Quality of life after involuntary psychiatric admission.

Studies seeking predictors of outcomes after involuntary admission, including quality of life (QoL), are limited and results inconsistent. We aimed to describe QoL 3 months after involuntary psychiatric admission and to investigate associated factors. One hundred and fifty-three involuntarily admitted inpatients were assessed for a range of sociodemographic and clinical variables. Structured scales included the Brief Psychiatric Rating Scale (BPRS), the MacArthur Admission Experience Survey, the Heinrichs Quality of Life Scale and the World Health Organisation Quality of Life Brief Assessment (WHOQOL-BREF, n = 124). The mean total score on the Heinrichs QoL scale at 3 months was 69.3 (SD = 24.1). Predictors of higher 3 month QoL after involuntary admission in a multiple regression model (adjusted R2 = 0.37, F = 7.1 (14, 138), p ≤0.001) were less severe negative symptoms on the BPRS at baseline (B = -4.56, p < 0.001), improvement in negative symptom scores between baseline and follow up (B = 4.58, p < 0.001) and higher current social class (B = -14.31, p = 0.001). Events during involuntary admission, such as being subject to coercive experiences, were not significantly associated with QoL after admission. The results suggest that a core determinant of service users' QoL after involuntary admission is negative symptom severity and change over time.

An open-source musculoskeletal model of the lumbar spine and lower limbs: a validation for movements of the lumbar spine.

Musculoskeletal models of the lumbar spine have been developed with varying levels of detail for a wide range of clinical applications. Providing consistency is ensured throughout the modelling approach, these models can be combined with other computational models and be used in predictive modelling studies to investigate bone health deterioration and the associated fracture risk. To provide precise physiological loading conditions for such predictive modelling studies, a new full-body musculoskeletal model including a detailed and consistent representation of the lower limbs and the lumbar spine was developed. The model was assessed against in vivo measurements from the literature for a range of spine movements representative of daily living activities. Comparison between model estimations and electromyography recordings was also made for a range of lifting tasks. This new musculoskeletal model will provide a comprehensive physiological mechanical environment for future predictive finite element modelling studies on bone structural adaptation. It is freely available on https://simtk.org/projects/llsm/.

Effects of the antifouling compound, Irgarol 1051, on a simulated estuarine salt marsh ecosystem.

Toxicity effects of the antifouling compound, Irgarol 1051, were examined using a simulated estuarine salt marsh ecosystem. The 35 day mesocosm exposure incorporated tidal flux and contained seawater, sediments, marsh grass, and estuarine biota. Irgarol (10.0 microg/l) caused a significant reduction in phytoplankton biomass and primary productivity. HPLC pigment analysis indicated significant effects of irgarol on both phytoplankton and periphyton community composition, with decreased concentrations of pigments representative of diatom species. There was also a significant decrease in dissolved oxygen levels in the 10.0 microg/l irgarol treatment. Growth of the hard shell clam was significantly reduced in the 1.0 and 10.0 microg/l irgarol treatments. The effects observed occurred at irgarol concentrations greater than those typically measured in the environment. Prolonged exposure, the accumulation of irgarol in sediments, plant, or animal tissues, and the interaction of irgarol with other chemicals in the environment; however, could increase risk.

Variable temperature magnetic circular dichroism studies of reduced nitrogenase iron proteins and [4Fe-4S]+ synthetic analog clusters.

Variable temperature magnetic circular dichroism (VTMCD) and EPR spectroscopies have been used to investigate the ground and excited-state properties of [4Fe-4S]+ clusters in Mo- and V-nitrogenase Fe-proteins from Azotobacter vinelandii and two synthetic analog clusters, [Fe4S4(SEt)4]3- and [Fe4S4(SC6H11)4]3-. The results indicate similar [4Fe-4S]+ clusters with analogous S = 1/2 and S = 3/2 ground states in both Fe-proteins. However, the Fe-proteins do differ in terms of the medium effects on the S = 1/2 and S = 3/2 spin mixtures in frozen solution. By utilizing medium effects in both Fe-proteins, the VTMCD characteristics of both the S = 1/2 and S = 3/2 forms of the [4Fe-4S]+ have been determined. Together with the VTMCD studies of [Fe4S4(SEt)4]3- and [Fe4S4(SC6H11)4]3-, which are shown to be predominantly S = 1/2 and 3/2, respectively, in frozen DMF/toluene solutions, the results demonstrate that the form of the VTMCD spectra provides a means of identifying and distinguishing S = 1/2 and S = 3/2 [4Fe-4S]+ clusters. Ground state zero-field splitting parameters for the S = 3/2 clusters are determined for both Fe-proteins. In addition to spin state heterogeneity, samples of the Mo-nitrogenase Fe-protein in the presence of 50% (v/v) ethylene glycol were found to exhibit heterogeneity in the S = 1/2 resonance. A rapidly relaxing axial resonance, g perpendicular = 1.94 and g parallel = 1.82, was observed in addition to the characteristic rhombic resonance, g = 2.05, 1.94 and 1.87. The origin of the heterogeneity exhibited by [4Fe-4S]+ clusters in frozen solution is discussed in light of these results.

