tbuckley/cabot-search huggingface dataset:
Abstract 3531: Different isoforms of drug-resistant genes may influence breast cancer survival
Authors: Yayha Elshimali, Daniel Chen, Yanyuan Wu, Jaydutt V. Vadgama
Journal: Cancer Research (2010)

Abstract One major impediment to the success of chemotherapy in cancer patients is the risk of developing drug resistance. One mechanism leading to multidrug resistance in cancer therapy is through the ABC transporters. The eukaryotic ABC genes are organized as transporters containing two transmembrane and two ATP binding domains. Alternative splicing is one major mechanism in which a single gene generates functional diversity by producing different spliced isoforms. To determine the variability of ABC transporters, we performed exhaustive search of the NCBI database for ABC transporter genes, in addition to using the Alternative Splicing Annotation Project (ASAP) and the Alternative Splicing Database (ASD). We conducted immunostaining for MRP1 and MDR1 on tissue micro array of 23 breast cancer patients and RNA mediated annealing, selection, extension and ligation (RASL) assay for analysis of mRNA splicing isoforms which was performed on exon/exon target. Tumor cells from chemotherapy resistant patients show specific expression patterns of drug-resistant ATP-binding cassette transporter. Our data showed alternative splicing in 3 and 4 exon/exon borders in MDR1 and PGP genes. Two splicing events in MDR1 and one in PGP transcripts were predicted to be alternatively spliced in ASAP database. Interestingly, exon11/12 border in MDR1 is found to be alternatively spliced. In summary, protein microarray analysis demonstrated significant correlation between MRP1 expression and survival rate within 5 years. In contrast, MDRI protein expression did not correlate with 5 year survival rate. This may be due to variations in the MDR1 isoforms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3531.
Quantification in vivo of increased LDL content and rate of LDL degradation in normal rabbit aorta occurring at sites susceptible to early atherosclerotic lesions.
Authors: D C Schwenke, T E Carew
Journal: Circulation Research (1988)

While the exact mechanisms that initiate atherosclerotic lesions are unknown, considerable evidence supports a role for low density lipoprotein (LDL). We investigated whether in the normal rabbit, LDL metabolism in areas of aorta that are destined to become lesioned during cholesterol feeding differed from the metabolism in adjacent lesion-resistant aorta. These studies took advantage of the predictable pattern of early atherosclerotic lesions in the cholesterol-fed rabbit. Early lesions occur diffusely in the aortic arch and ascending aorta and distal to branch orifices in the abdominal aorta and the descending thoracic aorta. Arterial rates of irreversible degradation of LDL and concentrations of intact LDL were measured in susceptible and resistant sites with homologous doubly labeled LDL. LDL was labeled directly with 131I and with 125I-tyramine cellobiose. The latter label provides a highly sensitive means to determine the sites and rates of lipoprotein degradation in vivo. The arterial concentration of intact LDL in the lesion-prone aortic arch was 3.12 +/- 0.45 micrograms LDL cholesterol/g (n = 14), 3.6 +/- 0.69 times that in the relatively lesion-resistant descending thoracic aorta (p less than 0.001). The rate of LDL degradation in the aortic arch was 3.14 +/- 0.41 micrograms LDL cholesterol/g/day, 2.14 +/- 0.24 times that in the descending thoracic aorta (p less than 0.001). In the abdominal aorta, the LDL (per gram wet weight) concentration and degradation rate (per square centimeter surface area) at branch sites exceeded that at nonbranch sites by 88 +/- 11% (p less than 0.001) and by 61 +/- 8% (p less than 0.001), respectively. These data provide evidence that in the normal rabbit, which does not develop atherosclerotic lesions, focal elevations of arterial LDL degradation rate and concentrations of intact LDL occur at sites that first develop atherosclerotic lesions in the hypercholesterolemic animal. These differences in LDL metabolism may be linked causally to the propensity to develop atherosclerotic lesions at these sites.
Divorce Among Physicians
Authors: Mohammadreza Hojat
Journal: JAMA (1989)

