tbuckley/cabot-search huggingface dataset:
Response to Imatinib Mesylate in Patients with Chronic Myeloproliferative Diseases with Rearrangements of the Platelet-Derived Growth Factor Receptor Beta
Authors: Jane F. Apperley, Martine Gardembas, Junia V. Melo, Robin Russell-Jones, Barbara J. Bain, E. Joanna Baxter, Andrew Chase, Judith M. Chessells, Marie Colombat, Claire E. Dearden, Sasa Dimitrijevic, François-X. Mahon, David Marin, Zariana Nikolova, Eduardo Olavarria, Sandra Silberman, Beate Schultheis, Nicholas C.P. Cross, John M. Goldman
Journal: New England Journal of Medicine (2002)

A small proportion of patients with chronic myeloproliferative diseases have constitutive activation of the gene for platelet-derived growth factor receptor beta (PDGFRB), which encodes a receptor tyrosine kinase. The gene is located on chromosome 5q33, and the activation is usually caused by a t(5;12)(q33;p13) translocation associated with an ETV6-PDGFRB fusion gene. The tyrosine kinase inhibitor imatinib mesylate specifically inhibits ABL, PDGFR, and KIT kinases and has impressive clinical efficacy in BCR-ABL–positive chronic myeloid leukemia.
Migraine and Functional Outcome From Ischemic Cerebral Events in Women
Authors: Pamela M. Rist, Julie E. Buring, Carlos S. Kase, Markus Schürks, Tobias Kurth
Journal: Circulation (2010)

Studies have linked migraine with aura to an increased risk of ischemic stroke, particularly among women. Data on the relationship of migraine and functional outcome from ischemic cerebral events are sparse.
On the Moral Asymmetry of Gametic Contributions
Authors: Pepe Lee Chang, Diana Buccafurni-Huber
Journal: The American Journal of Bioethics (2013)

An Ravelingien and Guido Pennings (2013) argue that donor-conceived children have a moral right to know the identity of their genetic fathers 1 in cases in which the genetic father is not the socia...
Detection of malignant melanoma in a giant congenital naevocytic naevus by positron emission tomography
Authors: T. Makosz, C. Assaf, J. Georgieva, C.E. Orfanos, C.C. Geilen
Journal: British Journal of Dermatology (2004)

T.M. and C.A. contributed equally to this work. Sir, Giant congenital naevocytic naevi are rare, occurring in fewer than one in 10 000 newborns. The lifelong risk for their malignant transformation is up to 12%,1 and therefore prophylactic removal of the involved area is indicated, if feasible and practical. Because the naevus cells are initially located in the upper dermis and subsequently descend into the deeper dermis along hair follicles later in life, extensive dermabrasion should be performed as early as possible.2 However, surgical removal may not always be applicable, and long‐term follow‐up may remain the only option for management.3 If textural alterations appear in a giant naevus they should be excised, but nonspecific changes rather than malignant transformation are frequently seen. We describe the use of fluorodeoxyglucose‐positron emission tomography (FDG‐PET) for detecting the intralesional development of malignant melanoma in a giant naevus. The possible value of FDG‐PET for monitoring patients with widespread naevocytic naevi is highlighted.
Regional neonatal intensive care: bias and benefit.
Authors: T G Powell, P O Pharoah
Journal: BMJ (1987)

Among very low birthweight infants born to residents of Merseyside in 1979-81 those booked at or transferred in utero to the regional unit were more likely to survive than those born elsewhere in the region. A study was carried out to determine whether the increased survival rate was attributable to better care or differences in the babies treated at the unit, or both. Four subpopulations were defined by district of maternal residence to obtain fairly comparable samples. Survival to 2 years increased as proportions treated at the regional unit increased, this "dose-response" effect being most pronounced among the smallest infants. Despite less favourable social state infants from the district housing the regional unit were apparently in the best condition at birth; had been managed most actively before, at, and after birth; and were the most likely to survive. This increased survival, however, was associated with a marginally significant increase in prevalence of major impairments. These data underline the need for routine surveillance of large representative samples of low birthweight survivors.
Glucagon: Physiologic and Clinical Considerations
Authors: Theodore B. Van Itallie
Journal: New England Journal of Medicine (1956)

