tbuckley/cabot-search huggingface dataset:
Abstract C47: 21-OH 6,19-epoxyprogesterone: A new dissociated glucocorticoid with anti-inflammatory properties but without antiapoptotic effects on chemotherapeutically treated mouse mammary tumor cells
Authors: Andres J. Orqueda, Adriana Veleiro, Elisa Bal de Kier Joffé, Edith Kordon, Gerardo Burton, Adali Pecci
Journal: Cancer Research (2009)

Abstract Glucocorticoids (GCs) are widely used as coadyuvants in the treatment of solid tumors with chemotherapics such as paclitaxel (PXL) and doxorubicin (DOXO). However, clinical evidence supports the idea that GCs may induce resistance to these antitumor therapies. To improve cancer treatment quality, intense efforts are being made to design new dissociated steroids (steroid receptor glucocorticoid modulators (SRGMs). These compounds should mimic only the beneficial aspects of glucocorticoid therapy without inducing the undesired side effects in cancer patients. We have previously shown that dexamethasone (Dex), a well-known synthetic GC, inhibits PXL or DOXO induced apoptosis in breast tumor cells through a mechanism involving Bcl-XL and Bcl-2 induction. Here, our goal was to compare Dex effects with those triggered by 21-OH-6,19-epoxyprogesterone (21-OH-6,19-OP), which is a rigid steroid considered a passive GC antagonist. Molecular dynamic simulation studies predicted that 21-OH-6,19OP is unable to induce GR/21-OH-6,19-OP complex homodimerization and/or binding to coactivators, making these complex incapable to directly activate gene transcription (Alvarez et al J Med Chem. 2008. 13:1352). The effects of 21-OH-6,19-OP on apoptosis induced by DOXO or PXL in the epithelial mouse mammary tumor cell line LM3 was determined by analyzing Caspase-3 activity and gene and protein expression of antiapoptotic members of the Bcl family, i.e. Bcl-2 and Bcl-XL. The results show that, contrary to Dex, 21-OH-6,19-OP cannot reverse apoptosis induced by DOXO or PXL in LM3 cells. In fact, 21-OH-6,19-OP and Dex differentially regulate Bcl-2 and Bcl-XL expression. Dex's reversion on chemotherapic induced apoptosis (Dex+DOXO o Dex+PXL) correlates with an increase in Bcl-XL levels, while 21-O-H-6, 19-OP does not affect neither cell death nor Bcl-XL levels. The relevance of Bcl-XL involvement in DOXO resistance of cells treated with Dex was confirmed by knocking-down Bcl-XL with specific siRNA. Silencing Bcl-XL expression directly implicated loss of antiapoptotic GC effects. On the other hand, 21-OH-6,19-OP antiinflammatory action was also evaluated on the lung epithelial tumor cell line A549 by determining Interleukin-8 (IL-8) and Cyclooxygenase-2 (COX-2) expression in the presence of the Tumor Necrosis Factor-alpha (TNF-α). Expression levels of IL-8 and COX-2, measured by qRT-PCR, indicate that 21-OH-6,19-OP may have antiinflammatory effects as it reverses these inflammation markers expression induced by TNF-α in lung epithelial cells. Together, these findings suggest that 21-OH-6,19-OP is a SRGM that keeps glucocorticoid antiinflammatory properties without antiapoptotic effects, thus becoming a novel candidate for treatment of solid tumors as breast cancer. Citation Information: Cancer Res 2009;69(23 Suppl):C47.
Identification of the principal proteoglycan-binding site in LDL. A single-point mutation in apo-B100 severely affects proteoglycan interaction without affecting LDL receptor binding.
Authors: J Borén, K Olin, I Lee, A Chait, T N Wight, T L Innerarity
Journal: Journal of Clinical Investigation (1998)

