tbuckley/cabot-search huggingface dataset:
Abstract 3840: Rap1 GTPase activating protein (Rap1GAP) is downregulated in DCIS and invasive ductal carcinoma
Authors: Sarah S. Rhee, Bora Lim, Hyoung-ha Kim, Yan Wang, Usman Aziz, Usman Butt, Waixing Tang, Lisa A. Vuchak, Angela DeMichele, Andrea B. Troxel, Michael D. Feldman, Judy L. Meinkoth, Marcia S. Brose
Journal: Cancer Research (2011)

Abstract Introduction: Rap1 and Rap2, both small GTPases of the Ras family, serve as crucial regulators in cell polarity, adhesion, migration, and lumen formation via crosstalk with cytoskeletal proteins. Rap1 GTPase activating protein (Rap1GAP), which negatively regulates Rap1 and Rap2 activity, has found to be downregulated in multiple cancers, including oropharyngeal squamous cell carcinoma, melanoma, papillary and follicular thyroid carcinoma, and colorectal carcinoma but has not yet been studied in breast cancer. In order to determine if Rap1GAP downregulation plays a role in breast cancer formation, we decided to expand our prior work to study its expression in breast cancer tissue. Methods: Twenty-one formalin-fixed paraffin-embedded human tissue blocks were selected on the basis that they contained normal breast tissue and either adjacent breast ductal carcinoma in situ (DCIS) or invasive ductal carcinoma. Using immunohistochemistry, we assessed the expression of Rap1GAP. We also assayed two human breast cancer cell lines with different levels of invasiveness, MCF7 (non-invasive) and MDA-MB-231 (invasive), to determine different levels of Rap1GAP expression and subsequent changes in Rap1 and Rap2 expression and activity. Results: Rap1GAP expression in both DCIS and invasive ductal carcinoma were found to be decreased compared to adjacent normal breast tissue. However, Rap1GAP expression was not statistically different between DCIS and invasive carcinoma lesions. Rap1GAP was found to be expressed highly in MCF7 but not in MDA-MB-231 cells. Moreover, only MDA-MB-231 cells exhibited high basal Rap2 activity. Activated Rap1 (RAP1-GTP) was not detected in either line. Conclusion: Our findings suggest that loss of Rap1GAP occurs as an early event in breast cancer tumorigenesis with a significant decrease in the transition from normal to DCIS, with a possible further decrement in the DCIS to invasive transition. Interestingly, while Rap1 and Rap2 were expressed in non-invasive and invasive cell lines, loss of Rap1GAP in the invasive cell line was associated with increase in active Rap2, but not active Rap1. These findings suggest that as in other cancers, loss of Rap1GAP may contribute to the invasive phenotype and thus further investigation is warranted. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3840. doi:10.1158/1538-7445.AM2011-3840
Impaired myocardial angiogenesis and ischemic cardiomyopathy in mice lacking the vascular endothelial growth factor isoforms VEGF164 and VEGF188
Authors: Peter Carmeliet, Yin-Shan Ng, Dieter Nuyens, Gregor Theilmeier, Koen Brusselmans, Ivo Cornelissen, Elisabeth Ehler, Vijay V. Kakkar, Ingeborg Stalmans, Virginie Mattot, Jean-Claude Perriard, Mieke Dewerchin, Willem Flameng, Andras Nagy, Florea Lupu, Lieve Moons, Désiré Collen, Patricia A. D'Amore, David T. Shima
Journal: Nature Medicine (1999)
The microbiota regulates neutrophil homeostasis and host resistance to Escherichia coli K1 sepsis in neonatal mice
Authors: Hitesh S Deshmukh, Yuhong Liu, Ogechukwu R Menkiti, Junjie Mei, Ning Dai, Claire E O'Leary, Paula M Oliver, Jay K Kolls, Jeffrey N Weiser, G Scott Worthen
Journal: Nature Medicine (2014)
Trauma, Stress and Immunity in Anaesthesia and Surgery
Authors: John M. Luber
Journal: JAMA (1983)

