tbuckley/cabot-search huggingface dataset:
Septal Function During Left Ventricular Unloading
Authors: Marc R. Moon, Ann F. Bolger, Abe DeAnda, Masashi Komeda, George T. Daughters, Srdjan D. Nikolic, D. Craig Miller, Neil B. Ingels
Journal: Circulation (1997)

Background Left ventricular (LV) unloading with mechanical support devices alters biventricular geometry and impairs right ventricular (RV) contractility, but its effect on septal systolic function remains unknown. Methods and Results To evaluate the effects of LV volume and pressure unloading on septal geometry and function, LV preload was abruptly reduced by clamping left atrial pressure between 0 and −2 mm Hg in seven open-chest, anesthetized dogs by use of a pressure-control servomechanism to withdraw blood from the left atrium. With left atrial pressure clamping, maximal LV pressure decreased 30±12% (mean±SD) ( P &lt;.0001) and LV end-diastolic cross-sectional area (determined by two-dimensional echocardiography) decreased by 53±16% ( P &lt;.0001). This caused the septum to shift toward the left (RV septal free-wall dimension increased; P &lt;.004) and flatten (radius of curvature increased; P &lt;.0002), while LV septal free-wall dimension fell ( P &lt;.0001). Septal end-diastolic thickness increased 23±15% ( P &lt;.0005), reflecting a decline in septal preload. Systolic septal thickening decreased ( P &lt;.002), while systolic septal output (Septal Output=Septal Thickening×Heart Rate) fell from 30±17 to 15±22 cm/min ( P &lt;.002). This was associated with movement along the septal Frank-Starling equivalent (septal output versus end-diastolic septal thickness [preload] relation) to a less productive portion of the curve. Conclusions LV unloading not only altered interventricular septal geometry but also reduced septal systolic thickening and output, all of which may contribute to impaired RV contractility during mechanical LV support.
Successful use of rituximab in a patient with Churg–Strauss syndrome and refractory central nervous system involvement: Figure 1
Authors: Jasemine Saech, Kasia Owczarzyk, Sylvia Rösgen, Hela Petereit, Michael Hallek, Andrea Rubbert-Roth
Journal: Annals of the Rheumatic Diseases (2009)