Spectroscopic characterization of flavocytochrome c-552 from the photosynthetic purple sulfur bacterium Chromatium vinosum.

The identities of the axial ligands to the two hemes of the flavocytochrome c-552 isolated from the photosynthetic purple sulfur bacterium Chromatium vinosum have been investigated by visible/near-infrared absorption and magnetic circular dichroism (MCD) spectroscopies, with parallel electron paramagnetic resonance (EPR) studies. One of the hemes has histidine and methionine as axial ligands and has a local environment that is relatively insensitive to the composition of the bulk medium. The second heme, the local environment of which is sensitive to changes in the composition of the bulk medium, exists as a mixture of two forms, only one of which has histidine/methionine axial ligation. On the basis of its EPR characteristics, the other form most likely has histidine/lysine axial ligation. In aqueous solution near neutral pH, more than half of the second heme is present as the histidine/lysine form, while in 50:50 water/ethylene glycol the histidine/methionine form is the dominant one.

Axial heme ligation in the cytochrome bc1 complexes of mitochondrial and photosynthetic membranes. A near-infrared magnetic circular dichroism and electron paramagnetic resonance study.

The combination of EPR and low-temperature near-IR magnetic circular dichroism spectroscopies have been used to investigate the axial ligation of the cytochromes in the cytochrome bc1 complexes from bovine heart mitochondria, Rhodobacter capsulatus, Rhodobacter sphaeroides, and Rhodospirillum rubrum, and the purified cytochromes c1 from bovine heart mitochondria, Rb. capsulatus and Rb. sphaeroides. The possibility of axial ligation of cytochrome c1 by the amino terminus of the polypeptide was also assessed by acetylating the N-terminus of Rb. capsulatus cytochrome c1 and comparing the properties of the acetylated and unmodified samples. The results are consistent with bis-histidine axial ligation for the high- and low-potential b-type cytochromes and histidine/methionine axial ligation for the c1-type cytochrome in the intact cytochrome bc1 complexes. Purified samples of cytochrome c1 are mixtures of two forms, one with histidine/methionine and the other with bis-histidine axial ligation. The form with bis-histidine axial ligation is also assembled in the M183L mutant of the Rb. capsulatus cyt bc1 complex in which the methionine residue coordinating cyt c1 is replaced by a leucine. The bis-histidine form appears to be an artifact of dissociation of cytochrome c1 from the cytochrome bc1 complex and is greatly enhanced particularly in the bacterial cytochromes c1 by sample handling and the addition of 50% (v/v) ethylene glycol or glycerol.

Phase II study of docetaxel in patients with epithelial ovarian carcinoma refractory to platinum.

We analyzed the efficacy and toxicity of docetaxel in patients with ovarian cancer who failed previous chemotherapy with platinum. Fifty-five patients with measurable ovarian cancer were entered in this Phase II study at The University of Texas M. D. Anderson Cancer Center. Treatment consisted of 100 mg/m2 docetaxel given i.v. every 3 weeks. Because of hypersensitivity reactions, premedication with steroids and antihistamine was initiated during the study. Twenty-two (40%) patients responded (there were 3 complete responders and 19 partial responders). Twenty-one (38%) patients had stable disease. The median survival was 10 months. The main toxicity was neutropenia (98% of patients), with 13 episodes of neutropenic fever. Cumulative fluid retention was the main reason for dose modification and required a combination of diuretics and steroids for palliation. Other side effects were alopecia (100%); anemia (87%); dermatitis (67%); gastrointestinal disorders (53%); stomatitis (49%); neurotoxicity (45%); excessive lacrimation (33%); and hypersensitivity reactions (11%), which in one case were life threatening (loss of consciousness, fluid resuscitation). Docetaxel as a single agent proved to be active in heavily pretreated ovarian cancer patients but is associated with significant side effects. Objective toxicity consisted mainly of neutropenia and fluid retention. Neutropenia was dose limiting and required therapy with granulocyte colony-stimulating factor. Fluid retention was improved but not eliminated by diuretics and corticosteroids. Additional studies of docetaxel in ovarian carcinoma are indicated to define the activity in relation to paclitaxel and in platinum combination therapy.

