tbuckley/cabot-search huggingface dataset:
Membrane Transporters and Channels
Authors: Ying Huang, Pascale Anderle, Kimberly J. Bussey, Catalin Barbacioru, Uma Shankavaram, Zunyan Dai, William C. Reinhold, Audrey Papp, John N. Weinstein, Wolfgang Sadée
Journal: Cancer Research (2004)

Abstract Membrane transporters and channels (collectively the transportome) govern cellular influx and efflux of ions, nutrients, and drugs. We used oligonucleotide arrays to analyze gene expression of the transportome in 60 human cancer cell lines used by the National Cancer Institute for drug screening. Correlating gene expression with the potencies of 119 standard anticancer drugs identified known drug-transporter interactions and suggested novel ones. Folate, nucleoside, and amino acid transporters positively correlated with chemosensitivity to their respective drug substrates. We validated the positive correlation between SLC29A1 (nucleoside transporter ENT1) expression and potency of nucleoside analogues, azacytidine and inosine-glycodialdehyde. Application of an inhibitor of SLC29A1, nitrobenzylmercaptopurine ribonucleoside, significantly reduced the potency of these two drugs, indicating that SLC29A1 plays a role in cellular uptake. Three ABC efflux transporters (ABCB1, ABCC3, and ABCB5) showed significant negative correlations with multiple drugs, suggesting a mechanism of drug resistance. ABCB1 expression correlated negatively with potencies of 19 known ABCB1 substrates and with Baker’s antifol and geldanamycin. Use of RNA interference reduced ABCB1 mRNA levels and concomitantly increased sensitivity to these two drugs, as expected for ABCB1 substrates. Similarly, specific silencing of ABCB5 by small interfering RNA increased sensitivity to several drugs in melanoma cells, implicating ABCB5 as a novel chemoresistance factor. Ion exchangers, ion channels, and subunits of proton and sodium pumps variably correlated with drug potency. This study identifies numerous potential drug-transporter relationships and supports a prominent role for membrane transport in determining chemosensitivity. Measurement of transporter gene expression may prove useful in predicting anticancer drug response.
A Core–Shell Albumin Copolymer Nanotransporter for High Capacity Loading and Two‐Step Release of Doxorubicin with Enhanced Anti‐Leukemia Activity
Authors: Yuzhou Wu, Susann Ihme, Michaela Feuring‐Buske, Seah Ling Kuan, Klaus Eisele, Markus Lamla, Yanran Wang, Christian Buske, Tanja Weil
Journal: Advanced Healthcare Materials (2012)

Abstract The native transportation protein serum albumin represents an attractive nano‐sized transporter for drug delivery applications due to its beneficial safety profile. Existing albumin‐based drug delivery systems are often limited by their low drug loading capacity as well as noticeable drug leakage into the blood circulation. Therefore, a unique albumin‐derived core‐shell doxorubicin (DOX) delivery system based on the protein denaturing‐backfolding strategy was developed. 28 DOX molecules were covalently conjugated to the albumin polypeptide backbone via an acid sensitive hydrazone linker. Polycationic and pegylated human serum albumin formed two non‐toxic and enzymatically degradable protection shells around the encapsulated DOX molecules. This core‐shell delivery system possesses notable advantages, including a high drug loading capacity critical for low administration doses, a two‐step drug release mechanism based on pH and the presence of proteases, an attractive biocompatibility and narrow size distribution inherited from the albumin backbone, as well as fast cellular uptake and masking of epitopes due to a high degree of pegylation. The IC 50 of these nanoscopic onion‐type micelles was found in the low nanomolar range for Hela cells as well as leukemia cell lines. In vivo data indicate its attractive potential as anti‐leukemia treatment suggesting its promising profile as nanomedicine drug delivery system.
Advanced glycation and lipidoxidation of the peritoneal membrane: Respective roles of serum and peritoneal fluid reactive carbonyl compounds
Authors: Toshio Miyata, Katsunori Horie, Yasuhiko Ueda, Yuji Fujita, Yuko Izuhara, Hiroshi Hirano, Koji Uchida, Akira Saito, Charles Van Ypersele De Strihou, Kiyoshi Kurokawa
Journal: Kidney International (2000)
Low proteasome activity as a means to track and target breast cancer stem cells in-vivo.
Authors: CH Lagadec, E Vlashi, L Dolla Donna, W McBride, F Pajonk
Journal: Cancer Research (2009)