Background: Xanthinuria type II is a rare autosomal purine disorder. This recessive defect of purine metabolism remains an underrecognized disorder. Methods: Mice with targeted disruption of the molybdenum cofactor sulfurase (Mocos) gene were generated to enable an integrated understanding of purine disorders and evaluate pathophysiological functions of this gene found in large number of pathways and known to be associated with autism. Results: Mocos deficient mice die with 4 weeks of age due to renal failure of distinct obstructive nephropathy with xanthinuria, xanthine deposits, cystic tublular dilatation, Tamm Horsfall (uromodulin) protein deposits, tubular cell necrosis with neutrophils and occasionally hypdronephrosis with urolithiasis. Obstructive nephropathy is associated with moderate interstitial inflammatory and fibrotic responses, anemia, reduced detoxification systems and important alterations of the metabolism of purines, amino acids and phospholipids.Conversely, heterozygous mice expressing reduced MOCOS protein are healthy with no apparent pathology. Conclusions: Mocos deficient mice develop a lethal obstructive nephropathy associated with profound metabolic changes. Studying MOCOS functions may provide important clues about the underlying pathogenesis of xanthinuria and other diseases requiring early diagnosis
HLA-G a putative susceptibility gene in scleroderma, but only in women
Authors: Doua F Azzouz, Julie Di Cristofaro, Sami B Kanaan, Jean Cabane, Dominique Farge, Yannick Allanore, Eric Hachulla, Jean Robert Harlé, Brigitte Granel, Marielle Martin, Jean Roudier, Christophe Picard, Nathalie Lambert
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Systemic sclerosis or Scleroderma (SSc) is an autoimmune disease affecting mostly women with a higher incidence between 40 and 60 years old. Several HLA class II genes have been associated with SSc depending on the clinical subset of the disease, limited cutaneous SSc (lc-SSc) or diffuse cutaneous SSc (dc-SSc) or on specific autoantibodies, anticentromere antibodies (ACA) or antitopoisomerase (ATA) antibodies, respectively hallmarks of the above clinical subsets. HLA-G is a non classical HLA molecule with tolerance functions that may play a role in inflammatory diseases. A 14 bp sequence insertion/deletion polymorphism (rs16375) in the 3′-untranslated region of the HLA-G gene has been associated to levels of soluble HLA-G (sHLA-G). The insertion is associated with lower levels. <h3>Objectives</h3> In the current study, the authors propose to analyse this polymorphism in patients with SSc compared to healthy individuals. The authors furthermore stratified patients according to sex, clinical subsets and autoantibody status. <h3>Patients and methods</h3> The authors genotyped 145 patients with SSc and 95 healthy controls by a previously developed two step multiplex SNaPshot method several HLA-G Single Nucleotide polymorphisms and the -14bp Ins/Del polymorphism. <h3>Results</h3> Patients with SSc tend to have higher frequency of ins/ins (29/145, 20.0%) genotypes compared with healthy controls (11/95, 11.6%, p=0.008). The frequency of Ins alleles compared to Del alleles is significantly increased among patients with SSc (p=0.024). This association reveals interesting patterns when patients are divided by sex (women, N=110 and men, N=35). Men had similar frequencies of Del/Del, Del/Ins, Ins/Ins genotypes than healthy controls (respectively, 45.7%, 42.9%, 11.4% and 50.5%, 37.9%, 11.6%), whereas women had different proportions of genotypes with Del/Del: 36.4%, Del/Ins: 40.9% and Ins/Ins: 22.7%. The difference in genotype repartition was statistically significant in women with SSc compared with healthy controls (p=0.047) and the difference in allele frequency even stronger (Ins: 43.1% compared with 30.5%, p=0.008). Apart from the gender association an association with dcSSc with the Ins allele (p=0.004), and a marginal association with lcSSc (p=0.08)were also observed. Interestingly both autoantibody subgroups, ATA and ACA, were associated with higher Ins allele frequencies (p=0.018 and p=0.03, respectively). <h3>Conclusion</h3> Women with SSc but not men have a genotype of low sHLA-G secretor. Further studies need to be conducted to better understand this gender dichotomy and its meaning in tolerance in a disease affecting mostly women in their childbearing years.
Managing Magnetic Nanoparticle Aggregation and Cellular Uptake: a Precondition for Efficient Stem‐Cell Differentiation and MRI Tracking
Authors: Delphine Fayol, Nathalie Luciani, Lenaic Lartigue, Florence Gazeau, Claire Wilhelm
Journal: Advanced Healthcare Materials (2012)

Abstract The labeling of stem cells with iron oxide nanoparticles is increasingly used to enable MRI cell tracking and magnetic cell manipulation, stimulating the fields of tissue engineering and cell therapy. However, the impact of magnetic labeling on stem‐cell differentiation is still controversial. One compromising factor for successful differentiation may arise from early interactions of nanoparticles with cells during the labeling procedure. It is hypothesized that the lack of control over nanoparticle colloidal stability in biological media may lead to undesirable nanoparticle localization, overestimation of cellular uptake, misleading MRI cell tracking, and further impairment of differentiation. Herein a method is described for labeling mesenchymal stem cells (MSC), in which the physical state of citrate‐coated nanoparticles (dispersed versus aggregated) can be kinetically tuned through electrostatic and magnetic triggers, as monitored by diffusion light scattering in the extracellular medium and by optical and electronic microscopy in cells. A set of statistical cell‐by‐cell measurements (flow cytometry, single‐cell magnetophoresis, and high‐resolution MRI cellular detection) is used to independently quantify the nanoparticle cell uptake and the effects of nanoparticle aggregation. Such aggregation confounds MRI cell detection as well as global iron quantification and has adverse effects on chondrogenetic differentiation. Magnetic labeling conditions with perfectly stable nanoparticles—suitable for obtaining differentiation‐capable magnetic stem cells for use in cell therapy—are subsequently identified.
Progenitor cell trafficking is regulated by hypoxic gradients through HIF-1 induction of SDF-1
Authors: Daniel J Ceradini, Anita R Kulkarni, Matthew J Callaghan, Oren M Tepper, Nicholas Bastidas, Mark E Kleinman, Jennifer M Capla, Robert D Galiano, Jamie P Levine, Geoffrey C Gurtner
Journal: Nature Medicine (2004)
Skeletal Manifestations in the Marfan Syndrome
Authors: Harvey I. Wilner, Nathaniel Finby
Journal: JAMA (1964)