To  Editor.—  Doherty and Burge1reported 43 and 82 divorces per 1000 among male and female physicians, respectively. They compared these findings with  corresponding figures of 55 and 106 in  employed population and concluded that the marriages of physicians—men and women alike— have a lower likelihood of ending in divorce than  rest of  employed population.  This conclusion could be misleading for  following reasons. These figures are based on a population 16 years of age and older. The fact that physicians have a tendency to marry at older ages than other employed populations,1,2coupled with  fact that  divorce rate is lower among older populations,3could lead to a spurious underestimation of divorce rates among physicians compared with other employed populations.  A better indicator of divorce rate among physicians is  percentage of marriages that eventually end in divorce (cohort approach).
Quasi-modal encounters of the third kind: The filling-in of visual detail
Authors: Frank H. Durgin
Journal: Behavioral and Brain Sciences (1998)

Although Pessoa et al. imply that many aspects of the filling-in debate may be displaced by a regard for active vision, they remain loyal to naive neural reductionist explanations of certain pieces of psychophysical evidence. Alternative interpretations are provided for two specific examples and a new category of filling-in (of visual detail) is proposed.
Immune responses to hair dyes containing toluene‐2,5‐diamine
Authors: J.D. Schmidt, J.D. Johansen, M.M. Nielsen, E. Zimersson, C. Svedman, M. Bruze, K. Engkilde, S.S. Poulsen, C. Geisler, C.M. Bonefeld
Journal: British Journal of Dermatology (2013)

Toluene-2,5-diamine (PTD) is the most frequently used dye in oxidative hair dyes on the Scandinavian market. However, little is known about immune responses to PTD-containing oxidative hair dyes.To study immune responses induced by PTD-containing hair dyes in mice.Immune responses against two different permanent hair dye products containing 1·60% (w/w) and 0·48% (w/w) PTD within the colour gel, and various concentrations of pure PTD were studied. The local inflammatory response was measured by ear swelling and cell infiltration, and T- and B-cell infiltration and proliferation was determined in the draining lymph nodes.Concentration-dependent immune responses were seen to PTD both in the skin and draining lymph nodes. The hair dye containing 1·60% PTD induced strong local inflammation and caused T- and B-cell infiltration and proliferation as well as an increased number of regulatory T cells in the draining lymph nodes. In contrast, the hair dye containing 0·48% PTD induced skin inflammation but only minor responses in the draining lymph nodes.Consumer-available PTD-containing permanent hair dyes can be potent immune activators inducing both pro- and anti-inflammatory responses. The outcome of the response is dependent on allergen dose, amount of additional allergens and exposure regime.
After a first episode of venous thromboembolism
Authors: C N Chesterman
Journal: BMJ (1995)

Several advances in the management of venous thromboembolism with anticoagulants have occurred over the past few years. The importance of rapid and adequate treatment with heparin is well established. So is the early introduction of oral warfarin,1 which results in patients being given heparin for shorter periods and having shorter stays in hospitalcompared with days gone by. Nomograms for warfarin have made initial dosing easier and more predictable.2 The widespread use of the international normalised ratio for reporting the effect of warfarin has resulted in more universally accepted recommendations regarding the desirable degree of anticoagulation in given clinical settings.

Two aspects of management require further systematic investigation: the correct place to be assigned to low molecular weight heparins and (the topic to be discussed here) the optimal duration of oral anticoagulant treatment after a first symptomatic thromboembolic event.

Despite pages covering mechanisms, drug interactions, and other information, instructions regarding the optimal duration of treatment in most textbooks are refreshingly terse and to the point: “Anticoagulation with warfarin is usually continued for 3-6 months.” …
Impact of TT virus infection in acute and chronic, viral- and non viral-related liver diseases
Authors: Rosella Tuveri, Franck Jaffredo, Francoise Lunel, Bertrand Nalpas, Stanislas Pol, Cyrille Feray, Patrick Marcellin, Vincent Thibault, Jean-Francois Delagneau, Pierre Opolon, Bachisio Scarpa, Christian Bréchot, Valerie Thiers
Journal: Journal of Hepatology (2000)
Medical Practice a la Mode
Authors: John F. Burnum
Journal: New England Journal of Medicine (1987)

That I might be a pawn of fashion first came home to me about 10 years ago when a number of new nonsteroidal antiinflammatory drugs were being introduced. In October 1978, sulindac (Clinoril) was introduced to the market and to the public in a press conference that resulted in extensive media coverage.Within a few hours of the first press reports, I was buried by an avalanche of urgent telephone requests for the new wonder drug. With ill humor, I complied. No credit to me that sulindac turned out to be a useful drug; I was merely kneeling to fashion. . . .
Key Role of the P2Y <sub>1</sub> Receptor in Tissue Factor–Induced Thrombin-Dependent Acute Thromboembolism
Authors: Catherine Léon, Monique Freund, Catherine Ravanat, Anthony Baurand, Jean-Pierre Cazenave, Christian Gachet
Journal: Circulation (2001)

