tbuckley/cabot-search huggingface dataset:
Regulatory roles of T mu and T gamma cells in the collaborative cellular initiation of the extrinsic coagulation pathway by bacterial lipopolysaccharide.
Authors: G A Levy, B S Schwartz, L K Curtiss, T S Edgington
Journal: Journal of Clinical Investigation (1985)

The Shwartzman reaction is a classic biologic response in which the coagulation system is activated in vivo. Cellular initiation of the extrinsic coagulation protease cascade can be mediated by one or more limbs of the lymphoid response to diverse biological stimuli. The T cell-instructed monocyte and macrophage responses that have been implicated are mediated by a number of different cellular pathways and are elicited not only by antigens and allogeneic cells but also by other stimuli such as immune complexes and the lipid A moiety of bacterial lipopolysaccharide (LPS). The latter response has been implicated in the pathogenesis of the disseminated intravascular coagulation associated with bacterial infection. In the rapid collaborative cellular pathway response to LPS, we have described a relatively rigorous requirement for T helper cells in induction of the biosynthesis of tissue factor and Factor VII by monocytes. To elucidate potential regulatory aspects of this cellular procoagulant response, we provide the first evidence for the existence of T suppressor cells for the cellular procoagulant response to LPS by the rapid T cell-instructed pathway. Human peripheral blood lymphocytes were separated by cytoaffinity into Fc gamma-positive and Fc mu-positive cells and were characterized for their functional properties in the procoagulant response. T mu cells mediated the monocyte response, consistent with their identity with instructor cells. T gamma cells suppressed the response of monocytes to LPS in the presence of T mu cells, suggesting that they possess suppressor function for this response. The T gamma suppressor cells required stimulation by LPS to express their suppressor function and they exerted their suppressive effect directly on the monocyte. The existence and participation of LPS-responsive T suppressor cells on the cellular procoagulant response in vitro add a new dimension to the complexity of the rapid pathway of the collaborative cellular procoagulant response and may be important in the pathogenesis of disseminated intravascular coagulation.
Preventive Medicine in Medical Education
Authors: John R. Ellis
Journal: New England Journal of Medicine (1965)

PREVENTIVE medicine is immensely old. Whether originating, as in the past, from the ideas and activities of the few at the top or, as now may more often be the case, from the ideas and aims of the majority of the masses, it is woven into the fabric of the life of every community. It had been organizing medical knowledge for hundreds of years before organized medicine began. It has been motivated by many powerful forces, including the social conscience of individuals and communities, compassion and gain. The community has now assumed more and more of the responsibility, and the . . .
SPONTANEOUS MEDIASTINAL EMPHYSEMA
Authors: Hayes W. Caldwell
Journal: JAMA (1941)

In recent years medical men's attention has been called to a syndrome that might aptly be called Hamman's syndrome, since he was the first to describe it.<sup>1</sup>He reported his observations in 1937 and more fully in 1939.<sup>2</sup>His cases had been seen over a period of five years. Scott<sup>3</sup>later in 1937 reported 2 cases with similar signs and sypmptoms. Since that time others have added to this series—Faulkner and Wagner<sup>4</sup>as well as Morey and Sosman.<sup>5</sup>Because of the importance of the subject I wish to add another case to those already published. Hamman's explanation for the cause of this condition is that, owing to some weakness in an alveolar wall, it ruptures and the released air dissects its way through the fibrous tissue about the blood vessels into the hilus of the lung and thence into the mediastinal tissue. If the amount
Analyzing the Evolution of RNA Secondary Structures in Vertebrate Introns Using Kimura's Model of Compensatory Fitness Interactions
Authors: R. Piskol, W. Stephan
Journal: Molecular Biology and Evolution (2008)