Understanding the physiological sequelae of surgical and anesthetic intervention represents the most complex learning task in the surgical specialties. There has been an accelerating accumulation of knowledge, but it is difficult to collate because it appears in diverse sources with which the practitioner may be unfamiliar. This volume attempts to organize in one source a large portion of this complex material.  While there are omissions, especially with regard to the reticuloendothelial system and CNS, the editors acknowledge these to be time and source availability limitations. They have appropriately chosen experts in the fields discussed and have organized the text into four lucid parts. The flow, from a discussion of basic concepts to psychological factors, while at times a bit disjointed, is a welcome synopsis. The bibliography is extensive and provides a logical and complete extrapolation of chapter material for the serious student.  This volume is a welcome addition to the
Adult Medulloblastoma Relapse Visualized by In-111 Octreotide Scintigraphy
Authors: Jose R. Infante, Juan I. Rayo, Justo Serrano, María L. Domínguez, Lucia García, Roman Sánchez
Journal: Clinical Nuclear Medicine (2006)

A 31-year-old woman with a history of desmoplastic medulloblastoma in the right cerebellar hemisphere had undergone a resection. Magnetic resonance imaging (MRI) was indicated with the aim of ruling out a relapse, but the results were inconclusive. In-111-DTPA octreotide scintigraphy was performed. Planar images and SPECT scan obtained after radiolabeled octreotide injection revealed elevated uptake in the posterior fossa suggestive of relapse. The patient underwent a craniotomy for surgical resection. Although medulloblastoma is the most common pediatric central nervous system malignancy, it is rare in adults with few cases studied with somatostatin receptor scintigraphy and described in the existing literature.
General practitioner knowledge of prohibited substances in sport.
Authors: P Greenway, M Greenway
Journal: British Journal of Sports Medicine (1997)

To assess general practitioner knowledge of banned substances in sport.Postal questionnaire sent to all general practitioners in West Sussex.Only 55 (35%) of those who responded (157 in total) were aware that guidelines are to be found in the British National Formulary, and 19 (12%) of respondents believed that medical practitioners are allowed to prescribe anabolic steroids for non-medical reasons.General practitioner knowledge of which substances are prohibited in sports is poor. There is a lack of awareness of Sports Council guidelines which are to be found in the British National Formulary. Tackling drug abuse in sport requires education of both athletes and doctors.
The Diagnosis of Pheochromocytoma
Authors: Edward L. Moorhead
Journal: JAMA (1966)

Twenty-six cases of pheochromocytoma were seen in a 14-year period (1951-1964) at the Henry Ford Hospital. The presenting complaint often seemed unrelated to the presence of pheochromocytoma. Only 13 patients (50%) gave a history of hypertension, and six were normotensive at the time of initial examination. In 14 of the 18 patients who complained of paroxysmal attacks, the diagnosis was made preoperatively or antemortem. In contrast, the diagnosis was not established clinically in the eight patients failing to report paroxysms. This would seem to point to the importance of ruling out pheochromocytoma in those thought to have primary or socalled essential hypertension. Because of the difficulty of excluding pheochromocytoma by means of clinical examination, it is recommended that ideally either a histamine or phentolamine test be done on every patient with newly diagnosed hypertension.
Abstract 3220: The effects of cholesterol treatment drugs alone and in combination on prostate tumor xenograft growth
Authors: Elizabeth M. Masko, Keith R. Solomon, Nikolaos A. Valilis, Alexis R. Gaines, Michael J. Muehlbauer, Christopher B. Newgard, Mark W. Dewhirst, Salvatore V. Pizzo, Stephen J. Freedland
Journal: Cancer Research (2012)

