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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 181) Sort By: Publication Date Relevance Took: 1.155 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 8 1 2 3 4 > Last >> (181 articles found) Hematuria due to urolithiasis in a child with chronic immune thrombocytopenic purpura. Dec 2002 Jagadeesh Ramdas,Smitha Warrier,Rajp Warrier Hematuria is an uncommon manifestation of chronic immune thrombocytopenic purpura. The occurrence of urolithiasis in children with chronic immune thrombocytopenic purpura has not been described. We report a case of hematuria due to urolithiasis in an 8-year-old boy with chronic immune thrombocytope... ( view more )nic purpura. This child, who had a history of immune thrombocytopenic purpura of 1 year's duration, presented to the emergency department with gross hematuria. The cause of hematuria was initially attributed to his primary disease process. A careful history, examination, and pertinent investigations revealed that the hematuria was secondary to urolithiasis. This report highlights the need to keep an open mind and to search for specific causes of bleeding, even in children with known bleeding disorders. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The effect of anemia and blood transfusions on mortality in closed head injury patients. Jun 15, 2008 Therèse M Duane,Julie Mayglothling,Ramesh Grandhi,Nisha Warrier,Michel B Aboutanos,Luke G Wolfe,Ajai K Malhotra,Rao R Ivatury BACKGROUND: The purpose of this study was to determine if anemia in isolated head trauma patients results in a higher mortality rate that would justify a more liberal use of blood transfusions. METHODS: A retrospective review of isolated blunt head trauma patients was performed between January 2001... ( view more ) and December 2006. Comparisons were made between survivors and nonsurvivors regarding demographics, laboratory values, transfusions received, and lengths of stay. RESULTS: There were 788 patients with 735 survivors who were significantly younger (46.3 y +/- 21.5 survivors versus 68.9 y +/- 18.8 nonsurvivors, P < 0.0001) and less injured [(ISS: 14.7 +/- 5.2 survivors versus 23.2 +/- 4.7 nonsurvivors, P < 0.0001), (head abbreviated injury severity: 3.7 +/- 0.7 survivors versus 4.7 +/- 0.5 nonsurvivors, P < 0.0001)] than those who died (n = 53). The survivors also had shorter lengths of stay (days) [(ICU: 2.4 +/- 4.2 versus 5.6 +/- 11.7, P = 0.03), (hospital: 6.3 +/- 9.8 versus 7.8 +/- 14.8, P = 0.02)]. Multivariate logistic regression showed age (OR 1.063, CI 1.042-1.084), ISS (OR 1.376, CI 1.270-1.491), minimum hemoglobin (OR 0.855, CI 0.732-1.000), and total blood products transfused (OR 1.073, CI 1.008-1.142) to be independent predictors of mortality with an ROC of 0.942. Outcome was independent of the operative procedures, hematocrit and packed red blood cells transfused at 24, 48, and 72 h. Hemoglobin levels of <8 mg/dL were more predictive of death than >8 mg/dL (P = 0.01). CONCLUSIONS: This study supports the need to balance mild anemia with judicious blood product use in the head trauma patient. Given the risk with blood product use, each transfusion should be carefully considered and the patient re-evaluated regularly to determine the need for further intervention. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles X-ray structure of 4,4'-dihydroxybenzophenone mimicking sterol substrate in the active site of sterol 14alpha-demethylase (CYP51). May 30, 2008 Ali Nasser Eddine,Jens P von Kries,Mikhail V Podust,Thulasi Warrier,Stefan H E Kaufmann,Larissa M Podust A universal step in the biosynthesis of membrane sterols and steroid hormones is the oxidative removal of the 14alpha-methyl group from sterol precursors by sterol 14alpha-demethylase (CYP51). This enzyme is a primary target in treatment of fungal infections in organisms ranging from humans to plan... ( view more )ts, and development of more potent and selective CYP51 inhibitors is an important biological objective. Our continuing interest in structural aspects of substrate and inhibitor recognition in CYP51 led us to determine (to a resolution of 1.95A) the structure of CYP51 from Mycobacterium tuberculosis (CYP51(Mt)) co-crystallized with 4,4'-dihydroxybenzophenone (DHBP), a small organic molecule previously identified among top type I binding hits in a library screened against CYP51(Mt). The newly determined CYP51(Mt)-DHBP structure is the most complete to date and is an improved template for three-dimensional modeling of CYP51 enzymes from fungal and prokaryotic pathogens. The structure demonstrates the induction of conformational fit of the flexible protein regions and the interactions of conserved Phe-89 essential for both fungal drug resistance and catalytic function, which were obscure in the previously characterized CYP51(Mt)-estriol complex. DHBP represents a benzophenone scaffold binding in the CYP51 active site via a type I mechanism, suggesting (i) a possible new class of CYP51 inhibitors targeting flexible regions, (ii) an alternative catalytic function for bacterial CYP51 enzymes, and (iii) a potential for hydroxybenzophenones, widely distributed in the environment, to interfere with sterol biosynthesis. Finally, we show the inhibition of M. tuberculosis growth by DHBP in a mouse macrophage model. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Asthma genetics: personalizing medicine. May 2008 Manoj R Warrier,Gurjit K Khurana Hershey Asthma is a chronic inflammatory lung disease that leads to significant morbidity, mortality, and economic burden. The clinical symptoms, which are a result of airway inflammation and reversible airway obstruction, have led to the mainstay of therapies for asthma: anti-inflammatory medications and ... ( view more )bronchodilators. However, the efficacies of the various classes of medications are not equal among all patients and may be affected by asthma phenotypes, environmental exposures, and genetic differences. Similarly, the risk for developing asthma and the natural history of the disease show great inter-individual variability due to these same factors. Over the past few decades, much effort has been focused on the genetics of asthma, and investigators have identified more than one hundred potential asthma susceptibility genes, of which at least ten have been replicated in numerous independent studies. In parallel, researchers have also identified genetic factors that impact the pharmacotherapeutic responses to the major classes of asthma medications. While the results of previous studies have been promising, future investigations need to combine genetics, pharmacogenetics, accurate disease phenotyping, and environmental exposures to build the foundation for personalized and predictive medicine for the 21st century. The ultimate goal is to enable physicians to identify those at risk for asthma, intervene to prevent or attenuate the disease, and select the optimal medical regimen for each individual patient. If successful, the resulting paradigm shift in medical practice will lead to improved clinical outcomes and decreased health care expenditures. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Role of sindbis virus capsid protein region II in nucleocapsid core assembly and encapsidation of genomic RNA. May 2008 Ranjit Warrier,Benjamin R Linger,Barbara L Golden,Richard J Kuhn Sindbis virus is an enveloped positive-sense RNA virus in the alphavirus genus. The nucleocapsid core contains the genomic RNA surrounded by 240 copies of a single capsid protein. The capsid protein is multifunctional, and its roles include acting as a protease, controlling the specificity of RNA t... ( view more )hat is encapsidated into nucleocapsid cores, and interacting with viral glycoproteins to promote the budding of mature virus and the release of the genomic RNA into the newly infected cell. The region comprising amino acids 81 to 113 was previously implicated in two processes, the encapsidation of the viral genomic RNA and the stable accumulation of nucleocapsid cores in the cytoplasm of infected cells. In the present study, specific amino acids within this region responsible for the encapsidation of the genomic RNA have been identified. The region that is responsible for nucleocapsid core accumulation has considerable overlap with the region that controls encapsidation specificity. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Volume of left Heschl's Gyrus and linguistic pitch learning. Apr 2008 Patrick C M Wong,Catherine M Warrier,Virginia B Penhune,Anil K Roy,Abdulmalek Sadehh,Todd B Parrish,Robert J Zatorre Research on the contributions of the human nervous system to language processing and learning has generally been focused on the association regions of the brain without considering the possible contribution of primary and adjacent sensory areas. We report a study examining the relationship between ... ( view more )the anatomy of Heschl's Gyrus (HG), which includes predominately primary auditory areas and is often found to be associated with nonlinguistic pitch processing and language learning. Unlike English, most languages of the world use pitch patterns to signal word meaning. In the present study, native English-speaking adult subjects learned to incorporate foreign pitch patterns in word identification. Subjects who were less successful in learning showed a smaller HG volume on the left (especially gray matter volume), but not on the right, relative to learners who were successful. These results suggest that HG, typically shown to be associated with the processing of acoustic cues in nonspeech processing, is also involved in speech learning. These results also suggest that primary auditory regions may be important for encoding basic acoustic cues during the course of spoken language learning. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Discrete influx events refill depleted Ca2+ stores in a chick retinal neuron. Jan 15, 2008 Salvador Borges,Sarah Lindstrom,Cameron Walters,Ajithkumar Warrier,Martin Wilson The depletion of ER Ca2+ stores, following the release of Ca2+ during intracellular signalling, triggers the Ca2+ entry across the plasma membrane known as store-operated calcium entry (SOCE). We show here that brief, local [Ca2+]i increases (motes) in the thin dendrites of cultured retinal amacrin... ( view more )e cells derived from chick embryos represent the Ca2+ entry events of SOCE and are initiated by sphingosine-1-phosphate (S1P), a sphingolipid with multiple cellular signalling roles. Externally applied S1P elicits motes but not through a G protein-coupled membrane receptor. The endogenous precursor to S1P, sphingosine, also elicits motes but its action is suppressed by dimethylsphingosine (DMS), an inhibitor of sphingosine phosphorylation. DMS also suppresses motes induced by store depletion and retards the refilling of depleted stores. These effects are reversed by exogenously applied S1P. In these neurons formation of S1P is a step in the SOCE pathway that promotes Ca2+ entry in the form of motes. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Ceftriaxone induced hemolysis complicated by acute renal failure. Jan 2008 Gaurav Kapur,Rudolph P Valentini,Tej K Mattoo,Indira Warrier,Abubakr A Imam Over the last decade, second and third generation cephalosporins have been the most common drugs causing hemolytic anemia (HA). Of these cases, 20% have been attributed to ceftriaxone. The clinical presentation of ceftriaxone-induced HA is usually abrupt with sudden onset of pallor, tachypnea, card... ( view more )io-respiratory arrest and shock. Acute renal failure (ARF) has been reported in 41% of such cases with a high fatality rate. We report a pediatric patient with ARF complicating ceftriaxone-induced HA who survived. Ceftriaxone is a commonly used drug, and early recognition of HA and institution of supportive care, including dialysis is likely to improve the outcome. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Delayed complications of silicone implants used in orbital fracture repairs. 2008 Sunil Warrier,Venkatesh C Prabhakaran,Garry Davis,Dinesh Selva Purpose: To report a series of patients who developed late complications secondary to silicone implants used in orbital fracture repairs and review the literature. Design: Retrospective interventional case series. Methods: Analysis of records of patients who developed complications following repair... ( view more ) of orbital wall fractures with silicone implants. Results: Over a 5-year period, 4 patients were seen with complications arising from a silicone orbital implant. There were 3 males and 1 female whose ages ranged from 41-73 years. The time interval between initial insertion of implant and development of complications was 1.5, 6, 10, and 20 years. The complications noted were worsening diplopia, recurrent orbital cellulitis, lower lid retraction with restricted upgaze, and orbital abscess. Computed tomographic scans demonstrated the implant in all cases. Histologic examination revealed nonspecific chronic inflammation and fibrosis in all cases and foci of squamous epithelium in one case. Treatment included surgical removal of the implant, resulting in complete resolution or significant improvement in symptoms and signs in all cases. Conclusion: The use of silicone implants is associated with a wide range of complications, which may occur many years following the original surgery. Surgical removal of the implant usually leads to resolution of symptoms. Given the potential of silicone implants to cause delayed complications, their use in orbital fracture repair is not recommended. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Effect of dialysis on all trans retinoic acid levels in a child with acute promyelocytic leukemia and renal failure. Dec 2007 Madhvi Rajpurkar,Patricia Alcasabas,Indulekha Warrier,Rudolph P Valentini,Nancy Fassinger,Daniel A C Frattarelli,Yaddanapudi Ravindranath All trans retinoic acid (ATRA) combined with chemotherapy has become the mainstay of treatment for patients with acute promyelocytic leukemia (APL). Renal dysfunction (RD) is commonly seen in patients with APL. We describe a patient with APL and multi-organ failure, who was on chronic veno-venous h... ( view more )emofiltration followed by hemodialysis (HD) and later peritoneal dialysis (PD), who received ATRA. ATRA levels were assessed as the body clearance of ATRA in children on HD and/or PD was unknown. Neither HD nor PD significantly affected ATRA levels, suggesting that dose modifications of ATRA may not be necessary for children with these forms of renal replacement therapy. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Increased lymphocyte Fas expression and high incidence of common variable immunodeficiency disorder in childhood Evans' syndrome. Dec 2007 Süreyya Sava?an,Indira Warrier,Steven Buck,Joseph Kaplan,Yaddanapudi Ravindranath Evans' syndrome (ES) is characterized by autoimmune hemolytic anemia and thrombocytopenia and has been associated with immune deficiency and lymphoproliferation in some cases. Abnormalities of Fas-mediated apoptosis have been reported in various immune dysregulation disorders associated with autoim... ( view more )munity and lymphoproliferation. We measured lymphocyte Fas expression and Fas-mediated T lymphocyte apoptosis in 7 children with ES, 7 with acute idiopathic thrombocytopenic purpura (ITP) and 9 with non-immune-mediated disorders. Patients with ES had higher Fas expression on peripheral blood T and B lymphocytes (P<0.001 and P=0.046, respectively) and increased Fas-mediated elimination of activated T lymphocytes compared with the control groups. While two ES patients had panhypogammaglobulinemia at testing, three more developed it later, reaching a frequency of 83%. Some children with ES have increased lymphocyte Fas expression and Fas-mediated T lymphocyte apoptosis and these may be early signs of common variable immunodeficiency disorder in ES. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Protein kinase inhibitors reduce GABA but not glutamate release in the nucleus accumbens. Dec 2007 Ajithkumar Warrier,Gregory O Hjelmstad We investigated the role of endogenous protein kinase activity on synaptic transmission in the rat nucleus accumbens slice. The isoquinolinesulfonamide H-7 (50muM), a non-selective serine/threonine protein kinase inhibitor, had no effect on pharmacologically isolated glutamatergic EPSCs. However, i... ( view more )t reduced GABA release in a dose-dependent manner. This effect of H-7 was not mimicked by the selective cAMP-dependent protein kinase inhibitor H-89, the PKC inhibitor Bisindolylmaleimide-1, or the cGMP-dependent protein kinase inhibitor KT5823. However, bath application of the myosin light chain kinase (MLCK) inhibitor, ML-7, significantly reduced IPSC amplitudes and partially occluded the reduction in IPSCs observed following bath application of H-7. These results suggest that endogenous protein kinase activity, specifically MLCK activity, regulates GABA, but not glutamate release, onto medium spiny neurons in the nucleus accumbens. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Small-molecule scaffolds for CYP51 inhibitors identified by high-throughput screening and defined by X-ray crystallography. Nov 2007 Larissa M Podust,Jens P von Kries,Ali Nasser Eddine,Youngchang Kim,Liudmila V Yermalitskaya,Ronald Kuehne,Hugues Ouellet,Thulasi Warrier,Markus Alteköster,Jong-Seok Lee,Jörg Rademann,Hartmut Oschkinat,Stefan H E Kaufmann,Michael R Waterman Sterol 14alpha-demethylase (CYP51), a major checkpoint in membrane sterol biosynthesis, is a key target for fungal antibiotic therapy. We sought small organic molecules for lead candidate CYP51 inhibitors. The changes in CYP51 spectral properties following ligand binding make CYP51 a convenient tar... ( view more )get for high-throughput screening technologies. These changes are characteristic of either substrate binding (type I) or inhibitor binding (type II) in the active site. We screened a library of 20,000 organic molecules against Mycobacterium tuberculosis CYP51 (CYP51(Mt)), examined the top type I and type II binding hits for their inhibitory effects on M. tuberculosis in broth culture, and analyzed them spectrally for their ability to discriminate between CYP51(Mt) and two reference M. tuberculosis CYP proteins, CYP130 and CYP125. We determined the binding mode for one of the top type II hits, alpha-ethyl-N-4-pyridinyl-benzeneacetamide (EPBA), by solving the X-ray structure of the CYP51(Mt)-EPBA complex to a resolution of 1.53 A. EPBA binds coordinately to the heme iron in the CYP51(Mt) active site through a lone pair of nitrogen electrons and also through hydrogen bonds with residues H259 and Y76, which are invariable in the CYP51 family, and hydrophobic interactions in a phylum- and/or substrate-specific cavity of CYP51. We also identified a second compound with structural and binding properties similar to those of EPBA, 2-(benzo[d]-2,1,3-thiadiazole-4-sulfonyl)-2-amino-2-phenyl-N-(pyridinyl-4)-acetamide (BSPPA). The congruence between the geometries of EPBA and BSPPA and the CYP51 binding site singles out EPBA and BSPPA as lead candidate CYP51 inhibitors with optimization potential for efficient discrimination between host and pathogen enzymes. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The immunophilin ligands cyclosporin A and FK506 suppress prostate cancer cell growth by androgen receptor-dependent and -independent mechanisms. Oct 2007 Sumudra Periyasamy,Manya Warrier,Manoranjani P M Tillekeratne,Weinian Shou,Edwin R Sanchez The androgen receptor (AR) contributes to growth of prostate cancer even under conditions of androgen ablation. Thus, new strategies to target AR activity are needed. The AR interacts with the immunophilin FK506-binding protein 52 (FKBP52), and studies in the FKBP52 knockout mouse have shown that t... ( view more )his protein is essential to AR activity in the prostate. Therefore, we tested whether the immunophilin ligand FK506 affected AR activity in prostate cancer cell lines. We also tested