Previous studies have shown that splicing efficiency, and thus maturation of pre-mRNA, depends on the correct folding of the RNA molecule into a secondary or higher order structure. When disrupted by a mutation, aberrant folding may result in a lower splicing efficiency. However, the structure can be restored by a second, compensatory mutation. Here, we present a logistic regression approach to analyze the evolutionary dynamics of RNA secondary structures. We apply our approach to a set of computationally predicted RNA secondary structures in vertebrate introns. Our results are consistent with the hypothesis of a negative influence of the physical distance between pairing nucleotides on the occurrence of covariations, as predicted by Kimura's model of compensatory evolution. We also confirm the hypothesis that longer local secondary structure elements (helices) can accommodate a larger number of covariations, wobbles, and mismatches. Furthermore, we find that wobbles and mismatches are more frequent in the middle of a helix, whereas covariations occur preferentially at the helix ends. The GC content is a major determinant of this pattern.
Cytokines in rheumatoid arthritis.
Authors: P Kahle, J Saal, G Pawelec
Journal: Annals of the Rheumatic Diseases (1991)

Cytokines in rheumatoid arthritisSir: In a recent interesting article Westacott et al reported on concentrations of the five cytokines interleukin 1 , interleukin 2, tumour necrosis factor a, interferons gamma and
Impact of the Starling Concepts on Clinical Cardiology
Authors: Carleton B. Chapman
Journal: JAMA (1963)

SINCE the eighteenth century it has been customary to speak with awe of the facility and speed with which the human circulatory system can adapt to changing needs. Indeed, Hales,<sup>1</sup>that indefatigable English parson and natural philosopher, used changing experimental condition in a most ingenious way in order to increase his knowledge of circulatory physiology. Although we are inclined, perhaps, to worship too much and too often at the shrines of our profession's intellectual father figures, no serious student of the circulatory system can afford to ignore Hales. We usually damn him with faint praise by according him credit for being the first to measure blood pressure, which is fair enough as far as it goes. But he actually did a great deal more than this, and it is highly pertinent to what follows to quote one passage, up to now largely overlooked, from his book,<i>Haemastaticks</i>. Referring
Progression From Precursor Disease to Multiple Myeloma
Authors: Thomas E. Finucane
Journal: JAMA (2011)

subgroup of acute myeloid leukemia with a distinctive gene expression profile that is uniquely associated with a favorable outcome. Blood. 2009;113(13):30883091. 4. Metzeler KH, Hummel M, Bloomfield CD, et al; Cancer and Leukemia Group B; German AML Cooperative Group. An 86-probe-set gene-expression signature predicts survival in cytogenetically normal acute myeloid leukemia. Blood. 2008; 112(10):4193-4201.
Human Papillomavirus Vaccine — Opportunity and Challenge
Authors: Lindsey R. Baden, Gregory D. Curfman, Stephen Morrissey, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2007)

In this issue of the Journal, we publish three Original Articles,1–3 two Perspective articles,4,5 two editorials,6,7 a letter to the editor,8 and an audio interview9 on the subject of human papillomavirus (HPV). We bring together this unique body of information in response to the enormity of the health problems that stem from HPV and the broad interest that has been kindled by the possibility of preventing HPV-related cervical cancer and other anogenital conditions through vaccination. The HPV vaccine is the first vaccine explicitly designed to prevent cancer induced by a virus. (The hepatitis B vaccine was not . . .
5-Aminosalicylic acid is a potent inhibitor of interleukin 1 beta production in organ culture of colonic biopsy specimens from patients with inflammatory bowel disease.
Authors: Y R Mahida, C E Lamming, A Gallagher, A B Hawthorne, C J Hawkey
Journal: Gut (1991)

Interleukin 1 beta in biopsy specimens from inflamed colonic mucosa of patients with active inflammatory bowel disease was studied. Compared with normal colonic mucosal biopsy specimens, a significantly greater amount of interleukin 1 beta was present in rectal mucosa before (median (range) 4.3 (2.0-11.8) v 119.2 (30.1-286.8) pg/mg; p less than 0.01) and produced during organ culture (39.1 (9.4-106.8) v 97.6 (28.2-991.6) pg/mg; p less than 0.01). Values of interleukin 1 beta after culture correlated with concentrations of thromboxane B2. Organ culture of inflamed biopsy specimens in the presence of 5 aminosalicylic acid and dexamethasone reduced the amount of interleukin 1 beta detected. At the doses studied, 5 aminosalicylic acid also reduced the amount of leukotriene B4 detected after culture.
A PRACTICAL OPHTHALMOSCOPE.
Authors: EDWARD JACKSON
Journal: JAMA (1896)

