tbuckley/cabot-search huggingface dataset:
Abstract 1303: Inhibition of human breast cancer cell (MDA-MB231) migration, neoangiogensis and tumor growth by selective disruption of annexin II function: in vitro and in vivo studies
Authors: Mahesh C. Sharma, Robert T. Ownbey, Marc R. Blackman, Meena Sharma
Journal: Cancer Research (2010)

Abstract Annexin II, an abundant phospholipid binding cell surface protein, binds tissue plasminogen activator (tPA) and functions as a regulator of fibrinolysis. Annexin II also mediates angiogenesis and enhances tumor growth and metastasis. However, the mechanism supporting this role is not known. Using a human breast cancer model we found that invasive human breast cancer cells (MDA-MB231) synthesize annexin II and tPA. Annexin II interacted with tPA in vitro leading to conversion of zymogen plasminogen to the reactive enzyme plasmin. Cell surface generated plasmin inhibited the migration of MDA-MB231 cells. Silencing of the annexin II gene in mDA-MB231 cells abolished tPA binding thereby inhibiting tPA dependent plasmin generation. Moreover these annexin II suppressed MDA-MB231 cells exhibited reduced motility. Immunohistochemical analysis of prediagnosed clinical specimens showed abundant secretion of tPA and expression of annexin II on the surface of invasive cancer cells which correlates with neovascularization of the tumor. Intravenous administration of the anti-annexin II antibody to mice bearing MDA-MB231 tumors significantly inhibited tumor growth possibly due to blocked neoangiogenic activity. Taken together, these data suggest that annexin II dependent plasmin generation may be an early event switching breast cancer from the prevascular phase to the vascular phase with the possibility of metastasis. Annexin II may be an attractive target for therapeutic strategies aimed to inhibit neoangiogenesis and breast cancer metastasis. 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 1303.
ROENTGEN-RAY APPEARANCE IN A CASE OF CONGENITAL HYDROCEPHALUS
Authors: R. A. Bartholomew
Journal: JAMA (1923)

Mrs. C. P., aged 26, white, primigravida, whose family, personal and menstrual history were negative, consulted me, Aug. 19, 1922, because of pregnancy. The last menstrual period had occurred, March 22, since which time there had been no show of blood. Nausea and vomiting had begun early in May, and continued moderately severe for about two months. Fetal movements had been noticed for the past several weeks. The patient was fairly well nourished, weighed 120 pounds (54.4 kg.), and was of average height. There was no general adenopathy and the heart and lungs were normal. The blood pressure was 110 systolic, and 65 diastolic. The abdomen was normal except for the enlargement of the uterus, which extended several centimeters above the umbilicus. Fetal movements were distinctly seen. The measurements of the inlet indicated a moderately flat type of pelvis, the diagonal conjugate measuring 11.5 cm.; but the outlet was normal.
Gauze as a Scarifier in Vaccination
Authors: F. J. McKinley
Journal: JAMA (1913)

<h3>To the Editor:</h3> —I am convinced that it is fully worth while to call further attention to a new method of vaccination, originated by the Public Health Service surgeons now in the Philippines. In this method a small piece of gauze (plain and sterile) is used as a scarifier. The gauze is simply drawn over the index-finger and held by the thumb and other fingers, and the point selected is briskly rubbed until slightly abraded over an area about equal to that of a thumb-nail. The virus is then deposited on the abraded area and allowed to dry. The gauze used to rub with can be bound over the point of vaccination, if desired, but should be discarded on the following day, as if allowed to remain it may adhere and give further trouble. This method is well suited for work on women and children. Its authors state that the
Protective actions of administered mesenchymal stem cells in acute kidney injury: relevance to clinical trials
Authors: Christof Westenfelder, Florian E. Togel
Journal: Kidney International Supplements (2011)

