tbuckley/cabot-search huggingface dataset:
Conjugated Equine Estrogens and Global Cognitive Function in Postmenopausal Women&lt;SUBTITLE&gt;Women's Health Initiative Memory Study&lt;/SUBTITLE&gt;
Authors: Mark A. Espeland
Journal: JAMA (2004)

The Women's Health Initiative Memory Study (WHIMS) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older. The effect of estrogen-alone therapy, also evaluated in WHIMS, on cognition has not been established for this population.To determine whether conjugated equine estrogen (CEE) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate (CEE plus MPA).A randomized, double-blind, placebo-controlled ancillary study of the Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence of probable dementia among community-dwelling women aged 65 to 79 years with prior hysterectomy from 39 US academic centers that started in June 1995. Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947 (92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women (95.3%) with a baseline and at least 1 follow-up measure of global cognitive function before the trial's termination on February 29, 2004.Participants received 1 daily tablet containing either 0.625 mg of CEE (n = 1387) or matching placebo (n = 1421).Global cognitive function measured annually with the Modified Mini-Mental State Examination (3MSE).During a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26 (0.13) units lower than among women assigned to CEE compared with placebo (P =.04). For pooled hormone therapy (CEE combined with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P =.006). Removing women with dementia, mild cognitive impairment, or stroke from the analyses lessened these differences. The adverse effect of hormone therapy was more pronounced among women with lower cognitive function at baseline (all P<.01). For women assigned to CEE compared with placebo, the relative risk of having a 10-unit decrease in 3MSE scores (>2 SDs) was estimated to be 1.47 (95% confidence interval, 1.04-2.07).For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment.
Studies on Chromated Erythrocytes. Effect of Sodium Chromate on Erythrocyte Glutathione Reductase*
Authors: George A. Koutras, Masao Hattori, Arthur S. Schneider, Frank G. Ebaugh, William N. Valentine
Journal: Journal of Clinical Investigation (1964)

The marked affinity of erythrocytes for hexa- valent chromate anion was reported in 1950 by Gray and Sterling (1).Since then, erythrocytes labeled with radioactive sodium chromate have been used extensively for the determination of erythrocyte survival in vivo (1-5) and the deter- mination of blood volume (4-6).The anionic hexavalent form of chromium is bound firmly to erythrocytes, is not reutilized, and is excreted mainly in the urine (2).Gray and Sterling sug- gested that the hexavalent form of chromium in the erythrocyte is probably bound to hemoglobin.Recent work, however, has shown that not all of the chromium is attached to hemoglobin, but that some of it is combined with a substance of low molecular weight, possibly glutathione (7).Ebaugh, Emerson, and Ross (2) showed that small amounts of chromate, up to 9.5 Fg of chromium per ml of blood, had no apparent effect on the survival of erythrocytes in vivo.When 35 pg per ml of blood was used, however, there was significant hemolysis in vivo during the first 24 hours.Donohue and associates (5) found that amounts below 25 ug of chromium per ml of erythrocytes did not affect erythrocyte survival, but that larger amounts were toxic.In this paper we report the results of studies of the effect of chromate on erythrocyte en- zymes.A marked inhibition of glutathione-re- ductase (GSSG-R) activity was observed.Upon incubation with acetylphenylhydrazine, chromate- treated erythrocytes had an increased tendency to form Heinz bodies, and there was some decrease in glutathione stability.
<i>Le bon dieu est dans le detail</i>: Is smiling the recognition of happiness?
Authors: José-Miguel Fernández-Dols, Pilar Carrera
Journal: Behavioral and Brain Sciences (2010)

Abstract We question two conceptual assumptions made by Niedenthal et al.: the dichotomy between true and false smiles and the close tie between recognition and experience of emotion. An excessive dependence on everyday language suggests overly parsimonious accounts of a complex set of relations between smile, experience, and context.
A Nurse-Associated Epidemic of Cardiac Arrests in an Intensive Care Unit
Authors: Jeffrey J. Sacks
Journal: JAMA (1988)

