tbuckley/cabot-search huggingface dataset:
Ultradeep Bisulfite Sequencing Analysis of DNA Methylation Patterns in Multiple Gene Promoters by 454 Sequencing
Authors: Kristen H. Taylor, Robin S. Kramer, J. Wade Davis, Juyuan Guo, Deiter J. Duff, Dong Xu, Charles W. Caldwell, Huidong Shi
Journal: Cancer Research (2007)

Abstract We developed a novel approach for conducting multisample, multigene, ultradeep bisulfite sequencing analysis of DNA methylation patterns in clinical samples. A massively parallel sequencing-by-synthesis method (454 sequencing) was used to directly sequence &amp;gt;100 bisulfite PCR products in a single sequencing run without subcloning. We showed the utility, robustness, and superiority of this approach by analyzing methylation in 25 gene-related CpG rich regions from &amp;gt;40 cases of primary cells, including normal peripheral blood lymphocytes, acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). A total of 294,631 sequences was generated with an average read length of 131 bp. On average, &amp;gt;1,600 individual sequences were generated for each PCR amplicon far beyond the few clones (&amp;lt;20) typically analyzed by traditional bisulfite sequencing. Comprehensive analysis of CpG methylation patterns at a single DNA molecule level using clustering algorithms revealed differential methylation patterns between diseases. A significant increase in methylation was detected in ALL and FL samples compared with CLL and MCL. Furthermore, a progressive spreading of methylation was detected from the periphery toward the center of select CpG islands in the ALL and FL samples. The ultradeep sequencing also allowed simultaneous analysis of genetic and epigenetic data and revealed an association between a single nucleotide polymorphism and the methylation present in the LRP1B promoter. This new generation of methylome sequencing will provide digital profiles of aberrant DNA methylation for individual human cancers and offers a robust method for the epigenetic classification of tumor subtypes. [Cancer Res 2007;67(18):8511–8]
A comparative study of the effects of two different doses of nedocromil sodium and placebo given by pressurised aerosol in exercise‐induced bronchoconstriction
Authors: A. Bundgaard, S. D. Enehjelm, A. Schmidt
Journal: Allergy (1988)

Fourteen adult subjects with stable asthma were treated using a double‐blind crossover, randomised protocol, with either nedocromil sodium (4 mg or 2 mg) or placebo. The agents were administered from matched pressurised aerosol inhalers 30 min before exposure to an exercise regimen which, on a previous screening day, resulted in a 24–53% (mean: 33.9%) decrease in peak expiratory flow (PEF). Both doses of nedocromil sodium were significantly superior to placebo in preventing the exercise‐induced decrease in PEF and were without side effects. This study confirms and extends the results of earlier trials with nedocromil sodium and further supports the contention that this new agent may be of benefit in the treatment of reversible obstructive airways disease in the adult patient.
Hypoxia-Inducible Factor-1α Promotes Nonhypoxia-Mediated Proliferation in Colon Cancer Cells and Xenografts
Authors: Duyen T. Dang, Fang Chen, Lawrence B. Gardner, Jordan M. Cummins, Carlo Rago, Fred Bunz, Sergey V. Kantsevoy, Long H. Dang
Journal: Cancer Research (2006)

Abstract Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor that directly transactivates genes important for the growth and metabolism of solid tumors. HIF-1α is overexpressed in cancer, and its level of expression is correlated with patient mortality. Increased synthesis or stability of HIF-1α can be induced by hypoxia-dependent or hypoxia-independent factors. Thus, HIF-1α is expressed in both nonhypoxic and hypoxic cancer cells. The role of HIF-1α in nonhypoxia-mediated cancer cell proliferation remains speculative. We have disrupted HIF-1α by targeted homologous recombination in HCT116 and RKO human colon cancer cells. Loss of HIF-1α significantly reduced nonhypoxia-mediated cell proliferation in vitro and in vivo. Paradoxically, loss of HIF-1α expression did not grossly affect the hypoxic compartments within tumor xenografts in vivo, although HIF-1α promoted cell proliferation and survival under hypoxia in vitro. To further test the role of HIF-1α within tumor compartments, we generated cells with combined disruptions of both HIF-1α and vascular endothelial growth factor (VEGF). In all xenografts, disruption of VEGF led to marked expansion of the hypoxic compartments and growth delay. Nonetheless, the presence or absence of HIF-1α did not grossly affect these expanded hypoxic compartments. These data provide compelling evidence that, in a subset of colon cancers, (a) HIF-1α is a positive factor for nonhypoxia-mediated cell proliferation in vitro and in vivo and (b) HIF-1α is a positive factor for cell proliferation and survival under hypoxic conditions in vitro, but does not grossly contribute to the tumor hypoxic compartments in vivo. (Cancer Res 2006; 66(3): 1684-93)
Preparation of young red cells for transfusion using the fenwal CS 3000 cell separator
Authors: Patricia Pisciotto, Thomas Kiraly, Debra Rosen, Lois Paradis, Ram M. Kakaiya, Edward E. Morse
Journal: American Journal of Hematology (1984)

