tbuckley/cabot-search huggingface dataset:
MinK: a double-hearted partner in cardiac repolarization
Authors: A. C.G. van Ginneken
Journal: Cardiovascular Research (2009)

Tight control of the cardiac repolarization process is essential to ensure adequate action potential duration. When cardiac repolarization is disturbed—e.g. by ion-channel mutations, drugs, or disease-related defects—rhythm disturbances may ensue. Thus, a delay in repolarization, apparent in the ECG as a long QT interval, may induce early afterdepolarizations that give rise to Torsades de Pointes and can lead to life-threatening arrhythmias.1 On the other hand, a premature repolarization, resulting in a short QT interval, has also been associated with a high rate of sudden cardiac death.2

Two important players in controlling repolarization and duration of the cardiac action potential are the delayed rectifying outward potassium currents, the fast activating I Kr and the slowly activating I Ks. In most species, repolarization seems to be dominated by activation of I Kr, since I Ks normally activates slowly and with a delay such that its magnitude is minute at the end of the action potential. Hence, I Ks is supposed to act as a safety net for repolarization,3 coming into play when repolarizing currents like I Kr fail. I Ks, therefore, acts as a repolarization reserve.4

In the control of the repolarization process, different time scales can … 

*Corresponding author. Tel: +3120-5664644. E-mail address: a.c.vanginneken{at}amc.uva.nl
Rethinking Screening for Breast Cancer and Prostate Cancer
Authors: Laura Esserman, Yiwey Shieh, Ian Thompson
Journal: JAMA (2009)

After 20 years of screening for breast and prostate cancer, several observations can be made. First, the incidence of these cancers increased after the introduction of screening but has never returned to prescreening levels. Second, the increase in the relative fraction of early stage cancers has increased. Third, the incidence of regional cancers has not decreased at a commensurate rate. One possible explanation is that screening may be increasing the burden of low-risk cancers without significantly reducing the burden of more aggressively growing cancers and therefore not resulting in the anticipated reduction in cancer mortality. To reduce morbidity and mortality from prostate cancer and breast cancer, new approaches for screening, early detection, and prevention for both diseases should be considered.
DETERMINATION OF INHERITED TRAITS OF H. INFLUENZAE BY DESOXYRIBONUCLEIC ACID FRACTIONS ISOLATED FROM TYPE-SPECIFIC CELLS
Authors: Hattie E. Alexander, Grace Leidy
Journal: The Journal of Experimental Medicine (1951)

Change of non-typable (R) strains of H. influenzae into the specific type of origin or new types (S) has been effected in vitro in a predictable fashion within a single 24 hour growth period, by a desoxyribonucleic acid-containing fraction isolated from type-specific cells of the type desired. Only a small proportion of the population of R cells are susceptible to the change induced in inherited characteristics by the desoxyribonucleic acid fraction. The data suggest that the number of susceptible cells present in any given population size varies with the specific type of origin of the R cells; a lesser degree of variation in different independent cultures of the same strain and population size has been demonstrated. The results suggest that the R H. influenzae cells which are susceptible to transformation arise as the result of mutation. It has been demonstrated that the reaction necessary for transformation takes place virtually immediately if susceptible cells are present. Furthermore it has been shown that the change which enables an R cell to form a colony of type-specific organisms has been completed within 15 minutes in an environment which does not permit cell multiplication.
ASL/LBD Phylogeny Suggests that Genetic Mechanisms of Root Initiation Downstream of Auxin Are Distinct in Lycophytes and Euphyllophytes
Authors: Yoan Coudert, Anne Dievart, Gaetan Droc, Pascal Gantet
Journal: Molecular Biology and Evolution (2012)