Development of a registration framework to validate MRI with histology for prostate focal therapy.

PURPOSE: Focal therapy has been proposed as an alternative method to whole-gland treatment for prostate cancer when aiming to reduce treatment side effects. The authors recently validated a radiobiological model which takes into account tumor location and tumor characteristics including tumor cell density, Gleason score, and hypoxia in order to plan optimal dose distributions for focal therapy. The authors propose that this model can be informed using multiparametric MRI (mpMRI) and in this study present a registration framework developed to map prostate mpMRI and histology data, where histology will provide the "ground truth" data regarding tumor location and biology. The authors aim to apply this framework to a growing database to develop a prostate biological atlas which will enable MRI based planning for prostate focal therapy treatment. METHODS: Six patients scheduled for routine radical prostatectomy were used in this proof-of-concept study. Each patient underwent mpMRI scanning prior to surgery, after which the excised prostate specimen was formalin fixed and mounted in agarose gel in a custom designed sectioning box. T2-weighted MRI of the specimen in the sectioning box was acquired, after which 5 mm sections of the prostate were cut and histology sections were microtomed. A number of image processing and registration steps were used to register histology images with ex vivo MRI and deformable image registration (DIR) was applied to 3D T2w images to align the in vivo and ex vivo MRI data. Dice coefficient metrics and corresponding feature points from two independent annotators were selected in order to assess the DIR accuracy. RESULTS: Images from all six patients were registered, providing histology and in vivo MRI in the ex vivo MRI frame of reference for each patient. Results demonstrated that their DIR methodology to register in vivo and ex vivo 3D T2w MRI improved accuracy in comparison with an initial manual alignment for prostates containing features which were readily visible on MRI. The average estimated uncertainty between in vivo MRI and histology was 3.3 mm, which included an average error of 3.1 mm between in vivo and ex vivo MRI after applying DIR. The mean dice coefficient for the prostate contour between in vivo and ex vivo MRI increased from 0.83 before DIR to 0.93 after DIR. CONCLUSIONS: The authors have developed a registration framework for mapping in vivo MRI data of the prostate with histology by implementing a number of processing steps and ex vivo MRI of the prostate specimen. Validation of DIR was challenging, particularly in prostates with few or mostly linear rather than spherical shaped features. Refinement of their MR imaging protocols to improve the data quality is currently underway which may improve registration accuracy. Additional mpMRI sequences will be registered within this framework to quantify prostate tumor location and biology.

Purification and characterization of Klebsiella aerogenes UreE protein: a nickel-binding protein that functions in urease metallocenter assembly.

The Klebsiella aerogenes ureE gene product was previously shown to facilitate assembly of the urease metallocenter (Lee, M.H., et al., 1992, J. Bacteriol. 174, 4324-4330). UreE protein has now been purified and characterized. Although it behaves as a soluble protein, UreE is predicted to possess an amphipathic beta-strand and exhibits unusually tight binding to phenyl-Sepharose resin. Immunogold electron microscopic studies confirm that UreE is a cytoplasmic protein. Each dimeric UreE molecule (M(r) = 35,000) binds 6.05 + 0.25 nickel ions (Kd of 9.6 +/- 1.3 microM) with high specificity according to equilibrium dialysis measurements. The nickel site in UreE was probed by X-ray absorption and variable-temperature magnetic circular dichroism spectroscopies. The data are most consistent with the presence of Ni(II) in pseudo-octahedral geometry with 3-5 histidyl imidazole ligands. The remaining ligands are nitrogen or oxygen donors. UreE apoprotein has been crystallized and analyzed by X-ray diffraction methods. Addition of nickel ion to apoprotein crystals leads to the development of fractures, consistent with a conformational change upon binding nickel ion. We hypothesize that UreE binds intracellular nickel ion and functions as a nickel donor during metallocenter assembly into the urease apoprotein.

