Compassion fatigue resiliency training: the experience of facilitators.

This qualitative evaluation examined compassion fatigue facilitators' perceptions of the effects of a compassion fatigue resiliency training program in an urban medical center in the midwestern United States. Nine months after completing a compassion fatigue resiliency facilitator training program, 15 participants wrote short narratives describing how the program affected them. Participants described how the training program benefited them both personally and professionally. Two main themes were identified from the narrative analysis: self-improvement and application of resiliency. All of the participants described one or more self-improvements as a result of the program, particularly in regard to emotional health. All of the participants also described how they regularly applied one or more of the resiliency skills taught in the class to improve their ability to manage stress and prevent compassion fatigue. This program shows promise in ameliorating compassion fatigue and burnout in health care providers.

The effectiveness of an educational program on preventing and treating compassion fatigue in emergency nurses.

The purpose of this qualitative study was to examine the treatment effectiveness of a multifaceted education program to decrease compassion fatigue (CF) and burnout (BO) symptoms and increase compassion satisfaction of emergency nurses participating in the training. The goal of the CF multifaceted intervention program was to demonstrate a statistically significant improvement in the 3 CF subscales: an increase on the Compassion Satisfaction (CS) subscale and a decrease on the Secondary Traumatic Stress (STS) and BO subscales in the participants' pretest and posttest scores as measured by The Professional Quality of Life test (B. H. , ). The study sites were 2 emergency departments in Colorado Springs, CO. A convenience sample consisted of emergency nurses who self-selected to participate in the study. Univariate statistics were used, and data were examined for normalcy of distribution. Because these data were not distributed normally, Wilcoxon signed-rank tests were used to evaluate the differences between the baseline and postintervention groups. The multifaceted education program resulted in a statistically significant increase in CS (p = 0.004) and a decrease in BO (p = 0.001 or less) and STS (p = 0.001) symptoms.

Notch signaling expands a pre-malignant pool of T-cell acute lymphoblastic leukemia clones without affecting leukemia-propagating cell frequency.

NOTCH1 pathway activation contributes to the pathogenesis of over 60% of T-cell acute lymphoblastic leukemia (T-ALL). While Notch is thought to exert the majority of its effects through transcriptional activation of Myc, it also likely has independent roles in T-ALL malignancy. Here, we utilized a zebrafish transgenic model of T-ALL, where Notch does not induce Myc transcription, to identify a novel Notch gene expression signature that is also found in human T-ALL and is regulated independently of Myc. Cross-species microarray comparisons between zebrafish and mammalian disease identified a common T-ALL gene signature, suggesting that conserved genetic pathways underlie T-ALL development. Functionally, Notch expression induced a significant expansion of pre-leukemic clones; however, a majority of these clones were not fully transformed and could not induce leukemia when transplanted into recipient animals. Limiting-dilution cell transplantation revealed that Notch signaling does not increase the overall frequency of leukemia-propagating cells (LPCs), either alone or in collaboration with Myc. Taken together, these data indicate that a primary role of Notch signaling in T-ALL is to expand a population of pre-malignant thymocytes, of which a subset acquire the necessary mutations to become fully transformed LPCs.

SGDI: system for genomic data integration.

This paper describes a framework for collecting, annotating, and archiving high-throughput assays from multiple experiments conducted on one or more series of samples. Specific applications include support for large-scale surveys of related transcriptional profiling studies, for investigations of the genetics of gene expression and for joint analysis of copy number variation and mRNA abundance. Our approach consists of data capture and modeling processes rooted in R/Bioconductor, sample annotation and sequence constituent ontology management based in R, secure data archiving in PostgreSQL, and browser-based workspace creation and management rooted in Zope. This effort has generated a completely transparent, extensible, and customizable interface to large archives of high-throughput assays. Sources and prototype interfaces are accessible at www.sgdi.org/software.

Differential effect of selected methylxanthine derivatives on radiosensitization of lung carcinoma cells.