The subendothelial retention of LDLs through their interaction with proteoglycans has been proposed to be a key process in the pathogenesis of atherosclerosis. In vitro studies have identified eight clusters of basic amino acids in delipidated apo-B100, the protein moiety of LDL, that bind the negatively charged proteoglycans. To determine which of these sites is functional on the surface of LDL particles, we analyzed the proteoglycan-binding activity of recombinant human LDL isolated from transgenic mice. Substitution of neutral amino acids for the basic amino acids residues in site B (residues 3359-3369) abolished both the receptor-binding and the proteoglycan-binding activities of the recombinant LDL. Chemical modification of the remaining basic residues caused only a marginal further reduction in proteoglycan binding, indicating that site B is the primary proteoglycan-binding site of LDL. Although site B was essential for normal receptor-binding and proteoglycan-binding activities, these activities could be separated in recombinant LDL containing single-point mutation. Recombinant LDL with a K3363E mutation, in which a glutamic acid had been inserted into the basic cluster RKR in site B, had normal receptor binding but interacted defectively with proteoglycans; in contrast, another mutant LDL, R3500Q, displayed defective receptor binding but interacted normally with proteoglycans. LDL with normal receptor-binding activity but with severely impaired proteoglycan binding will be a unique resource for analyzing the importance of LDL- proteoglycan interaction in atherogenesis. If the subendothelial retention of LDL by proteoglycans is the initial event in early atherosclerosis, then LDL with defective proteoglycan binding may have little or no atherogenic potential.
Straight Talk: Sexuality Education for Parents and Kids 4-7
Authors: Margaret McHugh
Journal: JAMA (1987)

With the increasing focus on the family as the primary source of information about sexuality, there is a need for material for parents to initiate and sustain this learning process. Straight Talk , written by Marilyn Ratner and Susan Chamlin and published by Planned Parenthood of Westchester, NY, is such a primer, providing in a clear, concise 40-page format the basic knowledge and a series of how-to presentations. Subtitled Sexuality Education for Parents and Kids 4-7, this book, best described as a workbook, has been divided into major areas of discussion followed by a four-page tear out of activities for children of specific ages, entitled Kids' Place. The discussion areas include a review of common parental concerns, identification of problems that parents confront in the realm of sexuality, and methods and ways to answer the questions posed by children.  Using the term askable parent, the authors begin with the parental perspective,
Long-term comparison of 3 controller regimens for mild-moderate persistent childhood asthma: The Pediatric Asthma Controller Trial
Authors: Christine A. Sorkness, Robert F. Lemanske, David T. Mauger, Susan J. Boehmer, Vernon M. Chinchilli, Fernando D. Martinez, Robert C. Strunk, Stanley J. Szefler, Robert S. Zeiger, Leonard B. Bacharier, Gordon R. Bloomberg, Ronina A. Covar, Theresa W. Guilbert, Gregory Heldt, Gary Larsen, Michael H. Mellon, Wayne J. Morgan, Mark H. Moss, Joseph D. Spahn, Lynn M. Taussig
Journal: Journal of Allergy and Clinical Immunology (2006)
Survival Strategies for New Scientists
Authors: Lawrence Grouse
Journal: JAMA (1988)

Behind the veneer of this "how-to" or "self-help" book for graduate students is a profoundly disturbing cynicism about the role of academic science in the United States today. By now, books that reveal the ways of the world to newcomers in a field are familiar. This one sets forth in many detailed flowcharts the various career pathways that scientists have and lists of considerations relevant to how to proceed with a career in science. However, I question the idea that students can control their progress up the academic ladder by reading a selfhelp book. For example, the author advises, "Risk... brown-nosing" to win favor with your thesis adviser. Is this useful advice? I still have the perhaps naive belief that scientific insight and effort will ultimately have the dominant effect on a student's future in academic science. I do not dispute that the book contains insights into the sociology and
Some Observations on the Relation of the High-Frequency Bed Ballistocardiogram to that Obtained from an Aperiodic Bed
Authors: DENNIS C. DEUCHAR, SAMUEL A. TALBOT, W. R. SCARBOROUGH
Journal: Circulation (1955)

A previous analysis of the mechanical behavior of current ballistocardiographic systems allowed the prediction of certain relationships between records from the Starr high-frequency bed and those representing undistorted forces applied to the body by the cardiovascular "generator." The latter were obtained by recording the acceleration of an "aperiodic mercury bed" platform. A relationship between the form of these two types of records from 80 subjects was sought. In varying types of normal and abnormal records the predicted relationship between the two different kinds of ballistocardiograms was consistently observed. It is concluded that records from the high-frequency bed grossly reflect the slower forces applied to the body, but are distorted with respect to phase, amplitude and frequency content, this being due in part to the elastic properties of the dorsal surface of the body and in part to the weight and stiffness of the platform support.
Expression and Prognostic Value of L1-CAM in Breast Cancer.
Authors: K. Milde-Langosch, C. Schröder, V. Mueller, U. Schumacher, R. Wirtz, P. Altevogt, S. Krenkel, F. Jaenicke
Journal: Cancer Research (2009)

