tbuckley/cabot-search huggingface dataset:
Resting and activated T cells display different requirements for CD8 molecules.
Authors: Z Cai, J Sprent
Journal: The Journal of Experimental Medicine (1994)

Clonotype-positive (1B2+) T cells from 2C T cell receptor (TCR) transgenic mice were used to define the role of CD8 molecules in the induction phase vs. the effector phase of the primary response to class I alloantigens. Three main findings are reported. First, in the presence of exogenous lymphokines, resting CD8+ 2C cells gave strong proliferative responses to two alloantigens, Ld and Kbm11. In the absence of added lymphokines, however, CD8+ 2C cells responded only to Ld and not to Kbm11; Ld stimulated both interleukin 2 (IL-2) and IL-2 receptor (R) synthesis, whereas Kbm11 elicited only IL-2R synthesis. The primary response of CD8+ 2C cells was thus helper-independent (HI) to Ld but helper-dependent (HD) to Kbm11, presumably reflecting that Ld is a stronger antigen than Kbm11. Second, in contrast to CD8+ cells, CD8- 2C cells mounted only an HD and not an HI response to the strong Ld antigen; conversely, selecting for a minor subset of CD8hi cells enabled 2C cells to mount an HI response to the weak Kbm11 antigen. These findings, together with experiments with heterozygous vs. homozygous stimulator cells, suggest that HI and HD responses reflect differences in the overall avidity of T antigen presenting cell (APC) interaction: high-avidity interaction leads to strong intracellular signaling and an HI response, whereas low-avidity interaction causes weak signaling and an HD response; high-avidity T/APC interaction is heavily dependent on CD8 expression. Third, CD8 expression was found to be less important for CTL activity than for primary proliferative responses. Thus, in contrast to HI proliferative responses, CTL responses of 2C cells to Ld were CD8 independent. However, 2C lysis of Ld targets became strongly CD8 dependent in the presence of limiting doses of anti-TCR (1B2) antibody. Collectively, the data suggest that, both for T cell induction and the expression of effector function, CD8 molecules play a decisive role in augmenting TCR-mediated signaling, either by promoting TCR contact with antigen or delivering kinases (p56lck) to the TCR/CD3 complex, or both.
PROGRESSIVE MUSCULAR DYSTROPHY
Authors: FRANCIS H. McCRUDDEN
Journal: JAMA (1918)

The tendency to enlarge on the functional rather than on the structural aspect of the so-called chronic and incurable diseases, and the tendency to consider them less as anatomic, and more as physiologic problems, as a result of the rapid advance of chemical physiology, has resulted in an auspicious change in point of view regarding the nature of disease, the purpose of diagnosis, and the object of treatment. From the new point of view, a diseased organ is one that is functionally unequal to its tasks. Determination of the structural nature and extent of organic defect is, accordingly, only partial, qualitative, anatomic diagnosis, which must be completed by quantitative, physiologic diagnosis, that is to say, measurement of functional capacity. Guided by such measurements, the therapeutist diminishes burdens and augments working powers in an endeavor to balance tasks and capacities. The most striking feature of this physiologic concept of disease is
Malnutrition soars in Horn of Africa as crisis worsens by the day
Authors: J. Zarocostas
Journal: BMJ (2011)

Rates of malnutrition and mortality among children are rising rapidly in drought stricken Ethiopia, Kenya, and Somalia, the United Nations and aid charities have warned. Unless humanitarian assistance is urgently dispatched and interventions scaled up, the crisis is expected to worsen, they say.

UN officials in the region told the BMJ that the rate of acute malnutrition is rising dramatically and that death rates have risen sixfold among children aged under 5 years in some of the worst affected areas.

The crisis, exacerbated by the severest drought in half a century, is getting worse by the day. The situation is most life threatening for the thousands of Somali refugees crossing over daily into Ethiopia and Kenya after having walked for days.

