tbuckley/cabot-search huggingface dataset:
Abstract 3985: Sorafenib modulates macrophages to promote T helper type 1 immunity.
Authors: Melek M. Sunay, James M. Leatherman, Gang Chen, Leisha A. Emens
Journal: Cancer Research (2013)

Abstract Multiple regulatory processes within the tumor microenvironment work in concert to limit local anti-tumor immunity, and it is likely that integrative cancer therapies that target multiple cellular components in the tumor will be required to optimize antitumor immunity. Sorafenib is a promiscuous small molecule tyrosine kinase inhibitor developed as an anti-angiogenesis agent. We have previously shown that Sorafenib treatment can shift bone-marrow derived macrophages activated with lipopolysaccharide (LPS) and prostaglandin E2 (PGE2) from the pro-tumorigenic IL-10 secreting phenotype to the anti-tumor IL-12 secreting phenotype. Here, we extend these studies to explore the effect of Sorafenib on tumor-associated macrophages (TAMs) in a murine model of HER2+ breast cancer. Sorafenib treatment effectively delays the outgrowth of HER-2-overexpressing tumors in FVB/N mice relative to vehicle-treated controls. Immunohistochemical analysis revealed increased infiltration of F480+ macrophages in Sorafenib-treated tumors. F480+ TAMs isolated from Sorafenib-treated tumors had greater levels of IL-12 gene expression, and secreted higher levels of monocyte chemotactic protein-1 (MCP-1); there was no difference in IL-10 gene expression. Furthermore, F480+ TAMs isolated from Sorafenib-treated tumors demonstrated a superior ability to stimulate CD4+ T cell proliferation, and intracellular cytokine staining of tumor infiltrating lymphocytes isolated from Sorafenib-treated tumors showed an increase in CD4+ IFNγ-secreting T cells. Taken together, these data suggest that Sorafenib may alter the activation state of TAMs to increase pro-immunogenic signals and promote T helper type 1 immunity in the tumor microenvironment. Citation Format: Melek M. Sunay, James M. Leatherman, Gang Chen, Leisha A. Emens. Sorafenib modulates macrophages to promote T helper type 1 immunity. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3985. doi:10.1158/1538-7445.AM2013-3985
Sarcomere dynamics in cat cardiac trabeculae.
Authors: P P de Tombe, H E ter Keurs
Journal: Circulation Research (1991)

The purpose of the present study was to describe sarcomere dynamics in thin trabeculae that were dissected from the right ventricle of kittens. The muscles were mounted in an experimental chamber and perfused with a modified Krebs-Henseleit solution (25 degrees C). Sarcomere length (SL) was measured by laser diffraction techniques; force, by a silicon strain gauge; and velocity of sarcomere shortening, by the "isovelocity release" technique. Contractile activation was varied by changing the calcium concentration in the bathing medium ([Ca2+]o). Slack SL was 1.85 +/- 0.04 microns. When length of the muscle was held constant, the sarcomeres in the central region of the muscle shortened during the twitch by up to 21%. Both peak sarcomere isometric twitch force and unloaded velocity of sarcomere shortening (Vo) were a sigmoidal function of [Ca2+]o. Maximum Vo was 9.8 +/- 0.2 microns/sec; maximum sarcomere isometric twitch force was 108 +/- 13.8 mN/mm2. The shape of the force-SL relation was a function of [Ca2+]o. At [Ca2+]o = 1.5 mM, the force-SL relation was curved with its convexity toward the abscissa; at [Ca2+]o = 6 mM, the relation was curved with its convexity toward the ordinate. Vo depended in a linear manner on SL up to 2.2 microns at [Ca2+]o = 1.5 mM. At [Ca2+]o = 6.0 mM, Vo depended also linearly on SL below 1.85 microns but became nearly independent of SL above 1.85 microns. Vo rose exponentially with time into the twitch up to 200 msec and remained constant thereafter at least up to 300 msec. Force, on the other hand, peaked at about 300 msec. These results are comparable with those found in rat myocardium, although cat myocardium is less sensitive to [Ca2+]o and twitch kinetics are significantly slower than those in rat myocardium.
Vitamin <scp>D</scp> deficiency induces <scp>T</scp>h2 skewing and eosinophilia in neonatal allergic airways disease
Authors: J. E. Vasiliou, S. Lui, S. A. Walker, V. Chohan, E. Xystrakis, A. Bush, C. M. Hawrylowicz, S. Saglani, C. M. Lloyd
Journal: Allergy (2014)

