tbuckley/cabot-search huggingface dataset:
Abnormal Myocardial Phosphorus-31 Nuclear Magnetic Resonance Spectroscopy in Women with Chest Pain but Normal Coronary Angiograms
Authors: Steven D. Buchthal, Jan A. den Hollander, C. Noel Bairey Merz, William J. Rogers, Carl J. Pepine, Nathaniel Reichek, Barry L. Sharaf, Steven Reis, Sheryl F. Kelsey, Gerald M. Pohost
Journal: New England Journal of Medicine (2000)

After hospitalization for chest pain, women are more likely than men to have normal coronary angiograms. In such women, myocardial ischemia in the absence of clinically significant coronary-artery obstruction has long been suspected. Most methods for the detection of the metabolic effects of myocardial ischemia are highly invasive. Phosphorus-31 nuclear magnetic resonance (31P-NMR) spectroscopy is a noninvasive technique that can directly measure high-energy phosphates in the myocardium and identify metabolic evidence of ischemia.
The Nephrotic Syndrome in Children with Diabetes Mellitus of Recent Onset
Authors: Rodrigo E. Urizar, Alicia Schwartz, Franklin Top, Robert L. Vernier, Susan P. Sisson
Journal: New England Journal of Medicine (1969)

In five children a nephrotic syndrome developed within one month (three cases), 11 months, and 10 years of the onset of diabetes mellitus. The syndrome, which responded to steroid therapy, was morphologically typical of the idiopathic nephrotic syndrome of childhood. In all patients light, fluorescence and electron microscopy performed on the initial kidney-biopsy specimens demonstrated normal glomerular basement-membrane thickness and early mesangial and arteriolar changes compatible with diabetes mellitus. Although this may represent a chance association, a metabolic defect in the basement membrane common to both diabetes mellitus and the nephrotic syndrome remains a possibility.
Osborn Waves of Hypothermia
Authors: A Patel, J Getsos
Journal: New England Journal of Medicine (1994)

Figure 1. Osborn Waves of Hypothermia. 12-lead electrocardiogram and rhythm strip were obtained in a 40-year-old alcoholic man with a core body temperature of 29 °C (84 °F) because of accidental exposure to the cold (Panel A). The tracing shows a bradycardic rhythm (probably sinus), prolonged QT intervals, a base-line artifact due to muscle tremors, and distinctive and characteristic Osborn waves (arrows). A second 12-lead electrocardiogram and rhythm strip obtained after the patient was rewarmed to 37.2 °C (99 °F) show sinus rhythm (Panel B). Both the Osborn waves and base-line artifact are absent. The QT interval is normal for . . .
Case 7-2004
Authors: Hensin Tsao, Arthur J. Sober, Kristin Baker Niendorf, Artur Zembowicz
Journal: New England Journal of Medicine (2004)

A 48-year-old woman with multiple pigmented skin lesions and a personal and family history of melanoma had been followed since the age of 32 in a clinic specializing in pigmented lesions. This Case Record reviews the classifications of familial mole and melanoma syndromes and discusses the role of genetic testing and the approach to management for this patient and her family.
Case 32-2007
Authors: Eric P. Winer, Jay R. Harris, Barbara L. Smith, Helen Anne D'Alessandro, Elena F. Brachtel
Journal: New England Journal of Medicine (2007)

A 62-year-old woman with a history of breast cancer was found to have a mass in the contralateral breast on magnetic resonance imaging performed for follow-up of the first cancer. Excision of the mass and examination of the biopsy specimen showed infiltrating and in situ ductal carcinoma, grade 3 of 3, positive for human epidermal growth factor receptor 2. Options for management are discussed in a multidisciplinary setting.
Knowledge Gaps in Cardiovascular Care of the Older Adult Population
Authors: Michael W. Rich, Deborah A. Chyun, Adam H. Skolnick, Karen P. Alexander, Daniel E. Forman, Dalane W. Kitzman, Mathew S. Maurer, James B. McClurken, Barbara M. Resnick, Win K. Shen, David L. Tirschwell
Journal: Journal of the American College of Cardiology (2016)
Exaggerated Response to Infused Norepinephrine in Familial Dysautonomia
Authors: Alfred A. Smith, Joseph Dancis
Journal: New England Journal of Medicine (1964)