<h3>The Sight-hole.</h3> —The principal use of the ophthalmoscope is to enable us to study the interior of the eye. The use of its lenses for the measurement of refraction is of much less importance. In most of the forms of the instrument employed in this country its principal use has been somewhat sacrificed to assist its less important function. To measure refraction with the ophthalmoscope it is necessary by using a large sight-hole to exaggerate the blurring caused by imperfect focusing. For the other uses of the ophthalmoscope this blurring should be reduced as much as possible. It can not be entirely corrected by lenses, because in all eyes, with the pupil dilated as in a dark room, there is irregular astigmatism which no lens can correct. Such blurring is reduced directly in proportion to the reduction in the size of the sight-hole; hence, the most distinct view of the
The authors reply as follows
Authors: A H CHESTER, G R MARTIN, M YACOUB
Journal: Cardiovascular Research (1991)

Journal Article The authors reply as follows Get access A H CHESTER, A H CHESTER Search for other works by this author on: Oxford Academic PubMed Google Scholar G R MARTIN, G R MARTIN *Wellcome Research Laboratories, Beckenham, Kent, United Kingdom Search for other works by this author on: Oxford Academic PubMed Google Scholar M YACOUB M YACOUB Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 25, Issue 3, March 1991, Pages 263–264, https://doi.org/10.1093/cvr/25.3.263b Published: 01 March 1991
Factors Influencing Threshold and Choice of Treatment for Hypertension in NIDDM: Cardiovascular Factors
Authors: John S Yudkin
Journal: Diabetes Care (1991)

In nondiabetic populations, there is an ∼40% increase in stroke risk and a 25% increase in coronary heart disease (CHD) risk with every 6-mmHg increase above 75mmHg in usual diastolic blood pressure. Diabetesincreases the risk of both conditions by two- to threefold, and in diabetic patients, hypertension further increases these risks. The benefits of lowering blood pressure in nondiabetic subjects have been subjected to metaanalysis, which has demonstrated benefits equivalent to 100% reversal of the excess risk for stroke but with only ∼50% of CHD risk reversible after 2–3 yr of treatment. In these analyses, the benefit of treating diastolic blood pressure is similar at all levels &amp;gt;90 mmHg. If these results are extrapolated to diabetic patients, possible benefits of therapy for mild hypertension could be two to three times greater than in nondiabetic subjects, but this could still correspond to 300 person-yr of treatment to prevent one nonfatal stroke and 2500 person-yr oftreatment to prevent one CHD death, with treatment that may deleteriously affect quality of life in 36% of all diabetic patients. There may also be risks in treating patients with mild hypertension who have existing CHDor left ventricular hypertrophy, which are more common in diabetes. Despite the theoretical risk of deleterious changes in several cardiovascular risk factors with thiazides or β-blockers, most of the newer agents have not yet been demonstrated to produce similarbenefits to the large prospective studies in which the aforementioned agents have been used. It is only with prospective studies in high-risk diabetic populations that the treatments can be compared and the possible risks of a J-shaped curve assessed.
Fellows’ Forum Forgotten?
Authors: Archie Bleyer
Journal: Journal of Clinical Oncology (2005)