AIM: Using caffeine as a reference derivative, this study was performed to investigate how other methylxanthine derivatives, theophylline, 3-isobutyl-methylxanthine and 1,3-dipropyl-7-methylxanthine, sensitize cells to radiation by modifying cell cycle checkpoints and inducing the apoptotic response. The effect of the methylxanthine derivatives was studied in response to gamma and ultraviolet radiation in a human large cell lung carcinoma cell line, null for p53, a normal lung epithelial cell line and the large cell lung carcinoma cell line stably transfected with p53. METHODS: Effects of theophylline, 3-isobutyl-methylxanthine and 1,3-dipropyl 7-methylxanthine on cell-radiosensitization in comparison to caffeine tested by clonogenic survival assay, MTT assay, ELISA based apoptotic assay, flow cytometry, caspase-3 activity, TUNEL assay, and western blot analysis. RESULTS: All the derivatives, except 3-isobutyl-methylxanthine, increased tumor cell sensitization to radiation by inducing apoptosis in the p53-null lung cancer cell line. The pattern of cell cycle progression revealed that these derivatives increased the number of cells in G1 phase by abrogating the G2/M checkpoint, directing the cells to apoptose through a p53-independent mechanism. In contrast, 3-isobutyl-methylxanthine was more potent than the other derivatives in radiosensitization of normal lung epithelial cells and the lung carcinoma cells stably transfected with wild-type p53. IBMX increased p53 protein level more than caffeine in lung carcinoma cells stably transfected with wild-type p53. CONCLUSION: Our results suggest that 3-isobutyl-methylxanthine might function through a p53-dependent mechanism.

Ewing's sarcoma of the mobile spine.

STUDY DESIGN: A retrospective analysis was performed. OBJECTIVES: To determine the oncological outcome of patients with nonmetastatic Ewing's sarcoma of the mobile spine treated with systemic multiagent chemotherapy combined with radiation therapy for definitive local control. SUMMARY OF BACKGROUND DATA: To our knowledge, there are no studies that evaluate the oncological outcome of patients with nonmetastatic Ewing's sarcoma of the mobile spine treated with systemic chemotherapy and radiation therapy for definitive local control. METHODS: Thirteen patients with nonmetastatic Ewing's sarcoma of the mobile spine were treated with high-dose multiagent chemotherapy combined with radiation therapy for definitive local control from 1971 to 2000 at a single institution. Patients were observed for a minimum of 2 years or until death. Neurological function, local recurrence, distant relapse, and treatment-related complications were evaluated. RESULTS: There were 8 females and 5 males with a mean age of 19 years (ranging from 7-26 years). The mean follow-up time was 65 months (median 28 months; ranging from 2 to 218 months). All patients presented with pain. Motor deficits were present in 6 patients. Ten patients had a decompressive laminectomy. Improved pain control, as determined by narcotic use, was noted in 12 (92%) patients. Ten patients maintained or improved motor function by at least 1 Frankel grade, while 3 had deterioration of motor function. The disease-free survival rate was 49% and 36% at 5 and 10 years. Five (38%) patients were free of disease at last follow-up. Seven patients developed metastatic disease. Three (23%) patients developed a local recurrence. One of these patients had paraplegia associated with the local recurrence. Five patients developed 8 treatment-related complications. Four of the 10 (40%) patients that had a laminectomy developed progressive kyphosis. Two of these patients also developed late-onset cauda equina syndrome along with the deformity. One of these patients also developed cardiomyopathy associated with adriamycin cardiotoxicity. One patient developed a nonhealing pressure ulcerover a prominent spinous process. CONCLUSIONS: The current study provides historical data on a relatively homogeneous group of patients withEwing's sarcoma of the mobile spine treated with multiagent chemotherapy combined with radiation therapy for definitive local control. Systemic chemotherapy combined with current spinal resection and reconstruction techniques may lead to improved oncological and clinical outcomes.

Training-as-treatment: effectiveness of the Certified Compassion Fatigue Specialist Training.

Mental health and other service professionals who work with trauma survivors often experience the debilitating effects of compassion fatigue and caregiver stress. Leaders within the field have called for effective, empirically supported interventions for professionals who experience these negative effects. In response to the call, this study examines the treatment effectiveness of the Certified Compassion Fatigue Specialist Training (CCFST) for 83 participating mental health professionals. Results show a statistically and clinically significant decrease in participants' compassion fatigue and burnout symptoms and increase in their compassion satisfaction. A "training-as-treatment" effect of CCFST is introduced, described, and evaluated. Discussion of these findings, clinical implications, limitations, and future directions are provided. CCFST appears to be an effective intervention for ameliorating compassion fatigue symptoms in mental health professionals.

Supplemental vitamin D3 concentration and biological type of steers. II. Tenderness, quality, and residues of beef.

