tbuckley/cabot-search huggingface dataset:
Common Genetic Variation and Human Traits
Authors: David B. Goldstein
Journal: New England Journal of Medicine (2009)

The human genome has been cracked wide open in recent years and is spilling many of its secrets. More than 100 genomewide association studies have been conducted for scores of human diseases, identifying hundreds of polymorphisms that are widely seen to influence disease risk. After many years in which the study of complex human traits was mired in false claims and methodologic inconsistencies, genomics has brought not only comprehensive representation of common variation but also welcome rigor in the interpretation of statistical evidence. Researchers now know how to properly account for most of the multiple hypothesis testing involved in mining . . .
IgE deposition in normal skin of patients with rheumatoid arthritis in relation to clinical and laboratory findings.
Authors: L S De Clerck, M L Westedt, A Cats, B J Vermeer, E F Weltevreden, C H Bridts, W J Stevens
Journal: Annals of the Rheumatic Diseases (1985)

Biopsy specimens from apparently normal skin of 28 patients with classical or definite rheumatoid arthritis (RA) were examined for the presence of IgE deposition by a direct immunofluorescence technique. IgE deposition was found in 12 patients (43%) and in none of the 10 controls. This deposition was mainly localised on mast cells, and in three patients perivascular IgE staining was also noted. The skin from nine of the 12 patients also showed deposition of IgM and complement C3 or C4 factor, or both. All 12 patients with skin IgE deposition had raised levels of IgM rheumatoid factor (RF) in the serum. Nine of these also had IgE RF. IgE-containing circulating immune complexes (IgE CIC), raised serum IgE levels, and extra-articular (EA) manifestations were present in respectively 10, nine, and eight skin IgE positive patients. It is suggested that IgE and IgE CIC may be involved in the pathogenesis of RA and its EA manifestations.
Issues MPs and the media have missed in Lansley's bill
Authors: J. R. W. Lister
Journal: BMJ (2011)

The Commons Public Accounts Committee review makes damning criticisms of Lansley’s deeply flawed Health and Social Care Bill, exposing the shallowness of parliamentary scrutiny.1 But it fails to note that the bill would end the accountability of the secretary of state for the continued provision of health services and ignores the loss of local accountability.2

GP consortiums, the …
Increased preload directly induces the activation of heat shock transcription factor 1 in the left ventricular overloaded heart
Authors: J Nishizawa
Journal: Cardiovascular Research (2002)

Objectives: The rapid induction of heat shock proteins (HSPs) by cardiac overload has been shown using in vivo models and it is assumed that HSPs are involved in myocardial protection against cardiac overload. However, the mechanisms for the induction of heat shock response by cardiac overload remain unclear. We examined whether increased preload as mechanical stress directly induces heat shock gene expression. Methods: Rat hearts were isolated and perfused with Krebs–Henseleit buffer by the Langendorff method. Whole-cell extracts were prepared for gel mobility shift assay using oligonucleotides containing the heat shock element. We examined the induction of the DNA-binding activity of heat shock transcription factor (HSF), by which the transcription of heat shock genes is mainly regulated, during increased preload of left ventricle (LV) or perfusion with the buffer containing epinephrine, norepinephrine, angiotensin II, or vasopressin. Results: In preloaded hearts, with LVEDP of both 30 and 50 mmHg, the DNA-binding activity of HSF1 was detected at 10 min, and increased at 20 and 60 min. At any time point, the activity with LVEDP of 50 mmHg was stronger than that with LVEDP of 30 mmHg. However, none of these hypertensive agents activated the DNA-binding activities of HSF. In afterloaded hearts, with the perfusion of norepinephrine, the activation of HSF was not induced. Conclusion: Our findings demonstrate that increased preload as mechanical stress directly induces the activation of HSF1 in the LV-overloaded heart.
RETENTION OF URINE
Authors: H. J. McCurrich
Journal: BMJ (1930)

ETFENTION of ulilne is onie of the most distressing symptomis affecting the humani race.It is, moreover, a symptom wlhiclh nian be overlooked when present, or diagnosed when absenit.'The fi-st of these pitfalls is due to retention with overflow beiing mistaken for true incontinenice.I once saw a patienit in the? padded loom of a mental-ward, whitlher he had been trainsferred froml a general hospital, wlhere the (liagnosis of miaima had been made.The patient 'was rollinig abouit the floor andl scratching his hy-pogastriumi with his finger-nails.He. hadl been in the pad(led roomi about tmwel-e hours.The attendant, in charge of hiim in- formed me that the pzatient lhadl beeni passing ulrine freely, btut that he was iniconitinent.Oni examiniing the patienit
Distress Over the Noneffect of Stress
Authors: David S. David
Journal: JAMA (1992)

