Plasmoid Formation and Strong Radiative Cooling in a Driven Magnetic Reconnection Experiment.

We present the first experimental study of plasmoid formation in a magnetic reconnection layer undergoing rapid radiative cooling, a regime relevant to extreme astrophysical plasmas. Two exploding aluminum wire arrays, driven by the Z machine, generate a reconnection layer (S_{L}≈120) in which the cooling rate far exceeds the hydrodynamic transit rate (τ_{hydro}/τ_{cool}>100). The reconnection layer generates a transient burst of >1 keV x-ray emission, consistent with the formation and subsequent rapid cooling of the layer. Time-gated x-ray images show fast-moving (up to 50 km s^{-1}) hotspots in the layer, consistent with the presence of plasmoids in 3D resistive magnetohydrodynamic simulations. X-ray spectroscopy shows that these hotspots generate the majority of Al K-shell emission (around 1.6 keV) prior to the onset of cooling, and exhibit temperatures (170 eV) much greater than that of the plasma inflows and the rest of the reconnection layer, thus providing insight into the generation of high-energy radiation in radiatively cooled reconnection events.

EJP18 peptide derived from the juxtamembrane domain of epidermal growth factor receptor represents a novel membrane-active cell-penetrating peptide.

Membrane-active peptides have been extensively studied to probe protein-membrane interactions, to act as antimicrobial agents and cell-penetrating peptides (CPPs) for the delivery of therapeutic agents to cells. Hundreds of membrane-active sequences acting as CPPs have now been described including bioportides that serve as single entity modifiers of cell physiology at the intracellular level. Translation of promising CPPs in pre-clinical studies have, however, been disappointing as only few identified delivery systems have progressed to clinical trials. To search for novel membrane-active peptides a sequence from the EGFR juxtamembrane region was identified (named EJP18), synthesised, and examined in its L- and D-form for its ability to mediate the delivery of a small fluorophore and whole proteins to cancer cell lines. Initial studies identified the peptide as being highly membrane-active causing extensive and rapid plasma membrane reorganisation, blebbing, and toxicity. At lower, non-toxic concentrations the peptides outperformed the well-characterised CPP octaarginine in cellular delivery capacity for a fluorophore or proteins that were associated with the peptide covalently or via ionic interactions. EJP18 thus represents a novel membrane-active peptide that may be used as a naturally derived model for biophysical protein-membrane interactions or for delivery of cargo into cells for therapeutic or diagnostic applications.

Haemorrhage following transoral robotic surgery.

BACKGROUND: To report our experience of postoperative haemorrhage in patients following transoral robotic surgery (TORS). METHODS: Data were collected on patients having TORS. Postoperative haemorrhage within 30 days was graded using the Mayo Clinic grading system. RESULTS: Transoral robotic surgery operations were performed on 122 patients. There were 23 bleeding events classified as minor to severe following 19 operations (16%). Haemorrhage requiring a return to the operating room occurred after 7 operations (6%). The odds of an emergent haemorrhage were 5.19 times greater in patients who had a staged neck dissection after TORS (P = .05). The odds of a postoperative bleeding event were 2.6 times greater in patients receiving a larger resection (P = .107). There were no haemorrhage events in the 36 patients who received a synchronous neck dissection with transcervical ligation of the external carotid artery. CONCLUSIONS: Surgical intervention for TORS haemorrhage occurred in 6% patients. No haemorrhage occurred in patients who had ligation of the external carotid artery.

Outcomes for patients with papillary thyroid cancer who do not undergo prophylactic central neck dissection.

