tbuckley/cabot-search huggingface dataset:
T-Cell Responses to Cyclin B1 Are Not Restricted to p53-Overexpressing Tumors
Authors: Michael S. von Bergwelt-Baildon, Alexander Shimabukuro-Vornhagen, Nela Klein-Gonzalez, Eisei Kondo
Journal: Clinical Cancer Research (2009)

To the Editors: In their elegant study, Sorensen et al. showed the existence of a T-cell response to two cyclin B1derived peptides in patients with advanced-stage breast cancer, confirming initial observations by Kao that cyclin B1 is an interesting target for immunotherapy (1, 2). However, the authors reported the absence of cyclin B1specific T cells in 10 of 10 healthy donors and concluded that they are only present after tumor-driven immune activation in patients with p53/cyclin B1overexpressing tumors.This is in contrast to our findings (3).11M.S. von Bergwelt-Baildon, unpublished results. We have characterized the cyclin B1 peptides 44(ALGDIGNKV), 204(ILIDWLVQV), and 218(LLQETMYMT) as immunogenic HLA-A*0201binding amino acid sequences. Antigen-specific T cells were detected in five of six T-cell cultures in all of three healthy donors without the need for a heteroclitic modification.How can this discrepancy be explained? The authors used a single stimulation with peptide-pulsed peripheral blood mononuclear cells. In our experience, repetitive use of purified, professional antigen-presenting cells is more efficient in expanding antigen-specific T cells. We therefore used an efficient expansion system based on CD40-activated B cells to identify cyclin B1 epitopes (3). Furthermore, the culture with high amounts of peptide (10 mol) in combination with nonprofessional antigen-presenting cells potentially promotes the expansion of low-avidity T cells, which would be peptide specific but not tumor reactive (4, 5). Taken together, the different results can be explained by the methodology alone.Nevertheless, it could be linked to the different epitope classes: peptides abundantly presented by MHC and thus efficiently elutable versus peptides identified by reverse immunology translating to differential thymic expression and deletion. However, for other cyclin family members, the absence of T cells in healthy donors had previously been suggested but seems to depend on the T-cell expansion system used (6), a major challenge in tumor antigen discovery (7).Our findings suggest that cyclin B1specific T cells are readily expandable in healthy individuals even if potentially at a lower frequency. For a tumor antigen, this is important. Why? First, cyclin B1 is overexpressed in several hematologic malignancies and thus could be targeted using ex vivo or in vivo expanded donor T cells in the context of allogeneic stem cell transplantation. Second, p53 mutation and thus cyclin B1 expression are events that occur early in tumorigenesis and are essential to tumor survival. Cyclin B1 is overexpressed in several major tumors. Thus, it has the hallmarks of an antigen for preventive cancer vaccination. If proven safe in advanced cancer patients, induction of a prophylactic cyclin B1directed T-cell response would be an intriguing strategy at least in high-risk cancer families.No potential conflicts of interest were disclosed.
Focused ultrasound and interleukin-4 receptor-targeted liposomal doxorubicin for enhanced targeted drug delivery and antitumor effect in glioblastoma multiforme
Authors: Feng-Yi Yang, Tai-Tong Wong, Ming-Che Teng, Ren-Shyan Liu, Maggie Lu, Hsiang-Fa Liang, Ming-Cheng Wei
Journal: Journal of Controlled Release (2012)
The Clinical Impact of Incomplete Left Atrial Appendage Closure With the Watchman Device in Patients With Atrial Fibrillation
Authors: Juan F. Viles-Gonzalez, Saibal Kar, Pamela Douglas, Srinivas Dukkipati, Ted Feldman, Rodney Horton, David Holmes, Vivek Y. Reddy
Journal: Journal of the American College of Cardiology (2012)
Rectal mucosal dysplasia in Crohn's disease.
Authors: B I Korelitz, G Y Lauwers, S C Sommers
Journal: Gut (1990)