Current therapies for acute kidney injury remain primarily supportive and have failed to reduce morbidity, mortality (>50%), and associated costs. This prompted our studies in which rats with bilateral ischemia/reperfusion-induced acute kidney injury were treated with bone marrow-derived, culture-expanded allogeneic mesenchymal stem cells. Their administration into the suprarenal aorta after reflow significantly protected renal function and hastened repair, mediated by complex antiapoptotic, mitogenic, anti-inflammatory, and immune modulating actions that were not elicited by isogeneic fibroblasts. Infused mesenchymal stem cells, recruited to renal sites of injury, did not significantly differentiate into target cells but rather disappeared from kidneys and other organs within 72 h. Furthermore, at 3 months, compared with vehicle-treated controls, renal function was well preserved and interstitial fibrosis was absent. These preclinical data served as the scientific basis for a recently completed Phase I Clinical Trial (http://www.clinicaltrials.gov; # NCT00733876), in which patients at high risk for cardiac surgery-associated AKI were treated with allogeneic mesenchymal stem cells. Until now, MSC therapy in the study subjects has been safe, and none of the patients has developed postoperative AKI or subsequent loss of renal function, suggesting that this novel form of therapy may have promise in this group of high-risk patients, which will be further investigated in a Phase II Trial.
Abstract 3378: Glutaminase activity determines cytotoxicity of L-asparaginases on leukemia cell lines
Authors: Jean-Hugues Parmentier, Maristella Maggi, Erika Tarasco, Claudia Scotti, Vassilios Avramis, Steven D. Mittelman
Journal: Cancer Research (2014)

Abstract L-Asparaginase (ASNase) is a front-line chemotherapy for acute lymphoblastic leukemia (ALL), which acts by deaminating asparagine (Asn) and glutamine (Gln). We and others have shown that its cytotoxicity depends more on Gln than Asn depletion. Novel ASNases with different activities have been developed in an attempt to decrease side effects and allergic reaction. To evaluate the importance of glutaminase activity, we developed a novel form of Helicobacter pylori ASNase (dm HpA) using site-directed mutagenesis, with amino acid substitutions M121C/T169M. This mutant form was designed to have the same asparaginase activity as wild type (wt), but lack glutaminase activity. WT and dm HpA were compared with the clinically used ASNases from E. coli (EcA-II) and Erwinia chrysanthemi (ErA). Asparaginase and glutaminase activities of each enzyme were measured with Nessler's assay at pH 8.6. The ratio of glutaminase/asparaginase activity was 1.4% for dm HPase, 7.5% for wt HPase, 41% for EcA-II, and 99% for ErA (at 0.6 IU), respectively. L-Asparaginases (0.01 to 3 IU/ml over 72 hrs) were tested on 8 human leukemia cell lines: pre B ALL (BV173, Nalm-6, RCH-ACV, RS4;11, SEM, SupB15), T cell ALL (Molt-4), and acute promyelocytic leukemia (HL-60). Viable cells were determined by trypan blue exclusion. Two cell lines which we had previously shown to be Asn-dependent (RS4;11 and SupB15) were equally sensitive to the asparaginase isoforms (&amp;gt;90% kill at 0.03 IU/mL). The other 6 lines were more sensitive to isoforms with higher glutaminase activities (Table). ErA was the most effective on all three cell lines on which it was tested. These data show that asparaginase activity alone may not be sufficient for ASNase cytotoxicity, and that glutaminase activity may be required for full efficacy. These sensitivities to ASNases match previous data on Asn- and Gln-dependent cell proliferation (Ehsanipour et al., Cancer Research, 2013). % cell growth inhibition at 3 IU/ml ASNase (n=1-2 for each cell line; nd: not done)Cell linedm HpAwt HpAEcA-IIErARS4;11919291ndSupB15919193ndRCH-ACV13362866SEM22484165BV17324326ndNalm-61621574HL-60204033ndMolt4325963nd Citation Format: Jean-Hugues Parmentier, Maristella Maggi, Erika Tarasco, Claudia Scotti, Vassilios Avramis, Steven D. Mittelman. Glutaminase activity determines cytotoxicity of L-asparaginases on leukemia cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3378. doi:10.1158/1538-7445.AM2014-3378
Anti-CD4 mediates clonal anergy during transplantation tolerance induction.
Authors: S E Alters, J A Shizuru, J Ackerman, D Grossman, K B Seydel, C G Fathman
Journal: The Journal of Experimental Medicine (1991)

Depletion of CD4+ cells using anti-CD4 monoclonal antibodies leads to allograft tolerance. Here we show that anti-CD4-mediated tolerance to pancreatic islets of Langerhans transplanted from an A/J (IEk) donor to a diabetic C57B1/6 (B6) (IE-) recipient occurs in the absence of clonal deletion of the potentially IE-reactive V beta 11+ T cells. Instead, a state of clonal anergy is induced in both the CD4+V beta 11+ and CD8+V beta 11+ T cell subsets. This clonal anergy can be partially overcome in vitro by the addition of recombinant interleukin 2.
Changing Physician Prescribing Practices
Authors: Robert L. Kane, Judith Garrard
Journal: JAMA (1994)