BACKGROUND: The role of prophylactic central neck dissection (CND) in the management of papillary thyroid cancer (PTC) is controversial. This report describes outcomes of an observational approach in patients without clinical evidence of nodal disease in PTC. METHODS: All patients who had surgery between 1986 and 2010 without CND for PTC were identified. All patients had careful clinical assessment of the central neck during preoperative and perioperative evaluation, with any suspicious nodal tissue excised for analysis. The cohort included patients in whom lymph nodes had been removed, but no patient had undergone a formal neck dissection. Recurrence-free survival (RFS), central neck RFS and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. RESULTS: Of 1798 patients, 397 (22.1 per cent) were men, 1088 (60.5 per cent) were aged 45 years or more, and 539 (30.0 per cent) had pT3 or pT4 disease. Some 742 patients (41.3 per cent) received adjuvant treatment with radioactive iodine. At a median follow-up of 46 months the 5-year DSS rate was 100 per cent. Five-year RFS and central neck RFS rates were 96.6 and 99.1 per cent respectively. CONCLUSION: Observation of the central neck is safe and should be recommended for all patients with PTC considered before and during surgery to be free of central neck metastasis.

Status of Competency-Based Medical Education in Endoscopy Training: A Nationwide Survey of US ACGME-Accredited Gastroenterology Training Programs.

OBJECTIVES: The Accreditation Council for Graduate Medical Education (ACGME) emphasizes the importance of medical trainees meeting specific performance benchmarks and demonstrating readiness for unsupervised practice. The aim of this study was to examine the readiness of Gastroenterology (GI) fellowship programs for competency-based evaluation in endoscopic procedural training. METHODS: ACGME-accredited GI program directors (PDs) and GI trainees nationwide completed an online survey of domains relevant to endoscopy training and competency assessment. Participants were queried about current methods and perceived quality of endoscopy training and assessment of competence. Participants were also queried about factors deemed important in endoscopy competence assessment. Five-point Likert items were analyzed as continuous variables by an independent t-test and χ(2)-test was used for comparison of proportions. RESULTS: Survey response rate was 64% (94/148) for PDs and 47% (546/1,167) for trainees. Twenty-three percent of surveyed PDs reported that they do not have a formal endoscopy curriculum. PDs placed less importance (1­very important to 5­very unimportant) on endoscopy volume (1.57 vs. 1.18, P<0.001), adenoma detection rate (2.00 vs. 1.53, P<0.001), and withdrawal times (1.96 vs. 1.68, P=0.009) in determining endoscopy competence compared with trainees. A majority of PDs report that competence is assessed by procedure volume (85%) and teaching attending evaluations (96%). Only a minority of programs use skills assessment tools (30%) or specific quality metrics (28%). Specific competencies are mostly assessed by individual teaching attending feedback as opposed to official documentation or feedback from a PD. PDs rate the overall quality of their endoscopy training and assessment of competence as better than overall ratings by trainees. CONCLUSIONS: Although the majority of PDs and trainees nationwide believe that measuring specific metrics is important in determining endoscopy competence, most programs still rely on procedure volume and subjective attending evaluations to determine overall competence. As medical training transitions from an apprenticeship model to competency-based education, there is a need for improved endoscopy curricula which are better suited to demonstrate readiness for unsupervised practice.

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

Practical opportunities to improve early detection and prevention of colorectal cancer (CRC) in members of high-risk families.

Colorectal cancer (CRC) incidence and mortality are steadily declining and CRC screening rates are increasing in the United States. Although this a very good news, several definable groups still have very low screening rates including younger (under age 50) members of high-risk CRC families. This opinion piece describes five strategies that could be incorporated into routine practice to improve identification and guideline-based screening in members of high-risk families. Routine incorporation of a simple family history screening tool and outreach to high-risk family members could substantially improve guideline-based screening in this population. Identification of CRCs and advanced adenomas in the endoscopy suite defines another group of high-risk families for similar outreach. Lynch syndrome families can be identified by testing CRCs and selected adenomas for microsatellite instability or loss of DNA repair protein expression. Finally, selective addition of aspirin to surveillance endoscopy can decrease the risk of new adenomas and CRCs. The rationale for these strategies as well as mechanisms for their implementation and evaluation in clinical practice is described.

Anaplastic thyroid carcinoma: a 25-year single-institution experience.