Abstract Background: The L1 cell adhesion molecule (L1-CAM) has been shown to be involved in cell motility, invasion, chemoresistance and tumor growth in various experimental models, and is associated with impaired prognosis in melanoma, colon and ovarian cancer. However, limited information about its expression in breast cancer is available.Methods: To analyse its role and possible prognostic value in primary breast cancers, L1-CAM mRNA and protein expression using microarray analysis (n=167) and Western Blotting (n=106) was performed. Its cellular distribution was demonstrated by immunohistochemistry. The results were correlated with classical histological data, biologically relevant disease markers and clinical data including disease outcome.Results: L1-CAM mRNA overexpression and protein expression was observed in 14-15% of the carcinomas and its expression was confirmed by immunohistochemical staining. Generally tumour cells at the tumour stroma interface were L1-positive. High L1-CAM expression was associated with nodal involvement, high grading, human epidermal growth receptor 2 (Her-2), plasminogen activator inhibitor 1 (PAI-1) and vascular endothelial growth factor (VEGF) expression and a negative estrogen receptor (ER) status, but not with neuroendocrine markers. High L1-CAM mRNA expression in primary breast cancers was associated with a significantly shorter disease-free (p=0.011) and overall survival (p=0.005).Conclusions Our results indicate that L1-CAM is highly expressed in a relatively agressive subgroup of breast cancers. Given the emerging functional role of L1-CAM in promoting tumor growth and metastasis our results suggest that L1 may have this function in breast cancer as well. Thus, L1-CAM might be a suitable target for specific immunotherapies in selected high-risk breast cancer patients. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3044.
AN ARTICLE CONTRIBUTED TO AN ANNIVERSARY VOLUME IN HONOR OF DOCTOR JOSEPH HERSEY PRATT
Authors: WALTER M. BOOTHBY
Journal: Annals of Internal Medicine (1937)

Article1 December 1937AN ARTICLE CONTRIBUTED TO AN ANNIVERSARY VOLUME IN HONOR OF DOCTOR JOSEPH HERSEY PRATTTHE VARIABILITY OF BASAL METABOLISM: SOME OBSERVATIONS CONCERNING ITS APPLICATION IN CONDITIONS OF HEALTH AND DISEASE*WALTER M. BOOTHBY, M.D., F.A.C.P., JOSEPH BERKSON, M.D., WILLIAM A. PLUMMER, M.D., F.A.C.P.WALTER M. BOOTHBY, M.D., F.A.C.P.Search for more papers by this author, JOSEPH BERKSON, M.D.Search for more papers by this author, WILLIAM A. PLUMMER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-11-6-1014 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptMeans, discussing the value of the basal metabolic rate, says: "It should be remembered that basal metabolic rates are never too low (except when a technical error or an inward leak in the apparatus occurs or when the subject goes to sleep). All the factors which tend to make a reading inaccurate tend to make it too high: food, failure to eat properly, emotion, fever and so forth. Therefore a single low reading has more significance than a single high one." Similar statements can be found in the writings of nearly all students of metabolism, including Benedict, DuBois, Krogh, Boothby...References1. BERKSONBOOTHBY JWM: Am. Jr. Physiol. (In press.) Google Scholar2. MEANS JH: The thyroid and its diseases, 1937, J. B. Lippincott Co., Philadelphia, p. 146. Google Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Rochester, Minnesota*Submitted for publication August 28, 1937. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited ByNeoplasms of the ThyroidDie Grundstoffe der NahrungZur Frage jahreszeitlicher Schwankungen des Ruhe-N�chternumsatzes des MenschenGesamtstoffwechsel und ErnährungThe Chemistry and Physiology of the ThyroidDie Darstellung von Faseraktionen der ruhenden Muskulatur am MenschenDas EnergetischeClinical Application of the Basal Metabolism TestBibliographyThe clinical significance of cholesterol 1 December 1937Volume 11, Issue 6Page: 1014-1023KeywordsEatingEmotionsFeversFoodSleep Issue Published: 1 December 1937 PDF DownloadLoading ...
Cancer charities warn that welfare changes could push patients into poverty
Authors: J. Carlowe
Journal: BMJ (2011)

The heads of 30 cancer charities have written to the works and pensions secretary warning that planned welfare reforms could push cancer patients into poverty.

In an open letter published in the Guardian, the chief executives of the UK’s leading cancer organisations, including Macmillan Cancer Support and Cancer Research UK, called on Iain Duncan Smith MP, to “consider the impact” his proposed reforms would have on people living with cancer in the UK.