Review of 2219 admissions to an intensive care unit at a large urban hospital from 1983 to 1985 revealed an epidemic of cardiac arrests during the evening shift from January 1984 to March 1985. Of the 88 evening-shift cardiac arrests during this time, one specific nurse (Nurse 14) was the care giver for 57 (65%). Eight of ten epidemic-period patients who experienced shift-specific circadian recurrences of cardiac arrests were patients of Nurse 14. No therapeutic intervention and no other health care provider was as strongly associated with evening-shift cardiac arrests as was Nurse 14. Multiple logistic regression analysis demonstrated that when risk of cardiac arrest was adjusted for age, sex, severity of illness, and postoperative status, patients of Nurse 14 were 47.5 times more likely to experience arrest than were other nurses' patients. An expert determined that, compared with other nurses, the cardiac arrests among Nurse 14's patients were more likely to be consistent with unexplained hyperkalemia, to be unexpected in timing, and to be inconsistent with the clinical course. The epidemic ceased when Nurse 14 left employment at the intensive care unit in March 1985. Epidemiologic surveillance of adverse outcomes in health care settings is recommended.
Gene transfer of endothelial nitric oxide synthase improves nitric oxide-dependent endothelial function in a hypertensive rat model
Authors: M Alexander
Journal: Cardiovascular Research (1999)

We have shown previously that there is a relative nitric oxide deficiency at the level of vascular endothelium in the stroke-prone spontaneously hypertensive rat (SHRSP), a model of human essential hypertension, as compared to its normotensive reference strain Wistar Kyoto (WKY) rat. The aim of the current study was to investigate whether adenoviral-mediated gene transfer of an endothelial nitric oxide synthase (eNOS) cDNA (AdCMVeNOS) into carotid arteries of the SHRSP may improve endothelial function.Enzyme activity of the recombinant eNOS protein encoded by AdCMVeNOS was tested using a Griess assay in endothelial cells in culture. Left carotid arteries of SHRSP were surgically isolated and exposed to either the AdCMVeNOS or control beta-galactosidase-containing virus, (2 x 10(9) pfu/ml) ex vivo and in vivo. The vessels were harvested 24 h after surgery and analysed by Western blotting, immunohistochemistry and by examining endothelial function ex vivo.Cultured endothelial cells showed almost 100% transduction with both viruses and a dose response of eNOS expression showed a five-fold increase in nitrite production for AdCMVeNOS with no change for beta-galactosidase-containing virus. Western blotting demonstrated a significant increase of eNOS expression in vessels infused with AdCMVeNOS when compared to controls. Immunohistochemistry showed highly positive staining with monoclonal antibodies against eNOS in the intact endothelial cells of the AdCMVeNOS infused vessels. The areas under the curve of the concentration responses to phenylephrine (10(-9) to 3 x 10(-6) M) in the absence and presence of NG-nitroarginine methyl ester (100 microM) showed increased basal nitric oxide bioavailability in the carotid arteries infused with AdCMVeNOS compared to the control (n = 6 for each; P = 0.0069; 95% CI, 0.864 to 3.277).Our results show that AdCMVeNOS is an effective tool for vascular gene transfer and that it can improve endothelial NO availability in the SHRSP, a genetic model of essential hypertension and endothelial dysfunction.
Histoplasmosis after Treatment with Anti–Tumor Necrosis Factor-α Therapy
Authors: Karen L. Wood, Chadi A. Hage, Kenneth S. Knox, Martin B. Kleiman, Aruna Sannuti, Richard B. Day, L. Joseph Wheat, Homer L. Twigg
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Section:ChooseTop of pageAbstract <<CASE REPORTSMETHODSRESULTSDISCUSSIONReferencesCITING ARTICLES
Adrenal function in patients with community-acquired pneumonia
Authors: S. Gotoh, N. Nishimura, O. Takahashi, H. Shiratsuka, H. Horinouchi, H. Ono, N. Uchiyama, N. Chohnabayashi
Journal: European Respiratory Journal (2008)

