tbuckley/cabot-search huggingface dataset:
Abstract B90: Eribulin mesylate alters immune homeostasis in mice bearing syngeneic tumors.
Authors: Diana I. Albu, Namita Kumar, Galina Kusnetzov, Shanqin Xu, Bruce Littlefield, Mary Woodall-Jappe
Journal: Cancer Research (2013)

Abstract Numerous studies indicate that certain tumor-infiltrating macrophage subsets can support neoplastic growth. Recent reports showed that spleen can serve as an important reservoir for macrophages and neutrophils that replicate in situ, then migrate to support tumor growth. Eribulin mesylate (Halaven®) is a microtubule-dynamics inhibitor approved for third line clinical use in patients with heavily pretreated metastatic breast cancer based upon statistically significant increase in median overall survival (OS) compared to treatment of physician's choice. In an effort to understand whether eribulin has additional effects beyond its anti-mitotic activity, the current study addressed the effects of eribulin mesylate on immune cells. Using the subcutaneous syngeneic murine tumor model Lewis lung carcinoma (LLC), we found that the tumor shrinking effect of eribulin correlated with increased extramedullary hematopoiesis observed in the spleens of treated mice. Eribulin was also found to inhibit the proliferation of M2 tumor-associated macrophages (TAMs) in the spleens of LLC-bearing mice. Early effects of eribulin were studied using the CT-26 colon tumor isograft model and included increased differentiation and death of CD4+ and CD8+ effector T cells. Furthermore, eribulin caused increased CD25 expression on CD4+ Foxp3- T cells but not on CD4+ Foxp3+ T regulatory cells. Finally, frequencies of exhausted CD8+ T cells were reduced following eribulin treatment. Taken together, these results suggest that eribulin-mediated modulation of immune homeostasis especially in the spleen, may contribute to its anti-tumor effect. Citation Format: Diana I. Albu, Namita Kumar, Galina Kusnetzov, Shanqin Xu, Bruce Littlefield, Mary Woodall-Jappe. Eribulin mesylate alters immune homeostasis in mice bearing syngeneic tumors. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B90.
475 Occult hepatitis B virus (OHBV) infection with and without anti-HBs antibodies - implications in the development of hepatocellular carcinoma
Authors: C.K. Tan, J.P.E. Chang, G.K. Lim, Z. Yi, L.L. Ooi, A. Chung, P. Chow, W.C. Chow
Journal: Journal of Hepatology (2006)
Withholding imaging in pregnancy may be hazardous
Authors: Kenneth Hodson, Jason Waugh, Catherine Nelson-Piercy
Journal: BMJ (2011)

Failure or reluctance to image pregnant women contributes to maternal mortality.1 Rajaraman and colleagues state that x ray imaging of mothers during pregnancy increases the risk of childhood cancer and leukaemia.2 However, the risk is small and not statistically significant. Although controls were similar for many identified confounding factors, …
Thomas Scott Wilson
Authors: Struan Robertson, George Forwell, Daniel Reid
Journal: BMJ (2005)

​FormerFormer medical offer of health Glasgow and community medicine specialist Greater Glasgow Health Board (b Glasgow 1921; q Glasgow 1944; MD, FRCP Glas, FFPHM), died from chronic obstructive pulmonary disease on 1 May 2005.




Figure 1




Scott Wilson was Glasgow's last medical officer of health. After house officer posts he spent three years in the Royal Army Medical Corps, where he attained the rank of major and served on troopships bringing service personnel back from Africa and the Far East. He then worked at Knightswood Hospital, Glasgow, before joining Glasgow Corporation's public health department, later becoming medical officer of health. After reorganisation of the NHS in 1974, Scott moved to the Greater Glasgow Health Board, retiring in 1986. He leaves a wife, Chrissie, and three children.
The Cytomegaloviruses: Ubiquitous Agents with Protean Clinical Manifestations
Authors: Thomas H. Weller
Journal: New England Journal of Medicine (1971)

Epidemiologic AspectsDistribution of CMVSurveys of unselected newborn infants in four cities in the United States and England indicate that some 1 per cent enter the world with an active infection as indicated by presence of viruria.36,128 129 130 Risk of acquired infection begins during birth. Thereafter, as imperfectly assayed by serologic technics, the cumulative risk during life is reflected in peak CF reactivity rates of the order of 80 per cent in adults in such disparate regions as Stockholm and Easter Island.131,132 The general picture that emerges is one of worldwide endemicity, but with marked variation in levels in differing . . .
CQC chairman admits to organisational failings
Authors: N. Hawkes
Journal: BMJ (2013)

England’s healthcare watchdog the Care Quality Commission had failed to “get under the skin” of the organisations it inspected and had given the public false reassurances on how good they were, the new chairman of the commission admitted at a seminar in London on 11 June.