Vitamin D3 was orally supplemented to determine the supplemental dose that improved beef tenderness in different cattle breed types. Feedlot steers (n = 142) were arranged in a 4 x 3 factorial arrangement consisting of four levels of supplemental vitamin D3 (0, 0.5, 1, and 5 million IU/steer daily) administered for eight consecutive days antemortem using three biological types (Bos indicus, Bos Taurus-Continental, and Bos Taurus-English). Warner-Bratzler shear force (WBSF) was measured at 3, 7, 10, 14, and 21 d postmortem, and trained sensory analysis was conducted at 7 d postmortem on LM, semimembranosus, gluteus medius, and supraspinatus steaks. Concentrations of vitamin D3 and the metabolites 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 were determined in the LM, liver, kidney, and plasma. Biological type of cattle did not interact (P > 0.10) with vitamin D3 supplementation for sensory or tenderness traits, suggesting that feeding vitamin D3 for 8 d before slaughter affected the different biological types of cattle similarly. Supplementing steers with 0.5, 1, or 5 million IU/(steer(d) decreased (P < 0.05) LM WBSF at 7, 10, 14, and 21 d postmortem compared with controls, and vitamin D3 treatments of 0.5, 1, and 5 million IU decreased (P < 0.05) semimembranosus WBSF at 3, 7, and 14 d postmortem. In general, vitamin D3-induced improvements in WBSF were most consistent and intense in LM steaks. Sensory panel tenderness was improved (P < 0.05) by all vitamin D3 treatments in LM steaks. Sensory traits ofjuiciness, flavor, connective tissue, and off-flavor were not (P > 0.05) affected by vitamin D3 treatments. All vitamin D3 treatments decreased micro-calpain activity and increased muscle Ca concentrations (P < 0.05). Vitamin D3 concentrations were increased (P < 0.05) by supplementation in all tissues tested (liver, kidney, LM, and plasma); however, cooking steaks to 71 degrees C decreased (P < 0.05) treatment residue effects. The vitamin D metabolite 1,25-dihydroxyvitamin D3 was increased (P < 0.05) only in plasma samples as a result of the vitamin D3 treatments. These results indicate that supplementation with vitamin D3 at 0.5 million IU/steer daily for eight consecutive days before slaughter improved tenderness in steaks from different subprimal cuts by affecting muscle Ca concentrations, micro-calpain activities, and muscle proteolysis, with only a small effect on tissue residues of vitamin D3.

Utilization of beef from different cattle phenotypes to produce a guaranteed tender beef product.

Cattle (n = 303) were visually selected from four feed yards to represent six phenotypes (English [EN; n = 50], 3/4 English-1/4 Brahman [ENB; n = 52], 1/2 English-1/2 Exotic [ENEX; n = 56], 1/2 English-1/4 Exotic-1/4 Brahman [ENEXB; n = 47], 3/4 Exotic-1/4 Brahman [EXB; n = 49], and 1/2 Exotic-1/4 English-1/4 Brahman [EXENB; n = 49]). Carcasses were processed at a commercial beef packing facility, and strip loins were collected after 48-h chilling. Strip loins were aged for 14 d at 2 degrees C and frozen at -20 degrees C for 3 to 5 d before three 2.5-cm-thick steaks were cut for Warner-Bratzler shear force (WBSF) determinations and sensory evaluations. Phenotype EN had the highest (P < 0.05) adjusted fat thickness, and EXB had adjusted fat thickness that was lower (P < 0.05) than all other phenotypes except EXENB. Carcasses of EN and ENB had smaller (P < 0.05) longissimus muscle areas than phenotypes ENEX, EXB, and EXENB. Phenotype EN produced carcasses with the highest (P < 0.05) numerical yield grade, whereas carcasses originating from phenotype EXB had lower (P < 0.05) numerical yield grades than all other phenotypes except ENEX. No differences (P > 0.05) were found among phenotypes for mean WBSF values or sensory panel ratings for initial and sustained tenderness, initial and sustained juiciness, beef flavor characteristics, and overall mouthfeel. More than 90% of steaks from carcasses of all phenotypes had WBSF values less than 3.6 kg when cooked to an internal cooked temperature of 70 degrees C. Results from this study indicated that all phenotypes represented in this study could be managed to produce tender beef.

Environmental effects on pig performance, meat quality, and muscle characteristics.

