Presumed primary cardiac mast cell tumor, pericardial effusion, and arrhythmia in a dog.

A 13-year-old female spayed border collie cross presented for pericardial effusion, arrhythmia, and a suspected cardiac mass. Echocardiogram revealed severe thickening and hypokinesis of the interventricular septum with a heterogenous, cavitated myocardium, concerning for neoplasia. Electrocardiogram revealed predominantly accelerated idioventricular rhythm with frequent periods of nonsustained ventricular tachycardia. Occasional prolonged PR intervals terminating in an aberrantly conducted QRS complex were present. These beats were postulated to represent either first-degree atrioventricular block with aberrant QRS conduction or atrioventricular dissociation. Cytology of the pericardial effusion revealed atypical, suspected neoplastic, mast cells. The patient was euthanized, and postmortem examination confirmed full-thickness infiltration of the interventricular septum by a mast cell tumor, with metastasis to the tracheobronchial lymph node and spleen. Given the anatomic location of the mass, the observed atrioventricular nodal conduction delay may represent neoplastic infiltration of the atrioventricular node. Neoplastic infiltration of the ventricle was suspected to cause the accelerated idioventricular rhythm and ventricular tachycardia. To the authors' knowledge, this is the first reported case of a primary cardiac mast cell tumor causing arrhythmia and pericardial effusion in a dog.

Long-term prognosis of burning mouth syndrome following treatment.

The purpose of this study was to evaluate the long-term prognosis of patients with burning mouth syndrome (BMS) after the termination or discontinuation of treatment and to identify the clinical characteristics that might affect that prognosis. Of 769 patients with an oral burning sensation, 202 with primary BMS who had been treated for at least 3 months were included. Among them, 28 patients who responded to the treatment and 25 patients who did not were assigned to responder and non-responder groups, respectively. Based on telephone interviews, the responders were classified into relapse and non-relapse subgroups, and the non-responder group into persistence and remission subgroups. The majority of responders reported no oral discomfort since their last visit. Compared with the non-relapse subgroup, the relapse subgroup had significantly higher levels of xerostomia at the first visit (P = 0.026) and taste disturbance at the last visit (P = 0.015). The majority of non-responders reported persistent oral discomfort since their last visit. No significant differences were found in the characteristics of oral symptoms between the persistence and remission subgroups. In conclusion, the treatment outcomes in the majority of responders and non-responders were maintained following treatment. Xerostomia and taste disturbance were associated with relapse of oral discomfort in the responders.

Characterization of rhodanine derivatives as potential disease-modifying drugs for experimental mouse osteoarthritis.

OBJECTIVE: This study was performed to characterize selected rhodanine derivatives as potential preclinical disease-modifying drugs for experimental osteoarthritis (OA) in mice. METHODS: Three rhodanine derivatives, designated rhodanine (R)-501, R-502, and R-503, were selected as candidate OA disease-modifying drugs. Their effects were evaluated by intra-articular (IA) injection in OA mouse models induced by DMM (destabilization of the medial meniscus) or adenoviral overexpression in joint tissues of hypoxia-inducible factor (HIF)-2α or zinc importer ZIP8. The regulatory mechanisms impacted by the rhodanine derivatives were examined in primary-culture chondrocytes and fibroblast-like synoviocytes (FLS). RESULTS: All three rhodanine derivatives inhibited OA development caused by DMM or overexpression of HIF-2α or ZIP8. Compared to vehicle-treated group, for example, IA injection of R-501 in DMM-operated mice reduced median OARSI grade from 3.78 (IQR 3.00-5.00) to 1.89 (IQR 0.94-2.00, P = 0.0001). R-502 and R-503 also reduced from 3.67 (IQR 2.11-4.56) to 2.00 (IQR 1.00-2.00, P = 0.0030) and 2.00 (IQR 1.83-2.67, P = 0.0378), respectively. Mechanistically, the rhodanine derivatives inhibited the nuclear localization and transcriptional activity of HIF-2α in chondrocytes and FLS. They did not bind to Zn2+ or modulate Zn2+ homeostasis in chondrocytes or FLS; instead, they inhibited the nuclear localization and transcriptional activity of the Zn2+-dependent transcription factor, MTF1. HIF-2α, ZIP8, and interleukin-1ß could upregulate matrix-degrading enzymes in chondrocytes and FLS, and the rhodanine derivatives inhibited these effects. CONCLUSION: IA administration of rhodanine derivatives significantly reduced OA pathogenesis in various mouse models, demonstrating that these derivatives have disease-modifying therapeutic potential against OA pathogenesis.

