tbuckley/cabot-search huggingface dataset:
Clinical Responses in a Phase II Study Using Adoptive Transfer of Short-term Cultured Tumor Infiltration Lymphocytes in Metastatic Melanoma Patients
Authors: Michal J. Besser, Ronnie Shapira-Frommer, Avraham J. Treves, Dov Zippel, Orit Itzhaki, Liat Hershkovitz, Daphna Levy, Adva Kubi, Einat Hovav, Natalia Chermoshniuk, Bruria Shalmon, Izhar Hardan, Raphael Catane, Gal Markel, Sara Apter, Alon Ben-Nun, Iryna Kuchuk, Avichai Shimoni, Arnon Nagler, Jacob Schachter
Journal: Clinical Cancer Research (2010)

Adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL) has shown promising results in metastatic melanoma patients. Although objective response rates of over 50% have been reported, disadvantages of this approach are the labor-intensive TIL production and a very high drop-out rate of enrolled patients, limiting its widespread applicability. Previous studies showed a clear correlation between short TIL culture periods and clinical response. Therefore, we used a new TIL production technique using unselected, minimally cultured, bulk TIL (Young-TIL). The use of Young-TIL is not restricted to human leukocyte antigen (HLA)-A2 patients. The purpose of this study is to explore the efficacy and toxicity of adoptively transferred Young-TIL following lympho-depleting chemotherapy in metastatic melanoma patients, refractory to interleukin-2 and chemotherapy.Young-TIL cultures for 90% of the patients were successfully generated, enabling the treatment of most enrolled patients. We report here the results of 20 evaluated patients.Fifty percent of the patients achieved an objective clinical response according to the Response Evaluation Criteria in Solid Tumors, including two ongoing complete remissions (20+, 4+ months) and eight partial responses (progression-free survival: 18+, 13+, 10+, 9, 6+, 4, 3+, and 3 months). All responders are currently alive. Four additional patients showed disease stabilization. Side effects were transient and manageable.We showed that lympho-depleting chemotherapy followed by transfer of short-term cultured TIL can mediate tumor regression in 50% of metastatic melanoma with manageable toxicity. The convincing clinical results combined with the simplification of the process may thus have a major effect on cell therapy of cancer.
Differing DNA Methylation Patterns and Gene Mutation Frequencies in Colorectal Carcinomas from Middle Eastern Countries
Authors: Annie O. Chan, Amr S. Soliman, Qing Zhang, Asif Rashid, Ahmed Bedeir, P. Scott Houlihan, Nadia Mokhtar, Nidal Al-Masri, Ugur Ozbek, Rami Yaghan, Ayten Kandilci, Sherif Omar, Yersu Kapran, Ferhunde Dizdaroglu, Melissa L. Bondy, Christopher I. Amos, Jean-Pierre Issa, Bernard Levin, Stanley R. Hamilton
Journal: Clinical Cancer Research (2005)

Abstract Purpose: The epidemiology of colorectal carcinoma is well known to differ among countries but the molecular characteristics are usually assumed to be similar. International differences in molecular pathology have not been studied extensively but have implications for the management of patients in different countries and of immigrant patients. Experimental Design: We evaluated the CpG island methylator phenotype pathway characterized by concordant methylation of gene promoters that often silences transcription of the genes, the microsatellite instability pathway, and K-ras and p53 gene status in 247 colorectal carcinomas from the three selected Middle Eastern countries of Egypt, Jordan, and Turkey. Results: Colorectal carcinoma from Egypt had the lowest frequencies of methylation. In multinomial logistic regression analysis, Jordanian colorectal carcinoma more frequently had methylation involving the p16 tumor suppressor gene (odds ratio, 3.5; 95% confidence interval, 1.2-10.6; P = 0.023) and MINT31 locus (odds ratio, 2.3; 95% confidence interval, 1.0-5.1; P = 0.041). The K-ras proto-oncogene was more frequently mutated in colorectal carcinoma from Turkey (odds ratio, 2.9; 95% confidence interval, 1.2-6.7; P = 0.016), but p53 overexpression was more common in both Jordanian and Turkish colorectal carcinoma than in Egyptian cases (odds ratio, 2.5; 95% confidence interval, 1.2-5.5; P = 0.019; and odds ratio, 3.6; 95% confidence interval, 1.8-7.1; P = 0.0003, respectively). The findings in Turkish colorectal carcinoma were most similar to those reported for Western cases. Conclusions: Colorectal carcinoma from Middle Eastern countries have differing gene methylation patterns and mutation frequencies that indicate dissimilar molecular pathogenesis, probably reflecting different environmental exposures. These molecular differences could affect prevention strategies, therapeutic efficacy, and transferability of clinical trial results.
Factor V Leiden (FVQ 506) is common in a Brazilian population
Authors: Valder R. Arruda, Joyce M. Annichino‐Bizzacchi, Fernando F. Costa, Pieter H. Reitsma
Journal: American Journal of Hematology (1995)