Abstract A pheresis procedure was devised to isolate young red cells by centrifugation using the Fenwal CS 3000 continuous flow cell separator. Young red cell enriched products were collected in a 2.5–3‐hour procedure. Large numbers of white cells and platelets were collected with the red cells, but cryopreservation and subsequent washing removed 99% of the contaminating cells. At the completion of all processing a product yielding 70% of the total hemoglobin content of a standard frozen/deglycerolized red cell unit was produced. Autologous radiochromium survival of young red cells, measured in 12 normal donors, showed an average 24‐hour recovery of 89.9% with a T 50 Cr of 40.8 days. In paired autologous studies (N = 4) there was a mean increase of 35% in the observed T 50 Cr of young red cells as compared to standard frozen red cells.
A COMBINED WATER AND ALBUMEN METHOD OF FIXING PARAFFIN SECTIONS ON THE SLIDE.
Authors: A. P. OHLMACHER
Journal: JAMA (1893)

Ever since anilin staining methods have been in vogue, there have been demands for a perfect method of fixing sections of tissue on the slide, preparatory to the staining. This demand has arisen from two conditions peculiar to anilin staining processes. The first condition is that only<i>sections</i>of tissue can be stained by any of the processes thus far perfected; that is, it is impossible to stain a piece of tissue in the bulk with the anilin dyes, as can be done with carmine and hematoxylin. The second condition is, that the sections are often so delicate that they are torn or lost in the manipulations required in the process of staining in the watch glass. To meet these difficulties, it has long been the practice of microtomists to secure the sections to the slide; this procedure being termed, "fixing sections on the slide." Numerous methods of fixing sections
Spontaneous Rupture of a Nontraumatic Intrasplenic Aneurysm
Authors: T. C. Windham, S. A. Risin, E. P. Tamm
Journal: New England Journal of Medicine (2000)

To the Editor: Spontaneous rupture of splenic lesions is a well-described complication of infectious, hematologic, and neoplastic diseases.1 Intrasplenic aneurysms are uncommon and have been found ...
1,25 Dihydroxy-Vitamin D_3 in Normal Man and Patients with Renal Failure
Authors: Arnold S. Brickman, Jack W. Coburn, Shaul G. Massry, Anthony W. Norman
Journal: Annals of Internal Medicine (1974)

The actions of 1,25 dihydroxy-vitamin D3 (1,25(OH)2D3), the most active form of vitamin D, were evaluated in 20 trials in 12 normal subjects and in 15 studies in 10 patients with advanced renal failure. The steroid was given orally, 0.027, 0.14, 0.68, and 2.7 µg/day (molar equivalent to 1, 5, 25, and 100 IU of vitamin D), for 7 to 16 days. In normal subjects, calcium absorption and urinary calcium increased after administration of 0.14 to 2.7 µg/day; 0.68 to 2.7 µxg/day augmented calcium absorption in the uremic patients. Fecal calcium fell significantly during metabolic balance studies. The marked action in normal subjects, compared with much larger doses of vitamin D3, emphasize the existence of regulation of the production of 1,25(OH)2D3 from its precursors. The steroid corrected the "vitamin D-resistance" of uremia, observations compatible with defective renal production of 1,25(OH)2D3 in uremia.
Seat-Belt Injuries To the Pregnant Uterus
Authors: Warren M. Crosby
Journal: JAMA (1966)

