Relationship between MEG global dynamic functional network connectivity measures and symptoms in schizophrenia.

An investigation of differences in dynamic functional network connectivity (dFNC) of healthy controls (HC) versus that of schizophrenia patients (SP) was completed, using eyes-open resting state MEG data. The MEG analysis utilized a source-space activity estimate (MNE/dSPM) whose result was the input to a group spatial independent component analysis (ICA), on which the networks of our MEG dFNC analysis were based. We have previously reported that our MEG dFNC revealed that SP change between brain meta-states (repeating patterns of network correlations which are allowed to overlap in time) significantly more often and to states which are more different, relative to HC. Here, we extend our previous work to investigate the relationship between symptomology in SP and four meta-state metrics. We found a significant correlation between positive symptoms and the two meta-state metrics which showed significant differences between HC and SP. These two statistics quantified 1) how often individuals change state and 2) the total distance traveled within the state-space. We additionally found that a clustering of the meta-state metrics divides SP into groups which vary in symptomology. These results indicate specific relationships between symptomology and brain function for SP.

Muscle Quality Improves with Extended High-Intensity Resistance Training after Hip Fracture.

BACKGROUND: Muscle mass deficits endure after hip fracture. Strategies to improve muscle quality may improve mobility and physical function. It is unknown whether training after usual care yields muscle quality gains after hip fracture. OBJECTIVES: To determine whether muscle quality improves after hip fracture with high-intensity resistance training and protein supplementation. DESIGN: Case series. SETTING: University of Utah Skeletal Muscle Exercise Research Facility. PARTICIPANTS: 17 community-dwelling older adults, 3.6+/-1.1 months post-hip fracture, recently discharged from usual-care physical therapy (mean age 77.0+/-12.0 years, 12 female), enrolled. INTERVENTION: Participants underwent 12 weeks (3x/week) of unilaterally-biased resistance training. METHODS/MATERIALS: Participants were measured via a 3.0 Tesla whole-body MR imager for muscle lean and intramuscular adipose tissue (IMAT) of the quadriceps before and after resistance training. Peak isometric knee extension force output was measured with an isokinetic dynamometer. Muscle quality was calculated by dividing peak isometric knee extension force (N) by quadriceps lean muscle mass (cm2). In addition, common physical function variables were measured before and after training. RESULTS: Surgical and nonsurgical lean quadriceps muscle mass improved among participants (mean change: 2.9 cm2+/-1.4 cm2, and 2.7 cm2+/-1.3 cm2, respectively), while IMAT remained unchanged. Peak force improved in the surgical limb by 43.1+/-23N, with no significant change in the nonsurgical limb. Significant gains in physical function were evident after training. CONCLUSION: Participants recovering from hip fracture demonstrated improvements in muscle mass, muscle strength, and muscle quality in the surgical limb after hip fracture. These were in addition to gains made in the first months after fracture with traditional care. Future studies should determine the impact that muscle quality has on long-term functional recovery in this population.

High-Intensity Multimodal Resistance Training Improves Muscle Function, Symmetry during a Sit-to-Stand Task, and Physical Function Following Hip Fracture.

OBJECTIVES: Post rehabilitation, older adults with hip fracture display low vertical ground reaction force (vGRF) on the involved lower extremity during a sit-to-stand task and low physical function. The purpose of this study was to test whether muscle performance, involved side vGRF during a sit-to-stand task, and physical function improved following multimodal high-intensity resistance training, when initiated after usual care (2 to 6 months after hip fracture). DESIGN: Case series study, 12 weeks extended high-intensity strength training intervention following hip fracture. SETTING: University hospital outpatient facility. PARTICIPANTS: Twenty-four community-dwelling older adults (mean age 78.4 years (SD 10.4), 16 female/8 male), 3.6 (SD 1.2) months post-hip fracture and discharged from physical therapy participated. Intervention/Measurement: All participants performed sit-to-stand tasks, muscle performance tests, and modified physical performance test (mPPT) before and after 12 weeks (3x/wk) of training. Variables were compared using paired t-tests. RESULTS: The vGRF rate of force development (RFD) and magnitude of discrepancy between limb loading during rising phase of sit-to-stand task (AREA) variables improved post-training (RFD ratio = Pre: 0.78 - Post: 0.82, AREA ratio = Pre: 0.79 - Post: 0.86). Surgical leg extension power gains were large (~65%) while strength gains were moderate (~34%); yielding improved symmetry in both strength (Pre: 0.74 - Post: 0.88) and power (Pre: 0.75 - Post: 0.82). Physical function improved pre-training 25 (SD 5.2) to post training 30 (SD 4.3), (p < 0.001). CONCLUSION: Unique to this study, participants recovering from hip fracture demonstrated improved symmetry in sit-to-stand vGRFs, muscle function, and physical function after training. However, a high percentage of patients continued to experience persistently low vGRF of the involved side compared to previous studies of healthy elderly controls. Developing alternative strategies to improve involved side vGRF may be warranted.