Adrenal insufficiency is believed to occur frequently in severe sepsis and septic shock. The aim of the present study was to determine whether adrenal function is also related to the severity of community-acquired pneumonia (CAP). In total, 64 Japanese patients with CAP were consecutively enrolled in the present study, which was carried out during 2005–2006. Serum adrenocorticotropic hormone (ACTH) and cortisol were measured in each subject, as was the response of cortisol secretion when 250 μg of cosyntropin was administered. Analyses were performed comparing these values with the score calculated according to the Pneumonia Patient Outcomes Research Team (PORT) cohort study, the number of in-hospital deaths and the length of hospital stay. As the PORT score increased, serum ACTH and cortisol also increased, while the response of cortisol secretion to the administration of cosyntropin decreased. In the analysis by receiver operating characteristic curves, adrenal dysfunction was related significantly to both the number of in-hospital deaths and the length of hospital stay. Adrenal dysfunction was shown to correlate with the Pneumonia Patient Outcomes Research Team score and the clinical outcomes, while adrenal insufficiency defined by the cosyntropin stimulation test was rare in the present study.
Randomised controlled trial of ultrasonography in diagnosis of acute appendicitis, incorporating the Alvarado score
Authors: C. D Douglas
Journal: BMJ (2000)

<h3>Abstract</h3> <b>Objectives:</b> To determine whether diagnosis by graded compression ultrasonography improves clinical outcomes for patients with suspected appendicitis. <b>Design:</b> A randomised controlled trial comparing clinical diagnosis (control) with a diagnostic protocol incorporating ultrasonography and the Alvarado score (intervention group). <b>Setting:</b> Single tertiary referral centre. <b>Participants:</b> 302 patients (age 5-82 years) referred to the surgical service with suspected appendicitis. 160 patients were randomised to the intervention group, of whom 129 underwent ultrasonography. Ultrasonography was omitted for patients with extreme Alvarado scores (1-3, 9, or 10) unless requested by the admitting surgical team. <b>Main outcome measures:</b> Time to operation, duration of hospital stay, and adverse outcomes, including non-therapeutic operations and delayed treatment in association with perforation. <b>Results:</b> Sensitivity and specificity of ultrasonography were measured at 94.7% and 88.9%, respectively. Patients in the intervention group who underwent therapeutic operation had a significantly shorter mean time to operation than patients in the control group (7.0 <i>v</i> 10.2 hours, P=0.016). There were no differences between groups in mean duration of hospital stay (53.4 <i>v</i> 54.5 hours, P=0.84), proportion of patients undergoing a non-therapeutic operation (9% <i>v</i> 11%, P=0.59) or delayed treatment in association with perforation (3% <i>v</i> 1%, P=0.45). <b>Conclusion:</b> Graded compression ultrasonography is an accurate procedure that leads to the prompt diagnosis and early treatment of many cases of appendicitis, although it does not prevent adverse outcomes or reduce length of hospital stay.
Molecular Profiling of Aromatase Inhibitor–Treated Postmenopausal Breast Tumors Identifies Immune-Related Correlates of Resistance
Authors: Anita K. Dunbier, Zara Ghazoui, Helen Anderson, Janine Salter, Ashutosh Nerurkar, Peter Osin, Roger A'hern, William R. Miller, Ian E. Smith, Mitch Dowsett
Journal: Clinical Cancer Research (2013)

Estrogen withdrawal by treatment with aromatase inhibitors is the most effective form of endocrine therapy for postmenopausal estrogen receptor-positive (ER+) breast cancer. However, response to therapy varies markedly and understanding of the precise molecular effects of aromatase inhibitors and causes of resistance is limited. We aimed to identify in clinical breast cancer those genes and pathways most associated with resistance to aromatase inhibitors by examining the global transcriptional effects of AI treatment.Baseline and 2-week posttreatment biopsies were obtained from 112 postmenopausal women with ER+ breast cancer receiving neoadjuvant anastrozole. Gene expression data were obtained from 81 baseline and 2-week paired samples. Pathway analysis identified (i) the most prevalent changes in expression and (ii) the pretreatment genes/pathways most related to poor antiproliferative response.A total of 1,327 genes were differentially expressed after 2-week treatment (false discovery rate < 0.01). Proliferation-associated genes and classical estrogen-dependent genes were strongly downregulated whereas collagens and chemokines were upregulated. Pretreatment expression of an inflammatory signature correlated with antiproliferative response to anastrozole and this observation was validated in an independent study. Higher expression of immune-related genes such as SLAMF8 and TNF as well as lymphocytic infiltration were associated with poorer response (P < 0.001) and validated in an independent cohort.The molecular response to aromatase inhibitor treatment varies greatly between patients consistent with the variable clinical benefit from aromatase inhibitor treatment. Higher baseline expression of an inflammatory signature is associated with poor antiproliferative response and should be assessed further as a novel biomarker and potential target for aromatase inhibitor-treated patients.
Elastase and alpha 1-proteinase inhibitor activity in tracheal aspirates during respiratory distress syndrome. Role of inflammation in the pathogenesis of bronchopulmonary dysplasia.
Authors: T A Merritt, C G Cochrane, K Holcomb, B Bohl, M Hallman, D Strayer, D K Edwards, L Gluck
Journal: Journal of Clinical Investigation (1983)