Adrian Edwards, a spokesman for the …
Phenotypic Manifestations of Mutations in Genes Encoding Subunits of Cardiac Potassium Channels
Authors: Wataru Shimizu, Minoru Horie
Journal: Circulation Research (2011)

Since 1995, when a potassium channel gene, hERG (human ether-à-go-go-related gene), now referred to as KCNH2 , encoding the rapid component of cardiac delayed rectifier potassium channels was identified as being responsible for type 2 congenital long-QT syndrome, a number of potassium channel genes have been shown to cause different types of inherited cardiac arrhythmia syndromes. These include congenital long-QT syndrome, short-QT syndrome, Brugada syndrome, early repolarization syndrome, and familial atrial fibrillation. Genotype-phenotype correlations have been investigated in some inherited arrhythmia syndromes, and as a result, gene-specific risk stratification and gene-specific therapy and management have become available, particularly for patients with congenital long-QT syndrome. In this review article, the molecular structure and function of potassium channels, the clinical phenotype due to potassium channel gene mutations, including genotype-phenotype correlations, and the diverse mechanisms underlying the potassium channel gene–related diseases will be discussed.
A Hydrolase of Trehalose Dimycolate Induces Nutrient Influx and Stress Sensitivity to Balance Intracellular Growth of Mycobacterium tuberculosis
Authors: Yong Yang, Kathleen Kulka, Ronald C. Montelaro, Todd A. Reinhart, James Sissons, Alan Aderem, Anil K. Ojha
Journal: Cell Host & Microbe (2014)
Methodologic and Logistic Issues in Conducting Longitudinal Birth Cohort Studies: Lessons Learned from the Centers for Children’s Environmental Health and Disease Prevention Research
Authors: Brenda Eskenazi, Eleanor A. Gladstone, Gertrud S. Berkowitz, Christina H. Drew, Elaine M. Faustman, Nina T. Holland, Bruce Lanphear, Stefanie J. Meisel, Frederica P. Perera, Virginia A. Rauh, Anne Sweeney, Robin M. Whyatt, Kimberly Yolton
Journal: Environmental Health Perspectives (2005)

In anticipation of the National Children's Study, lessons can be learned from the smaller birth cohort studies conducted by five Centers for Children's Environmental Health and Disease Prevention Research funded by the National Institute of Environmental Health Sciences and the U.S. Environmental Protection Agency. The populations studied are diverse in ethnicity and social class and reside in urban and rural environments. Although almost all of the centers chose to enroll participants through medical care facilities, they had to develop independent staffs and structures because of the overburdened medical care system. Some of the lessons learned by the centers include the importance of continuous funding, building community partnerships to conduct culturally appropriate research, hiring bilingual and bicultural staff from the community, prioritizing research goals, developing biorepositories to ensure future utility of samples, instituting quality control procedures for all aspects of specimen and data collection, maintaining frequent contact with study participants, ensuring ethical conduct of the research in a changing medical-legal climate, and communicating results in a timely and appropriate manner to participants and the wider community. All centers underestimated the necessary start-up time, staff, and costs in conducting these birth cohort studies. Despite the logistical complexity and added expenses, all centers emphasize the importance of studying the impact of environmental exposures on those children most at risk, those living in minority and low-income communities. These centers present barriers encountered, solutions found, and considerations for future research, with the hope that the lessons learned can help inform the planning and conduct of the National Children's Study.
Ending night calls is good for MPs
Authors: J. Warden
Journal: BMJ (1995)

From next week members of the British parliament will begin to benefit from both a generous pay rise and shorter working hours. Neither will help to endear MPs to the public generally—and certainly not to general practitioners, who are currently up in arms about the government's expectation that they should continue to carry 24 hour responsibility for miserly rates of pay (see p 63).

The MPs' pay rise—at double the rate of inflation—is justified as a catching up exercise. The shorter hours have a more complex background, rooted in parliament's addiction to late nights. As an experiment the House of Commons has resolved to conclude its business by 10 pm each night, to sit on Wednesday mornings, and to stop sitting on …
Alteration of the glycolipid binding specificity of the pig edema toxin from globotetraosyl to globotriaosyl ceramide alters in vivo tissue targetting and results in a verotoxin 1-like disease in pigs.
Authors: B Boyd, G Tyrrell, M Maloney, C Gyles, J Brunton, C Lingwood
Journal: The Journal of Experimental Medicine (1993)