ALTHOUGH glucagon (hyperglycemic glycogenolytic factor) was discovered and named thirty-four years ago, it has yet to achieve unqualified acceptance as a hormone.1 , 2 With one possible exception, no clinical disorder attributable to a deficiency of glucagon has been identified.3 Nor is there general agreement concerning the site of origin of this substance.4 , 5 These objections, however, are not as decisive as might at first be imagined. For example, there is no question about the hormonal nature of epinephrine; yet no syndrome referable to a deficiency of adrenal medullary secretion has been described. And, although the site of origin of glucagon has not . . .
The prior question: Do <i>human</i> primates have a theory of mind?
Authors: Robert M. Gordon
Journal: Behavioral and Brain Sciences (1998)

Given Heyes's construal of “theory of mind,” there is still no convincing evidence of theory of mind in human primates, much less non human. Rather than making unfounded assumptions about what underlies human social competence, one should ask what mechanisms other primates have and then inquire whether more sophisticated elaborations of those might not account for much of human competence.
Cost-of-illness studies: concepts, scopes, and methods
Authors: Changik Jo
Journal: Clinical and Molecular Hepatology (2014)

Liver diseases are one of the main causes of death, and their ever-increasing prevalence is threatening to cause significant damage both to individuals and society as a whole. This damage is especially serious for the economically active population in Korea. From the societal perspective, it is therefore necessary to consider the economic impacts associated with liver diseases, and identify interventions that can reduce the burden of these diseases. The cost-of-illness study is considered to be an essential evaluation technique in health care. By measuring and comparing the economic burdens of diseases to society, such studies can help health-care decision-makers to set up and prioritize health-care policies and interventions. Using economic theories, this paper introduces various study methods that are generally applicable to most disease cases for estimating the costs of illness associated with mortality, morbidity, disability, and other disease characteristics. It also presents concepts and scopes of costs along with different cost categories from different research perspectives in cost estimations. By discussing the epidemiological and economic grounds of the cost-of-illness study, the reported results represent useful information about several evaluation techniques at an advanced level, such as cost-benefit analysis, cost-effectiveness analysis, and cost-utility analysis.
Peripheral nerve function in patients with chronic bronchitis receiving almitrine or placebo.
Authors: M B Allen, K Prowse
Journal: Thorax (1989)

A double blind prospective study of the effect of almitrine bismesylate and placebo on peripheral-nerve function was carried out in 12 patients with chronic bronchitis and arterial hypoxaemia (mean (SD) FEV1% predicted 38 (16), arterial oxygen tension (PaO2) 7.56 (0.76) kPa). Of the seven patients who took placebo, none developed symptoms or signs of peripheral neuropathy. One patient who had abnormal lower limb sensory nerve conduction initially showed improvement of sensory conduction but deterioration in motor conduction during the 12 month study period. Two further patients developed some slowing of motor conduction velocities in their right lateral popliteal nerve. Five patients received almitrine and all showed an improvement in PaO2 (mean from 7.0 to 7.9 kPa). None had symptoms or signs of peripheral neuropathy on entry to the study; one patient had evidence of impaired nerve conduction on electrophysiological testing. Three patients developed symptoms and signs of peripheral neuropathy during the 12 months of the study and a fourth developed peripheral neuropathy at 18 months, having continued to receive almitrine. Studies of nerve physiology showed abnormalities in the lower limbs of all four patients. Recovery was poor, possibly because of the long half life of almitrine. The studies suggest that almitrine may precipitate peripheral neuropathy in patients with chronic obstructive pulmonary disease. Patients should be warned of this potential complication so that the drug can be stopped as soon as symptoms develop.
Mould's Medical Anecdotes
Authors: Norman Cousins
Journal: JAMA (1985)

The materials presented in this book are not to be confused with informal medical case histories. The governing principle for selection is less scientific than literary. If you were looking for this book in a library, you probably would turn to a shelf containing Beaconsfield's<i>Liter-</i><i>ary Curiosities</i>even before you would explore titles in the neighborhood of<i>Anomalies of Medicine</i>. <i>Mould's Medical Anecdotes</i>, then, is a variorum of short items intended to amuse rather than to inform, to titilate rather than to educate. This basket of curiosa ranges from a mini essay on how to shrink a head to a short article carrying the title, "Was Sherlock Holmes a Drug Addict?" In between, you can find any number of brief items such as "Circumcision and the Birth of Twins," "Lead Poisoning in the Cement World," and "The Erythema of Caterpillars." I think I have said enough to indicate that
The Possible Role of Calcium in Excitation-Contraction Coupling of Heart Muscle
Authors: Chandler McC. Brooks, SAUL WINEGRAD
Journal: Circulation (1961)

