tbuckley/cabot-search huggingface dataset:
Abstract 77: Genetic variations in the stem cell pathway predict for toxicity following radiotherapy in lung cancer.
Authors: Heath D. Skinner, Xia Pu, Joe Chang, Charles Lu, Ritsuko Komaki, Xifeng Wu
Journal: Cancer Research (2013)

Abstract Lung cancer is a devastating malignancy leading to over 150,000 deaths in the US annually. One primary modality in the treatment of locally advanced lung cancer is radiotherapy in combination with chemotherapy. However, this treatment can lead to significant local toxicity in as many as 50% of all patients and, in some cases, is fatal. Though post-radiation toxicity significantly affects adherence to treatment, quality of life and clinical outcome, it is difficult to predict. Further, no genetic markers have yet been found to be useful in a clinical setting. Because stem cell recruitment is part of the post-radiation tissue repair response, we hypothesize that alterations in stem cell signaling may predict for toxicity following radiotherapy. To investigate this question we examined 441 SNPs related to stem cell signaling in the peripheral blood lymphocytes in 159 patients with stage III-IV lung cancer treated with chemoradiotherapy. After adjusting for treatment-related and demographic factors, we found 47 SNPs significantly associated with symptomatic radiation pneumonitis (p&amp;lt;0.05) and 51 SNPs associated with symptomatic esophagitis (p&amp;lt;0.05). For example, patients with at least one risk allele for WNT9Brs:2165846 had a 46% risk of symptomatic pneumonitis, compared to 31% in those who did not, for a 2.23 fold increase in risk (CI: 1.05-4.07, p=0.04). On analysis of a 141 patient validation set with similar characteristics, variant WNT9Brs:2165846 was confirmed to be associated with symptomatic radiation pneumonitis (OR 2.6, CI: 1.1-6.16, p=0.03). Analysis on this confirmation set is ongoing; however, the preliminary results are indicative of the importance of stem cell signaling in modulating repair following radiotherapy and, in combination with clinical factors, may allow for better management of these patients. Citation Format: Heath D. Skinner, Xia Pu, Joe Chang, Charles Lu, Ritsuko Komaki, Xifeng Wu. Genetic variations in the stem cell pathway predict for toxicity following radiotherapy in lung cancer. [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 77. doi:10.1158/1538-7445.AM2013-77
Peripheral blood t-cell subpopulations in the very low birth weight (less than 1,500-g) infant
Authors: Mark Ballow, K. Lynn Cates, Jonelle C. Rowe, Cynthia Goetz, Alexander G. Pantschenko
Journal: American Journal of Hematology (1987)

Abstract The development of monoclonal antibodies to cell‐surface antigens has provided method for characterizing distinct subpopulations of T‐cells. In the present study we have quantified peripheral blood T‐cell subpopulations in premature infants born weighing less than 1,500 g (1123 ± 223 g) and ranging in gestational age from 25 to 32 weeks. The relative proportion of T4 cells in the very low birth weight (VLBW) infants was markedly higher at l week and 1 month of age (mean ± SEM; 67.5 ± 4.1 and 59.2 ± 1.6) than in adult controls (47.2 ± 1.5). The percentage of T4 cells remained elevated until 6 months of age, when it decreased to a level comparable to that in adults. In contrast, the proportion of T8 cells was significantly lower than the adult level at 1 week and 1 month of age. The T4/T8 ratio in the VLBW infants was higher at 1 week (4.3 ± 0.5) and 1 month (3.5 ± 0.2) than in adult controls (2.0 ± 0.1). Thereafter, the T4/T8 ratio decreased but was still significantly higher than that in adult controls at 6 months of age (2.6 ± 0.2). The absolute numbers of total T‐cells (T3) and T8 and T4 cells were significantly higher in VLBW infants. The numbers of T8 cells were significantly lower in the first month of life than at 3‐6 months of age. These alterations in the T‐cell subsets in the first 6 months of life suggest that postnatal T‐cell phenotypic changes in VLBW infants may parallel the T‐cell ontogenetic process which occurs during the last trimester of pregnancy in fullterm infants.
The Effect of Daily Apolipoprotein A-I Mimetic Therapy on T15-Type Autoantibodies Against Oxidized Phosphatidylcholine in a Murine Model of Asthma
Authors: K.S. Konduri, S.D. Nandedkar, D. Weilrauch, D.A. Rickaby, N. Duzgunes, K.A. Pritchard
Journal: Journal of Allergy and Clinical Immunology (2007)
The Medical and Surgical Aspects of Intratracheal Goiter
Authors: Judson Randolph, Jerome A. Grunt, Gordon F. Vawter
Journal: New England Journal of Medicine (1963)

