ABSTRACT
OBJECTIVE: Epidemiological studies on inflammatory myopathies (IMs) show widely variable results, and studies on Asians are lacking. Despite emerging interest in the cardiovascular disease (CVD) risk associated with IMs, the prevalence of CVD in IM patients and its impact on mortality remain unclear. We conducted a nationwide, population-based study on the incidence, mortality, and associated major CVD events of IMs in the Republic of Korea over 11 years. METHOD: Using the nationwide, population-based National Health Insurance claims database and the Rare Intractable Disease registration programme, we estimated incidence, mortality, and CVD occurrence. Survival was examined using the Kaplan-Meier method. Mortality rate in IMs with CVD was analysed by Cox proportional hazards regression. RESULTS: There were 3014 incident cases, 640 of whom died during the study period. The mean annual incidence was 7.16/106. Dermatomyositis (DM) and polymyositis (PM) had 5 year survival rates of 76.8% and 79.3%, respectively. Cardiovascular events occurred in 155 patients and 40.6% of IM patients with CVD died. Acute myocardial infarction in men had the highest risk of any CVD event in both DM [standardized incidence ratio (SIR) 4.2, 95% confidence interval (95% CI) 2.4-7.2] and PM (SIR 3.5, 95% CI 1.8-7.0). Haemorrhagic stroke had the highest hazard ratio (HR) in both DM (HR 2.31, 95% CI 1.13-4.70) and PM patients (HR 2.10, 95% CI 1.03-4.27) compared with the general population with CVD. CONCLUSION: We found persistently low incidence, poor survival, and high major CVD incidence in IMs, and increased mortality in IMs with CVD.
Subject(s)
Cardiovascular Diseases/mortality , Myositis/complications , Registries , Adult , Aged , Aged, 80 and over , Cardiovascular Diseases/etiology , Female , Humans , Incidence , Male , Middle Aged , Republic of Korea/epidemiology , Young AdultABSTRACT
INTRODUCTION: True non-traumatic radial artery aneurysms (RAAs) are extremely rare, and few cases have been described. The majority of RAAs are post-traumatic or iatrogenic pseudo-aneurysms following arterial cannulation. However, RAAs due to other causes have also been described. Here a rare case of true idiopathic distal RAA, which was managed by surgical resection and repair with interposition vein graft, is described. REPORT: A 62 year old female with a known medical history of hypertension and hyperlipidaemia presented with left wrist swelling of one year duration, associated with a pulsatile lump that was increasing in size. Duplex ultrasound and computed tomography angiography revealed a distal RAA. She underwent open surgical resection and repair with interposition vein graft using the distal left cephalic vein. Histopathology of the specimen revealed an aneurysm with atherosclerosis. She recovered well post-operatively with no complications. DISCUSSION: True idiopathic RAAs are rare. Surgical treatment is almost always recommended in view of the risk of complications. A case of true idiopathic distal RAA is presented here, which was managed successfully by surgical resection and repair with interposition vein graft.
ABSTRACT
BACKGROUND AND PURPOSE: Acute disseminated encephalomyelitis followed by optic neuritis (ADEM-ON) is a rare demyelinating syndrome that is different from multiple sclerosis and neuromyelitis optica spectrum disorder. The aim of this study was to describe the disease course, treatment response and outcome of children with ADEM-ON. METHODS: Children of <18 years of age were identified from six countries of the EU Paediatric Demyelinating Disease Consortium. Patients fulfilled the diagnostic criteria for ADEM followed by at least one ON. Anti-myelin oligodendrocyte glycoprotein (MOG) antibodies were tested in all patients. RESULTS: In this study of 17 patients (nine boys) with ADEM-ON, anti-myelin oligodendrocyte glycoprotein (MOG) antibodies were identified in 16 patients. Age at onset was 6.1 years (interquartile range, 5.1-9.2 years). Twelve patients received oral prednisolone and 10 received maintenance immunosuppression (e.g. azathioprine, intravenous immunoglobulins, Rituximab). During a follow-up of 5.3 years (interquartile range, 1.8-10.2 years), 54 relapses occurred with a median of 3 relapses per patient (range, 1-9 per patient). Patients relapsed on all treatments but no relapses occurred on a prednisolone dose >10 mg/day. Visual and cognitive residual deficits were common in this group. CONCLUSIONS: Acute disseminated encephalomyelitis followed by optic neuritis is an anti-MOG antibody-associated relapsing disorder that can have a heterogeneous disease course. Patients were refractory for maintenance immunosuppression and appeared to be corticosteroid-dependent. Further international collaborations are now required to unify guidelines in this difficult-to-manage group of patients.