<h3>To the Editor.</h3> —The article on the effect of nonpharmacologic interventions on blood pressure of persons with high normal levels was interesting.<sup>1</sup>I would just like to comment about the lack of an observed effect from stress management. First, as the authors pointed out, although the patients were compliant, there was no evidence of effective stress management training on the Hassles questionnaire. So, it doesn't appear that the perception of one's stresses was affected by the stress management. The authors are quite correct in stating that what is even more important than the "hassles" one perceives is one's reaction to them.<sup>2</sup>The authors did state that they collected data on cardiovascular reactivity and urinary excretion of catecholamines and cortisol. However, the difficulty with these 24-hour urinary studies is they will not only measure baseline secretion, but also acute secretion of those hormones in response to the events that
1053-210 Incidence and prognosis of ventricular tachycardia and ventricular fibrillation after non-ST elevation acute coronary syndromes: Insights from the global registry of acute coronary events
Authors: Álvaro Avezum, Marcos Knobel, Robert J Goldberg, Immad Sadiq, Gordon Saperia, Tristam Smyth, Richard Paoloni, David Brieger, Polina Kuznetsova, Joel M Gore
Journal: Journal of the American College of Cardiology (2004)
Morphology and relationship to extensibility curves of human mitral valve chordae tendineae.
Authors: K O Lim, D R Boughner
Journal: Circulation Research (1976)

Human mitral valve chordae tendineae in which elastic response curves are nonlinear have also been found to exhibit extensibility that increases with chordal size and decreases with chordal age. We used selective enzymatic digestion and scanning transmission electron microscopy to explain these observations. Removal of the outer elastin sheath by enzymatic digestion did not significantly affect the elastic response of this tissue. Scanning electron microscopy revealed that the collagen fibers in the central core of young chordae exhibited a very wavy pattern but the pattern in adult specimens was relatively straight. The increased waviness accounted for the greater extensibility of the young specimens. The collagen fibers from young and old chordae consisted of a network of collagen fibrils that became more collapsed when the tissue was fixed under tension. This network arrangement of the fibrils explains the nonlinearity in the elastic response of the tissue. Transmission electron micrographs showed that the density of collagen fibrils decreased as chordal size increased. The number of fibrils per 10(-8) cm2 of the central core decreased from 182.4 (SE = 1.3) to 131.3 (SE = 1.6) as average chordal cross-sectional area increased from 0.0016 cm2 to 0.0268 cm2. This difference in fibril density provides an explanation for the greater extensibility shown by the thicker chordae. The collagen fibril diameters ranged from 516 A to 552 A.
Abstract 2549: Efficacy of the Chk1 inhibitor PF-00477736 and pemetrexed in human mesothelioma
Authors: Alessandra Blasina, Jill F. Hallin, Wei Tan, Gerrit Los, Jitesh P. Jani
Journal: Cancer Research (2011)

Abstract Malignant pleural mesothelioma (MPM) is a highly aggressive malignancy with the median survival of less than 1 year from diagnosis. Pemetrexed (PTX), a multi-targeted antifolate drug in combination with cisplatin, has been used as front-line treatment. PTX-treatments causes S-phase cell cycle arrest allowing cancer cells to repair damaged DNA critical for cell survival and proliferation. The Chk1 kinase, a central regulator of cell cycle progression and a principal mediator of cell cycle checkpoints in response to genotoxic stress is overexpressed in mesothelioma. We evaluated the in-vitro activity of the Chk1 kinase inhibitor, PF-00477736, in combination with PTX in MPM. PF-00477736 treatments abrogated the PTX-induced S-phase cell cycle arrest and enhanced cytotoxicity of PTX in a dose-dependent manner (∼81% cell proliferation inhibition, vs. ∼13% with PTX alone). PTX and PF-00477736 treatments alone enhanced the levels of γH2AX (6% and 16%, respectively), however, their combination had significantly higher effect (∼60% increase) compared to control cells. These results suggest that when Chk1 is inhibited, PTX-induced replication stress is converted into additional DNA damage due to checkpoint abrogation and lack of DNA repair. The sensitization of mesothelioma cells to PTX by PF-00477736 was also associated with a marked increase in apoptosis (∼11-fold increase compared to PTX of PF-00477736 treatments alone). Collectively, these results show a therapeutic potential of combining Chk1 inhibitors and PTX for the treatment of mesothelioma. 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 2549. doi:10.1158/1538-7445.AM2011-2549
Inhibition of α–Ketoglutarate Dehydrogenase Activity by A Distinct Population of Autoantibodies Recognizing Dihydrolipoamide Succinyltransferase in Primary Biliary Cirrhosis
Authors: David R. Fregeau, Thomas Prindiville, Ross L. Coppel, Marshall Kaplan, Rolland E. Dickson, Eric M. Gershwin
Journal: Hepatology (1990)

