[Severe blunt thoracic trauma caused by ski collision]. / Schweres stumpfes Thoraxtrauma nach Skikollision.

An approximately 25-year-old skier collided in a ski-run intersection. At high speed, he first hit another skier and then smashed into a snow cannon. He died from his injuries a short time later in hospital. A whole-body CT scan was conducted under resuscitation conditions, which was followed by an autopsy. The investigation revealed a severe blunt thoracic trauma as cause of death. The detailed analysis was the result of the combination of the two methods of investigation, CT scan and autopsy. The methods complemented each other effectively and allowed for a detailed presentation of the injury pattern. In conjunction with the additional analytical accident report, this combination of CT scan and autopsy contributes towards a reconstruction of accidents and the development of prevention measures and related protective systems.

Postmortem computed tomography (PMCT) and autopsy in deadly gunshot wounds--a comparative study.

INTRODUCTION: Postmortem computed tomography (PMCT) data in gunshot-related death were evaluated by two reader groups and compared to the gold standard autopsy for the determination of forensic pathology criteria. MATERIALS AND METHODS: Reader group I consisted of two board-certified radiologists whereas one board-certified radiologist and one board-certified forensic pathologist formed group II. PMCT data of 51 gunshot-related deaths were evaluated for the forensic pathology criteria number of gun shots, localization of gunshot injury, caliber, and direction of the gunshot differentiating between entry and exit wound as well as associated injury to surrounding tissue. The results of both reader groups were compared to the each other and to autopsy findings considered as gold standard. RESULTS: Reader groups I and II and as gold standard the autopsy evaluation showed in general a good correlation between all results. The overall discrepancy rate was 12/51 (23.4%) cases for group I and 8/51 (15.6%) for group II. DISCUSSION: Ultimately, the designated reader is able to draw the following conclusion from the presented data. At first, physical autopsy is better than PMCT regarding the localization of most gunshot injuries. Second, PMCT presents with better results than physical autopsy in locating fragmented bullets/fragment clouds, and finally, PMCT results of two radiologists were equivalent to the results of one evaluating radiologist and one pathologist with the exception of caliber assessment. However, referring to the pure numbers, the slight but not significant difference in the overall discrepancy rate of both reader groups might indicate the advantage of combining expertise in evaluating imaging in cases of gunshot-related death.

MRI of the Prostate in Germany: Online Survey among Radiologists.

PURPOSE: To assess structural, technical, and communicative aspects of dedicated MR examinations of the prostate (MRP) offered by radiologists in Germany. MATERIALS AND METHODS: We conducted an eight-item online survey among members of the German Radiology Society (DRG). Radiological institutions were asked about their structure, i.e., either hospital department (HD) or private practice (PP), number of board-certified radiologists, postal regions, number of MRPs in 2011, MR technology and MR sequences applied, ways to communicate results, and feedback from referring physicians on results of subsequent tests and procedures. Submissions were cleared of redundancies and anonymized. Differences in the number of positive replies to each item were statistically significant at p < 0.05 for two-tailed testing in 2 x 2 tables. RESULTS: The survey represented board-certified radiologists in 128 institutions (63 HDs and 65 PPs) in 67/95 German postal regions (71%). Almost two-thirds of institutions performed 11 to 50 MRPs in 2011, more often at 1.5 T (116/128, 91%) than at 3.0 T (36/128, 28%), and most frequently with surface coils (1.5 T, 88/116, 76%; 3.0 T, 34/36, 94%; chi-square, 1.9736, 0.1 < p < 0.25). About two-thirds of 1.5 T users and 90% of 3.0 T users applied at least one functional MR modality (diffusion-weighted imaging, dynamic contrast-enhanced imaging, or MR spectroscopy) for MRP. Reports including graphic representations of the prostate were applied by 21/128 institutions (16%). Clinical feedback after MRP to radiologists other than upon their own request was infrequent (HDs, 32-45%, PPs, 18-32%). CONCLUSION: MRP was a widely available, small-volume examination among radiologists in Germany in 2011. The technology mainstay was a 1.5 T surface coil examination including at least one functional MR modality. Dedicated reporting and feedback mechanisms for quality control were underdeveloped. KEY POINTS: MRI of the prostate was available in at least 67 of 95 German postal regions (71%) in 2011. MRI of the prostate was most often performed at 1.5 T without an endorectal coil in Germany in 2011. At least two thirds of MRI-examinations of the prostate included both T2WI and at least one functional MR test (mostly DWI, less frequently MRS or DCE) in Germany in 2011. Structured reporting including graphic elements was offered by less than 20% of participating radiological institutions. Feedback to radiologists from referring physicians on subsequent test results in patients with MRI of the prostate most frequently came only upon special request by the radiologist.