Paleobotanical studies suggest that roots evolved at least twice independently during land plant diversification, once in lycophytes and once in euphyllophytes. Auxin promotes postembryonic root initiation in both groups but from different cell types. In several euphyllophytes, such as Arabidopsis, rice, and maize, AS2/LOB-domain (ASL/LBD) proteins act directly downstream of auxin and are conserved elements necessary for root initiation. It is currently unknown whether similar or different genetic mechanisms act downstream of auxin for root initiation in lycophytes and euphyllophytes. We searched for ASL/LBD proteins in genome sequences spanning the tree of life to retrace their evolutionary history. We performed a phylogenetic analysis of ASL/LBD proteins and mapped the functions of all characterized ASL/LBD onto the phylogenetic trees. We identified a clade specifically associated with root development, which includes no lycophyte sequence. This points toward the existence of distinct genetic mechanisms downstream of auxin for root initiation in lycophytes and euphyllophytes.
Prospective Randomized Trial of Trimethoprim/Sulfamethoxazole versus Pyrimethamine and Sulfadiazine in the Treatment of Ocular Toxoplasmosis
Authors: Masoud Soheilian, Mohammad-Mehdi Sadoughi, Mehdi Ghajarnia, Mohammad H. Dehghan, Shahin Yazdani, Hassan Behboudi, Arash Anisian, Gholam A. Peyman
Journal: Ophthalmology (2005)
Honey allergy is rare in patients sensitive to pollens
Authors: R. Kiistala, M. Hannuksela, S. Mäkinen‐Kiljunen, A. Niinimäki, T. Haahtela
Journal: Allergy (1995)

We challenged in a double‐blind manner 46 pollen‐allergic patients with 30 g of honey and another 32 patients with a placebo (30 g of syrup). Minor, mostly subjective, symptoms were seen in or reported by 26% of those challenged with honey and 41% of those challenged with placebo. In no case could the symptoms with certainty be related to the challenge. Eight commercially available honeys were examined for allergen activity by RAST inhibition and immunospot methods. Both pollen and insect allergen activity was found in all honeys, and they could cause allergic reactions. However, no serious or even obvious reaction occurred in pollen‐allergic patients challenged with honey.
An Atlas of Hair Pathology—with Clinical CorrelationsSperlingLeonard C158 pp Price £66.99 ISBN 1-84214-203-8 (h/b) London: Parthenon, 2003
Authors: Rodney Dawber
Journal: Journal of the Royal Society of Medicine (2003)

Leon Sperling has long been known for his hair pathology expertise and his Atlas of Hair Pathology also reveals his skills as a clinician. The visual components cross in a well-balanced way between disease morphology and pathology. Normal follicular anatomy is covered in detail, in particular the technical processing needed to produce the sections for horizontal viewing: this methodology is of great value for the histopathology of chronic telogen effluvium and androgenetic alopecia. In 28 chapters Sperling deals with all the areas of hair and scalp diseases, including detailed attention to differential diagnosis—particularly well covered in the fibrosing alopecias. The sections on senile alopecia (senescent balding) are very important; many clinicians and skin pathologists in their ignorance doubt the existence of this entity—but it does exist, as shown here with great clarity. I cannot imagine any dermatopathologist not wanting to possess this atlas.
Correlation of epidermal plasminogen activator activity with disease activity in psoriasis
Authors: J.E. FRAKI, G.S. LAZARUs, R.S. GILGOR, PATRICIA MARCHASE, KAY H. SINGER
Journal: British Journal of Dermatology (1983)

The specific activity of plasminogen activator was increased in clinically involved psoriatic epidermis compared with the uninvolved skin of the same eight patients. Alterations in plasminogen activator activity correlated with disease activity as measured by extent of body surface involved with psoriasis. Levels of plasminogen activator increased in uninvolved epidermis of psoriatic patients during retinoid therapy.
Activation of Stat3 in Human Melanoma Promotes Brain Metastasis
Authors: Tong-xin Xie, Feng-Ju Huang, Kenneth D. Aldape, Shin-Hyuk Kang, Mingguang Liu, Jeffrey E. Gershenwald, Keping Xie, Raymond Sawaya, Suyun Huang
Journal: Cancer Research (2006)