IT is well recognized that thyroid tissue may be ectopically situated in various locations in the neck. Lingual thyroid tissue, thyroglossal-duct remnants and aberrant lateral cervical thyroid have been accurately described. Thyroid tissue that is located within the lumen of the trachea, however, has received only sparse attention in the English literature. In the commonly used textbooks of medicine, pediatrics and surgery little mention is made of intratracheal goiter. In contrast, a survey of the European literature discloses more than 90 case reports and a clinical familiarity with this interesting lesion. Recent study of a patient with an intratracheal goiter . . .
Abstract S2-4: Final Results of a Prospectively Planned Biomarker Analysis: HER1-3 as Predictive Markers of Benefit from Early Treatment with Aromatase Inhibitors Versus Tamoxifen in the TEAM Pathology Sub-Study.
Authors: JMS Bartlett, CL Brookes, CJH van de Velde, D Stocken, FM Campbell, A Hasenburg, C Kay, D Kiebeck, C Markopoulos, E Meershoek-Klein Kranenbarg, EA Mallon, L Dirix, T Robson, C Seynaeve, DW. Rea
Journal: Cancer Research (2010)

Abstract Background: The Tamoxifen and Exemestane Adjuvant Multinational (TEAM) trial included prospectively planned biomarker studies to identify predictive biomarkers for patients receiving endocrine therapy. Quantitative IHC data for ER/PgR, HER1, HER2, HER3 and FISH analysis of HER2 in all cases was available for the current analysis relative to outcome of estrogen receptor-positive (ER+) early breast cancer patients treated with exemestane versus tamoxifen. Patients &amp; Methods: Pathology blocks from 4598 TEAM patients were collected and tissue microarrays constructed. Quantitative analysis of receptors (HER1/2/3) by conventional IHC, and FISH (for HER2 only) were analysed relative to disease-free survival and treatment on an intent to treat basis using survival data for the first 2.75 years of the TEAM trial. Results: Of 4595 eligible cases samples received, 16 were excluded, and 4010 had complete biomarker data for all markers (HER1/HER2 &amp; HER3) for the final biomarker analysis, 3.5% were HER1 positive, 13% HER2 positive &amp; 21% HER3 positive. 1248 (31%) cases were HER1or2or3 positive (HER1-3+ve). HER1-3 positivity was associated with poor outcome (HR=1.6 95%CI=1.3-2.0). In HER1-3 negative patients the hazard ratio (for risk of relapse on exemestane versus tamoxifen in the first 2.75 years) was 0.68 (95% CI = 0.52-0.89), for the HER1-3 positive cases the hazard ratio was 1.14 (95% CI = 0.83-1.56) with a significant treatment by marker interaction (HR=1.68 95%CI=1.1-2.5; p=0.0014 in multivariate analysis). Trends for similar effects were seen for HER1 negative (-ve) vs HER1 positive (+ve) (HRs 0.80, 95%CI=0.65-0.99 vs 1.63 95%CI=0.74-3.59), HER2-ve vs HER2+ve (HRs 0.71, 95%CI=0.57- 0.9 vs 1.69 95%CI=108-2.63) and HER3-ve vs HER3+ve (HRs 0.78 95%CI=0.62-0.99 vs 1.04 95%CI=0.67-1.62) breast cancers. Conclusion: Preferential exemestane versus tamoxifen treatment benefit was seen in HER1/2/3 negative cases, whilst HER1/2/3 positive cases had a poor prognosis in this endocrine treated population (suggesting a degree of resistance to endocrine therapy), and no evidence of additional benefit from AIs versus tamoxifen. These three Type I receptor tyrosine kinases appear to identify breast cancers with relative resistance to all forms of endocrine therapy. This prospectively planned and powered treatment by marker analysis provides high level scientific evidence which may assist clinicians and patients in determining optimal AI schedules for women with early breast cancer. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr S2-4.
Systemic Therapy in the Palliative Management of Advanced Salivary Gland Cancers
Authors: Scott A. Laurie, Lisa Licitra
Journal: Journal of Clinical Oncology (2006)