Pulmonary effluent samples were obtained from 26 preterm or term infants throughout the period of endotracheal intubation. Infants with respiratory distress syndrome, infants with this disorder developing bronchopulmonary dysplasia, and intubated infants without lung disease were compared daily in terms of lung effluent cellularity, albumin, elastase activity, alpha 1-proteinase content and activity, and elastase inhibitory capacity. The elastase activity was determined to be neutrophilic in origin. Polyacrylamide gel electrophoresis of pulmonary effluents from two infants with respiratory distress syndrome and exposed to FiO2 greater than or equal to 0.6 up to 6 d revealed cleavage of alpha 1-proteinase inhibitor to a 47,000-mol weight fragment suggestive of oxidation. Pulmonary effluent neutrophils, macrophages, and elastase activity were increased by day 3 of life in infants with respiratory distress syndrome eventually developing bronchopulmonary dysplasia. Elastase inhibitory capacity and alpha 1-proteinase inhibitor activity were reduced in infants developing chronic lung disease. Bronchopulmonary dysplasia developed in infants with enhanced inflammatory response, but with less or inhibited antiprotease activity.
Gammaretrovirus-mediated correction of SCID-X1 is associated with skewed vector integration site distribution in vivo
Authors: Kerstin Schwarzwaelder, Steven J. Howe, Manfred Schmidt, Martijn H. Brugman, Annette Deichmann, Hanno Glimm, Sonja Schmidt, Claudia Prinz, Manuela Wissler, Douglas J.S. King, Fang Zhang, Kathryn L. Parsley, Kimberly C. Gilmour, Joanna Sinclair, Jinhua Bayford, Rachel Peraj, Karin Pike-Overzet, Frank J.T. Staal, Dick de Ridder, Christine Kinnon, Ulrich Abel, Gerard Wagemaker, H. Bobby Gaspar, Adrian J. Thrasher, Christof von Kalle
Journal: Journal of Clinical Investigation (2007)

We treated 10 children with X-linked SCID (SCID-X1) using gammaretrovirus-mediated gene transfer. Those with sufficient follow-up were found to have recovered substantial immunity in the absence of any serious adverse events up to 5 years after treatment. To determine the influence of vector integration on lymphoid reconstitution, we compared retroviral integration sites (RISs) from peripheral blood CD3+ T lymphocytes of 5 patients taken between 9 and 30 months after transplantation with transduced CD34+ progenitor cells derived from 1 further patient and 1 healthy donor. Integration occurred preferentially in gene regions on either side of transcription start sites, was clustered, and correlated with the expression level in CD34+ progenitors during transduction. In contrast to those in CD34+ cells, RISs recovered from engrafted CD3+ T cells were significantly overrepresented within or near genes encoding proteins with kinase or transferase activity or involved in phosphorus metabolism. Although gross patterns of gene expression were unchanged in transduced cells, the divergence of RIS target frequency between transduced progenitor cells and post-thymic T lymphocytes indicates that vector integration influences cell survival, engraftment, or proliferation.
Mycophenolate Mofetil Treatment Improves Hypertension in Patients with Psoriasis and Rheumatoid Arthritis
Authors: Jose Herrera, Atilio Ferrebuz, Ernesto García MacGregor, Bernardo Rodriguez-Iturbe
Journal: Journal of the American Society of Nephrology (2006)