Abstract Background: Epidemiologic data suggest cholesterol-lowering drugs may prevent the progression of prostate cancer (PC), but not the incidence of the disease. This may occur by lowering levels of low-density lipoproteins (LDL). Statins and cholesterol-uptake inhibitors like ezetimibe lower serum LDL and are commonly prescribed for patients with high cholesterol. In this study, we determined the therapeutic role of simvastatin, ezetimibe, or both in vitro using several PC cell lines and in vivo using a LAPC-4 xenograft model. Methods: We treated 4 PC cell lines (LAPC-4, CWR22rv1, PC-3, and DU145) with varying concentrations of simvastatin (0-1000nM) or ezetimibe (0-100μM) for 0-5 days. MTS assays were performed to determine cell proliferation, and the IC50 was calculated using BioDataFit 1.02. For our in vivo study, a total of 90 athymic male nude mice were fed a high-fat, high-cholesterol diet (HFHC; 40% fat, 17% protein, 43% carbohydrates, 1.25% cholesterol), subcutaneously injected with 1 x 10^5 LAPC-4 cells, and randomized 2 weeks later to 1 of 4 treatments: vehicle control, 11mg/kg/day simvastatin (delivered via osmotic pump), 30mg/kg diet ezetimibe (delivered in the food), or simvastatin + ezetimibe. Mice remained on study for 42 days post-randomization, at which point they were harvested and samples analyzed. Results: In vitro, simvastatin directly reduced PC cell proliferation in a dose-dependent, cell line-specific manner, but ezetimibe had no inhibitory effect. In vivo, treatment of low continuous dosing of simvastatin or ezetimibe for 42 days had no effect on tumor growth compared to control. However, relative to control, the combination of simvastatin and ezetimibe accelerated tumor growth (p=0.01). The simvastatin-ezetimibe mice also showed lower fat infiltration in the liver and lower serum cholesterol, but higher tumor cholesterol levels than control. Conclusions: Our results suggest that low continuous dosing of simvastatin or ezetimibe may have no effect on PC growth in a slow-growing LAPC-4 xenograft model, but the combination of simvastatin and ezetimibe may accelerate PC growth, possibly by stimulating cholesterol uptake within the tumor. This novel finding may be important in implementing new treatments for men with slow growing PC and high cholesterol. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3220. doi:1538-7445.AM2012-3220
EFFECTS OF ANGIOTENSIN II RECEPTOR BLOCKER ON CORONARY COLLATERAL FUNCTION AFTER DRUG-ELUTING STENT IMPLANTATION IN HYPERTENSIVE PATIENTS
Authors: Nobuyoshi Tanaka, Mitsuyasu Terashima, Tsuyoshi Itoh, Maoto Habara, Kenya Nasu, Masashi Kimura, Tatsuya Itoh, Yoshihisa Kinoshita, Mariko Ehara, Etsuo Tsuchikane, Keiko Asakura, Yasushi Asakura, Osamu Katoh, Takahiko Suzuki
Journal: Journal of the American College of Cardiology (2011)
Fireworks in Iran
Authors: J. O. Drife
Journal: BMJ (2009)

When you say you’re going to Tehran in December, your colleagues look worried. This means someone else playing Santa at the Christmas party. And Iran has an image problem. No one actually says “axis of evil,” but everyone thinks hostages, and some people just don’t like the name. Why can’t it still be called Persia?

My visa arrived in the nick of time after increasingly terse emails to and from WHO. As we landed at Imam Khomeini airport the stewardesses …
Prevalence of Lymphedema in Women With Breast Cancer 5 Years After Sentinel Lymph Node Biopsy or Axillary Dissection: Patient Perceptions and Precautionary Behaviors
Authors: Sarah A. McLaughlin, Mary J. Wright, Katherine T. Morris, Michelle R. Sampson, Julia P. Brockway, Karen E. Hurley, Elyn R. Riedel, Kimberly J. Van Zee
Journal: Journal of Clinical Oncology (2008)

Sentinel lymph node (SLN) biopsy was adopted for the staging of the axilla with the assumption that it would reduce the risk of lymphedema in women with breast cancer. This study was undertaken to examine patient perceptions of lymphedema and use of precautionary behaviors several years after axillary surgery.Nine hundred thirty-six women who underwent SLN biopsy (SLNB) alone or SLNB followed by axillary lymph node dissection (SLNB/ALND) between June 1, 1999, and May 30, 2003, were evaluated at a median of 5 years after surgery. Patient-perceived lymphedema and avoidant behaviors were assessed through interview and administered a validated instrument, and compared with arm measurements.Current arm swelling was reported in 3% of patients who received SLNB alone versus 27% of patients who received SLNB/ALND (P < .0001), as compared with 5% and 16%, respectively, with measured lymphedema. Only 41% of patients reporting arm swelling had measured lymphedema, and 5% of patients reporting no arm swelling had measured lymphedema. Risk factors associated with reported arm swelling were greater body weight (P < .0001), higher body mass index (P < .0001), infection (P < .0001), and injury (P = .007) in the ipsilateral arm since surgery. Patients followed more precautions if they had measured or perceived lymphedema.Body weight, infection, and injury are significant risk factors for perceiving lymphedema. There is significant discordance between the presence of measured and patient-perceived lymphedema. When compared to SLNB/ALND, SLNB-alone results in a significantly lower rate of patient-perceived arm swelling 5 years postoperatively, and is perceived by fewer women than are measured to have it.
Comment on: Saisho et al. -Cell Mass and Turnover in Humans: Effects of Obesity and Aging. Diabetes Care 2013;36:111-117
Authors: Sofia A. Gargani, Francois Pattou, Julie Kerr-Conte
Journal: Diabetes Care (2013)