Background —ADP plays a key role in hemostasis, acting through 2 platelet receptors: the P2Y 1 receptor and an unidentified P2 receptor, called P2cyc, coupled to adenylyl cyclase inhibition, which is the target of the antiplatelet drug clopidogrel. We showed that the P2Y 1 receptor is an essential cofactor in thrombotic states induced by intravenous infusion of collagen and epinephrine. The aim of the present study was to assess the role of this receptor in thrombin-dependent tissue factor–induced thromboembolism. Methods and Results —Human thromboplastin was injected intravenously into wild-type or P2Y 1 -deficient mice, and the effects on platelet count and mortality were determined and plasma thrombin–antithrombin III (TAT) complexes were quantified. P2Y 1 -deficient mice were resistant to the thromboembolism induced by injection of thromboplastin. Whereas the platelet count decreased sharply in wild-type mice, there was no significant drop in platelets in P2Y 1 -knockout mice. The platelet consumption in wild-type mice was probably due to thrombin generation, because it was abolished by hirudin. Thromboplastin also led to a rise in TAT complexes in plasma, again reflecting thrombin formation. This effect, however, was less important in P2Y 1 -knockout mice than in wild-type mice, indicating that less thrombin was generated in the absence of P2Y 1 . Similar results were obtained after intravenous administration of N 6 -methyl-2′-deoxyadenosine-3′:5′-bisphosphate, a selective antagonist of the P2Y 1 receptor, to wild-type mice. Conclusions —Our results demonstrate a role of the P2Y 1 receptor in thrombotic states involving thrombin generation and provide further evidence for the potential relevance of this receptor as a target for antithrombotic drugs.
THE SURGICAL MANAGEMENT OF PATIENTS WITH GOITER
Authors: W. D. HAINES
Journal: JAMA (1923)

Perhaps in no other morbid condition does preoperative management count for more than in the patient with toxic goiter. In many respects, such patients react to surgical intervention not unlike epileptic and other neurotic patients; that is to say, one should be prepared for the unexpected. Despite intensive, continuous studies by the clinician, the goiter problem has baffled all attempts at standardization.  Disease of the thyroid is marked by distinct periods of rise and fall in the severity of the symptoms and intervals of quiescence. It is chiefly in the misinterpretation of the ebb and flow of these clinical phenomena that we ride to a fall in the management of patients with goiter. The history sheet should indicate the status on admission, i. e., whether the symptoms are increasing in severity, becoming less annoying, or are stationary.  One should determine as fully as the means at his command will admit
More than 90% of urgent cancer referrals seen within two weeks
Authors: S. Mayor
Journal: BMJ (2001)

More than 90% of patients in England urgently referred to a hospital specialist for any suspected cancer were seen within two weeks, although there was considerable variation between different regions, according to figures published last week.

Referral figures for April to June 2001 showed that 92.4% of patients with urgent referrals for cancer were seen by a specialist within two weeks. The findings, which applied to patients whose referrals were received by hospitals within 24 hours of seeing their GPs, indicated that many hospitals are meeting the two week target set out in the national …
Functionalized nanoscale β-1,3-glucan to improve Her2+ breast cancer therapy: In vitro and in vivo study
Authors: Zahra Nasrollahi, Shahla Roudbar Mohammadi, Esmail Mollarazi, Mohammad Hossein Yadegari, Zuhair Mohammad Hassan, Fatemeh Talaei, Rassoul Dinarvand, Hassan Akbari, Fatemeh Atyabi
Journal: Journal of Controlled Release (2015)
Staphylococcus aureus: colonizing features and influence of an antibacterial treatment in adults with atopic dermatitis
Authors: K. Breuer, S. HAussler, A. Kapp, T. Werfel
Journal: British Journal of Dermatology (2002)