Changing physicians' behavior is not easy.<sup>1</sup>Although we would like to believe in a world where health professionals incorporate well-analyzed valid information into their daily practices, in fact, putting scientifically vetted information to use is slow and arduous. Translating consensus conference results into practice has proven a greater challenge than reaching consensus.<sup>2,3</sup>The guidelines now being promulgated by the Agency for Health Care Policy and Research face the same difficulties.
Asphyxiation, Bulimia, and Insulin Levels in Huntington Disease (Chorea)
Authors: John R. Whittier
Journal: JAMA (1976)

<h3>To the Editor.—</h3> It is well known that patients with Huntington disease (hereditary chorea) frequently die because of asphyxiation or bronchopneumonia following aspiration of food at mealtime. This is usually due to dysphagia resulting from chorea and from pseudobulbar paresis that interferes with chewing and swallowing, breathing, and the coordination of these functions, which may be compounded by hasty spoon-feeding, even of pureed diet, during short mealtimes. Unfortunately, in some cases, but not all, bulimia is a striking symptom among those affected by Huntington disease. Voracious appetite is then added to the feeding handicaps. The symptom has usually been thought to be an obvious result of an increased need for additional energy arising from chorea, but bulimia is often present with obesity and very little chorea. There are recent conflicting data, the resolution of which might add to our knowledge of the symptom of bulimia. Podolsky et al<sup>1</sup>reported
Angiographic Diagnosis of Traumatic Head and Neck Lesions
Authors: John A. Campbell
Journal: JAMA (1961)

An analysis of the diagnostic yield of angiography for head and neck trauma showed that this safe method should be offered to any patient with a deteriorated neurological state, even if comatose. Indications were cases of suspected chronic subdural hematoma, progressive neurologic signs after head injury, and neck trauma with neurological deficits. Contraindications included infants, patients in shock, and those with rapidly clearing sensorium. Angiography permitted a more adequate surgical approach to traumatic lesions and reduced the incidence of negative trephinations. Angiography provides the best method of diagnosing and localizing interhemispheric and intracerebral hematomas associated with subdural hematomas, traumatic arteriovenous fistulas, and vascular trauma in the neck. The use of low carotid, brachial, or subclavian injection of contrast medium has demonstrated angiographically specific lesions of the neck vasculature.
Videotaping of general practice consultations: effect on patient satisfaction
Authors: L M. Campbell, F. Sullivan, T S. Murray
Journal: BMJ (1995)

Videotaping of general practice consultations has assumed a high profile recently with its proposed use in summative assessment of general practice trainees, fellowship by assessment, and the membership examination of the Royal College of General Practitioners. The presence of a video camera does not alter doctors' behaviour,1 2 and most patients are happy to give consent to videotaping.3 Videotaping might, however, adversely affect the consultation from the patient's point of view: one study found that most patients would feel uncomfortable during consultations that were being videotaped.4

We compared patient satisfaction scores after videotaped consultations and after consultations that were not videotaped, on the basis that if patiens felt …
Sharing of Antigenic Determinants between the Nicotinic Acetylcholine Receptor and Proteins in<i>Escherichia coli, Proteus vulgaris,</i>and<i>Klebsiella pneumoniae</i>
Authors: Kari Stefansson, Michael E. Dieperink, David P. Richman, Christopher M. Gomez, Linda S. Marton
Journal: New England Journal of Medicine (1985)

THE causes of autoimmune diseases in human beings are in most instances unknown. There are, however, countless hypotheses about what may be responsible for an immunologic attack on autoantigens during autoimmune processes. Some of these hypotheses involve infectious agents. One popular notion is that many autoimmune diseases may be caused directly or indirectly by viral infections.1 , 2 Viruses may launch autoimmune processes by altering the host's immune system, by causing the release or expression of sequestered antigens, or through antigenic determinants shared by the virus and the host cells. There is now considerable published evidence that antigenic determinants are shared by . . .
P252 Once-daily NVA237 improves symptoms, and reduces COPD exacerbations and associated hospitalisations: the GLOW1 trial
Authors: A. D'Urzo, J. A. van Noord, C. Martin, R. Horton, D. Banerji, Y. Lu, V. K. T. Alagappan, T. Overend
Journal: Thorax (2011)

