Showing papers by "University of Pittsburgh published in 2002"

Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer.

Abstract: Background We conducted a randomized study to determine whether any of three chemotherapy regimens was superior to cisplatin and paclitaxel in patients with advanced non–small-cell lung cancer. Methods A total of 1207 patients with advanced non–small-cell lung cancer were randomly assigned to a reference regimen of cisplatin and paclitaxel or to one of three experimental regimens: cisplatin and gemcitabine, cisplatin and docetaxel, or carboplatin and paclitaxel. Results The response rate for all 1155 eligible patients was 19 percent, with a median survival of 7.9 months (95 percent confidence interval, 7.3 to 8.5), a 1-year survival rate of 33 percent (95 percent confidence interval, 30 to 36 percent), and a 2-year survival rate of 11 percent (95 percent confidence interval, 8 to 12 percent). The response rate and survival did not differ significantly between patients assigned to receive cisplatin and paclitaxel and those assigned to receive any of the three experimental regimens. Treatment with cisplatin...

Sloan digital sky survey: Early data release

Abstract: The Sloan Digital Sky Survey (SDSS) is an imaging and spectroscopic survey that will eventually cover approximately one-quarter of the celestial sphere and collect spectra of ≈106 galaxies, 100,000 quasars, 30,000 stars, and 30,000 serendipity targets. In 2001 June, the SDSS released to the general astronomical community its early data release, roughly 462 deg2 of imaging data including almost 14 million detected objects and 54,008 follow-up spectra. The imaging data were collected in drift-scan mode in five bandpasses (u, g, r, i, and z); our 95% completeness limits for stars are 22.0, 22.2, 22.2, 21.3, and 20.5, respectively. The photometric calibration is reproducible to 5%, 3%, 3%, 3%, and 5%, respectively. The spectra are flux- and wavelength-calibrated, with 4096 pixels from 3800 to 9200 A at R ≈ 1800. We present the means by which these data are distributed to the astronomical community, descriptions of the hardware used to obtain the data, the software used for processing the data, the measured quantities for each observed object, and an overview of the properties of this data set.

Dysfunction of Mitochondria in Human Skeletal Muscle in Type 2 Diabetes

Abstract: Skeletal muscle is strongly dependent on oxidative phosphorylation for energy production. Because the insulin resistance of skeletal muscle in type 2 diabetes and obesity entails dysregulation of the oxidation of both carbohydrate and lipid fuels, the current study was undertaken to examine the potential contribution of perturbation of mitochondrial function. Vastus lateralis muscle was obtained by percutaneous biopsy during fasting conditions from lean (n = 10) and obese (n = 10) nondiabetic volunteers and from volunteers with type 2 diabetes (n = 10). The activity of rotenone-sensitive NADH:O(2) oxidoreductase, reflecting the overall activity of the respiratory chain, was measured in a mitochondrial fraction by a novel method based on providing access for NADH to intact mitochondria via alamethicin, a channel-forming antibiotic. Creatine kinase and citrate synthase activities were measured as markers of myocyte and mitochondria content, respectively. Activity of rotenone-sensitive NADH:O(2) oxidoreductase was normalized to creatine kinase activity, as was citrate synthase activity. NADH:O(2) oxidoreductase activity was lowest in type 2 diabetic subjects and highest in the lean volunteers (lean 0.95 +/- 0.17, obese 0.76 +/- 0.30, type 2 diabetes 0.56 +/- 0.14 units/mU creatine kinase; P < 0.005). Also, citrate synthase activity was reduced in type 2 diabetic patients (lean 3.10 +/- 0.74, obese 3.24 +/- 0.82, type 2 diabetes 2.48 +/- 0.47 units/mU creatine kinase; P < 0.005). As measured by electron microscopy, skeletal muscle mitochondria were smaller in type 2 diabetic and obese subjects than in muscle from lean volunteers (P < 0.01). We conclude that there is an impaired bioenergetic capacity of skeletal muscle mitochondria in type 2 diabetes, with some impairment also present in obesity.

Results of a Prospective Study of Acute Liver Failure at 17 Tertiary Care Centers in the United States

Abstract: Acetaminophen overdose and idiosyncratic drug reactions have replaced viral hepatitis as the most frequent causes of acute liver failure. The cause of liver failure and coma grade at admission were...