The skin of up to 100% of patients with atopic dermatitis (AD) is colonized with Staphylococcus aureus. Of all S. aureus strains isolated from lesional skin, up to 65% have been shown to produce exotoxins with superantigenic properties. Patients colonized with S. aureus have been treated with antibiotics in several open and double-blind placebo-controlled studies, with conflicting results. These studies did not consider the anterior nares as a reservoir of S. aureus, or the possibility of transmission between patients and their contacts. Moreover, adult patients have not so far been investigated.To investigate the colonizing features of S. aureus in adults with AD and in their contacts, and the effect of an antimicrobial treatment of the patients and their partners.Swabs were taken from the skin and anterior nares of 66 adults with AD. S. aureus strains were screened for the production of exotoxins in 32 patients. Ten patients (two with toxigenic strains, eight with non-toxigenic strains) were treated orally with cefalexin, chlorhexidine ointment was applied to the skin, and the anterior nares were treated with mupirocin ointment. A bath containing potassium permanganate was taken daily. In addition, their partners were treated topically.Sixty-two of 66 patients (94%) were carriers of S. aureus, and mostly harboured the bacteria on both skin and anterior nares. Ten of 32 (31%) patients were colonized with toxigenic strains. The Severity Scoring in AD (SCORAD) score decreased in nine of 10 patients who received antimicrobial treatment (P < 0.001), and this effect was more pronounced in patients with a baseline SCORAD > 50.S. aureus may play an important role as an aggravating factor in adults with AD, as antimicrobial treatment leads to a significant improvement of AD in patients who are colonized with the bacterium.
Anti-P-selectin monoclonal antibody attenuates reperfusion injury to the rabbit ear.
Authors: R K Winn, D Liggitt, N B Vedder, J C Paulson, J M Harlan
Journal: Journal of Clinical Investigation (1993)

Neutrophil adherence and/or aggregation has been implicated in ischemia reperfusion injuries. We examined the role of P-selectin in PMN-mediated injury after reperfusion of the rabbit ear. The ear was partially amputated, and then reattached leaving the central artery and vein intact. To induce ischemia the central artery was then occluded. Treatment was at reperfusion with either saline or one of two murine P-selectin mAbs, designated PB1.3 and PNB1.6 mAb PB1.3 cross-reacts with rabbit P-selectin and prevents histamine-induced leukocyte rolling, whereas PNB1.6 does not. Using a peroxidase-antiperoxidase system P-selectin was detected in the ischemic ear, but not in the nonischemic ear. Ear volume increased to 5.3 times baseline in the saline-treated animals (n = 8), 6.6 times baseline in the nonblocking mAb PNB1.6-treated animals (n = 2), and 3.7 times baseline in the blocking mAb PB1.3-treated animals (n = 8). Estimated tissue necrosis of the combined saline- and PNB1.6-treated animals was 46 vs. 2.7% for the mAb PB1.3-treated animals. We conclude that: (a) P-selectin is expressed in ischemia reperfusion; (b) P-selectin participates in PMN-endothelial cell interactions in ischemia reperfusion; and (c) inhibiting P-selectin adhesion significantly reduces reperfusion injury.
Early Environmental Origins of Neurodegenerative Disease in Later Life
Authors: Philip J. Landrigan, Babasaheb Sonawane, Robert N. Butler, Leonardo Trasande, Richard Callan, Daniel Droller
Journal: Environmental Health Perspectives (2005)

Parkinson disease (PD) and Alzheimer disease (AD), the two most common neurodegenerative disorders in American adults, are of purely genetic origin in a minority of cases and appear in most instances to arise through interactions among genetic and environmental factors. In this article we hypothesize that environmental exposures in early life may be of particular etiologic importance and review evidence for the early environmental origins of neurodegeneration. For PD the first recognized environmental cause, MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), was identified in epidemiologic studies of drug abusers. Chemicals experimentally linked to PD include the insecticide rotenone and the herbicides paraquat and maneb; interaction has been observed between paraquat and maneb. In epidemiologic studies, manganese has been linked to parkinsonism. In dementia, lead is associated with increased risk in chronically exposed workers. Exposures of children in early life to lead, polychlorinated biphenyls, and methylmercury have been followed by persistent decrements in intelligence that may presage dementia. To discover new environmental causes of AD and PD, and to characterize relevant gene-environment interactions, we recommend that a large, prospective genetic and epidemiologic study be undertaken that will follow thousands of children from conception (or before) to old age. Additional approaches to etiologic discovery include establishing incidence registries for AD and PD, conducting targeted investigations in high-risk populations, and improving testing of the potential neurologic toxicity of chemicals.
Hepatitis B in a West Indian population in the United Kingdom
Authors: M J Godley, P W Laidler, J E Banatvala
Journal: BMJ (1986)