Resistance to activated protein C (APC) is the most common risk factor in venous thrombosis. A missense mutation in the factor V gene (factor V Leiden) is the molecular basis for this phenotype. Factor V Leiden was previously found in about 20% of unselected patients with thrombosis but also occurred in 3-5% of healthy Dutch controls. In the present study of Brazilian patients with venous thrombosis we also observed a frequency of 20% for this factor. In addition, in healthy Brazilian controls the frequency of the mutation was 2%. These data suggest that factor V Leiden has a similar distribution worldwide irrespective of the ethnic origin of the population.
Elevated Risk of Carrying Gentamicin-Resistant <i>Escherichia coli</i> among U.S. Poultry Workers
Authors: Lance B. Price, Jay P. Graham, Leila G. Lackey, Amira Roess, Rocio Vailes, Ellen Silbergeld
Journal: Environmental Health Perspectives (2007)

BackgroundAntimicrobial use in food-animal production is an issue of growing concern. The application of antimicrobials for therapy, prophylaxis, and growth promotion in broiler chicken production has been associated with the emergence and dissemination of antimicrobial-resistant enteric bacteria. Although human exposure to antimicrobial-resistant bacteria through food has been examined extensively, little attention has been paid to occupational and environmental pathways of exposure.ObjectiveOur objective was to measure the relative risk for colonization with antimicrobial-resistant Escherichia coli among poultry workers compared with community referents.MethodsWe collected stool samples and health surveys from 16 poultry workers and 33 community referents in the Delmarva region of Maryland and Virginia. E. coli was cultured from stool samples, and susceptibility to ampicillin, ciprofloxacin, ceftriaxone, gentamicin, nitrofurantoin, and tetracycline was determined for each E. coli isolate. We estimated the relative risk for carrying antimicrobial-resistant E. coli among poultry workers compared with community referents.ResultsPoultry workers had 32 times the odds of carrying gentamicin-resistant E. coli compared with community referents. The poultry workers were also at significantly increased risk of carrying multidrug-resistant E. coli.ConclusionsOccupational exposure to antimicrobial-resistant E. coli from live-animal contact in the broiler chicken industry may be an important route of entry for antimicrobial-resistant E. coli into the community.
Peak expiratory flow in rural residents of Tamil Nadu, India.
Authors: D Ray, A Rajaratnam, J Richard
Journal: Thorax (1993)

In a country such as India that covers several latitudes, climatic zones, ethnic groups, and dietary habits lung function within the normal population would be expected to vary. Several studies have looked at normal values of peak expiratory flow (PEF) in different regions of urban India but none has looked at rural South India. A study of PEF has now been carried out in a rural population of Tamil Nadu.All subjects were of Dravidian stock and lived at sea level with rice as their staple food. Ten five year age groups from 10 to 59 years with 100 males and 100 females in each were studied. Peak flow was measured by mini-Wright peak flow meter, and height was also measured. Regression equations for predicting normal PEF were calculated.Peak flow ranged from 150 to 680 l/min in males and from 150 to 500 l/min in females. Maximum values of PEF were attained at the age of 32.5 years in men and 35.6 years in women. There was a significant linear correlation between height and PEF and a curvilinear relation between age and PEF in both sexes.Regression equations are now available for PEF values in normal subjects from rural South India. PEF was related to age and height and values were greatest in the fourth decade.
Sudden unilateral painless loss of vision
Authors: I. Georgalas, D. Pagoulatos, C. Koutsandrea, M. Pavlidis
Journal: BMJ (2014)