Subject(s)
Encephalomyelitis, Acute Disseminated/diagnosis , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Optic Neuritis/diagnosis , Adolescent , Autoantibodies , Azathioprine/therapeutic use , Child , Child, Preschool , Disease Progression , Encephalomyelitis, Acute Disseminated/drug therapy , Encephalomyelitis, Acute Disseminated/immunology , Female , Humans , Male , Myelin-Oligodendrocyte Glycoprotein/immunology , Optic Neuritis/drug therapy , Optic Neuritis/immunology , Prednisolone/therapeutic use , Rituximab/therapeutic use , Treatment OutcomeABSTRACT
BACKGROUND: The KK Women's and Children's Hospital is a tertiary obstetric unit with approximately 11000 deliveries per year. Epidural analgesia is used in about 40% of laboring women. We reviewed the incidence and management of post-dural puncture headache over a nine-year period. METHODS: A retrospective audit of labor epidural analgesia database records from 1 June 2005 to 31 May 2014 was conducted, identifying an "event" as an accidental dural puncture, an inadvertent intrathecal catheter insertion and/or development of a post-dural puncture headache. RESULTS: A total of 43434 epidural records were reviewed. Sixty-three events were identified (an incidence of 0.15%). Women had median age of 30years and median body mass index of 27.6kg/m2; 69.8% (44/63) delivered vaginally. Procedures performed by less experienced anesthesiologists and those performed outside office hours were associated with a higher incidence of accidental dural puncture. An intrathecal catheter was inserted in 52 of 58 women (89.7%). Headache developed in 24 of 38 (63.1%) women in whom there was a witnessed accidental dural puncture. Most women who developed post-dural puncture headache presented during the primary admission (36/39; 92.3%). Paracetamol and non-steroidal anti-inflammatory drugs were the most commonly prescribed medications. Six women (9.5%) received an epidural blood patch which led to resolution of headache. CONCLUSION: A retrospective audit over a nine-year period at a tertiary teaching hospital found the overall incidence of post-dural puncture headache and associated events to be 0.15%, with a decreasing trend coinciding with improvement in the teaching and supervision of trainees in labor epidural procedures.
Subject(s)
Clinical Audit/statistics & numerical data , Post-Dural Puncture Headache/epidemiology , Post-Dural Puncture Headache/therapy , Acetaminophen/therapeutic use , Adult , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Blood Patch, Epidural/statistics & numerical data , Clinical Competence/statistics & numerical data , Female , Humans , Incidence , Pregnancy , Retrospective Studies , Singapore/epidemiology , Tertiary Care Centers/statistics & numerical dataSubject(s)
Hematologic Neoplasms/therapy , Hematopoietic Stem Cell Transplantation , Pentamidine/administration & dosage , Pneumocystis carinii , Pneumonia, Pneumocystis/prevention & control , Adult , Aged , Allografts , Female , Humans , Male , Middle Aged , Pneumonia, Pneumocystis/etiology , Retrospective StudiesABSTRACT
OBJECTIVE: The aim of the study was to investigate the relationships between the Symptom Checklist-90-Revision (SCL-90-R) and the Minnesota Multiphasic Personality Inventory (MMPI) in temporomandibular disorders (TMD) patients with psychological problems. MATERIALS AND METHODS: Subjective symptoms, objective signs, and psychological characteristics of 36 TMD patients with psychological problems were analyzed. The symptom severity index (SSI) and craniomandibular index (CMI) were used to assess subjective symptoms and objective signs of patients with TMD, respectively. The SCL-90-R and MMPI were used for psychological evaluation. RESULTS: The SSI was not significantly correlated with the CMI in TMD patients with psychological problems, and these indices displayed significant correlations with the SCL-90-R and MMPI in several selected subscales. The results of SCL-90-R had a limited relationship with those of MMPI in these patients. Based on the MMPI diagnosis, the SCL-90-R somatization subscale showed moderate to high sensitivity and specificity, but the SCL-90-R depression subscale showed moderate to low sensitivity and specificity. CONCLUSIONS: Considering the limited relationship between the SCL-90-R and MMPI in TMD patients with psychological problems, more comprehensive psychological tests are recommended when clinicians suspect patients with TMD of having accompanying psychological problems.