Topically applied treatments for external genital warts in nonimmunocompromised patients: a systematic review and network meta-analysis.

Selecting a topical treatment from among the numerous topical agents for external genital warts remains challenging without clear evidence. Our aim was to evaluate comparatively the efficacy and safety of topical agents for external genital warts using a network meta-analysis. We included all randomized controlled trials that evaluated any topically applied treatment for external genital warts. Using the R package netmeta, network meta-analyses were performed with a frequentist approach. We identified 41 relevant studies comprising 6371 patients. Among conventional agents, podophyllotoxin 0·5% solution (odds ratio 1·94, 95% confidence interval 1·02-3·71) was significantly more efficacious than imiquimod 5% cream for lesion clearance; however, it was associated with a higher overall adverse event rate. Sinecatechins 15% ointment (odds ratio 0·21, 95% confidence interval 0·12-0·34) was significantly less efficacious than imiquimod 5% cream. Idoxuridine, polyhexamethylene biguanide, cidofovir and SB206 showed comparable therapeutic efficacies with conventional therapies. None of the treatments were significantly different from each other with respect to recurrence, patients with severe adverse events, or patients who withdrew because of treatment-related adverse events. Conventional modalities were efficacious and well tolerated, although each of them had their advantages and disadvantages. Additional efficacy and safety studies are warranted for unconventional agents.

Intraoperative Management to Prevent Cardiac Collapse in a Patient With a Recurrent, Large-volume Pericardial Effusion and Paroxysmal Atrial Fibrillation During Liver Transplantation: A Case Report.

BACKGROUND: Pericardial effusion is a common feature of end-stage liver disease. In this case report we describe the intraoperative management of recurrent pericardial effusion, without re-pericardiocentesis, to prevent circulatory collapse during a critical surgical time-point; that is, during manipulation of the major vessels and graft reperfusion. METHODS: A 47-year-old woman with hepatitis B was scheduled to undergo deceased donor liver transplantation (LT). A large pericardial effusion was preoperatively identified using transthoracic echocardiography (TTE). The patient also had paroxysmal atrial fibrillation. Two days before surgery, preemptive pericardiocentesis was performed and the 1150-mL effusion was drained. Intraoperatively, recurrence of the large pericardial effusion was identified using transesophageal echocardiography (TEE). During inferior vena cava manipulation, the surgeon consulted the anesthesiologist to evaluate the hemodynamic changes in the patient. After 3 attempts, the transplant team was able to determine the most appropriate anastomosis site, defined as that with the least impact on cardiac function. To prevent the development of severe postreperfusion syndrome, 10% MgSO4 (2 g) was gradually infused 20 minutes before portal vein declamping, and immediately before graft reperfusion a 100-µg bolus of epinephrine was administered. RESULTS: During graft reperfusion, there was no evidence of heart chamber collapse or flow disturbance, as seen on the TEE findings. Postoperatively, the patient recovered completely and was discharged from the hospital. Six months after surgery, there was no sign of pericardial effusion on follow-up TTE. CONCLUSION: Our intraoperative strategy may prevent cardiac collapse in patients with pericardial effusion detected during LT. Intraoperative TEE plays an important role in guiding hemodynamic management.

Correction to: Factors associated with poorer outcomes in the surgical treatment of multiligament knee injuries.

The author would like to correct the following errors in the publication of the original article.

Factors predictive of poorer outcomes in the surgical repair of multiligament knee injuries.