<h3>Background</h3> Poisonings are a common cause of morbidity and mortality among adolescents. Yet surveillance data indicating current incidence rates (IRs) and time trends are lacking, making policy development and service planning difficult. We utilised population based primary care data to estimate adolescent poisoning rates according to intent across the UK. <h3>Methods</h3> A cohort study of 1 311 021 adolescents aged 10–17 years, between 1992 and 2012, was conducted using routine primary care data from The Health Improvement Network. IRs and adjusted IRRs with 95% CIs were calculated for all poisonings, intentional, unintentional, unknown intent and alcohol related poisonings, by age, sex, calendar time and socioeconomic deprivation. <h3>Results</h3> Overall poisoning incidence increased by 27% from the period 1992–1996 to 2007–2012, with the largest increases in intentional poisonings among females aged 16–17 years (IR 391.4/100 000 person years (PY), CI 328.9 to 465.7 for age 17 years in 1992–1996; 767.0/100 000 PY, CI 719.5 to 817.7 in 2007–2012) and alcohol related poisonings in females aged 15–16 years (IR 65.7/100 000 PY, CI 43.3 to 99.8 rising to 130.0/100 000 PY, CI 110.0 to 150.0 for age 15 years). A strong socioeconomic gradient for all poisonings persisted over time, with higher rates among the more deprived (IRR 2.63, CI 2.41 to 2.88 for the most vs least deprived quintile in 2007–2012). <h3>Conclusions</h3> Adolescent poisonings, especially intentional poisonings, have increased substantially over time and remain associated with health inequalities. Social and psychological support for adolescents should be targeted at more deprived communities, and child and adolescent mental health and alcohol support service provision should be commissioned to reflect the changing need.
Intra-tumor heterogeneity: lessons from microbial evolution and clinical implications
Authors: Elza C de Bruin, Tiffany B Taylor, Charles Swanton
Journal: Genome Medicine (2013)

Multiple subclonal populations of tumor cells can coexist within the same tumor. This intra-tumor heterogeneity will have clinical implications and it is therefore important to identify factors that drive or suppress such heterogeneous tumor progression. Evolutionary biology can provide important insights into this process. In particular, experimental evolution studies of microbial populations, which exist as clonal populations that can diversify into multiple subclones, have revealed important evolutionary processes driving heterogeneity within a population. There are transferrable lessons that can be learnt from these studies that will help us to understand the process of intra-tumor heterogeneity in the clinical setting. In this review, we summarize drivers of microbial diversity that have been identified, such as mutation rate and environmental influences, and discuss how knowledge gained from microbial experimental evolution studies may guide us to identify and understand important selective factors that promote intra-tumor heterogeneity. Furthermore, we discuss how these factors could be used to direct and optimize research efforts to improve patient care, focusing on therapeutic resistance. Finally, we emphasize the need for longitudinal studies to address the impact of these potential tumor heterogeneity-promoting factors on drug resistance, metastatic potential and clinical outcome.
The repair of impaired epidermal barrier function in rats by the cutaneous application of linoleic acid
Authors: C. PROTTEY, P.J. HARTOP, J.G. BLACK, J.I. McCORMACK
Journal: British Journal of Dermatology (1976)

Epidermal barrier function in rats was experimentally impaired by two separate means, namely, by rendering the animals deficient in essential fatty acids and by evoking a primary cutaneous irritant response by treating with a solution of sodium laurate. Impaired barrier function was manifested by a greatly increased rate of transepidermal water loss. Application to the skin of sunflower seed oil, which is rich in linoleic acid, rapidly restored to normal the abnormally high rates of transepidermal water loss in both experimental cases, and it was shown with the essential fatty acid-deficient rats that there was a concomitant incorporation of linoleic acid of the sunflower seed oil into epidermal lipids. Cutaneous application of olive oil, which is low in linoleic acid but rich in the non-essential oleic acid, did not influence epidermal barrier function. A close relationship of barrier function and essential fatty acids is indicated.
Physicians' Needs and Interests in Continuing Medical Education
Authors: C. Hilmon Castle
Journal: JAMA (1968)