Speaking just a few days before the CQC’s proposed regulatory model was due to be published for consultation, David Prior was scathing about the failings of the organisation he now chairs, saying that it “wasn’t set up to inspect hospitals in any meaningful way” and that credit for drawing attention to the failures at Mid Staffordshire NHS Foundation Trust had been primarily due to the campaigner Julie Bailey and nine others who met in a cafe in Stafford, not to the regulators, the medical royal colleges, NHS managers, or the clinicians or nurses at the trust. Bailey, whose mother died at Stafford Hospital, set up the group Cure the NHS to draw attention to the poor care at the trust. …
Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment
Authors: F. Meier, S. Busch, K. Lasithiotakis, D. Kulms, C. Garbe, E. Maczey, M. Herlyn, B. Schittek
Journal: British Journal of Dermatology (2007)

In melanoma, several signalling pathways are constitutively activated. Among them, the RAS/RAF/MEK/ERK (MAPK) and PI3K/AKT (AKT) signalling pathways are activated through multiple mechanisms and appear to play a major role in melanoma development and progression.In this study, we examined whether targeting the MAPK and/or AKT signalling pathways would have therapeutic effects against melanoma.Using a panel of pharmacological inhibitors (BAY 43-9006, PD98059, U0126, wortmannin, LY294002) we inhibited the MAPK and AKT signalling pathways at different levels and evaluated the effects on growth, survival and invasion of melanoma cells in monolayer and organotypic skin culture.Antiproliferative and proapoptotic effects of inhibitors alone in monolayer culture were disappointing and varied among the different cell lines. In contrast, combined targeting of the MAPK and AKT signalling pathways significantly inhibited growth and enhanced apoptosis in monolayer culture. To verify our data in a more physiological context we incorporated melanoma cells into regenerated human skin mimicking the microenvironment of human melanoma. Combinations of MAPK and AKT inhibitors completely suppressed invasive tumour growth of melanoma cells in regenerated human skin.Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment and should encourage further in-depth investigations.
Role for IKK2 in muscle: waste not, want not
Authors: Michael Karin
Journal: Journal of Clinical Investigation (2006)

Activation of transcription factor NF-κB, the major regulator of the inflammatory response, depends on the inhibitor of NF-κB kinase (IKK) complex, which is composed of 2 catalytic subunits, IKK1 and IKK2 (also known as IKKα and IKKβ), and a regulatory subunit, IKKγ (also known as NEMO). In this issue of the JCI, Mourkioti et al. show that muscle-specific disruption in mice of the gene encoding IKK2 prevents NF-κB activation in response to denervation or toxin-induced injury (see the related article beginning on page 2945). Importantly, this genetic manipulation prevents muscle wasting, thereby providing strong evidence in support of a major pathogenic role for inflammation in a variety of muscular dystrophies characterized by progressive muscle fiber degeneration.
Interactions of spectrin in hereditary elliptocytes containing truncated spectrin beta-chains.
Authors: S W Eber, S A Morris, W Schröter, W B Gratzer
Journal: Journal of Clinical Investigation (1988)

