tbuckley/cabot-search huggingface dataset:
The PML/RARalpha fusion protein inhibits tumor necrosis factor-alpha-induced apoptosis in U937 cells and acute promyelocytic leukemia blasts.
Authors: U Testa, F Grignani, P Samoggia, C Zanetti, R Riccioni, F Lo Coco, D Diverio, N Felli, C G Passerini, M Grell, P G Pelicci, C Peschle
Journal: Journal of Clinical Investigation (1998)

We investigated the effect of the acute promyelocytic leukemia (APL) specific PML/RARalpha fusion protein on the sensitivity to TNF-alpha-mediated apoptosis. The U937 leukemia cell line was transduced with PML/RARalpha cDNA. PML/RARalpha expression caused a markedly reduced sensitivity to TNF-alpha, even if apoptosis was triggered by agonistic antibodies to TNF-alpha receptors I and II (TNF-alphaRI, II). PML/RARalpha induced a 10-20-fold decrease of the TNF-alpha-binding capacity via downmodulation of both TNF-alphaRI and TNF-alphaRII: this may mediate at least in part the reduced sensitivity to TNF-alpha. Furthermore, the fusion protein did not modify Fas expression (CD95) or sensitivity to Fas-mediated apoptosis. The pathophysiological significance of these findings is supported by two series of observations. (a) Fresh APL blasts exhibit no TNF-alpha binding and are resistant to TNF-alpha-mediated apoptosis. Conversely, normal myeloblasts-promyelocytes show marked TNF-alphaR expression and are moderately sensitive to TNF-alpha-mediated cytotoxicity. Similarly, blasts from other types of acute myeloid leukemia (AML M1, M2, and M4 FAB types) show an elevated TNF-alpha binding. (b) The NB4 APL cell line, which is PML/RARalpha+, shows low TNF-alphaR expression capacity and is resistant to TNF-alpha-triggered apoptosis; conversely a PML/RARalpha- NB4 subclone (NB4.306) exhibits detectable TNF-alpha-binding capacity and is sensitive to TNF-alpha-mediated cytotoxicity. These studies indicate that the PML/RARalpha fusion protein protects against TNF-alpha-induced apoptosis, at least in part via downmodulation of TNF-alphaRI/II: this phenomenon may play a significant role in APL, which is characterized by prolonged survival of leukemic blasts.
Hypotension Associated with Prekallikrein Activator (Hageman-Factor Fragments) in Plasma Protein Fraction
Authors: Barbara M. Alving, Yoshio Hojima, John J. Pisano, Bobby L. Mason, Richard E. Buckingham, Milton M. Mozen, J. S. Finlayson
Journal: New England Journal of Medicine (1978)

Thirteen lots of plasma protein fraction made by one manufacturer were implicated in 23 recent reports of hypotension in surgical patients. Four of these patients required resuscitation after rapid administration of the product in the postoperative period. All implicated lots had prekallikrein-activator activity but low levels of bradykinin and kallikrein. The prekallikrein activator was identified as Hageman-factor fragments by molecular weight (35,000 as estimated by gel chromatography), isoelectric point (4.2 to 4.4), and inhibition by antibody to Hageman factor. These data suggest that Hageman-factor fragments are potent hypotensive agents, presumably because they trigger the generation of bradykinin in recipients. Prekallikrein-activator activity, usually at levels lower than those in the initial 13 implicated lots, was frequently detected in plasma protein fraction made by other manufactures. Several of these lots were associated with additional reports of hypotension. Prekallikrein-activator activity rarely occurred in albumin.
Abstract 4146: Quantitative cell signaling analysis for cetuximab sensitivity prediction in colorectal cancer
Authors: Matsuo Teppei, Satoshi Nishizuka, Takeshi Iwaya, Kazushige Ishida, Hironobu Noda, Miyuki Ikeda, Megumi Kozai, Go Wakabayashi
Journal: Cancer Research (2010)