To the Editor:  Are there better methods of automobile and airplane restraints than the seat belt? With the current interest in automobile and aircraft safety, it is noteworthy that there are essentially no scientific data regarding the physiological and pathological effects of crashes on pregnant women, nor is there any indication that the heralded automobile and aircraft seat belt might not be more harmful in the latter half of pregnancy than not having it in place at all.  My colleagues at the Federal Aviation Agency and the US Air Force are conducting a series of experiments attempting to elucidate some of these factors. I would appreciate receiving any information from readers ofThe Journalconcerning cases of pregnant women involved in automobile or aircraft accidents. Any information whether any obvious injury was apparent or not would be welcomed, but more detail with regard to length of gestation, type of injury,
To Bind Up the Wounds: Catholic Sister Nurses in the US Civil War
Authors: Maggie Hadro Venzke
Journal: JAMA (1990)

<i>To Bind Up the Wounds</i>is a comprehensive, historical account of the important role of Catholic sister nurses in the Civil War and their contributions to the development of the American nursing profession. Civil War texts devoted to detailed descriptions of major battles and military strategies pay little attention to the roles of women and nurses in the war. Maher's book provides supportive evidence that Catholic sisters played a major role in caring for the wounded soldier and provided organization and structure to the provision of health care in mid-19th-century America. The first several chapters discuss the beginnings of communities of sisters in the United States. Sister communities evolved from their European counterparts and were similar in maintaining their commitment to vows of poverty, celibacy, and obedience; dedicating their lives to service to others; and living in a community of like-minded women. Most Americans viewed such groups with skepticism and
"Missed pill" conception: fact or fiction?
Authors: B G Molloy, K A Coulson, J M Lee, J K Watters
Journal: BMJ (1985)

A study of 19 healthy nulliparous women 20-30 years who were using the low dose combined oral contraceptive (OC)  demonstrated ovarian folliculogenesis during the 7-day  withdrawal in 28 day  cycles.  This makes the genuine occurrence of   conceptions seem less mythical. All of the women had normal menstrual histories before OC use.  They had been on treatment for at least 3 months and had regular monthly withdrawal bleeds.  Ultrasonographic examination of the ovaries was performed on the last day of 1  pack (day 21) on the last pill  day (day 28) and on the 7th day of the next  pack (day 7).  An Elscint Dynex sector scanner with a 3.5 MHz probe was used which is capable of measuring down to 1.5 mm.  All subjects showed some ovarian follicular activity by the last day of the pill-free phase and half developed multiple follicles with a dominant follicular diameter of 7 mm or greater the diameter seen on day 7 of the normal cycle.  Continuation of the gonadotrophin stimulation of these dominant follicles would have led to ovulation.  By the 7th day of the new  pack the follicular appearance had returned to the dormant condition shown by the 1st scan in all but 1 subject and she showed reduction in follicular diameter.  No pills were missed by any subject during the study cycles.  In 2 subjects small cysts were detected at the 1st scan and at the 2nd and 3rd examinations unaffected by the development and regression of the other follicles.  1 subject inadvertently missed a  on day 5 of a cycle after completing the study.  She was examined 24 hours later and a 10 mm follicle was seen.  She was unable to attend for further examination.  With the current 21 day  pack it is strongly recommended that alternative contraception be used when a  is missed during the first 7 days of a pack even if the woman has been using OC for some time.  This is most likely not necessary when a  is missed later in the course.  Women using OCs should also be warned of the danger of delaying restarting treatment after the 7  free days.
Oral-Contraceptive-Induced Benign Liver Tumors—The Magnitude of the Problem
Authors: Hershel Jick
Journal: JAMA (1978)