Sera from patients with primary biliary cirrhosis contain autoantibodies that recognize mitochondrial proteins. Five of the target autoantigens have now been identified as enzymes of three related multienzyme complexes: the pyruvate dehydrogenase complex, the branched chain alpha-ketoacid dehydrogenase complex and the alpha-ketoglutarate dehydrogenase complex. Each complex consists of component enzymes designated E1, E2 and E3. In this report, we confirm that primary biliary cirrhosis sera react with dihydrolipoamide succinyltransferase, the E2 component of alpha-ketoglutarate dehydrogenase complex. Seventy-three of 188 (39%) primary biliary cirrhosis sera reacted with alpha-ketoglutarate dehydrogenase complex-E2 when immunoblotted against purified alpha-ketoglutarate dehydrogenase complex; one of these sera also reacted with the E1 component. In addition, primary biliary cirrhosis sera possessing alpha-ketoglutarate dehydrogenase complex-E2 reactivity specifically inhibited enzyme function of alpha-ketoglutarate dehydrogenase complex. Enzyme activity was not affected by primary biliary cirrhosis sera that contained autoantibodies to pyruvate dehydrogenase complex-E2 and/or branched chain alpha-ketoacid dehydrogenase complex-E2, which lacked alpha-ketoglutarate dehydrogenase complex-E2 reactivity. Furthermore, affinity-purified primary biliary cirrhosis sera against alpha-ketoglutarate dehydrogenase complex-E2 inhibited only alpha-ketoglutarate dehydrogenase complex activity but did not alter enzyme activity of either pyruvate dehydrogenase complex or branched chain alpha-ketoacid dehydrogenase complex. Finally, alpha-ketoglutarate dehydrogenase complex-E2 specific affinity-purified antisera did not react on immunoblot with any component enzymes of pyruvate dehydrogenase complex or branched chain alpha-ketoacid dehydrogenase complex.(ABSTRACT TRUNCATED AT 250 WORDS)
Frequency, prognosis and predictors of improvement of systolic left ventricular function in patients with ‘classical’ clinical diagnosis of idiopathic dilated cardiomyopathy
Authors: Mariantonietta Cicoira, Luisa Zanolla, Loredana Latina, Andrea Rossi, Giorgio Golia, Giovanna Brighetti, Piero Zardini
Journal: European Journal of Heart Failure (2001)
Deaths from rhesus haemolytic disease in England and Wales in 1977: accuracy of records and assessment of anti-D prophylaxis.
Authors: C Clarke, A G Whitfield
Journal: BMJ (1979)

All the death certificates for deaths in 1977 where haemolytic disease of the newborn (HDN) was the principal, an antecedent, or a contributory cause were obtained from the Office of Population Censuses and Surveys (OPCS). The hospital notes of all 54 of the live-born cases and all of the 101 stillbirths were also obtained. The cause of the death indicated by the notes was compared with the cause and coding on the death certificate. In about a quarter of the cases death was not due to haemolytic disease of any type. The commonest errors arose because the International Classification of Diseases (8th edition) stipulates that hydrops without mention of cause should be coded as HDN and because stillbirths to rhesus-negative mothers tend to be attributed to rhesus HDN automatically. Though deaths from HDN may be overestimated in this way, they are also underestimated because rhesus disease, although mentioned on the certificate, is not selected as the underlying cause, which it may be. These cases were found through multiple coding of all the contributory causes of death, which OPCS performs on a 25% sample of all death certificates for research purposes. These two sources of inaccuracy tend to cancel each other out, but statistics from death certificates give a misleading picture of the efficacy of anti-D prophylaxis because anti-D can never prevent cases which are not in fact due to rhesus HDN. Most of the mothers studied had become immunised before anti-D became available, but in those who could have been treated 75% had not received prophylaxis. As this was a sample of deaths, however, it would not be accurate to extrapolate this high figure to the population at risk. Nevertheless, the organisation of prophylaxis is clearly deficient and should be remedied before providing antenatal anti-D to supplement postnatal treatment.
The Pathogenesis of Malignant Hypertension
Authors: G. W. PICKERING
Journal: Circulation (1952)