Spectroscopic Target Selection in the Sloan Digital Sky Survey: The Main Galaxy Sample

Abstract: We describe the algorithm that selects the main sample of galaxies for spectroscopy in the Sloan Digital Sky Survey (SDSS) from the photometric data obtained by the imaging survey. Galaxy photometric properties are measured using the Petrosian magnitude system, which measures flux in apertures determined by the shape of the surface brightness profile. The metric aperture used is essentially independent of cosmological surface brightness dimming, foreground extinction, sky brightness, and the galaxy central surface brightness. The main galaxy sample consists of galaxies with r-band Petrosian magnitudes r ≤ 17.77 and r-band Petrosian half-light surface brightnesses μ50 ≤ 24.5 mag arcsec-2. These cuts select about 90 galaxy targets per square degree, with a median redshift of 0.104. We carry out a number of tests to show that (1) our star-galaxy separation criterion is effective at eliminating nearly all stellar contamination while removing almost no genuine galaxies, (2) the fraction of galaxies eliminated by our surface brightness cut is very small (~0.1%), (3) the completeness of the sample is high, exceeding 99%, and (4) the reproducibility of target selection based on repeated imaging scans is consistent with the expected random photometric errors. The main cause of incompleteness is blending with saturated stars, which becomes more significant for brighter, larger galaxies. The SDSS spectra are of high enough signal-to-noise ratio (S/N > 4 per pixel) that essentially all targeted galaxies (99.9%) yield a reliable redshift (i.e., with statistical error less than 30 km s-1). About 6% of galaxies that satisfy the selection criteria are not observed because they have a companion closer than the 55'' minimum separation of spectroscopic fibers, but these galaxies can be accounted for in statistical analyses of clustering or galaxy properties. The uniformity and completeness of the galaxy sample make it ideal for studies of large-scale structure and the characteristics of the galaxy population in the local universe.

Cardiovascular Disease Outcomes During 6.8 Years of Hormone Therapy: Heart and Estrogen/Progestin Replacement Study Follow-up (HERS II)

Abstract: 1.22); HERS II, 1.00 (95% CI, 0.77-1.29); and overall, 0.99 (0.84-1.17). The overall RHs were similar after adjustment for potential confounders and differential use of statins between treatment groups (RH, 0.97; 95% CI, 0.82-1.14), and in analyses restricted to women who were adherent to randomized treatment assignment (RH, 0.96; 95% CI, 0.77-1.19). Conclusions Lower rates of CHD events among women in the hormone group in the final years of HERS did not persist during additional years of follow-up. After 6.8 years, hormone therapy did not reduce risk of cardiovascular events in women with CHD. Postmenopausal hormone therapy should not be used to reduce risk for CHD events in women with CHD.

Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study.

Abstract: ContextMild cognitive impairment (MCI) may be a precursor to dementia, at least in some cases. Dementia and MCI are associated with neuropsychiatric symptoms in clinical samples. Only 2 population-based studies exist of the prevalence of these symptoms in dementia, and none exist for MCI.ObjectiveTo estimate the prevalence of neuropsychiatric symptoms in dementia and MCI in a population-based study.DesignCross-sectional study derived from the Cardiovascular Health Study, a longitudinal cohort study.Setting and ParticipantsA total of 3608 participants were cognitively evaluated using data collected longitudinally over 10 years and additional data collected in 1999-2000 in 4 US counties. Dementia and MCI were classified using clinical criteria and adjudicated by committee review by expert neurologists and psychiatrists. A total of 824 individuals completed the Neuropsychiatric Inventory (NPI); 362 were classified as having dementia, 320 as having MCI; and 142 did not meet criteria for MCI or dementia.Main Outcome MeasurePrevalence of neuropsychiatric symptoms, based on ratings on the NPI in the previous month and from the onset of cognitive symptoms.ResultsOf the 682 individuals with dementia or MCI, 43% of MCI participants (n = 138) exhibited neuropsychiatric symptoms in the previous month (29% rated as clinically significant) with depression (20%), apathy (15%), and irritability (15%) being most common. Among the dementia participants, 75% (n = 270) had exhibited a neuropsychiatric symptom in the past month (62% were clinically significant); 55% (n = 199) reported 2 or more and 44% (n = 159) 3 or more disturbances in the past month. In participants with dementia, the most frequent disturbances were apathy (36%), depression (32%), and agitation/aggression (30%). Eighty percent of dementia participants (n = 233) and 50% of MCI participants (n = 139) exhibited at least 1 NPI symptom from the onset of cognitive symptoms. There were no differences in prevalence of neuropsychiatric symptoms between participants with Alzheimer-type dementia and those with other dementias, with the exception of aberrant motor behavior, which was more frequent in Alzheimer-type dementia (5.4% vs 1%; P = .02).ConclusionsNeuropsychiatric symptoms occur in the majority of persons with dementia over the course of the disease. These are the first population-based estimates for neuropsychiatric symptoms in MCI, indicating a high prevalence associated with this condition as well. These symptoms have serious adverse consequences and should be inquired about and treated as necessary. Study of neuropsychiatric symptoms in the context of dementia may improve our understanding of brain-behavior relationships.