<h3>Introduction</h3> Symptoms profoundly impact daily life of COPD patients. We assessed the influence of the once-daily (qd) long-acting muscarinic antagonist (LAMA) NVA237 (glycopyrronium bromide) on symptoms and exacerbations in patients with moderate-to-severe COPD. <h3>Methods</h3> Patients were randomised (2:1) to 26 weeks double-blind treatment with NVA237 50 μg qd or placebo (PBO) via a single-dose dry powder inhaler (Breezhaler<sup>®</sup> device). Efficacy was assessed by bronchodilation (trough FEV<sub>1</sub> at Week 12), breathlessness on the transition dyspnoea index (TDI), HRQoL via the St. George9s Respiratory Questionnaire (SGRQ), and rescue medication use. The effect on COPD exacerbations and related hospitalisations was also assessed. <h3>Results</h3> 822 patients were randomised; 80.5% completed. NVA237 significantly increased total TDI focal score vs PBO at Week 26 (difference 1.04, 95% CI 0.583 to 1.504; p&lt;0.0001); exceeding the minimum clinically important difference ([MCID] =1 point). Significantly more patients achieved MCID in TDI score with NVA237 (61.3% vs 48.3%; OR 1.74, 95% CI 1.249 to 2.415; p=0.001). SGRQ total score was significantly reduced with NVA237 (−2.81; p=0.004); % of patients achieving a clinically meaningful improvement in SGRQ (=4 point reduction) was significantly higher with NVA237 (56.8% vs 46.3%; OR 1.58, 95% CI 1.138 to 2.196; p=0.006). NVA237 significantly reduced rescue medication use at Week 26 (−0.46 puffs/day, p=0.005). NVA237 significantly prolonged time to first moderate/severe COPD exacerbation by 31% (HR 0.69, 95% CI 0.50 to 0.949; p=0.023) and time to first severe COPD exacerbation necessitating hospitalisation (HR 0.35, 95% CI 0.141 to 0.857; p=0.022). NVA237 significantly reduced hospitalisations due to COPD exacerbation (OR 0.34; p=0.024). <h3>Conclusion</h3> Once-daily NVA237 provided significant improvements in dyspnoea and SGRQ total score, with lower rescue medication use, and reduced risk of exacerbation and associated hospitalisations vs PBO.
<i>Neuropilin-1</i> Stimulates Tumor Growth by Increasing Fibronectin Fibril Assembly in the Tumor Microenvironment
Authors: Usman Yaqoob, Sheng Cao, Uday Shergill, Kumaravelu Jagavelu, Zhimin Geng, Meng Yin, Thiago M. de Assuncao, Ying Cao, Anna Szabolcs, Snorri Thorgeirsson, Martin Schwartz, Ju Dong Yang, Richard Ehman, Lewis Roberts, Debabrata Mukhopadhyay, Vijay H. Shah
Journal: Cancer Research (2012)

The tumor microenvironment, including stromal myofibroblasts and associated matrix proteins, regulates cancer cell invasion and proliferation. Here, we report that neuropilin-1 (NRP-1) orchestrates communications between myofibroblasts and soluble fibronectin that promote α5β1 integrin-dependent fibronectin fibril assembly, matrix stiffness, and tumor growth. Tumor growth and fibronectin fibril assembly were reduced by genetic depletion or antibody neutralization of NRP-1 from stromal myofibroblasts in vivo. Mechanistically, the increase in fibronectin fibril assembly required glycosylation of serine 612 of the extracellular domain of NRP-1, an intact intracellular NRP-1 SEA domain, and intracellular associations between NRP-1, the scaffold protein GIPC, and the nonreceptor tyrosine kinase c-Abl that augmented α5β1 fibronectin fibril assembly activity. Analysis of human cancer specimens established an association between tumoral NRP-1 levels and clinical outcome. Our findings indicate that NRP-1 activates the tumor microenvironment, thereby promoting tumor growth. These results not only identify new molecular mechanisms of fibronectin fibril assembly but also have important implications for therapeutic targeting of the myofibroblast in the tumor microenvironment.
Abstract PL4-1: Immunotherapy of established lesions caused by high-risk HPV
Authors: C.J.M. Melief, M.J.P. Welters, A.R.P.M. Valentijn, T.M.A. Berends-van der Meer, M.J.G. Löwik, A.P.G. Vloon, F. Essahsah, L.M. Fathers, R. Offringa, J.W. Drijfhout, J. Oostendorp, G.J. Fleuren, S.H. van der Burg, G.G. Kenter
Journal: Clinical Cancer Research (2010)