In the letter, published ahead of the Welfare Reform Bill’s second reading in the Commons on 9 March, the charity leaders wrote that they welcomed proposals to simplify the welfare system but they had major concerns about planned changes to disability benefits. They warned …
Stopping drinking and risk of oesophageal cancer
Authors: K K Cheng, S W Duffy, N E Day, T H Lam, S F Chung, P Badrinath
Journal: BMJ (1995)

<h3>Abstract</h3> <b>Objective</b>: To examine the effect of stopping drinking on the risk of oesophageal cancer. <b>Design</b>: Hospital based case-control study. <b>Setting</b>: Surgical departments of four district general hospitals and general practices in Hong Kong. <b>Subjects</b>: Cases were 400 consecutive admissions of patients with histologically confirmed diagnosis of oesophageal cancer during a 21 month period in 1989-90 (87% response rate). Controls were 1598 patients selected from the same surgical departments as the cases and from the general practices from which the cases were originally referred (95% response rate). <b>Main outcome measure</b>: Relative risk of developing oesophageal cancer after stopping drinking (adjusted for age, education, place of birth, smoking, and diet). <b>Results</b>: Current light drinking (&lt;200 g ethanol/week) was not associated with significant increase in risk. Among former drinkers risk fell more quickly in moderate (200-599 g/week) than heavy (&gt;/=600 g/week) drinkers. Even among heavy drinkers, however, risk had dropped substantially after five to nine years of not drinking. The results suggest that the time taken for risk to return to that in subjects who never drink was 10-14 years for moderate drinkers and 15 years or more, if ever, for heavy drinkers. <b>Conclusion</b>: Risk of oesophageal cancer decreases fairly rapidly with time after abstaining from drinking. This new finding could be used in health promotion to encourage behavioural changes, especially in heavy drinkers, who have a very high risk of developing oesophageal cancer. It also suggests that alcoholic beverages have a strong effect on the late stage of carcinogenesis. <h3>Key messages</h3> Key messages Current light drinking (&lt;200 g ethanol a week) was not associated with significant increase in risk Among former drinkers, risk had dropped substantially after five to nine years of cessation. The time taken for risk to return to that of people who never drink was 10-14 years for moderate drinkers (200-599 g a week) and 15 years or more, if ever, for heavy drinkers (&gt;/=600 g a week) This new finding could be used in health promotion to encourage behavioural changes. It suggests that alcoholic beverages have a strong effect on the late stage of carcinogenesis
CLINICAL COUNTERPOINT: Vitamin D: New Actions, New Analogs, New Therapeutic Potential*
Authors: DANIEL D. BIKLE
Journal: Endocrine Reviews (1992)

AN EXCITING new era has developed in the vitamin D field with the discovery of new target tissues, mechanisms of action, and selective analogs. As a clinical counterpoint article, this review will emphasize the potential clinical applications of these new discoveries. Many of the applications to be discussed remain untested, whereas others remain in their infancy. A major reason for optimism in predicting an expanding list of therapeutic applications for the vitamin D metabolites and analogs stems from the development of analogs of calcitriol that differ in their biological effects. In particular, analogs are now available that appear to separate the effects of calcitriol on growth and differentiation from effects on intestinal calcium absorption or bone mobilization. This apparent selectivity may reflect altered pharmacokinetic properties or may involve mechanistic differences at the cellular level as well. Regardless, the development of these drugs is likely to lead to clinical applications in which raising serum calcium need not accompany other actions. The initial portion of this review is devoted to a discussion of these analogs. The main goal of this article is to review those areas in which calcitriol and its analogs are being used in new ways and to describe potential applications that are suggested by the newly discovered actions of calcitriol. Thus, new concepts in vitamin D action have led to clinical trials of calcitriol and its analogs in the management of hyperparathyroidism and psoriasis, and trials of these drugs in certain malignancies or immunological disorders may not be far off. None of the clinical applications discussed are approved applications for these drugs. Rather, this review is intended to link the laboratory observations of the past decade with the bedside of the next decade.
Lyme Arthritis: Not Confined to the East Coast
Authors: Zenonas Danilevicius
Journal: JAMA (1979)