FAMILIAL dysautonomia is an inherited disease with a complex but fairly well defined symptomatology. Alacrima, postural hypotension, poor motor co-ordination and a relative indifference to pain are among the more prominent and consistent symptoms. The disease commonly affects siblings and is largely if not entirely restricted to Jews.1 A previous study has demonstrated that in dysautonomia, the urinary excretion of homovanillic acid is increased and that of vanillyl-mandelic acid is decreased,2 suggesting that such patients may suffer from a deficiency of endogenous epinephrine and norepinephrine. Chronic deficiency of norepinephrine may lead to increased sensitivity of adrenergic receptors.3 The possibility that . . .
Functional Gastrointestinal Disorders: Lessons Learned from Military Medicine
Authors: James A. Halsted
Journal: New England Journal of Medicine (1946)

IT HAS long been customary to treat functional gastrointestinal disorders by means of smooth diets, antispasmodics, sedatives and rest. Hospitalization is sometimes recommended in severe cases. Experience in the management of soldiers with these disorders demonstrated that this type of treatment was not only unsuccessful in relieving symptoms but also harmful from a military point of view because it rendered the men unnecessarily ineffective as soldiers. The reason for this was that at least 80 per cent of the cases were psycho-genic. Dealing with the personality disturbance directly and promptly, with a minimum of emphasis on medical study and organic . . .
Cytokeratin 19, a Cancer Stem Cell Marker in Hepatocellular Carcinoma
Authors: T. Kawai, K. Yasuchika, T. Ishii, H. Katayama, E.Y. Yoshitoshi, S. Ogiso, S. Kita, K. Yasuda, K. Fukumitsu, M. Mizumoto, E. Hatano, S. Uemoto
Journal: Annals of Oncology (2014)
Efficacy Of Bendamustine and Rituximab In Patients With Relapsed/Refractory Chronic Lymphocytic Leukemia
Authors: Elena Kataeva, Anatoly Golenkov, Elena Triphonova, Galina Dudina, Tatyana Mitina, Tatyana Lutskaya, Ludmila Vysotskaya, Yulliya Chernykh, Sergey Zakharov
Journal: Blood (2013)
Philadelphia chromosome mosaicism in chronic granulocytic leukemia.
Authors: Z A Arlin, S Jhanwar, B Clarkson
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.7.1149 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3459813 Philadelphia chromosome mosaicism in chronic granulocytic leukemia. Z A ArlinxZ A ArlinSearch for articles by this author , S JhanwarxS JhanwarSearch for articles by this author , B ClarksonxB ClarksonSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.7.1149 PDF "Philadelphia chromosome mosaicism in chronic granulocytic leukemia.." Journal of Clinical Oncology, 4(7), pp. 1149–1150© 1986 by American Society of Clinical Oncology
Neutrophils and Emphysema
Authors: Stephen E. McGowan, Gary W. Hunninghake
Journal: New England Journal of Medicine (1989)

IN this issue of the Journal, MacNee and associates1 report that intense cigarette smoking for about half an hour was associated with the retention of circulating neutrophils in the lungs of the smokers. This was not so in a similar group of cigarette smokers who abstained from smoking for at least one hour or in nonsmokers. This observation is consistent with evidence that neutrophils are important in the pathogenesis of emphysema associated with cigarette smoking.In 1963, Laurell and Erickson observed that subjects whose serum was deficient in α1-antitrypsin, now more appropriately referred to as α1 . . .
P61 Respiratory ill health in the silica exposed brick manufacturing sector
Authors: D Fishwick, J Sumner, CM Barber, E Robinson, A Codling, L Lewis, C Young, N Warren
Journal: Thorax (2015)