Abstract Brain metastasis is a major cause of morbidity and mortality in patients with melanoma. The molecular changes that lead to brain metastasis remain poorly understood. In this study, we developed a model to study human melanoma brain metastasis and found that Stat3 activity was increased in human brain metastatic melanoma cells when compared with that in cutaneous melanoma cells. The expression of activated Stat3 is also increased in human brain metastasis specimens when compared with that in the primary melanoma specimens. Increased Stat3 activation by transfection with a constitutively activated Stat3 enhanced brain metastasis, whereas blockade of Stat3 activation by transfection with a dominant-negative Stat3 suppressed brain metastasis of human melanoma cells in animal models. Furthermore, altered Stat3 activity profoundly affected melanoma angiogenesis in vivo and melanoma cell invasion in vitro and significantly affected the expression of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-2 (MMP-2) in vivo and in vitro. Finally, Stat3 activity transcriptionally regulated the promoter activity of bFGF in addition to VEGF and MMP-2 in human melanoma cells. These results indicated that Stat3 activation plays an important role in dysregulated expression of bFGF, VEGF, and MMP-2 as well as angiogenesis and invasion of melanoma cells and contributes to brain metastasis of melanoma. Therefore, Stat3 activation might be a new potential target for therapy of human melanoma brain metastases. (Cancer Res 2006; 66(6): 3188-96)
miR-204-5p Inhibits Proliferation and Invasion and Enhances Chemotherapeutic Sensitivity of Colorectal Cancer Cells by Downregulating RAB22A
Authors: Yuan Yin, Binbin Zhang, Weili Wang, Bojian Fei, Chao Quan, Jiwei Zhang, Mingxu Song, Zehua Bian, Qifeng Wang, Shujuan Ni, Yaling Hu, Yong Mao, Leyuan Zhou, Yugang Wang, Jian Yu, Xiang Du, Dong Hua, Zhaohui Huang
Journal: Clinical Cancer Research (2014)

miR-204-5p was found to be downregulated in colorectal cancer tissues in our preliminary microarray analyses. However, the function of miR-204-5p in colorectal cancer remains unknown. We therefore investigated the role, mechanism, and clinical significance of miR-204-5p in colorectal cancer development and progression.We measured the expression of miR-204-5p and determined its correlation with patient prognoses. Ectopic expression in colorectal cancer cells, xenografts, and pulmonary metastasis models was used to evaluate the effects of miR-204-5p on proliferation, migration, and chemotherapy sensitivity. Luciferase assay and Western blotting were performed to validate the potential targets of miR-204-5p after the preliminary screening by a microarray analysis and computer-aided algorithms.miR-204-5p is frequently downregulated in colorectal cancer tissues, and survival analysis showed that the downregulation of miR-204-5p in colorectal cancer was associated with poor prognoses. Ectopic miR-204-5p expression repressed colorectal cancer cell growth both in vitro and in vivo. Moreover, restoring miR-204-5p expression inhibited colorectal cancer migration and invasion and promoted tumor sensitivity to chemotherapy. Mechanistic investigations revealed that RAB22A, a member of the RAS oncogene family, is a direct functional target of miR-204-5p in colorectal cancer. Furthermore, RAB22A protein levels in colorectal cancer tissues were frequently increased and negatively associated with miR-204-5p levels and survival time.Our results demonstrate for the first time that miR-204-5p acts as a tumor suppressor in colorectal cancer through inhibiting RAB22A and reveal RAB22A to be a new oncogene and prognostic factor for colorectal cancer.
Experience with Perfusion Hypothermia Using an Improved Rotating Disc Oxygenator
Authors: F. Gerbode, J. J. Osborn, J. B. Johnston
Journal: Thorax (1960)