Associations between vitamin D status and childhood asthma are increasingly reported, but direct causation and mechanisms underlying an effect remain unknown. We investigated the effect of early-life vitamin D deficiency on the development of murine neonatal allergic airways disease (AAD).
Doctor who was sacked in Baby P case claims unfair dismissal
Authors: C. Dyer
Journal: BMJ (2009)

The paediatrician who was sacked after failing to spot that Baby P had a broken back and eight fractured ribs two days before he died has launched a claim of unfair dismissal against her former employers, Great Ormond Street Hospital for Children NHS Trust.

Sabah Al-Zayyat is taking her case to an employment tribunal, which has the power to award up to £66 200 (€79 000; $109 000) if she succeeds in her claim.

The severely abused 17 month old boy, now known as Baby …
Gentamicin blockade of slow Ca++ channels in atrial myocardium of guinea pigs.
Authors: H R Adams, L R Durrett
Journal: Journal of Clinical Investigation (1978)

Cardiac dysfunction is occasionally detected in patients undergoing treatment with amino-glycoside antibiotics, however, the mechanism responsible for the negative inotropic effect of these agents has not been identified. In the present investigation electrically driven left atria of guinea pigs were used to study the effects of gentamicin on calcium ion (Ca++)-dependent contractile events in heart muscle isolated from in vivo influences. When atria were first inactivated by excess potassium ion (K+; 22mM) and contractions were then restored by isoproterenol (an experimental model that accentuates the contractile dependence of myocardial fibers on influx of Ca++ through specific "slow channels" of the sarcolemma), the cardiac depressant activity of gentamicin (0.1 mM) was profoundly augmented. Conversely, the negative inotropic effect of tetrodotoxin (23.5 micron) was abolished by the same experimental conditions. Also, gentamicin (1 mM) and La+++ (0.5 mM) markedly decreased the positive inotropic response to increased frequency of stimulation; whereas, D600 (1.05 micron) converted the positive frequency-force relationship to a negative relationship. Present data indicate a direct cardiac depressant action of gentamicin, and suggest that this antibiotic adversely affects either the transport system responsible for Ca++ movement through slow channels of the sarcolemma, the availability of Ca++ for translocation to these sites, or both.
The Thr224Asn mutation in the VPS45 gene is associated with the congenital neutropenia and primary myelofibrosis of infancy
Authors: Polina Stepensky, Ann Saada, Marianne Cowan, Adi Tabib, Ute Fischer, Yackov Berkun, Hani Saleh, Natalia Simanovsky, Aviram Kogot-Levin, Michael Weintraub, Hamam Ganaiem, Avraham Shaag, Shamir Zenvirt, Arndt Borkhardt, Orly Elpeleg, Nia J. Bryant, Dror Mevorach
Journal: Blood (2013)
Neonatal screening for cystic fibrosis using immunoreactive trypsinogen and direct gene analysis: four years' experience
Authors: E Ranieri, B D Lewis, R L Gerace, R G Ryall, C P Morris, P V Nelson, W F Carey, E F Robertson
Journal: BMJ (1994)