Subject(s)
Checklist , MMPI , Mental Disorders/complications , Temporomandibular Joint Disorders/diagnosis , Temporomandibular Joint Disorders/psychology , Adolescent , Adult , Arthralgia/etiology , Depression/complications , Facial Pain/etiology , Female , Humans , Male , Pain Measurement , Psychiatric Status Rating Scales , Self Report , Sensitivity and Specificity , Severity of Illness Index , Sleep Wake Disorders/complications , Somatoform Disorders/complications , Statistics, Nonparametric , Temporomandibular Joint Disorders/complications , Young AdultABSTRACT
The new McDonald 2010 criteria have been recommended in paediatric multiple sclerosis (PMS). We aimed to assess the utility of McDonald 2010 criteria in comparison with 2007 International Paediatric Multiple Sclerosis Study Group (IPMSSG)-recommended criteria for PMS diagnosis. Retrospective analysis of 38 PMS cases from three UK demyelination clinics was conducted. Dissemination in space (DIS) and time (DIT) for both McDonald and IPMSSG criteria were noted on initial and follow-up magnetic resonance imaging (MRI). At first MRI scan, IPMSSG DIS criteria were fulfilled in 68% of scans and McDonald DIS criteria in 84%. In total, 11/18 children given gadolinium contrast fulfilled both McDonald DIS and DIT criteria on initial scan. The 2010 McDonald criteria appear more sensitive than IPMSSG and may allow PMS diagnosis at first presentation of CIS in at least a half of cases.
Subject(s)
Brain/pathology , Magnetic Resonance Imaging , Multiple Sclerosis/diagnosis , Adolescent , Age Factors , Child , Contrast Media , England , Female , Humans , Male , Multiple Sclerosis/drug therapy , Multiple Sclerosis/pathology , Predictive Value of Tests , Prognosis , Retrospective Studies , Sensitivity and Specificity , Severity of Illness Index , Time FactorsABSTRACT
UNLABELLED: The association between proximal femoral geometry and hip fracture risk were investigated. The risk of intertrochanteric fractures increased 1.64-fold and 2.32-fold with 1 standard deviation (sd) increase of hip axis length and neck-shaft angle, respectively, while the risk of femur neck fracture 2.03-fold with 1 sd decrease in femoral head offset. INTRODUCTION: The purpose of this study was to determine the association between proximal femoral geometry (PFG) and the risk of hip fracture in femur neck (FN) and intertrochanteric (IT) fractures in a Korean population. METHODS: The study included 151 patients (57 patients with IT fractures, 43 patients with FN fractures, and 51 control patients). Data on BMD, PFG parameters (hip axis length [HAL], neck-shaft angle [NSA], neck length, femoral head offset, neck diameter, shaft diameter (SD), and demographics [age, gender, height, and body weight]) were collected. Descriptive statistics and odds ratios of PFG parameters corrected with demographic variables were obtained using logistic regressions. RESULTS: HAL (p = 0.046) and NSA (p = 0.003) were significantly greater in the patients with IT fracture than in the control patients, while neither parameter was significantly greater in patients with FN fractures than the control patients. The femoral head offset was significantly shorter in the patients with FN fractures (p = 0.003) compared with the control patients. In patients with IT fractures, the fracture risk increased 1.64-fold (p = 0.048) with a 1 sd increase of the HAL, while it increased 2.32-fold (p = 0.003) with a 1 sd increase of the NSA. In FN fractures, the fracture risk increased 2.03-fold (p = 0.012) with a 1 sd decrease in femoral head offset. CONCLUSIONS: Our study showed that some PFG parameters as well as BMD values predict hip fractures in a Korean population, and their evaluation may be useful in the understanding of the biomechanics of hip fractures.