Cancers of the salivary glands are unusual lesions that vary widely in their histologic appearance and molecular characteristics. Likewise, there is a wide spectrum of biologic behavior, ranging from low-grade, minimally invasive tumors, to highly lethal malignancies. There are few data on the role of systemic therapies in the management of these cancers, and chemotherapy is generally reserved for the palliative management of advanced disease that is not amenable to local therapies such as surgery and/or radiation. The majority of patients for whom systemic therapy is considered will have either adenoid cystic carcinoma, mucoepidermoid carcinoma, or high-grade adenocarcinoma. This article will review the available literature regarding the use of palliative chemotherapy for patients with advanced salivary gland cancer of these histologies, with an emphasis on the potential role of targeted agents. There is a need for a determined, coordinated effort to conduct high-quality clinical trials in patients with these rare cancers.
TCT-607 Sex-related differences in fractional flow reserve guided treatment
Authors: Jing Li, Charanjit Rihal, Yoshiki Matsuo, Muhamad Elrashidi, Andreas Flammer, Moo-Sik Lee, Andrew Cassar, Ryan Lennon, Joerg Herrmann, Malcolm Bell, David Holmes, John Bresnahan, Qi Hua, Lilach O. Lerman, Amir Lerman
Journal: Journal of the American College of Cardiology (2013)
The Air Transportable Hospital
Authors: George O. Lewis
Journal: JAMA (1973)

<h3>To the Editor.—</h3> I read with interest Dr. Gerald A. Faich's article, "Earthquake Brings Health Planning Lessons," inThe Journal(223:733, 1973). I would like to make a few comments regarding the medical care provided by the air transportable hospital. The personnel of the US Air Force's First Tactical Hospital, MacDill AFB, Fla, were notified at 4:00 PM on Dec 23, 1972 that they and the Air Transportable Hospital would be deployed to Managua to provide medical care for the earthquake victims. This Air Force, not US Army, hospital arrived via C-141 aircraft about 7:00 AM on Dec 24, 1972, and arrived on the grounds of the General Hospital at 11:00 AM. It was set up on a baseball field immediately adjacent to the rear of the General Hospital. The hospital had full capability for triage, casting, roentgenography, surgery, command, and two wards by 4:00 PM the afternoon of Dec 24.
Exercise training in patients with chronic heart failure delays ventilatory anaerobic threshold and improves submaximal exercise performance.
Authors: M J Sullivan, M B Higginbotham, F R Cobb
Journal: Circulation (1989)

We have recently demonstrated that exercise training can induce important hemodynamic and metabolic adaptations in patients with chronic heart failure due to severe left ventricular dysfunction. This study examines the accompanying changes in submaximal exercise performance and the ventilatory response to exercise in these patients. Before and after 16-24 weeks of exercise training, subjects underwent two symptom-limited bicycle exercise tests, one with an incremental graded workload, and one with a constant workload that represented 79 +/- 11% of the pretraining peak oxygen consumption. Breath-by-breath expired gas analysis was performed continuously during each test, and central hemodynamic, leg blood flow, and blood lactate measurements were obtained during the incremental protocol. The ventilatory anaerobic threshold was determined during the incremental exercise study from coplotted breath-by-breath ventilatory data with standard criteria by observers who were unaware of patient identity or training status. As previously reported, exercise training increased peak oxygen consumption by 23% from 16.8 +/- 3.8 to 20.6 +/- 4.7 ml/kg/min and reduced blood lactate levels during submaximal exercise. The training-induced decrease in lactate accumulation was accompanied by a decrease in carbon dioxide production, respiratory exchange ratio, and ventilation during submaximal exercise. The ventilatory anaerobic threshold was delayed from 284 +/- 43 to 352 +/- 91 seconds of exercise (p = 0.02), and it occurred at an increased oxygen consumption (10.1 +/- 1.2 vs. 12.1 +/- 2.6 ml/kg/min, p = 0.01). Exercise duration during the constant workload protocol increased from 938 +/- 410 to 1,429 +/- 691 seconds (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Stanley Laurie Kaye
Authors: J. Kaye
Journal: BMJ (2008)

Stanley Laurie Kaye was an exceptional doctor with a diverse and unique practice that could not be emulated in the modern NHS.