Economic Reasons for Conserving Wild Nature

Abstract: On the eve of the World Summit on Sustainable Development, it is timely to assess progress over the 10 years since its predecessor in Rio de Janeiro. Loss and degradation of remaining natural habitats has continued largely unabated. However, evidence has been accumulating that such systems generate marked economic benefits, which the available data suggest exceed those obtained from continued habitat conversion. We estimate that the overall benefit:cost ratio of an effective global program for the conservation of remaining wild nature is at least 100:1.

The Timing of Action-Monitoring Processes in the Anterior Cingulate Cortex

Abstract: The anterior cingulate cortex (ACC) has been shown to respond to conflict between simultaneously active, incompatible response tendencies. This area is active during high-conflict correct trials and also when participants make errors. Here, we use the temporal resolution of high-density event-related potentials (ERPs) in combination with source localization to investigate the timing of ACC activity during conflict and error detection. We predicted that the same area of the ACC is active prior to high-conflict correct responses and following erroneous responses. Dipole modeling supported this prediction: The frontocentral N2, occurring prior to the response on correct conflict trials, and the ERN, occurring immediately following error responses, could both be modeled as having a generator in the caudal ACC, suggesting the same process to underlie both peaks. Modeling further suggested that the rostral area of the ACC was also active following errors, but later in time, contributing to the error positivity (PE), and peaking at 200-250 msec following the ERN peak. Despite the inherent limitations of source localization, these data may begin to shed light on the timing of action-monitoring processes. First, the time course of caudal ACC activity follows the time course as predicted by the conflict theory of this region. Second, caudal ACC activity might be temporally dissociated from rostral ACC activity during error trials, which possibly reflects a separate, affective component of the evaluative functions of the ACC.

Predictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health Study.

Abstract: Background Sleep-disordered breathing (SDB) is common, but largely undiagnosed in the general population. Information on demographic patterns of SDB occurrence and its predictive factors in the general population is needed to target high-risk groups that may benefit from diagnosis. Methods The sample comprised 5615 community-dwelling men and women aged between 40 and 98 years who were enrolled in the Sleep Heart Health Study. Data were collected by questionnaire, clinical examinations, and in-home polysomnography. Sleep-disordered breathing status was based on the average number of apnea and hypopnea episodes per hour of sleep (apnea-hypopnea index [AHI]). We used multiple logistic regression modeling to estimate cross-sectional associations of selected participant characteristics with SDB defined by an AHI of 15 or greater. Results Male sex, age, body mass index, neck girth, snoring, and repeated breathing pause frequency were independent, significant correlates of an AHI of 15 or greater. People reporting habitual snoring, loud snoring, and frequent breathing pauses were 3 to 4 times more likely to have an AHI of 15 or greater vs an AHI less than 15, but there were weaker associations for other factors with an AHI of 15 or greater. The odds ratios (95% confidence interval) for an AHI of 15 or greater vs an AHI less than 15 were 1.6 and 1.5, respectively, for 1-SD increments in body mass index and neck girth. As age increased, the magnitude of associations for SDB and body habitus, snoring, and breathing pauses decreased. Conclusions A significant proportion of occult SDB in the general population would be missed if screening or case finding were based solely on increased body habitus or male sex. Breathing pauses and obesity may be particularly insensitive for identifying SDB in older people. A better understanding of predictive factors for SDB, particularly in older adults, is needed.