Multimodal Neuroimaging in Schizophrenia: Description and Dissemination.

In this paper we describe an open-access collection of multimodal neuroimaging data in schizophrenia for release to the community. Data were acquired from approximately 100 patients with schizophrenia and 100 age-matched controls during rest as well as several task activation paradigms targeting a hierarchy of cognitive constructs. Neuroimaging data include structural MRI, functional MRI, diffusion MRI, MR spectroscopic imaging, and magnetoencephalography. For three of the hypothesis-driven projects, task activation paradigms were acquired on subsets of ~200 volunteers which examined a range of sensory and cognitive processes (e.g., auditory sensory gating, auditory/visual multisensory integration, visual transverse patterning). Neuropsychological data were also acquired and genetic material via saliva samples were collected from most of the participants and have been typed for both genome-wide polymorphism data as well as genome-wide methylation data. Some results are also presented from the individual studies as well as from our data-driven multimodal analyses (e.g., multimodal examinations of network structure and network dynamics and multitask fMRI data analysis across projects). All data will be released through the Mind Research Network's collaborative informatics and neuroimaging suite (COINS).

Tropospheric Emissions: Monitoring of Pollution (TEMPO).

TEMPO was selected in 2012 by NASA as the first Earth Venture Instrument, for launch between 2018 and 2021. It will measure atmospheric pollution for greater North America from space using ultraviolet and visible spectroscopy. TEMPO observes from Mexico City, Cuba, and the Bahamas to the Canadian oil sands, and from the Atlantic to the Pacific, hourly and at high spatial resolution (~2.1 km N/S×4.4 km E/W at 36.5°N, 100°W). TEMPO provides a tropospheric measurement suite that includes the key elements of tropospheric air pollution chemistry, as well as contributing to carbon cycle knowledge. Measurements are made hourly from geostationary (GEO) orbit, to capture the high variability present in the diurnal cycle of emissions and chemistry that are unobservable from current low-Earth orbit (LEO) satellites that measure once per day. The small product spatial footprint resolves pollution sources at sub-urban scale. Together, this temporal and spatial resolution improves emission inventories, monitors population exposure, and enables effective emission-control strategies. TEMPO takes advantage of a commercial GEO host spacecraft to provide a modest cost mission that measures the spectra required to retrieve ozone (O3), nitrogen dioxide (NO2), sulfur dioxide (SO2), formaldehyde (H2CO), glyoxal (C2H2O2), bromine monoxide (BrO), IO (iodine monoxide),water vapor, aerosols, cloud parameters, ultraviolet radiation, and foliage properties. TEMPO thus measures the major elements, directly or by proxy, in the tropospheric O3 chemistry cycle. Multi-spectral observations provide sensitivity to O3 in the lowermost troposphere, substantially reducing uncertainty in air quality predictions. TEMPO quantifies and tracks the evolution of aerosol loading. It provides these near-real-time air quality products that will be made publicly available. TEMPO will launch at a prime time to be the North American component of the global geostationary constellation of pollution monitoring together with the European Sentinel-4 (S4) and Korean Geostationary Environment Monitoring Spectrometer (GEMS) instruments.

