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GST Primary GST Primary Best Strategies for Health Care Quality Im... Best Strategies for Health Care Quality Improvement - Diabetes Quality Improvement Strategies for Antibio... Kathryn McDonald, Stanford-UCSF Evidence-b... Systematic review assessing the effect of ... Quality Improvement Strategies for Antibiotics Management Kathryn McDonald, Stanford-UCSF Evidence-based Practice Center, 117 Encina Commons, Stanford, CA 94305-6019, Kathy.mcdonald@stanford.edu Systematic review assessing the effect of quality improvement strategies on appropriate prescribing of antibiotics and appropriate choice of antibiotics. Adherence Adherence Assistive Devices Assistive Devices Childhood Burn Hanson MacMillan Childhood Burn Hanson MacMillan CLSA_9 CLSA_9 Cyberabuse Cyberabuse Cognitive Behavioural Therapy for Violent ... This review included randomized trials abo... Cognitive Behavioural Therapy for Violent Men who Batter Their Partners This review included randomized trials about the effects of cognitive behavioral therapy on domestic violence. The intervention included programs based on the Duluth Model. The violence had to be committed by a male toward his female partner. The violence also had to be physical. The primary outcomes were new arrests and convictions, and new reports of violence. CABG vs PCI CABG vs PCI Quality Improvement Strategies for Prevent... Quality Improvement Strategies for Preventing Nosocomial Infections (Created 17-Feb-06) Quality Improvement Strategies for Asthma ... Quality Improvement Strategies for Asthma Control Erectile Dysfunction (Created 30-Jan-06) Erectile Dysfunction (Created 30-Jan-06) Inequality - Smoking Cessation to Reduce S... This review was the first part of a projec... Inequality - Smoking Cessation to Reduce Socio-Economic Differences This review was the first part of a project about inequality. It included randomized trials about the effect of smoking cessation interventions on reducing socio-economic differences. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Diet and Physical Activity to Reduce Socio... This review was the second part in a proje... Diet and Physical Activity to Reduce Socio-Economic Differences This review was the second part in a project about inequality. It included randomized trials about the effect of interventions on reducing socio-economic differences in diet and physical activity. The studies had to report data either on persons with low socio-economic groups status or, preferably, on both low and high socio-economic groups. Workfare The data in SRS are not identical to the d... Workfare The data in SRS are not identical to the data in the published report. We used SRS only for an updated search. The review included randomized trials about the effect of welfare-to-work programs. Participants were welfare recipients. There were basically two types of programs. The educational type tried to build knowledge and skills in order to help the welfare recipients acquire jobs that could support them economically. The "work first" approach was more aimed at getting the participants quickly into a job. Exercise interventions for the management ... The objective of this systematic review wa... Exercise interventions for the management of frailty The objective of this systematic review was to examine the effectiveness of current exercise interventions on the management of frailty. A comprehensive search of Medline, Embase, Psycinfo, Cinahl, Scopus, Ageline, Eric, and SportDiscus databases was conducted and produced 1808 citations. So far we have completed 2 levels of “title and abstract” screening and we ended up with 262 articles. We have just started the full text screening. Eligibility criteria included original studies whose participants were identified as frail or prefrail with specific criteria and in which structured physical activity was included as at least one component of the intervention. Create a free account, build a dictionary with saved terms to re-use later! Public Domestic Violence - Using Cognitive Behavior Therapy Smoking Cessation to Reduce Socio-Economic Differences Diet and Physical Activity to Reduce Socio-Economic Differences Workfare Exercise Interventions for the Management of Frailty Search     Simple Advanced Refine (3 coded questions)  Any of these:   Exact Phrase: All of these: None of these: Author: Periodical: Projects: No restrictions   Libraries: Public   Select SRS Projects Show Saved Terms Select Library Show articles that do not have abstracts  Humans or Animals Humans Animals Ages All Infant: birth-23 months All Child: 0-18 years All Adult: 19+ years Newborn: birth-1 month Infant: 1-23 months Preschool Child: 2-5 years Child: 6-12 years Adolescent: 13-18 years Adult: 19-44 years Middle Aged: 45-64 years Middle Aged + Aged: 45+ years Aged: 65+ years 80 and over: 80+ years Undetermined Type of Article Clinical Trial Editorial Letter Meta-Analysis Practice Guideline Randomized Controlled Trial Review Addresses Bibliography Biography Case Reports Classical Article Clinical Conference Clinical Trial, Phase I Clinical Trial, Phase II Clinical Trial, Phase III Clinical Trial, Phase IV Comment Comparative Study Consensus Development Conference Consensus Development Conference, NIH Controlled Clinical Trial Corrected and Republished Article Dictionary Directory Duplicate Publication English Abstract Evaluation Studies Festschrift Government Publications Guideline Historical Article Interview In Vitro Journal Article Lectures Legal Cases Legislation Multicenter Study News Newspaper Article Overall Patient Education Handout Periodical Index Published Erratum Retracted Publication Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Retraction of Publication Scientific Integrity Review Support of Research Technical Report Twin Study Validation Studies Not a Primary Study or Review Unknown Primary Study Case Series Case Control Cohort Study Observational Study Qualitative Research CBA or ITS Registry Double Blind Controlled before after study Quasi-randomized trial Simple before after study Cluster-RCT Non-Randomized Study Report Book Book chapter Dissertation Conference procedings