the hypothesis that the AR interacts with another immunophilin, cyclophilin 40 (Cyp40), and is regulated by its cognate ligand cyclosporin A (CsA). We show that levels of FKBP52, FKBP51, Cyp40, and a related co-chaperone PP5 were much higher in prostate cancer cells lines [(LNCaP), PC-3, and DU145] compared with primary prostate cells, and that the AR of LNCaP cells can interact with Cyp40. In the absence of androgen, CsA caused inhibition of cell growth in the AR-positive LNCaP and AR-negative PC-3 and DU145 cell lines. Interestingly, FK506 only inhibited LNCaP cells, suggesting a dependence on the AR for this effect. Both CsA and FK506 inhibited growth without inducing apoptosis. In LNCaP cells, CsA completely blocked androgen-stimulated growth, whereas FK506 was partially effective. Further studies in LNCaP cells revealed that CsA and FK506 were able to block or attenuate several stages of AR signaling, including hormone binding, nuclear translocation, and activity at several AR-responsive reporter and endogenous genes. These findings provide the first evidence that CsA and FK506 can negatively modulate proliferation of prostate cells in vitro. Immunophilins may now serve as new targets to disrupt AR-mediated prostate cancer growth. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Neonatal facial coding system scores and spectral characteristics of infant crying during newborn circumcision. Jun 2007 Victoria Tutag Lehr,Philip Sanford Zeskind,John P Ofenstein,Eugene Cepeda,Indulekha Warrier,J V Aranda OBJECTIVE: To determine the relations between Neonatal Facial Coding System (NFCS) scores and measures of infant crying during newborn circumcision. METHODS: Video and audio recordings were made of infant facial activity and cry sounds, respectively, during the lysis phase of circumcisions of 44 he... ( view more )althy term males (<3 d of age). All infants received topical analgesia before circumcision. NFCS scores were determined by blinded assistant from video recordings of facial activity. Measures of infant crying were determined via spectrum analysis of audio recordings by a blinded, independent researcher. Pearson product-moment correlations were used to examine relationship between NFCS scores and measures of crying. Principal component factor analysis detected dimensions underlying related measures of crying. Factor scores from a factor analysis were used in stepwise linear regression to predict NFCS scores. RESULTS: Higher NFCS scores correlated with lower peak fundamental frequency of crying (P<0.01) and with higher amplitudes of crying at peak fundamental frequency and dominant frequency and in overall cry sample (P<0.01). The factor analysis showed 3 significant orthogonal dimensions underlying measures of crying: Power and Velocity (amplitude and rapidity), Pitch of Crying (frequency characteristics), and Infant Arousal (turbulence and intensity) accounting for 42.3%, 17.8%, and 14.6% of variance, respectively. A regression analysis showed all 3 factor scores accounted for significant and separate portions of variance (P<0.001). The best predictor of NFCS score was Power and Velocity (P<0.002), followed by Infant Arousal (P<0.002), and Pitch of Crying (P<0.007). DISCUSSION: These data provide some of the first known evidence linking specific measures of infant crying with an independent, validated measure of pain. ( view less ) View Full Abstract View Article Details   Related Articles Full recovery from Baylisascaris procyonis eosinophilic meningitis. Jun 2007 Poulomi J Pai,Brian G Blackburn,Kevin R Kazacos,Rajasekharan P Warrier,Rodolfo E Bégué Infection by Baylisascaris procyonis is an uncommon but devastating cause of eosinophilic meningitis. We report the first case-patient, to our knowledge, who recovered from B. procyonis eosinophilic meningitis without any recognizable neurologic deficits. The spectrum of illness for this organism m... ( view more )ay be wider than previously recognized. ( view less ) View Full Abstract View Article Details   Related Articles Functional requirements of the yellow fever virus capsid protein. Jun 2007 Chinmay G Patkar,Christopher T Jones,Yu-hsuan Chang,Ranjit Warrier,Richard J Kuhn Although it is known that the flavivirus capsid protein is essential for genome packaging and formation of infectious particles, the minimal requirements of the dimeric capsid protein for virus assembly/disassembly have not been characterized. By use of a trans-packaging system that involved packag... ( view more )ing a yellow fever virus (YFV) replicon into pseudo-infectious particles by supplying the YFV structural proteins using a Sindbis virus helper construct, the functional elements within the YFV capsid protein (YFC) were characterized. Various N- and C-terminal truncations, internal deletions, and point mutations of YFC were analyzed for their ability to package the YFV replicon. Consistent with previous reports on the tick-borne encephalitis virus capsid protein, YFC demonstrates remarkable functional flexibility. Nearly 