Vascular Cognitive Impairment

Abstract: Cerebrovascular disease is the second most common cause of acquired cognitive impairment and dementia and contributes to cognitive decline in the neurodegenerative dementias. The current narrow definitions of vascular dementia should be broadened to recognise the important part cerebrovascular disease plays in several cognitive disorders, including the hereditary vascular dementias, multi-infarct dementia, post-stroke dementia, subcortical ischaemic vascular disease and dementia, mild cognitive impairment, and degenerative dementias (including Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies). Here we review the current state of scientific knowledge on the subject of vascular brain burden. Important non-cognitive features include depression, apathy, and psychosis. We propose use of the term vascular cognitive impairment, which is characterised by a specific cognitive profile involving preserved memory with impairments in attentional and executive functioning. Diagnostic criteria have been proposed for some subtypes of vascular cognitive impairment, and there is a pressing need to validate and further refine these. Clinical trials in vascular cognitive impairment are in their infancy but support the value of therapeutic interventions for symptomatic treatment.

Schizophrenia as a Disorder of Neurodevelopment

Abstract: A combination of genetic susceptibility and environmental perturbations appear to be necessary for the expression of schizophrenia. In addition, the pathogenesis of the disease is hypothesized to be neurodevelopmental in nature based on reports of an excess of adverse events during the pre- and perinatal periods, the presence of cognitive and behavioral signs during childhood and adolescence, and the lack of evidence of a neurodegenerative process in most individuals with schizophrenia. Recent studies of neurodevelopmental mechanisms strongly suggest that no single gene or factor is responsible for driving a highly complex biological process. Together, these findings suggest that combinatorial genetic and environmental factors, which disturb a normal developmental course early in life, result in molecular and histogenic responses that cumulatively lead to different developmental trajectories and the clinical phenotype recognized as schizophrenia.

Strategic alliances as social capital: a multidimensional view

Abstract: Defining social capital in terms of the information benefits available to a firm due to its strategic alliances we present a theory of social capital that conceptualizes it as a multidimensional construct. We draw from the literature to argue that social capital yields three distinctly different kinds of information benefits in the form of information volume, information diversity, and information richness. This extends current theoretical and empirical research by specifying and empirically demonstrating three interrelated yet distinct dimensions of social capital. Firms vary in their levels of social capital not just on their structural position in an alliance network but also in the dynamics that underlie alliance formation and maintenance. More importantly, the different dimensions of social capital theoretically provide differential benefits. We establish the construct validity of our proposed three-dimensional conceptualization of social capital using longitudinal data on the population of strategic alliances formed during the period 1980–94 by firms in the global steel industry. In addition, we establish predictive validity by demonstrating that the information dimensions have differential effects on firm performance, using firm nationality as a contingency. Copyright © 2002 John Wiley & Sons, Ltd.

Decline in physical activity in black girls and white girls during adolescence.

Abstract: Background Physical activity declines during adolescence, but the underlying reasons remain unknown. Methods We prospectively followed 1213 black girls and 1166 white girls enrolled in the National Heart, Lung, and Blood Institute Growth and Health Study from the ages of 9 or 10 to the ages of 18 or 19 years. We used a validated questionnaire to measure leisure-time physical activity on the basis of metabolic equivalents (MET) for reported activities and their frequency in MET-times per week; a higher score indicated greater activity. Results The respective median activity scores for black girls and white girls were 27.3 and 30.8 MET-times per week at base line and declined to 0 and 11.0 by year 10 of the study (a 100 percent decline for black girls and a 64 percent decline for white girls, P<0.001). By the age of 16 or 17 years, 56 percent of the black girls and 31 percent of the white girls reported no habitual leisure-time activity. Lower levels of parental education were associated with greater declin...

Guiding Principles for Fostering Productive Disciplinary Engagement: Explaining an Emergent Argument in a Community of Learners Classroom

Abstract: This article suggests that productive disciplinary engagement can be fostered by designing learning environments that support (a) problematizing subject matter, (b) giving students authority to address such problems, (c) holding students accountable to others and to shared disciplinary norms, and (d) providing students with relevant resources. To provide empirical support for this suggestion, we use these 4 guiding principles to explain a case of productive disciplinary engagement from a Fostering Communities of Learners classroom. We use the principles to understand 1 group of students' emergent and sustained controversy over a species' classification. The students became passionately engaged, used evidence in scholarly ways, developed several arguments, and generated questions regarding biological classification. We propose the controversy as an example of productive disciplinary engagement, and show how it was supported by: the treatment of the classification as a legitimate problem by the students and...