Evidence for sensitisation of DNA to oxidative damage during isolation.

The oxidative base lesion 8-oxo-deoxyguanosine (8-oxo-dG) has been identified in DNA isolated from normal tissue and may occur at elevated levels during disease. However, the use of phenol during DNA extraction may artificially elevate the detected levels of this lesion. Herein, we have performed a comparative methodological study using both pronase E and phenol extraction techniques; native or oxidatively stressed DNA was isolated to determine the validity of each extraction technique for the subsequent determination of 8-oxo-dG. Whilst the yields of DNA were comparable, after pronase E extraction there was no detectable induction of 8-oxo-dG in reextracted naked DNA or peripheral blood mononuclear cell DNA that had been oxidatively stressed. However, phenol extraction enhanced the basal levels of 8-oxo-dG detected, and also induced a significant increase in levels of the modified base after exposure to oxidative stress. The latter was dependent on the presence of foetal calf serum in the extracellular medium. We have confirmed that phenol extraction sensitises native DNA to subsequent oxidative damage. In addition, this work shows that the extent of sensitisation occurring during phenol extraction varies with the degree of oxidative damage already incurred and infers that labile guanine sites generated during oxidative stress may be detected as 8-oxo-dG residues after phenol extraction.

Spectroscopic identification of the heme axial ligation of cytochrome b558 in the NADPH oxidase of porcine neutrophils.

The combination of electron paramagnetic resonance (EPR), near-infrared magnetic circular dichroism (NIR-MCD) and resonance Raman (RR) spectroscopies at cryogenic temperatures has been used to identify the axial heme ligation of the low spin cytochrome b558 component of NADPH oxidase from porcine blood neutrophils. The EPR and NIR-MCD results indicate the presence of two distinct forms in frozen solution; one with a low field g-value at 3.23 and porphyrin(pi)-to-Fe(III) charge transfer maximum at 1660 nm and the other a low field g-value at 3.00 and porphyrin(pi)-to-Fe(III) charge transfer maximum at 1510 nm. On the basis of these properties and the RR studies, both are attributed to forms of cytochrome b558 with bis-histidine axial ligation. The origin of the observed heterogeneity, the location and identity of the specific histidines involved in ligating the heme, and the role of the heme prosthetic group in O2- production are discussed in light of these results.

A novel HPLC procedure for the analysis of 8-oxoguanine in DNA.

The chromatographic quantitation of 8-oxoguanine adducts in DNA is widespread in the literature, although results obtained by HPLC of 8-oxodeoxyguanosine do not always agree with levels determined by GC-MS. To help explain this discrepancy, here we describe a novel procedure for the analysis of 8-oxoguanine adducts in DNA. Although it proved difficult to directly quantitate 8-oxoguanine in the presence of high levels of endogenous guanine using conventional reversed-phase HPLC, a simple preincubation of DNA acid hydrolysates with guanase allowed such analyses. The assay relied on our observation that 8-oxoguanine was not a substrate for guanase, and on sensitive electrochemical detection. The limit of detection for 8-oxoguanine was 5 nM or 250 fmol on column. Using this procedure, the background level of 8-oxoguanine in commercially available calf thymus DNA was 0.4 nmol/mg DNA or 3.2 mol/10(5) mol guanine.

The effect of chronic hypertension on skin blood flow.