Serial sections of 812 rectal biopsy specimens from 356 Crohn9s disease patients were analysed for mucosal epithelial dysplasia. Dysplasia was found in 18 patients (5%), with four showing dysplasia on repeat biopsy specimen. In these 22 biopsy specimens the dysplasia was mild in 13, moderate in nine, and severe in none. Subsequently, three patients (17%) developed neoplasms including carcinoma in two and an adenomatous polyp in one. In colectomy specimens which showed dysplasia, significantly more dysplastic changes were found in seven patients who underwent colonic resection than in 10 others who underwent operation but had no prior dysplasia (p less than 0.001). Thirteen patients still have their rectum in situ and remain at risk of developing colonic cancer. Four carcinomas developed in patients with Crohn9s disease who did not have dysplasia on rectal biopsy specimen.
Biomass Fuels for Cooking: Clear that Smoke
Authors: Navneet Singh
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

I readwith interest the recent article byRegalado and colleagues, wherein the authors have assessed the impact of cooking with biomass fuels (BMFs) on respiratory symptoms and lung function among rural women in a developing country (1). They found the presence of increased respiratory symptoms (predominantly an increase in phlegm) as well as a decline in spirometric indices, both of which correlated with the duration of exposure. These findings reinforce the observations of previous studies done at my institute that BMFs have deleterious effects on respiratory functions of nonsmoking individuals. However, two important aspects related to cooking with domestic fuels merit attention. First, it is worthwhile to note that exposure to kerosene (another commonly used fuel for domestic cooking in rural areas that do not have access to liquefied petroleum gas [LPG]) also leads to an increase in respiratory symptoms. In fact, increase in respiratory symptoms was maximal with the use of mixed fuels (both BMFs as well as kerosene) compared with either of the two alone (2, 3). These effects occur not only in adults but also in children (4). Moreover, patients with preexisting obstructive airway disease tend to have an increase in respiratory symptoms as well as worsening lung functions after exposure to domestic cooking fuels (5). Second, in addition to obstructive airway disease, exposure to BMFs and mixed fuels can lead to bronchial hyperresponsiveness as well as restrictive defects on spirometry (6, 7). Combined exposure to tobacco smoke and domestic cooking fuels (like BMFs and mixed fuels) leads to much more morbidity than either of them alone (2, 7). In developing countries, and especially in rural areas, using LPG for cooking is often not possible either due to economic constraints or lack of access to the same. The need to use BMFs and other alternate fuels for domestic cooking is compounded by the absence of proper ventilation in houses, and this enhances the adverse effects of such fuels. The key to avoiding the deleterious effects of these fuels (on respiratory symptoms and function) is to advocate the use of smokeless devices for cooking as well as to improve the ventilation in houses, especially in the area where domestic cooking is done. After all, prevention is better than cure.
The Columnar Epithelial Cell of the Small Intestine: Digestion and Transport
Authors: Jerry D. Gardner, Michael S. Brown, Leonard Laster
Journal: New England Journal of Medicine (1970)

Hexose AbsorptionAfter direct evidence was obtained for the role of the intestinal epithelial cell in sugar absorption,94 it was shown that mucosal sheets, intact rings and isolated villi from hamster small intestine can accumulate such an amount of sugar that tissue concentration exceeds medium concentration95 and sugar uptake is energy dependent and exhibits Michaelis–Menten kinetics,80 mutual competitive inhibition and phlorizin inhibition.55, 95 96 97 98 99 Sugar entry and accumulation were attributed to a carrier mechanism in the brush-border membrane, with entry reflecting unidirectional movement into the tissue and accumulation reflecting the tissue concentration at which sugar entry equals exit.For absorption of sugars . . .
Alopecia From Oral Contraceptives
Authors: Eduard Eichner
Journal: JAMA (1967)