<b>Background:</b> Immunoglobulin G4-related disease (IgG4-RD) is a systemic disorder which may involve the lungs, airways and pleura. <b>Objective:</b> To describe novel findings in pleural involvement by IgG4-RD. <b>Methods:</b> A case series of patients with histologically proven IgG4-RD treated for pleural effusion in our clinic. <b>Results:</b> We identified 4 male patients (aged 68-84) with pleural effusion caused by IgG4-RD. Effusions were lymphocytic exudates in all cases, with high protein concentrations (5.6-7.4 g/dL). All patients had hyperglobulinemia, elevated serum immunoglobulin G (IgG) levels and elevated levels of IgG subclasses 1 and 4 (IgG1 and IgG4). In two patients, levels of adenosine deaminase (ADA) were measured in the effusion and were elevated (309 and 108 IU/L). Tuberculosis was excluded in both cases by pleural biopsy. Thoracic lymphadenopathy was prominent in all patients. One patient developed radiological findings compatible with rounded atelectasis (<b>Figure</b>). In all cases, effusion responded to corticosteroids therapy. <b>Conclusions:</b> IgG4-RD may cause an ADA-positive, lymphocytic exudate with a high protein concentration, resembling tuberculous effusion. Thoracic lymphadenopathy, hyperglobulinemia, and an increased total IgG, IgG1, IgG4 may suggest the diagnosis. Previously undescribed, IgG4-RD pleural inflammation may result in rounded atelectasis. <b>Figure: Rounded atelectasis in a patient with IgG4-RD</b>
Small-Bowel Occlusion after Operative Laparoscopy: Our Experience and Review of the Literature
Authors: C. Romagnolo, L. Minelli
Journal: Endoscopy (2001)

Bowel complications as a consequence of laparoscopic surgery are usually due to direct injuries; on the other hand, bowel occlusion is a rarely described event. We have retrospectively analyzed our data in this field. Out of 2652 laparoscopies performed between July 1996 and March 2000, three cases of small-bowel occlusion were observed. Two cases were due to bowel hernia through a 5-mm trocar port incision, the third was a consequence of an adhesion between the ileum and lost fragment of myoma. Two cases were treated laparoscopically, while in the third a laparotomy was required. At the time of writing, all the patients are well after a mean follow-up of 6 months. It appears important to also perform closure of the fascia and peritoneum after a 5-mm trocar port incision where there has been extensive manipulation.
Reduced cadmium levels in human kidney cortex in sweden.
Authors: L Friis, L Petersson, C Edling
Journal: Environmental Health Perspectives (1998)

Environmental pollution with the nephrotoxic metal cadmium is considered a potential health risk for the general population. In 1976 it was reported that the cadmium concentration in human kidney cortex in Sweden had increased in parallel with increasing levels in soil and grain during the twentieth century. Since the cadmium concentration in farming lands is still increasing, the present study was undertaken to further elucidate whether the cadmium concentration in the kidney is still increasing. Kidney cortex biopsies were collected at 171 autopsies of victims to sudden and accidental death during 1995 and 1996, and the cadmium concentrations were determined and compared with previously published Swedish data obtained from forensic autopsies. The geometric mean cadmium concentration in kidney cortex in subjects 40 years of age and younger was about 40% of the concentration found in the 1970s, while the reduction was less pronounced among older people. The highest individual concentration of cadmium was 41.5 microg/g wet weight (ww). The geometric mean concentration was less than 14 microg/g ww at ages around 50 years of age, when the cadmium concentration in kidney cortex is highest, as compared with approximately 20 microg/g ww in the 1970s. There was also a reduction in cadmium concentrations among nonsmokers; thus, a decrease in tobacco smoking in Sweden during the last decades is not the only explanation for the reduction of cadmium in the kidney cortex. Other reasons for this reduction could be changes in dietary habits and reduced cadmium contamination from Swedish industries.
Seven years of famine: health care after the crunch
Authors: M. Gray
Journal: BMJ (2009)

The future is not a place, like the Isle of Wight, awaiting our arrival; it is more like the Great Western Railway, something that we have to imagine, design, and build. If we do not build it, other people will.

Designing the future does not require vision, because, in the words of the science fiction writer William Gibson, “the future is already here, it’s just not evenly distributed.” By looking about we can see many examples of leading edge work that just needs to be generalised. We do not need vision or dreams, although Pharoah’s dream is probably a perfectly apt theme for health care after the credit crunch: we have had seven or so years of plenty, and we all know what comes after that. Furthermore, post-crunch health care also arises at the appropriate moment for low carbon health care, for health care in an era of sustainability. Even if money were to flow, health services would need to focus on the carbon footprint consequences of their development and achieve a reduction in the amount of energy used. One hospital I know is planning to double its …
Auscultatory and Phonocardiographic Assessment of Fallot's Tetralogy
Authors: LOUIS VOGELPOEL, VELVA SCHRIRE
Journal: Circulation (1960)