THE MARFAN SYNDROME is a heritable disease of connective tissue which involves many organ systems but has its chief clinical significance in abnormalities of the ocular, cardiovascular, and skeletal structures. The fully developed syndrome is readily recognized clinically in a tall patient with arachnodactyly who exhibits bilateral lens dislocation and dissecting aneurysm of the aorta. It is important to note, however, that the basic abnormality is generalized in the connective tissue and is not a congenital malformation of viscera. Therefore, the incidence of clinically detectable malformations will increase with age, and clinical abnormality may not be evident in every individual with the syndrome. Accurate diagnosis is extremely difficult, especially without the full spectrum of clinical abnormality. Although more than 400 cases have been reported in the literature as examples of the Marfan syndrome, fewer than 10% of these are documented with pathological study<sup>1,2</sup>; the remainder have usually been diagnosed
Temporal Alternation of Atrial Flutter Sounds
Authors: D. EMSLIE-SMITH, E. H. O. PARRY
Journal: Circulation (1968)

A case of atrial flutter is reported in which the hearing of "systoles en écho" led to the recognition in the phonocardiogram of a regularly alternating time interval between successive atrial sounds during the ventricular standstill caused by stimulation of the carotid sinus. A possible explanation is proposed involving alternating pathways of atrial excitation.
THE ASSOCIATION BETWEEN CONCOMITANT PROTON-PUMP INHIBITOR USE AND CLINICAL OUTCOMES IN PATIENTS WITH ACUTE CORONARY SYNDROMES TREATED WITH PRASUGREL VERSUS CLOPIDOGREL AND MANAGED WITHOUT REVASCULARIZATION: INSIGHTS FROM THE TRILOGY ACS STUDY
Authors: Jose C. Nicolau, Deepak Bhatt, Matthew Roe, Benjamin Neely, Ramon Corbalan, Jose Leiva-Pons, Felipe Martinez, Shaun Goodman, Eileen Brown, Freek Verheugt, Paul Armstrong, Harvey White, Keith Fox, Dorairaj Prabhakaran, E. Magnus Ohman
Journal: Journal of the American College of Cardiology (2013)
Acid protease activity in thyroid gland from patients with Graves' disease
Authors: Mototaka Yoshinari, Kenjiro Inoue, Toshiro Nakashima, Ken Okamura, Akiyo Shiroozu, Hirokazu Nishitani, Teruo Omae, Motomichi Torisu, Shirou Noguchi
Journal: Metabolism (1983)
Abuse of Trihexyphenidyl
Authors: Gary E. Pakes
Journal: JAMA (1978)

<h3>To the Editor.—</h3> In his article "Abuse of Antiparkinsonism Drugs: Feigning of Extrapyramidal Symptoms To Obtain Trihexyphenidyl" (239:2365, 1978), Jonathan S. Rubinstein, MD, remarked about the scarcity of reports, such as his, involving psychotic patients using trickery to obtain prescriptions for trihexyphenidyl hydrochloride (Artane), which they may then wrongly use for hallucinogenic purposes. Certainly, as Dr Rubenstein emphasized, physicians should be more wary of the practice of automatically prescribing these antiparkinsonism agents, especially when treating patients with a long history of drug abuse. However, not all patients want the trihexyphenidyl solely to get a "high," even though they may feign an extrapyramidal reaction to obtain it. As the former director of pharmacy services at the Buffalo General Hospital Community Mental Health Center in Buffalo, my associates and I recorded an incidence of trihexyphenidyl abuse among 7% of our outpatients.<sup>1</sup>Most of our patients were welfare recipients, and two, in
Opposing Function of the Proprotein Convertases Furin and PACE4 on Breast Cancer Cells' Malignant Phenotypes: Role of Tissue Inhibitors of Metalloproteinase-1
Authors: Marion Lapierre, Geraldine Siegfried, Nathalie Scamuffa, Yannick Bontemps, Fabien Calvo, Nabil G. Seidah, Abdel-Majid Khatib
Journal: Cancer Research (2007)