Dissecting x-ray-emitting gas around the center of our galaxy.

Most supermassive black holes (SMBHs) are accreting at very low levels and are difficult to distinguish from the galaxy centers where they reside. Our own Galaxy's SMBH provides an instructive exception, and we present a close-up view of its quiescent x-ray emission based on 3 megaseconds of Chandra observations. Although the x-ray emission is elongated and aligns well with a surrounding disk of massive stars, we can rule out a concentration of low-mass coronally active stars as the origin of the emission on the basis of the lack of predicted iron (Fe) Kα emission. The extremely weak hydrogen (H)-like Fe Kα line further suggests the presence of an outflow from the accretion flow onto the SMBH. These results provide important constraints for models of the prevalent radiatively inefficient accretion state.

EFFECT OF JOB SKILLS TRAINING ON EMPLOYMENT AND JOB SEEKING BEHAVIORS IN AN AMERICAN INDIAN SUBSTANCE ABUSE TREATMENT SAMPLE.

Employment difficulties are common among American Indian individuals in substance abuse treatment. To address this problem, the Southwest Node of NIDA's Clinical Trials Network conducted a single-site adaptation of its national Job Seekers Workshop study in an American Indian treatment program, Na'Nizhoozhi Center (NCI). 102 (80% men, 100% American Indian) participants who were in residential treatment and currently unemployed were randomized to (1) a three session, manualized program (Job seekers workshop: JSW) or (2) a 40-minute Job Interviewing Video: JIV). Outcomes were assessed at 3-month follow up: 1) number of days to a new taxed job or enrollment in a job-training program, and 2) total hours working or enrolled in a job-training program. No significant differences were found between the two groups for time to a new taxed job or enrollment in a job-training program. There were no significant differences between groups in substance use frequency at 3-month follow-up. These results do not support the use of the costly and time-consuming JSW intervention in this population and setting. Despite of the lack of a demonstrable treatment effect, this study established the feasibility of including a rural American Indian site in a rigorous CTN trial through a community-based participatory research approach.

The development of a protoplanetary disk from its natal envelope.

Class 0 protostars, the youngest type of young stellar objects, show many signs of rapid development from their initial, spheroidal configurations, and therefore are studied intensively for details of the formation of protoplanetary disks within protostellar envelopes. At millimetre wavelengths, kinematic signatures of collapse have been observed in several such protostars, through observations of molecular lines that probe their outer envelopes. It has been suggested that one or more components of the proto-multiple system NGC 1333-IRAS 4 (refs 1, 2) may display signs of an embedded region that is warmer and denser than the bulk of the envelope. Here we report observations that reveal details of the core on Solar System dimensions. We detect in NGC 1333-IRAS 4B a rich emission spectrum of H2O, at wavelengths 20-37 microm, which indicates an origin in extremely dense, warm gas. We can model the emission as infall from a protostellar envelope onto the surface of a deeply embedded, dense disk, and therefore see the development of a protoplanetary disk. This is the only example of mid-infrared water emission from a sample of 30 class 0 objects, perhaps arising from a favourable orientation; alternatively, this may be an early and short-lived stage in the evolution of a protoplanetary disk.

The NASA Spitzer Space Telescope.

The National Aeronautics and Space Administration's Spitzer Space Telescope (formerly the Space Infrared Telescope Facility) is the fourth and final facility in the Great Observatories Program, joining Hubble Space Telescope (1990), the Compton Gamma-Ray Observatory (1991-2000), and the Chandra X-Ray Observatory (1999). Spitzer, with a sensitivity that is almost three orders of magnitude greater than that of any previous ground-based and space-based infrared observatory, is expected to revolutionize our understanding of the creation of the universe, the formation and evolution of primitive galaxies, the origin of stars and planets, and the chemical evolution of the universe. This review presents a brief overview of the scientific objectives and history of infrared astronomy. We discuss Spitzer's expected role in infrared astronomy for the new millennium. We describe pertinent details of the design, construction, launch, in-orbit checkout, and operations of the observatory and summarize some science highlights from the first two and a half years of Spitzer operations. More information about Spitzer can be found at http://spitzer.caltech.edu/.