An abnormal spectrin, in which one subunit is truncated, has been detected in a large German family. The inheritance is autosomal dominant. The affected members of the family suffer in widely varying degree from a microcytic hemolytic anemia. The red cell morphology varies correspondingly from smooth elliptocytes to predominantly poikilocytes. The abnormal spectrin makes up approximately 30% of the total and is almost entirely present as the dimer. The truncated chain is not phosphorylated by the endogenous cAMP-independent kinase, and it has been identified as a chain of beta-type, using monoclonal antibodies. Because a univalent terminal spectrin alpha-chain fragment will bind to normal dimers with an association constant lower by only a factor of two than that for the self-association of the dimers, it would be expected that the mutant dimers (alpha beta') would readily enter into an association with normal (alpha beta) dimers to give alpha 2 beta beta' tetramers (though not with each other). In dilute solution this is indeed observed, and the diminution in tetramer concentration when 30% of normal spectrin is replaced by alpha beta' dimers, amounts to only a small proportion. Moreover, in the membrane skeleton, if there is pairwise apposition of dimer units, only 9% of pairings will be between units that cannot associate. We have shown that the failure of alpha beta' dimers to enter into heterologous associations in situ is not due to the elimination of the ankyrin binding site near the truncated end of the beta-chain: this site is fully functional, as judged by rebinding to spectrin-depleted vesicles. When the spectrin is extracted from the membrane in the cold, the material released initially consists almost entirely of alpha beta' dimers; when the spectrin of normal membranes is partly dissociated to dimers in situ by warming at low ionic strength, extraction in the cold then leads similarly to much more rapid release of the dimer than of the tetramer. The similar rates of liberation of normal and abnormal dimer make it unlikely that the interaction of the latter with the membrane is in any way defective. When mixtures of alpha beta and alpha beta' dimers are bound to spectrin-depleted inside-out membrane vesicles from normal cells and tetramers are allowed to form by equilibration at 30 degrees C, the proportion of the abnormal species appearing in the tetramer is much lower than would be expected on a statistical basis. The relation of the self-association equilibrium on the membrane to that of spectrin in dilute solution is analyzed.
Abstract 5383: Evaluation of immune response in preclinical settings
Authors: Caroline Mignard, Francis Bichat, Guillaume Serin, Olivier Duchamp, Jean-François Mirjolet
Journal: Cancer Research (2012)

Abstract Among all new strategies against cancer, the treatments with vaccines, biologics, antibodies, antibody fragments, and other immunological modulators are promising. All of them aim to be more targeted, more effective, and less toxic than other therapies. In order to be developed and accurately evaluated, these immunological related therapies need appropriated preclinical models and relevant immunological readouts. Most of these immunological readouts should be analyzed in vitro, in vivo and ex vivo. A panel of tools from rodents to the bench was evaluated toward the modulation of the immune system by new therapies. All these protocols were developed and validated properly to evaluate these new immunology related cancer therapies. In immunocompetent mice, the immune cells were studied for their cell surface activation markers detection, induction of proliferative phenotype, antigen-specific T lymphocyte detection, secretion of soluble mediators such as cytokines … using FACS phenotyping, cytometric bead assay (CBA) or Luminex multiplex technologies and ELISPOT. In immunodeficient mice, the reconstitution of the mature human immune system with PBMC or naïve human immune system using hematopoietic stem cells were used to evaluate the modulation of those immune cells by therapies through human cytokine release, onset of graft versus host disease. Among other examples, characterization of antibody function (Fab and Fc mediated activities), quantification of the existence and function of antigen-specific T cell clones, phenotyping study of immune cells for activation markers as well as multiplex assays to understand the cytokines network, differentiation of hematopoietic cells by colony formation unit will be described. All of them will be presented in the context either of rodent syngenic model or humanized mouse model. All results, integrative data and examples will be presented in the poster. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5383. doi:1538-7445.AM2012-5383
Non-haemolytic adverse reaction after transfusion of a blood unit containing penicillin.
Authors: J Michel, R Sharon
Journal: BMJ (1980)

returned within one day (cases 1 and 2) and 10 days (case 4).In addition, two patients (cases 2 and 3) almost lost their sweats when taking cimetidine.This is a preliminary report.Further investigations, including a-randomised double-blind trial (which we are now doing), are required before this drug can be generally recommended for pruritus in Hodgkin's disease.
Diagnosis and Management of Delirium near the End of Life
Authors: David J. Casarett, Sharon K. Inouye
Journal: Annals of Internal Medicine (2001)