Evidence that was obtained in several experimental models and in strains of hypertensive rats indicates that infiltration of inflammatory cells and oxidative stress in the kidney play a role in the induction and maintenance of hypertension. Similar evidence is lacking in human hypertension, at least in part, because immunosuppressive treatment is unjustified in patients with hypertension. For addressing this issue, patients who were prescribed by their private physicians mycophenolate mofetil (MMF) for the treatment of psoriasis or rheumatoid arthritis and had, in addition, grade I essential hypertension and normal renal function were studied. Eight patients were studied before MMF was started, during MMF treatment, and 1 mo after MMF treatment had been discontinued. Other treatments and diet were unchanged in the three phases of the study. MMF therapy was associated with a significant reduction in systolic, diastolic, and mean BP. Urinary excretion of TNF-α was reduced progressively by MMF treatment and increased after MMF was discontinued. Reduction of urinary malondialdehyde, TNF-α, and RANTES excretion during MMF administration did not reach statistical significance but had a direct positive correlation with the BP levels. These data are consistent with the hypothesis that renal immune cell infiltration and oxidative stress play a role in human hypertension.
Strand Symmetry Around the β-Globin Origin of Replication in Primates
Authors: M. Pilar Francino*, Howard Ochman
Journal: Molecular Biology and Evolution (2000)

Certain mutations are known to occur with differing frequencies on the leading and lagging strands of DNA. The extent to which these mutational biases affect the sequences of higher eukaryotes has been difficult to ascertain because the positions of most replication origins are not known, making it impossible to distinguish between the leading and lagging strands. To resolve whether strand biases influence the evolution of primate sequences, we compared the substitution patterns in noncoding regions adjacent to an origin of replication identified within the β-globin complex. Although there was limited asymmetry around the β-globin origin of replication, patterns of substitutions do not support the existence of a mutational bias between the leading and lagging strands of chromosomal DNA replication in primates.
Angioscopic follow-up study of coronary ruptured plaques in nonculprit lesions
Authors: Masamichi Takano, Shigenobu Inami, Fumiyuki Ishibashi, Kentaro Okamatsu, Koji Seimiya, Takayoshi Ohba, Shunta Sakai, Kyoichi Mizuno
Journal: Journal of the American College of Cardiology (2005)
Dicer1 and miR-219 Are Required for Normal Oligodendrocyte Differentiation and Myelination
Authors: Jason C. Dugas, Trinna L. Cuellar, Anja Scholze, Brandon Ason, Adiljan Ibrahim, Ben Emery, Jennifer L. Zamanian, Lynette C. Foo, Michael T. McManus, Ben A. Barres
Journal: Neuron (2010)
Coordinated transcriptional regulation of bone homeostasis by Ebf1 and Zfp521 in both mesenchymal and hematopoietic lineages
Authors: Riku Kiviranta, Kei Yamana, Hiroaki Saito, Daniel K. Ho, Julius Laine, Kati Tarkkonen, Vappu Nieminen-Pihala, Eric Hesse, Diego Correa, Jorma Määttä, Lino Tessarollo, Evan D. Rosen, William C. Horne, Nancy A. Jenkins, Neal G. Copeland, Soren Warming, Roland Baron
Journal: The Journal of Experimental Medicine (2013)

Bone homeostasis is maintained by the coupled actions of hematopoietic bone-resorbing osteoclasts (OCs) and mesenchymal bone-forming osteoblasts (OBs). Here we identify early B cell factor 1 (Ebf1) and the transcriptional coregulator Zfp521 as components of the machinery that regulates bone homeostasis through coordinated effects in both lineages. Deletion of Zfp521 in OBs led to impaired bone formation and increased OB-dependent osteoclastogenesis (OC-genesis), and deletion in hematopoietic cells revealed a strong cell-autonomous role for Zfp521 in OC progenitors. In adult mice, the effects of Zfp521 were largely caused by repression of Ebf1, and the bone phenotype of Zfp521(+/-) mice was rescued in Zfp521(+/-):Ebf1(+/-) mice. Zfp521 interacted with Ebf1 and repressed its transcriptional activity. Accordingly, deletion of Zfp521 led to increased Ebf1 activity in OBs and OCs. In vivo, Ebf1 overexpression in OBs resulted in suppressed bone formation, similar to the phenotype seen after OB-targeted deletion of Zfp521. Conversely, Ebf1 deletion led to cell-autonomous defects in both OB-dependent and cell-intrinsic OC-genesis, a phenotype opposite to that of the Zfp521 knockout. Thus, we have identified the interplay between Zfp521 and Ebf1 as a novel rheostat for bone homeostasis.