Differential expression of miR-17~92 identifies BCL2 as a therapeutic target in BCR-ABL-positive B-lineage acute lymphoblastic leukemia.

Despite advances in allogeneic stem cell transplantation, BCR-ABL-positive acute lymphoblastic leukaemia (ALL) remains a high-risk disease, necessitating the development of novel treatment strategies. As the known oncomir, miR-17~92, is regulated by BCR-ABL fusion in chronic myeloid leukaemia, we investigated its role in BCR-ABL translocated ALL. miR-17~92-encoded miRNAs were significantly less abundant in BCR-ABL-positive as compared to -negative ALL-cells and overexpression of miR-17~19b triggered apoptosis in a BCR-ABL-dependent manner. Stable isotope labelling of amino acids in culture (SILAC) followed by liquid chromatography and mass spectroscopy (LC-MS) identified several apoptosis-related proteins including Bcl2 as potential targets of miR-17~19b. We validated Bcl2 as a direct target of this miRNA cluster in mice and humans, and, similar to miR-17~19b overexpression, Bcl2-specific RNAi strongly induced apoptosis in BCR-ABL-positive cells. Furthermore, BCR-ABL-positive human ALL cell lines were more sensitive to pharmacological BCL2 inhibition than negative ones. Finally, in a xenograft model using patient-derived leukaemic blasts, real-time, in vivo imaging confirmed pharmacological inhibition of BCL2 as a new therapeutic strategy in BCR-ABL-positive ALL. These data demonstrate the role of miR-17~92 in regulation of apoptosis, and identify BCL2 as a therapeutic target of particular relevance in BCR-ABL-positive ALL.

Upgrade to iterative image reconstruction (IR) in MDCT imaging: a clinical study for detailed parameter optimization beyond vendor recommendations using the adaptive statistical iterative reconstruction environment (ASIR) Part2: The chest.

PURPOSE: To compare the image quality in dose-reduced 64-row CT of the chest at different levels of adaptive statistical iterative reconstruction (ASIR) to full-dose baseline examinations reconstructed solely with filtered back projection (FBP) in a realistic upgrade scenario. MATERIALS AND METHODS: A waiver of consent was granted by the institutional review board (IRB). The noise index (NI) relates to the standard deviation of Hounsfield units in a water phantom. Baseline exams of the chest (NI = 29; LightSpeed VCT XT, GE Healthcare) were intra-individually compared to follow-up studies on a CT with ASIR after system upgrade (NI = 45; Discovery HD750, GE Healthcare), n = 46. Images were calculated in slice and volume mode with ASIR levels of 0 - 100 % in the standard and lung kernel. Three radiologists independently compared the image quality to the corresponding full-dose baseline examinations (-2: diagnostically inferior, -1: inferior, 0: equal, + 1: superior, + 2: diagnostically superior). Statistical analysis used Wilcoxon's test, Mann-Whitney U test and the intraclass correlation coefficient (ICC). RESULTS: The mean CTDIvol decreased by 53 % from the FBP baseline to 8.0 ± 2.3 mGy for ASIR follow-ups; p < 0.001. The ICC was 0.70. Regarding the standard kernel, the image quality in dose-reduced studies was comparable to the baseline at ASIR 70 % in volume mode (-0.07 ± 0.29, p = 0.29). Concerning the lung kernel, every ASIR level outperformed the baseline image quality (p < 0.001), with ASIR 30 % rated best (slice: 0.70 ± 0.6, volume: 0.74 ± 0.61). CONCLUSION: Vendors' recommendation of 50 % ASIR is fair. In detail, the ASIR 70 % in volume mode for the standard kernel and ASIR 30 % for the lung kernel performed best, allowing for a dose reduction of approximately 50 %.

[Legal considerations regarding radiological examinations of bodypackers ordered by police officers]. / Röntgenuntersuchungen von Bodypackern auf Anordnung durch Polizeibeamte.