<h3>To the Editor:—</h3> F.E. Cormia, MD, in his comments (<b>201</b>:635, 1967) reports five patients with alopecia<i>associated with</i>contraceptives, not proven as "from" contraceptives. He categorically states "Progestogens are 19-nor-steroids..." yet the progestational agent in case 4 is a 17-hydroxy substituted progesterone which has no androgenicity, and in cases 2 and 3 the type of progestogen is not listed. In case 4, where extensive neurodermatitis had been treated with corticoids, and in whom emotional factors were very prominent, he holds that 17 months is prolonged therapy. In this subject the total progestational dose was five day's of progestogen ( 12.5 mg) per cycle. Assuming 20 cycles maximum in the period of treatment, this patient received not over 250 mg of the material, a minimal amount of an agent with no proven androgenicity. There is no doubt that alopecia has occurred in some patients following the use of these agents. Dr.
Effects of recombinant human tumor necrosis factor alpha, lymphotoxin, and Escherichia coli lipopolysaccharide on hemodynamics, lung microvascular permeability, and eicosanoid synthesis in anesthetized sheep.
Authors: E A Kreil, E Greene, C Fitzgibbon, D R Robinson, W M Zapol
Journal: Circulation Research (1989)

We infused recombinant human tumor necrosis factor alpha (rhTNF alpha), lymphotoxin (rhLT), and Escherichia coli 0111:B4 lipopolysaccharide (LPS) into anesthetized sheep with a lung lymph fistula to compare their effects on systemic and pulmonary hemodynamics, lung lymph dynamics, and eicosanoid release. rhTNF alpha (25-150 micrograms/kg, n = 6 sheep), but not rhLT (25 micrograms/kg, n = 3), rapidly increased lung lymph and plasma levels of 6-keto-prostaglandin F1 alpha (6-k-PGF1 alpha) and caused profound systemic vasodilation and hypotension. Meclofenamate pretreatment (10 mg/kg) of three other sheep given 25 micrograms/kg rhTNF alpha prevented the increase of lymph and plasma 6-k-PGF1 alpha levels, systemic vasodilation, and the early (less than 2 hrs) but not the late (4-6 hours) hypotension caused by rhTNF alpha. LPS (1 micrograms/kg, n = 11) induced a briefer increase of lymph 6-k-PGF1 alpha levels than did rhTNF alpha while plasma 6-k-PGF1 alpha levels did not increase. LPS induced more gradual hypotension than did rhTNF alpha but did not cause systemic vasodilation. LPS and rhTNF alpha, but not rhLT, increased lymph thromboxane B2 (TXB2) levels during the first hour of study, whereas only LPS acutely increased plasma TXB2 levels. LPS caused acute pulmonary vasoconstriction and greater acute pulmonary artery hypertension than did either rhTNF alpha or rhLT. Whereas LPS-treated sheep required less fluid transfusion than rhTNF alpha-treated sheep to maintain mean systemic arterial pressure greater than 50 mm Hg, LPS infusion caused a greater increase of lung lymph protein clearance. rhTNF alpha caused minimal alterations of lung microvascular permeability. We conclude that eicosanoid mediators contribute importantly to differences of systemic and pulmonary hemodynamics caused by these agents in sheep. rhTNF alpha cannot account for all of the LPS-induced hemodynamic, lung lymph, and eicosanoid responses in sheep.
CARCINOMATOUS MUCOSAL EXCRESCENCE OF THE RECTUM
Authors: Michael Weingarten
Journal: JAMA (1952)

There has been much discussion as to the pathogenesis of intestinal polyps and the possible evolution of benign adenomas into invasive carcinomas. No direct valid evidence of such a transformation has been offered, because of the necessity for complete removal of a lesion for microscopic examination to permit determination of its true histopathological character, thus rendering further study in situ impossible. However, considerable collateral evidence for malignant transformation is presented both on histological grounds, by Atwater and Bargen,<sup>1</sup>and on a clinical basis, by Helwig.<sup>2</sup>It is generally agreed that colonic polyps, if not already malignant, are potentially malignant and that, whenever observed, they should be extirpated, whether or not they are at the time producing symptoms. With regard to the smaller polyps, sometimes referred to as mucosal excrescences, there are, however, statements in the literature that tend to create a more complacent attitude. In many instances, these
NHS should become a membership organisation, think tank says
Authors: C. Dyer
Journal: BMJ (2014)