PURPOSE: To investigate the influence of injury and treatment factors on clinical/functional outcomes in multiligament knee injuries (MLKI). METHODS: Thirty-nine consecutive patients with confirmed and surgically treated MLKI who met inclusion criteria were scheduled for a follow-up visit to obtain: SF-12 and subjective feeling of normalcy between the operated and healthy knee, and IKDC, active range of motion (ROM), and stability exam (Lachman test, posterior drawer, and dial test at 30°). A chart review was used to obtain data on injury and treatment factors. RESULTS: The postoperative mean (SD) outcomes were: IKDC score 62.7 (25.9), flexion-extension ROM 125° (29°), and percentage of normalcy 74% (20%). The postoperative normal/nearly normal stability exam was: Lachman test 36 (95%) patients, posterior drawer at 90° 38 (97%) patients, and dial test of 39 (100%) patients. There were 24 (61.5%) and 23 (59%) patients with complications and reoperations, respectively. The presence of bicruciate injuries was associated with worse Lachman (p = 0.03) and posterior drawer tests (p = 0.03). Presence of injury to meniscal structures was associated with worse Lachman test (p = 0.03), lower percentage of normalcy (p = 0.02) and extension lag (p = 0.04). Injury to cartilage structures was associated with worse IKDC scores (p = 0.04). IKDC was lower in cases of posterolateral corner reconstruction (p = 0.03) and use of allograft tendons for reconstruction (p = 0.02); ROM was lower in allograft reconstruction (p = 0.02) and need for meniscal repair (p = 0.01). Bicruciate reconstruction led to worst posterior drawer test (p = 0.006). CONCLUSIONS: The outcomes of MLKI might be negatively influenced by bicruciate ligament, meniscal, and cartilage injuries; with regards to treatment characteristics, need for posterolateral corner or bicruciate ligament reconstruction, use of allografts, or need for meniscal repair may similarly diminish outcomes. While surgical treatment provides good overall function, ROM and stability, it rarely results in a "normal" knee and the chances of complications and reoperations are high. LEVEL OF EVIDENCE: Cross-sectional comparative study, Level III.

Perioperative Changes in the Psoas Muscle Index in Patients Undergoing ABO-Incompatible Living-Donor Liver Transplantation: A Single-Center Experience.

INTRODUCTION: In the era of rituximab, ABO-incompatible living-donor liver transplantation (ABOi LDLT) is clinically accepted as a feasible therapy for end-stage liver disease. To date, no data on postoperative sarcopenic changes in patients undergoing ABOi LDLT are available. PATIENTS AND METHODS: Thirty-six adult patients undergoing ABOi LDLT between October 2010 and July 2017 at our hospital were retrospectively analyzed. The cross-sectional areas of both psoas muscles between the third and fourth lumbar vertebrae were manually estimated from abdominal computed tomography images obtained within 1 month before surgery, and 1 and 3 weeks, 6 months, and 1 year after surgery. The mean psoas muscle areas were calculated and normalized by the height squared to create psoas muscle indices (PMIs). RESULTS: The PMIs on postoperative days (PODs) 7 and 21 were significantly lower than the preoperative PMI in each whole study and male cohort. In whole study cohort, the absolute and relative PMIs on POD 7 were 308.8 (271.5-375.8) mm2/m2 and 95.3% (89.9%-101.1%). On POD 21, the values were 297.8 (258.5-349.6) mm2/m2 and 90.7% (81.1%-99.2%). In men, they were 335.3 (276.7-389.4) mm2/m2 and 94.2% (89.0%-98.8%) on POD 7, and 305.0 (271.6-357.0) mm2/m2 and 89.2% (83.2%-98.2%) on POD 21. In women, they were 281.2 (231.1-313.7) mm2/m2 and 101.4% (95.2%-106.0%) on POD 7, and 260.7 (245.9-273.9) mm2/m2 and 98.9% (77.9%-124.3%) on POD 21. CONCLUSION: Patients undergoing ABOi LDLT were most vulnerable to core muscle loss soon after surgery.

The Processing Time for Recanalization and Size of Ischemic Lesions on DWI is Related With Complete Reperfusion After Mechanical Thrombectomy.

Recent studies demonstrated that modified thrombolysis in cerebral infarction (TICI) 3 reperfusion have better functional outcomes than modified TICI 2b after mechanical thrombectomy in acute ischemic stroke with large vessel occlusion. The purpose of this study was to determine significant factors to forecast the presence of complete reperfusion after mechanical thrombectomy based on multimodal magnetic resonance imaging (MRI). We investigated 96 consecutive patients with acute large intracranial artery occlusion of anterior circulation who based on multimodal MRI. Also, we compared clinical and radiologic parameters between patients with modified TICI 3 and those with modified TICI 0-2b. Among 96 eligible subjects received mechanical thrombectomy, 39 patients (40.6%) showed complete reperfusion and 57 partial or nonreperfusion (mTICI 2b-26, mTICI 2a-9, mTICI 1-8, and mTICI 0-14) after mechanical thrombectomy. Patients with mTICI 3 had significantly smaller initial Diffusion weighted images (DWI) lesion volume (P < .01) and much shorter time interval from onset to reperfusion (P < .01) than those patients with mTICI (0-2b). In multivariate analysis, smaller initial DWI volume (odds ratio [OR], 1.78; 95% confidence interval [CI], 1.23-2.57; P < .01) and faster reperfusion time (OR, 1.07; 95% CI 1.01-1.14; P = .015) had an independence significance for complete reperfusion after mechanical thrombectomy. In this study, the ischemic lesion volume on DWI and faster processing time are critical factor to predict the state of complete reperfusion after mechanical thrombectomy.

