tbuckley/cabot-search huggingface dataset:
Mutations in MTFMT Underlie a Human Disorder of Formylation Causing Impaired Mitochondrial Translation
Authors: Elena J. Tucker, Steven G. Hershman, Caroline Köhrer, Casey A. Belcher-Timme, Jinal Patel, Olga A. Goldberger, John Christodoulou, Jonathon M. Silberstein, Matthew McKenzie, Michael T. Ryan, Alison G. Compton, Jacob D. Jaffe, Steven A. Carr, Sarah E. Calvo, Uttam L. RajBhandary, David R. Thorburn, Vamsi K. Mootha
Journal: Cell Metabolism (2011)
Identification of a Disease-Defining Gene Fusion in Epithelioid Hemangioendothelioma
Authors: Munir R. Tanas, Andrea Sboner, Andre M. Oliveira, Michele R. Erickson-Johnson, Jessica Hespelt, Philip J. Hanwright, John Flanagan, Yuling Luo, Kerry Fenwick, Rachael Natrajan, Costas Mitsopoulos, Marketa Zvelebil, Benjamin L. Hoch, Sharon W. Weiss, Maria Debiec-Rychter, Raf Sciot, Rob B. West, Alexander J. Lazar, Alan Ashworth, Jorge S. Reis-Filho, Christopher J. Lord, Mark B. Gerstein, Mark A. Rubin, Brian P. Rubin
Journal: Science Translational Medicine (2011)

A newly identified gene fusion defines the vascular cancer epithelioid hemangioendothelioma and encodes a chimeric transcription factor.
Altered mRNA expression of glycosyltransferases in human colorectal carcinomas and liver metastases
Authors: T Petretti
Journal: Gut (2000)

<h3>BACKGROUND/AIMS</h3> Biosynthesis of carbohydrate structures is tissue specific and developmentally regulated by glycosyltransferases such as fucosyltransferases, sialyltransferases, and <i>N</i>-acetylgluco- saminyltransferases. During carcinogenesis, aberrant glycosylation leads to the development of tumour subpopulations with different adhesion properties. Therefore alterations in glycosyltransferase mRNA expression in colorectal carcinomas were examined by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). <h3>METHODS</h3> Colorectal carcinoma specimens were classified and characterised according to the WHO/UICC system. Expression of fucosyltransferases FT-I, FT-III, FT-IV, FT-V, FT-VI, and FT-VII, sialyltransferases ST3Gal-I, ST3Gal-III, ST3Gal-IV, and ST6Gal-I, β1,4-galacto- syltransferase, and β1,6-<i>N</i>acetylgluco- saminyltransferase V (GNT-V) was screened simultaneously in extracts of 22 homogenised tumour specimens by RT-PCR and compared with corresponding mucosa from each patient. Also 12 adenomas and 17 liver metastases of colorectal carcinomas were examined. <h3>RESULTS</h3> GNT-V expression was enhanced in colorectal adenomas (p = 0.039), carcinomas (p&lt;0.001), and liver metastases of colorectal carcinomas (p&lt;0.001). Also, expression of fucosyltransferase FT-IV was increased in colorectal adenomas (p = 0.039) and carcinomas (p&lt;0.001). In addition, fucosyltransferase FT-I (p&lt;0.001) and sialyltransferases ST6Gal-I (p = 0.004) and ST3Gal-III (p = 0.001) showed increased expression in carcinoma specimens. On the other hand, fucosyltransferase FT-III was less abundantly expressed in carcinomas exhibiting distant metastases (p = 0.046) and in highly invasive tumours (p = 0.041). <h3>CONCLUSIONS</h3> Glycosyltransferase mRNA expression is significantly altered in colorectal adenomas and carcinomas isolated from surgical specimens. RT-PCR determination of specific glycosyltransferases may be helpful for earlier detection of carcinomas and for tumour prognosis.
A hand-held friction meter
Authors: J.S. COMAISH, P.R.H. HARBOROW, D.A. HOFMAN
Journal: British Journal of Dermatology (1973)