He qualified with a gold medal from Charing Cross Hospital in 1943 and then joined the Royal Army Medical Corps, seeing action in Africa and Italy before being captured at Arnhem. As medical officer in the prisoner of war camp, …
Pulmonary Embolism
Authors: Donald V. Baker, Richard Warren, John Homans, David Littmann
Journal: New England Journal of Medicine (1950)

A VOLUMINOUS literature dealing with pulmonary embolism testifies that neither venous interruption nor the use of anticoagulants has entirely prevented this accident. Allen1 observed 12 cases of fatal embolism following femoral-vein interruption in 2578 patients. Deaths from pulmonary embolism during the use of anticoagulants have been reported by Jorpes2 and by Wise et al.3 Physicians, therefore, must still thoughtfully consider the management not only of established thromboembolism but also of postoperative, post-traumatic and decompensated cardiac conditions in which it is commonly encountered.Most published reports have come from clinics where either venous interruption or anticoagulant therapy has been used as . . .
`Catch-up' Hepatitis Protection for Adolescents
Authors: Charles Marwick
Journal: JAMA (1994)

YOUNG ADOLESCENTS are urged to get immunized against hepatitis B. At its October meeting at the Centers for Disease Control and Prevention (CDC), Atlanta, Ga, the Advisory Committee on Immunization Practices unanimously voted to recommend that children who had not been vaccinated against hepatitis B should be immunized by the time they reach age 11 to 12 years. The committee's recommendation is part of a general statement on adolescent immunization that is in the drafting stage and probably will be issued early next year. Hepatitis B vaccine has been available since 1982, yet both acute and chronic hepatitis B infection remain a public health problem (<i>MMWR</i>. 1994; 43:605-608). Vaccination of adolescents has been part of the considered strategy to prevent disease transmission, but reaching this age group has been difficult because they do not routinely attend health care clinics or go to see physicians. "The concept is catch-up immunization. We
EFFICACY OF ANTIARRHYTHMIC DRUGS FOR ATRIAL FIBRILLATION IS DIFFERENTLY DEPENDENT ON LEFT ATRIAL REMODELING
Authors: Hoyoun Won, Hye Jin Hwang, Jaemin Shim, Jae-Sun Uhm, Boyoung Joung, Hui-Nam Pak, Moon-Hyoung Lee
Journal: Journal of the American College of Cardiology (2012)
Adaptive Evolution of Variable Region Genes Encoding an Unusual Type of Immunoglobulin in Camelids
Authors: Chen Su, Viet Khong Nguyen, Masatoshi Nei
Journal: Molecular Biology and Evolution (2002)

A typical immunoglobulin (Ig) molecule is composed of four polypeptide chains: two identical heavy (H) chains and two identical light (L) chains. This tetrameric structure is conserved in almost all jawed vertebrate species. However, it has been discovered that camels and llamas (family: Camelidae) possess a type of dimeric Ig that consists of two H chains only. These H chains do not associate with L chains, and they do not have the first constant region (CH1), which is present in the conventional Ig. In spite of these changes, the dimeric Ig maintains the normal immune function. To understand the evolution of the dimeric Ig, we studied the phylogenetic relationships of the variable region (VHH) genes of the dimeric Ig from Camelidae and those (VH) of the conventional Ig from mammals. The results showed that the VHH genes form a monophyletic cluster within one of the mammalian VH groups, group C. We examined the type of selective force in complementarity-determining regions (CDRs) and framework regions (FRs) by comparing the rate of synonymous (dS) and nonsynonymous (dN) substitutions. We found that the results obtained from VHH genes were similar to those from VH genes in that CDRs showed an excess of dN over dS (indicating positive selection), whereas the reverse was true for FRs (purifying selection). However, when the extent of positive selection or purifying selection was investigated at each codon site, three major differences between VHH and VH genes were found. That is, very different types of selective force were observed between VHH and VH genes (1) at the sites that contact the L chain in the conventional Ig, (2) at the sites that interact with the CH1 region in the conventional Ig, and (3) in the H1 loop. Our findings suggest that adaptive evolution has occurred in the functionally important sites of the VHH genes to maintain the normal immune function in the dimeric Ig.
Comparison of oral iron chelator L1 and desferrioxamine in iron-loaded patients
Authors: N.F. Olivieri, M.H. Freedman, G. Koren, C. Hermann, Y. Bentur, D. Chung, J. Klein, N.F. Olivieri, G. Koren, M.H. Freedman, P. St. Louis, D.M. Templeton, R.A. McClelland, D.M. Templeton
Journal: The Lancet (1990)
Helping Patients to Handle Their Medicines
Authors: M. G. Jacoby
Journal: JAMA (1983)