<h3>Introduction</h3> Exposure at work to inhaled respirable crystalline silica (RCS) has previously been linked with silicosis, tuberculosis, lung cancer and COPD. Whilst the risk of developing silicosis is largely a function of cumulative lifetime RCS exposures, current workplace exposures contribute to this risk. <h3>Methods</h3> A cross sectional GB based workplace study of brick manufacturers was carried out, in order to identify a subsequent longitudinal cohort. Participating worksites were using silica to make bricks for various uses. Consenting workers were asked to complete an interviewer led questionnaire, undergo lung function testing and complete a full occupational history including details of lifetime exposure to RCS. Consenting workers had a PA Chest Radiograph using a mobile facility, and levels of RCS exposure in the personal breathing zone were taken. <h3>Results</h3> 189 workers took part, with a mean age of 45.9 years and 22 years median (range 0.08–47) years worked overall in industry. Three had radiological evidence of silicosis (ILO standards used; 2 definite and one probable case). Respiratory symptoms were common; for example 14.3% reported cough, 21.2% wheeze in the last 12 months, 14.3% reported ever having asthma. 13.2% reported at least one work related respiratory symptom. Mean lung function values were as follows; mean (SD) percentage predicted FEV<sub>1</sub> 98.1 (15.2) and FVC 102.4 (13.9). Fourteen workers had measured airways obstruction (as defined by an FEV<sub>1</sub>/FVC &lt;0.7); in this cross sectional analysis its presence did not significantly relate to current smoking status or lifetime duration of RCS exposure, although was significantly associated with an increased time worked in the current work area. Airways obstruction was also associated with the reporting of a diagnosis of (ever having) asthma and wheeze in the last 12 months. <h3>Conclusions</h3> This cross sectional study of silica exposed brick workers has identified a cohort for longer term follow up. Future work will allow the development of dose response relationships, corrected for other relevant factors, between cumulative RCS exposure and FEV<sub>1</sub> decline and will assist in the development of workplace interventions to reduce the health risks associated with RCS exposure in this group of workers.
Final results from a phase I study of oral TRC102 (methoxyamine HCl), an inhibitor of base-excision repair, to potentiate the activity of pemetrexed in patients with refractory cancer.
Authors: G. J. Weiss, M. S. Gordon, L. S. Rosen, P. Savvides, B. J. Adams, D. Alvarez, L. Liu, Y. Xu, S. L. Gerson, B. R. Leigh
Journal: Journal of Clinical Oncology (2010)

2576 Background: TRC102 is a small-molecule inhibitor of base-excision repair (BER) that is nearly completely bioavailable after oral administration. TRC102 covalently binds to apurinic/apyrimidinic (AP) sites induced by alkylator or antimetabolite chemotherapy. TRC102-bound DNA is not a substrate for BER enzymes and is instead cleaved by topoisomerase II resulting in double-strand breaks that trigger apoptosis. Methods: The safety, pharmacokinetics (PK), and pharmacodynamics (PD) of oral TRC102 combined with i.v. pemetrexed was evaluated in patients with advanced refractory cancer. Patients were required to have ECOG PS ≤ 1 and adequate organ function. TRC102 alone was administered on days 1- 4 of a 2-week cycle followed by TRC102 (D1-4) and 500 mg/m2 pemetrexed (D1) every 3 weeks thereafter. Results: 28 patients were enrolled and treated with a total of 93 cycles of TRC102 at 15 mg/m2 (n=4), 30 mg/m2 (n=7), 60 mg/m2 (n=11) and 100 mg/m2 (n=6). The maximum tolerated dose (MTD) was exceeded at 100 mg/m2 due to grade 3 anemia in 50% of patients. No other DLTs were reported. Other adverse events possibly related to TRC102 included grade 3/4 neutropenia without fever, grade 3 thrombocytopenia, grade 1/2 fatigue, and grade 1/2 asthenia. TRC102 plasma concentrations required for in vivo activity were achieved at all dose levels studied (Cmax > 50 ng/mL, t3/4 > 24 hr). PD studies confirmed that TRC102 binds pemetrexed-induced AP sites. One patient at 30 mg/m2 TRC102 with tonsillar squamous cell cancer metastatic to the lung had RECIST-defined PR that is ongoing in cycle 14. Stable disease for ≥ 3 cycles was seen in 3 patients at 30 mg/m2, 2 patients at 60 mg/m2, and 4 patients at 100 mg/m2, including one patient with squamous cell lung cancer who had SD for 9 cycles. Conclusions: Daily oral TRC102 is well-tolerated at doses expected to inhibit BER and potentiate the activity of chemotherapy. The recommended phase II dose is 60 mg/m2 p.o. for 4 days in combination with standard dose pemetrexed. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration TRACON Pharma TRACON Pharma TRACON Pharma TRACON Pharma
Abstract B19: Inactivation of KLF4 in T cell acute lymphoblastic leukemia promotes the expansion of leukemia cells by activating the Map2k7/Jnk pathway.
Authors: Ye Shen, Koramit Suppipat, Chun Shik Park, Toni-Ann Mistretta, Terzah Horton, Karen Rabin, Daniel Lacorazza
Journal: Cancer Research (2016)