A portable hand‐held friction meter has been devised which will measure the coefficient of friction between a reference material and skin at any body site regardless of position. The reference surface can be made of any of a number of materials, such as steel, nylon, PTFE, leather or even fabrics. The effects of disease and topically applied medicaments on the skin are being studied quantitatively with this machine, which may also have industrial applications.
A LIN28B-RAN-AURKA Signaling Network Promotes Neuroblastoma Tumorigenesis
Authors: Robert W. Schnepp, Priya Khurana, Edward F. Attiyeh, Pichai Raman, Sara E. Chodosh, Derek A. Oldridge, Maria E. Gagliardi, Karina L. Conkrite, Shahab Asgharzadeh, Robert C. Seeger, Blair B. Madison, Anil K. Rustgi, John M. Maris, Sharon J. Diskin
Journal: Cancer Cell (2015)
Activity map of the tammar X chromosome shows that marsupial X inactivation is incomplete and escape is stochastic
Authors: Shafagh Al Nadaf, Paul D Waters, Edda Koina, Janine E Deakin, Kristen S Jordan, Jennifer Am Graves
Journal: Genome biology (2010)

X chromosome inactivation is a spectacular example of epigenetic silencing. In order to deduce how this complex system evolved, we examined X inactivation in a model marsupial, the tammar wallaby (Macropus eugenii). In marsupials, X inactivation is known to be paternal, incomplete and tissue-specific, and occurs in the absence of an XIST orthologue. We examined expression of X-borne genes using quantitative PCR, revealing a range of dosage compensation for different loci. To assess the frequency of 1X- or 2X-active fibroblasts, we investigated expression of 32 X-borne genes at the cellular level using RNA-FISH. In female fibroblasts, two-color RNA-FISH showed that genes were coordinately expressed from the same X (active X) in nuclei in which both loci were inactivated. However, loci on the other X escape inactivation independently, with each locus showing a characteristic frequency of 1X-active and 2X-active nuclei, equivalent to stochastic escape. We constructed an activity map of the tammar wallaby inactive X chromosome, which identified no relationship between gene location and extent of inactivation, nor any correlation with the presence or absence of a Y-borne paralog. In the tammar wallaby, one X (presumed to be maternal) is expressed in all cells, but genes on the other (paternal) X escape inactivation independently and at characteristic frequencies. The paternal and incomplete X chromosome inactivation in marsupials, with stochastic escape, appears to be quite distinct from the X chromosome inactivation process in eutherians. We find no evidence for a polar spread of inactivation from an X inactivation center.
Predictors of Discontinuation of Adjuvant Hormone Therapy in Patients With Breast Cancer
Authors: Wei He, Fang Fang, Catherine Varnum, Mikael Eriksson, Per Hall, Kamila Czene
Journal: Journal of Clinical Oncology (2015)

To identify predictors of discontinuation of adjuvant hormone therapy in patients with breast cancer.We conducted a record-linkage study based on data from Stockholm-Gotland Breast Cancer Register, Swedish Prescribed Drug Register, and self-reported questionnaire. Women diagnosed with breast cancer between 2005 and 2008 in Stockholm, Sweden, were prospectively followed for 5 years until 2013, starting from their first prescription of tamoxifen or aromatase inhibitors (N = 3,395).Family history of ovarian cancer (hazard ratio [HR], 1.55; 95% CI, 1.19 to 2.02); younger (< 40 years; HR, 1.39; 95% CI, 1.08 to 1.78) and older (≥ 65 years; HR, 1.15; 95% CI, 1.03 to 1.28) age; higher Charlson comorbidity index (≥ 2 v 0; HR, 1.35; 95% CI, 1.03 to 1.76); and use of analgesics (HR, 1.33; 95% CI, 1.16 to 1.52), hypnotics/sedatives (HR, 1.24; 95% CI, 1.07 to 1.43), GI drugs (HR, 1.25; 95% CI, 1.08 to 1.43), and hormone replacement therapy (HR, 1.27; 95% CI, 1.08 to 1.49) were identified as baseline predictors for hormonal treatment discontinuation. Use of analgesics (HR, 1.22; 95% CI, 1.08 to 1.37), hypnotics/sedatives (HR, 1.21; 95% CI, 1.07 to 1.37), antidepressants (HR, 1.22; 95% CI, 1.06 to 1.40), or GI drugs (HR, 1.27; 95% CI, 1.13 to 1.43), and switching therapy between tamoxifen and aromatase inhibitors (HR, 1.50; 95% CI, 1.23 to 1.83) during the first year of hormonal treatment were associated with increased risk of discontinuation during the next 4 years.Predictors identified in our study can be used in developing targeted intervention to prevent adjuvant hormone therapy discontinuation and subsequently to improve breast cancer outcomes.
Effects of hypoxia on heparan sulfate in bovine aortic and pulmonary artery endothelial cells.
Authors: J B Karlinsky, S Rounds, H W Farber
Journal: Circulation Research (1992)