A 28-year-old woman was arrested for body packing. One pack was removed from her vagina by the forensic pathologist. She was referred by the police to an emergency surgical department to obtain a radiological examination of the abdomen in order to rule out the presence of further packs in the intestines. In the case of a negative result it would not be necessary to be kept under arrest. For this reason the woman agrees to the examination. The surgeon in the emergency department refused to perform an examination involving radiation exposure to a young woman without any medical indications according to the German X-Ray Ordinance § 23 subsection I. Generally a physician can refuse to perform examinations ordered by state authorities; however, the provision of expert testimony in legal proceedings by a judge, a state attorney or a high ranking police officer makes collaboration mandatory in accordance with § 75 of the German penal code of procedures. However, any relevant harm caused by the examination must be excluded with a very high degree of certainty.

U-2932: two clones in one cell line, a tool for the study of clonal evolution.

Genetic heterogeneity is common in tumors, explicable by the development of subclones with distinct genetic and epigenetic alterations. We describe an in vitro model for cancer heterogeneity, comprising the diffuse large B-cell lymphoma cell line U-2932 which expresses two sets of cell surface markers representing twin populations flow-sorted by CD20 vs CD38 expression. U-2932 populations were traced to subclones of the original tumor with clone-specific immunoglobulin IgVH4-39 hypermutation patterns. BCL6 was overexpressed in one subpopulation (R1), MYC in the other (R2), both clones overexpressed BCL2. According to the combined results of immunoglobulin hypermutation and cytogenetic analysis, R1 and R2 derive from a mother clone with genomic BCL2 amplification, which acquired secondary rearrangements leading to the overexpression of BCL6 (R1) or MYC (R2). Some 200 genes were differentially expressed in R1/R2 microarrays including transcriptional targets of the aberrantly expressed oncogenes. Other genes were regulated by epigenetic means as shown by DNA methylation analysis. Ectopic expression of BCL6 in R2 variously modulated new candidate target genes, confirming dual silencing and activating functions. In summary, stable retention of genetically distinct subclones in U-2932 models tumor heterogeneity in vitro permitting functional analysis of oncogenes against a syngenic background.

Upgrade to iterative image reconstruction (IR) in abdominal MDCT imaging: a clinical study for detailed parameter optimization beyond vendor recommendations using the adaptive statistical iterative reconstruction environment (ASIR).

PURPOSE: To compare the image quality of dose-reduced 64-row abdominal CT reconstructed at different levels of adaptive statistical iterative reconstruction (ASIR) to full-dose baseline examinations reconstructed with filtered back-projection (FBP) in a clinical setting and upgrade situation. MATERIALS AND METHODS: Abdominal baseline examinations (noise index NI = 29; LightSpeed VCT XT, GE) were intra-individually compared to follow-up studies on a CT with an ASIR option (NI = 43; Discovery HD750, GE), n = 42. Standard-kernel images were calculated with ASIR blendings of 0 - 100 % in slice and volume mode, respectively. Three experienced radiologists compared the image quality of these 567 sets to their corresponding full-dose baseline examination (- 2: diagnostically inferior, - 1: inferior, 0: equal, + 1: superior, + 2: diagnostically superior). Furthermore, a phantom was scanned. Statistical analysis used the Wilcoxon - the Mann-Whitney U-test and the intra-class correlation (ICC). RESULTS: The mean CTDIvol decreased from 19.7 ±â€Š5.5 to 12.2 ±â€Š4.7 mGy (p < 0.001). The ICC was 0.861. The total image quality of the dose-reduced ASIR studies was comparable to the baseline at ASIR 50 % in slice (p = 0.18) and ASIR 50 - 100 % in volume mode (p > 0.10). Volume mode performed 73 % slower than slice mode (p < 0.01). CONCLUSION: After the system upgrade, the vendor recommendation of ASIR 50 % in slice mode allowed for a dose reduction of 38 % in abdominal CT with comparable image quality and time expenditure. However, there is still further dose reduction potential for more complex reconstruction settings.

[Diffusion-weighted MRI of the prostate]. / Diffusionsgewichtete MRT der Prostata.

Diffusion-weighted magnetic resonance imaging (DWI) can complement MRI of the prostate in the detection and localization of prostate cancer, particularly after previous negative biopsy. A total of 13 original reports and 2 reviews published in 2010 demonstrate that prostate cancer can be detected by DWI due to its increased cell density and decreased diffusiveness, either qualitatively in DWI images or quantitatively by means of the apparent diffusion coefficient (ADC). In the prostate, the ADC is influenced by the strength of diffusion weighting, localization (peripheral or transitional zone), presence of prostatitis or hemorrhage and density and differentiation of prostate cancer cells. Mean differences between healthy tissue of the peripheral zone and prostate cancer appear to be smaller for ADC than for the (choline + creatine)/citrate ratio in MR spectroscopy. Test quality parameters vary greatly between different studies but appear to be slightly better for combined MRI and DWI than for MRI of the prostate alone. Clinical validation of DWI of the prostate requires both increased technical conformity and increased numbers of patients in clinical studies.

