluation of Electrical Impedance Myography and Quantitative Ultrasound for the Assessment of Duchenne Muscular Dystrophy in a Clinical Trial Setting

BACKGROUND Electrical impedance myography and quantitative ultrasound are two noninvasive, painless, and effort-independent approaches for assessing neuromuscular disease. Both techniques have potential to serve as useful biomarkers in clinical trials in Duchenne muscular dystrophy. However, their comparative sensitivity to disease status and how they relate to one another are unknown. METHODS We performed a cross-sectional analysis of electrical impedance myography and quantitative ultrasound in 24 healthy boys and 24 with Duchenne muscular dystrophy, aged 2 to 14 years with trained research assistants performing all measurements. Three upper and three lower extremity muscles were studied unilaterally in each child, and the data averaged for each individual. RESULTS Both electrical impedance myography and quantitative ultrasound differentiated healthy boys from those with Duchenne muscular dystrophy (P < 0.001 for both). Quantitative ultrasound values correlated with age in Duchenne muscular dystrophy boys (rho = 0.45; P = 0.029), whereas electrical impedance myography did not (rho = -0.31; P = 0.14). However, electrical impedance myography phase correlated with age in healthy boys (rho = 0.51; P = 0.012), whereas quantitative ultrasound did not (rho = -0.021; P = 0.92). In Duchenne muscular dystrophy boys, electrical impedance myography phase correlated with the North Star Ambulatory Assessment (rho = 0.65; P = 0.022); quantitative ultrasound revealed a near-significant association (rho = -0.56; P = 0.060). The two technologies trended toward a moderate correlation with one another in the Duchenne muscular dystrophy cohort but not in the healthy group (rho = -0.40; P = 0.054 and rho = -0.32; P = 0.13, respectively). CONCLUSIONS Electrical impedance myography and quantitative ultrasound are complementary modalities for the assessment of boys with Duchenne muscular dystrophy; further study and application of these two modalities alone or in combination in a longitudinal fashion are warranted.

Minimal training is required to reliably perform quantitative ultrasound of muscle.

Introduction: Quantitative ultrasound can measure skeletal muscle pathology. We investigated whether inexperienced evaluators could accurately obtain and analyze ultrasound images. Methods: Two examiners underwent a 20‐minute training session before obtaining ultrasound images of several limb muscles in 21 healthy boys and 19 boys with Duchenne muscular dystrophy (DMD). Gray scale levels (GSLs) of muscle and subcutaneous fat were then measured by 2 analysts: a trained research assistant and a radiologist. We compared results between examiners and analysts. Results: Interrater reliability of muscle GSLs was high between examiners (ICC ≥ 0.85) and analysts (ICC ≥ 0.84). As anticipated, GSLs were higher in dystrophic than in healthy muscles (P < 0.001). Fat GSLs were less reliable (ICC = 0.5–0.89) than muscle and increased with age and body size. Conclusions: GSLs from ultrasound images of healthy and dystrophic skeletal muscle, but not from subcutaneous fat, can be obtained reliably and can be analyzed by inexperienced evaluators with minimal training. Muscle Nerve 50: 124–128, 2014