The NHS risks bankruptcy within five years unless the way it delivers services and is funded changes radically, says a report from the independent think tank Reform, which accuses the Labour Party and the coalition government of ignoring the developing crisis.1

Coauthored by Norman Warner, a Labour peer who was minister for health reform in Tony Blair’s government, the report articulates “the great unspoken truth of British politics . . . that the NHS, as it …
Incidence and prognostic relevance of genetic variations in T-cell lymphoblastic lymphoma in childhood and adolescence
Authors: Bettina R. Bonn, Marius Rohde, Martin Zimmermann, David Krieger, Ilske Oschlies, Felix Niggli, Grazyna Wrobel, Andishe Attarbaschi, Gabriele Escherich, Wolfram Klapper, Alfred Reiter, Birgit Burkhardt
Journal: Blood (2013)
Pressure and Volume Loading of the Right Ventricle Have Opposite Effects on Left Ventricular Ejection Fraction
Authors: Eric K. Louie, Steve S. Lin, Sandra I. Reynertson, Bruce H. Brundage, Sidney Levitsky, Stuart Rich
Journal: Circulation (1995)

Background Left ventricular ejection fraction has been reported to be depressed in patients with right ventricular volume overload (RVVO) due to Ebstein’s anomaly and uncomplicated atrial septal defect, whereas it is usually preserved in right ventricular pressure overload (RVPO) due to congenital pulmonic stenosis. In the present study, we examined the hypothesis that the differential timing of active displacement of the ventricular septum into the left ventricle in RVPO (end systole) and RVVO (end diastole) results in opposite effects of RVPO and RVVO on left ventricular ejection fraction. Methods and Results Ten patients with severe tricuspid regurgitation after tricuspid valve resection for endocarditis and 10 patients with primary pulmonary hypertension were studied as models of isolated RVVO and RVPO, respectively. Left ventricular ejection fraction, end-diastolic volume, and regional systolic shortening were measured with the use of echocardiographic techniques in these 20 patients and 10 healthy control subjects. In RVPO, despite marked underfilling of the left ventricle relative to the healthy control subjects (end-diastolic volume, 48±26 versus 77±20 mL; P &lt;.02), left ventricular ejection fraction was similar to that of the control subjects (56±5% versus 60±4%; P =.07) and only 1 of 10 RVPO patients had an ejection fraction of less than 50%. In contrast, in RVVO the left ventricle was volume replete (end-diastolic volume, 84±26 versus 77±20 mL; P =NS), but left ventricular ejection fraction was significantly depressed (51±4% versus 60±4%, P &lt;.001) compared with the control subjects, and 4 of 10 RVVO patients had an ejection fraction of less than 50%. Analysis of systolic fractional shortening along two perpendicular short-axis diameters and the mutually orthogonal long axis demonstrated isolated augmentation of fractional shortening in the ventricular septal–to–posterolateral free wall dimension in RVPO (47.4±13.7% versus 34.2±13.1%, P &lt;.05) and isolated depression of fractional shortening along that same dimension in RVVO (13.7±11.8% versus 34.2±13.1%, P &lt;.001) compared with the control subjects. Conclusions End-systolic leftward ventricular septal shift in RVPO results in isolated augmentation of systolic shortening in the septal–to–free wall dimension, whereas end-diastolic leftward ventricular septal shift in RVVO results in isolated reduction in systolic shortening in the septal–to–free wall dimension. As a result, despite relative underfilling of the left ventricle in RVPO, resting left ventricular ejection fraction is preserved, whereas ejection fraction is depressed for the volume-replete left ventricle of patients with RVVO.
Phagocytosis of apoptotic bodies by hepatic stellate cells induces NADPH oxidase and is associated with liver fibrosis<i>in vivo</i>
Authors: Shan-Shan Zhan, Joy X. Jiang, Jian Wu, Charles Halsted, Scott L. Friedman, Mark A. Zern, Natalie J. Torok
Journal: Hepatology (2006)