Whether hypertension follows the benign or the malignant course depends chiefly on the severity of the hypertension. Malignant hypertension may develop in hypertension due to any cause, provided it is sufficiently severe. The evidence for this hypothesis is as follows: 1. The characteristic finding in malignant hypertension during life is albuminuric retinitis (hypertensive neuroretinopathy) which differs from the retinitis of benign hypertension (arteriosclerotic retinitis) in the presence of neuroretinal edema. This neuroretinal edema is due to raised intracranial pressure, which in turn seems to be a consequence of the high level of diastolic arterial pressure. 2. The characteristic finding in malignant hypertension after death is acute arteriolar necrosis, the occurrence of which in the kidneys is chiefly responsible for the rapid renal failure which is so often the cause of death. Evidence from animal experiments suggest that the chief factor determining these arteriolar necroses is the high level of arterial pressure. 3. Albuminuric retinitis, rapid renal failure and acute arteriolar necroses may occur in essential hypertension, acute and chronic nephritis, pyelonephritis, polycystickidney, Cushing's syndrome and toxemia of pregnancy; these conditions may terminate therefore in the malignant phase. Alternatively, the hypertension may be stable, and, provided the underlying disease is stationary, the patient's condition may remain unchanged for many years; the hypertension may thus have the characteristics of the benign type. 4. In patients whose hypertension changes from the benign to the malignant phase, it is usual to find that the arterial pressure is higher in the malignant than in the benign phase. 5. It has been proved tha thypertension can be reversed from the malignant to the benign phase by measures which reduce the arterial pressure. It would therefore seem correct to speak of the malignant phase of hypertension and to relate this to the underlying malady whether this be essential hypertension, pyelonephritis or the like. The diagnosis of the malignant phase of hypertension carries a single and urgent therapeutic implication, namely, the prompt and persistent lowvering of arterialpressure.
Abstract 2500: Analysis of protein biomakers in prostate and colorectal tumor lysates.
Authors: Laurie L. Stephen, Marc Damour, Josh Kemp, Karri L. Ballard, Ralph L. McDade, James P. Mapes
Journal: Cancer Research (2013)

Abstract Traditional tumor biomarkers are proteins that have been shed in the bloodstream and have been critical in identifying and treating cancer. We sought to survey proteins relevant to oncology in colon and prostate tumors; in order to identify potential proteins of interest for cancer research. Four colon and three prostate tumors were homogenized and 115 proteins were analyzed from the Oncology MAP 2.0. Each tumor had 2 fractions homogenized to look at heterogeneity of the protein with the tumor. In all of the samples measured 102 of the 115 protein showed levels above the LLOQ. Five proteins (PSP94, Tenascin-X, lipocalin-1, Tie-1 and BAFF) were 100 fold higher in prostate tumors compared to colon tumors (P&amp;lt;0.001). PSP94 has been shown to be a prostate cancer marker in serum; however, none of the other markers have been shown to be markers of prostate tumors. Eight proteins (PECAM-1, CA 72-4, Eotaxin-2, HGF-R, CA 15-3, TATI, CEACAM6 and CEA) were greater than 10 fold higher in colon tumors compared to prostate tumors (P&amp;lt;0.001). Although oncology MAP 2.0 was developed for serum biomarkers, it may provide a valuable tool for examining proteins biomarkers in tumors. Citation Format: Laurie L. Stephen, Marc Damour, Josh Kemp, Karri L. Ballard, Ralph L. McDade, James P. Mapes. Analysis of protein biomakers in prostate and colorectal tumor lysates. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2500. doi:10.1158/1538-7445.AM2013-2500
An Approach to Measuring the Cost of Mental Illness
Authors: RONALD W. CONLEY, MARGARET CONWELL, MILDRED B. ARRILL
Journal: American Journal of Psychiatry (1967)