To improve the quality of patient care, continuing medical education must be oriented to the individual physician's practice and must be related to his particular interests and needs. All physicians are interested in learning when they have a need to know and when they are able to get help on their own terms. They want to become more efficient in their practices as well as to learn how to practice better. We know very little about the practical educational needs of the practicing physician and there are few instruments available to assist us or him in diagnosing his needs. Even if he manages to diagnose his own needs, few opportunities exist for him to express them. It is also true that on their own, individuals tend not to express precisely what they need, but rather their interests. A first step, therefore, would seem to be to engage physicians in a
Understanding Exercise Beliefs and Behaviors in Women With Gestational Diabetes Mellitus
Authors: Danielle Symons Downs, Jan S. Ulbrecht
Journal: Diabetes Care (2006)

The purpose of this study was to examine the exercise beliefs and behaviors of postpartum women who had gestational diabetes mellitus (GDM) during a recent pregnancy.Postpartum women with GDM (n = 28) completed a mail survey assessing their self-reported exercise beliefs (advantages, barriers, and important social influences) and behaviors.We found that 1) the strongest perceived advantage of exercise during pregnancy was controlling blood glucose and postpartum it was controlling weight, 2) the most common barrier to exercise during pregnancy was fatigue and postpartum it was a lack of time, 3) women's husband/partner most strongly influenced their exercise during pregnancy and postpartum, 4) women exercised more during the postpartum period than before or during pregnancy, and 5) the number of exercise advantages was positively associated with women's pregnancy and postpartum exercise behavior.To increase exercise behavior and reduce the risk of type 2 diabetes in women with GDM, researchers and health care professionals are encouraged to use women's exercise beliefs, that is, advantages, social influences, and perceived barriers to exercise, as a framework for designing effective diabetes treatment and prevention programs.
Emergence of Orai3 activity during cardiac hypertrophy
Authors: Youakim Saliba, Mathilde Keck, Alexandre Marchand, Fabrice Atassi, Aude Ouillé, Olivier Cazorla, Mohamed Trebak, Catherine Pavoine, Alain Lacampagne, Jean-Sébastien Hulot, Nassim Farès, Jérémy Fauconnier, Anne-Marie Lompré
Journal: Cardiovascular Research (2014)

Stromal interaction molecule 1 (STIM1) has been shown to control a calcium (Ca2+) influx pathway that emerges during the hypertrophic remodelling of cardiomyocytes. Our aim was to determine the interaction of Orai1 and Orai3 with STIM1 and their role in the constitutive store-independent and the store-operated, STIM1-dependent, Ca2+ influx in cardiomyocytes. We characterized the expression profile of Orai proteins and their interaction with STIM1 in both normal and hypertrophied adult rat ventricular cardiomyocytes. Orai1 and 3 protein levels were unaltered during the hypertrophic process and both proteins co-immunoprecipitated with STIM1. The level of STIM1 and Orai1 were significantly greater in the macromolecular complex precipitated by the Orai3 antibody in hypertrophied cardiomyocytes. We then used a non-viral method to deliver Cy3-tagged siRNAs in vivo to adult ventricular cardiomyocytes and silence Orai channel candidates. Cardiomyocytes were subsequently isolated then the voltage-independent, i.e. store-independent and store-operated Ca2+ entries were measured on Fura-2 AM loaded Cy3-labelled and control isolated cardiomyocytes. The whole cell patch-clamp technique was used to measure Orai-mediated currents. Specific Orai1 and Orai3 knockdown established Orai3, but not Orai1, as the critical partner of STIM1 carrying these voltage-independent Ca2+ entries in the adult hypertrophied cardiomyocytes. Orai3 also drove an arachidonic acid-activated inward current. Cardiac Orai3 is the essential partner of STIM1 and drives voltage-independent Ca2+ entries in adult cardiomyocytes. Arachidonic acid-activated currents, which are supported by Orai3, are present in adult cardiomyocytes and increased during hypertrophy.
Phase I study of oral irinotecan, temozolomide, and vincristine for children with refractory solid tumors: A Children's Oncology Group study
Authors: J. P. Perentesis, L. M. Wagner, M. M. Ames, J. M. Reid, C. F. Stewart, A. M. Ingle, S. M. Blaney, P. C. Adamson
Journal: Journal of Clinical Oncology (2007)