All members of the verotoxin (VT) family specifically recognize globo-series glycolipids on the surface of susceptible cells. Those toxins that are associated with human disease, VT1, VT2, and VT2c, bind to globotriaosyl ceramide (Gb3) while VT2e, which is associated with edema disease of swine, binds preferentially to globotetraosyl ceramide (Gb4). We were recently able to identify, using site-directed mutagenesis, amino acids in the binding subunit of these toxins that are important in defining their glycosphingolipid (GSL) binding specificity (Tyrrell, G. J., K. Ramotar, B. Boyd, B. W. Toye, C. A. Lingwood, and J. L. Brunton. 1992. Proc. Natl. Acad. Sci. USA. 89:524). The concomitant mutation of Gln64 and Lys66 in the VT2e binding subunit to the corresponding residues (Glu and Gln, respectively) found in VT2 effectively converted the GSL binding specificity of the mutant toxin from Gb4 to Gb3 in vitro. We now report that the altered carbohydrate recognition of the mutant toxin (termed GT3) has biological significance, resulting in a unique disease after intravascular injection into pigs as compared with classical VT2e-induced edema disease. The tissue localization of radiolabeled GT3 after intravascular injection was elevated in neural tissues compared with VT2e accumulation, while localization of GT3 to the gastrointestinal tract was relatively reduced. Accordingly, the pathological lesions after challenge with GT3 involved gross edema of the cerebrum, cerebellum, and brain stem, while purified VT2e caused hemorrhage and edema of the cerebellum, and submucosa of the stomach and large intestine. In addition, both radiolabeled toxins bound extensively to tissues not directly involved in the pathology of disease. VT2e, unlike GT3 or VT1, bound extensively to red cells, which have high levels of Gb4. The overall tissue distribution of VT2e was thus found to be influenced by regional blood flow to each organ and not solely by the Gb4 levels of these tissues. Conversely, the distribution of GT3 (and VT1), which cleared more rapidly from the circulation, correlated with respective tissue Gb3 levels rather than blood flow. These studies indicate the primary role of carbohydrate binding specificity in determining systemic pathology, suggest that the red cells act as a toxin carrier in edema disease, and indicate that red cell binding does not protect against the pathology of systemic verotoxemia.
Declining altruism in medicine
Authors: R. Jones
Journal: BMJ (2002)

Altruism, the performance of cooperative unselfish acts beneficial to others, has been studied in several medical contexts, including the donation of organs and genetic material and patients' participation in potentially hazardous experiments and trials.1 Physicians' altruism towards their patients and others has been less well studied and is implicit, rather than explicit, in statements about medical professional values and attitudes. Altruism is, however, embodied in many cultural stereotypes of the “good doctor,” such as John Berger's country practitioner in A Fortunate Man. 2

Altruistic behaviour by physicians might include, for example, continuing to work or providing informal medical advice outside contracted hours, giving free treatment to poor patients in fee for service healthcare systems, and a general willingness to go the extra mile in professional activities. There is much evidence that many doctors work beyond their contracted hours, but there is also a growing feeling that altruism in medicine, if not dying, is at least declining.

This might be expressed, for example, in the anaesthetist's …
COMPARATIVE VALUE OF IPECAC AND ITS ALKALOIDS IN TREATMENT OF INTESTINAL ENDAMEBIASIS
Authors: SIDNEY K. SIMON
Journal: JAMA (1918)

There is universal concurrence of opinion at the present time in regard to the highly specific effect of ipecac, as well as of its constituent alkaloids, on the vegetative forms of the pathogenic endameba. Though the ipecacuanha plant, and especially its root, has been employed since remote times as an empiric remedy in the treatment of many varieties of intestinal disorders, it is only within comparatively recent years that recognition of its sole and distinctive value in endamebic disease has been definitely reached.  An interesting and diversified history surrounds the earlier use of ipecac as a therapeutic agent, traceable back as far even as the beginning of the Middle Ages. It was first introduced into Europe in 1648 in the guise of a secret remedy for dysentery, having gained considerable repute originally among the natives of Brazil for its usefulness in this class of affections. The story is related that
Venous limb gangrene and fatal hemorrhage: Adverse consequences of hit “overdiagnosis” in a patient with antiphospholipid syndrome
Authors: Maureen A. Smythe, Theodore E. Warkentin, Amy L. Woodhouse, Dana Zakalik
Journal: American Journal of Hematology (2010)

