Citations

SRSF2, SF3B1, and U2AF35 (U2AF1) are the three most frequent genes involved with spliceosome mutations in myeloid malignancies. SF3B1 mutations are most frequent (~80%) in myelodysplastic syndromes (MDS) with ring sideroblasts (RS) but lack prognostic relevance. SRSF2 mutations are associated with shortened overall (OS) and leukemia‐free survival (LFS) in both MDS and myelofibrosis. In this study of 226 patients with chronic myelomonocytic leukemia (CMML), mutational frequencies were 40% for SRSF2 (all affecting P95), 6% for SF3B1 (primarily K700E) and 9% for U2AF35 (mostly S34F and Q157P/R). These mutations were mutually exclusive and 54% of the patients displayed at least one mutation. The three mutation groups were phenotypically similar, with the exception of higher RS% (P < 0.0001) in patients with SF3B1 mutations. At a median follow‐up of 15 months, 176 (78%) deaths and 32 (14%) leukemic transformations were documented. OS (median survivals of 17, 16, 17, and 20 months; P = 0.48) and LFS (leukemic transformation rates of 17, 13, 15, and 5%; P = 0.63) were similar among patients with none of the three mutations, SRSF2, SF3B1, or U2AF35 mutations, respectively. We conclude that SRSF2 is the most frequently mutated spliceosome gene in CMML but neither it nor SF3B1 or U2AF35 mutations are prognostically relevant. Am. J. Hematol. 88:201–206, 2013. © 2012 Wiley Periodicals, Inc.

In this study, we compared gains in student content learning over a 10-yr period in which the introductory biology laboratory curriculum was changed in two ways: an increase of inquiry and a reduction of content. Three laboratory formats were tested: traditional 1-wk-long cookbook laboratories, two 7-wk-long inquiry laboratories, and one 14-wk-long inquiry laboratory. As the level of inquiry increased, student learning gains on content exams trended upward even while traditional content coverage taught decreased. In a quantitative assessment of content knowledge, students who participated in the 14-wk-long inquiry laboratory format outscored their peers in both 7- and 1-wk-long lab formats on Medical College Admissions Test exam questions (scores of 64.73%, 61.97%, and 53.48%, respectively, P < 0.01). In a qualitative study of student opinions, surveys conducted at the end of semesters where traditional 1-wk laboratories ( n = 167 students) were used had low response rates and predominately negative opinions (only 20% of responses were positive), whereas those who participated in 7-wk ( n = 543) or 14-wk ( n = 308) inquiry laboratories had high response rates and 71% and 96% positive reviews, respectively. In an assessment of traditional content coverage in courses, three indexes were averaged to calculate traditional forms of coverage and showed a decrease by 44% over the study period. We believe that the quantitative and qualitative data support greater student-driven inquiry in the classroom laboratory, which leads to deeper learning in fewer topic areas (less teaching) and can reap gains in scientific thinking and fundamental understanding applicable to a broader range of topic areas (more learning) in introductory biology.

The “effervescent gallbladder” sign, the sonographic finding of tiny echogenic foci rising from the dependent portion of the gallbladder, reminiscent of bubbles rising in a glass of champagne, has been reported previously as a finding of emphysematous cholecystitis. We report two additional cases of this unusual finding in an asymptomatic patient and in a patient with acute, gangrenous cholecystitis, confirmed in both cases by CT, to be secondary to the release of gas from gallstones. These two cases cast doubt on the sonographic sign as a pathognomonic finding of emphysematous cholecystitis. © 2012 Wiley Periodicals, Inc. J Clin Ultrasound 41:50–53, 2013

Abstract Folate receptors (FR) may be of use for targeted delivery of cytotoxic drugs in invasive urothelial carcinoma (iUC), for which improved therapy is needed. FR expression and function in iUC were explored and the antitumor activity and toxicity of a folate-targeted vinblastine conjugate were evaluated in dogs with naturally occurring iUC, an excellent model for human iUC. FR immunohistochemistry was carried out on iUC and normal human and dog bladder tissues together with nuclear scintigraphy in dogs to monitor iUC folate uptake. Dose escalation of a folate-targeted vinblastine compound, EC0905, was conducted in dogs with biopsy-confirmed, FR-positive iUC. FRs were detected by immunohistochemistry (PU17) in most primary iUC and many nodal and lung metastases from dogs, and scintigraphy confirmed folate uptake in both primary and metastatic lesions. The maximum tolerated dose of EC0905 in dogs was 0.25 mg/kg IV weekly, with neutropenia at higher doses. Tumor responses included partial remission (≥50% reduction in tumor volume) in five dogs and stable disease (&lt;50% change in tumor volume) in four dogs. Immunoreactivity to PU17 was similar in humans (78% of primary iUC, 80% of nodal metastases). Less immunoreactivity to mab343 (22% of cases) occurred. FR-β was noted in 21% of human iUC cases. Our findings suggest folate-targeted therapy holds considerable promise for treating iUC, where FR-β may be important in addition to FR-α. Cancer Res; 73(2); 875–84. ©2012 AACR.

Background and Purpose— Previous studies have suggested that family members with intracranial aneurysms (IAs) often harbor IAs in similar anatomic locations. IA location is important because of its association with rupture. We tested the hypothesis that anatomic susceptibility to IA location exists using a family-based IA study. Methods— We identified all affected probands and first-degree relatives (FDRs) with a definite or probable phenotype in each family. We stratified each IA of the probands by major arterial territory and calculated each family’s proband-FDR territory concordance and overall contribution to the concordance analysis. We then matched each family unit to an unrelated family unit selected randomly with replacement and performed 1001 simulations. The median concordance proportions, odds ratios (ORs), and P values from the 1001 logistic regression analyses were used to represent the final results of the analysis. Results— There were 323 family units available for analysis, including 323 probands and 448 FDRs, with a total of 1176 IAs. IA territorial concordance was higher in the internal carotid artery (55.4% versus 45.6%; OR, 1.54 [1.04–2.27]; P =0.032), middle cerebral artery (45.8% versus 30.5%; OR, 1.99 [1.22–3.22]; P =0.006), and vertebrobasilar system (26.6% versus 11.3%; OR, 2.90 [1.05–8.24], P =0.04) distributions in the true family compared with the comparison family. Concordance was also higher when any location was considered (53.0% versus 40.7%; OR, 1.82 [1.34–2.46]; P <0.001). Conclusions— In a highly enriched sample with familial predisposition to IA development, we found that IA territorial concordance was higher when probands were compared with their own affected FDRs than with comparison FDRs, which suggests that anatomic vulnerability to IA formation exists. Future studies of IA genetics should consider stratifying cases by IA location.