TO THE EDITOR: Jennifer Armstrong was a new oncology Fellow in Manhattan (New York, NY) when the Sept. 11 World Trade Center tragedy occurred. In the November 1, 2004, issue of the Journal, she describes how the war against cancer in which she had become entrenched prevented her from mourning, grieving, and commiserating with the rest of the nation and half the world. Her experiences with patients dying of cancer were too overwhelming for her to feel the loss at “Ground Zero.” After learning how her own war was affecting her, she found articles in the cancer literature about programs that had been designed to aid in this process. She then sought administrative help in setting up a program to help Fellows cope with dying, pain, and suffering in their patients. By July 2003, she launched a Fellows’ forum that she described as follows: Twice a month, we invited the medical oncology fellows to a lunch-time forum to discuss the psychosocial aspects of clinical oncology. We encouraged fellows to share any clinical encounters that had remained with them for more than 24 hours. The sessions were cofacilitated by me and a fellow in psychiatry, with supervision from an attending physician in psychiatry. The initial sessions were gritty. Fellows appeared in great numbers and recounted stories about patients they had cared for who had stayed with them for months or even years. One fellow explained the outpouring as, “We’re thirsty for this venue.” The obvious need was translated into a successful program for the Fellows that has continued to this day. What’s striking to me is that the same need was observed during my Fellowship a third of a century ago, and a nearly identical solution was provided. The sessions were held weekly exclusively for the Fellows and co-facilitated by a psychiatrist and an oncologist. Dr. Armstrong may have missed the first iteration of such a forum, perhaps because it was too long ago. In medicine, as in all endeavors of life, history does repeat itself. Most hopefully, we have learned from history to avoid a repeat of the event that occurred elsewhere in Manhattan 3 years ago.
Hypoxanthine Uptake in Isolated Rat Renal Cortical Tubule Fragments
Authors: John W. Foreman, Stanton Segal
Journal: Journal of Clinical Investigation (1979)

Isolated renal tubule fragments prepared from adult Sprague-Dawley rats were used to study the cellular uptake of hypoxanthine. This uptake was rapid, reaching a steady state after 30 min of incubation. Analysis of the intracellular pool during the initial uptake and at the steady state revealed a concentration gradient of hypoxanthine consistent with active transport, although only one-third of the transported hypoxanthine remained unmetabolized. The remainder of the transported hypoxanthine was converted to inosine and inosinic acid, but detectable conversion to uric acid was not noted. A kinetic analysis of uptake revealed that two systems for cellular entry of hypoxanthine existed with Km1 = 0.005 and Km2 = 0.80 mM. Hypoxanthine uptake at physiologic concentrations was oxygen, sodium, and temperature dependent, but the addition of metabolic fuels and alteration of the medium pH over the range of from 6.1 to 7.4 had no effect. Adenine, guanine, and inosine inhibited the uptake of hypoxanthine via the low-Km system which mediates the majority of uptake at physiologic levels. Xanthine, uric acid, and probenecid inhibited uptake via the high-Km system, but did not affect uptake via the low-Km system. The data indicate that hypoxanthine at physiologic levels is transported into the renal tubule cell via a system different from that for other oxypurines.
IKKβ and NF-κB Transcription Govern Lymphoma Cell Survival through AKT-Induced Plasma Membrane Trafficking of GLUT1
Authors: Thomas G. Sommermann, Kathleen O'Neill, David R. Plas, Ellen Cahir-McFarland
Journal: Cancer Research (2011)

Abstract All cancer cells require increased nutrient uptake to support proliferation. In this study, we investigated the signals that govern glucose uptake in B-cell lymphomas and determined that the inhibitor of NF-κB-kinase β (IKKβ) induced glucose transporter-1 (GLUT1) membrane trafficking in both viral and spontaneous B-cell lymphomas. IKKβ induced AKT activity, whereas IKKβ-driven NF-κB transcription was required for GLUT1 surface localization downstream of AKT. Activated NF-κB promoted AKT-mediated phosphorylation of the GLUT1 regulator, AKT substrate of 160kD (AS160), but was not required for AKT phosphorylation of the mTOR regulator Tuberous Sclerosis 2 (TSC2). In Epstein-Barr virus–transformed B cells, NF-κB inhibition repressed glucose uptake and induced caspase-independent cell death associated with autophagy. After NF-κB inhibition, an alternate carbon source ameliorated both autophagy and cell death, whereas autophagy inhibitors specifically accelerated cell death. Taken together, the results indicate that NF-κB signaling establishes a metabolic program supporting proliferation and apoptosis resistance by driving glucose import. Cancer Res; 71(23); 7291–300. ©2011 AACR.
Abstract B43: An accurate seven-gene signature plus Gleason score for prostate cancer prognosis
Authors: Xin Chen, Zhenyu Jia, Mercola Dan
Journal: Cancer Research (2012)