40 residues of YFC could be removed from the N terminus while the ability to package replicon RNA was retained. Additionally, YFC containing a deletion of approximately 27 residues of the C terminus, including a complete deletion of C-terminal helix 4, was functional. Internal deletions encompassing the internal hydrophobic sequence in YFC were, in general, tolerated to a lesser extent. Site-directed mutagenesis of helix 4 residues predicted to be involved in intermonomeric interactions were also analyzed, and although single mutations did not affect packaging, a YFC with the double mutation of leucine 81 and valine 88 was nonfunctional. The effects of mutations in YFC on the viability of YFV infection were also analyzed, and these results were similar to those obtained using the replicon packaging system, thus underscoring the flexibility of YFC with respect to the requirements for its functioning. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles cAMP microdomains and L-type Ca2+ channel regulation in guinea-pig ventricular myocytes. May 1, 2007 Sunita Warrier,Gopalakrishnan Ramamurthy,Richard L Eckert,Viacheslav O Nikolaev,Martin J Lohse,Robert D Harvey Many different receptors can stimulate cAMP synthesis in the heart, but not all elicit the same functional responses. For example, it has been recognized for some time that prostaglandins such as PGE1 increase cAMP production and activate PKA, but they do not elicit responses like those produced by... ( view more ) beta-adrenergic receptor (betaAR) agonists such as isoproterenol (isoprenaline), even though both stimulate the same signalling pathway. In the present study, we confirm that isoproterenol, but not PGE1, is able to produce cAMP-dependent stimulation of the L-type Ca(2+) current in guinea pig ventricular myocytes. This is despite finding evidence that these cells express EP(4) prostaglandin receptors, which are known to activate G(s)-dependent signalling pathways. Using fluorescence resonance energy transfer-based biosensors that are either freely diffusible or bound to A kinase anchoring proteins, we demonstrate that the difference is due to the ability of isoproterenol to stimulate cAMP production in cytosolic and caveolar compartments of intact cardiac myocytes, while PGE1 only stimulates cAMP production in the cytosolic compartment. Unlike other receptor-mediated responses, compartmentation of PGE1 responses was not due to concurrent activation of a G(i)-dependent signalling pathway or phosphodiesterase activity. Instead, compartmentation of the PGE1 response in cardiac myocytes appears to be due to transient stimulation of cAMP in a microdomain that can communicate directly with the bulk cytosolic compartment but not the caveolar compartment associated with betaAR regulation of L-type Ca(2+) channel function. ( view less ) View Full Abstract View Article Details   Related Articles Hospitalized patients with asthma who leave against medical advice: characteristics, reasons, and outcomes. Apr 2007 Alan P Baptist,Indulekha Warrier,Rachna Arora,Joel Ager,R Michael Massanari BACKGROUND: A discharge against medical advice (AMA) after an asthma hospitalization is a frustrating problem for health care providers, yet little is known about this occurrence. OBJECTIVE: To determine the baseline characteristics, reasons for leaving, and clinical outcomes of patients with asthm... ( view more )a who leave AMA. METHODS: A retrospective study from 1999 to 2004 of all asthma discharges from 3 large hospitals in Detroit compared those who left AMA with those who left with medical approval. RESULTS: There were 180 patients who left AMA and 3457 patients who had a standard discharge. Patients with asthma who left AMA were more likely to be younger, male, have Medicaid or lack insurance, require intensive care unit admission, and have a lower socioeconomic status than patients with asthma discharged with approval (P < .05 for all comparisons). There was no difference in race, day of the week admitted, or month admitted. Among records that documented a reason for leaving AMA, the most common was dissatisfaction with care, although a variety of motives were found. Finally, patients who left AMA were more likely to have an asthma relapse within 30 days. This included both emergency department revisits (21.7% vs 5.4%; P < .001) and readmission to the hospital (8.5% vs 3.2%; P < .001). CONCLUSION: Patients with asthma who leave AMA have demographic and hospital admission characteristics that differ from those who leave with approval. The reasons why patients with asthma leave AMA are varied. Within 30 days, patients with asthma who leave AMA have much higher readmission and emergency department return rates. CLINICAL IMPLICATIONS: Patients with asthma who leave AMA are at increased risk of relapse. ( view less ) View Full Abstract View Article Details   Related Articles Synthesis of dioxane-based antiviral agents and evaluation of their biological activities as inhibitors of Sindbis virus replication. Apr 1, 2007 Ha