The objective of this experiment was to determine the effect of diverse production systems on pig performance, muscle characteristics, and their relation to pork quality measures. Birth and rearing conditions were evaluated using 48 barrows during the fall/winter months. Pigs were farrowed in either indoor crates or outdoor huts. At weaning, indoor- and outdoor-born pigs were allotted randomly to treatments arranged in a 2 x 2 factorial design with two birth (indoor vs. outdoor) and rearing (indoor vs. outdoor) environments. Pigs housed indoors were on concrete-slatted flooring (1.2 m2/pig), and pigs housed outdoors were on an alfalfa pasture (212 m2/pig). Body weight data were collected. Muscle samples were removed within 1 h postmortem from the longissimus (LM) and semimembranosus (SM) muscles. Muscle samples were stained histochemically to identify type I, IIA, and IIB/X muscle fibers. Boneless loins were collected from the left side of each carcass and aged for 14 d. Objective and subjective color measurements were taken on the longissimus muscle at the 10th rib on d 14 postmortem. Loin chops were evaluated for sensory attributes, shear force, and retail display features. Pigs born outdoors were heavier and had a greater ADG at most growth intervals postweaning (d 28, 56, and 112; P < 0.05) than pigs born indoors. Pigs reared outdoors were heavier (P = 0.02) at d 140 (120.1 vs. 112.9 +/- 4.9 kg), and had higher (P = 0.01) ADG (2.2 vs. 1.9 kg/d) and gain:feed ratios (0.41 vs. 0.37) than did pigs reared indoors. Birth x rearing environment interactions were not significant (P > 0.10) for most measures. Carcass and meat quality measures did not differ (P > 0.05) among treatment groups, but loin chops from outdoor born or reared pigs had higher (P < 0.05) a* values than chops from pigs born or reared indoors. The LM muscle of pigs born outdoors had a higher (P < 0.01) percentage of type I, and a lower (P < 0.05) percentage of type IIA fibers than did pigs born indoors. Pigs reared outdoors had a higher (P < 0.01) percentage of IIA fibers and a lower (P < 0.05) percentage of IIB/X fibers than did pigs reared indoors for the LM and SM muscles. Outdoor production systems may influence growth, pork color, and muscle fiber types.

Impact of spontaneous exercise on performance, meat quality, and muscle fiber characteristics of growing/finishing pigs.

The objective of this experiment was to determine if increased space and exercise for finisher pigs (0.90 vs 9.45 m2/pig) affects performance, meat quality, or muscle fiber characteristics. Newsham barrows (n = 32, 4 pens/treatment) were placed in one of two space allocations: control space allowance (CONT) or in a long pen with increased space allowance (10x). Pigs were weighed every 28 d and feed intake/pen was calculated. Pigs were filmed for behavioral analysis on d 70 and 100 using video recorders to determine walking distances over a 24-h period. After a 5-h transport and 2-h rest period, pigs (approximately 115 kg) were slaughtered on the same day at a commercial facility. Muscle samples were obtained from the longissimus lumborum (LL) and semimembranosus (SM) muscles within 1 h postmortem for muscle fiber typing. Backfat thickness and pH decline were measured on the left side of each carcass. After 24-h chilling, a boneless loin was collected from each pig and stored at 2 degrees C until analyzed. On d 14 postmortem, loins were cut at the 10th rib for color evaluations, and chops were cut for Warner-Bratzler shear (WBS) force and sensory analysis. Histochemical staining methods were used for the detection of type I, IIA, and IIB/X muscle fiber types. There were no significant differences (P > 0.10) in live weight, ADG, ADFI, or G:F ratio of the two experimental groups evaluated. Pigs finished in 10x pens walked a greater (P < 0.01) distance over a 24-h period than pigs finished in the CONT pens. Pigs finished in the lOx pens were fatter (P < 0.05) at the last lumbar vertebra than pigs finished in the CONT pens, but no significant differences were found in loineye area, loin color, marbling scores, WBS, sensory panel scores, retail display measures, or muscle fiber type percentages. Expanded space allowance to increase exercise resulted in no improvements in pig performance, pork loin measures, or muscle characteristics.

Diverse birth and rearing environment effects on pig growth and meat quality.