MR-perfusion (MRP) and diffusion-weighted imaging (DWI) in prostate cancer: quantitative and model-based gadobenate dimeglumine MRP parameters in detection of prostate cancer.

BACKGROUND: Various MR methods, including MR-spectroscopy (MRS), dynamic, contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI) have been applied to improve test quality of standard MRI of the prostate. PURPOSE: To determine if quantitative, model-based MR-perfusion (MRP) with gadobenate dimeglumine (Gd-BOPTA) discriminates between prostate cancer, benign tissue, and transitional zone (TZ) tissue. MATERIAL AND METHODS: 27 patients (age, 65±4 years; PSA 11.0±6.1 ng/ml) with clinical suspicion of prostate cancer underwent standard MRI, 3D MR-spectroscopy (MRS), and MRP with Gd-BOPTA. Based on results of combined MRI/MRS and subsequent guided prostate biopsy alone (17/27), biopsy and radical prostatectomy (9/27), or sufficient negative follow-up (7/27), maps of model-free, deconvolution-based mean transit time (dMTT) were generated for 29 benign regions (bROIs), 14 cancer regions (cROIs), and 18 regions of transitional zone (tzROIs). Applying a 2-compartment exchange model, quantitative perfusion analysis was performed including as parameters: plasma flow (PF), plasma volume (PV), plasma mean transit time (PMTT), extraction flow (EFL), extraction fraction (EFR), interstitial volume (IV) and interstitial mean transit time (IMTT). Two-sided T-tests (significance level p<0.05) discriminated bROIs vs. cROIs and cROIs vs. tzROIs, respectively. RESULTS: PMTT discriminated best between bROIs (11.8±3.0 s) and cROIs (24.3±9.6 s) (p<0.0001), while PF, PV, PS, EFR, IV, IMTT also differed significantly (p 0.00002-0.0136). Discrimination between cROIs and tzROIs was insignificant for all parameters except PV (14.3±2.5 ml vs. 17.6±2.6 ml, p<0.05). CONCLUSIONS: Besides MRI, MRS and DWI quantitative, 2-compartment MRP with Gd-BOPTA discriminates between prostate cancer and benign tissue with several parameters. However, distinction of prostate cancer and TZ does not appear to be reliable.

[Psychiatric effects and side effects of the alpha-2-antagonist yohimbine: a review of literature and case report]. / Yohimbin, ein Alpha-2-Antagonist: Literaturübersicht zu psychiatrisch relevanten Wirkungen und Nebenwirkungen mit aktuellem Fallbericht.

We describe a 21-year old female patient who had taken the alpha-2-antagonist yohimbine for weight-loss. The patient reported alterations in alcohol- and cocaine-seeking along with changes in defensive behaviour, including suicidal tendencies. Pre-clinical and clinical studies are discussed, which support the hypothesis of a causal relationship. We added an overview of relevant psychiatric effects and side effects of yohimbine.

[The relationship between emotional distress, cognitive performance and health - related quality of life in patients with hepatitis C prior to antiviral treatment]. / Der Zusammenhang zwischen emotionalen Befindlichkeitsstörungen, kognitiver Leistungsfähigkeit und gesundheitsbezogener Lebensqualität bei mit dem Hepatitis-C-Virus infizierten Patienten vor einer antiviralen Therapie.