Abstract Abstract #5055 Based on clinical observations, the existence of cancer stem cells (CSCs)/cancer initiating cells (CICs) in solid cancers has been postulated by radiation biologists and oncologists for decades. According to the stem cell hypothesis, only a small number of CSCs/CISs within a tumor have the ability to repopulate an entire tumor while their progeny does not. CSCs/CISs in solid tumors can now be identified prospectively in gliomas, head &amp; neck cancers, pancreatic cancers, colon cancers, prostate cancers, melanomas, and in breast cancers. CSCs/CISs are thought to be mostly quiescent and relatively resistant to conventional anti-cancer therapy.&amp;#x2028; Breast CSCs/CICs are enriched in cell populations with high CD44 and low or absent CD24 expression. Unfortunately, detection of breast CSCs/CISs, using CD44 and CD24 expression analysis, requires dissociation of the tumors and antibody staining for surface markers. We recently discovered that cancer stem cells, and specially breast CSCs/CICs, have low proteasome activity. In order to utilize this novel marker for the identification of breast CSCs/CICs, we developed retroviral vectors coding for fusion proteins between thymidine kinase (TK), the fluorescent protein ZsGreen and the c-terminal degron of murine ornithine decarboxylase (cODC). We stably transfected human breast cancer cells lines (MCF-7, MDA-MB-231, T47-D) with this reporter gene construct for 26S proteasome activity.&amp;#x2028; Our reporter construct allowed us to track CSCs/CICs responses to radiation therapy in vivo via fluorescent imaging, but also to target them selectively using suicide gene (TK) therapy. Thus, the use of thymidine kinase in our fusion constructs allows for specific elimination of this cell population by ganciclovir preventing self-renewal in-vitro and causing T47-D and MDA-MB-231 tumor xenograft regression in vivo. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5055.
Ethics of clinical trials from a bayesian and decision analytic perspective: whose equipoise is it anyway?
Authors: R. J Lilford
Journal: BMJ (2003)

<i>Should the equipoise of the patient, or that of the doctor, determine whether a patient enters a clinical trial? People asking patients to consent to trials are glossing over the ethical complexities. Choices should be based both on probabilities of events (which experts might know) and on the value that a patient places on those events (which only the patient can know)</i>
ISOPRAL AND CHLORAL HYDRATE.COMMENTS ON THE ABOVE CRITICISM BY IMPENS.
Authors: REID HUNT
Journal: JAMA (1907)

Impens brings forward nothing new in this communication. Nearly half the article is taken up with quotations from other writers to support his previous contentions; the remainder is devoted to a criticism of Hatcher's methods. A very little examination suffices to show that Impens presents the matter from a most prejudiced point of view. By selecting only the parts favorable to his side and ignoring everything unfavorable his quotations of certain authors give an entirely erroneous impression of their attitude toward some of the chief points under discussion; he attributes experiments to one author (Frey) when there is evidence that this author never performed such experiments. He accepts without question other experiments, apparently favorable to his contentions, although a very little examination shows that they were made in such an unscientific way that no conclusions can safely be drawn from them. His discussion of Hatcher's results is likewise one-sided and
Letting the Genome out of the Bottle — Will We Get Our Wish?
Authors: David J. Hunter, Muin J. Khoury, Jeffrey M. Drazen
Journal: New England Journal of Medicine (2008)

Interview with Muin Khoury on personal genomics services being offered directly to consumers. (06:45)Download It may happen soon. A patient, perhaps one you have known for years, who is overweight and does not exercise regularly, shows up in your office with an analysis of his whole genome at multiple single-nucleotide polymorphisms (SNPs). His children, who were concerned about his health, spent $1,000 to give him the analysis as a holiday gift. The test report states that his genomic profile is consistent with an increased risk of both heart disease and diabetes, and because the company that performed the analysis stated that the test was "not a clinical service to be used as the basis . . .
Tumor Marker–Guided PET in Breast Cancer Patients—A Recipe for a Perfect Wedding
Authors: Laura Evangelista, Anna Rita Cervino, Cristina Ghiotto, Adil Al-Nahhas, Domenico Rubello, Pier Carlo Muzzio
Journal: Clinical Nuclear Medicine (2012)