The relationship between clinical characteristics including presence of exposed lesions and health-related quality of life (HRQoL) in patients with psoriasis: analysis from the nationwide epidemiologic study for psoriasis in Korea (EPI-PSODE study).

BACKGROUND: Psychological aspect and quality of life should be considered in treating patients with psoriasis. OBJECTIVE: We sought to ascertain which clinical characteristics including presence of exposed lesions are associated with impairment of health-related quality of life (HRQoL) in patients with psoriasis. METHODS: The EPI-PSODE study was a nationwide, multicenter, cross-sectional study conducted in Korea that included 1260 adult patients with psoriasis. In addition to clinical characteristics including presence of exposed lesions, data were collected using the Psoriatic Arthritis (PsA) Screening and Evaluation (PASE), Dermatology Life Quality Index (DLQI), MOS 36-Item Short-Form Health Survey (SF-36), Work Productivity and Activity Impairment Questionnaire Psoriasis (WPAI: PSO) and Medication Satisfaction Questionnaire (MSQ). RESULTS: Patients with a DLQI score > 5 (n = 990) were younger, had an earlier onset of psoriasis, scored higher on the Psoriasis Area and Severity Index (PASI), had higher body surface area (BSA) and had higher PASE scores than patients with DLQI ≤ 5 (n = 266). The group of patients with exposed lesions (n = 871) were younger and male predominance, earlier onset of psoriasis, longer disease duration, higher PASI/BSA score and a higher proportion with drinking and smoking history each than the group of patients without exposed lesions (n = 389). Presence of exposed lesions negatively influenced DLQI, 36-Item Short-Form Health Survey (SF-36) (mental component), presenteeism, total work productivity impairment and total activity impairment in the WPAI: PSO. In multiple regression model, PASI score was the only variable which was significantly associated with all HRQoL measures. Presence of exposed lesions was a significant factor affecting DLQI and SF-36 (mental). CONCLUSION: The presence of exposed lesions has a negative impact on quality of life, mental health and work productivity. Therefore, effective treatments are particularly needed for psoriasis patients with exposed lesions.

Neutrophilic urticarial dermatosis and Sweet-like neutrophilic dermatosis: under-recognized neutrophilic dermatoses in lupus erythematosus.

Background/Objectives Neutrophilic dermatoses can be associated with autoimmune connective tissue diseases such as systemic lupus erythematosus (SLE). We analyzed clinical and histological features of neutrophilic urticarial dermatosis (NUD) and Sweet-like neutrophilic dermatosis (SLND)-the most recently delineated entities of the neutrophilic dermatoses. Methods We retrieved database medical records of patients with SLE whose skin biopsy demonstrated a neutrophilic-predominant infiltrate of the skin, and included those whose biopsies revealed findings of SLND or NUD. Results SLND skin lesions lasted longer than those of NUD and were localized to sun-exposed areas. All NUD cases resolved within one week either spontaneously or with treatment such as antihistamines, but SLND skin lesions lasted longer than one week; prednisone was used in four of these five patients. All NUD cases were found in existing SLE patients and were not associated with systemic signs of flare-up of SLE. However, 80% of SLND cases experienced flare-up of SLE; and in 60%, SLND developed concomitantly with SLE as a presenting sign. Conclusion Different clinical courses and relationships with SLE suggest that NUD and SLND have different pathogeneses for neutrophilic inflammatory reactions.

Pre-stroke glycemic control is associated with early neurologic deterioration in acute atrial fibrillation-related ischemic stroke.