Abstract One of the major problems in the development of prostate cancer prognostic biomarkers is the composition heterogeneity in tissue samples, which causes the inconsistency among different studies. To deal with this problem, we developed two-step strategy. In the first step, the proposed two-step cluster analysis model accounting for the cell-type composition percentage was used to identify 324 genes strongly associated with biochemical recurrence status and in the second step the 324 identified genes was further investigated by SAM (significance analysis of microarray) leading to a seven-gene classifier. The classifier was then validated on two independent data sets with overall accuracy and sensitivity of 71% and 76%, respectively. The seven-gene classifier stratified the test samples into two risk groups that are highly associated with biochemical relapse status (hazard ratio = 2.6 with p value = 0.03). The study also showed that the inclusion of the Gleason sum to the seven-gene classifier raised the sensitivity and accuracy to 76% and 83% respectively when tested on the independent data sets. These results indicated that our seven-gene classifier with the Gleason score can be used for predicting outcomes for prostate cancer patients. Citation Format: Xin Chen, Zhenyu Jia, Mercola Dan. An accurate seven-gene signature plus Gleason score for prostate cancer prognosis [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr B43.
Conscience, good character, integrity, and to hell with philosophical medical ethics?
Authors: R Gillon
Journal: BMJ (1985)

Gillon, in one of a series of articles on philosophical medical ethics, rebuts the contention of many physicians that philosophical medical ethics is irrelevant to medical education and practice. His opponents hold that the ethical education of the physician is accomplished by the development of conscience, good character, and integrity in conjunction with medical skills. Gillon argues that accepting these virtues as sufficient in themselves, without requiring any philosophical analysis of the moral assumptions and objectives of medical practice, is akin to specifying a syllabus for therapeutics while claiming that a knowledge of pharmacology is unnecessary.
Do Lower Respiratory Tract Infections in Early Childhood Cause Chronic Obstructive Pulmonary Disease?
Authors: Seif O. Shaheen, David J. P. Barker, Stephen T. Holgate
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

The hypothesis that lower respiratory tract infections (LRTI) in early childhood lead to chronic obstructive pulmonary disease (COPD) in late adult life has been difficult to test. However, a unique opportunity arose when records were discovered in the counties of Hertfordshire and Derbyshire, England, that contained information about childhood LRTI recorded 60 to 70 years ago. The lung function of some men still living in these counties was examined. In Hertfordshire men, bronchitis or pneumonia in infancy was associated with reduced mean FEV1, adjusted for age and height. In Derbyshire men, pneumonia before 2 yr of age was associated with a large and highly significant reduction in mean FEV1, adjusted for age and height. These findings were independent of smoking and social class. These data support a causal relationship between LRTI in early life and subsequent COPD.
Epidermal abnormalities in Refsum's disease
Authors: M. G. DAVIES, R. MARKS, P.J. DYKES, D. REYNOLDS
Journal: British Journal of Dermatology (1977)

A female patient with severe Refsum's disease is described. She had striking ichthyosis and detailed investigations into the structure of the epidermis were performed. Light microscopy and transmission electron microscopy revealed lipid-containing vacuoles in the epidermis. Scanning electron microscopy of the stratum corneum showed disruption and the presence of microvilli on individual horn cells consistent with a high output state of epidermal cell production.
B cell–derived exosomes can present allergen peptides and activate allergen-specific T cells to proliferate and produce TH2-like cytokines
Authors: Charlotte Admyre, Barbara Bohle, Sara M. Johansson, Margarete Focke-Tejkl, Rudolf Valenta, Annika Scheynius, Susanne Gabrielsson
Journal: Journal of Allergy and Clinical Immunology (2007)
Shared Savings in Accountable Care Organizations
Authors: Matthew DeCamp, Jeremy Sugarman, Scott Berkowitz
Journal: JAMA (2014)

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