Birth and rearing conditions were evaluated for their effects on pig growth, body composition, and pork quality using 48 barrows during the spring and summer months. Pigs were either farrowed in indoor crates or outdoor huts. At weaning, indoor-born and outdoor-born pigs were randomly allotted to indoor or outdoor treatments for growing/finishing. Body weight data were collected. Pigs were transported 5 h to a commercial processing plant, allowed 2 h of rest, and then processed as a group under commercial conditions. Boneless loins were collected from the left side of each carcass and aged for 14 d. Objective and subjective color measurements were taken on the longissimus muscle at the 10th rib on d 14 postmortem. Loin chops were evaluated for sensory attributes, shear force, and retail display features. Pigs born outdoors were heavier and had greater ADG at all growth intervals after weaning (d 28, 56, 112, and final weight, P < 0. 05) than pigs born indoors. Outdoor-born pigs had heavier carcass weights (91.2 vs 81.3+/-3.4 kg, P < 0.001), larger loineye areas (54.6 vs 49.7+/-0.2 cm , P < 0.05), and higher pork flavor intensity scores (6.5 vs 6.1+/-0.10, P < 0.01) than indoor-born pigs. Birth x rearing environment interactions were not significant for most measures. Backfat measurements at the last rib were greater (3.2 vs 2.8+/-0.05 cm, P < 0.05) for the pigs reared outdoors than for the pigs reared indoors. Pigs finished outdoors had more reddish pink color scores, lower shear force values, and lower L* values, indicating darker-colored pork, compared with pigs finished indoors (P < 0.05). Pig birth environment played a significant role in improving growth rates of outdoor-born pigs and increasing pork flavor intensity scores of loin chops from pigs born outdoors. Finishing pigs outdoors may improve pork color and tenderness but also may increase backfat thickness when they are fed conventional diets.

Alternative housing systems for pigs: influences on growth, composition, and pork quality.

Effects of pig birth (first 3-wk period) and rearing environments on growth and muscle quality characteristics of loins were evaluated in three experiments over seasons in west Texas and central Missouri. Housing systems included indoor slatted-floor buildings, indoor deep-bedded buildings, outdoor housing on dirt, and outdoor housing on alfalfa pasture. Experiments were conducted during the growing/finishing phases and pigs were slaughtered at the same age. Loins were collected, vacuum-packaged, and stored for 14 d at 2 degrees C. Pigs born and finished in an outdoor environment during the summer months (Exp. 1) had a greater ADG (0.92 vs 0.82+/-0.06 kg/d, P < 0.05) and had heavier carcass weights (87.9 vs 78.4+/-2.4 kg, P < 0.05) than pigs born and finished in an indoor environment with a slatted-floor finishing building. Carcasses from the outdoor-reared group measured a larger (P < 0.05) loineye area and were fatter (P < 0.01) at the first rib, last rib, and last lumbar vertebra measurements than carcasses from the indoor-reared group. Loin chops from outdoor-reared pigs had darker color scores in the retail display case throughout the 4-d period, measured lower L* values on d 1, and had more discoloration and browning on d 4 than loin chops from the indoor-reared group. During the winter months (Exp. 2), no difference was detected in ADG, carcass measurements, sensory characteristics, or shear force values from indoor-born pigs placed in either an outdoor or indoor finishing environment. Pigs finished on deep bedding (Exp. 3) had heavier carcass weights and more backfat (P < 0.01) than pigs finished on slats, but no differences were detected in sensory panel or shear force results. Overall, carcass measurements, pH, drip loss, sensory panel, and shear force values were similar among the groups finished in different housing systems. Outdoor or deep-bedded systems may increase growth rates of pigs if suitable land area and resources are available, but pork quality of loins will be similar for pigs finished in either conventional or alternative systems.

Deletional analysis of the murine IL-12 p35 promoter comparing IFN-gamma and lipopolysaccharide stimulation.

IL-12, pivotal to the development of Th1 cells and formed by association of p35 and p40 subunits, is made by macrophages and the macrophage cell line RAW264.7. In this study, the promoter for p35 was cloned and analyzed. The murine IL-12 p35 gene has promoters upstream from each of the first two exons. The exon 1 and exon 2 promoters, cloned into a reporter vector, were responsive to LPS or IFN-gamma/CD40 ligation in transfected RAW264.7 cells. The exon 2 promoter containing bp -809 to +1 has significant homology to the human p35 promoter. Thus, deletion analysis was performed to determine the regions required for responsiveness to LPS, CD40, and/or IFN-gamma. Base pairs -809 to -740 influenced responsiveness to LPS. In contrast, bp -740to -444 and bp -122 to -100 were required for responses to IFN-gamma, IFN-gamma/LPS, or IFN-gamma/CD40 ligation. Removal of bp -444 to -392 increased the response of the exon 2 promoter to each stimulant. IFN regulatory factor (IRF)-1 is involved in the activity of this promoter at bp -108 to -103 because levels of nuclear IRF-1 correlated with exon 2 promoter activity in response to IFN-gamma and IRF-1 overexpression stimulated and enhanced exon 2 promoter activity. Also, site or deletion mutation of the IRF-1 element at bp -108 to -103 reduced the responsiveness of the promoter and IRF-1 bound to an oligonucleotide containing bp -108 to -103. The data suggest that the response of the p35 promoter to IFN-gamma requires a distinct IRF-1 positive regulatory element at bp -108 to -103.