A clinical and phonocardiographic study has been made on 62 cases of Fallot's tetralogy in order to determine the value of auscultation and phonocardiography in assessing the severity of the stenosis. The severity of the tetralogy, as determined by clinical methods, was correlated with the length and loudness of the murmur and other auscultatory signs. Increasingly severe stenosis was shown to be associated with a shorter, earlier, and softer systolic murmur. In extreme tetralogy, the murmur was invariably soft and very short, being confined to early systole and ending in midsystole. An aortic ejection sound was usually audible and the second sound invariably loud and single. In severe tetralogy, the murmur was usually loud and short, with its crescendo before midsystole and termination before the aortic second sound. A pulmonary component was never audible. In moderate cases, the murmur was loud and longer, with its crescendo at midsystole and termination before or at the aortic second sound, which was never obscured by the murmur. A very soft pulmonary component was only rarely recorded. In mild cases, the murmur was loud and more prolonged with the crescendo in the latter half of systole and extension into, but rarely much beyond, the aortic component. Although at times loud at the aortic component, the murmur totally obscured this sound in only 1 case. A pulmonary component was frequently recorded and often heard; it was extremely soft and localized, but occasionally relatively loud. Splitting was always wide (average 0.09 second). The loud, long murmur reflected good pulmonary flow; the audible or recordable pulmonary component, a relatively normal pulmonary arterial pressure. Since the length and loudness of the systolic murmur reflect the volume rate of blood ejected through the stenosis, auscultation is believed to be a most valuable method of assessing both the severity of stenosis and fluctuations in blood flow, which may result from changes in systemic resistance and tonus of the infundibulum of the right ventricle. The change in murmur during cyanotic or syncopal attacks has thrown considerable light on the mechanism of such attacks.
Left ventricular end-systolic volume as the major determinant of survival after recovery from myocardial infarction.
Authors: H D White, R M Norris, M A Brown, P W Brandt, R M Whitlock, C J Wild
Journal: Circulation (1987)

Impairment of left ventricular function is the major predictor of mortality after acute myocardial infarction, but it is not known whether this is best described by ejection fraction or by end-systolic or end-diastolic volume. We measured volumes, ejection fractions, and severity of coronary arterial occlusions and stenoses in 605 male patients under 60 years of age at 1 to 2 months after a first (n = 443) or recurrent (n = 162) myocardial infarction and followed these patients for a mean of 78 months for survivors (range 15 to 165 months). There were 101 cardiac deaths, 71 (70%) of which were sudden (instantaneous or found dead). Multivariate analysis with log rank testing and the Cox proportional hazards model showed that end-systolic volume (chi 2 = 82.9) had greater predictive value for survival than end-diastolic volume (chi 2 = 59.0) or ejection fraction (chi 2 = 46.6), whereas stepwise analysis showed that once the relationship between survival and end-systolic volume had been fitted, there was no additional significant predictive information in either end-diastolic volume or ejection fraction. Severity of coronary occlusions and stenoses showed additional prediction of only borderline significance (p = .04 in one analysis), but continued cigarette smoking did remain an independent risk factor after stepwise analysis. For a subset of patients (n = 200) who had taken part in a randomized trial of coronary artery surgery after recovery from infarction, surgical "intention to treat" showed no predictive value.(ABSTRACT TRUNCATED AT 250 WORDS)
Respiratory Syncytial Virus Infection of the Newborn
Authors: G. A. Neligan, H. Steiner, P. S. Gardner, J. McQuillin
Journal: BMJ (1970)

In an outbreak of respiratory syncytial (R.S.) virus infection in a maternity hospital the respiratory illness was of a mild nature and the virus was not found in infants without respiratory symptoms. This confirms the suggestion that R.S. virus can infect infants at a very early age. Rapid diagnosis was achieved by applying the direct fluorescent antibody technique to cells in nasal secretions. This proved to be more sensitive than culture techniques where there was delay between the onset of respiratory symptoms and submission of specimens to the laboratory.
Abstract A15: High-Content screen for inhibitors of cell migration in cancer metastasis using adenoviral knock-down
Authors: Remko de Pril, Annemarie Lekkerkerker, Desire van Steenhoven, Ilhem Maghrani, Tim Perera, Janine Arts, David Fischer, Richard Janssen
Journal: Cancer Research (2012)

