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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 (4 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  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. 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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 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 Language English French German Italian Japanese Russian Spanish Afrikaans Albanian Unknown Arabic Armenian Azerbaijani Bosnian Bulgarian Catalan Chinese Croatian Czech Danish Dutch Esperanto Estonian Finnish Georgian Greek, Modern Hebrew Hindi Hungarian Icelandic Indonesian Kinyarwanda Korean Latin Latvian Lithuanian Macedonian Malay Malayalam Maori Multiple Languages Norwegian Persian Polish Portuguese Pushto Romanian Sanskrit Scottish gaelic Serbian Slovak Slovenian Swedish Thai Turkish Ukrainian Vietnamese Not English Not French Results(1-25 of 1,594) Sort By: Publication Date Relevance Took: 1.685 seconds to search 17,750,454  Action: Copy Results to new Clipboard Build Search Link Page 1 of 64 1 2 3 4 > Last >> (1594 articles found) Mitochondrial assembly in respiration-deficient mutants of Saccharomyces cerevisiae. IV. Effects of nuclear amber suppressors on the accumulation of a mitochondrially made subunit of cytochrome c oxidase. Jan 25, 1975 B I Ono,G Fink,G Schatz Earlier studies from this laboratory have shown that cytochrome c oxidase from bakers' yeast contains seven subunits, three of which are made in the mitochondrion (Mason, T. L., and Schatz, G. (1973) J. Biol. Chem. 248, 1355). Moreover, a cytochrome c oxidase-less yeast mutant (pet 494-1) was isol... ( view more )ated which lacked one of the mitochondrially made subunits (Ebner, E., Mason, T. L., and Schatz, G. (1973) J. Biol. Chem. 248, 5369). Surprisingly, the mutated gene was localized in the nucleus. The results presented here demonstrate that this mutant phenotype can be suppressed by nuclear amber suppressors which affect translation on cytoplasmic ribosomes. This fact was established by two methods, (a) By constructing pet 494-1 strains possessing various amber and ochre markers, isolating respiring revertants from these strains, and demonstrating co-reversion of the amber (but not of the ochre) markers. (b) By coupling the pet 494-1 allele with the well characterized amber suppressor gene SUP 4-3. These data show that suppressor genes located on nuclear chromosomes may control the accumulation of a mitochondrially synthesized polypeptide. The present results also allow some tentative conclusions about the mechanism of the pet 494 mutation. Because it is highly unlikely that the cytoplasmic and the mitochondrial translation system share a common suppressor, the pet 494 locus probably does not code for the missing mitochondrially made subunit, but for a cytoplasmically made protein. This as yet unidentified protein seems to control the synthesis or the integration of the mitochondrially made subunit. Nuclear suppressor genes may thus be useful tools for studying the role of cytoplasmic protein synthesis in mitochondrial formation. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Cytochrome c oxidase from bakers' yeast. V. Arrangement of the subunits in the isolated and membrane-bound enzyme. Jan 25, 1975 G D Eytan,G Schatz Cytochrome c oxidase from baker's yeast contains three mitochondrially made subunits (I to III) which are relatively hydrophobic and four cytoplasmically made subunits (IV to VII) which are relatively hydrophilic (Mason, T. L., Poyton, R. O., Wharton, D.C., and Schatz, G. (1973) J. Biol. Chem. 248,... ( view more ) 1346-1354 and Poyton, R. O., and Schatz, G. (1975) J. Biol. Chem. 250, 752-761). In order to explore the arrangement of these subunits in the holoenzyme, the reactivity of each subunit with a variety of "surface probes" was tested with isolated cytochrome c oxidase, with cytochrome c oxidase incorporated into liposomes, and with mitochondrially bound cytochrome c oxidase. The surface probes included iodination with lactoperoxidase and coupling with p-diazonium benzenesulfonate. In addition, external subunits were identified by linking them to bovine serum albumin carrying a covalently bound isocyanate group. In the membrane-bound enzyme, Subunit I was almost completely inaccessible and Subunit II was partly inaccessible to all surface probes. All of the other subunits were accessible. Similar results were obtained with the solubilized enzyme, except that the differences in reactivity between the individual subunits were less clear-cut. The results obtained with liposome-bound cytochrome c oxidase resembled those obtained with the mitochondrially bound enzyme. These data suggest that the two largest mitochondrially made subunits are localized in the interior of the enzyme and that they are genuine components of cytochrome c oxidase. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles No alterations in the frequency of FOXP3+ regulatory T-cells in type 1 diabetes. Mar 2007 Todd Brusko,Clive Wasserfall,Kieran McGrail,Richard Schatz,Hilla Lee Viener,Desmond Schatz,Michael Haller,Jennifer Rockell,Peter Gottlieb,Michael Clare-Salzler,Mark Atkinson Regulatory T-cells (Tregs) play a critical role in maintaining dominant peripheral tolerance. Previous characterizations of Tregs in type 1 diabetes have used antibodies against CD4 and alpha-chain of the interleukin-2 receptor complex (CD25). This report extends those investigations by the additio... ( view more )n of a more lineage-specific marker for Tregs, transcription factor forkhead box P3 (FOXP3), in subjects with type 1 diabetes, their first-degree relatives, and healthy control subjects. With inclusion of this marker, two predominant populations of CD4(+)CD25(+) T-cells were identified: CD4(+)CD25(+)FOXP3(+) as well as CD4(+)FOXP3(-) T-cells expressing low levels of CD25 (CD4(+)CD25(LOW)FOXP3(-)). In all study groups, the frequency of CD4(+)CD25(+)FOXP3(+) cells was age independent, whereas CD4(+)CD25(LOW)FOXP3(-) cell frequencies strongly associated with age. In terms of additional markers for delineating cells of Treg lineage, FOXP3(+) cells were CD127(-) to CD127(LOW) whereas CD25(+) cells were less restricted in their expression of this marker, with CD127 expressed across a continuum of levels. Importantly, no differences were observed in the frequency of CD4(+)CD25(+)FOXP3(+) T-cells in individuals with or at varying degrees of risk for type 1 diabetes. These investigations suggest that altered peripheral blood frequencies of Tregs, as defined by the expression of FOXP3, are not specifically associated with type 1 diabetes and continue to highlight age as an important variable in analysis of immune regulation. ( view less ) View Full Abstract View Article Details   Related Articles Narrow plasmonic/photonic extinction and scattering line shapes for one and two dimensional silver nanoparticle arrays. Dec 22, 2004 Shengli Zou,George C Schatz The interaction of light with silver nanoparticle arrays can in some cases produce mixed plasmonic/photonic bands that have extremely narrow (<1 meV) line shapes in extinction and scattering. In this paper we extend computational electrodynamics results of a recent communication [S. Zou, N. Janel, ... ( view more )and G. C. Schatz, J. Chem. Phys. 120, 10871 (2004)] where this effect was first described to study how these narrow bands are influenced by a number of structural factors, and to determine how useful these arrays might be for sensing applications. Included are studies of the effect of disorder in the array structure on plasmon intensity and width, of the effect of orientation of the array relative to the polarization and propagation direction of the incident light, and of the effect of particle shape (comparing results for silver spheres and cylindrical disks). Our results show that the narrow lines are remarkably robust to array disorder, but vacancy defects can easily destroy the effect. The narrowest lines are associated with one dimensional arrays in which both polarization and wave vectors are perpendicular to the array axis. For two dimensional arrays, the narrowest lines are associated with the wave vector perpendicular to the plane of the array and polarization in the plane. Arrays composed of oblate cylinders generate more intense and more redshifted plasmon/photonic peaks than do prolate or spherical particles under comparable conditions. Finally, for sensing applications in which analyte binding is determined by the plasmon wavelength shift associated with change in the surface refractive index, we show that the arrays have greater sensitivity than isolated nanoparticles. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Structural requirements for the stabilization of metarhodopsin II by the C terminus of the alpha subunit of transducin. Jan 26, 2001 L Aris,A Gilchrist,S Rens-Domiano,C Meyer,P J Schatz,E A Dratz,H E Hamm The retinal receptor rhodopsin undergoes a conformational change upon light excitation to form metarhodopsin II (Meta II), which allows interaction and activation of its cognate G protein, transducin (G(t)). A C-terminal 11-amino acid peptide from transducin, G(talpha)-(340-350), has been shown to ... ( view more )both bind and stabilize the Meta II conformation, mimicking heterotrimeric G(t). Using a combinatorial library we identified analogs of G(talpha)-(340-350) that bound light-activated rhodopsin with high affinity (Martin, E. L., Rens-Domiano, S., Schatz, P. J., and Hamm, H. E. (1996) J. Biol. Chem. 271, 361-366). We have made peptides with key substitutions either on the background of the native G(talpha)-(340-350) sequence or on the high affinity sequences and used the stabilization of Meta II as a tool to determine which amino acids are critical in G protein-rhodopsin interaction. Removal of the positive charge at the N termini by acylation or delocalization of the charge by K to R substitution enhances the affinity of the G(talpha)-(340-350) peptides for Meta II, whereas a decrease was observed following C-terminal amidation. Cys-347, a residue conserved in pertussis toxin-sensitive G proteins, was shown to interact with a hydrophobic site in Meta II. These studies provide further insight into the mechanism of interaction between the G(talpha) C terminus and light-activated rhodopsin. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles The relationship of maternal personality characteristics to birth outcomes and infant development. Mar 2000 D Schatz,D Harder,M Schatz,K Harden,L Chilingar,D Fox,C Hoffman BACKGROUND: Previous studies reported an association between maternal psychological factors and adverse pregnancy outcomes. The objective of this study was to evaluate the relationships between maternal personality characteristics, as determined by the Minnesota Multiphasic Personality Inventory (M... ( view more )MPI), and infant birth outcomes and development. METHOD: The inventory was administered during pregnancy to 638 pregnant women enrolled in a staff model health maintenance organization. MMPI validity as well as clinical and research scales were evaluated in relationship to infant birth outcomes (low birthweight, preterm birth) and 15-month-old infant development as assessed by the Bayley Scales of Infant Development. RESULTS: Mothers of low birthweight infants scored significantly lower on the hypochondriasis scale, a relationship which was no longer significant after controlling for ethnicity. No other relationships were observed between infant birth outcomes and maternal MMPI scale scores. A higher infant Mental Developmental Index (MDI) was related to higher maternal masculinity-femininity and ego-strength scale scores and lower lie and hypochondriasis scale scores. Only the relationship between infant MDI and maternal masculinity-femininity scale score remained significant after controlling for ethnicity and socioeconomic index (beta = 0.104, p = 0.036). CONCLUSIONS: Maternal personality characteristics, as determined by the MMPI, did not appear to be significantly related to the occurrence of preterm birth or low birthweight in this healthy, general population. Maternal personality characteristics reflected in the MMPI masculinity-femininity scale appeared to be related to infant mental development, above and beyond the effects of socioeconomic status and ethnicity. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Diabetic microvascular complications and growth factors. 1995 A Pfeiffer,H Schatz Diabetes mellitus is associated with typical patterns of long term vascular complications which vary with the organ involved. The microvascular kidney disease (Olgemoller and Schleicher, 1993) is characterized by thickening of the capillary basement membranes and increased deposition of extracellul... ( view more )ar matrix components (ECM), while loss of microvessels with subsequent neovascularisation is predominant in the eye and peripheral nerves. On the other hand macrovascular disease is characterized by accelerated atherosclerosis. These complications are dependent on long term hyperglycemia. Specific biochemical pathways linking hyperglycaemia to microvascular changes were proposed: the polyol pathway (Greene et al., 1987), non-enzymatic glycation of proteins (Brownlee et al., 1988), glucose autooxidation and oxidative stress (Hunt et al., 1990), hyperglycemic pseudohypoxia (Williamson et al., 1993) enhanced activation of protein kinase C by de novo-synthesis of diacyl glycerol (Lee et al., 1989; DeRubertis and Craven 1994) and others. These pathways are not mutually exclusive (Larkins and Dunlop, 1992; Pfeiffer and Schatz, 1992). They may be linked to alterations in the synthesis of growth factors particularly since atherosclerosis and angioneogenesis are associated with increased proliferation of endothelial and smooth muscle cells. Increased synthesis of ECM components is stimulated by growth factors like transforming growth factor beta (TGF beta) (Derynck et al., 1984) and insulin-like growth factor I (IGF-I) (Moran et al., 1991). This review will summarize some of the recent evidence for an involvement of growth factors in diabetic vascular complications and will attempt to assign their emergence in the sequence of events leading to vascular complications. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Yeast mitochondria lacking the two import receptors Mas20p and Mas70p can efficiently and specifically import precursor proteins. May 27, 1994 T Lithgow,T Junne,C Wachter,G Schatz Mas20p and Mas70p are integral proteins of the yeast mitochondrial outer membrane that appear to function as receptors for precursor proteins imported from the cytosol. Loss of either receptor alone does not block import or kill the cells, but deletion of Mas20p causes loss of respiration (Ramage, ... ( view more )L., Junne, T., Hahne, K., Lithgow, T., and Schatz, G. (1993) EMBO J. 12, 4115-4123). Here we show that this respiratory deficiency is only temporary; given time to adapt, virtually all cells lacking MAS20p regain respiration without regaining MAS20p. The respiratory defect can also be suppressed (at a frequency of about 10(-6)) by a dominant mutation of a single nuclear gene. The suppressed cells, unlike the unsuppressed ones, tolerate disruption of the MAS70 gene. The resulting double disruptants lack both Mas20p and Mas70p, yet are viable and able to respire. Protein import into mitochondria isolated from these cells is efficient, specific, and highly sensitive to protease treatment. We propose that at least one additional mitochondrial surface protein can function as a protein import receptor and that the activity of this component is up-regulated by a stress response or by an extragenic suppressor. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Precursor binding to yeast mitochondria. A general role for the outer membrane protein Mas70p. Jan 5, 1993 V Hines,G Schatz Binding of precursors to import receptors on the mitochondrial surface is one of the earliest steps of protein import into mitochondria. In yeast, one of these receptors is a 70-kDa outer membrane protein termed Mas70p. Pulse-chase studies with intact yeast cells had indicated that Mas70p accelerat... ( view more )es the import of all mitochondrial precursors tested. In contrast, import experiments with isolated mitochondria suggested that Mas70p accelerated import of only a subset of precursors (Hines, V., Brandt, A., Griffiths, G., Horstmann, H., Brütsch, H., and Schatz, G. (1990) EMBO J. 9, 3191-3200). To resolve this discrepancy, we have now studied the interaction of Mas70p-deficient and wild-type yeast mitochondria