Young Kim,Richard J Kuhn,Chinmay Patkar,Ranjit Warrier,Mark Cushman The crystal structure of the Sindbis virus capsid protein contains one or two solvent-derived dioxane molecules in the hydrophobic binding pocket. A bis-dioxane antiviral agent was designed by linking the two dioxane molecules with a three-carbon chain having R,R connecting stereochemistry, and a s... ( view more )tereospecific synthesis was performed. This resulted in an effective antiviral agent that inhibited Sindbis virus replication with an EC(50) of 14 microM. The synthesis proceeded through an intermediate (R)-2-hydroxymethyl-[1,4]dioxane, which unexpectedly proved to be a more effecting antiviral agent than the target compound, as evidenced by its EC(50) of 3.4 microM as an inhibitor of Sindbis virus replication. Both compounds were not cytotoxic in uninfected BHK cells at concentrations of 1mM. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Synthesis of biocompatible hydrophobic silica-gelatin nano-hybrid by sol-gel process. Mar 15, 2007 S Smitha,P Shajesh,P Mukundan,T D R Nair,K G K Warrier Silica-biopolymer hybrid has been synthesised using colloidal silica as the precursor for silica and gelatin as the biopolymer counterpart. The surface modification of the hybrid material has been done with methyltrimethoxysilane leading to the formation of biocompatible hydrophobic silica-gelatin ... ( view more )hybrid. Here we are reporting hydrophobic silica-gelatin hybrid and coating precursor for the first time. The hybrid gel has been evaluated for chemical modification, thermal degradation, hydrophobicity, particle size, transparency under the UV-visible region and morphology. FTIR spectroscopy has been used to verify the presence of CH(3) groups which introduce hydrophobicity to the SiO2-MTMS-gelatin hybrids. The hydrophobic property has also been tailored by varying the concentration of methyltrimethoxysilane. Contact angle by Wilhelmy plate method of transparent hydrophobic silica-gelatin coatings has been found to be as high as approximately 95 degrees . Oxidation of the organic group which induces the hydrophobic character occurs at 530 degrees C which indicates that the surface hydrophobicity is retained up to that temperature. Optical transmittance of SiO2-MTMS-gelatin hybrid coatings on glass substrates has been found to be close to 100% which will enable the hybrid for possible optical applications and also for preparation of transparent biocompatible hydrophobic coatings on biological substrates such as leather. ( view less ) View Full Abstract View Article Details   Related Articles Allergen-dependent solubilization of IL-13 receptor alpha2 reveals a novel mechanism to regulate allergy. Feb 2007 Michael O Daines,Weiguo Chen,Yasuhiro Tabata,Bradley A Walker,Aaron M Gibson,J Alexander Masino,Manoj R Warrier,Cori L Daines,Sally E Wenzel,Gurjit K Khurana Hershey BACKGROUND: Allergic sensitization affects half of western populations and often precedes the development of allergic disorders including asthma. Despite the critical role of allergens in the pathogenesis of these disorders, little is known about how allergens modulate the immune response. IL-13 re... ( view more )ceptor alpha2 (IL-13Ralpha2) is a decoy receptor for IL-13. OBJECTIVE: Although the existence of soluble IL-13Ralpha2 has been documented, the mechanisms underlying its generation are unknown. Many allergens possess protease activity; we investigated whether IL-13Ralpha2 is solubilized in response to allergen treatment. METHODS: We evaluated the ability of allergens to solubilize IL-13Ralpha2 in vitro and in vivo and examined the effect on IL-13 signaling and responses. RESULTS: We determined that treatment of cells with house dust mite (HDM) allergen or purified Dermatophagoides pteronyssinus or Dermatophagoides farinae, but not other allergens, resulted in release of soluble IL-13Ralpha2 that was biologically active and inhibited IL-13 signaling. Prolonged exposure to HDM or treatment with mold allergens resulted in IL-13Ralpha2 degradation. This was associated with increased IL-13 signaling. A single treatment of HDM in vivo resulted in release of IL-13Ralpha2 into the bronchoalveolar lavage (BAL) fluid. BAL fluid from humans also contained IL-13Ralpha2; BAL fluid from individuals with asthma contained less IL-13Ralpha2 than that from controls. CONCLUSION: Allergen exposure can directly affect the level of soluble IL-13Ralpha2 in a way that affects IL-13 signaling and responses. CLINICAL IMPLICATIONS: Soluble IL-13Ralpha2 may be an important biomarker of environmental allergen exposure and asthma. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Pulmonary embolism-experience at a single children's hospital. 