<h3>To the Editor.—</h3> Twenty-five years ago, I made a house call and, in the patient's kitchen, I found a list of her medications taped to the front of the refrigerator; a pill was to be taken every hour of the day. Horrified at this, I began drawing up charts in the office to help patients with their pills, their tablets, and their medicines. I found it so successful that I had blank forms printed up that can be used for patients taking medications one, two, three, or four times per day (Figure). Many articles on patient compliance seem to be almost adversary procedures. The use of this form, rather, is to be an aid to the patient in working his way through a maze of medicines with the partnership support of his physician. Whenever a patient is taking more than two medications, I make out a form, telling him to
Simvastatin Inhibits Airway Hyperreactivity
Authors: Amir A. Zeki, Lisa Franzi, Jerold Last, Nicholas J. Kenyon
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Rationale: Statin use has been linked to improved lung health in asthma and chronic obstructive pulmonary disease. We hypothesize that statins inhibit allergic airway inflammation and reduce airway hyperreactivity via a mevalonate-dependent mechanism.Objectives: To determine whether simvastatin attenuates airway inflammation and improves lung physiology by mevalonate pathway inhibition.Methods: BALB/c mice were sensitized to ovalbumin over 4 weeks and exposed to 1% ovalbumin aerosol over 2 weeks. Simvastatin (40 mg/kg) or simvastatin plus mevalonate (20 mg/kg) was injected intraperitoneally before each ovalbumin exposure.Measurements and Main Results: Simvastatin reduced total lung lavage leukocytes, eosinophils, and macrophages (P < 0.05) in the ovalbumin-exposed mice. Cotreatment with mevalonate, in addition to simvastatin, reversed the antiinflammatory effects seen with simvastatin alone (P < 0.05). Lung lavage IL-4, IL-13, and tumor necrosis factor-α levels were all reduced by treatment with simvastatin (P < 0.05). Simvastatin treatment before methacholine bronchial challenge increased lung compliance and reduced airway hyperreactivity (P = 0.0001).Conclusions: Simvastatin attenuates allergic airway inflammation, inhibits key helper T cell type 1 and 2 chemokines, and improves lung physiology in a mouse model of asthma. The mevalonate pathway appears to modulate allergic airway inflammation, while the beneficial effects of simvastatin on lung compliance and airway hyperreactivity may be independent of the mevalonate pathway. Simvastatin and similar agents that modulate the mevalonate pathway may prove to be treatments for inflammatory airway diseases, such as asthma.
758. A Multipurpose Vector System for the Simultaneous Screening of Libraries in Bacteria, Insect and Mammalian Cells and Expression In Vivo
Authors: Olli H. Laitinen, Kari J. Airenne, Vesa P. Hytönen, Erik Peltomaa, Anssi J. Mähönen, Thomas Wirth, Miia M. Lind, Kari A. Mäkelä, Pyry I. Toivanen, Diana Schenkwein, Tommi Heikura, Henri R. Nordlund, Markku S. Kulomaa, Seppo Ylä-Herttuala
Journal: Molecular Therapy (2005)

Top of pageAbstract
The post-genomic era necessitates new tools to decode the vast nucleotide sequence data into biologically relevant knowledge. This problem has created a new field in molecular biology and genetics called functional genomics, which addresses the functions of genes and gene products at the level of whole organisms. Viral vector systems have been explored as one solution to solve these problems. We have constructed a new baculovirus expression vector system (BEVS) based tetra-promoter vector (pBVboostFG) that enables screening of gene or cDNA libraries for functional genomic studies. The vector enables an all-in-one strategy for gene expression in mammalian, insect and bacterial cells. In addition, it is also suitable for direct use in vivo in gene therapy. Recombinant virus preparation is based on an improved mini Tn7 transpositional system that allows straightforward and fast production of baculoviruses with high diversity and negligible background.

Genes or cDNAs were cloned into pBVboostFG using the bacteriophage lambda's recombination system and production of 20 different proteins was studied in bacteria, insect and mammalian cells. As an example of using the vector for library screening, a chromophoric Thr65-Tyr-Gly67-stretch of EGFP was destroyed and subsequently restored by PCR and the EGFP library was screened for the color variants.

All studied proteins were efficiently produced using pBVboostFG system and with different expression hosts. In addition, three different fluorescent protein variants were screened out from the generated chromophore library. Finally, the BVboostFG vector was used without any additional subcloning steps to efficiently transduce choroid plexus epithelial cells in rat brain in vivo.

The pBVboostFG system enables easy and efficient production of desired proteins or screening of genome-wide libraries in multiple cell types with one-step cloning. This makes it an efficient new platform technology for functional genomics and gene therapy.