Abstract Proteolytic cleavage of various cancer-related substrates by the proprotein convertases (PC) was reported to be important in the processes of neoplasia. These enzymes are inhibited by their naturally occurring inhibitors, the prosegments (ppPC), and by the engineered general PC inhibitor, the serpin variant α1-PDX. In the present study, we sought to compare the effect of these PC inhibitors on malignant phenotypes of breast cancer cells. Overexpression in a stable manner of α1-PDX and the prosegment ppPACE4 in MDA-MB-231 breast cancer cells resulted in increased matrix metalloproteinase (MMP)-9 (but not MMP-2) activity and a reduced secretion of tissue inhibitor of metalloproteinase 1 (TIMP-1). This was associated with significant enhancement in cell motility, migration, and invasion of collagen in vitro. In contrast, ppFurin expression in these cells decreased MMP-9 activity and diminished these biological functions, but had no significant effect on TIMP-1 secretion. Taken together, these data showed the specific and opposing roles of Furin and PACE4 in the regulation of MMP-9/TIMP-1–mediated cell motility and invasion. [Cancer Res 2007;67(19):9030–4]
Incidence of Lower Limb Amputations and Diabetes
Authors: Christoph Trautner, Burkhard Haastert, Guido Giani, Michael Berger
Journal: Diabetes Care (1996)

OBJECTIVE We collected data on the incidence rates of amputations and their relative risk in diabetic subjects compared with the nondiabetic population. RESEARCH DESIGN AND METHODS From all three hospitals in a city of ∼ 160,000 inhabitants, we obtained complete lists of nontraumatic lower limb amputations. From each patient record, diabetic status was determined. We estimated age-specific and standardized incidence rates of amputations in the diabetic and nondiabetic populations and in the entire population, as well as the relative and attributable risks due to diabetes. RESULTS Nontraumatic lower limb amputations were performed on 106 residents of Leverkusen (Germany) in 1990 and 1991. Of them, 82 (77.4%) had diabetes. Mean age was 72.0 years. In the case of multiple amputations, only the highest level was counted for the analysis. The following results were standardized to the German population. Incidence rates (100,000−1 · year−1) were determined to be as follows: for all amputations per total population, 33.8; for amputations in diabetic individuals per diabetic population, 209.2; for amputations in nondiabetic individuals per nondiabetic population, 9.4. Relative risk was 22.2; attributable risk among exposed, 0.96; population attributable risk, 0.72. When the study is repeated to monitor the St. Vincent targets (50% reduction), a reduction in the amputation rate in the diabetic population by 46% will be detected with 90% power. CONCLUSIONS We found incidence rates similar to those in the non-Indian population of the U.S. Great relative and population-attributable risks indicate that improving foot care in diabetic individuals appears to be the main target for the reduction of amputations in the general population.
BREATHING EXERCISES WITH MOVING ARMS
Authors: H. Hill
Journal: BMJ (1927)

TMDIBOURiKkS particular value of flexiblc scar tisstue at tlie flexures of the body and at tendinous areas need niot be mentioned.In large voluintarily supported institutions the econiomical aspect-tlie saving in tiiiie and material-is also a coni- sideration.
Co-existence of pemphigus, anti-skeletal muscle antibody and a retroperitoneal paraganglioma
Authors: P.H. McKEE, M. McCLELLAND, J.C. SANDFORD
Journal: British Journal of Dermatology (1978)

Occasional reports have appeared in the literature describing a relationship between pemphigus vulgaris and malignancy (Krain & Bierman, 1974; Tagami et al., 1976). Carcinoma of the ovary, stomach, breast, endometrium and bronchus have all been associated with pemphigus (Krain, 1974). The association between pemphigus and thymoma is well known (Stillmand & Baer, 1972). Pemphigus has also been described in connection with various lymphoproliferative malignancies (Naysmith & Hancock, 1976). The purpose of this paper is to describe a patient who suffered from a rare retroperitoneal tumour in association with pemphigus vulgaris. His serum contained a high titre of anti-skeletal muscle antibody, although he showed no clinical manifestations of myasthenia gravis. He also had immunological manifestations suggestive of lupus erythematosus.
Extracellular Signal–Regulated Kinase 1/2 Mitogen-Activated Protein Kinase Pathway Is Involved in Myostatin-Regulated Differentiation Repression
Authors: Wei Yang, Yan Chen, Yong Zhang, Xueyan Wang, Ning Yang, Dahai Zhu
Journal: Cancer Research (2006)