Early detection of breast cancer (BC) recurrence is a fundamental issue during follow-up. Although the utilization of new therapeutic protocols aimed at reducing the recurrence risk is defined, the diagnostic approach for early detection remains to be clarified. We aim to provide a critical overview of recently published reports and perform a meta-analysis on the use of tumor markers in BC patients as a guide for fluorodeoxyglucose positron emission tomography (PET) imaging.Medline and Google Scholar were used for searching English and non-English articles that evaluate the role of PET in BC recurrence when an increase in tumor markers is found. All complete studies were reviewed; thus, quantitative and qualitative analyses were performed.From 2001 to May 2011, we found 19 complete articles that critically evaluated the role of PET in BC recurrence detection in the presence of elevated tumor markers. The meta-analysis of the 13 studies provided the following results: pooled sensitivity 0.878 (95% CI: 0.838-0.909), pooled specificity 0.693 (95% CI: 0.553-0.805), and pooled accuracy 0.828 (95% CI: 0.762-0.878).The current experience confirms the potential of fluorodeoxyglucose PET, and in particular of PET/CT, in detecting occult soft tissue and bone metastases in the presence of a progressive increase of serum tumor markers in BC patients, but this should be better defined in the current practical recommendations.
The Graying of Grand Rounds
Authors: Franz J. Ingelfinger
Journal: New England Journal of Medicine (1978)

Once upon a time, Grand Rounds, so popular and populous that they came to be held in a hospital's auditorium or similar facility, were well organized, decorous, stately and punctual exercises. The chief and other leaders of the service occupied the front rows, and behind them, in hierarchical tiers, sat staff, house officers, students and others. At the appointed hour, the case presentation began, and the patient's story was then unfolded, usually by a house officer or student so intimately acquainted with the facts that reference to written work, numbers or notes was unnecessary. Frequently, a diagram on the blackboard, . . .
The effects of oxygen and dopamine on renal and aortic blood flow in chronic obstructive pulmonary disease with hypoxemia and hypercapnia.
Authors: T Q Howes, C R Deane, G E Levin, S V Baudouin, J Moxham
Journal: American Journal of Respiratory and Critical Care Medicine (1995)

Renal blood flow is reduced in patients with chronic respiratory failure caused by chronic obstructive pulmonary disease (COPD), and changes in renal hemodynamics are likely to be important in the pathogenesis of the edematous state of cor pulmonale. We therefore examined the hypothesis that this renal vasoconstriction is reversible by comparing the effects of oxygen therapy and the renal vasodilator dopamine on renal hemodynamics in both hypoxemic patients with COPD and those who were also hypercapnic. We assessed renal hemodynamics noninvasively with color-flow Doppler ultrasound. In order to validate the technique we recorded renal hemodynamics in a group of healthy volunteers before and during a dopamine infusion, and in a subgroup we simultaneously measured effective renal plasma flow (ERPF) with para-aminohippurate clearance. In the healthy volunteers there was a 22.5% rise in time-adjusted mean arterial velocity (Tamx) measured by Doppler compared with a 22% rise in ERPF with dopamine. This rise was significant (p < 0.05). In hypoxemic, normocapnic subjects Tamx rose by 25% with oxygen (p < 0.005), 20% with dopamine (p < 0.005), and 24% with both therapies. There was no significant change in aortic flow whether the subjects received air, oxygen, or dopamine (p = 0.77). In the hypercapnic patients there was no significant change in aortic or renal velocities while receiving oxygen or dopamine (p = 0.85 and 0.86). We conclude that color-flow Doppler velocity measurements can accurately detect changes in renal blood flow. Oxygen and dopamine are equipotent renal vasodilators in hypoxic COPD, but the effect is not additive.(ABSTRACT TRUNCATED AT 250 WORDS)
B-Cell and T-Cell Markers in Lymphoid Proliferations
Authors: Maxime Seligmann
Journal: New England Journal of Medicine (1974)

The recent discovery of surface markers considered to be specific for human thymus-derived (T) and bone marrow-derived (B) cells has provided new insights into the pathogenesis of immunoproliferative and immunodeficiency diseases.1 However, the diagnostic value of these markers needs critical evaluation, and the interpretation of investigative results requires much caution.The spontaneous formation of rosettes with sheep erythrocytes appears to be a specific property of T lymphocytes. However, quantitation of rosette-forming T cells is not standardized, and the fundamental nature of the phenomenon is unknown. Most heteroantiserums "specific" for human T or B cells are only relatively specific and are . . .
Back treatment needs revolution, says report
Authors: K. McKenzie, F. B Charatan
Journal: BMJ (1994)

Management of acute back pain in Britain may be contributing to chronic problems and disability, said the Clinical Standards Advisory Group last week. Its 160 page report says that back pain is increasing and that a revolution in existing services is needed.