BACKGROUND: Anaplastic thyroid carcinoma (ATC) is among the most aggressive solid tumors accounting for 1-5 % of primary thyroid malignancies. In this retrospective review, we aim to evaluate the prognostic factors, treatment approaches, and outcomes of patients with ATC treated at a single institution. MATERIALS AND METHODS: We retrospectively identified 95 patients with ATC from an institutional database between 1985 and 2010. A total of 83 patients with sufficient records were included in this study. Patient, tumor, and treatment characteristics were recorded. Disease-specific survival (DSS) was determined by the Kaplan-Meier method, and factors predictive of outcome were determined by univariate and multivariate analysis. RESULTS: Of the 83 patients, 41 were male and 42 were female. The median age at presentation was 60 years (range 28-89 years) with a median survival of 8 months. The 1- and 2-year DSS were 33 and 23 %, respectively. On univariate analysis, age less than 60 years, clinically N0 neck, absence of clinical extrathyroidal extension (cETE), gross total resection, and multimodality treatment were statistically significant predictors of improved survival. On multivariate analysis, absence of cETE, multimodality therapy, and gross total resection were predictors of improved outcome. CONCLUSIONS: In patients with locoregional limited disease, multimodality treatment with gross total surgical resection and postoperative radiotherapy with or without chemotherapy offers the best local control and DSS.

Regulation of neuronal plasticity and fear by a dynamic change in PAR1-G protein coupling in the amygdala.

Fear memories are acquired through neuronal plasticity, an orchestrated sequence of events regulated at circuit and cellular levels. The conventional model of fear acquisition assumes unimodal (for example, excitatory or inhibitory) roles of modulatory receptors in controlling neuronal activity and learning. Contrary to this view, we show that protease-activated receptor-1 (PAR1) promotes contrasting neuronal responses depending on the emotional status of an animal by a dynamic shift between distinct G protein-coupling partners. In the basolateral amygdala of fear-naive mice PAR1 couples to Gαq/11 and Gαo proteins, while after fear conditioning coupling to Gαo increases. Concurrently, stimulation of PAR1 before conditioning enhanced, but afterwards it inhibited firing of basal amygdala neurons. An initial impairment of the long-term potentiation (LTP) in PAR1-deficient mice was transformed into an increase in LTP and enhancement of fear after conditioning. These effects correlated with more frequent 2-amino-3-(5-methyl-3-oxo-1,2-oxazol-4-yl)propanoic acid (AMPA) receptor-mediated miniature post synaptic events and increased neuronal excitability. Our findings point to experience-specific shifts in PAR1-G protein coupling in the amygdala as a novel mechanism regulating neuronal excitability and fear.

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research.

BACKGROUND: Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC. METHODS: The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan-Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis. RESULTS: The OS was 49% for patients with LND0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures. CONCLUSION: This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.

Clinical nodal stage is a significant predictor of outcome in patients with oral cavity squamous cell carcinoma and pathologically negative neck metastases: results of the international consortium for outcome research.

BACKGROUND: We aimed to study the importance of clinical N classification (cN) in a subgroup of patients with oral cavity squamous cell carcinoma (OSCC) and pathologically negative neck nodes (pN-). METHODS: A total of 2,258 patients from 11 cancer centers who underwent neck dissection for OSCC (1990-2011) had pN- disease. The median follow-up was 44 months. 5-year overall survival (OS), disease-specific survival (DSS), disease free survival, local control, locoregional control, and distant metastasis rates were calculated by the Kaplan-Meier method. cN classification and tumor, node, metastasis classification system staging variables were subjected to multivariate analysis. RESULTS: A total of 345 patients were preoperatively classified as cN+ and 1,913 were classified as cN-. The 5-year OS and DSS of cN- patients were 73.6 and 82.2 %, respectively. The 5-year OS and DSS of cN+ patients were 64.9 and 76.9 %, respectively (p < 0.0001 each). A cN+ classification was a significant predictor of worse OS (p = 0.03) and DSS (p = 0.016), regardless of treatment, depth of invasion, or extent of neck dissection. cN classification was associated with recurrence-free survival (p = 0.01) and locoregional (neck and primary tumor) control (p = 0.004), but not with local (p = 0.19) and distant (p = 0.06) recurrence rates. CONCLUSIONS: Clinical evidence of neck metastases is an independent predictor of outcome, even in patients with pN- nodes.