Cooling the living organism slows the rate of the metabolic processes.Bigelow, Lindsay, and Greenwood (1950) showed that one effect of hypothermia was that an animal would survive for a longer period when deprived of its circulation.For the first time, therefore, it became possible to shut off the circulation completely, open one of the chambers of the heart, and repair certain intracardiac abnor- malities (Lewis, Varco, and Taufic, 1954; Swan, Zeavin, and Blount, 1953).Serious obstacles were soon met when attempts were made to extend the application of this principle in the treatment of more complicated defects.If the surgeon required more than eight or 10 minutes of circulatory occlusion, he found himself sailing between Scylla and Charybdis, for prolonging the period of circulatory occlusion resulted in permanent damage to the central nervous system and further lowering of the temperature inevitably caused ventricular fibrillation.A wealth of time and effort has been spent in trying to overcome fibrillation associated with hypothermia, but, although a new ray of hope appears every few months, there is still no certain method of preventing it.Thus the early promise of hypothermia was not immediately fulfilled, and attention continued to be focused on the development of extracorporeal circulation.In the past five years the pioneering work of Miller, Gibbon, and Fineberg (1953) and many others has gone forward on many fronts, resulting in the development of cardiopulmonary bypass systems which are highly efficient and which carry minimal risk to the patient when employed by expert teams.And yet the enthusiasts of hypothermia were not idle.The direct attack on ventricular fibrillation had failed for the moment, but recently an outfilanking manceuvre has made it possible to deal with this hazard.The heart was apparently the weak link in
Effect of angiotensin-converting-enzyme inhibition compared with conventional therapy on cardiovascular morbidity and mortality in hypertension: the Captopril Prevention Project (CAPPP) randomised trial
Authors: Lennart Hansson, Lars H Lindholm, Leo Niskanen, Jan Lanke, Thomas Hedner, Anders Niklason, Kimmo Luomanmäki, Björn Dahlöf, Ulf de Faire, Claes Mörlin, Bengt E Karlberg, PO Wester, Jan-Erik Björck
Journal: The Lancet (1999)
Bipolar Depression in a Low-Income Primary Care Clinic
Authors: Mark Olfson, Amar K. Das, Marc J. Gameroff, Daniel Pilowsky, Adriana Feder, Raz Gross, Rafael Lantigua, Steven Shea, Myrna M. Weissman
Journal: American Journal of Psychiatry (2005)

OBJECTIVE: This study estimated the proportion of patients attending an urban general medical practice with current major depression and a history of bipolar disorder and compared the history, presentation, and treatment of patients with unipolar and bipolar depression. METHOD: A group of 1,143 patients was assessed with measures of past and current mental health and treatment. Patients were partitioned into bipolar and unipolar groups based on a predefined cutoff on the Mood Disorder Questionnaire. The groups were compared on sociodemographic characteristics, depressive symptoms, comorbid mental disorders, and mental health treatment. RESULTS: Approximately one-quarter of the patients with major depression had lifetime bipolar depression. Patients with unipolar and bipolar depression did not significantly differ on background or health characteristics. Patients with bipolar depression were significantly more likely to report hallucinations, current suicidal ideation, and low self-esteem than patients with unipolar depression but less likely to report disturbed appetite. Patients with bipolar depression were significantly more likely to have an alcohol use disorder and to report inpatient psychiatric care and antipsychotic treatment during the past month than patients with unipolar depression. Nearly one-half of the patients with bipolar depression had taken an antidepressant in the last month, but most were not also being treated with an antipsychotic or mood stabilizer. CONCLUSIONS: Bipolar depression is common in urban general medicine practice. When patients took antidepressants, they seldom received concurrent antimanic medications. Because of the risks of treating bipolar disorder with antidepressant monotherapy, physicians should assess their depressed patients for mania before prescribing antidepressants.
Functional Vascular Endothelial Growth Factor −634G&amp;gt;C SNP Is Associated With Proliferative Diabetic Retinopathy
Authors: Flavia I.V. Errera, Luís Henrique Canani, Maria Elisabeth R. Silva, Erika Yeh, Walter Takahashi, Katia G. Santos, Katia E.P. Souto, Balduíno Tschiedel, Israel Roisenberg, Jorge Luis Gross, Maria Rita Passos-Bueno
Journal: Diabetes Care (2007)