OBJECTIVE: To determine whether the cutaneous microvasculature of the spontaneously hypertensive rat (SHR) is affected by chronic hypertension. DESIGN: We used laser Doppler techniques to measure skin blood flow in 22 SHR and in 22 non-hypertensive Wistar-Kyoto (WKY) rats over a 1-year time span, beginning at age 3 months. Sites of measurement included the back, leg, and root of the tail, areas with a predominantly nutritive perfusion, and the plantar surface of the paw, which has a large contribution from large arterioles and venules. Flow was measured at basal skin temperature and at the maximally heat-stimulated condition of 44 degrees C. Systolic tail arterial blood pressures were measured concurrently. RESULTS: At baseline, systolic blood pressures were considerably higher in the SHR (190 +/- 4 mmHg) than they were in the WKY rats (138 +/- 2 mmHg). Skin blood flow values at the three nutritive sites were similar in the two species. However, at 44 degrees C, flow was significantly higher at the paw in the SHR (46.8 +/- 3.5 versus 34.3 +/- 2.2 ml/min per 100 g). We attribute this difference to the effect of high perfusion pressure on large arterioles. During the 1-year measurement period, there was no appreciable change in blood flow in the WKY rats. In contrast, the SHR showed a steady progressive decline in skin blood flow at all sites. The largest decline was at the paw with a rate of fall of about 2.4%/month. After 1 year, there was no difference between paw blood flow in the SHR (27.5 +/- 1.8 ml/min per 100 g) and in the WKY rats (27.6 +/- 1.9 ml/min per 100 g). CONCLUSIONS: Skin blood flow reserve falls in response to chronic hypertension. The rate of fall is greater at sites with significant arteriovenous perfusion that at nutritive sites.

Variable expression of the interleukin-2 receptor alpha chain and MYC genes in lymphocytes from renal cell carcinoma patients treated with interleukin-2.

We have studied the expression of the interleukin-2 receptor alpha chain, c-MYC and L-MYC genes in lymphocytes obtained from four renal cell carcinoma patients undergoing an interleukin-2 clinical trial. Two of these patients exhibited stable disease after the interleukin-2 therapy and two exhibited progressive disease. Analysis of mRNA levels by dot blot hybridization indicated that changes in the expression of both the interleukin-2 receptor alpha chain and c-MYC genes were erratic and varied widely between patients. L-MYC expression was not observed in any sample. There appeared to be little correlation between the changes in gene expression and parameters such as thymidine incorporation, the proportion of CD25 positive cells present or cytotoxic activity. The situation in vivo therefore appears to be more complex than would be predicted from in vitro studies.

Elevated levels of MDM-2 and p53 expression are associated with high grade non-Hodgkin's lymphomas.

The role of p53 in the evolution of non-Hodgkin's lymphomas (NHL) is unclear. Mutations of the p53 gene appear to be relatively uncommon but stabilized p53 protein, as detected by immunohistochemistry, has indicated a more frequent involvement of p53. As dysfunction of p53 protein has also been suggested to occur after overexpression of the mdm-2 protein, we have therefore investigated a series of non-malignant hyperplastic reactive lymphoid tissues and NHL to examine whether the levels of expression of MDM-2 correlated to positivity of p53 protein staining. Northern blot analysis of MDM-2 expression was compared to glucose-6-phosphate dehydrogenase (G6PD) expression by densitometry to quantify the relative levels of MDM-2 expression. Consistent low levels of MDM-2 expression were observed in non-malignant lymphoid tissue and in low grade NHL, however, 13/15 high grade NHL exhibited a 2-15-fold increase in MDM-2 expression. Interestingly similar elevations in p53 mRNA expression were also observed in 6/15 high grade NHL. Positive staining of the p53 protein did not, however, correlate with elevated mRNA levels of either MDM-2 or p53. The significance of these observations is discussed.

The active form of the ferric heme in neutrophil cytochrome b(558) is low-spin in the reconstituted cell-free system in the presence of amphophil.

The spin state of the heme in superoxide (O(2)(.)(-))-producing cytochrome b(558) purified from pig neutrophils was examined by means of room-temperature magnetic circular dichroism (MCD) under physiological conditions. Cytochrome b(558) with varying amounts of low-spin and high-spin heme was prepared by either pH adjustment or heat treatment, and the O(2)(.)(-)-forming activity in a cell-free system was found to correlate with the low-spin heme content. The possibility that the O(2)(.)(-)-forming activity results from a transient high-spin ferric heme form that is induced during activation by anionic amphophils has also been investigated. EPR spectra of cytochrome b(558) activated by either arachidonic acid or myristic acid, showed that a transient high-spin ferric species accounting for approximately 50% of the heme appeared in the presence of arachidonic acid, but not in the presence of myristic acid. Hence the appearance of a transient high-spin ferric heme species on activation with an amphophil does not afford a common activation mechanism in the NADPH oxidase system. The EPR results for cytochrome b(558) activated with arachidonic acid showed that the transient high-spin ferric heme can bind cyanide. However, the high-spin ferric heme does not contribute to the O(2)(.)(-) production of cytochrome b(558) in cell-free assays in the presence of cyanide.