In order to provide a rough estimate of the annual number of benign liver tumors induced by oral contraceptives (OCs) in the U.S. the resources of the Commission on Professional and Hospital Activities (CPHA) in Ann Arbor Michigan were used.  CPHA obtains discharge diagnosis information on about 40% of patients discharged from U.S. hospitals.  From this data base the CPHA in cooperation with IMS America Limited has constructed a sample of about 1% of all short-term general hospital discharges in the U.S.  Using this sample CPHA identified all women younger than age 48 who were discharged during the period 1970-76 with a diagnosis of benign tumor of the liver or biliary passages.  The information provided allowed for telephone contact with the physician attending in order to obtain histologic diagnosis of the tumor and information on OC use before diagnosis.  There were 7 cases for whom the histologic diagnosis was consistent with the type reported to be associated with OC use: hamartoma 3;  adenoma 3;  and focal nodular hyperplasia 1.  Positive evidence of OC use was recorded in 3 of these 7 cases.  In the remaining 4 it was impossible to obtain information on OC use.  For the purpose of estimating the annual number of cases of benign liver tumors induced by OCs it has been assumed that all of the remaining 7 cases were induced by OCs and that none of the 2 cases whose exact diagnosis were unknown were related to OC use.  From these data it is estimated that there were 700 cases in the U.S. during the 1970-76 period about 100/year.  From data of Vana et al. 1977 it is estimated that the annual number of benign liver tumors induced by OCs is about 140 - an estimation similar to that obtained from the CPHA hospital data.  Both of these estimates provide sufficient information to conclude that the annual number of benign liver tumors induced by OCs in the U.S. is likely to be in the hundreds rather than in the thousands.
1011-110 The HNO/nitric oxide donor Angeli's salt enhances myocyte contractility in a PKA-dependent manner
Authors: Carlo G Tocchetti, Tatsuo Katori, Manuela Zaccolo, Daniele Mancardi, Diego F Belardi, Katrina M Miranda, David A Wink, David A Kass, Nazareno Paolocci
Journal: Journal of the American College of Cardiology (2004)
Two distinct phases of calcium signalling under flow
Authors: Bo Liu, Shaoying Lu, Shuai Zheng, Zonglai Jiang, Yingxiao Wang
Journal: Cardiovascular Research (2011)

High shear stress (HSS) can have significant impact on angiogenesis and atherosclerosis in collateral arteries near the bifurcation and curvature regions. Here, we investigate the spatiotemporal pattern of HSS-induced intracellular calcium alteration. Genetically encoded biosensors based on fluorescence resonance energy transfer were targeted in the cytoplasm and the endoplasmic reticulum (ER) to visualize the subcellular calcium dynamics in bovine aortic endothelial cells under HSS (65 dyn/cm2). Upon HSS application, the intracellular Ca2+ concentration ([Ca2+]i) increased immediately and maintained a sustained high level, while the ER-stored calcium had a significant decrease only after 300 s. The perturbation of calcium influx across the plasma membrane (PM) by the removal of extracellular calcium or the blockage of membrane channels inhibited the early phase of [Ca2+]i increase upon HSS application, which was further shown to be sensitive to the magnitudes of shear stress and the integrity of cytoskeletal support. In contrast, Src, phospholipase C(PLC), and the inositol 1,4,5-trisphosphate receptor (IP3R) can regulate the late phase of HSS-induced [Ca2+]i increase via the promotion of the ER calcium efflux. The HSS-induced [Ca2+]i increase consists of two well-co-ordinated phases with different sources and mechanisms: (i) an early phase due to the calcium influx across the PM which is dependent on the mechanical impact and cytoskeletal support and (ii) a late phase originated from the ER-calcium efflux which is regulated by the Src, PLC, and IP3R signalling pathway. Therefore, our work presented new molecular-level insights into systematic understanding of mechanotransduction in cardiovascular systems.
P2-239: A randomized phase III study of carboplatin-gemcitabine (CG) versus carboplatin-paclitaxel (CP) in elderly patients (pts) with advanced non-small cell lung cancer (NSCLC) with emphasis on geriatric assessment and quality of life (QoL): The NVALT-3 study
Authors: Bonne Biesma, Machteld N. Wymenga, Andrew Vincent, Otilia Dalesio, Jos A. Stigt, Hans J. Smit, Harry J. Groen
Journal: Journal of Thoracic Oncology (2007)
Glyceryl Trinitrate in Angina Pectoris
Authors: Henry I. Russek, J. Cambell Howard
Journal: JAMA (1964)