The purpose of this study was to evaluate the effect of the single nucleotide polymorphism (SNP) -634G>C at the 5' regulatory region of the vascular endothelial growth factor (VEGF) in the risk of proliferative diabetic retinopathy (PDR) in the Brazilian population of European ancestry with type 2 diabetes.A case-control study was conducted in 501 type 2 diabetic patients of European ancestry. Patients underwent a standardized clinical, ophthalmological, and laboratory evaluation. Of these, 167 patients had PDR (case patients), and 334 were considered as control subjects (patients without PDR) for PDR. A reference population (110 individuals of European ancestry) was also evaluated.No evidence of association between -634G>C/VEGF and the presence of diabetic retinopathy or type 2 diabetes was observed (P > 0.05). However, CC homozygous for the SNP -634G>C was significantly more frequent in patients with PDR (37 of 167; 22.2%) than in the corresponding control group (40 of 334; 12%) in accordance with a recessive model (P = 0.003). This effect was further observed when creatinine, BMI, sex, duration of type 2 diabetes, HDL cholesterol, and systolic blood pressure were taken into account (odds ratio 1.9 [95% CI 1.01-3.79], P = 0.04).The presence of the allele -634C/VEGF in homozygosity is an independent risk factor for the development of PDR in type 2 diabetic patients of European ancestry.
The Effect of Malpractice Reform on Emergency Department Care
Authors: Daniel A. Waxman, Michael D. Greenberg, M. Susan Ridgely, Arthur L. Kellermann, Paul Heaton
Journal: New England Journal of Medicine (2014)

Many believe that fear of malpractice lawsuits drives physicians to order otherwise unnecessary care and that legal reforms could reduce such wasteful spending. Emergency physicians practice in an information-poor, resource-rich environment that may lend itself to costly defensive practice. Three states, Texas (in 2003), Georgia (in 2005), and South Carolina (in 2005), enacted legislation that changed the malpractice standard for emergency care to gross negligence. We investigated whether these substantial reforms changed practice.Using a 5% random sample of Medicare fee-for-service beneficiaries, we identified all emergency department visits to hospitals in the three reform states and in neighboring (control) states from 1997 through 2011. Using a quasi-experimental design, we compared patient-level outcomes, before and after legislation, in reform states and control states. We controlled for characteristics of the patients, time-invariant hospital characteristics, and temporal trends. Outcomes were policy-attributable changes in the use of computed tomography (CT) or magnetic resonance imaging (MRI), per-visit emergency department charges, and the rate of hospital admissions.For eight of the nine state-outcome combinations tested, no policy-attributable reduction in the intensity of care was detected. We found no reduction in the rates of CT or MRI utilization or hospital admission in any of the three reform states and no reduction in charges in Texas or South Carolina. In Georgia, reform was associated with a 3.6% reduction (95% confidence interval, 0.9 to 6.2) in per-visit emergency department charges.Legislation that substantially changed the malpractice standard for emergency physicians in three states had little effect on the intensity of practice, as measured by imaging rates, average charges, or hospital admission rates. (Funded by the Veterans Affairs Office of Academic Affiliations and others.).
Oral chemotherapy safety practices at US cancer centres: questionnaire survey
Authors: Saul N Weingart, Jonathan Flug, Daniela Brouillard, Laurinda Morway, Ann Partridge, Sylvia Bartel, Lawrence N Shulman, Maureen Connor
Journal: BMJ (2007)

<b>Objective</b> To characterise current safety practices for the use of oral chemotherapy. <b>Design</b> Written questionnaire survey of pharmacy directors of cancer centres. <b>Setting</b> Comprehensive cancer centres in the United States. <b>Results</b> Respondents from 42 (78%) of 54 eligible centres completed the survey, after consulting with 89 colleagues. Clinicians at 29 centres used handwritten prescriptions, two used preprinted paper prescriptions, and six used electronic systems for most oral chemotherapy prescribing. For six commonly used oral chemotherapies, on average 10 centres required a diagnosis on the prescription, 11 required the protocol number, four required the cycle number, nine required double checking by a second clinician, 14 required a calculation of body surface area, and 14 required a calculation of dose per square metre of body surface area. Only a third of centres requested patients9 written informed consent when oral chemotherapy was given off protocol. Nearly a quarter (10) of centres had no formal process for monitoring patients9 adherence. In the past year respondents at 10 centres reported at least one serious adverse drug event related to oral chemotherapy, and respondents at 13 centres reported a serious near miss. <b>Conclusion</b> Few of the safeguards routinely used for infusion chemotherapy have been adopted for oral chemotherapy at US cancer centres. There is currently no consensus at these centres about safe medication practices for oral chemotherapy.