BACKGROUND: It has been suggested that AF-related ischemic stroke (IS) that is accompanied by atherosclerotic burden have poorer outcomes. The aim of this study was to investigate the importance of pre-stroke glycemic control (PSGC) on the early neurologic deterioration (END) of patients with acute AF-related IS. METHODS: We retrospectively recruited 121 patients with AF-related IS who also had Diabetes mellitus (DM). The HbA1C level was measured in all subjects. END was defined as an increase in the National Institute of Health Stroke Scale (NIHSS) score of 4 NIHSS points within 7 days of symptom onset compared to the initial NIHSS score. RESULTS: In this study, 20.7% (25 patients) were classified as having a poor PSGC status with a HbA1C level above 8.0%. In the univariate analysis, a poor PSGC status (p < 0.01), smoking (p = 0.01), severe neurologic deficits at admission (p = 0.01), and a larger size of ischemic lesions on DWI (p < 0.01) were associated with the occurrence of END. In the multivariate model, a poor PSGC status (p = 0.02) and larger size of ischemic lesions on MRI (p < 0.01) were independent predictors of END in acute AF-related IS. CONCLUSION: The HbA1c level upon admission was independently associated with significant prediction of END in acute AF-related IS.

Expression of programmed death-1 in cutaneous extranodal natural killer/T-cell lymphoma and its effect on clinical findings and biological behaviour.

BACKGROUND: Recent studies have evaluated the expression of programmed death-1 (PD-1) and its prognostic value in malignant T-cell lymphomas. OBJECTIVES: This study investigated whether the positivity of PD-1 was associated with the clinical characteristics of cutaneous extranodal NK/T-cell lymphoma (ENKTL) and evaluated its effects on survival outcomes. METHODS: Forty-one patients with cutaneous ENKTL were included. Clinical features and survival outcomes were analysed according to the positivity of PD-1. RESULTS: There was no significant difference between primary cutaneous ENKTL and secondary cutaneous ENKTL in the expression of PD-1. The degree of disease dissemination was not affected by the positivity of PD-1. Higher positivity for PD-1 was associated with lesions presenting erythematous to purpuric patches that are mainly composed of small tumour cells. Cutaneous ENKTL presenting nodular lesions had a significantly lower number of PD-1-positive infiltrating cells than those with other clinical morphologies. There was no significant effect of PD-1 expression on outcomes such as overall and progression-free survival. LIMITATIONS: This study used a retrospective design and had a small sample size. CONCLUSION: Higher PD-1 positivity is associated with small-cell-predominant cutaneous ENKTL. However, PD-1 expression has no prognostic value in cutaneous ENKTL.

A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMETTM Plus platform.

Genetic association studies on the pharmacokinetics of tacrolimus have reported conflicting results, except for the role of the CYP3A5*3 polymorphism. The objective of this study was to identify genetic variants affecting the pharmacokinetics of tacrolimus using the DMETTM Plus microarray in 42 healthy males. Aside from CYP3A5*3, the rs3814055 polymorphism in the NR1I2 gene was associated with the tacrolimus pharmacokinetics based on false discovery rate-corrected multiple tests and the least absolute shrinkage and selection operator analysis. The area under the concentration-time curve to the last quantifiable time point (AUClast) was 3.42 times greater in subjects with homozygous mutations in both genes (CYP3A5*3/*3 and NR1I2 T/T) than in wild-type subjects. The two variants explained the 54% variability in the tacrolimus AUClast. An in vitro luciferase reporter assay indicated that downregulation of PXR expression is the likely molecular mechanism responsible for the increased exposure to tacrolimus in subjects carrying the rs3814055 C>T variant.

Posterolateral portal tibial tunnel drilling for posterior cruciate ligament reconstruction: technique and evaluation of safety and tunnel position.

PURPOSE: To evaluate the safety for neurovascular structures and accuracy for tunnel placement of the posterolateral portal tibial tunnel drilling technique in posterior cruciate ligament (PCL) reconstruction. METHODS: Fifteen fresh-frozen human cadaveric knees were used. The tibial tunnel for the PCL was created using a flexible reamer from the posterolateral portal. Then, the flexible pin was left in place, and the distance from the posterolateral portal, the flexible pin, and the tibial tunnel to the peroneal nerve and popliteal artery was measured. Additionally, the distance between the tibial tunnel and several landmarks related to the PCL footprint was measured, along with the distance from the exit point of the flexible pin to the superficial medial collateral ligament and gracilis tendon. RESULTS: The peroneal nerve and the popliteal neurovascular bundle were not damaged in any of the specimens. The median (range) distance in mm from the peroneal nerve and popliteal artery to the posterolateral portal and flexible pin was: 52 (40-80) and 50 (40-61), and 35 (26-51) and 22 (16-32), respectively. The median (range) distance from the tibial tunnel to the popliteal artery was 21 mm (15-38). The tibial tunnel was located at a median (range) distance in mm of 3 (2-6), 6 (3-12), 5 (2-7), 4 (1-8), 9 (3-10), 10 (4-19), and 19 (6-24) to the champagne-glass drop-off, lateral cartilage point, shiny white fibre point, medial groove, medial meniscus posterior root, lateral meniscus posterior root, and posterior aspect of the anterior cruciate ligament, respectively. CONCLUSIONS: The posterolateral portal tibial tunnel technique is safe relative to neurovascular structures and creates an anatomically appropriate tibial tunnel location. The clinical relevance of study is that this technique may be safely and accurately used in PCL reconstruction to decrease the risk of neurovascular damage (avoid use of a posteriorly directed pin), avoid the use of intraoperative fluoroscopy, and avoid the sharp turn during graft passage.