Using a new conceptual framework, the authors present a comprehensive estimate of the cost of mental illness. They identify and quantify components of this cost that add up to almost $20 billion annually. Almost half the cost, they note, is borne by persons other than those whose emotional difficulties actually cause the loss. Because of its relevance for policy decisions in regard to mental health programs, the authors also discuss the relationship between the costs of mental illness and benefit-cost analysis.
PSYCHIATRIC INTAKE IN GROUPS: A PILOT STUDY OF PROCEDURES, PROBLEMS AND PROSPECTS
Authors: DAVID ABRAHAMS, JOHN B. ENRIGHT
Journal: American Journal of Psychiatry (1965)

This study explored the feasibility of evaluating the pathology and motivation of 50 applicants to a public mental health clinic in 4 intake groups. Each group met for 5 or 8 sessions with a leader and observer. Diagnoses proved difficult to make in some cases, but dispositions of most applicants were made with confidence. In comparing the dispositional status of these applicants with others who went through traditional individual intake, no significant differences were found in no-show or drop-out rates, or in number still in treatment 6 months later.
A stimulating way to improve T cell responses to poxvirus-vectored vaccines
Authors: Stuart N. Isaacs
Journal: Journal of Clinical Investigation (2010)

Vaccines remain one of the most cost-effective public health measures. Despite ongoing efforts, protective vaccines against cancer and many infectious diseases, including malaria, tuberculosis, and HIV/AIDS, are still not in hand. Most investigators believe that to succeed against these difficult targets, vaccines that generate potent T cell responses are needed. In this issue of the JCI, Salek-Ardakani et al. show how the relative virulence of a virus/vaccine vector affects the memory CD8+ T cells generated and how the response may be enhanced. The work has important implications for the development of future vaccines that aim to trigger CD8+ T cell responses.
Role of 2c T Cell Receptor Residues in the Binding of Self–And Allo–Major Histocompatibility Complexes
Authors: Peter U.Y. Lee, Hywyn R.O. Churchill, Mark Daniels, Stephen C. Jameson, David M. Kranz
Journal: The Journal of Experimental Medicine (2000)

T cell clone 2C recognizes the alloantigen Ld and the positive selecting major histocompatibility complex (MHC), Kb. To explore the molecular basis of T cell antigen receptor (TCR) binding to different peptide/MHC (pMHC) complexes, we performed alanine scanning mutagenesis of the 2C TCR. The TCR energy maps for QL9/Ld and SIYR/Kb were remarkably similar, in that 16 of 41 Vα and Vβ alanine mutants showed reduced binding to both ligands. Several TCR residues varied in the magnitude of energy contributed to binding the two ligands, indicating that there are also unique interactions. Residues in complementarity determining region 3α showed the most notable differences in binding energetics among the ligands QL9/Ld, SIYR/Kb, and the clonotypic antibody 1B2. Various lines of evidence suggest that these differences relate to the mobility of this loop and point to the key role of conformational dynamics in pMHC recognition.
Realizing Potential of MR Coronary Angiography May Ease Patients' Test Load and Diagnosis Costs
Authors: Marsha F. Goldsmith
Journal: JAMA (1994)

ABSTRACT A ONE-STOP SHOP where you can get all the information you need about the  is being visualized by some forward-looking cardiologists. The medium for this noninvasive message is magnetic resonance (MR) imaging, said speakers at the 66th annual scientific sessions of the American Heart Association (AHA), held in Atlanta, Ga.A dozen years after the enormous potential of MR in many areas of medicine began to be forecast (JAMA. 1982;247: 151-159 and 1984;251:869-877), Gerald M. Pohost, MD, director, Division of Cardiovascular Diseases, University of Alabama School of Medicine, Birmingham, says the now widely distributed $2-million imaging systems are living up to their advance billing. Not very long ago, their efficacy in diagnosing heart disease was in serious question; now, says Pohost, once the magnets are able to be used to their full potential, they will provide not only superior images but substantial cost savings.The reduction in imaging time
Promotion of bone formation by simvastatin in polyethylene particle-induced osteolysis
Authors: Fabian von Knoch, Christian Wedemeyer, Anja Heckelei, Guido Saxler, Gero Hilken, Jochen Brankamp, Thomas Sterner, Stefan Landgraeber, Frank Henschke, Franz Löer, Marius von Knoch
Journal: Biomaterials (2005)