Newly synthesized heparan sulfates purified from the cell layer of bovine aortic endothelial cells (BAECs) and main pulmonary artery endothelial cells (BPAECs) cultured under either normoxic (21% oxygen) or hypoxic (3% oxygen) conditions were characterized by size, charge, and capacity to bind to antithrombin III. Incorporation of radiolabeled sulfate into cell layer-associated heparan sulfate was reduced by 70% in BAECs and by 45% in BPAECs during exposure to 3% oxygen; degradation of radiolabeled heparan sulfate was not affected by hypoxia. However, the percentage of total radiolabeled heparan sulfate that bound to antithrombin III was increased by 33% for BAECs and by 120% for BPAECs when compared with radiolabeled heparan sulfate synthesized during the 21% oxygen exposure. Both the high- and low-antithrombin III affinity radiolabeled heparan sulfate consisted of two components of different sizes; the low-affinity components (mean sizes, 60 and 40 kd) generated under normoxic conditions were smaller than their respective high-affinity components (mean sizes, 70 and 55 kd) by molecular sieve chromatography. The components of low-antithrombin III affinity heparan sulfate generated during exposure to 3% oxygen were increased in size compared with the corresponding low-affinity components generated during the 21% oxygen exposure for both BPAECs and BAECs. In addition, the amount of the larger high-antithrombin III affinity component was reduced in both cell types exposed to hypoxia. There was no difference in functional heparin-like activity per dish between cells cultured at 3% and 21% oxygen; BAECs had twofold to threefold greater activity per dish than did BPAECs at both levels of oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)
HEALTH STATUS ASSESSMENT METHODS FOR ADULTS: Past Accomplishments and Future Challenges
Authors: Colleen A. McHorney
Journal: Annual Review of Public Health (1999)

▪ Abstract Over the past 30 years, health status assessment methods for adults have proliferated. Numerous generic, disease-specific, and preference-based measures now exist that tap diverse aspects of functioning, well-being, symptom states, and subjective perceptions of health. The evolution of the state of the art in adult health status assessment is reviewed. Applications of these tools in health services research, health policy, and clinical practice are discussed. Recommendations are offered for selecting among the armamentaria of tools. Conceptual and methodological challenges that confront instrument users and developers alike are identified and discussed.
Endothelial Function
Authors: Ulf Landmesser, Burkhard Hornig, Helmut Drexler
Journal: Circulation (2004)

Common conditions predisposing to atherosclerosis, such as hypercholesterolemia, hypertension, diabetes, and smoking, are associated with endothelial dysfunction. Endothelial function has largely been assessed as endothelium-dependent vasomotion, at least in part based on the assumption that impaired endothelium-dependent vasodilation also reflects the alteration of other important functions of the endothelium. An important rationale for this approach has been the observation that endothelium-derived nitric oxide (NO), a major mediator of endothelium-dependent vasodilation, has important anti-inflammatory and antithrombotic properties, ie, inhibiting leukocyte adhesion, limiting platelet adhesion and aggregation, and the expression of plasminogen activator inhibitor-1 (PAI-1), a prothrombotic protein. Accumulating data suggest that the degree of impairment of endothelium-dependent vasomotion has profound and independent prognostic implications. A common mechanism underlying endothelial dysfunction relates to increased vascular production of reactive oxygen species. Recent studies also suggest that inflammation per se and C-reactive protein in particular may directly contribute to endothelial dysfunction. These findings raise the question of whether assessment of endothelial function can be used in the clinical setting to identify patients at high risk. New insights into mechanisms of endothelial dysfunction, such as a better understanding of the regulation of important vascular sources of oxygen radicals, may lead to novel therapeutic strategies with the potential to improve prognosis.
Neamine Inhibits Prostate Cancer Growth by Suppressing Angiogenin-Mediated rRNA Transcription
Authors: Soichiro Ibaragi, Norie Yoshioka, Shuping Li, Miaofen G. Hu, Saori Hirukawa, Peter M. Sadow, Guo-fu Hu
Journal: Clinical Cancer Research (2009)