Secondary Research Not RCT Results(1-25 of 109) Sort By: Publication Date Relevance Took: 2.127 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 5 1 2 3 4 > Last >> (109 articles found) Hemodynamics instability score in chronic fatigue syndrome and in non-chronic fatigue syndrome. Dec 2002 Jochanan E Naschitz,Edmond Sabo,Shaul Naschitz,Itzhak Rosner,Michael Rozenbaum,Madeline Fields,Hillel Isseroff,Renata Musafia Priselac,Luis Gaitini,Samuel Eldar,Eli Zukerman,Daniel Yeshurun,Fields Madelain,Hillel Isseroff OBJECTIVE: In studying patients with chronic fatigue syndrome (CFS) we developed a method that confers numerical expression to the degree of blood pressure and heart rate lability, ie, the 'hemodynamic instability score' (HIS). The HIS in CFS patients differed significantly from healthy subjects. T... ( view more )he present investigation compares the HIS in CFS, non-CFS chronic fatigue and patients with recurrent syncope. METHODS: Patients with CFS (n = 21), non-CFS chronic fatigue (n = 24), syncope of unknown cause (n = 44), and their age and sex-matched healthy controls (n = 21) were evaluated with a standardized head-up tilt test (HUTT). Abnormal reactions (endpoints) on HUTT were classified 'clinical outcomes' (cardioinhibitory or vasodepressor reaction, orthostatic hypotension, postural tachycardia syndrome) and 'HIS endpoint', i.e. HIS >-0.98. RESULTS: The highest incidence of endpoints was noted in patients with CFS (79%), followed by patients with syncope of unknown cause (46%), non-CFS chronic fatigue (35%), and healthy subjects (14%). Presyncope or syncope during tilt occurred in 38% of CFS patients, 21% of patients with non-CFS chronic fatigue, and 43% of patients with recurrent syncope. The average HIS values were: CFS = +2.02 (SD 4.07), non-CFS chronic fatigue = -2.89 (SD 3.64), syncope = -3.2 (SD 3.0), healthy = -2.48 (4.07). The odds ratios for CFS patients to have HIS >-0.98 was 8.8 compared with non-CFS chronic fatigue patients, 14.6 compared with recurrent syncope patients, and 34.8 compared with healthy subjects. CONCLUSION: The cardiovascular reactivity in patients with CFS has certain features in common with the reactivity in patients with recurrent syncope or non-CFS chronic fatigue, such as the frequent occurrence of vasodepressor reaction, cardioinhibitory reaction, and postural tachycardia syndrome. Apart from to these shared responses, the large majority of CFS patients exhibit a particular abnormality which is characterized by HIS values >-0.98. Thus, HIS >-0.98 lends objective criteria to the assessment of CFS. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Dynamics of neutrophil infiltration during cutaneous wound healing and infection using fluorescence imaging. Jul 2008 Min-Ho Kim,Wei Liu,Dori L Borjesson,Fitz-Roy E Curry,Lloyd S Miller,Ambrose L Cheung,Fu-Tong Liu,R Rivkah Isseroff,Scott I Simon Neutrophil influx is an early inflammatory response that is essential for the clearance of bacteria and cellular debris during cutaneous wounding. A non-invasive real-time fluorescence imaging technique was developed to examine the kinetics of enhanced green fluorescence protein-polymorphonuclear l... ( view more )eukocyte (EGFP-PMN) influx within a wound. We hypothesized that infection or systemic availability would directly regulate the dynamics of EGFP-PMN recruitment and the efficiency of wound closure. Neutrophil recruitment increased dramatically over the first 24 hours from 10(6) at 4 hours up to a maximum of 5 x 10(6) EGFP-PMNs at 18 hours. A high rate of EGFP-PMN turnover was evidenced by approximately 80% decrease in EGFP signal within 6 hours. In response to wound colonization by Staphylococcus aureus or injection of GM-CSF, systemic PMNs increased twofold above saline control. This correlated with an increase in EGFP-PMN recruitment up to approximately 10(7) within the wound. Despite this effect by these distinct inflammatory drivers, wound closure occurred at a rate similar to the saline-treated control group. In summary, a non-invasive fluorescence-based imaging approach combined with genetic labeling of neutrophils provides a dynamic inner view of inflammation and the kinetics of neutrophil infiltration into the wounded skin over extended durations. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Direct Binding of Integrin {alpha}v{beta}3 to FGF1 Plays a Role in FGF1 Signaling. Jun 27, 2008 Seiji Mori,Chun-Yi Wu,Satoshi Yamaji,Jun Saegusa,Biao Shi,Zi Ma,Yasuko Kuwabara,Kit S Lam,R Rivkah Isseroff,Yoko K Takada,Yoshikazu Takada Integrins play a role in fibroblast growth factor (FGF) signaling through cross-talk with FGF receptors (FGFRs), but the mechanism underlying the cross-talk is unknown. We discovered that FGF1 directly bound to soluble and cell-surface integrin alphavbeta3 (K(D) about 1 mum). Antagonists to alphavb... ( view more )eta3 (monoclonal antibody 7E3 and cyclic RGDfV) blocked this interaction. alphavbeta3 was the predominant, if not the only, integrin that bound to FGF1, because FGF1 bound only weakly to several beta1 integrins tested. We presented evidence that the CYDMKTTC sequence (the specificity loop) within the ligand-binding site of beta3 plays a role in FGF1 binding. We found that the integrin-binding site of FGF1 overlaps with the heparin-binding site but is distinct from the FGFR-binding site using docking simulation and mutagenesis. We identified an FGF1 mutant (R50E) that was defective in integrin binding but still bound to heparin and FGFR. R50E was defective in inducing DNA synthesis, cell proliferation, cell migration, and chemotaxis, suggesting that the direct integrin binding to FGF1 is critical for FGF signaling. Nevertheless, R50E induced phosphorylation of FGFR1 and FRS2alpha and activation of AKT and ERK1/2. These results suggest that the defect in R50E in FGF signaling is not in the initial activation of FGF signaling pathway components, but in the later steps in FGF signaling. We propose that R50E is a useful tool to identify the role of integrins in FGF signaling. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Label-retaining cells of the bladder: candidate urothelial stem cells. Jun 2008 Eric A Kurzrock,Deborah K Lieu,Lea A Degraffenried,Camie W Chan,Roslyn R Isseroff Adult tissue stem cells replicate infrequently, retaining DNA nucleotide label (BrdU) for much longer periods than mature, dividing cells in which the label is diluted during a chase period. Those "label-retaining cells" (LRCs) have been identified as the tissue stem cells in skin, cornea, intestin... ( view more )e, and prostate. However, in the urinary tract uroepithelial stem cells have not yet been identified. In this study, BrdU administration identified urothelial LRCs in the rat bladder with 9% of the epithelial basal cells retaining BrdU label 1 yr after its administration. Markers for stem cells in other tissues, Bcl, p63, cytokeratin 14, and beta1 integrin, were immunolocalized in the basal bladder epithelium in or near urothelial LRCs, but not uniquely limited to these cells. Flow cytometry demonstrated that urothelial LRCs were small, had low granularity, and were uniquely beta4 integrin bright. Urothelium from long-term labeled bladders was cultured and LRCs were found to be significantly more clonogenic and proliferative, characteristics of stem cells, than unlabeled urothelial cells. Thus, this work demonstrates that LRCs in the bladder localize to the basal layer, are small, low granularity, uniquely beta4 integrin rich, slowly cycling and demonstrate superior clonogenic and proliferative ability compared with unlabeled epithelial cells. We propose that LRCs represent putative urothelial stem cells. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Electrocardiographic QT interval and cardiovascular reactivity in fibromyalgia differ from chronic fatigue syndrome. May 2008 Jochanan E Naschitz,Gleb Slobodin,Dauod Sharif,Madeline Fields,Hillel Isseroff,Edmond Sabo,Itzhak Rosner BACKGROUND: Fibromyalgia (FM) and chronic fatigue syndrome (CFS) frequently overlap clinically and have been considered variants of one common disorder. We have recently shown that CFS is associated with a short corrected electrocardiographic QT interval (QTc). In the present study, we evaluated wh... ( view more )ether FM and CFS can be distinguished by QTc. METHODS: The study groups were comprised of women with FM (n=30) and with CFS (n=28). The patients were evaluated with a 10 min supine-30 min head-up tilt test. The electrocardiographic QT interval was corrected for heart rate (HR) according to Fridericia's equation (QTc). In addition, cardiovascular reactivity was assessed based on blood pressure and HR changes and was expressed as the 'hemodynamic instability score' (HIS). RESULTS: The average supine QTc in FM was 417 ms (SD 25) versus 372 ms (SD 22) in CFS (p<0.0001); the supine QTc cut-off <385.7 ms was 79% sensitive and 87% specific for CFS vs. FM. The average QTc at the 10th minute of tilt was 409 ms (SD 18) in FM versus 367 ms (SD 21) in CFS (p<0.0001); the tilt QTc cut-off <383.3 ms was 71% sensitive and 91% specific for CFS vs. FM. The average HIS in FM patients was -3.52 (SD 1.96) versus +3.21 (SD 2.43) in CFS (p<0.0001). CONCLUSION: A relatively short QTc and positive HIS characterize CFS patients and distinguish them from FM patients. These data may support the contention that FM and CFS are separate disorders. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Beta2-adrenergic receptor signaling mediates corneal epithelial wound repair. May 2008 Shahed Y Ghoghawala,Mark J Mannis,Christine E Pullar,Mark I Rosenblatt,R Rivkah Isseroff PURPOSE: Beta-adrenergic receptor (AR) antagonists are frequently prescribed ophthalmic drugs, yet previous investigations into how catecholamines affect corneal wound healing have yielded conflicting RESULTS: With the use of an integrated pharmacologic and genetic approach, the authors investigate... ( view more )d how the beta-AR impacts corneal epithelial healing. METHODS: Migratory rates of cultured adult murine corneal epithelial (AMCE) cells and in vivo corneal wound healing were examined in beta2-AR(+/+) and beta2-AR(-/-) mice. Signaling pathways were evaluated by immunoblotting. results. The beta-AR agonist isoproterenol decreased AMCE cell migratory speed to 70% of untreated controls, and this was correlated with a 0.60-fold decrease in levels of activated phospho-ERK (P-ERK). Treatment with the beta-AR antagonist (timolol) increased speed 33% and increased P-ERK 2.4-fold (P < 0.05). The same treatment protocols had no effect on AMCE cells derived from beta2-AR(-/-) mice; all treatment groups showed statistically equivalent migratory speeds and ERK phosphorylation. In beta2-AR(+/+) animals, the beta-AR agonist (isoproterenol) delayed the rate of in vivo corneal wound healing by 79%, whereas beta-AR antagonist (timolol) treatment increased the rate of healing by 16% (P < 0.05) compared with saline-treated controls. In contrast, in the beta2-AR(-/-) mice, all treatment groups demonstrated equivalent rates of wound healing. Additionally, murine corneal epithelial cell expressed the catecholamine-synthesizing enzyme tyrosine hydroxylase and detectable levels of epinephrine (184.5 pg/mg protein). CONCLUSIONS: The authors provide evidence of an endogenous autocrine catecholamine signaling pathway dependent on an intact beta2-AR for the modulation of corneal epithelial wound repair. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Responses of the 27-kDa heat shock protein to UVB irradiation in human epidermal melanocytes. Feb 2008 Biao Shi,Jennifer C Grahn,Debra A Reilly,Theresa C Dizon,R Rivkah Isseroff Solar ultraviolet radiation (UVR) is a major environmental hazard for the skin, and UVB (280-320 nm) has been proposed to be a main factor for melanoma development. In response to sunlight exposure, the skin has adapted a number of innate resistance mechanisms. Among them is the small heat shock pr... ( view more )otein of 27 kDa (HSP27) known to play a role in the protection of cells from variety of environmental insults including UV irradiation. In this study, we demonstrated that UVB irradiation of cultured normal epidermal melanocytes initiates changes in HSP27 phosphorylation and localization. In unstressed melanocytes, HSP27 was present as the non-phosphorylated isoform. UVB irradiation with a physiological dose (7-25 mJ/cm(2)) resulted in the formation of a mono-phosphorylated isoform and sometimes a bi-phosphorylated isoform. The UVB-induced HSP27 phosphorylation was inhibited when melanocytes were treated with the antioxidant N-acetyl cysteine or inhibitor of p38 MAP kinase prior to UVB exposure, suggesting that UVB induced HSP27 phosphorylation through reactive oxygen species/p38 MAP kinase pathway. In response to UBV irradiation, HSP27 in melanocytes translocated from the cytoplasm to the nucleus. The HSP27 responses may provide some protective role against UVB-induced cell damage in the skin. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Association between the use of beta-adrenergic receptor agents and the development of venous leg ulcers. Oct 2007 David J Margolis,Ole Hoffstad,R Rivkah Isseroff OBJECTIVE: To explore an association between the use of beta-adrenergic receptor agonists or antagonists and the onset of venous leg ulcers (VLUs). DESIGN: Retrospective cohort study. SETTING: Ambulatory setting of general practice in the United Kingdom. Patients Patients followed by participating ... ( view more )physicians. MAIN OUTCOME MEASURE: Onset of VLU. RESULTS: A total of 414 887 patients registered in the General Practice Research Database met our study criteria for eligibility. Of these individuals, 62 886 were exposed to a beta-adrenergic receptor agonist and 54 861 were exposed to a beta-adrenergic receptor antagonist (6620 used both beta-adrenergic receptor antagonists and agonists). Of those exposed to a beta-adrenergic receptor agonist, 15.5% developed a VLU, whereas 18.4% of those who were not exposed developed a VLU. Of those exposed to a beta-adrenergic receptor antagonist, 18.2% developed a VLU, whereas 19.9% of those not exposed developed a VLU. The odds ratio (OR) of association between beta-adrenergic receptor antagonist and VLUs was 1.02 (95% confidence interval [CI], 0.99-1.04); for the association between beta-adrenergic receptor agonist and VLUs, 0.84 (95% CI, 0.82-0.86). The fully adjusted ORs were 1.04 (95% CI, 0.98-1.11) and 0.44 (95% CI, 0.42-0.45), respectively. Furthermore, using propensity score models, we were able to confirm the association for beta-adrenergic receptor agonist users. In addition, beta-adrenergic receptor antagonist users in many of the propensity score quintiles were also protected from developing VLUs. CONCLUSIONS: A protective association between beta-adrenergic receptor agonists and perhaps beta-adrenergic receptor antagonists and VLUs exists. There is strong laboratory evidence to support these epidemiologic findings. The evidence in this study should not be used as a rationale for treatment of VLUs with beta-adrenergic receptor agents but should be compelling for the consideration of a randomized clinical trial. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Beta adrenergic receptors in keratinocytes. Oct 2007 Raja K Sivamani,Susanne T Lam,R Rivkah Isseroff Beta2 adrenergic receptors were identified in keratinocytes more than 30 years ago, but their function in the epidermis continues to be elucidated. Abnormalities in their expression, signaling pathway, or in the generation of endogenous catecholamine agonists by keratinocytes have been implicated i... ( view more )n the pathogenesis of cutaneous diseases such as atopic dermatitis, vitiligo, and psoriasis. New studies also indicate that the beta2AR also modulates keratinocyte migration, and thus can function to regulate wound reepithelialization. This review focuses on the function of these receptors in keratinocytes and their contribution to cutaneous physiology and disease. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Economical LED based, real-time, in vivo imaging of murine corneal wound healing. Jun 2007 S Y Ghoghawala,M J Mannis,C J Murphy,M I Rosenblatt,R R Isseroff An optimal system for monitoring in vivo corneal wound healing is inexpensive, has utility for wounding and imaging, and is able to provide previews before photography. We outline such an imaging system that takes advantage of a consumer digital camera and an LED-based light source for fluorescein ... ( view more )excitation. Using FVB/NJ mice, 2mm diameter, circular, axial corneal epithelial defects were created using a crescent blade. The corneal wounds were imaged every four hours until healed using a Nikon Coolpix 5400 camera attached to a Nikon SMZ-10A stereomicroscope, using the illumination from a 16 LED 464nm flashlight. The wound area was calculated, and the linear regressions of the linear phase of wound healing were compared using the F-test. The slopes of the linear regressions for the 6 trials of 4 mice/trial had an average of -52.95microm/h (SEM=0.55microm/h) and were statistically equivalent (p>0.05). The mean of the R(2) values for the linear regressions was 0.9546 (SEM=0.0121). The equivalent linear regressions and R(2)>0.90 suggest that the imaging system could precisely monitor the wound healing of multiple trials and of animals within each trial, respectively. Using a consumer digital camera and LED-based illumination, we have established a system that is economical, is used in both wounding and imaging, is operated by a single person, and is able to provide real-time previews to monitor corneal wound healing precisely. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Beta-adrenergic receptor agonists delay while antagonists accelerate epithelial wound healing: evidence of an endogenous adrenergic network within the corneal epithelium. Apr 2007 Christine E Pullar,Min Zhao,Bing Song,Jin Pu,Brian Reid,Shahed Ghoghawala,Colin McCaig,R Rivkah Isseroff Wound healing is a complex and well-orchestrated biological process. Corneal epithelial cells (CECs) must respond quickly to trauma to rapidly restore barrier function and protect the eye from noxious agents. They express a high level of beta2-adrenergic receptors but their function is unknown. Her... ( view more )e, we report the novel finding that they form part of a regulatory network in the corneal epithelium, capable of modulating corneal epithelial wound repair. Beta-adrenergic receptor agonists delay CEC migration via a protein phosphatase 2A-mediated mechanism and decrease both electric field-directed migration and corneal wound healing. Conversely, beta-adrenergic receptor antagonists accelerate CEC migration, enhance electric field-mediated directional migration, and promote corneal wound repair. We demonstrate that CECs express key enzymes required for epinephrine (beta-adrenergic receptor agonist) synthesis in the cytoplasm and can detect epinephrine in cell extracts. We propose that the mechanism for the pro-motogenic effect of the beta-adrenergic antagonist is blockade of the beta2-adrenergic receptor preventing autocrine catecholamine binding. Further investigation of this network will improve our understanding of one of the most frequently prescribed class of drugs. ( view less ) View Full Abstract View Article Details   Related Articles Urothelial progenitor cells: regional differences in the rat bladder. Apr 2007 M M Nguyen,D K Lieu,L A deGraffenried,R R Isseroff,E A Kurzrock OBJECTIVES: Because the trigone is a unique region in the caudal bladder with a higher risk of neoplasia, we hypothesized that this area would have a high proportion of progenitor cells. As yet there is no marker nor methodology to specifically isolate urothelial stem cells, and thus demonstrate mu... ( view more )lti-potential differentiation and self-renewal. Here, our goal was to evaluate the distribution of progenitor cells that carry two general major attributes of stem cells: clonogenicity and proliferative capacity. MATERIALS AND METHODS: The bladders of Fisher rats were divided into caudal and cephalic segments and primary cultures were established from the harvested urothelial cells. RESULTS: We found that colony-forming efficiency was almost 2-fold higher for cells from the caudal bladder compared to the cephalic bladder. Doubling time was significantly faster for cells harvested from the caudal bladder at initial plating. This suggested that the caudal bladder harbours a higher density of urothelial progenitor cells. With passage to p4, the differences between the upper and lower bladder were lost, suggesting selection of proliferative cells with serial passage. Based on Ki-67 staining, there was no geographical difference in cell proliferation under normal homeostatic in vivo conditions. CONCLUSIONS: These results demonstrate geographical sequestration of urothelial progenitor cells to the area of the bladder that encompasses the bladder neck and trigone, which may be a factor in pathological disparities between the trigone and remaining bladder. ( view less ) View Full Abstract View Article Details   Related Articles Beta1 integrin expression pattern in transitional urothelium does not allow for efficient stem cell enrichment as in other epithelia. Feb 2007 Deborah K Lieu,Lea A Degraffenried,Roslyn R Isseroff,Eric A Kurzrock With a lack of distinct stem cell markers, isolation of tissue-specific stem cells for tissue engineering and gene therapy is a great challenge. Beta (beta)(1) integrin expression has been used as a way of enriching for putative epithelial stem cells through rapid adhesion to collagen IV or flow cy... ( view more )tometry. This is a first report of enrichment of putative urothelial stem cells using rapid adhesion and flow cytometric methods. We assessed our success by determining the clonogenic and proliferative potential of the isolated cells. We demonstrated that enrichment based on beta(1) integrin expression with flow cytometry yields highly clonogenic and proliferative urothelial cells, whereas the rapid adhesion method is not as efficient, possibly because of the unique nature of urothelium, a transitional epithelium, compared to results reported in stratified and columnar epithelia. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Wound re-epithelialization: modulating keratinocyte migration in wound healing. 2007 Raja,K Sivamani,Miki Shirakawa Garcia,R Rivkah Isseroff An essential feature of a healed wound is the restoration of an intact epidermal barrier through wound epithelialization, also known as re-epithelialization. The directed migration of keratinocytes is critical to wound epithelialization and defects in this function are associated with the clinical ... ( view more )phenotype of chronic non-healing wounds. A complex balance of signaling factors and surface proteins are expressed and regulated in a temporospatial manner that promote keratinocyte motility and survival to activate wound re-epithelialization. The majority of this review focuses on the mechanisms that regulate keratinocyte migration in the re-epithelialization process. This includes a review of cell attachments via desmosomes, hemidesmosomes, and integrins, the expression of keratins, the role of growth factors, cytokines and chemokines, eicosanoids, oxygen tension, antimicrobial peptides, and matrix metalloproteinases. Also reviewed are recently emerging novel mediators of keratinocyte motility including the role of electric fields, and signaling via the acetylcholine and beta-adrenergic receptors. These multiple regulators impact the ability of keratinocytes to migrate from the wound edge or other epidermal reservoirs to efficiently re-epithelialize a breach in the integrity of the epidermis. New discoveries will continue to uncover the elegant network of events that result in restoration of epidermal integrity and complete the wound repair process. ( view less ) View Full Abstract View Article Details   Related Articles beta4 integrin and epidermal growth factor coordinately regulate electric field-mediated directional migration via Rac1. Nov 2006 Christine E Pullar,Brian S Baier,Yoshinobu Kariya,Alan J Russell,Basil A J Horst,M Peter Marinkovich,R Rivkah Isseroff Endogenous DC electric fields (EF) are present during embryogenesis and are generated in vivo upon wounding, providing guidance cues for directional cell migration (galvanotaxis) required in these processes. To understand the role of beta (beta)4 integrin in directional migration, the migratory pat... ( view more )hs of either primary human keratinocytes (NHK), beta4 integrin-null human keratinocytes (beta4-), or those in which beta4 integrin was reexpressed (beta4+), were tracked during exposure to EFs of physiological magnitude (100 mV/mm). Although the expression of beta4 integrin had no effect on the rate of cell movement, it was essential for directional (cathodal) migration in the absence of epidermal growth factor (EGF). The addition of EGF potentiated the directional response, suggesting that at least two distinct but synergistic signaling pathways coordinate galvanotaxis. Expression of either a ligand binding-defective beta4 (beta4+AD) or beta4 with a truncated cytoplasmic tail (beta4+CT) resulted in loss of directionality in the absence of EGF, whereas inhibition of Rac1 blinded the cells to the EF even in the presence of EGF. In summary, both the beta4 integrin ligand-binding and cytoplasmic domains together with EGF were required for the synergistic activation of a Rac-dependent signaling pathway that was essential for keratinocyte directional migration in response to a galvanotactic stimulus. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Shortened QT interval: a distinctive feature of the dysautonomia of chronic fatigue syndrome. Oct 2006 Jochanan Naschitz,Madeline Fields,Hillel Isseroff,Dauod Sharif,Edmond Sabo,Itzhak Rosner PURPOSE: Because autonomic nervous functioning is frequently abnormal in chronic fatigue syndrome (CFS), we examined whether the corrected QT interval (QTc) in CFS differs from QTc in other populations. METHODS: The QTc was calculated at the end of 10 minutes of recumbence and the end of 10 minutes... ( view more ) of head-up tilt. In a pilot study, groups of 15 subjects, CFS, and controls, matched for age and sex, were investigated. In a second phase of the study, the QTc was measured in larger groups of CFS (n = 30) and control patients (n = 96) not matched for demographic features. RESULTS: In the pilot study, the average supine QTc in CFS was 0.371 +/- 0.02 seconds and QTc on tilt, 0.385 +/- 0.02 seconds, significantly shorter than in controls (P = .0002 and .0003, respectively). Results of phase II confirmed this data. CONCLUSIONS: Relative short QTc intervals are features of the CFS-related dysautonomia. The significance of this finding is discussed. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles UVB irradiation-induced changes in the 27-kd heat shock protein (HSP27) in human corneal epithelial cells. Sep 2006 Biao Shi,Bin Han,Ivan R Schwab,R Rivkah Isseroff PURPOSE: This study investigated the presence of the 27-kd heat shock protein (HSP27) and its responses to ultraviolet B (UVB) irradiation in human corneal epithelium and in cultured corneal epithelial cells. METHODS: Human corneal epithelial cells including presumed corneal epithelial stem cells w... ( view more )ere cultured in vitro. HSP27 expression and intracellular localization in normal corneas or cultured corneal cells were examined using immunofluorescence staining. The expression of HSP27 in cultured corneal cells was also detected using western blotting, and the phosphorylated isoforms of HSP27 were identified using isoelectric focusing. RESULTS: In normal corneal tissue, HSP27 was present in limbal basal and suprabasilar epithelial cells. In cultured epithelial corneal cells, HSP27 expression was heterogeneous: Some cells expressed virtually no HSP27 and others showed relatively strong expression. HSP27 was localized to the cytoplasm in nonstressed cells and translocated to the perinuclear and nuclear areas after UVB irradiation. UVB irradiation also induced the phosphorylation of HSP27, resulting in the increase in monophosphorylated isoform and formation of biphosphorylated isoform. UV induced the phosphorylation of HSP27 apparently through activation of p38 mitogen-activated protein kinase. CONCLUSION: HSP27 is present mainly as a nonphosphorylated isoform in corneal epithelium and cultured corneal epithelial cells under nonstressed conditions. The constitutional expression of HSP27 suggests that it plays a physiologic role in the cornea. After UVB irradiation, HSP27 undergoes rapid phosphorylation and translocation. This stress response may be related to a protective role of HSP27 for survival of UVB-exposed corneal cells. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles beta-Adrenergic receptor antagonists accelerate skin wound healing: evidence for a catecholamine synthesis network in the epidermis. Jul 28, 2006 Christine E Pullar,Amilcar Rizzo,R Rivkah Isseroff The skin is our primary defense against noxious environmental agents. Upon injury, keratinocytes migrate directionally into the wound bed to initiate re-epithelialization, essential for wound repair and restoration of barrier integrity. Keratinocytes express a high level of beta2-adrenergic recepto... ( view more )rs (beta2-ARs) that appear to play a role in cutaneous homeostasis as aberrations in either keratinocyte beta2-AR function or density are associated with various skin diseases. Here we report the novel finding that beta-AR antagonists promote wound re-epithelialization in a "chronic" human skin wound-healing model. beta-AR antagonists increase ERK phosphorylation, the rate of keratinocyte migration, electric field-directed migration, and ultimately accelerate human skin wound re-epithelialization. We demonstrate that keratinocytes express two key enzymes required for catecholamine (beta-AR agonist) synthesis, tyrosine hydroxylase and phenylethanolamine-N-methyl transferase, both localized within keratinocyte cytoplasmic vesicles. Finally, we confirm the synthesis of epinephrine by measuring the endogenously synthesized catecholamine in keratinocyte extracts. Previously, we have demonstrated that beta-AR agonists delay wound re-epithelialization. Here we report that the mechanism for the beta-AR antagonist-mediated augmentation of wound repair is due to beta2-AR blockade, preventing the binding of endogenously synthesized epinephrine. Our work describes an endogenous beta-AR mediator network in the skin that can temporally regulate skin wound repair. Further investigation of this network will improve our understanding of both the skin repair process and the multiple modes of action of one of the most frequently prescribed class of drugs, hopefully resulting in a new treatment for chronic wounds. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The beta 2-adrenergic receptor activates pro-migratory and pro-proliferative pathways in dermal fibroblasts via divergent mechanisms. Feb 1, 2006 Christine E Pullar,R Rivkah Isseroff Dermal fibroblasts are required for skin wound repair; they migrate into the wound bed, proliferate, synthesize extracellular matrix components and contract the wound. Although fibroblasts express beta2-adrenergic receptors (beta2-AR) and cutaneous keratinocytes can synthesize beta-AR agonists (cat... ( view more )echolamines), the functional significance of this hormonal mediator network in the skin has not been addressed. Emerging studies from our laboratory demonstrate that beta2-AR activation modulates keratinocyte migration, essential for wound re-epithelialization. Here we describe an investigation of the effects of beta2-AR activation on the dermal component of wound healing. We examined beta2-AR-mediated regulation of biological processes in dermal fibroblasts that are critical for wound repair: migration, proliferation, contractile ability and cytoskeletal conformation. We provide evidence for the activation of at least two divergent beta2-AR-mediated signaling pathways in dermal fibroblasts, a Src-dependent pro-migratory pathway, transduced through the epidermal growth factor receptor and extracellular signal-regulated kinase, and a PKA-dependent pro-proliferative pathway. beta2-AR activation attenuates collagen gel contraction and alters the actin cytoskeleton and focal adhesion distribution through PKA-dependent mechanisms. Our work uncovers a previously unrecognized role for the adrenergic hormonal mediator network in the cutaneous wound repair process. Exploiting these divergent beta2-AR agonist responses in cutaneous cells may generate novel therapeutic approaches for the control of wound healing. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Arsenite pre-conditioning reduces UVB-induced apoptosis in corneal epithelial cells through the anti-apoptotic activity of 27 kDa heat shock protein (HSP27). Feb 2006 Biao Shi,R Rivkah Isseroff Exposure to ultraviolet (UV) light poses a health risk for eye disease, and solar ultraviolet in the B range (UVB, 280-320 nm) is known to be related to various corneal disorders. In this study, we investigated whether pre-conditioning of cells with arsenite (AsO2(-1)) can reduce UVB-induced apopto... ( view more )sis in human corneal epithelial cells, and whether the anti-apoptotic activity of 27 kDa heat shock protein (HSP27), a small heat shock protein, plays a role in this protection. UVB at levels comparable to physiologic solar exposure induces apoptosis of corneal epithelial cells in culture, demonstrated by activation of caspase 9 and caspase 3, and DNA fragmentation. When cells were pre-conditioned with arsenite prior to UVB exposure, the UVB-induced cell death was reduced, and UVB-induced activation of caspases and DNA fragmentation was inhibited. When cells were pre-treated with SB 203580, which inhibits HSP27 phosphorylation through inhibition of p38 MAP kinase activation, the arsenite-induced reduction of UVB-induced apoptosis was partially reversed. Arsenite pre-conditioning inhibited UVB-induced apoptosis in a two-phase pattern, which was temporally correlated with arsenite-induced HSP27 expression and phosphorylation. Neutralization of intracellular HSP27 with its antibody reduced arsenite's inhibition of UVB-induced caspase3 activation. Our results suggest that forms of stress that upregulate HSP27 and its phosphorylation may be useful as novel approaches to prevent adverse ocular effects arising from UV exposure in humans. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Characterization of palladium nanoparticles by using X-ray reflectivity, EXAFS, and electron microscopy. Jan 17, 2006 Yuan Sun,Anatoly I Frenkel,Rebecca Isseroff,Cheryl Shonbrun,Michelle Forman,Kwanwoo Shin,Tadanori Koga,Henry White,Lihua Zhang,Yimei Zhu,Miriam H Rafailovich,Jonathan C Sokolov We compared the characteristics of dodecanethiolate palladium nanoparticles synthesized by two different techniques, a one-phase method and a two-phase method. From transmission electron microscopy (TEM), we determined that the particle sizes were 46 +/- 10 angstroms and 20 +/- 5 angstroms for the ... ( view more )one- and two-phase particles, respectively. Electron diffraction confirmed that their structure was face-centered cubic (fcc). The lattice constant a0 was 3.98 +/- 0.01 angstroms and 3.90 +/- 0.01 angstroms for the one- and two-phase particles, respectively. High-resolution TEM (HRTEM) showed that the one-phase particles had an ordered core surrounded by a disordered shell structure, while the two-phase particles appeared to be crystalline throughout. The particles were also analyzed with extended X-ray absorption fine structure (EXAFS). A cuboctahedral fcc model was used to fit the data, which implied particle sizes of less than 10 angstroms for both the one- and two-phase particles. The discrepancy between the two techniques was attributed to the presence of a disordered phase, which we presumed was composed of Pd-S compounds. Compared with the bulk palladium, lattice expansion was observed in both one- and two-phase particles by electron diffraction, HRTEM, and EXAFS. At the air/water interface, a uniform film that produced surface pressure/area isotherms could only be obtained from the two-phase particles. The one-phase particles did not wet the water surface. X-ray reflectivity data indicated that the Langmuir monolayer of the two-phase particles was only 13 angstroms thick. TEM revealed the diameter of the particles in this layer to be 23 angstroms; hence the particles assumed an oblate structure after spreading. EXAFS examination of a stack of 750 Langmuir monolayers indicated far fewer Pd-S compounds, which may have dissolved in the water. The data were consistent with a model of a monolayer of truncated cuboctahedron Pd particles that were 7 angstroms thick and 19 angstroms in diameter. ( view less ) View Full Abstract View Article Details   Related Articles Microneedle array for measuring wound generated electric fields. 