In the article by Saisho et al. (1), the effect of obesity on β-cell mass and turnover was addressed by indirectly estimating β-cell mass from human pancreatic specimens after death related to disease or trauma. Although these results are consistent with the direct measurement of islet volume after isolation from abruptly deceased healthy organ donors, the correlation between β-cell mass and BMI remains weak ( r ≤ 0.5) (2,3). The authors admit that cross-sectional studies provide limited information on the mechanisms that potentially link obesity with this increased (50%) β-cell mass. Rather unexpectedly, for example, no measurable difference in β-cell …
The Healers: The Rise of the Medical Establishment
Authors: Lester S. King
Journal: JAMA (1977)

One of the great gaps in medical literature has been a brief history of medicine in America. Monographs and specialized studies, biographies and critical analyses are abundant, but there has been no recent comprehensive exposition. Duffy's new book is therefore very welcome indeed. The author provides a panorama of medicine in America that ranges from the early 16th century to the third quarter of the 20th, and from Indian medicine of pre-Columbian times to malpractice insurance in the 1970s. The presentation up to the latter 19th century follows the traditional pattern—the Colonial period, the special difficulties that medicine faced in the New World, the gradual progress in the 18th century, medicine in the Revolution, the rise of hospitals and medical schools, medicine on the frontier, the decline of "heroic medicine," the rise of medical sects and "popular" medicine, the great developments in medical science and art, including the discovery of
Low Usefulness of Potassium Monitoring Among Healthy Young Women Taking Spironolactone for Acne
Authors: Molly Plovanich, Qing Yu Weng, Arash Mostaghimi
Journal: JAMA Dermatology (2015)

Spironolactone has been shown to be an effective treatment option for hormonally mediated acne but can cause hyperkalemia. The prevalence of hyperkalemia among healthy young women taking spironolactone for acne is unclear.To measure the rate of hyperkalemia in healthy young women taking spironolactone for acne or for an endocrine disorder with associated acne.Retrospective study of healthy young women taking spironolactone for acne. Data from December 1, 2000, through March 31, 2014, were obtained from a clinical data repository. Outpatient data were collected from 2 tertiary care centers in the United States. We analyzed rates of hyperkalemia in 974 healthy young women taking spironolactone for acne. We also analyzed 1165 healthy young women taking and not taking spironolactone to obtain a profile for the baseline rate of hyperkalemia in this population. Exclusion criteria were cardiovascular disease, renal failure, and the use of medications that affect the renin-angiotensin-aldosterone system.The rate of hyperkalemia in healthy young women taking spironolactone for acne was calculated. Secondary measures included spironolactone prescriber profiles and potassium monitoring practices.There were 13 abnormal serum potassium measurements in 1802 measurements obtained among young women receiving spironolactone therapy, yielding a hyperkalemia rate of 0.72%, equivalent to the 0.76% baseline rate of hyperkalemia in this population. Repeat testing in 6 of 13 patients demonstrated normal values, suggesting that these measurements may have been erroneous. In the remaining 7 patients, no action was taken.The rate of hyperkalemia in healthy young women taking spironolactone for acne is equivalent to the baseline rate of hyperkalemia in this population. Routine potassium monitoring is unnecessary for healthy women taking spironolactone for acne.
The Early Phase of Acute Myocardial Infarction: Pharmacologic Aspects of Therapy
Authors: STEPHEN E. EPSTEIN
Journal: Annals of Internal Medicine (1973)

Most deaths from acute myocardial infarction occur before arrival of medical aid: the terminal mechanism appears to be ventricular fibrillation. Circumstantial evidence suggests that sinus bradycardia, commonly observed during the prehospital phase of acute myocardial infarction, predisposes to ventricular fibrillation and thereby contributes importantly to early death. It was found, however, that moderately severe bradycardia accompanying experimental acute myocardial infarction did not predispose to serious ventricular arrhythmias. Moreover, the frequency of serious arrhythmia increased when either spontaneous or postatropine heart rate was above 80. Explanations for these findings are that decreasing heart rate during acute myocardial infarction reduces ischemic injury and increases electrical stability of the myocardium and that vagal stimulation per se increases electrical stability. On the other hand, nitroglycerin exerted marked beneficial effects on ischemic injury and electrical stability. The clinical implications of these findings on pharmacologic therapy of acute myocardial infarction are presented.
Arginase I–Producing Myeloid-Derived Suppressor Cells in Renal Cell Carcinoma Are a Subpopulation of Activated Granulocytes
Authors: Paulo C. Rodriguez, Marc S. Ernstoff, Claudia Hernandez, Michael Atkins, Jovanny Zabaleta, Rosa Sierra, Augusto C. Ochoa
Journal: Cancer Research (2009)