Abstract [Background] Anti-human EGFR monoclonal antibody (cetuximab) has been widely used in the treatment of colorectal cancer (CRC). However it is thought that a reliable predictor for therapeutic efficacy should be established because the benefit of cetuximab treatment is often still uncertain. Our preliminary study showed that the prediction of therapeutic efficacy using a conventional chemosensitivity test using growth suppression assay is generally not informative because cetuximab does not seem to have as strong a cytotoxicity as other anticancer drugs. KRAS mutation status has been used as a biomarker to predict therapeutic efficiency but it is not sensitive enough to determine the absolute indication. [Purpose] We hypothesized that we could predict therapeutic efficacy by evaluating expected molecular reaction when cetuximab is administrated in vitro. In the present study, we build up an in vitro EGFR signaling model for a new chemosensitivity test based on protein monitoring in response to cetuximab administration. [Materials and Methods] Three growth factors (EGF, TGF-α, and IGF) and the inhibitor (cetuximab) were added to HT29 (KRAS wild type, EGFR positive) in six combinations. Cell pellets were harvested at 5 time points over a 15min time course, each of which was processed for cell lysate. The lysates were analyzed by Western blotting to see if the proteins involved in the EGFR signaling pathway responded over time. [Results] We confirmed the activation of signaling stimulated by EGF, TGF-α, and IGF; and the effect on signaling by cetuximab in HT29 with Western blotting. Intriguingly, the phosphorylation level of EGFR was rapidly elevated and declined by EGF stimulating in the absence of cetuximab whereas dephosphorylation was prolonged in the presence of cetuximab. In the administration of either TGF-α or IGF, the phosphorylation pattern of EGFR, c-RAF, MEK, MAPK, ERK, PI3K, AKT, PTEN, and STAT was different from that of EGF alone. [Conclusions] These results shows that:(i) EGF is not EGFR's only ligand; (ii) cetuximab can't inhibit every signaling pathway starting from EGFR; and (iii) TGF-α and IGF activate signaling pathway starting from EGFR partially but not thoroughly. An additional reliable predictor of cetuximab efficacy should be identified based on functional protein characteristics. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4146.
Interferon Beta and Long-term Disability in Multiple Sclerosis
Authors: Afsaneh Shirani, Yinshan Zhao, Mohammad Ehsanul Karim, Charity Evans, Elaine Kingwell, Mia L. van der Kop, Joel Oger, Paul Gustafson, John Petkau, Helen Tremlett
Journal: JAMA Neurology (2013)
Rescue of thymocytes from glucocorticoid-induced cell death mediated by CD28/CTLA-4 costimulatory interactions with B7-1/B7-2.
Authors: D H Wagner, J Hagman, P S Linsley, W Hodsdon, J H Freed, M K Newell
Journal: The Journal of Experimental Medicine (1996)

During the differentiation of thymocytes to mature T cells the processes of positive and negative selection result in signals that either protect thymocytes from cell death, or delete, through apoptosis, thymocytes with self-reactive T cell receptors (TCR). Glucocorticoids have been shown to induce thymocyte apoptosis and are produced within the thymic microenvironment. Furthermore, steroid-induced apoptosis of thymocytes has been suggested as a potential mechanism for removal of nonselected thymocytes. In this report, we demonstrate that thymocytes can be rescued from glucocorticoid-induced apoptosis by incubation with cells that express high levels of B7-1 or B7-2. In addition, the ability to be rescued by B7-1 and/or B7-2 can precede expression of the TCR. We demonstrate that CD3(+)-depleted or CD3+/ TCR-beta(+)-doubly depleted thymocytes can be rescued from glucocorticoid-induced apoptosis through the interaction of CD28 or CTLA-4 on thymocytes with cells bearing high levels of B7-1 or B7-2. Furthermore, these transfected cells are major histocompatibility complex (MHC) class II negative and, while they may express MHC class I, there is no preferential rescue of CD8+ thymocytes in the presence of glucocorticoids. Together, these data suggest that the rescue of thymocytes from glucocorticoids can be independent of the TCR. We also demonstrate that, in addition to CD28, CTLA-4 is expressed on thymocytes, suggesting that rescue from glucocorticoid-induced cell death can be mediated by both CD28 and CTLA-4. A CTLA-4Ig fusion protein which binds to both B7-1 and B7-2 was shown to completely block the rescue of thymocytes from glucocorticoid-induced cell death. Therefore, we conclude that interactions between B7-1/B7-2 and CD28/CTLA-4 are sufficient and necessary for rescue of thymocytes from glucocorticoid-induced cell death.
HLA-DR antigens on human macrophages from bronchoalveolar lavage fluid.
Authors: U Costabel, K J Bross, R Andreesen, H Matthys
Journal: Thorax (1986)