Giving way event during a combined stepping and crossover cutting task in an individual with anterior cruciate ligament deficiency.

STUDY DESIGN: Case study. OBJECTIVE: To compare knee kinematics and moments of nongiving way trials to a giving way trial during a combined stepping and crossover cutting activity. BACKGROUND: The knee kinematics and moments associated with giving way episodes suggest motor control strategies that lead to instability and recovery of stability during movement. METHODS AND MEASURES: A 27-year-old woman with anterior cruciate ligament deficiency reported giving way while performing a combined stepping and crossover cutting activity. A motion analysis system recorded motion of the pelvis, femur, tibia, and foot using 3 infrared emitting diodes placed on each segment at 60 Hz. Force plate recordings at 300 Hz were combined with limb inertial properties and position data to estimate net knee joint moments. The stance time, foot progression angle, and cutting angle were also included to evaluate performance between trials. RESULTS: Knee internal rotation during the giving way trial increased 3.2 degrees at 54% of stance relative to the nongiving way trials. Knee flexion during the giving way trial increased to 33.1 degrees at 66% of stance, and the knee moment switched from a nominal flexor moment to a knee extensor moment at 64% of stance. The knee abductor moment and external rotation moment during the giving way trial deviated in early stance. CONCLUSIONS: The observed response to the giving way event suggests that increasing knee flexion may enhance knee stability for this subject. The transverse and frontal plane moments appear important in contributing to the giving way event. Further research that assists clinicians in understanding how interventions can impact control of movements in these planes is necessary.

PM2.5 chemical source profiles for vehicle exhaust, vegetative burning, geological material, and coal burning in Northwestern Colorado during 1995.

PM2.5 (particles with aerodynamic diameters less than 2.5 microm) chemical source profiles applicable to speciated emissions inventories and receptor model source apportionment are reported for geological material, motor vehicle exhaust, residential coal (RCC) and wood combustion (RWC), forest fires, geothermal hot springs; and coal-fired power generation units from northwestern Colorado during 1995. Fuels and combustion conditions are similar to those of other communities of the inland western US. Coal-fired power station profiles differed substantially between different units using similar coals, with the major difference being lack of selenium in emissions from the only unit that was equipped with a dry limestone sulfur dioxide (SO2) scrubber. SO2 abundances relative to fine particle mass emissions in power plant emissions were seven to nine times higher than hydrogen sulfide (H2S) abundances from geothermal springs, and one to two orders of magnitude higher than SO2 abundances in RCC emissions, implying that the SO2 abundance is an important marker for primary particle contributions of non-aged coal-fired power station contributions. The sum of organic and elemental carbon ranged from 1% to 10% of fine particle mass in coal-fired power plant emissions, from 5% to 10% in geological material, >50% in forest fire emissions, >60% in RWC emissions, and >95% in RCC and vehicle exhaust emissions. Water-soluble potassium (K+) was most abundant in vegetative burning profiles. K+/K ratios ranged from 0.1 in geological material profiles to 0.9 in vegetative burning emissions, confirming previous observations that soluble potassium is a good marker for vegetative burning.

Manubrium-sparing sternotomy and off-pump coronary artery bypass grafting in patients with tracheal stoma.

The presence of a tracheal stoma in patients with previous total laryngectomy who require cardiac operations is associated with an increased risk of wound complications and tracheal injuries when a full sternotomy is used. The aim of this report is to describe a technique of manubrium-sparing sternotomy, which can be used in patients undergoing coronary artery bypass grafting without cardiopulmonary bypass.

Heteroarotinoids inhibit head and neck cancer cell lines in vitro and in vivo through both RAR and RXR retinoic acid receptors.

A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu/nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0. 05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RARalpha, RXRalpha, and RXRbeta were similar in the two cell lines, while RARbeta expression was higher in SCC-2 over SCC-38, and RARgamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.

Evaluation of locus heterogeneity and EXT1 mutations in 34 families with hereditary multiple exostoses.