Subject(s)
Femur/anatomy & histology , Hip Fractures/epidemiology , Hip Joint/anatomy & histology , Absorptiometry, Photon , Aged , Aged, 80 and over , Bone Density , Case-Control Studies , Female , Femoral Neck Fractures/diagnostic imaging , Femoral Neck Fractures/epidemiology , Femur/diagnostic imaging , Hip Fractures/diagnostic imaging , Hip Joint/diagnostic imaging , Humans , Logistic Models , Male , Republic of Korea/epidemiology , Risk Assessment , Risk FactorsABSTRACT
There is a paucity of literature on the epidemiology of severe acute disseminated encephalomyelitis (ADEM). We describe a Paediatric Intensive Care Unit (PICU) population-based study to determine the epidemiology and clinical characteristics of children with ADEM requiring PICU admission or resulting in death. Anonymized data from the Paediatric Intensive Care Audit Network (PICANet) were obtained for all children under 16 years with a diagnosis of ADEM admitted to 25 PICUs in England and Wales (2004-2008). The Office for National Statistics (ONS) mortality database was also searched. In total, 27 PICANet cases (13 females:14 males; median age 4.8 years) were ascertained and all were alive on discharge. In addition, three cases were identified from the ONS mortality database. Of the 27 PICANet cases, clinical features included; seizures (n = 5); upper airway respiratory obstruction/stridor (n = 2); unspecified encephalopathy (n = 27); and polyfocal neurological deficits (n = 6). The median duration of ventilation was 3 days. Inotropic support was required in 4/27 patients, and one patient had invasive intracranial pressure monitoring. None received plasmapheresis. We conclude that the incidence of childhood ADEM admitted to the PICU in England and Wales is approximated at 0.5 per million children/year, thus representing approximately one quarter of children admitted with ADEM (denominator: 2009 Canadian surveillance data).
Subject(s)
Encephalomyelitis, Acute Disseminated/epidemiology , Intensive Care Units, Pediatric/statistics & numerical data , Child , Child, Preschool , Encephalomyelitis, Acute Disseminated/complications , Female , Humans , Infant , MaleABSTRACT
UNLABELLED: Aicardi-Goutières syndrome is a genetic childhood encephalopathy characterized by basal ganglia calcification, chronic cerebrospinal lymphocytosis and elevated cerebrospinal fluid interferon-alpha, mimicking acquired congenital viral infections. As more is discovered about the pathogenesis of Aicardi-Goutières, it is becoming evident that a dysfunction of the immune system is likely to be responsible for the disease phenotype. We describe a previously healthy 2-month-old female infant who presented with haematemesis and seizures and was subsequently diagnosed with Aicardi-Goutières syndrome. To our knowledge, this is the first documented case of Aicardi-Goutières syndrome presenting with haematemesis. The gastrointestinal tract is an area of high cell loss, revealing early signs of systemic inflammation and we postulate that a systemic proinflammatory milieu occurs in Aicardi-Goutières syndrome. CONCLUSION: Aicardi-Goutières syndrome can present with haematemesis, adding to the growing evidence that the Aicardi-Goutières syndrome spectrum encompasses an immune-mediated multisystem involvement. Gastrointestinal inflammation should also be considered in these patients and treated appropriately.
Subject(s)
Abnormalities, Multiple/diagnosis , Brain Diseases/diagnosis , Hematemesis/etiology , Abnormalities, Multiple/genetics , Autoimmune Diseases of the Nervous System/genetics , Brain Diseases/complications , Brain Diseases/genetics , Female , Gastrointestinal Tract/pathology , Humans , Infant , Inflammation , Magnetic Resonance Imaging , Seizures/etiology , Syndrome , Tomography, X-Ray ComputedABSTRACT
Autoantibodies to glutamic acid decarboxylase (GAD65) have been reported in sera from the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis (JNCL), and in individuals with this fatal paediatric neurodegenerative disorder. To investigate the existence of other circulating autoreactive antibodies, we used sera from patients with JNCL and other forms of neuronal ceroid lipofuscinosis (NCL) as primary antisera to stain rat and human central nervous system sections. JNCL sera displayed characteristic patterns of IgG, but not IgA, IgE or IgM immunoreactivity that was distinct from the other forms of NCL. Immunoreactivity of JNCL sera was not confined to GAD65-positive (GABAergic) neurons, but also stained multiple other cell populations. Preadsorption of JNCL sera with recombinant GAD65 reduced the intensity of the immunoreactivity, but did not significantly change its staining pattern. Moreover, sera from Stiff Person Syndrome and Type I Diabetes, disorders in which GAD65 autoantibodies are present, stained with profiles that were markedly different from JNCL sera. Collectively, these studies provide evidence of the presence of autoreactive antibodies within multiple forms of NCL, and are not exclusively directed towards GAD65.