The expression of HLA-DR (Ia-like) antigens on human macrophages was investigated by analyses of cells from bronchoalveolar lavage fluid obtained from 12 patients with pulmonary sarcoidosis, six patients with extrinsic allergic alveolitis, nine patients with cryptogenic fibrosing alveolitis, 11 normal non-smokers, and 12 normal smokers. The HLA-DR antigen was demonstrated by the mouse monoclonal antibody OKIa by a peroxidase-antiperoxidase method performed on glass slides. No differences were found in the percentage of alveolar macrophages that expressed DR antigens between the five study groups. OKIa positivity was observed on more than 90% of macrophages in all cases. These observations suggest that the previously reported enhanced antigen presentation by alveolar macrophages in sarcoidosis is not linked with an increase in the percentage of DR+ macrophages in the lung.
Harmonic imaging and single frame “triggered mode” data acquisition enhance delineation of myocardial perfusion defects by volume-rendered 3-dimensional echocardiography
Authors: Qi-Ling Cao, Navroz Masani, Alain Delabays, Giuseppina Magni, Philippe Acar, Cleo Laskari, Jiefen Yao, Stefano De Castro, Natesa Pandian
Journal: Journal of the American College of Cardiology (1996)
Churg-Strauss vasculitis and ascaris infection.
Authors: A Chauhan, D G Scott, J Neuberger, J S Gaston, P A Bacon
Journal: Annals of the Rheumatic Diseases (1990)

A patient with Churg-Strauss vasculitis presenting with mononeuritis multiplex, who developed obstructive jaundice, is described. On investigation the jaundice proved to be due to ascaris infestation. As the immune abnormalities associated with ascaris infection are also typical of those seen in the Churg-Strauss syndrome it is speculated that the vasculitis occurred because of a failure to regulate the anti-ascaris immune response.
Circles--a community response for convicted sex offenders
Authors: S. Hanvey
Journal: BMJ (2011)

Circles of Support and Accountability (Circles) is a community response to the challenge raised by Delamothe in his Observations piece “What should we do with child sex offenders?”1

Circles draws on the skills, humanity, and commitment of carefully selected, trained, and professionally supervised volunteers, who work closely with statutory partners and …
Regional Variation in Hip Fracture: Is It due to Increased Milk Consumption in the North, 50 Years Ago?
Authors: Alan H. Bierlein
Journal: JAMA (1990)

In Reply.—  Dr Bierlein makes a good point that the decreased incidence of hip fracture in the North is striking, with historical milk and milk product consumption providing an attractive etiologic hypothesis. As we mentioned, however, good data with which to test this hypothesis are, to our knowledge, lacking. We have, however, been able to locate state-specific milk production data dating back to 1909. 1 These data show that of an estimated 7.5 million gallons of milk produced, 3.2 million gallons was produced in the East North Central and West North Central census divisions, and an additional 1.3 million gallons was produced in the Middle Atlantic states. The South Atlantic, East South Central, and West South Central combined to produce an estimated 1.5 million gallons of milk.  While these data are suggestive, the association is tenuous at best. Data on milk production may not necessarily reflect milk consumption. For example,
DNA repair capacities of cutaneous fibroblasts: effect of sun exposure, age and smoking on response to an acute oxidative stress
Authors: S. Sauvaigo, M. Bonnet-Duquennoy, F. Odin, F. Hazane-Puch, N. Lachmann, F. Bonté, R. Kurfürst, A. Favier
Journal: British Journal of Dermatology (2007)

Sun irradiation causes skin ageing and cancer through the accumulation of damage to cell components. Intrinsic ageing is also associated with accumulation of oxidized macromolecules.In this study we investigated the effects of sun exposure on response to an acute in vitro oxidative stress (H(2)O(2)) using normal human fibroblasts prepared from biopsies from 10 volunteers taken from sun-protected and sun-exposed sites.Time-course experiments measuring repair of DNA strand-breaks and formamidopyrimidine DNA N-glycosylase-sensitive sites were conducted using the single-cell gel electrophoresis (comet) assay.Our results demonstrated that repair of strand-breaks was slower in sun-exposed compared with sun-protected cells. Interestingly, ageing was also associated with decreased DNA repair capacities for single-strand breaks in both sun-exposed and sun-protected cells whereas for formamidopyrimidine glycosylase (Fpg)-sensitive sites, this feature was in evidence only in sun-protected cells. Smoking, associated with age, was shown to have a markedly negative impact on DNA repair.Taken together our data suggest that stresses like ageing, sun exposure and smoking might have an additive effect contributing to the overall heterogeneity and decrease of DNA repair capacities in human cells and so increase the danger of sun exposure for health. They also emphasize the importance of the quality of the biological samples when repair studies on skin cells are to be conducted.
Reactive Hypoglycemia and A-Cell (`Pancreatic') Glucagon Deficiency in the Adult
Authors: Piero P. Foà, Joseph C. Dunbar, Sander P. Klein, Stanley H. Levy, Magsood A. Malik, Barbara B. Campbell, Naomi L. Foà
Journal: JAMA (1980)