Recent epidemiologic studies suggest that more than 175 million individuals are infected with hepatitis C virus (HCV) worldwide. In the past few years, outcome studies in chronic HCV patients are no longer focusing solely on traditional end points such as mortality rates but on psychosocial well-being such as health-related quality of life (HRQoL), emotional states, and neuropsychological functioning. The purpose of our exploratory study was to assess cross sectionally the frequency of depression, posttraumatic stress symptoms, cognitive deficits, and impairments in HRQoL in chronic HCV patients prior to antiviral treatment, and to investigate how cognitive impairments and emotional distress were related to quality of life. We recruited 34 chronic HCV patients who had presented for initial assessment of the need for antiviral therapy. Psychometric observer-rating and self-rating scales were administered to evaluate posttraumatic stress symptoms (PTSS-10), depressive symptoms (BDI), HRQoL (SF-36 Health Status Questionnaire), and cognitive functioning (SKT). 32.4 % (n = 11) of the sample suffered from clinical depression, and 8.8 % (n = 3) had a posttraumatic stress syndrome. 8.8 % (n = 3) of the sample showed cognitive impairments. Significant impairments in HRQoL were found in the health-related domains vitality, role-emotional, and role-physical. The severity of emotional distress as measured on the BDI and PTSS-10 was associated with decrements in HRQoL. However, lower cognitive function scores on the SKT were not associated with lower HRQoL SF-36 values. Chronic HCV patients seem to face a major risk of depression, posttraumatic stress symptoms, and cognitive dysfunction, and the presence of emotional distress is associated with impairments in quality of life. We therefore underscore the need for early and comprehensive bio-psycho-social diagnosis and therapy of chronic HCV patients in order to treat emotional distress and enhance patients; quality of life at an early stage before initiating antiviral therapy, as well as to expand the pool of patients eligible to receive antiviral therapy.

[Multi-detector computed tomography in non-traumatic urologic emergencies]. / Multidetektor-CT bei nichttraumatischen urologischen Notfällen.

Today's modern multi-detector computer tomography (MDCT) with its fast gantry rotation enables scanning of large body volumes with high temporal and spatial resolution. The fast acquisition of data and subsequent data reconstruction enables multiphase protocols with short time gaps between consecutive scan series so that large numbers of scans within one respiratory pause are possible and even in cases of non-cooperative patients acceptable quality of image data is provided. The acquired thin-slice raw data with isotropic submillimeter voxels can be visualized with different reconstruction algorithms. The advantages of imaging for diagnostics in urologic emergencies are the excellent visualization of acute arterial and venous pathologies, detailed assessment of renal parenchyma and the precise depiction of the urinary tract. In non-trauma settings this enables detailed visualization of inflammatory diseases and differentiation of obstructive or post-therapeutic pathologies along the upper and lower urinary tract. Based on these MDCT findings adequate therapy planning and planning of interventional or surgical procedures can be carried out.

SOCS2: inhibitor of JAK2V617F-mediated signal transduction.

Janus kinase 2 (JAK2)V617F-activating mutations (JAK2mu) occur in myeloproliferative disorders (MPDs) and myelodysplastic syndromes (MDSs). Cell lines MB-02, MUTZ-8, SET-2 and UKE-1 carry JAK2V617F and derive from patients with MPD/MDS histories. Challenging the consensus that expression of JAK2V617F is the sole precondition for cytokine independence in class I cytokine receptor-positive cells, two of four of the JAK2mu cell lines were growth factor-dependent. These cell lines resembled JAK2wt cells regarding JAK2/STAT5 activation: cytokine deprivation effected dephosphorylation, whereas erythropoetin or granulocyte colony-stimulating factor induced phosphorylation of JAK2 and STAT5. Cytokine independence correlated with low expression and cytokine dependence with high expression of the JAK/STAT pathway inhibitor suppressor of cytokine signaling 2 (SOCS2) suggesting a two-step mechanism for cytokine independence of MPD cells: (i) activation of the oncogene JAK2V617F and (ii) inactivation of the tumor suppressor gene SOCS2. Confirming that SOCS2 operates as a negative JAK2V617F regulator, SOCS2 knockdown induced constitutive STAT5 phosphorylation in JAK2mu cells. CpG island hypermethylation is reported to promote SOCS gene silencing in malignant diseases. Accordingly, in one of two cytokine-independent cell lines and in two of seven MPD patients, we found SOCS2 hypermethylation associated with reduced promoter access to transcription factors. Our results provide solid evidence that SOCS2 epigenetic downregulation might be an important second step in the genesis of cytokine-independent MPD clones.

Inhibition of Abl tyrosine kinase enhances nerve growth factor-mediated signaling in Bcr-Abl transformed cells via the alteration of signaling complex and the receptor turnover.