This unfortunate patient case highlights the problems with "overdiagnosis" of HIT. Despite "positive" tests for HIT antibodies, the low pretest probability for HIT and the known propensity of patients with APS to yield false-positive HIT antibody results suggests that the patient did not have a true diagnosis of HIT. Moreover, the early administration of warfarin and the choice of argatroban for parenteral anticoagulation when monitoring was hindered by a prolonged baseline aPTT likely play a key factor in the progression of UE DVT to VLG. Ironically, the problems of anticoagulant monitoring posed by the prolonged baseline aPTT likely contributed to the subsequent overanticoagulation and fatal pulmonary hemorrhage. With benefit of hindsight, avoiding the temptation to test for HIT in a low pretest probability situation, and treatment with either heparin using anti-factor Xa monitoring or with non-aPTT-monitored therapy such as LMWH or fondaparinux would likely have resulted in a more favorable clinical course.
Reply to N. Personeni et al
Authors: Jean-Nicolas Vauthey, Antoine Brouquet, Andreas Andreou, Scott Kopetz
Journal: Journal of Clinical Oncology (2011)

seven (10%) did not complete TSR because of technical reasons generally arising after the first stage of portal vein embolization.From a surgical standpoint, these figures might lead to questioning of the TSR strategy, which was associated with a 6% mortality rate after the second stage. 1 In the last decade, alternative one-stage approaches, including ultrasound-guided hepatectomy, 7 which does not require portal vein embolization, have been developed.In this respect, our recent article 8 discussesthelong-termfollow-upofpatientswithfourormorebilobarCLM treated at our institution between 2001 and 2007, reporting a low 23% morbidity rate and no postoperative 90-day deaths.Regarding oncologic outcomes, after a median follow-up of 14 months, 14 (54%) of 26 patients experienced recurrence, even though one third of these patients did not receive preoperative chemotherapy, and none received postoperative chemotherapy.Nevertheless, with a necessary note of caution when interpreting data from different series, the 14-month disease-free survival rate we reported (46%) 8 favorably compares with the 1-year 39% rate reported by Brouquet et al. 1 Furthermore, intraoperative ultrasonography may improve the detection of additional CLM otherwise missed preoperatively, 8 which may in part explain early recurrences occurring in the future liver remnant after first-stage hepatectomy.In light of the expanding indications for resection in patients with bilobar CLM, novel controversies pertaining not only to systemic treatments but also to surgical strategies will need to be tackled to define the optimal approach for the individual patient.
Experimental Prevention of Myocardial Infarction by Bronchial Collateral Circulation
Authors: Kazi Mobin-Uddin, Manuel Viamonte, Luis O. Martinez, Sylvester E. Gould, James R. Jude
Journal: JAMA (1969)

Myocardial infarction in dogs, resulting from gradual total occlusion of the left circumflex coronary artery by an ameroid constricting ring, was prevented by lingular cardiopneumonopexy (after ligation of the lingular branch of the left pulmonary artery). Ventriculography demonstrated adequate contractility of the left ventricle, and selective intercostobronchial angiography in vivo revealed abundant bronchomediastinal-coronary collateral circulation as early as three weeks postoperatively. Corrosion casts of hearts following selective injection of the bronchial arteries demonstrated bronchomediastinal collaterals and their anastomosis with the coronary arteries. Serial histologic sections of myocardium and attached pulmonary tissue revealed blood vessels (arterioles measuring 100μ or more in external diameter) directly connecting lung tissue to epicardium. All control animals in which an ameroid ring was applied but lingular cardiopneumonopexy was not performed suffered large posterobasal myocardial infarcts.
P1220 MODELING PREDICTS CLINICALLY MEANINGFUL SVR RATES IN GENOTYPE 1 TREATMENT-EXPERIENCED PATIENTS BASED ON RESULTS IN GENOTYPE 1 TREATMENT-NAIVE PATIENTS TREATED WITH SOFOSBUVIR + PEGINTERFERON + RIBAVIRIN FOR 12 WEEKS
Authors: A. Muir, D.R. Nelson, S.C. Gordon, J.J. Feld, K. Patel, E. Lawitz, A.M. Sheikh, D.M. Brainard, W.T. Symonds, J.G. McHutchison, B.N. Bekele, A. Mangia, E.J. Gane
Journal: Journal of Hepatology (2014)
An Internet‐based survey of anaphylactic reactions to foods
Authors: P. A. Eigenmann, F. D. Pastore, S. A. Zamora
Journal: Allergy (2001)