with a precursor (pre-alcohol dehydrogenase III) whose import into isolated mitochondria is not accelerated by Mas70p under the usual assay conditions. Mas70p enhanced binding of pre-alcohol dehydrogenase III to the surface of mitochondria in which the electrochemical potential across the inner membrane had been dissipated by an uncoupler; the bound precursor could be efficiently chased into the mitochondria if the potential was restored. The precursor to cytochrome c1 was also bound to mitochondria in a Mas70p-dependent manner. Mas70p also enhanced the direct import of pre-alcohol dehydrogenase III into isolated mitochondria, provided the precursor was first denatured with urea. Under these conditions, the import rate in vitro was more similar to that in intact cells. Mas70p had no effect on the binding or the import of artificial precursors containing mouse dihydrofolate as the "mature" domain. We conclude that Mas70p is an import receptor for most, if not all authentic mitochondrial precursor proteins, but that its function is not always rate-limiting in import experiments with isolated mitochondria. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Emergent use of balloon-expandable coronary artery stenting for failed percutaneous transluminal coronary angioplasty. Sep 1992 H C Herrmann,M Buchbinder,M W Clemen,D Fischman,S Goldberg,M B Leon,R A Schatz,P Tierstein,C M Walker,J W Hirshfeld BACKGROUND. The balloon-expandable intracoronary stent developed by Palmaz and Schatz is undergoing clinical evaluation for use in unfavorable anatomic situations and in the prevention of restenosis. Because the stent's mechanism of action would suggest effectiveness in salvaging certain percutaneo... ( view more )us transluminal coronary angioplasty (PTCA) failures, we retrospectively examined the results of emergency unplanned coronary artery stenting for failed PTCA procedures, including acute occlusion. METHODS AND RESULTS. The study population consisted of all US patients receiving emergency unplanned stent implantation in a nonrandomized fashion at seven centers over a 2 1/2-year period (n = 56). All available medical records and angiograms were reviewed to determine retrospectively the reason for stenting: Group 1 consisted of 23 patients with a suboptimal angioplasty result; group 2 included patients with evidence of impending vessel closure after PTCA (n = 15); and group 3 were patients with frank acute occlusion after PTCA (n = 18). The immediate and final (30-day) results of stenting were examined with respect to major complications, which included death, need for coronary artery bypass graft surgery, and occurrence of myocardial infarction. Finally, restenosis rates (greater than or equal to 50% stenosis) based on follow-up angiography were calculated. Baseline characteristics of the study population included a mean +/- SD age of 58 +/- 11 years and a large prevalence of angiographic characteristics generally considered unfavorable for PTCA, which include lesion eccentricity (49%), intimal dissection (9%), or angiographically visible thrombus (6%). After conventional balloon angioplasty, there was an increased incidence of intimal dissection (74%) and thrombus formation (38%), and overall stenosis severity was unchanged (75 +/- 12% versus 70 +/- 27%, p = NS). Successful stent deployment was achieved in 55 (98%) of 56 patients with initial success (freedom from death, surgery, and infarction) in 52 (93%) of 56 patients. The success rate at 1 month fell to 71% primarily because of the occurrence of subacute stent thrombosis (16%) and its associated complications. Overall, major complications occurred in 16 (29%) of 56 patients within 30 days. The only predictor of subacute stent thrombosis in multiple stepwise logistic regression analysis was the presence of angiographically visible thrombus after stenting (p = 0.03). Angiographic restenosis was documented in eight (23%) of 35 eligible patients. CONCLUSIONS. Emergency stenting may be a useful and effective treatment for failed angioplasty. High initial success rates (greater than 90%) can be achieved, but subsequent complications, often related to subacute thrombosis, occur in a substantial portion of patients. Patients who receive stents on an emergency basis, particularly those with previous acute occlusion, should be considered to be at greater than usual risk for complications and receive more careful anticoagulation and follow-up. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Protein import into the yeast mitochondrial matrix. A new translocation intermediate between the two mitochondrial membranes. Nov 5, 1991 S T Hwang,C Wachter,G Schatz Import of authentic or artificial precursor proteins into the matrix of isolated yeast mitochondria can proceed via a translocation intermediate that is lodged between the two mitochondrial membranes. The intermediate accumulates when import is arrested by depleting mitochondria of ATP. Generation ... ( view more )of the intermediate requires a potential across the inner membrane. The intermediate is membrane-bound, partly or completely processed (depending on the precursor), and chased into the matrix by added ATP. This chase does not require a potential across the inner membrane. The properties of this intermediate support the proposal (Hwang, S., Jascur, J., Vestweber, D., Pon, L., and Schatz, G. (1989) J. Cell Biol. 109, 487-493) that import into the matrix involves two distinct translocation systems in the outer and the inner mitochondrial membrane that are not permanently coupled to each other. Only translocation across the inner membrane requires ATP in the matrix. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Binding of a tightly folded artificial mitochondrial precursor protein to the mitochondrial outer membrane involves a lipid-mediated conformational change. Feb 15, 1989 T Endo,M Eilers,G Schatz An artificial mitochondrial precursor protein (the presequence of cytochrome oxidase subunit IV fused to mouse dihydrofolate reductase) binds to isolated yeast mitochondrial outer membranes and to liposomes whose phospholipid composition resembles that of outer membranes. In both cases, binding is ... ( view more )strongly inhibited by low temperature or methotrexate (which stabilizes the dihydrofolate reductase moiety) and partly inhibited by adriamycin (which binds to acidic phospholipids). Binding is accompanied by partial unfolding of the protein. Binding of the urea-denatured fusion protein to outer membranes or liposomes is insensitive to low temperature, methotrexate, or adriamycin. These results, and those reported in the accompanying paper (Eilers, M., Endo, T., and Schatz, G. (1989) J. Biol. Chem. 264, 2945-2950) suggest that import of this fusion protein into isolated mitochondria involves at least partial unfolding by acidic phospholipids on the mitochondrial surface. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Adriamycin, a drug interacting with acidic phospholipids, blocks import of precursor proteins by isolated yeast mitochondria. Feb 15, 1989 M Eilers,T Endo,G Schatz Acidic phospholipids such as cardiolipin partially unfold an artificial precursor protein which consists of a mitochondrial presequence fused to mouse dihydrofolate reductase (Endo, T., and Schatz, G. (1988) EMBO J. 7, 1153-1158). We now show that import of this precursor protein into isolated yeas... ( view more )t mitochondria is blocked by adriamycin, a drug binding to cardiolipin and other acidic phospholipids. This inhibition is lessened if the precursor's dihydrofolate reductase moiety is labilized by point mutations; inhibition is abolished altogether if the "wild-type" precursor is presented to mitochondria in a urea-denatured state. These and other observations suggest that adriamycin interferes with the generation of a translocation-competent, loose structure of the precursor protein. They imply that acidic phospholipids such as cardiolipin participate, directly or indirectly, in the translocation of this fusion protein into isolated mitochondria. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Disruption of the outer membrane restores protein import to trypsin-treated yeast mitochondria. Jul 1987 M Ohba,G Schatz Treatment of isolated yeast mitochondria with high levels (1 mg/ml) of trypsin severely inhibits protein import but does not destroy the integrity of the outer membrane or abolish mitochondrial energy coupling. If the outer membrane of these trypsin-inactivated mitochondria is disrupted by osmotic ... ( view more )shock, the resulting mitoplasts are again able to import proteins. Protein import into mitoplasts, like that into intact mitochondria, is energy-dependent; however, whereas import into mitochondria is inhibited by antibody against 45-kd proteins of the outer membrane [Ohba and Schatz, EMBO J., 6, 2109-2115 (1987)], import into mitoplasts not affected by this antibody. Protein import into mitoplasts appears to bypass one or more steps normally occurring at the mitochondrial surface. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [The tumor markers CEA, TPA and CA 19-9 and ferritin and osteocalcin in follow-up studies in breast cancer] Dec 6, 1985 C Schatz,H von Lieven,M Mulders,J Rowold,H Stracke,H Müller,S F Grebe,H Schatz Radioimmunological determinations of the tumour markers CEA, TPA, CA 19-9, ferritin and also osteocalcin were carried out in 250 patients with ablatio mammae for breast cancer over a follow-up period of at least 1 year. Metastases were detected in 49 of the 250 patients. The normal control group co... ( view more )mprised 193 healthy persons. CEA proved to be the most valuable tumour marker, but TPA and ferritin were also significantly elevated in metastatic breast cancer. Combined determination of all 3 parameters gave the best results. Additional measurement of CA 19-9 was helpful in only one of the 49 patients with metastases in whom the 3 other parameter were negative throughout. Hence, determination of CA 19-9 appears unnecessary in breast cancer. In progressive disease the markers generally increased and fell again following successful therapy. In a few cases the opposite was found or no changes were observed. Cases with small local recurrence or an additional carcinoma at an early stage did not exhibit increased marker values as compared to patients without metastases. Not infrequently the increase in markers preceded the manifestation of metastases by several months. Very high concentrations of tumour markers signify a poor prognosis. Osteocalcin was elevated in patients with bone metastases, but not soft tissue metastases. In general, however, it paralleled the serum alkaline phosphatase level. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Osteocalcin, a marker in diseases with elevated bone metabolism] Sep 20, 1985 H Stracke,C Schatz,H Pralle,J Ullmann,H Schatz Osteocalcin is synthesized by osteoblasts and its concentration in serum is increased when bone metabolism is raised. Radioimmunoassay of serum from 88 healthy adults gave a mean osteocalcin value for the whole group of 4.11 +/- 1.43 ng/ml. The level rose with age. In seven patients with primary hy... ( view more )perparathyroidism the mean value was markedly raised to 19.37 +/- 9.2 ng/ml, in 23 with metastasizing carcinoma of the breast it was elevated to 6.57 +/- 2.98 ng/ml. Serial measurements in 14 female patients over seven months revealed different changes in osteocalcin and alkaline phosphatase in some of them. In patients with breast cancer and soft-tissue metastases or without metastases both osteocalcin and alkaline phosphatase levels were normal. Three of 17 patients with multiple myeloma had increased osteocalcin levels. These results indicate that it is clinically helpful to know osteocalcin levels in primary hyperparathyroidism. Determination of osteocalcin concentration, in addition to that of alkaline phosphatase, can be of value in the postmastectomy management of patients with breast cancer, especially in the early recognition of bone metastases. The diagnostic value of osteocalcin levels in multiple myeloma remains undecided. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Import of proteins into mitochondria. Energy-dependent, two-step processing of the intermembrane space enzyme cytochrome b2 by isolated yeast mitochondria. Nov 10, 1982 G Daum,S M Gasser,G Schatz Import of in vitro-synthesized cytochrome b2 (a soluble intermembrane space enzyme) was studied wih isolated yeast mitochondria. Import requires an electrochemical gradient across the inner membrane and is accompanied by cleavage of the precursor to the corresponding mature form. This conversion pr... ( view more )oceeds via an intermediate form of cytochrome b2, which can be detected as a transient species when mitochondria are incubated with the cytochrome b2 precursor for short times or at low temperatures. Conversion of the precursor to the intermediate form is energy-dependent and catalyzed by an o-phenanthroline-sensitive protease located in the soluble matrix. The intermediate is subsequently converted to mature cytochrome b2 in a reaction which is o-phenanthroline-insensitive and requires neither an energized inner membrane nor a soluble component of the intermembrane space. Whereas mature cytochrome b2 is soluble, the intermediate formed by isolated mitochondria is membrane-bound and exposed to the intermembrane space. The same intermediate is detected as a transient species during cytochrome b2 maturation in intact yeast cells (Reid, G. A., Yonetani, T., and Schatz, G (1982) J. Biol. Chem. 257, 13068-13074). The in vitro studies reported here suggest that a part of the cytochrome b2 precursor polypeptide chain is transported to the matrix where it is cleaved to a membrane-bound intermediate form by the same protease that processes polypeptides destined for the matrix space or for the inner membrane. In a second reaction, the cytochrome b2 intermediate is converted to mature cytochrome b2 which is released into the intermembrane space. The binding of heme is not necessary for converting the intermediate to the mature polypeptide. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Import of proteins into mitochondria. Yeast cells grown in the presence of carbonyl cyanide m-chlorophenylhydrazone accumulate massive amounts of some mitochondrial precursor polypeptides. Nov 10, 1982 G A Reid,G Schatz Cytoplasmically synthesized precursors of mitochondrial polypeptides have previously been observed in trace amounts after pulse labeling of yeast spheroplasts or after in vitro translation of yeast mRNA (Maccecchini, M. L., Rudin, Y., Blobel, G., and Schatz, G. (1979) Proc. Natl. Acad. Sci. U. S. A... ( view more ). 76, 343-347). Some of these precursors are shown here to accumulate in large amounts (up to 150 micrograms/g of cell protein) during growth of a cytoplasmic petite (rho-) mutant in the presence of carbonyl cyanide m-chlorophenylhydrazone, an uncoupler of oxidative phosphorylation. Cytochrome c1 precursor accumulated under these conditions is unstable; it is degraded with a half-life of about 10 min. In contrast, the F1-ATPase beta-subunit precursor is degraded considerably more slowly and, following removal of the uncoupler, can be post-translationally imported into mitochondria where it is processed to the mature polypeptide. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Estradiol fatty acid esters. The isolation and identification of the lipoidal derivative of estradiol synthesized in the bovine uterus. May 25, 1982 S H Mellon-Nussbaum,L Ponticorvo,F Schatz,R B Hochberg The bovine uterus, like other estrogen-responsive organs of man and rat, synthesizes an unusual nonpolar metabolite of estradiol (Schatz, F., and Hochberg, R. B. (1981) Endocrinology 109, 697-703). This compound, the lipoidal derivative of estradiol (LE2), was synthesized from estradiol by bovine e... ( view more )ndometrial tissue in vitro, and it was purified by extensive chromatography on two adsorption columns, a reversed phase partition celite column and three different high pressure liquid chromatography columns. LE2 was separated into nine fractions which were analyzed by direct probe mass spectroscopy and by gas chromatography mass spectroscopy after cleavage of the lipoidal moieties. In this manner, 10 fatty acid esters of estradiol, exclusively esterified at C-17 of the steroid nucleus, were identified. The unsaturated fatty acid esters of estradiol comprise more than 85% of the total LE2 and estradiol 17 beta-arachidonate is the most abundant component. The cholesterol esters and phospholipids of the bovine endometrium were also purified and it was found that the distribution of fatty acids in these lipids is far different from that of LE2. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles [Significance of thyroglobulin as a tumor marker in the serum of patients with differentiated thyroid carcinoma: longitudinal and cross-sectional studies (author's transl)] May 3, 1982 H Schatz,S Grebe,E Mäser,J Teuber,W Horn,O Schröder,C Schatz For evaluating the clinical significance of thyroglobulin measurements for the follow-up of patients with differentiated thyroid carcinoma, thyroglobulin was determined radioimmunologically during the past 2 years (up to 12 times) in 40 patients after withdrawal of thyroid hormone. Thyroglobulin va... ( view more )lues were compared with whole-body scintigrams after radioiodine. Thyroglobulin antibodies, which may interfere in the radioimmunoassay for thyroglobulin, were also estimated by a radioimmunologic method. In the majority of cases, thyroglobulin levels corresponded to the scintigrams, however, the thyroglobulin level appeared to be a more precise index for changes in tumor tissue mass. In one patient the scintigram was negative, whereas considerable amounts of thyroglobulin were measured in the serum: X-ray tomography revealed a lung metastase in this case. On the other hand, thyroglobulin was undetectable in the sera of patients who exhibited distinct metastases in the scintigram. Thyroglobulin can be regarded as a tumor marker in patients thyroidectomized for differentiated thyroid carcinoma. However, its determination can certainly not replace whole-body scintigraphy as postulated by several authors, although thyroglobulin measurement appears to be superior to scanning in some cases. A combined application of iodine scanning and thyroglobulin radioimmunoassay is thus advisable in the follow-up of patients with differentiated thyroid carcinoma. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Transport of proteins across the mitochondrial outer membrane. A precursor form of the cytoplasmically made intermembrane enzyme cytochrome c peroxidase. Aug 25, 1979 M L Maccecchini,Y Rudin,G Schatz Cytochrome c peroxidase, a cytoplasmically made enzyme located between the inner and outer membrane of yeast mitochondria, is synthesized as larger precursor in a reticulocyte cell-free lysate as well as in pulsed yeast spheroplasts. When the pulsed spheroplasts are chased, the precursor is convert... ( view more )ed to the mature apoprotein. When the in vitro synthesized precursor is incubated with isolated yeast mitochondria in the absence of protein synthesis, it is cleaved to the mature form; the mature form co-sediments with the mitochondria and is resistant to externally added proteases. These results, in conjunction with those reported earlier (Maccecchini, M.-L., Rudin, Y., Blobel, G., and Schatz, G. (1979) Proc. Natl. Acad. Sci. U.S.A. 76, 343-347) suggest that the mechanism of protein transport into the mitochondrial intermembrane space is quite similar to that of protein transport into the matrix or the inner membrane. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Cytochrome c1 of bakers' yeast. II. Synthesis on cytoplasmic robosomes and influence of oxygen and heme on accumulation of the apoprotein. Apr 10, 1976 E Ross,G Schatz In the preceding paper (Ross, E., and Schatz, G. (1976) J. Biol. Chem. 251, 1991-1996) yeast cytochrome c1 was characterized as a 31,000 dalton polypeptide with a covalently bound heme group. In order to determine the site of translation of this heme-carrying polypeptide, yeast cells were labeled w... ( view more )ith [H]leu(be under the following conditions: (a) in the absence of inhibitors, (b) in the presence of acriflavin (an inhibitor of mitochondrial translation), or (c) in the presence of cycloheximide (an inhibitor of cytoplasmic translation). The incorporation of radioactivity into the hemeprotein was measured by immunoprecipitating it from mitochondrial extracts and analyzing it by dodecyl sulfate-polyacrylamide gel electrophoresis. Label was incorporated into the cytochrome c1 apoprotein only in the presence of acriflavin or in the absence of inhibitor, but not in the presence of cycloheximide. Cytochrome c1 is thus a cytoplasmic translation product. This conclusion was further supported by the demonstration that a cytolasmic petite mutant lacking mitochondrial protein synthesis still contained holocytochrome c1 that was indistinguishable from cytochrome c1 of wild type yeast with respect to molecular weight, absorption spectru, the presence of a covalently bound heme group, and antigenic properties. Cytochrome c1 in the mitochondria of the cytoplasmic petite mutant is firmly bound to the membrane, and its concentration approaches that typical of wild type mitochondria. However, its lability to proteolysis appeared to be increased. A mitochondrial translation product may thus be necessary for the correct conformation or orientation of cytochrome c1 in the mitochondrial inner membrane. Accumulation of cytochrome c1 protein in mitochondria is dependent on the abailability of heme. This was shown with a delta-aminolevulinic acid synthetase-deficient yeast mutant which lacks heme and any light-absorbing peaks attributable to cytochromes. Mitochondria from mutant cells grown without added delta-aminolevulinic acid contained at least 20 times less protein immunoprecipitable by cytochrome c1-antisera than mitochondria from cells grown in the presence of the heme precursor. Similarly, the respiration-deficient promitochondria of anaerobically grown wild type cells are almost completely devoid of material cross-reacting with cytochrome c1-antisera. A 105,000 X g supernatant of aerobically grown wild type cells contains a 29,000 dalton polypeptide that is precipitated by cytochrome c1-antiserum but not by nonimmune serum. This polypeptide is also present in high speed supernatants from the heme-deficient mutant or from anaerobically gorwn wild type cells. The possible identity of this polypeptide with soluble apocytochrome c1 is being investigated. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Electronic excitations and spectra in single-stranded DNA. Jun 18, 2008 Stefano Tonzani,George C Schatz Using density functional theory and molecular dynamics simulations, we show that delocalized states extending over three bases can be directly excited in single-stranded poly(A) DNA. The results are in semiquantitative agreement with recent experimental results for the delocalization length of thes... ( view more )e states in single- and double-stranded DNA. The structures used in these molecular dynamics calculations are validated by comparing calculated circular dichroic spectra for d(A)2 and d(A)4 with experiment. These spectra, which arise from highly stacked structures, are in good agreement with experiment, suggesting that the short delocalization in ssDNA arises in spite of strong stacking. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Autologous umbilical cord blood infusion for type 1 diabetes. Jun 2008 Michael J Haller,Hilla-Lee Viener,Clive Wasserfall,Todd Brusko,Mark A Atkinson,Desmond A Schatz OBJECTIVE: The physical, emotional, and economic costs of type 1 diabetes (T1D) mandate continued efforts to develop effective strategies to prevent or reverse the disease. Herein, we describe the scientific and therapeutic rationale underlying efforts utilizing umbilical cord blood (UCB) as a ther... ( view more )apy for ameliorating the progression of this autoimmune disease. MATERIALS AND METHODS: We recently embarked on a pilot study to document the safety and potential efficacy of autologous UCB infusion in subjects with T1D. Under this protocol, patients recently diagnosed with the disease and for whom autologous cord blood is stored, undergo infusion. Studies are performed before infusion and every 3 to 6 months postinfusion for immunologic and metabolic assessment. To date, 15 autologous infusions have been performed. RESULTS: Preliminary observations suggest that autologous cord blood transfusion is safe and provides some slowing of the loss of endogenous insulin production in children with T1D. Mechanistic studies demonstrate that umbilical cord blood contains highly functional populations of regulatory T cells (Treg) and that increased Treg populations may be found in the peripheral blood of subjects more than 6 months after cord blood infusion. We provide the rationale for cord blood-based therapies, a summary of our initial protocol, and plans for future studies designed to explore the potential of cord blood-derived regulatory T cells to treat T1D. CONCLUSIONS: Prolonged follow-up and additional mechanistic efforts are urgently needed to determine if umbilical cord blood-derived stem cells can be used as part of safe and effective therapies for T1D. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Matrix metalloproteinase 9 (MMP9) expression in preeclamptic decidua and MMP9 induction by tumor necrosis factor alpha and interleukin 1 beta in human first trimester decidual cells. Jun 2008 Charles J Lockwood,Ceyda Oner,Yesim H Uz,Umit A Kayisli,S Joseph Huang,Lynn F Buchwalder,William Murk,Edmund F Funai,Frederick Schatz Extravillous trophoblasts (EVTs) invade human decidua via sequential integrin-mediated binding and proteolysis of basement membrane proteins in the extracellular matrix (ECM). In preeclampsia, shallow EVT invasion impairs spiral artery and arteriole remodeling to reduce uteroplacental blood flow. E... ( view more )xcess decidual cell-expressed matrix metalloproteinases (MMPs) 2 and 9, in response to preeclampsia-related interleukin 1 beta (IL1B) and tumor necrosis factor alpha (TNF), may inappropriately degrade these basement membrane proteins and impede EVT invasion. This study found significantly higher immunohistochemical MMP9 levels in decidual cells and adjacent interstitial trophoblasts in placental sections of preeclamptic versus gestational age-matched control women. In contrast, immunostaining for MMP2 and tissue inhibitor of matrix metalloproteinases 1 and 2 (TIMP1 and TIMP2) were similar in preeclamptic and control groups. First-trimester decidual cells were incubated with estradiol (E(2)) or E(2) + medroxyprogesterone acetate (MPA), with or without TNF or IL1B. As measured by ELISA, both cytokines elicited concentration-dependent increases in secreted MMP9 levels that were unaffected by MPA. In contrast, secreted levels of MMP2, TIMP1, and TIMP2 were unchanged in all treatment groups. Substrate gel zymography and Western blotting confirmed that each cytokine increased secreted levels of MMP9 but not MMP2. Similarly, quantitative RT-PCR found that TNF and IL1B enhanced MMP9, but not MMP2, mRNA levels. At the implantation site, inflammatory cytokine-enhanced MMP9 may promote preeclampsia by disrupting the decidual ECM to interfere with normal stepwise EVT invasion. ( view less ) View Full Abstract View Article Details View Coded Data Related Articles Page 1 of 64 1 2 3 4 > Last >> (1594 articles found)

      
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