2006 E V Mukerjee,R R Isseroff,R Nuccitelli,S D Collins,R L Smith A microneedle array has been fabricated and applied to the measurement of transdermal skin potentials in human subjects. Potential changes were recorded in the vicinity of superficial wounds, confirming the generation of a lateral electric field in human skin. The measured electric field decays wit... ( view more )h distance from the wound edge, and is directed towards the wound. The measurement of endogenous fields in skin is a prelude to the study of the therapeutic efficacy of applied electric fields to chronic non-healing wounds. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Beta2-adrenergic receptor activation delays wound healing. Jan 2006 Christine E Pullar,Jennifer C Grahn,Wei Liu,R Rivkah Isseroff Keratinocytes migrate directionally into the wound bed to initiate re-epithelialization, necessary for wound closure and restoration of barrier function. They solely express the beta2-adrenergic receptor (beta2-AR) subtype of beta-ARs and can also synthesize beta-AR agonists generating a hormonal m... ( view more )ediator network in the skin. Emerging studies from our laboratory demonstrate that beta-AR agonists decrease keratinocyte migration via a protein phosphatase (PP) 2A-dependent mechanism. Here we have extended our investigations to observe the effects of beta2-AR activation on keratinocyte polarization, migration, and ERK phosphorylation at the wound edge, cytoskeletal organization, phospho-ERK intracellular localization, proliferation, human skin wound re-epithelialization, wound-induced ERK phosphorylation, and murine skin wound healing. We demonstrate that in keratinocytes, beta2-AR activation is anti-motogenic and anti-mitogenic with both mechanisms being PP2A dependent. beta2-AR activation dramatically alters the organization of the actin cytoskeleton and prevents localization of phospho-ERK to the lamellipodial edge and its colocalization with vinculin. Finally, we demonstrate a beta2-AR-mediated delay in re-epithelialization and decrease in wound-induced epidermal ERK phosphorylation in human skin wounds and a delay in re-epithelialization in murine tail-clip wounds. Our work uncovers novel keratinocyte biology and a previously unrecognized role for the adrenergic hormonal mediator network in the wound repair process. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Topical negative pressure devices: use for enhancement of healing chronic wounds. Nov 2005 Miki Shirakawa,R Rivkah Isseroff Chronic wounds present a significant challenge, because there are few available treatment options for timely healing. Topical negative pressure devices have been used in a number of different types of wounds, including chronic wounds. They are believed to hasten wound healing by (1) maintaining a m... ( view more )oist environment, (2) removing wound exudates, (3) increasing local blood flow, (4) increasing granulation tissue formation, (5) applying mechanical pressure to promote wound closure, and (6) reducing bacterial loads in the wound. Multiple nonrandomized, noncontrolled studies have reported that the use of these devices results in faster healing times and more successful closures. Five small randomized, controlled trials have also shown favorable outcomes with the use of topical negative pressure devices compared with conventional treatment. Adverse effects include discomfort, pain, and excessive tissue growth into the dressing. Complications are limited if the device is used properly. In light of the current treatment options, topical negative pressure devices may be considered useful as adjuvant therapy for chronic wounds; however, there is inadequate definitive evidence that wound healing is substantially better with these devices than with traditional therapy. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Factors modulating p63 expression in cultured limbal epithelial cells. Oct 2005 Hani Salehi-Had,Lenio S Alvarenga,Rivkah Isseroff,Ivan R Schwab PURPOSE: The expression pattern of p63, a homologue of the transcription factor p53, and whether it can be used as a corneal epithelial stem cell specific marker remain controversial. We investigated the p63 expression pattern in cultured limbal epithelial cells at different time points in culture,... ( view more ) in sparse and confluent cultures, after growth factor starvation, and in single-cell-derived colonies. METHODS: Harvested limbal epithelial cells were plated at 2.5 (sparse) or 5 (dense) x 10 cells/cm and evaluated for p63 expression at day 1, day 4, day 7, after starvation for 72 hours, or in colonies derived from single cells. Expression of corneal lineage specific differentiation marker keratin 3 (K3) was correlated with p63 expression. Results were compared by 1-way ANOVA. RESULTS: More than 85% (85%-90%) of cells expressed p63 on day 1 regardless of cell plating density. On day 4, sparsely plated cultures were subconfluent and demonstrated high p63 expression (87.4%), whereas densely plated cells were confluent and had markedly reduced p63 expression (16.9%). Starvation of subconfluent cultures arrested cell division but did not decrease p63 expression. High-p63-expressing cultures expressed low levels of K3, and this trend was reversed in confluent cultures. Most cells in all colonies derived from single cells expressed p63. CONCLUSIONS: The majority of corneal limbal epithelial cells express p63 in colonies derived from single cells and in subconfluent cultures regardless of time in culture or continuance of cell division. This suggests that p63 expression in culture cannot be used as a marker for stem cells. Significantly reduced number of cells express p63 in confluent cultures, associated with increased cell-cell contact. It is notable that these cells continue to express p63 amid areas of increased cell-cell contact several days after cultures have attained full confluency. This may represent a unique subpopulation of cells that retain proliferative potential in a confluent culture and may be analogous to a subpopulation of stem cells present in vivo. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 5 1 2 3 4 > Last >> (109 articles found)

      
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