The role of sentinel lymph node biopsy in the management of head and neck desmoplastic melanoma.

BACKGROUND: Desmoplastic melanoma (DM), a variant of spindle cell melanoma, has a higher propensity for local recurrence and a lower incidence of nodal metastasis. In this retrospective review, we evaluated the risk for regional nodal metastases and the need for sentinel lymph node biopsy (SLNB) in patients with head and neck DM. METHODS: We identified 103 patients with DM from an institutional database of patients with head and neck melanomas treated between 1985 and 2009. Forty-seven patients had their primary treatment at Memorial Sloan-Kettering Cancer Center, and 56 patients were treated for recurrent or metastatic disease. RESULTS: Of the 47 study patients, 27 were men and 20 were women with a median age of 71 years. All patients underwent wide excision, and 21 (44 %) underwent SLNB. None of the patients who underwent SLNB had positive nodes. The mean Breslow thickness for the 45 reported patients was 6.1 mm, with 84 % of tumors >2 mm in thickness and 55 % >4 mm. All known Clark thickness levels (n = 40) were IV or V. The overall survival was 73 %, with disease-specific survival of 84 %, local recurrence-free survival of 75 %, and neck recurrence-free survival of 97 % at 5 years. CONCLUSIONS: Although DM is diagnosed at higher Breslow thickness and Clark level, neck metastases are rare and prognosis is favorable compared to conventional melanoma. The low incidence of lymphovascular invasion, high frequency of histopathologically negative sentinel lymph nodes, and low neck recurrence rates indicate that staging of neck disease by SLNB is not necessary in patients with pure DM of the head and neck.

Optimization of switch diagnostics on the MAIZE linear transformer driver.

The MAIZE Linear Transformer Driver consists of 40 capacitor-switch-capacitor "bricks" connected in parallel. When these 40 bricks are charged to ±100-kV and then discharged synchronously, the MAIZE facility generates a 1-MA current pulse with a 100-ns rise time into a matched load impedance. Discharging each of the capacitors in a brick is carried out by the breakdown of a spark-gap switch, a process that results in the emission of light. Monitoring this output light with a fiber optic coupled to a photomultiplier tube (PMT) and an oscilloscope channel provides information on switch performance and timing jitter-whether a switch fired early, late, or in phase with the other switches. However, monitoring each switch with a dedicated detector-oscilloscope channel can be problematic for facilities where the number of switches to be monitored (e.g., 40 on MAIZE) greatly exceeds the number of detector-oscilloscope channels available. The technique of using fibers to monitor light emission from switches can be optimized by treating a PMT as a binary digit or bit and using a combinatorial encoding scheme, where each switch is monitored by a unique combination of fiber-PMT-oscilloscope channels simultaneously. By observing the unique combination of fiber-PMT-oscilloscope channels that are turned on, the prefiring or late-firing of a single switch on MAIZE can be identified by as few as six PMT-oscilloscope channels. The number of PMT-oscilloscope channels, N, required to monitor X switches can be calculated by 2N = X + 1, where the number "2" is selected because the PMT-oscilloscope acts as a bit. In this paper, we demonstrate the use of this diagnostic technique on MAIZE. We also present an analysis of how this technique could be scaled to monitor the tens of thousands of switches proposed for various next generation pulsed power facilities.

Zeeman spectroscopy as a method for determining the magnetic field distribution in self-magnetic-pinch diodes (invited).