The transfer of Ca 45 at rest and during contraction has been measured in isolated guinea-pig atria. During contraction, the rate of transfer increases considerably. The increment in the uptake of calcium by the cells of the atria during contraction is closely correlated with the strength of contraction. This relationship is maintained at different frequencies of stimulation and at different concentrations of external calcium.
1117-91 Invasive therapy along with glycoprotein IIb/IIIa inhibitors and intracoronary stents improves survival in non-ST-segment elevation acute coronary syndromes
Authors: Anthony A Bavry, Dharam J Kumbhani, Rene Quiroz, Suneil R Ramchandani, Satish Kenchaiah
Journal: Journal of the American College of Cardiology (2004)
Aging and biomedicine 2005: Where should we go from here?
Authors: M BARTON
Journal: Cardiovascular Research (2005)

Aging has become a central issue in science and society in view of demographic changes anticipated in the next decades due to longevity and low birth rates [1–3]. The steady growth of the world's population from approximately 2.5 billion in 1950 to 6.4 billion today is expected to increase even further to more than 9 billion by 2050 [4] (Fig. 1). The reasons for living longer [5] involve a decline in old-age mortality [6] due to advances in disease management and drug discovery, which have been made possible through continued economic stability. However, despite these advances, today's clinical practice faces an increasing number of geriatric patients with multi-morbidity that requires special care adjusted to the high age of the patients.



Fig. 1 
Projected development of the world population. In addition to an expected growth of the world population from currently 6.2 billion to more than 9 billion in 2050, individuals aged 50 years and older will increase by a factor of 2 to 5 in both men and women, resulting in a pronounced shift in the overall population profile. Adapted from data provided by the U.S. Census Bureau, International Programs Center, International Data Base [5].



Age remains the main cause of death after age 28 in industrialized nations [7]. The majority of aging theories favors cumulative injury resulting in cellular senescence as a causative mechanism [8]. This results in genomic … 

*Tel.: +41 1 255 5663; fax: +41 1 255 8747. Email address: barton{at}usz.ch
Lethal Congenital Anomalies
Authors: Aubrey Milunsky
Journal: JAMA (1983)

The Western world has witnessed waning infant mortality rates from infectious diseases these past few decades. At the same time has come the increasing recognition of the importance of congenital anomalies as a major cause of perinatal, neonatal, and infant deaths. Today, 2% to 3% of all births are associated with a major congenital anomaly. 1 Such anomalies, mental retardation, and genetic disorders together account for 25% to 30% of admissions to children's hospitals in North America. Pain and suffering of both children and family inexorably follow the birth and death of many affected infants (estimate, 109,380 in 1981 in the United States). This heavy personal and societal burden is aggravated by the realization that a recognizable cause is not found in some 60% of major congenital anomalies. 2   Infants with congenital anomalies frequently have low birth weights. While the causes of these low birth weights are frequently unknown, certain
497. Central CART Gene Delivery by Recombinant AAV Vector Decreases Lean Body Mass in Diet-Induced Obese Male Rats
Authors: Keyun Qing, Yanyun Chen
Journal: Molecular Therapy (2006)

Cocaine- and amphetamine-regulated transcript (CART) peptide is a neuro-peptide implied in the regulation of energy homeostasis. CART mRNA and its encoded peptide have been localized in many brain regions that regulate energy balance. To study the physiological function of CART in the diet-induced obese (DIO) rats, we constructed and packaged recombinant adeno-associated virus 2 (AAV) vector containing CMV promoter driven rat CART cDNA and a reporter gene hrGFP (AAV-rCART-hrGFP). Approximately 1x1011 particles of AAV-rCART-hrGFP or control vector AAV-IRES- hrGFP were injected through intra-cerebro-ventricular (ICV) into 100 days old male DIO Long-Evans rats (n=9).
Effect of Renal Artery Stenting on Renal Function and Size in Patients with Atherosclerotic Renovascular Disease
Authors: Paul S. Watson, Peter Hadjipetrou, Stephen V. Cox, Thomas C. Piemonte, Andrew C. Eisenhauer
Journal: Circulation (2000)