Hepatic stellate cell activation is a main feature of liver fibrogenesis. We have previously shown that phagocytosis of apoptotic bodies by stellate cells induces procollagen α1 (I) and transforming growth factor beta (TGF-β) expression in vitro . Here we have further investigated the downstream effects of phagocytosis by studying NADPH oxidase activation and its link to procollagen α1 (I) and TGF-β1 expression in an immortalized human stellate cell line and in several models of liver fibrosis. Phagocytosis of apoptotic bodies in LX-1 cells significantly increased superoxide production both in the extracellular and intracellular milieus. By confocal microscopy of LX-1 cells, increased intracellular reactive oxygen species (ROS) were detected in the cells with intracellular apoptotic bodies, and immunohistochemistry documented translocation of the NADPH oxidase p47phox subunit to the membrane. NADPH oxidase activation resulted in upregulation of procollagen α1 (I); in contrast, TGF-β1 expression was independent of NADPH oxidase activation. This was also confirmed by using siRNA to inhibit TGF-β1 production. In addition, with EM studies we showed that phagocytosis of apoptotic bodies by stellate cells occurs in vivo . In conclusion, these data provide a mechanistic link between phagocytosis of apoptotic bodies, production of oxidative radicals, and the activation of hepatic stellate cells. Supplementary material for this article can be found on the HEPATOLOGY website ( http://interscience.wiley.com/jpages/0270-9139/suppmat/index.html ). (Hepatology 2006;43:435–443.)
Guidelines on HIV prophylaxis must be implemented
Authors: R. U Sidwell, J. S A Green, V. Novelli
Journal: BMJ (1999)

EDITOR—Duff et al's telephone survey of surgeons' and occupational health departments' awareness of guidelines on post-exposure prophylaxis for hospital staff who had been exposed to HIV raised two points.1 Firstly, although surgeons are indeed at risk of percutaneous exposure to HIV, it should be reiterated that there is a risk for all junior doctors and healthcare workers. Secondly, there seems to have been no assessment within the survey of how local policies are actually implemented. The survey assumed that if the occupational health department had …
Flipping the cancer switch
Authors: Mitch Leslie
Journal: The Journal of Experimental Medicine (2009)

On [page 819][1] Hosui et al. show how a cancer-fighting molecular pathway turns traitor and becomes a cancer promoter. The work clarifies how chronic liver damage can lead to tumors.

![Figure][2] 

STAT3 (red) levels surge in liver cells lacking both kinds of STAT5.



Alcoholism and
Stenosis of the Right Main Pulmonary Artery
Authors: LAWRENCE L. LUAN, JOSEPH LLOYD D'SILVA, BENJAMIN M. GASUL, ROBERT F. DILLON
Journal: Circulation (1960)

Ten cases of isolated stenosis of the right main pulmonary artery are presented, 7 with associated anomalies. Although right heart catheterization and angiocardiography are usually necessary to demonstrate this malformation, a knowledge of the existence of this anomaly correlated with auscultatory and roentgenologic findings may often lead to a correct clinical diagnosis.
357 PRE-S HBV MUTANTS DO NOT AFFECT HBSAG SERUM LEVELS IN HBEAG NEGATIVE GENOTYPE D CARRIERS, BUT ARE ASSOCIATED WITH LIVER DISEASE STAGE AND OLDER AGE
Authors: A. Stabile, P. Colombatto, F. Oliveri, F. Moriconi, D. Cavallone, B. Cherubini, P. Ciccorossi, B. Coco, C. Rastelli, V. Romagnoli, F. Bonino, M.R. Brunetto
Journal: Journal of Hepatology (2011)
Milan's appeals court is asked to rule on woman who has been in vegetative state for 16 years
Authors: F. Turone
Journal: BMJ (2008)

An Italian court will be asked on 8 October to decide the fate of a 37 year old woman, Eluana Englaro, who has been in a persistent vegetative state since 1992.