Abdominal aortic aneurysms infected by Escherichia coli.

Three cases of atherosclerotic abdominal aneurysms infected by Escherichia coli urinary tract sepsis are presented together with a review of four additional cases of E. coli-infected aneurysms. Pathophysiology and a current system of classification of aortic infection are discussed. Important clinical features of gram-negative aortic infection include a diagnostic triad and the tendency to early rupture. Resection of infected tissue and extra-anatomic bypass for revascularization are the cornerstones of operative management. The mortality rate of E. coli aortic infection is high, with one known survivor. Death is contributed to by the high frequency of preoperative rupture, the age of the patient, and the extent of atherosclerotic disease.

Investigation of the expression of housekeeping genes in non-Hodgkin's lymphoma.

Studies of quantitative changes in gene expression in malignant cells have often used housekeeping genes as controls against which the level of expression of a gene under study could be compared. We have now examined whether the expression of the most commonly used of these housekeeping genes can be regarded as reliable controls for gene expression studies in non-Hodgkin's lymphoma (NHL). We have used Northern blot analysis to compare the levels of expression of beta-actin, alpha-tubulin, beta 2-microglobulin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) to that of ribosomal RNA. These studies demonstrated that whereas there was a reasonable correlation between the relative levels of rRNA and housekeeping gene expression in reactive hyperplastic nodes, there were major differences in the relative levels of expression of the housekeeping genes in both low and high grade lymphomas; only GAPDH showed any degree of consistency. These observations indicated that housekeeping gene expression was not a reliable control for estimating changes in the level of expression of other genes in NHL, and instead suggested that 18S or 28S rRNA expression offered a more accurate method of RNA quantitation.

MDR-1 expression in non-Hodgkin's lymphomas is unrelated to treatment intensity or response to therapy.

Over-expression of the MDR-1 gene, which codes for P-glycoprotein, is thought to be an important mechanism in the drug resistance exhibited by many tumours. A number of chemotherapeutic agents which induce MDR-1 expression are also components of combination chemotherapies that are used in the treatment of high grade non-Hodgkin's lymphomas (NHL). We have therefore examined expression of MDR-1 in a series of NHL by Northern blot analysis as well as investigated the localization of P-glycoprotein by immunohistochemistry. The series included 11 hyperplastic reactive nodes and tonsils, 17 low grade NHL and 15 high grade NHL. The levels of MDR-1 mRNA were quantified by scanning densitometry and comparison with levels of glucose-6-phosphate dehydrogenase (G6PD). The MDR-1 mRNA was observed in both non-malignant and NHL tissues. Immunohistochemical staining revealed that expression of MDR-1 mRNA in reactive nodes was related to the presence of P-glycoprotein in lymphocytes, however, P-glycoprotein was apparent in both the reactive lymphocytes and tumour cells in the NHL samples. Elevated mRNA levels (2-3 fold increase) were observed in some low grade and high grade NHL relative to those observed in reactive lymphoid tissue. There appeared to be little correlation, however, between expression of the MDR-1 gene and either treatment intensity or response to therapy. The drug resistance that is often encountered in NHL patients is therefore likely to involve mechanisms other than over-expression of P-glycoprotein.

Activation of MYCN in a case of non-Hodgkin's lymphoma.

We have examined a series of non-Hodgkin's lymphomas (NHL) for evidence of expression of the MYC gene family. Northern blot analysis of RNA samples derived from 11 non-malignant reactive lymphoid tissues and 33 NHL was used to investigate expression of MYC, MYCL and MYCN. As expected MYC expression was detected in all samples. The levels of MYC expression were quantified by densitometry and appeared to be 3-8 fold higher in high grade NHL than in the low grade NHL or non-malignant lymphoid tissue. No expression of MYCL was detected in any sample. Expression of MYCN was however observed in one sample, which had been diagnosed as a T-cell high grade NHL. A detailed cytogenetic analysis of this sample proved difficult to obtain but, by using fluorescence in-situ hybridization (FISH), we were able to demonstrate that on one of the chromosomes 2 the MYCN gene was localised to a translocation breakpoint region. It therefore appears that in NHL it is possible for MYCN, like MYC in Burkitt lymphoma, to be activated as a result of a chromosome translocation event.