Some medical discoveries happen to be initiated by laymen. In November 1975 a mother from the town of Old Lyme, Conn, informed the state health department of an unusually high incidence of an illness diagnosed as juvenile rheumatoid arthritis in her small community. Another mother in the same town soon reported a cluster of similar illness in her family; her husband, two of their children, and several neighbors all had the same type of arthritis. Soon a team of physicians from the Yale University School of Medicine began investigating the unusual outbreak of the supposed juvenile rheumatoid arthritis in Connecticut. In three contiguous Connecticut communities, Steere et al<sup>1</sup>studied the cases of 51 residents (39 children and 12 adults) who had an illness characterized by a symmetric swelling and pain in a few large joints, some of them with an edematous papule that developed into an expanding red annular
Virological monitoring and resistance to first-line highly active antiretroviral therapy in adults infected with HIV-1 treated under WHO guidelines: a systematic review and meta-analysis
Authors: Ravindra K Gupta, Andrew Hill, Anthony W Sawyer, Alessandro Cozzi-Lepri, Viktor von Wyl, Sabine Yerly, Viviane Dias Lima, Huldrych F Günthard, Charles Gilks, Deenan Pillay
Journal: The Lancet Infectious Diseases (2009)
Insulin Therapy Is Associated With Platelet Dysfunction in Patients With Type 2 Diabetes Mellitus on Dual Oral Antiplatelet Treatment
Authors: Dominick J. Angiolillo, Esther Bernardo, Celia Ramírez, Marco A. Costa, Manel Sabaté, Pilar Jimenez-Quevedo, Rosana Hernández, Raul Moreno, Javier Escaned, Fernando Alfonso, Camino Bañuelos, Theodore A. Bass, Carlos Macaya, Antonio Fernandez-Ortiz
Journal: Journal of the American College of Cardiology (2006)
Structure-inherent targeting of near-infrared fluorophores for parathyroid and thyroid gland imaging
Authors: Hoon Hyun, Min Ho Park, Eric A Owens, Hideyuki Wada, Maged Henary, Henricus J M Handgraaf, Alexander L Vahrmeijer, John V Frangioni, Hak Soo Choi
Journal: Nature Medicine (2015)
PSYCHIATRIC NIGHT TREATMENT UNIT IN A GENERAL HOSPITAL
Authors: A. E. MOLL
Journal: American Journal of Psychiatry (1957)

The advantages of a night centre may be briefly summarized as follows: (1) the main function is to enable individuals to undergo psychiatric treatment without interruption of their working hours; (2) it facilitates the acceptance of psychiatric treatment by those individuals who, for reasons other than financial, would refuse treatment if this involves hospitalization. Not infrequently the fear of insanity is such that hospitalization is interpreted by the patient as confirmatory evidence of their unwarranted belief of being "insane"; (3) it enables individuals to accept psychiatric treatment without disclosing this need to anyone apart from the immediate members of the family. This is especially important to the employee who fears the loss of his job or jeopardy of promotions, should his employer know that he is "a psychiatric case"; (4) it is economical to both the patient and the hospital; (5) treatment at the night centre does not interfere with the patient's social activities, particularly since he has the weekends to himself. This, together with the fact that he is employed during the day, tends to minimize the regressive phenomena contingent to hospitalization and overdependence upon the hospital; (6) it facilitates the weaning process of patients previously hospitalized in the inpatient section or in the day centre, by giving the patient some support during the early stages of his re-adjustment to work; (7) it makes it possible for individuals to undergo psychiatric treatment during the only time they can be spared from their daily activities, e. g., the mother who can undergo treatment only after the husband has come home to take care of the children; (8) it offers facilities to individuals who can be helped by weekly psychotherapeutic interviews after working hours; (9) it provides an over-night service for the emergency psychiatric night cases who appear in the casualty department of the hospital. I trust that the enumeration of these several advantages does not lead one to the assumption that a night treatment unit is the answer to the immense problem of the treatment of mental illness. It is purely a small extension of the psychiatric service which any large general hospital should be able to provide. It is, however, a new venture, and I trust a seed which, in time, may sprout and lead to the establishment of night treatment facilities in other hospitals and possibly also in specialties other than psychiatry.
Alan Eastling Ridley
Authors: J. Pooley
Journal: BMJ (2014)

Alan Eastling Ridley was born in Newcastle; his parents were Arthur and Nance Ridley. Arthur was a manager for British Rail, and Nance was a milliner. Alan grew up in Whitley Bay, an only child. He attended Whitley Bay Grammar School, where he excelled both academically and on the sports field. He maintained a lifelong love for rugby, cricket, and tennis, and was still playing squash in his 50s.

Alan did his junior doctor training in general practice and maternity. He enjoyed sharing stories of delivering babies by lamp light on farm kitchen tables to his …