Abstract The cytokines of transforming growth factor β (TGF-β) and its superfamily members are potent regulators of tumorigenesis and multiple cellular events. Myostatin is a member of TGF-β superfamily and plays a negative role in the control of cell proliferation and differentiation. We now show that myostatin rapidly activated the extracellular signal–regulated kinase 1/2 (Erk1/2) cascade in C2C12 myoblasts. A more remarkable Erk1/2 activation stimulated by myostatin was observed in differentiating cells than proliferating cells. The results also showed that Ras was the upstream regulator and participated in myostatin-induced Erk1/2 activation because the expression of a dominant-negative Ras prevented myostatin-mediated inhibition of Erk1/2 activation and proliferation. Importantly, the myostatin-suppressed myotube fusion and differentiation marker gene expression were attenuated by blockade of Erk1/2 mitogen-activated protein kinase (MAPK) pathway through pretreatment with MAPK/Erk kinase 1 (MEK1) inhibitor PD98059, indicating that myostatin-stimulated activation of Erk1/2 negatively regulates myogenic differentiation. Activin receptor type IIb (ActRIIb) was previously suggested as the only type II membrane receptor triggering myostatin signaling. In this study, by using synthesized small interfering RNAs and dominant-negative ActRIIb, we show that myostatin failed to stimulate Erk1/2 phosphorylation and could not inhibit myoblast differentiation in ActRIIb-knockdown C2C12 cells, indicating that ActRIIb was required for myostatin-stimulated differentiation suppression. Altogether, our findings in this report provide the first evidence to reveal functional role of the Erk1/2 MAPK pathway in myostatin action as a negative regulator of muscle cell growth. (Cancer Res 2006; 66(3): 1320-6)
Abstract 5593: Are variants in the syndecan-1 gene associated with breast cancer risk in older women
Authors: Margaret M. Madeleine, Alexa J. Resler, Lisa G. Johnson, Mari Malkki, Effie W. Petersdorf, Barbara McKnight, Kathleen E. Malone
Journal: Cancer Research (2011)

Abstract Syndecans are transmembrane proteins on the cell surface that act as receptors for ligands from a number of protein families. These proteoglycans are involved in a large number of important normal cell functions, including signaling, proliferation, and cell-matrix adhesion; they are also involved in aberrant cell functions such as inflammation, angiogenesis, and carcinogenesis. In a recent pathway directed re-analysis of GWAS data (Menashe, Cancer Research, 2010), variants in the syndecan-1 (SDC1) gene on chromosome 2p were found to be associated with excess risk of breast cancer. We sought to extend this finding by investigating the association between tagging SNPs in the SDC1 gene and risk of breast cancer in our case-control study (The PACE study) in older women. This population-based study includes 845 women who were 65-79 years old at diagnosis of incident breast cancer and 807 age-matched unaffected controls from the Seattle area. The analysis was restricted to Caucasian women. A total of 11 SNPs were chosen to represent 10 bins using Snagger, with double coverage of one large bin. Five SNPs failed genotyping, leaving six SNPs for analysis. At the gene level, a P-min permutation test was not significant for SDC1 (p=0.10). Three SNPs, rs10495704, rs2002090, and rs3771240, were in high linkage disequilibrium in our controls (r2 0.81-0.87) and all three were separately associated with marginally increased risks of breast cancer (OR 1.2, 95% CI 1.0-1.4). One of these SNPs, rs10495704, is in the 5’UTR and thus could be associated with protein processing. No excess risk of breast cancer was associated with the other three SDC1 variants: rs4432408, rs2348478, or rs2015110. A similar pattern of marginally increased risk for the three polymorphisms in high LD (rs10495704, rs2002090, and rs3771240) was found in two subsequent analyses restricted to women with ductal histology and luminal type tumors. We are currently assessing other genes related to inflammation that may be related to breast cancer risk in this study population. The data for SDC1 in the PACE study cannot rule out a modest association with breast cancer risk. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5593. doi:10.1158/1538-7445.AM2011-5593
Six Months in Sudan: A Young Doctor in a War-Torn Village
Authors: Dennis Rosen
Journal: JAMA (2009)

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6- MONTHS FOLLOW UP IN A REAL LIFE SITUATION AFTER RENAL DENERVATION
Authors: Willemien Verloop, Wilko Spiering, Pierfrancesco Agostoni, Pieter Stella, Kevin Onsea, P. Doevendans, Michiel Voskuil, UMC Utrecht
Journal: Journal of the American College of Cardiology (2012)
Web-Based Alcohol Screening and Brief Intervention for University Students
Authors: Kypros Kypri, Tina Vater, Steven J. Bowe, John B. Saunders, John A. Cunningham, Nicholas J. Horton, Jim McCambridge
Journal: JAMA (2014)

Unhealthy alcohol use is a leading contributor to the global burden of disease, particularly among young people. Systematic reviews suggest efficacy of web-based alcohol screening and brief intervention and call for effectiveness trials in settings where it could be sustainably delivered.