Differential response of the murine IL-12 p35 gene to lipopolysaccharide compared with interferon-gamma and CD40 ligation.

Expression of the heterodimeric cytokine interleukin-(IL-)12 is induced by pattern recognition receptors responding to microbial stimuli such as lipopolysaccharide (LPS) and products of the immune system such as interferon-gamma (IFN-gamma) and CD40L. The formation of bioactive IL-12 requires equimolar synthesis of p35 and p40 subunits. However, p35 expression limits the amount of IL-12 formed. Transcription of the gene for the p35 subunit of IL-12 initiates within the first exon, an alternate first exon (exon 1a), or second exon. Here we show that LPS and IFN-gamma/CD40 ligation increase the amount of total p35 mRNA in splenic adherent cells (SAC) to a similar extent. However, the exon 1 transcript was a smaller fraction of total p35 mRNA in IFN-gamma/CD40-stimulated cells than in unstimulated or LPS-stimulated cells. Despite comparable levels of total p35 mRNA, LPS-induced p35 exon 1 transcripts led to significantly more bioactive IL-12 from SAC than IFN-gamma/CD40-induced exon 1a/exon 2 transcripts as measured by ELISA. The data suggest that LPS-inducible p35 synthesis from exon 1 p35 transcripts leads to greater amount of bioactive IL-12 than IFN-gamma/CD40-induced p35 expression from alternate p35 exon 1a/exon 2 transcripts.

Respiratory failure caused by Chiari I malformation with associated syringomyelia.

The authors report a case of a 38-year-old male with a Chiari I malformation and syringomyelia that presented with acute respiratory distress. Pulmonary function testing was consistent with respiratory muscle weakness. A suboccipital craniectomy and C1, 2, 3 laminectomies were performed on an emergent basis. Postoperatively the patient had significant improvement in his respiratory status associated with a reduction in the size of the syringomyelia on follow-up imaging.

Subarachnoid-pleural fistula treated with noninvasive positive-pressure ventilation. Case report.

The authors describe the case of a 24-year-old man who underwent an L-1 corpectomy for spinal decompression and stabilization following an injury that caused an L-1 burst fracture. Postoperatively, an accumulation of spinal fluid developed in the pleural space, which was refractory to 1 week of thoracostomy tube drainage and lumbar cerebrospinal fluid (CSF) diversion. The authors then initiated a regimen of positive-pressure ventilation in which a bi-level positive airway pressure (PAP) mask was used. After 5 days, the CSF collection in the pleural space resolved. Use of a bi-level PAP mask represents a safe, noninvasive method of reducing the negative intrathoracic pressure that promotes CSF leakage into the pleural cavity and may be a useful adjunct in the treatment of subarachnoid-pleural fistula.

Nerve growth factor activation of nuclear factor kappaB through its p75 receptor is an anti-apoptotic signal in RN22 schwannoma cells.

Recent evidence indicates that nerve growth factor (NGF) produces its effects through signaling contributions from both TrkA and the p75 receptor. In contrast to its trophic actions through TrkA, NGF binding to p75 has been shown to activate programmed cell death through a mechanism involving the stress kinase JNK. However, this receptor also activates nuclear factor kappaB (NF-kappaB), the role of which has yet to be determined. We investigated the function of p75-mediated NF-kappaB stimulation in regulating cell survival in the rat schwannoma cell line RN22, which expresses p75, but not TrkA. Gel shift assays demonstrated activation of NF-kappaB in response to NGF within 30 min and lasting at least 4 h. NGF also stimulated JNK in the cells (detected by in vitro kinase assays) with a similar time course. Preventing activation of NF-kappaB with the specific inhibitor SN50 resulted in NGF-induced cell loss. Similarly, transfection of the cells with a mutant form of the endogenous NF-kappaB inhibitor (IkappaBalphaDeltaN), which cannot be degraded and therefore remains bound to NF-kappaB, preventing its activation, resulted in a significant increase in the number of apoptotic cells following NGF treatment. These results suggest that NGF activation of NF-kappaB through the p75 receptor promotes survival, counterbalancing the pro-apoptotic signal.