Delirium is a common and distressing symptom that constitutes a significant challenge for end-of-life care. However, reliable techniques are available for the diagnosis of delirium, and effective therapies exist as well. This consensus paper uses a case-based format that begins with an overview of the definition and presentation of delirium. Next, strategies for diagnosis are suggested, with attention to the unique challenges that clinicians face in pursuing a diagnostic work-up for patients near the end of life. The paper concludes with a review of therapeutic options.
Caught in the middle: should the World Trade Organization settle environmental disputes?
Authors: C W Schmidt
Journal: Environmental Health Perspectives (1999)

Since its inception in 1995, the World Trade Organization (WTO) has arbitrated trade disputes between its members in part by deciding whether unilateral actions by its 134 member nations such as trade bans or restrictions violate international free trade rules and authorizing penalties against members that are found to be noncompliant with such rules. The WTO is criticized by those who believe its emphasis on free trade undermines national environmental and public health protection efforts. Recent disputes over the importation of hormone-treated beef and genetically modified crops have focused attention on how the WTO arbitrates disputes having environmental and public health implications and sparked criticisms as to whether the organization is qualified to do so.
QUANTITATIVE ASSESSMENT OF MITRAL ANNULAR CALCIFICATION BY CARDIAC CT IN A DIABETIC POPULATION: ASSOCIATION WITH CARDIOVASCULAR RISK FACTORS AND CORONARY ARTERY CALCIUM
Authors: Hashmi Rafeek, Suraj Rasania, Timothy Churchill, Claire Mulvey, Victor Ferrari, Saurabh Jha, Karen Terembula, Muredach Reilly, Atif Qasim, Steven Kawut
Journal: Journal of the American College of Cardiology (2012)
Younger, premenopausal women with major depressive disorder have more abdominal fat and increased serum levels of prothrombotic factors: implications for greater cardiovascular risk
Authors: Farideh Eskandari, Sejal Mistry, Pedro E. Martinez, Sara Torvik, Christine Kotila, Nancy Sebring, Bart E. Drinkard, Catherine Levy, James C. Reynolds, Gyorgy Csako, Philip W. Gold, McDonald Horne, Giovanni Cizza
Journal: Metabolism (2005)
Arteriovenous Shunt Produced by Metastatic Hypernephroma
Authors: Hubert I. Caplan
Journal: JAMA (1961)

BONE metastases from renal cell carcinoma are relatively common (as high as 55% in one series)1and frequently present as the initial clinical manifestation of the disease. However, pulsating tumors produced by these metastases are rare, with only sporadic cases having been reported.2,3In none of the reported cases have signs of an arteriovenous shunt been demonstrated.  The following is a report of a patient in whom signs of an arteriovenous shunt were produced by a large volume of blood passing through an iliac bone metastasis from an otherwise asymptomatic renal cell carcinoma.  Report of a Case  A 66-year-old retired tannery worker was admitted to the Boston Veterans Administration Hospital for the second time on Nov. 7, 1960, because of a pain in his left calf of 3 weeks' duration. Fifteen months previously he was admitted to another hospital for evaluation of persistent dull ache and stiffness
Authors' reply to Marjoribanks and colleagues, Rossouw and colleagues, Schroll and Lundh, and McPherson
Authors: L. L. Schierbeck, L. Kober, J.-E. B. Jensen
Journal: BMJ (2012)

We are grateful for all of the interest in our paper1; more extensive answers are available at bmj.com (www.bmj.com/content/345/bmj.e6409/rr/612351).

Although randomisation is an important part of any trial, we acknowledge that performance and detection bias exist in open label trials,2 3 but these biases are less important when endpoints are driven by mortality. Furthermore, no trial of hormone replacement therapy (HRT)—including the Women’s Health Initiative—conducted in women with a uterus is completely blinded.4 5 …
Chronic Cor Pulmonale
Authors: Harold I. Palevsky
Journal: JAMA (1990)

