The myc family of cellular oncogenes contains three known members. The N-myc and c-myc genes have 5'-noncoding exons, strikingly homologous coding regions, and display similar oncogenic potential in an in vitro transformation assay. The L-myc gene is less well characterized, but shows homology to N-myc and c-myc (ref. 6; also see below). c-myc is expressed in most dividing cells, and deregulated expression of this gene has been implicated in the development of many classes of tumours. In contrast, expression of N-myc has been found only in a restricted set of tumours, most of which show neural characteristics; these include human neuroblastoma, retinoblastoma and small cell lung carcinoma (SCLC). L-myc expression has so far been found only in SCLC. Activated N-myc and L-myc expression has been implicated in oncogenesis; for example, although N-myc expression has been found in all neuroblastomas tested, activated (greatly increased) N-myc expression, resulting from gene amplification, is correlated with progression of the tumour. We now report that high-level expression of N- and L-myc is very restricted with respect to tissue and stage in the developing mouse, while that of c-myc is more generalized. Furthermore, we demonstrate that N-myc is not simply a neuroectoderm-specific gene; both N- and L-myc seem to be involved in the early stages of multiple differentiation pathways. Our findings suggest that differential myc gene expression has a role in mammalian development and that the normal expression patterns of these genes generally predict the types of tumours in which they are expressed or activated.

N-myc, a cellular gene related to the c-myc proto-oncogene, was originally identified on the basis of its very frequent amplification and overexpression in a restricted set of tumours, most notably human neuroblastomas. That N-myc may have a causal role in the genesis of these tumours is suggested by the observation that in the rat embryo fibroblast co-transformation assay it has a transforming potential similar to that of c-myc. The apparent structural and functional homology of N-myc and c-myc suggests that they may be members of the same protooncogene family. However, despite these apparent similarities, expression of the two genes appears to be dramatically different with respect to tumour specificity, as well as tissue and developmental stage specificity. To further elucidate the common and unique aspects of N-myc and c-myc gene structure and function in normal and transformed cells, we have determined the organization of human N-myc and the nucleotide sequence of its messenger product, and we report here that N-myc and c-myc have a similar intron/exon structure and that their protein products share regions of significant homology.

To investigate the role of intronic immunoglobulin heavy chain (IgH) enhancer (E mu) in generating accessibility of the JH locus for VDJ recombination, we generated ES cells in which E mu or its flanking sequences were mutated by replacement with or insertion of an expressed neor gene. Heterozygous mutant ES cells were used to generate chimeric mice from which pre‐B cell lines were derived by transformation of bone marrow cells with Abelson murine leukemia virus (A‐MuLV). Comparison of the rearrangement status of the normal and mutated alleles in individual pre‐B cell lines allowed us to assay for cis‐acting effects of the mutations. Replacement of a 700 bp region immediately downstream from the core E mu [which includes part of the 3′ matrix associated region (MAR) and the I mu exon] had no obvious effect on rearrangement of the targeted allele, indicating that insertion of a transcribed neor gene into the JH‐C mu intron does not affect JH accessibility. In contrast, replacement of an overlapping 1 kb DNA fragment that contains the E mu resulted in a dramatic cis‐acting inhibition of rearrangement, demethylation and germline transcription of the associated JH locus. Surprisingly, insertion of the neor gene into the 5′ MAR sequence approximately 100 bp upstream of the core E mu also dramatically decreased recombination of the linked JH locus; but, in many lines, did not prevent demethylation of this locus. We conclude that integrity of the E mu and upstream flanking sequences is required for efficient rearrangement of the JH locus and that demethylation of this locus, per se, does not necessarily make it a good substrate for VDJ recombination.