Hereditary multiple exostoses (EXT) is an autosomal dominant disorder characterized by growth of benign bone tumors. Three chromosomal loci have been implicated in this genetically heterogeneous disease: EXT1 at 8q24, EXT2 at 11p13, and EXT3 on 19p. EXT1 and EXT2 were recently cloned. We evaluated 34 families with EXT to estimate the proportion of disease attributable to EXT1, EXT2, and EXT3 and to investigate the spectrum of EXT1 mutations. Linkage analyses combined with heterogeneity testing provides strong evidence in favor of linkage of disease to both chromosomes 8 and 11, but does not support evidence of linkage to chromosome 19 in this data set. The 11 EXT1 exons were PCR-amplified and sequenced in all 11 isolated cases and in 20 of the 23 familial cases. Twelve different novel EXT1 mutations were detected, including 5 frame-shift deletions or insertions, 1 codon deletion, and 6 single base-pair substitutions distributed across 8 of the exons. Only 2 of the mutations were detected in more than one family. Three mutations affect sites in which alterations were previously reported. Nonchain-terminating missense mutations were identified in codons 280 and 340, both coding for conserved arginine residues. These residues may be crucial to the function of this protein. Although the prevalence of EXT has been estimated to be approximately 1/50,000 individuals, the disease has been reported to occur much more frequently in the Chamorro natives on Guam. Our detection of an EXT1 mutation in one Chamorro subject will allow investigation of a possible founder effect in this population. Combined mutational and heterogeneity analyses in this set of families with multiple exostoses suggest that 66% of our total sample, including 45% of isolated and 77% of familial cases, are attributable to abnormalities in EXT1.

Partial left ventriculectomy to treat end-stage heart disease.

BACKGROUND: It is reasoned that reducing left ventricular diameter (Laplace's law) in patients with dilated cardiomyopathy, will improve ventricular function. METHODS: Partial left ventriculectomy was performed in 120 patients with end-stage dilated cardiomyopathies of varying causes. Most patients were in New York Heart Association functional class IV. The procedure consisted of removal of a wedge of left ventricular muscle from the apex to the base of the heart. Depending on the distance between the two papillary muscles, the mitral valve apparatus was either preserved, repaired, or replaced with a tissue prosthesis. RESULTS: The 30-day mortality was 22% and the 2-year survival was 55%. Although 10% of surviving patients showed no improvement in New York Heart Association functional class, most of the surviving patients were in either class I (57%) or II (33.3%), and the others were in class III and IV. CONCLUSIONS: Partial left ventriculectomy can be used to treat end-stage dilated cardiomyopathy. Further studies and a longer follow-up period are needed to fully assess the effects of this procedure.

Optimal size matching in single lung transplantation.

BACKGROUND: Single lung transplantation for patients with end-stage obstructive lung disease has been highly effective in providing symptomatic relief, and it has been performed at a much increased frequency since 1983. However, there still lacks a convincing study showing the effect of size match and other preoperative variables in predicting functional outcome of patients after transplantation. METHODS: We evaluated 23 single lung transplantations performed for obstructive lung disease over a 34-month period. Multiple physiologic variables and size match criteria were evaluated for their contribution in determining the postoperative forced expiratory volume in 1 second at 3 months after transplantation. RESULTS: The size match ratio that was based on inframammary chest wall circumference was the most useful criterion to adopt, and the optimal donor/recipient size match ratio was 0.89. Furthermore, forced expiratory volume in 1 second at 3 months after transplantation could be predicted with a simple mathematical model that was based on the size match ratio and the recipient's calculated vital capacity of the transplanted hemithorax. CONCLUSIONS: This model could be applied in a clinical setting to maximize functional outcome of the recipients undergoing single lung transplantation.

Incidence of phrenic neuropathy after isolated lung transplantation. The Loyola University Lung Transplant Group.