Myeloid-derived suppressor cells (MDSC) producing arginase I are increased in the peripheral blood of patients with renal cell carcinoma (RCC). MDSC inhibit T-cell function by reducing the availability of L-arginine and are therefore considered an important tumor escape mechanism. We aimed to determine the origin of arginase I-producing MDSC in RCC patients and to identify the mechanisms used to deplete extracellular L-arginine. The results show that human MDSC are a subpopulation of activated polymorphonuclear (PMN) cells expressing high levels of CD66b, CD11b, and VEGFR1 and low levels of CD62L and CD16. In contrast to murine MDSC, human MDSC do not deplete L-arginine by increasing its uptake but instead release arginase I into the circulation. Activation of normal PMN induces phenotypic and functional changes similar to MDSC and also promotes the release of arginase I from intracellular granules. Interestingly, although activation of normal PMN usually ends with apoptosis, MDSC showed no increase in apoptosis compared with autologous PMN or PMN obtained from normal controls. High levels of VEGF have been shown to increase suppressor immature myeloid dendritic cells in cancer patients. Treatment of RCC patients with anti-VEGF antibody bevacizumab, however, did not reduce the accumulation of MDSC in peripheral blood. In contrast, the addition of interleukin-2 to the treatment increased the number of MDSC in peripheral blood and the plasma levels of arginase I. These results may provide new insights on the mechanisms of tumor-induced anergy/tolerance and may help explain why some immunotherapies fail to induce an antitumor response.
Identifying Signatures of Selection at the Enhancer of split Neurogenic Gene Complex in Drosophila
Authors: Stuart J. Macdonald, Anthony D. Long
Journal: Molecular Biology and Evolution (2004)

The Enhancer of split gene complex (E(spl)-C) is one of the more highly annotated gene regions in Drosophila, and the 12 genes within the complex help determine the spacing and patterning of adult bristles. Any E(spl)-C coding, transcribed, or cis-regulatory regions experiencing nonneutral evolution are strong candidates to harbor polymorphisms contributing to naturally occurring variation in bristle number. We confirm that the E(spl)-C is strongly conserved and show that 74% of regulatory elements previously identified in D. melanogaster are conserved in D. pseudoobscura. Regulatory elements in enhancer regions show lower nucleotide diversity and more rare polymorphisms compared with adjacent nonregulatory DNA, suggesting they are under purifying selection, and these effects are particularly pronounced when considering only conserved regulatory elements. The ratio of polymorphism to divergence was significantly different between binding sites and nonbinding sites for transcription factors within enhancer regions, suggesting the action of some form of selection. Too few polymorphisms in regions of the 3′ UTR harboring regulatory motifs prevents adequate comparison of diversity and the polymorphism frequency spectrum between 3′ UTR motif and nonmotif sequence. We identified at least two broad regions of the gene complex showing strong population subdivision among four populations, which is suggestive of local adaptation or background selection. Finally, two regions of the E(spl)-C exhibit low nucleotide diversity, a high level of rare polymorphisms, and an increase in linkage disequilibrium, which together suggest the action of positive selection. Notably, the gene m2 shows a significant deviation from neutrality by the McDonald-Kreitman test and resides in one of the two regions putatively experiencing a selective sweep. All sites in regions apparently visible to various selective forces are candidates for future work to determine their phenotypic effects.
Hypercalcaemia in cancer
Authors: Simon Conroy, Brendan O'Malley
Journal: BMJ (2005)

The commonest cause of hypercalcaemia in hospitalised patients is malignancy, so the tendency is to presume that hypercalcaemia in a patient with cancer is related to malignancy.This may not be the case, however. Case reportsCase 1 A 50 year old woman underwent a wide local excision and axillary node clearance for breast cancer in July 1999.She received postoperative chemo-radiotherapy and made a good recovery.A year later she presented with fatigue and distal paraesthesia.Her adjusted serum calcium concentration was 2.69 mmol/l (normal range 2.2-2.6).She was investigated for metastatic breast cancer, including a bone scan, and was advised that her cancer had recurred.Four months later, she remained anxious but well; her serum calcium was 2.71 mmol/l, and a paired serum parathyroid hormone concentration of 10.9 pmol/l (normal range 1.1-7.5)confirmed primary hyperparathyroidism.After careful follow-up, a left lower pole parathyroid adenoma was removed.The patient's postoperative calcium concentration was in the normal range (2.57mmol/l).