Abstract Enhanced cell migration is a hallmark of metastatic cancer cells. The propensity of cancer cells to close an open wound in a cell monolayer is thought to predict this ability. Using our adenoviral shRNA knockdown library we have established a high-throughput wound healing assay to identify novel genes involved in cell migration. A 96-pin tool was designed to apply a constant mechanical scratch-wound in the cellular monolayer. We used transmitted light imaging for segmentation and quantification of the scratch wound that remained open. Genes whose knockdown inhibit cell migration can be identified by their effect on the open wound. We demonstrated that two knockdown constructs targeting a known player in motility, CXCR4, inhibit wound healing, thereby validating our approach. Using this wound healing assay we have identified a number of novel genes associated with cancer cell motility. These targets have consecutively been validated for their role in 3-D invasion using Boyden chambers. As our adenoviral knockdown libraries focus on druggable targets, these validated targets can quickly be employed to generate small-molecule compounds or antibody therapeutics targeting cancer metastasis. Citation Format: Remko de Pril, Annemarie Lekkerkerker, Desire van Steenhoven, Ilhem Maghrani, Tim Perera, Janine Arts, David Fischer, Richard Janssen. High-Content screen for inhibitors of cell migration in cancer metastasis using adenoviral knock-down [abstract]. In: Proceedings of the AACR Special Conference on Chemical Systems Biology: Assembling and Interrogating Computational Models of the Cancer Cell by Chemical Perturbations; 2012 Jun 27-30; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2012;72(13 Suppl):Abstract nr A15.
Abciximab Improves Both Epicardial Flow and Myocardial Reperfusion in ST-Elevation Myocardial Infarction
Authors: James A. de Lemos, Elliott M. Antman, C. Michael Gibson, Carolyn H. McCabe, Robert P. Giugliano, Sabina A. Murphy, Stephanie A. Coulter, Keaven Anderson, Joel Scherer, Martin J. Frey, R. Van der Wieken, Frans Van de Werf, Eugene Braunwald
Journal: Circulation (2000)

Background —In the presence of ST-elevation myocardial infarction, patients with successful epicardial reperfusion (TIMI 3 flow) but persistent ST elevation on a 12-lead ECG are at high risk for subsequent death and left ventricular dysfunction. In the TIMI 14 trial, a dose-ranging angiographic study, combined therapy with abciximab plus reduced-dose tPA enhanced the speed and efficacy of epicardial reperfusion. We determined whether the combination of abciximab plus reduced-dose tPA provided additional benefit in terms of myocardial reperfusion, as evidenced by greater resolution of ST elevation. Methods and Results —All 346 patients with interpretable baseline and 90-minute ECGs, treated with either tPA alone or abciximab plus reduced-dose tPA (combination therapy), were included. Patients receiving combination therapy (n=221) had a 59% rate of complete (≥70%) ST resolution at 90 minutes versus 37% in those treated with tPA alone (n=125) ( P &lt;0.0001). When the analysis was limited to patients with TIMI 3 flow, patients treated with combination therapy (n=151) remained significantly more likely to achieve complete ST resolution than those receiving tPA alone (n=80) (69% versus 44%; P =0.0002). Conclusions —Combination therapy with abciximab and reduced-dose tPA improves myocardial (microvascular) reperfusion, as reflected in greater ST-segment resolution, in addition to epicardial flow. This finding may translate into improved clinical outcomes by enhancing myocardial salvage.
Use of specific IgE in assessing the relevance of fungal and dust mite allergens to atopic dermatitis: A comparison with asthmatic and nonasthmatic control subjects☆☆☆★
Authors: Deolinda M.F. Scalabrin, Sevim Bavbek, Matthew S. Perzanowski, Barbara B. Wilson, Thomas A.E. Platts-Mills, Lisa M. Wheatley
Journal: Journal of Allergy and Clinical Immunology (1999)
A Call for Accurate Pharmacogenetic Labeling
Authors: Wylie Burke, Kenneth Thummel
Journal: JAMA Internal Medicine (2014)

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