BACKGROUND: Isolated lung transplantation is a viable therapeutic option for many patients with end-stage pulmonary disease. Other intrathoracic surgical procedures have a well documented incidence of phrenic nerve dysfunction, although the incidence after lung transplantation has not been studied. METHODS: Thirty-one patients who underwent lung transplantation were evaluated for evidence of phrenic nerve dysfunction and subsequent recovery. Risk factors contributing to the incidence of injury were examined. Phrenic nerve injury was defined by two separate diagnostic tests (Transcutaneous Phrenic Nerve Conduction Studies and Fluoroscopic evaluation of diaphragmatic movement) used in combination. RESULTS: Of the 27 patients who were completely evaluated after the operation, eight had defining criteria for nerve injury--an incidence of 29.6%. Of those affected, the majority of injuries (89%) resulted in complete paralysis of the affected hemidiaphragm. The highest incidence of injury occurred in patients who underwent bilateral single lung transplantation (41%), with the right phrenic nerve being injured most often (78%). Fortunately, no significant postoperative morbidity was attributable to the occurrence of phrenic nerve injury when compared with those patients who did not sustain injury. CONCLUSIONS: The analysis of possible risk factors resulted in the hypothesis that the likely mechanism of injury in these patients was due to stretching or direct instrumentation of the nerve, and thus measures should be instituted to minimize the possibility of injury.

Management of cervical lymph nodes in squamous carcinomas of the head and neck.

Due to the overwhelming prognostic significance of regional metastases, proper management of cervical lymph nodes in cases of squamous cell carcinoma of the head and neck is essential for an optimal outcome. Better understanding of the predictability of incidence and patterns of metastases of these tumors in recent years has led us away from the radical neck dissection as the only surgical therapeutic or staging procedure done on the neck. Recent studies suggest that selective removal of lymph node groups at risk in clinically negative necks, or modified neck dissections that save important structures, like the jugular vein, XI nerve, and sternocleidomastoid muscle, in clinically positive necks, are appropriate in many patients. Careful selection of the type of neck dissection and judicious use of postoperative radiation therapy can optimize cure rates as well as functional and cosmetic results.

Accumulation of the p53 tumor-suppressor gene product in oral leukoplakia.

OBJECTIVES: (1) To determine whether the protein of the suppressor gene p53 accumulates in leukoplakia of the oral cavity in individuals who use snuff; and (2) to determine whether a correlation exists between the accumulation of p53 protein and the degree of epithelial dysplasia present in oral leukoplakia. DESIGN: Retrospective analysis of archival tissue specimens. SETTING: The University Hospital, a tertiary referral hospital affiliated with the Oklahoma University Medical Center, Oklahoma City, Oklahoma. PATIENTS: In the first part of the study, biopsy specimens of leukoplakia from 12 persons who used snuff were compared with specimens from uninvolved oral mucosa of the same persons and with biopsy specimens from 12 nontobacco-using persons. In the second part of the study, accumulation of p53 protein was determined in 42 archival paraffin-embedded specimens from oral leukoplakia and correlated with the degree of epithelial dysplasia. METHODS: Accumulation of p53 protein was assessed by immunoperoxidase staining with four different primary antibodies. Positive cells were counted in five consecutive high-power fields. RESULTS: In part one, the average number of positive cells in the leukoplakia of snuff-users (21.89 +/- 4.33; mean +/- SE) was higher than that of normal-appearing mucosa (4.00 +/- 1.0; p < 0.05) and that of nontobacco-using controls (7.00 +/- 5.04). In part two, the average number of positive cells was higher in the moderately dysplastic (140.36 +/- 30.03) and severely dysplastic lesions (232.86 +/- 26.85) than in the mildly dysplastic lesions (14.53 +/- 3.33; p < 0.05). The correlation between the degree of epithelial dysplasia and the number of cells positive is strong (Spearman's correlation coefficient = 0.853). CONCLUSIONS: The accumulation of p53 protein in leukoplakia of snuff-users is higher than in normal-appearing oral mucosa from both snuff-users and nontobacco-using controls. A strong correlation exists between the degree of epithelial dysplasia present in oral leukoplakia and the number of cells staining positive for p53. The accumulation of p53 protein holds potential as an intermediate end point in studies of chemoprevention of oral cancer.