Gene therapy progress and prospects: nonviral vectors.

Abstract: The success of gene therapy is largely dependent on the development of the gene delivery vector. Recently, gene transfection into target cells using naked DNA, which is a simple and safe approach, has been improved by combining several physical techniques, for example, electroporation, gene gun, ultrasound and hydrodynamic pressure. Chemical approaches have been utilized to improve the efficiency and cell specificity of gene transfer. Novel gene carrier molecules, which facilitate DNA escape from the endosome into the cytosol, have been developed. Several functional polymers, which enable controlled release of DNA in response to an environmental change, have also been reported. Plasmids with reduced number of CpG motifs, the use of PCR fragments and the sequential injection method have been established for the reduction of immune response triggered by plasmid DNA. Construction of a long-lasting gene expression system is also an important theme for nonviral gene therapy. To date, tissue-specific expression, self-replicating and integrating plasmid systems have been reported. Improvement of delivery methods together with intelligent design of the DNA itself has brought about large degrees of enhancement in the efficiency, specificity and temporal control of nonviral vectors.

Distrust, Race, and Research

Abstract: Background: Investigators have voiced concerns that distrust of research and the medical community inpedes successful recruitment of African Americans into clinical research. Objective: To examine possible differences in distrust by race and to determine to what extent other sociodemographic factors explain any racial differences in distrust. Methods: We analyzed data from 527 African American and 382 white respondents of a national telephone survey on participation in clinical research. Our main outcome was a 7-item index of distrust. Results: African American respondents were more likely that white respondents not to trust that their physicians would fully explain research participation (41.7% vs 23.4%,P<.01)and to state that they believed their physicians exposed them to unnecessary risks (45.5% vs 34.8%,P<.01). African American respondents had a significantly higher mean distrust index score than white respondents(3.1 vs 1.8,P<.01). After controlling for other sociodemographic variables in a logistic regression model, race remained strongly associated with a highter distrust score (prevalence odds ratio, 4.7;95% confidence interval,2.9-7.7). Conclusions: Even after controlling for markers of social class, African Americans were less trusting than white Americans. Racial differences in disturst have important implications for investigation as they engage African Americans in research.

Distributed model predictive control

Abstract: The article presents results for distributed model predictive control (MPC), focusing on i) the coordination of the optimization computations using iterative exchange of information and ii) the stability of the closed-loop system when information is exchanged only after each iteration. Current research is focusing on general methods for decomposing large-scale problems for distributed MPC and methods for guaranteeing stability when multiple agents are controlling systems subject to abrupt changes.

Biomechanical Analysis of an Anatomic Anterior Cruciate Ligament Reconstruction

Abstract: Background:The focus of most anterior cruciate ligament reconstructions has been on replacing the anteromedial bundle and not the posterolateral bundle.Hypothesis:Anatomic two-bundle reconstruction restores knee kinematics more closely to normal than does single-bundle reconstruction.Study Design:Controlled laboratory study.Methods:Ten cadaveric knees were subjected to external loading conditions: 1) a 134-N anterior tibial load and 2) a combined rotatory load of 5-N·m internal tibial torque and 10-N·m valgus torque. Resulting knee kinematics and in situ force in the anterior cruciate ligament or replacement graft were determined by using a robotic/universal force-moment sensor testing system for 1) intact, 2) anterior cruciate ligament deficient, 3) single-bundle reconstructed, and 4) anatomically reconstructed knees.Results:Anterior tibial translation for the anatomic reconstruction was significantly closer to that of the intact knee than was the single-bundle reconstruction. The in situ force normalize...

Frailty and Activation of the Inflammation and Coagulation Systems With and Without Clinical Comorbidities Results From the Cardiovascular Health Study