Receptor tyrosine kinase-mediated signaling is tightly regulated by a number of cytoplasmic signaling molecules. In this report, we show that Bcr-Abl transformed chronic myelogenous leukemia (CML) cell lines, K562 and Meg-01, express the receptor for nerve growth factor (NGF), TrkA, on the cell surface; however, the NGF-mediated signal is not particularly strong. Treatment with imatinib, a potent inhibitor of Bcr-Abl tyrosine kinase, downmodulates phosphorylation of downstream molecules. Upon stimulation with NGF, Erk and Akt are phosphorylated to a much greater degree in imatinib-treated cells than in untreated cells. Knockdown of expression of Bcr-Abl using small interfering RNA technique also enhanced NGF-mediated Akt phosphorylation, indicating that Bcr-Abl kinase modifies NGF signaling directly. Imatinib treatment also enhanced NGF signaling in rat adrenal pheochromocytoma cell line PC12 that expresses TrkA and c-Abl, suggesting that it is not only restoration of responsiveness to NGF after blocking oncoprotein activity, but also c-Abl tyrosine kinase per se may be a negative regulator of growth factor signaling. Furthermore, inhibition of Abl tyrosine kinase enhanced clearance of surface TrkA after NGF treatment and simultaneously enhanced NGF-mediated signaling, suggesting that as in neuronal cells 'signaling endosomes' are formed in hematopoietic cells. To examine the role of TrkA in CML cells, we studied cell growth or colony formation in the presence or absence of imatinib with or without NGF. We found that NGF treatment induces cell survival in imatinib-treated CML cell lines, as well as colony formation of primary CD34+ CML cells, strongly suggesting that NGF/TrkA signaling contributes to aberrant signaling in CML.

[Imaging procedures to diagnose prostate cancer]. / Bildgebende Verfahren bei der Diagnose des Prostatakarzinoms.

Prostate cancer is one of the most frequent malignant diseases in men. Despite constant progress achieved in imaging procedures, prostate biopsy is the gold standard for diagnosing prostate cancer. For the assessment of lymph node status, only staging lymphadenectomy provides valid information. The aim of this work is to analyze the imaging procedures available in Germany and their value in primary and lymph node staging as well as biochemical recurrence.

Visualization of bronchial lesions using multidetector CT and endobronchial ultrasound (EBUS).

OBJECTIVE: Staging of bronchial carcinoma presents a diagnostic challenge. In addition to CT scans, endobronchial ultrasound is used. The aim of this study was to compare the diagnostic accuracy of high-resolution multidetector CT (MSCT) with that of endobronchial ultrasound with respect of detection and extension of the bronchial lesions. METHODS: 24 patients with lesions in the central bronchial area were examined using both EBUS and MSCT. Multiplanar reconstructions (MPR) as well as virtual endoscopy (VE) were used as adjuncts in this investigation of the comparative diagnostic accuracy of MSCT and EBUS in the imaging of bronchial lesions. RESULTS: No significant difference could be established between EBUS and MSCT in detecting and extension of bronchial lesions. With both procedures, the use of supplementary techniques may be advantageous and helpful in individual cases. CONCLUSIONS: When compared with EBUS, MSCT with post-processing has equally high sensitivity with regard to the visualization of malign endobronchial lesions.

FMIP controls the adipocyte lineage commitment of C2C12 cells by downmodulation of C/EBP alpha.

Fms interacting protein (FMIP) is a substrate for Fms tyrosine kinase, and a nuclear/cytoplasm shuttling protein with a leucine zipper. As the phosphorylation of FMIP is observed in insulin-stimulated preadipocytes, we examined the role of FMIP in adipocyte differentiation, using the mesenchymal multipotent stem cells, C2C12 cells, that can differentiate into adipocytes, muscle cells and osteoblasts. Ectopic expression of FMIP in C2C12 impairs the adipocyte differentiation induced by treatment with insulin, dexamethasone and 3-isobutyl-1-methylxanthine. These cells exhibit muscle phenotype with multinuclear morphology. Furthermore, knockdown of endogenous FMIP expression by small interfering RNA improves adipocytic lineage commitment of C2C12 cells, while impairing muscle differentiation. Upon stimulation with insulin, CCAAT/enhancer binding protein (C/EBP)beta, but not C/EBPalpha, is upregulated in cells expressing ectopic FMIP, whereas in FMIP knockdown cells, C/EBPalpha is constitutively expressed. Ectopic expression of C/EBPalpha counteracts the effects of FMIP, whereas C/EBPalpha knockdown partially mimics the effects of FMIP in this system. Northern blot analysis and reverse transcriptase-polymerase chain reaction study reveal that ectopic FMIP-expressing cells do not contain the polyadenylated C/EBPalpha mRNA, but contain the C/EBPalpha pre-mRNA, suggesting that FMIP plays a role in RNA processing and/or export. Indeed, a member of the THO complex that plays a role in mRNA export, THOC1, is co-precipitated with FMIP. The data we have acquired on FMIP suggest that it is a target for tyrosine kinase receptors that potentiate mRNA export.