Serum glucose, A-cell (IRG<sub>A</sub>) and total glucagon (IRG<sub>T</sub>), insulin, growth hormone, cortisol, triiodothyronine, and thyroxine values were measured in the fasting state and in response to oral glucose, intravenously administered arginine, and a meal of pan-broiled ground beef in 31 symptomatic patients and 11 normal subjects. Twenty-four patients and 11 control subjects had normal glucose tolerance (group 1); seven patients had reactive hypoglycemia (group 2). Under all conditions, serum IRG<sub>A</sub>value was significantly lower in group 2 than in group 1. Glucose, arginine, or meat increased serum IRG<sub>T</sub>levels. This response did not differ significantly in the two groups, nor did the secretion of the other measured hormones. We conclude that A-cell insufficiency can contribute to reactive hypoglycemia in the adult. (<i>JAMA</i>244:2281-2285, 1980)
Decline and ail
Authors: Theodore Dalrymple
Journal: BMJ (2008)

<h3>Background and Objectives</h3> Postarrest prognostication research does not typically account for the sequential nature of real-life data acquisition and interpretation and reports nonintuitive estimates of uncertainty. Bayesian approaches offer advantages well suited to prognostication. We used Bayesian regression to explore the usefulness of sequential prognostic indicators in the context of prior knowledge and compared this with a guideline-concordant algorithm. <h3>Methods</h3> We included patients hospitalized at a single center after cardiac arrest. We extracted prospective data and assumed these data accrued over time as in routine practice. We considered predictors demographic and arrest characteristics, initial and daily neurologic examination, laboratory results, therapeutic interventions, brain imaging, and EEG. We fit Bayesian hierarchical generalized linear multivariate models predicting discharge Cerebral Performance Category (CPC) 4 or 5 (poor outcomes) vs 1–3 including sequential clinical and prognostic data. We explored outcome posterior probability distributions (PPDs) for individual patients and overall. As a comparator, we applied the 2021 European Resuscitation Council and European Society of Intensive Care Medicine (ERC/ESICM) guidelines. <h3>Results</h3> We included 2,692 patients of whom 864 (35%) were discharged with a CPC 1–3. Patients9 outcome PPDs became narrow and shifted toward 0 or 1 as sequentially acquired information was added to models. These changes were largest after arrest characteristics and initial neurologic examination were included. Using information typically available at or before intensive care unit admission, sensitivity predicting poor outcome was 51% with a 0.6% false-positive rate. In our most comprehensive model, sensitivity for poor outcome prediction was 76% with 0.6% false-positive rate (FPR). The ERC/ESICM algorithm applied to 547 of 2,692 patients and yielded 36% sensitivity with 0% FPR. <h3>Discussion</h3> Bayesian models offer advantages well suited to prognostication research. On balance, our findings support the view that in expert hands, accurate neurologic prognostication is possible in many cases before 72 hours postarrest. Although we caution against early withdrawal of life-sustaining therapies, rapid outcome prediction can inform clinical decision making and future clinical trials.
Apoptosis in Myelodysplastic Syndromes
Authors: G Lambertenghi Deliliers, L Caneva
Journal: New England Journal of Medicine (1999)

Figure 1. A 45-year-old man presented with pancytopenia due to myelodysplastic syndrome. The bone marrow showed marked trilineage dysplasia. Electron microscopy revealed that the majority of hematopoietic cells in the marrow had ultrastructural features of various stages of apoptosis ranging from margination and condensation of nuclear chromatin (arrowhead) to full nuclear pyknosis and vacuolization of the cytoplasm, with polarization of the organelles (arrow, ×3700). These findings suggest that in myelodysplasia, the proliferation of hematopoietic cells is outstripped by a simultaneous increase in the rate of apoptosis in the bone marrow.
The Teaching of Psychotherapy to Medical Students An Aspect of Training in Psychosomatic Medicine
Authors: D.A. Sturgeon, W. Knauss
Journal: Psychotherapy and Psychosomatics (1979)

Since so many patients have mingled with their illness psychological factors which require psychological help, the teaching of psychodynamic understanding of illness is very important. However, little (if any) systematic teaching of psychotherapeutic methods in the treatment of illness is given to medical students in most universities of Europe. This study is a joint ongoing project between the Psychosomatic Clinic of the University of Heidelberg and the Department of Psychological Medicine, University College Hospital, London. It looks at the establishment of psychotherapy supervision for medical students which has existed for several years at University College Hospital. However, many important local and national differences have become apparent, including the type of patient selected, the mode of selection, the way in which supervision groups are used by supervisors and students, and the status of such a scheme within the general curriculum of medical education. Many of the problems which have emerged during the course of this project, and some ways of solving them, are discussed. It is hoped that this project will be of use to other Centres which may be considering such a scheme as part of their own medical curriculum.
Acute Hyperparathyroidism with Electrocardiographic Changes
Authors: B. A. Bradlow, N. Segel
Journal: BMJ (1956)