Abstract Acute lymphoblastic leukemia is the most common hematological malignancy in pediatric patients, and disease relapse is the leading cause of cancer-associated death in children. Despite steadily improved outcomes in patients with newly diagnosed disease, little progress has been made to treat relapse leukemia and to reduce the incidence of relapse by increasing the cure rates of frontline therapy. Targeted therapy is currently not available for T-ALL and the development of novel agents requires a better understanding of how leukemia-initiating cells (LIC) are maintained. In contrast to normal blood cells, we found that the transcription factor KLF4 is significantly downregulated in pediatric T-ALL. Next-generation bisulfite sequencing revealed that the KLF4 promoter is hypermethylated in lymphoblasts from T-ALL patients but not in normal bone marrow cells, T cells, and pediatric B-ALL. Deletion of the Klf4-floxed gene with Vav-iCre transgene and transplantation of Klf4Δ/Δ bone marrow cells transduced with the Notch1-L1601P-ΔP mutant resulted in a significant acceleration of T-ALL due to a 9-fold expansion of LIC and increased G1-S transition in leukemic T cells. A combined analysis of global gene expression and genome-wide binding revealed that KLF4 directly represses the dual specificity mitogen-activated protein kinase 7 (Map2k7) and thus Klf4Δ/Δ T-ALL mice exhibit increased Map2k7 expression. Most remarkably, T-ALL cells from both mouse model and pediatric patients showed elevated levels of total and phosphorylated Map2k7 and subsequent activation of downstream targets JNK, c-Jun, and ATF2. Finally, we tested several JNK inhibitors in T-ALL cell lines, primary patient samples, and pre-clinical xenograft models of T-ALL and confirmed that JNK inhibition blocks ATF2 activation and controls expansion of leukemia cells, validating the Map2k7/Jnk pathway as a selective target for T-ALL therapy. Thus, KLF4 emerges as a novel tumor suppressor in T-ALL and Jnk inhibition as a novel therapeutic approach for adjunctive therapy in T-ALL patients with refractory or relapse disease. Citation Format: Ye Shen, Koramit Suppipat, Chun Shik Park, Toni-Ann Mistretta, Terzah Horton, Karen Rabin, Daniel Lacorazza. Inactivation of KLF4 in T cell acute lymphoblastic leukemia promotes the expansion of leukemia cells by activating the Map2k7/Jnk pathway.. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Pediatric Cancer Research: From Mechanisms and Models to Treatment and Survivorship; 2015 Nov 9-12; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(5 Suppl):Abstract nr B19.
The Effect of 12/15-Lipoxygenase on Expression of Selected Genes during Dermatophagoides Pteronyssinus Induced Airway Inflammation in Mice
Authors: Krzysztof Kowal, Pawel Bernatowicz, Pawel Bielecki, Ewa Sacharzewska, Lech Chyczewski, Jacek Niklinski, Otylia Kowal-Bielecka
Journal: Journal of Allergy and Clinical Immunology (2016)
In silico design of novel anticancer antibody mimetic molecules targeting HER2
Authors: H. Nakajima, S. Tanuma, I. Fujiwara, N. Mizuta, K. Sakaguchi
Journal: Journal of Clinical Oncology (2007)

14149 Background: HER2 is a unique receptor molecule for which no ligand has been found and functions as a coreceptor to form homo-and hetero-dimers with other three HER (1, 3 and 4) family members. The dimerization results in the activation of HER tyrosine kinase. This, in turn, promotes the tyrosine phosphorylation of certain proteins, leading to the stimulation of cell proliferation, invasion, and antiapoptosis. The overexpression of HER2 in breast cancer correlates with increased tumor growth and metastatic potential, and thereby poor long-term survival for the patient. A monoclonal antibody against HER2, named trastuzumab, is approved for breast cancer patients, while pertuzumab is currently in phaseIIclinical trial. The two antibodies bind to different epitopes in the extracellular domains of HER2. Trastuzumab binding mainly mediates the antibody-dependent cytotoxicity (ADCC). On the other hand, pertuzumab binding directly inhibits HER2 dimerization with its partner receptors, blocking the growth signaling and inducing apoptosis. Furthermore, the unique binding pockets on HER2 for trastuzumab and pertuzumab have been resolved and provide the important target domains for creation of new anticancer drugs. Methods: Based on these mechanisms, we are trying to design and create both antibodies-mimetic molecules using our in silico methodologies COSMOS (Conversion to small molecules through optimized-peptide strategy) and SARM (Self-assembling regulatory molecule). We design HRAP (HER2 reactive peptide)- SARM and HRAP- SARM- FAB (Fc?-binding peptide). HRAP-SARM may bind to HER2 pertuzumab binding site and sterically interferes with HER2 dimerization and induces apoptosis. HRAP- SARM- FAB is expected to induce both ADCC and apoptosis. Results and Conclusion: In this presentation, we will show the preliminary results and functions of the Ab-mimetics, HRAP- SARM and HRAP- SARM- FAB on human breast cancer cells overexpressing HER2, as compared to those of trastuzumab and pertuzumab. Since those Ab-mimetics are small molecules and cheap, the successful results are sure to promise the revolutionary therapy for refractory breast cancer. No significant financial relationships to disclose.
Fibrin degradation by rtPA enhances the delivery of nanotherapeutics to A549 tumors in nude mice
Authors: Bo Zhang, Ting Jiang, Xiaojian She, Shun Shen, Sheng Wang, Jun Deng, Wei Shi, Heng Mei, Yu Hu, Zhiqing Pang, Xinguo Jiang
Journal: Biomaterials (2016)
Assessing the risk for development of Venous Thromboembolism (VTE) in surgical patients using Adapted Caprini scoring system
Authors: Kanchan Bilgi, Anitha Muthusamy, Mohsina Subair, Sanjeev Srinivasan, Arun Kumar, Ramya Ravi, Ranjith Kumar, Sathasivam Sureshkumar, T. Mahalakshmy, Pankaj Kundra, Vikram Kate
Journal: International Journal of Surgery (2016)
Incidence of Cancer in 161 Families Affected by Ataxia–Telangiectasia
Authors: Michael Swift, Daphne Morrell, Ruby B. Massey, Charles L. Chase
Journal: New England Journal of Medicine (1991)