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Cesarean delivery is a commonly performed operation and accounts for nearly one-third of all births in the United States. Although it is a safe procedure, cesarean delivery has a variety of acute and chronic complications that prompt imaging with ultrasonography (US), computed tomography, and magnetic resonance imaging. Acute complications include hematomas in specific locations that are unique to the procedure, as well as a variety of infections. A bladder flap hematoma occurs in the space between the bladder and the lower uterine segment, whereas a subfascial hematoma is an extraperitoneal collection located in the prevesical space posterior to the rectus muscles and anterior to the peritoneum. Puerperal infections after cesarean delivery include abscesses, wound infections and dehiscence, uterine dehiscence and rupture, and pelvic thrombophlebitis. The prevalence of chronic complications related to the healed cesarean delivery scar is unknown, but the scar may result in technical limitations for pelvic US due to the adhesions between the anterior lower uterine segment and the anterior abdominal wall. The cesarean delivery scar also leaves the patient susceptible to several unique diagnoses. A cesarean scar "niche" is a tethering of the endometrium that can serve as a reservoir for intermenstrual blood and fluid. Intrauterine devices can be malpositioned in the cesarean delivery scar, and endometrial implants can develop in the abdominal wall years after surgery. These patients are also at increased risk for implantation abnormalities including cesarean scar ectopic pregnancy, retained products of conception, and placenta accreta. Familiarity with the normal postoperative findings following cesarean delivery is necessary to recognize acute and chronic complications, which are being encountered with increasing frequency.

Functionally and spatially distinct PI 3-K pathways act either early to promote myelination downstream of axonal Neuregulin1 or late to inhibit myelination downstream of α6β4 integrin and Sgk1.

Adenomyosis is a common benign uterine condition and a frequent cause of pelvic pain in premenopausal women. Transvaginal US is now considered the primary imaging modality for the diagnosis of adenomyosis, and thus radiologists should be familiar with its sonographic appearance. US findings can be divided into three categories, which parallel the histology of adenomyosis: (a) ectopic endometrial glands and stroma, (b) muscular hyperplasia/hypertrophy, and (c) increased vascularity. Ectopic endometrial glands manifest as echogenic nodules and striations, radiating from the endometrium into the myometrium. When the glands contain fluid, myometrial cysts and fluid-filled striations may be visible at US. Muscular hyperplasia and hypertrophy cause focal or diffuse myometrial thickening and globular uterine enlargement, often with thin "venetian blind" shadows. The combination of these findings results in a heterogeneous myometrium, with blurring of the endometrial border. Adenomyosis increases uterine vascularity, depicted as a pattern of penetrating vessels at color Doppler US. Other US techniques that are helpful in the diagnosis of adenomyosis include obtaining cine clips and coronal reformatted images, both of which can survey the entire endometrial-myometrial border, and performing saline-infusion sonohysterography, during which ectopic glands frequently fill with either air or fluid. While most cases of adenomyosis develop spontaneously, there are specific inciting causes that include tamoxifen use, postendometrial ablation syndrome, and deep-infiltrating endometriosis. Mimics of adenomyosis include leiomyomas, uterine contractions, neoplasms, and vascular malformations. This article reviews the pathophysiology of adenomyosis and correlates it with the US findings, highlights specific causes of adenomyosis, and describes how to distinguish this common diagnosis from a variety of mimics. Online supplemental material is available for this article. RSNA, 2018.

Background:The published return-to-play (RTP) rates for Major League Baseball (MLB) pitchers who have undergone surgical repair of superior labrum anterior-posterior (SLAP) tears vary widely and are generally accepted to be lower in the subset of competitive throwers. The efficacy of surgical treatment for MLB players is largely unknown.Purpose:To examine the RTP rate and performance of MLB pitchers who have undergone SLAP tear repair between 2003 and 2010.Study Design:Descriptive epidemiological study.Methods:A retrospective review of MLB pitchers undergoing SLAP repair was performed using the MLB disabled list. Data collected included the following player statistics: earned run average (ERA), walks plus hits per inning pitched (WHIP), and innings pitched (IP). The mean values for performance variables both before and after surgery were compared. A definition of return to prior performance (RTPP) was established as an ERA within 2.00 and WHIP within 0.500 of preoperative values.Results:Twenty-four MLB players met inclusion criteria, of which 62.5% were able to RTP at the MLB level after SLAP repair surgery. Of those able to RTP, 86.7% were able to RTPP. However, the overall rate of RTPP, including those unable to RTP, was 54.2%. Mean performance analysis of the RTP group revealed a statistically significant decrease in IP for MLB pitchers throwing a mean 101.8 innings before injury and 65.53 innings after injury (P = .004).Conclusion:Of those pitchers able to RTP, chances of a full recovery were good (86.7%). Our results indicate the need for future research aimed at proper surgical selection of who will return to play, as they will likely achieve full recovery. We believe this information can help surgeons advise high-level overhead-throwing athletes about expected outcomes for surgical treatment of SLAP tears.