Subject(s)
Autoantibodies/analysis , Brain/immunology , Neuronal Ceroid-Lipofuscinoses/immunology , Adsorption , Animals , Antibody Specificity , Diabetes Mellitus, Type 1/immunology , Glutamate Decarboxylase/immunology , Humans , Immunoglobulin G/immunology , Isoenzymes/immunology , Male , Rats , Rats, Sprague-Dawley , Stiff-Person Syndrome/immunologyABSTRACT
Atoms in an ultracold highly excited sample are strongly coupled through the dipole-dipole interaction. In an effort to understand and manipulate the complicated interactions in this system we are investigating their dependence on the relative orientation of the dipoles. By focusing a 480 nm beam from a tunable dye laser into a magneto-optical trap, we produce a nearly one-dimensional sample of Rydberg atoms. The trap lies at the center of four conducting rods with which we can vary the magnitude and direction of the electric field at the trap, thus controlling the orientation of the dipoles with respect to the sample axis. We have measured the strength of the interaction for a variety of relative orientations.
ABSTRACT
We study the evolution of ultracold plasmas by measuring the electron temperature. Shortly after plasma formation, competition between heating and cooling mechanisms drives the electron temperature to a value within a narrow range regardless of the initial energy imparted to the electrons. In agreement with theory predictions, plasmas exhibit values of the Coulomb coupling parameter Gamma less than 1.
ABSTRACT
The systematic comparison of genomic sequences from different organisms represents a central focus of contemporary genome analysis. Comparative analyses of vertebrate sequences can identify coding and conserved non-coding regions, including regulatory elements, and provide insight into the forces that have rendered modern-day genomes. As a complement to whole-genome sequencing efforts, we are sequencing and comparing targeted genomic regions in multiple, evolutionarily diverse vertebrates. Here we report the generation and analysis of over 12 megabases (Mb) of sequence from 12 species, all derived from the genomic region orthologous to a segment of about 1.8 Mb on human chromosome 7 containing ten genes, including the gene mutated in cystic fibrosis. These sequences show conservation reflecting both functional constraints and the neutral mutational events that shaped this genomic region. In particular, we identify substantial numbers of conserved non-coding segments beyond those previously identified experimentally, most of which are not detectable by pair-wise sequence comparisons alone. Analysis of transposable element insertions highlights the variation in genome dynamics among these species and confirms the placement of rodents as a sister group to the primates.
Subject(s)
Conserved Sequence/genetics , Evolution, Molecular , Genomics , Vertebrates/genetics , Animals , Chromosomes, Human, Pair 7/genetics , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , DNA Transposable Elements/genetics , Genome , Humans , Mammals/genetics , Mutagenesis/genetics , Phylogeny , Sequence Alignment , Sequence Homology, Nucleic Acid , Species SpecificityABSTRACT
To investigate HLA-associated genetic susceptibility to Meniere's disease in relation to type II collagen (CII) autoimmunity status, HLA-DRB1 genotyping and ELISA measurement of anti-CII antibody were performed in 41 Korean patients with Meniere's disease. In the anti-CII positive subgroup (20%) of patients, the frequency of HLA-DRB1*0405 was significantly increased (uncorrected) compared with both controls (63% vs 16%) and anti-CII negative patients (63% vs 12%). In the anti-CII negative subgroup, HLA-DRB1*1201 was significantly increased (uncorrected) (27% vs 10%) and DRB1*13 was decreased (6% vs 24%) compared with controls; these alleles appeared to confer susceptibility and resistance to the development of the disease. Association of HLA-DRB1*0405 with anti-CII positive Meniere's disease in this study suggests that it shares a specific HLA-DR sequence, QRRAA, as a genetic susceptibility factor with the anti-CII positive rheumatoid arthritis. In conclusion, whilst type II collagen autoimmunity may have a partial role in Meniere's disease, different HLA-DR alleles may also be associated with either susceptibility or resistance to the development of the disease in relation to anti-CII antibody status.