Angiogenin (ANG) undergoes nuclear translocation and stimulates rRNA transcription in both prostate cancer cells and endothelial cells. The purpose of this study is to assess the antitumor activity of neamine, a nontoxic degradation product of neomycin that blocks nuclear translocation of ANG.The anti-prostate cancer activity of neamine was first evaluated in a xenograft animal model. It was then examined in the murine prostate-restricted AKT transgenic mice that develop prostate intraepithelial neoplasia (PIN) owing to AKT transgene overexpression.Neamine inhibits xenograft growth of PC-3 human prostate cancer cells in athymic mice. It blocks nuclear translocation of ANG and inhibits rRNA transcription, cell proliferation, and angiogenesis. Neamine also prevents AKT-induced PIN formation as well as reverses fully developed PIN in murine prostate-restricted AKT mice, accompanied by a decrease in rRNA synthesis, cell proliferation, and angiogenesis and an increase in prostate epithelial cell apoptosis.We confirmed that ANG is a molecular target for cancer drug development and that blocking nuclear translocation of ANG is an effective means to inhibit its activity. Our results also suggested that neamine is a lead compound for further preclinical evaluation.
Possibility of selection against mtDNA mutations in tumors
Authors: M Khaidakov, RJ Shmookler Reis
Journal: Molecular Cancer (2005)

Abstract Several studies of tumors have revealed substantial numbers of clonally expanded somatic mutations in mitochondrial DNA (mtDNA), not observed in adjacent intact tissues. These findings were interpreted as indicating the involvement of mtDNA mutations in tumorigenesis. Such comparisons, however, ignore an important confounding factor: the monoclonal origin of tumors as opposed to the highly polyclonal nature of normal tissues. Analysis of recently published data on the incidence of somatic mutations in nontumor monoclonal cells suggests that, contrary to the prevailing view, the process of tumorigenesis may be accompanied by active selection against detrimental mtDNA mutations.
Human immunodeficiency virus type 1 activates the classical pathway of complement by direct C1 binding through specific sites in the transmembrane glycoprotein gp41.
Authors: C F Ebenbichler, N M Thielens, R Vornhagen, P Marschang, G J Arlaud, M P Dierich
Journal: The Journal of Experimental Medicine (1991)

Human immunodeficiency virus type 1 (HIV-1), in contrast to animal retroviruses such as murine leukemia virus, is not lysed by human complement. Nevertheless, HIV-1 activates complement via the classical pathway independent of antibody, and C3b deposition facilitates infection of complement receptor-bearing cells. Using gel exclusion chromatography on Sephacryl S-1000, purified virions were found to bind 125I-labeled C1q, but not 125I-labeled dimeric proenzyme C1s. Virions activated the C1 complex, reconstituted from C1q, proenzyme C1r, and 125I-labeled proenzyme C1s, to an extent comparable with that obtained with immunoglobulin G-ovalbumin immune complexes. To determine the activating viral component, recombinant viral proteins were used: in the solid phase, soluble gp41 (sgp41) (the outer membrane part of gp41, residues 539-684 of gp160) bound C1q, but not dimeric proenzyme C1s, while gp120 was ineffective. In the fluid phase, sgp41 activated the C1 complex in a dose- and time-dependent manner, more efficiently than aggregated Ig, but less efficiently than immune complexes. To localize the C1 activating site(s) in gp41, synthetic peptides (15-residue oligomers spanning amino acids 531-695 of gp160) were used. Peptides covering positions 591-605 and 601-620 and, to a lesser extent, positions 561-575, had both the ability to bind C1q and to induce C3 deposition. These data provide the first experimental evidence of a direct interaction between the C1 complex and HIV-1, and indicate that C1 binding and activation are mediated by specific sites in gp41.
Psychiatric Disorders and Repeat Incarcerations: The Revolving Prison Door
Authors: Jacques Baillargeon, Ingrid A Binswanger, Joseph V Penn, Brie A Williams, Owen J Murray
Journal: American Journal of Psychiatry (2008)

A number of legal, social, and political factors over the past 40 years have led to the current epidemic of psychiatric disorders in the U.S. prison system. Although numerous investigations have reported substantially elevated rates of psychiatric disorders among prison inmates compared with the general population, it is unclear whether mental illness is a risk factor for multiple episodes of incarceration. The authors examined this association in a retrospective cohort study of the nation's largest state prison system.The study population included 79,211 inmates who began serving a sentence between September 1, 2006, and August 31, 2007. Data on psychiatric disorders, demographic characteristics, and history of incarceration for the preceding 6-year period were obtained from statewide medical information systems and analyzed.Inmates with major psychiatric disorders (major depressive disorder, bipolar disorders, schizophrenia, and nonschizophrenic psychotic disorders) had substantially increased risks of multiple incarcerations over the 6-year study period. The greatest increase in risk was observed among inmates with bipolar disorders, who were 3.3 times more likely to have had four or more previous incarcerations compared with inmates who had no major psychiatric disorder.Prison inmates with major psychiatric disorders are more likely than those without to have had previous incarcerations. The authors recommend expanding interventions to reduce recidivism among mentally ill inmates. They discuss the potential benefits of continuity of care reentry programs to help mentally ill inmates connect with community-based mental health programs at the time of their release, as well as a greater role for mental health courts and other diversion strategies.
MANAGEMENT OF ADULTS WITH CONGENITAL HEART DISEASE: An Increasing Problem
Authors: Jane Somerville, MD, FRCP, FACC, FESC
Journal: Annual Review of Medicine (1997)