Comparaison des serums de 195 noirs nes aux Indes Occidentales, 259 nes en Grande-Bretagne de parents nes la-bas et 180 sujets de race blanche, tous adultes heterosexuels. La frequence des marqueurs de l'hepatite virale B est augmentee nettement dans le premier groupe seulement, ce qui indique que les facteurs de milieu sont plus importants que les facteurs genetiques
Three year follow up of patients with raised blood pressure identified at health checks in general practice.
Authors: D. Mant, C. McKinlay, A. Fuller, T. Randall, E. M. Fullard, J. Muir
Journal: BMJ (1989)

OBJECTIVE--To assess the extent of three year follow up of blood pressure, weight, and smoking habit in patients with raised blood pressure identified at health checks. DESIGN--Retrospective audit of medical and nursing records. SETTING--Three general practices in Oxfordshire. PATIENTS--386 of 448 patients with raised blood pressure (diastolic greater than or equal to 90 or systolic greater than or equal to 160 mm Hg) identified from 2935 patients aged 35-64 attending health checks in 1982-4. MEASUREMENTS and MAIN RESULTS--All records of blood pressure, weight, and smoking habit in the medical record were abstracted for three years after the initial health check. All 42 patients with an initial diastolic blood pressure greater than or equal to 105 mm Hg and 316 of 344 patients with an initial pressure of 90-104 mm Hg had at least one further measurement of their blood pressure. Follow up of smoking habit and of weight was less complete with only half of the 100 smokers and 67 of the 87 obese patients (body mass index greater than or equal to 30) having any documented follow up of these risk factors. Annual follow up in the second and third years occurred in 228/297 (76.8%) and 232/320 (72.5%) in patients with blood pressure greater than 95 mm Hg at the beginning of each year. For patients who smoked annual follow up in these years occurred in fewer than a third and for those who were obese in just over half. On the assumption that those not followed up had not changed, at the end of three years the proportion of patients with diastolic blood pressure greater than or equal to 100 mm Hg had fallen from 61 patients (15.8%) to 31 (8.1%); the proportion of smokers had fallen from 103 (26.7%) to 94 (24.4%); and the proportion of obese patients had fallen from 87 (22.5%) to 79 (20.5%). CONCLUSIONS--These changes were modest and in the absence of a control group cannot be attributed necessarily to health checks. Although the standard of follow up was better than in previously reported studies of the management of hypertension, the results emphasise the need to develop formal protocols for dietary and antismoking interventions and to evaluate formally the effectiveness (and cost effectiveness) of health checks.
The allergen specificity of the late asthmatic reaction
Authors: M. Hatzivlassiou, C. Grainge, V. Kehagia, L. Lau, P. H. Howarth
Journal: Allergy (2009)

Allergen inhalation challenge in asthma may induce both early (EAR) and late (LAR) asthmatic reactions. The EAR is IgE and mast cell dependent. The mechanism of the LAR is less well defined and we have hypothesized may be allergen dependent. The aim of this study was to investigate the allergen specificity of the LAR to allergen inhalation in asthma.In a randomized, double-blind, crossover design six asthmatic volunteers with dual sensitization to house dust mite (HDM) allergen and grass pollen (GP) allergen underwent inhalation allergen challenge with these separate allergens on two occasions separated by 14 days. Lung function changes were followed for 8-h postchallenge. Bronchial reactivity (histamine PC(20)) and airway inflammation, assessed by induced sputum differential cell count, were measured 24-h pre and postallergen challenge. The allergen inhalation challenges were matched to achieve the same magnitude of EAR.Despite comparable group mean EAR percent falls in FEV(1) (25.8% following GP and 28.0% following HDM (P = 0.917), the LAR was statistically greater on the HDM challenge day (13.0%vs 22.8% [P = 0.046]) and was associated with a significant airway eosinophil recruitment (mean (SD) of 5.4 (4.8)% to 22.1 (18.2)% (P = 0.028) that was not evident on the GP allergen challenge day.These findings identify the allergen specificity of the LAR and indicate that factors independent of IgE contribute to the LAR. Such findings have relevance both to the understanding of the allergen-induced airway responses in asthma and the need for homogeneity in inhaled-allergen challenge studies in asthma.