Subject(s)
Collagen Type II/immunology , HLA-DR Antigens/genetics , Meniere Disease/genetics , Meniere Disease/immunology , Adult , Aged , Alleles , Autoantibodies/blood , Autoimmunity , Female , Genetic Predisposition to Disease , HLA-DR Antigens/analysis , HLA-DR Antigens/immunology , HLA-DRB1 Chains , Humans , Male , Serologic TestsABSTRACT
The inflammation-induced subcellular redistribution of key cytoskeletal and junctional proteins in cultured human lung microvessel endothelial cells is investigated as part of a study on the posttranslational regulation of paracellular permeability. Inflammatory agonist-stimulated cells are detergent fractionated into three subcellular compartments followed by quantitative immunoblot analysis. Actin, gamma-catenin, and VE-cadherin increasingly associate with the cytoskeletal fraction upon thrombin stimulation. Concomitantly, actin is reduced in the cytosol fraction, whereas gamma-catenin and VE-cadherin are reduced in the membrane fraction. alpha- and beta-catenin show baseline distributions similar to those of VE-cadherin and gamma-catenin, but do not significantly redistribute. Additionally, vimentin is found exclusively in the cytoskeletal fraction and also does not significantly redistribute following thrombin treatment. The VE-cadherin response is independent of the presence of F-actin or actin redistribution. Immunofluorescence microscopy reveals that membrane and cytoskeletal VE-cadherin is present in alternating patches along the cell junctions. Furthermore, VE-cadherin is lost from zones of interendothelial cell pore formation. A model is formulated describing these membrane-associated VE-cadherin patches as predetermined zones of potential intercellular gap formation. During inflammation, VE-cadherin is lost from these zones and sequestered at the remaining cell-cell contact sites, anchored to the cytoskeleton in an actin-independent fashion.
Subject(s)
Actins/metabolism , Cadherins/metabolism , Cytoskeletal Proteins/drug effects , Endothelium, Vascular/metabolism , Inflammation/physiopathology , Lung/blood supply , Antigens, CD , Blotting, Western , Cell Adhesion Molecules/analysis , Cell Adhesion Molecules/metabolism , Cell Compartmentation/immunology , Cells, Cultured , Cytoskeletal Proteins/analysis , Cytoskeletal Proteins/metabolism , Cytosol/metabolism , Desmoplakins , Endothelium, Vascular/immunology , Humans , Inflammation/chemically induced , Inflammation/pathology , Intercellular Junctions/chemistry , Intercellular Junctions/drug effects , Intercellular Junctions/immunology , Microscopy, Fluorescence , Thrombin/pharmacology , Time Factors , gamma CateninABSTRACT
We study the formation of Rydberg atoms in expanding plasmas at temperatures of 1-1000 K and densities from 10(5)-10(10) cm(-3). Up to 20% of the initially free charges recombine in about 100 micros, and the binding energy of the Rydberg atoms approximately equals the increase in the kinetic energy of the remaining free electrons. Three-body recombination is expected to dominate in this regime, yet most of our results are inconsistent with this mechanism.
ABSTRACT
Protein distribution profiles may be used to characterize both physiological and pathophysiological cellular changes, but rigorous biochemical assays for measuring such movements are lacking. This paper reports on a protein redistribution assay that combines reversible metal chelate-based total protein detection with a four-fraction subcellular detergent fractionation procedure. TNF-alpha stimulated cultured human omental microvessel endothelial cells are fractionated into cytosol, membrane/organelle, nuclear (envelope and associated), and cytoskeletal/DNA compartments. Protein fractions are separated electrophoretically and electroblotted or slot-blotted onto PVDF membranes without electrophoretic separation. A key feature is that total protein is measured and analyzed directly on the resultant PVDF membrane, using a Ferrozine/ferrous metal-chelate stain, without the added step of a prior solution-phase protein assay. As a result, factors that may adversely affect NFkappaB quantification, such as saturation of the solid-support membrane, are rigorously evaluated and controlled. Following removal of the Ferrozine/ferrous total protein stain, NFkappaB distribution is determined via standard immunodetection procedures. This assay reveals a new level of complexity regarding NFkappaB distribution and translocation. NFkappaB is shown to translocate from the cytosol to the membrane/organelle and cytoskeletal/DNA fractions, whereas trace levels of NFkappaB are observed in the nuclear (envelope and associated) fraction. Dose-curve analysis reveals that the response is initiated at 10 U/ml of TNF-alpha, plateaus at approximately 1000 U/ml, and remains essentially constant up to 2000 U/ml. Time-course analysis demonstrates a measurable response as early as 5 min and a peak response at approximately 30 min, after which the distribution begins to return to baseline. The assay should provide a valuable tool for rapid evaluation and mechanistic studies of NFkappaB redistribution.