Cor pulmonale is right ventricular enlargement secondary to pulmonary hypertension. Although most often caused by parenchymal lung disease, derangements of the ventilatory drive, the respiratory pumping mechanism, or the pulmonary vascular bed may also result in right ventricular hypertrophy and dilatation. Arterial hypoxemia (and resultant polycythemia), hypercapnia, and respiratory acidosis all contribute to the increased afterload on the right ventricle. Diagnosis is often difficult, since pulmonary vascular disease, pulmonary hypertension, and cor pulmonale have few specific manifestations, especially early in their evolution. Treatment is primarily directed at the underlying pulmonary or ventilatory disorder, rather than at the right ventricular failure per se. Supplemental oxygen is essential to avoid hypoxia; corticosteroids, anticoagulants, vasodilators, and other specific therapies are used as indicated to treat the underlying pulmonary disorders. When medical therapies fail, lung or heart-lung transplantation has become a possibility for selected patients.
Favorable Remodeling Enhances Recovery of Regional Myocardial Function in the Weeks After Infarction in Ischemically Preconditioned Hearts
Authors: Michael V. Cohen, Xi-Ming Yang, Till Neumann, Gerd Heusch, James M. Downey
Journal: Circulation (2000)

Background —In a previous study, we found that recovery of segment shortening in the ischemic zone of conscious, chronically instrumented rabbits was significantly better in ischemically preconditioned than control animals after 72 hours of reperfusion. However, although this period of reperfusion was felt to be sufficient to allow recovery from stunning, regional function was disproportionately low for the size of the infarcts. Methods and Results —To further characterize the recovery of left ventricular regional function, rabbits were chronically instrumented with a balloon occluder around a branch of the left coronary artery and a pair of ultrasonic crystals to monitor segment shortening in the ischemic zone. The preconditioned group had 1 cycle of 5-minute occlusion/10-minute reperfusion before a 30-minute occlusion, whereas control rabbits experienced only the 30-minute occlusion. All monitored segments were either dyskinetic or akinetic during the 30-minute occlusion. There was no difference in function between the 2 groups until 24 hours of reperfusion. At 72 hours, systolic shortening in control hearts averaged only 5% of the preischemic value, whereas shortening was 29% of baseline in preconditioned hearts. By day 21, systolic shortening averaged 26% in control hearts and 65% in preconditioned hearts ( P &lt;0.02) and appeared to have reached a plateau. Infarct size was 31.4±2.8% and 15.5±2.1% in control and preconditioned hearts, respectively. Moreover, in ischemically preconditioned hearts, the recovery of regional function was better than in controls for any given amount of microinfarction in the myocardial segment between crystals ( P =0.02). Conclusions —The progressive improvement in preconditioned hearts is most consistent with favorable remodeling in the ischemic zone, which the preconditioning process seems to accentuate.
Effects of non-REM sleep on ventilation and respiratory mechanics in adults with cystic fibrosis.
Authors: R D Ballard, J M Sutarik, C W Clover, B Y Suh
Journal: American Journal of Respiratory and Critical Care Medicine (1996)

To determine the effects of sleep upon respiratory function, five adult patients with cystic fibrosis (CF) were monitored during sleep in a horizontal body plethysmograph. Tidal volume (VT) decreased during non-rapid-eye-movement (NREM) sleep, resulting in a NREM sleep-associated decrement in minute ventilation (VI = 11.10 +/- 0.67, 9.32 +/- 0.91, and 9.17 +/- 1.42 L during wakefulness, stage 2, and stages 3-4, respectively, p < 0.05). There were no NREM sleep-associated changes in respiratory frequency (f) or inspiratory time (Ti), but respiratory neuromuscular output was reduced during NREM sleep P0.1 = 3.33 +/- 0.57, 1.79 +/- 0.23, and 1.99 +/- 0.21 cm H2O during wakefulness, stage 2, and stages 3-4, respectively, p = 0.005). Upper airway resistance (Rua), lower airway resistance (RIa), and lung volume did not change in association with NREM sleep. Functional residual capacity (FRC) measurements made using helium dilution indicated large volumes of trapped gas, likely a result of peripheral airways that were closed at FRC. We conclude that in adult patients with CF, NREM sleep is associated with a decrement in VT and VI, NREM sleep does not alter airflow resistance or lung volume, and the observed reductions in VT and VI apparently result from a NREM sleep-associated decrease in respiratory neuromuscular output.
Noradrenaline is a stress-associated metaplastic signal at GABA synapses
Authors: Wataru Inoue, Dinara V Baimoukhametova, Tamás Füzesi, Jaclyn I Wamsteeker Cusulin, Kathrin Koblinger, Patrick J Whelan, Quentin J Pittman, Jaideep S Bains
Journal: Nature Neuroscience (2013)