The advisory group, which is funded by the Department of Health, wants to see fundamental changes in the treatment of back pain, which accounts for the loss of an estimated 52 million work days a year. The condition also costs pounds sterling 1.4bn …
Partial Stunning in Thyroid Remnant After Administration of Scanning Dose Followed By 100 mCi I-131 Therapy
Authors: HÜLYA YAGCLOGLU, ELOÇIN ÖZALP, ERKAN IBIS, GÜLSEREN ARAS
Journal: Clinical Nuclear Medicine (1996)

A 24-year-old woman with papillary thyroid carcinoma was imaged with 5 mCi of I-131, 2 months after thyroid surgery. Preablation imaging demonstrated focal uptake in six different areas in the thyroid remnant. After administration of 100 mCi of an ablation dose, repeat imaging was performed on the fifth day when the patient's residual activity fell below 30 mCi. Only two focal radioiodine uptake areas were observed in the neck region, whereas four of six other focuses in the preablation scan showed no uptake. Although the exact explanation of the partial suppression of the thyroid remnant, as in this interesting case, is not known, it may be due to an elevated radioiodine uptake and suppression by the 5 mCi scanning dose of I-131 on the areas without uptake. The authors conclude that future investigations on this findings are necessary.
HLA-B27 antigen in diagnosis of atypical seronegative inflammatory arthropathy.
Authors: G Joliat, A Ferro, M Jeannet, H Ott
Journal: Annals of the Rheumatic Diseases (1976)

Eighteen patients with an inflammatory pauciarticular peripheral arthropathy not typical of any known entity showed an asymmetrical pattern of disease, with a predilection for the lower extremities. Destructive joint changes and deformities were absent (mean follow-up 10 years). Although spondylitis and sacroiliitis were absent on x-rays, HLA-B27 antigen was found in 8 patients (44%). This antigen and similar joint symptoms are also found in other forms of arthritis.
Thanks for Throwaways
Authors: OSCAR F. ROSENOW
Journal: Annals of Internal Medicine (1972)

Letters, Comments, and Corrections1 September 1972Thanks for ThrowawaysOSCAR F. ROSENOW, M.D.OSCAR F. ROSENOW, M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-77-3-485_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptTo the editor: In the May 1972 issue (Ann Intern Med 76:837) Dr. Joe D. Hull writes about receiving "junk" mail, as he terms it. It is evident that he is a recent graduate and not in practice, judging'from the dates through which he saved the so-called junk mail. Most of the complaints that I have seen in the past years about throwaway journals received have been by younger physicians.I find every throwaway publication of value; throughout the year there is always some excellent educational material that has practical application. Many of the free publications are of more educational... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Riverside Medical Building Columbus, Ohio PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 September 1972Volume 77, Issue 3Page: 485-486KeywordsGraduate medical education ePublished: 1 December 2008 Issue Published: 1 September 1972 PDF downloadLoading ...
GPs' income fell for the second year in a row in 2007-8
Authors: N. Hawkes
Journal: BMJ (2010)

The incomes of GPs declined for the second year in a row in 2007-8, latest figures show.

Income before tax for the average GP on a General Medical Services (GMS) contract was £100 324 (€110 000; $150 000) before tax, a fall of just more than £3000 on 2006-7, and £6000 on the peak year, 2005-6, when the new contract came into force. Expenses have risen and gross earnings have remained much the same, squeezing the net income GP principals earned from their practices.