It is the latest but possibly not the last move in a legal saga that has gone on for nine years since Eluana’s father, Beppino Englaro, first started the battle for the legal right to remove her feeding tube.

The case has moved through numerous courts, but in July Milan’s appeals court said that Eluana had the right to die through the withdrawal of food and water. The ruling specified that the withdrawal had to be taken in a public healthcare facility under the care of health professionals.

But since …
Impact of vitamin D deficiency on the clinical presentation and prognosis of patients with newly diagnosed multiple myeloma
Authors: Alvin C. Ng, Shaji K. Kumar, S. Vincent Rajkumar, Matthew T. Drake
Journal: American Journal of Hematology (2009)

Abstract Vitamin D is a fundamental mediator of skeletal metabolism. It also has important nonskeletal actions. We hypothesized that vitamin D deficiency may play an important role in skeletal morbidity and clinical outcomes in MM. We studied 148 newly diagnosed MM patients from January 1, 2004 through December 31, 2008 who had a serum 25‐hydroxyvitamin D [25(OH)D] obtained within 14 days of diagnosis. Subjects with vitamin D deficiency [25(OH)D level less than 50 nmol/L (20 ng/mL)] had higher mean values of serum C‐reactive protein (CRP) (2.40 mg/L vs. 0.84 mg/L, P = 0.02) and creatinine (1.75 mg/dL vs. 1.24 mg/dL, P = 0.03) and lower serum albumin values (3.12 g/dL vs. 3.39 g/dL, P = 0.003) compared to subjects without vitamin D deficiency. The prevalence of vitamin D deficiency increased in parallel with International Staging System (ISS): 16% of subjects in Stage I, 20% in Stage II, and 37% in Stage III ( P = 0.03) were vitamin D deficient. No differences were detected between the two groups in terms of skeletal morbidity. Association of vitamin D deficiency with higher serum CRP, serum creatinine and ISS stage at time of diagnosis suggests that vitamin D deficiency may portend poorer outcomes in subjects with MM. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.
Letter: Isolation system for General Hospitals.
Authors: H G Easton
Journal: BMJ (1974)

clude the possibility of a direct effect of metoclopramide and propantheline on absorption across the intestinal mucosa.We have tested the effects of these compounds and of phenobarbitone on D-xylose absorption from rat small intestine in vitro.Everted sacs were used with Krebs phosphate buffer containing calci,um and glucose.' Transport of 50 mM xylose was measured with a concentration gradient- that is, with buffer only and no xylose initially within the sac.The drugs were added to the mucosal and serosal solutions of alternative sacs at a concentration of 1 rmnol/l.Phenobarbitone and metoclopramide significantly reduced xylose transport but propantheline had no such effect.Our finding of inhibition by metoclo- pramide agrees with the clinical findings of Kendall' in individuals with normal gastro- intestinal function.He also showed that propantheline increased urinary excretion, and presumably intestinal absorption, of xylose in one case of carcinoid syndrome.No such effect of propantheline was ob- served in our investigation in vitro.The in-situ intestinal loop preparation with anaesthetized rats has been used to study antibiotic absorption.This showed good correlation when predicting antibiotic absorption in man.By contrast, results with the everted sac as a model for gastro- intestinal absorption had to be interpreted with extreme caution.5Our results agree with this latter view.Thus phenobarbitone6 and metoclopramide show similar effects on xylose absorption both in vivo and in vitro but there is no such correlation with pro- pantheline.-Weare, etc.,