Ataxia—telangiectasia is an autosomal recessive syndrome in which cancers develop in affected homozygotes at a rate approximately 100 times higher than in unaffected age—matched subjects. Retrospective studies have shown that persons heterozygous for the ataxia—telangiectasia gene, who make up about 1 percent of the general population, also have an excess risk of cancer, particularly breast cancer in women. Patients with ataxia—telangiectasia and cells derived from homozygotes and heterozygotes are unusually sensitive to ionizing radiation.
Resection of the Carina and Main-Stem Bronchi with the Use of Extracorporeal Circulation
Authors: Francis M. Woods, Wilford B. Neptune, Alberto Palatchi
Journal: New England Journal of Medicine (1961)

THE principal use of extracorporeal perfusion has been to make possible operative procedures with-in the heart. Pump oxygenators are used to replace the function of both the heart and lungs while such operations are in progress. Open-heart procedures usually require a pump oxygenator. This technic has not been needed for lung operations because one lung may undergo repair while the other supports ventilation. However, maintenance of ventilation may be inadequate with extensive resections of the trachea or carina. When an operation is indicated in this portion of the pulmonary system the pump oxygenator can make the procedure feasible.It is . . .
PTU-082 Responders to haemopoietic stem cell transplantation for crohn’s disease: Abstract PTU-082 Table 1
Authors: C Hawkey, M Allez, M Clark, M Labopin, J Lindsay, E Ricart, G Rogler, J Satsangi, P Kaye, C Sharratt, D Farge
Journal: Gut (2015)

<h3>Introduction</h3> We recently reported that about one third of patients with Crohn’s disease experience prolonged regression of ileocolonic disease following haemopoietic stem cell transplantation (HSCT). Here we compare the characteristics of responders and non-responders. <h3>Method</h3> Patients with impaired quality-of-life from active Crohn’s disease not amenable to surgery despite treatment with at least 3 immunosuppressive agents all underwent stem cell mobilisation before randomisation to immuno-ablation followed by unselected cyclophosphamide-based conditioning and HSCT after one month (Early HRCT) or one-year (Delayed HS CT). Patients in whom all endoscopic evidence of Crohn’s disease disappeared (SES-CD score of zero) were classified as Responders. Supporting histology was available in 17 of them. <h3>Results</h3> Forty four patients with ileocolonic involvement underwent mobilisation before randomisation to Early or Delayed HSCT. Of 38 patients that could be classified 14 were Responders. Ten had SES-CD of zero after 1 year, (maintained in the second in 3 of 4 with available data) and 4 achieved responder status in year 2. Four of 6 followed to 4 years remain free of Crohn’s disease vs 1 of 15 non-responders. Responders were significantly more likely to have histologically normal segments post HSCT (Table 1) A Responder status tended to be more likely with no family history (39% vs 20%), in non-smokers (54% vs 30%), with early-onset of disease (Montreal A1, 46% vs 32%)) and with more than 10 year history (46% vs 17%); those with pure colonic involvement (L2) were less likely to respond than those with ileal involvement (L1, L3, 14% vs 43%) but these fell short of statistical significance on univariate analysis. <h3>Conclusion</h3> A group of patients can be identified who have a substantial and long lasting regression of Crohn’s disease following HSCT. Endoscopic response following HSCT is associated with regression of histological evidence of Crohn’s disease. <h3>Disclosure of interest</h3> None Declared.