GPs on Personal Medical Services (PMS) contracts did better. They earned an average of £106 072, …
Pulmonary arterial hypertension: an autoimmune disease?
Authors: L. Mouthon, L. Guillevin, M. Humbert
Journal: European Respiratory Journal (2005)

Pulmonary arterial hypertension (PAH) is a rare condition that occurs as a consequence of chronic obstruction of small pulmonary arteries due to endothelial cell, vascular smooth muscle cell and fibroblast dysfunction and proliferation 1. In recent years, major advances have been achieved in the understanding of PAH pathophysiology 1–7. It has been firmly demonstrated that pulmonary artery endothelial dysfunction leads to chronically impaired production of vasodilators, such as nitric oxide and prostacyclin, along with overexpression of vasoconstrictors such as endothelin-1 8–10. Moreover, genetic studies have shown that germline mutations in the gene coding for bone morphogenetic protein receptor type II (BMPR2) certainly play a critical role in a proportion of patients with familial and idiopathic PAH 2, 3. Immune disturbances are also believed to contribute to PAH 5. This is particularly clear in PAH related to connective tissue diseases 5, 11. In addition, there is a long standing association between autoimmunity and PAH of various origins including idiopathic PAH. However, it remains uncertain how autoimmune mechanisms contribute to the pathogenesis of PAH. In the current issue of the European Respiratory Journal , Nicolls et al. 7 review available data documenting the association of autoimmunity and PAH and speculate on the possible role of autoimmune injury in the pathogenesis of the disease.

PAH is a common …
Psychophysical responses to a speech stressor: Correlation of plasma beta-endorphin levels at rest and after psychological stress with thermally measured pain threshold in patients with coronary artery disease
Authors: David S. Sheps, Martha N. Ballenger, Guy E. De Gent, Rungroj Krittayaphong, Eileen Dittman, William Maixner, William McCartney, Robert N. Golden, Gary Koch, Kathleen C. Light
Journal: Journal of the American College of Cardiology (1995)
Coupling and Uncoupling of Tumor Immunity and Autoimmunity
Authors: Wilbur B. Bowne, Roopa Srinivasan, Jedd D. Wolchok, William G. Hawkins, Nathalie E. Blachere, Ruben Dyall, Jonathan J. Lewis, Alan N. Houghton
Journal: The Journal of Experimental Medicine (1999)

Self-antigens, in the form of differentiation antigens, are commonly recognized by the immune system on melanoma and other cancers. We have shown previously that active immunization of mice against the melanocyte differentiation antigen, a tyrosinase-related protein (TRP) gp75TRP-1 (the brown locus protein) expressed by melanomas, could induce tumor immunity and autoimmunity manifested as depigmentation. In this system, tumor immunity and autoimmunity were mediated by autoantibodies. Here, we characterize immunity against another tyrosinase family glycoprotein TRP-2 (the slaty locus protein), using the same mouse model and method of immunization. As observed previously for gp75TRP-1, immunity was induced by DNA immunization against a xenogeneic form of TRP-2, but not against the syngeneic gene, and depended on CD4+ cells. Immunization against TRP-2 induced autoantibodies and autoreactive cytotoxic T cells. In contrast to immunization against gp75TRP-1, both tumor immunity and autoimmunity required CD8+ T cells, but not antibodies. Only autoimmunity required perforin, whereas tumor immunity proceeded in the absence of perforin. Thus, immunity induced against two closely related autoantigens that are highly conserved throughout vertebrate evolution involved qualitatively different mechanisms, i.e., antibody versus CD8+ T cell. However, both pathways led to tumor immunity and identical phenotypic manifestations of autoimmunity.
Fabrication of tubular tissue constructs by centrifugal casting of cells suspended in an in situ crosslinkable hyaluronan-gelatin hydrogel
Authors: Vladimir Mironov, Vladimir Kasyanov, Xiao Zheng Shu, Carol Eisenberg, Leonard Eisenberg, Steve Gonda, Thomas Trusk, Roger R. Markwald, Glenn D. Prestwich
Journal: Biomaterials (2005)
Medical Care for the Final Years of Life
Authors: David B. Reuben
Journal: JAMA (2009)

The case of an 83-year-old man who has had a fall-related injury and continues to be the sole caregiver for his wife who has dementia exemplifies a common situation that clinicians face--planning for the final years of an elderly individual's life. To appropriately focus on the patient's most pressing issues, the approach should begin with an assessment of life expectancy and incorporation of evidence-based care whenever possible. Short-term issues are focused on efforts to restore the patient to his previous state of health. Mid-range issues address providing preventive care, identifying geriatric syndromes, and helping him cope with the psychosocial needs of being a caregiver. Long-term issues relate to planning for his eventual decline and meeting his goals for the end of life. Unfortunately, the workload and inefficiencies of primary care practice present barriers to providing optimal care for older patients. Systematic approaches, including team care, are needed to adequately manage chronic diseases and coordinate care.