2007 Madhvi Rajpurkar,Indira Warrier,Meera Chitlur,Cynthia Sabo,Mary Jane Frey,Wendy Hollon,Jeanne Lusher INTRODUCTION: Pulmonary embolism in children is a rare, potentially life threatening condition. The clinical characteristics of pediatric pulmonary embolism have not been well studied and the exact incidence in children is not known. We report a case series of fourteen patients with pulmonary embol... ( view more )ism and describe their clinical characteristics. MATERIALS AND METHODS: Inpatient and outpatient clinic charts of patients with proven pulmonary embolism (PE) followed at the Hemostasis and Thrombosis Center at Children's Hospital of Michigan were reviewed for relevant clinical and laboratory information. RESULTS: All patients with PE were symptomatic but accurate diagnosis of PE was often delayed in the outpatient setting. Screening testing with D-dimer was normal in 40% of patients. Acquired risk factors and lower extremity clots were more common in patients analyzed. Treatment regimens differed but most patients had resolution of pulmonary emboli on follow-up. CONCLUSIONS: A high index of suspicion is needed for the diagnosis of pediatric PE. D-Dimer may be normal in some children with PE. Pediatric multicenter trials are needed to evaluate clinical characteristics, risk factors, long-term outcome and effects of PE on pulmonary and cardiac function. ( view less ) View Full Abstract View Article Details   Related Articles Design and synthesis of novel derivatives of the muscarinic agonist tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (CDD-0304): effects of structural modifications on the binding and activity at muscarinic receptor subtypes and chimeras. Dec 14, 2006 Frederick R Tejada,Peter I Nagy,Min Xu,Cindy Wu,Tricia Katz,Jason Dorsey,Melissa Rieman,Elizabeth Lawlor,Manya Warrier,William S Messer As part of a continuing effort to design and synthesize highly selective muscarinic agonists for different muscarinic receptor subtypes, several tetra(ethylene glycol)(3-methoxy-1,2,5-thiadiazol-4-yl) [3-(1-methyl-1,2,5,6-tetrahydropyrid-3-yl)-1,2,5-thiadiazol-4-yl] ether (1) analogues were prepare... ( view more )d and characterized. Different analogues were synthesized having hydrophilic spacers of di-, tri-, tetra-, penta(ethylene glycol) and tri(propylene glycol) separating the 1,2,5,6-tetrahydropyridine ring from the terminal heterocycle, which was either a 1,2,5-thiadiazole or 1,2,4-thiadiazole ring. Chimeric receptor and molecular modeling studies also were conducted to determine how the ligands interact with muscarinic receptors. The studies revealed that varying the distance of the terminal thiadiazole and the positioning of the methoxy group can increase binding affinity for certain muscarinic receptor subtypes (at M(2) for 13d and M(4) for 1) and enhance functional efficacy at M(4) receptors for 13e and 18b. Moreover, compound 1 exhibited antipsychotic activity as assessed by reversal of apomorphine-induced sensory motor gating deficits, suggesting potential utility in the treatment of schizophrenia. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Allergy-driven alternative splicing of IL-13 receptor alpha2 yields distinct membrane and soluble forms. Dec 1, 2006 Yasuhiro Tabata,Weiguo Chen,Manoj R Warrier,Aaron M Gibson,Michael O Daines,Gurjit K Khurana Hershey IL-13 is a key mediator of allergic inflammation. Its diverse functions are mediated by a complex receptor system including IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2. IL-4Ralpha and IL-13Ralpha1 form a high-affinity signaling heterodimer. IL-13Ralpha2 binds IL-13 with high affinity and has been fo... ( view more )und to exist in membrane and soluble forms. Soluble IL-13Ralpha2 has been postulated as a critical endogenous modulator of IL-13 responses. However, the mechanism of generation for the soluble form remains unclear. We present the initial study that a mechanism for generation of the soluble form is alternative splicing and that alternative splicing yields a distinct form of soluble IL-13Ralpha2. We found that several mouse organs expressed two IL-13Ralpha2 transcripts, the 1152-bp transcript encoding the full-length protein and the 1020-bp transcript lacking exon10, which encodes the transmembrane region. Deletion of exon 10 (DeltaEx10) caused a frameshift resulting in a different amino acid sequence from position 327 to position 339 and early termination. Constructs encoding both splice variants were transfected into WEHI-274.1 cells. Transfectants expressing the full-length transcript had IL-13Ralpha2 on the cell surface but produced minimal soluble IL-13Ralpha2 in the supernatants. In contrast, transfectants expressing the DeltaEx10 transcript displayed no membrane IL-13Ralpha2 but secreted high levels of soluble IL-13Ralpha2 capable of inhibiting IL-13 signaling. Both variants bound IL-13, but the DeltaEx10 variant displayed approximately 2-fold increase in IL-13 binding activity. Expression of the two IL-13Ralpha2 transcripts was differentially regulated in vivo in an experimental allergic asthma model. Thus, alternatively spliced variants of IL-13Ralpha2 may have a distinct biologic function in vivo. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 8 1 2 3 4 > Last >> (181 articles found)

      
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