Impact of paraaortic lymphadenectomy for endometrial cancer with positive pelvic lymph nodes: A Korean Radiation Oncology Group study (KROG 13-17).

AIM: We investigated the role of paraaortic lymph node dissection (PALND) in patients with stage IIIC1 endometrial carcinoma after surgery followed by adjuvant radiotherapy (RT) alone or chemoradiotherapy (CTRT). METHODS: We performed a subgroup analysis in 151 patients treated with adjuvant pelvic RT. Paraaortic-recurrence free survival, disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: In adjuvant RT alone, PALND was significantly related to reduced risk of paraaortic recurrence (0% vs. 17.1%) and distant metastasis (4.5% vs. 19.5%) compared with the no PALND group. PALND affected 5-year DFS (90.2% vs. 58.9%, p = 0.016) and OS (100% vs. 83.1%, p = 0.022). For the CTRT group, the paraaortic recurrence rate was 19.5% for the no PALND group and 12.8% for the PALND group (p = 0.682). Of patients who underwent PALND in the CTRT group, less extensive PALND was significantly related to increased paraaortic recurrence (≤10 vs. >10 dissected LNs, 17.1% vs. 0%). In the no PALND group (n = 82), 5-year paraaortic-recurrence free survival was 79.4% for the CTRT group and 76.2% for the RT alone group (p = 0.941). In multivariate analysis, PALND was significantly associated with reduced risk of disease-specific death (HR, 0.50; 95% CI, 0.26-0.96; p = 0.037). CONCLUSION: PALND provided excellent paraaortic control and improved outcome in stage IIIC1 endometrial cancer with favorable tumor features treated with adjuvant RT alone. Less extensive PALND was associated with significantly increased paraaortic recurrence in patients with advanced tumor features treated with adjuvant CTRT. Combined CTRT did not affect disease control in the paraaortic region compared with RT alone.

Characterization of MUDENG, a novel anti-apoptotic protein.

MUDENG (Mu-2-related death-inducing gene, MuD) is revealed to be involved in cell death signaling. Astrocytes, the major glial cell type in the central nervous system, are a source of brain tumors. In this study, we examined MuD expression and function in human astroglioma cells. Stimulation of U251-MG cells with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) resulted in a 40% decrease in cell viability and a 33% decrease in MuD protein levels, although not in MuD mRNA levels. To study the functional relevance of MuD expression, stable transfectants expressing high levels of MuD were generated. Stimulation of these transfectants with TRAIL resulted in enhanced cell survival (77% for stable and 46% for control transfectants). Depletion of MuD led to a marked reduction upon TRAIL stimulation in cell viability (22% in MuD-depleted cells and 54% in control cells). In addition, we observed that MuD depletion increased the susceptibility of the cells to TRAIL by enhancing the cleavage of caspase-3/-9 and BH3-interacting domain death agonist (Bid). A unique 25-kDa fragment of B-cell lymphoma 2 (Bcl-2) lacking BH4 was observed 60-180 min post TRAIL treatment in MuD-depleted cells, suggesting that Bcl-2 is converted from its anti-apoptotic form to the truncated pro-apoptotic form. Importantly, the TRAIL-mediated decrease in cell viability in MuD-depleted cells was abrogated upon Bid depletion, indicating that the role of MuD in apoptotic signaling takes place at the Bid and Bcl-2 junction. MuD localizes predominantly in the endoplasmic reticulum and partly in the mitochondria and its amounts are reduced 6 h post TRAIL stimulation, presumably via caspase-3-mediated MuD cleavage. Collectively, these results suggest that MuD, a novel signaling protein, not only possesses an anti-apoptotic function but may also constitute an important target for the design of ideal candidates for combinatorial treatment strategies for glioma cells.