The results support the belief that the adrenal inhibition test will prove of value in distinguishing Cushing's syndrome due to adrenal hyperplasia from cases of the syndrome due to carcinoma.Our thanks are due to Miss Elizabeth Black and to Miss Olwen Jenkins for performing most of the analyses; to the Medical Research Council for a grant for the former; and to Dr. Russell
Localization of transforming growth factor-alpha RNA and protein in the skin of psoriatic patients receiving therapy
Authors: P. WATTS, G.S. STABLES, R.J. AKHURST, R.M. MACKIE
Journal: British Journal of Dermatology (1994)

Summary Fourteen patients with chronic plaque psoriasis requiring in-patient therapy were treated with a variety of antipsoriatic agents. All had four skin biopsies taken: two prior to therapy, one from a psoriatic plaque and one from adjacent clinically normal skin, and two further biopsies, one 2–3 weeks after starting therapy, and one at clinical clearance, taken from an area where there was previously a psoriatic plaque. In addition, three biopsies were taken from clinically normal skin of non-psortatics. Transforming growth factor-alpha (TGF-α) RNA and protein distributions were estimated in these biopsies, using in situ hybridization with a cRNA TGF-α probe, and an antibody to TGF-α polypeptide. Prior to therapy, grain counts showed elevated levels of TGF-α RNA in the subcorneal layers of the epidermis. These levels decreased during clearance of the psoriasis. In one patient whose plaques did not clear, there was no decrease of TGF-α mRNA. Antibody studies showed the presence of TGF-α polypeptide in the epidermis prior to therapy, with a relative concentration of immunoprotein in the upper epidermal layers, compared with a more uniform distribution of immunoprotein after treatment, and in uninvolved skin of the same psoriatic patient. These studies extend our knowledge of the relationship between TGF-α and psoriatic skin.
Change in Swedish Health Care
Authors: Budd N. Shenkin
Journal: New England Journal of Medicine (1980)

Sweden is more like the United States than we might imagine. Certainly there are obvious differences — a homogeneous population of 8.3 million versus a heterogeneous one of 222 million, socialized medicine versus whatever it is that we have, and a culture of consensus versus one of conflict. But per capita wealth is similar, per cent of gross national product spent on health is similar in both extent and trend, and, perhaps most strikingly, in a climate of economic stress both countries are trying desperately to reconcile the deeply held but conflicting Western values of equality, quality and expertise, and . . .
Cryptosporidiosis in infancy and childhood mortality in Guinea Bissau, west Africa.
Authors: K Molbak, N Hojlyng, A Gottschau, J C Sa, L Ingholt, A P da Silva, P Aaby
Journal: BMJ (1993)

OBJECTIVE--To investigate the epidemiology of and mortality from cryptosporidiosis in young children in Guinea Bissau, West Africa. DESIGN--Three year community study of an open cohort followed up weekly. SETTING--301 randomly selected houses in a semi-urban area in the capital, Bissau. SUBJECTS--1315 children aged less than 4 years. MAIN OUTCOME MEASURES--Cryptosporidium infection detected by examination of stools during episode of diarrhoea and death of a child. RESULTS--Cryptosporidium spp were found in 239 (7.4%) out of 3215 episodes of diarrhoea. The parasite was most common in younger children (median age 12 months) and at the beginning of the rainy seasons. The prevalence of cryptosporidiosis was 15% (77/513) in cases of persistent diarrhoea compared with 6.1% (148/2428) in diarrhoea lasting less than two weeks (p &lt; 0.0001). Cryptosporidiosis was associated with excess mortality in children who had the infection in infancy, and this excess mortality persisted into the second year of life (relative mortality 2.9 (95% confidence interval 1.7 to 4.9)). The excess mortality could not be explained by malnutrition, or by socioeconomic factors, hygienic conditions, or breast feeding. CONCLUSIONS--Cryptosporidiosis is an important cause of death in otherwise healthy children in developing countries.
Calcium channel inhibition accelerates polycystic kidney disease progression in the Cy/+ rat
Authors: S. Nagao, K. Nishii, D. Yoshihara, H. Kurahashi, K. Nagaoka, T. Yamashita, H. Takahashi, T. Yamaguchi, J.P. Calvet, D.P. Wallace
Journal: Kidney International (2007)