Renal artery stenting is widely performed, but little is known about its effectiveness in preserving renal function and size in patients with renovascular disease and chronic renal insufficiency. We studied the effect of renal artery stenting on renal function and size in patients with obstructive renovascular disease and chronic renal insufficiency.Stent deployment was performed in patients with chronic renal insufficiency (creatinine >1.5 mg. dL(-1)) and global renovascular obstruction (bilateral renal artery stenosis or unilateral stenosis in the presence of a solitary or single functional kidney). The effect of renal artery stenting on renal function was assessed by comparing the slopes of the regression lines derived from the reciprocal of serum creatinine versus time plotted before and after stent deployment. Renal size was assessed by serial ultrasound of pole-to-pole kidney length. Stenting was successful in all 61 vessels in 33 patients. Twenty-five patients had complete follow-up (mean 20+/-11 months). Before stent deployment, all patients exhibited a negative slope, indicating progressive renal insufficiency. After stent deployment, the slopes were positive in 18 and less negative in 7 patients. Thus, the mean slope increased from -0.0079 to 0.0043 dL. mg(-1). mo(-1) (P:<0.001). Ultrasonography on 41 kidneys revealed preservation of size, with the kidney length measuring 10.4+/-1.4 cm at baseline and 10.4+/-1.1 cm at last follow-up (P:=NS). Patient survival at 20+/-11 months was 90%.In patients with chronic renal insufficiency and global obstructive atherosclerotic renovascular disease, renal artery stenting improves or stabilizes renal function and preserves kidney size.
Relaxin as a New Hormone*
Authors: GILLIAN D. BRYANT-GREENWOOD
Journal: Endocrine Reviews (1982)

RELAXIN was described as a hormone some 55 years ago but despite some persistent pioneering work, passed into relative obscurity for a long period of time. The present status of relaxin is such that it directly impinges on reproductive endocrinology and perhaps on those endocrinologists who appreciate that connective tissue metabolism is controlled by hormones and who wish to share in the task of refurbishing a hormone long left on the shelf. There is no question but that work on relaxin was at a low ebb for 40 years after its initial discovery by Frederick Hisaw in 1926. Certainly part of the resurgence of work on relaxin in the early 1970s is identified with initiatives of Dr. Steinetz, and there is now a sufficient body of knowledge to warrant its integration into general endocrinology. A documentation of the reasons for the neglect of relaxin would make an interesting exercise in the history of endocrinology but is outside the scope of this review. I mention my perceptions below because they may become applicable to other fields of endeavor in endocrinology as reductions in Federal funding for research encourage scientists to look to the private sector for support.
Death of a KAPI
Authors: J. Hollis-Triantafillou
Journal: BMJ (1996)

Regular readers of this column may remember that it is just two years since I first wrote of the lively activities at our Open Care Community Centre for Older People, or KAPI, where we provide medical, social, and recreational facilities for people over 60 at the neighbourhood level. Our centre was the prototype for more than 350 KAPIs throughout Greece. During the 18 years of its existence it received frequent visitors from home and abroad, participated in studies relating to health and illness in old age, and contributed in numerous ways to the life of the local community.

The success of the KAPI network as …
SOME POINTS IN THE APPLICATION OF VACCINE THERAPY
Authors: ERNEST E. IRONS
Journal: JAMA (1910)

The literature of the past year on vaccine therapy is characterized by a tendency to study more carefully the methods of use and the limitations of vaccines rather than to extend the range of their application. We have much theory in regard to the various methods of aiding Nature in the establishment of immunity, but our knowledge of what really happens when we inject a bacterial emulsion into a patient is still incomplete.  Those who have studied vaccine therapy from both the laboratory and the clinical sides will, I believe, agree that the method, either alone or in conjunction with other appropriate measures, may accomplish definite results, especially in localized infections, and that while control by means of serum and leukocytic reactions is often a valuable aid, the chief guide in the selection of cases and of the vaccines for their cure must come from clinical observations.  I wish to
Nitrinergic and peptidergic innervation of the human oesophagus.
Authors: C Singaram, A Sengupta, M A Sweet, D J Sugarbaker, R K Goyal
Journal: Gut (1994)