In the self-magnetic-pinch diode, the electron beam, produced through explosive field emission, focuses on the anode surface due to its own magnetic field. This process results in dense plasma formation on the anode surface, consisting primarily of hydrocarbons. Direct measurements of the beam's current profile are necessary in order to understand the pinch dynamics and to determine x-ray source sizes, which should be minimized in radiographic applications. In this paper, the analysis of the C IV doublet (580.1 and 581.2 nm) line shapes will be discussed. The technique yields estimates of the electron density and electron temperature profiles, and the method can be highly beneficial in providing the current density distribution in such diodes.

Diagnostic and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography for recurrent head and neck squamous cell carcinoma.

PURPOSE: Patients with recurrent head and neck squamous cell carcinoma (HNSCC) present a diagnostic and therapeutic challenge. We evaluated the diagnostic accuracy and prognostic value of [(18)F]fluorodeoxyglucose positron emission tomography (PET) in this patient population. PATIENTS AND METHODS: We performed a retrospective review of 143 patients with previously treated HNSCC who underwent 181 PET scans at our institution from May 1996 through April 2001 to detect recurrent disease. Disease recurrence within 6 months was used as the gold standard for assessing true disease status at PET. RESULTS: With equivocal sites considered positive, the sensitivity and specificity of PET for detecting recurrence overall were 96% and 72%, respectively. PET was highly sensitive and specific at regional and distant sites. At local sites, sensitivity was high, but specificity was lower because of false-positive findings. One fifth of all false-positive PET scans occurred at sites of known inflammation or infection. The area under the curve for a receiver operator characteristic curve on the basis of standardized uptake value (SUV) was 0.882 +/- 0.025. PET interpretation, SUV, and physical examination were independent predictors of relapse-free and overall survival in a time-dependent, multivariate proportional hazards model. An increase in SUV by one unit increased the relative risk (RR) of relapse by 11% and the RR of death by 14%. A positive PET interpretation increased the RR of relapse by four-fold and the RR of death by seven-fold. CONCLUSION: PET was a highly sensitive method of detecting recurrent HNSCC and provided important prognostic information for relapse-free and overall survival.

Technique for fabrication of ultrathin foils in cylindrical geometry for liner-plasma implosion experiments with sub-megaampere currents.

In this work, we describe a technique for fabricating ultrathin foils in cylindrical geometry for liner-plasma implosion experiments using sub-MA currents. Liners are formed by wrapping a 400 nm, rectangular strip of aluminum foil around a dumbbell-shaped support structure with a non-conducting center rod, so that the liner dimensions are 1 cm in height, 6.55 mm in diameter, and 400 nm in thickness. The liner-plasmas are imploded by discharging ∼600 kA with ∼200 ns rise time using a 1 MA linear transformer driver, and the resulting implosions are imaged four times per shot using laser-shadowgraphy at 532 nm. This technique enables the study of plasma implosion physics, including the magneto Rayleigh-Taylor, sausage, and kink instabilities on initially solid, imploding metallic liners with university-scale pulsed power machines.

Cytokine gene transfer enhances herpes oncolytic therapy in murine squamous cell carcinoma.

Replication-competent, attenuated herpes simplex viruses (HSV) have been demonstrated to be effective oncolytic agents in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the utility of combining these two approaches, two oncolytic HSV vectors (NV1034 and NV1042) were designed to express the murine GM-CSF and murine IL-12 genes, respectively. These cytokine-carrying variants were compared with the analogous non-cytokine-carrying control virus (NV1023) in the treatment of murine SCC VII squamous cell carcinoma. All three viruses demonstrated similar infection efficiency, viral replication, and cytotoxicity in vitro. SCC VII cells infected by NV1034 and NV1042 effectively produced GM-CSF and IL-12, respectively. In an SCC VII subcutaneous flank tumor model in immunocompetent C3H/HeJ mice, intratumoral injection with each virus caused a significant reduction in tumor volume compared with saline injections. The NV1042-treated tumors showed a striking reduction in tumor volume compared with the NV1023- and NV1034-treated tumors. On subsequent rechallenge in the contralateral flank with SCC VII cells, 57% of animals treated with NV1042 failed to develop tumors, in comparison with 14% of animals treated with NV1023 or NV1034, and 0% of naive animals. The increased antitumor efficacy seen with NV1042 in comparison with NV1023 and NV1034 was abrogated by CD4(+) and CD8(+) lymphocyte depletion. NV1042 is a novel, attenuated, oncolytic herpesvirus that effectively expresses IL-12 and elicits a T lymphocyte-mediated antitumor immune response against murine squamous cell carcinoma. Such combined oncolytic and immunomodulatory strategies hold promise in the treatment of cancer.