Background: A favorable outcome of anaphylaxis depends on the rapidity of adequate initial management and epinephrine injection. However, few data on the management of anaphylactic reactions are available. The aim of this study was to investigate the management and awareness of anaphylaxis to foods by mean of an Internet‐based survey. Methods: Visitors to a website with information on food allergy were invited to join the survey. Items in the survey included the management of anaphylactic reactions, investigations done by the diagnosing physician, and information given to the responder in anticipation of a new anaphylactic reaction. Results: Almost all of the 264 responders were from North America, Europe, Australia, or New Zealand (263/264). The most recent reaction was treated by epinephrine injection in 68.7% (180/262) of cases, or by antihistamines in 14.1% (37/262). Epinephrine was the first treatment for the most severe reaction in only 43.9% (101/230), while antihistamines were given first in 43.5% (100/230). One‐third (62/210=29.5%) of the responders diagnosed by a physician received neither a diagnostic blood test nor a skin test. Responders diagnosed by an allergist were more often investigated (91/105=86.7%) than those diagnosed by a pediatrician or an internist (29/44=65.9%), a general practitioner (22/45=48.9%), or another physician (6/16=37.5%) ( P &lt;0.001). Most responders had received instructions on how to deal with a new episode of anaphylaxis (244/263=92.8%). Responders instructed by an allergist were most frequently satisfied with the instructions (115/131=87.8%). Conclusions: A large number of responders did not receive epinephrine for treatment of their most severe, or most recent anaphylactic reaction, and did not undergo allergy tests. The conventional management of anaphylaxis might still be improved.
Toll-like receptor (TLR) 2 promoter and intron 2 polymorphisms are associated with increased risk for spontaneous bacterial peritonitis in liver cirrhosis
Authors: H.D. Nischalke, C. Berger, K. Aldenhoff, L. Thyssen, M. Gentemann, F. Grünhage, F. Lammert, J. Nattermann, T. Sauerbruch, U. Spengler, B. Appenrodt
Journal: Journal of Hepatology (2011)
Is there a schizophrenic language?
Authors: Steven Schwartz
Journal: Behavioral and Brain Sciences (1982)

Abstract Among the many peculiarities of schizophrenics perhaps the most obvious is their tendency to say odd things. Indeed, for most clinicians, the hallmark of schizophrenia is “thought disorder” (which is usually defined tautologically as incoherent speech). Decades of clinical observations, experimental research, and linguistic analyses have produced many hypotheses about what, precisely, is wrong with schizophrenic speech and language. These hypotheses range from assertions that schizophrenics have peculiar word association hierarchies to the notion that schizophrenics are suffering from an intermittent form of aphasia. In this article, several popular hypotheses (and the observations on which they are based) are critically assessed. Work in the area turns out to be flawed by errors in experimental method, faulty observations, tautological reasoning, and theoretical models that ignore the complexities of both speech and language. This does not mean that schizophrenics are indistinguishable from nonschizophrenics. They are clearly deviant in many situations. Their problem, however, appears to be in processing information and in selective attention, not in language itself.
Prenatal probiotic administration can influence Bifidobacterium microbiota development in infants at high risk of allergy
Authors: Sampo J. Lahtinen, Robert J. Boyle, Satu Kivivuori, Frances Oppedisano, Katherine R. Smith, Roy Robins-Browne, Seppo J. Salminen, Mimi L.K. Tang
Journal: Journal of Allergy and Clinical Immunology (2009)
Connections of the Cerebral Cortex
Authors: Walle J. H. Nauta
Journal: JAMA (1964)

Not often a book summarizing two decades of study is nevertheless only the author's sixth formal pub lication on the subject. Such is the case with<i>Connections of the Cerebral Cortex</i>. The first and largest section is devoted to cortico-subcortical and associational connections, traced by serial chartings of Marchi degenerations from nearly 200 experimental lesions in the monkey. The material in this chapter alone could easily have been disseminated over a score of separate journal publications. To have it all available in one volume is a convenience for which the author deserves commendation. Successive chapters discuss the anatomy of the thalamus and thalamocortical radiation, and compare findings in the monkey with the author's earlier studies on the rat. The book concludes with an annotated atlas in which the experimental findings are applied to the human brain. Cytoarchitectonic studies have led the author to introduce several modifications of Brodmann's plan of