Despite universal belief in the efficacy of glyceryl trinitrate (nitroglycerin) for the treatment of angina pectoris, some investigators have challenged the validity of clinical impression and declared the drug to be inert. That it is capable of preventing pain as well as ischemic electrocardiographic changes following standard exercise by patients with angina pectoris is well documented. As a further test of efficacy a careful double-blind study of exercise tolerance correlated with electrocardiographic response was carried out in 15 patients receiving placebo and glyceryl trinitrate respectively. The ability of glyceryl trinitrate to increase work performance was unequivocally demonstrated in 14 patients. The efficacy of the drug in angina pectoris should continue to provide a standard by which the potency of other agents may be measured and classified.
In the AMA, Policy Follows Science: A Case History of Tobacco
Authors: George D. Lundberg
Journal: JAMA (1985)

In the evolution of health policy we can trace a cycle beginning with need, followed by a perception of that need, leading to questions (see Fig 1). The questions result in the challenge of thinking and research, generating data, which become information and are distributed. Over time, new knowledge may lead to changed attitudes. As some individuals change, they work to change the policies and practices of their institutions so they will reflect the new knowledge. Those whose attitudes have not changed will resist policy changes, and a struggle follows. If the force of the new knowledge and attitudes is strong enough, new policies will result. These will be followed by the implementation of new procedures, their subsequent evaluation, and further questions. The process cycles endlessly as humans and systems cycle. Subsequently changing human behavior on a large scale is perhaps the most difficult change, and it may happen slowly
Cytosine Deaminase-Uracil Phosphoribosyltransferase and Interleukin (IL)-12 and IL-18: A Multimodal Anticancer Interface Marked by Specific Modulation in Serum Cytokines
Authors: Aparajita Khatri, Yasmin Husaini, Kim Ow, Jane Chapman, Pamela J. Russell
Journal: Clinical Cancer Research (2009)

To test the effects of a new combination, cytosine deaminase (CD) + uracil phosphoribosyltransferase (UPRT)-mediated gene-directed enzyme prodrug therapy (GDEPT) with interleukin (IL)-12 and IL-18, on (a) growth of murine prostate and remote tumor deposits, (b) mouse survival, and (c) T helper (Th) 1/Th2 serum cytokine balance with a special focus to assess correlation with tumor burden/survival.Efficacy of intraprostatic administration of adenovirally delivered murine IL-12 and IL-18 against orthotopic RM1 tumors and lung pseudometastases was assessed in C57BL/6 mice. At necropsy, tumor growth, lung colony counts, effects on immune cell infiltration, vasculature, apoptosis, and proliferation were estimated. Next, CDUPRT-GDEPT + cytokines were tested at suboptimal doses in mice with RM1CDUPRT prostate tumors/RM1 lung deposits and analyzed as above. Effects on mouse survival were also assessed. Host immune responses to different treatments were assessed by monitoring 11 serum cytokines using Luminex technology.Our data show that IL-12 and IL-18, when combined with CDUPRT-GDEPT, caused significant reduction in local RM1 tumors and lung colonies with enhanced long-term survival versus individual treatments. A dramatic enhancement of tumor infiltration by a wider repertoire of immune cells and disruption of vasculature implied the combination to be more immunostimulatory and antiangiogenic. Remarkably, lowering of serum IL-4 and monocyte chemoattractant protein-1 (MCP-1) was consistently associated with lower tumor burden (local and systemic), and this, rather than an increase in Th1 cytokines, better predicted treatment efficacy. In addition, mouse survival correlated with substantially higher cytokine (Th1/Th2) levels after treatment.Locoregional application of CDUPRT-GDEPT and IL-12/IL-18 was effective against local and systemic prostate cancer and improved survival. Monitoring serum levels of IL-4 and MCP-1 may accurately reflect tumor burden and, hence, host response to therapy.
Palonosetron Improves Dietary Intake Compared to Granisetron in Patients Undergoing Highly Emetogenic Chemotherapy
Authors: N. Shibata, T. Hidaka, A. Shirado, M. Sueta, M. Nakazato, K. Nakamura, K. Chijiiwa, K. Shimoda
Journal: Annals of Oncology (2013)