Abstract: Background The biological basis of frailty has been difficult to establish owing to the lack of a standard definition, its complexity, and its frequent coexistence with illness. Objective To establish the biological correlates of frailty in the presence and absence of concurrent cardiovascular disease and diabetes mellitus. Methods Participants were 4735 community-dwelling adults 65 years and older. Frail, intermediate, and nonfrail subjects were identified by a validated screening tool and exclusion criteria. Bivariate relationships between frailty level and physiological measures were evaluated by Pearson χ 2 tests for categorical variables and analysis of variance F tests for continuous variables. Multinomial logistic regression was performed to evaluate multivariable relationships between frailty status and physiological measures. Results Of 4735 Cardiovascular Health Study participants, 299 (6.3%) were identified as frail, 2147 (45.3%) as intermediate, and 2289 (48.3%) as not frail. Frail vs nonfrail participants had increased mean ± SD levels of C-reactive protein (5.5 ± 9.8 vs 2.7 ± 4.0 mg/L), factor VIII (13 790 ± 4480 vs 11 860 ± 3460 mg/dL), and, in a smaller subset, D dimer (647 ± 1033 vs 224 ± 258 ng/mL) ( P ≤.001 for all, χ 2 test for trend). These differences persisted when individuals with cardiovascular disease and diabetes were excluded and after adjustment for age, sex, and race. Conclusions These findings support the hypothesis that there is a specific physiological basis to the geriatric syndrome of frailty that is characterized in part by increased inflammation and elevated markers of blood clotting and that these physiological differences persist when those with diabetes and cardiovascular disease are excluded.

The persistence of knowledge‐based advantage: an empirical test for product performance and technological knowledge

Abstract: Resource-based theory maintains that intrinsic characteristics of resources and capabilities, such as their tacitness, complexity, and specificity, prevent imitation and thereby prolong exceptional performance. There is little direct evidence to verify these claims, yet a substantial literature encourages firms to formulate competitive strategies around resources with these attributes. Further, work outside the resource-based tradition suggests that these attributes can slow innovation, and it is not clear when this effect outweighs the benefits of inimitability. This paper seeks to clarify whether and how the complexity, tacitness, and specificity of a firm's knowledge affect the persistence of its performance advantages. We find that the complexity and tacitness of technological knowledge are useful for defending a firm's major product improvements from imitation, but not for protecting its minor improvements. The design specificity of technological knowledge delayed imitation of minor improvements in this study. Copyright © 2002 John Wiley & Sons, Ltd.

The sensorimotor system, part I: the physiologic basis of functional joint stability.

Abstract: Objective To define the nomenclature and physiologic mechanisms responsible for functional joint stability. Data sources Information was drawn from an extensive MEDLINE search of the scientific literature conducted in the areas of proprioception, neuromuscular control, and mechanisms of functional joint stability for the years 1970 through 1999. An emphasis was placed on defining pertinent nomenclature based on the original references. Data synthesis Afferent proprioceptive input is conveyed to all levels of the central nervous system. They serve fundamental roles in optimal motor control and sensorimotor control over functional joint stability. Conclusions/applications Sensorimotor control over the dynamic restraints is a complex process that involves components traditionally associated with motor control. Recognizing and understanding the complexities involved will facilitate the continued development and institution of management strategies based on scientific rationales.

Human SIR2 deacetylates p53 and antagonizes PML/p53-induced cellular senescence

Abstract: The yeast Sir2 protein mediates chromatin silencing through an intrinsic NAD-dependent histone deacetylase activity. Sir2 is a conserved protein and was recently shown to regulate lifespan extension both in budding yeast and worms. Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12). SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation. Moreover, we show that SIRT1 and p53 co-localize in nuclear bodies upon PML upregulation. When overexpressed in primary mouse embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence. Taken together, our data establish the SIRT1 deacetylase as a novel negative regulator of p53 function capable of modulating cellular senescence.

Identification of a novel population of muscle stem cells in mice potential for muscle regeneration

Abstract: Three populations of myogenic cells were isolated from normal mouse skeletal muscle based on their adhesion characteristics and proliferation behaviors. Although two of these populations displayed satellite cell characteristics, a third population of long-time proliferating cells expressing hematopoietic stem cell markers was also identified. This third population comprises cells that retain their phenotype for more than 30 passages with normal karyotype and can differentiate into muscle, neural, and endothelial lineages both in vitro and in vivo. In contrast to the other two populations of myogenic cells, the transplantation of the long-time proliferating cells improved the efficiency of muscle regeneration and dystrophin delivery to dystrophic muscle. The long-time proliferating cells' ability to proliferate in vivo for an extended period of time, combined with their strong capacity for self-renewal, their multipotent differentiation, and their immune-privileged behavior, reveals, at least in part, the basis for the improvement of cell transplantation. Our results suggest that this novel population of muscle-derived stem cells will significantly improve muscle cell–mediated therapies.