Abstract Therapeutic vaccination with a synthetic long peptide (SLP®) vaccine mediated the eradication of established human papilloma virus type 16 (HPV16)-positive tumors in mice and controlled wart growth and latent virus infection in rabbits persistently infected with cottontail rabbit papilloma virus. Subsequent phase I/II studies with an HPV16 SLP® vaccine, consisting of 13 long peptides covering the HPV16 E6 and E7 antigens, in patients with advanced HPV16-positive cervical cancer, revealed that this vaccine was safe and highly immunogenic. The purpose of the current study was to test the clinical efficacy of this HPV16 SLP® vaccine in HPV16-induced high grade vulvar intraepithelial neoplasia (VIN3), a premalignant epithelial disorder, spontaneous regression of which occurs in less than 2% of patients and in which recurrence after standard treatment is high. In a phase 2 trial, 20 women with VIN3 were vaccinated three times sc in the limbs with a mix of the HPV16 E6 and E7 synthetic long peptides formulated in Montanide ISA-51. The endpoints were objective clinical responses, defined as reduction of at least 50% in lesion size (partial response) or complete regressions, and HPV16-specific T-cell responses, determined before and after vaccination. The vaccine was safe, as no side effects exceeding CTC grade 2 were observed. At 3 and 12 months after the last vaccination an objective response was observed in 12/20 (60%) and 15/19 (79%) patients respectively. Nine of them showed a complete and durable regression of the lesions at 12 months and at 24 months. The strength of the vaccine-induced HPV16-specific T-cell response was significantly higher in the group of patients with a complete regression of their lesions as compared to non-responders. This study shows that in women with VIN3 objective clinical responses can be achieved by therapeutic vaccination with synthetic long peptides that is able to induce effective HVP16-specific T-cell responses. Citation Information: Clin Cancer Res 2010;16(7 Suppl):PL4-1
Postmenopausal Hormone Therapy and Risk of Stroke
Authors: Joel A. Simon, Judith Hsia, Jane A. Cauley, Cynthia Richards, Fran Harris, Josephine Fong, Elizabeth Barrett-Connor, Stephen B. Hulley
Journal: Circulation (2001)

Background —Observational studies have shown that postmenopausal hormone therapy may increase, decrease, or have no effect on the risk of stroke. To date, no clinical trial has examined this question. To investigate the relation between estrogen plus progestin therapy and risk of stroke among postmenopausal women, we analyzed data collected from the Heart &amp; Estrogen-progestin Replacement Study (HERS), a secondary coronary heart disease prevention trial. Methods and Results —Postmenopausal women (n=2763) were randomly assigned to take conjugated estrogen plus progestin or placebo. Primary outcomes for these analyses were stroke incidence and stroke death during a mean follow-up of 4.1 years. The number of women with strokes was compared with the number of women without strokes. A total of 149 women (5%) had 1 or more strokes, 85% of which were ischemic, resulting in 26 deaths. Hormone therapy was not significantly associated with risk of nonfatal stroke (relative hazard [RH] 1.18; 95% CI 0.83 to 1.66), fatal stroke (RH 1.61; 95% CI 0.73 to 3.55), or transient ischemic attack (RH 0.90; 95% CI 0.57 to 1.42). Independent predictors of stroke events included increasing age, hypertension, diabetes, current cigarette smoking, and atrial fibrillation. Black women were at increased risk compared with white women, and unexpectedly, body mass index was inversely associated with stroke risk. Conclusions —Hormone therapy with conjugated equine estrogen and progestin had no significant effect on the risk for stroke among postmenopausal women with coronary disease.
Rubella Virus Transport In Pregnancy
Authors: Marvin S. Amstey
Journal: JAMA (1974)

<h3>To the Editor.—</h3> The article by Fleet et al (227:621, 1974) demonstrating isolation of rubella virus from the eye of an aborted fetus is interesting and important. It clearly demonstrates that vaccine virus crosses the placenta and is probably teratogenic. However, a discrepancy requires clarification. It is stated that a saline abortion was done at 13 weeks of gestation. Without information on the patient's last menstrual period and uterine size, it is difficult to comprehend that the amniotic cavity could be located with ease, and hypertonic saline injected at 13 weeks of gestation. In keeping with the concept that this patient may have been more than 13 weeks pregnant, and was<i>vaccinated within three weeks of conception</i>, is the unlikely possibility that rubella vaccine virus will persist seven weeks as a viremia and be disseminated transplacentally to the conceptus. The original vaccine trials by Meyer et al (<i>N Engl J Med</i>