9563 Background: Both temozolomide (TEM) and vincristine (VCR) can increase the preclinical activity of low-dose protracted irinotecan (IRN) against pediatric solid tumors. Because these drugs have different dose-limiting toxicities (DLTs) and mechanisms of action, we combined these three agents and sought to determine the maximum tolerated dose (MTD) of orally administered IRN when given with fixed- dose TEM and VCR in children with relapsed or refractory solid tumors, using the antibiotic cefixime to reduce IRN-associated diarrhea. Methods: We studied two dose levels of oral IRN (35 or 50 mg/m 2 ) administered on days 1–5 and 8–12, combined with oral TEM 100 mg/m 2 on days 1–5 and intravenous VCR 1.5 mg/m 2 on days 1 and 8. Courses were repeated every 21 days. Oral cefixime was started 5 days before chemotherapy and continued daily. Results: Of 21 patients enrolled, 17 (ages 3–21, median 14 yrs) were evaluable for toxicity and have to date received 46 courses (range 1–8, median 2). At the IRN dose of 50 mg/m 2 /d, 4 of 12 patients had DLT, including elevated ALT/AST (1), abdominal pain (1), hypokalemia (1), anorexia (1), thrombocytopenia (1), and fatal liver failure in a patient with metastatic disease in the liver and porta hepatis (1). In contrast, none of 5 patients treated at the dose of 35 mg/m 2 /d experienced first-course DLT, defining this dose as the MTD. UGT1A1 genotype did not correlate with DLT in this small trial. The median SN-38 lactone area under the curve (0–6h) at the IRN dose of 50 mg/m 2 /day was 13.5 ng/ml*h (range 3.8 to 30.9); pharmacokinetic analysis of patients treated at 35 mg/m 2 /day is ongoing. Six patients with the following tumors received more than 2 courses: neuroblastoma, ependymoma, hepatoblastoma, fibrillary astrocytoma, osteosarcoma, and Ewing sarcoma. Central review of response data is underway. Three patients continue on therapy at the MTD. Conclusions: Oral administration of IRN together with TEM and VCR was feasible and well tolerated at the MTD of 35 mg/m 2 given dx5x2. Further study using a shorter 5-day course of oral IRN is planned. No significant financial relationships to disclose.
Neuromodulation of Circuits with Variable Parameters: Single Neurons and Small Circuits Reveal Principles of State-Dependent and Robust Neuromodulation
Authors: Eve Marder, Timothy O'Leary, Sonal Shruti
Journal: Annual Review of Neuroscience (2014)

Neuromodulation underlies many behavioral states and has been extensively studied in small circuits. This has allowed the systematic exploration of how neuromodulatory substances and the neurons that release them can influence circuit function. The physiological state of a network and its level of activity can have profound effects on how the modulators act, a phenomenon known as state dependence. We provide insights from experiments and computational work that show how state dependence can arise and the consequences it can have for cellular and circuit function. These observations pose a general unsolved question that is relevant to all nervous systems: How is robust modulation achieved in spite of animal-to-animal variability and degenerate, nonlinear mechanisms for the production of neuronal and network activity?
Cardiovascular, renal, and endocrine response to atrial natriuretic peptide in angiotensin II mediated hypertension.
Authors: B S Edwards, T R Schwab, R S Zimmerman, D M Heublein, N S Jiang, J C Burnett
Journal: Circulation Research (1986)

Studies done in vitro have demonstrated that atrial natriuretic peptide (ANP) antagonizes angiotensin II-mediated contraction of vascular smooth muscle. The present studies were designed to examine the in vivo actions of ANP in acute angiotensin II-mediated hypertension. The cardiovascular, renal, and hormonal effects of intravenous ANP were evaluated in anesthetized normotensive (n = 6) and hypertensive (n = 6) dogs. In both groups, ANP (3.0 micrograms/kg bolus, 0.3 micrograms/kg/min continuous infusion) reduced arterial pressure and cardiac output without changing systemic vascular resistance. ANP specifically reduced renal vascular resistance and increased sodium excretion. The natriuresis observed was greater in hypertensive than in normotensive dogs. This occurred without a significant change in glomerular filtration rate or aldosterone. The ANP-mediated reduction in arterial pressure was associated with an increase in circulating arginine vasopressin and catecholamines but not in renin. These studies demonstrate that ANP-mediated hypotension results from a reduction in cardiac output without changing systemic vascular resistance, ANP acts as a specific renal vasodilator, ANP-mediated natriuresis can occur without alteration in glomerular filtration rate or aldosterone, and ANP specifically inhibits the release of renin without inhibiting the release of other circulating vasoconstrictors.