▪ Abstract A small new population of patients in cardiology, the grown-up (adult) congenital hearts (GUCH), need superspecialist care and expertise, particularly those patients with complex defects previously operated on in childhood or who were not operated on. Arrhythmias are the most common cardiologic reason for admission to the hospital, and atrial flutter is the most frequent disorder of rhythm, usually related to hemodynamic disturbances. The GUCHs need solutions to problems of transition of care, ideally an adolescent area for the younger patients, knowledge of which and when to investigate each anomaly, expertise in cardiac catheterization and interventions, cardiac surgeons experienced in congenital as well as adult disease since one in five admissions are for cardiac surgery, at-risk pregnancy service, counseling on life's problems, and most of all a few dedicated centers with cardiologists and surgeons trained in this subspecialty. The profession needs to achieve optimal care for these precious patients, particularly those with complicated lesions and complex surgery, particularly with valve replacements. Although small in number and high in expense, GUCH patients should be centralized so expertise and experience can be concentrated despite the need to cross barriers of finance and bureaucracy. Currently, with the exception of a few expert centers, these patients receive suboptimal medical management.
Radiofrequency Ablation of Intra-Atrial Reentrant Tachycardia After Surgical Palliation of Congenital Heart Disease
Authors: John K. Triedman, J. Philip Saul, Steven N. Weindling, Edward P. Walsh
Journal: Circulation (1995)

Background Intra-atrial reentrant tachycardia (IART), also called atrial flutter, is a common and potentially lethal complication of surgical correction of congenital heart disease. Medical management of IART is often problematic, which prompts an investigation of the utility of radiofrequency (RF) ablation for management of these arrhythmias. Methods and Results Ten consecutive patients referred for treatment of recurrent IART after surgery for congenital heart disease were studied. Median age was 18.4 years, and median duration of arrhythmia was 6.4 years; a median of three antiarrhythmic drugs had been tried. Surgical procedures used were Fontan (6), Mustard/Senning (2), and biventricular repair (2). Intracardiac electrophysiological study demonstrated 30 distinct IART circuits, defined by activation sequence and cycle length. Mean IART cycle length was 323±114 ms. Cycle length was significantly longer in IART circuits that were successfully ablated compared with those that were not (381 versus 248 ms, P &lt;.001). RF ablation was attempted in 22 of these circuits. Ablation sites were targeted to presumed exit points from zones of slow conduction by electrophysiological criteria. Sites chosen in this manner clustered in four distinct areas of the right atrium. Of 22 IART circuit ablations attempted, 17 (77%) resulted in acute termination of the tachycardia. In 8 of 10 patients in whom at least one IART circuit was successfully ablated, 4 are free of clinical tachycardia and 3 are improved over short-term follow-up. No complications were encountered. Conclusions Multiple IART circuits may be present in patients after surgery for congenital heart defects. Activation sequences observed were diverse and different from those observed in atrial flutter in patients with normal anatomy. Interruption of IART circuits by RF ablation is feasible using mapping techniques aimed at identifying an exit point from a zone of slow conduction. Short-term follow-up suggests that RF ablation may be a useful adjunct in management of IART in these difficult patients.
Fine specificity of idiotope suppression in the A/J anti-azophenylarsonate response.
Authors: T L Rothstein, M N Margolies, M L Gefter, A Marshak-Rothstein
Journal: The Journal of Experimental Medicine (1983)

Two hapten-inhibitable murine monoclonal antiidiotopic antibodies identified two idiotopes expressed by the heavy chain of hybridoma protein 36-65, whose amino acid sequence is encoded in the germ line of A/J mice. Among cross-reactive idiotype-positive hybridoma proteins and p-azophenylarsonate-immune antibodies, the two idiotopes were not always expressed together; some diversified antibodies expressed one idiotope without the other. Suppression that was induced by the two antiidiotopes was idiotope specific and corresponded to the fine specificities of these two reagents.