Two distal Sp1-binding cis-elements regulate fibroblast growth factor receptor 1 (FGFR1) gene expression in myoblasts.

Skeletal myoblast cell proliferation and subsequent differentiation are dependent on developmentally regulated expression of the fibroblast growth factor receptor 1 (FGFR1) gene. We have previously reported the isolation and initial characterization of the chicken FGFR1 gene (cek1) promoter. Both distal and proximal regions of the promoter were identified as necessary for developmentally regulated transcriptional activity in proliferating myoblasts, including its down-regulation in differentiated muscle fibers in vitro. Here we report detailed characterization of the molecular mechanism regulating FGFR1 promoter activity via the distal promoter region in proliferating myoblasts. This region was identified as a 242 base pair segment located greater than 1 kilobase upstream from the start of transcription that conferred increased transcriptional activity to a minimal thymidine kinase promoter. This segment contains two Sp1 binding sites. Site directed mutagenesis and transfection studies indicated that both Sp1 sites are functional and both are required for FGFR1 promoter activity. Furthermore, Sp1 binding to the two sites was synergistic enhancing FGFR1 promoter activity. The specificity of Sp1 binding to the two distal promoter cis-elements was verified by electromobility shift and transfection assays employing an Sp1 expression construct. Differences in myoblast versus fibroblast-specific protein-DNA complex formation at these sites correlated with high promoter activity in myoblasts and significantly reduced promoter activity in fibroblasts. These studies for the first time establish a molecular mechanism regulating FGFR1 gene expression during myoblast proliferation.

Regulation of avian fibroblast growth factor receptor 1 (FGFR-1) gene expression during skeletal muscle differentiation.

Myogenic cell proliferation and differentiation are regulated by a fibroblast growth factor (FGF) signal transduction cascade mediated by a high-affinity fibroblast growth factor receptor (FGFR). Exogenous FGF added to myogenic cultures has a mitogenic effect promoting myoblast proliferation while repressing differentiation. We have examined the regulation of the FGFR-1 gene (cek-1) in avian myogenic cultures by immunocytochemistry and Northern blot analysis. FGFR-1 protein was readily detected in undifferentiated myoblast cultures and was significantly reduced in differentiated muscle fiber cultures. Similarly, FGFR-1 mRNA was 2.5-fold more abundant in myoblast cultures than in differentiated cultures. To define the molecular mechanism regulating FGFR-1 gene expression in proliferating myoblasts and post-mitotic muscle fibers, we have isolated and partially characterized the avian FGFR-1 gene promoter. Transfection of FGFR-1 promoter-chloramphenicol acetyltransferase gene constructs into myogenic cultures identified two regions regulating expression of this gene in myoblasts. A distal region of 2226 bp conferred a high level of expression in myoblasts. This region functioned in an orientation-dependent manner and interacted with a promoter element(s) in a proximal 1058 bp promoter region to direct transcription. Deletion analysis revealed a 78 bp region that confers a high level of cek1 promoter activity in myoblasts. This DNA segment also contains Spl binding sites and interacts with a component in myoblast nuclear protein extracts. The proximal promoter region alone demonstrated no activity in directing transcription in either myoblasts or muscle fibers. Using the full-length promoter, gene expression was significantly decreased in differentiated muscle fibers relative to undifferentiated myoblasts indicating that the promoter-reporter gene constructs contain elements regulating expression of the endogenous FGFR-1 gene in both myoblasts and muscle fibers.