The distribution, colocalisation, and interconnections of nitrinergic and peptidergic neurons and nerves in the human oesophagus were examined. Cryosections of surgically resected tissues from eight subjects were studied with indirect immunofluorescence for the presence of 11 neuropeptides and neuron specific enolase. After immunohistochemistry, nitric oxide synthase was shown on the same sections with the beta nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase histochemical reaction. The histochemical findings were verified immunohistochemically on other sections with an antiserum against nitric oxide synthase. Most myenteric neurons (55%) were nitrinergic. Most (96%) received terminations positive for vasoactive intestinal polypeptide (VIP), calcitonin gene related peptide (CGRP) (80%), and galanin (59%). The neuronal somata of 14% also contained VIP, while 10% had galanin. Of the NADPH-diaphorase containing fibers seen in the muscle layers, many had closely associated VIP and galanin, but only rarely CGRP and substance P. Thus, despite abundant representation of both peptidergic and nitrinergic systems in oesophageal smooth muscle, only VIP and galanin colocalised to any significant extent with the nitrinergic elements. These findings provide morphological support for the role of nitric oxide as the non-adrenergic non-cholinergic inhibitory mediator in the human oesophagus and for its possible interactive role with the peptidergic system.
Abstract LB-10: Rational design of small molecules targeting the Ras GEF, SOS1
Authors: Chris Evelyn, Xin Duan, Jacek Biesiada, William Seibel, Jaroslaw Meller, Yi Zheng
Journal: Cancer Research (2014)

Abstract Ras GTPases regulate multiple intracellular signaling processes involved in gene expression, cell proliferation, and cell survival. Driver mutations of Ras signaling components including K,N,H-Ras, EGFR, PDGFR, Raf, PI3K, and Akt have been found in many types of human cancers. The activation of Ras is catalyzed by guanine-nucleotide exchange factors (GEFs), which stimulate the exchange of GDP for GTP. SOS1 is a major RasGEF that transduces receptor tyrosine kinase signals to Ras and associated ERK/Akt pathways. SOS1 gain-of-function mutations have been found in Noonan syndrome patients. In addition, SOS1 has been shown to be differentially expressed in prostate and breast cancer cells, and is involved in malignancies dependent upon aberrant Ras signaling. In the current studies, we undertake a structure-based virtual screening approach, coupled with biochemical and cell biological validations, to identify lead chemical inhibitors targeting the Ras catalytic domain of SOS1. From a 118,500 compound subset of the NCI/DTP Open Chemical Repository, 135 showed optimal docking energy to a grid of the SOS1 catalytic site from which 36 were selected for experimental screening by a guanine nucleotide exchange assay, i.e. FL-GDP dissociation of Ras under the catalysis of SOS1. Two compounds were confirmed as true hits (NSC-674954 and NSC-658497), of which NSC-658497 displayed micromolar IC50s in both inhibiting FL-GDP dissociation (IC50 - 22.2 µM) from Ras and TR-GTP loading (IC50 - 40.8 µM) of Ras catalyzed by Sos1. In addition, NSC-658497 displayed a target binding Kd of ∼7.0 µM as assayed by microscale thermophoresis, along with dose-dependently disrupting the SOS1 interaction with Ras as assayed by a GST-Ras pull-down analysis. Mutagenesis studies mapped NSC-658497 action site to the catalytic site in SOS1, involving specifically residues I825, T828, T829, and Y912. SAR analysis revealed that NSC-658497 elicits its inhibitory effect on SOS1 through a benzopyran and nitrophenyl moiety. In fibroblast cells, NSC-658497 showed dose-dependent efficacy in inhibiting EGF-stimulated Ras and ERK/AKT activities. Furthermore, NSC-658497 dose-dependently inhibited NIH/3T3, MEF, and MIA-PaCa-2 pancreatic cancer cell proliferation in conjunction with their respective downstream Ras-dependent ERK/AKT activities. Thus, we have identified a class of lead chemical inhibitors targeting SOS1 that can serve as useful tools for studying SOS1 mediated oncogenesis and as hits for further development of future cancer therapeutics. Citation Format: Chris Evelyn, Xin Duan, Jacek Biesiada, William Seibel, Jaroslaw Meller, Yi Zheng. Rational design of small molecules targeting the Ras GEF, SOS1. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr LB-10. doi:10.1158/1538-7445.AM2014-LB-10